10.1021/jo034719b
The research explores the chemoselectivity of electron-poor indoles in [4 + 2] cycloadditions, focusing on the competition between Diels-Alder (DA) and hetero-Diels-Alder (HDA) reactions. The study aims to demonstrate the influence of electronic and structural parameters on the reactivity of indoles, leading to either DA or HDA products. The researchers used various indole derivatives, such as indole-3-carboxaldehyde, indole-3-glyoxalate, and N-substituted indole-3-glyoxamides, along with dienes like 2,3-dimethylbutadiene and Danishefsky diene. The reactions were activated thermally, under high pressure, or with the aid of Lewis acids like zinc chloride and europium tris(6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octanedionate) (EuFOD). The conclusions highlight the ability to modulate the reactivity of the indole dienophile to favor either the classical DA process or the HDA reaction, with the products strongly depending on the type of electron-withdrawing substituent on the indole, the diene used, and the activation method. The study also reveals a remarkable reversal of chemoselectivity based on the number and nature of substituents on the acyclic nitrogen atom of the indole-3-glyoxamides.
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