Given
the ubiquity of heterocycles in biologically active
molecules,
transformations with the capacity to modify such molecular skeletons
with modularity remain highly desirable. Ring expansions that enable
interconversion of privileged heterocyclic motifs are especially interesting
in this regard. As such, the known mechanisms for ring expansion and
contraction determine the classes of heterocycle amenable to skeletal
editing. Herein, we report a reaction that selectively cleaves the
N–N bond of pyrazole and indazole cores to afford pyrimidines
and quinazolines, respectively. This chlorodiazirine-mediated reaction
provides a unified route to a related pair of heterocycles that are
otherwise typically prepared by divergent approaches. Mechanistic
experiments and DFT calculations support a pathway involving pyrazolium
ylide fragmentation followed by cyclization of the ring-opened diazahexatriene
intermediate to yield the new diazine core. Beyond enabling access
to valuable heteroarenes from easily prepared starting materials,
we demonstrate the synthetic utility of skeletal editing in the synthesis
of a Rosuvastatin analog as well as in an aryl vector-adjusting direct
scaffold hop.