Ligand-Enabled β-C(sp3 )-H Lactamization of Tosyl-Protected Aliphatic Amides Using a Practical Oxidant

Abstract

The development of C(sp³ )-H functionalization reactions that use common protecting groups and practical oxidants remains a significant challenge. Herein we report a monoprotected aminoethyl thioether (MPAThio) ligand-enabled β-C(sp³ )-H lactamization of tosyl-protected aliphatic amides using tert-butyl hydrogen peroxide (TBHP) as the sole oxidant. This protocol features exceedingly mild reaction conditions, reliable scalability, and the use of practical oxidants and protecting groups. Further derivatization of the β-lactam products enables the synthesis of a range of biologically important motifs including β-amino acids, γ-amino alcohols, and azetidines.

Keywords: Carboxylic Acids; C−H Activation; Lactamization; Ligand Design; Palladium.