Enantioselective addition of dialkylzincs to aldehydes promoted by chiral amino alcohols. Mechanism and nonlinear effect

M. Kitamura, S. Okada, Seiji Suga, R. Noyori

Research output: Contribution to journalArticle

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Abstract

In the presence of a catalytic amount of (-)-3-exo-(dimethylamino)isoborneol (DAIB), reaction of dialkylzincs and aldehydes is accelerated markedly to give, after hydrolysis, the corresponding S-alcohols in high enantiomeric purity. The reaction mechanism and origin of the enantioselection have been elucidated on the basis of the kinetic measurement, alkyl-scrambling experiments, single-crystal X-ray analysis, 1H NMR study, molecular weight determination of certain key intermediates. Reaction of DAIB and dimethylzinc in a 1:1 molar ratio produces a single dinuclear zinc chelate complex, which does not alkylate benzaldehyde but acts as catalyst precursor. The alkylation proceeds via a dinuclear zinc species containing the DAIB auxiliary, an aldehyde ligand, and three alkyl groups, where it is the bridging alkyl group, rather than the terminal alkyls, that migrates from zinc to the aldehyde carbon. Kinetic measurements and temperature effects on the enantioselectivity indicate that the alkyl transfer process is the turnover-limiting and stereodetermining step. A new type of nonlinear effect has been observed in this enantioselective alkylation. For example, reaction of benzaldehyde and diethylzinc in the presence of 8 mol % of (-)-DAIB in 15% ee leads to (S)-1-phenyl-1-propanol in 95% ee. This unusual phenomenon is a result of a marked difference in chemical properties of the diasteromeric dinuclear complexes formed from dialkylzincs and the DAIB auxiliary. Reaction of equimolar amounts of dimethylzinc and enantiomerically pure DAIB affords a dinuclear chelate complex with C2 chirality, which acts as the active catalyst precursor of the alkylation. By contrast, dimethylzinc and racemic DAIB generate a more stable, but much less reactive, dinuclear complex possessing a meso, Ci structure, rather than a racemic mixture of the chiral complex.

Original languageEnglish
Pages (from-to)4028-4036
Number of pages9
JournalJournal of the American Chemical Society
Volume111
Issue number11
Publication statusPublished - 1989
Externally publishedYes

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Amino alcohols
Amino Alcohols
Alkylation
Aldehydes
Zinc
Catalysts
Kinetics
Chirality
Enantioselectivity
X ray analysis
Propanol
Thermal effects
Chemical properties
Hydrolysis
Alcohols
Molecular weight
Ligands
Nuclear magnetic resonance
Single crystals
Carbon

ASJC Scopus subject areas

  • Chemistry(all)

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Enantioselective addition of dialkylzincs to aldehydes promoted by chiral amino alcohols. Mechanism and nonlinear effect. / Kitamura, M.; Okada, S.; Suga, Seiji; Noyori, R.

In: Journal of the American Chemical Society, Vol. 111, No. 11, 1989, p. 4028-4036.

Research output: Contribution to journalArticle

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abstract = "In the presence of a catalytic amount of (-)-3-exo-(dimethylamino)isoborneol (DAIB), reaction of dialkylzincs and aldehydes is accelerated markedly to give, after hydrolysis, the corresponding S-alcohols in high enantiomeric purity. The reaction mechanism and origin of the enantioselection have been elucidated on the basis of the kinetic measurement, alkyl-scrambling experiments, single-crystal X-ray analysis, 1H NMR study, molecular weight determination of certain key intermediates. Reaction of DAIB and dimethylzinc in a 1:1 molar ratio produces a single dinuclear zinc chelate complex, which does not alkylate benzaldehyde but acts as catalyst precursor. The alkylation proceeds via a dinuclear zinc species containing the DAIB auxiliary, an aldehyde ligand, and three alkyl groups, where it is the bridging alkyl group, rather than the terminal alkyls, that migrates from zinc to the aldehyde carbon. Kinetic measurements and temperature effects on the enantioselectivity indicate that the alkyl transfer process is the turnover-limiting and stereodetermining step. A new type of nonlinear effect has been observed in this enantioselective alkylation. For example, reaction of benzaldehyde and diethylzinc in the presence of 8 mol {\%} of (-)-DAIB in 15{\%} ee leads to (S)-1-phenyl-1-propanol in 95{\%} ee. This unusual phenomenon is a result of a marked difference in chemical properties of the diasteromeric dinuclear complexes formed from dialkylzincs and the DAIB auxiliary. Reaction of equimolar amounts of dimethylzinc and enantiomerically pure DAIB affords a dinuclear chelate complex with C2 chirality, which acts as the active catalyst precursor of the alkylation. By contrast, dimethylzinc and racemic DAIB generate a more stable, but much less reactive, dinuclear complex possessing a meso, Ci structure, rather than a racemic mixture of the chiral complex.",
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