Acetyltrimethylsilane, trifluoromethyltrimethylsilane, and prenyl esters: a three-component system for the synthesis of gem-difluoroanalogues of monoterpenes.

The preparation of 3,3-difluoro-6-methylhept-5-en-2-one 1, a key intermediate for the synthesis of 4,4-difluoroterpenes, and applications in linalool and geraniol series are described. The process involves 1,1-difluoro-2-trimethylsilyoxypropene, an enol silyl ether prepared from acetyltrimethylsilane and trifluoromethyltrimethylsilane, and its reaction in situ with prenyl benzoate, under catalysis by trimethylsilyl trifluoromethanesulfonate. Optimized conditions leading to either the desired enol silyl ether or the unprecedented methyl(trifluoromethyl)trimethylsilyl carbinol 4 have been achieved. The prenylation of the enol silyl ether gives a 9/1 mixture of regioisomers, in favor of the expected ketone 1. Treatment of 1 with vinylmagnesium bromide leads to (+/-)-4,4-difluorolinalool 7. Reaction with the lithium enolate of ethyl diethylphosphonoacetate, and then LAH reduction, converts 1 to 4,4-difluorogeraniol 11, with complete stereoselectivity.