Few enantioselective reductions of ketones in inclusion complexes with cyclomaltoheptaose (p-cyclodextrin, /3CD) have been reported. Sakuraba et aE.l noted that treatment of such complexes with NaBH, in aqueous NaCl at 0" gave optically active alcohols, although the optical purity was not high.
During studies of the Baeyer-Villiger reaction*, NaBH, reduction3, and pinacol rearrangement4 in the solid state, we found that treatment of pCD-ketone inclusion complexes in the solid state with NaBH, resulted in enantioselective reduction, although the enantioselectivity was not high. The (BH,),-ethylenediamine complex (1) also works well as a reducing reagent in the solid state and reactions are accelerated by ultrasound. The ketones studied were RCOCH, and RCOCF,, where R = phenyl, 1-naphthyl, and 2-naphthyl.
When a mixture of the 1: 1 @CD-ketone complex and NaBH, was kept at room temperature for 6 days, the optically active alcohol was obtained in the yields shown in Table I (entries 1,3,5,6, and8), although the optical purity was not high. The reduction was accelerated by ultrasound (entries 2 and 4), although the enantioselectivity remained low. The (BH,),-ethylenediamine complex (1) can be used instead of NaBH, (entries 7 and 9).
Since it took a long time to extract the product-alcohol from the reaction mixture (see Experimental), the alcohol must remain in the cavity of the @CD so that the reduction also occurs in the cavity, thereby resulting in enantioselectivity. Reduction of the ketone in aqueous PCD with NaBH, gave the racemic alcohol. It is not clear yet how the reducing agents penetrate into the cavity of PCD. It is possible that the carbonyl group of the ketone is located at the entrance of the cavity, and this point should be clarified by the X-ray crystal structural study of PCD-ketone complexes now in progress.