Borane-Catalyzed C(sp3)-F Bond Arylation and Esterification Enabled by Transborylation

The activation and functionalization of carbon-fluorine bonds represent a significant synthetic challenge, given the high thermodynamic barrier to C-F bond cleavage. Stoichiometric hydrid oborane-mediated C-F functionalization has recently emerged, but is yet to be rendered catalytic. Herein, the borane-catalyzed coupling of alkyl fluorides with arenes (carbon-carbon bond formation) and carboxylic acids (carbon-oxygen bond formation) has been developed using transborylation reactions to achieve catalytic turnover. Successful C-C and C-O coupling across a variety of structurally and electronically differentiated arenes and carboxylic acids was achieved using 9-borabicyclo[3.3.1]nonane (H-B-9-BBN) as the catalyst and pinacol-borane (HBpin), with broad functional group tolerance. Experimental and computational studies suggest a mechanistic dichotomy for the carbon-carbon and carbon-oxygen coupling reactions. B-F transborylation (B-F/ B-H metathesis) between F-B-9-BBN and HBpin enabled catalytic turnover for carbon-carbon bond formation, whereas direct exchange between the alkyl fluoride and acyloxyboronic ester (C-F/B-O metathesis) was proposed for carbon-oxygen coupling, where H-B-9-BBN catalyzed the dehydrocoupling of the carboxylic acid with HBpin.

Automated summary

This study presents a borane-catalyzed coupling method for alkyl fluorides with arenes and carboxylic acids, achieving C-C and C-O bond formation with H-B-9-BBN and HBpin as catalysts, demonstrating broad functional group tolerance. Experimental and computational studies reveal a mechanistic dichotomy between the carbon-carbon and carbon-oxygen coupling reactions.