Photoredox generated carbonyl ylides from epoxides
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Cyclic ethers, specifically, tetrahydro-, dihydro-, and furans, are pervasive and essential features in biologically active natural products and pharmaceuticals. The synthesis of cyclic ethers with atom, redox, and time economy is therefore desirable. Herein, we describe studies that led to the conception and development of photoredox methodologies that are able to catalytically generate carbonyl ylides from epoxides. These can be engaged in [3+2] dipolar cycloadditions with dipolarophiles to afford densely functionalized cyclic ethers in a sole, redox-neutral chemical operation. The invention of this technology hinged on the discovery of two unique photoredox catalysts that, in parallel, are able to mitigate the emerging challenges of generating electronically diverse carbonyl ylides. Empirical and theoretical studies of this reaction ultimately led to the proposal and validation of a general paradigm that can be used to assert a priori whether carbonyl ylide formation is possible from an epoxide. Lastly, the application of this methodology to a bioinspired, unified synthesis of the classical lignan family of natural products is described. This chemistry was accomplished by intercepting Nature’s route at a pivotal intermediate, which served as a nodal scaffold for the synthesis of all eight members found within classical lignans.