Radical 1,2-Nitrogen Migration Cascades of β-Bromo α-Amino Acid Esters to Access β-Amino Acid Motifs Enabled by Cooperative Ni/Diboron Catalysis

Abstract

Amino acid esters serve as crucial intermediates in protein synthesis and as common structural elements in biologically active natural compounds. Herein, we present an efficient radical cascade reaction involving 1,2-nitrogen migration and C(sp2)–H intramolecular cyclization, enabling access to a diverse array of β-amino acid motifs. Upon cooperative Ni/diboron catalysis, a π-system-independent 1,2-N-shift of β-bromo α-amino acid esters is achieved, which allows the formation of two new bonds, including a C(sp3)–C(sp2) bond and a C(sp3)–N bond. The cascade reaction exhibits extensive substrate compatibility and high diastereoselectivity and proceeds without the need for oxidants, toxic radical initiators, and/or elevated temperatures. It has been observed that diboron compounds serve as both an activating reagent for inert C–N bond cleavage/migration and a reductant for the Ni catalytic cycle. This sheds light on the radical remote migration of N-functionalities without the need for π-systems. The radical cascades involving a 1,2-N-shift followed by intermolecular halogenation or selenation are also demonstrated.