[3 + 2] Cycloaddition of Isocyanides with Aryl Diazonium Salts: Catalyst-Dependent Regioselective Synthesis of 1,3- and 1,5-Disubstituted 1,2,4-Triazoles

Abstract

An unprecedented catalyst-dependent regioselective [3 + 2] cycloaddition of isocyanides with aryl diazonium salts is reported. 1,3-Disubstituted 1,2,4-triazoles were selectively obtained in high yield under Ag(I) catalysis, whereas 1,5disubstituted 1,2,4-triazoles were formed by Cu(II) catalysis. These catalytic methodologies provide a controlled, modular, and facile access to 1,2,4-triazole scaffolds with high efficiency, broad substrate scope, and excellent functional group compatibility.

Aryl DiazoniumSalt‐TriggeredCyclization and Cycloaddition Reactions: Past, Present, and Future

“…Subsequently, a divergent intermolecular addition and cyclization of isocyanides 111 with aryl diazonium salts 30 was presented by Bi and co‐workers (Scheme 28). [ 156 ] Based on the protocols of Matsumoto and van Leusen (Scheme 24), the additions of Cu and Ag catalysts allowed the regiospecific access to 1,5‐ and 1,3‐disubstituted 1,2,4‐triazoles ( 112 and 113 ), respectively. The regio‐differentiation hinges on the Cu‐induced addition of isocyanide's terminal carbon ( 114 ) and Ag‐induced addition of isocyanide's α‐carbon ( 115 ) to the aryl diazonium ion.…”

Silver‐Induced [3+2] Cycloaddition of Isocyanides with Acyl Chlorides: Regioselective Synthesis of 2,5‐Disubstituted Oxazoles

“…Then, the AgMOF catalyst interacts with 6 to form a nitrilium intermediate 7 . A subsequent 1,3‐H shift occurs to give intermediate 8 , which can be transformed to the desired product 3 through two possible pathways. One pathway is similar to El Kaïm's work (Pathway B) in which species 8 undergoes a deprotonation sequence to form nitrilium adduct 10 that subsequently cyclizes to form the desired product 3 .…”

Design and synthesis of coumarin-triazole hybrids: biocompatible anti-diabetic agents, in silico molecular docking and ADME screening

“…Five-membered heterocycles, specifically, 1,2,4-triazoles plays a pivotal role in medicinal chemistry for their versatile applications. 1,2,4-Triazoles were synthesized by; a cycloaddition of nitriles and amidines in the presence MCM-41/copper(I) complex as heterogeneous catalyst [12], iodine catalyzed multicomponent reaction of aryl hydrazines, paraformaldehyde, NH 4 OAc, and alcohols under electrochemical conditions [13], regio-selective synthesis involving Ag(I) catalyzed reaction of ethyl cyanoacetate with aryldiazoniumtetrafluoroborate in water at 0 C [14], Iodine catalyzed environmentally benign C-N bond formation from isothiocyanates in water at room temperature [15], palladium and copper catalyzed arylation of styrene [16], triflic anhydride activated microwave-induced one-pot synthesis involving secondary amides and hydrazides [17], and by the reaction of hydrazides with isothiocyanate under optimized reaction conditions [18] 1,2,4-Triazoles were reported to show DHFR inhibitor [19], and antimicrobial [20] activities.…”