Abstract
To obtain an efficient and practical route to a novel glucokinase activator, we investigated a novel synthetic method for the preparation of its key intermediate (S)-5-(1-(tert-butoxycarbonyl)pyrrolidin-2-yl)-2-methylthiophene-3-carboxylic acid through the asymmetric transfer hydrogenation of a pyrroline derivative. The hydrogenation of this pyrroline derivative using the iridium (III)-prolinamide complex Cp*IrCl[(R)-PA] at atmospheric pressure provided an initial intermediate in approximately 50% ee. Further purification via recrystallization provided the desired key intermediate in an excellent enantiopurity, which was applicable to practical use.
Graphical Abstract
![](/cms/asset/77156608-88a4-4e10-82b4-892cafd9f12a/lsyc_a_1570267_uf0001_b.jpg)
Acknowledgments
We are grateful to Dr. Masao Sakairi for his advice regarding our manuscript. We also thank Hamari Chemicals, Ltd. for their synthetic support.