Denitrogenative Transformations of Pyridotriazoles and Related Compounds: Synthesis of N-Containing Heterocyclic Compounds and Beyond

Abstract

The high demand for new and efficient routes toward synthesis of nitrogencontaining heterocyclic scaffolds has inspired organic chemists to discover several methodologies over recent years. This Perspective highlights one standout approach, which involves the use of pyridotriazoles and related compounds in denitrogenative transformations. Readily available pyridotriazoles undergo ring−chain isomerization to produce uniquely reactive α-diazoimines. Such reactivity, enabled by metal catalysts, additives, or visible-light irradiation, can be applied in transannulation, insertion, cyclopropanation, and many other transformations.

Access to 6-hydroxy indolizines and related imidazo[1,5-a]pyridines through the SN2 substitution/condensation/tautomerization cascade process

“…[6][7][8][9][10][11] As a consequence, much effort has been devoted to their synthesis and functionalization, and thus many methods have been developed. [12][13][14] In addition to classical Scholtz or Tschichibabin reactions, a variety of straightforward and efficient methods have been reported in recent years 15-20 including 1,3-dipolar cycloaddition of pyridinium salts and intramolecular cyclization catalyzed by transition metals and intermolecular cyclization. Despite the efficiency of these methods, they suffer from the requirement of specic preorganized substrates, necessity of expensive metal catalysts, multistep synthesis, and a lack of product diversity.…”

Azide–alkyne cycloadditions with an electronically activated alkyne: indole formationvia1-aryl-1,2,3-triazole-derived imino carbenes

“…With metal catalysts, triazoles have been shown to participate in a diverse range of denitrogenative coupling reactions, thereby converting readily available triazoles into valuable nitrogen heterocycles and complex products. 4–6 These transformations are efficiently promoted by metal-carbene formation from the diazo form, which is induced by electron-withdrawing substituents such as acyl or sulfonyl groups bound to the triazole nitrogen atoms. In view of the Dimroth rearrangement, 7 in which triazoles bearing amino groups on the carbon atoms readily undergo isomerisation via diazo-imine intermediates, the reactive ring-opened diazo form is also favoured in triazoles featuring electron-rich exocyclic substituents on the carbon atom.…”

“…Under the thermal reaction conditions, the triazoles appear to be thermally unstable and readily extrude dinitrogen to furnish reactive α-imino carbene intermediates. 4–6 Generation of transient carbenes in our reactions is likely promoted by the electron-donating piperidyl substituents, which provide electronic and steric stabilisation to the carbene centre. They then seem to readily undergo an intramolecular ortho -C–H activation (C–C activation in the case of 3 ) at the aryl ring to afford the indole products.…”

Transannulation of Pyridotriazoles with Naphthoquinones and Indoles: Synthesis of Benzo[f]Pyrido[1,2‐a]Indoles and Indolizino[3,2‐b]indoles

“…Denitrogenative transformation of pyridotriazoles with different nucleophiles to generate N-containing heterocycles are of paramount important molecules in drugs, and material chemistry. [1] Among various N-heterocycles, pyridine fused heterocycles are important intermediates in both medicinal chemistry and drug development. [2a] One of the pyridine fused heterocycle indolizine is an isoster of indole and frequently found in bioactive compounds and received much attention in recent years due to their various pharmaceutical applications.…”

“…The reaction of 5-methoxynaphthalene-1,4-dione with ethyl[1,2,3]triazolo[1,5-a]pyridine-3-carboxylate and n-butyl [1,2,3]triazolo [1,5-a]pyridine-3-carboxylate gave the desired annulated products 3 z and 3 aa in 62% and 78% yields respectively. We also checked the reaction of 1,2 naphthoquinone with ethyl[1,2,3] Table 1.…”