Nickel-Catalyzed Carbonylative Coupling of Alkylzinc Reagents and α-Bromo-α,α-difluoroacetamides

Abstract

AbstractWe report a nickel-catalyzed carbonylative cross-coupling of alkyl zinc reagents with α,α-difluorobromoacetamides to obtain α,α,-difluoro-β-ketoamides in moderate to good yields. The reaction is catalyzed by a bench-stable nickel(II) pincer complex, in contrast to other reports involving palladium catalysts. The carbonylative reaction is performed in a two-chamber system (COware) in which carbon monoxide (CO) is generated ex situ from the solid precursor SilaCOgen, and then consumed in the adjacent chamber. The reaction operates at low temperatures using near-stoichiometric amounts of CO. Isotopically labeled products can be effortlessly accessed, as demonstrated by using 13C-labeled SilaCOgen.