Insertion of Diazo Esters into C-F Bonds toward Diastereoselective One-Carbon Elongation of Benzylic Fluorides: Unprecedented BF3 Catalysis with C-F Bond Cleavage and Re-formation

Selective transformation of C-F bonds remains a significant goal in organic chemistry, but C-F insertion of a onecarbon-atom unit has never been established. Herein we report the BF3-catalyzed formal insertion of diazo esters as one-carbon-atom sources into C-F bonds to accomplish one-carbon elongation of benzylic fluorides. A DFT calculation study revealed that the BF3 catalyst could contribute to both C-F bond cleavage and re-formation. This elongation provided alpha-fluoro-alpha,beta-diaryl esters with a high level of diastereoselectivity. Various benzylic fluorides and diazo esters were applicable. The synthetic utility of this method was demonstrated by the synthesis of a fluoro analogue of a compound that is used as a transient receptor and potential canonical channel inhibitor.

Automated summary

The study reports a new method catalyzed by BF3 for carbon elongation of benzylic fluorides. Through DFT calculation study, it was found that the BF3 catalyst could contribute to both C-F bond cleavage and re-formation. This method shows high diastereoselectivity and can be applied to various benzylic fluorides and diazo esters for synthesis.