Denitrogenative Imidoyl Radical Cyclization: Synthesis of 2-Substituted Benzoimidazoles from 1-Azido-2-isocyanoarenes

Abstract

A novel access to 2-substituted benzoimidazoles, through unprecedented denitrogenative imidoyl radical cyclization of 1-azido-2-isocyanoarenes, has been developed. This tandem radical process was initiated by adding a C- or P-centered radical to isocyanide, followed by cycloaddition of the imidoyl radical to the azido group. Then, nitrogen loss and hydrogen abstraction of the resulting aminyl radical from surroundings delivered 2-substituted benzoimidazoles. Carbon radicals generated from another annulation process could also be applied, furnishing various heterocycle linked benzoimidazole derivatives.

Mn(III)‐Mediated Regioselective 6‐endo‐trig Radical Cyclization of o‐Vinylaryl Isocyanides to Access 2‐Functionalized Quinolines

“…In 2012, Chatani and coworkers disclosed that with the oxidation of Mn(III) salts arylboronic acids could generate aryl radical for the synthesis of phenanthridines. [9][10]24] We initiated this study by establishing optimal experiment conditions using the model reaction of 1-isocyano-2-(1-phenylvinyl)benzene 1 a with phenylboronic acid 2 a in the presence of manganese (III) salts. [9][10]24] We initiated this study by establishing optimal experiment conditions using the model reaction of 1-isocyano-2-(1-phenylvinyl)benzene 1 a with phenylboronic acid 2 a in the presence of manganese (III) salts.…”

“…[26] In light of the significance of these compounds, the development of efficient methods for CÀ P bond construction attracts continuous interests. [9][10]28] To further expand the application of this protocol, the reactions of o-vinyl arylisocyanides 1 with diaryl phosphine oxides 4 in the presence of Mn(III)-salt were conducted. [9][10]28] To further expand the application of this protocol, the reactions of o-vinyl arylisocyanides 1 with diaryl phosphine oxides 4 in the presence of Mn(III)-salt were conducted.…”

“…[23] Afterward, the generation of aryl radical form arylboronic acids to initiate cascade cyclization of isocyanides for the synthesis of functionalized heterocycles has also been reported. [9][10]24] We initiated this study by establishing optimal experiment conditions using the model reaction of 1-isocyano-2-(1-phenylvinyl)benzene 1 a with phenylboronic acid 2 a in the presence of manganese (III) salts. After extensive screening of various reaction parameters including catalyst loadings, solvents, temperature, etc., the optimized reaction conditions were established as follows: 1 a (0.2 mmol), 2 a (2.0 equiv.…”

“…[4] Notably, ortho-functionalized aromatic isocyanides have been applied as valuable synthons in radical cascade reactions for the synthesis of N-heterocycle scaffolds, due to their capability to incorporate various substituents simultaneously with the construction of ring systems, showing remarkable operational simplicity and atom-/stepeconomy. )-or carbon (aryl or alkyl)-centered radicals to generate corresponding imidoyl radicals, which subsequently undergo intramolecular cyclization after addition to their adjacent functionalities to eventually afford various N-heterocycles, including phenanthridines, [6] quinolines, [7] quinoxalines, [8] benzimidazoles, [9] benzothiazoles, [10] benzoselenazoles, [11] etc ( Figure 1). )-or carbon (aryl or alkyl)-centered radicals to generate corresponding imidoyl radicals, which subsequently undergo intramolecular cyclization after addition to their adjacent functionalities to eventually afford various N-heterocycles, including phenanthridines, [6] quinolines, [7] quinoxalines, [8] benzimidazoles, [9] benzothiazoles, [10] benzoselenazoles, [11] etc ( Figure 1).…”

“…[5] For instance, a number of ortho-functionalized aromatic isocyanides have been employed as radical acceptors reacting with heteroatom (P, S, Si, etc. )-or carbon (aryl or alkyl)-centered radicals to generate corresponding imidoyl radicals, which subsequently undergo intramolecular cyclization after addition to their adjacent functionalities to eventually afford various N-heterocycles, including phenanthridines, [6] quinolines, [7] quinoxalines, [8] benzimidazoles, [9] benzothiazoles, [10] benzoselenazoles, [11] etc (Figure 1).…”