Chemoselective Nucleophilic Fluorination Induced by Selective Solvation of the SN2 Transition State

• Published in: The journal of physical chemistry. B 2007-02, Vol.111 (7), p.1752-1758
• Main Authors: Pliego, Josefredo R, Piló-Veloso, Dorila
• Format: Article
• Language: English
• ISSN: 1520-6106; 1520-5207
• DOI: 10.1021/jp066580p

Reaction of the fluoride ion with secondary alkyl halides leads to 90% of elimination reaction and only 10% of nucleophilic substitution in dipolar aprotic solvents. Adding water to the organic phase, the SN2 yield increases in the cost of decreased reactivity. Using ab initio calculations, we have shown that it is possible to increase the reaction rate and the selectivity toward the SN2 process through supramolecular organocatalysis. The catalytic concept is based on selective solvation of the transition state through two hydrogen bonds provided by the 1,4-benzenedimethanol. The two hydrogen bonds between the catalyst and the SN2 transition state favor this pathway while just one strong hydrogen bond between the catalyst and the fluoride ion leads to a lower stabilization of the nucleophile, resulting in a higher reaction rate. Our calculations predict that the substitution product increases to 40% yield because of the selective catalysis provided by the 1,4-benzenedimethanol.