过渡金属催化氮原子α位Csp3—H键官能团化反应研究进展

doi:10.6023/cjoc202404040

摘要/Abstract

在有机合成化学中, C—H键的官能团化是一个十分重要的研究领域. 在众多处于不同化学环境的C—H键中, N-α位的C_sp3—H键因氮原子的诱导效应使其相较于其他的C_sp3—H键具有更高的反应活性, 并且在导向基团作用下可以更好地实现N-α位C_sp3—H键的区域选择性官能团化反应, 因此氮原子α位C_sp3—H键官能团化是一种非常实用的合成策略, 这为含有氮原子的有机化合物(如尼可刹米、奎宁等)的结构修饰及药物开发提供了更多可能. 综述了近二十年来过渡金属催化氮原子α位C_sp3—H键官能团化的发展现状, 并展望了此方法在有机合成化学中的潜力.

关键词: 氮原子, C_sp3—H, 官能团化, 过渡金属催化

Functionalization of C—H bonds is a very important research field in organic synthetic chemistry. In many C—H bonds located in different chemical environments, the induced effect of the nitrogen atom makes the α-C_sp3—H bond more active compared to other C_sp3—H bonds, and the regioselective functionalization of the α-C_sp3—H bond is also better achieved with the help of directing groups. Therefore, the functionalization of the α-C_sp3—H bond of nitrogen atoms is a very practical synthetic strategy, which provides more possibilities for the structural modification and development of drugs containing nitrogen atoms (such as nicotinamide and quinine). The current development of transition metal-catalyzed functionalization of the α-C_sp3—H bond of nitrogen atoms in the past twenty years is reviewed and the potential of this synthetic methodology in the future is looked forward.

Key words: nitrogen atom, C_sp3—H, functionalization, transition metal-catalyzed

引用此文

张腾飞, 常喆, 陈春霞, 彭进松. 过渡金属催化氮原子α位C_sp3—H键官能团化反应研究进展[J]. 有机化学, 2025, 45(1): 168-188.

Tengfei Zhang, Zhe Chang, Chunxia Chen, Jinsong Peng. Progress in Functionalization of N-α-C_sp3—H Bond Catalyzed by Transition Metals[J]. Chinese Journal of Organic Chemistry, 2025, 45(1): 168-188.

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图/表 55

图式1. 含有氮原子的天然产物

Scheme 1. Natural products containing nitrogen atoms

图式2. Chul-Ho Jun报道的钌催化烷基化反应

Scheme 2. Ru-catalyzed alkylation reported by Chul-Ho Jun

图式3. Shinji Murai报道的钌催化烷基化反应

Scheme 3. Ru-catalyzed alkylation reported by Shinji Murai

图式4. Chae S. Yi报道的钌催化烷基化反应

Scheme 4. Ru-catalyzed alkylation reported by Chae S. Yi

图式5. Michael J. Krische报道的钌催化烷基化反应

Scheme 5. Ru-catalyzed alkylation reported by Michael J. Krische

图式6. 钌催化N-α-Csp3—H对共轭烯烃的1,4-加成反应机理

Scheme 6. Proposed mechanism of Ru-catalyzed 1,4-addition of N-α-Csp3—H to conjugated olefins

图式7. Dalibor Sames报道的钌催化芳基化

Scheme 7. Ru-catalyzed arylation reported by Dalibor Sames

图式8. 钌催化N-α-Csp3—H芳基化反应可能机理

Scheme 8. Proposed mechanism of Ru-catalyzed arylation of N-α-Csp3—H

图式9. Bert U. W. Maes报道的钌催化芳基化反应

Scheme 9. Ru-catalyzed arylation reported by Bert U. W. Maes

图式10. Bert U. W. Maes课题组报道的钌催化芳基化反应

Scheme 10. Ru-catalyzed arylation reported by Bert U. W. Maes

图式11. 张敏报道的钌催化C—H芳基化反应

Scheme 11. Ru-catalyzed C—H arylation reported by Min Zhang

图式12. 钌催化C—H芳基化反应的推测机理

Scheme 12. Proposed mechanism of Ru-catalyzed C—H arylation

图式13. Shinji Murai报道的铑催化N-α-羰基化反应

Scheme 13. Rh-catalyzed N-α-carbonylation reported by Shinji Murai

图式14. Shinji Murai报道的铑催化脂环胺α位羰基化反应

Scheme 14. Rh-catalyzed α-carbonylation of alicyclic amines reported by Shinji Murai

图式15. Huw M. L. Davies报道的铑催化脂环胺α位烷基化

Scheme 15. Rh-catalyzed α-alkylation of alicyclic amines reported by Huw M. L. Davies

图式16. 余志祥报道的铑催化烯丙胺分子内C—H烷基化

Scheme 16. Rh-catalyzed intramolecular C—H alkylation of allylamines reported by Zhi Xiang Yu

图式17. Michael Schnürch报道的铑催化苄胺α位Csp3—H烷基化反应

Scheme 17. Rh-catalyzed N-α-Csp3—H alkylation of benzylamines reported by Michael Schnürch

图式18. Frank Glorius报道的铑催化环胺α位Csp3—H芳基化反应

Scheme 18. Rh-catalyzed N-α-Csp3—H arylation of cycloamines reported by Frank Glorius

图式19. In Su Kim报道的铑催化脂环胺α位Csp3—H胺化反应

Scheme 19. Rh-catalyzed N-α-Csp3—H amidation of alicyclic amines reported by In Su Kim

图式20. 铑催化脂环胺α位Csp3—H胺化反应可能机理

Scheme 20. Proposed Rh-catalyzed mechanism of N-α-Csp3—H amidation of alicyclic amines

图式21. 余金权报道的钯催化脂环胺α位Csp3—H芳基化反应

Scheme 21. Pd-catalyzed N-α-Csp3—H arylation of alicyclic amines reported by Jin Quan Yu

图式22. 钯催化脂环胺α位Csp3—H不对称芳基化反应

Scheme 22. Pd-catalyzed asymmetric N-α-Csp3—H arylation of alicyclic amines

图式23. 龚流柱报道的钯催化脂环胺α位Csp3—H不对称芳基化反应

Scheme 23. Pd-catalyzed asymmetric N-α-Csp3—H arylation of alicyclic amines reported by Liu-Zhu Gong

图式24. 叶智识报道的钯催化分子内N-α位芳基化反应

Scheme 24. Pd-catalyzed intramolecular N-α-arylation reported by Zhi-Shi Ye

图式25. 石航报道的钯催化磺酰胺α位Csp3—H芳基化反应

Scheme 25. Pd-catalyzed N-α-Csp3—H arylation of sulfonamides reported by Hang Shi

图式26. 余金权报道的钯催化胺α位Csp3—H乙酰氧基化反应

Scheme 26. Pd-catalyzed N-α-Csp3—H acetoxylation of amines reported by Jin Quan Yu

图式27. Takanori Shibata报道的铱催化胺α位不对称烷基化

Scheme 27. Ir-catalyzed asymmetric N-α-alkylation of amines reported by Takanori Shibata

图式28. 铱催化不对称烷基化反应可能机理

Scheme 28. Proposed mechanism of Ir-catalyzed asymmetric N-α-alkylation of amines

图式29. Till Opatz报道的铱催化脂肪胺α位烷基化反应

Scheme 29. Ir-catalyzed α-alkylation of aliphatic amines reported by Till Opatz

图式30. 余金权报道的铱催化脂环胺α位Csp3—H烷基化反应

Scheme 30. Ir-catalyzed N-α-Csp3—H alkylation of alicyclic amines reported by Jin Quan Yu

图式31. Daisuke Yamauchi报道的铱催化N-甲基脲N-α位Csp3—H烷基化反应

Scheme 31. Ir-catalyzed N-α-Csp3—H alkylation of N-methylureas reported by Daisuke Yamauchi

图式32. 余金权报道的铱催化脂环胺N-α位Csp3—H烷基化反应

Scheme 32. Ir-catalyzed N-α-Csp3—H alkylation of alicyclic amines reported by Jin Quan Yu

图式33. 铱催化脂环胺N-α位Csp3—H烷基化反应可能机理

Scheme 33. Proposed Ir-catalyzed mechanism of N-α-Csp3—H alkylation of alicyclic amines

图式34. Takahiro Nishimura报道的苯并咪唑导向的铱催化脂环胺N-α位Csp3—H烷基化反应

Scheme 34. Ir-catalyzed benzimidazole-directed N-α-Csp3—H alkylation of alicyclic amines reported by Takahiro Nishimura

图式35. Dalibor Sames报道的铱催化不饱和脂环酰胺分子内N-α位Csp3—H烯基化反应

Scheme 35. Ir-catalyzed intramolecular N-α-Csp3—H vinylation of unsaturated alicyclic amides reported by Dalibor Sames

图式36. Takanori Shibata报道的铱催化酰胺N-α位Csp3—H烯基化反应

Scheme 36. Ir-catalyzed N-α-Csp3—H vinylation of amides reported by Takanori Shibata

图式37. Takanori Shibata报道的铱催化2-烷氨基吡啶N-α-Csp3—H烯基化反应

Scheme 37. Ir-catalyzed N-α-Csp3—H vinylation of 2-alkyl- aminopyridines reported by Takanori Shibata

图式38. 李朝军报道的铜催化四氢异喹啉N-α-Csp3—H烷基化

Scheme 38. Cu-catalyzed N-α-Csp3—H alkylation of tetrahydroisoquinolines reported by Chao Jun Li

图式39. Masahiro Miura报道的铜催化N-α-Csp3—H参与的氧化环加成反应

Scheme 39. Cu-catalyzed oxidative annulation of N-α-Csp3—H reported by Masahiro Miura

图式40. 张玉红报道的铜催化N-α-Csp3—H氧化芳基化反应

Scheme 40. Cu-catalyzed N-α-Csp3—H oxidative arylation reported by Yu hong Zhang

图式41. Yu hong Zhang推测的铜催化N-α-Csp3—H芳基化机理

Scheme 41. Cu-catalyzed arylation mechanism of N-α-Csp3—H proposed by Yu hong Zhang

图式42. 李朝军报道的铜催化N-α-Csp3—H炔基化反应

Scheme 42. Cu-catalyzed alkynylation of N-α-Csp3—H reported by Chao Jun Li

图式43. Christopher D. Maycock报道的铜催化分子内N-α-Csp3—H醚化反应

Scheme 43. Cu-catalyzed intramolecular etherification of N-α- Csp3—H reported by Christopher D. Maycock

图式44. 赵德鹏报道的铜催化N-α-Csp3—H羟基化反应

Scheme 44. Cu-catalyzed hydroxylation of N-α-Csp3—H reported by De peng Zhao

图式45. 李朝军报道的铜催化N-α-Csp3—H氧化交叉偶联反应引入酯基官能团反应

Scheme 45. Cu-catalyzed oxidative cross-coupling for the introduction of ester group reported by Chao Jun Li

图式46. Kazuya Yamaguchi报道的金催化脂环胺N-α-Csp3—H炔基化反应

Scheme 46. Au-catalyzed N-α-Csp3—H alkynylation of alicyclic amines reported by Kazuya Yamaguchi

图式47. 史大永报道的铁催化叔胺N-α-Csp3—H炔基化反应

Scheme 47. Fe-catalyzed N-α-Csp3—H alkynylation of tertiary amines reported by Da yong Shi

图式48. Laurel L. Schafer报道的钽催化N-甲基仲胺N-α-Csp3—H烷基化反应

Scheme 48. Ta-catalyzed N-α-Csp3—H alkylation of N-methyl secondary amines reported by Laurel L. Schafer

图式49. Laurel L. Schafer提出的钽催化N-α-Csp3—H烷基化反应机理

Scheme 49. Ta-catalyzed mechanism of N-α-Csp3—H alkylation proposed by Laurel L. Schafer

图式50. 石航报道的镍催化N-α-Csp3—H烷基化反应

Scheme 50. Ni-catalyzed alkylation of N-α-Csp3—H reported by Hang Shi

图式51. 镍催化N-α-Csp3—H烷基化反应可能机理

Scheme 51. Proposed Ni-catalyzed N-α-Csp3—H alkylation mechanism

图式52. 肖力军报道的镍催化N-α-Csp3—H立体选择性烷基化反应

Scheme 52. Ni-catalyzed steroselective alkylation of N-α-Csp3—H reported by Li-Jun Xiao

图式53. 叶萌春报道的镍催化N-α-Csp3—H烯基化反应

Scheme 53. Ni-catalyzed vinylation of N-α-Csp3—H reported by Mengchun Ye

图式54. 石航课题报道的镍催化不对称N-α-Csp3—H烯基化反应

Scheme 54. Ni-catalyzed asymmetric vinylation of N-α-Csp3—H reported by Hang Shi

图式55. M. Christina White报道的锰催化N-α-Csp3—H羟基化反应

Scheme 55. Mn-catalyzed N-α-Csp3—H hydroxylation reported by M. Christina White

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