Electrochemical Synthesis of a Sitagliptin Precursor.
Elisabeth K OehlPaul T JirschJasmin HammesAndreas StengleinMaría MéndezSven RufSiegfried R WaldvogelPublished in: The Journal of organic chemistry (2024)
A novel synthesis of sitagliptin based on a redox-active ester derived from the chiral pool is reported. The key step is an electrochemical nickel-catalyzed sp 2 -sp 3 cross-coupling reaction using inexpensive nickel foam in an undivided cell. It was successfully applied to 21 examples in up to 88% yield. These sitagliptin-analogue precursors could potentially interact with the DPP4 enzyme. A full synthesis based on our new reaction pathway provided sitagliptin in an overall yield of 33%.