Palladium-Catalyzed Direct Dehydroxylative Cross-Electrophile Couplings of Unactivated Carboxylic Acids with Aryl Bromides for Accessing Ketones.

A palladium-catalyzed straightforward dehydroxylative cross-electrophile coupling of unactivated carboxylic acids with aryl bromides with the aid of cyanuric chloride (TCT) as an efficient dehydroxylative reagent was developed. The cross-couplings proceeded smoothly at room temperature in THF under the assistance of the palladium catalyst, cyanuric chloride, 4-methylmorpholine (NMM), magnesium turnings, and lithium chloride, allowing easy access to a broad range of structurally varied unsymmetrical ketones in modest to good yields with good functional group tolerance. Additionally, scaled-up synthesis and the use of the coupling protocol in the postmodification of bioactive complex molecules could also be successfully accomplished. Preliminary mechanistic investigations disclosed that in situ-generated triazine-based triester and aryl magnesium reagent might function as the two pivotal intermediates of the reductive cross-coupling.