光酶催化不对称自由基加成反应研究进展

doi:10.6023/cjoc202408004

摘要/Abstract

光催化能够在温和的反应条件下生成高活性自由基物种, 从而参与多种化学反应. 然而, 光催化在化学选择性和对映选择性的控制方面始终面临挑战. 酶催化作为一种绿色且高选择性的催化方式, 与光催化相结合形成的光酶催化模式已被证明能够有效控制自由基反应的选择性, 因此, 这一领域引起了广泛关注并迅速发展. 总结了近年来光酶催化在不对称自由基加成反应中的应用, 并根据反应类型分为分子内自由基加成和分子间自由基加成, 每一种反应类型再按照自由基的生成方式分为单电子还原途径和单电子氧化途径两个方面进行详细阐述和讨论. 希望本综述能为研究人员提供有价值的参考, 推动该领域的进一步发展.

关键词: 光催化, 酶催化, 自由基加成, 不对称催化

Photocatalysis can generate highly reactive radical species under mild reaction conditions, thereby participating in various chemical reactions. However, the precise control of chemical selectivity and enantioselectivity always remains a formidable challenge due to the high reactivity of radicals. Enzymatic catalysis, known for its green and highly selective properties, when combined with photocatalysis to form photoenzymatic catalysis, has been proven effective in controlling the selectivity of radical reactions. Consequently, this area has garnered widespread attention and rapid development. This review summarizes the recent applications of photoenzymatic catalysis in asymmetric radical addition reactions, dividing them into intramolecular and intermolecular radical additions based on the reaction type. Each type of reaction is further discussed in detail according to the generation pathway of radicals, categorized into single-electron reduction pathways and single-electron oxidation pathways. It is hoped that this review will provide valuable references for researchers and promote further development in this field.

Key words: photocatalysis, enzyme catalysis, radical addition, asymmetric catalysis

引用此文

蒋晨阳, 尹艳丽, 江智勇. 光酶催化不对称自由基加成反应研究进展[J]. 有机化学, 2025, 45(5): 1614-1633.

Chenyang Jiang, Yanli Yin, Zhiyong Jiang. Advances in Photoenzyme-Catalyzed Asymmetric Radical Addition Reactions[J]. Chinese Journal of Organic Chemistry, 2025, 45(5): 1614-1633.

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图/表 28

图式1. 光激发黄素酶实现立体选择性的自由基环化反应

Scheme 1. Photoexcitation of flavoenzymes promotes a stereoselective radical cyclization

图式2. 黄素依赖的烯烃还原酶催化的不对称氧化还原中性自由基环化反应

Scheme 2. Flavin-dependent ‘ene’-reductases facilitate asymmetric redox-neutral radical cyclization

图式3. 光酶促生成不稳定烷基自由基: 一种不对称还原环化反应

Scheme 3. Photoenzymatic formation of reactive alkyl radicals: an asymmetric reductive cyclization

图式4. 利用工程化黄素依赖“烯”还原酶的光酶促α-叔胺合成

Scheme 4. Synthesis of α‑tertiary amines through photoenzymatic processes using engineered flavin-dependent “ene”-reductases

图式5. 光酶催化的脱卤自由基分子内环加成反应

Scheme 5. Photoenzyme catalyzed dehalogenated radical intramolecular cycloaddition reaction

图式6. 光酶催化对映选择性合成含氧苯稠合并杂环

Scheme 6. Photoenzymatic enantioselective synthesis of oxygen-containing benzo-fused heterocycles

图式7. 利用酶调控氮中心自由基进行对映选择性加氢胺化

Scheme 7. Utilizing enzymes to regulate nitrogen-centered radicals for enantioselective hydroamination

图式8. 脂肪酸光脱羧酶实现对映体分歧的光生物催化自由基环化反应

Scheme 8. Stereodivergent photobiocatalytic radical cyclization using fatty acid photodecarboxylases

图式9. 光酶催化对映选择性分子间自由基氢烷基化

Scheme 9. Enantioselective intermolecular radical hydroalkylation catalyzed by photoenzymes

图式10. 通过四元电荷转移复合物实现烯烃的分子间氢烷基化反应

Scheme 10. Intermolecular hydroalkylation of alkenes enabled by a quaternary charge-transfer complex

图式11. 光诱导酶催化实现对映选择性自由基共轭加成反应

Scheme 11. Enantioselective radical conjugate addition enabled by photoinduced enzymatic catalysis

图式12. 烯还原酶催化的C(sp3)—C(sp3)对映选择性亲电交叉偶联反应

Scheme 12. Ene-reductase-catalyzed enantioselective electrophilic C(sp3)—C(sp3) cross-coupling reaction

图式13. 酶促光氧化还原催化硝基烷烃的不对称C—H烷基化反应

Scheme 13. Enzyme-promoted photoredox catalysis of asymmetric C—H alkylation of nitroalkanes

图式14. 酶促氢原子转移实现氮杂芳烃的远端立体控制

Scheme 14. Remote stereocontrol with azaarenes via enzymatic hydrogen atom transfer

图式15. 光酶催化自由基介导的重氮化合物和烯烃发生的不对称氢烷基化反应

Scheme 15. Asymmetric hydroalkylation of diazo compounds and alkenes via photoenzymatic radical catalysis

图式16. 光酶催化烯烃的不对称氢磺酰化反应

Scheme 16. Photoenzymatic asymmetric hydrosulfonylation of alkenes

图式17. 光酶催化烯烃的不对称碳羟基化反应

Scheme 17. Photoenzymatic asymmetric carbohydroxylation of alkenes

图式18. 光酶催化氮中心自由基介导的分子间不对称氢胺化反应

Scheme 18. Photoenzymatic nitrogen-centered radical-mediated intermolecular asymmetric hydroamination reaction

图式19. 通过协同光氧化还原-吡哆醛自由基生物催化实现立体选择性氨基酸合成

Scheme 19. Stereoselective synthesis of amino acids through combined photoredox and pyridoxal radical biocatalysis

图式20. 光生物催化氧化偶联立体选择性合成氨基酸

Scheme 20. Stereoselective amino acid synthesis by photobiocatalytic oxidative coupling

图式21. 光酶协同催化使用苏氨酸醛缩酶合成α-三级氨基酸

Scheme 21. Synergistic photoenzymatic catalysis enables synthesis of α-tertiary amino acids using threonine aldolases

图式22. 苏氨酸醛缩酶催化的非传统光诱导自由基引发氨基酸的对映选择性α-烷基化

Scheme 22. Threonine aldolase catalyzed enantioselective α‑ alkylation of amino acids via unconventional photoinduced radical initiation

图式23. 通过光酶促氢烷基化反应实现烯烃的不对称合成α-氯酰胺

Scheme 23. Asymmetric synthesis of α‑chloroamides via photoenzymatic hydroalkylation of olefins

图式24. 基于亚胺还原酶的光酶催化手性胺的模块化合成

Scheme 24. Modular access to chiral amines via imine reductase-based photoenzymatic catalysis

图式25. 不对称光酶促反应将含氟基团引入烯烃

Scheme 25. Asymmetric photoenzymatic incorporation of fluorinated motifs into olefins

图式26. 可见光直接激发黄素蛋白用于氧化还原中性的不对称自由基氢芳基化反应

Scheme 26. Direct visible-light-excited flavoproteins for redox-neutral asymmetric radical hydroarylation

图式27. 利用光酶协同催化的对映选择性脱羧烷基化反应

Scheme 27. Enantioselective decarboxylative alkylation using synergistic photoenzymatic catalysis

图式28. 光酶催化下芳基磺酸钠和α-甲基苯乙烯的不对称氢磺酰化反应

Scheme 28. Asymmetric hydrosulfonylation of aryl sulfonates and α-methylstyrene catalyzed by photoenzymes

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