A novel synthetic method of the (±)-(3aα,8aα)-ethyl 8β-hydroxy-6β-methyl-2-oxooctahydro-2H-cyclohepta[b]furan-3α-carboxylate and its chemical transformation to (±)-(3aα,8aα)-3α,6β-dimethyl-3,3a,4,5,6,8a-hexahydro-2H-cyclohepta[b]furan-2-one, (+)- and (-)-7β-(2-acetoxy-1α-methylethyl)-4β-methyl-2-cyclohepten-1β-ol, and (+)- and (-)-7β-(2-acetoxy-1α-methylethyl)-4β-methyl-2-cyclohepten-1-one.: Possible common synthetic intermediates for pseudoguaianolides, 4,5-secopseudoguaianolides, guaianolides, 4,5-secoguaianolides, and octalactins

The catalytic hydrogenation of ethyl 8-hydroxy-6-methyl-2-oxo-2H-cyclohepta[b] (6), which was derived regioselectively from 4-methyltropolone (1) in four steps in 62% overall yield, gave (3a alpha,8a alpha)-ethyl 8 beta-hydroxy-6 beta-methyl-2-oxooctahydro-2H-cyclohepta[b]furan-3 alpha-carboxylate (8b) in 45% yield. It is noteworthy that four asymmetric centers newly introduced on the seven-membered ring of 8b were controlled to be syn-oriented by the single operation. The latter was transformed to (3a alpha,8a alpha)-3 alpha,6 beta-dimethyl-3,3a,4,5,6,8a-hexahydro-2H-cyclohepta[b]furan-2-one (17a) in 77% overall yield in five steps, Reduction of 17a with LiAlH4 gave (+/-)-7 beta-(2-hydroxy-1 alpha-methylethyl)-4 beta-methyl-2-cyclohepten-1 beta-ol (22), whose enantioselective acetylation was achieved by vinyl acetate in the presence of Lipase PS to give (+)-7 beta-(2-acetoxy-1 alpha-methylethyl)-4 beta-methyl-2-cyclohepten-1 beta-ol (24) in 48% yield (93% ee) or in 52% yield (77% ee) and (-)-22 in 52% yield (70% ee) or 44% yield (89% ee). Oxidation of (+)-24 with MnO2 gave (-)-7 beta-(2-acetoxy-1 alpha-methyl ethyl)-4 beta-methyl-2-cyclohepten-1-one (-)-(25). Similarly, acetylation of (-)-22 followed by oxidation of resulting (-)-24 gave (+)-25.