Site-Selective Radical Aromatic C-H Functionalization of Alloxazine and Flavin through Ground-State Single Electron Transfer

Angew Chem Int Ed Engl. 2024 Apr 16:e202403417. doi: 10.1002/anie.202403417. Online ahead of print.ABSTRACTFlavins and their alloxazine isomers are key chemical scaffolds for bioinspired electron transfer strategies. Their properties can be fine-tuned by functional groups, which must be introduced at an early stage of the synthesis as their aromatic ring is inert towards post-functionalization. We show that the introduction of a remote metal-binding redox site on alloxazine and flavin activates their aromatic ring towards direct C-H functionalization. Mechanistic studies are consistent with a synthetic sequence involving ground state single electron transfer (SET) with an electrophilic source followed by radical-radical coupling. This unprecedented reactivity opens new opportunities in molecular editing of flavins by direct aromatic post-functionalization and the utility of the method is demonstrated with the site-selective C6 functionalization of alloxazine and flavin with a CF3 group, Br or Cl, that can be further elaborated into OH and aryl for chemical diversification.PMID:38627209 | DOI:10.1002/anie.202403417

Source: Angewandte Chemie - April 16, 2024 Category: Chemistry Authors: Agnideep Das Oscar Charpentier Cheriehan Hessin Jules Schleinitz David Pianca Nolwenn Le Breton Sylvie Choua Laurence Grimaud Christophe Gourlaouen Marine Desage-El Murr Source Type: research