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

doi:10.6023/cjoc202511002

研究论文

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).

文章分享

1. cjoc202511002辅助材料.pdf(9751KB)

摘要/Abstract

发展了一种由易得的手性联萘P-N-O三齿配体与铱组成的催化体系,用于简单芳香酮的高效不对称氢化。该体系以前手性芳香酮为底物,在温和条件下,能够以高达>99%的产率和97%的对映选择性获得相应手性醇。系统性的条件优化表明,配体L1、Ba(OH)₂作为碱添加剂以及95%乙醇作为溶剂是实现优异性能的关键。该催化体系展现出优良的底物普适性,适用于多种带不同取代基的芳香酮及杂芳酮。此外,本研究成功将该方法应用于抗抑郁药(S)-度洛西汀的关键手性中间体——(S)-3-(二甲氨基)-1-(噻吩-2-基)丙-1-醇的合成,以98%的产率和90%的ee值获得目标产物,充分证明了其在实际合成中的巨大应用潜力。

关键词: P-N-O配体, 铱催化, 不对称氢化, 芳香酮, 手性醇

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

引用此文

张文杰, 段正超, 胡向平. 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[J]. 有机化学, doi: 10.6023/cjoc202511002.

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.

导出引用 EndNote|Reference Manager|ProCite|BibTeX|RefWorks

分享此文

参考文献

[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.