Divergent Construction of Heterocycles by SOMOphilic Isocyanide Insertion under N-Heterocyclic Carbene Catalysis

Abstract

A variety of phenanthridines are rapidly constructed by an N-heterocyclic carbene (NHC)-catalyzed SOMOphilic isocyanide insertion-initiated homolytic aromatic substitution-type radical cyclization in the absence of any light, transition metals, and external oxidants. The aldehyde-free, scalable, and operationally simple protocol tolerates diverse functionalized biaryl isonitriles and activated α-halides. Moreover, it can be further applied to the divergent construction of other Nheterocycles. Preliminary mechanistic studies disclose that an NHC-derived radical cation intermediate is possibly involved.

Metal-Free Generation of γ-Cyanoalkyl Radicals by N-Heterocyclic Carbene Catalysis: Assembly of 6-Cyanoalkyl Phenanthridines

“…In view of the above experimental results and literature reports, ,,,− we put forward a plausible mechanism for this NHC-catalyzed cyanoalkylation transformation (Scheme ). Initially, α-carbon radical B was generated from cyclobutaone oxime ester 2a under NHC catalysis via a single-electron transfer (SET) process. , The downstream isocyanide SOMOphilic (SOMO = single occupied molecular orbital) insertion would afford an imidoyl radical C , , which rapidly experienced a HAS-type cyclization ,,, to give 6-cyanoalkyl phenanthridine 3a , followed by reviving of the NHC catalyst.…”

“…As a result, exploring other NHC-catalyzed aldehyde-free mechanistic routes will no doubt provide promising solutions. In this background, we have recently uncovered a series of new conversions, allowing for the divergent construction of highly functionalized N-heterocycles through NHC catalysis (Scheme b). As part of our continuous research interest and ceaseless efforts toward N-heterocycle construction/C–H functionalization, , here, we disclose a new constructing method of 6-cyanoalkyl phenanthridine frameworks by redox-neutral NHC catalysis under light-, transition-metal-, and tin-free conditions through γ-cyanoalkyl radical insertion into isocyanide-triggered homolytic aromatic substitution (HAS)-type radical cyclization (Scheme c).…”

On the Redox Properties of the Dimers of Thiazol-2-ylidenes That Are Relevant for Radical Catalysis

“…For instance, imidazol-2-ylidenes perform stoichiometric reduction of the ferrocenium cation ( E = +0.38 V vs SCE) and the trityl cation ( E = +0.27 V vs SCE) . Wang and co-workers recently proposed that thiazol-2-ylidenes A could promote radical transformations in the absence of aldehydes via SET to α-bromocarbonyl compounds and transient formation of radical A •+ . − …”