Electrochemically Driven Site-Selective N-Hydroxymethylation of Indoles and Derivatives.

Described herein is a facile electrochemical strategy for the generation of formaldehyde from N,N-dimethylacetamide (DMA) and water (HO) 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/HO under electrochemical conditions serves as a formaldehyde surrogate. The developed methodology features mild, base- and metal catalyst-free conditions.

Electro-oxidative Methylation of 2-Isocyanobiaryls Using N,N-dimethylformamide (DMF) as Carbon Source: Synthesis of 6-Methylphenanthridines.

A benign electrochemical method to access 6-methylphenanthridines from 2-isocyanobiaryls using N,N-dimethylformamide (DMF) as a methyl source is reported. The protocol operates at ambient temperature without the need for harmful methylating reagents. Mechanistic studies suggested that DMF delivered a methylene synthon, followed by reduction at the cathode and tautomerization.

Electrochemical trifluoromethylation of 2-isocyanobiaryls using CFSONa: synthesis of 6-(trifluoromethyl)phenanthridines.

An efficient trifluoromethylation of 2-isocyanobiaryls was developed through the constant current electrolysis, employing sodium trifluoromethanesulfinate (CFSONa) as the trifluoromethyl source. The method enabled the syntheses of a series of 6-(trifluoromethyl)phenanthridine derivatives in moderate to high yields under metal- and oxidant-free conditions. A gram-scale synthesis highlights the synthetic versatility of the reported protocol.

Alkanethiol-Mediated Cyclization of -Alkynylisocyanobenzenes: Synthesis of Bis-Thiolated Indole Derivatives.

Reactions of -alkynylisocyanobenzenes with a variety of alkanethiols (Alk-SH) provide the corresponding bis-thiolated indole derivatives. The advantages of the reaction include metal-free, room-temperature, mild reaction conditions and broad functional group compatibility. The reaction proceeds via nucleophilic addition of an alkanethiol to an isonitrile moiety, 5- cyclization, followed by nucleophilic addition of an alkanethiol to a 3-alkylidene indole intermediate.