Ag-catalyzed and difluorocarbene-promoted amide-ylide rearrangement: synthesis of 3-salicyloylpyridines†

Abstract

Herein, we report an Ag-catalyzed and difluorocarbene-promoted amide-ylide rearrangement strategy. This strategy utilizes an unconventional transformation between difluorocarbene and amide functionalities to successfully synthesize 3-salicyloylpyridines. Preliminary mechanistic studies suggest that the reaction initially involves the coordination of the amide with the metal, followed by a reaction with difluorocarbene to form the RNCF₂H intermediate, which then facilitates the formation of the N-ylide intermediate, a crucial step for the synthesis of the target compound. Subsequently, selective C–N bond cleavage is followed by a rearrangement and elimination of formaldehyde. This rearrangement strategy demonstrates broad substrate applicability. Under identical reaction conditions, it enables the reaction of chromones with various β-ketones (such as 1,3-dicarbonyl compounds, β-keto esters, acetophenone, acetone, pentanone, and 2-bromoacetophenone) to produce 3-salicyloylpyridines (>47 examples, up to 91% yield), showing excellent efficiency and functional group tolerance.