Catalytic Intermolecular Carboamination of Unactivated Alkenes via Directed Aminopalladation

An intermolecular 1,2-carbo­amination of unactivated alkenes proceeding via a Pd­(II)/Pd­(IV) catalytic cycle has been developed. To realize this transformation, a cleavable bidentate directing group is used to control the regio­selectivity of amino­palladation and stabilize the resulting organo­palladium­(II) intermediate, such that oxidative addition to a carbon electro­phile outcompetes potential β-hydride elimination. Under the optimized reaction conditions, a broad range of nitrogen nucleo­philes and carbon electro­philes are compatible coupling partners in this reaction, affording moderate to high yields. The products of this reaction can be easily converted to free γ-amino acids and γ-lactams, both of which are common structural motifs found in drug molecules and bioactive compounds. Reaction kinetics and DFT calculations shed light on the mechanism of the reaction and explain empirically observed reactivity trends.