Asymmetric Synthesis of Unnatural Amino Acids and Tamsulosin Chiral Intermediate

Abstract

An efficient and enantioselective hydrogenation of N-acetylamino phenyl acrylic acids was successfully developed by using ruthenium catalyst. This methodology is important in the field of pharmaceuticals and provides a new process for the preparation of unnatural amino acids and tamsulosin chiral intermediate.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource: Full experimental and spectral details.]

GRAPHICAL ABSTRACT

Keywords:

• Asymmetric hydrogenation
• chiral metal catalyst
• [(S)-BINAPRuCl (benzene)]Cl
• tamsulosin intermediate
• unnatural amino acids

ACKNOWLEDGMENT

The authors are grateful to Suven Life Sciences management for allowing them to publish these results.

Notes

^a Isolated yields for two stages (1 to 3).

^a Conversion was determined by ¹ H NMR spectra.

^b ee were determined by chiral HPLC. Chiral ratio of the products was 81:19 (for bromo 4d) to 96:4 (for fluoro 4b).

^c Isolated yield.

^a Conversion was determined by TLC.

^b ee were determined by chiral HPLC. Chiral ratio of the products was 85.9:14.1 (for 5i) to 99.7:0.23 (for bromo 5d).

^c Isolated yield.