A Novel Synthetic Method of the (±)-(3aα,8aα)-Ethyl 8β-Hydroxy-6β-methyl-2-oxooctahydro-2<i>H</i>-cyclohepta[<i>b</i>]furan-3α- carboxylate and Its Chemical Transformation to (±)-(3aα,8aα)-3α,6β-Dimethyl-3,3a,4,5,6,8a-hexahydro-2<i>H</i>- cyclohepta[<i>b</i>]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

Abstract

The catalytic hydrogenation of ethyl 8-hydroxy-6-methyl-2-oxo-2 H -cyclohepta[ b ]furan-3-carboxylate ( 6 ), which was derived regioselectively from 4-methyltropolone ( 1 ) in four steps in 62% overall yield, gave (3aα,8aα)-ethyl 8β-hydroxy-6β-methyl-2-oxooctahydro-2 H -cyclohepta[ b ]furan-3α-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 (3aα,8aα)-3α,6β-dimethyl-3,3a,4,5,6,8a-hexahydro-2 H -cyclohepta[ b ]furan-2-one ( 17a ) in 77% overall yield in five steps. Reduction of 17a with LiAlH 4 gave (±)-7β-(2-hydroxy-1α-methylethyl)-4β-methyl-2-cyclohepten-1β-ol ( 22 ), whose enantioselective acetylation was achieved by vinyl acetate in the presence of Lipase PS to give (+)-7β-(2-acetoxy-1α-methylethyl)-4β-methyl-2-cyclohepten-1β-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 MnO 2 gave (−)-7β-(2-acetoxy-1α-methyl ethyl)-4β-methyl-2-cyclohepten-1-one (−)-( 25 ). Similarly, acetylation of (−)- 22 followed by oxidation of resulting (−)- 24 gave (+)- 25 .