Transition‐Metal‐Free [4+1] Cycloaddition for the Synthesis of 1,2,3‐Triazole from α,α‐Difluoro‐N‐Tosylhydrazone and Amine through C‐F Bond Cleavage

Abstract

An efficient synthesis of 1,4‐disubstituted and 1,4,5‐trisubstituted 1,2,3‐triazole from α,α‐difluoro‐N‐tosylhydrazone and amine through a C−F bond cleavage protocol has been developed. α,α‐Difluoro‐N‐tosylhydrazone is used as a new reagent, which can transform amines to 1,2,3‐triazoles with high efficiency and excellent functional group compatibility without using transition‐metal catalysts, azide reagents and oxidants.

Multiple-fold C–F bond functionalization for the synthesis of (hetero)cyclic compounds: fluorine as a detachable chemical handle

“…In multifarious reports, Wang and co-workers were able to establish a sequential defluorination/aza-Michael addition/intramolecular cyclization cascade for the synthesis of 1,4-disubstituted and 1,4,5-trisubstituted 1,2,3-triazoles from α,α-difluoro- N -tosylhydrazones and amines (Scheme 32A). 62 The reaction proceeded through the scission of two inert C(sp 3 )–F bonds under metal-free, azide-free, and oxidant-free conditions. Nevertheless, the reaction of α,α,α-trifluoro- N -tosylhydrazone and p -toluidine was conducted to give a three C–F bonds cleaved product 32-4 in 9% yield.…”

Emerging Trends in N‐Tosylhydrazone Mediated Transition‐Metal‐Free Reactions

“…Zhou et al [82] suggested a highly effective technique for the synthesis of 1,4-disubstituted and 1,4,5-trisubstituted triazole 50 employing difluoro-N-tosylhydrazone and amine via carbon-fluoro bond cleavage in a transition metal-free, mild conditions. The substrate with the electron-donating group in the aromatic amine provided a great yield; however, when the aromatic amine's para-position was switched with the electron-withdrawing ester group, the productivity decreased.…”

Recent Progress in Catalytic Synthesis of 1,2,3-Triazoles

“…A review of 2017 summarized the sign of progress in the synthesis of 1,2,3-triazoles without any transition metal or azide [58], but very recently, different works were reported in the literature on the green cycloaddition of tosylhydrazones with a suitable leaving group in α-position. Zhou et al, in 2019, used α,α-difluoro-N-tosylhydrazones 44 to carry out the synthesis of 1,2,3-triazoles through the cleavage of C-F bonds, despite this is one of the strongest single bonds [59]. In this way, it was possible to perform this reaction also on aryl substrates, unlike α,α-dichloro-N-tosylhydrazones, which limited the reactivity to the alkyl groups.…”