Base-Mediated Chemo- and Stereoselective Addition of 5-Aminoindole/Tryptamine and Histamines onto Alkynes

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• 作者：Akhilesh K. Verma ; Monika Patel ; Megha Joshi ; Pravin R. Likhar ; Rakesh K. Tiwari ; Keykavous Parang
• 刊名：Journal of Organic Chemistry
• 出版年：2014
• 出版时间：January 3, 2014
• 年：2014
• 卷：79
• 期：1
• 页码：172-186
• 全文大小：751K
• ISSN：1520-6904

文摘

Transition-metal-free chemo- and stereoselective addition of 5-aminoindole (1a), tryptamine (1b), and histamine (1c) to alkynes 2a鈥?b>s to synthesize the indolyl/imidazolyl enamines 3a鈥?b>p, 5a鈥?b>o, and 6a鈥?b>e using superbasic solutions of alkali-metal hydroxides in DMSO is described. The addition of N-heterocycles onto alkynes takes places chemoselectively without affecting the 1掳 amino groups (aromatic and aliphatic) of 5-aminoindole, tryptamine, and histamine. The stereochemistry of the products was found to be dependent upon reaction time; an increase in reaction time leads to the formation of a mixture of E/Z isomers and the thermodynamically stable E addition product. The chemoselective addition of N-heterocycle 1a onto alkyne over thiophenol 7 and phenol 8 is supported by control experiments. Competitive experiments showed that 5-aminoindole was more reactive than tryptamine, and histamine was found to be the least reactive. The present methodology provides an efficient chemoselective method to synthesize a variety of (Z)-enamines of 5-aminoindole, tryptamine, and histamine without affecting the 1掳 amino group. The presence of the free amino group in enamines could be further used for synthetic elaboration, which proved to be highly advantageous for structural and biological activity assessments.