钯催化3-(2-氨基嘧啶-4-基)吲哚2位C—H键芳基化反应的研究

doi:10.6023/cjoc202304012

摘要/Abstract

以N-甲基-3-(2-氨基嘧啶-4-基)吲哚衍生物和碘代芳烃为起始原料, 详细探讨了钯催化吲哚2位选择性C—H键活化/芳基化反应过程. 以醋酸钯为催化剂, 三苯基膦为配体, 碳酸银为添加剂, 碳酸钠为碱, 在120 ℃下于1,4-二氧六环中反应24 h, 可获得较高产率的2-芳基化吲哚衍生物. 在此标准条件下, 通过改变两种反应底物的结构, 探究了该合成方法的适用范围与局限性, 合成得到的系列吲哚衍生物经¹H NMR、¹³C NMR和HRMS结构表征.

关键词: 钯催化, 碳氢键活化, 芳基化, 嘧啶导向基团, 吲哚衍生物

Using N-methyl-3-(2-aminopyrimidin-4-yl)indole derivatives and aryl iodides as starting materials, palladium- catalyzed selective C—H bond activation/arylation at the C-2 position of indole was investigated in detail. With palladium acetate as the catalyst, triphenylphosphine as the ligand, silver carbonate as the additive and sodium carbonate as the base, various 2-arylindole products were obtained in high yields in 1,4-dioxane at 120 ℃ for 24 h. Under these standard conditions, the scope and limitation of the synthetic method were explored by changing the structure of two substrates, and the synthesized indole derivatives were characterized by ¹H NMR, ¹³C NMR and HRMS spectra.

Key words: palladium-catalysis, C—H bond activation, arylation, pyrimidine directing group, indole derivatives

引用此文

孙美娇, 谭晶, 谭玉, 彭进松, 陈春霞. 钯催化3-(2-氨基嘧啶-4-基)吲哚2位C—H键芳基化反应的研究[J]. 有机化学, 2023, 43(11): 3945-3959.

Meijiao Sun, Jing Tan, Yu Tan, Jinsong Peng, Chunxia Chen. Pd-Catalyzed C(2)—H Arylation of 3-(2-Aminopyrimidin-4-yl)indoles[J]. Chinese Journal of Organic Chemistry, 2023, 43(11): 3945-3959.

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参考文献 28

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Entry	Catalyst/Ligand	Additive	Base	Yield^b/%
1	Pd(OAc)₂/Pyridine	Ag₂CO₃	Na₂CO₃	52/57^c
2	Pd(OAc)₂/o-Phenanthroline	Ag₂CO₃	Na₂CO₃	Trace
3	Pd(OAc)₂/Bipyridine	Ag₂CO₃	Na₂CO₃	Trace
4	Pd(OAc)₂/PCy₃	Ag₂CO₃	Na₂CO₃	12
5	Pd(OAc)₂/TFP	Ag₂CO₃	Na₂CO₃	36
6	Pd(OAc)₂/ClPPh₂	Ag₂CO₃	Na₂CO₃	11
7	Pd(OAc)₂/PPh₃	Ag₂CO₃	Na₂CO₃	23/66^c
8	Pd(OAc)₂/P(o-tol)₃	Ag₂CO₃	Na₂CO₃	8
9	Pd(OAc)₂/JohnPhos^d	Ag₂CO₃	Na₂CO₃	Trace
10	Pd(OAc)₂/CyJohnPhos^d	Ag₂CO₃	Na₂CO₃	16
11^c	PdCl₂/Pyridine	Ag₂CO₃	Na₂CO₃	34
12^c	Pd(TFA)₂/Pyridine	Ag₂CO₃	Na₂CO₃	11
13^c	PdCl₂(CH₃CN)₂/Pyridine	Ag₂CO₃	Na₂CO₃	31
14^c	PdCl₂(PPh₃)₂/Pyridine	Ag₂CO₃	Na₂CO₃	30
15^c	Pd₂(dba)₃/Pyridine	Ag₂CO₃	Na₂CO₃	50
16^c	Pd(OAc)₂/Pyridine	None	Na₂CO₃	4
17^c^,^e	Pd(OAc)₂/Pyridine	Ag₂CO₃	Na₂CO₃	24
18^c^,^e	Pd(OAc)₂/Pyridine	Ag₂SO₄	Na₂CO₃	19
19	Pd(OAc)₂/Pyridine	AgNO₃	Na₂CO₃	Trace
20	Pd(OAc)₂/Pyridine	AgSbF₆	Na₂CO₃	11
21	Pd(OAc)₂/Pyridine	AgOTf	Na₂CO₃	14
22^f	Pd(OAc)₂/PPh₃	Ag₂CO₃	Na₂CO₃	76
23^g	Pd(OAc)₂/PPh₃	Ag₂CO₃	Na₂CO₃	91
24^g	Pd(OAc)₂/PPh₃	Ag₂CO₃	K₂CO₃	91
25^g	Pd(OAc)₂/PPh₃	Ag₂CO₃	NaHCO₃	85
26^g	Pd(OAc)₂/PPh₃	Ag₂CO₃	NaOH	Trace
27^g	Pd(OAc)₂/PPh₃	Ag₂CO₃	KOH	85
28^g	Pd(OAc)₂/PPh₃	Ag₂CO₃	NaO^tBu	11
29^g	Pd(OAc)₂/PPh₃	Ag₂CO₃	KO^tBu	35
30^g	Pd(OAc)₂/PPh₃	Ag₂CO₃	Et₃N	61
31^g	Pd(OAc)₂	Ag₂CO₃	None	5

Entry	Catalyst/Ligand	Additive	Base	Yield^b/%
1	Pd(OAc)₂/Pyridine	Ag₂CO₃	Na₂CO₃	52/57^c
2	Pd(OAc)₂/o-Phenanthroline	Ag₂CO₃	Na₂CO₃	Trace
3	Pd(OAc)₂/Bipyridine	Ag₂CO₃	Na₂CO₃	Trace
4	Pd(OAc)₂/PCy₃	Ag₂CO₃	Na₂CO₃	12
5	Pd(OAc)₂/TFP	Ag₂CO₃	Na₂CO₃	36
6	Pd(OAc)₂/ClPPh₂	Ag₂CO₃	Na₂CO₃	11
7	Pd(OAc)₂/PPh₃	Ag₂CO₃	Na₂CO₃	23/66^c
8	Pd(OAc)₂/P(o-tol)₃	Ag₂CO₃	Na₂CO₃	8
9	Pd(OAc)₂/JohnPhos^d	Ag₂CO₃	Na₂CO₃	Trace
10	Pd(OAc)₂/CyJohnPhos^d	Ag₂CO₃	Na₂CO₃	16
11^c	PdCl₂/Pyridine	Ag₂CO₃	Na₂CO₃	34
12^c	Pd(TFA)₂/Pyridine	Ag₂CO₃	Na₂CO₃	11
13^c	PdCl₂(CH₃CN)₂/Pyridine	Ag₂CO₃	Na₂CO₃	31
14^c	PdCl₂(PPh₃)₂/Pyridine	Ag₂CO₃	Na₂CO₃	30
15^c	Pd₂(dba)₃/Pyridine	Ag₂CO₃	Na₂CO₃	50
16^c	Pd(OAc)₂/Pyridine	None	Na₂CO₃	4
17^c^,^e	Pd(OAc)₂/Pyridine	Ag₂CO₃	Na₂CO₃	24
18^c^,^e	Pd(OAc)₂/Pyridine	Ag₂SO₄	Na₂CO₃	19
19	Pd(OAc)₂/Pyridine	AgNO₃	Na₂CO₃	Trace
20	Pd(OAc)₂/Pyridine	AgSbF₆	Na₂CO₃	11
21	Pd(OAc)₂/Pyridine	AgOTf	Na₂CO₃	14
22^f	Pd(OAc)₂/PPh₃	Ag₂CO₃	Na₂CO₃	76
23^g	Pd(OAc)₂/PPh₃	Ag₂CO₃	Na₂CO₃	91
24^g	Pd(OAc)₂/PPh₃	Ag₂CO₃	K₂CO₃	91
25^g	Pd(OAc)₂/PPh₃	Ag₂CO₃	NaHCO₃	85
26^g	Pd(OAc)₂/PPh₃	Ag₂CO₃	NaOH	Trace
27^g	Pd(OAc)₂/PPh₃	Ag₂CO₃	KOH	85
28^g	Pd(OAc)₂/PPh₃	Ag₂CO₃	NaO^tBu	11
29^g	Pd(OAc)₂/PPh₃	Ag₂CO₃	KO^tBu	35
30^g	Pd(OAc)₂/PPh₃	Ag₂CO₃	Et₃N	61
31^g	Pd(OAc)₂	Ag₂CO₃	None	5