Chiral P-N-O Ligands for Iridium-Catalyzed Asymmetric Hydrogenation of Aromatic Ketones

doi:10.6023/cjoc202511002

Chinese Journal of Organic Chemistry ›› 2026, Vol. 46 ›› Issue (5): 2129-2137.DOI: 10.6023/cjoc202511002 Previous Articles Next Articles

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手性P-N-O配体促进的铱催化芳香酮不对称氢化反应

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 发布日期:2026-01-30
基金资助:
国家自然科学基金(21267009); 国家自然科学基金(21262011)

Chiral P-N-O Ligands for Iridium-Catalyzed Asymmetric Hydrogenation of Aromatic Ketones

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

^a School of Chemistry and Environmental Engineering, Hubei Minzu University, Enshi, Hubei 445000
^b Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning 116023

Received:2025-11-03 Revised:2025-12-18 Published:2026-01-30
Contact: * E-mail: 1997015@hbmzu.edu.cn; xiangping@dicp.ac.cn
Supported by:
National Natural Science Foundation of China(21267009); National Natural Science Foundation of China(21262011)

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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 (R)-2-(((2'-(diphenylphosphaneyl)-[1,1'-binaph- thalen]-2-yl)amino)methyl)phenol (L1) as the ligand, Ba(OH)₂ as the base additive, and 95% (ϕ) 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

Wenjie Zhang, Zhengchao Duan, Xiangping Hu. Chiral P-N-O Ligands for Iridium-Catalyzed Asymmetric Hydrogenation of Aromatic Ketones[J]. Chinese Journal of Organic Chemistry, 2026, 46(5): 2129-2137.

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References 21

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手性P-N-O配体促进的铱催化芳香酮不对称氢化反应

Chiral P-N-O Ligands for Iridium-Catalyzed Asymmetric Hydrogenation of Aromatic Ketones

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Entry	Ligand	Solvent	Base	Conv.^b/%	ee^c/%
1	L1	EtOH	Ba(OH)₂	>99	93
2	L2	EtOH	Ba(OH)₂	>99	92
3	L3	EtOH	Ba(OH)₂	76	82
4	L4	EtOH	Ba(OH)₂	>99	73
5	L5	EtOH	Ba(OH)₂	>99	80
6	L6	EtOH	Ba(OH)₂	>99	62
7	L7	EtOH	Ba(OH)₂	>99	73
8	L1	EtOH	t-BuONa	>99	81
9	L1	EtOH	Na₂CO₃	6	16
10	L1	EtOH	Cs₂CO₃	>99	52
11	L1	EtOH	t-BuOK	>99	65
12	L1	EtOH	LiOH	>99	82
13	L1	EtOH	KOH	>99	62
14	L1	EtOH	NaOH	>99	87
15	L1	EtOH	CH₃ONa	>99	80

Entry	Ligand	Solvent	Base	Conv.^b/%	ee^c/%
1	L1	DCM	Ba(OH)₂	—	—
2	L1	DCE	Ba(OH)₂	—	—
3	L1	Toluene	Ba(OH)₂	—	—
4	L1	1-Propanol	Ba(OH)₂	>99	85
5	L1	DMF	Ba(OH)₂	—	—
6	L1	THF	Ba(OH)₂	—	—
7	L1	MeOH	Ba(OH)₂	>99	93
8	L1	98% EtOH	Ba(OH)₂	>99	93.8
9	L1	95% EtOH	Ba(OH)₂	>99	94.4
10	L1	90% EtOH	Ba(OH)₂	>99	94.2
11	L1	85% EtOH	Ba(OH)₂	96	91
12	L1	80% EtOH	Ba(OH)₂	72	86
13	L1	75% EtOH	Ba(OH)₂	67	81
14^d	L1	95% EtOH	Ba(OH)₂	>99	93.8
15^e	L1	95% EtOH	Ba(OH)₂	>99	91.3
16^f	L1	95% EtOH	Ba(OH)₂	>99	95
17^g	L1	95% EtOH	Ba(OH)₂	>99	93
18^h	L1	95% EtOH	Ba(OH)₂	80	88
19ⁱ	L1	95% EtOH	Ba(OH)₂	>99 (99)	95

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