Electrochemically Driven Site-Selective N-Hydroxymethylation of Indoles and Derivatives
Thanathip Chomphunuch1,2, Kannika La-Ongthong1,2, Praewpan Katrun3,4
1Department of Chemistry, Faculty of Science, Mahidol University, Rama VI Road, Bangkok, 10400, Thailand.
Abstract:
Described herein is a facile electrochemical strategy for the generation of formaldehyde from N,N-dimethylacetamide (DMA) and water (H2O) toward a direct and site-selective N-hydroxymethylation of indoles and derivatives. Mechanistic studies suggested that N-(hydroxymethyl)-N-methylacetamide generated in situ from DMA/H2O under electrochemical conditions serves as a formaldehyde surrogate. The developed methodology features mild, base- and metal catalyst-free conditions. The reaction can accommodate a broad range of substrate scopes and offers an alternative route to access a series of N-hydroxymethylated indole, bis-indole, carbazole, and indazole derivatives. A gram-scale synthesis was demonstrated to show the scaled-up applicability of this transformation.
More Related Videos
Related Concept Videos
Phase II Reactions: Methylation Reactions
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...
ortho–para-Directing Activators: –CH3, –OH, –⁠NH2, –OCH3
Aldehydes and Ketones with Amines: Imine Formation Mechanism
Imines are formed under mildly acidic conditions. A pH of 4.5 is ideal for the reaction.
If the pH is low or the solution is too acidic, the reaction slows down in the...
Regioselectivity of Electrophilic Additions to Alkenes: Markovnikov's Rule
The hydrohalogenation of an unsymmetrical alkene can yield two haloalkane products, depending on which vinylic carbon takes up the halogen. However, one product usually predominates, where hydrogen adds to the vinylic carbon bearing the...
Aldehydes and Ketones with Amines: Imine and Enamine Formation Overview
Preparation of Amines: Reduction of Oximes and Nitro Compounds
Though catalytic hydrogenation can reduce nitrobenzenes, the reduction is nonselective in the presence of other functional groups. For instance, if nitrobenzene contains an aldehyde group,...


