C(sp²)–H Functionalization of 2H-Indazoles at C3-Position via Palladium(II)-Catalyzed Isocyanide Insertion Strategy Leading to Diverse Heterocycles

Abstract

Herein, we have reported an efficient Pd-catalyzed C-H functionalization of 2H-indazole at C3-position via an isocyanide insertion strategy for the synthesis of unprecedented benzoxazinoindazoles, indazoloquinaoxalines and benzoxazinoindazolones for the first time. Our new method provides an operationally simple and versatile route for a selective synthesis of 2-(2H-indazol-2-yl)phenols. Furthermore, we developed a sequential one-pot strategy for the synthesis of benzoxazinoindazolone under metal-oxidant-free conditions. We also achieved the isocyanide insertion between C(sp(2))-H and oxygen heteroatom for the first time. The key features of the present protocol are construction of 4 bonds in one-pot, synthesis of new skeletally diverse scaffolds, broad substrate scope, high yields and environmentally benign conditions.

Recent Advances in Indazole-Containing Derivatives: Synthesis and Biological Perspectives

“…Indazole derivatives scarcely occur in nature, but this particular nucleus in a variety of synthetic compounds possesses a wide range of pharmacological activities, such as anti-inflammatory, antiarrhythmic, antitumor, antifungal, antibacterial, and anti-HIV activities [ 3 , 4 , 5 , 6 , 7 , 8 ].…”

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

“…By aiming this, more recently we have accomplished the making of annulated indazoles via direct C−H activation of indazole at C3‐position under metal‐oxidant‐free condition by using isocyanide as one carbon synthon (Scheme , eq. 2a) . In accordance with our goal for C3‐functionalization of 2 H ‐indazole via sp 2 C−H activation, we envisioned to synthesize C3‐annulated indazoles 5 by sp 3 C−H functionalization of benzylamine through intermediate ( III ) obtained by transimination strategy (Scheme ).…”

A Ligand/Additive/Base‐Free C(sp2)‐H Activation and Isocyanide Insertion in PEG‐400: Synthesis of Indolizine/Imidazoline‐Fused Heterocycles

“…Recently Sharada et al . demonstrated the Pd‐catalyzed C−H activation of 2‐(2 H‐ indazol‐2‐yl)aniline at C3‐position v ia an isocyanide insertion in the presence of CuCl 2 .2H 2 O and Cs 2 CO 3 in toluene . However, these methods are performed by using expensive ligands, base, metal oxidant, and organic solvents.…”