Triazolopyridines are an important class of heterocycles in the pharmaceutical industry and materials sciences. In particular, 1,2,3triazolo1,5apyridines have emerged as stable and versatile diazo compound precursors for performing carbene-mediated transformations. Despite their wide range of applications in chemical synthesis, their preparation is often reliant on oxidative cyclization methods using stoichiometric oxidants in an organic solvent, limiting their application in chemoenzymatic synthesis. We have recently discovered that vanadium-dependent haloperoxidase (VHPO) enzymes are effective catalysts for performing the oxidative cyclization of 2-pyridyl ketone hydrazones to give 1,2,3triazolo1,5apyridines through cryptic diazo formation. Herein, we have developed a chemoenzymatic protocol for conversion of 2-pyridyl ketones to 1,2,3triazolo1,5apyridines in a single vessel through the in situ generation of 2-pyridyl ketone hydrazones followed by VHPO-catalyzed oxidative cyclization to give 1,2,3triazolo1,5apyridines in high yield and chemoselectivity.
Sharma et al. (Mon,) studied this question.