A novel synthesis of (2S)-3-(2,4,5-trifluorophenyl)propane-1,2-diol by sharpless asymmetric epoxidation method

Abstract

Synthesis of (2S)-3-(2,4,5-trifluorophenyl)propane-1,2-diol by the Sharpless asymmetric epoxidation reaction has been achieved. 2,4,5-Trifluorobenzaldehyde with methyl 2-(triphenyl-λ⁵-phosphanylidene)acetate gave methyl (E)-3-(2,4,5-trifluorophenyl)acrylate in 83% yield. The reduction of ester group with DibalH followed by Sharpless asymmetric epoxidation gave ((2R,3R)-3-(2,4,5-trifluorophenyl)oxiran-2-yl)methanol. Pd/C-catalyzed hydrogenation of epoxy alcohol furnished (2S)-3-(2,4,5-trifluorophenyl)propane-1,2-diol with >90% ee and 71% yield.

Graphical Abstract

Keywords:

• β-hydroxy acid
• β-amino acid
• propane-1,2-diol
• Sharpless asymmetric epoxidation
• sitagliptin

Acknowledgments

The authors thank Dr. Savaş Yeşilyurt for his critical reading of this article and Bilal Altundaş for his linguistic editing.

Additional information

Funding

The authors are grateful to Atatürk University and TÜBİTAK for their financial support (Grant No: 2211-D).