Fluoride-triggered homoallylic trifluoromethylation of allyl fluorides with gem-difluoroalkenes

Abstract

Asymmetric allylic alkylations (AAA) enable the catalytic construction of new C-C and C-X bonds at allylic positions in a stereoselective manner. Around 1970, Trost discovered the first AAA catalysed by transition metals (TM). More recently, Lewis-base catalysed AAA reactions have been developed using Morita-Baylis-Hilman (MBH) adducts, that depending on different parameters can proceed either via SN2’- SN2’ for γ-alkylations or via SN2'-SN2 for α-alkylations. The aim of this TFG is the development of a new homoallylic trifluoromethylation reaction between MBH fluorides and gem-difluoroalkenes promoted by catalytic amounts of a fluoride salt. Firstly, fluoride adds to the gem-difluoroalkene to in situ generate the nucleophile. Subsequently, this fleeting nucleophile attacks the α-position of the MBH fluoride to form the new C-C bond while releasing fluoride as leaving group. Hence, fluoride ion plays a dual role as a catalytic promoter and as leaving group. As it is continuously regenerated and incorporated to the final product as trifluoromethyl group, the reaction becomes highly atom economic. Overall, this new methodology permits the synthesis of trifluoromethylated alkenes with good regioselectivities and perfect E/Z diastereoselectivity. This TFG thesis has involved the synthesis of the starting materials, the optimisation of the reaction using diverse spectroscopic and chromatographic techniques to assess the selectivity, the conversion, the yield, and the characterisation of the final products