- Effect of Bronsted Acids and Bases, and Lewis Acid (Sn2+) on the Regiochemistry of the Reaction of Amines with Trifluoromethyl-β-diketones: Reaction of 3-Aminopyrrole to Selectively Produce Regioisomeric 1H-Pyrrolo[3,2-b]pyridines
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Reaction of 3-aminopyrrole (as its salt) with trifluoromethyl-β-diketones gave γ-1H-pyrrolo[3,2-b]pyridines via reaction at the less reactive carbonyl group. The trifluoromethyl group increased the electrophilicity of the adjacent carbonyl group and decreased the basicity of the hydroxyl group of the CF3 amino alcohol formed. This amino alcohol was formed faster, but its subsequent dehydration to the β-enaminone was slow resulting in the preferential formation of the γ-regioisomer. Reaction of 4,4,4-trifluoro-1-phenyl-1,3-butadione with 3-aminopyrrole was carried out using a series of 6 amine buffers. Yields of the α-1H-pyrrolo[3,2-b]pyridine increased as the pKa of the amine buffer decreased. Surprisingly the yield went down at higher pKas. There was a change in mechanism as the reaction mixture became more basic. With strong amines trifluoromethyl-β-diketones were present mainly or completely as the enolate. Under reductive conditions (3-nitropyrrole/Sn/AcOH/trifluoromethyl-β-diketone) the α-1H-pyrrolo[3,2-b]pyridine was the major product as a result of Lewis acid catalysis by Sn2+. Similar α-regiochemistry was observed when the reaction of the 3-aminopyrrole salt with trifluoromethyl-β-diketones was carried out in the presence of base and tin(II) acetate.
- De Rosa, Michael,Arnold, David,Hartline, Douglas,Truong, Linda,Verner, Roman,Wang, Tianwei,Westin, Christian
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p. 12288 - 12299
(2016/01/09)
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- Condensed Heteroaromatic Ring Systems. VI. Synthesis of Indoles and Pyrrolopyridines from o-Nitroarylacetylenes
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Catalytic hydrogenation of o-nitrophenylacetaldehyde diethyl acetal over palladium-carbon, followed by intramolecular cyclization of the resulting o-aminophenylacetaldehyde diethyl acetal with hydrochloric acid, gave indole.Similarly, 4-methylindole, ethyl 5-indolecarboxylate, and various pyrrolopyridines were synthesized from the corresponding o-nitroarylacetaldehyde derivatives.The preparation of the desired o-nitroarylacetaldehydes was accomplished by the condensation of o-halonitroaromatics with trimethylsilylacetylene in the presence of dichloro-bis(triphenylphosphine)palladium as a catalyst, followed by ethanolysis of the resulting o-(trimethylsilylethenyl)nitroaromatics.Keywords - o-halonitroaromatic; o-cyanohaloaromatic; trimethylsilylacetylene; palladium-catalyzed reaction; cyclization; indole; pyrrolopyridine
- Sakamoto, Takao,Kondo, Yoshinori,Yamanaka, Hiroshi
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p. 2362 - 2368
(2007/10/02)
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