Nickel-Catalyzed Highly Selective Reductive Carbonylation Using Oxalyl Chloride as the Carbonyl Source

Abstract

Nickel-catalyzed carbonylative cross-electrophile coupling which emerges as a powerful, efficient, and low-cost method for constructing challenging carbonyl derivatives has attracted increasing attention of organic chemists. To avoid the generation of a poisonous, volatile, and inert nickel carbonyl complex, it is critical to develop an efficient, cheap, and easily available CO surrogate. Oxalyl chloride, a cheap commercially available chemical, is one of the most versatile organic reagents used in chemical reactions. In this work, high chemoselectivity can be achieved with a 1:1:1 ratio of Ar–I to alkyl-I to oxalyl chloride. A wide range of alkyl aryl ketones which present an important class of molecules in synthetic and medicinal chemistry are accessed from alkyl halides, aryl iodides, under mild conditions. Primary and secondary alkyl iodides were suitable substrates. Various functional groups were well tolerated, affording up to 90% yields. This protocol was also used in the derivatization of natural products and drug molecules. Mechanistic investigation indicates that the reaction of Zn and oxalyl chloride under mild reaction conditions could release CO slowly. This knowledge should be useful for the further development of multicomponent carbonylative cross-coupling reactions.