Demonstrates efficient skeletal remodeling of oxetanes, suggesting a significant advancement in drug discovery.
Deleting an atom from a heterocycle to reduce ring size or remodel the skeleton represents a unique approach to navigate untapped regions of the chemical space. However, compared with well-established nitrogen-deletion manifolds, the precise recognition and excision of an oxygen atom from a functionalized cyclic ether remains challenging. Here we report a catalyst-free photoinduced oxygen deletion strategy that achieves highly chemo- and regioselective restructuring of oxetanes. The reaction involves a deoxygenative ring deconstruction step to generate an acyclic diiodide intermediate using iodoform under photoirradiation, followed by intramolecular reductive coupling or cyclization/functionalization. This method enables efficient ring contraction or skeletal remodeling of oxetanes, granting streamlined access to families of cyclopropane and benzoheterocycle frameworks in a straightforward fashion. Excellent functional group tolerance is demonstrated through late-stage functionalization and simplified syntheses of pharmaceuticals, which are expected to make a profound impact on drug discovery by reducing the synthetic burden of assembling bioactive molecules.
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Zhang et al. (2026) studied this question.
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