Enantioselective Fluorination of β‐Ketoamides Catalyzed by Ar‐BINMOL‐derived SalanCopper Complex

Abstract

AbstractA facile and powerful enantioselective construction of CF containing molecules was successfully developed through asymmetric fluorination of β‐ketoamides catalyzed by Ar‐BINMOL‐derived salan–CuII system (Ar‐BINMOL=1,1′‐Binaphthalene‐2‐α‐arylmethanol‐2′‐ol, Cu = copper). The present catalytic system exhibited excellent enantioselectivity and a broad substrate scope for indanone‐derived β‐ketoamides under mild conditions (up to 99 % ee and 99 % yields). Notably, the biomimetic salan‐copper complex was demonstrated for the first time to be a highly efficient catalyst in the fluorination of β‐ketoamides. Experimental results and mechanistic studies indicated that both excess amount of copper salt and electrophilic attack of cationic fluorine to activated methylene assisted by amide group on the β‐ketoamides were key factors for high yield and excellent enantioselectivity, respectively, in this enantioselective fluorination, which was controlled by the two‐point binding between the salan–copper complex with cyclic β‐ketoamides and hydrogen‐bonding activation of the electrophilic fluorinating reagent.magnified image