TBHP-Initiated Transamidation of Secondary Amides via C−N Bond Activation: A Metal-Free Approach

Abstract

In the present study, a facile, efficient, and environmentally benign approach for secondary amide transamidation by using tert-butyl hydroperoxide (TBHP) as a radical initiator has been developed. The method involves a two-step approach in which the first step is the C−N bond activation via N-functionalization with Boc to weaken the amide C−N bond by making amide non-planar and electronically destabilized. In the second step, an N-Boc-activated secondary amides undergoes transamidation with the various primary, secondary, aliphatic, aromatic, as well as the sterically hindered amines, using TBHP as a radical initiator to give the products in good to excellent yields. TBHP is easily available, inexpensive, and an environmentally friendly radical initiator. A broad substrate scope with extensive functional group tolerance, metal and catalyst-free approach, and operational simplicity are the important characteristics of the present protocol. © 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim