Stereochemistry of the reduction of bicyclo[3.3.1]nonane-2,9-dione by complex hydrides

Abstract

Bicyclo[3.3.1]nonane-2,9-dione (1) has been reduced by sodium borohydride, lithium aluminium hydride and sodium cyanoborohydride. The regio- and diastereo-selectivity, as well as the product distribution of the four possible diastereoisomeric diols and four possible hydroxy ketones has been determined by a combination of GC and NMR spectroscopy. The first reduction step showed low regioselectivity between the two carbonyl groups but essentially total diastereoselectivity at reduction of either the 2- or the 9-carbonyl group. The 9-(catechol)acetal, which is regioselectively formed, gives an entry to the only diol which is not obtained in direct reduction of 1. Benzoate or p-bromobenzoate esters were subjected to chiral chromatographic resolution on triacetylcellulose and CD spectroscopy gave information on the diastereochemistry as well as on the absolute configuration. Conformational preferences were established by molecular mechanics computations. The chair–chair conformation was calculated to be the most stable form of all the studied compounds except 1, for which a chair–boat conformation is preferred. Transition structures for all possible lithium hydride additions to 1 were analysed by MNDO and ab initio methods.