Catalytic, Asymmetric r-Fluorination of Acid Chlorides: Dual Metal-Ketene Enolate Activation

In many ways, medicinal chemistry has entered the “age of fluorine”. The number of drugs and drug candidates that contain fluorine has increased exponentially over the past few years, making its installation in a stereoselective (especially an enantioselective) manner of vital importance to the synthetic chemist.1 Along these lines, several impressive examples of catalytic, enantioselective fluorination have recently appeared in which â-keto esters, imides, and aldehydes serve as substrates to produce products in high enantioselectivity and yield.2 However, one very important complementary piece of the puzzle would be an enantioselective R-fluorination of ketene enolates that could produce simple, optically enriched R-fluorinated carboxylic acid derivatives directly.3 In this Communication, we report a catalytic, highly enantioselective R-fluorination of acid chlorides to produce products of broad scope and in excellent yield. This new reaction exploits a recently developed “dual activation ” strategy from our