Electroreductive intramolecular coupling of 1-indolealkanones
Naoki Kise1, Toshiyuki Mano, Toshihiko Sakurai
1Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori University, Koyama, Tottori 680-8552, Japan. kise@bio.tottori-u.ac.jp
Organic Letters
|September 19, 2008
Summary
Electroreduction of indolealkanones yields specific cyclic products. The mechanism differs based on substituents, as confirmed by DFT calculations, revealing distinct reductive coupling pathways.
Area of Science:
- Organic electrochemistry
- Synthetic organic chemistry
- Computational chemistry
Background:
- Indole derivatives are crucial in medicinal chemistry and materials science.
- Electrochemical methods offer sustainable routes for complex molecule synthesis.
- Understanding reaction mechanisms is key to controlling stereoselectivity.
Purpose of the Study:
- To investigate the stereospecificity of electroreduction for 1-indolealkanones.
- To explore the influence of a methoxycarbonyl substituent on electroreduction outcomes.
- To elucidate the distinct reaction mechanisms of substituted indolealkanones using DFT.
Main Methods:
- Electrochemical reduction in isopropanol.
- Analysis of cyclized products using stereochemical methods.
- Density Functional Theory (DFT) calculations for radical anions.
Main Results:
- Stereospecific formation of five-, six-, and seven-membered trans-cyclized products from 1-indolealkanones.
- Formation of diastereomeric mixtures of trans- and cis-cyclized products from 3-methoxycarbonyl-1-indolealkanones.
- DFT calculations indicated different reductive coupling mechanisms for the two substrate types.
Conclusions:
- The electroreduction of 1-indolealkanones proceeds stereospecifically to form trans-cyclized products.
- The presence of a 3-methoxycarbonyl group alters the electroreduction pathway, leading to both cis and trans products.
- Distinct reaction mechanisms govern the reductive coupling of 1-indolealkanones and their 3-methoxycarbonyl derivatives.
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