Novel Iridium(I) Complexes Bearing Chelating NHC-Phosphine Ligands as Catalysts for C—H Functionalisation Processes

The development of C—H bond functionalization processes has driven significant progress in both organic synthesis and transition metal catalysis.[1] In this realm, hydrogen isotope exchange (HIE) reactions exploits C—H activation to enable ready access to isotopically enriched molecules, an integral part of the drug development process with crucial role for the timely execution of ADME studies.[2] Herein we report a new class of Ir(I) complexes (1), bearing a chelating N-heterocyclic carbene-phosphine (NHC-P) ligand, and their application in the HIE of substrates with sterically demanding directing groups (2-3). Combined theoretical and experimental mechanistic studies unveiled a rich behaviour in solution, leading to improved understanding of catalytic activity. Insights gathered from these studies ultimately led to a catalytic method for the synthesis of saturated heterocycles from versatile carboxylic acids (4) via sequential C—H activation and C—C bond formation, providing access to important scaffolds with high atom efficiency.