Organic Letters
Letter
[RuCl2(PPh3)2(BIDN)] (98.31°),12b which forces a close
proximity of the phenyl rings of the DPEphos to the chiral
center and, therefore, is expected to induce the reactants close to
the chiral center. This unique spatial orientation would produce a
Bugles-like chiral pocket, which not only facilitates the sterically
hindered β,β-disubstituted enone to enter the chiral pocket but
also benefits to confine it into the defined chiral environment. As
shown in Figure 2, the enone approach to the Ru complex via an
Y. J. Org. Chem. 2009, 74, 5920. (e) Ma, X.; Li, W. F.; Li, X. M.; Tao, X.
M.; Fan, W. Z.; Xie, X. M.; Ayad, T.; Ratovelomanana-Vidal, V.; Zhang,
Z. G. Chem. Commun. 2012, 48, 5352.
(2) For selected recent examples of asymmetric reduction of α,β-
unsaturated ketones to access chiral allylic alcohols using non-
hydrogenation methods, see: (a) Lipshutz, B. H.; Frieman, B. A.;
Tomaso, A. E. Angew. Chem., Int. Ed. 2006, 45, 1259. (b) Vorogushin, A.
V.; Wulff, W. D.; Hansen, H.-J. Tetrahedron 2008, 64, 949. (c) Kim, J.;
Bruning, J.; Park, K. E.; Lee, D. J.; Singaram, B. Org. Lett. 2009, 11, 4358.
(d) Li, X.; Li, L.; Tang, Y.; Zhong, L.; Cun, L.; Zhu, J.; Liao, J.; Deng, J. J.
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̌ ́
Org. Chem. 2010, 75, 2981. (e) Moser, R.; Boskovic, Z. V.; Crowe, C. S.;
Lipshutz, B. H. J. Am. Chem. Soc. 2010, 132, 7852. (f) He, P.; Liu, X.;
Zheng, H.; Li, W.; Lin, L.; Feng, X. Org. Lett. 2012, 14, 5134.
(3) (a) Ohkuma, T.; Kitamura, M.; Noyori, R. In Catalytic Asymmetric
Synthesis, 2nd ed.; Ojima, I., Ed.; Wiley-VCH: New York, 2000; p 1.
(b) Noyori, R.; Ohkuma, T. Angew. Chem., Int. Ed. 2001, 40, 40.
(c) Ohkuma, T.; Noyori, R. In The Handbook of Homogeneous
Hydrogenation; de Vries, J. G., Elsevier, C. J., Eds.; Wiley-VCH:
Weinheim, Germany, 2007; p 1105. (d) Xie, J.-H.; Zhou, Q.-L. Acta
Chim. Sinica 2012, 70, 1427. (e) Yang, X.-H.; Xie, J.-H.; Zhou, Q.-L. Org.
Chem. Front. 2014, 1, 190.
(4) (a) Ohkuma, T.; Ooka, H.; Hashiguchi, S.; Ikariya, T.; Noyori, R. J.
Am. Chem. Soc. 1995, 117, 2675. (b) Ohkuma, T.; Ooka, H.; Ikariya, T.;
Noyori, R. J. Am. Chem. Soc. 1995, 117, 10417. (c) Doucet, H.; Ohkuma,
T.; Murata, K.; Yokozawa, T.; Kozawa, M.; Katayama, E.; England, A. F.;
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(d) Ohkuma, T.; Ishii, D.; Takeno, H.; Noyori, R. J. Am. Chem. Soc.
Figure 2. Transition state for asymmetric hydrogenation.
outer-sphere pathway, Hδ+−N−Ru-Hδ−, should capture the
carbonyl of the ketonic substrate from the Re face of enone,
delivering the corresponding allylic alcohol with S-configuration.
In contrast, the Si face attack model would lead to large steric
hindrance between the phenyl rings that come from the substrate
and DPEphos ligand.
In summary, we have demonstrated for the first time that
asymmetric hydrogenation of sterically hindered β,β-disubsti-
tuted alkyl vinyl ketones to chiral allylic alcohols is feasible. The
reaction was catalyzed by a ruthenium catalyst prepared from a
simple achiral diphosphane and a rigid chiral diamine, which
demonstrated high enantioselectivities (up to 97% ee) and
activities (up to 50000 TON) for a wide range of enones.
Applications of this type of catalyst in other asymmetric
transformations are currently under investigation.
2000, 122, 6510. (e) Ohkuma, T.; Koizumi, M.; Muniz, K.; Hilt, G.;
̃
Kabuto, C.; Noyori, R. J. Am. Chem. Soc. 2002, 124, 6508.
(5) For selected examples, see: (a) Sandoval, C. A.; Ohkuma, T.;
Muniz, K.; Noyori, R. J. Am. Chem. Soc. 2003, 125, 13490. (b) Xie, J.-H.;
Wang, L.-X.; Fu, Y.; Zhu, S.-F.; Fan, B.-M.; Duan, H.-F.; Zhou, Q.-L. J.
Am. Chem. Soc. 2003, 125, 4404. (c) Wu, J.; Ji, J.-X.; Guo, R.; Yeung, C.-
H.; Chan, A. S. C. Chem.Eur. J. 2003, 9, 2963. (d) Ohkuma, T.;
Hattori, T.; Ooka, H.; Inoue, T.; Noyori, R. Org. Lett. 2004, 6, 2681.
(e) Ohkuma, T.; Sandoval, C. A.; Srinivasan, R.; Lin, Q.; Wei, Y.; Muniz,
K.; Noyori, R. J. Am. Chem. Soc. 2005, 127, 8288. (f) Arai, N.; Suzuki, K.;
Sugizaki, S.; Sorimachi, H.; Ohkuma, T. Angew. Chem., Int. Ed. 2008, 47,
1770. (g) Li, W.; Sun, X.; Zhou, L.; Hou, G.; Yu, S.; Zhang, X. J. Org.
Chem. 2009, 74, 1397.
(6) (a) 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. (b) Arai, N.; Azuma, K.; Nii, N.; Ohkuma,
T. Angew. Chem., Int. Ed. 2008, 47, 7457. (c) Ohkuma, T.; Hattori, T.;
Ooka, H.; Inoue, T.; Noyori, R. Org. Lett. 2004, 6, 2681.
(7) Zhang, Q.-Q.; Xie, J.-H.; Yang, X.-H.; Xie, J.-B.; Zhou, Q.-L. Org.
Lett. 2012, 14, 6158.
(8) CuH complex has been applied for catalytic asymmetric reduction
of β,β-disubstituted enones, but relative lower selectivities and activities
were observed. See: Voigtritter, K. R.; Isley, N. A.; Moser, R.; Aue, D. H.;
Lipshutz, B. H. Tetrahedron 2012, 68, 3410.
(9) (a) Martin Castro, A. M. Chem. Rev. 2004, 104, 2939.
(b) Antonietti, F.; Brenna, E.; Fuganti, C.; Gatti, F. G.; Giovenzana,
T.; Grande, V.; Malpezzi, L. Synthesis 2005, 7, 1148. (c) Harutyunyan, S.
R.; Hartog, T. D.; Geurts, K.; Minnaard, A. J.; Feringa, B. L. Chem. Rev.
2008, 108, 2824.
ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental details and full spectroscopic data for all new
compounds. This material is available free of charge via the
AUTHOR INFORMATION
Corresponding Author
■
Notes
The authors declare no competing financial interest.
(10) (a) Zhu, Q.; Huang, H.; Shi, D.; Shen, Z.; Xia, C. Org. Lett. 2009,
11, 4536. (b) Shi, D.; Xie, Y.; Zhou, H.; Xia, C.; Huang, H. Angew. Chem.,
Int. Ed. 2012, 51, 1248.
(11) (a) Jing, Q.; Zhang, X.; Sun, J.; Ding, K. Adv. Synth. Catal. 2005,
347, 1193. (b) Liang, Y.; Wang, Z.; Ding, K. Adv. Synth. Catal. 2006, 348,
1533. (c) Jing, Q.; Sandoval, C. A.; Wang, Z.; Ding, K. Eur. J. Org. Chem.
2006, 3606.
(12) (a) Zhu, Q.; Shi, D.; Xia, C.; Huang, H. Chem.Eur. J. 2011, 17,
7760. (b) Zhou, H.; Huang, H. ChemCatChem 2013, 5, 2253.
(13) CCDC 995443 contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge from The
ACKNOWLEDGMENTS
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This research was supported by the Chinese Academy of
Sciences, the National Natural Science Foundation of China
(21222203, 21172226, and 21133011).
REFERENCES
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