Nucleophilic difluoromethylation of N,N-acetals with TMSCF2SO2Ph reagent promoted by trifluoroacetic acid: A facile access to α-difluoromethylated tertiary amines

A protocol for the synthesis of difluoromethylated tertiary amines by nucleophilic difluoromethylation of N,N-acetals using TMSCF2SO2Ph reagent is developed. The reaction proceeds smoothly in 1,4-dioxane using K2CO3 as the initiator. A key feature of the reaction is that the in situ generated iminiums (from N,N-acetals and CF3COOH) could be fluoroalkylated in an efficient way.

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► Nucleophilic difluoromethylation of N,N-acetals with TMSCF2SO2Ph is developed.
► Iminium species could be in situ generated from N,N-acetals and CF3COOH.
► Potassium carbonate activates the TMSCF2SO2Ph during difluoromethylation.