Construction of N-Polyheterocycles by N-Heterocyclic Carbene Catalysis via a Regioselective Intramolecular Radical Addition/Cyclization Cascade

Abstract

N-Polyheterocycles are rapidly accessed by N-heterocyclic carbene (NHC) catalysis through regioselective sequential radical addition/cyclization in the absence of any metals or oxidants. The transformation occurs under mild conditions and enjoys a wide substrate scope with excellent functional group compatibility. Furthermore, a gram-scale synthesis is also conducted. Preliminary mechanistic studies reveal the potential involvement of an NHC radical cation intermediate.N-Polyheterocycles are interesting organic molecules constructed by two or more heterocyclic moieties (containing at least one nitrogen atom) connected in diverse forms (merged, bound, fused, linked, or spaced). N-Polyheterocycles are widely present in a variety of natural products, pharmaceuticals, organic dyes, and agrochemicals (Figure 1). 1 They have

Redox-Neutral Generation of Iminyl Radicals by N-Heterocyclic Carbene Catalysis: Rapid Access to Phenanthridines from Vinyl Azides

“…In 2020, Severin et al reported that stoichiometric amounts of an NHC could donate one electron to the trityl cation . Moreover, we further uncovered a trail of NHC-catalyzed radical coupling reactions , (Scheme a–c) in which the NHC catalyst directly served as a SET reductant for various α-halides, unlike previous reports stemming from Breslow intermediates. As part of our continuous research interest in the construction of diverse heterocycles, , herein we demonstrate a sustainable and redox-neutral route to phenanthridines through NHC-catalyzed intermolecular alkyl radical addition to vinyl azide.…”

“…On the basis of preliminary mechanistic investigation and previous literature, ,− , we proposed a mechanism for this NHC-catalyzed radical process (Scheme ). First, an α-carbon radical B was assumed to be generated in the presence of the NHC catalyst via a SET process. − Subsequent radical addition of B to vinyl azide 1a , followed by N 2 extrusion, resulted in the formation of an iminyl radical C .…”

“…On the basis of preliminary mechanistic investigation and previous literature, ,− , we proposed a mechanism for this NHC-catalyzed radical process (Scheme ). First, an α-carbon radical B was assumed to be generated in the presence of the NHC catalyst via a SET process. − Subsequent radical addition of B to vinyl azide 1a , followed by N 2 extrusion, resulted in the formation of an iminyl radical C . Once generated, C would smoothly undergo a feasible HAS process driven by the aromatization trend to give rise to related phenanthridine product 3a and regenerate the NHC catalyst under the action of the base, thus fulfilling the catalytic cycle.…”

“…Moreover, we further uncovered a trail of NHC-catalyzed radical coupling reactions , (Scheme a–c) in which the NHC catalyst directly served as a SET reductant for various α-halides, unlike previous reports stemming from Breslow intermediates. As part of our continuous research interest in the construction of diverse heterocycles, , herein we demonstrate a sustainable and redox-neutral route to phenanthridines through NHC-catalyzed intermolecular alkyl radical addition to vinyl azide. The reaction is initiated by a homolytic aromatic substitution (HAS) process in the absence of any external hypervalent iodine reagents or transition-metal catalysts (Scheme d).…”

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

“…In spite of these significant breakthroughs, the transformations mentioned above are overwhelmingly dependent on aldehyde substrates. In this context, we try to expand the substrate compatibility of this Breslow intermediate-based radical chemistry to much wider aldehyde-free functionalities and thereby unlock series of new pathways for the construction of heterocycles (Scheme b) . As part of our consistent effort to develop redox-neutral catalysis and heterocycle construction, we here report the first example of NHC-catalyzed, SOMOphilic isocyanide insertion-initiated HAS (homolytic aromatic substitution)-type radical cyclization, resulting in the facile assembly of structurally functionalized phenanthridine scaffolds (Scheme c), which are quite common in many natural products and pharmaceuticals.…”