Abstract
Fluoride ion solvated in polar aprotic solvents works like bases and reacts with secondary alkyl bromide substrates mainly via E2 reactions, with minor formation of S(N)2 fluorination products. The use of KF combined with crown ether increases the S(N)2 yield. However, secondary substrates remain a challenge for nucleophilic fluorination. It has recently been demonstrated that crown ethers combined with the fluorinated tert-butyl alcohol (TBOH) TBOH-F3 can increase the KF salt reactivity and selectivity toward S(N)2 reactions. These observations can be explained by the microsolvation of the fluoride ion with hydrogen bond donor species. This study explores computationally the effect of bulky diols in the reaction of KF(18-crown-6) with 2-bromopropane as a model substrate. This study investigates the microsolvation by TBOH, TBOH-F3, and the bulky diols pinacol and BDMb-F6, aimed at evaluating their effect on the S(N)2:E2 product ratio. Considering the competitive pathways, results show that TBOH is the least effective, while bulky alcohol TBOH-F3, pinacol, and BDMb-F6 favor the S(N)2 pathway by 0.5, 1.6, and 5.6 kcal mol(-1). Thus, the study's findings indicate that pinacol and especially the BDMb-F6 diol are highly promising alcohols for achieving greater S(N)2:E2 selectivity in nucleophilic substitution reactions utilizing KF(18-crown-6).