Metal‐Free Regioselective Dual C‐H Functionalization in a Cascade Fashion: Access to Isocryptolepine Alkaloid Analogues

Abstract

A metal‐free regioselective approach to annulated indazoles is presented via dual C−H functionalization of indazole and benzylamine in a cascade fashion. The salient features of the present protocol are regioselective C3‐functionalization, one‐pot synthesis of annulated scaffolds, metal‐free, peroxide‐free, operationally simple and wide substrate scope.

A Sydnone-Based Route to Indazolo[2,3-a]quinoxaline Derivatives

“…The first one involves a C3-functionalization of 2 H -indazoles in one of three ways: I 2 -mediated sp 2 C–H activation in the presence of benzylamines, 4 Pd(II)-catalyzed isocyanide insertion, 5 or intramolecular cyclization of imine intermediates, followed by oxidation with DDQ. 6 The second approach is based on a visible-light-induced radical coupling of ortho -substituted aryl isocyanides with radicals generated from phenyliodine(III) dicarboxylate reagents, affording the required polyaromatic structures under mild conditions (Scheme 1 ).…”

Synthesis of pyrazino[1,2-b]indazoles via cascade cyclization of indazole aldehydes with propargylic amines

“…To date, this has been the only case reported on the synthesis of pyrazino[1,2- b ]indazole. 9 For the preparation of π-expanded pyrazino[1,2- b ]indazoles, the primary strategy involves C–H functionalization of 2-(2 H -indazol-2-yl)anilines, which can be carried out in one of three distinct manners: (1) iodine-mediated annulation cascade of indazoles with benzylamines (Scheme 2b-1), 10 (2) palladium( ii )-catalyzed isocyanide insertion (Scheme 2b-2), 11 or (3) microwave-assisted acid-catalyzed tandem cyclization of 2-(2 H -indazol-2-yl)anilines with aldehydes, followed by DDQ-mediated oxidative aromatization (Scheme 2b-3). 12 In 2022, another interesting method starting from aryl azide derivatives was developed by the Taran group to afford π-expanded pyrazino[1,2- b ]indazoles (Scheme 2b-4).…”

Microwave‐assisted Transition Metal‐catalyzed Coupling Approach to Indazole Diversity

“…[11][12][13][14][15][16][17][18][19] Recently, palladium-catalyzed coupling methods have shown essential synthetic tools for functionalization and formation of variety heterocycles. [11][12][13][14][15][16][17][18][19] Recently, palladium-catalyzed coupling methods have shown essential synthetic tools for functionalization and formation of variety heterocycles.…”

“…Many synthetic methods involving indazoles utilize thermal or transition metal‐catalyzed indazole formation to create useful organic compounds …”