KIO4-mediated Selective Hydroxymethylation/Methylenation of Imidazo-Heteroarenes: A Greener Approach

Herein, we report a KIO4-mediated, sustainable and chemoselective approach for the one-pot C(sp(2))-H bond hydroxymethylation or methylenation of imidazo-heteroarenes with formaldehyde, generated in situ via the oxidative cleavage of ethylene glycol or glycerol (renewable reagents) through the Malaprade reaction. In the presence of ethylene glycol, a series of 3-hydroxymethyl-imidazo-heteroarenes was obtained in good to excellent yields. These compounds are important intermediates to access pharmaceutical drugs, e.g., Zolpidem. Furthermore, by using glycerol, bis(imidazo[1,2-a]pyridin-3-yl)methane derivatives were selectively obtained in good to excellent yields.

Automated summary

In this study, a sustainable and chemoselective approach for the C(sp(2))-H bond hydroxymethylation or methylenation of imidazo-heteroarenes was reported using KIO4 as a mediator. The use of renewable reagents such as ethylene glycol or glycerol generated formaldehyde in situ, leading to the formation of important pharmaceutical intermediates in good to excellent yields.