Mechanochemical Grignard Reactions with Gaseous CO2 and Sodium Methyl Carbonate

Grignard reactions invert the intrinsic electrophilic reactivity of organohalides to form C–C bonds with other electrophiles. With carbon dioxide (CO2) as electrophile carboxylic acids can be prepared. Although scattered examples of mechanochemical reactions with CO2 have been reported, its synthetic application as C1-synthon has remained underexplored. Here, we developed a one-pot three-step protocol for the preparation of Grignard reagents from organobromides in a ball mill and their subsequent reaction with gaseous CO2 or sodium methyl carbonate to provide aryl and alkyl carboxylic acids in up to 82% yield. Noteworthy are the short reaction times and the significantly reduced solvent amount [2.0 equiv. for liquid assisted grinding (LAG) conditions]. Unexpectedly, aryl bromides with methoxy substituents lead to symmetric ketones as major products.