(243f) Enantioselective Hydrogenation of C=N Double Bond by RuTsDPEN Catalyst – Spectral and DFT Investigation of the Mechanism

Chiral compounds are of key importance for a broad range of life sciences and fine chemical products, particularly for pharmaceuticals and agrochemicals. Catalytic enantioselective synthesis is one of the most important synthetic methods for the manufacturing of chiral compounds. Among these methods catalytic asymmetric hydrogenation plays outstanding role both on laboratory and industrially scale. Nowadays asymmetric hydrogenation of C=N has an important role from the practical point of view. For its hydrogenation are reported two different methods using gaseous hydrogen or phase transfer hydrogenation. The assymetric transfer hydrogenation (ATH) is from the practical point of view very useful method which uses organic sources of hydrogen, e.g. propane-2-ol, formic acid. In 1995, Noyori and coworkers published a paper [1], reporting the TsDPEN-coordinated (TsDPEN = N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine) Ru(II) complex (Ru-TsDPEN) to be an excellent catalyst for the asymmetric reduction of aromatic ketones and imines. As a hydrogen source can be used a mixture of formic acid and triethylamine (HCOOH/TEA). Our work was focused on studies of a mechanism involved in the transfer hydrogenation using HCOOH/base as a hydrogen donor catalyzed by RuCl-(p-cymene)-TsDPEN. Various spectroscopic methods were applied to study intermediates formed during the course of the reaction. It was used direct in situ NMR, FT-MS, ECD, and VCD studies of the catalyst under reaction conditionse. The special attention was paid to the influence of amine on the course of the hydride formation and hydrogenation of imines followed by in-situ NMR. A range of amines with a combination of HCOOH was tested. DFT molecular modeling using Gaussian 03 package allowed us to visualize the structure of particular transition states and stable intermediates during the course of ATH and confirm our experimental results, which are clear evidences for participation of a base in the formation of diastereomeric transition states and thus it directly influences the enantioselectivity of ATH.

Acknowledgement

The work was supported by the Grant Agency of the Czech Republic (Grant 104/09/1497)

References

[1] R. Noyori, M. Yamakawa, S. Hashiguchi, J. Org. Chem. 66 (24), 7931 (2001).