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

Nickel-catalyzed carbonylative cross-electrophile couplingwhichemerges as a powerful, efficient, and low-cost method for constructingchallenging carbonyl derivatives has attracted increasing attentionof 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 cheapcommercially available chemical, is one of the most versatile organicreagents used in chemical reactions. In this work, high chemoselectivitycan be achieved with a 1:1:1 ratio of Ar-I to alkyl-I to oxalylchloride. A wide range of alkyl aryl ketones which present an importantclass of molecules in synthetic and medicinal chemistry are accessedfrom alkyl halides, aryl iodides, under mild conditions. Primary andsecondary alkyl iodides were suitable substrates. Various functionalgroups were well tolerated, affording up to 90% yields. This protocolwas also used in the derivatization of natural products and drug molecules.Mechanistic investigation indicates that the reaction of Zn and oxalylchloride under mild reaction conditions could release CO slowly. Thisknowledge should be useful for the further development of multicomponentcarbonylative cross-coupling reactions.