自由基途径的[1.1.1]螺桨烷官能化研究进展

doi:10.6023/cjoc202512007

摘要/Abstract

双环[1.1.1]戊烷(BCP)作为一种具有三维立体结构的桥环骨架, 因其可作为苯环、叔丁基及炔烃等基团的生物电子等排体, 已在药物化学领域得到广泛应用. 目前, 通过[1.1.1]螺桨烷的自由基开环反应, 已成为构建BCP衍生物最常用的策略. 传统[1.1.1]螺桨烷自由基官能团化反应的条件苛刻, 官能团兼容性较差. 近年来, 随着光催化在有机合成中的迅速发展, 多种光催化的[1.1.1]螺桨烷官能团化策略相继被报道, 并被成功应用于药物分子的合成. 对基于自由基途径的[1.1.1]螺桨烷官能化研究进展进行简要综述.

关键词: 1.1.1]螺桨烷, 双环[1.1.1]戊烷, 自由基, 光催化, 官能团化

Bicyclo[1.1.1]pentane (BCP), a three-dimensional bridged ring scaffold, has been widely used in medicinal chemistry due to its role as a bioisostere for groups such as benzene rings, tert-butyl groups, and alkynes. Currently, the radical ring-opening reaction of [1.1.1]propellane has become the most common strategy for constructing BCP derivatives. Traditional radical functionalization of [1.1.1]propellane typically requires harsh conditions and exhibits poor functional group compatibility. In recent years, with the rapid development of photocatalysis in organic synthesis, various photocatalytic functionalizations of [1.1.1]propellane have been reported and successfully applied in the synthesis of drug molecules. Herein, a concise overview of recent advances in radical-based functionalization of [1.1.1]propellane is provided.

Key words: 1.1.1]propellane, bicyclo[1.1.1]pentane, radical, photocatalysis, functionalization

引用此文

董建洋, 薛东. 自由基途径的[1.1.1]螺桨烷官能化研究进展[J]. 有机化学, 2026, 46(4): 1464-1480.

Jianyang Dong, Dong Xue. Research Progress on the Functionalization of [1.1.1]Propellane via Radical Pathways[J]. Chinese Journal of Organic Chemistry, 2026, 46(4): 1464-1480.

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图/表 40

图式1. 含BCP结构的生物活性分子

Scheme 1. Bioactive molecules featuring the BCP motif

图式2. 传统方法合成BCP衍生物

Scheme 2. Synthesis of BCP derivatives using traditional methods

图式3. [1.1.1]螺桨烷的合成

Scheme 3. Synthesis of [1.1.1]propellane

图式4. [1.1.1]螺桨烷的自由基官能团化

Scheme 4. Radical functionalization of [1.1.1]propellane

图式5. 锰催化[1.1.1]螺浆烷的氢胺化反应

Scheme 5. Manganese-catalyzed hydroamination of [1.1.1]pro- pellane

图式6. 铁催化[1.1.1]螺浆烷的碳胺化反应

Scheme 6. Iron-catalyzed carboamination of [1.1.1]propellane

图式7. [1.1.1]螺桨烷官能团化构筑C—S键

Scheme 7. Functionalization of [1.1.1]propellane for C—S bond formation

图式8. BCP卤化物的合成及转化

Scheme 8. Synthesis and transformation of BCP halides

图式9. [1.1.1]螺桨烷的叠氮-杂芳基化反应

Scheme 9. Azidoheteroarylation of [1.1.1]propellane

图式10. 非对映选择性合成BCP亚磺酰胺

Scheme 10. Diastereoselective synthesis of BCP sulfinamides

图式11. 铜催化合成酰基取代的BCP衍生物

Scheme 11. Copper-catalyzed synthesis of acyl-substituted BCP derivatives

图式12. 铁催化的[1.1.1]螺桨烷、烷基卤化物和芳基格氏试剂的三组分偶联反应

Scheme 12. Iron-catalyzed three-component coupling of [1.1.1]- propellane with alkyl halides and aryl Grignard reagents

图式13. 五氟化硫取代的BCP衍生物的合成

Scheme 13. Synthesis of pentafluorosulfur-substituted BCP derivatives

图式14. 光催化[1.1.1]螺桨烷的双乙酰化反应

Scheme 14. Photo-promoted diacetylation of [1.1.1]propellane

图式15. 光/镍协同催化合成BCP酮

Scheme 15. Synthesis of BCP ketones via synergistic photoredox/nickel catalysis

图式16. 光催化[1.1.1]螺桨烷与烷基羧酸和醛的三组分反应合成BCP酮

Scheme 16. Synthesis of BCP ketones via photocatalytic three-component reaction of [1.1.1]propellane with alkyl carboxylic acids and aldehydes

图式17. 光/NHC协同催化合成BCP酮

Scheme 17. Synthesis of BCP ketones via synergistic photoredox/NHC catalysis

图式18. 光催化[1.1.1]螺桨烷与NHPI酯/Katritzky盐和醛的三组分反应合成BCP酮

Scheme 18. Synthesis of BCP ketones via photocatalytic three- component reaction of [1.1.1]propellane with NHPI esters/Katri- tzky salts and aldehydes

图式19. 汞灯照射下BCP卤化物的合成

Scheme 19. Synthesis of BCP halides under mercury lamp irradiation

图式20. 光催化[1.1.1]螺桨烷的卤化反应

Scheme 20. Photocatalytic halogenation of [1.1.1]propellane

图式21. 光催化α-手性与α-季碳BCP衍生物的合成

Scheme 21. Photocatalytic synthesis of α-chiral and α-quaternary BCP derivatives

图式22. 光催化[1.1.1]螺桨烷的四组分反应合成氟烷基取代BCP

Scheme 22. Synthesis of fluoroalkyl-substituted BCPs via a photocatalytic four-component reaction of [1.1.1]propellane

图式23. 光催化二氟亚甲基取代BCP的合成

Scheme 23. Photocatalytic synthesis of difluoromethylene- substituted BCP

图式24. 光催化[1.1.1]螺桨烷与脂肪烃及醛的苄醇化反应

Scheme 24. Photo-promoted benzylation of [1.1.1]propellane with alkyl hydrocarbons and aldehydes

图式25. 光催化烷基胺与杂芳基取代的BCP衍生物的合成

Scheme 25. Photocatalytic synthesis of alkylamine- and heteroaryl-substituted BCP derivatives

图式26. 姜昕鹏课题组关于光催化[1.1.1]螺桨烷的三组分反应研究

Scheme 26. Photocatalytic three-component reaction of [1.1.1]propellane developed by the Jiang group

图式27. 光催化吡啶取代的BCP衍生物的合成

Scheme 27. Photo-promoted synthesis of pyridine-substituted BCP derivatives

图式28. 光催化全氟烷基取代BCP衍生物的合成

Scheme 28. Photo-promoted synthesis of perfluoroalkyl- substituted BCP derivatives

图式29. 光催化杂芳基取代BCP的合成

Scheme 29. Photo-promoted synthesis of heteroaryl-substituted BCP

图式30. 光催化[1.1.1]螺桨烷与杂芳基砜的双官能团化反应

Scheme 30. Light-induced difunctionalization of [1.1.1]pro- pellane with heteroaryl sulfones

图式31. 光/铜协同催化合成炔基取代BCP衍生物

Scheme 31. Synthesis of alkynyl-substituted BCPs via synergistic photoredox/copper catalysis

图式32. 光/镍协同催化合成BCP腈

Scheme 32. Synthesis of BCP nitriles via synergistic photoredox/Ni catalysis

图式33. 光催化BCP磷酸酯的合成

Scheme 33. Photo-promoted synthesis of BCP phosphonate

图式34. 光催化[1.1.1]螺桨烷官能团化构筑C—P键

Scheme 34. Photo-promoted functionalization of [1.1.1]propellane for C—P bond formation

图式35. 光催化[1.1.1]螺桨烷的硼化反应

Scheme 35. Photo-promoted borylation of [1.1.1]propellane

图式36. 光催化苯硒基取代BCP的合成

Scheme 36. Photo-promoted synthesis of phenylseleno-sub- stituted BCP

图式37. 光/铜协同催化[1.1.1]螺桨烷的三组分交叉偶联反应

Scheme 37. Photo/copper-catalyzed three-component cross- coupling of [1.1.1]propellane

图式38. 光催化酰胺取代的BCP衍生物的合成

Scheme 38. Photocatalytic synthesis of amide-substituted BCPs

图式39. 光催化BCP砜类化合物的合成

Scheme 39. Photocatalytic synthesis of BCP sulfones

图式40. 电化学驱动的[1.1.1]螺桨烷官能团化

Scheme 40. Electrochemically driven functionalization of [1.1.1]propellane

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