Palladium-Catalyzed Cross-Coupling of Aziridinylmetal Species, Generated by Sulfinyl-Magnesium Exchange, with Aryl Bromides: Reaction Optimization, Scope, and Kinetic Investigations

A series of novel, highly substituted N-PMP aziridines have been accessed in high yields by palladium-catalyzed cross-coupling of intact aziridines. The cross-coupling employed aryl bromides and tertiary organometallic aziridines, generated from sulfinylaziridines by sulfinylmagnesium exchange and transmetalation to the aziridinylzinc with zinc chloride. A wide range of electron-rich and electron-poor aryl bromides were utilized to afford the functionalized aziridine products as single diastereoisomers with retention of configuration at the reacting center. Assessment of the reaction kinetics showed zero-order in both the aziridine species and the aryl bromide. This indicated that the rate-determining step was reductive elimination from the palladium(II) species bearing both the aziridine and aryl groups to form the hindered C-C bond. The intermediate aziridinylzinc species underwent a progressive, background degradation that led to a plateau in yield and afforded reduced yields in substrates with ortho-substituted aryl groups, which are less reactive due to the additional steric demands.