Palladium-Catalyzed Decarbonylative Borylation of Carboxylic Acids: Tuning Reaction Selectivity by Computation

Decarbonylative borylation of carboxylic acids is reported. Carbon electrophiles are generated directly after reagent-enabled decarbonylation of the in situ accessible sterically-hindered acyl derivative of a carboxylic acid under catalyst controlled conditions. The scope and the potential impact of this method are demonstrated in the selective borylation of a variety of aromatics (> 50 examples). This strategy was used in the late-stage derivatization of pharmaceuticals and natural products. Computations reveal the mechanistic details of the unprecedented C-O bond activation of carboxylic acids. By circumventing the challenging decarboxylation, this strategy provides a general synthetic platform to access arylpalladium species for a wide array of bond formations from abundant carboxylic acids. The study shows a powerful combination of experiment and computation to predict decarbonylation selectivity.