Lewis Base-Catalyzed Interhalogenation of Terminal Allenes: Selective Strategy for Accessing Vicinal Vinylic, Allylic Heterodihalides

Abstract

Though precedent remains limited, the selective interhalogenation of allenes offers a valuable synthetic strategy to access products where each halide exhibits orthogonal reactivity. Here, we describe a Lewis base-catalyzed approach for the dihalogenation (bromochlorination, iodochlorination, iodobromination, and dibromination) of terminal allenes. By employing just 1 mol % of triphenylphosphine oxide or hexamethylphosphoramide to activate thionyl halides in the presence of electrophilic halogenation reagents, we achieve the conversion of monosubstituted allenes to vicinal allylic, vinylic dihalides with up to 93% yield and >20:1 regioisomeric ratio, favoring the branched dihalogenated product. A range of functional groups is tolerated, including nitrile, ester, phosphate, sulfonamide, and silyl groups, and the reaction proved to be scalable. The utility of various dihalide products was investigated in substitution and cross-coupling chemistry, highlighting the distinct reactivity among the different classes.