Recyclable and Scale-Up-Compatible Ag/I-Mediated Synthesis of Aryl α-Keto Acids from Terminal Alkenes Using Dioxygen as the Terminal Oxidant

Abstract

Abstract α-Keto acids are vital intermediates in organic synthesis and biological metabolism, yet existing synthetic methods suffer from low efficiency, harsh conditions, or poor environmental compatibility. Herein, we report a recyclable and scale-up-compatible Ag/I-mediated aerobic oxidation system for converting terminal aryl alkenes to aryl α-keto acids. The reaction uses commercially available Ag2O as the silver source, molecular oxygen as the terminal oxidant, and iodine-containing species as recyclable redox mediators in dimethyl sulfoxide (DMSO)/H2O under a stepwise heating protocol. This method delivers up to 85% isolated yield across various substrates. For the model reaction, scale-up from 1 to 100 mmol resulted in only a modest decrease in isolated yield from 75 to 69% under atmospheric O2 flow. Notably, the Ag-containing solid and iodine-containing species could be recovered and reused over five cycles. Mechanistic studies support a plausible sequential pathway involving silver-mediated epoxidation, DMSO-mediated ring-opening and oxidation, and iodine-promoted oxidation of the α-keto aldehyde intermediate. Process-relevant oxygen-delivery experiments further showed that pressurized continuous O2 flow at 1.0 MPa afforded the model aryl α-keto acid in 80% LC yield within 8 h, corresponding to the highest space-time yield among the examined modes. This Ag/I-mediated aerobic oxidation provides a practical complementary route to aryl α-keto acids from readily available terminal alkenes, while identifying oxygen delivery and off-gas management as important parameters for further scale-up.