Chiral Synthesis via Organoboranes. 22. Selective Reductions. 44. The Effect of the Steric Requirements of the Alkyl Substituent in Isopinocampheylalkylchloroboranes for the Asymmetric Reduction of Representative Ketones

Article abstract of DOI:10.1021/jo00268a018

Diisopinocampheylchloroborane, ^dIpc2BCl, is an excellent reagent for the chiral reduction of aralkyl ketones and α-tert-alkyl ketones.Modifications, of this reagent to make new reagents applicable to additional classes of ketones, were explored.Reagents with alkyl groups of varying steric requirements, such as ^dIpcBRCl, where R = Me, Et, i-Pr, Cyp, t-Bu, and Thx, were prepared, and their effectiveness in achieving chiral reduction of acetophenone and 3-methyl-2-butanone was examined.Whereas all of the reagents produced (S)-3-methyl-2-butanol in a modest range of 22-48percent ee, the reagents with R = Me, Et, i-Pr, and Cyp produced (S)-1-phenethanol in the range of 15-84percent ee, while the reagents with R = t-Bu and Thx gave (R)-1-phenethanol in 96percent and 83percent ee, respectively.Thus the reagent, ^dIpcB-t-BuCl achieves high asymmetric reduction of acetophenone in the range achieved by ^dIpc2BCl, but the product posseses the opposite configuration, R, instead of S.The general effectiveness of the new reagent, ^dIpcB-t-BuCl, was explored by reducing the ten standard ketones. ^dIpcB-t-BuCl reduces acetophenone, 2-chloroacetophenone, and 3-acetylpyridine in 96percent, 98percent, and 96percent ee, respectively, highly enriched in the R isomer.Methyl benzoylformate was reduced in 91percent ee (S). trans-4-Phenyl-3-buten-2-one and cyclohexenone were reduced in 84percent and 46percent ee, respectively, enriched in the R isomer. 2,2-Dimethylcyclopentanone and 3-methyl-2-butanone were reduced in 34percent ee (R) and 44percent ee (S), respectively.This study clearly demonstrates a major effect of the steric requirements of the R group in the reagents, ^dIpcBRCl, both on the effectiveness of the chiral reduction achieved and the absolute configuration of the product.