Nucleophilic substitution reactions promoted by oligoethylene glycols: a mechanistic study of ion-pair SN2 processes facilitated by Lewis base

Abstract

We present a mechanistic study for nucleophilic substitution (SN2) reactions facilitated by multifunctional n-oligoethylene glycols (n-oligoEGs) using alkali metal salts MX (M+ = Cs+, K+, X– = F–, Br–, I–, CN–) as nucleophilic agents. Density functional theory method is employed to elucidate the underlying mechanism of the SN2 reaction. We found that the nucleophiles react as ion pairs, whose metal cation is ‘coordinated’ by the oxygen atoms in oligoEGs acting as Lewis base to reduce the unfavorable electrostatic effects of M+ on X–. The two terminal hydroxyl (−OH) function as ‘anchors’ to collect the nucleophile and the substrate in an ideal configuration for the reaction. Calculated barriers of the reactions are in excellent agreement with all experimentally observed trends of SN2 yields obtained by using various metal cations, nucleophiles and oligoEGs. The reaction barriers are calculated to decrease from triEG to pentaEG, in agreement with the experimentally observed order of efficiency (triEG CN– > Br– > I–, elucidating the observation that the yield was lowest for F–. It is suggested that the role of oxygen atoms in the promoters is equivalent to that of –OH group in bulky alcohols (tert-butyl or amyl-alcohol) for SN2 fluorination reactions previously studied in our lab. Copyright © 2012 John Wiley & Sons, Ltd.