Mechanism and Diastereoselectivity of the Photo-/NHC Cocatalyzed Fluoroacylation of Benzofurans: A Theoretical View

The NHC/photoredox cocatalysis proposes an alternative to conventional methods for acylation of the unsaturated bonds. But it is still a great challenge to effectively control the stereoselectivities stemming from couplings of the ketyl radicals and the alkyl radicals. In this work, we have selected the photo-/NHC cocatalyzed fluoroaroylation of benzofurans as the computational model for density functional theory (DFT) studies, intending to unveil mechanisms of the fluorine-induced diastereoselectivities and thus to provide guidance to future rational design of promising catalytic reactions with high stereoselectivities. The computational results reveal that a fluorine-bearing zwitterion intermediate is yielded after nucleophilic addition of the NHC catalyst to the acyl fluorides, because fluorine anion is a poor leaving group. The cross-coupling of the ketyl radical and the tertiary carbon radical is the diastereoselectivity-determining step, and the configuration with the bulky NHC-stabilized ketyl radical bonded trans to the α-fluorine substitution is energetically favor over that giving the cis configuration. The distortion–interaction energy calculations combined with the geometry analysis indicate that the repulsion of the α-fluorine atom on the neighboring carbon results in significant distortions of the two coupling partners in the cis-configuration transition state and therefore leads to high diastereoselectivities. In addition, it is unveiled that the nucleophilicity of the carbene atom could be substantially influenced by electron delocalization. Moreover, the steric hindrance arose from the N(2)-phenyl group warrants attention as it may reduce remarkable geometry distortions with approach of the acyl fluoride compound.