手性配体在钯催化配位辅助对映选择性C(sp3)—H键官能团化反应中的应用

doi:10.6023/cjoc202406002

摘要/Abstract

过渡金属催化的对映选择性C(sp³)—H键官能团化反应已成为构建手性分子的一种有效策略. 与其他过渡金属相比, 钯催化体系显示出良好的反应活性、多功能性和官能团耐受性, 是目前最常用的催化体系之一, 实现了一系列对映选择性C(sp³)—H键官能团化反应. 在这些反应中, 手性配体起到了举足轻重的作用, 是反应活性和立体选择性控制的关键因素. 聚焦于手性配体, 总结了近年来钯催化配位辅助对映选择性C(sp³)—H键官能团化反应的最新进展, 并着重介绍了手性配体的设计理念、反应机制和立体控制模型.

关键词: 钯催化, C(sp³)—H键官能团化, 手性配体, 对映选择性

Abstract Enantioselective C(sp³)—H functionalization reactions have emerged as a powerful and straightforward strategy in the construction of chiral molecules. Palladium, highlighted by its remarkable reactivity, versatility, and functional group tolerance, stands out among transition metal catalysts and is one of the most prevalently employed in enantioselective C(sp³)—H functionalization reactions. In these reactions, chiral ligands play a pivotal role, serving as a decisive factor in controlling both reactivity and stereoselectivity. Focusing on chiral ligands, the latest progress in palladium-catalyzed coordination-assisted enantioselective C(sp³)—H bond functionalization reactions in recent years is summarized, emphasizing the design concept, reaction mechanism, and stereocontrol model of chiral ligands.

Key words: palladium catalysis, C(sp³)—H functionalization, chiral ligands, enantioselectivity

引用此文

袁晨晖, 焦雷. 手性配体在钯催化配位辅助对映选择性C(sp³)—H键官能团化反应中的应用[J]. 有机化学, 2025, 45(2): 602-619.

Chen-Hui Yuan, Lei Jiao. Chiral Ligands for Palladium-Catalyzed Coordination-Assisted Enantioselective C(sp³)—H Functionalization Reactions[J]. Chinese Journal of Organic Chemistry, 2025, 45(2): 602-619.

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图/表 34

图式1. 钯催化对映选择性C(sp3)—H键官能团化反应的三种模式

Scheme 1. Three modes of Pd-catalyzed enantioselective C(sp3)—H functionalization reactions

图式2. MPAA配体的结构与C—H键官能化催化循环

Scheme 2. Structure of MPAA ligands and the catalytic cycle of Pd/MPAA-catalyzed C—H functionalization

图式3. MPAA配体控制的2-异丙基吡啶的去对称烷基化

Scheme 3. MPAA ligand-controlled desymmetrical alkylation of 2-isopropylpyridine

图式4. MPAA配体控制的N-对氰基全氟苯基环丙甲酰胺的去对称化

Scheme 4. MPAA ligand-controlled desymmetrization of N-(4- cyanoperfluorophenyl)cyclopropanecarboxamide

图式5. MPAA配体控制的三氟甲磺酰胺导向环丙基去对称芳基化

Scheme 5. MPAA ligand-controlled cyclopropyl desymmetrical arylation of trifluoromethanesulfonamide

图式6. MPAA配体控制的羧酸导向环丙基去对称化

Scheme 6. MPAA ligand-controlled carboxylic acid-directed cyclopropyl desymmetrization

图式7. MPAA配体控制的二级胺导向偕二甲基去对称化

Scheme 7. MPAA ligand-controlled secondary amine-directed gem-dimethyl desymmetrization

图式8. MPAA配体控制的三级胺导向去对称化

Scheme 8. MPAA ligand-controlled tertiary amine-directed de- symmetrization

图式9. 从MPAA配体到N-单酰基保护氨基-氮配体的结构变化

Scheme 9. Structural changes of MPAA ligands to protected amino-N-block ligands

图式10. MPAHA配体控制的环丁基和偕二甲基去对称化

Scheme 10. MPAHA ligand-controlled desymmetrization of cyclobutyl and gem-dimethyl groups

图式11. APAQ配体控制的亚甲基和环己基去对称化

Scheme 11. APAQ ligand-controlled desymmetrization of methylene and cyclohexyl groups

图式12. APAO配体控制的去对称化硼化

Scheme 12. APAO ligand-controlled desymmetrical borylation

图式13. APAO配体控制的异丙基及偕二甲基去对称化

Scheme 13. APAO ligand-controlled desymmetrization of isopropyl and gem-dimethyl groups

图式14. APAO配体控制的三氟甲磺酰胺去对称化与动力学拆分

Scheme 14. APAO ligand-controlled desymmetrization and kinetic resolution of trifluoromethanesulfonamide

图式15. MPAAM配体控制的羧酸的去对称化

Scheme 15. MPAAM ligand-controlled desymmetrization of carboxylic acids

图式16. MPAA配体到N-单酰基保护氨基-硫配体的结构变化

Scheme 16. Structural changes of MPAA ligands to protected amino-S-block ligands

图式17. APASO配体控制的N-全氟苯基环丙甲酰胺的去对称化

Scheme 17. APASO ligand-controlled desymmetrization of N-(perfluorophenyl)cyclopropanecarboxamide

图式18. APAThio配体控制的环丙甲胺的去对称化

Scheme 18. APAThio ligand-controlled desymmetrization of cyclopropylmethylamine

图式19. APAThio配体控制的环丙甲酸的去对称化

Scheme 19. APAThio ligand-controlled desymmetrization of cyclopropyl carboxylic acids

图式20. N-酰基配体到手性羟基吡啶配体的结构变化

Scheme 20. Structural changes of N-acyl ligands to chiral hydroxypyridine ligands

图式21. SOHP配体控制的三级脂肪酰胺的β位对映选择性芳基化

Scheme 21. SOHP ligand-controlled enantioselective β-arylation of tertiary aliphatic amides

图式22. SOHP配体控制的一级脂肪胺的γ位对映选择性芳基化

Scheme 22. SOHP ligand-controlled enantioselective γ-arylation of primary aliphatic amines

图式23. TZ配体控制的环烷基羧酸的对映选择性远程芳基化

Scheme 23. TZ ligand-controlled enantioselective remote arylation of cycloalkane carboxylic acids

图式24. CPA配体控制的8-氨基喹啉导向的去对称化

Scheme 24. CPA ligand-controlled 8-aminoquinoline-directed desymmetrization

图式25. CPA配体控制的吡啶-2-甲酰胺导向的去对称化

Scheme 25. CPA ligand-controlled pyridine-2-carboxamide-directed desymmetrization

图式26. CPA配体控制的PIP导向的去对称化

Scheme 26. CPA ligand-controlled PIP-directed desymmetrization

图式27. CPA配体控制的硫代酰胺导向的去对称化与动力学拆分

Scheme 27. CPA ligand-controlled thioamide-directed desymmetrization and kinetic resolution

图式28. CPA配体控制的二级胺导向的去对称化

Scheme 28. CPA ligand-controlled secondary amine-directed desymmetrization

图式29. BINOL配体控制的PIP导向的对映选择性官能团化

Scheme 29. BINOL ligand-controlled PIP-directed enantioselective functionalization

图式30. BINOL配体控制的8-氨基喹啉导向的去对称化

Scheme 30. BINOL ligand-controlled 8-aminoquinoline-dire- cted desymmetrization

图式31. BINOL配体控制的PIP导向磷手性中心构建

Scheme 31. BINOL ligand-controlled PIP-directed P-stereogenic center construction

图式32. 手性亚磷酰胺配体控制的8-氨基喹啉导向的去对称化

Scheme 32. Chiral phosphoramidite ligand-controlled 8-aminoquinoline-directed desymmetrization

图式33. 手性亚磷酰胺配体控制的硫代酰胺导向的去对称化

Scheme 33. Chiral phosphoramidite ligand-controlled thioamide-directed desymmetrization

图式34. SOHP配体诱导手性环钯中间体的制备与转化

Scheme 34. Preparation and transformation of palladacycle with SOHP ligand-induced-chirality

参考文献 50

[1]	(a) Guillemard, L.; Kaplaneris, N.; Ackermann, L.; Johansson, M. J. Nat. Rev. Chem. 2021, 5, 522. doi: 10.1038/s41570-021-00300-6 pmid: 37117588
	(b) Lam, N. Y. S.; Wu, K.; Yu, J.-Q. Angew. Chem., Int. Ed. 2021, 60, 15767. pmid: 37117588
	(c) Sinha, S. K.; Ghosh, P.; Jain, S.; Maiti, S.; Al-Thabati, S. A.; Alshehri, A. A.; Mokhtar, M.; Maiti, D. Chem. Soc. Rev. 2023, 52, 7461. pmid: 37117588
[2]	(a) Achar, T. K.; Maiti, S.; Jana, S.; Maiti, D. ACS Catal. 2020, 10, 13748.
	(b) Liu, B.; Romine, A. M.; Rubel, C. Z.; Engle, K. M.; Shi, B.-F. Chem. Rev. 2021, 121, 14957.
	(c) Zhan, B.-B.; Jin, L.; Shi, B.-F. Trends Chem. 2022, 4, 220.
[3]	Siegbahn, P. E. M. J. Phy. Chem. 1995, 99, 12723.
[4]	Han, Y.-Q.; Shi, B.-F. Acta Chim. Sinica 2023, 81, 1522 (in Chinese).
	(韩叶强, 史炳锋, 化学学报, 2023, 81, 1522.) doi: 10.6023/A23070336
[5]	(a) Rouquet, G.; Chatani, N. Angew. Chem., Int. Ed. 2013, 52, 11726. pmid: 30033454
	(b) Sambiagio, C.; Schönbauer, D.; Blieck, R.; Dao-Huy, T.; Potot- schnig, G.; Schaaf, P.; Wiesinger, T.; Zia, M. F.; Wencel-Delord, J.; Besset, T.; Maes, B. U. W.; Schnürch, M. Chem. Soc. Rev. 2018, 47, 6603. doi: 10.1039/c8cs00201k pmid: 30033454
[6]	(a) Wang, P.-S.; Gong, L.-Z. Chin. J. Chem. 2023, 41, 1841.
	(b) Wang, P.-S.; Gong, L.-Z. Acc. Chem. Res. 2020, 53, 2841.
[7]	(a) Baudoin, O. Acc. Chem. Res. 2017, 50, 1114.
	(b) Vyhivskyi, O.; Kudashev, A.; Miyakoshi, T.; Baudoin, O. Chem.-Eur. J. 2021, 27, 1231.
[8]	He, Y.-M.; Cheng, Y.-Z.; Duan, Y.; Zhang, Y.-D.; Fan, Q.-H.; You, S.-L.; Luo, S.; Zhu, S.-F.; Fu, X.-F.; Zhou, Q.-L. CCS Chem. 2023, 5, 2685.
[9]	(a) Shi, B.-F.; Maugel, N.; Zhang, Y.-H.; Yu, J.-Q. Angew. Chem., Int. Ed. 2008, 47, 4882.
	(b) Shao, Q.; Wu, K.; Zhuang, Z.; Qian, S.; Yu, J.-Q. Acc. Chem. Res. 2020, 53, 833.
[10]	Wasa, M.; Engle, K. M.; Lin, D. W.; Yoo, E. J.; Yu, J.-Q. J. Am. Chem. Soc. 2011, 133, 19598.
[11]	Chan, K. S. L.; Fu, H.-Y.; Yu, J.-Q. J. Am. Chem. Soc. 2015, 137, 2042.
[12]	Hu, L.; Shen, P.-X.; Shao, Q.; Hong, K.; Qiao, J. X.; Yu, J.-Q. Angew. Chem., Int. Ed. 2019, 58, 2134.
[13]	He, C.; Gaunt, M. J. Angew. Chem., Int. Ed. 2015, 54, 15840.
[14]	Rodrigalvarez, J.; Nappi, M.; Azuma, H.; Flodén, N. J.; Burns, M. E.; Gaunt, M. J. Nat. Chem. 2020, 12, 76. doi: 10.1038/s41557-019-0393-8 pmid: 31863014
[15]	Rodrigalvarez, J.; Reeve, L. A.; Miró, J.; Gaunt, M. J. J. Am. Chem. Soc. 2022, 144, 3939.
[16]	Xiao, K.-J.; Lin, D. W.; Miura, M.; Zhu, R.-Y.; Gong, W.; Wasa, M.; Yu, J.-Q. J. Am. Chem. Soc. 2014, 136, 8138.
[17]	(a) Chen, G.; Gong, W.; Zhuang, Z.; Andrä, M. S.; Chen, Y.-Q.; Hong, X.; Yang, Y.-F.; Liu, T.; Houk, K. N.; Yu, J.-Q. Science 2016, 353, 1023.
	(b) Andrä, M. S.; Schifferer, L.; Pollok, C. H.; Merten, C.; Gooßen, L. J.; Yu, J.-Q. Chem.-Eur. J. 2019, 25, 8503.
[18]	(a) He, J.; Shao, Q.; Wu, Q.; Yu, J.-Q. J. Am. Chem. Soc. 2017, 139, 3344.
	(b) Wu, Q.-F.; Shen, P.-X.; He, J.; Wang, X.-B.; Zhang, F.; Shao, Q.; Zhu, R.-Y.; Mapelli, C.; Qiao, J. X.; Poss, M. A.; Yu, J.-Q. Science 2017, 355, 499.
	(c) Shao, Q.; Wu, Q.-F.; He, J.; Yu, J.-Q. J. Am. Chem. Soc. 2018, 140, 5322.
[19]	Shen, P.-X.; Hu, L.; Shao, Q.; Hong, K.; Yu, J.-Q. J. Am. Chem. Soc. 2018, 140, 6545.
[20]	Jerhaoui, S.; Djukic, J.-P.; Wencel-Delord, J.; Colobert, F. ACS Catal. 2019, 9, 2532. doi: 10.1021/acscatal.8b04946
[21]	Zhuang, Z.; Yu, J.-Q. J. Am. Chem. Soc. 2020, 142, 12015. doi: 10.1021/jacs.0c04801 pmid: 32605367
[22]	Zhuang, Z.; Herron, A. N.; Yu, J.-Q. Angew. Chem., Int. Ed. 2021, 60, 16382.
[23]	Wang, P.; Farmer, M. E.; Huo, X.; Jain, P.; Shen, P.-X.; Ishoey, M.; Bradner, J. E.; Wisniewski, S. R.; Eastgate, M. D.; Yu, J.-Q. J. Am. Chem. Soc. 2016, 138, 9269.
[24]	Wang, Y.-J.; Yuan, C.-H.; Chu, D.-Z.; Jiao, L. Chem. Sci. 2020, 11, 11042. doi: 10.1039/d0sc02246b pmid: 34094351
[25]	Yuan, C.-H.; Wang, X.-X.; Jiao, L. Angew. Chem., Int. Ed. 2023, 62, e202300854.
[26]	Yuan, C.-H.; Jiao, L. Org. Lett. 2024, 26, 29.
[27]	Zhang, T.; Zhang, Z.-Y.; Kang, G.; Sheng, T.; Yan, J.-L.; Yang, Y.-B.; Ouyang, Y.; Yu, J.-Q. Science 2024, 384, 793. doi: 10.1126/science.ado1246 pmid: 38753778
[28]	(a) Maji, R.; Mallojjala, S. C.; Wheeler, S. E. Chem. Soc. Rev. 2018, 47, 1142.
	(b) Li, X.; Song, Q. Chin. Chem. Lett. 2018, 29, 1181.
[29]	Connon, S. J. Angew. Chem., Int. Ed. 2006, 45, 3909.
[30]	(a) Wang, P.-S.; Gong, L.-Z. Synthesis 2021, 54, 4795.
	(b) Sumit; Chandra, D.; Sharma, U. Chem. Commun. 2023, 59, 9288.
[31]	Yan, S.-B.; Zhang, S.; Duan, W.-L. Org. Lett. 2015, 17, 2458.
[32]	Wang, H.; Tong, H.-R.; He, G.; Chen, G. Angew. Chem., Int. Ed. 2016, 55, 15387.
[33]	Bay, K. L.; Yang, Y.-F.; Houk, K. N. J. Org. Chem. 2018, 83, 14786.
[34]	Zhang, Q.; Shi, B.-F. Acc. Chem. Res. 2021, 54, 2750.
[35]	Yan, S.-Y.; Han, Y.-Q.; Yao, Q.-J.; Nie, X.-L.; Liu, L.; Shi, B.-F. Angew. Chem., Int. Ed. 2018, 57, 9093.
[36]	Han, Y.-Q.; Zhang, Q.; Yang, X.; Jiang, M.-X.; Ding, Y.; Shi, B.-F. Org. Lett. 2021, 23, 97.
[37]	Jain, P.; Verma, P.; Xia, G.; Yu, J.-Q. Nat. Chem. 2017, 9, 140.
[38]	Jiang, H.-J.; Zhong, X.-M.; Liu, Z.-Y.; Geng, R.-L.; Li, Y.-Y.; Wu, Y.-D.; Zhang, X.; Gong, L.-Z. Angew. Chem., Int. Ed. 2020, 59, 12774.
[39]	Smalley, A. P.; Cuthbertson, J. D.; Gaunt, M. J. J. Am. Chem. Soc. 2017, 139, 1412. doi: 10.1021/jacs.6b12234 pmid: 28064488
[40]	Han, Y.-Q.; Ding, Y.; Zhou, T.; Yan, S.-Y.; Song, H.; Shi, B.-F. J. Am. Chem. Soc. 2019, 141, 4558.
[41]	(a) Ding, Y.; Han, Y.-Q.; Wu, L.-S.; Zhou, T.; Yao, Q.-J.; Feng, Y.-L.; Li, Y.; Kong, K.-X.; Shi, B.-F. Angew. Chem., Int. Ed. 2020, 59, 14060. pmid: 33683896
	(b) Wu, L.-S.; Ding, Y.; Han, Y.-Q.; Shi, B.-F. Org. Lett. 2021, 23, 2048. doi: 10.1021/acs.orglett.1c00204 pmid: 33683896
[42]	(a) Han, Y.-Q.; Yang, X.; Kong, K.-X.; Deng, Y.-T.; Wu, L.-S.; Ding, Y.; Shi, B.-F. Angew. Chem., Int. Ed. 2020, 59, 20455.
	(b) Yang, X.; Jiang, M.-X.; Zhou, T.; Han, Y.-Q.; Xu, X.-T.; Zhang, K.; Shi, B.-F. Chem. Commun. 2021, 57, 5562.
[43]	Zhou, T.; Jiang, M.-X.; Yang, X.; Yue, Q.; Han, Y.-Q.; Ding, Y.; Shi, B.-F. Chin. J. Chem. 2020, 38, 242.
[44]	Jiang, M.-X.; Yang, X.; Han, Y.-Q.; Zhou, T.; Xu, X.-T.; Zhang, K.; Shi, B.-F. Org. Chem. Front. 2021, 8, 2903.
[45]	Tong, H.-R.; Zheng, W.; Lv, X.; He, G.; Liu, P.; Chen, G. ACS Catal. 2020, 10, 114.
[46]	Wang, C.-Y.; Zhou, T.; Shi, B.-F. ACS Catal. 2024, 14, 7213.
[47]	Tong, H.-R.; Zheng, S.; Li, X.; Deng, Z.; Wang, H.; He, G.; Peng, Q.; Chen, G. ACS Catal. 2018, 8, 11502.
[48]	Jiang, H.-J.; Zhong, X.-M.; Yu, J.; Zhang, Y.; Zhang, X.; Wu, Y.-D.; Gong, L.-Z. Angew. Chem., Int. Ed. 2019, 58, 1803.
[49]	Suseelan, A. S.; Dutta, A.; Lahiri, G. K.; Maiti, D. Trends Chem. 2021, 3, 188.
[50]	Yuan, C.-H.; Wang, X.-X.; Huang, K.; Jiao, L. Angew. Chem., Int. Ed. 2024, 63, e202405062.

手性配体在钯催化配位辅助对映选择性C(sp³)—H键官能团化反应中的应用

Chiral Ligands for Palladium-Catalyzed Coordination-Assisted Enantioselective C(sp³)—H Functionalization Reactions

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