Chiral P-N-O Binaphthyl Ligands for Iridium-Catalyzed Enantioselective Hydrogenation of Simple Aromatic Ketones

doi:10.6023/cjoc202511002

Chinese Journal of Organic Chemistry Previous Articles Next Articles

ARTICLE

手性P-N-O配体促进的铱催化芳香酮不对称氢化反应研究

张文杰^a,b, 段正超^*,a, 胡向平^*,b

(^a湖北民族大学化学与环境工程学院湖北恩施 445000)
(^b中国科学院大连化学物理研究所辽宁大连 116023)

收稿日期:2025-11-03 修回日期:2025-12-18
基金资助:
国家自然科学基金(No. 21267009,21262011)资助项目.

Chiral P-N-O Binaphthyl Ligands for Iridium-Catalyzed Enantioselective Hydrogenation of Simple Aromatic Ketones

Zhang Wenjie^a,b, Duan Zhengchao^*,a, Hu Xiangping^*,b

(^aSchool of Chemistry and Environmental Engineering, Hubei Minzu University, Enshi 445000)
(^bDalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023)

Received:2025-11-03 Revised:2025-12-18
Contact: ^*E-mail: 1997015@hbmzu.edu.cn; xiangping@dicp.ac.cn
Supported by:
Project supported by the National Natural Science Foundation of China (No. 21267009, 21262011).

1. .pdf(9751KB)

Abstract

A catalytic system comprising a readily available chiral binaphthyl-based P-N-O tridentate ligand and iridium has been developed for the highly efficient asymmetric hydrogenation of simple aromatic ketones. Using prochiral aromatic ketones as substrates, this system gives the corresponding chiral alcohols in up to >99% yield and 97% enantioselectivity under mild conditions. Systematic optimization of reaction conditions revealed that ligand L1, Ba(OH)₂ as the base additive, and 95% ethanol as the solvent were critical for achieving excellent performance. The catalytic system exhibits good substrate generality, being applicable to various aromatic ketones and heteroaromatic ketones with different substituents. Furthermore, this method was successfully applied to the synthesis of (S)-3-(dimethylamino)-1-(thiophen-2-yl)propan-1-ol, a key chiral intermediate of the antidepressant (S)-duloxetine, affording the target product with 98% yield and 90% ee, which fully demonstrates its great application potential in practical synthesis.

Key words: P-N-O ligands, iridium catalysis, asymmetric hydrogenation, aromatic ketones, chiral alcohols

Cite this article

Zhang Wenjie, Duan Zhengchao, Hu Xiangping. Chiral P-N-O Binaphthyl Ligands for Iridium-Catalyzed Enantioselective Hydrogenation of Simple Aromatic Ketones[J]. Chinese Journal of Organic Chemistry, doi: 10.6023/cjoc202511002.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

References

[1] Deeter J.; Frazier J.; Staten G.; Staszak M.; Weigel L. Tetrahedron Lett.1990, 31, 7101-7104.
[2] (a) Garland M.; Kirkpatrick, P. Nat. Rev. Drug Discovery2004, 3, 385-386.
(b) Lin K.-S.; Ding, Y.-S. Bioorg. Med. Chem.2005, 13, 4658-4666.
[3] Clader, J.-W. Curr. Top. Med. Chem.2005, 5, 243-256.
[4] Cao M.; Wang H.; Hou F.; Zhu Y.; Liu Q.; Tung C. H.; Liu, L. J. Am. Chem. Soc.2024, 146, 18396-18406.
[5] Wan Q.; Wang Z.; Sun H.; Song D.; Wang X.; Liu, L. Chem. Cat. Chem.2024, 16, e202301757.
[6] 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.
[7] 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.
[8] Ohkuma T.; Ooka H.; Hashiguchi S.; Ikariya T.; Noyori R.J. Am. Chem. Soc. 1995, 117, 2675-2676.
[9] Jiang Y.-T.; Jiang Q.-Z.; Zhang, X.-M. J. Am. Chem. Soc.1998, 120(15), 3817-3818.
[10] Li W.; Hou G.-H.; Wang C.-J.; Jiang Y.-T.; Zhang X.-M. Chem. Commun.2010, 46(22), 3979-3981.
[11] Xie J.-H.; Liu X.-Y.; Xie J.-B.; Wang L.-X.; Zhou, Q.-L. Angew. Chem. Int. Ed.,2011, 50(32), 7329-7332.
[12] Zhang F.-H.; Zhang F.-J.; Li M.-L.; Xie J.-H.; Zhou Q.-L. Nature Catalysis,2020, 3(8), 621-627.
[13] Yu J.-F.; Duan M.; Wu W.-L.; Qi X.-T.; Xue P.; Lan Y.; Dong X.-Q.; Zhang, X.-M. Chem. Eur. J.2017, 23(4), 970-975.
[14] Niu T.; Liu L.-X.; Wu B.; Zhou, Y.-G. J. Org. Chem.2023, 88, 7863-7871.
[15] Wu W.-L.; Zhao N.; Liu Y.-Y.; Du S.-S.; Wang X.-X.; Mo W.-Z.; Yan X.-H.; Xu C.-Y.; Zhou Y.; Ji B.-M. Org. Lett.2023, 25, 8845-8849.
[16] Yu J.-F.; Long J.; Yang Y.-H.; Wu W.-L.; Xue P.; Chung L.-W.; Dong X.-Q.; Zhang X.-M. Org. Lett.2017, 19, 690-693.
[17] Császár Z.; Guóth M.; Kovács M.; Bényei A.-C.; Bakos J.; Farkas G. Molecules2024, 29, 3743.
[18] Garnier J.-M.; Liu, F. Org. Biomol. Chem.2009, 7, 1272-1275.
[19] Garnier J.-M.; Anstiss C.; Liu, F. Adv. Synth. Catal.2009, 351, 331-338.
[20] Anstiss C.; Liu F. Tetrahedron2010, 66, 5486e5491
[21] Chen X.; Liu Z.-Q.; Lin C.-P.; Zheng Y.-G. Bioorg. Chem.2016, 65, 82-89.

手性P-N-O配体促进的铱催化芳香酮不对称氢化反应研究

Chiral P-N-O Binaphthyl Ligands for Iridium-Catalyzed Enantioselective Hydrogenation of Simple Aromatic Ketones

PDF

Supporting Info.

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	Hui Zhu, Peng Wu, Chenming Zhong, Shuming Li, Gang Lin, Xuefen Liu, Shuping Luo. Design and Synthesis of Donor-Acceptor-Donor (D-A-D) Type Aromatic Ketones for Photocatalytic C(sp³)—H Coupling Reactions [J]. Chinese Journal of Organic Chemistry, 2025, 45(9): 3441-3449.
[2]	Qishu Chen, Bo Yang, Qiwei Lang, Xiaobing Ding, Xiuxiu Li, Xumu Zhang. Ir/f-Amphox-Catalyzed Asymmetric Hydrogenation of 1-(Pyridin-2-yl)ketones to Chiral Pyridyl Alcohols^★ [J]. Chinese Journal of Organic Chemistry, 2025, 45(9): 3326-3334.
[3]	Lanxing Ren, A'na Xu, Xilin Xiao, Hengzhi You, Lijuan Song. Theoretical Study on the Solvent Effect on the Enantioselectivity of Iridium-Catalyzed Asymmetric Hydrogenation Reactions [J]. Chinese Journal of Organic Chemistry, 2025, 45(8): 2904-2912.
[4]	Ting Mao, Linyuan Zeng, Jilin Wen, Jia Jia. Visible Light-Mediated Iridium-Catalyzed Debromocyclization of Aliphatic α-Bromotrifluoromethyl Groups [J]. Chinese Journal of Organic Chemistry, 2025, 45(7): 2520-2528.
[5]	Minhao Li, Zeming Wang, Qing Huang, Weiwei Zuo. Cobalt(II)-Catalyzed Asymmetric Hydrogen Transfer Reactions of Ketones [J]. Chinese Journal of Organic Chemistry, 2025, 45(7): 2451-2460.
[6]	Zhen Liang, Weiyan Xu, Yi Chen, Huayu Qiu, Yezhe Zhao, Jiabin Shen, Min Wang. Iridium-Catalyzed Synthesis of Indole Derivatives from N-Aryl-2-aminopyridines and Vinylene Carbonate [J]. Chinese Journal of Organic Chemistry, 2025, 45(6): 2149-2156.
[7]	Qian Chen, Zhaobin Han, Kuiling Ding. Transition Metal Catalyzed Carbocycle-Selective Asymmetric Hydrogenation of Aromatic Rings [J]. Chinese Journal of Organic Chemistry, 2024, 44(7): 2063-2076.
[8]	Yiwen Lü, Haihua Liao, Wenjun Tang. Synthesis of a Sitagliptin Intermediate via Ruthenium-Catalyzed Asymmetric Hydrogenation of Enamine Ester [J]. Chinese Journal of Organic Chemistry, 2024, 44(12): 3720-3726.
[9]	Yangyang Chu, Zhaobin Han, Kuiling Ding. Progresses in the Application of Kinetic Resolution in Transition Metal Catalyzed Asymmetric (Transfer) Hydrogenation [J]. Chinese Journal of Organic Chemistry, 2023, 43(6): 1934-1951.
[10]	Wang Jiang, Zhuangzhi Shi. Recent Progress in meta-/para-Selective Aromatic C—H Borylation [J]. Chinese Journal of Organic Chemistry, 2023, 43(5): 1691-1705.
[11]	Tongli Zhang, Jun Yan, Jingli He, Xuezhen Kou, Jiefeng Shen, Delong Liu, Wanbin Zhang. Synthesis of Chiral 5-Aryl-2-oxazolidinones via an Ir-BiphPHOX Catalyzed Enantioselective Hydrogenation [J]. Chinese Journal of Organic Chemistry, 2022, 42(6): 1747-1758.
[12]	Binyang Jiang, Shi-Liang Shi. Recent Progress in Upgrading of Alcohol and Amine via Asymmetric Dehydrogenative Coupling [J]. Chinese Journal of Organic Chemistry, 2022, 42(10): 3263-3279.
[13]	Yuxuan Zhang, Limin Xu, Yan Lu, Zhaoguo Zhang. Progress in Asymmetric Catalytic Reduction of Diketones [J]. Chinese Journal of Organic Chemistry, 2022, 42(10): 3221-3239.
[14]	Chenguang Liu, Qiang Liu. Earth-Abundant Metal-Catalyzed Asymmetric Hydrogenation of Carbon-Nitrogen Unsaturated Bonds [J]. Chinese Journal of Organic Chemistry, 2022, 42(10): 3213-3220.
[15]	Fang Zhao, Wenjing Ye, Kai Wang. Advancement of Chiral Monodentate Phosphite Ligands in Asymmetric Hydrogenation [J]. Chinese Journal of Organic Chemistry, 2021, 41(7): 2650-2665.