Research Progress in Radical Addition Reaction of Alkenes Involving Chloroform

doi:10.6023/cjoc202303016

Abstract

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

Cite this article

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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Fig. & Tab. 23

Figure 1. Natural products containing polychlorinated methyl substitution fragments

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

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

Scheme 3. Possible mechanism of N-arylacrylamides with CHCl3

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

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

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

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

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

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

Scheme 10. Possible mechanism of alkoxytrichloromethylation of styrenes

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

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

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

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

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

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

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

Scheme 18. Medal-free hydrodichloromethylation of alkenes with CHCl3

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

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

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

Scheme 22. Possible mechanism of α-chloroacetophenones

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