![Page 1: Noyori Reduction (Asymmetric Hydrogenation)...2012/04/30 · Ryoji Noyori •Born in 1938 in Kobe, Japan •Received B.S. and Ph.D. from Kyoto University •Postdoctoral work with](https://reader036.vdocuments.us/reader036/viewer/2022071401/60ea97580fbbe854d122cfef/html5/thumbnails/1.jpg)
Noyori Reduction
(Asymmetric Hydrogenation)
Daniel Tao
Overman Group Meeting
4/30/12
![Page 2: Noyori Reduction (Asymmetric Hydrogenation)...2012/04/30 · Ryoji Noyori •Born in 1938 in Kobe, Japan •Received B.S. and Ph.D. from Kyoto University •Postdoctoral work with](https://reader036.vdocuments.us/reader036/viewer/2022071401/60ea97580fbbe854d122cfef/html5/thumbnails/2.jpg)
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
![Page 3: Noyori Reduction (Asymmetric Hydrogenation)...2012/04/30 · Ryoji Noyori •Born in 1938 in Kobe, Japan •Received B.S. and Ph.D. from Kyoto University •Postdoctoral work with](https://reader036.vdocuments.us/reader036/viewer/2022071401/60ea97580fbbe854d122cfef/html5/thumbnails/3.jpg)
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.
![Page 4: Noyori Reduction (Asymmetric Hydrogenation)...2012/04/30 · Ryoji Noyori •Born in 1938 in Kobe, Japan •Received B.S. and Ph.D. from Kyoto University •Postdoctoral work with](https://reader036.vdocuments.us/reader036/viewer/2022071401/60ea97580fbbe854d122cfef/html5/thumbnails/4.jpg)
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%
![Page 5: Noyori Reduction (Asymmetric Hydrogenation)...2012/04/30 · Ryoji Noyori •Born in 1938 in Kobe, Japan •Received B.S. and Ph.D. from Kyoto University •Postdoctoral work with](https://reader036.vdocuments.us/reader036/viewer/2022071401/60ea97580fbbe854d122cfef/html5/thumbnails/5.jpg)
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.
![Page 6: Noyori Reduction (Asymmetric Hydrogenation)...2012/04/30 · Ryoji Noyori •Born in 1938 in Kobe, Japan •Received B.S. and Ph.D. from Kyoto University •Postdoctoral work with](https://reader036.vdocuments.us/reader036/viewer/2022071401/60ea97580fbbe854d122cfef/html5/thumbnails/6.jpg)
Catalytic Cycle
![Page 7: Noyori Reduction (Asymmetric Hydrogenation)...2012/04/30 · Ryoji Noyori •Born in 1938 in Kobe, Japan •Received B.S. and Ph.D. from Kyoto University •Postdoctoral work with](https://reader036.vdocuments.us/reader036/viewer/2022071401/60ea97580fbbe854d122cfef/html5/thumbnails/7.jpg)
Application in Dynamic Kinetic Resolution
Noyori, R. et al. J. Am. Chem. Soc. 1989, 111, 9134–9135.
Proposed Transition State
![Page 8: Noyori Reduction (Asymmetric Hydrogenation)...2012/04/30 · Ryoji Noyori •Born in 1938 in Kobe, Japan •Received B.S. and Ph.D. from Kyoto University •Postdoctoral work with](https://reader036.vdocuments.us/reader036/viewer/2022071401/60ea97580fbbe854d122cfef/html5/thumbnails/8.jpg)
Dynamic Resolution in Synthesis
![Page 9: Noyori Reduction (Asymmetric Hydrogenation)...2012/04/30 · Ryoji Noyori •Born in 1938 in Kobe, Japan •Received B.S. and Ph.D. from Kyoto University •Postdoctoral work with](https://reader036.vdocuments.us/reader036/viewer/2022071401/60ea97580fbbe854d122cfef/html5/thumbnails/9.jpg)
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.
![Page 10: Noyori Reduction (Asymmetric Hydrogenation)...2012/04/30 · Ryoji Noyori •Born in 1938 in Kobe, Japan •Received B.S. and Ph.D. from Kyoto University •Postdoctoral work with](https://reader036.vdocuments.us/reader036/viewer/2022071401/60ea97580fbbe854d122cfef/html5/thumbnails/10.jpg)
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.
![Page 11: Noyori Reduction (Asymmetric Hydrogenation)...2012/04/30 · Ryoji Noyori •Born in 1938 in Kobe, Japan •Received B.S. and Ph.D. from Kyoto University •Postdoctoral work with](https://reader036.vdocuments.us/reader036/viewer/2022071401/60ea97580fbbe854d122cfef/html5/thumbnails/11.jpg)
Other Ligands for Noyori Reduction
Noyori, R.; Ohkuma, T. Pure Appl. Chem. 2001, 73, 227–232.
![Page 12: Noyori Reduction (Asymmetric Hydrogenation)...2012/04/30 · Ryoji Noyori •Born in 1938 in Kobe, Japan •Received B.S. and Ph.D. from Kyoto University •Postdoctoral work with](https://reader036.vdocuments.us/reader036/viewer/2022071401/60ea97580fbbe854d122cfef/html5/thumbnails/12.jpg)
Other Ligands for Noyori Reduction
Noyori, R.; Ohkuma, T. Pure Appl. Chem. 2001, 73, 227–232.
![Page 13: Noyori Reduction (Asymmetric Hydrogenation)...2012/04/30 · Ryoji Noyori •Born in 1938 in Kobe, Japan •Received B.S. and Ph.D. from Kyoto University •Postdoctoral work with](https://reader036.vdocuments.us/reader036/viewer/2022071401/60ea97580fbbe854d122cfef/html5/thumbnails/13.jpg)
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)