Ru-catalyzed enantioselective preparation of methyl (R)-o-chloromandelate and its application in the synthesis of (S)-Clopidogrel

The preparation of methyl (R)-o-chloromandelate via Ru-catalyzed asymmetric hydrogenation and transfer hydrogenation was investigated. With Ru-(R,R)-2,4,6-triisopropyl C6H2SO2-DPEN as the catalyst and HCOOH–Et3N azeotrope as the hydrogen donor, up to 92% ee was obtained in an optional condition. The synthesis of (S)-Clopidogrel was also studied.

Graphical abstractThe preparation of methyl (R)-o-chloromandelate via Ru-catalyzed asymmetric hydrogenation and transfer hydrogenation was investigated. With Ru-(R,R)-2,4,6-i-Pr3-C6H2SO2DPEN as the catalyst and HCOOH–Et3N azeotrope as the hydrogen donor, up to 92% ee was obtained in an optional condition.Figure optionsDownload full-size imageDownload as PowerPoint slide