Stereochemical outcomes of C-F activation reactions of benzyl fluoride.

In recent years, the highly polar C-F bond has been utilised in activation chemistry despite its low reactivity to traditional nucleophiles, when compared to other C-X halogen bonds. Paquin's group has reported extensive studies on the C-F activation of benzylic fluorides for nucleophilic substitutions and Friedel-Crafts reactions, using a range of hydrogen bond donors such as water, triols or hexafluoroisopropanol (HFIP) as the activators. This study examines the stereointegrity of the C-F activation reaction through the use of an enantiopure isotopomer of benzyl fluoride to identify whether the reaction conditions favour a dissociative (S(N)1) or associative (S(N)2) pathway. [H-2]-Isotopomer ratios in the reactions were assayed using the Courtieu H-2 NMR method in a chiral liquid crystal (poly-gamma-benzyl-L-glutamate) matrix and demonstrated that both associative and dissociative pathways operate to varying degrees, according to the nature of the nucleophile and the hydrogen bond donor.