Mechanochemical Grignard Reactions with Gaseous CO2 and Sodium Methyl Carbonate

Abstract

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.Another scarcely examined area in mechanochemistry is the Grignard reaction. Although 120 years have passed since Victor Grignard elaborated the insertion of magnesium into a C-X bond, [10] its potential in mechanochemistry has not been fully exploited yet. Mechanochemical adaptions of Grignard reactions essentially halted at the attempt to isolate solvent-free, reactive organomagnesiums by Harrowfield et al. (Scheme 1, c). [11] Their experiments required an excess of magnesium to obtain a manipulable powder that could readily be removed from the milling vessel. When scavenging the Grignard reagents with ketones, however, this excess magnesium promoted the formation of the respective alkenes through McMurry-type reactions besides the anticipated tertiary alcohols and other byproducts. In search of a mechanochemical way to conduct Grignard reactions which hardly occur, if at all, in solution, Speight and Hanusa found that ball milling facilitates the insertion of magnesium into a C-F-bond as detected by the respective binaphthyls, albeit in low yields (Scheme 1, d). [12,13] Scheme 1. Previously reported mechanochemical reactions with CO2 (a and b), [7,8] mechanochemical Grignard reactions (c and d), [11,12] and mechanochemically conducted Grignard reactions with CO2 in this work.