Radical 1,4‐Aryl Migration Enabled Remote Cross‐Electrophile Coupling of α‐Amino‐β‐Bromo Acid Esters with Aryl Bromides

Abstract

We report an unprecedented, efficient nickel-catalysed radical relay for the remote cross-electrophile coupling of β-bromo-α-benzylamino acid esters with aryl bromides via 1,4-aryl migration/arylation cascades. β-Bromo-α-benzylamino acid esters are considered as unique molecular scaffolds allowing for aryl migration reactions, which are conceptually novel variants for the radical Truce-Smiles rearrangement. This reaction enables the formation of two new C(sp³ )-C(sp² ) bonds using a bench-stable Ni/bipyridine/Zn system featuring a broad substrate scope and excellent diastereoselectivity, which provides an effective platform for the remote aryl group migration and arylation of amino acid esters via redox-neutral C(sp³ )-C(sp² ) bond cleavage. Mechanistically, this cascade reaction is accomplished by combining two powerful catalytic cycles consisting of a cross-electrophile coupling and radical 1,4-aryl migration through the generation of C(sp³ )-centred radical intermediates from the homolysis of C(sp³ )-Br bonds and the switching of the transient alkyl radical into a robust α-aminoalkyl radical.