Cu(I)‐Catalyzed Three‐Component Coupling of Trifluoromethyl KetoneN‐Tosylhydrazones, Alkynes and Azides: Synthesis of Difluoromethylene Substituted 1,2,3‐Triazoles

Abstract

A CuI-catalyzed three-component coupling of trifluoromethyl ketone N-tosylhydrazones, alkynes and azides has been developed. The reaction represents a straightforward method to access difluoromethylene substituted 1,2,3-triazoles. Mechanistically, it has been proposed that the reaction follows a pathway involving the formation of Cu(I) triazolide intermediate, Cu(I) carbene formation, migratory insertion, and β-fluoride elimination. The transformation is featured by mild conditions, wide substrate scope and high efficiency. Scheme 1 Cu(I)-catalyzed three-component reaction involving triazolide copper carbene intermediateExperimental General procedure for the Cu(I)-catalyzed reaction Under nitrogen atmosphere, CuI (7.6 mg, 0.04 mmol, 20 mol%), LiO t Bu (32 mg, 0.4 mmol, 2.0 equiv.) CF 3bearing N-tosylhydrazones (1, 0.20 mmol) were succes-COMMUNICATION Zhang et al. 388 www.cjc.wiley-vch.de

Transition-Metal-Catalyzed Cross-Couplings through Carbene Migratory Insertion

“…Recently, Wang and co-workers disclosed that the use of trifluoromethyl ketone derived N -tosylhydrazones as substrates would produce difluoromethylene substituted 1,2,3-triazoles ( 606 ) . Instead of protonation process, a β-fluoride elimination occurs exclusively to finish the catalytic cycle in this transformation (Scheme b).…”

“…Recently, Wang and co-workers disclosed that the use of trifluoromethyl ketone derived N-tosylhydrazones as substrates would produce difluoromethylene substituted 1,2,3-triazoles (606). 301 Instead of protonation process, a β-fluoride elimination occurs exclusively to finish the catalytic cycle in this transformation (Scheme 90b). These two reactions serve as good examples on the combination of click chemistry with carbene coupling process and provide a general methodology to access highly functionalized 1,2,3-triazoles in a regioselective manner.…”

Transition‐Metal‐Catalyzed Reactions Involving Trifluoro Diazo Compounds and Their Surrogates

“…They continued to explore an efficient and regioselective method for the synthesis of difluoromethylene substituted 1,4,5‐trisubstituted 1,2,3‐triazoles 194 through CuI‐catalyzed three‐component coupling of trifluoromethyl ketone N ‐tosylhydrazones 191 , alkynes 192 and azides 193 in 2017 (Scheme 30). [61] Mechanistically, they proposed that the reaction follows a cascade process involving the formation of [2+3] cycloaddition, Cu(I) carbene formation, migratory insertion, and β ‐fluoride elimination.…”

C–F bond functionalizations via fluorinated carbenes

“…96 Furthermore, they found that CF 3 -bearing N-tosylhydrazones with other substrates could undergo [3 + 2] cycloaddition and a consequent fluorine elimination pathway to generate multisubstituted 5-(difluoromethylene)-1,2,3-triazoles (Scheme 32). 97 Under the promotion of copper and a base, terminal alkynes and azides undergo a In 2020, Koenig and colleagues demonstrated that 2,2,2-trifluorodiazo derivatives could undergo a C-H bond insertion and C-F functionalization reaction with indoles at room temperature under palladium-catalyzed conditions, allowing for the direct one-step synthesis of gem-difluoroolefin analogues. They proposed a reasonable reaction pathway.…”

“…96 Furthermore, they found that CF 3 -bearing N -tosylhydrazones with other substrates could undergo [3 + 2] cycloaddition and a consequent fluorine elimination pathway to generate multisubstituted 5-(difluoromethylene)-1,2,3-triazoles (Scheme 32). 97 Under the promotion of copper and a base, terminal alkynes and azides undergo a click transformation to produce copper triazolide intermediate A via metalation of the triazole C–H bond. Then this intermediate A is trapped by trifluoromethyl N -tosylhydrazone 77 to produce copper-complex B , which is followed by the 1,2-shift of triazole and β-fluoride elimination to give corresponding products 101 via intermediate C .…”