Intramolecular Inverse Electron-Demand [4 + 2] Cycloadditions of Ynamides with Pyrimidines: Scope and Density Functional Theory Insights
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- 作者：Guillaume Duret ; Robert Quinlan ; Boyang Yin ; Rainer E. MartinPhilippe Bisseret ; Markus Neuburger ; Vincent Gandon ; Nicolas Blanchard
- 刊名：Journal of Organic Chemistry
- 出版年：2017
- 出版时间：February 3, 2017
- 年：2017
- 卷：82
- 期：3
- 页码：1726-1742
- 全文大小：1186K
- ISSN：1520-6904
文摘
4-Aminopyridines are valuable scaffolds for the chemical industry in general, from life sciences to catalysis. We report herein a collection of structurally diverse polycyclic fused and spiro-4-aminopyridines that are prepared in only three steps from commercially available pyrimidines. The key step of this short sequence is a [4 + 2]/retro-[4 + 2] cycloaddition between a pyrimidine and an ynamide, which constitutes the first examples of ynamides behaving as electron-rich dienophiles in [4 + 2] cycloaddition reactions. In addition, running the ihDA/rDA reaction in continuous mode in superheated toluene, to overcome the limited scalability of MW reactions, results in a notable production increase compared to batch mode. Finally, density functional theory investigations shed light on the energetic and geometric requirements of the different steps of the ihDA/rDA sequence.