Unveiling the mechanism of N-methylation of indole with dimethylcarbonate using either DABCO or DBU as catalyst

Depending on the catalyst used, N-methylation of indole with dimethylcarbonate (DMC)-an environmentally friendly alkylation agent-yields different products. With 1,4-diazabicyclo[2.2.2]octane (DABCO), the reaction forms only N-methylated indole, but with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), both N-methylated and N-methoxycarbonylated indole are formed. Using direct ESI(+)-MS monitoring to collect actual snapshots of the changing ionic composition of the reaction solution, we report on the interception and characterization of key intermediates for such reactions. Although a mechanism has been proposed with methoxycarbonylated base as the key intermediate for both DBU and DABCO, the ESI(+)-MS data and B3LYP-D3/6-311+G** calculations suggest that the reaction of DMC with indole under either DABCO or DBU catalysis follows contrasting mechanisms.

Automated summary

The N-methylation of indole with dimethylcarbonate produces different products depending on the catalyst used. Direct ESI(+)-MS monitoring allows for the interception and characterization of key intermediates in the reaction process. Contrasting mechanisms are observed in the reaction of DMC with indole under either DABCO or DBU catalysis.