Access to Chiral Tetrahydro-γ-carbolines via Iridium-Catalyzed Asymmetric Cascade Allylation/iso-Pictet-Spengler Cyclization

doi:10.6023/cjoc202602006

Chinese Journal of Organic Chemistry Previous Articles Next Articles

ARTICLE

铱催化不对称串联烯丙基化/iso-Pictet-Spengler环化反应合成手性四氢-γ-咔啉

黄锦龙^a,†, 肖帆^a,†, 吴慧敏^a,†, 董秀琴^a,*, 王春江^a,b,*

^a武汉大学化学与分子科学学院基础科学-化学湖北省研究中心武汉 430072 中国;
^b中国科学院上海有机化学研究所金属有机化学全国重点实验室上海 200032 中国

收稿日期:2026-02-03 修回日期:2026-03-19
作者简介:^†共同第一作者
基金资助:
国家重点研发计划项目(No. 2023YFA1506700), 中央高校基本科研业务费专项资金项目(2042025kf0032)和国家自然科学基金(No. 22271226和22371216).

Access to Chiral Tetrahydro-γ-carbolines via Iridium-Catalyzed Asymmetric Cascade Allylation/iso-Pictet-Spengler Cyclization

Jin-Long Huang^a,†, Fan Xiao^a,†, Hui-Min Wu^a,†, Xiu-Qin Dong^a,*, Chun-Jiang Wang^a,b,*

^aHubei Research Center of Fundamental Science-Chemistry, College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072, China;
^bState Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Shanghai 230021, People’s Republic of China

Received:2026-02-03 Revised:2026-03-19
Contact: *E-mail: cjwang@whu.edu.cn, xiuqindong@whu.edu.cn
About author:^†(These authors contributed equally to this work).
Supported by:
Project supported by the National Key R&D Program of China (2023YFA1506700), the Fundamental Research Funds for the Central Universities (2042025kf0032), and the Natural Science Foundation of China (No. 22271226 and 22371216).

1. .pdf(8873KB)

Abstract

An efficient and highly stereoselective protocol has been developed for the construction of chiral tetrahydro-γ-carbolines bearing two non-adjacent stereocenters via an iridium-catalyzed asymmetric cascade allylation/iso-Pictet-Spengler cyclization between iminomalonates and readily accessible indolyl allylic alcohols with Lewis acid Zn(OTf)₂ as the promoter. A broad range of chiral tetrahydro-γ-carboline derivatives containing two non-adjacent stereocenters could be obtained in moderate to good yields (50%-80%) with excellent stereocontrol (>20:1 dr, 96%->99% ee). This protocol features high atom economy, generating water as the sole byproduct.

Key words: Asymmetric catalytic cascade reaction, Asymmetric allylation, iso-Pictet-Spengler cyclization, Iridium catalysis, Chiral tetrahydro-γ-carbolines;

Cite this article

Jin-Long Huang, Fan Xiao, Hui-Min Wu, Xiu-Qin Dong, Chun-Jiang Wang. Access to Chiral Tetrahydro-γ-carbolines via Iridium-Catalyzed Asymmetric Cascade Allylation/iso-Pictet-Spengler Cyclization[J]. Chinese Journal of Organic Chemistry, doi: 10.6023/cjoc202602006.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

References

[1] (a) Mei H.-B.; Aradi K.; Kiss L.; Han, J.-L. Chin. Chem. Lett. 2023, 34, 108657. (b) Alekseyev1 R. S.; Kurkin1 A. V.; Yurovskaya, M. A. Chem. Heterocycl. Compd.2011, 46, 1169-1198. (c) Herbert C. A.; Plattner J. J.; Welch, W. M. J. Med. Chem.1980, 23, 635-643. (d) Khorana, N.; Smith, C.; Herrick-Davis, K.; Purohit, A.; Teitler, M.; Grella, B.; Dukat, M.; Glennon, R. A.J. Med. Chem. 2003, 46, 3930-3937.
[2] (a) Bridoux, A.; Millet, R.; Pommery, J.; Pommery, N.; Henichart, J.-P.Med. Chem. 2010, 18, 3910. (b) Wang S.; Wang Y.; Liu W.; Liu N.; Zhang Y.; Dong G.; Liu Y.; Li Z.; He X.; Miao Z.; Yao J.; Li J.; Zhang W.; Sheng, C. ACS Med. Chem. Lett.2014, 5, 506-511. (c) Makhaeva, G. F.; Lushchekina, S. V.; Makhaeva, G. F.; Lushchekina, S. V.; Boltneva, N. P.; Sokolov, V. B.; Grigoriev, V. V.; Serebryakova, O. G.; Vikhareva, E. A.; Aksinenko, A. Y.; Barreto, G. E.; Aliev, G.; Bachurin, S. O.Sci. Rep. 2015, 5, 13164.(d) Sarges, R.; Howard, H.R.; Bordner, J. et al. J. Med. Chem. 1986, 29, 8-19., 791-810.
[3] (a) Ivachtchenko A. V.; Frolov E. B.; Mitkin O. D.; Kysil V. M.; Khvat A. V.; Okun I. M.; Tkachenko, S. E. Bioorg. Med. Chem. Lett.2009, 19, 3183-3187. (b) Ramachandran P. V.; Reddy M. V. R.; Brown, H. C. Tetrahedron Lett.2000, 41, 583-586. (c) Doody, R.; Gavrilova, S.; Gavrilova, S. I.; Sano, M.; Thomas, R. G.; Aisen, P. S.; Bachurin, S. O.; Seely, L.; Hung, D.Lancet. 2008, 372, 207-215.(d) Kalin, J.; Butler, K.; Akimova, T.; Hancock, W. W.; Kozikowski, A. J. Med. Chem. 2012, 55, 639-651., 1522-1527.
[4] Calcaterra A.; Mangiardi L.; Monache G. D.; Quaglio D.; Balducci S.; Berardozzi S.; Iazzetti A.; Franzini R.; Botta B.; Ghirga F.Molecules 2020, 25, 414.
[5] Lee Y.; Klausen R. S.; Jacobsen, E. N. Org. Lett.2011, 13, 5564-5567.
[6] Sun X.-X.; Zhang H.-H.; Li G.-H.; He Y.-Y.; Shi, F. Chem. Eur. J.2016, 22, 17526-17532.
[7] Yang W.-L.; Li C.-Y.; Qin W.-J.; Tang F.-F.; Yu X.; Deng W.-P. ACS Catal.2016, 6, 5685-5690.
[8] Liu Y.-Z.; Shang S.-J.; Zhu J.-Y.; Yang W.-L.; Deng, W.-P. Adv. Synth. Catal.2018, 360, 2191-2203.
[9] (a) Cheng, Q.; Tu, H.-F.; Zheng, C.; Qu, J.-P.; Helmchen, G.; You, S.-L. Chem. Rev. 2019, 119, 1855-1969; (b) Hartwig, J. F.; Pouy, M. J. Top. Organomet. Chem. 2011, 34, 169-208. (c) Liu, W.-B.; Xia, J.-B.; You, S.-L. Top. Organomet. Chem. 2012, 38, 155-208. (d) Qu, J.; Helmchen, G. Acc. Chem. Res. 2017, 50, 2539-2555. (e) Zhang, H.; Gu, Q.; You, S.-L. Chin. J. Org. Chem. 2019, 39, 15-27 (in Chinese). (张慧君, 顾庆, 游书力, 有机化学, 2019, 39, 15-27.).
[10] Xu S.-M.; Wei L.; Shen C.; Xiao L.; Tao H.-Y.; Wang C.-J. Nat. Commun.2019, 10, 5553.
[11] Xiao F.; Xu S.-M.; Dong X.-Q.; Wang C.-J. Org. Lett.2021, 23, 3, 706-710.
[12] (a) Schafroth M. A.; Sarlah D.; Krautwald S.; Carreira, E. M. J. Am. Chem. Soc.2012, 134, 20276-20278. (b) Krautwald S.; Sarlah D.; Schafroth M. A.; Carreira, E. M. Science 2013, 340,1065-1068. (c) Krautwald, S.; Schafroth, M. A.; Sarlah, D.; Carreira, E. M. J. Am. Chem. Soc. 2014, 136, 3020-3023.(d) Bhaskararao, B.; Sunoj, R. B. J. Am. Chem. Soc. 2015, 137, 15712-15722., 7598-7604.

[1]	Wenjie Zhang, Zhengchao Duan, Xiangping Hu. Chiral P-N-O Ligands for Iridium-Catalyzed Asymmetric Hydrogenation of Aromatic Ketones [J]. Chinese Journal of Organic Chemistry, 2026, 46(5): 2129-2137.
[2]	Ting Mao, Linyuan Zeng, Jilin Wen, Jia Jia. Visible Light-Mediated Iridium-Catalyzed Debromocyclization of Aliphatic α-Bromotrifluoromethyl Groups [J]. Chinese Journal of Organic Chemistry, 2025, 45(7): 2520-2528.
[3]	Zhen Liang, Weiyan Xu, Yi Chen, Huayu Qiu, Yezhe Zhao, Jiabin Shen, Min Wang. Iridium-Catalyzed Synthesis of Indole Derivatives from N-Aryl-2-aminopyridines and Vinylene Carbonate [J]. Chinese Journal of Organic Chemistry, 2025, 45(6): 2149-2156.
[4]	Wang Jiang, Zhuangzhi Shi. Recent Progress in meta-/para-Selective Aromatic C—H Borylation [J]. Chinese Journal of Organic Chemistry, 2023, 43(5): 1691-1705.
[5]	Fangfang Song, Shiyang Zhu, Hao Wang, Gong Chen. Iridium-Catalyzed Intermolecular N—N Coupling for Hydrazide Synthesis Using N-Benzoyloxycarbamates as Acyl Nitrene Precursor [J]. Chinese Journal of Organic Chemistry, 2021, 41(10): 4050-4058.
[6]	Tian Fei, Zhang Jian, Yang Wulin, Deng Weiping. Progress in Iridium-Catalyzed Asymmetric Allylic Substitution Reactions via Synergetic Catalysis [J]. Chinese Journal of Organic Chemistry, 2020, 40(10): 3262-3278.
[7]	Gong Baoxiang, Yan Long, Chen Mengyuan, Deng Jin, Fu Yao. Preparation of D-Sorbitol by Catalytic Hydrogenation of D-Glucose with Semi Sandwich Iridium Catalyst [J]. Chin. J. Org. Chem., 2017, 37(12): 3170-3176.
[8]	Deng Yingying, Yang Wen, Yang Xin, Yang Dingqiao. Progress in Iridium-Catalyzed Asymmetric Allylic Substitution Reactions with Allylic Esters [J]. Chin. J. Org. Chem., 2017, 37(12): 3039-3059.
[9]	Wang Yingjie, Zhang Zhenfeng, Zhang Wanbin. Asymmetric Hydrogenation of Cyclic Dehydroamino Acids and Their Derivatives [J]. Chin. J. Org. Chem., 2015, 35(3): 528-538.
[10]	TU Qing-Qiang, YANG Ding-Qiao. Progress in Iridium-Catalyzed Oxidation Reaction [J]. Chin. J. Org. Chem., 2010, 30(08): 1164-1174.
[11]	BIAN Hong-Xu, YANG Ding-Qiao. Progress of Iridium-Catalyzed Cycloaddition Reactions [J]. Chin. J. Org. Chem., 2010, 30(04): 506-514.
[12]	TUN Yu-Juan, YANG Ding-Jiao, LONG Yu-Hua. Progress in Iridium-Catalyzed Asymmetric Allylic Substitution Reactions [J]. Chin. J. Org. Chem., 2009, 29(10): 1522-1532.
[13]	Zhang, Junfang; Yang, Dingqiao*; Long, Yuhua. Progress in Iridium-Catalyzed Asymmetric Hydrogenation Reactions [J]. Chin. J. Org. Chem., 2009, 29(06): 835-847.
[14]	CHEN Wan-Suo*,CHEN Zhi-Rong. Quantum Chemical Study on Asymmetric Allylation of Benzaldehyde [J]. Chin. J. Org. Chem., 2005, 25(07): 822-825.

铱催化不对称串联烯丙基化/iso-Pictet-Spengler环化反应合成手性四氢-γ-咔啉

Access to Chiral Tetrahydro-γ-carbolines via Iridium-Catalyzed Asymmetric Cascade Allylation/iso-Pictet-Spengler Cyclization

PDF

Supporting Info.

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 14

Recommended Articles

Metrics

Comments