Development of a General Organophosphorus Radical Trap: Deoxyphosphonylation of Alcohols

J Am Chem Soc. 2024 Mar 27;146(12):7942-7949. doi: 10.1021/jacs.4c00557. Epub 2024 Mar 12.

Abstract

Here we report the design of a general, redox-switchable organophosphorus alkyl radical trap that enables the synthesis of a broad range of C(sp3)-P(V) modalities. This "plug-and-play" approach relies upon in situ activation of alcohols and O═P(R2)H motifs, two broadly available and inexpensive sources of molecular complexity. The mild, photocatalytic deoxygenative strategy described herein allows for the direct conversion of sugars, nucleosides, and complex pharmaceutical architectures to their organophosphorus analogs. This includes the facile incorporation of medicinally relevant phosphonate ester prodrugs.