Iminyl Radicals from Acyl Oximes by <i>N</i>-Heterocyclic Carbene Catalysis: A Rapid Approach to Phenanthridines

The phenanthridine motif is a ubiquitous feature in a wide array of natural products, medicines, and functional compounds.Due to their remarkable pharmacological activities in medicinal chemistry, phenanthridine and its analogues have garnered significant attention over the years.Consequently, numerous endeavors have been devoted to developing adaptable techniques for synthesizing phenanthridines with various modifications.Notably, cyclization reactions involving iminyl radicals have emerged as a prominent tactics, prized for their exceptional atom economy and superior catalytic effectiveness.Traditionally, iminyl radicals are accessed from acyl oximes through homolytic N-O bond cleavage under harsh conditions, including microwave heating at elevated temperatures (up to 240 ) or UV irradiation.Alternatively, the N-O bond of acyl oximes can undergo single-electron reduction to yield iminyl radicals and acyloxy anions.Despite recent breakthroughs in this field, many of these transformations rely on transition metals, which can result in problematic metal residues, particularly in pharmaceutical applications.Furthermore, they often require extrinsic precious photosensitizers, such as pyridyl-iridium complexes and artificially complicated compounds.These limitations render related methods less than ideal in terms of synthetic functionality, cost-effectiveness, and environmental sustainability.Consequently, there is a pressing need to develop more environmentally sustainable and user-friendly methods for generating iminyl radicals using low-cost and eco-friendly catalysts.As part of our ongoing research into radical chemistry and heterocycle construction, we have recently disclosed several metal-free, environmentally-benign intermolecular radical-addition triggered homolytic aromatic substitution (HAS) reactions to functionalize phenanthridines using N-heterocyclic carbene (NHC) catalysis from vinyl azides or biaryl isonitriles.These promising results motivated us to further explore the possibility of constructing the phenanthridine core structure directly from acyl oximes by more straightforward intramolecular reactions.Herein, we have developed a novel and environmentally benign approach for generating iminyl radicals from acyl oximes via NHC catalysis, obviating the need for transition metals, oxidants, or light.This methodology has enabled the expedient synthesis of a diverse range of phenanthridines bearing various functional groups.Furthermore, the established protocol is proposed to proceed through a single electron transfer (SET) radical process.