A Three-Component Reaction for the One-Pot Preparation of β-Amino-α,α-Difluoroketones from Trimethyl(trifluoromethyl)silane (CF₃TMS), Acylsilanes and Imines

Abstract

A methodology allowing the direct preparation of β-amino-α,α-difluoroketones from the Ruppert–Prakash reagent (CF₃TMS), acyltrimethylsilanes and N-Boc or N-(diphenylphosphinyl)imines is reported. The process, initiated by a catalytic amount of tetra-n-butylammonium difluorotriphenylsilicate (TBAT), involves the addition of CF₃TMS to the acylsilane, followed by a Brook rearrangement and elimination of a fluoride anion. The latter promotes the addition of the resulting difluoroenoxysilane to the imine. The higher electrophilicity of the acylsilane compared to the imine allows the direct mixing of all the reagents in a three-component, one-pot process.

Key words

Mannich reactions - fluorine - tandem reaction - multicomponent reaction - Ruppert–Prakash reagent

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