Theoretical Study on the Solvent Effect on the Enantioselectivity of Iridium-Catalyzed Asymmetric Hydrogenation Reactions

doi:10.6023/cjoc202502003

Chinese Journal of Organic Chemistry ›› 2025, Vol. 45 ›› Issue (8): 2904-2912.DOI: 10.6023/cjoc202502003 Previous Articles Next Articles

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溶剂效应对Ir催化的不对称氢化反应对映选择性影响的理论研究

任揽星^a, 徐阿娜^b, 肖锡林^a^,^*(), 游恒志^b^,^*(), 宋利娟^b^,^*()

^a 南华大学化学化工学院湖南衡阳 421000
^b 哈尔滨工业大学(深圳)理学院广东深圳 518055

收稿日期:2025-02-04 修回日期:2025-03-19 发布日期:2025-04-07
基金资助:
深圳市科技研究基金(JSGG20201103153807021); 深圳市科技研究基金(GXWD20220811173736002); 深圳市科技研究基金(KCXFZ20230731094904009); 广东省自然科学基金(2021A- 1515110366); 广东省自然科学基金(2022A1515011859); 国家自然科学基金(22302048); 国家自然科学基金(82204231); 国家自然科学基金(22203023)

Theoretical Study on the Solvent Effect on the Enantioselectivity of Iridium-Catalyzed Asymmetric Hydrogenation Reactions

Lanxing Ren^a, A'na Xu^b, Xilin Xiao^a^,^*(), Hengzhi You^b^,^*(), Lijuan Song^b^,^*()

^a School of Chemistry and Chemical Engineering, University of South China, Hengyang, Hunan 421000
^b School of Science, Harbin Institute of Technology (Shenzhen), Shenzhen, Guangdong 518055

Received:2025-02-04 Revised:2025-03-19 Published:2025-04-07
Contact: *E-mail:songlijuan@hit.edu.cn;youhengzhi@hit.edu.cn;xiaoxilin@usc.edu.cn
Supported by:
Shenzhen Science and Technology Research Fund(JSGG20201103153807021); Shenzhen Science and Technology Research Fund(GXWD20220811173736002); Shenzhen Science and Technology Research Fund(KCXFZ- 20230731094904009); Natural Science Foundation of Guangdong Province(2021A1515110366); Natural Science Foundation of Guangdong Province(2022A1515011859); National Natural Science Foundation of China(22302048); National Natural Science Foundation of China(82204231); National Natural Science Foundation of China(22203023)

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Abstract

This study investigates the transformation mechanism of an efficient solvent-controlled Ir-catalyzed enantioselective hydrogenation system for quinoxalines through rational mechanistic hypotheses combined with density functional theory (DFT) calculations. Experimental results demonstrate that this catalytic system, under additive-free conditions, successfully produces both enantiomers of 2-aryl tetrahydroquinoxalines by simply switching the reaction solvent. Specifically, the product obtained in the toluene/dioxane solvent system has an R-configuration with an ee value of 98%, while the product in the ethanol solvent system exhibits an S-configuration with an ee value of 93%. The objective of this work is to combine mechanistic experiments with DFT calculations to elucidate the role of solvents in modulating the enantioselectivity of this catalytic system and to provide a theoretical foundation and guidance for the development of other solvent-controlled enantioselective catalytic systems.

Key words: asymmetric hydrogenation, transition metal catalysis, density functional theory, solvent effect

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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.

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Fig. & Tab. 8

Figure 1. Examples of bioactive compounds featuring chiral THQ motifs

Scheme 1. Asymmetric catalytic systems: (A) Asymmetric hydrogenation of alkyl-substituted quinoxalines; (B) Asymmetric hydrogenation of disubstituted quinoxalines; (C) Solvent-contro- lled enantiodivergent hydrogenation of quinoxaline

Scheme 2. Outer-sphere mechanism for quinoxaline asymmetric hydrogenation

Figure 2. DFT-calculated energy potential surface in a toluene/1,4-dioxane system

Figure 3. Selectivity analysis: (A) IGMH analysis; (B) Distortion-interaction analysis

Figure 4. DFT-calculated energy potential surface in an ethanol system

Figure 5. Selectivity analysis: (A) IGMH analysis; (B) Distortion-interaction analysis

Scheme 3. Proposed mechanism of iridium-catalyzed asymmetric hydrogenation reactions in different solvents: (A) toluene/dioxane system; (B) ethanol system

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溶剂效应对Ir催化的不对称氢化反应对映选择性影响的理论研究

Theoretical Study on the Solvent Effect on the Enantioselectivity of Iridium-Catalyzed Asymmetric Hydrogenation Reactions

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References 31

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