Catalytic Asymmetric Fluorination of Copper Carbene Complexes: Preparative Advances and a Mechanistic Rationale

The Cu-catalyzed reaction of substituted α-diazoesters with fluoride gives α-fluoroesters with ee values of up to 95 %, provided that chiral indane-derived bis(oxazoline) ligands are used that carry bulky benzyl substituents at the bridge and moderately bulky isopropyl groups on their core. The apparently homogeneous solution of CsF in C₆F₆/hexafluoroisopropanol (HFIP) is the best reaction medium, but CsF in the biphasic mixture CH₂Cl₂/HFIP also provides good results. DFT studies suggest that fluoride initially attacks the Cu- rather than the C-atom of the transient donor/acceptor carbene intermediate. This unusual step is followed by 1,2-fluoride shift; for this migratory insertion to occur, the carbene must rotate about the Cu−C bond to ensure orbital overlap. The directionality of this rotatory movement within the C₂-symmetric binding site determines the sense of induction. This model is in excellent accord with the absolute configuration of the resulting product as determined by X-ray diffraction using single crystals of this a priori wax-like material grown by capillary crystallization.