Photocatalytic Asymmetric Oxidation of Phosphines with Water

Abstract

P-chiral tertiary phosphine oxides (TPOs) hold significant synthetic value due to their capacity to serve as versatile precursors for a wide range of valuable P-chiral phosphorus-containing compounds. However, the direct asymmetric oxidation of readily available phosphines into these TPOs remains a substantial challenge, as no efficient and practical methods have been reported to date. In this study, we present the first catalytic asymmetric approach to access P-chiral TPOs through a photoredox-mediated radical process. This strategy is conceptually inspired by a known photoredox catalytic system employed in phosphine-mediated deoxygenation reactions, wherein TPOs are typically formed as side products. The method utilizes an azaarene-substituted ketone-based oxidant, which, upon single-electron reduction, generates a highly reactive radical anion base. This key intermediate facilitates the activation of a chiral phosphoric acid (CPA), releasing a CPA anion that plays a critical role in stereocontrol during the hydration of phosphine radical cations. The reaction proceeds with high efficiency (up to 96% yield) and excellent stereoselectivity (up to 99% ee), employing water as a sustainable oxygen source. The operational simplicity and atom economy of this methodology are further demonstrated through successful application in 18 O-isotopic labeling experiments using H 2 18 O, thereby enabling the efficient synthesis of isotopically labeled P-chiral TPOs. Beyond exemplifying an innovative transformation that converts byproducts into valuable chemical entities, this work significantly expands the synthetic potential of Brønsted base catalysis in controlling radical reactivity with precise stereochemical outcomes.

Topics & Concepts