Synthesis and aminomethylation of 6-hydroxyindoles

“…Moreover, 6-hydroxyindoles are formed in the so-called 'anti-Nenitzescu reaction' which occurs via a 1,2-addition followed by an intramolecular Michael addition [15,23]. Especially, reactions of N-aryl-substituted enaminoesters at low temperatures are known to generate 6-hydroxyindoles [41]. O-acylated 4,5-dihydroxyindoles are Besides 5-hydroxyindoles and benzofurans, a diverse range of alternative reaction products, including 6-hydroxyindoles [32][33][34], O-acylated 4,5-dihydroxyindoles [33,[35][36][37][38], pyrroloindoles [39], furo [2,3-f ]benzofurans [40], and dimeric indoles [35], have been isolated (Scheme 2).…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, 6-hydroxyindoles are formed in the so-called 'anti-Nenitzescu reaction' which occurs via a 1,2-addition followed by an intramolecular Michael addition [15,23]. Especially, reactions of N-aryl-substituted enaminoesters at low temperatures are known to generate 6-hydroxyindoles [41]. O-acylated 4,5-dihydroxyindoles are com-mon (by)products in acetic or propanoic acid [33,[35][36][37][38], and are formed by the nucleophilic attack of the carboxylate on 5-hydroxyindole intermediate I4 [33,[35][36][37][38].…”

Section: Introductionmentioning

confidence: 99%

Exploration of the Divergent Outcomes for the Nenitzescu Reaction of Piperazinone Enaminoesters

et al. 2023

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The Nenitzescu reaction is a condensation reaction between an enamine and a quinone, which can give rise to a wide variety of reaction products depending on the nature of the starting material and the reaction conditions. The most commonly observed products are 5-hydroxyindoles and 5-hydroxybenzofurans. Both classes are of interest since they are known to possess a variety of promising bioactivities. Despite the high chemodivergency for this reaction, it remains an interesting synthetic strategy thanks to the mild reaction conditions, easily accessible starting materials and simple reaction procedures. For these reasons, our research group investigated the Nenitzescu reaction of piperazinone enaminoesters, resulting in the unexpected formation of rearranged 2-imidazolidinone benzofurans. In this work, we aimed to develop reaction conditions that favor the formation of 5-hydroxyindoles via an extensive, multivariate optimization study. This led to valuable insights into the parameters that influence regio- and chemoselectivity. Furthermore, two novel products were obtained, a pyrrolo[2,3-f]indole and a benzofuranone, both of which are rarely reported in the literature.

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“…16 The Nenitzescu indole synthesis with enaminones normally affords 5-hydroxyindoles. However, 6-hydroxyindoles 17 or 5-hydroxybenzofurans 18 have also been obtained as side products or even main products.…”

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confidence: 99%

2-Imidazolidinone benzofurans as unexpected outcome of the Lewis acid mediated Nenitzescu reaction

et al. 2022

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Synthesis and aminomethylation of 6-hydroxyindoles

Cited by 8 publications

References 2 publications

Methods for the Synthesis of Isogramines and Their Chemical Properties. (Review)

Methods for the Synthesis of Isogramines and Their Chemical Properties. (Review)

Exploration of the Divergent Outcomes for the Nenitzescu Reaction of Piperazinone Enaminoesters

2-Imidazolidinone benzofurans as unexpected outcome of the Lewis acid mediated Nenitzescu reaction

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