Ligand-Enabled γ-C(sp3)-H Olefination of Amines: En Route to Pyrrolidines

Abstract

© 2016 American Chemical Society. Pd(II)-catalyzed olefination of γ-C(sp3)-H bonds of triflyl (Tf) and 4-nitrobenzenesulfonyl (Ns) protected amines is achieved. Subsequent aza-Wacker oxidative cyclization or conjugate addition of the olefinated intermediates provides a variety of C-2 alkylated pyrrolidines. Three pyridine- and quinoline-based ligands are developed to match different classes of amine substrates, demonstrating a rare example of ligand-enabled C(sp3)-H olefination reactions. The use of Ns protecting group to direct C(sp3)-H activation of alkyl amines is also a significant step toward practical C-H functionalizations of alkyl amines.