Abstract
Enzymatic resolution of racemic 1,4,5,6‐tetrachloro‐2‐(hydroxymethyl)‐7,7‐dimethoxybicyclo[2.2.1]hept‐5‐ene (rac‐1) using various lipases in vinyl acetate as acetyl source was studied. The obtained enantiomerically enriched (+)‐(1,4,5,6‐tetrachloro‐7,7‐dimethoxybicyclo[2.2.1]hept‐5‐en‐2‐yl)methyl acetate ((+)‐2; 94% ee), upon treatment with Na in liquid NH~3~, followed by Amberlyst‐15 resin in acetone, provided (−)‐5‐(hydroxymethyl)bicyclo[2.2.1]hept‐2‐en‐7‐one ((−)‐7), which is a valuable precursor for the synthesis of carbasugar derivatives. Subsequent Baeyer–Villiger oxidation afforded a nonseparable mixture of bicyclic lactones, which was subjected to LiAlH~4~ reduction and then acetylation. The resultant compounds (−)‐11 and (+)‐12 were submitted to a cis‐hydroxylation reaction, followed by acetylation, to afford the novel carbasugar derivatives (1__S__,2__R__,3__S__,4__S__,5__S__)‐4,5‐bis(acetoxymethyl)cyclohexane‐1,2,3‐triyl triacetate ((−)‐(13)) and (1__R__,3__R__,4__R__,6__R__)‐4,6‐bis(acetoxymethyl)cyclohexane‐1,2,3‐triyl triacetate ((−)‐(14)), respectively, with pseudo‐C~2~‐symmetric configuration. The absolute configuration of enantiomerically enriched unreacted alcohol (−)‐1 (68% ee) was determined by X‐ray single‐crystal analysis by anchoring optically pure (R)‐1‐phenylethanamine. Based on the configurational correlation between (−)‐1 and (+)‐2, the absolute configuration of (+)‐2 was determined as (1__R__,2__R__,4__S__).