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

Abstract

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 or 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 as well as B3LYP‐D3/6‐311+G** calculations suggest that the reaction of DMC with indole under either DABCO or DBU catalysis follow contrasting mechanisms.