SUBSTITUENT EFFECTS IN THE ENANTIOSELECTIVE REDUCTION OF ACETOPHENONES WITH NABH4 IN THE PRESENCE OF BETA-CYCLODEXTRIN

The effect of substituent groups on asymmetric induction by beta-cyclo dextrin (beta-CD) was investigated in the reduction of a series of o-, m-, and p-substituted acetophenones (X = H, Br, Cl, CH3, NO2, OCH3) w ith aqueous NaBH4. The inclusion of the ketones studied in beta-CD led to water-insoluble compounds so that the reaction proceeded in the so lid state. The substitutions resulted generally in higher enantioselec tivities than that obtained for acetophenone indicating stronger host- guest interactions. Acetophenone and its m- and p-derivatives gave pre ponderantly the (-)-alcohol while the prevailing enantiomer was the ()-alcohol in the case of the o-derivatives. The enantioface selectivit y was found to be mainly governed by steric demands imposed by the siz e and the shape of the beta-CD cavity in the case of the o-substituted acetophenones and by hydrophobic interactions in the case of the m-de rivatives. A more complicated situation arose from the asymmetic reduc tion of p-derivatives where a combination of these factors with hydrog en bonding of the carbonyl group to the hydroxyls of beta-CD are respo nsible for the enantioselectivity. (C) 1994 Wiley-Liss, Inc.