Classifications

• • 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
  • B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
  • B01J31/12—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides containing organo-metallic compounds or metal hydrides
  • B01J31/14—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides containing organo-metallic compounds or metal hydrides of aluminium or boron
  • B01J31/146—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides containing organo-metallic compounds or metal hydrides of aluminium or boron of boron
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
  • C07B35/00—Reactions without formation or introduction of functional groups containing hetero atoms, involving a change in the type of bonding between two carbon atoms already directly linked
  • C07B35/02—Reduction
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
  • C07B43/00—Formation or introduction of functional groups containing nitrogen
  • C07B43/04—Formation or introduction of functional groups containing nitrogen of amino groups
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
  • C07C209/44—Preparation of compounds containing amino groups bound to a carbon skeleton by reduction of carboxylic acids or esters thereof in presence of ammonia or amines, or by reduction of nitriles, carboxylic acid amides, imines or imino-ethers
  • C07C209/52—Preparation of compounds containing amino groups bound to a carbon skeleton by reduction of carboxylic acids or esters thereof in presence of ammonia or amines, or by reduction of nitriles, carboxylic acid amides, imines or imino-ethers by reduction of imines or imino-ethers
• • 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
  • C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
  • C07F5/02—Boron compounds
  • C07F5/027—Organoboranes and organoborohydrides
• • 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
• • 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

Definitions

• the present invention pertains to frustrated Lewis pair catalysts and their uses for reduction reactions. More particularly, the present invention pertains to frustrated Lewis pair catalysts comprising a borenium complex, and the use of the borenium-containing frustrated Lewis pair catalysts in direct hydrogenation reactions.
• Hydrogenation is one of the most utilized and important reactions in chemistry.
• the hydrogenation of organic substrates using H 2 directly is mediated by a transition metal catalyst.
• main group hydrides such as NaBH 4 and LiAlH 4 afford stoichiometric reductions, with complementary chemo- and regioselectivity to metal catalysis.
• M. B. Smith and J. March, in March's Advanced Organic Chemistry, New York, 5th Ed., 2001, pp. 1197-1204 and pp. 1544-1564. For these reagents in industrial scale reduction processes, cost, chemical efficacy and waste disposal are significant concerns.
• transition metal-free catalysts could address the cost and waste remediation issues associated with main group hydrides, as well as avoid the expense and potentially toxic nature of precious metal catalysts.
• a number of transition metal-free hydrogenation reactions are known within the field of organocatalysis.
• An object of the present invention is to provide a process for the use of a frustrated Lewis pair catalyst in hydrogenation and reduction reactions.
• Another object of the present application is to provide a frustrated Lewis pair catalyst comprising a borenium complex, a weakly coordinating anion, and a Lewis base, which can be a frustrated Lewis base.
• a process for reducing an unsaturated substrate comprising reacting the substrate with hydrogen in the presence of a catalyst, the catalyst comprising: a borenium complex having the structure of formula (I),
• R 1 and R 2 are alkyl, aryl, -SR 4 , -OR 4 or -NR 4 R 4 , and wherein R 4 is independently C 2 -8 alkyl, each of which is optionally substituted, or R 1 and R 2 can form a cyclic structure together with the boron atom to which they are attached; and
• R 3 is a strong base
• the Lewis base is NR 3 , PR 3 or CR 3 , wherein R is alkyl or aryl, each of which is optionally substituted.
• the weakly coordinating anion is
• the borenium complex has the structure of formula (I), and R 3 is carbene or phosphene.
• R 3 is a carbene, for example an N-heterocyclic carbene, or a mono-amino-carbene (CAAC), or bent allene species.
• the borenium complex is chiral.
• each R is alkyl or aryl, each of which is optionally substituted.
• the catalyst is
• each R is independently alkyl or aryl, which is optionally substituted.
• the borenium complex is
• each R 7 is independently alkyl or aryl, each of which is optionally substituted.
• the substrate is an imine, enamine, aromatic amine, or aromatic N-heterocycle.
• the resulting reduced substrate is chiral.
• the process is carried out in the presence of a base.
• composition comprising: a borenium complex having the structure of formula (I)
• R 1 and R 2 are alkyl, aryl, -SR 4 , -OR 4 or -NR 4 R 4 , and wherein R 4 is independently C 2 -8 alkyl, each of which is optionally substituted, or R 1 and R 2 can form a cyclic structure together with the boron atom to which they are attached; and
• R 3 is a strong base
• the Lewis base is NR 3 , CR 3 or PR 3 , wherein R is alkyl or aryl, each of which is optionally substituted.
• the borenium complex has the structure of formula (I), and R 3 is carbene or phosphene.
• R 3 is a carbene, for example an N-heterocyclic carbene, or a mono-amino-carbene (CAAC), or bent allene species.
• CAAC mono-amino-carbene
• the weakly coordinating anion is
• the weakly coordinating anion is B(C 6 F 5 ) 4 -
• the borenium complex is chiral. [0028] In accordance with another embodiment, the borenium complex is
• each R is independently alkyl, aryl, each of which is optionally substituted.
• the composition comprises
• the borenium complex is
• the composition is for use in hydrogenation of an unsaturated bond in a substrate.
• each R is independently alkyl or aryl, each of which is optionally substituted.
• each R 7 is independently alkyl or aryl, each of which is optionally substituted.
• Figures 1 depicts a Persistence of Vision (POV) depiction of the borenium complex [I( Pr)2-BBN] + having B-C bond lengths (BBN) of 1.554A and 1.561A, , and a B-C (NHC) bond length of 1.585A, and atomic charges on C-(BBN) of -0.657, C-(NHC) of 0.099, and 1.065 on B;
• POV Persistence of Vision
• Figure 2 depicts a POV depiction of the borohydride I(/Pr) 2 -BBN hydride complex having B-C bond lengths (BBN) of 1.643 A and 1.644 A, and a B-C (NHC) bond length of 1.640A; and
• Figure 3 is a photograph of the the borohydride I(7Pr) 2 -BBN hydride complex in solid form.
• the second component as used herein is chemically different from the other components or first component.
• a “third” component is different from the other, first, and second components, and further enumerated or “additional” components are similarly different.
• suitable means that the selection of the particular compound or conditions would depend on the specific synthetic manipulation to be performed, and the identity of the molecule(s) to be transformed, but the selection would be well within the skill of a person trained in the art. All process/method steps described herein are to be conducted under conditions sufficient to provide the product shown. A person skilled in the art would understand that all reaction conditions, including, for example, reaction solvent, reaction time, reaction temperature, reaction pressure, reactant ratio and whether or not the reaction should be performed under an anhydrous or inert atmosphere, can be varied to optimize the yield of the desired product and it is within their skill to do so.
• alkyl refers to a linear, branched or cyclic, saturated or unsaturated hydrocarbon group, such as a C 1-2 o alkyl, a Ci-io alkyl or a Ci_6 alkyl, which can be unsubstituted or is optionally substituted with one or more substituent.
• saturated straight or branched chain alkyl groups include, but are not limited to, methyl, ethyl,
• alkyl encompasses cyclic alkyls, or cycloalkyl groups.
• cycloalkyl refers to a non-aromatic, saturated monocyclic, bi cyclic or tricyclic hydrocarbon ring system containing at least 3 carbon atoms.
• C3-C12 cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, norbornyl, adamantyl, bicyclo[2.2.2]oct-2-enyl, and bicyclo[2.2.2]octyl.
• alkenyl refers to a straight, branched or cyclic hydrocarbon group containing at least one double bond which is unsubstituted or optionally substituted with one or more substituents.
• an alkenyl can be a C2-20 alkenyl, a C2-10 alkenyl, or a C2-6 alkenyl.
• alkynyl refers to an unsaturated, straight or branched chain hydrocarbon group containing at least one triple bond which is unsubstituted or optionally substituted with one or more substituents.
• an alkynyl can be a C2-20 alkynyl, a C2-10 alkynyl, or a C2-6 alkynyl.
• allenyl refers to a straight or branched chain hydrocarbon group containing a carbon atom connected by double bonds to two other carbon atoms, which is unsubstituted or optionally substituted with one or more substituents.
• aryl refers to hydrocarbons derived from benzene or a benzene derivative that are unsaturated aromatic carbocyclic groups of from 6 to 100 carbon atoms which may or may not be a fused ring system. In some embodiments, the aryl group is an unsaturated aromatic carbocyclic group of from 6 to 50, or from 6 to 25, or from 6 to 15 carbon atoms. The aryls can have a single or multiple rings. The term "aryl” as used herein also includes substituted aryls.
• Examples include, but are not limited to, substituted and unsubstituted phenyl, naphthyl, xylene, phenylethane, 1,2,3,4-tetrahydronaphthyl, indanyl, indenyl, anthracenyl, 1,2-dihydronaphthyl, fluorenyl, and the like.
• substituted and unsubstituted phenyl naphthyl, xylene, phenylethane, 1,2,3,4-tetrahydronaphthyl, indanyl, indenyl, anthracenyl, 1,2-dihydronaphthyl, fluorenyl, and the like.
• heteroaryl refers to an aryl that includes from 1 to 10, or from 1 to 4, heteroatoms selected from oxygen, nitrogen and sulfur, which can be substituted or unsubstituted.
• alkylene as used herein, means a bivalent alkyl group.
• substituted refers to the structure having one or more substituents.
• a substituent is an atom or group of bonded atoms that can be considered to have replaced one or more hydrogen atoms attached to a parent molecular entity.
• substituents include aliphatic groups, halogen, arylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, alkoxycarbonyl, aminocarbonyl, alkylthiocarbonyl, alkoxyl, phosphate ester, phosphonato, phosphinato, cyano, tertiary amino, tertiary acylamino, tertiary amide, imino, alkylthio, arylthio, sulfonato, sulfamoyl, tertiary sulfonamido, nitrile, trifluoromethyl, heterocyclyl, aromatic, and heteroaromatic moieties, ether, ester, boron-containing moieties, tertiary phosphines, and silicon-containing moieties.
• optionally substituted means unsubstituted or substituted.
• olefin also called alkene, refers to an unsaturated hydrocarbon containing one or more pairs of carbon atoms linked by a double bond, and includes cyclic or acyclic (aliphatic) olefins, in which the double bond is located between carbon atoms forming part of a cyclic (closed-ring) or of an open-chain grouping, respectively, and monoolefins, diolefins, triolefins, etc., in which the number of double bonds per molecule is, respectively, one, two, three, or some other number.
• Such olefins can be substituted or unsubsituted .
• olefins include, but are not limited to, substituted or unsubsituted 1-propene, 1-butene, 1-pentene, 1- hexene, and 1-octene and substituted or unsubstitued norbornene.
• electron withdrawing group refers to an electronegative group capable of polarizing a bond with a carbon atom.
• electron withdrawing groups are halogens, CF 3 , nitro, nitrile, carbonyl and substituted carbonyl.
• a "heteroatom” refers to an atom that is not carbon or hydrogen, such as nitrogen, oxygen, sulfur, phosphorus, chlorine, bromine, and iodine.
• heteroatom refers to a five- or six-membered aromatic ring comprising at least one hetermoiety selected from O, S, N, NH and NCi- 4 alkyl.
• Heteroaromatic groups include, for example, furanyl, thiophenyl, pyrrolyl, 1,2- or 1,3- oxazolyl, 1,2- or 1,3-diazolyl, 1,2,3- or 1,2,4-triazolyl, and the like.
• heteroatom-containing moiety means a heteroatom-containing moiety.
• heterocycle is an aromatic or nonaromatic monocyclic or bicyclic ring of carbon atoms and from 1 to 4 heteroatoms selected from oxygen, nitrogen and sulfur, and which can be substituted or unsubstituted. Included within the term
• heterocycle are heteroaryls, as defined above.
• Examples of 3- to 9-membered heterocycles include, but are not limited to, aziridinyl, oxiranyl, thiiranyl, azirinyl, diaziridinyl, diazirinyl, oxaziridinyl, azetidinyl, azetidinonyl, oxetanyl, thietanyl, piperidinyl, piperazinyl, morpholinyl, pyrrolyl, oxazinyl, thiazinyl, diazinyl, triazinyl, tetrazinyl, imidazolyl, benzimidazolyl, tetrazolyl, indolyl, isoquinolinyl, quinolinyl, quinazolinyl, pyrrolidinyl, purinyl, isoxazolyl, benzisox
• ring system refers to a carbon-containing ring system containing the specified number of carbon atoms and includes monocyclic and poly cyclic rings. Ring systems include saturated, unsaturated or aromatic rings, or mixtures thereof. Where specified the ring system is optionally substituted and/or may optionally contain one or more heteromoieties, such as O, S, N, NH and NCi- 4 alkyl.
• poly cyclic means a group that contains more than one ring linked together and includes, for example, groups that contain two (bicyclic), three (tricyclic) or four (tetracyclic) rings.
• the rings may be linked through a single bond, a single atom (spirocyclic) or through two atoms (fused and bridged).
• halogen or halo refers to F, CI, Br or I.
• fluoro-substituted refers to a group in which one or more, including all, of the hydrogen atoms have been replaced with a fluorine atom.
• electrophilic activation means to increase reactivity of a specific atom or functional group (e.g., a carbonyl or carboxyl group) by removal of electron density from that atom or functional group.
• heteroatom substituent refers to any chemical group that comprises at least heteroatom with one lone pair of electrons and that is capable of donating electron density to neighbouring atoms.
• groups include, but are not limited to, groups comprising, or consisting of, I, CI, Br, S, O, N, and Se.
• the heteroatom substituent further comprises one or more Ci- 4 alkyl and/or C6-ioaryl groups that are optionally further substituted by one or more halo, Ci-4alkyl and/or OCi- 4 alkyl.
• the heteroatom in the lone pair-containing heteroatom substituent is the point of attachment of the substituent to the remainder of the molecule.
• protecting group refers to a chemical moiety which protects or masks a reactive portion of a molecule to prevent side reactions in those reactive portions of the molecule, while manipulating or reacting a different portion of the molecule. After the manipulation or reaction is complete, the protecting group is removed under conditions that do not degrade or decompose the remaining portions of the molecule.
• PG protecting group
• the selection of a suitable protecting group can be made by a person skilled in the art. Many conventional protecting groups are known in the art, for example as described in "Protective Groups in Organic Chemistry” McOmie, J.F. W. Ed., Plenum Press, 1973, in Greene, T. W.
• Suitable protecting groups include but are not limited to t-BOC, Ts, Ms, TBDMS, TBDPS, Tf, Bn, allyl, Fmoc, Ci-i 6 acyl and the like, t- BOC, as used herein, refers to the group f-butyloxy carbonyl. Ac, as used herein, refers to the group acetyl.
• Ts (tosyl) as used herein refers to the group /?-toluenesulfonyl.
• Ms refers to the group methanesulfonyl.
• TBDMS refers to the group t- butyldimethylsilyl.
• TBDPS refers to the group f-butyldiphenylsilyl.
• Tf refers to the group trifluoromethanesulfonyl, also known as triflate.
• Ns as used herein, refers to the group naphthalene sulphonyl.
• Bn refers to the group benzyl.
• Fmoc refers to the group fiuorenylmethoxy carbonyl
• Lewis acid refers to an electron deficient molecule, complex, fragment or fragment thereof, or ion that can act as an electron-pair acceptor, and is able to react with a Lewis base to form a Lewis adduct, by sharing the electron pair made available from the Lewis base.
• Lewis base refers to a molecule, complex, fragment or fragment thereof, or ion that can act as an electron pair donor, and is able to react with a Lewis acid to form a Lewis adduct by sharing its electron pair.
• borenium complex refers to a cationic organic boron species wherin the boron atom is positively charged. It is understood that the positive charge can be delocalized depending on the structure of the complex. Therefore, though the borenium complex is often depicted with the cationic charge on the boron atom, it is understood that resonance structures can exist.
• the term “carbene” refers to a molecule comprising a neutral carbon atom with a valence of two, and two valence electrons available for formation of a bond, for example with a boron atom.
• the term “carbene” is understood to be a bivalent carbon donor.
• An "N-heterocyclic carbene” or “NHC” is a type of carbene in which the carbenic carbon is part of a nitrogen-containing heterocycle, such as an imidazole.
• NHC NHC
• sNHC diamino heterocyclic carbenes in which the carbenic carbon connects the two nitrogen atoms, and the remaining carbon atoms in the heterocycle are saturated (i.e., they are connected via single bonds).
• the sNHC is a five membered or a six membered heterocycle.
• the term "weakly coordinating anion” refers to a species that retains a negative charge, in which the charge is delocalized over the fragment and/or sterically protected. This species of anion is a poor donor to a Lewis acidic centre. In the extreme, such anions become non-coordinating anion but typically establish an equilibrium between coordination and non-coordination in which the latter dominates. In the presently described system, the charge derealization and/or sterics of this species prevent it from blocking the reactivity of the borenium complex.
• reducing refers to reactions commonly known in the art wherein two hydrogen atoms are added across an unsaturated bond. For example, a double bond can be reduced to generate a single bond.
• Common double bond types that can serve as substrates for reduction reactions are imines, alkenes, enamines, ketones, olefins, alkynes, and aromatic and heteroaromatic substrates including phenyl and heterocycles.
• substrate refers to the chemical species that is the starting material for the present hydrogenation reactions.
• Substrates used in the presently described reactions are those having at least one reduceable bond that is unsaturated.
• Some examples of reduceable bonds include imines, alkenes, alkynes, aromatic groups and ketones.
• strong base refers to a basic chemical species that is used to form a bond with and stabilize the borenium.
• the combination of the borenium complex and the strong base forms the borenium complex or Lewis acid species.
• Non- limiting examples of a strong base are amine, phosphine or carbene.
• the present application describes a process for catalytic hydrogenation of a variety of organic substrates using the catalysts as described herein.
• the present reactions do not require the use of an additional metal or metal catalyst to carry out the hydrogenation reactions.
• the presently described catalysts can catalyse the reduction of a variety of different substrates to form hydrogenated products. Some example reduction reactions are summarized in Table 1 below.
• FLPs have been shown to be capable of performing the hydrogenating reactions shown in Table 2.
• Table 2 Chose, P. A., Welch, G. C, Jurca, T., Stephan, D. W. Angew. Chem. Int. Ed. 2007, 46, 8050 -8053; Spies, P., Schwendemann, S., Lange, S., Kehr, G, Frolich, R, Erker G. Angew. Chem. Int. Ed. 2008, 47, 7543 -7546; Wang, H., Frohlich, R., Kehr G, Erker, G. Chem.
• the catalysts are useful for direct reduction of an unsaturated bond reaction in the presence of H 2 .
• the substrate is exposed to the H 2 reducing reagent in the presence of a presently described catalyst, affording direct hydrogenation of the substrate.
• the present catalysts can assist in the direct hydrogenation of the substrate with molecular hydrogen.
• the present catalysts can also be employed in stoichiometric, and sub-stoichiometric amounts or catalytic amounts, to arrive at the reduced product.
• the present catalysts are formed from reaction of a secondary boron with a strong base to form a borohydride zwitterion. Further reaction of this zwitterion with a hydride abstractor results in abstraction of a hydride from the zwitterion to generate the borenium complex.
• the general reaction scheme is shown in scheme 1.
• the secondary boron species can be any boron atom bound to two non- hydrogen atoms and one hydrogen atom.
• the non-hydrogen atoms can be any suitable group that forms a bond with boron.
• Non-limiting examples of the non-hydrogen atoms are alkyl, alkoxy, dialkylamine, alkylsilane, alkylphosphone, and thioalkyl.
• Some preferred examples of secondary boron species are dialkyl boron hydrides. Abstraction of the hydride from the B- H bond in the boron hydride species generates a borenium, which is the Lewis acid in the frustrated Lewis pair of the active complex.
• a strong base such as but not limited to amine, phosphine or carbene, is used to form a bond with and stabilize the borenium.
• the combination of the borenium complex and the strong base forms the borenium complex or Lewis acid species.
• a carbene is any species that has a carbon atom with an electron pair capable of forming a bond with the secondary boron species.
• the carbene can be saturated or unsaturated, acyclic or part of a cyclic structure. If part of a cyclic structure, the cyclic structure can be non- aromatic, aromatic or heteroaromatic. In one preferred embodiment, the carbene is chiral.
• One example of a strong base that can stabilize the boron is N-heterocyclic carbene (NHC).
• Other examples of strong bases are mono-amino-carbene (CAAC), and bent allene species.
• a strong hydride abstracting agent is required for abstracting the proton from the secondary boron species to generate the borenium complex.
• the hydride abstracting agent is a Bronsted or Lewis acid capable of forming a strong bond with hydride, and of abstracting the hydride from the boron zwitterion.
• acceptable hydride removing agents are iminium, carbocations, trialkylphosphonium, or trityl cation.
• the hydride abstractor with the added hydride subsequent to abstraction from the boron zwitterion is the Lewis base in the frustrated Lewis pair.
• the abstraction can also be effected by treatment with an acid that provides a weakly coordinating anion. One example of this is triflic acid. This will result in the evolution of H 2 and formation of the borenium.
• a weakly coordinating anion functions to charge stabilize the borenium complex.
• This species has an overall negative charge, in which the charge is delocalized to minimize coordination with the borenium complex but maintain charge balance in the composition.
• Non-limiting examples of these anions are carboranes, bulky
• tetraalkoxyaluminates or B(R 5 ) 4 ⁇ , wherein each R 5 is independently phenyl or C 1-8 alkyl optionally substituted with halogen
• Some specific examples of anions are than [B(C 6 F 5 ) 4 ] " , " OTf or NHTf 2 .
• the weakly coordinating anion can be incorporated into the catalyst complex by way of addition of the weakly coordinating anion as a salt with the hydride abstracting agent.
• One general example of this is [PhsC][BR4].
• trityl tetrakis(pentafluorophenyl)borate also referred to herein as [trityl] [BArF]
• trityl tetrakis(pentafluorophenyl)borate
• an acidic reagent can be used to remove the B-H hydride from the boron hydride species. This generates the active borenium catalyst, which is the Lewis acid partner of the frustrated Lewis catalyst pair.
• the Lewis acid portion of the complex, specifically the borenium has a positive charge that is stabilized in the catalyst composition by the weakly coordinating anion.
• the charges are not point charges, but can be delocalized depending on the strucutre of the complex. It is understood that thought the cationic charge is depicted on the boron atom in the borenium complex, the denoted charge is indicative of the charge of the complex generally, and that the charge may be delocalized in the complex.
• the carbene is an N-heterocyclic carbene and the boron formed is an NHC-boreneium complex.
• Bromobenzene-c j, chlorobenzene, dichloromethane, and dichloromethane- ⁇ were each dried over CaH 2 , vacuum-transferred into a Young bomb, and stored over 4 A molecular sieves.
• Toluene-c3 ⁇ 4 was dried over Na/benzophenone, vacuum-transferred into a Young bomb, and stored over 4 A molecular sieves. All solvents were thoroughly degassed after purification (three freeze-pump-thaw cycles).
• NMR spectra were recorded at 25°C on a Bruker Avance 400 MHz spectrometer or an Agilent DD2 500MHz spectrometer unless otherwise noted.
• Hydrogen gas (Grade 5.0) was obtained from Linde and purified through a
• Ratio of C 6 H 5 C1 to was determined by 3 ⁇ 4i NMR and confirmed by elemental analysis.
• 3 ⁇ 4 NMR 400 MHz, CD 2 C1 2 , 298 K
• the present catalysts can be activated in situ to form the active borenium complex.
• the activation is carried out with a hydride abstractor to remove hydride from the boron to yield the borenium complex.
• the borenium complex is the Lewis acid in the frustrated Lewis pair, and the conjugate base of the hydride abstractor and/or the substrate is the Lewis base in the frustrated Lewis pair.
• N-benzylidene-ieri-butylamine (68.2 mg, 0.423 mmol, 10 eq.) were weighed into vials. The contents of the vials were transferred to a J-Young NMR tube with 0.6 niL C 6 D 5 Br. The tube was sealed and subjected to three freeze-pump-thaw cycles. The sample was then frozen and the tube was backfilled with hydrogen gas, sealed and carefully thawed. Conversion of N-benzylidene-ferf-butylamine to N-benzyl-ferf-butylamine was observed by ⁇ -NMR.
• N-benzylidene-ferf-butylamine 255.4 mg, 1.584 mmol, 100 eq.
• N-benzylidene-ieri-butylamine and I Pr 2 -BBN were transferred to the vial containing [iBu3PH][B(C6Fs)4] using 0.6 mL toluene.
• the vial was equipped with a stir bar and placed in a Parr pressure reactor. The reactor was sealed, removed from the glovebox and attached to a thoroughly purged hydrogen gas line. The reactor was purged ten times at 50 atm hydrogen and ten times at 102 atm hydrogen.
• N-Benzyl-ferf-butylamine Froyen, P.; Juvvik, P. Tetrahedron Lett. 1995, 36, 9555-9558;
• N-Benzyl-(diphenylmethyl)amine Likhar, P. R.; Arundhathi, R.; Kantam, M. L.; Prathima,
• N-benzyl-phenylsulfonamine Not detected
• N-ferf-butyl-(3-methoxy)-benzyl amine 3 ⁇ 4 NMR (400 MHz, CD 2 C1 2 , 298 K): ⁇ 7.20 (t, 1H), 6.93-6.88 (m, 2H), 6.77-6.72 (m, 1H), 3.79 (s, 3H), 3.69 (s, 2H), 1.14 (s, 9H), No observable N-H. NMR (101 MHz, CD 2 C1 2 , 298 K): 160.2, 144.3, 129.7, 120.9, 114.2, 112.4,
• N-cyclopentylpiperidine 3 ⁇ 4 NMR (400 MHz, CD 2 C1 2 , 298 K): ⁇ 2.55-2.30 (m, 5H), 1.90- 1.79 (m, 2H), 1.75-1.30 (m, 12H).
• N-benzylidene-ieri-butylamine (68.2 mg, 0.423 mmol, 10 eq.) were weighed into vials. The contents of the vials were transferred to a J-Young NMR tube with 0.6 mL C 6 D 5 Br. The tube was sealed and subjected to three freeze-pump-thaw cycles. The sample was then frozen and the tube was backfilled with hydrogen gas, sealed and carefully thawed. Conversion of N-benzylidene-ferf-butylamine to N-benzyl-ferf-butylamine was observed by ⁇ -NMR.
• Example 4 Hvdrogenation reactions with borenium catalyst generated in situ with trityl tetrakis(pentafluorophenyl)borate
• Example 5 Hydrogenation reactions with borenium catalyst generated in situ with Bis(trifluoromethanesulfonyl)imide
• This Example demonstrates that the borenium complex was required for an active catalyst. Specifically, if a borenium complex is not generated, no catalysis occurred. The zwitterionic borohydride species was therefore the "unactivated" or inactive species in the catalytic cycle.
• Example 7 Hvdrogenation Catalysis in the presence of an Additional Base
• Procedure 1 (Entries 2, 8, 10): In an inert atmosphere glovebox,
• the reactor was sealed, removed from the glovebox and attached to a thoroughly purged hydrogen gas line.
• the reactor was purged ten times at 50 atm with hydrogen gas and ten times at 102 atm with hydrogen gas.
• the reactor was sealed under 102 atm hydrogen gas and placed on a stir plate for 2 or 4 hours at room temperature.
• the reactor was slowly vented and an NMR sample was taken in toluene-c g or CDCI 3 . Conversion of unsaturated substrate to amine product was determined by 3 ⁇ 4 NMR spectroscopy.
• Entry 9 was isolated by removal of solvent in vacuo followed by column chromatography using 99: 1 hexanes : EtOAc using silica gel pre-treated with diethylamine.
• Procedure 2 (Entries 1, 4-7, 9, 11): In an inert atmosphere glovebox,
• the reactor was sealed under 102 atm hydrogen gas and placed on a stir plate for 2 or 4 hours at room temperature. The reactor was slowly vented and an NMR sample was taken in CDCI 3 . Conversion of unsaturated substrate to amine product was determined by 3 ⁇ 4 NMR spectroscopy.
• Entries 2, 5, 6, 7, and 12 were isolated by removal of solvent in vacuo followed by column chromatography using 9: 1 hexanes : EtOAc using silica gel pre-treated with diethylamine.
• Procedure 3 (Entry 4): Procedure 1 was followed with the modification that toluene was used in place of C 6 H5CI.
• N-ieri-butyl-(3-methoxybenzyl)amine (colourless oil Yield: 0.309 g, 88%)
• N-cyclohexylpiperidine Spies, P.; Schwendemann, S.; Lange, S.; Kehr, G.; Frohlich, R.; Erker, G. Angew. Chem. Int. Ed. 2008, 47, 7543-7546.
• N-cyclopentylpiperidine (colourless oil Yield: 0.262 g, 94%) 3 ⁇ 4 NMR (CDCI 3 , 400 MHz): ⁇ 2.30 (m, 5H, CH 2 N and CH); 1.70, 1.53, 1.46, 1.38, and 1.29 (m, 14 ⁇ , CH 2 CH 2 CH 2 N and CHCH 2 CH 2 ).
• N-(1-Phenylethyl)aniline T. Kawakami, T. Sugimoto, I. Shibata, A. Baba, H. Matsuda and N. Sonoda, J. Org. Chem., 1995, 60, 2677-2682.
• (+)-diispinocampheylborane (378.4 mg,
• (+)-diispinocampheylborane 396.3 mg
• Example 12 Asymmetric induction in borenium-catalyzed hydrogenation reactions

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