Photoredox-Catalyzed Vinylogous Benzylation of 2-Silyloxyfurans via Divergent Radical Pathways

The use of 2-silyloxyfurans as versatile vinylogous nucleophiles[1] has enabled the synthesis of diverse γ-butenolide and butyrolactone scaffolds, which display many biological activities.[2] Despite their well-established role in polar transformations, their application in radical chemistry remains underexplored. In a recent work,[3] we developed two complementary, visible light-mediated benzylation strategies involving 2-silyloxyfurans 1 and redox-active esters 2 as radical precursors (Scheme 1). Central to both approaches is the photoredox generation[4] of benzyl radical species 2•, which engage in divergent reaction pathways. In one case, oxidation of the silyloxyfuran leads to a reactive silyl radical cation 1•+, enabling radical-radical coupling. Alternatively, with electron-rich systems, a radical-polar crossover occurs to form a benzyl carbocation (2+), hence promoting a Mukaiyama-type benzylation. These pathways grant access to a range of chiral γ-benzyl butenolides 3, which serve as valuable intermediates in the synthesis of phenyl-γ-valerolactone derivatives with demonstrated anti-inflammatory and antioxidant properties. The synthesis optimization and scope, the regioselectivity issues, as well as experimental and DFT-supported insights supporting the proposed mechanisms will be discussed.