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US 5,292,893 AGranted
Catalytic asymmetric and non-asymmetric reduction of times and oximes using metal catalysts
AssigneeMassachusetts Institute of Technology
InventorsStephen L. Buchwald, Christopher A. Willoughby
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Abstract
A process is provided for catalytically reducing imines, oximes, hydrazones and related compounds. Moreover, there is provided a process for the catalytic asymmetric reduction of imines, oximes, hydrazones, and the like, using enantiomerically enriched catalysts, to provide chiral amine reaction products which are enriched in one enantiomer. Catalytic asymmetric reduction can also be carried out using an achiral precatalyst in combination with a The U.S. Government has rights in this invention pursuant to NIH Grant Number GM 34917.
Claims45
A catalytic asymmetric reduction process, comprising the steps of:
- providing a catalytic amount of an active species of an enantiomerically enriched chiral catalyst selected from the group consisting of M(L)(L')(L"), M(L)(L')(L")(L'"), M(L)(L')(L")(L'") (L.sup.iv), and M(L)(L')(L")(L'")(L.sup.iv)L.sup.v), where M is a group 3, 4, 5 or 6 metal, a lanthanide or an actinide, and L, L', L", L'", L.sup.iv, L.sup.v, independently, is some combination of H, alkyl, aryl Si(R)(R')(R"), halogen, --OR, --SR, or --NR(R'), or a cyclopentadienyl group having the formula ##STR3## where R, R', and R" is H, alkyl, or aryl and may be different or the same, and where R.sup.0, R.sup.1, R.sup.2, R.sup.3, and R.sup.4 are hydrogen, alkyl, aryl, trialkylsilyl, triarylsilyl, (dialkyl)arylsilyl, or (diaryl)alkylsilyl groups in any combination:
- adding a silane compound to the catalyst;
- reacting a substrate, selected from the group consisting of imines, oximes, hydrazones, oxime O-alkyl ethers, oxime O-aryl ethers, N,N-dialkylhydrazones, N,N-diarylhydrazones, and N-alkyl-N-arylhydrazones, in the presence of said catalyst and the silane compound;
- and
- recovering and purifying an amine reaction product having a high level of enantiomeric purity.
2 more elements
A process for the catalytic reduction of a substrate to yield an amine, comprising the steps of:
- providing a catalytic amount of an active species of a catalyst selected from the group consisting of M(L)(L')(L"), M(L)(L')(L")(L'"), M(L)(L')(L")(L'")(L.sup.iv), and M(L)(L')(L")(L'") (L.sup.iv)(L.sup.v), where M is a group 3, 4, 5 or 6 metal, a lanthanide or an actinide, and L, L', L", L'", L.sup.iv, L.sup.v, independently, is some combination of H, alkyl, aryl, S(R)(R')(R"), halogen, --OR, --SR, --NR(R'), or a cyclopentadienyl group having the formula ##STR5## where R, R', and R" is H, alkyl or aryl and may be different or the same, and where R.sup.0, R.sup.1, R.sup.2, R.sup.3, and R.sup.4 may be hydrogen, alkyl, aryl, trialkylsilyl, triarylsilyl, (dialkyl)arylsilyl, or (diaryl)alkylsilyl groups in any combination;
- adding a stoichiometric amount of a silane compound to the catalyst;
- reacting a substrate, selected from the group consisting of imines, oximes, hydrazones, oxime O-alkyl ethers, oxime O-aryl ethers, N,N-dialkylhydrazones, N,N-diarylhydrazones, N-alkyl-N-arylhydazones, in the presence of said catalyst and the silane compound;
- and
- recovering and purifying an amine reaction product.
2 more elements
A catalytic asymmetric reduction process, comprising the steps of:
- providing a mixture of (i) a catalytic amount of an active species of a catalyst selected from the group consisting of M(L)(L')(L")(L"), M(L)(L')(L")(L'"), M(L)(L')(L")(L'")(L.sup.iv), and M(L)(L')(L")(L'")(L.sup.iv)(L.sup.v), where M is a group 3, 4, 5 or 6 metal, a lanthanide or an actinide, and L, L', L", L'", L.sup.iv, L.sup.v, independently, is some combination of H, alkyl, aryl, Si(R)(R')(R"), halogen, --OR, --SR, --NR(R'), or a cyclopentadienyl group having the formula ##STR7## where R, R', and R" is H, alkyl, or aryl and may be different or the same, and where R.sup.0, R.sup.1, R.sup.2, R.sup.3, and R.sup.4 may be hydrogen, alkyl, aryl, trialkylsilyl, triarylsilyl, (dialkyl)arylsilyl, or (diaryl)alkylsilyl groups in any combination;
- (ii) a chiral additive;
- and (iii) a silane compound able to supply a hydride ion during the reduction reaction;
- reacting a substrate, selected from the group consisting of imines, oximes, hydrazones, oxime O-alkyl ethers, oxime O-aryl ethers, N,N-dialkylhydrazones, N,N-diarylhydrazones, and N-alkyl-N-arylhydrazones, with the mixture;
- and
- recovering and purifying an amine reaction product enriched in one enantiomer.
3 more elements
A catalytic asymmetric reduction process, comprising the steps of:
- providing a catalytic amount of an active species of an enantiomerically enriched chiral catalyst selected from the group consisting of M(L)(L')(L"), M(L)(L')(L")(L'"), M(L)(L')(L")(L'")(L.sup.iv), and M(L)(L')(L")(L'")(L.sup.iv)(L.sup.v), where M is a group 3, 4, 5 or 6 metal, a lanthanide or an actinide, and L, L', L", L'", L.sup.iv, L.sup.v, independently, is some combination of H, alkyl, aryl, Si(R)(R')(R"), halogen, --OR, --SR, or --NR(R'), or a cyclopentadienyl group having the formula ##STR8## where R, R', and R" are H, alkyl, aryl, and may be different or the same, and where R.sup.0, R.sup.1, R.sup.2, R.sup.3, and R.sup.4 is hydrogen, alkyl, aryl, trialkylsilyl, triarylsilyl, (dialkyl)arylsilyl, or (diaryl)alkylsilyl groups in any combination;
- reacting a substrate, selected from the group consisting of imines, oximes, hydrazones, oxime O-alkyl ethers, oxime O-aryl ethers, N,N-dialkylhydrazones, N,N-diarylhydrazones, and N-alkyl-N-arylhydrazones in a hydrogen atmosphere in the presence of said catalyst, where hydrogen serves as the reducing agent;
- and
- recovering and purifying an amine reaction product having a high level of enantiomeric purity.
1 more element
A process for the catalytic reduction of a substrate to yield an amine, comprising the steps of:
- providing a catalytic amount of an active species of a non-macrocyclic metal catalyst selected from the group consisting of M(L)(L')(L.increment.), M(L)(L')(L")(L'"), M(L)(L')(L")(L'")(L.sup.iv), and M(L)(L')(L'")(L.sup.iv)(L.sup.v), where M is a group 3, 4, 5 or 6 metal, a lanthanide or an actinide, and L, L', L", L'", L.sup.iv, L.sup.v, independently, is some combination of H, alkyl, aryl, Si(R)(R')(R"), halogen, --OR, --SR, --NR(R'), or a cyclopentadienyl group having the formula ##STR9## where R, R', and R" are H, alkyl or aryl and may be different or the same, and where R.sup.0, R.sup.1, R.sup.2, R.sup.3, and R.sup.4 is hydrogen, alkyl, aryl trialkylsilyl, triarylsilyl, (dialkyl)arylsilyl, or (diaryl)alkylsilyl groups in any combination;
- reacting a substrate, selected from the group consisting of imines, oximes, hydrazones, oxime O-alkyl ethers, oxime O-aryl ethers, N,N-dialkylhydrazones, N,N-diarylhydrazones, and N-alkyl-N-arylhydrazones in a hydrogen atmosphere in the presence of said catalyst, wherein hydrogen serves as the reducing agent;
- recovering and purifying an amine reaction product.
A catalyst asymmetric reduction process, comprising the steps of:
- providing a mixture of (i) a catalytic amount of an active species of a catalyst selected from the group consisting of M(L)(L')(L"), M(L)(L')(L")(L'"), M(L)(L')(L")(L'")(L.sup.iv), and M(L)(L')(L")(L'")(L.sup.iv)(L.sup.v), where M is a group 3, 4, 5 or 6 metal, a lanthanide or an actinide, and L, L', L", L'", L.sup.iv, L.sup.v, independently, is some combination of H, alkyl, aryl, Si(R)(R')(R"), halogen, --OR, --SR, --NR(R'), or a cyclopentadienyl group having the formula ##STR10## where R, R', and R" are H, alkyl or aryl and may be different or the same, and where R.sup.0, R.sup.1, R.sup.2, R.sup.3, and R.sup.4 is hydrogen, alkyl, aryl, trialkylsilyl, triarylsilyl, (dialkyl)arylsilyl, or (diaryl)alkylsilyl groups in any combination;
- and (ii) a chiral additive;
- reacting a substrate, selected from the group consisting of imines, oximes, hydrazones, oxime O-alkyl ethers, oxime O-aryl ethers, N,N-dialkylhydrazones, N,N-diarylhydrazones, and N-alkyl-N-arylhydrazones, with the mixture in a hydrogen atmosphere where hydrogen serves as the reducing agent;
- and
- recovering and purifying an amine reaction product enriched in one enantiomer.
2 more elements
Dependencies are inferred from the claim text.