Nucleophilic Radiofluorination Using Tri--Butanol Ammonium as a Bifunctional Organocatalyst: Mechanism and Energetics.

We present a quantum chemical analysis of the F-fluorination of 1,3-ditosylpropane, promoted by a quaternary ammonium salt (tri-(-butanol)-methylammonium iodide (TBMA-I) with moderate to good radiochemical yields (RCYs), experimentally observed by Shinde et al. We obtained the mechanism of the S2 process, focusing on the role of the -OH functional groups facilitating the reactions. We found that the counter-cation TBMA acts as a bifunctional promoter: the -OH groups function as a bidentate 'anchor' bridging the nucleophile [F]F and the -OTs leaving group or the third -OH. These electrostatic interactions cooperate for the formation of the transition states of a very compact configuration for facile S2 F-fluorination.