氯仿参与的烯烃自由基加成反应的研究进展

doi:10.6023/cjoc202303016

摘要/Abstract

多卤甲基化合物, 尤其是具有二氯甲基或三氯甲基结构的多氯甲基化合物, 被广泛应用于医药、农业及有机功能材料等领域. 此外, 多氯甲基还可以很容易地转化为氨基、羟基、羧基和羰基等各种官能团, 这些官能团可进一步用于构建复杂的环状结构. 因此, 开发有效的多氯甲基化策略, 在许多具有生物活性的天然分子的合成中具有重要的意义. 氯仿是一种容易获得的化学资源, 在自由基引发剂存在下可发生自由基转化, 通过氢原子转移(HAT)形成•CCl₃自由基或通过卤素原子转移(XAT)形成•CHCl₂自由基. 按照氯仿产生自由基种类的不同, 对氯仿参与烯烃自由基加成, 从而构建多氯甲基取代化合物的最新研究进展进行了梳理和总结, 并对反应范围、局限性以及部分机理进行了讨论.

关键词: 多卤甲基化合物, 多氯甲基化, 氯仿, 烯烃, 自由基加成

Polyhalomethyl compounds, especially those with dichloromethyl or trichloromethyl structures, are widely used in fields, such as medicine, agriculture and organic functional materials. In addition, polychloromethyl could also be easily converted into various functional groups, such as amino, hydroxyl, carboxyl and carbonyl groups, which could be further used to construct complex ring structures. Therefore, the development of effective polychlorinated methylation strategies has important research significance in the synthesis of many natural molecules with biological activities. Chloroform is an easily available chemical resource that can undergo free radical transformation in the presence of free radical initiators, forming •CCl₃ radical through hydrogen atom transfer (HAT) and •CHCl₂ radical through halogen atom transfer (XAT). According to the different types of free radicals produced by chloroform, the latest research progress of chloroform participating radical addition of alkenes to construct polychloromethyl substituted compounds is summarized, and the reaction range, limitations and some mechanisms are also discussed.

Key words: polyhalomethyl compound, polychlorinated methylation, chloroform, alkene, radical addition

引用此文

张建涛, 张聪, 莫诺琳, 罗佳婷, 陈莲芬, 刘卫兵. 氯仿参与的烯烃自由基加成反应的研究进展[J]. 有机化学, 2023, 43(9): 3098-3106.

Jiantao Zhang, Cong Zhang, Nuolin Mo, Jiating Luo, Lianfen Chen, Weibing Liu. Research Progress in Radical Addition Reaction of Alkenes Involving Chloroform[J]. Chinese Journal of Organic Chemistry, 2023, 43(9): 3098-3106.

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图/表 23

图1. 含多氯甲基取代片段的天然产物

Figure 1. Natural products containing polychlorinated methyl substitution fragments

图式1. 氯仿选择性发生C—H键和C—Cl键断裂

Scheme 1. Selective cleavage of C—H bond and C—Cl bond in chloroform

图式2. N-芳基丙烯酰胺与氯仿的三氯甲基化/环化反应

Scheme 2. Trichloromethylation/cyclization reaction of N-aryl- acrylamides with CHCl3

图式3. N-芳基丙烯酰胺与氯仿可能的反应机理

Scheme 3. Possible mechanism of N-arylacrylamides with CHCl3

图式4. 酰肼基丙烯酰胺与氯仿在激发态的共轭加成

Scheme 4. Conjugate addition of acrylanilides with CHCl3 from the excited state

图式5. 锰促进邻氰基芳基丙烯酰胺与氯仿的三氯甲基化/环化反应

Scheme 5. Mn-mediated trichloromethylation/cyclization reaction of ortho-cyanoarylacrylamides with CHCl3

图式6. 无金属催化N-烯丙基芳胺与氯仿的三氯甲基化/环化反应

Scheme 6. Metal-free trichloromethylation/cyclization reaction of N-allyl anlines with CHCl3

图式7. 烯醇硅醚与氯仿的三氯甲基自由基加成/消除反应

Scheme 7. Trichloromethyl radical addition/elimination of enol silyl ethers with CHCl3

图式8. 铜介导呋喃与氯仿和醇的烷氧羰基化反应

Scheme 8. Cu-mediated alkoxycarbonylation of furans with CHCl3 and alcohols

图式9. 自由基介导烯烃与氯仿和醇的烷氧基三氯甲基化反应

Scheme 9. Radical-mediated alkoxytrichloromethylation of styrenes with CHCl3 and alcohols

图式10. 烯烃烷氧基三氯甲基化反应机理

Scheme 10. Possible mechanism of alkoxytrichloromethylation of styrenes

图式11. 烯烃与氯仿和氮亲核试剂的三组分光还原1,2-烷基胺化反应

Scheme 11. Three-component photoredox 1,2-alkylamination of styrenes with CHCl3 and nitrogen nucleophiles

图式12. 非活化烯烃与氯仿的自由基多氯甲基化/环化反应

Scheme 12. Radical polychloromethylation/cyclization reaction of unactivated alkenes with CHCl3

图式13. 可见光介导的烯烃与氯仿的多氯化反应

Scheme 13. Visible light-mediated polychlorination of alkenes with CHCl3

图式14. 无金属作用的烯烃与氯仿和过氧叔丁醇的二氯甲基化-过氧化反应

Scheme 14. Medal-free dichloromethylation-peroxidation of alkenes with CHCl3 and TBHP

图式15. 铜催化烯烃二氯甲基化-过氧化反应机理

Scheme 15. Possible mechanism of Cu-catalyzed dichloromethylation-peroxidation of alkenes

图式16. α?氨基自由基介导的烯烃与氯仿的双官能化反应

Scheme 16. α?Amino radical-mediated diverse difunctionalization of alkenes with CHCl3

图式17. 烯烃与氯仿、三乙胺和过氧叔丁醇四组分串联反应

Scheme 17. Four-component sequential reactions of alkenes with CHCl3, Et3N and TBHP

图式18. 无金属作用的烯烃与氯仿的氢-二氯甲基化反应

Scheme 18. Medal-free hydrodichloromethylation of alkenes with CHCl3

图式19. 可见光照射下烯酮与氯仿的二氯甲基化反应

Scheme 19. Visible-light-irradiated dichloromethylation of enones with CHCl3

图式20. 可见光诱导烯烃与氯仿的1,1-二氯甲基化反应

Scheme 20. Visible-light-induced 1,1-dichloromethylation of alkenes with CHCl3

图式21. 可见光照射条件下烯烃与氯仿合成α-氯代酮

Scheme 21. Synthesis of α-chloroketones from olefins with CHCl3 under visible-light irradiation conditions

图式22. α-氯代苯乙酮的反应机理

Scheme 22. Possible mechanism of α-chloroacetophenones

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