Single atom transformations in modern synthetic chemistry are increasingly desirable to enable retrosynthetically intuitive permutations of privileged scaffolds but are often limited in scope. Herein, we report a reaction that selectively cleaves the N-N bond of pyrazoles and indazoles cores to afford pyrimidine and quinazolines respectively by use of aryl carbynyl cation equivalents. As previously used for the skeletal editing of pyrroles and indoles, α-chlorodiazirines serve as convenient chlorocarbene precursors, allowing for quick thermal access to the requisite intermediate. Additionally, one-step preparation of the diazirines via the oxidation of a wide variety of commercially available amidinium salts facilitates access to a wide variety of carbynl cation equivalents. DFT calculations support a unique ring opened vinyl di-imine intermediate that rapidly cyclizes to yield the new azine core after deprotonation. Furthermore, successful editing of pharmaceutical cores and precursors using this methodology provides further evidence for the utility of skeletal editing in late-stage settings.

Skeletal editing of pyrazoles and indazoles mediated by chlorodiazirines

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