Intramolecular Inverse Electron-Demand [4 + 2] Cycloadditions of Ynamides with Pyrimidines: Scope and Density Functional Theory Insights.
J Org Chem
; 82(3): 1726-1742, 2017 02 03.
Article
em En
| MEDLINE
| ID: mdl-28059511
ABSTRACT
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.
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01-internacional
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MEDLINE
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article