ORGANIC
LETTERS
2
000
Vol. 2, No. 12
749-1751
General Asymmetric Hydrogenation of
Hetero-aromatic Ketones
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Takeshi Ohkuma, Masatoshi Koizumi, Makoto Yoshida, and Ryoji Noyori*
Department of Chemistry and Research Center for Materials Science,
Nagoya UniVersity, Chikusa, Nagoya 464-8602, Japan
Received April 11, 2000
ABSTRACT
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trans-RuCl [(R)-xylbinap][(R)-daipen] or the S,S complex acts as an efficient catalyst for asymmetric hydrogenation of hetero-aromatic ketones.
The hydrogenation proceeds with a substrate-to-catalyst molar ratio of 1000−40000 to give chiral alcohols in high ee and high yield. The
enantioselectivity appears to be little affected by the properties of the hetero-aromatic ring. This method allows for asymmetric synthesis of
duloxetine, an inhibitor of serotonin and norepinephrine uptake carriers.
A variety of chiral transition metal catalysts effect the
asymmetric hydrogenation of CdC and CdO bonds, assisted
by the coordination of a neighboring heteoatom to the
bicp](tmeda), (R,R)-1,2-diphenylethylenediamine, and KOH
is known to enantioselectively hydrogenate certain hetero-
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cyclic, mostly thienyl, ketones. However, it is highly
1
metallic center. It is only during recent years that certain
(5) For example, see: (a) Uskokovi c´ , M. R.; Lewis, R. L.; Partridge, J.
homogeneous catalysts have been used to enantioselectively
hydrogenate simple ketones lacking coordinative functional
J.; Despreaux, C. W.; Pruess, D. L. J. Am. Chem. Soc. 1979, 101, 6742-
6
5
744. (b) Schmidt, U.; Gleich, P. Angew. Chem., Int. Ed. Engl. 1985, 24,
69-571. (c) Drueckhammer, D. G.; Barbas, C. F., III; Nozaki, K.; Wong,
2
groups. In this regard, however, the substrates have been
C.-H.; Wood, C. Y.; Ciufolini, M. A. J. Org. Chem. 1988, 53, 1607-1611.
(d) Kusakabe, M.; Kitano, Y.; Kobayashi, Y.; Sato, F. J. Org. Chem. 1989,
3
4
limited largely to simple aromatic and olefinic ketones.
5
3
4, 2085-2091. (e) Waldmann, H. Tetrahedron Lett. 1989, 30, 3057-
058. (f) Deeter, J.; Frazier, J.; Staten, G.; Staszak, M.; Weigel, L.
Asymmetric hydrogenation of hetero-aromatic ketones is also
important because the chiral alcoholic products are useful
Tetrahedron Lett. 1990, 31, 7101-7104. (g) Astleford, B. A.; Weigel, L.
O. In Chirality in Industry II; Collins, A. N., Sheldrake, G. N., Crosby, J.,
Eds.; Wiley: Chichester, 1997; Chapter 6. (h) Shioiri, T.; Hayashi, K.;
Hamada, Y. Tetrahedron 1993, 49, 1913-1924. (i) Corey, E. J.; Roberts,
B. E. J. Am. Chem. Soc. 1997, 119, 12425-12431. (j) Uenishi, J.; Takagi,
T.; Ueno, T.; Hiraoka, T.; Yonemitsu, O.; Tsukube, H. Synlett 1999, 41-
44.
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as building blocks of biologically active compounds and
chiral ligands.6 A ternary system consisting of RuCl
,7
2
[(R,R)-
(1) Noyori, R. Asymmetric Catalysis in Organic Synthesis; Wiley: New
York, 1994; Chapter 2.
(6) (a) Bolm, C.; Zehnder, M.; Bur, D. Angew. Chem., Int. Ed. Engl.
1990, 29, 205-207. (b) Sablong, R.; Newton, C.; Dierkes, P.; Osborn, J.
A. Tetrahedron Lett. 1996, 37, 4933-4936. (c) Sablong, R.; Osborn, J. A.
Tetrahedron Lett. 1996, 37, 4937-4940. (d) Chen. G.-M.; Brown, H. C.;
Ramachandran, P. V. J. Org. Chem. 1999, 64, 721-725.
(7) Asymmetric reduction of hetero-aromatic ketones: (a) Ramachandran,
P. V.; Brown, H. C. Reductions in Organic Synthesis: Recent AdVances
and Practical Applications (ACS symposium series 641); American Chemical
Society: Washington, DC, 1996; Chapter 5. (b) Corey, E. J.; Helal, C. J.
Angew. Chem., Int. Ed. 1998, 37, 1986-2012. (c) Midland, M. M.;
McLoughlin, J. I.; Gabriel, J. J. Org. Chem. 1989, 54, 159-165. (d)
Quallich, G. J.; Woodall, T. M. Tetrahedron Lett. 1993, 34, 785-788. (e)
Prasad, K. R. K.; Joshi, N. N. Tetrahedron: Asymmetry 1997, 8, 173-176.
(f) Fujii, A.; Hashiguchi, S.; Uematsu, N.; Ikariya, T.; Noyori, R. J. Am.
Chem. Soc. 1996, 118, 2521-2522. (g) Masui, M.; Shioiri, T. Synlett 1997,
273-274, and references therein.
(
(
2) Noyori, R.; Ohkuma, T. Pure. Appl. Chem. 1999, 71, 1493-1501.
3) (a) Ohkuma, T.; Ooka, H.; Hashiguchi, S.; Ikariya, T.; Noyori, R. J.
Am. Chem. Soc. 1995, 117, 2675-2676. (b) Doucet, H.; Ohkuma, T.;
Murata, K.; Yokozawa, T.; Kozawa, M.; Katayama, E.; England, A. F.;
Ikariya, T.; Noyori, R. Angew. Chem., Int. Ed. 1998, 37, 1703-1707. (c)
Mikami, K.; Korenaga, T.; Terada, M.; Ohkuma, T.; Pham, T.; Noyori, R.
Angew. Chem., Int. Ed. 1999, 38, 495-497. (d) Ohkuma, T.; Koizumi, M.;
Ikehira, H.; Yokozawa, T.; Noyori, R. Org. Lett. 2000, 2, 659-662.
(
4) (a) Ohkuma, T.; Ooka, H.; Ikariya, T.; Noyori, R. J. Am. Chem. Soc.
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995, 117, 10417-10418. (b) Ohkuma, T.; Ikehira, H.; Ikariya, T.; Noyori,
R. Synlett 1997, 467-468. (c) Ohkuma, T.; Doucet, H.; Pham, T.; Mikami,
K.; Korenaga, T.; Terada, M.; Noyori, R. J. Am. Chem. Soc. 1998, 120,
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086-1087. (d) Ohkuma, T.; Koizumi, M.; Doucet, H.; Pham, T.; Kozawa,
M.; Murata, K.; Katayama, E.; Yokozawa, T.; Ikariya, T.; Noyori, R. J.
Am. Chem. Soc. 1998, 120, 13529-13530.
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0.1021/ol0000814 CCC: $19.00 © 2000 American Chemical Society
Published on Web 05/20/2000