Chiral Synthesis via Organoboranes. 42. Selective Reductions. 57. Efficient Kinetic Resolution of Representative α-Tertiary Ketones withB-Chlorodiisopinocampheylborane

Abstract

Kinetic resolution of racemic α-tertiary ketones with 0.5−0.6 molar equiv of B-chlorodiisopinocampheylborane provides the product alcohols in very high diastereomeric and enantiomeric excess, with the unreacted ketone recovered in very high ee. For example, ethyl 1-methyl-2-oxocyclopentane- and -cyclohexanecarboxylates are partially reduced to recover the ketone in 91 to ≥99% ee and the product alcohols in up to 94% de, with >90% ee for the major diastereomer. Bicyclic ketones, such as 1-methyl- and 1-ethylnorcamphor, camphor, and camphenilone, are readily resolved to provide the ketone in 92 to ≥99% ee, with the product alcohol recovered in high de and ee. Dihydrospiro[bicyclo[3.2.1]octane-2,2‘(3‘H)-furan]-3-one is resolved to provide the ketone in ≥99% ee and the product alcohol in ≥99% de. In all the cases studied, the R-isomer of the ketone is recovered when dIpc2BCl is used for kinetic resolution, while lIpc2BCl provides the S-ketone. Optimum conditions for obtaining the product alcohol, or the ketone, or both, in very high yields and ee have been established.