Palladium-Catalyzed Intramolecular Heck/Amination of Unactivated Alkenes for the Synthesis of Spiroindolines

doi:10.6023/cjoc202604014

Chinese Journal of Organic Chemistry ›› 2026, Vol. 46 ›› Issue (8): 3139-3146.DOI: 10.6023/cjoc202604014 Previous Articles Next Articles

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钯催化非活化烯烃的分子内Heck/胺化反应合成螺吲哚啉

林艳如^a^,^b, 周倩^b, 秦景灏^b, 宋德威^b, 宋芳芳^b, 高媛媛^b, 包欢^a, 李飞^a^,^*(), 姜恒^a^,^*(), 刘澜涛^b^,^*()

^a 辽宁石油化工大学石油化工学院辽宁抚顺 113001
^b 商丘师范学院化学化工学院河南省药物绿色合成工程研究中心河南商丘 476000

收稿日期:2026-04-07 修回日期:2026-05-17 发布日期:2026-05-27
通讯作者: 李飞, 姜恒, 刘澜涛
基金资助:
河南省自然科学基金(262300421296); 河南省自然科学基金(252300423729)

Palladium-Catalyzed Intramolecular Heck/Amination of Unactivated Alkenes for the Synthesis of Spiroindolines

Yanru Lin^a^,^b, Qian Zhou^b, Jinghao Qin^b, Dewei Song^b, Fangfang Song^b, Yuanyuan Gao^b, Huan Bao^a, Fei Li^a^,^*(), Heng Jiang^a^,^*(), Lantao Liu^b^,^*()

^a School of Petrochemical Engineering, Liaoning Petrochemical University, Fushun, Liaoning 113001
^b Henan Engineering Laboratory of Green Synthesis for Pharmaceuticals, School of Chemistry and Chemical Engineering, Shangqiu Normal University, Shangqiu, Henan 476000

Received:2026-04-07 Revised:2026-05-17 Published:2026-05-27
Contact: Fei Li, Heng Jiang, Lantao Liu
Supported by:
Natural Science Foundation of Henan Province(262300421296); Natural Science Foundation of Henan Province(252300423729)

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Abstract

Spiroindolines are widely present in natural alkaloids and biologically active compounds. Herein, a palladium- catalyzed intramolecular Heck/amination of unactivated alkenes was developed to construct a series of spiroindoline frame- works. The reaction employs the intrinsic intramolecular N—H moiety as the sole nucleophile, affording the desired products in good to moderate yields. In addition, preliminary attempts toward an asymmetric version of this reaction have also been conducted, providing optically active spiroindolines in up to 85% yield and 65% ee. This work provides a novel and straightforward approach for the synthesis of spiroindolines with potential applications in medicinal chemistry.

Key words: spiroindolines, palladium-catalyzed, Heck/amination reaction, intramolecular cyclization

Cite this article

Yanru Lin, Qian Zhou, Jinghao Qin, Dewei Song, Fangfang Song, Yuanyuan Gao, Huan Bao, Fei Li, Heng Jiang, Lantao Liu. Palladium-Catalyzed Intramolecular Heck/Amination of Unactivated Alkenes for the Synthesis of Spiroindolines[J]. Chinese Journal of Organic Chemistry, 2026, 46(8): 3139-3146.

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Entry	Ligand	[Pd]	Base	T/℃	Yield^b/%
1	PPh₃	Pd(dba)₂	Cs₂CO₃	110	48
2	S-Phos	Pd(dba)₂	Cs₂CO₃	110	47
3	DavePhos	Pd(dba)₂	Cs₂CO₃	110	34
4	PCy₃	Pd(dba)₂	Cs₂CO₃	110	16
5	(4-MeC₆H₄)₃P	Pd(dba)₂	Cs₂CO₃	110	57
6	(4-MeOC₆H₄)₃P	Pd(dba)₂	Cs₂CO₃	110	40
7	(4-ClC₆H₄)₃P	Pd(dba)₂	Cs₂CO₃	110	58
8	(4-CF₃C₆H₄)₃P	Pd(dba)₂	Cs₂CO₃	110	71
9	(4-CF₃C₆H₄)₃P	Pd(PPh₃)₄	Cs₂CO₃	110	23
10	(4-CF₃C₆H₄)₃P	PdCl₂	Cs₂CO₃	110	22
11	(4-CF₃C₆H₄)₃P	Pd(PPh₃)₂Cl₂	Cs₂CO₃	110	17
12	(4-CF₃C₆H₄)₃P	Pd(dba)₂	K₂CO₃	110	70
13	(4-CF₃C₆H₄)₃P	Pd(dba)₂	CsOAc	110	49
14	(4-CF₃C₆H₄)₃P	Pd(dba)₂	Et₃N	110	NR
15	(4-CF₃C₆H₄)₃P	Pd(dba)₂	Cs₂CO₃	90	55
16	—	Pd(dba)₂	Cs₂CO₃	110	NR
17	(4-CF₃C₆H₄)₃P	—	Cs₂CO₃	110	NR

Entry	Ligand	[Pd]	Base	T/℃	Yield^b/%
1	PPh₃	Pd(dba)₂	Cs₂CO₃	110	48
2	S-Phos	Pd(dba)₂	Cs₂CO₃	110	47
3	DavePhos	Pd(dba)₂	Cs₂CO₃	110	34
4	PCy₃	Pd(dba)₂	Cs₂CO₃	110	16
5	(4-MeC₆H₄)₃P	Pd(dba)₂	Cs₂CO₃	110	57
6	(4-MeOC₆H₄)₃P	Pd(dba)₂	Cs₂CO₃	110	40
7	(4-ClC₆H₄)₃P	Pd(dba)₂	Cs₂CO₃	110	58
8	(4-CF₃C₆H₄)₃P	Pd(dba)₂	Cs₂CO₃	110	71
9	(4-CF₃C₆H₄)₃P	Pd(PPh₃)₄	Cs₂CO₃	110	23
10	(4-CF₃C₆H₄)₃P	PdCl₂	Cs₂CO₃	110	22
11	(4-CF₃C₆H₄)₃P	Pd(PPh₃)₂Cl₂	Cs₂CO₃	110	17
12	(4-CF₃C₆H₄)₃P	Pd(dba)₂	K₂CO₃	110	70
13	(4-CF₃C₆H₄)₃P	Pd(dba)₂	CsOAc	110	49
14	(4-CF₃C₆H₄)₃P	Pd(dba)₂	Et₃N	110	NR
15	(4-CF₃C₆H₄)₃P	Pd(dba)₂	Cs₂CO₃	90	55
16	—	Pd(dba)₂	Cs₂CO₃	110	NR
17	(4-CF₃C₆H₄)₃P	—	Cs₂CO₃	110	NR

钯催化非活化烯烃的分子内Heck/胺化反应合成螺吲哚啉

Palladium-Catalyzed Intramolecular Heck/Amination of Unactivated Alkenes for the Synthesis of Spiroindolines

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