Nucleophilic Fluorination of a Secondary Alkyl Bromide with KF(18-Crown-6) and Bulky Diols: Microsolvation Causes Chemoselectivity Inversion in the Free Energy Profile.

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_N2 fluorination products. The use of KF combined with crown ether increases the S_N2 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_N2 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 s

SUBMITTER: Resende LF 

PROVIDER: S-EPMC12352739 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature