Yeongyu Hwang1, Yoonsu Park1, Sukbok Chang1. 1. Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141 (Republic of Korea) and Center for Catalytic Hydrocarbon Functionalizations, Institute for Basic Science (IBS), Daejeon, 34141, Republic of Korea.
Abstract
Described herein is a mechanism-based approach to develop a versatile C-H amidation protocol under IrIII catalysis. Reaction kinetics of a key C-N coupling step with acyl azide and 1,4,2-dioxazol-5-one led us to conclude that dioxazolones are much more efficient in mediating the formation of a carbon-nitrogen bond from an iridacyclic intermediate. Computational analysis revealed that the origin of higher reactivity is asynchronous decarboxylation motion, which may facilitate the formation of Ir-imido species. Importantly, stoichiometric reactivity was successfully translated into catalytic activity with a broad range of substrates (18 different types), many of which are regarded as challenging to functionalize. Application of the new method enables late-stage functionalization of drug molecules.
Described herein is a mechanism-based approach to develop a versatile C-H amidation protocol under IrIII catalysis. Reaction kinetics of a key C-N coupling step with acyl azide and n class="Chemical">1,4,2-dioxazol-5-one led us to conclude that dioxazolones are much more efficient in mediating the formation of a carbon-nitrogen bond from an iridacyclic intermediate. Computational analysis revealed that the origin of higher reactivity is asynchronous decarboxylation motion, which may facilitate the formation of Ir-imido species. Importantly, stoichiometric reactivity was successfully translated into catalytic activity with a broad range of substrates (18 different types), many of which are regarded as challenging to functionalize. Application of the new method enables late-stage functionalization of drug molecules.