Electrophile‐Induced Cyclization of 3‐Alkynyl‐2‐arylquinoxalines: A Method for Benzo‐ and Naphthophenazine Synthesis

Abstract

A facile synthesis of benzo[a]‐, naphtho[1,2‐a]‐ and naphtho[2,1‐a]phenazines by ICl‐promoted 6‐endo‐dig cyclization of 3‐alkynyl‐2‐arylquinoxalines has been developed. The starting 3‐alkynyl‐2‐arylquinoxalines were synthesized from 2,3‐dichloroquinoxaline by two successive Sonogashira and Suzuki–Miyaura reactions. The method works well for 3‐alkynyl‐2‐arylquinoxalines bearing various functional groups at the alkyne moiety. The arrangement and nature of the substituent in the 2‐aryl fragment affect the regioselectivity of the cyclization. For the substrate of one particular type, namely 2‐(4‐methoxyphenyl)‐3‐(p‐tolylethynyl)quinoxaline, the treatment with ICl leads to the alternative 5‐endo‐dig cyclization followed by demethylation of the methoxy group to give a spirocyclohexadienone derivative.

Synthesis and Characterization of Pyridine‐, Pyrazine‐, and Quinoxaline‐Derived [4]Helicenes and S‐Shaped Double [4]Helicenes

“…To explore the feasibility of the electrophilic cyclization strategy, the reactions of 3‐alkynyl‐2‐naphthylazines 8a – 8e and the ICl electrophile were examined (Table ). It should be noted that dry dichloromethane was used as a solvent in an earlier ICl‐promoted cyclization of 3‐alkynyl‐2‐arylquinoxalines into benzophenazines . However, dry acetonitrile proved to be a more suitable, and the reactions of quinoxaline derivatives 8a and 8b with ICl (1.2 equiv.)…”

“…[10i] The former is the dihedral angle between the four adjacent inner helix carbon atoms, and the latter is the angle between the two terminal aromatic rings. It is easy to see that all of the 1‐aza[4]helicenes (i.e., 9f , 9c , and 13 ) are not as twisted as [4]helicene itself. The interplanar angle between the two terminal rings A and D of the [4]helicene is equal to 26.68° whereas 1,4‐diaza[4]helicene 9c is practically planar (1.4°).…”

“…Transition‐metal‐catalyzed cycloisomerizations, oxidative radical cyclizations, and electrophile‐induced cyclizations of ortho ‐alkynyl‐substituted biaryls (heterobiaryls) are widely used for the synthesis of polynuclear aromatics . We recently reported the facile synthesis of benzo[ a ]‐, naphtho[1,2‐ a ]‐, and naphtho[2,1‐ a ]phenazines 2 through the ICl‐promoted cyclization of 3‐alkynyl‐2‐arylquinoxalines 1 (Scheme ) . The cyclization of naphthyl derivative 3 led to the formation of naphtho[1,2‐ a ]phenazine 4 that contains a 1,4‐diaza[4]helicene fragment.…”

Cu–N‐heterocyclic carbene‐catalysed synthesis of 2‐aryl‐3‐(arylethynyl)quinoxalines from one‐pot tandem coupling ofo‐phenylenediamines and terminal alkynes

“…Later, reports appeared of the synthesis of diverse substituted quinoxalines with alkyl/aryl and aralkynyl substituents on 2,3‐positions with regard to which are however limited; moreover they can be prepared in two to three sequential steps. In one way, these can be constructed following Sonogashira and Suzuki–Miyaura couplings of 2,3‐dichloroquinoxalines 11a. In 2016 Thamsanqa and Nxumalo reported their preparation from Sonogashira coupling followed by reaction with n ‐BuLi 11b.…”

“…In one way, these can be constructed following Sonogashira and Suzuki–Miyaura couplings of 2,3‐dichloroquinoxalines 11a. In 2016 Thamsanqa and Nxumalo reported their preparation from Sonogashira coupling followed by reaction with n ‐BuLi 11b. Noticeably these reports reveal multi‐step synthesis, requiring sensitive reaction conditions, with by‐product formation in long time at a high catalyst load for overall steps in non‐green solvents.…”