Research Progress on the Synthesis of Chiral Lactams via Transition Metal-Catalyzed Asymmetric Hydrogenation

doi:10.6023/cjoc202606009

Chinese Journal of Organic Chemistry ›› 2026, Vol. 46 ›› Issue (10): 3783-3803.DOI: 10.6023/cjoc202606009 Previous Articles Next Articles

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过渡金属催化不对称氢化合成手性内酰胺的研究进展

刘春萌^a^,^b, 魏雨晴^b, 袁乾家^b, 毛国梁^a^,^*(), 张万斌^b^,^*()

^a 东北石油大学化学化工学院黑龙江省聚烯烃新材料重点实验室黑龙江省聚烯烃新材料重点实验室黑龙江大庆 163318
^b 上海交通大学化学化工学院上海市手性药物分子工程重点实验室上海市手性药物分子工程重点实验室上海 200240

收稿日期:2026-06-09 修回日期:2026-06-23 发布日期:2026-06-26
通讯作者: 毛国梁, 张万斌
基金资助:
上海市科技重大专项、上海市自然科学基金(24ZR1439600); 国家重点研发计划(2023YFA1506400); 上海尚思自然科学研究院资助项目

Research Progress on the Synthesis of Chiral Lactams via Transition Metal-Catalyzed Asymmetric Hydrogenation

Chunmeng Liu^a^,^b, Yuqing Wei^b, Qianjia Yuan^b, Guoliang Mao^a^,^*(), Wanbin Zhang^b^,^*()

^a Heilongjiang Provincial Key Laboratory of Polyolefin New Materials, College of Chemistry & Chemical Engineering, Northeast Petroleum University, Daqing, Heilongjiang 163318
^b Shanghai Key Laboratory of Molecular Engineering of Chiral Drugs, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai 200240

Received:2026-06-09 Revised:2026-06-23 Published:2026-06-26
Contact: Guoliang Mao, Wanbin Zhang
Supported by:
Shanghai Municipal Science and Technology Major Project, the Natural Science Foundation of Shanghai City(24ZR1439600); National Key R&D Program of China(2023YFA1506400); Shanghai Academy of Natural Sciences

Chiral lactams are widely found in natural products and pharmaceutical molecules, and also serve as important synthetic intermediates. Therefore, the efficient asymmetric construction of chiral lactams is of significant research value. Transition metal-catalyzed asymmetric hydrogenation features atom economy, high catalytic efficiency, and operational simplicity, making it one of the most industrially promising technologies for the synthesis of chiral compounds. In recent years, catalytic asymmetric hydrogenation systems based on transition metals such as iridium, rhodium, ruthenium, palladium, and nickel have been successively developed, enabling the highly efficient synthesis of chiral lactams. Classified according to the transition metal catalyst type, different catalytic systems are summarized in terms of their characteristics, including the substrate scope, the origin of stereoselectivity, and the mechanism, as well as their applications in the synthesis of pharmaceuticals and natural products. Finally, the current challenges and future prospects of this field are discussed, with the aim of providing useful guidance for the efficient synthesis of chiral lactams.

Key words: lactam, asymmetric hydrogenation, asymmetric catalysis, transition metal

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Chunmeng Liu, Yuqing Wei, Qianjia Yuan, Guoliang Mao, Wanbin Zhang. Research Progress on the Synthesis of Chiral Lactams via Transition Metal-Catalyzed Asymmetric Hydrogenation[J]. Chinese Journal of Organic Chemistry, 2026, 46(10): 3783-3803.

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Fig. & Tab. 35

Scheme 1. Iridium-catalyzed enantioselective hydrogenation of the exocyclic α,β-unsaturated carbonyl compounds

Scheme 2. H8-BINOL-derived phosphine-oxazoline/iridium-catalyzed hydrogenation of unsaturated lactams

Scheme 3. Iridium-catalyzed asymmetric hydrogenation of cyclic α-alkylidene carbonyl compounds

Scheme 4. Iridium-catalyzed asymmetric hydrogenation of racemic β-keto lactams via dynamic kinetic resolution

Scheme 5. Iridium/phosphoramidite-catalyzed asymmetric hydrogenation of β,γ-unsaturated γ-lactams

Scheme 6. Iridium-catalyzed asymmetric hydrogenolysis of racemic γ-hydroxy γ-lactams

Scheme 7. Mechanism for the asymmetric hydrogenolysis of racemic γ-hydroxy γ-lactams

Scheme 8. Ir/BiphPHOX-catalyzed asymmetric hydrogenation of α-alkylidene-β-lactams

Scheme 9. Ir/Phosphite sulfoximine-catalyzed asymmetric hydrogenation of α,β-unsaturated lactams

Scheme 10. Ir/Phosphite thioether-catalyzed asymmetric hydrogenation of α,β-unsaturated lactams

Scheme 11. Ir-catalyzed asymmetric hydrogenation of exocyclic α,β-unsaturated lactams

Scheme 12. Iridium-catalyzed asymmetric hydrogenation for the construction of chiral lactams via coordination modulation

Scheme 13. Control experiments

Scheme 14. Ir-catalyzed asymmetric hydrogenation of β,γ-unsaturated δ-lactam

Scheme 15. Construction of chiral lactams via tandem condensation/asymmetric hydrogenation

Scheme 16. Mechanism for the construction of chiral lactams via tandem condensation/asymmetric hydrogenation

Scheme 17. Asymmetric hydrogenation of lactam-based β-aminoacrylic acid

Scheme 18. Asymmetric hydrogenation of α,β-unsaturated γ-lactams with Rh/ZhaoPhos

Scheme 19. Asymmetric hydrogenation of α,β-unsaturated lactams with Rh/ZhaoPhos

Scheme 20. Asymmetric hydrogenation of exocyclic α,β-unsaturated carbonyl compounds with Rh/ZhaoPhos

Scheme 21. Rh-catalyzed asymmetric hydrogenation of α,β-disubstituted unsaturated lactams

Scheme 22. Rh/f-SpiroPhos-catalyzed asymmetric hydrogenation of α-trifluoromethylmethylene lactams

Scheme 23. Rh/Bisphosphine-thiourea-catalyzed asymmetric hydrogenation of α,β-unsaturated γ-lactams and its applications

Scheme 24. Ru-catalyzed asymmetric hydrogenation of β-keto γ-lactams

Scheme 25. Ru-catalyzed dynamic kinetic resolution asymmetric hydrogenation of β-keto γ-lactams

Scheme 26. Ru-catalyzed dynamic kinetic asymmetric reductive amination

Scheme 27. Ru-catalyzed asymmetric reductive amination/cyclization cascade reaction

Scheme 28. Ru-catalyzed direct asymmetric reductive amination of levulinic acid and ester

Scheme 29. Ru-catalyzed asymmetric hydrogenation of α,β-unsaturated γ-lactams

Figure 1. DFT calculation of ruthenium-catalyzed hydrogenation of α,β-unsaturated γ-lactams

Scheme 30. Construction of chiral δ-lactams via palladium-catalyzed asymmetric hydrogenation

Scheme 31. Mechanism for Pd-catalyzed asymmetric hydrogenation to access chiral δ-lactams

Scheme 32. Pd-catalyzed diastereoselective hydrogenation of α,β-unsaturated γ-lactams

Scheme 33. Pd-catalyzed diastereoselective hydrogenation of α,β-unsaturated γ-lactams for the synthesis of Brivaracetam

Scheme 34. Ni-catalyzed dynamic kinetic resolution asymmetric hydrogenation of α-keto-β-lactams

References 36

[1]	(a) Nay B.; Riache N.; Evanno L. Nat. Prod. Rep. 2009, 26, 1044. doi: 10.1039/B903905H pmid: 33373523
	(b) Royer J. Asymmetric Synthesis of Nitrogen Heterocycles, Wiley-VCH, Weinheim, 2009. pmid: 33373523
	(c) Bregman H.; Chakka N.; Guzman-Perez A.; Gunaydin H.; Gu Y.; Huang X.; Berry V.; Liu J.; Teffera Y.; Huang L.; Egge B.; Mullady E. L.; Schneider S.; Andrews P. S.; Mishra A.; Newcomb J.; Serafino R.; Strathdee C. A.; Turci S. M.; Wilson C.; DiMauro E. F. J. Med. Chem. 2013, 56, 4320. doi: 10.1021/jm4000038 pmid: 33373523
	(d) Fisher J. F.; Mobashery S. Chem. Rev. 2021, 121, 3412. doi: 10.1021/acs.chemrev.0c01010 pmid: 33373523
	(e) Tan M.; Peters B. B. C.; Andersson P. G.; Zhou T. Org. Chem. Front. 2024, 11, 2934. doi: 10.1039/D4QO00227J pmid: 33373523
	(f) Shen J.; Wang Y.; Wu Z.; Xu D.; Zhang W. Chin. J. Org. Chem. 2025, 45, 2637 (in Chinese). doi: 10.6023/cjoc202502011 pmid: 33373523
	(沈健, 王彦博, 吴正兴, 徐德锋, 张万斌, 有机化学, 2025, 45, 2637.) doi: 10.6023/cjoc202502011 pmid: 33373523
[2]	(a) France S.; Weatherwax A.; Taggi A. E.; Lectka T. Acc. Chem. Res. 2004, 37, 592. doi: 10.1021/ar030055g pmid: 37039110
	(b) Pitts C. R.; Lectka T. Chem. Rev. 2014, 114, 7930. doi: 10.1021/cr4005549 pmid: 37039110
	(c) Martelli G.; Orena M.; Rinaldi S. Curr. Org. Chem. 2014, 18, 1373. doi: 10.2174/1385272819666140407212959 pmid: 37039110
	(d) Ye L.-W.; Shu C.; Gagosz F. Org. Biomol. Chem. 2014, 12, 1833. doi: 10.1039/C3OB42181C pmid: 37039110
	(e) Saura-Sanmartin A.; Andreu-Ardil L. Org. Biomol. Chem. 2023, 21, 3296. doi: 10.1039/d3ob00309d pmid: 37039110
[3]	(a) Xie J.-H.; Zhu S.-F.; Zhou Q.-L. Chem. Rev. 2011, 111, 1713. doi: 10.1021/cr100218m
	(b) Ager D. J.; de Vries A. H. M.; de Vries J. G. Chem. Soc. Rev. 2012, 41, 3340. doi: 10.1039/c2cs15312b
	(c) Zhang Z.; Butt N. A.; Zhang W. Chem. Rev. 2016, 116, 14769. doi: 10.1021/acs.chemrev.6b00564
	(d) Yuan Q.; Zhang W. Chin. J. Org. Chem. 2016, 36, 274 (in Chinese). doi: 10.6023/cjoc201509016
	(袁乾家, 张万斌, 有机化学, 2016, 36, 274.) doi: 10.6023/cjoc201509016
	(e) Chu Y.; Han Z.; Ding K. Chin. J. Org. Chem. 2023, 43, 1934 (in Chinese). doi: 10.6023/cjoc202303001
	(褚杨杨, 韩召斌, 丁奎岭, 有机化学, 2023, 43, 1934.) doi: 10.6023/cjoc202303001
	(f) Behera P.; Ramakrishna D. S.; Chandrasekhar M. M.; Kotha-kapu S. R. Chirality 2023, 35, 477. doi: 10.1002/chir.v35.8
	(g) Chakrabortty S.; de Bruin B.; de Vries J. G. Angew. Chem., Int. Ed. 2024, 63, e202315773.
	(h) Zhang J.; Song Y.; Zhang Z.; Zhang W. Asian J. Org. Chem. 2025, 14, e202400584.
	(i) Chen Q.; Yang B.; Lang Q.; Ding X.; Li X.; Zhang X. Chin. J. Org. Chem. 2025, 45, 3326 (in Chinese). doi: 10.6023/cjoc202505032
	(陈奇姝, 杨泊, 稂琪伟, 丁小兵, 李秀秀, 张绪穆, 有机化学, 2025, 45, 3326.) doi: 10.6023/cjoc202505032
[4]	Adam D. Chemistry Nobel 2001, Nature 2001. https://doi.org/10.1038/news011011-17.
[5]	(a) Johnson N. B.; Lennon I. C.; Moran P. H.; Ramsden J. A. Acc. Chem. Res. 2007, 40, 1291. doi: 10.1021/ar700114k
	(b) Biosca M.; Diéguez M.; Zanotti-Gerosa A. Adv. Catal. 2021, 68, 341.
	(c) Zhang M.; Yin Q. Chin. J. Org. Chem. 2024, 44, 3258 (in Chinese). doi: 10.6023/cjoc202400049
	(张满刚, 殷勤, 有机化学, 2024, 44, 3258.) doi: 10.6023/cjoc202400049
[6]	Zhou Q.-L. Privileged Chiral Ligands and Catalysts, Wiley-VCH, Weinheim, Germany, 2011.
[7]	(a) Lückemeier L.; Pierau M.; Glorius F. Chem. Soc. Rev. 2023, 52, 4996. doi: 10.1039/d3cs00329a pmid: 37427715
	(b) Wang P.; He Z.-L.; Xia Z.-F.; Wei J.; Dong X.-Q. Chin. J. Chem. 2024, 42, 3135. doi: 10.1002/cjoc.v42.23 pmid: 37427715
	(c) Li L.-J.; He Y.; Yang Y.; Guo J.; Lu Z.; Wang C.; Zhu S.; Zhu S.-F. CCS Chem. 2024, 6, 537. doi: 10.31635/ccschem.023.202303412 pmid: 37427715
[8]	Tian F.; Yao D.; Liu Y.; Xie F.; Zhang W. Adv. Synth. Catal. 2010, 352, 1841. doi: 10.1002/adsc.v352:11/12
[9]	Li Q.; Wan P.; He Y.; Zhou Y.; Li L.; Chen B.; Duan K.; Cao R.; Zhou Z.; Qiu L. Asian J. Org. Chem. 2014, 3, 774. doi: 10.1002/ajoc.v3.7
[10]	Liu X.; Han Z.; Wang Z.; Ding K. Angew. Chem., Int. Ed. 2014, 53, 1978. doi: 10.1002/anie.201309521 pmid: 24446418
[11]	Bao D.-H.; Gu X.-S.; Xie J.-H.; Zhou Q.-L. Org. Lett. 2017, 19, 118. doi: 10.1021/acs.orglett.6b03397
[12]	Yuan Q.; Liu D.; Zhang W. Org. Lett. 2017, 19, 1144. doi: 10.1021/acs.orglett.7b00171
[13]	Yuan Q.; Liu D.; Zhang W. Org. Lett. 2017, 19, 1886. doi: 10.1021/acs.orglett.7b00651
[14]	Xia J.; Nie Y.; Yang G.; Liu Y.; Gridnev I. D.; Zhang W. Chin. J. Chem. 2018, 36, 612. doi: 10.1002/cjoc.v36.7
[15]	Biosca M.; Pàmies O.; Diéguez M. J. Org. Chem. 2019, 84, 8259. doi: 10.1021/acs.joc.9b00829 pmid: 31117569
[16]	Faiges J.; Borràs C.; Pastor I. M.; Pàmies O.; Besora M.; Dié-guez M. Organometallics 2021, 40, 3424. doi: 10.1021/acs.organomet.1c00450
[17]	Biosca M.; de la Cruz-Sánchez P.; Faiges J.; Margalef J.; Salo-mó E.; Riera A.; Verdaguer X.; Ferré J.; Maseras F.; Besora M.; Pàmies O.; Diéguez M. ACS Catal. 2023, 13, 3020. doi: 10.1021/acscatal.2c05579 pmid: 36910869
[18]	Zhang R.; Xu S.; Luo Z.; Liu Y.; Zhang J. Angew. Chem., Int. Ed. 2023, 62, e202213600.
[19]	Zhang K.; Cui P.; Miao M.; Zeng M.; Wang X.; Zhang M.; Chen Q.; Song H.; Ke B.; Qin Y. Org. Chem. Front. 2024, 11, 1456. doi: 10.1039/D3QO02034G
[20]	Massaro L.; Mallick R. K.; Yang J.; Peters B. B. C.; Ferrara F.; Xiao Y.; Andersson P. G. ACS Catal. 2026, 16, 1264. doi: 10.1021/acscatal.5c06880
[21]	Campello H. R.; Parker J.; Perry M.; Ryberg P.; Gallagher T. Org. Lett. 2016, 18, 4124. doi: 10.1021/acs.orglett.6b02074 pmid: 27508307
[22]	Lang Q.; Gu G.; Cheng Y.; Yin Q.; Zhang X. ACS Catal. 2018, 8, 4824. doi: 10.1021/acscatal.8b00827
[23]	Huang Y.; Li P.; Dong X.-Q.; Zhang X. Org. Biomol. Chem. 2018, 16, 8819. doi: 10.1039/c8ob02231c pmid: 30406248
[24]	Yang J.; Li X.; You C.; Li S.; Guan Y.-Q.; Lv H.; Zhang X. Org. Biomol. Chem. 2020, 18, 856. doi: 10.1039/C9OB02536G
[25]	Yin C.; Pan Y.; Zhang X.; Yin Q. Org. Lett. 2022, 24, 675. doi: 10.1021/acs.orglett.1c04132
[26]	Xie C.; Guo Q.; Yang Z.; Zi G.; Huang Y.; Hou G. Org. Chem. Front. 2023, 10, 2498. doi: 10.1039/D3QO00319A
[27]	Feng K.; Chen L.; Liu T.; Zhang X.; Feng W.; Huang A.; Shen F.; Song D.; Ling F.; Zhong W. Org. Lett. 2026, 28, 6574. doi: 10.1021/acs.orglett.6c01366
[28]	Magnus N. A.; Astleford B. A.; Laird D. L. T.; Maloney T. D.; McFarland A. D.; Rizzo J. R.; Ruble J. C.; Stephenson G. A.; Wepsiec J. P. J. Org. Chem. 2013, 78, 5768. doi: 10.1021/jo400589j
[29]	Lynch D.; Deasy R. E.; Clarke L.-A.; Slattery C. N.; Khandavilli U. B. R.; Lawrence S. E.; Maguire A. R.; Magnus N. A.; Moynihan H. A. Org. Lett. 2016, 18, 4978. doi: 10.1021/acs.orglett.6b02416
[30]	Lou Y.; Hu Y.; Lu J.; Guan F.; Gong G.; Yin Q.; Zhang X. Angew. Chem., Int. Ed. 2018, 57, 14193. doi: 10.1002/anie.v57.43
[31]	Shi Y.; Tan X.; Gao S.; Zhang Y.; Wang J.; Zhang X.; Yin Q. Org. Lett. 2020, 22, 2707. doi: 10.1021/acs.orglett.0c00669
[32]	Chakrabortty S.; Zheng S.; Kallmeier F.; Baráth E.; Tin S.; de Vries J. G. ChemSusChem 2023, 16, e202202353.
[33]	Ding Z.; Luo Y.; Yuan Q.; Wang G.; Yu Z.; Zhao M.; Liu D.; Zhang W. J. Am. Chem. Soc. 2024, 146, 25312. doi: 10.1021/jacs.4c09794
[34]	Wagener T.; Lückemeier L.; Daniliuc C. G.; Glorius F. Angew. Chem., Int. Ed. 2021, 60, 6425. doi: 10.1002/anie.202016771 pmid: 33460521
[35]	Guo S.; Ma B.; Chen G.-Q.; Zhang X. Org. Lett. 2023, 25, 2426. doi: 10.1021/acs.orglett.3c00532
[36]	Wang F.; Tan X.; Wu T.; Zheng L.-S.; Chen G.-Q.; Zhang X. Chem. Commun. 2020, 56, 15557. doi: 10.1039/D0CC05599A

过渡金属催化不对称氢化合成手性内酰胺的研究进展

Research Progress on the Synthesis of Chiral Lactams via Transition Metal-Catalyzed Asymmetric Hydrogenation

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Fig. & Tab. 35

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