Base-Promoted Tandem S_NAr/Boulton–Katritzky Rearrangement: Access to [1,2,4]Triazolo[1,5-a]pyridines

Abstract

A base-promoted tandem S N Ar/Boulton−Katritzky rearrangement is developed. It offers a simple and straightforward method for the formation of functionalized [1,2,4]triazolo [1,5-a]pyridines from 1,2,4-oxadiazol-3-amines or 3-aminoisoxazoles with 2-fluoropyridines.[1,2,4]Triazolo[1,5-a]pyridine is one of the most privileged skeletons and has been extensively found in many bioactive natural products, drug candidates, and pharmaceuticals (Figure 1). 1 Due to their biological importance, [1,2,4]triazolo[1,5a]pyridine compounds have attracted a great deal of interest from the synthetic community. Many elegant approaches have been developed and applied for their syntheses. Such structures are generally acquired through metal-mediated or metal-free oxidative cyclization from N-(2-pyridyl) amidines and dehydrative cyclization from N′-hydroxy-N-formimidamides. 2,3 Despite this success, exploring more straightforward and practical methods for the construction of this class of biologically important structures is still highly desirable.

Ionic Liquid Supported on Magnetic Graphene Oxide as a Highly Efficient and Stable Catalyst for the Synthesis of Triazolopyrimidines

“…It is known that the condensation of triazole and pyrimidine leads to the formation of bicyclic heterocycles known as triazolopyrimidines, which exhibit a wide range of biological properties. [38][39][40] Triazolopyrimidines can be used in a variety of synthetic pharmacophores. In addition, they are valuable building blocks for the structure of many herbicides such as penoxsulam, diclosulam, flumetsulam, azafenidin, and floransulan.…”

Structural Evidence for Aromatic Heterocycle N–O Bond Activation via Oxidative Addition

“…Medicinal chemistry routinely employs heterocyclic scaffolds, which are found in a large number of marketed pharmaceuticals . Isoxazoles and related heterocycles containing N–X (X = N, O, S) bonds are widely utilized, − rendering cross-coupling of substrates bearing these scaffolds a particularly important transformation. ,− There are many examples of reactions in which the N–O bond of isoxazoles, benzisoxazoles, or anthranils is functionalized, either under thermal, , Brønsted basic, − Lewis acidic, or transition-metal-catalyzed conditions. − Isoxazoles are also known to decompose under basic conditions, for example, in the Kemp elimination or the Boulton–Katritzky rearrangement. ,, These transformations provide information on possible decomposition pathways during attempted cross-coupling.…”

“…17−19 Isoxazoles are also known to decompose under basic conditions, for example, in the Kemp elimination 18 or the Boulton−Katritzky rearrangement. 13,14,20 These transformations provide information on possible decomposition pathways during attempted cross-coupling.…”

Structural Evidence for Aromatic Heterocycle N–O Bond Activation via Oxidative Addition

“…1 Isoxazoles and related heterocycles containing N-X (X = N, O, S) bonds are widely utilized, [1][2][3][4][5][6][7] rendering crosscoupling of substrates bearing these scaffolds a particularly important transformation. 3,[8][9][10] There are many examples of reactions in which the N-O bond of isoxazoles, benzisoxazoles or anthranils is functionalized, either under thermal, 11,12 Bronsted basic, [13][14][15] Lewis acidic 16 or transition-metal catalyzed conditions. [17][18][19] Isoxazoles are also known to decompose under basic conditions, for example in the Kemp elimination 18 or the Boulton-Katritzky rearrangement.…”

“…[17][18][19] Isoxazoles are also known to decompose under basic conditions, for example in the Kemp elimination 18 or the Boulton-Katritzky rearrangement. 13,14,20 These transformations provide information on possible decomposition pathways during attempted cross-coupling.…”