Pd-Catalyzed C(2)—H Arylation of 3-(2-Aminopyrimidin-4-yl)indoles

doi:10.6023/cjoc202304012

Abstract

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

Cite this article

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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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

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