Stereoselective Horse Liver Alcohol Dehydrogenase Catalyzed Oxidoreductions of Some Bicyclic [2.2.1] and [3.2.1] Ketones and Alcohols

Abstract

The asymmetric synthesis potential of horse liver alcohol dehydrogenase (HLADH) with respect to some 2-oxy-bicyclic [2.2.1] and [3.2.1] substrates has been examined. Preparative-scale (up to 1 g) HLADH-catalyzed oxidoreductions of (±)-2-norbornanone (1), (±)-bicyclo[3.2.1]-2-octanone (5), and (±)-exo-2-norbornanol (11) have been found to proceed enantioselectively and with very high epimeric specificity. HLADH-catalyzed reductions of (±)-1 give rise to (—)-(1R, 4S)-1 and (-t-)-(1S,2R,4R)-eni/o-2-norbornanol of up to 66% optical purity. Similarly, (±)-5 yields enantiomerically enriched (—)-(1R,5R)-5 and (—)-(1S,2S,5S)-exo-bicyclo[3.2.1]-2-octanol (83% optically pure), while HLADH-mediated oxidation of (±)-11 leads to (+)-(1R,2R,4S)-11 and (+)-(1S,4R)-1 of 71 and 68% optical purities, respectively. Furthermore, the optical purities of the products can be manipulated by varying the extent of the reaction. The stereospecificities observed are all interpretable in terms of an updated diamond lattice model of the active site. This enzymic approach is the most convenient singlestep process for preparing research-scale quantities of enantiomerically enriched 2-oxynorbornanes and 2-oxy[3.2.1]octanes. In addition, enantiomerically pure samples of each stereoisomer of the 2-hydroxy- and 2-ketonorbornanes have been prepared by classical procedures. © 1976, American Chemical Society. All rights reserved.