New Ligandless C−H Activation Procedure for The Decoration of C‐3 Position of 1H‐Indazole Derivatives. Issue 9 (2nd March 2023)

• Record Type: Journal Article
• Authors: Guariento, Sara; Chesi, Mattia; Bellina, Fabio; Copelli, Diego; Venturi, Luca; Bua, Emanuela; Moretti, Elisa; Ronchi, Paolo
• Is Part Of: ChemistrySelect. Volume 8:Issue 9(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2023-03-02
• Subjects: 1H-indazole -- C−H activation -- direct arylation -- ligandless -- sustainability; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/slct.202203916
• Languages: English
• ISSNs: 2365-6549

Abstract

Abstract: Arylation of heteroaromatic rings is one of the most important strategy for the chemical space exploration (e. g. applied in medicinal chemistry). In the last two decades C−H activation reactions emerged as powerful and more sustainable synthetic methods for this kind of functionalization if compared to the classical Pd‐catalysed cross‐coupling reactions (e. g. Suzuki, Stille, Negishi, Hiyama). A further step in the direction of greater sustainability has been done developing ligandless C−H activation procedures with higher appeal for industrial application. Among the various N‐based heterocycles exploited in medicinal chemistry, there is no reported ligandless C−H activation for 1 H ‐indazole core, although its potential pharmaceutical applications. In this work we describe a novel synthetic procedure for the direct arylation/heteroarylation of C‐3 position of 1 H ‐indazole which was optimized using the Design of Experiment (DoE) (yield up to 72 %) and confirmed a fulfilling robustness among various aryl/heteroaryl and indazole scopes. Abstract : In this work is described a novel synthetic procedure for the direct arylation/heteroarylation of C‐3 position of 1 H ‐indazole which was optimized using the Design of Experiment (DoE) (yield up to 72 %) and confirmed a fulfilling robustness among various aryl/heteroaryl and indazole scopes.