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 intermedia te for the synthesis of 4,4-difluoroterpenes, and applications in linalool and geraniol series are described. The process involves 1,1-difluoro-2-trim ethylsilyoxypropene, an enol silyl ether prepared from acetyltrimethylsilan e and trifluoromethyltrimethylsilane, and its reaction in situ with prenyl benzoate, under catalysis by trimethylsilyl trifluoromethanesulfonate. Opti mized conditions leading to either the desired enol silyl ether or the unpr ecedented methyl(trifluoromethyl)trimethylsilyl carbinol 4 have been achiev ed. The prenylation of the enol silyl ether gives a 9/1 mixture of regioiso mers, in favor of the expected ketone 1. Treatment of 1 with vinylmagnesium bromide leads to (+/-)-4,4-difluorolinalool 7. Reaction with the lithium e nolate of ethyl diethylphouphonoacetate, and then LAH reduction, converts 1 to 4,4-difluorogeraniol 11, with complete stereoselectivity.