The Effects of Structural Modifications of Bis-tert-alcohol-Functionalized Crown-Calix[4]arenes as Nucleophilic Fluorination Promotors and Relations with Computational Predictions

초록

We prepared four structurally modified bis-tert-alcohol functionalized crown ether-strapped calix[4]arene promoters, that is, bis-tert-alcohol functionalized crown-5-calix[4]arene (BA5C), bis-tert-alcohol functionalized crown-7-calix[4]arene (BA7C), bis-1,1-dimethylbutanol functionalized crown 6-calix[4]arene (B3A6C), and bis-1,1-dimethylhexanol functionalized crown 6-calix[4]arene (B5AC6C). Nucleophilic fluorinations were conducted using alkali metal fluorides to investigate phase-transfer catalytic activities with respect to the sizes of crown ether-strapped calix[4]arene (CEC) subunits and lengths of alkyl chain spacers between tert-alcohol and CEC subunits. The reactivity of potassium fluoride was significantly enhanced by BA5C promoter because its crown-5-calix[4]arene subunit had cavity size appropriate for K+ capture. In contrast, BA7C did not efficiently enhance cesium fluoride S(N)2 fluorination because its crown-7-calix[4]arene cavity was too large to capture Cs+. The alkyl spacer of bis-tert-alcohol functionalized CEC provided sufficient distance between F- and Cs+. In particular, the three-component alkyl carbon chain of B3A6C was optimal in terms of increasing CsF reactivity. Systematic quantum chemical analysis predicted that fluorination reactions facilitated by bis-tert-alcohol-substituted crown-6-calix[4]arene (BACCA) and B3A6C might proceed via separated ion-pair type pre-reaction complexes, which suggested that these two promotors act as Lewis bases that essentially separate CsF ion-pairs. The lower (by 0.4 kcal/mol) Gibbs free energy of activation for the reaction promoted by B3A6C than that facilitated by BACCA concurred with the experimentally observed slightly greater efficiency of B3A6C than BACCA.

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