TMSCF2 Br-Enabled Fluorination-Aminocarbonylation of Aldehydes: Modular Access to α-Fluoroamides.

A protocol for the modular assembly of the α-fluoroamide motif has been developed, which provides a practical method for the efficient synthesis of structurally diverse α-fluoroamides from easily available aldehydes and tertiary amines through a three-component fluorination-aminocarbonylation process. The key to the success of this process is taking advantage of the multiple roles of the unique difluorocarbene reagent TMSCF2 Br (TMS=trimethylsilyl). The mechanism of the process involves the 1,2-fluorine and oxygen migrations of the in situ formed TMS-protected α-aminodifluoromethyl carbinol intermediates, which represents a new type of deoxyfluorination reaction.