Reaching Green: Heterocycle Synthesis by Transition Metal‐Catalyzed C−H Functionalization in Sustainable Medium

Abstract

Catalytic CÀHf unctionalization has emerged as an efficient alternative to traditional coupling reactions. However,s omeo ft hese reactions depend on environmentally harmful solvents, weakening the overall green nature of these methods. As organic processes consume large amount of solvents, the use of less harmful solvents enhance the sustainability of these reactions. Herein, we present an overview of transition metal-catalyzed CÀHf unctionalization reactions for the synthesis of heterocycles in sustainable solvents based on CHEM21 solvent selection guide.[a] Dr.

Recent Advances in Radical C−H Bond Functionalization of Imidazoheterocycles

“…In 2017, Sun group developed a visible light-induced C3-sulfonamidation of imidazo[1,2-a]pyridines 1 with N-alkylsulfonamides 64 using Ir(ppy) 3 (dtbbpy)PF 6 as the photocatalyst and aqueous NaClO solution as an oxidant in 1,4-dioxane at room temperature for 5 h (Scheme 41). [63] This method was also applicable to other related imidazoheterocycles (2)(3)(4)(5) to give the products 65 in 42-75% yields. Comparatively, EDGs containing N-methyl-sulfonamides 64 yielded the desired products 65 in better yields.…”

“…In 2017 Fu group [31] reported C3-difluroacetylation of imidazo[1,2-a]pyridines 1 with difluroacetyl source (BrCF 2 COOEt) using similar reaction conditions as described by Xu and co-workers [30] Recently, Xu and co-workers described a visible light-induced, TMEDA-mediated difluoroalkylation of imidazo[1,2-a]pyridines 1 using 2-bromo-2,2-difluoroethanones 25 in CH 3 CN at room temperature under inert atmosphere (Scheme 14). [32] Different substituted imidazoheterocycles (1)(2)(3) worked well under the established reaction conditions and produced the desired products 26 in 46-88% yields. The use of TEMPO in the reaction completely quenched the reaction while use of DPE in the reaction significantly reduced the yield of the product and 1,1-diphenylethylene (DPE) adduct of CF 2 COPh was isolated in 70% yield.…”

“…Substrates with strongly electron-withdrawing groups (EWGs) on any of the rings of imidazo [1,2-a]pyridine afforded lower yields as compared to the substrates with electron-donating groups (EDGs). The method was successfully applied to imidazo [2,1-b]thiazoles (2) and imidazo [2,1-b]benzothiazoles (3). Mechanistic studies revealed that the bridging methylene group arises from DMSO and reaction proceeds through a radical pathway as the addition of radical inhibitors like TEMPO (2,2,6,6-Tetramethyl-1-piperidinyloxy) or BHT (butylated hydroxytoluene) resulted in complete inhibition of the product formation.…”

“…The direct functionalization of CÀ H bonds has emerged as a powerful synthetic tool in organic synthesis in last two decades. [1] Various strategies using transition metal catalysis, [2] photocatalysis, [3] organocatalysis, [4] electrocatalysis, [5] enzyme catalysis, [6] and metal-free reactions [7] have been developed for the direct CÀ H bond functionalization. In recent years, radical-mediated direct CÀ H bond functionalization has emerged as promising and ideal approach in organic synthesis due to relatively high atom-and step-economy.…”

Metal-Promoted Heterocyclization: A Heterosynthetic Approach to Face a Pandemic Crisis

“…Metal-catalyzed protocols, involving all metals from transition to rare-earth metals, have attracted the attention of chemists as compared to other synthetic methodologies because they directly employ easily available substrates to build multi-substituted complex molecules under mild conditions. Metal-catalyzed heterocyclization starting from acyclic precursors is considered a very performant tool in drug synthesis [ 26 ]. In this review, we focus our attention on metal-catalyzed heterocyclization methodologies for achieving pivotal scaffolds associated with molecules showing anti-COVID-19 properties.…”