Professor and Director Sukbok Chang
Korea Advanced Institute of Science & Technology (KAIST) and Institute for Basic Science (IBS)
Title: C-H Amidation via Metal Nitrenoid Transfer: Reaction Development and Validation of Nitrene Intermediacy
Bio: See this link.
Abstract: The direct amidation of C–H bonds is a highly desirable reaction due to the widespread utility of amidated products in total synthesis, medicinal chemistry, and materials science. In this context, we have developed a new methodology utilizing custom-designed Ir-based catalyst systems in combination with dioxazolones as robust and practical amino sources. This approach facilitates the generation of a transient metal-nitrenoid intermediate, ultimately enabling the C–H amidation through an outer-sphere C–H insertion pathway. Building on this foundation, we recently introduced an iridium-based catalyst system for asymmetric C−H amidation, providing an efficient route to synthesize chiral lactams from readily available commodity chemicals. The involvement of nitrenoid intermediates was thoroughly investigated using experimental and computational mechanistic approaches. In this context, we designed a chromophoric octahedral rhodium complex featuring a bidentate dioxazolone ligand, where photoinduced metal-to-ligand charge transfer initiates catalytic C–H amidation. X-Ray photocrystallographic analysis of Rh-dioxazolone complexes enabled structural characterization of the Rh-acylnitrenoid intermediate and provided definitive evidence that the singlet nitrenoid species is primarily responsible for acylamino transfer reactions. Furthermore, in crystallo monitoring of the reaction between a nucleophile and the in situ generated Rh-acylnitrenoid established a crystallographically traceable system, capturing key mechanistic snapshots of nitrenoid transfer.
Keywords: Transition metal catalysis, C-H amidation, hydroamidation, nitrenoid intermediacy