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

Marcelo Straesser Franco; Sumbal Saba; Jamal Rafique; Antonio Luiz Braga

doi:10.1002/anie.202104503

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

Angew Chem Int Ed Engl. 2021 Aug 16;60(34):18454-18460. doi: 10.1002/anie.202104503. Epub 2021 Jul 16.

Authors

Marcelo Straesser Franco¹, Sumbal Saba², Jamal Rafique³, Antonio Luiz Braga^{1

4}

Affiliations

¹ Departamento de Química, Universidade Federal de Santa Catarina-UFSC, Florianópolis, 88040-900, SC-Brazil.
² Instituto de Química, Universidade Federal de Goiás-UFG, Goiânia, 74690-900, GO-Brazil.
³ Instituto de Química, Universidade, Federal do Mato Grosso do Sul-UFMS, Campo Grande, 79074-460, MS-Brazil.
⁴ Department of Chemical Sciences, Faculty of Science, University of Johannesburg, Doornfontein, 2028, South Africa.

PMID: 34097781
DOI: 10.1002/anie.202104503

Abstract

Herein, we report a KIO₄ -mediated, sustainable and chemoselective approach for the one-pot C(sp² )-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.

Keywords: C(sp2)−H functionalization; KIO4; green chemistry; hydroxymethylation; imidazo-heteroarenes.

Publication types

Research Support, Non-U.S. Gov't