钯催化吲哚-3-羧酸酯和三亚甲基甲烷的环加成去芳构化反应

doi:10.6023/cjoc202602022

摘要/Abstract

发展了钯催化吲哚-3-羧酸酯和三亚甲基甲烷(TMM)给体的[3＋2]环加成反应. 该反应经钯催化的去芳构化过程高效构建了一系列取代的2,3-环戊烷并吲哚啉(产率最高达99%). 在标准反应条件下, 该反应对吲哚衍生物具有良好的官能团兼容性. 值得注意的是, 产物可进行酯水解、N-Ts基团脱除、Sonogashira偶联反应以及酯和卤素的还原等系列衍生化转化, 充分证实了该合成方法的实用性和应用潜力.

关键词: 环加成, 去芳构化, 吲哚, 钯催化, 三亚甲基甲烷

A formal [3＋2] cycloaddition between indole-3-carboxylate derivatives and trimethylenemethane (TMM) donor is disclosed. The reaction proceeds smoothly in toluene at ambient conditions via a Pd-catalyzed dearomatization process, delivering a series of substituted 2,3-fused cyclopentannulated indolines (up to 99% yield). The reaction exhibits high functional group tolerance for indole derivatives under the standard conditions. Remarkably, the synthetic utility of this method was demonstrated by transformation of the products such as hydrolysis of ester, removal of Ts group, Sonogashira coupling reaction and reduction of ester and halogen.

Key words: cycloaddition, dearomatization, indole, palladium catalysis, trimethylenemethane

引用此文

张青霞, 谢佳豪, 顾庆, 游书力. 钯催化吲哚-3-羧酸酯和三亚甲基甲烷的环加成去芳构化反应[J]. 有机化学, 2026, 46(9): 3759-3768.

Qingxia Zhang, Jiahao Xie, Qing Gu, Shuli You. Pd-Catalyzed [3＋2] Cycloaddition/Dearomatization of Indole-3-carboxylates with Trimethylenemethane[J]. Chinese Journal of Organic Chemistry, 2026, 46(9): 3759-3768.

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Entry	Ligand	Solvent	[Pd]	t/h	Yield^b/%
1	L1	Toluene	Pd₂dba₃	5	>95
2	L2^d	Toluene	Pd₂dba₃	36	n.d.^c
3	L3^e	Toluene	Pd₂dba₃	36	n.d.^c
4	L4^f	Toluene	Pd₂dba₃	36	n.d.^c
5	L5^g	Toluene	Pd₂dba₃	36	n.d.^c
6	L6^h	Toluene	Pd₂dba₃	36	n.d.^c
7	L1	THF	Pd₂dba₃	16	93
8	L1	1,4-Dioxane	Pd₂dba₃	6	94
9	L1	DCM	Pd₂dba₃	16	52
10	L1	CH₃CN	Pd₂dba₃	16	29
11	L1	Toluene	Pd(dba)₂	5	92
12ⁱ	L1	Toluene	Pd₂dba₃	5	94
13ⁱ^,^j	L1	Toluene	Pd₂dba₃	9	95
14ⁱ^,^j^,^k	L1	Toluene	Pd₂dba₃	10	95^l

Entry	Ligand	Solvent	[Pd]	t/h	Yield^b/%
1	L1	Toluene	Pd₂dba₃	5	>95
2	L2^d	Toluene	Pd₂dba₃	36	n.d.^c
3	L3^e	Toluene	Pd₂dba₃	36	n.d.^c
4	L4^f	Toluene	Pd₂dba₃	36	n.d.^c
5	L5^g	Toluene	Pd₂dba₃	36	n.d.^c
6	L6^h	Toluene	Pd₂dba₃	36	n.d.^c
7	L1	THF	Pd₂dba₃	16	93
8	L1	1,4-Dioxane	Pd₂dba₃	6	94
9	L1	DCM	Pd₂dba₃	16	52
10	L1	CH₃CN	Pd₂dba₃	16	29
11	L1	Toluene	Pd(dba)₂	5	92
12ⁱ	L1	Toluene	Pd₂dba₃	5	94
13ⁱ^,^j	L1	Toluene	Pd₂dba₃	9	95
14ⁱ^,^j^,^k	L1	Toluene	Pd₂dba₃	10	95^l

Entry	Substrate	Temp./℃	t/h	Yield^b/%	ee^c/%
1	1a	25	0.5	92	39
2	1a	0	1.5	90	53
3	1a	-20	4	93	59
4	1a	-40	24	90	63
5	1f	-20	24	97	61
6	1h	-20	24	93	61

Entry	Substrate	Temp./℃	t/h	Yield^b/%	ee^c/%
1	1a	25	0.5	92	39
2	1a	0	1.5	90	53
3	1a	-20	4	93	59
4	1a	-40	24	90	63
5	1f	-20	24	97	61
6	1h	-20	24	93	61

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