ACS Catalysis
Page 4 of 6
Thanks to the ligand/substrate structural similarity, the
ACKNOWLEDGMENT
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synthetic utility of this new catalysis protocol was further
explored to establish a three-step preparation of a chiral (1-
(pyridine-2-yl)methanmine ligand in its enantio-pure form (>
99% ee). As shown in Scheme 2, asymmetric transfer
hydrogenation of cyclohexyl 2-pyridyl ketone under the above
defined standard conditions provided (S)-configured alcohol
42 in 76% yield and 84% ee. A single recrystallization
furnished this intermediate in enantiomerically pure form (>
99% ee). The subsequent stereochemical inversion was
achieved under Mitsunobu conditions (PPh3, DIAD,
diphenylphosphoroazidate (DPPA), and DBU) leading to the
azide 43 in 87% yield.13 Catalytic reduction of 43 produced
the desired cyclohexyl (1-(pyridine-2-yl)methanmine in 90%
yield and > 99% ee. The method is more efficient and
economic than the conventional chiral auxiliary-based
strategy.14
We wish to thank Shenzhen Nobel Prize Scientists Laboratory
Project (grant C17783101) and SUSTech Research Start-up Funds
for Chen Xu (21/Y01216128) for financial support. Professor
Sarah E. Reisman and Dr. Arthur Han are acknowledged for
revising the manuscript. We also thank Dr. Yupeng Pan for
assistance in solving the X-ray structures of B10, B12, and 31.
REFERENCES
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42
43
44
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Scheme 2. A Concise Synthesis of Chiral Amine Ligand
PPh3/DIAD
DPPA
Standard
Conditions
Pd/C, H2
N
O
N
N
N
EtOH, 23 o
2 h
C
THF, 0-23 o
24 h
C
HO
N3
H2N
42
76% yield, 84% ee
> 99% ee
43
87% yield
> 99% ee
90% yield,
(61% yield,
)
In summary, we have described the design and discovery of
new Ru-catalysts in which a single element of chirality
induces high enantioselectivity in the asymmetric transfer
hydrogenation for a broad range of carbonyl substrates (39
examples, > 90% ee), including substrates that are not possible
with literature-known protocols. This work would suggest a
strategy for catalyst design and help stimulate structural
tailoring of some catalysts towards high levels of simplicity,
efficiency and practicality. Ongoing research that includes
modification of the catalysts and exploration of their extended
application in asymmetric catalysis is in progress.
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the
ACS
Publications
website.
Experimental procedures and characterization data (1H and 13C
NMR, HRMS) for all new compounds (PDF)
Crystallographic information for B10 (CIF)
Crystallographic information for B12 (CIF)
Crystallographic information for 31 (CIF)
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chiral ligands and applications. Chem. Soc. Rev. 2006, 35, 226–
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1,2-anti-disubstitution in monotosylated diamine ligands for
ruthenium(II)-catalysed asymmetric transfer hydrogenation.
Tetrahedron: Asymmetry 2004, 15, 2079-2084.
7. (a) Sandoval, C. A.; Li, Y.; Ding, K.; Noyori, R. The
hydrogenation/transfer hydrogenation network in asymmetric
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T.; Utsumi, N.; Tsutsumi, K.; Murata, K.; Sandoval, C.; Noyori,
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asymmetric hydrogenation of ketones with chiral 6-arene/N-
tosylethylenediamine–ruthenium(II) J. Am. Chem. Soc. 2006,
128, 8724–8725. (c) Noyori, R.; Yamakawa, M.; Hashiguchi, S.
Metal–ligand bifunctional catalysis: a nonclassical mechanism
AUTHOR INFORMATION
Corresponding Author
*xingxy@sustech.edu.cn
*xuc@sustech.edu.cn
Present Addresses
†Danzao sub-bureau administration of social insurance fund of
Fushan Nanhai District, Foshan, China, 528216
‡Shenzhen UV-ChemTech. Shenzhen, China, 518057
Author Contributions
§These authors contributed equally.
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