Oxidative Cyclization of 2-Aryl-3-arylamino-2-alkenenitriles to N-Arylindole-3-carbonitriles Mediated by NXS/Zn(OAc)₂

Abstract

A variety of 2-aryl-3-arylamino-2-alkenenitriles were converted to N-arylindole-3-carbonitriles in a one-pot manner through NBS- or NCS-mediated halogenation followed by Zn(OAc)(2)-catalyzed intramolecular cyclization. It is postulated that the process involves the formation of arylnitrenium ion intermediates, which undergo the electrophilic aromatic substitution to give the cyclized N-arylindole product.

Indole synthesis – something old, something new

“…77 N-Aryl-2alkylindoles can also be synthesized in a similar manner via enamine halogenation with N-chlorosuccinimide or N-bromosuccinimide followed by cyclization with zinc acetate. 78 The cyclization of benzyl oxime esters proceeds under palladium catalysis; as the initial step is an oxidative addition of palladium(0) into the N-O bond, this process is overall redox neutral and so no oxidant is required (Scheme 36). 79…”

Chiral Phosphoric Acid Catalyzed Enantioselective Desymmetrization of 1,4‐Dihydropyridines by C(sp3)−H Bromination

“…Firstly, the enamine double bond of 1,4‐DHP is enantioselectively brominated with bromine source 2 c under catalytic CPA ( R )‐C5, which could activate 2 c and adjust 1,4‐DHP to 2 c through hydrogen bonding interactions ( Ts I ). Then the enantio‐enrich imine intermediate 1 a‐1 is converted to enamine intermediate 1 a‐2 , which finally affords the desired product via intramolecular [1–3]‐Br transfer [14d, 20] …”

N-Halo Reagents: Modern Synthetic Approaches for Heterocyclic Synthesis

“…Qi, Zhao, and co-workers reported an elegant oxidative cyclization of 2-aryl-3-(arylamino)alk-2-enenitriles 284 promoted by NXS/Zn(OAc) 2 to access 1-arylindole-3-carbonitriles 286 (Scheme 69). 130 The reaction was conducted using NCS or NBS as halogenating reagents in one-pot fashion via an unprecedented benzylic bromination of 2-aryl-3-(arylamino)alk-2-enenitriles, followed by intramolecular cyclization of 285 catalyzed by Zn(OAc) 2 , affording the desired 1-arylindole-3-carbonitriles 286 in good to excellent yields.…”