Ligand-Enabled β-C(sp 3 )-H Lactamization of Tosyl-Protected Aliphatic Amides Using a Practical Oxidant.

The development of C(sp ³ )-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(sp ³ )-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.
(© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)