JPH0454679B2 - - Google Patents

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Publication number
JPH0454679B2
JPH0454679B2 JP58016346A JP1634683A JPH0454679B2 JP H0454679 B2 JPH0454679 B2 JP H0454679B2 JP 58016346 A JP58016346 A JP 58016346A JP 1634683 A JP1634683 A JP 1634683A JP H0454679 B2 JPH0454679 B2 JP H0454679B2
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JP
Japan
Prior art keywords
formula
diphenylphosphino
methyl
pyrrolidine
tolylphosphino
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.)
Expired - Lifetime
Application number
JP58016346A
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Japanese (ja)
Other versions
JPS58146593A (en
Inventor
Arubin Buroogaa Emiiru
Kurameri Ibo
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.)
F Hoffmann La Roche AG
Original Assignee
F Hoffmann La Roche AG
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Filing date
Publication date
Application filed by F Hoffmann La Roche AG filed Critical F Hoffmann La Roche AG
Publication of JPS58146593A publication Critical patent/JPS58146593A/en
Priority to AU32720/84A priority Critical patent/AU570880B2/en
Publication of JPH0454679B2 publication Critical patent/JPH0454679B2/ja
Granted legal-status Critical Current

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    • 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
    • B01J31/2414—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 comprising aliphatic or saturated rings
    • 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
    • B01J31/2495—Ligands comprising a phosphine-P atom and one or more further complexing phosphorus atoms covered by groups B01J31/1845 - B01J31/1885, e.g. phosphine/phosphinate or phospholyl/phosphonate ligands
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D207/12—Oxygen or sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/26—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D307/30—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D307/32—Oxygen atoms
    • C07D307/33—Oxygen atoms in position 2, the oxygen atom being in its keto or unsubstituted enol form
    • 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
    • C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
    • C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
    • C07F15/0073—Rhodium 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
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
    • C07F9/572—Five-membered rings
    • 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
    • B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
    • B01J2531/02—Compositional aspects of complexes used, e.g. polynuclearity
    • B01J2531/0238—Complexes comprising multidentate ligands, i.e. more than 2 ionic or coordinative bonds from the central metal to the ligand, the latter having at least two donor atoms, e.g. N, O, S, P
    • B01J2531/0258—Flexible ligands, e.g. mainly sp3-carbon framework as exemplified by the "tedicyp" ligand, i.e. cis-cis-cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclopentane
    • 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
    • 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)

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

Description

【発明の詳細な説明】[Detailed description of the invention]

本発明は一般式 〔式中、Ｒはアリールを表わし、そしてR1は式 The present invention is based on the general formula [In the formula, R represents aryl, and R 1 is the formula

【式】【formula】

【式】又は[Formula] or

【式】の基 を表わし、ここでR2はアリール、ジアリールア
ミノ、ジ（低級アルキル）アミノ、ヒドロキシ、
アリーロキシ又は低級アルコキシを表わす〕 の新規なキラルなホスフイン類に関する。 更に、本発明は式のホスフインの製造方法及
びその不斉水素化反応における使用に関する。 本発明の範囲において、「アリール」なる語は
随時パラ及び／又はメタ位に低級アルキル又は低
級アルコキシ基、好ましくはメチル又はメトキシ
基、或いはジ（低級アルキル）アミノ基、好まし
くはジメチルアミノ基を有していてもよいフエニ
ルを意味する。更に、同一の燐原子に結合した２
つのアリール基はｏ−位を介して直接に或いはメ
チレン、エチレン又はプロピレン基を介して相互
に統合していてもよい。「アリーロキシ」なる語
はアリール残基が上述の意味を有する基を示す。
「低級アルキル」なる語は、本発明の範囲におい
て、炭素原子数１〜７個の直鎖状及び分岐鎖状の
アルキル、例えばメチル、エチル、プロピル、イ
ソプロピル、ｎ−ブチル、イソブチル、tert−ブ
チルなどを意味する。「低級アルコキシ」なる語
はアルキル残基が上述の意味を有する基を示す。
更に結合「−」は対応する基が分子の平面の上に
位置し、一方「…」は対応する基が分子の平面の
下に位置することを意味する。 式の好適なホスフイン類は、Ｒがフエニル、
ｐ−トリル、ｍ−トリル又は３，５−キシリルを
表わし、基R1中のR2がフエニル、ｐ−トリル、
ｍ−トリル、フエノキシ又はジ（低級アルキル）
アミノを表わすものである。更に好適なホスフイ
ン類はR1が基represents a group of [formula], where R 2 is aryl, diarylamino, di(lower alkyl)amino, hydroxy,
aryloxy or lower alkoxy]. Furthermore, the present invention relates to a process for the preparation of phosphines of formula and their use in asymmetric hydrogenation reactions. Within the scope of the present invention, the term "aryl" optionally has a lower alkyl or lower alkoxy group, preferably a methyl or methoxy group, or a di(lower alkyl)amino group, preferably a dimethylamino group, in the para and/or meta position. means phenyl which may be Furthermore, 2 bonded to the same phosphorus atom
The two aryl groups may be joined to each other directly via the o-position or via methylene, ethylene or propylene groups. The term "aryloxy" refers to groups in which the aryl residue has the meaning given above.
Within the scope of the present invention, the term "lower alkyl" refers to straight-chain and branched alkyl having 1 to 7 carbon atoms, such as methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, tert-butyl. etc. The term "lower alkoxy" refers to groups in which the alkyl residue has the above meaning.
Further, a bond "-" means that the corresponding group is located above the plane of the molecule, while "..." means that the corresponding group is located below the plane of the molecule. Preferred phosphines of the formula include R is phenyl;
represents p-tolyl, m-tolyl or 3,5-xylyl, and R 2 in the group R 1 is phenyl, p-tolyl,
m-tolyl, phenoxy or di(lower alkyl)
It represents amino. Further preferred phosphines are those in which R 1 is a group

【式】を表わすものである。 、 次は好適な式の化合物の例である。 （2S，4S）−４−（ジフエニルホスフイノ）−２
−〔（ジフエニルホスフイノ）−メチル〕−１−（ジ
フエニルホスフイニル）−ピロリジン；（2S，4S）
−４−（ジ−ｐ−トリルホスフイノ）−２−〔（ジ−
ｐ−トリルホスフイノ）−メチル〕−１−（ジフエ
ニルホスフイニル）−ピロリジン； （2S，4S）−４−（ジ−ｍ−トリルホスフイノ）
−２−〔（ジ−ｍ−トリルホスフイノ）−メチル〕−
１−（ジフエニルホスフイニル）−ピロリジン； （2S，4S）−４−（ジ−３，５−キシリルホス
フイノ）−２−〔（ジ−３，５−キシリルホスフイ
ノ）−メチル〕−１−（ジフエニルホスフイニル）−
ピロリジン； （2S，4S）−４−（ジフエニルホスフイノ）−２
−〔（ジフエニルホスフイノ）−メチル〕−１−（ジ
−ｐ−トリルホスフイニル）−ピロリジン； （2S，4S）−４−（ジフエニルホスフイノ）−２
−〔（ジフエニルホスフイノ）−メチル〕−１−（ジ
−ｍ−トリルホスフイニル）−ピロリジン； ジフエニル〔（2S，4S）−４−（ジフエニルホス
フイノ）−２−〔（ジフエニルホスフイノ）メチル〕
−１−ピロリジニル〕−ホスホネート； ジフエニル〔（2S，4S）−４−（ジ−ｐ−トリル
ホスフイノ）−２−〔ジ−ｐ−トリルホスフイノメ
チル〕−１−ピロリジニル〕−ホスホネート； ジフエニル〔（2S，4S）−４−（ジ−ｍ−トリル
ホスフイノ）−２−〔（ジ−ｍ−トリルホスフイノ）
メチル〕−１−ピロリジニル〕−ホスホネート； 〔（2S，4S）−４−（ジフエニルホスフイノ）−
２−〔（ジフエニルホスフイノ）−メチル〕−１−ピ
ロリジニル〕−Ｎ，Ｎ，N′，N′−テトラメチルホ
スホン酸ジアミド； 〔（2S，4S）−４−（ジ−ｐ−トリルホスフイ
ノ）−２−〔（ジ−ｐ−トリルホスフイノ）−メチ
ル〕−１−ピロリジニル〕−Ｎ，Ｎ，N′，N′−テ
トラメチルホスホン酸ジアミド； 〔（2S，4S）−４−（ジ−ｍ−トリルホスフイ
ノ）−２−〔（ジ−ｍ−トリルホスフイノ）−メチ
ル〕−１−ピロリジニル〕−Ｎ，Ｎ，N′，N′−テ
トラメチルホスホン酸ジアミド； 〔（2S，4S）−４−（ジフエニルホスフイノ）−
２−〔（ジフエニルホスフイノ）−メチル〕−１−ピ
ロリジニル〕−ジフエニルホスフイン； 〔（2S，4S）−２−（5H−ジベンゾホスホル−
５−イルメチル）−４−（5H−ジベンゾホスホル
−５−イル）−１−ピロリジニル〕−ジフエニルホ
スフインオキサイド； ５−〔（2S，4S）−２−〔（ジフエニルホスフイ
ノ）メチル〕−４−（ジフエニルホスフイル）−１
−ピロリジニル〕−5H−ジベンゾホスホル−５−
オキサイド； 〔（2S，4S）−２−〔５（10H）−アクリドホスフ
イニルメチル〕−４−（５（10H）−アクリドホスフ
イニル〕−１−ピロリジニル〕ジフエニルホスフ
インオキサイド； ５−〔（2S，4S）−２−〔（ジフエニルホスフイ
ノ）メチル〕−４−（ジフエニルホスフイノ）−１
−ピロリジニル〕−５，10−ジヒドロアクリドホ
スフイン５−オキサイド； ５−〔（2S，4S）−２−（5H−ジベンゾホスホ
ル）−５−イルメチル）−４−（5H−ジベンゾホス
ホル−５−イル）−１−ピロリジニル〕−5H−ジ
ベンゾホスホル−５−オキサイド； 〔（2S，4S）−２−〔（ジフエニルホスフイノ）
メチル〕−４−（ジフエニルホスフイノ）−１−ピ
ロリジニル〕ジフエニルホスフインスルフイド。 本発明による式の化合物は、 (a) 一般式 〔式中、Ｒは前記の意味を有する〕 の化合物を、一般式It represents [Formula]. , The following are examples of compounds of suitable formulas. (2S,4S)-4-(diphenylphosphino)-2
-[(diphenylphosphino)-methyl]-1-(diphenylphosphinyl)-pyrrolidine; (2S, 4S)
-4-(di-p-tolylphosphino)-2-[(di-
p-Tolylphosphino)-methyl]-1-(diphenylphosphinyl)-pyrrolidine; (2S,4S)-4-(di-m-tolylphosphino)
-2-[(di-m-tolylphosphino)-methyl]-
1-(diphenylphosphinyl)-pyrrolidine; (2S,4S)-4-(di-3,5-xylylphosphino)-2-[(di-3,5-xylylphosphino)-methyl ]-1-(diphenylphosphinyl)-
Pyrrolidine; (2S,4S)-4-(diphenylphosphino)-2
-[(diphenylphosphino)-methyl]-1-(di-p-tolylphosphinyl)-pyrrolidine; (2S,4S)-4-(diphenylphosphino)-2
-[(diphenylphosphino)-methyl]-1-(di-m-tolylphosphinyl)-pyrrolidine; diphenyl[(2S,4S)-4-(diphenylphosphino)-2-[(diphenyl phosphino)methyl]
-1-pyrrolidinyl]-phosphonate; diphenyl[(2S,4S)-4-(di-p-tolylphosphino)-2-[di-p-tolylphosphinomethyl]-1-pyrrolidinyl]-phosphonate; diphenyl[(2S ,4S)-4-(di-m-tolylphosphino)-2-[(di-m-tolylphosphino)
Methyl]-1-pyrrolidinyl]-phosphonate; [(2S,4S)-4-(diphenylphosphino)-
2-[(diphenylphosphino)-methyl]-1-pyrrolidinyl]-N,N,N',N'-tetramethylphosphonic acid diamide; [(2S,4S)-4-(di-p-tolylphosphino)- 2-[(di-p-tolylphosphino)-methyl]-1-pyrrolidinyl]-N,N,N',N'-tetramethylphosphonic acid diamide; [(2S,4S)-4-(di-m-tolylphosphino) -2-[(di-m-tolylphosphino)-methyl]-1-pyrrolidinyl]-N,N,N',N'-tetramethylphosphonic acid diamide; [(2S,4S)-4-(diphenylphosphino) −
2-[(diphenylphosphino)-methyl]-1-pyrrolidinyl]-diphenylphosphine; [(2S,4S)-2-(5H-dibenzophosphor-
5-ylmethyl)-4-(5H-dibenzophosphor-5-yl)-1-pyrrolidinyl]-diphenylphosphine oxide; 5-[(2S,4S)-2-[(diphenylphosphino)methyl] -4-(diphenylphosphyl)-1
-pyrrolidinyl]-5H-dibenzophosphor-5-
Oxide; [(2S,4S)-2-[5(10H)-acridophosphinylmethyl]-4-(5(10H)-acridophosphinyl]-1-pyrrolidinyl] diphenylphosphine oxide; 5-[(2S,4S)-2-[(diphenylphosphino)methyl]-4-(diphenylphosphino)-1
-pyrrolidinyl]-5,10-dihydroacrydophosphine 5-oxide; 5-[(2S,4S)-2-(5H-dibenzophosphor)-5-ylmethyl)-4-(5H-dibenzophosphor- 5-yl)-1-pyrrolidinyl]-5H-dibenzophosphor-5-oxide; [(2S,4S)-2-[(diphenylphosphino)
Methyl]-4-(diphenylphosphino)-1-pyrrolidinyl]diphenylphosphine sulfide. Compounds according to the invention of the formula (a) have the general formula [In the formula, R has the above meaning] A compound of the general formula

【式】【formula】

【式】又は 〔式中、R2は前記の意味を有し、R3は塩素又
は弗素を表わす〕 の化合物と反応させるか、或いは (b) 一般式 〔式中、R1は前記の意味を有し、R4はアリー
ル又は低級アルキルを表わす〕 の化合物を、一般式 〔式中、Ｒは前記の意味を有し、R5はリチウ
ム、ナトリウム、カリウム又はマグネシウムハ
ライドを表わす〕 の化合物と反応させる、 ことによつて製造できる。 式の化合物の、式ａ〜ｃの化合物との反
応はそれ自体公知の方法で行なうことができる。
その際該反応は酸素を完全に排除して、即ち不活
性な気体雰囲気下（例えば、窒素、アルゴン下な
ど）で行なわなければならない。便宜的には、反
応は不活性な有機容媒例えば芳香族炭化水素（例
えばベンゼン、トルエンなど）又はエーテル（例
えばジエチルエーテル、テトラヒドロフラン、ジ
オキサンなど）中において、また必要ならば第三
級アミンを添加して行なうことができる。反応を
行なう際の温度及び圧力は厳密でなく、従つて反
応は凡そ室温及び大気圧で容易に行なうことがで
きる。 出発物質として用いる式及びａ〜ｃの化
合物は公知の化合物であるか、或いは公知の化合
物の製造と同様の方法で容易に製造できる公知の
化合物の同族体である。 式の化合物の、式の化合物との反応はそれ
自体公知の方法で行なうことができる。その際該
反応は酸素を完全に排除して、即ち不活性な気体
雰囲気下（例えば窒素、アルゴン下など）で行な
わなければならない。便宜的には、反応は所望な
らば炭化水素（例えばヘキサン、ベンゼン、トル
エンなど）の存在下にエーテル（例えばテトラヒ
ドロフラン、ジオキサン、ジエチルエーテルな
ど）の如き不活性な有機容媒中で行なわれる。反
応は便宜上約−15℃−凡そ室温、好ましくは約−
10℃〜約０℃の温度で行なわれる。反応を行なう
圧力は厳密でなく、従つて、反応は大気圧で容易
に行なうことができる。 出発物質として用いる式の化合物は新規な化
合物であり、本発明の目的でもある。しかしなが
らそれらはそれ自体公知の方法により、例えば下
記の反応式及びに従つて製造できる。これら
の反応式においてTsはトシル基を、またＡは基
[Formula] or [wherein R 2 has the above meaning and R 3 represents chlorine or fluorine] or (b) a compound of the general formula [In the formula, R 1 has the above-mentioned meaning, and R 4 represents aryl or lower alkyl] A compound of the general formula [In the formula, R has the above-mentioned meaning and R 5 represents lithium, sodium, potassium or magnesium halide]. The reaction of a compound of formula with a compound of formula a to c can be carried out in a manner known per se.
The reaction must then be carried out with complete exclusion of oxygen, ie under an inert gas atmosphere (for example under nitrogen, argon, etc.). Conveniently, the reaction is carried out in an inert organic medium such as an aromatic hydrocarbon (e.g. benzene, toluene, etc.) or an ether (e.g. diethyl ether, tetrahydrofuran, dioxane, etc.), and if necessary with the addition of a tertiary amine. You can do it by doing this. The temperature and pressure at which the reaction is carried out are not critical; therefore, the reaction can be easily carried out at about room temperature and atmospheric pressure. The compounds of formulas and a to c used as starting materials are known compounds, or homologs of known compounds that can be easily produced by methods similar to those for producing known compounds. The reaction of a compound of the formula with a compound of the formula can be carried out in a manner known per se. The reaction must then be carried out with complete exclusion of oxygen, ie under an inert gas atmosphere (for example under nitrogen, argon, etc.). Conveniently, the reaction is carried out in an inert organic medium such as an ether (eg, tetrahydrofuran, dioxane, diethyl ether, etc.) in the presence of a hydrocarbon (eg, hexane, benzene, toluene, etc.) if desired. The reaction is conveniently carried out at about -15°C - about room temperature, preferably at about -
It is carried out at a temperature of 10°C to about 0°C. The pressure at which the reaction is carried out is not critical; therefore, the reaction can easily be carried out at atmospheric pressure. The compounds of formula used as starting materials are novel compounds and are also the object of the present invention. However, they can be prepared by methods known per se, for example according to the reaction scheme and according to the following. In these reaction formulas, Ts is a tosyl group, and A is a group

【式】【formula】

【式】又は[Formula] or

【式】を意 味する。 出発物質として使用される式の化合物は公知
であるか或いは公知の化合物の製造と同様の方法
で容易に製造できる公知の化合物の同族体であ
る。 本発明によつて提供される式のホスフインは
ロジウムと錯体を形成し、これは不斉水素化反応
（asymmetric hydrogenation）の触媒として使
用できる。これらの触媒、即ちロジウムと式の
ホスフインとの錯体は新規であり、本発明の目的
でもある。これらの触媒は簡単な且つそれ自体公
知の方法に従い、例えば式の化合物を適当な不
活性な有機溶媒中でロジウムを与える化合物と反
応させることによつて製造できる。適当なロジウ
ムを与える化合物は、例えば三塩化ロジウム水和
物、三臭化ロジウム水和物、硫酸ロジウム或いは
有機ロジウム錯体、即ちエチレン、プロピレンな
どとの並びにビスオレフイン例えば１，５−シク
ロオクタジエン、１，５−ヘキサジエン、ビシク
ロ−２，２，１−ヘプタ−２，５−ジエンとの又
はロジウムと容易に溶解する錯体を形成する他の
ジエンとの錯体である。好適なロジウムを与える
化合物は、ｕ，u′−ジクロル−ビス−〔ビス−（オ
レフイン）−ロジウム（）〕、例えばｕ，u′−ジ
クロル−ビス−（１，５−シクロオクタジエン−
ロジウム（）〕又はｕ，u′−ジクロル−ビス−
〔（ノルボルナジエン）−ロジウム（）〕である。 前述したように、本発明によつて提供されるホ
スフインは、不斉水素化反応の触媒として使用さ
れるロジウム錯体の配位子として役立つ。それら
は特にα−ケト−カルボン酸エステルの対応する
α−ヒドロキシカルボン酸エステルへの、またジ
ヒドロ−４，４−ジメチル−２，３−フランジオ
ン（ケトパントラクトン）の対応するＲ−（α−
ヒドロキシ）−β，β−ジメチル−γ−ブチロラ
クトン）〔Ｒ−（−）−パントラクトン〕への不斉
水素化反応との関連で興味があるものである。 上述の不斉水素化反応を行なう場合、式のホ
スフインはそのままで、水素化すべき不斉化合物
を溶液の形でロジウムを与える化合物と接触させ
ることができる。一方式のホスフインは最初に
適当な溶媒中においてロジウムを与える化合物と
反応させて、対応する触媒錯体とし、次いでこれ
を水素化すべき不斉化合物の溶液に添加してもよ
い。 式のホスフインの、ロジウムを与える化合物
との反応ばかりでなく、上述の不斉水素化反応
は、反応条件下に不活性である適当な有機溶媒中
で行なうことができる。特に適当な有機溶媒は、
低級アルカノール例えばメタノール又はエタノー
ル、芳香族炭化水素例えばベンゼン又はトルエ
ン、環式エーテル例えばテトラヒドロフラン又は
ジオキサン、エステル例えば酢酸エチル又はこれ
らの混合物などである。ロジウムと式の配位子
との比は、便宜上式の配位子１モル当りロジウ
ム約0.05〜約５モル、好ましくは約0.5〜約２モ
ルである。式の配位子を有する錯体中のロジウ
ムと水素化すべき化合物との比は、便宜上約
0.00001〜約５重量％、好ましくは約0.001〜約0.5
重量％である。 式の配位子を有するロジウム錯体を用いる不
斉水素化反応は、便宜上約20〜約100℃、好まし
くは約40〜約90℃の温度で行なわれる。これらの
水素化は便宜上加圧下に、特に約１〜100バール、
好ましくは２〜50バールの圧力下に行なうことが
できる。 次の実施例は本発明をさらに説明するものであ
る。 実施例 １ 撹拌機、温度計、滴下斗及びアルゴン通気管
を備えた500mlのスルホン化フラスス中に、 （2S，4S）−４−ジフエニルホスフイノ−２−
ジフエニルホスフイノメチルピロリジン1.01ｇ
（2.33ミリモル）、Ｎ−メチルモルフオリン1.46ml
（13.38ミリモル）及びトルエン30mlを入れた。次
いで撹拌しながら、トルエン10ml中ジフエニルホ
スフイニルクロライド0.79ｇ（3.35ミリモル）の
溶液を室温で10分間に亘つて滴々に添加した。反
応は７時間後に終了した。次いで混合物をガラス
フイルターを通して過し、液を回転蒸発機に
より60℃／17ミリバールで蒸発させた。この残渣
（22ｇ）をジエチルエーテル30ml中に入れ、3N塩
酸30mlで処理した。次いでエーテル相を分離し、
水性相をジエチルエーテル30mlずつで２回抽出し
た。抽出物を硫酸ナトリウムで乾燥し、別し、
回転蒸発機により60℃／17ミリバールで濃縮し
た。精製のために、残渣（1.57ｇ）を
Kieselgel60（粒径0.063〜0.20mm）の140ｇでのク
ロマトグラフイーにより処理した。流出液として
はベンゼン／酢酸エチル／エタノール（８：２：
１）の混合物を用いた。溶媒を蒸発させ、１ミリ
バールで16時間乾燥させた後、純粋な（2S，4S）
−４−（ジフエニルホスフイノ）−２−〔（ジフエニ
ルホスフイノ）メチル〕−１−（ジフエニルホスフ
イニル）−ピロリジン1.12ｇ（76.8％）を得た。
融点：65℃から失透し、130℃で透明に溶融。
〔α〕20 D＝−21.4°（ｃ＝0.5，ベンゼン中）。 同様の方法で次の化合物も製造した： （2S，4S）−４−（ジ−ｐ−トリルホスフイノ）
−２−〔（ジ−ｐ−トリルホスフイノ）−メチル〕−
１−（ジフエニルホスフイニル）−ピロリジン、
〔α〕20 D＝−33.2℃（ｃ＝0.5，ベンゼン中）； （2S，4S）−４−（ジ−ｍ−トリルホスフイノ）
−２−〔（ジ−ｍ−トリルホスフイノ）−メチル〕−
１−（ジフエニルホスフイニル）−ピロリジン、
〔α〕20 D＝−25.8°（ｃ＝0.6、ベンゼン中）； （2S，4S）−４−（ジフエニルホスフイノ）−２
−〔（ジフエニルホスフイノ）−メチル〕−１−（ジ
−ｐ−トリルホスフイニル）−ピロリジン、〔α〕
20 D＝−13.8°（ｃ＝0.5，ベンゼン中）； （2S，4S）−４−（ジフエニルホスフイノ）−２
−〔（ジフエニルホスフイノ）−メチル〕−１−（ジ
−ｍ−トリルホスフイニル）−ピロリジン、〔α〕
20 D＝−21.3°（ｃ＝0.6，ベンゼン中）； 〔（2S，4S）−４−（ジフエニルホスフイノ）−
２−〔（ジフエニルホスフイノ）−メチル〕−１−ピ
ロリジニル〕−ジフエニルホスフイン、〔α〕20 D＝
−64.0°（ｃ＝0.6，ベンゼン中）； ジフエニル〔（2S，4S）−４−（ジフエニルホス
フイノ）−２−〔（ジフエニルホスフイノ）メチル〕
−１−ピロリジニル〕−ホスホネート、〔α〕20 D＝
−63.3°（ｃ＝0.6、ベンゼン中）； 〔（2S，4S）−４−（ジフエニルホスフイノ）−
２−〔（ジフエニルホスフイノ）−メチル−１−ピ
ロリジニル〕−Ｎ，Ｎ，N′，N′−テトラメチルホ
スホン酸ジアミド、〔α〕20 D＝−60.7°（ｃ＝0.6，ベ
ンゼン中）。 参考例 １ 撹拌機、温度計、２つの滴下斗、アルゴン送
入管及び冷却浴を備えた200mlのスルホン化フラ
スコ中において、ジフエニルホスフイン7.5ｇ
（38ミリモル）をテトラヒドロフラン25mlに溶解
し、この溶液を０℃に冷却した。次いで1.5Mn−
ブチルリチウム溶液28ml（ヘキサン；42ミリモ
ル）を撹拌しながら滴々に添加した。最初無色の
溶液が強い橙色になつた。次いでテトラヒドロフ
ラン50ml中（2S，4R）−１−（ｐ−トリルスルホ
ニル）−４−〔（ｐ−トリルスルホニル）オキシ〕−
２−ピロリジニルメチルｐ−トルエンスルホネー
ト9.7ｇ（16.7ミリモル）の溶液を−５℃で30分
間に亘つて滴々に添加した。溶液は淡黄色になつ
た。０℃で５時間反応させた後、数滴の水を添加
し、次いで溶液を回転蒸発機により60℃／17ミリ
バールで蒸発させた。この残渣をベンゼン100ml
に溶解し、水100mlずつで３回洗浄し、水性相を
ベンゼン100mlで逆洗浄した。併せたベンゼン抽
出物を回転蒸発機により60℃／17ミリバールで蒸
発させた。得られた生成物（黄色を帯びた油、
15.2ｇ）は放置すると部分的に結晶化するが、こ
れを精製するためにベンゼンに溶解し、溶液を
Kieselgel60（粒径0.63〜0.20mm）240ｇを通して
過した。溶媒を蒸発させ、40℃／17ミリバールで
16時間乾燥させた後、（2S，4S）−４−（ジフエニ
ルホスフイノ）−２−〔（ジフエニルホスフイノ）−
メチル〕−１−（ｐ−トリルスルホニル）−ピロリ
ジン6.5ｇ（63.9％）を無色の泡状物として得た。
〔α〕20 D＝−125.8°（ｃ＝１，ベンゼン中）。 出発物質として用いた（2S，4R）−１−（ｐ−
トリルスルホニル）−４−〔（ｐ−トリルスルホニ
ル）−オキシ〕−２−ピロリジニルメチルｐ−トル
エンスルホネートは次のようにして製造した： 撹拌機、滴下斗、温度計及び凝縮器を備えた
750mlのスルホン化フラスコ中において、（2S，
4R）−４−ヒドロキシプロリン35.6ｇ（0.27モル）
を2N水酸化ナトリウム300ml（0.60モル）に溶解
した。次いで10分間に亘り、ジエチルエーテル
180ml中ｐ−トルエンスルホニルクロライド63ｇ
（0.33モル）の溶液を滴々に添加した。温度は水
浴によつて16〜20℃に保つた。室温で16時間激し
く撹拌した後、反応は終了した。水性相（PH約
７）を分離し、ジエチルエーテル250mlで逆洗浄
した。次いでエーテル相を脱イオン水100mlずつ
で２回洗浄した。併せた水性相を、５℃に氷冷し
ながら濃（27％）塩酸25mlでPH２の酸性にし、５
℃で1.5時間撹拌した。分離した結晶を吸引別
し、脱イオン水１で洗浄し、真空乾燥中にお
いて40℃／17ミリバール下に16時間乾燥した。得
られた生成物（融点142〜145℃の白色の結晶76.2
ｇ）を、精製のために熱エタノール／水（１：
4ν／ν）200mlに溶解し、次いで撹拌且つ５℃ま
でゆつくり冷却することによつて再結晶した。乾
燥後に得られた白色の結晶（73.4ｇ）を前述した
ようにエタノール／水（１：4ν／ν）150mlから
再び再結晶し、真空乾燥炉中において50℃／17ミ
リバール下に乾燥した。この結果融点146〜147℃
の（2S，4R）−４−ヒドロキシ−１−（ｐ−トリ
ルスルホニル）−２−ピロリジンカルボン酸69.4
ｇ（89.6％）が得られた。〔α〕20 D＝−87.6°（ｃ＝
１，エタノール中）。 撹拌機、温度計、滴下斗、外端がアセトン洗
浄フラスコに連結された凝縮器及びアルゴン送入
管を備えた1.5のスルホン下フラスコ中におい
て、（2S，4S）−４−ヒドロキシ−１−（ｐ−トリ
ルスルホニル）−２−ピロリジンカルボン酸57ｇ
（0.20モル）をテトラヒドロフラン300mlに溶解し
た。次いで1Mジボラン溶液（テトラヒドロフラ
ン；0.50モル）500mlを、５〜10℃で撹拌しなが
ら1.2時間に亘つて滴々に添加した。反応混合物
を室温で夜通し撹拌した。次いで脱イオン水50ml
を０〜５℃でゆつくりと滴々に添加することによ
つて混合物を分解し（発熱反応）、次いで回転蒸
発機により50℃／17ミリバールで蒸発させた。残
渣を脱イオン水150ml中に入れ、酢酸エチル300ml
ずつで６回抽出した。この抽出物を飽和塩化ナト
リウム溶液150mlずつで３回洗浄し、硫酸ナトリ
ウムで乾燥し、回転蒸発機により50℃／17ミリバ
ールで蒸発させた。精製のために、得られた残渣
を酢酸エチル100mlから再結晶した。得られた結
晶を吸引別し、乾燥炉中において40℃／17ミリ
バール下に乾燥した。この結果融点133−134℃の
（2S，4S）−４−ヒドロキシ−１−（ｐ−トリルス
ルホニル）−２−ピロリジン−メタノール34ｇ
（62.7％）を得た。〔α〕20 D＝−47.4°（ｃ＝１，エ
タ
ノール中）。 撹拌機、温度計、滴下斗、アルゴン送入管及
び氷浴を備えた200mlのスルホン化フラスコ中に
おいて、（2S，4R）−４−ヒドロキシ−１−（ｐ−
トリルスルホニル）−２−ピロリジンメタノール
6.8ｇ（0.025モル）をピリジン20mlに溶解した。
次いでピリジン20ml中ｐ−トルエンスルホニルク
ロライド12ｇ（0.063モル）の溶液を、０〜３℃
で撹拌しながら45分間に亘つて滴々に添加した。
約１時間後にピリジン塩酸塩が沈澱しはじめた。
この混合物を室温で夜通し撹拌し、次いで脱イオ
ン水100mlを０〜10℃で滴々に注意しながら添加
した（強い発熱反応）。この結果白色の結晶のス
ラリーが分離した。氷浴中で３時間撹拌した後、
結晶を吸引別し、冷脱イオン水40mlずつで４回
洗浄し、乾燥炉中において60℃／17ミリバール下
に２時間乾燥した。精製のために、得られた生成
物を酢酸エチル50mlから再結晶させた。分離した
結晶を吸引別し、乾燥炉中において40℃／17ミ
リバール下に乾燥した。この結果融点131〜134℃
の（2S，4R）−１−（ｐ−トリルスルホニル）−４
−〔（ｐ−トリルスルホニル）オキシ〕−２−ピロ
リジニルメチル−ｐ−トルエンスルホネート9.8
ｇ（67.6％）を得た；〔α〕20 D＝−77.2°（ｃ＝１，
ベンゼン中）。 参考例 ２ １の撹拌式スチール製オートクレーブをジヒ
ドロ−４，４−ジメチル−２，３−フランジオン
50ｇ（0.39モル）及びトルエン300mlを入れた。
系から空気を除くために、オートクレーブを高真
空ポンプで５回脱気し、その度に水素10バールを
導入した。40℃に加熱したオートクレーブを再び
脱気した。次いでクロルノルボルナジエン−ロジ
ウム（）二量体0.029ｇ（0.063ミリモル）及び
（2S，4S）−４−（ジフエニルホスフイノ）−２−
〔（ジフエニルホスフイノ）メチル〕−１−（ジフエ
ニルホスフイニル）ピロリジン0.082ｇ（0.126ミ
リモル）からトルエン50ml中で調製した黄色の触
媒溶液を導入し、次いで、オートクレーブを水素
40バールで加圧した。次いで激しく撹拌し且つ水
素圧を40バールに一定に保ちながら40℃で水素化
を行ない、20時間後に反応を終了した。次いでオ
ートクレーブから淡黄色の溶液をトルエンで洗い
出し、溶媒を回転蒸発機により60℃／17ミリバー
ルで留去した。この残渣（54.7ｇ）を130〜150℃
（浴温）及び0.05ミリバールで蒸溜した。この結
果光学純度84.3％の粗Ｒ−（α−ヒドロキシ−β，
β−ジメチル−γ−ブチロラクトン）50.2ｇ
（98.9％）を得た。〔α〕20 D＝−43.1°（ｃ＝１，水
中）。 参考例 ３ １の撹拌式スチール製オートクレーブをジヒ
ドロ−４，４−ジメチル−２，３−フランジオン
50ｇ（0.39モル）及び酢酸エチル300mlを入れた。
系から空気を除くために、オートクレーブを高真
空ポンプで５回脱気し、その度に水素10バールを
導入した。40℃に加熱したオートクレーブを再び
脱気した。次いでクロルノルボルナジエン−ロジ
ウム（）二量体0.029ｇ（0.063ミリモル）及び
（2S，4S）−４−（ジフエニルホスフイノ）−２−
〔（ジフエニルホスフイノ）メチル〕−１−（ｐ−ト
リルスルホニル）ピロリジン0.076ｇ（0.126ミリ
モル）から酢酸エチル50ml中で調製した黄色の触
媒溶液を導入し、次いでオートクレーブを水素40
バールで加圧した。次いで激しく撹拌し且つ水素
圧を40バールに一定に保ちながら40℃で水素化を
行ない、８時間後に反応を終了した。次いでオー
トクレーブから淡黄色の溶液を酢酸エチルで洗い
出し、溶媒を回転蒸発機により60℃／17ミリバー
ルで留出した。この残渣（59.9ｇ）を130〜150℃
（浴温）及び0.05ミリバールで蒸留した。この結
果光学純度81.8％の粗Ｒ−（α−ヒドロキシ−β，
β−ジメチル−γ−ブチロラクトン）50.6ｇ
（99.8％）を得た。 〔20〕20 D＝−41.7°（ｃ＝１、水中）。[Formula] means. The compounds of the formula used as starting materials are known or are homologs of known compounds that can be easily prepared by methods analogous to the preparation of known compounds. Phosphine of the formula provided by the present invention forms a complex with rhodium, which can be used as a catalyst for asymmetric hydrogenation reactions. These catalysts, ie complexes of rhodium with a phosphine of the formula, are new and are also the object of the present invention. These catalysts can be prepared according to simple and per se known methods, for example by reacting a compound of the formula with a rhodium-providing compound in a suitable inert organic solvent. Suitable rhodium-giving compounds are, for example, rhodium trichloride hydrate, rhodium tribromide hydrate, rhodium sulfate or organorhodium complexes, i.e. with ethylene, propylene, etc., as well as bisolefins such as 1,5-cyclooctadiene, Complexes with 1,5-hexadiene, bicyclo-2,2,1-hepta-2,5-diene or with other dienes that form readily soluble complexes with rhodium. Suitable rhodium-giving compounds are u,u'-dichloro-bis-[bis-(olefin)-rhodium()], such as u,u'-dichloro-bis-(1,5-cyclooctadiene-
rhodium ()] or u,u'-dichloro-bis-
[(norbornadiene)-rhodium ()]. As mentioned above, the phosphine provided by the present invention serves as a ligand for a rhodium complex used as a catalyst for an asymmetric hydrogenation reaction. They are particularly applicable to the conversion of α-keto-carboxylic acid esters to the corresponding α-hydroxycarboxylic esters and of dihydro-4,4-dimethyl-2,3-furandione (ketopantolactone) to the corresponding R-(α-
It is of interest in connection with the asymmetric hydrogenation reaction to (hydroxy)-β,β-dimethyl-γ-butyrolactone)[R-(−)-pantolactone]. When carrying out the asymmetric hydrogenation reaction described above, the asymmetric compound to be hydrogenated can be brought into contact with the rhodium-providing compound in the form of a solution, with the phosphine of the formula intact. One-type phosphine may first be reacted with a rhodium-giving compound in a suitable solvent to give the corresponding catalyst complex, which is then added to the solution of the asymmetric compound to be hydrogenated. The asymmetric hydrogenation reaction described above, as well as the reaction of the phosphine of formula with a compound to give rhodium, can be carried out in a suitable organic solvent that is inert under the reaction conditions. Particularly suitable organic solvents are:
Lower alkanols such as methanol or ethanol, aromatic hydrocarbons such as benzene or toluene, cyclic ethers such as tetrahydrofuran or dioxane, esters such as ethyl acetate or mixtures thereof. The ratio of rhodium to ligand of formula is conveniently from about 0.05 to about 5 moles of rhodium, preferably from about 0.5 to about 2 moles of rhodium per mole of ligand of formula. The ratio of rhodium in the complex with a ligand of formula to the compound to be hydrogenated is conveniently approximately
0.00001 to about 5% by weight, preferably about 0.001 to about 0.5
Weight%. Asymmetric hydrogenation reactions using rhodium complexes having ligands of the formula are conveniently carried out at temperatures of from about 20 to about 100°C, preferably from about 40 to about 90°C. These hydrogenations are conveniently carried out under pressure, in particular about 1 to 100 bar,
Preferably it can be carried out under a pressure of 2 to 50 bar. The following examples further illustrate the invention. Example 1 In a 500 ml sulfonation flask equipped with a stirrer, thermometer, dropping funnel and argon vent, (2S,4S)-4-diphenylphosphino-2-
Diphenylphosphinomethylpyrrolidine 1.01g
(2.33 mmol), N-methylmorpholine 1.46 ml
(13.38 mmol) and 30 ml of toluene were added. Then, with stirring, a solution of 0.79 g (3.35 mmol) of diphenylphosphinyl chloride in 10 ml of toluene was added dropwise at room temperature over a period of 10 minutes. The reaction was completed after 7 hours. The mixture was then filtered through a glass filter and the liquid was evaporated in a rotary evaporator at 60° C./17 mbar. This residue (22 g) was taken up in 30 ml of diethyl ether and treated with 30 ml of 3N hydrochloric acid. Then the ether phase is separated,
The aqueous phase was extracted twice with 30 ml portions of diethyl ether. The extract was dried with sodium sulfate, separated,
It was concentrated in a rotary evaporator at 60° C./17 mbar. For purification, the residue (1.57 g) was
Processed by chromatography on 140 g of Kieselgel 60 (particle size 0.063-0.20 mm). The effluent was benzene/ethyl acetate/ethanol (8:2:
A mixture of 1) was used. After evaporating the solvent and drying at 1 mbar for 16 h, the pure (2S,4S)
1.12 g (76.8%) of -4-(diphenylphosphino)-2-[(diphenylphosphino)methyl]-1-(diphenylphosphinyl)-pyrrolidine was obtained.
Melting point: devitrifies from 65℃ and melts transparently at 130℃.
[α] 20 D = -21.4° (c = 0.5, in benzene). The following compound was also prepared in a similar manner: (2S,4S)-4-(di-p-tolylphosphino)
-2-[(di-p-tolylphosphino)-methyl]-
1-(diphenylphosphinyl)-pyrrolidine,
[α] 20 D = -33.2℃ (c = 0.5, in benzene); (2S,4S)-4-(di-m-tolylphosphino)
-2-[(di-m-tolylphosphino)-methyl]-
1-(diphenylphosphinyl)-pyrrolidine,
[α] 20 D = −25.8° (c = 0.6, in benzene); (2S,4S)-4-(diphenylphosphino)-2
-[(diphenylphosphino)-methyl]-1-(di-p-tolylphosphinyl)-pyrrolidine, [α]
20 D = -13.8° (c = 0.5, in benzene); (2S,4S)-4-(diphenylphosphino)-2
-[(diphenylphosphino)-methyl]-1-(di-m-tolylphosphinyl)-pyrrolidine, [α]
20 D = -21.3° (c = 0.6, in benzene); [(2S,4S)-4-(diphenylphosphino)-
2-[(diphenylphosphino)-methyl]-1-pyrrolidinyl]-diphenylphosphine, [α] 20 D =
-64.0° (c=0.6, in benzene); Diphenyl [(2S,4S)-4-(diphenylphosphino)-2-[(diphenylphosphino)methyl]
-1-pyrrolidinyl]-phosphonate, [α] 20 D =
-63.3° (c=0.6, in benzene); [(2S,4S)-4-(diphenylphosphino)-
2-[(diphenylphosphino)-methyl-1-pyrrolidinyl]-N,N,N',N'-tetramethylphosphonic acid diamide, [α] 20 D = -60.7° (c = 0.6, in benzene). Reference Example 1 7.5 g of diphenylphosphine in a 200 ml sulfonation flask equipped with a stirrer, a thermometer, two dropping funnels, an argon inlet tube and a cooling bath.
(38 mmol) was dissolved in 25 ml of tetrahydrofuran and the solution was cooled to 0°C. Then 1.5Mn−
28 ml of butyllithium solution (hexane; 42 mmol) was added dropwise with stirring. The initially colorless solution turned a strong orange color. Then (2S,4R)-1-(p-tolylsulfonyl)-4-[(p-tolylsulfonyl)oxy]- in 50 ml of tetrahydrofuran.
A solution of 9.7 g (16.7 mmol) of 2-pyrrolidinylmethyl p-toluenesulfonate was added dropwise at -5 DEG C. over a period of 30 minutes. The solution turned pale yellow. After reacting for 5 hours at 0° C., a few drops of water were added and the solution was then evaporated in a rotary evaporator at 60° C./17 mbar. Add this residue to 100ml of benzene.
and washed three times with 100 ml of water each time, and the aqueous phase was backwashed with 100 ml of benzene. The combined benzene extracts were evaporated in a rotary evaporator at 60° C./17 mbar. The resulting product (yellowish oil,
15.2g) partially crystallizes when left to stand, but in order to purify it, it is dissolved in benzene and the solution is
It was passed through 240 g of Kieselgel 60 (particle size 0.63-0.20 mm). Evaporate the solvent at 40°C/17 mbar.
After drying for 16 hours, (2S,4S)-4-(diphenylphosphino)-2-[(diphenylphosphino)-
6.5 g (63.9%) of methyl]-1-(p-tolylsulfonyl)-pyrrolidine were obtained as a colorless foam.
[α] 20 D = -125.8° (c = 1, in benzene). (2S,4R)-1-(p-
Tolylsulfonyl)-4-[(p-tolylsulfonyl)-oxy]-2-pyrrolidinylmethyl p-toluenesulfonate was prepared as follows: equipped with a stirrer, dropping funnel, thermometer and condenser.
In a 750 ml sulfonation flask, (2S,
4R)-4-hydroxyproline 35.6g (0.27mol)
was dissolved in 300 ml (0.60 mol) of 2N sodium hydroxide. then diethyl ether for 10 minutes.
63g p-toluenesulfonyl chloride in 180ml
(0.33 mol) was added dropwise. The temperature was maintained at 16-20°C by a water bath. After 16 hours of vigorous stirring at room temperature, the reaction was complete. The aqueous phase (PH approx. 7) was separated and backwashed with 250 ml of diethyl ether. The ether phase was then washed twice with 100 ml portions of deionized water. The combined aqueous phases were acidified to a pH of 2 with 25 ml of concentrated (27%) hydrochloric acid while cooling on ice at 5°C.
Stirred at ℃ for 1.5 hours. The separated crystals were suctioned off, washed with 1 portion of deionized water and dried in a vacuum dryer at 40° C./17 mbar for 16 hours. The product obtained (white crystals with melting point 142-145 °C 76.2
g) in hot ethanol/water (1:
4v/v) and then recrystallized by stirring and slowly cooling to 5°C. The white crystals (73.4 g) obtained after drying were recrystallized again from 150 ml of ethanol/water (1:4 v/v) as described above and dried in a vacuum drying oven at 50° C./17 mbar. As a result, the melting point is 146-147℃.
(2S,4R)-4-hydroxy-1-(p-tolylsulfonyl)-2-pyrrolidinecarboxylic acid 69.4
g (89.6%) was obtained. [α] 20 D = -87.6° (c =
1, in ethanol). (2S,4S)-4-hydroxy-1-( p-Tolylsulfonyl)-2-pyrrolidinecarboxylic acid 57g
(0.20 mol) was dissolved in 300 ml of tetrahydrofuran. Then, 500 ml of 1M diborane solution (tetrahydrofuran; 0.50 mol) was added dropwise over 1.2 hours with stirring at 5-10°C. The reaction mixture was stirred at room temperature overnight. Then 50ml deionized water
The mixture was decomposed by adding slowly dropwise at 0-5° C. (exothermic reaction) and then evaporated in a rotary evaporator at 50° C./17 mbar. Take the residue in 150 ml deionized water and 300 ml ethyl acetate.
Extracted 6 times each. The extract was washed three times with 150 ml of saturated sodium chloride solution, dried over sodium sulfate and evaporated in a rotary evaporator at 50° C./17 mbar. For purification, the residue obtained was recrystallized from 100 ml of ethyl acetate. The crystals obtained were suctioned off and dried in a drying oven at 40° C./17 mbar. As a result, 34 g of (2S,4S)-4-hydroxy-1-(p-tolylsulfonyl)-2-pyrrolidine-methanol with a melting point of 133-134°C
(62.7%). [α] 20 D = -47.4° (c = 1, in ethanol). (2S,4R)-4-hydroxy-1-(p-
(Tolylsulfonyl)-2-pyrrolidinemethanol
6.8 g (0.025 mol) was dissolved in 20 ml of pyridine.
A solution of 12 g (0.063 mol) of p-toluenesulfonyl chloride in 20 ml of pyridine was then added at 0-3°C.
The mixture was added dropwise over 45 minutes with stirring.
After about 1 hour, pyridine hydrochloride began to precipitate.
The mixture was stirred at room temperature overnight, then 100 ml of deionized water was carefully added dropwise at 0-10°C (strongly exothermic reaction). As a result, a slurry of white crystals was separated. After stirring in an ice bath for 3 hours,
The crystals were suctioned off, washed four times with 40 ml portions of cold deionized water and dried in a drying oven at 60° C./17 mbar for 2 hours. For purification, the product obtained was recrystallized from 50 ml of ethyl acetate. The separated crystals were suctioned off and dried in a drying oven at 40° C./17 mbar. As a result, the melting point is 131-134℃.
(2S,4R)-1-(p-tolylsulfonyl)-4
-[(p-Tolylsulfonyl)oxy]-2-pyrrolidinylmethyl-p-toluenesulfonate 9.8
g (67.6%); [α] 20 D = −77.2° (c = 1,
in benzene). Reference Example 2 The stirred steel autoclave of 1 was used for dihydro-4,4-dimethyl-2,3-furandione.
50 g (0.39 mol) and 300 ml of toluene were added.
To remove air from the system, the autoclave was evacuated five times with a high vacuum pump, each time introducing 10 bar of hydrogen. The autoclave heated to 40°C was degassed again. Then 0.029 g (0.063 mmol) of chlornorbornadiene-rhodium() dimer and (2S,4S)-4-(diphenylphosphino)-2-
A yellow catalyst solution prepared from 0.082 g (0.126 mmol) of [(diphenylphosphino)methyl]-1-(diphenylphosphinyl)pyrrolidine in 50 ml of toluene is introduced and the autoclave is then flushed with hydrogen.
Pressurized at 40 bar. Hydrogenation was then carried out at 40° C. with vigorous stirring and keeping the hydrogen pressure constant at 40 bar, and the reaction was terminated after 20 hours. The pale yellow solution was then washed out of the autoclave with toluene and the solvent was distilled off in a rotary evaporator at 60° C./17 mbar. This residue (54.7g) was heated to 130-150℃.
(bath temperature) and 0.05 mbar. As a result, crude R-(α-hydroxy-β,
β-dimethyl-γ-butyrolactone) 50.2g
(98.9%). [α] 20 D = -43.1° (c = 1, underwater). Reference Example 3 The stirred steel autoclave of 1 was used for dihydro-4,4-dimethyl-2,3-furandione.
50 g (0.39 mol) and 300 ml of ethyl acetate were added.
To remove air from the system, the autoclave was evacuated five times with a high vacuum pump, each time introducing 10 bar of hydrogen. The autoclave heated to 40°C was degassed again. Then 0.029 g (0.063 mmol) of chlornorbornadiene-rhodium() dimer and (2S,4S)-4-(diphenylphosphino)-2-
A yellow catalyst solution prepared from 0.076 g (0.126 mmol) of [(diphenylphosphino)methyl]-1-(p-tolylsulfonyl)pyrrolidine in 50 ml of ethyl acetate was introduced and the autoclave was heated to 40 ml of hydrogen.
Pressure was applied with a crowbar. Hydrogenation was then carried out at 40° C. with vigorous stirring and keeping the hydrogen pressure constant at 40 bar, and the reaction was terminated after 8 hours. The pale yellow solution was then washed out of the autoclave with ethyl acetate and the solvent was distilled off on a rotary evaporator at 60° C./17 mbar. This residue (59.9g) was heated to 130-150℃.
(bath temperature) and 0.05 mbar. As a result, crude R-(α-hydroxy-β,
β-dimethyl-γ-butyrolactone) 50.6g
(99.8%). [20] 20 D = -41.7° (c = 1, underwater).

Claims (1)

【特許請求の範囲】 １ 一般式 ［式中、Ｒはアリールを表わし、そしてR1は式 【式】【式】又は【式】 の基を表わし、ここでR2はアリール、ジアリー
ルアミノ、ジ（低級アルキル）アミノ、ヒドロキ
シ、アリーロキシ又は低級アルコキシを表わす］ のキラルなホスフイン類。 ２ Ｒがアリールを表わし、そしてR1が式 【式】又は【式】を基を表わし、 ここでR2がアリール、ジアリールアミノ、ジ
（低級アルキル）アミノ、ヒドロキシ、アリーロ
キシ又は低級アルコキシを表わす特許請求の範囲
第１項記載のキラルなホスフイン類。 ３ R1が式【式】の基を表わす特許請求の範 囲第１又は２項記載のキラルなホスフイン類。 ４ Ｒがフエニル、ｐ−トリル又はｍ−トリルを
表わし、そして基R1中のR2がフエニル、Ｐ−ト
リル又はｍ−トリルを表わす特許請求の範囲第１
〜３項のいずれかに記載のキラルなホスフイン
類。 ５ （2S，4S）−４−（ジフエニルホスフイノ）−
２−［（ジフエニルホスフイノ）−メチル］−１−
（ジフエニルホスフイニル）−ピロリジンである特
許請求の範囲第１項のキラルなホスフイン類。 ６ （2S，4S）−４−（ジ−ｐ−トリルホスフイ
ノ）−２−［（ジ−ｐ−トリルホスフイノ）−メチ
ル］−１−（ジフエニルホスフイニル）−ピロリジ
ンである特許請求の範囲第１項記載のキラルなホ
スフイン類。 ７ （2S，4S）−４−（ジ−ｍ−トリルホスフイ
ノ）−２−［（ジ−ｍ−トリルホスフイノ）−メチ
ル］−１−（ジフエニルホスフイニル）−ピロリジ
ンである特許請求の範囲第１項記載のキラルなホ
スフイン類。 ８ （2S，4S）−４−（ジフエニルホスフイノ）−
２−［（ジフエニルホスフイノ）−メチル］−１−
（ジ−ｐ−トリルホスフイニル）−ピロリジンであ
る特許請求の範囲第１項記載のキラルなホスフイ
ン類。 ９ （2S，4S）−４−（ジフエニルホスフイノ）−
２−［（ジフエニルホスフイノ）−メチル］−１−
（ジ−ｍ−トリルホスフイニル）−ピロリジンであ
る特許請求の範囲第１項記載のキラルなホスフイ
ン類。 １０ 一般式 ［式中、Ｒはアリールを表わし、そしてR1は式 【式】【式】又は【式】の 基を表わし、ここでR2はアリール、ジアリール
アミノ、ジ（低級アルキル）アミノ、ヒドロキ
シ、アリーロキシ又は低級アルコキシを表わす］ のキラルなホスフイン類を製造するにあたり、 (a) 一般式 ［式中、Ｒは前記の意味を有する］ の化合物を一般式 【式】a、【式】b又は 【式】c ［式中、R2は前記の意味を有し、R3は塩素又
は弗素を意味する］ の化合物と反応させるか、或いは (b) 一般式 ［式中、R1は前記の意味を有し、R4はアリー
ル又は低級アルキルを意味する］ の化合物を一般式 ［式中、Ｒは前記の意味を有し、R5はリチウ
ム、ナトリウム、カリウム又はマグネシウムハ
ライドを表わす］ の化合物と反応させる、 ことを特徴とする前記一般式のキラルなホス
フイン類の製造方法。[Claims] 1. General formula [wherein R represents aryl, and R 1 represents a group of formula [formula] [formula] or [formula], where R 2 represents aryl, diarylamino, di(lower alkyl)amino, hydroxy, aryloxy or lower alkoxy] chiral phosphines. 2 Patents in which R represents aryl and R 1 represents a group of the formula [Formula] or [Formula], where R 2 represents aryl, diarylamino, di(lower alkyl)amino, hydroxy, aryloxy or lower alkoxy Chiral phosphines according to claim 1. 3. Chiral phosphines according to claim 1 or 2, wherein R 1 represents a group of the formula [Formula]. 4 R represents phenyl, p-tolyl or m-tolyl, and R 2 in the group R 1 represents phenyl, p-tolyl or m-tolyl, claim 1
The chiral phosphine according to any one of items 1 to 3. 5 (2S,4S)-4-(diphenylphosphino)-
2-[(diphenylphosphino)-methyl]-1-
The chiral phosphines of claim 1 which are (diphenylphosphinyl)-pyrrolidine. 6 (2S,4S)-4-(di-p-tolylphosphino)-2-[(di-p-tolylphosphino)-methyl]-1-(diphenylphosphinyl)-pyrrolidine Claim 1 Chiral phosphines as described in Section. 7 (2S,4S)-4-(di-m-tolylphosphino)-2-[(di-m-tolylphosphino)-methyl]-1-(diphenylphosphinyl)-pyrrolidine Claim 1 Chiral phosphines as described in Section. 8 (2S,4S)-4-(diphenylphosphino)-
2-[(diphenylphosphino)-methyl]-1-
Chiral phosphines according to claim 1, which are (di-p-tolylphosphinyl)-pyrrolidine. 9 (2S,4S)-4-(diphenylphosphino)-
2-[(diphenylphosphino)-methyl]-1-
Chiral phosphines according to claim 1, which are (di-m-tolylphosphinyl)-pyrrolidine. 10 General formula [wherein R represents aryl, and R 1 represents a group of formula [formula] [formula] or [formula], where R 2 represents aryl, diarylamino, di(lower alkyl)amino, hydroxy, aryloxy or lower alkoxy] In producing a chiral phosphine, (a) general formula [wherein R has the above meaning] A compound of the general formula [Formula] a , [Formula] b or [Formula] c [wherein R 2 has the above meaning and R 3 is chlorine or fluorine] or (b) with the general formula [wherein R 1 has the above meaning and R 4 means aryl or lower alkyl] A method for producing chiral phosphines of the above general formula, characterized in that the compound is reacted with a compound of the formula [wherein R has the above-mentioned meaning and R 5 represents lithium, sodium, potassium or magnesium halide].
JP58016346A 1982-02-05 1983-02-04 Phosphorus compound Granted JPS58146593A (en)

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EP0158875B1 (en) * 1984-04-19 1989-12-13 F. Hoffmann-La Roche Ag Chiral-rhodium-diphosphine complexes for asymetric hydrogenations
JP2816555B2 (en) * 1988-03-07 1998-10-27 富士薬品工業株式会社 Novel phosphinopyrrolidine compound and asymmetric synthesis method using the same
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