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.