Enantioselective imine Michael reaction for the preparation of the (8′R,8a′S)-8,8a′-dimethyl-1′,3′,4′,7′,8′,8a′-hexahydrospiro-[1,3-dioxolane-2,2′(6′H)naphthalen]-6′-one building block.: A formal synthesis of (+)-valencenol

The enantioselective Michael addition of a chiral imine of 4-protected 2-methylcyclohexane-1,4-dione to phenyl crotonate led after cyclization. to the corresponding bicyclic lactam. Reductive cleavage of the chiral moiety followed by saponification gave the corresponding keto-acid, which was cyclized to afford a lactone. Belleau-Fujimoto reaction of the lactone then led to the title building block (diastereoselectivity 96:4, e.e. > 98%) in 11% overall yield from the starting dione. (8R, 8aS)-(+)-8,8a-Dimethyl-3,4,6,7,8,8a-hexahydronaphthalen-2 (1H)-one was obtained after reduction of the carbonyl group, acetylation, and reductive cleavage-deprotection (52% overall yield), representing a formal synthesis of (+)-valencenol. (C) 2001 Elsevier Science Ltd. All rights reserved.