Metal-free syntheses ofN-functionalized andNH-1,2,3-triazoles: an update on recent developments

Abstract

An overview of the latest developments (2016–August 2020) in the metal-free synthesis of non-benzo-fused N-functionalized and NH-1,2,3-triazoles is provided in this feature article.

4,5,6,7-Tetrahydroindol-4-Ones as a Valuable Starting Point for the Synthesis of Polyheterocyclic Structures

“…Very recently, our group reported the synthesis and spectroscopic properties of novel 1,2,3-triazole BOPAHY dyes and their corresponding triazolium salts ( Scheme 30 ) [ 84 ]. Thus, we started from N -tosyl-4,5,6,7-tetrahydroindol-4-one 118 and performed our in-house developed general metal-free triazolization reaction [ 85 , 86 , 87 , 88 , 89 ]. This route toward 1,2,3-triazoles starts from enolizable ketones, primary amines and 4-nitrophenyl azide as diazo-transfer agent.…”

Recent advances in transition metal-free annulation toward heterocycle diversity based on the C–N bond cleavage of enaminone platform

“…As easily accessible and highly reactive building blocks, enaminones and analogous stable enamines have been widely used in the construction of cyclic compounds, especially nitrogen-containing heterocyclic compounds. 1 Generally, depending on the substitution style of the amino group in enaminones and/or reaction conditions, the amino group in enaminones may undergo two major types of transformations: the cleavage of C–N bonds or the nucleophilic reaction of the amino group without C–N bond cleavage. Actually, both transformation modes have found broad and significant application in devising highly enriched synthetic methods.…”

1-(4-Nitrophenyl)-1H-1,2,3-Triazole-4-carbaldehyde: Scalable Synthesis and Its Use in the Preparation of 1-Alkyl-4-Formyl-1,2,3-triazoles

“…Interestingly, a procedure was developed starting from FNPT 1a and primary amines that allowed for protein modification in excellent conversions without isolating the targeted aldehydes 7. Following our ongoing interest in the synthesis of 1,2,3-triazoles [36][37][38], we recognized the potential of this approach for the metal-free synthesis of 1-alkyl-4-formyl-As described by L'abbé, the equilibrium of the Cornforth rearrangement is shifted toward the triazole with the most electron-deficient substituent on the imine nitrogen. Fletcher et al, who further studied this rearrangement in 2018, observed the same trend [34].…”

“…Interestingly, a procedure was developed starting from FNPT 1a and primary amines that allowed for protein modification in excellent conversions without isolating the targeted aldehydes 7. Following our ongoing interest in the synthesis of 1,2,3-triazoles [36][37][38], we recognized the potential of this approach for the metal-free synthesis of 1-alkyl-4-formyl-1,2,3-triazoles 7. However, to the best of our knowledge, a metal-free and straightforward synthesis of FNPT 1a on a preparative scale was still lacking.…”

“…To the best of our knowledge, the reaction of aminoacroleins with azides was not further studied. As enamines are among the best known starting materials for the synthesis of 1,2,3-triazoles [36,37,40,41], it is rather surprising that the commercially available and rather inexpensive 3-dimethylaminoacrolein 9a somehow remained unnoticed as a possible reagent for the synthesis of 4-formyl-1,2,3-triazoles.…”