Generation of Axially Chiral Fluoroallenes through a Copper-Catalyzed Enantioselective β-Fluoride Elimination

Herein we report the copper-catalyzed silylation of propargylic difluorides to generate axially chiral, tetrasubstituted monofluoroallenes in both good yields (27 examples >80%) and enantioselectivities (82-98% ee). Compared to previously reported synthetic routes to axially chiral allenes (ACAs) from prochiral substrates, a mechanistically distinct reaction has been developed: the enantiodiscrimination between enantiotopic fluorides to set an axial stereocenter. DFT calculations and vibrational circular dichroism (VCD) suggest that beta-fluoride elimination from an alkenyl copper intermediate likely proceeds through a syn-beta-fluoride elimination pathway rather than an anti-elimination pathway. The effects of the C1-symmetric Josiphos-derived ligand on reactivity and enantioselectivity were investigated. Not only does this report showcase that alkenyl copper species (like their alkyl counterparts) can undergo can undergo beta-fluoride elimination, but this elimination can be achieved in an enantioselective fashion.

Automated summary

In this study, the copper-catalyzed silylation of propargylic difluorides was successfully used to generate axially chiral, tetrasubstituted monofluoroallenes with good yields and high enantioselectivities. A novel mechanistically distinct reaction was developed, which involves enantiodiscrimination between enantiotopic fluorides to set an axial stereocenter. The effects of the C1-symmetric Josiphos-derived ligand on reactivity and enantioselectivity were investigated, showing that enantioselective beta-fluoride elimination can be achieved in alkenyl copper species.