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The Effects of Structural Modifications of Bis‐ tert‐ alcohol‐Functionalized Crown‐Calix[4]arenes as Nucleophilic Fluorination Promotors and Relations with Computational Predictions
Author(s) -
Han Hae Ji,
Lee SungSik,
Kang Seok Min,
Kim Yerin,
Park Chanho,
Yoo Suah,
Kim Chul Hee,
Oh YoungHo,
Lee Sungyul,
Kim Dong Wook
Publication year - 2020
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201901746
Subject(s) - chemistry , nucleophile , reactivity (psychology) , alkyl , alcohol , crown ether , medicinal chemistry , calixarene , selectivity , polymer chemistry , catalysis , stereochemistry , organic chemistry , molecule , ion , medicine , alternative medicine , pathology
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.