An improved synthesis of 4-O-benzoyl-2,2-difluorooleandrose from L-rhamnose.: Factors determining the synthesis of 2,2-difluorocarbohydrates from 2-uloses

4-O-Benzoyl-2,2-difluorooleandrose (16) has been synthesized from L-rhamnose. The key steps are the formation of a difluoromethylene group in 12 by reacting ulose 11 with DAST and the chemoselective methylation of diol 13 to give compound 14. To obtain the 2,2-difluoro compound 12, the substituents in the neighborhood of the carbonyl group in ulose 11 must be equatorial and the sugar ring must have restricted conformational mobility. This was done using 1,1,2,2-tetramethoxycyclohexane (TMC) to protect the hydroxyls at positions 3 and 4 in the sugar ring.