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

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 ß-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 ß-lactam products enables the synthesis of a range of biologically important motifs including ß-amino acids, γ-amino alcohols, and azetidines.