Asymmetric Reductions of Prochiral Ketones with B-3-Pinanyl-9-borabicyclononane (Alpine-Borane) at Elevated Pressures

Article abstract of DOI:10.1021/jo00262a036

The reduction of unhindered ketones, such as acetylenic ketones, with B-3-pinanyl-9-borabicyclo<3.3.1>nonane (Alpine-Borane, prepared by hydroboration of α-pinene with 9-BBN) provides a simple means of forming chiral, nonracemic alcohols of known absolute configuration in high enantiomeric purity.A dehydroboration-reduction mechanism leading to racemic alcohol is believed to be responsible for erosion of the enantiomeric efficiency with more hindered ketones.The use of elevated pressures (2000-6000 atm) accelerates the asymmetric reduction mode while suppressing the undesired dehydroboration mode.The use of high pressure permits a studyof the scope and utility of Alpine-Borane in the absence of the competing side reaction.The reduction of ketones containing chiral centers was studied with use of the reagent from (+)-α-pinene. d-Carvone is reduced while l-carvone is not.Methyl-substituted cyclohexanones show no discrimination between enantiomers.For example, 2-methylcyclohexanone is reduced to a 1:1 mixture of cis- and trans-2-methylcyclohexanol, each of which is about 65 percent ee.In all cases, one may predict the absolute configuration of the product based on a simple model.The relative steric requirements of groups on the ketone may be catagorized as very small (CCH, CN, H, D); small (CH3, CO2CH3); medium (n-alkyl, trans-RHC=CH); medium large (CF3, i-Pr); large (Ar); and too large (tert-butyl).Effective asymmetric reductions are achieved when groups from nonadjacent catagories are attached to the carbonyl.