Lipase-catalyzed asymmetric synthesis of (R)- and (S)-4-tert-butyldimethylsilyloxy-2,6,6-trimethyl-2-cyclohexenone and their dihydro derivatives

Article abstract of DOI:10.1016/0957-4166(95)00159-M

Racemic 4-hydroxy-2,6,6-trimethyl-2-cyclohexenone, trans- and cis-2,6,6-trimethyl-2-cyclohexene-1,4-diols were prepared by reduction of 4-oxoisophorone with sodium borohydride-cerium chloride. Lipase (PS-30)-catalyzed kinetic resolution of (±)-cis-2,6,6-trimethyl-2-cyclohexene-1,4-diol with vinyl acetate led to (1R, 4S)-4-acetoxy-2,6,6-trimethyl-2-cyclohexen-1-ol (81%ee) and (1S,4R)-1-acetoxy-2,6,6-trimethyl-2-cyclohexene-4-ol (92%ee). Hydrolysis of the former monoacetate and recrystallization of the resulting material afforded enantiomerically pure (1R, 4S)-2,6,6-trimethyl-2-cyclohexene-1,4-diol. On the other hand, recrystallization of (1S,4R) monoacetate itself provided an optically pure sample, which was then hydrolyzed to give (1S, 4R)-2,6,6-trimethylcyclohexene-1,4-diol. Transformation of both diols into (S)- and (R)-4-tert-butyldimethylsilyloxy-2,6,6-trimethyl-2-cyclohexenone was conducted in two steps including silylation and oxidation. Catalytic hydrogenation of these (S)- and (R)-silyloxy enones over Raney nickel afforded the corresponding dihydro derivatives.