Effect of Bronsted Acids and Bases, and Lewis Acid (Sn2+) on the Regiochemistry of the Reaction of Amines with Trifluoromethyl-尾-diketones: Reaction of 3-Aminopyrrole to Selectively Produce Regioisome

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• 作者：Michael De Rosa ; David Arnold ; Douglas Hartline ; Linda Truong ; Roman Verner ; Tianwei Wang ; Christian Westin
• 刊名：Journal of Organic Chemistry
• 出版年：2015
• 出版时间：December 18, 2015
• 年：2015
• 卷：80
• 期：24
• 页码：12288-12299
• 全文大小：507K
• ISSN：1520-6904

文摘

Reaction of 3-aminopyrrole (as its salt) with trifluoromethyl-尾-diketones gave 纬-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 尾-enaminone was slow resulting in the preferential formation of the 纬-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 伪-1H-pyrrolo[3,2-b]pyridine increased as the pK_a of the amine buffer decreased. Surprisingly the yield went down at higher pK_as. There was a change in mechanism as the reaction mixture became more basic. With strong amines trifluoromethyl-尾-diketones were present mainly or completely as the enolate. Under reductive conditions (3-nitropyrrole/Sn/AcOH/trifluoromethyl-尾-diketone) the 伪-1H-pyrrolo[3,2-b]pyridine was the major product as a result of Lewis acid catalysis by Sn²⁺. Similar 伪-regiochemistry was observed when the reaction of the 3-aminopyrrole salt with trifluoromethyl-尾-diketones was carried out in the presence of base and tin(II) acetate.