Organic Letters
Letter
optically pure 2a could be further recrystallized from IPA/
hexane in 86% isolated yield.
In conclusion, we have developed a highly efficient method
for enantioselective synthesis of cis-3-quinuclidinols via Ru-
catalyzed DKR asymmetric transfer hydrogenation. The
products are efficiently accessed in good yields and excellent
diastereo- and enantioselectivities (up to 99:1 dr, 95−99% ee)
catalyzed by in-house developed Ru−diamine complexes using
ammonium formate as the hydrogen donor. This mild and
operationally simple method provides an alternative route to
cis 2-substituted-3-quinuclidinols and expands the scope for
asymmetric transfer hydrogenation of bicyclic ketones.
Furthermore, the practical utility of this method was
demonstrated by the efficient gram-scale asymmetric transfer
hydrogenation of 1a with perfect enantioselectivity through
simple recrystallization.
Author Contributions
⊥Z.L. and Z.W. contributed equally to this work.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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We gratefully acknowledge financial support from the State
Key Laboratory of Anti-Infective Drug Development (Sun-
shine Lake Pharma Co., Ltd), (N0. 2015DQ780357). We
thank Jiangzhong Zhong (HEC Pharm Co., Inc.) for NMR
assistance and Yanling Liu (HEC Pharm Co., Inc.) for HPLC
and optical rotation assistance.
REFERENCES
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ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
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Optimization tables, experimental procedure, and
characterization data for all of the substrates and
AUTHOR INFORMATION
Corresponding Authors
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Zhongqing Wang − State Key Laboratory of Anti-Infective Drug
Development, Sunshine Lake Pharma Co., Ltd., Dongguan
523871, P.R. China; Hunan Provincial Key Laboratory of
Xiangnan Rare-Precious Metals Compounds Research and
Application, Xiangnan University, Chenzhou 423000, China;
Lei Zhang − School of Biology and biological Engineering, South
China University of Technology, Guangzhou 510640, P.R.
̈
Yonetoku, Y.; Okamoto, Y.; Toyoshima, A.; Ikeda, K.; Takeuchi, M.
Med. Chem. 2015, 58, 4131−4164.
Authors
Zhonghua Luo − School of Biology and biological Engineering,
South China University of Technology, Guangzhou 510640,
P.R. China; State Key Laboratory of Anti-Infective Drug
Development, Sunshine Lake Pharma Co., Ltd., Dongguan
523871, P.R. China
Guodong Sun − State Key Laboratory of Anti-Infective Drug
Development, Sunshine Lake Pharma Co., Ltd., Dongguan
Weilin Jian − State Key Laboratory of Anti-Infective Drug
Development, Sunshine Lake Pharma Co., Ltd., Dongguan
523871, P.R. China
Fengkai Jiang − State Key Laboratory of Anti-Infective Drug
Development, Sunshine Lake Pharma Co., Ltd., Dongguan
523871, P.R. China
Baolei Luan − State Key Laboratory of Anti-Infective Drug
Development, Sunshine Lake Pharma Co., Ltd., Dongguan
Ridong Li − Institute of Systems Biomedicine, School of Basic
Medical Sciences, Peking University Health Science Center,
Beijing 100191, PR China
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Complete contact information is available at:
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