Difluorocarbene‐Promoted O−O Bond Activation of Peroxy Acids for Electrophilic Carboxylation of Boronic Acids

• Published in: Chemistry, an Asian journal an Asian journal, 2024-10, Vol.19 (19), p.e202400613-n/a
• Main Authors: Niu, Hao‐Lin, Luo, Peng‐Xi, Zhang, Song‐Lin
• Format: Article
• Language: English
• Subjects: Boronic acids; Carboxylation; Difluorocarbene; Esterification; Esters; Functional groups; Hydrogen bonds; Metal-free; O−O activation; Peracids
• ISSN: 1861-4728; 1861-471X; 1861-471X
• DOI: 10.1002/asia.202400613

In this study, a difluorocarbene‐promoted O−O bond activation of peroxy acids is developed through the insertion of difluorocarbene into O−H bond. This activation strategy in synergy with O−B coordination with boronic acids/ester greatly polarizes the O−O bond for in‐situ generation of carboxylium species that reacts with the nucleophilic part of boronic acids in a concerted way to produce carboxylic esters. Good efficiency and functional group tolerance are demonstrated. Application of this method to the functionalization of a boronic acid drug used as HSL enzyme inhibitor produces smoothly the ester derivative. This difluorocarbene‐mediated O−O bond activation strategy is conceptually different from traditional radical type methods, and is also complementary to conventional esterification methods with a distinct retro‐synthetic disconnection. Difluorocarbene promotes the reaction of peroxy carboxylic acids and boronic acids/esters to produce carboxylic esters, through polarizing the O−O bond by difluoromethylation and O−B interaction for intrinsic generation and functionalization of carboxylium species in a concerted way.