WO2002040491A1 - Ortho substituted chiral phosphines and phosphinites and their use in asymmetric catayltic reactions - Google Patents

Ortho substituted chiral phosphines and phosphinites and their use in asymmetric catayltic reactions Download PDF

Info

Publication number
WO2002040491A1
WO2002040491A1 PCT/US2001/043779 US0143779W WO0240491A1 WO 2002040491 A1 WO2002040491 A1 WO 2002040491A1 US 0143779 W US0143779 W US 0143779W WO 0240491 A1 WO0240491 A1 WO 0240491A1
Authority
WO
WIPO (PCT)
Prior art keywords
group
aryl
independently selected
alkyl
substituted
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2001/043779
Other languages
French (fr)
Inventor
Xumu Zhang
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Penn State Research Foundation
Original Assignee
Penn State Research Foundation
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Penn State Research Foundation filed Critical Penn State Research Foundation
Priority to CA002427579A priority Critical patent/CA2427579C/en
Priority to EP01996543A priority patent/EP1341797A4/en
Priority to AU2002216719A priority patent/AU2002216719A1/en
Priority to JP2002543499A priority patent/JP4167899B2/en
Publication of WO2002040491A1 publication Critical patent/WO2002040491A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
    • C07F9/6581—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms
    • C07F9/6584—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms having one phosphorus atom as ring hetero atom
    • C07F9/65848—Cyclic amide derivatives of acids of phosphorus, in which two nitrogen atoms belong to the ring
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
    • B01J31/18—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms
    • B01J31/1845—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms the ligands containing phosphorus
    • B01J31/1875—Phosphinites (R2P(OR), their isomeric phosphine oxides (R3P=O) and RO-substitution derivatives thereof)
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
    • B01J31/24—Phosphines, i.e. phosphorus bonded to only carbon atoms, or to both carbon and hydrogen atoms, including e.g. sp2-hybridised phosphorus compounds such as phosphabenzene, phosphole or anionic phospholide ligands
    • B01J31/2404—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring
    • B01J31/2409—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring with more than one complexing phosphine-P atom
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
    • B01J31/24—Phosphines, i.e. phosphorus bonded to only carbon atoms, or to both carbon and hydrogen atoms, including e.g. sp2-hybridised phosphorus compounds such as phosphabenzene, phosphole or anionic phospholide ligands
    • B01J31/2404—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring
    • B01J31/2442—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring comprising condensed ring systems
    • B01J31/2447—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring comprising condensed ring systems and phosphine-P atoms as substituents on a ring of the condensed system or on a further attached ring
    • B01J31/2452—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring comprising condensed ring systems and phosphine-P atoms as substituents on a ring of the condensed system or on a further attached ring with more than one complexing phosphine-P atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B53/00—Asymmetric syntheses
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C231/00—Preparation of carboxylic acid amides
    • C07C231/16—Preparation of optical isomers
    • C07C231/18—Preparation of optical isomers by stereospecific synthesis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/49—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reaction with carbon monoxide
    • C07C45/50—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reaction with carbon monoxide by oxo-reactions
    • C07C45/505—Asymmetric hydroformylation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
    • C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
    • C07C45/72—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction of compounds containing >C = O groups with the same or other compounds containing >C = O groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
    • C07C67/303—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by hydrogenation of unsaturated carbon-to-carbon bonds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
    • C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
    • C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/46—Phosphinous acids [R2POH], [R2P(= O)H]: Thiophosphinous acids including[R2PSH]; [R2P(=S)H]; Aminophosphines [R2PNH2]; Derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/48—Phosphonous acids [RP(OH)2] including [RHP(=O)(OH)]; Thiophosphonous acids including [RP(SH)2], [RHP(=S)(SH)]; Derivatives thereof
    • C07F9/4866—Phosphonous acids [RP(OH)2] including [RHP(=O)(OH)]; Thiophosphonous acids including [RP(SH)2], [RHP(=S)(SH)]; Derivatives thereof the ester moiety containing a substituent or structure which is considered as characteristic
    • C07F9/4875—Esters with hydroxy aryl compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/48—Phosphonous acids [RP(OH)2] including [RHP(=O)(OH)]; Thiophosphonous acids including [RP(SH)2], [RHP(=S)(SH)]; Derivatives thereof
    • C07F9/4883—Amides or esteramides thereof, e.g. RP(NR'2)2 or RP(XR')(NR''2) (X = O, S)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/50—Organo-phosphines
    • C07F9/5027—Polyphosphines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/655—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms
    • C07F9/65515—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a five-membered ring
    • C07F9/65517—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a five-membered ring condensed with carbocyclic rings or carbocyclic ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/655—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms
    • C07F9/6552—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a six-membered ring
    • C07F9/65522—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a six-membered ring condensed with carbocyclic rings or carbocyclic ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/655—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms
    • C07F9/65525—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a seven-(or more) membered ring
    • C07F9/65527—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a seven-(or more) membered ring condensed with carbocyclic rings or carbocyclic ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
    • C07F9/6571—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and oxygen atoms as the only ring hetero atoms
    • C07F9/657163—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and oxygen atoms as the only ring hetero atoms the ring phosphorus atom being bound to at least one carbon atom
    • C07F9/65719—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and oxygen atoms as the only ring hetero atoms the ring phosphorus atom being bound to at least one carbon atom the ring phosphorus atom and, at least, one ring oxygen atom being part of a (thio)phosphonous acid derivative
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
    • C07F9/6571—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and oxygen atoms as the only ring hetero atoms
    • C07F9/6574—Esters of oxyacids of phosphorus
    • C07F9/65744—Esters of oxyacids of phosphorus condensed with carbocyclic or heterocyclic rings or ring systems
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
    • B01J2231/60—Reduction reactions, e.g. hydrogenation
    • B01J2231/64—Reductions in general of organic substrates, e.g. hydride reductions or hydrogenations
    • B01J2231/641—Hydrogenation of organic substrates, i.e. H2 or H-transfer hydrogenations, e.g. Fischer-Tropsch processes
    • B01J2231/643—Hydrogenation of organic substrates, i.e. H2 or H-transfer hydrogenations, e.g. Fischer-Tropsch processes of R2C=O or R2C=NR (R= C, H)
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
    • B01J2231/60—Reduction reactions, e.g. hydrogenation
    • B01J2231/64—Reductions in general of organic substrates, e.g. hydride reductions or hydrogenations
    • B01J2231/641—Hydrogenation of organic substrates, i.e. H2 or H-transfer hydrogenations, e.g. Fischer-Tropsch processes
    • B01J2231/645—Hydrogenation of organic substrates, i.e. H2 or H-transfer hydrogenations, e.g. Fischer-Tropsch processes of C=C or C-C triple bonds
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
    • B01J2531/02—Compositional aspects of complexes used, e.g. polynuclearity
    • B01J2531/0261—Complexes comprising ligands with non-tetrahedral chirality
    • B01J2531/0266—Axially chiral or atropisomeric ligands, e.g. bulky biaryls such as donor-substituted binaphthalenes, e.g. "BINAP" or "BINOL"
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
    • B01J2531/80—Complexes comprising metals of Group VIII as the central metal
    • B01J2531/82—Metals of the platinum group
    • B01J2531/821—Ruthenium
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
    • B01J2531/80—Complexes comprising metals of Group VIII as the central metal
    • B01J2531/82—Metals of the platinum group
    • B01J2531/822—Rhodium
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/07—Optical isomers
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2602/00—Systems containing two condensed rings
    • C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
    • C07C2602/04—One of the condensed rings being a six-membered aromatic ring
    • C07C2602/08—One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2602/00—Systems containing two condensed rings
    • C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
    • C07C2602/04—One of the condensed rings being a six-membered aromatic ring
    • C07C2602/10—One of the condensed rings being a six-membered aromatic ring the other ring being six-membered, e.g. tetraline

Definitions

  • the present invention relates to novel chiral ligands derived from 3,3'- substituted biaryl phosphines and phosphinites. More particularly, the present invention relates to transition metal complexes of these chiral phosphine ligands.
  • transition metal complexes are useful as catalysts in asymmetric reactions, such as, hydrogenation, hydride transfer, allylic alkylation, hydrosilylation, hydroboration, hydrovinylation, hydroformylation, olefin metathesis, hydrocarboxylation, isomerization, cyclopropanation, Diels- Alder reaction, Heck reaction, isomerization, Aldol reaction, Michael addition, epoxidation, kinetic resolution and [m+n] cycloaddition.
  • asymmetric reactions such as, hydrogenation, hydride transfer, allylic alkylation, hydrosilylation, hydroboration, hydrovinylation, hydroformylation, olefin metathesis, hydrocarboxylation, isomerization, cyclopropanation, Diels- Alder reaction, Heck reaction, isomerization, Aldol reaction, Michael addition, epoxidation, kinetic resolution and [m+n] cycloaddition.
  • BINAP (1) is one of the most frequently used chiral ligands.
  • the axially dissymmetric, fully aromatic BINAP has demonstrated to be highly effective for many asymmetric reactions (Noyori, R. et al. Ace. Chem. Res. 1990, 23, 345, Ohkuma, T. et al. J. Am. Chem. Soc. 1998, 120, 13529).
  • Recent results show that partially hydrogenated BINAP with a larger bite angle, H8- BINAP (2), is a better ligand for certain asymmetric reactions due to restriction of conformational flexibility (Zhang X. et al. Synlett 1994, 501).
  • NAPHOS (6) another example of a prior art compound has been prepared (Tamao, K. et al. Tetrahedron Lett. 1977, 1389) and was found to be not effective for asymmetric hydrogenation reaction.
  • the corresponding ligands with the N linker, BDPAB (7) and H8-BDPAB (8) have also been made and tested for asymmetric hydrogenation reactions (Zhang, F. et al. J. Am. Chem. Soc. 1998, 120, 5808).
  • the present invention includes a ligand represented by the formula or its enantiomer:
  • each X and X' is independently selected from the group consisting of: alkyl, aryl, substituted alkyl, substituted aryl, OR, SR, NR 2 , COOR, halide, SiR 3 , P(O)R 2 , P(O)(OR) 2 and P(OR) 2 ; wherein each Z and Z ⁇ is independently selected from the group consisting of: alkyl, aryl, substituted alkyl, substituted aryl, OR, SR, NR 2 , COOR, halide, SiR 3 , P(O)R 2 , P(O)(OR) 2 and P(OR) 2 ; or wherein Z and Z_ together form the bridging group A-B-Ai; wherein each Z', Z", Z and Z " is independently selected from the group consisting of: H, alkyl, aryl, substituted alkyl, substituted aryl, OR, SR, NR 2 , COOR, halide, SiR 3 ,
  • the present invention further includes a catalyst prepared by a process, which includes: contacting a transition metal salt, or a complex thereof, and a ligand according to the present invention.
  • the present invention still further includes a process for preparation of an asymmetric compound including: contacting a substrate capable of forming an asymmetric product by an asymmetric reaction and a catalyst prepared by a process including: contacting a transition metal salt, or a complex thereof, and a ligand according to the present invention.
  • the metal complexes are useful as catalysts in asymmetric reactions, such as, hydrogenation, hydride transfer, allylic alkylation, hydrosilylation, hydroboration, hydrovinylation, hydroformylation, olefin metathesis, hydrocarboxylation, isomerization, cyclopropanation, Diels- Alder reaction, Heck reaction, isomerization, Aldol reaction, Michael addition, epoxidation, kinetic resolution and [m+n] cycloaddition.
  • the metal complexes are particularly effective in Ru-catalyzed asymmetric hydrogenation of beta-ketoesters to beta- hydroxyesters and Ru-catalyzed asymmetric hydrogenation of enamides to beta amino acids.
  • the present invention includes 3, 3 '-substituted chiral biaryl phosphines and phosphinites and related ligands for applications in asymmetric catalysis.
  • Introduction of 3,3 '-substituted groups can restrict the rotation of substituents adjacent to the phosphines. Control of orientations of these groups around the phosphine can lead to effective chiral induction for asymmetric reactions.
  • Metal complexes of these phosphines, phosphinites and related non-C symmetric ligands with ortho substitution are useful for a large variety of asymmetric reactions.
  • a number of chiral ligands can be made having the desired structure in which the 3,3' positions are substituted, with the proviso that at least one ortho position is occupied by a group other than H atom.
  • ortho substituted groups play an important role for asymmetric catalysis.
  • the 3,3' substituted chiral biaryl phosphines, phosphinites and related ligands of the present invention are described below.
  • An important feature of these ligands is that at least one of the 3 and 3' positions must be occupied by a group other than hydrogen.
  • the ligands are represented by the formula:
  • each X and X' is independently selected from the group consisting of: alkyl, aryl, substituted alkyl, substituted aryl, OR, SR, NR 2 , COOR, halide, SiR 3 , P(O)R 2 , P(O)(OR) 2 and P(OR) 2 ; wherein each Z and Z ⁇ is independently selected from the group consisting of: alkyl, aryl, substituted alkyl, substituted aryl, OR, SR, NR 2 , COOR, halide, SiR 3 , P(O)R 2 , P(O)(OR) 2 and P(OR) 2 ; or wherein Z and Z ⁇ together form the bridging group A-B-A ⁇ wherein each Z', Z", Z ⁇ and Z_" is independently selected from the group consisting of: H, alkyl, aryl, substituted alkyl, substituted aryl, OR, SR, NR 2 , COOR, halide, SiR
  • the alkylene group includes compounds represented by the formula: -(CH 2 ) n -, wherein n is an integer in the range of from 1 to 8.
  • the present invention also includes the corresponding enantiomer of each of the above ligands.
  • the substituted alkyl group can have one or more substituents and each substituent can independently be halogen, ester, ketone, carboxylic acid, hydroxy, alkoxy, aryloxy, thiol, alkylthio or dialkylamino.
  • the aryl groups can optionally have one or more substituents, each of which can independently be halogen, ester, ketone, sulfonate, phosphonate, hydroxy, alkoxy, aryloxy, thiol, alkylthiol, nitro, amino, vinyl, substituted vinyl, carboxylic acid, sulfonic acid or phosphine.
  • the arylene groups optionally can have one or more substituents, each of which can independently be halogen, ester, ketone, sulfonate, phosphonate, hydroxy, alkoxy, aryloxy, thiol, alkylthiol, nitro, amino, vinyl, substituted vinyl, carboxylic acid, sulfonic acid or phosphine.
  • each of the arylene groups can be 1,2- divalent phenyl, 2,2'-divalent-l,l '-biphenyl, 2,2' -divalent- l,l'-binaphthyl or fe ⁇ ocene, i.e., a -Fc- group.
  • the present invention includes compounds represented by the following formulas:
  • each X and X' is independently selected from the group consisting of: alkyl, aryl, substituted alkyl, substituted aryl, OR, SR, NR 2 , COOR, halide, SiR 3 , P(O)R 2 , P(O)(OR) 2 and P(OR) 2 ; wherein each Z and Z ⁇ is independently selected from the group consisting of: alkyl, aryl, substituted alkyl, substituted aryl, OR, SR, NR 2 , COOR, halide, SiR 3 , P(O)R 2 , P(O)(OR) 2 and P(OR) 2 ; or wherein Z and Zj.
  • each Z', Z", Z ⁇ and Z " is independently selected from the group consisting of: H, alkyl, aryl, substituted alkyl, substituted aryl, OR, SR, NR 2 , COOR, halide, SiR 3 , P(O)R 2 , P(O)(OR) 2 and P(OR) 2 ; or wherein Z' and Z together form the bridging group A'-B-A; Z' and Z together form a fused cycloaliphatic or aromatic group; Zi and Z ⁇ together fonn the bridging group Ai- Bj-Ai'; and/or Z ⁇ and Z ⁇ together form a fused cycloaliphatic or aromatic group; wherein each A, A', A ⁇ and A ⁇ is independently selected from the group consisting of: O, CH 2 , NH, NR, S, CO and a bond; wherein each B and B ⁇ is independently selected from
  • the present invention includes compounds represented by the following formulas:
  • each X is independently selected from the group consisting of: alkyl, aryl, substituted alkyl, substituted aryl, OR, SR, NR 2 , COOR, halide, SiR 3 , P(O)R 2 , P(O)(OR) 2 and P(OR) 2 ; wherein each X' is independently selected from the group consisting of: hydrogen, alkyl, aryl, substituted alkyl, substituted aryl, OR, SR, NR 2 , COOR, halide, SiR 3 , P(O)R 2 , P(O)(OR) 2 and P(OR) 2 ; wherein each Z and Zi is independently selected from the group consisting of: alkyl, aryl, substituted alkyl, substituted aryl, OR, SR, NR 2 , COOR, halide, SiR 3 , P(O)R 2 , P(O)(OR) 2 and P(OR) 2 ; wherein each Z and Zi is independently selected
  • the ligands of the present invention can be a racemic mixture of enantiomers.
  • the ligand is a non-racemic mixture of enantiomers, and more preferably, the ligand is one of the enantiomers.
  • the ligand has an optical purity of at least 85% ee, and more preferably, the ligand has an optical purity of at least 95% ee.
  • Selected examples of the chiral ligands according to the present invention are represented by the following formulas:
  • the present invention also includes a catalyst prepared by a process comprising contacting a transition metal salt, or a complex thereof, and a ligand according to the present invention.
  • the catalyst may be prepared in situ or as an isolated compound.
  • the catalyst of the present invention can be a racemic mixture of enantiomers.
  • the catalyst is a non-racemic mixture of enantiomers, and more preferably, the catalyst is one of the enantiomers.
  • the catalyst has an optical purity of at least 85% ee, and more preferably, the catalyst has an optical purity of at least 95% ee.
  • Suitable transition metals for the preparation of the catalyst include Ag, Pt, Pd Rh, Ru, Ir, Cu, Ni, Mo, Ti, V, Re and Mn.
  • the catalyst can be prepared by contacting a transition metal salt or its complex and a ligand according to the present invention.
  • Suitable transition metal salts or complexes include the following:
  • L is a solvent and the counteranion X can be halogen, BF4, B(Ar)4 wherein Ar is fluorophenyl or 3,5- di-trifluoromethyl-1 -phenyl, CIO4, SbF6, PF CF3SO3 ; RCOO or a mixture thereof -
  • the present invention includes a process for preparation of an asymmetric compound using the catalysts described above.
  • the process includes the step of contacting a substrate capable of forming an asymmetric product by an asymmetric reaction and a catalyst according to the present invention prepared by contacting a transition metal salt, or a complex thereof, and a ligand according to the present invention.
  • the asymmetric reaction is hydrogenation and the substrate to be hydrogenated is an ethylenically unsaturated compound, imine, enamine, enamide, vinyl ester or a ketone, including a ketone such as a beta-ketoester.
  • the use of Ru as the transition metal to produce an asymmetric beta-hydroxyester and beta amino acid, respectively is preferred, particularly when the ligand is a compound represented by one of the following formulas:
  • each R is independently selected from the group consisting of: alkyl, aryl, substituted alkyl, substituted aryl and SiR 3 ; and wherein each Ar is independently selected from the group consisting of: phenyl, substituted phenyl, aryl and substituted aryl;
  • Optical rotation was obtained on a Perkin-Elmer 241 polarimeter. MS spectra were recorded on a KRATOS mass spectrometer MS 9/50 for LR-EI and HR-EI. GC analysis was carried on Helwett-Packard 6890 gas chromatography using chiral capillary columns. HPLC analysis was carried on WatersTM 600 chromatography.
  • Chiral bisphosphinite ligands (lla-L20, llb-L18, llc-L31, lid) were made through reaction of chlorodiaryl phosphine with the corresponding chiral diols (lOa-lOc) in high yields.
  • Chiral bisphosphine 15 was made from 3,3'- diphenyl-2,3'dihydroxyl-l,r- binaphthyl (10b) in a few steps.
  • Compounds 12-14 were synthesized according to a reported procedure (Xiao, D. et al. Org. Lett. 1999, 1, 1679). Representative examples can be synthesized by a variety of methods. Several such methods suitable for use in the synthesis of chiral 3,3'disubstituted bisaryl phosphines, are described below:
  • Rh-phosphine complex was made in situ by mixing Rh(COD) 2 PF 6 (3.7 mg, 0.008 mmol) and a chiral phosphine ligand (0.8 ml of IQmg/mL ligand in toluene, 0.012 mmol) in 19.2 ml of CH2CI2. The mixture was stirred for 30 min. Then 2.5 ml of this solution was transferred to a 10 ml vial with an enamide substrate (0.1 mmol).
  • the hydrogenation was performed at room temperature under 20 psi of hydrogen pressure for 24 h. The hydrogen was released carefully and the reaction mixture was passed through a silica gel plug eluted with EtOAc. The enantiomeric excess was measured by GC or HPLC using a chiral GC or HPLC column without further purification. The absolute configuration of products was determined by comparing the sign of optical rotation with the reported data.
  • the 3,3'-disubstituted bisphosphine 15 is a better ligand for Rh-catalyzed asymmetric hydrogenation than NAPHOS (6).
  • a number of beta-ketoesters can be reduced in high ee's using a Ru- 3, 3 'substituted BINAPO (lid) compound as the catalysts.
  • the R group is aryl, hetereoaryl, substituted aryl, alkyl and substituted alkyl species.
  • Typical procedure The starting material methyl 3-acetamido-3-phenyl-2- propenoate can be conveniently synthesized from cheap acetophenone in three steps according to known literature procedure in good yields.
  • the literatures are Zhu, G.; Zhen, Z.; Zhang, X. J Org. Chem. 1999, 64, 6907-6910; Krapcho, A. P. Diamanti, J. Org. Synth. 1973, 5, 198-201.
  • 3-acetamido-3-aryl-2-propenoates and 3-Acetamido-3- hetero-aryl-2-propenoates can be prepared through a new route by reacting acetamide with the corresponding beta-keto esters.
  • a related example is demonstrated by Tschaen et al. J Org. Chem. 1995, 60, 4324.
  • the typical procedure involves addition of the corresponding beta keto-ester, an acetamide or other amide such as enamide, Amberlyst 15 or other acid catalysts in toluene. The mixture was heated at reflux for some hours with removal of water using a Dean- Stark trap. The end product was obtained after evaporating the solvent.
  • DMF (must be degassed by freeze-thaw cycles) (1 ml) is introduced under stream of argon. The solution is stirred at 100 °C for 10 min under argon, giving a clear reddish brown solution.
  • reaction mixture is cooled and concentrated at 1 mmHg at 50 °C with vigorous stirring and then at 0.1 mmHg for 1 h to give a reddish brown solid, which is used as hydrogenation catalyst.
  • substrate methyl 3-acetamido-3-phenyl-2-propenoate 109 mg, 0.5 mmol.
  • the hydrogenation was performed at 50 °C under 78 psi of hydrogen foi ⁇ ls hours (not be optimized).
  • the bomb was then cooled to room temperature and hydrogen carefully released. The solvent was removed and the residue dissolved in ether.
  • the ether solution was washed with water and brine and dried over sodium sulfate.
  • the ether solution was passed through a short silica gel column and concentrated to dryness to give pure products methyl 3 -acetamido-3 -phenyl - 2-propanoate (known compound, see: Zhu, G.; Zhen, Z.; Zhang, X. J. Org. Chem. 1999, 64, 6907-6910 (Rh/Duphos and BICP, 65% ee); Lubell, W. D.; Kitamura, M.; Noyori, R. Tetrahedron: Asymmetry 1991, 2, 543 (Ru/BINAP, poor ee)).
  • known compound see: Zhu, G.; Zhen, Z.; Zhang, X. J. Org. Chem. 1999, 64, 6907-6910 (Rh/Duphos and BICP, 65% ee); Lubell, W. D.; Kitamura, M.; Noyori, R. Tetrahedron: Asymmetry 1991, 2, 543 (Ru/BINAP, poor
  • Ar Ph, Py, aryl, heteroaryl, subtituted aryl
  • the CH 2 CI 2 was removed under reduced pressure and the residue solidified.
  • the tan solid was broken up and stirred well with 1 liter of ether. This was filtered and the residue was washed well with ether.
  • the ether was evaporated under reduced pressure to yield a tan solid.
  • the solid was placed in a 5 liter flask with 3 liters of ligroin (bp: 90-110°C) and heated with stirring to 80°C.
  • the hot solution was decanted from the brown oil and the hot yellow solution was allowed to cool at room temperature for 3hr.
  • the white needles was filtered off and dried to yield 74g (63 %) of 17.
  • the reaction mixture was concentrated under reduced pressure to remove THF and 400ml of CH 2 CI2 was then added.
  • the CH 2 CI 2 layer was washed with water (200ml) and brine (200ml), dried over Na2SO 4 , and evaporated.
  • the solid residue was recrystallized from EtOAc (100ml) to give off-white product 22 (23g).
  • the mother liquid was passed through a silica gel column to give another 4g of product 22. The total yield was 98%.
  • the salt was recrystallized one more time from 25ml i-PrOH and l.lg of solid was obtained.
  • the solid was dissolved in 50ml of CH 2 C1 2 , washed with 3N NaOH (2x 50ml) and water (3x 50mL), dried over Na 2 SO , and evaporated.
  • the solid (91.1%, 0.86g) was recrystallized from acetone to give enantiomerically pure product 25 (0.69g, 60%>, ee>99.5%>).
  • HSiCl 3 (542mg, 0.4mL) and NBu 3 (1.48g, 1.9mL) were added to diphosphine oxide (31, 70mg, 0. lmmol) in xylene (5mL) solution under N 2 atmosphere.
  • the reaction mixture was heated to reflux for 3 hours. The mixture was allowed to cool down to room temp. Then the degassed NaOH aq. solution (10%), 5mL) was added to reaction mixture at 0°C and stir for one hour.
  • the organic layer was washed with degassed water (2x1 OmL), NH 4 C1 aq. solution (1 OmL), brine (1 OmL) and dried (Na 2 SO 4 ). The solvent was removed under vacuum to give a pale yellow solid.
  • Rh-complexes with (-) (3, 3'-diphenyl-4,4',5,5', 6, 6'- hexamethoxybiphenyl-2,2'-diyl)bis(diphenylphosphine) (26) are good catalysts for hydrogenation of enamides.
  • Introduction of 3, 3' substituted groups have some effects on enantioselectivity of asymmetric hydrogenation of enamides.
  • Cyclic enamides can be hydrogenated with good enantioselectivity.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Biochemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Inorganic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Materials Engineering (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Catalysts (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

3,3'-substituted chiral biaryl phosphine and phosphinite ligands and metal complexes based on such chiral ligands useful in asymmetric catalysis are disclosed. The metal complexes are useful as catalysts in asymmetric reactions, such as, hydrogenation, hydride transfer, allylic alkylation, hydrosilylation, hydroboration, hydrovinylation, hydroformylation, hydroformylation, olefin metathesis, hydrocarboxylation, isomerization, cyclopropanation, Diels-Alder reaction, Heck reaction, isomerization, Aldol reaction, Michael addition, epoxidation, Kinetic resolution and [m+n] cycloaddition. The metal complexes are particularly effective in Ru-catalyzed asymmetric hydrogenation of beta-ketoesters to beta-hydroxyesters and Ru-catalyzed asymmetric hydrogenation of enamides to beta amino acids.

Description

ORTHO SUBSTITUTED CHIRAL PHOSPHINES AND PHOSPHINITES AND THEIR USE IN ASYMMETRIC CATALYTIC REACTIONS
BACKGROUND OF THE INVENTION
1. FIELD OF THE INVENTION
The present invention relates to novel chiral ligands derived from 3,3'- substituted biaryl phosphines and phosphinites. More particularly, the present invention relates to transition metal complexes of these chiral phosphine ligands. The transition metal complexes are useful as catalysts in asymmetric reactions, such as, hydrogenation, hydride transfer, allylic alkylation, hydrosilylation, hydroboration, hydrovinylation, hydroformylation, olefin metathesis, hydrocarboxylation, isomerization, cyclopropanation, Diels- Alder reaction, Heck reaction, isomerization, Aldol reaction, Michael addition, epoxidation, kinetic resolution and [m+n] cycloaddition.
2. DESCRIPTION OF THE PRIOR ART
Discovery of new chiral ligands is crucial in developing highly enantioselective transition metal-catalyzed reactions. Many chiral ligands have been made for applications in asymmetric catalysis, however, relatively few of these chiral ligands are commonly used in industry for the synthesis of chiral molecules.
Several chiral ligands having a biaryl backbone are known in the prior art.
These are summarized below: BINAP BINAPO
Figure imgf000003_0002
Figure imgf000003_0001
Figure imgf000003_0003
BIPHEMP MeO-BIPHEP NAPHOS
Figure imgf000003_0004
BDPAB H8-BDPAB
Among these ligands, BINAP (1) is one of the most frequently used chiral ligands. The axially dissymmetric, fully aromatic BINAP has demonstrated to be highly effective for many asymmetric reactions (Noyori, R. et al. Ace. Chem. Res. 1990, 23, 345, Ohkuma, T. et al. J. Am. Chem. Soc. 1998, 120, 13529). Recent results show that partially hydrogenated BINAP with a larger bite angle, H8- BINAP (2), is a better ligand for certain asymmetric reactions due to restriction of conformational flexibility (Zhang X. et al. Synlett 1994, 501). Chiral BINAPO (3) was made and it was not effective due to the conformational flexibility (Grubbs, R. et al. Tetrahedron Lett. 1977, 1879). Other axially dissymmetric ligands such as BIPHEMP (4) and MeO-BIPHEP (5) were developed and used for a number of asymmetric reactions (Scl mid, R. et al. Pure & Appl. Chem. 1996, 68, 131; Schmide, R. et al. Helv. Chim. Ada, 1988, 71, 897). However, the present inventor is not aware of any examples of related 3,3' substituted chiral biaryl phosphines, the subject of the present invention, being disclosed in the prior art (Broger , E. A. et al., WO 92/16536 and Broger, E. A. et al, WO93/15089). NAPHOS (6), another example of a prior art compound has been prepared (Tamao, K. et al. Tetrahedron Lett. 1977, 1389) and was found to be not effective for asymmetric hydrogenation reaction. The corresponding ligands with the N linker, BDPAB (7) and H8-BDPAB (8) have also been made and tested for asymmetric hydrogenation reactions (Zhang, F. et al. J. Am. Chem. Soc. 1998, 120, 5808).
SUMMARY OF THE INVENTION
The present invention includes a ligand represented by the formula or its enantiomer:
Figure imgf000004_0001
wherein each X and X' is independently selected from the group consisting of: alkyl, aryl, substituted alkyl, substituted aryl, OR, SR, NR2, COOR, halide, SiR3, P(O)R2, P(O)(OR)2 and P(OR)2; wherein each Z and Z\ is independently selected from the group consisting of: alkyl, aryl, substituted alkyl, substituted aryl, OR, SR, NR2, COOR, halide, SiR3, P(O)R2, P(O)(OR)2 and P(OR)2; or wherein Z and Z_ together form the bridging group A-B-Ai; wherein each Z', Z", Z and Z " is independently selected from the group consisting of: H, alkyl, aryl, substituted alkyl, substituted aryl, OR, SR, NR2, COOR, halide, SiR3, P(O)R2, P(O)(OR)2 and P(OR)2, or wherein Z' and Z together form the bridging group A'-B-A; Z' and Z together form a fused cycloaliphatic or aromatic group; Z\ and Zi' together form the bridging group Aj- B^A ; and/or Z\ and Zi' together form a fused cycloaliphatic or aromatic group; wherein each A, A',
Figure imgf000005_0001
is independently selected from the group consisting of: O, CH2, NH, NR, S, CO and a bond; wherein each B and Bi is independently selected from the group consisting of: linear, branched or cyclic alkylene of 1 to 6 carbon atoms, arylene of 6 to 12 carbon atoms, O, CH2, NH, NR, S, CO, SO2, P(O)R, P(O)OR, POR, SiR2 and a bond; wherein each T is independently selected from the group consisting of: alkyl, substituted alkyl, aryl, substituted aryl, alkoxide, aryloxide, R, R', R", YR', YR", Y'R' and Y"R"; or wherein two T groups together form an alkylene, arylene, alkylenediamino, arylenediamino, alkelenedioxyl or arylenedioxyl; wherein each T' is independently selected from the group consisting of: alkyl, substituted alkyl, aryl, substituted aryl, alkoxide, aryloxide, R, R', R", YR', YR", Y'R' and Y"R"; or wherein two T' groups together form an alkylene, arylene, alkylenediamino, arylenediamino, alkelenedioxyl or arylenedioxyl; wherein each R, R' and R" is independently selected from the group consisting of: alkyl, substituted alkyl, aryl, aralkyl and alkaryl of 1 to 22 carbon atoms; or wherein two R groups, two R' groups or two R" group together form an alkylene or arelene group; and wherein each Y, Y' and Y" is independently selected from the group consisting of: O, CH2, NH, S and a bond between carbon and phosphorus; with the proviso that when the Y group at the 2' position is a bond between carbon and phosphorus, X' is hydrogen.
The present invention further includes a catalyst prepared by a process, which includes: contacting a transition metal salt, or a complex thereof, and a ligand according to the present invention.
The present invention still further includes a process for preparation of an asymmetric compound including: contacting a substrate capable of forming an asymmetric product by an asymmetric reaction and a catalyst prepared by a process including: contacting a transition metal salt, or a complex thereof, and a ligand according to the present invention.
The metal complexes are useful as catalysts in asymmetric reactions, such as, hydrogenation, hydride transfer, allylic alkylation, hydrosilylation, hydroboration, hydrovinylation, hydroformylation, olefin metathesis, hydrocarboxylation, isomerization, cyclopropanation, Diels- Alder reaction, Heck reaction, isomerization, Aldol reaction, Michael addition, epoxidation, kinetic resolution and [m+n] cycloaddition. The metal complexes are particularly effective in Ru-catalyzed asymmetric hydrogenation of beta-ketoesters to beta- hydroxyesters and Ru-catalyzed asymmetric hydrogenation of enamides to beta amino acids.
DETAILED DESCRIPTION OF THE INVENTION
The present invention includes 3, 3 '-substituted chiral biaryl phosphines and phosphinites and related ligands for applications in asymmetric catalysis. Introduction of 3,3 '-substituted groups can restrict the rotation of substituents adjacent to the phosphines. Control of orientations of these groups around the phosphine can lead to effective chiral induction for asymmetric reactions. Metal complexes of these phosphines, phosphinites and related non-C symmetric ligands with ortho substitution are useful for a large variety of asymmetric reactions. A number of chiral ligands can be made having the desired structure in which the 3,3' positions are substituted, with the proviso that at least one ortho position is occupied by a group other than H atom.
In the non-C2 symmetric ligands, ortho substituted groups play an important role for asymmetric catalysis. The 3,3' substituted chiral biaryl phosphines, phosphinites and related ligands of the present invention are described below. An important feature of these ligands is that at least one of the 3 and 3' positions must be occupied by a group other than hydrogen.
The ligands are represented by the formula:
Figure imgf000007_0001
wherein each X and X' is independently selected from the group consisting of: alkyl, aryl, substituted alkyl, substituted aryl, OR, SR, NR2, COOR, halide, SiR3, P(O)R2, P(O)(OR)2 and P(OR)2; wherein each Z and Z\ is independently selected from the group consisting of: alkyl, aryl, substituted alkyl, substituted aryl, OR, SR, NR2, COOR, halide, SiR3, P(O)R2, P(O)(OR)2 and P(OR)2; or wherein Z and Zλ together form the bridging group A-B-A^ wherein each Z', Z", Z\ and Z_" is independently selected from the group consisting of: H, alkyl, aryl, substituted alkyl, substituted aryl, OR, SR, NR2, COOR, halide, SiR3, P(O)R2, P(O)(OR)2 and P(OR)2; or wherein Z' and Z together form the bridging group A'-B-A; Z' and Z together form a fused cycloaliphatic or aromatic group; Z\ and Zi' together form the bridging group A\- Bi-Ai'; and/or Z1 and Z\ together form a fused cycloaliphatic or aromatic group; wherein each A, A', A1 and Aj' is independently selected from the group consisting of: O, CH , NH, NR, S, CO and a bond; wherein each B and B\ is independently selected from the group consisting of: linear, branched or cyclic alkylene of 1 to 6 carbon atoms, arylene of 6 to 12 carbon atoms, O, CH2, NH, NR, S, CO, SO2, P(O)R, P(O)OR, POR, SiR2 and a bond; wherein each T is independently selected from the group consisting of: alkyl, substituted alkyl, aryl, substituted aryl, alkoxide, aryloxide, R, R', R", YR', YR", Y'R' and Y"R"; or wherein two T groups together form an alkylene, arylene, alkylenediamino, arylenediamino, alkelenedioxyl or arylenedioxyl; wherein each T' is independently selected from the group consisting of: alkyl, substituted alkyl, aryl, substituted aryl, alkoxide, aryloxide, R, R', R", YR', YR", Y'R' and Y"R"; or wherein two T' groups together form an alkylene, arylene, alkylenediamino, arylenediamino, alkelenedioxyl or arylenedioxyl; wherein each R, R' and R" is independently selected from the group consisting of: alkyl, substituted alkyl, aryl, aralkyl and alkaryl of 1 to 22 carbon atoms; or wherein two R groups, two R' groups or two R" group together form an alkylene or arelene group; and wherein each Y, Y' and Y" is independently selected from the group consisting of: O, CH2, NH, S and a bond between carbon and phosphorus; with the proviso that when the Y group at the 2' position is a bond between carbon and phosphorus, X' is hydrogen. Preferably the alkylene group includes compounds represented by the formula: -(CH2)n-, wherein n is an integer in the range of from 1 to 8. The present invention also includes the corresponding enantiomer of each of the above ligands.
The substituted alkyl group can have one or more substituents and each substituent can independently be halogen, ester, ketone, carboxylic acid, hydroxy, alkoxy, aryloxy, thiol, alkylthio or dialkylamino. The aryl groups can optionally have one or more substituents, each of which can independently be halogen, ester, ketone, sulfonate, phosphonate, hydroxy, alkoxy, aryloxy, thiol, alkylthiol, nitro, amino, vinyl, substituted vinyl, carboxylic acid, sulfonic acid or phosphine. The arylene groups optionally can have one or more substituents, each of which can independently be halogen, ester, ketone, sulfonate, phosphonate, hydroxy, alkoxy, aryloxy, thiol, alkylthiol, nitro, amino, vinyl, substituted vinyl, carboxylic acid, sulfonic acid or phosphine. Preferably, each of the arylene groups can be 1,2- divalent phenyl, 2,2'-divalent-l,l '-biphenyl, 2,2' -divalent- l,l'-binaphthyl or feιτocene, i.e., a -Fc- group.
In a preferred embodiment, the present invention includes compounds represented by the following formulas:
Figure imgf000009_0001
wherein each X and X' is independently selected from the group consisting of: alkyl, aryl, substituted alkyl, substituted aryl, OR, SR, NR2, COOR, halide, SiR3, P(O)R2, P(O)(OR)2 and P(OR)2; wherein each Z and Z\ is independently selected from the group consisting of: alkyl, aryl, substituted alkyl, substituted aryl, OR, SR, NR2, COOR, halide, SiR3, P(O)R2, P(O)(OR)2 and P(OR)2; or wherein Z and Zj. together form the bridging group A-B-Ai; wherein each Z', Z", Z\ and Z " is independently selected from the group consisting of: H, alkyl, aryl, substituted alkyl, substituted aryl, OR, SR, NR2, COOR, halide, SiR3, P(O)R2, P(O)(OR)2 and P(OR)2; or wherein Z' and Z together form the bridging group A'-B-A; Z' and Z together form a fused cycloaliphatic or aromatic group; Zi and Z\ together fonn the bridging group Ai- Bj-Ai'; and/or Z\ and Z\ together form a fused cycloaliphatic or aromatic group; wherein each A, A', A\ and A\ is independently selected from the group consisting of: O, CH2, NH, NR, S, CO and a bond; wherein each B and B\ is independently selected from the group consisting of: linear, branched or cyclic alkylene of 1 to 6 carbon atoms, arylene of 6 to 12 carbon atoms, O, CH2, NH, NR, S, CO, SO2, P(O)R, P(O)OR, POR, SiR2 and a bond; wherein each YR', YR", Y'R' and Y"R" is independently selected from the group consisting of: alkyl, substituted alkyl, aryl, substituted aryl, alkoxide and aryloxide; or wherein two YR', YR", Y' or Y"R" groups together form an alkylene, arylene, alkylenediamino, arylenediamino, alkelenedioxyl or arylenedioxyl; wherein each R, R' and R" is independently selected from the group consisting of: alkyl, substituted alkyl, aryl, aralkyl and alkaryl of 1 to 22 carbon atoms; or wherein two R groups, two R' groups or two R" group together form an alkylene or arelene group; and wherein each Y, Y' and Y" is independently selected from the group consisting of: O, CH2, NH, S and a bond between carbon and phosphorus; with the proviso that when the Y group at the 2' position is a bond between carbon and phosphorus, X' is hydrogen.
In another preferred embodiment, the present invention includes compounds represented by the following formulas:
Figure imgf000011_0001
Figure imgf000011_0002
wherein each X is independently selected from the group consisting of: alkyl, aryl, substituted alkyl, substituted aryl, OR, SR, NR2, COOR, halide, SiR3, P(O)R2, P(O)(OR)2 and P(OR)2; wherein each X' is independently selected from the group consisting of: hydrogen, alkyl, aryl, substituted alkyl, substituted aryl, OR, SR, NR2, COOR, halide, SiR3, P(O)R2, P(O)(OR)2 and P(OR)2; wherein each Z and Zi is independently selected from the group consisting of: alkyl, aryl, substituted alkyl, substituted aryl, OR, SR, NR2, COOR, halide, SiR3, P(O)R2, P(O)(OR)2 and P(OR)2; wherein each Z', Z", Z and Zi" is independently selected from the group consisting of: H, alkyl, aryl, substituted alkyl, substituted aryl, OR, SR, NR2, COOR, halide, SiR3, P(O)R2, P(O)(OR)2 and P(OR)2; wherein each A, A', Ai and A\ is independently selected from the group consisting of: O, CH2, NH, NR, S, CO and a bond; wherein each B and Bi is independently selected from the group consisting of: linear, branched or cyclic alkylene of 1 to 6 carbon atoms, arylene of 6 to 12 carbon atoms, O, CH2, NH, NR, S, CO, SO2, P(O)R, P(O)OR, POR, SiR2 and a bond; wherein each R and R' is independently selected from the group consisting of: alkyl, substituted alkyl, aryl, substituted aryl, aralkyl and alkaryl of 1 to 22 carbon atoms, alkoxide and aryloxide; or wherein two R groups or two R' groups together form an alkylene, arelene, alkylenediamino, arylenediamino, alkelenedioxyl or arylenedioxyl groups.
The ligands of the present invention can be a racemic mixture of enantiomers. Preferably, the ligand is a non-racemic mixture of enantiomers, and more preferably, the ligand is one of the enantiomers. Preferably, the ligand has an optical purity of at least 85% ee, and more preferably, the ligand has an optical purity of at least 95% ee. Selected examples of the chiral ligands according to the present invention are represented by the following formulas:
Figure imgf000013_0001
L15 L16 L17
Figure imgf000014_0001
Figure imgf000015_0001
Figure imgf000016_0001
Figure imgf000017_0001
Figure imgf000018_0001
Figure imgf000019_0001
L114 L115 L116
Figure imgf000020_0001
Figure imgf000021_0001
Figure imgf000022_0001
Figure imgf000023_0001
Figure imgf000024_0001
L192 L193 LI 94 L195
Figure imgf000025_0001
Figure imgf000026_0001
Figure imgf000027_0001
Figure imgf000028_0001
Figure imgf000029_0001
Figure imgf000030_0001
29
Figure imgf000031_0001
L318
Figure imgf000032_0001
Figure imgf000033_0001
Figure imgf000034_0001
Figure imgf000035_0001
Figure imgf000036_0001
Figure imgf000036_0002
The present invention also includes a catalyst prepared by a process comprising contacting a transition metal salt, or a complex thereof, and a ligand according to the present invention. The catalyst may be prepared in situ or as an isolated compound.
The catalyst of the present invention can be a racemic mixture of enantiomers. Preferably, the catalyst is a non-racemic mixture of enantiomers, and more preferably, the catalyst is one of the enantiomers. Preferably, the catalyst has an optical purity of at least 85% ee, and more preferably, the catalyst has an optical purity of at least 95% ee.
Suitable transition metals for the preparation of the catalyst include Ag, Pt, Pd Rh, Ru, Ir, Cu, Ni, Mo, Ti, V, Re and Mn.
As mentioned above, the catalyst can be prepared by contacting a transition metal salt or its complex and a ligand according to the present invention.
Suitable transition metal salts or complexes include the following:
AgX; Ag(OTf); Ag(OTf)2; AgOAc; PtCl2; H2PtCl4; Pd2(DBA)3; Pd(OAc)2; PdCl2(RCN)2; (Pd(allyl)Cl)2; Pd(PR3)4; (Rh(NBD)2)X; (Rh (NBD)C1)2; (Rh(COD)Cl)2; (Rh(COD)2)X; Rh(acac)(CO)2; Rh(ethylene)2(acac); (Rh(ethylene)2Cl) 2; RhCl(PPh3) 3; Rh(CO)2Cl2; RuHX(L)2(diphosphine), RuX2(L)2 (diphosphine), Ru(arene)X2(diphosphine), Ru(aryl group)X2; Ru(RCOO)2(diphosphine); Ru(methallyl)2(diphosphine); Ru(aryl group)X2(PPh3) 3; Ru(COD)(COT); Ru(COD)(COT)X; RuX2(cymen); Ru(COD)n; Ru(aryl group)X2(diphosphine); RuCl2(COD); (Ru(COD)2)X; RuX2(diphosphine); RuCl2(=CHR)(PR'3)2; Ru(ArH)Cl2; Ru(COD)(methallyl)2;
& (Ir (NBD)2C1)2; (Ir(NBD)2)X; (Ir(COD)2Cl)2; (Ir(COD)2)X; CuX (NCCH3)4; Cu(OTf); Cu(OTf)2; Cu(Ar)X; CuX; Ni(acac)2; NiX2; (Ni(allyl)X)2; Ni(COD)2; MoO2(acac)2; Ti(OiPr)4; NO(acac)2; MeReO3; MnX2 and Mn(acac)2; wherein each R and R' is independently selected from the group consisting of: alkyl or aryl; Ar is an aryl group; and X is a counteranion.
In the above transition metal salts and complexes, L is a solvent and the counteranion X can be halogen, BF4, B(Ar)4 wherein Ar is fluorophenyl or 3,5- di-trifluoromethyl-1 -phenyl, CIO4, SbF6, PF CF3SO3; RCOO or a mixture thereof -
In another aspect, the present invention includes a process for preparation of an asymmetric compound using the catalysts described above. The process includes the step of contacting a substrate capable of forming an asymmetric product by an asymmetric reaction and a catalyst according to the present invention prepared by contacting a transition metal salt, or a complex thereof, and a ligand according to the present invention.
Suitable asymmetric reactions include asymmetric hydrogenation, hydride transfer, allylic alkylation, i.e., palladium-catalyzed allylic alkylation of an allylic ester, hydrosilylation, hydroboration, hydrovinylation, hydroformylation, olefin metathesis, hydrocarboxylation, isomerization, cyclopropanation, Diels-Alder reaction, Heck reaction, isomerization, Aldol reaction, Michael addition; epoxidation, kinetic resolution, i.e., palladium-catalyzed allylic alkylation of a racemic allylic ester, and [m+n] cycloaddition wherein m = 3 to 6 and n = 2, i.e., silver-catalyzed asymmetric [3 +2] cycloaddition of an azomethine ylide with a dipolarophile.
Preferably, the asymmetric reaction is hydrogenation and the substrate to be hydrogenated is an ethylenically unsaturated compound, imine, enamine, enamide, vinyl ester or a ketone, including a ketone such as a beta-ketoester. In the case of beta-ketoesters and enamides, the use of Ru as the transition metal to produce an asymmetric beta-hydroxyester and beta amino acid, respectively, is preferred, particularly when the ligand is a compound represented by one of the following formulas:
(a)
Figure imgf000039_0001
wherein each R is independently selected from the group consisting of: alkyl, aryl, substituted alkyl, substituted aryl and SiR3; and wherein each Ar is independently selected from the group consisting of: phenyl, substituted phenyl, aryl and substituted aryl;
(b)
Figure imgf000039_0002
(c)
Figure imgf000039_0003
32 (d)
Figure imgf000040_0001
or a combination thereof.
The detailed description of ligand synthesis and asymmetric reactions thereof is provided below.
General procedures
All reactions and manipulations were performed in a nitrogen-filled glove box or using standard Schlenk techniques. THF and toluene were dried and distilled from sodium-benzophenone ketyl under nitrogen. Methylene chloride was distilled from CaH2. Methanol was distilled from Mg under nitrogen. (R, R)- BDNPB was made a solution of 1 Omg/ml in toluene before use. Column chromatography was performed using EM silica gel 60 (230-400 mesh). ^H, ^C and 3 !P NMR were recorded on Bruker WP-200, AM-300, and AMX-360 spectrometers. Chemical shifts were reported in ppm down field from tetramethylsilane with the solvent resonance as the internal standard. Optical rotation was obtained on a Perkin-Elmer 241 polarimeter. MS spectra were recorded on a KRATOS mass spectrometer MS 9/50 for LR-EI and HR-EI. GC analysis was carried on Helwett-Packard 6890 gas chromatography using chiral capillary columns. HPLC analysis was carried on Waters™ 600 chromatography.
Ligand Synthesis Ligand Synthesis
Several chiral ligands have been prepared and used for asymmetric hydrogenation reactions. Scheme 1 shows the synthesis of these ligands. The starting material, enantiomerically pure BINOL can be converted to many chiral phosphines and phosphinites (lla-L20, llb-L18, llc-L31, lid and 15-L38). 3,3'-disubstituted BINOL was prepared from (S)-BINOL according to known literature methods (Cox, P. J. et al. Tetrahedron Lett. 1992, 33, 2253; Simonsen, K. B. et al. J. Org. Chem. 1998, 63, 7536).
Figure imgf000041_0001
10a: R = Me 10b: R = Ph
10c: R = 3,5-Me2C6H4
Figure imgf000041_0002
Scheme 1. Ligand Synthesis
Chiral bisphosphinite ligands (lla-L20, llb-L18, llc-L31, lid) were made through reaction of chlorodiaryl phosphine with the corresponding chiral diols (lOa-lOc) in high yields. Chiral bisphosphine 15 was made from 3,3'- diphenyl-2,3'dihydroxyl-l,r- binaphthyl (10b) in a few steps. Compounds 12-14 were synthesized according to a reported procedure (Xiao, D. et al. Org. Lett. 1999, 1, 1679). Representative examples can be synthesized by a variety of methods. Several such methods suitable for use in the synthesis of chiral 3,3'disubstituted bisaryl phosphines, are described below:
Examples of Ligand Synthesis
BuLi orLDA
Figure imgf000042_0002
I LAH or silane
Figure imgf000042_0003
Figure imgf000042_0001
ArB(OH)2, Suzuki Coupling
Figure imgf000042_0004
LAH or silane
Figure imgf000042_0005
Figure imgf000042_0006
Figure imgf000042_0007
EXAMPLE 1
Synthesis of a 3,3'-Disubstituted Chiral BINOL (10b)
(R)-2,2'-Bismethoxymethoxy-l,l'-binaphthyl
Figure imgf000043_0001
To a THF (200 ml) solution of NaH (5.52 g, 230 mmol) was added (R)- BINOL (28.6g, 100 mmol) solution in THF (50 ml) under nitrogen at zero temperature, after 30 min, chloromethyl methyl ether (17.09 ml, 225 mmol) in 30 ml THF was added dropwise. The mixture was stirred overnight at room temperature. 3 ml water was added carefully to destroy the excess NaH, and filtered to remove the inorganic salt. The solution was passed a silica gel plug (hexane/ethyl acetate = 1/1) to give pure product (97% yield).
(R)-3,3' -diiodo-2,2' -Bism ethoxy methoxy-1 ,1 ' -binaphthyl
Figure imgf000043_0002
To a solution of (R)-2,2'-Bismethoxymethoxy-l,l'-binaphthyl (37.4g, lOOmmol) in diethyl ether (400 ml) was added rø-BuLi (100 ml, 2.5 M in hexane, 250 mmol) at room temperature under nitrogen, the mixture was stirred for 3 hours, then was cooled to 0°C, 200 ml THF was added, after 10 min, a solution of iodine (300 mol, 76.2g) in THF (60 ml) was added dropwise. The mixture was allowed to warm to room temperature over 4 hours. 100 ml saturated Na2SO3 aqueous was added to destroy the excess iodine, then extracted with ethyl acetate, organic phase was washed with 100 ml saturated Na2SO3, 3X100 ml water, dried over sodium sulfate and evaporated. The residue was purified by a silica gel column eluted with (hexane /ethyl acetate = 7/1) to give product as a yellow solid (80%o yield, contain 5-7% monoiodo-substituted product).
(R)-3,3'-diphenyl-2,2'-Bismethoxymethoxy-l,l'-binaphthyl
Figure imgf000044_0001
To a solution of (R)-3,3'-diiodo-2,2'-Bismethoxymethoxy-l,r-binaphthyl (90 mmol, 56.3g) and phenylboronic acid (25.2 g, 225 mmol) in THF 800 ml, was added Pd(PPh3)4 (2.3 g, 2 mmol) and degassed IM K2CO3 aqueous solution (400 ml, 400 mmol). The reaction mixture was heated at reflux for 20 hours. The mixture was extracted with ethyl acetate, and combined organic layer was washed with brine. Evaporation of the solvent gave a yellow solid (47g). The residue was used to next step without other purification.
Figure imgf000045_0001
(R)-3,3'-diphenyl-l,r-binaphthol
To a solution of (R)-3,3'-diphenyl-2,2'-Bismethoxymethoxy-l, binaphthyl (47 g) in a mixture solvent of 200 ml DCM and 500 ml EtOH was added concentrated HCl (90 ml). The reaction mixture was heated at reflux under nitrogen for 16 hours. The volatile components were removed under reduced pressure, and the residue was purified by column chromatography on silica gel (DCM/hexanes=4/6) to give the product (25.2 g, 57.6 mmol, 64% yield for two steps)
EXAMPLE 2
Alternative Route for the Synthesis of a 3,3'-Disubstituted Chiral BINOL (10b)
(S)-2,2'-Dimethoxy-l,l'-dinaphthyl
To a solution of (S)-2,2'-dihydroxy-l,l'-dinaphthyl (lOOg, 349.7 mmol) in lOOOml 95% EtOH was added dimethyl sulfate (93.1ml, 981.7 mmol, 2.8eq.) and followed by dropwise addition of a solution of NaOH (175g) in 300ml H2O. After the addition, the resulting system was heated to reflux for 3 h, and then cooled. The reaction mixture was filtered, the precipitate was collected and washed with 10%> aqueous NaOH (3x150 ml), and recrystallized from toluene (reflux to dissolve into 700 ml toluene, then let it stay at 0 °C overnight) to yield 84. lg white crystal product (S)-2,2' -dimethoxy- l,r-dinaphthyl (yield = 76.6%). 1H-NMR (CDCl3):δ7.985(d, J=9.0Hz, 2H, Ar-H), 7.875(d, J=8.1Hz, 2H, Ar-H), 7.468(d, J=9.0Hz, 2H, Ar-H), 7.300-7.326(t, 2H, Ar-H), 7.199-7.218(t, 2H, Ar- H), 7.118(d, J=8.1Hz, 2H, Ar-H), 3.773(s, 6H, -OCH3).
(S)-3,3'-Bis(dihydroxyborane)-2,2'-Dimethoxy-l,l'-dinaphthyl
Under N2, in a 500 ml Schlenk flask were placed 300 ml of dry t-butyl- methyl ether and TMEDA (14.4 ml, 95.5 mmol, 3equiv). To this solution was added 2.5M rz-BuLi in hexane(39.5 ml, 98.7 mmol, 3.1 equiv), the resulting solution was stirred for 30 min. at room temperature, solid (S)-2,2'-dimethoxy- l,l '-dinaphthyl (lOg, 31.8mmol) was added in one portion under N2 flow, the reaction system was stirred at room temperature for 3hrs.The resulting brown slurry was cooled to -78°C, and B(OEt)3 (33.9 ml, 197.5 mmol, 6.2equiv) was dropwise introduced over a period of 15min. The reaction system was allowed to warm room temperature and was left stirring overnight. The reaction was quenched with 150ml aqueous IM HCl solution, and was stirred for another 2 h. The phase was separated, the organic phase was washed with aqueous IM HCl solution (3 x lOOmL) and saturated aqueous NaCl solution (3 x 100 ml), and dried over Na2SO . The solvent was removed, and the resulting white solid were recrystallized twice from 70ml toluene (reflux to dissolve into 700ml toluene, then let it stay at 0 °C overnight, and recrystallization once can't remove by-product completely) to give the product (S)-3 ,3 ' -Bis(dihydroxyborane)-2,2 ' -Dimethoxy- l,l '-dinaphthyl 9.33g (Yield = 73.3%).1H-NMR(Acetone-d6):δ 8.556(s, 2H, Ar- H), 8.041(d, J=8.1Hz, 2H, Ar-H), 7.454(t, 2H, Ar-H), 7.335(t, 2H, Ar-H), 7.112(d, J=8.1Hz, 2H, Ar-H), 3.773(s, 6H, -OCH3). 1H-NMR shows that toluene is very difficult to remove completely, but there is no any influence on the secondary reaction. (S)-3,3'-Diphenyl-2,2'-dimethoxy-l,l'-dinaphthyl
In a 50ml Schlenk flask were placed (S)-3,3'-bis(dihydroxyborane)-2,2'- dimethoxy-l,l '-dinaphthyl(1.206 g, 3 mmol), Ba(OH)2.8H2O (2.739g, 8.7mmol, 2.9 equiv), and Pd(PPh3) (183 mg, 0.15 mmol, 5%> mol), the reaction system was evacuated and filled with N2 for three times, l,4-dioxane(18ml), H2O(8ml), and bromobenzen(1.89ml,18mmol, 6eq.) were added. The reaction system was heated under reflux for 24 hrs under N2 and cooled to room temperature. The 1 ,4-dioxane was removed, and the resulting mixture was redissolved into 100ml CH2CI2, and washed with aqueous IM HCl solution (3x 50 ml) and saturated aqueous NaCl solution(2 x 50 ml), and dried over Na2SO4. The solvent was removed to yield crude product (S)-3,3'-diphenyl-2,2'-dimethoxy-l, -dinaphthyl 1.513 g as orange syrup.
This intermediate was not isolated and was used directly in the final step.
(S)-3,3'-Diphenyl-2,2'-dihydroxy-l,l'-dinaphthyl (10b)
The crude product diphenyl-2,2' -dimethoxy- l,l'-dinaphthyl (1.513g, approximately 3mmol) was dissolved into 80 ml dry CH2CI2, and cooled to -78°C, BBr3( 1.5 ml) was added in 10 min., and the reaction system was stirred for 18 h at room temperature. The resulting slight brown solution was cooled to 0°C, and 200 ml H2O was added carefully. The phase was separated, and the organic phase was washed with H2O (5 x 80 ml) and saturated aqueous NaCl solution (2 x 50 ml), and dried over Na2SO4. The solvent was removed, and the resulting solid was recrystallized from 10 ml MeOH to yield (S)-10b as white-gray powder (overall yield of coupling and deprotection steps, 61.8%). 1H-NMR(CDCl3):δ8.029(s, 2H, Ar-H), 7.929(d, J= 7.9Hz, 2H, Ar-H), 7.741(dd, 4H, J= 7.9 1.4Hz Ar-H), 7.499(t, 4H, Ar-H), 7.376-7.434 (m, 4H, Ar- H), 7.325 (td, 2H, J= 7.9 1.3Hz Ar-H), 7.250(t, 2H, Ar-H), 5.364(br, 2H, -OH).
EXAMPLE 3
Synthesis of a 3,3'-Disubstituted Chiral Phosphinite, (R)-3,3'-diphenyl-2,2'- bisdiphenylphosphinooxy-l,l'-binaphthyI (llb)
To a solution of (R)-3,3'-diphenyl-l,r-binaphthol (876 mg, 2 mmol) in 20 ml THF at -78°C was added rc-BuLi (2.8 ml, 4.5 mmol) dropwise, the mixture was warmed to room temperature and stirred for 30 min, then cooled to -78°C, PI12PCI (0.9 ml, 5 mmol) was added via syringe, then warmed to room temperature and stirred overnight. The THF was removed under reduced pressure, the residue was purified by basic Al2O3 (EtOAc/Hexane/Et3N = 90/8/2) to give pure product (1.41 g, 87% yield).
1H-NMR (CD2CI2, 360 MHz) 6.80-7.20 (m, 24H), 7.35-7.48 (m, 12H), 7.50-7.65 (m, 4H). ). 31P-NMR (CD2C12, 360 MHz) 112.78. ). 13C-NMR (CD2C12, 360 MHz) 124-150 (m). [α]D 20=114.7 (c, 0.38, CHCI3). MS: 203 (100), 387 (65), 439 (48), 807 (50). HRMS C56H41O2P2 807.2566 Cal: 807.2582.
EXAMPLE 4
General Procedure for Catalytic Asymmetric Hydrogenation of Enamides
In a glove box, the Rh-phosphine complex was made in situ by mixing Rh(COD)2PF6 (3.7 mg, 0.008 mmol) and a chiral phosphine ligand (0.8 ml of IQmg/mL ligand in toluene, 0.012 mmol) in 19.2 ml of CH2CI2. The mixture was stirred for 30 min. Then 2.5 ml of this solution was transferred to a 10 ml vial with an enamide substrate (0.1 mmol).
The hydrogenation was performed at room temperature under 20 psi of hydrogen pressure for 24 h. The hydrogen was released carefully and the reaction mixture was passed through a silica gel plug eluted with EtOAc. The enantiomeric excess was measured by GC or HPLC using a chiral GC or HPLC column without further purification. The absolute configuration of products was determined by comparing the sign of optical rotation with the reported data.
EXAMPLE 5
Results of Asymmetric Hydrogenation of Enamides
To examine the effectiveness of new chiral ligands, hydrogenation of a typical dehydroamino acid derivative and an enamide was carried out. The results are summarized in Table 1. The 3,3'disubstituted bisphosphinite ligands (lla-d) are more effective than BINAPO (3) for asymmetric hydrogenation.
In the similar way, the 3,3'-disubstituted bisphosphine 15 is a better ligand for Rh-catalyzed asymmetric hydrogenation than NAPHOS (6).
We conclude that introduction of 3,3' substituted groups can restrict the rotation of phenyl groups adjacent to phosphines and therefore a well-defined chiral pocket around the transition metal is formed. The conformational rigidity is crucial for achieving high enantioselectivity for a number of asymmetric reactions. Table 1. Rh(I) -catalyzed asymmetric hydrogenation
Substrate
JMHAc NHAc
Ligand COOMe Ph
entry 1
entry 2
entry 3
entry 4
entry 5
entry 6
Figure imgf000050_0001
entry 7 99% ee 82% ee
Figure imgf000050_0002
The reaction was carried out at rt under 3atm of H2 for 12 h in 3ml of THF with complete conversion (S/C = 100). Ar = 3,5-Me2C6H4 EXAMPLE 6
Asymmetric Hydrogenation of Beta-keto Esters
A number of beta-ketoesters can be reduced in high ee's using a Ru- 3, 3 'substituted BINAPO (lid) compound as the catalysts. Particularly, the R group is aryl, hetereoaryl, substituted aryl, alkyl and substituted alkyl species. These reactions can be carried out at low pressure and low temperature, which shows advantages over the reaction carried out with Ru-BINAP complex (90 atm, 90 °C).
Asymmetric Hydrogenation
Figure imgf000051_0001
EXAMPLE 7
Asymmetric Synthesis of Beta- Amino Acids
Synthesis of Starting Material 3-Acetamido-3-Aryl-2-Propenoates and 3- Acetamido-3-hetero-Aryl-2-Propenoates
Typical procedure: The starting material methyl 3-acetamido-3-phenyl-2- propenoate can be conveniently synthesized from cheap acetophenone in three steps according to known literature procedure in good yields. The literatures are Zhu, G.; Zhen, Z.; Zhang, X. J Org. Chem. 1999, 64, 6907-6910; Krapcho, A. P. Diamanti, J. Org. Synth. 1973, 5, 198-201. 1H-NMR (CDC13, 360 MHz) δ (Z isomer) 2.17 (s, 3H), 3.77 (s, 3H), 5.29 (s, IH), 7.37-7.45 (m, 5H); (E isomer) 2.38 (s, 3H), 3.77 (s, 3H), 6.65 (s, IH), 7.37-7.45 (m, 5H).
An Effective New Way to Make Enamides
NHCOR" . R"CONH2, H+
JJ j ^ ROOC^ *R' + H20
R'^^^OR Reflux
E/Z mixture
R', R" = alkyl, substituted alkyl, aryl, substituted aryl, hetereoaryl R = alkyl, aryl
Alternatively, 3-acetamido-3-aryl-2-propenoates and 3-Acetamido-3- hetero-aryl-2-propenoates can be prepared through a new route by reacting acetamide with the corresponding beta-keto esters. A related example is demonstrated by Tschaen et al. J Org. Chem. 1995, 60, 4324. The typical procedure involves addition of the corresponding beta keto-ester, an acetamide or other amide such as enamide, Amberlyst 15 or other acid catalysts in toluene. The mixture was heated at reflux for some hours with removal of water using a Dean- Stark trap. The end product was obtained after evaporating the solvent.
Asymmetric Hydrogenation of methyl 3-acetamido-3-phenyl-2-propenoate
A dry Schlenk tube is charged with [Ru(cymene)Cl2]2 (1.53 mg, FW = 612, 0.0025 mmol), chiral ligand 3,3'-diphenyl-xylyl BINAPO (lid, 4.82 mg, FW = 918, 0.0053 mmol), and then is evacuated and filled with argon. DMF (must be degassed by freeze-thaw cycles) (1 ml) is introduced under stream of argon. The solution is stirred at 100 °C for 10 min under argon, giving a clear reddish brown solution. The reaction mixture is cooled and concentrated at 1 mmHg at 50 °C with vigorous stirring and then at 0.1 mmHg for 1 h to give a reddish brown solid, which is used as hydrogenation catalyst. To a solution of above catalyst in EtOH/DCM (4 ml, 3/1) in a glove box was added substrate methyl 3-acetamido-3-phenyl-2-propenoate (109 mg, 0.5 mmol). The hydrogenation was performed at 50 °C under 78 psi of hydrogen foi¬ ls hours (not be optimized). The bomb was then cooled to room temperature and hydrogen carefully released. The solvent was removed and the residue dissolved in ether. The ether solution was washed with water and brine and dried over sodium sulfate. The ether solution was passed through a short silica gel column and concentrated to dryness to give pure products methyl 3 -acetamido-3 -phenyl - 2-propanoate (known compound, see: Zhu, G.; Zhen, Z.; Zhang, X. J. Org. Chem. 1999, 64, 6907-6910 (Rh/Duphos and BICP, 65% ee); Lubell, W. D.; Kitamura, M.; Noyori, R. Tetrahedron: Asymmetry 1991, 2, 543 (Ru/BINAP, poor ee)). 1H- NMR (CDC13, 360 MHz) δ 1.92 (s, 3H), 2.76-2.83 (m, 2H), 3.53 (s, 3H), 5.34 (m, IH), 6.65 (br, IH), 7.18-7.27 (m, 5H). Chiral GC Condition: Chiral Select-1000 column (dimensions 15m X 0.25 mm (i.d.)). Carrier gas: He (1 ml/min), 180 °C, isothermal; (S) ti = 11.68 min; (R) t2 = 12.04 min.
Asymmetric Hydrogenation Product Ligand
Figure imgf000053_0001
Ar = Ph, Py, aryl, heteroaryl, subtituted aryl
Figure imgf000053_0002
EXAMPLE 8
Asymmetric Allylic Alkylation
Using 3,3'disubstituted BINAPO as ligands, the Pd-catalyzed asymmetric allylic alkylation can be carried out and some results are listed below:
Pd-Catalyzed asymmetric allylic substitution
Figure imgf000054_0001
Ligand Ligand ee ee
Figure imgf000054_0002
Ee values are determined by chiral HPLC (OJ Column H/IPA = 95/5) EXAMPLE 9
Asymmetric Allylic Alkylation with nitrogen nucleophile
Using 3,3'disubstituted BINAPO as ligands, Pd-catalyzed asymmetric allylic alkylation with nitrogen nucleophiles can be carried out and some results are listed below:
Pd-Catalyzed asymmetric allylic substitution
Figure imgf000055_0001
Ee values are determined by chiral HPLC (OJ Column H/IPA = 85/15) EXAMPLE 10 Synthesis of 3,3'-disubstituted biaryl phosphines(-)-(3,3'-diphenyl- 4,4',5,5',6,6'-hexamethoxybiphenyl-2,2'diyπbis(diphenylphosphine)
Figure imgf000056_0001
16 17 18
Figure imgf000056_0002
19 20
Figure imgf000056_0003
24
HSiCI3, NBu3 Xylene
Figure imgf000056_0004
Figure imgf000056_0005
Synthesis of 4-bromo-2, 6-dimethoxy-phenoI 17
To a 2 liter flask equipped with a magnetic stirrer, thermometer, and nitrogen inlet, was added 77g (0.5 mol) of pyrogallol 1, 3 -dimethyl ether, 5.8 ml of MeOH, and 750ml of CH2C12. To this solution was added 126mg (5mmol) of NaH (95%)). The solution was stirred while cooling to -45°C with a dry-ice acetone bath. 94g (0.53mol) of powdered N-bromosuccinimide was added rapidly. The reaction mixture was then stirred for lhour at -35°C, heated to room temperature over next 30min, and finally refluxed for 30min. The CH2CI2 was removed under reduced pressure and the residue solidified. The tan solid was broken up and stirred well with 1 liter of ether. This was filtered and the residue was washed well with ether. The ether was evaporated under reduced pressure to yield a tan solid. The solid was placed in a 5 liter flask with 3 liters of ligroin (bp: 90-110°C) and heated with stirring to 80°C. The hot solution was decanted from the brown oil and the hot yellow solution was allowed to cool at room temperature for 3hr. The white needles was filtered off and dried to yield 74g (63 %) of 17.
Ref: J Org. Chem. Vol. 50, 1985, 1099.
Synthesis of 3,4, 5-trimethoxybromobenzene 18
A mixture of 74g (0.32mol) of 4-bromo-2, 6-dimethoxy-phenol 17 and 32g (0.8mol) of NaOH in 850ml of H2O was cooled to 10°C and 45ml (0.48mmol) of dimethyl sulfate was added. The mixture was refluxed for 3h and an equal amount of dimethyl sulfate (total 0.96mol) was then added. The mixture was refluxed for another 3h. Upon cooling overnight, the gray product solidified and was filtered off and dissolved in 1.2 1 of ether. The ether solution was filtered to remove insoluble impurity and washed sequentially with 5% NaOH solution (200ml), water (2 X 200mL), and brine (200mL). The ether phase was dried over Na2SO4 to give a off-white solid, which was recrystallized in hexane (300ml) to give 62.3g (79%) of l8.
Synthesis of (3, 4, 5-trimethoxyphenyl)diphenylphosphine 19
To a solution of 3,4,5 -trimethoxybromobenzene 18 (62.3g, 0.25mol) in dry THF (200ml) was added BuLi solution (169ml, 1.6M in hexane, 0.27mol) dropwise at -78°C within 45min. The resulting beige-colored suspension was stirred for an additional lh at -78°C. Then PPh2Cl (61g, 0.277mol, 49.7ml) was added dropwise. The addition was complete within 2h. The resulting yellow solution was allowed to warm to 0°C within 2h and quenched by addition of NH C1 solution (200ml). The organic layer was separated, washed with brine (250ml), dried (Na2SO4), filtered, and evaporated. The solid was recrystallized from methanol to give 69.5g(80%>) of 19.
Ref: Helvetica ChimicaActa Vol. 74, 1991, 370-389
Synthesis of 3, 4, 5-trimethoxyphenyl)diphenylphosphine oxide 20
To a suspension of 19 (69.5g, 0.2mmol) in MeOH (500 ml) was added dropwise 30% H2O2 (24.5g, 0.215mol) at 0°C. The resulting clear solution was stirred at ambient temperature for lh. Then it was treated with sat. Na2SO3 solution (75 ml) and IN HCl solution (50 ml). The mixture was concentrated under reduced pressure to remove the MeOH. The solid residue was dissolved in CH2C12 (300ml), washed with water (2x200 ml) and brine (200 ml), dried over Na2SO4, and evaporated. To the resulting white solid was added 300ml hexane and the resulting suspension was stirred vigorously at room temperature. Filtration of the white solid powder gave 67.2g (0.182mol, 91%>) of pure 20.
Ref: Helvetica Chimica Ada Vol. 74, 1991, 370-389 Synthesis of (2-iodo-3,4,5-trimethoxyphenyl)diphenyIphosphine oxide 21
To a solution of (i-Pr)2NH (31.88ml, 23.02g, 0.227mol) in dry THF (200ml)was added n-BuLi solution (125ml, 1.6M in hexane, 0.2mol) dropwise at -78°C. The addition was complete within 15min. After stirred at 0°C for lOmin, the LDA solution was re-cooled to -78°C. It was then added via cannula to a flask containing a solution of 20 (67.2g, 0.182mol) in dry THF (200ml) over 20min. During the addition, the mixture was turned reddish-brown, and eventually a beige suspension was formed. After the reaction mixture was stirred for an additional 15min at -78°C, a solution of I2 (50.6g, 0.2mol) in THF (200ml) was added dropwise. The addition was complete in 3h. A reddish-brown viscous paste was formed at the end of the addition. Then, the cooling bath was removed, and the mixture was allowed to warm to 0°C to form a clear red solution. The mixture was quenched by the addition of aNa2S2O3 solution (12g in 100ml H2O). The solution was concentrated to remove THF. The residue was dissolved in 300ml of CH2C12, washed with water (2 x 200 ml) and brine (200ml), dried over Na2SO , and evaporated. The brown paste was recrystallized in EtOAc (100ml) to give 55g (62%) of 21.
Ref: Helvetica Chimica Ada Vol. 74, 1991, 370-389
Synthesis of (2-phenyl-3,4,5-trimethoxyphenyl)diphenylphosphine oxide 22
To a 2 liter Schlenk flask was added (2-iodo-3,4,5-trimethoxyphenyl) diphenylphosphine oxide 21 (30g, 61mmol), phenylboronic acid (1 l.lg, 91mmol), and degassed THF (800ml). A solution of degassed saturated K2CO3 (400ml) was added afterwards. The whole mixture was degassed with nitrogen for an additional lOmin. Then, Pd(PPh3)4 (1.22mmol, 1.4g) was added in the solution through one portion. The mixture was stirred at reflux under nitrogen for 24hrs. In situ PNMR showed that the reaction was complete. The reaction mixture was concentrated under reduced pressure to remove THF and 400ml of CH2CI2 was then added. The CH2CI2 layer was washed with water (200ml) and brine (200ml), dried over Na2SO4, and evaporated. The solid residue was recrystallized from EtOAc (100ml) to give off-white product 22 (23g). The mother liquid was passed through a silica gel column to give another 4g of product 22. The total yield was 98%.
Synthesis of (2-iodo-6-phenyl-3,4,5-trimethoxyphenyI)diphenylphosphine oxide 23
To a solution of (2-phenyl-3,4,5-trimethoxyphenyl)diphenylphosphine oxide 22 (26.5g, 59.7mmol) in dry THF (500ml) was added t-BuLi (47.7ml, 1.5M in pentane, 71.6mmol) dropwise at -90°C. The addition was complete within 2hrs. The solution was allowed to warm to -78°C and stirred for an additional 3h. Then a solution of I2 in THF (100ml) was added dropwise at this temperature. The addition was complete in 2h. The resulting dark solution was allowed to warm to room temperature and stirred overnight. A solution of Na2S2O3 (12g in 100ml H2O) was added. The resulting yellow solution was concentrated under reduced pressure. To the residue was added 500ml of CH2CI2. The CH2CI2 layer was washed with water (100ml) and brine (100ml), dried over Na2SO4, and evaporated. The residue was recrystallized from EtOAc (100ml) to give a pure brown solid 23 (24g). The mother liquid was passed through a silica gel column to give another 5g of product. The total yield is 85%.
Synthesis of (RS)-(3,3'-diphenyI-4,4',5,5',6,6,-hexamethoxybiphenyI-2,2'- diyI)bis(diphenyIphosphine oxide) 24
A mixture of (2-iodo-6-phenyl-3,4,5-trimethoxyphenyl)diphenylphosphine oxide 23 (7.4g, 12.6mmol), Cu powder (252mmol, 16g, activated by I2 treatment), and DMF (200ml) was stirred at 155°C for lhr. The cold mixture was evaporated to dryness at the rotor evaporator at 70°C. The residue was treated for a few min with CH2CI2 (200ml). The solid was removed by filtration and washed with CH2C12 (200ml). The combined filtrate was washed with sat. NH4C1 solution (2 X lOOmL), dried over Na2SO4, and evaporated. The residue was crystallized from EtOAc (100ml) to give 5g (90%) of white product 24.
Resolution of (S^'-di henvM^'^S'^ό'-hexa etho ybiphenyl^^'- divDbis(diphenylphosphine oxide) 25
To a mixture of (RS)-(3,3'-diphenyl-4,4',5,5',6,6'-hexamethoxybiphenyl- 2,2'-diyl)bis(diphenylphosphine oxide) 24 (2.3g, 2.5mmol) and (-)-DTTA (- 0.966g, 2.5mmol) was added 40ml of i-PrOH. The resulting slurry was heated to reflux to get a clear solution. Then it was cooled slowly to room temperature and stirred overnight. The salt of (-)-25 and (-)-DTTA was obtained as white powder through filtration( ee: 95%>). The salt was recrystallized one more time from 25ml i-PrOH and l.lg of solid was obtained. The solid was dissolved in 50ml of CH2C12, washed with 3N NaOH (2x 50ml) and water (3x 50mL), dried over Na2SO , and evaporated. The solid (91.1%, 0.86g) was recrystallized from acetone to give enantiomerically pure product 25 (0.69g, 60%>, ee>99.5%>).
Synthesis of (- -(3,3,- iphenyl-4,4^5,5^6,6,-hexamethoxybiphenyl-2,2,- divDbis(diphenylphosphine 26.
To a solution of (-)-(3,3'-diphenyl-4,4',5,5',6,6'-hexamethoxybiρhenyl- 2,2'-diyl)bis(diphenylphosphine oxide) 25 (700mg, 0.79mmol, resolved from (-)- DTT A), tributylamine (6.5ml, 27.3mmol), and xylene (100 ml) was added HSiCl3 (1.72 ml, 17mmol) dropwise at 0°C. The reaction was stirred at reflux for 2days. Some precipitates came out during the course. After cooled down, the reaction mixture was quenched with 30%) degassed NaOH solution (20ml) in an ice-water bath. The resulting solution was kept at 60°C for lh. The organic phase was transferred into another Schlenk flask through can ula. The water phase was re- washed with CH2CI2 (30ml*2). The combined organic phase was washed with water (50 ml), dried over Na2SO4, and evaporated under reduced pressure. The resulting yellow residue was dissolved in CH2CI2 (10 ml) and passed through a basic Ai2θ3 column to give a pure white solid 26 (400 mg, 59%).
EXAMPLE 11
Synthesis of 2,2'-(diphenyIphosphanyI)-3, 6, 3',6'-tetramethoxybiphenyl
Figure imgf000062_0001
27 28
Figure imgf000062_0002
(-)-DTTA, i-PrOH HSiCl3 , NBu3 Xylene
Figure imgf000062_0004
Figure imgf000062_0003
31 32
(2,5-Dimethoxyphenyl)diphenylphosphine oxide
At -78°C, 2.5M n-BuLi in hexane (48mL, 0.12mol) was slowly added to a solution of l-Bromo-2,5-dimethoxybenzene (27, 25g, 0.115mol) in THF (250mL) causing the solution to become dark yellow (solid suspension). The reaction mixture was stir at this temp for about 30 minutes, following by addition of diphenylchlorophosphine (21.5 ml, 0.12 mol). During the addition, control the temp below -50°C (add slowly). The resulting yellow solution was allowed to warm up to room temp (take about two hours). The saturated NH C1 solution (200 ml) was added and reaction mixture form two layers. The organic layer was washed with brine (2x 1 OOmL) and dried (Na2SO ). The solvent was removed under vacuum to give a white solid.
Add MeOH (200mL) to the resulting white solid to form suspension. At 0°C, 33% H2O2 (14ml, 0.13mol) was slowly added to above MeOH suspension. The addition process takes about 20 minutes and the solid vanished promptly after all H2O2 was added. The mixture was allowed to stir for one hour at 0°C, follow by adding saturated NaHSO3 solution (15ml) and stir for 30 minutes (the KI- Starch paper was applied here to make sure all peroxide was reduced). The solvent was removed under vacuum to give a white solid. The resulting solid was dissolved in CH2CI2 (200mL) and was washed with water (150mL) and brine
(150mL), dried (Na2SO4). The solvent was also removed under vacuum to give a white solid. The crude product was treated with hot hexane (2x 1 OOmL) (to remove trace amount of impurity) to give pure product (28, 37.3g, 95.8%).
(3,6-Dimethoxy-2-iodophenyl)diphenylphosphine oxide
A solution of LDA (6mmoI) 1.5M in pentane was slowly added to the phosphine oxide (28, 1.69g, 5mmol) in THF (60mL) at 100°C. The resulting dark yellow solution (solid suspension) was allowed to warm up to -78°C (take 30 minutes) and then stirred 3.5 hours at this temp, during which time the white solid precipitated. Solid I2 (l-78g, 7mmol) was added against a counter flow of N2 to the anion in THF at -78°C. The reaction was allowed to come to 0°C and quenched with Na2S2θ3 aq. solution (lOmL). The solvent was removed under vacuum and the residue was extracted with CH2CI2 (50mL), washed with water (50mL), brine (50ml) and dried (Na2SO4). The solvent was remoyed and the brown oil residue was treated with EtOAc (lOmL) (to wash out most of the color impurities, the product form white solid in EtOAc). Then the vacuum filtration gives the white solid (29, l.Og, 43%)
2,2'-(Diphenylphosphinoyl)3,3',6,6'-tetramethoxybiphenyl
Copper powder (320mg, 5mmol) was added to a solution of the iodide (29, 116mg, 0.25mmol) in DMF (lOmL) and the reaction mixture heated to reflux for 8 hours. During the reflux, white solid formed along the wall of flask. The mixture was treated under vacuum to remove most of the solvent (before it cooled). The residue was extracted with CH2CI2 (20mL) and washed with water (2 lOmL), brine (lOmL) and dried (Na2SO4). The solvent was removed under vacuum and the resulting solid was washed with EtOAc (2mL) to give a white solid (30, 70mg, 83%).
Resolution of 2,2'-(diphenylphosphinoyl)3,3'?6,6'-tetramethoxybiphenyl
(-) DTTA (0.579g, 1.5mmol) was added to diphosphine oxide (30, 0.674g, lmmol) in EtOH (29mL) solution(at this time, DTTA can not dissolve in EtOH solution). The reaction mixture was heated up to reflux until all solid suspension was completely dissolved (take about 20 minutes). The resulting solution was allowed to stir overnight until crystal formed. The mixture was filtrated under vacuum and washed with cold EtOH (5mL). The resulting solid (0.405g, 75.1%) was added to CH2C12 (20mL) and NaOH (20mL, 10% aq.) solution for about 5 minutes, and the entire insoluble solid disappeared. The organic layer was washed with water (2x 1 OmL), brine (1 OmL) and dried (Na2SO ). The solvent was removed under vacuum to give a white solid (31, 99.3%) ee).
2,2'-DiphenyIphosphanyI-3,6,3',6'-tetramethoxybiphenyl
HSiCl3 (542mg, 0.4mL) and NBu3 (1.48g, 1.9mL) were added to diphosphine oxide (31, 70mg, 0. lmmol) in xylene (5mL) solution under N2 atmosphere. The reaction mixture was heated to reflux for 3 hours. The mixture was allowed to cool down to room temp. Then the degassed NaOH aq. solution (10%), 5mL) was added to reaction mixture at 0°C and stir for one hour. The organic layer was washed with degassed water (2x1 OmL), NH4C1 aq. solution (1 OmL), brine (1 OmL) and dried (Na2SO4). The solvent was removed under vacuum to give a pale yellow solid. After a short plug (silica gel, elute with CH2Cl2:Hexane=l :1), the solvent was evaporated under vacuum to give a white solid (still not pure white, a little bit pale yellow color) (32, 50mg, 75%).
EXAMPLE 12
Asymmetric Hydrogenation of Enamides Facilitated by Rh-Complexes with (-) (3, S'-di henyM^'^S', 6, 6'-hexamethoxybiphenyI-2,2'-divDbis- (diphenylphosphine) (26)
Rh-complexes with (-) (3, 3'-diphenyl-4,4',5,5', 6, 6'- hexamethoxybiphenyl-2,2'-diyl)bis(diphenylphosphine) (26) are good catalysts for hydrogenation of enamides. Introduction of 3, 3' substituted groups have some effects on enantioselectivity of asymmetric hydrogenation of enamides. Cyclic enamides can be hydrogenated with good enantioselectivity.
Rh-Catalyzed Asymmetric Hydrogenation
Figure imgf000065_0001
The present invention has been described with particular reference to the preferred embodiments. It should be understood that the foregoing descriptions and examples are only illustrative of the invention. Various alternatives and modifications thereof can be devised by those skilled in the art without departing from the spirit and scope of the present invention. Accordingly, the present invention is intended to embrace all such alternatives, modifications, and variations that fall within the scope of the appended claims.

Claims

WHAT IS CLAIMED IS:
1. A ligand represented by the formula or its enantiomer:
Figure imgf000067_0001
wherein each X and X' is independently selected from the group • consisting of: alkyl, aryl, substituted alkyl, substituted aryl, OR, SR, NR2, COOR, halide, SiR3, P(O)R2, P(O)(OR)2 and P(OR)2; wherein each Z and Z\ is independently selected from the group consisting of: alkyl, aryl, substituted alkyl, substituted aryl, OR, SR, NR2, COOR, halide, SiR3, P(O)R2, P(O)(OR)2 and P(OR)2; or wherein Z and Z together form the bridging group A-B - A 1 ; wherein each Z', Z", Z and Zi" is independently selected from the group consisting of: H, alkyl, aryl, substituted alkyl, substituted aryl, OR, SR, NR2, COOR, halide, SiR3, P(O)R , P(O)(OR)2 and P(OR)2; or wherein Z' and Z together form the bridging group A'-B-A; Z' and Z together form a fused cycloaliphatic or aromatic group; Zi and Z together form the bridging group Ai- B1-A1'; and/or Z\ and Z\ together form a fused cycloaliphatic or aromatic group; wherein each A, A', Ai and Ai' is independently selected from the group consisting of: O, CH2, NH, NR, S, CO and a bond; wherein each B and Bj is independently selected from the group consisting of: linear, branched or cyclic alkylene of 1 to 6 carbon atoms, arylene of 6 to 12 carbon atoms, O, CH2, NH, NR, S, CO, SO2, P(O)R, P(O)OR, POR, SiR2 and a bond; wherein each T is independently selected from the group consisting of: alkyl, substituted alkyl, aryl, substituted aryl, alkoxide, aryloxide, R, R', R", YR', YR", Y'R' and Y"R"; or wherein two T groups together form an alkylene, arylene, alkylenediamino, arylenediamino, alkelenedioxyl or arylenedioxyl; wherein each T' is independently selected from the group consisting of: alkyl, substituted alkyl, aryl, substituted aryl, alkoxide, aryloxide, R, R', R", YR', YR", Y'R' and Y"R"; or wherein two T' groups together form an alkylene, arylene, alkylenediamino, arylenediamino, alkelenedioxyl or arylenedioxyl; wherein each R, R' and R" is independently selected from the group consisting of: alkyl, substituted alkyl, aryl, aralkyl and alkaryl of 1 to 22 carbon atoms; or wherein two R groups, two R' groups or two R" group together form an alkylene, arelene or substituted arylene group; and wherein each Y, Y' and Y" is independently selected from the group consisting of: O, CH2, NH, S and a bond between carbon and phosphorus; with the proviso that when the Y group at the 2' position is a bond between carbon and phosphorus, X' is hydrogen.
2. The ligand of claim 1, wherein said substituted alkyl has one or more substituents, each independently selected from the group consisting of: halogen, ester, ketone, carboxylic acid, hydroxy, alkoxy, aryloxy, thiol, alkylthio and dialkylamino.
3. The ligand of claim 1, wherein said alkylene is selected from the group consisting of compounds represented by the formula: -(CH2)n-, wherein n is an integer in the range of from 1 to 8.
4. The ligand of claim 1 , wherein each of said aryl groups optionally has one or more substituents, each independently selected from the group consisting of: halogen, ester, ketone, sulfonate, phosphonate, hydroxy, alkoxy, aryloxy, thiol, alkylthiol, nitro, amino, vinyl, substituted vinyl, carboxylic acid, sulfonic acid and phosphine.
5. The ligand of claim 1 , wherein each of said arylene groups optionally has one or more substituents, each independently selected from the group consisting of: halogen, ester, ketone, sulfonate, phosphonate, hydroxy, alkoxy, aryloxy, thiol, alkylthiol, nitro, amino, vinyl, substituted vinyl, carboxylic acid, sulfonic acid and phosphine.
6. The ligand of claim 1, wherein each of said arylene groups is independently selected from the group consisting of: 1,2-divalent phenyl, 2,2'- divalent-l,l '-biphenyl, 2, 2 '-divalent- 1,1 ' -binaphthyl and ferrocene.
7. The ligand of claim 1, wherein said ligand is a racemic mixture of enantiomers.
8. The ligand of claim 1, wherein said ligand is a non-racemic mixture of enantiomers.
9. The ligand of claim 1, wherein said ligand is one of the enantiomers.
10. The ligand of claim 1 , having an optical purity of at least 85% ee.
11. The ligand of claim 1 , having an optical purity of at least 95%> ee.
12. The ligand of claim 1, wherein said ligand is selected from the group consisting of compounds represented by the following formulas:
Figure imgf000070_0001
wherein each X and X' is independently selected from the group consisting of: alkyl, aryl, substituted alkyl, substituted aryl, OR, SR, NR2, COOR, halide, SiR3, P(O)R2, P(O)(OR)2 and P(OR)2; wherein each Z and Zi is independently selected from the group consisting of: alkyl, aryl, substituted alkyl, substituted aryl, OR, SR, NR2, COOR, halide,
69 SiR3, P(O)R2, P(O)(OR)2 and P(OR)2; or wherein Z and Z> together form the bridging group A-B-Ai; wherein each Z Z", Zi ' and Zi" is independently selected from the group consisting of: H, alkyl, aryl, substituted alkyl, substituted aryl, OR, SR, NR2, COOR, halide, SiR3, P(O)R2, P(O)(OR)2 and P(OR)2; or wherein Z' and Z together form the bridging group A'-B-A; Z' and Z together form a fused cycloaliphatic or aromatic group; Z\ and Zi' together form the bridging group A\- B1-A1'; and/or Z\ and Zj' together form a fused cycloaliphatic or aromatic group; wherein each A, A', Ai and Ai' is independently selected from the group consisting of: 0, CH2, NH, NR, S, CO and a bond; wherein each B and Bi is independently selected from the group consisting of: linear, branched or cyclic alkylene of 1 to 6 carbon atoms, arylene of 6 to 12 carbon atoms, 0, CH2, NH, NR, S, CO, SO2, P(O)R, P(O)OR, POR, SiR2 and a bond; wherein each YR', YR", Y'R' and Y"R" is independently selected from the group consisting of: alkyl, substituted alkyl, aryl, substituted aryl, alkoxide and aryloxide; or wherein two YR', YR", Y'R' or Y"R" groups together form an alkylene, arylene, alkylenediamino, arylenediamino, alkelenedioxyl or arylenedioxyl; wherein each R, R' and R" is independently selected from the group consisting of: alkyl, substituted alkyl, aryl, aralkyl and alkaryl of 1 to 22 carbon atoms; or wherein two R groups, two R' groups or two R" group together form an alkylene or arelene group; and wherein each Y, Y' and Y" is independently selected from the group consisting of: O, CH2, NH, S and a bond between carbon and phosphorus; with the proviso that when the Y group at the 2' position is a bond between carbon and phosphorus, X' is hydrogen.
13. The ligand of claim 1 , wherein said ligand is selected from the group consisting of compounds represented by the following formulas:
Figure imgf000072_0001
Figure imgf000072_0002
71
SUBSTITUTE SHEET (RULE wherein each X is independently selected from the group consisting of: alkyl, aryl, substituted alkyl, substituted aryl, OR, SR, NR2, COOR, halide, SiR3, P(O)R2, P(O)(OR)2 and P(OR)2; wherein each X' is independently selected from the group consisting of: hydrogen, alkyl, aryl, substituted alkyl, substituted aryl, OR, SR, NR2, COOR, halide, SiR3, P(O)R2, P(O)(OR)2 and P(OR)2; wherein each Z and Z\ is independently selected from the group consisting of: alkyl, aryl, substituted alkyl, substituted aryl, OR, SR, NR2, COOR, halide, SiR3, P(O)R2, P(0)(OR)2 and P(OR)2; wherein each Z Z", Z\ ' and Z|" is independently selected from the group consisting of: H, alkyl, aryl, substituted alkyl, substituted aryl, OR, SR, NR2, COOR, halide, SiR3, P(O)R2, P(O)(OR)2 and P(OR)2; wherein each A, A', At and Ai' is independently selected from the group consisting of: O, CH2, NH, NR, S, CO and a bond; wherein each B and Bi is independently selected from the group consisting of: linear, branched or cyclic alkylene of 1 to 6 carbon atoms, arylene of 6 to 12 carbon atoms, O, CH2, NH, NR, S, CO, SO2, P(O)R, P(O)OR, POR, SiR2 and a bond; wherein each R and R' is independently selected from the group consisting of: alkyl, substituted alkyl, aryl, substituted aryl, aralkyl and alkaryl of 1 to 22 carbon atoms, alkoxide and aryloxide; or wherein two R groups or two R' groups together form an alkylene, arelene, alkylenediamino, arylenediamino, alkelenedioxyl or arylenedioxyl groups.
14. The ligand of claim 1 , wherein said ligand is selected from the group consisting of compounds represented by the formulas:
72
-
Figure imgf000074_0001
L15 L16
L17
73
SUBSTITUTE SHEET (RULE 26
Figure imgf000075_0001
74 TE SHEE Kuutf
Figure imgf000076_0001
Figure imgf000077_0001
Figure imgf000078_0001
Figure imgf000079_0001
Figure imgf000080_0001
LI 14 L115 LI 16
Figure imgf000081_0001
Figure imgf000082_0001
81
SUBSTITUTE HEET RULE 26
Figure imgf000083_0001
82
Figure imgf000084_0001
Figure imgf000085_0001
Figure imgf000086_0001
85 SHEET RULE 26)
Figure imgf000087_0001
Figure imgf000088_0001
87
Figure imgf000089_0001
Figure imgf000090_0001
L283 L284
L28S L286
Figure imgf000091_0001
Figure imgf000092_0001
L318
Figure imgf000093_0001
10
Figure imgf000094_0001
Figure imgf000095_0001
94 iBSTITUTE SHEET RULE 26
Figure imgf000096_0001
Figure imgf000097_0001
Figure imgf000097_0002
96 TE SHEET RULE 26
15. The ligand of claim 1, represented by the formula:
Figure imgf000098_0001
or
Figure imgf000098_0002
wherein each R is independently selected from the group consisting of: alkyl, aryl, substituted alkyl, substituted aryl and SiR3; and wherein each Ar is independently selected from the group consisting of: phenyl, substituted phenyl, aryl and substituted aryl.
16. The ligand of claim 1, represented by the formula:
Figure imgf000098_0003
17. The ligand of claim 1 , represented by the formula:
Figure imgf000099_0001
32
18. A catalyst prepared by a process comprising: contacting a transition metal salt, or a complex thereof, and a ligand selected from the group consisting of compounds represented by the formula or its enantiomer:
Figure imgf000099_0002
wherein each X and X' is independently selected from the group consisting of: alkyl, aryl, substituted alkyl, substituted aryl, OR, SR, NR2, COOR, halide, SiR3, P(O)R2, P(O)(OR)2 and P(OR)2; wherein each Z and Z\ is independently selected from the group consisting of: alkyl, aryl, substituted alkyl, substituted aryl, OR, SR, NR2, COOR, halide, SiR3, P(O)R2, P(O)(OR)2 and P(OR)2; or wherein Z and Z\ together form the bridging group A-B-Ai; wherein each Z', Z", Zi' and Zi" is independently selected from the group consisting of: H, alkyl, aryl, substituted alkyl, substituted aryl, OR, SR, NR2, COOR, halide, SiR3) P(O)R2, P(O)(OR)2 and P(OR)2, or wherein Z' and Z together form the bridging group A'-B-A; and Z together form a fused cycloaliphatic or aromatic group; Zt and Z\ together form the bridging group A\- Bi-Ai '; and/or Zi and Z\ ' together form a fused cycloaliphatic or aromatic group; wherein each A, A', Ai and Ai' is independently selected from the group consisting of: O, CH2, NH, NR, S, CO and a bond; wherein each B and Bi is independently selected from the group consisting of: linear, branched or cyclic alkylene of 1 to 6 carbon atoms, arylene of 6 to 12 carbon atoms, O, CH2, NH, NR, S, CO, SO2, P(O)R, P(O)OR, POR, SiR2 and a bond; wherein each T is independently selected from the group consisting of: alkyl, substituted alkyl, aryl, substituted aryl, alkoxide, aryloxide, R, R', R", YR', YR", Y'R' and Y"R"; or wherein two T groups together form an alkylene, arylene, alkylenediamino, arylenediamino, alkelenedioxyl or arylenedioxyl; wherein each T' is independently selected from the group consisting of: alkyl, substituted alkyl, aryl, substituted aryl, alkoxide, aryloxide, R, R', R", YR', YR", Y'R' and Y"R"; or wherein two T' groups together form an alkylene, arylene, alkylenediamino, arylenediamino, alkelenedioxyl or arylenedioxyl; wherein each R, R' and R" is independently selected from the group consisting of: alkyl, substituted alkyl, aryl, aralkyl and alkaryl of 1 to 22 carbon atoms; or wherein two R groups, two R' groups or two R" group together form an alkylene or arelene group; and wherein each Y, Y' and Y" is independently selected from the group consisting of: O, CH2, NH, S and a bond between carbon and phosphorus; with the proviso that when the Y group at the 2' position is a bond between carbon and phosphorus, X' is hydrogen.
19. The catalyst of claim 18, wherein said substituted alkyl has one or more substituents, each independently selected from the group consisting of: halogen, ester, ketone, carboxylic acid, hydroxy, alkoxy, aryloxy, thiol, alkylthio and dialkylamino.
20. The catalyst of claim 18, wherein said alkylene is selected from the group consisting of compounds represented by the formula: -(CH2)n-, where n is an integer in the range of from 1 to 8.
21. The catalyst of claim 18, wherein each of said aryl groups optionally has one or more substituents, each independently selected from the group consisting of: halogen, ester, ketone, sulfonate, phosphonate, hydroxy, alkoxy, aryloxy, thiol, alkylthiol, nitro, amino, vinyl, substituted vinyl, carboxylic acid, sulfonic acid and phosphine.
22. The catalyst of claim 18, wherein each of said arylene groups optionally has one or more substituents, each independently selected from the group consisting of: halogen, ester, ketone, sulfonate, phosphonate, hydroxy, alkoxy, aryloxy, thiol, alkylthiol, nitro, amino, vinyl, substituted vinyl, carboxylic acid, sulfonic acid and phosphine.
23. The catalyst of claim 18, wherein each of said arylene groups is independently selected from the group consisting of: 1,2-divalent phenyl, 2,2'- divalent-l,r-biphenyl, 2,2 '-divalent- 1,1 ' -binaphthyl and ferrocene.
24. The catalyst of claim 18, wherein said ligand is a racemic mixture of enantiomers.
25. The catalyst of claim 18, wherein said ligand is a non-racemic mixture of enantiomers.
26. The catalyst of claim 18, wherein said ligand is one of the enantiomers.
27. The catalyst of claim 18, having an optical purity of at least 85% ee.
28. The catalyst of claim 18, having an optical purity of at least 95% ee.
29. The catalyst of claim 18, wherein said transition metal is selected from the group consisting of: Ag, Pt, Pd, Rh, Ru, Ir, Cu, Ni, Mo, Ti, V, Re and Mn.
30. The catalyst of claim 18, wherein said transition metal is selected from the group consisting of: Pt, Pd, Rh and Ru.
31. The catalyst of claim 18, wherein said transition metal salt, or complex thereof, is selected from the group consisting of: AgX; Ag(OTf); Ag(OTf)2; AgOAc; PtCl2; H2PtCl4; Pd2(DBA)3; Pd(OAc)2; PdCl2(RCN)2;
(Pd(allyl)Cl)2; Pd(PR3)4; (Rh(NBD)2)X; (Rh (NBD)C1)2; (Rh(COD)Cl)2;
(Rh(COD)2)X; Rh(acac)(CO) ; Rh(ethylene)2(acac); (Rh(ethylene)2Cl) 2;
RhCl(PPh3)3; Rh(CO)2Cl2; RuHX(L)2(diphosphine), RuX2(L)2 (diphosphine),
Ru(arene)X2(diphosphine), Ru(aryl group)X2; Ru(RCOO)2(diphosphine); Ru(methallyl)2(diphosphine); Ru(aryl group)X2(PPh3) 3; Ru(COD)(COT);
Ru(COD)(COT)X; RuX2(cymen); Ru(COD)n; Ru(aryl group)X2(diphosphine);
RuCl2(COD); (Ru(COD)2)X; RuX2(diphosphine); RuCl2(=CHR)(PR'3)2;
Ru(ArH)Cl2; Ru(COD)(methalIyl)2; (Ir (NBD)2C1)2; (Ir(NBD)2)X; (Ir(COD)2Cl)2;
(Ir(COD)2)X; CuX (NCCH3)4; Cu(OTf); Cu(OTf)2; Cu(Ar)X; CuX; Ni(acac)2; NiX2; (Ni(allyl)X)2; Ni(COD)2; MoO2(acac)2; Ti(OiPr)4; VO(acac)2; MeReO3;
MnX2 and Mn(acac)2; wherein each R and R' is independently selected from the group consisting of: alkyl or aryl; Ar is an aryl group; and X is a counteranion.
32. The catalyst of claim 31 , wherein L is a solvent molecule and wherein said counteranion X is selected from the group consisting of: halogen,
BF4, B(Ar)4; wherein Ar is fluorophenyl or 3,5-di-trifluoromethyl-l -phenyl, CIO4, SbF6, PF6, CF3SO3, RCOO and a mixture thereof -
33. The catalyst of claim 18 , prepared in situ or as an isolated compound.
34. The catalyst of claim 18, wherein said transition metal salt, or a complex thereof is selected from the group consisting of: [Rh(COD)Cl]2, [Rh(COD)2]X, [Ir(COD)Cl]2, [Ir(COD)2]X, Rh(acac)(CO)2, Ni(allyl)X, Pd2(dba)3, [Pd(allyl)Cl] 2, Ru(RCOO)2(diphosphine), RuX2(diphosphine), Ru(methylallyl)2(diphosphine) and Ru(aryI)X2(diphosphine), wherein X is selected from the group consisting of: BF4, CIO4, SbF6, CF3SO3, Cl and Br; and wherein said ligand is selected from the group consisting of compounds represented by the formula: (a)
Figure imgf000103_0001
wherein each R is independently selected from the group consisting of: alkyl, aryl, substituted alkyl, substituted aryl and SiR3; and wherein each Ar is independently selected from the group consisting of: phenyl, substituted phenyl, aryl and substituted aryl; (b)
Figure imgf000103_0002
(C)
Figure imgf000103_0003
32 (d)
Figure imgf000104_0001
and a combination thereof.
35. A process for preparation of an asymmetric compound comprising: contacting a substrate capable of forming an asymmetric product by an asymmetric reaction and a catalyst prepared by a process comprising: contacting a transition metal salt, or a complex thereof, and a ligand selected from the group consisting of compounds represented by the formula or its enantiomer:
Figure imgf000104_0002
wherein each X and X' is independently selected from the group consisting of: alkyl, aryl, substituted alkyl, substituted aryl, OR, SR, NR2, COOR, halide, SiR3, P(O)R2, P(O)(OR)2 and P(OR)2; wherein each Z and
Figure imgf000104_0003
is independently selected from the group consisting of: alkyl, aryl, substituted alkyl, substituted aryl, OR, SR, NR2, COOR, halide, SiR3, P(O)R2, P(0)(OR)2 and P(OR)2; or wherein Z and Z| together form the bridging group A-B-Ai; wherein each Z', Z", Z and Zi" is independently selected from the group consisting of: H, alkyl, aryl, substituted alkyl, substituted aryl, OR, SR, NR2, COOR, halide, SiR3, P(O)R2, P(O)(OR)2 and P(OR)2, or wherein Z' and Z together form the bridging group A'-B-A; Z' and Z together form a fused cycloaliphatic or aromatic group; Z\ and Z\ together form the bridging group Ar Bj-Ai'; and/or Z] and Z\ together form a fused cycloaliphatic or aromatic group; wherein each A, A', A\ and A] ' is independently selected from the group consisting of: 0, CH2, NH, NR, S, CO and a bond; wherein each B and Bi is independently selected from the group consisting of: linear, branched or cyclic alkylene of 1 to 6 carbon atoms, arylene of 6 to 12 carbon atoms, 0, CH2, NH, NR, S, CO, SO2, P(O)R, P(0)OR, POR, SiR2 and a bond; wherein each T is independently selected from the group consisting of: alkyl, substituted alkyl, aryl, substituted aryl, alkoxide, aryloxide, R, R', R", YR', YR", Y'R' and Y"R"; or wherein two T groups together form an alkylene, arylene, alkylenediamino, arylenediamino, alkelenedioxyl or arylenedioxyl; wherein each T' is independently selected from the group consisting of: alkyl, substituted alkyl, aryl, substituted aryl, alkoxide, aryloxide, R, R', R", YR', YR", Y'R' and Y"R"; or wherein two T' groups together form an alkylene, arylene, alkylenediamino, arylenediamino, alkelenedioxyl or arylenedioxyl; wherein each R, R' and R" is independently selected from the group consisting of: alkyl, substituted alkyl, aryl, aralkyl and alkaryl of 1 to 22 carbon atoms; or wherein two R groups, two R' groups or two R" group together form an alkylene or arelene group; and wherein each Y, Y' and Y" is independently selected from the group consisting of: O, CH2, NH, S and a bond between carbon and phosphorus; with the proviso that when the Y group at the 2' position is a bond between carbon and phosphorus, X' is hydrogen.
36. The process of claim 35, wherein said asymmetric reaction is selected from the group consisting of: hydrogenation, hydride transfer, allylic alkylation, hydrosilylation, hydroboration, hydrovinylation, hydroformylation, olefin metathesis, hydrocarboxylation, isomerization, cyclopropanation, Diels- Alder reaction, Heck reaction, isomerization, Aldol reaction, Michael addition, epoxidation, kinetic resolution and [m+n] cycloaddition wherein m = 3 to 6 and n = 2.
37. The process of claim 36, wherein said transition metal is selected from the group consisting of:
Ag, Pt, Pd Rh, Ru, Ir, Cu, Ni, Mo, Ti, V, Re and Mn.
38. The process of claim 36, wherein said asymmetric reaction is hydrogenation and said substrate is selected from the group consisting of: imine, ketone, ethylenically unsaturated compound, enamine, enamide and vinyl ester.
39. The process of claim 36, wherein said asymmetric reaction is a silver-catalyzed asymmetric [3 +2] cycloaddition of an azomethine ylide with a dipolarophile.
40. The process of claim 36, wherein said asymmetric reaction is a palladium-catalyzed allylic alkylation and said substrate is an allylic ester.
41. The process of claim 36, wherein said asymmetric palladium- catalyzed allylic alkylation reaction is a kinetic resolution reaction and said substrate is a racemic allylic ester.
42. The process of claim 36, wherein said asymmetric reaction is hydrogenation, said substrate is a beta-ketoester, said transition metal is Ru and said asymmetric compound is a beta-hydroxyester.
43. The process of claim 36, wherein said asymmetric reaction is hydrogenation, said substrate is an enamide, said transition metal is Ru and said asymmetric compound is a beta amino acid.
44. The process of claim 36, wherein said ligand is selected from the group consisting of compounds represented by the formula:
(a)
Figure imgf000107_0001
wherein each R is independently selected from the group consisting of: alkyl, aryl, substituted alkyl, substituted aryl and SiR ; and wherein each Ar is independently selected from the group consisting of: phenyl, substituted phenyl, aryl and substituted aryl;
(b)
Figure imgf000107_0002
(c)
Figure imgf000108_0001
32
(d)
Figure imgf000108_0002
and a combination thereof.
45. The process of claim 44, wherein said asymmetric reaction is hydrogenation, said substrate is a beta-ketoester, said transition metal is Ru and said asymmetric compound is a beta-hydroxyester.
46. The process of claim 44, wherein said asymmetric reaction is hydrogenation, said substrate is an enamide, said transition metal is Ru and said asymmetric compound is a beta amino acid.
PCT/US2001/043779 2000-11-17 2001-11-16 Ortho substituted chiral phosphines and phosphinites and their use in asymmetric catayltic reactions Ceased WO2002040491A1 (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
CA002427579A CA2427579C (en) 2000-11-17 2001-11-16 Ortho substituted chiral phosphines and phosphinites and their use in asymmetric catalytic reactions
EP01996543A EP1341797A4 (en) 2000-11-17 2001-11-16 Ortho substituted chiral phosphines and phosphinites and their use in asymmetric catayltic reactions
AU2002216719A AU2002216719A1 (en) 2000-11-17 2001-11-16 Ortho substituted chiral phosphines and phosphinites and their use in asymmetriccatayltic reactions
JP2002543499A JP4167899B2 (en) 2000-11-17 2001-11-16 Ortho-substituted chiral phosphines and phosphinites and their use in asymmetric catalysis

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US24953700P 2000-11-17 2000-11-17
US60/249,537 2000-11-17
US30122101P 2001-06-27 2001-06-27
US60/301,221 2001-06-27

Publications (1)

Publication Number Publication Date
WO2002040491A1 true WO2002040491A1 (en) 2002-05-23

Family

ID=26940144

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2001/043779 Ceased WO2002040491A1 (en) 2000-11-17 2001-11-16 Ortho substituted chiral phosphines and phosphinites and their use in asymmetric catayltic reactions

Country Status (7)

Country Link
US (2) US6653485B2 (en)
EP (1) EP1341797A4 (en)
JP (1) JP4167899B2 (en)
CN (1) CN1610688A (en)
AU (1) AU2002216719A1 (en)
CA (1) CA2427579C (en)
WO (1) WO2002040491A1 (en)

Cited By (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003033142A1 (en) * 2001-10-12 2003-04-24 Basf Aktiengesellschaft Phosphinites
EP1386901A1 (en) * 2002-07-30 2004-02-04 Takasago International Corporation Method for producing an optically active beta-amino acid
WO2004078766A1 (en) * 2003-02-27 2004-09-16 Mitsubishi Chemical Corporation Optically active phosphites and phosphoramides bearing biphenol skeletons with axial chirality, and their use in catalytic asymmetric reactions
WO2004085378A1 (en) * 2003-03-19 2004-10-07 Merck & Co. Inc. Process for the preparation of chiral beta amino acid derivatives by asymmetric hydrogenation
JP2006521385A (en) * 2003-03-28 2006-09-21 ダウ グローバル テクノロジーズ インコーポレイティド Asymmetric catalyst made from optically active bisphosphite bridged by achiral diol
US7173157B2 (en) 2002-08-30 2007-02-06 Mitsubishi Chemical Corporation Method for producing an allyl compound
CN1309728C (en) * 2004-07-30 2007-04-11 中国科学院上海有机化学研究所 Chiral organic, inorganic polymer assembled catalyst, synthesis method and use
US7312347B2 (en) 2005-09-22 2007-12-25 Takasago International Corporation Substituted optically active disphosphine compound
US7425656B2 (en) * 2004-09-15 2008-09-16 Lg Chem, Ltd Phosphorus-containing catalyst composition and process for hydroformylation reaction using the same
US7495123B2 (en) 2004-04-05 2009-02-24 Solvias Ag Process for the preparation of enantiomerically enriched beta amino acid derivatives
WO2009125594A1 (en) * 2008-04-11 2009-10-15 日本曹達株式会社 Optically active dibenzazepine derivatives
WO2009116883A3 (en) * 2008-03-19 2010-04-01 Bial - Portela & Ca., S. A. Catalytic asymetric hydrogenation
WO2011061439A1 (en) 2009-11-17 2011-05-26 Universite De Strasbourg Catalytic phosphination method
EP2420507A1 (en) 2005-09-20 2012-02-22 Takeda Pharmaceutical Company Limited Diphosphine ligand and transition metal complex using the same
JP2012082209A (en) * 2004-04-20 2012-04-26 Kyushu Electric Power Co Inc Phosphorus-containing organic semiconductor compound and method for producing the same
US8183415B2 (en) 2007-06-21 2012-05-22 Amgen, Inc. Methods of synthesizing cinacalcet and salts thereof
WO2012173572A1 (en) * 2011-06-10 2012-12-20 Nanyang Technological University Stereoselective synthesis of highly substituted enamides
EP3088406A1 (en) * 2015-04-29 2016-11-02 Evonik Degussa GmbH Novel monophosphit compounds with an ether group
EP3088405A1 (en) * 2015-04-29 2016-11-02 Evonik Degussa GmbH Novel monophosphit compounds with a methyl group
CN114671743A (en) * 2022-04-20 2022-06-28 石家庄手性化学有限公司 Preparation method of (S) -1- (3-bromo-2-methoxyphenyl) ethan-1-ol
US12521703B1 (en) 2022-08-02 2026-01-13 Inv Nylon Chemicals Americas, Llc Arsenic-containing ligands, catalytic compositions containing such ligands, and catalytic processes utilizing such catalytic compositions
US12600737B2 (en) 2022-08-02 2026-04-14 Inv Nylon Chemicals Americas, Llc Bidentate phosphite ligands, catalytic compositions containing such ligands, and catalytic processes utilizing such catalytic compositions

Families Citing this family (30)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6794553B2 (en) * 2001-11-09 2004-09-21 Shell Oil Company Process for the telomerization of a conjugated diene, catalyst and bidentate ligand useful therein
US6660876B2 (en) * 2001-11-26 2003-12-09 E. I. Du Pont De Nemours And Company Phosphorus-containing compositions and their use in hydrocyanation, isomerization and hydroformylation reactions
US7396947B2 (en) * 2003-06-13 2008-07-08 Lanxess Deutschland Gmbh Chiral ligands for application in asymmetric syntheses
US7094725B2 (en) 2003-07-11 2006-08-22 The Hong Kong Polytechnic University Biphenyldiphosphine compounds
DE10352757A1 (en) * 2003-11-12 2005-06-16 Studiengesellschaft Kohle Mbh Chiral di- and triphosphites
KR100547587B1 (en) * 2004-06-12 2006-01-31 주식회사 엘지화학 Catalyst composition comprising phosphorus and hydroformylation method using the same
US9109081B2 (en) * 2005-02-16 2015-08-18 Sumitomo Chemical Company, Limited Method for producing aromatic polymer
DE102006017588A1 (en) * 2006-04-13 2007-10-18 Wacker Chemie Ag Hydrosilylation process in the presence of ruthenium catalysts
WO2007129664A1 (en) * 2006-05-02 2007-11-15 National University Corporation Nagoya University Chiral tetradentate ligand for asymmetric catalytic action and use thereof
CN100415755C (en) * 2006-08-10 2008-09-03 上海交通大学 2,2',6,6'-tetrasubstituted nitrogen phosphine ligand and its synthesis method
JP4829722B2 (en) * 2006-08-31 2011-12-07 三井化学株式会社 Organic electroluminescent device and aromatic compound
JP2008169201A (en) * 2006-12-11 2008-07-24 Tokyo Univ Of Agriculture & Technology Novel optically active biaryl phosphorus compound and method for producing the same
DE102006058682A1 (en) * 2006-12-13 2008-06-19 Evonik Oxeno Gmbh Bisphosphite ligands for transition metal-catalyzed hydroformylation
EP2098531A1 (en) * 2008-03-05 2009-09-09 National University Corporation Tokyo University of Agriculture and Technology Axially asymmetric phosphorus compound and production method thereof
JP5283175B2 (en) * 2009-01-28 2013-09-04 国立大学法人 岡山大学 Novel diphosphine compound, process for producing the same, and metal complex containing the same
JP5546294B2 (en) * 2010-03-08 2014-07-09 国立大学法人東京農工大学 Axial asymmetric phosphine compound and method for producing the same
AU2011301115B2 (en) * 2010-09-10 2015-10-08 Kanata Chemical Technologies Inc. Biaryl diphosphine ligands, intermediates of the same and their use in asymmetric catalysis
US9994599B2 (en) 2013-09-13 2018-06-12 University Of Florida Research Foundation, Inc. Biaryl ligands
KR101982789B1 (en) 2015-12-04 2019-05-27 주식회사 엘지화학 Ligand compound, organo chromium compound, catalyst system for oligomerization of olefins and method for oligomerization of olefins using the catalyst system
CN106622376B (en) * 2016-12-08 2019-10-11 武汉凯特立斯科技有限公司 A kind of isomerization of internal olefin and hydroformylation reaction method and catalyst
CN106824282B (en) 2017-01-12 2019-10-11 武汉凯特立斯科技有限公司 A kind of hydroformylation reaction method and catalyst using rhodium ruthenium bimetallic and four tooth Phosphine ligands
CN108586529A (en) * 2018-03-06 2018-09-28 上海交通大学 A kind of chipal compounds and the preparation method and application thereof containing biphenyl backbone
CN110372747B (en) * 2018-04-12 2020-10-23 中国科学院大连化学物理研究所 C containing trifluoromethyl3Ligand TunePhos and its synthesis method
CN110372513B (en) * 2018-04-12 2022-03-15 中国石油化工股份有限公司 Vinyl acetate hydroformylation method
KR102819124B1 (en) * 2018-10-02 2025-06-12 주식회사 글라세움 Catalyst for asymmetric hydrogenation of compound having carbon double bond
CN109364998B (en) * 2018-10-15 2021-07-06 天津科技大学 A kind of catalyst for olefin metathesis reaction and preparation and application method thereof
CN110586195B (en) * 2019-06-05 2022-06-14 成都信立诺医药科技有限公司 Chiral catalyst and preparation method and application thereof
EP4023626A1 (en) * 2020-12-31 2022-07-06 Studiengesellschaft Kohle mbH Process for the asymmetric synthesis of isopiperitenol
JP7636272B2 (en) * 2021-06-18 2025-02-26 住友化学株式会社 Method for producing polymer compound, compound, palladium complex, and composition
CN114736239B (en) * 2022-05-26 2024-01-16 重庆理工大学 A bidentate phosphine ligand and its preparation method and application

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5312996A (en) * 1992-06-29 1994-05-17 Union Carbide Chemicals & Plastics Technology Corporation Hydroformylation process for producing 1,6-hexanedials
EP1160237A2 (en) * 2000-05-31 2001-12-05 Bayer Ag Method for the preparation of optically active trimethyllactic acid and its esters

Family Cites Families (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DK350383A (en) * 1982-08-27 1984-02-28 Hoffmann La Roche phosphorus compounds
DK350283A (en) * 1982-08-27 1984-02-28 Hoffmann La Roche PROCEDURE FOR THE MANUFACTURING OF OPTICAL ACTIVE RELATIONS
WO1992016536A1 (en) 1991-03-15 1992-10-01 F. Hoffmann-La Roche Ag Chiral phosphines
TW213465B (en) * 1991-06-11 1993-09-21 Mitsubishi Chemicals Co Ltd
ES2116435T3 (en) 1992-01-31 1998-07-16 Hoffmann La Roche DIPHOSPHINE LIGANDS.
DE4427836A1 (en) * 1994-08-05 1996-02-08 Hoechst Ag Compounds from the range of phosphines, processes for their preparation and their use
DE19522293A1 (en) * 1995-06-20 1997-01-02 Bayer Ag New bisphospins as catalysts for asymmetric reactions
DE19609336C1 (en) * 1996-03-11 1997-03-13 Hoechst Ag New substd. di:phenyl-di:phosphane cpds. used e.g. as complexing agents
JPH1045775A (en) * 1996-04-30 1998-02-17 Mitsubishi Chem Corp Method for producing bisphosphite compound
JP3812046B2 (en) * 1996-04-30 2006-08-23 三菱化学株式会社 Bisphosphite compound and hydroformylation method using the same
JP3493266B2 (en) * 1996-08-27 2004-02-03 高砂香料工業株式会社 Novel optically active diphosphine compound, method for producing the compound, transition metal complex having the compound as ligand, and method for producing optically active substance using the complex
US6162951A (en) * 1996-09-20 2000-12-19 Oxford Asymmetry International Plc Phosphine ligands
JP3445451B2 (en) * 1996-10-24 2003-09-08 高砂香料工業株式会社 Method for producing optically active diphosphine ligand
JP3148136B2 (en) * 1996-12-26 2001-03-19 高砂香料工業株式会社 Novel chiral diphosphine compound, intermediate for producing the same, transition metal complex having the diphosphine compound as a ligand, and asymmetric hydrogenation catalyst containing the complex
ZA986369B (en) * 1997-07-29 2000-01-17 Du Pont Hydrocyanation of diolefins and isomerization of nonconjugated 2-alkyl-3-monoalkenenitriles.
JP3892118B2 (en) * 1997-07-31 2007-03-14 高砂香料工業株式会社 2,2'-bis (diarylphosphino) -6,6'-bis (trifluoromethyl) -1,1'-biphenyl, transition metal complex having this as a ligand, and optically active 3-hydroxybutyric acid ester Derivative or process for producing β-butyrolactone
JP3846020B2 (en) * 1998-04-07 2006-11-15 三菱化学株式会社 Bisphosphite compound and method for producing aldehydes using the compound
ATE243216T1 (en) * 1998-11-19 2003-07-15 Solvias Ag CHIRAL DIPHENYLDIPHOSPHINE AND D-8 METAL COMPLEXES THEREOF
BR0014567A (en) * 1999-09-20 2002-06-18 Du Pont Hydrocyanation process, multidentate phosphite binder and catalyst composition
US6307107B1 (en) * 1999-09-20 2001-10-23 E.I. Du Pont De Nemours And Company Hydroformylation of acyclic monoethylenically unsaturated compounds to corresponding terminal aldehydes
JP2001131192A (en) * 1999-10-29 2001-05-15 Takasago Internatl Corp A novel optically active diphosphine compound, a production intermediate thereof, a transition metal complex having the compound as a ligand, and an asymmetric hydrogenation catalyst containing the complex.
JP4092863B2 (en) * 2000-08-29 2008-05-28 三菱化学株式会社 Method for producing allyl compounds
JP2002105026A (en) * 2000-09-29 2002-04-10 Mitsubishi Chemicals Corp Method for producing allyl compound

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5312996A (en) * 1992-06-29 1994-05-17 Union Carbide Chemicals & Plastics Technology Corporation Hydroformylation process for producing 1,6-hexanedials
EP1160237A2 (en) * 2000-05-31 2001-12-05 Bayer Ag Method for the preparation of optically active trimethyllactic acid and its esters

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
DATABASE CAPLUS [online] CHEMICAL ABSTRACT, COLUMBUS OH, USA; ZHANG ET AL.: "Synthesis of chiral bisphoshines with tunable bite angles and their applications in asymmetric hydrogenation of .beta.ketoesters", XP002909219, accession no. STN Database accession no. 2000:574233 *
DATABASE CAPLUS [online] CHEMICAL ABSTRACTS (COLUMBUS OH, USA); SRIGES, W. ET AL.: "Method for the preparation of optically active trimethylactic acid and its esters", XP002909218, accession no. STN Database accession no. 2001:885409 *
JOURNAL OF ORGANIC CHEMISTRY, vol. 65, no. 19, 2000, pages 6223 - 6226 *
See also references of EP1341797A4 *

Cited By (34)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003033142A1 (en) * 2001-10-12 2003-04-24 Basf Aktiengesellschaft Phosphinites
EP1386901A1 (en) * 2002-07-30 2004-02-04 Takasago International Corporation Method for producing an optically active beta-amino acid
US7173157B2 (en) 2002-08-30 2007-02-06 Mitsubishi Chemical Corporation Method for producing an allyl compound
WO2004076464A3 (en) * 2003-02-27 2004-12-16 Mitsubishi Chem Corp Optically active phosphites and phosphoramidites and their use in asymmetric reactions
WO2004078766A1 (en) * 2003-02-27 2004-09-16 Mitsubishi Chemical Corporation Optically active phosphites and phosphoramides bearing biphenol skeletons with axial chirality, and their use in catalytic asymmetric reactions
WO2004085378A1 (en) * 2003-03-19 2004-10-07 Merck & Co. Inc. Process for the preparation of chiral beta amino acid derivatives by asymmetric hydrogenation
JP2006521385A (en) * 2003-03-28 2006-09-21 ダウ グローバル テクノロジーズ インコーポレイティド Asymmetric catalyst made from optically active bisphosphite bridged by achiral diol
US7495123B2 (en) 2004-04-05 2009-02-24 Solvias Ag Process for the preparation of enantiomerically enriched beta amino acid derivatives
JP2012082209A (en) * 2004-04-20 2012-04-26 Kyushu Electric Power Co Inc Phosphorus-containing organic semiconductor compound and method for producing the same
US9406910B2 (en) 2004-04-20 2016-08-02 Daiden Co., Ltd Organic electroluminescent element and manufacturing method thereof, and phosphorus-containing organic compound and manufacturing method thereof
CN1309728C (en) * 2004-07-30 2007-04-11 中国科学院上海有机化学研究所 Chiral organic, inorganic polymer assembled catalyst, synthesis method and use
US7425656B2 (en) * 2004-09-15 2008-09-16 Lg Chem, Ltd Phosphorus-containing catalyst composition and process for hydroformylation reaction using the same
EP1789185B2 (en) † 2004-09-15 2018-07-25 LG Chem, Ltd. Phsphorus-containing catalyst composition and process for hydroformylation using the same
US8981147B2 (en) 2005-09-20 2015-03-17 Takeda Pharmaceutical Company Limited Diphosphine ligand and transition metal complex using the same
US8691718B2 (en) 2005-09-20 2014-04-08 Takeda Pharmaceutical Company Limited Diphosphine ligand and transition metal complex using the same
EP2420507A1 (en) 2005-09-20 2012-02-22 Takeda Pharmaceutical Company Limited Diphosphine ligand and transition metal complex using the same
US7312347B2 (en) 2005-09-22 2007-12-25 Takasago International Corporation Substituted optically active disphosphine compound
US8183415B2 (en) 2007-06-21 2012-05-22 Amgen, Inc. Methods of synthesizing cinacalcet and salts thereof
US8957222B2 (en) 2008-03-19 2015-02-17 Bial-Portela & Ca, S.A. Process for preparing intermediates of peripherally-selective inhibitors of dopamine-β-hydroxylase involving catalytic asymmetric hydrogenation
CN102056846A (en) * 2008-03-19 2011-05-11 比亚尔-坡特拉有限公司 Catalytic asymetric hydrogenation
WO2009116883A3 (en) * 2008-03-19 2010-04-01 Bial - Portela & Ca., S. A. Catalytic asymetric hydrogenation
US8507669B2 (en) 2008-04-11 2013-08-13 Nippon Soda Co., Ltd. Optically active dibenzazepine derivatives
WO2009125594A1 (en) * 2008-04-11 2009-10-15 日本曹達株式会社 Optically active dibenzazepine derivatives
WO2011061439A1 (en) 2009-11-17 2011-05-26 Universite De Strasbourg Catalytic phosphination method
WO2012173572A1 (en) * 2011-06-10 2012-12-20 Nanyang Technological University Stereoselective synthesis of highly substituted enamides
EP3088405A1 (en) * 2015-04-29 2016-11-02 Evonik Degussa GmbH Novel monophosphit compounds with a methyl group
DE102015207864A1 (en) * 2015-04-29 2016-11-03 Evonik Degussa Gmbh New monophosphite compounds with an ether group
DE102015207860A1 (en) * 2015-04-29 2016-11-03 Evonik Degussa Gmbh New monophosphite compounds with a methyl group
US9605011B2 (en) 2015-04-29 2017-03-28 Evonik Degussa Gmbh Monophosphite compounds having an ether group
US9605010B2 (en) 2015-04-29 2017-03-28 Evonik Degussa Gmbh Monophosphite compounds having a methyl group
EP3088406A1 (en) * 2015-04-29 2016-11-02 Evonik Degussa GmbH Novel monophosphit compounds with an ether group
CN114671743A (en) * 2022-04-20 2022-06-28 石家庄手性化学有限公司 Preparation method of (S) -1- (3-bromo-2-methoxyphenyl) ethan-1-ol
US12521703B1 (en) 2022-08-02 2026-01-13 Inv Nylon Chemicals Americas, Llc Arsenic-containing ligands, catalytic compositions containing such ligands, and catalytic processes utilizing such catalytic compositions
US12600737B2 (en) 2022-08-02 2026-04-14 Inv Nylon Chemicals Americas, Llc Bidentate phosphite ligands, catalytic compositions containing such ligands, and catalytic processes utilizing such catalytic compositions

Also Published As

Publication number Publication date
US6855657B2 (en) 2005-02-15
US20040068126A1 (en) 2004-04-08
CA2427579C (en) 2009-11-03
CA2427579A1 (en) 2002-05-23
EP1341797A1 (en) 2003-09-10
JP2004513950A (en) 2004-05-13
EP1341797A4 (en) 2005-06-15
AU2002216719A1 (en) 2002-05-27
CN1610688A (en) 2005-04-27
US6653485B2 (en) 2003-11-25
JP4167899B2 (en) 2008-10-22
US20020128501A1 (en) 2002-09-12

Similar Documents

Publication Publication Date Title
WO2002040491A1 (en) Ortho substituted chiral phosphines and phosphinites and their use in asymmetric catayltic reactions
JP3148136B2 (en) Novel chiral diphosphine compound, intermediate for producing the same, transition metal complex having the diphosphine compound as a ligand, and asymmetric hydrogenation catalyst containing the complex
JP4488739B2 (en) P-chiral phosphoranes and phosphocyclic compounds and their use in asymmetric catalysis
JP4754753B2 (en) Chiral ferrocenephosphine and its use in asymmetric catalysis
JP4837857B2 (en) Chiral ligands, their transition metal complexes and their use in asymmetric reactions
JP2003509513A (en) Chiral phosphines, their transition metal complexes and their use in asymmetric reactions
EP2556077B1 (en) Monophosphorus ligands and their use in cross-coupling reactions
WO2004076464A2 (en) Optically active phosphites and phosphoramidites and their use in asymmetric reactions
US20040229846A1 (en) P-chiral phospholanes and phosphocyclic compounds and their use in asymmetric catalytic reactions
JP5454756B2 (en) Diphosphine compounds, transition metal complexes thereof, catalysts containing the transition metal complexes, phosphine oxide compounds and diphosphine oxide compounds
WO2006028977A2 (en) Chiral spiro compounds and their use in asymmetric catalytic reactions
EP1095946B1 (en) Optically active diphosphine compound, production intermediates therefor, transition metal complex containing the compound as ligand and asymmetric hydrogenation catalyst containing the complex
US20040072680A1 (en) Chiral phosphorus cyclic compounds for transition metal-catalyzed asymmetric reactions
US5648548A (en) Optically active asymmetric diphosphine and process for producing optically active substance in its presence
CN110128472B (en) Synthesis and application of an oxaspirocyclic PNN-type ligand
JP2008169201A (en) Novel optically active biaryl phosphorus compound and method for producing the same
JP2012031119A (en) Axially chiral isoquinoline derivative, its production method, and asymmetric synthesis method
JP5546294B2 (en) Axial asymmetric phosphine compound and method for producing the same
JP2016166170A (en) Optically active binaphthyl compound

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
WWE Wipo information: entry into national phase

Ref document number: 2427579

Country of ref document: CA

WWE Wipo information: entry into national phase

Ref document number: 018190677

Country of ref document: CN

Ref document number: 2002543499

Country of ref document: JP

WWE Wipo information: entry into national phase

Ref document number: 2001996543

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 2001996543

Country of ref document: EP

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

WWW Wipo information: withdrawn in national office

Ref document number: 2001996543

Country of ref document: EP