细微差别取代化合物的手性识别及不对称催化反应研究进展★

doi:10.6023/cjoc202506025

有机化学 ›› 2025, Vol. 45 ›› Issue (9): 3163-3174.DOI: 10.6023/cjoc202506025 上一篇下一篇

综述与进展

细微差别取代化合物的手性识别及不对称催化反应研究进展^★

吕亚, 何贵含, 刘剑剑, 陈永正^*()

遵义医科大学药学院贵州省化学药物创制全省重点实验室贵州遵义 563003

收稿日期:2025-06-18 修回日期:2025-09-03 发布日期:2025-09-11
基金资助:
国家自然科学基金(32271537); 国家自然科学基金(22061049); 贵州省科技厅(QKHRCPTGCC-2023-003); 贵州省科技厅(GHJD-2025-001); 及遵义市科技局(ZSKRPT2020-5); 及遵义市科技局(ZSKH-2018-3); 及遵义市科技局(ZSKRPT-2021-5)

Advances in Chiral Recognition and Asymmetric Catalysis of Minimal Structural Differences Compounds^★

LüYa, Guihan He, Jianjian Liu, Yongzheng Chen^*()

Guizhou Provincial Key Laboratory of Innovation and Manufacturing for Pharmaceuticals, School of Pharmacy, Zunyi Medical University, Zunyi, Guizhou 563003

Received:2025-06-18 Revised:2025-09-03 Published:2025-09-11
Contact: *E-mail: yzchen@zmu.edu.cn
About author:
^★ Academic Papers of the 27^th Annual Meeting of the China Association for Science and Technology.
Supported by:
National Natural Science Foundation of China(32271537); National Natural Science Foundation of China(22061049); Science and Technology Department of Guizhou Province(QKHRCPTGCC-2023-003); Science and Technology Department of Guizhou Province(GHJD-2025-001); Science and Technology Department of Zunyi City(ZSKRPT2020-5); Science and Technology Department of Zunyi City(ZSKH-2018-3); Science and Technology Department of Zunyi City(ZSKRPT-2021-5)

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摘要/Abstract

不对称催化是合成手性化合物的一种直接且高效的方法, 其核心在于开发高效的手性催化剂, 以实现对底物的前手性面或前手性中心进行精准的手性识别. 尽管该领域在过去几十年中已取得显著进展, 但目前大多数工作都集中在含有芳基和烷基的底物上, 当取代基具有非常相似的空间和电性时, 却难以实现高对映选择性. 对仅有微小差异的取代基团进行精确的手性识别仍然是一个重大挑战. 传统方法中手性催化剂主要利用催化剂和底物之间的空间相互作用来控制立体选择性, 自然界中的酶则是利用有限的活性位点对有机转化进行精确控制. 综述了近年来基于细微差别取代化合物的精准识别及不对称催化反应研究进展, 涵盖金属催化、有机小分子催化和生物催化等内容.

关键词: 细微差别取代, 精准识别, 不对称合成, 酶催化

Asymmetric catalysis is a direct and efficient method for synthesizing chiral compounds, with its core focus lying in the development of highly efficient chiral catalysts to achieve precise chiral recognition of prochiral faces or prochiral centers in substrates. Although significant progress has been made in this field over the past few decades, most current studies concentrate on substrates containing aryl and alkyl groups, while achieving high enantioselectivity remains challenging when substituents exhibit minimal steric and electronic differences. The precise chiral discrimination of substituents with subtle differences still constitutes a major challenge. In traditional approaches, chiral catalysts primarily rely on steric interactions between the catalyst and substrate to control stereoselectivity, whereas enzymes in nature utilize confined active sites to achieve precise regulation of organic transformations. The recent advances in the precise recognition of minimally diffe- rentiated substrates and their applications in asymmetric catalytic reactions, covering metal catalysis, organocatalysis, biocatalysis, and related areas are summarized.

Key words: minimal structural difference, accurate identification, asymmetric synthesis, enzyme catalysis

引用此文

吕亚, 何贵含, 刘剑剑, 陈永正. 细微差别取代化合物的手性识别及不对称催化反应研究进展^★[J]. 有机化学, 2025, 45(9): 3163-3174.

LüYa, Guihan He, Jianjian Liu, Yongzheng Chen. Advances in Chiral Recognition and Asymmetric Catalysis of Minimal Structural Differences Compounds^★[J]. Chinese Journal of Organic Chemistry, 2025, 45(9): 3163-3174.

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图/表 20

图式1. 基于细微差别取代的不对称催化转化

Scheme 1. Asymmetric catalytic conversion based on minimal structural differences

图式2. 相似基团取代酮的不对还原胺化

Scheme 2. Asymmetric reductive amination of ketones replaced by similar groups

图式3. 相似基团取代酮的不对称硅氢化

Scheme 3. Asymmetric hydrosilylation of ketones replaced by similar groups

图式4. 相似烷基取代酮的不对称氢化反应

Scheme 4. Asymmetric hydrogenation reaction of similar alkyl-substituted ketones

图式5. 相似芳基取代酮的不对称氢化反应

Scheme 5. Asymmetric hydrogenation reactions of similar arylsubstituted ketones

图式6. 相似基团取代酮的不对称氰硅化反应

Scheme 6. Asymmetric cyanosilylation reaction of ketones substituted by similar groups

图式7. 相似基团取代亚胺的不对称氢化反应

Scheme 7. Asymmetric hydrogenation reaction of similar group-substituted imines

图式8. 二烷基酮亚胺的对映选择性硼化

Scheme 8. Enantioselective borylation of dialkyl ketimines

图式9. 叔丁基的“伞形”效应

Scheme 9. The “umbrella” effect of tert-butyl

图式10. 叔丁基亚磺酰酮亚胺的不对称还原和加成反应

Scheme 10. Asymmetric reductions and additions of N-tert-butylsulfinyl ketimines

图式11. 细微差别取代的酮亚胺/烯胺α位不对称官能化反应

Scheme 11. Asymmetric α-functionalization of ketimines/ena- mines with minimally different substituents

图式12. 二取代烯烃的不对称硼氢化反应

Scheme 12. Asymmetric reaction hydroboration of disubstituted alkenes

图式13. 拆分辅基策略不对称合成下细微差别取代的手性醇

Scheme 13. Kinetic resolution auxiliary strategy for synthesizing chiral alcohols bearing minimally different substituents

图式14. 手性磷酸催化的去对称化反应

Scheme 14. Desymmetry catalyzed by chiral phosphoric acid

图式15. 铁催化硫化物不对称胺化反应

Scheme 15. Iron-catalyzed asymmetric imidation of sulfides

图式16. 相似基团取代的烷基自由基的不对称胺化

Scheme 16. Asymmetric amination of alkyl radicals substituted by similar groups

图式17. 羟腈裂解酶催化2-丁酮的不对称氰基化

Scheme 17. Asymmetric cyanation of 2-butanone catalyzed by hydroxynitrile lyase

图式18. 多酶氧化还原体系实现亚砜的去消旋化

Scheme 18. Multienzyme redox system for deracemization of sulfoxides

图式19. 生物催化叔碳C—H键的对映选择性伯胺化

Scheme 19. Biocatalytic, enantioenriched primary amination of tertiary C—H bonds

图式20. 相似基团取代酮的不对称硅氢化

Scheme 20. Asymmetric hydrosilylation of ketones replaced by similar groups

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细微差别取代化合物的手性识别及不对称催化反应研究进展^★

Advances in Chiral Recognition and Asymmetric Catalysis of Minimal Structural Differences Compounds^★

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细微差别取代化合物的手性识别及不对称催化反应研究进展★

Advances in Chiral Recognition and Asymmetric Catalysis of Minimal Structural Differences Compounds★

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细微差别取代化合物的手性识别及不对称催化反应研究进展^★

Advances in Chiral Recognition and Asymmetric Catalysis of Minimal Structural Differences Compounds^★