基于C—H键断裂的多氯烷基化反应研究进展

doi:10.6023/cjoc202211018

摘要/Abstract

多氯代烃在有机合成和化学工业, 特别是制药和材料领域中尤其重要, 引起了化学家们的广泛关注, 诞生了各种合成氯代有机化合物的方法. 引入多氯烷基能够作为关键成分改变化合物的药物活性, 同时, 多氯烷基可以作为前体转化为醛、酮和羧酸等具有不同功能性的官能团, 为实现天然产物的后期合成和修饰提供强有力的支持. 通过断裂多氯烷烃中的C—H键来构建多氯代化合物的策略, 由于具有高步骤经济性, 已成为化学家们的研究热点, 取得了重要的研究进展. 总结了利用二氯甲烷、三氯甲烷作为多氯烷基的前体, 从不同的反应体系(过渡金属催化、可见光介导、无金属参与)出发, 综述了近十年来基于C—H键断裂策略的多氯烷基化反应的相关工作, 并对反应设计、机理研究、研究展望等给予评述.

关键词: 多氯烷基化, 氯代烷烃, 自由基反应, C—H键断裂

Polychlorinated hydrocarbons are particularly important in organic synthesis and chemical industries, especially in the fields of pharmaceuticals and materials, which have attracted wide attention of chemists and given birth to various methods for the synthesis of chlorinated organic compounds. The introduction of polychloroalkyl can be used as key component to change the drug activity of the compound. At the same time, polychloroalkyl can be used as precursors to transform into aldehydes, ketones, carboxylic acids and other functional groups with different functions, providing strong support for the realization of late synthesis and modification of natural products. The strategy of constructing polychlorinated compounds by breaking C—H bonds in polychloroalkanes has become a hot research topic among chemists due to its high step economy and has made significant progress in research. In this paper, the use of dichloromethane and trichloromethane as precursors of polychloroalkyl is summarized, starting from different reaction systems (transition metal catalyzed, visible light mediated, metal-free involved), the relevant work of polychloroalkylation reactions based on C—H bond breaking strategy in the last decade is reviewed, and the reaction design, mechanism research, and research prospects are reviewed.

Key words: polychlorinated alkylation, chlorinated alkanes, radical reaction, C—H bond cleavage

引用此文

黄芬, 罗维纬, 周俊. 基于C—H键断裂的多氯烷基化反应研究进展[J]. 有机化学, 2023, 43(7): 2368-2390.

Fen Huang, Weiwei Luo, Jun Zhou. Research Progress of Polychloroalkylation Based on C—H Bond Cleavage[J]. Chinese Journal of Organic Chemistry, 2023, 43(7): 2368-2390.

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图/表 15

图1. 具有生物活性的多氯代有机化合物

Figure 1. Biologically active polychlorinated organic compounds

图式1. 铁催化活化烯烃的碳二氯烷基化反应的可能机理

Scheme 1. Possible mechanism of iron-catalyzed carbodichloride alkylation of activated alkenes

图式2. 铜促进烯烃的多氯代烷基化反应机理

Scheme 2. Mechanism of copper-promoted polychlorinated alkylation of olefins

图式3. 邻氰基丙烯酰胺的碳氯烷基化反应

Scheme 3. Cascade carbochloroalkylation of ortho-cyanoarylacrylamides

图式4. 邻氰基丙烯酰胺和N-(芳基磺酰基)丙烯酰胺的碳氯烷基化反应机理

Scheme 4. Mechanism of carbochloroalkylation of ortho-cyanoarylacrylamides and N-(arylsulfonyl)acrylamides

图式5. 1,6-二烯与烷基氯化物的5-exo-trig环化反应机理

Scheme 5. Mechanism of 5-exo-trig cyclization of 1,6-dienes with alkyl chlorides

图式6. 光氧化还原苯乙烯与多氯烷烃和氮亲核试剂的1,2-烷基化反应机理

Scheme 6. Mechanism of photoredox 1,2-alkylation of styrene with polychlorinated alkanes and nitrogen nucleophiles

图式7. Eosin Y催化活性烯烃与卤甲烷的碳三氯烷基化的反应机理

Scheme 7. Mechanism of Eosin Y-catalyzed carbotrichloride alkylation of activated alkenes with halomethane

图式8. 环丙烯与三氯甲基自由基的反应机理

Scheme 8. Reaction mechanism of cyclopropene with trichlo- romethyl radical

图式9. 未活化亚胺与芳烃和氯仿的三组分反应的机理

Scheme 9. Mechanism of three-component reaction of unactivated imines with aromatic hydrocarbons and chloroform

图式10. 肉桂酸与1,2-二氯乙烷的脱羧偶联反应

Scheme 10. Decarboxylation coupling reaction of cinnamic acid and 1,2-dichloroethane

图式11. 自由基促进氯烷烃与肉桂酸和β-硝基苯乙烯烯化反应机理

Scheme 11. Mechanism of free radical-promoted alkenylation of chloroalkanes with cinnamic acid and β-nitrostyrene

图式12. N-烯丙基苯甲酰胺与多氯甲烷反应的可能机理

Scheme 12. Plausible mechanism of the reactions of N-allylbenzamides with polychloromethanes

图式13. N-烯丙基苯酰胺与氯烷烃的串联环化反应机理

Scheme 13. Mechanism of cascade cyclization of N-allylbenzamide with chloroalkanes

图式14. N-苄基丙烯酰胺与多卤代烷烃的螺环化反应机理

Scheme 14. Mechanism of spirocyclization of N-benzylacrylamides with polyhaloalkanes

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