3월7일(월)특별세미나 Prof. Yujiro Hayashi(Tohoku University)

Pot Economy in Total Synthesis

 

 

One-pot operations are an effective method for both carrying out several transformations and forming several bonds in a single-pot, while at the same time cutting out several purifications, minimizing chemical waste generation, and saving time. Thus, a one-pot reaction can be not only efficient, but also green and environmentally friendly, and “pot-economy” should be considered in planning a synthesis.1

 

Organocatalyst is an effective catalyst to carry out several reactions in a same vessel. Our group2 and Jørgensen’s group3 independently discovered that diphenylprolinol silyl ether, which is easily synthesized from proline, is an effective organocatalyst in the reaction involving enamine and iminium ion as a reactive intermediate. We have been investigating the application of this catalyst to the one-pot synthesis of biologically active compounds.

 

We have already reported three pot synthesis of (-)-oseltamivir, a neuraminidase inhibitor used in the treatment of human influenza, based on the diphenylprolinol silyl ether mediated Michael reaction of aldehyde and nitroalkene as a key step. Recently we have accomplished “one-pot” synthesis of (-)-oseltamivir without evaporation nor solvent exchange by the modification of the previous three pot synthesis.4

 

We further applied one-pot synthetic strategy to the total synthesis of prostaglandin E1 methyl ester, and accomplished three “one-pot” synthesis of this biologically important molecule.5 Recently (S)-baclofen was synthesized via one-pot sequential reaction from the commercially available compounds.

 

A recent progress in the one-pot synthesis will be described.

References

1) Y. Hayashi, Chem. Sci. 2016, 7, 866.

2) Y. Hayashi, H. Gotoh, T. Hayashi, M. Shoji, Angew. Chem. Int. Ed. 2005, 44, 4212.

3) M. Marigo, T. C. Wabnitz, D. Fielenbach, K. A. Jørgensen, Angew. Chem. Int. Ed. 2005, 44, 794.

4) T. Mukaiyama, H. Ishikawa, H. Koshino, Y. Hayashi, Chem. Eur. J. 2013, 19, 17789.

5) Y. Hayashi, S. Umemiya, Angew. Chem. Int. Ed. 2013, 52, 3450.

6) Y. Hayashi, D. Sakamoto, D. Okamura, Org. Lett. 2016, 18, 4.

20160307_특별세미나_Prof. Yujiro Hayashi.hwp