CHIRAL SYNTHESIS VIA ORGANOBORANES .37. ENANTIOSELECTIVE SYNTHESIS OF CONJUGATED ACYCLIC ALPHA-CHIRAL (E)-ALKENONES

A highly enantioselective synthesis of conjugated acyclic alpha-chiral (E)-alkenones has been achieved from representative prochiral alkenes. Enantiomerically pure (E)-1-alkenylalkylborinic esters, R*B(HC=CHR)OR', required for the synthesis of the (E)-alkenones, are obtained either by the reaction of enantiomerically pure boronic esters, R*B(OR)2, with (E)-1-lithio-1-alkenes, followed by treatment with ethereal hydrogen chloride, or by the hydroboration of a terminal alkyne with an enantiomerically pure isopinocampheylalkylborane, IpcR*BH, followed by elimination of the Ipc group as alpha-pinene by treatment with an aldehyde. These (E)-l-alkenylalkylborinic esters react smoothly with alpha,alpha-dichloromethyl methyl ether (DCME) in the presence of a hindered base (the DCME reaction) to yield, after oxidation with hydrogen peroxide in pH 8 phosphate buffer, conjugated acyclic alpha-chiral (E)-alkenones. The alkenones retain the same stereo- and enantiomeric purity of the chiral borinic esters. To our knowledge, this is the first general synthesis of conjugated acyclic alpha-chiral (E)-alkenones in high enantiomeric purity (greater-than-or-equal-to 99% ee).