基于小分子硫-氟砌块的磺酰氟化合物的合成研究进展

doi:10.6023/cjoc202407019

摘要/Abstract

硫氟交换点击化学作为一种新兴的合成技术, 自2014年提出以来迅速发展. 该技术基于磺酰氟基团, 实现了高效快速的磺酰基化合物合成. 磺酰氟化合物因其独特的亲电功能, 在有机合成、化学生物学、新药研发及新材料开发等领域展现出广泛的应用. 近年来, 硫氟交换点击化学不仅推动了高价硫氟类化合物的合成, 还成功应用于抗肿瘤、抗菌、抗氧化等多种药物研究, 显著提升了药物的生物活性. 作者基于小分子硫-氟砌块的设计与开发, 详细介绍了近年来磺酰氟类化合物的合成. 磺酰氟化合物作为关键中间体, 将在更多高科技领域发挥重要作用, 推动化学、材料科学及生物医学的持续发展.

关键词: 硫氟交换, 点击化学, 磺酰氟, 硫-氟砌块

The sulfur-fluoride exchange click chemistry, as an emerging synthetic technique, has developed rapidly since its inception in 2014. Leveraging the sulfonyl fluoride group, this technology enables efficient and rapid synthesis of sulfonyl compounds. Sulfonyl fluorides, owing to their unique electrophilic properties, have found widespread applications in fields such as organic synthesis, chemical biology, new drug discovery, and novel material development. In recent years, sulfur-fluoride exchange click chemistry not only has facilitated the synthesis of high-value sulfur-fluoride compounds but also has been successfully applied in the research of anti-tumor, anti-bacterial, anti-oxidant, and other drugs, significantly enhancing the biological activity of these medications. Drawing upon the design and development of small-molecule sulfur-fluoride building blocks, the author provides a detailed account of the synthesis of sulfonyl fluorides in recent years. As key intermediates, sulfonyl fluorides will play a pivotal role in numerous high-tech sectors, driving the continuous advancement of chemistry, materials science, and biomedical research.

Key words: sulfur-fluoride exchange, click chemistry, sulfonyl fluoride, sulfur-fluoride building blocks

引用此文

冷静, 黄浩, 徐洁, 秦华利. 基于小分子硫-氟砌块的磺酰氟化合物的合成研究进展[J]. 有机化学, 2025, 45(4): 1223-1238.

Jing Leng, Hao Huang, Jie Xu, Huali Qin. Research Progress on the Synthesis of Sulfonyl Fluoride Compounds Based on Small Molecule Sulfur-Fluoride Building Blocks[J]. Chinese Journal of Organic Chemistry, 2025, 45(4): 1223-1238.

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图/表 40

图式1. 氟-氯交换合成磺酰氟化合物

Scheme 1. Synthesis of sulfonyl fluoride compounds through fluorine-chlorine exchange

图式2. ESF的化学合成

Scheme 2. Chemical synthesis of ESF

图式3. 亲核试剂对ESF的Michael加成反应

Scheme 3. Michael addition reaction of nucleophiles to ESF

图式4. ESF与环状烯烃和呋喃环的Diels-Alder反应

Scheme 4. Diels-Alder reaction of ESF with cyclic olefins and furans

图式5. ESF与马来酰亚胺的[2＋2]环加成反应

Scheme 5. [2＋2] cycloaddition reaction between ESF and maleimide

图式6. 光催化下ESF与羧酸的自由基加成反应

Scheme 6. Radical addition reaction of ESF with carboxylic acid under photocatalysis

图式7. Heck偶联反应合成2-取代乙烯基磺酰氟

Scheme 7. Synthesis of 2-substituted vinyl sulfonyl fluorides via heck coupling reaction

图式8. 铑(III)催化下定位基导向的碳-氢键活化合成2-芳基乙烯基磺酰氟

Scheme 8. Rhodium(III)-catalyzed site-selective C—H activation for the synthesis of 2-arylvinyl sulfonyl fluorides

图式9. 钯催化下无定位基导向的碳-氢键活化合成2-芳基乙烯基磺酰氟

Scheme 9. Palladium-catalyzed non-directed C—H activation for the synthesis of 2-arylvinyl sulfonyl fluorides

图式10. BESF的合成路线

Scheme 10. Synthetic route to BESF

图式11. BESF参与的环加成、Micheal加成、Suzuki偶联反应

Scheme 11. Cycloaddition, Michael addition, and Suzuki coupling reactions involving BESF

图式12. DESF与肟、叠氮、胺发生的环化反应

Scheme 12. Cyclization reactions of DESF with oximes, azides, and amines

图式13. BESF与叠氮的环加成反应

Scheme 13. Cycloaddition reaction of BESF with azides

图式14. BESF与氮杂环化合物的环加成反应

Scheme 14. Cycloaddition reactions of BESF with heterocyclic nitrogen compounds

图式15. ASF的合成与应用

Scheme 15. Synthesis and applications of ASF

图式16. BTESF的合成与应用

Scheme 16. Synthesis and applications of BTESF

图式17. SASF的合成及其在DOC合成领域的应用

Scheme 17. Synthesis of SASF and its application in the field of DOC synthesis

图式18. SASF与烯烃的自由基加成反应

Scheme 18. Radical addition reaction of SASF with olefins

图式19. BDF的合成与应用

Scheme 19. Synthesis and application of BDF

图式20. SO2F2与酚/酚醚的反应

Scheme 20. Reaction of SO2F2 with phenols/phenol ethers

图式21. SO2F2与酮/酚的反应

Scheme 21. Reaction of SO2F2 with ketones/ phenols

图式22. SO2F2与羟胺的反应

Scheme 22. Reaction of SO2F2 with hydroxylamine

图式23. SO2F2与氮亲核试剂的反应

Scheme 23. Reaction of SO2F2 with nitrogen nucleophiles

图式24. SO2F2与烯炔前体、胺的反应

Scheme 24. Reaction of SO?F? with enyne precursor and amine

图式25. SO2F2与格氏试剂的反应

Scheme 25. Reaction between SO?F? and Grignard reagent

图式26. FDIT的合成及其反应性质

Scheme 26. Synthesis of FDIT and its reactive properties

图式27. FSAP的设计合成与应用

Scheme 27. Synthesis and application of FSAP

图式28. EDSF的合成与应用

Scheme 28. Synthesis and application of EDSF

图式29. MeO-ESF的合成与应用

Scheme 29. Synthesis and application of MeO-ESF

图式30. BCASF的合成与应用

Scheme 30. Synthesis and application of BCASF

图式31. CESF的合成与应用

Scheme 31. Synthesis and application of CESF

图式32. BPESF在环化反应中的应用

Scheme 32. Application of BPESF in cyclization reactions

图式33. ClSO2F参与的烯烃加成反应

Scheme 33. Addition reaction of ClSO2F with olefins

图式34. ClSO2F参与的炔烃加成反应

Scheme 34. Addition reaction of ClSO2F with alkynes

图式35. FSI的合成与应用

Scheme 35. Synthesis and application of FSI

图式36. FABI的合成与应用

Scheme 36. Synthesis and application of FABI

图式37. FABI与两分子烯烃的串联加成反应

Scheme 37. Tandem addition reaction of FABI with two molecules of olefins

图式38. MDSF的合成与应用

Scheme 38. Synthesis and application of MDSF

图式39. MDF的合成与应用

Figure 39. Synthesis and application of MDF

图式40. AISF的合成及其反应性质

Scheme 40. Synthesis of AISF and its reactive properties

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