Impact of Carbon-Based Anode Materials on Selectivity in a Shono Oxidation and Scale Up to Deca-Kilogram Scale

We report the development of a selective and scalable Shono oxidation process of Boc- l -proline methyl ester (Boc- l -Pro-OMe) using flow electrosynthesis. A key feature of the reaction is the preferential methoxylation of Boc- l -Pro-OMe at its C5 carbon over oxidation at its C2 carbon. Different forms of carbon-based materials (porous graphite, resin-filled graphite, graphite foil, and graphite felts) were explored for the anode material in a Shono oxidation of Boc- l -Pro-OMe, and their impact on selectivity was characterized. Ultimately, an inexpensive carbon-based anode that is able to accommodate high current density was identified, thus enabling high productivity for the formation of the N,O-acetal product. We demonstrate the electrochemical process on two different scales using a parallel plate electrochemical reactor operating in a recirculating mode. A lab-scale setup with a footprint fitting within a standard fume hood was used to process ca. 0.7 kg of Boc- l -Pro-OMe per day. The use of a pilot-scale parallel plate reactor equipped with 0.4 m 2 anode surface area of inexpensive electrode materials enabled deca-kilogram scale deployment of the process suitable to electrolyze 13 kg of Boc- l -Pro-OMe per day.