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

doi:10.6023/cjoc202602006

有机化学 ›› 2026, Vol. 46 ›› Issue (9): 3769-3776.DOI: 10.6023/cjoc202602006 上一篇下一篇

研究论文

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
^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

收稿日期:2026-02-03 修回日期:2026-03-19 发布日期:2026-04-02
作者简介:
^† 共同第一作者.
基金资助:
国家重点研发计划(2023YFA1506700); 中央高校基本科研业务费专项资金(2042025kf0032); 国家自然科学基金(22271226); 国家自然科学基金(22371216)

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

Jinlong Huang^a, Fan Xiao^a, Huimin Wu^a, Xiuqin Dong^a^,^*(), Chunjiang Wang^a^,^b^,^*()

^a Hubei Research Center of Fundamental Science-Chemistry, College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072
^b State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Shanghai 200032

Received:2026-02-03 Revised:2026-03-19 Published:2026-04-02
Contact:
^* E-mail: xiuqindong@whu.edu.cn;
cjwang@whu.edu.cn
About author:
Dedicated to the 100th anniversary of the birth of Professor Xikui Jiang.
^† The authors contributed equally to this work
Supported by:
National Key R&D Program of China(2023YFA1506700); Fundamental Research Funds for the Central Universities(2042025kf0032); National Natural Science Foundation of China(22271226); National Natural Science Foundation of China(22371216)

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摘要/Abstract

发展了一种高效、高立体选择性的合成方法, 成功构建了具有两个立体中心的手性四氢-γ-咔啉类化合物. 通过铱催化亚胺基丙二酸酯与方便易得的吲哚基烯丙醇之间的不对称串联烯丙基化/iso-Pictet-Spengler环化反应, 在路易斯酸Zn(OTf)₂促进下进行. 通过该方法获得了一系列含有两个非相邻手性中心的手性四氢-γ-咔啉衍生物, 产率中等至良好(50%~80%), 并表现出优异的立体控制水平(>20∶1 dr, 96%~>99% ee). 该策略具有高原子经济性, 反应仅生成水这一副产物.

关键词: 不对称催化串联反应, 不对称烯丙基化, iso-Pictet-Spengler环化反应, 铱催化, 手性四氢-γ-咔啉

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

引用此文

黄锦龙, 肖帆, 吴慧敏, 董秀琴, 王春江. 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[J]. 有机化学, 2026, 46(9): 3769-3776.

Jinlong Huang, Fan Xiao, Huimin Wu, Xiuqin Dong, Chunjiang Wang. Access to Chiral Tetrahydro-γ-carbolines via Iridium-Catalyzed Asymmetric Cascade Allylation/iso-Pictet-Spengler Cyclization[J]. Chinese Journal of Organic Chemistry, 2026, 46(9): 3769-3776.

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参考文献 12

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Entry	Acid (mol%)	Solvent	Yield^b/%	ee^c/%
1	Cl₃CCO₂H (25)	DCE	54	81
2	F₃CCO₂H (25)	DCE	45	98
3	Yb(OTf)₃ (25)	DCE	73	11
4	Sc(OTf)₃ (25)	DCE	64	23
5	Zn(OTf)₂ (25)	DCE	40	96
6^d	Zn(OTf)₂ (25)	DCE	62	96
7^d	Zn(OTf)₂ (50)	DCE	67	96
8^d	Zn(OTf)₂ (100)	DCE	68	96
9^d	Zn(OTf)₂ (50)	DCM	53	81
10^d	Zn(OTf)₂ (50)	THF	63	98
11^d	Zn(OTf)₂ (50)	1,4-Dioxane	67	99
12^d	Zn(OTf)₂ (50)	PhMe	58	93

Entry	Acid (mol%)	Solvent	Yield^b/%	ee^c/%
1	Cl₃CCO₂H (25)	DCE	54	81
2	F₃CCO₂H (25)	DCE	45	98
3	Yb(OTf)₃ (25)	DCE	73	11
4	Sc(OTf)₃ (25)	DCE	64	23
5	Zn(OTf)₂ (25)	DCE	40	96
6^d	Zn(OTf)₂ (25)	DCE	62	96
7^d	Zn(OTf)₂ (50)	DCE	67	96
8^d	Zn(OTf)₂ (100)	DCE	68	96
9^d	Zn(OTf)₂ (50)	DCM	53	81
10^d	Zn(OTf)₂ (50)	THF	63	98
11^d	Zn(OTf)₂ (50)	1,4-Dioxane	67	99
12^d	Zn(OTf)₂ (50)	PhMe	58	93

Entry	R/R'	3	Yield^b/%	ee^c/%
1	C₆H₅/Et (1a)	3aa	67	99
2	p-MeC₆H₄/Et (1b)	3ba	60	98
3	m-MeC₆H₄/Et (1c)	3ca	62	96
4^d	o-MeC₆H₄/Et (1d)	3da	65	－>99
5	p-ClC₆H₄/Et (1e)	3ea	70	>99
6	m-ClC₆H₄/Et (1f)	3fa	64	96
7	o-ClC₆H₄/Et (1g)	3ga	62	98
8	p-MeOC₆H₄/Et (1h)	3ha	64	>99
9	m-MeOC₆H₄/Et (1i)	3ia	64	>99
10	p-BrC₆H₄/Et (1j)	3ja	65	>99
11	2-Naphthyl/Et (1k)	3ka	60	>99
12	Thiophen-2-yl/Et (1l)	3la	63	98
13	p-ClC₆H₄/ⁱPr (1m)	3ma	70	>99
14^d	Cy/Et (1n)	3na	58	－98

Entry	R/R'	3	Yield^b/%	ee^c/%
1	C₆H₅/Et (1a)	3aa	67	99
2	p-MeC₆H₄/Et (1b)	3ba	60	98
3	m-MeC₆H₄/Et (1c)	3ca	62	96
4^d	o-MeC₆H₄/Et (1d)	3da	65	－>99
5	p-ClC₆H₄/Et (1e)	3ea	70	>99
6	m-ClC₆H₄/Et (1f)	3fa	64	96
7	o-ClC₆H₄/Et (1g)	3ga	62	98
8	p-MeOC₆H₄/Et (1h)	3ha	64	>99
9	m-MeOC₆H₄/Et (1i)	3ia	64	>99
10	p-BrC₆H₄/Et (1j)	3ja	65	>99
11	2-Naphthyl/Et (1k)	3ka	60	>99
12	Thiophen-2-yl/Et (1l)	3la	63	98
13	p-ClC₆H₄/ⁱPr (1m)	3ma	70	>99
14^d	Cy/Et (1n)	3na	58	－98

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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

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