Diazo Activation with Diazonium Salts: Synthesis of Indazole and 1,2,4-Triazole

Abstract

A donor/acceptor diazo activation strategy, processing via condensation using diazonium salts without the addition of any other catalysts or reagents, is reported. The diazenium intermediate was found to undergo cyclization to give indazoles in excellent yields. Alternatively, in the presence of nitriles, substituted 1,2,4-triazoles were obtained in good to excellent yields. This interesting diazenium route provides a new approach to achieve complex heterocycle synthesis under mild conditions.

Cu‐Catalysed Three‐Component Reaction of Aryldiazonium Salts with Fluorinated Diazo Reagents and Nitriles: Access to Difluoro‐ and Trifluoromethylated N1‐Aryl‐1,2,4‐triazoles

“…Subsequently, Wan and Bao developed a [3+2] annulation reaction of ester‐derived nitrile ylides with aryldiazonium salts to form N 1 ‐aryl‐5‐carboxylic‐1,2,4‐triazoles . Inspired by these studies and as part of our continuing interest in fluoroalkyl heterocycles, here we present the synthesis of both difluoro‐ and trifluoromethylated N 1 ‐aryl‐1,2,4‐triazoles enabled by a novel multicomponent reaction of aryldiazonium salts with fluorinated diazo reagents and nitriles (Scheme b) . The regioselectivity is controlled by a copper‐catalysed [3+2] annulation process of in situ formed nitrile ylide intermediate with aryldiazonium salt.…”

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

“…Very recently, Shi and Wang disclosed a new indazole synthesis from aryl diazonium salts 30 and aryl diazo esters 70 (Sheme 16). [ 97 ] The reaction proceeds through the formation of diazenium 72 as the key intermediate. This practical catalyst‐free protocol allows the preparation of a broad scope of 3‐ester‐ functionalized indazoles 71 in moderate to good yields.…”

“…In the report by Shi and Wang, a metal‐free synthesis of tri‐substituted 1,2,4‐triaozoles 122 was presented by using donor/ acceptor diazo compounds [ 97 ] (Scheme 30). α‐Substituted diazoester 121 could form resonance hybrid 123 , which served as a nucleophile (donor) to attack the terminal nitrogen of aryl diazonium ion (acceptor).…”

Metal‐free Decarboxylative Annulation of 2‐Aryl‐2‐isocyano‐acetates with Aryldiazonium Salts: General Access to 1,3‐Diaryl‐1,2,4‐triazoles

“…Since Krapcho-type decarboxylation was proposed in triazole synthesis with methyl diazoacetate, [16] we also probed such feasibility in the protocol. In the presence of excess sodium 4-tert-butylbenzoate as base, 3 a was formed with the concomitant isolation of methyl 4-tert-butylbenzoate 9 in 40% yield (Scheme 6g).…”