Metal-Free Hydroxymethylation of Indole Derivatives with Formic Acid as an Alternative Way to Indirect Utilization of CO2

The selective N-alkylation of indole substrates remains an ongoing research challenge for the relative attenuated nucleophilicity toward nitrogen. Herein, we developed the hydroxymethylation of indole derivatives to afford N-alkylated indole products with formic acid. This metal-free process was promoted by the organic base 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) using phenylsilane as the reductant under mild conditions. Besides, this strategy represents an alternative way for indirect utilization of CO2, considering the facile hydrogenation of CO2 to produce HCOOH.

Automated summary

In this study, a selective method for the synthesis of N-alkylated indole products was developed via hydroxymethylation using formic acid. This metal-free process under mild conditions, using an organic base as the catalyst, represents an alternative strategy for the indirect utilization of CO2. This method has significant practical value.