Noyori Reduction

(Asymmetric Hydrogenation)

Daniel Tao

Overman Group Meeting

4/30/12

Ryoji Noyori

•Born in 1938 in Kobe, Japan

•Received B.S. and Ph.D. from Kyoto

University

•Postdoctoral work with E.J. Corey before

returning to Nagoya University in Japan •Shared the 2001 Nobel Prize with K.B. Sharpless and W.S. Knowles

www.nobelprize.org/nobel_prizes/chemistry/laureates/2001/noyori-photo.html

Initial Work in the 1980’s

Noyori, R. et al. J. Am. Chem. Soc. 1980, 102, 7932–7934.

Noyori, R. et al. J. Am. Chem. Soc. 1984, 106, 5208–5217.

Switching to Ru(II) Catalyst

Noyori, R.; Ohta, M.; Hsiao, Y.; Kitamura, M. J. Am. Chem. Soc., 1986, 108, 7117–7119.

•23 °C for 2–3 days

•4 atm H2

•Yields almost quantitative •ee’s >95%

Asymmetric Reduction of Ketones

Noyori, R. et al. J. Am. Chem. Soc. 1987, 109, 5856–5858.

Noyori, R. et al. J. Am. Chem. Soc. 1988, 110, 629–631.

Beck, G.; Jendralla, H.; Kesseler, K. Synthesis 1995, 1014–1018.

Catalytic Cycle

Application in Dynamic Kinetic Resolution

Noyori, R. et al. J. Am. Chem. Soc. 1989, 111, 9134–9135.

Proposed Transition State

Dynamic Resolution in Synthesis

Noyori Reduction in Synthesis

Taber, D.F.; Wang, Y. J. Am. Chem. Soc. 1997, 119, 22–26.

Rychnovsky, S.D.; Hoye, R.C. J. Am. Chem. Soc. 1994, 116, 1753–1765.

Other Ligands for Noyori Reduction

Burk, M.J.; Harper, T.G.; Kalberg, C.S. J. Am. Chem. Soc. 1995, 117, 4423–4424.

Pye, P.J.; Rossen, K.; Reamer, R.A.; Volante, R.P.; Reider, P.J. Tetrahedron Lett. 1998, 39, 4441–4444.

Other Ligands for Noyori Reduction

Noyori, R.; Ohkuma, T. Pure Appl. Chem. 2001, 73, 227–232.

Other Ligands for Noyori Reduction

Noyori, R.; Ohkuma, T. Pure Appl. Chem. 2001, 73, 227–232.

Summary

•The Noyori reduction is asymmetric with

typically high enantioselectivity

•Using a Ru-based catalyst with a variety of

ligands, the transition state may be 4-

centered or 6-centered

•The substrate scope is large, based mainly

on proximity to a heteroatom (vinylic to

homoallylic)