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

以三叔丁醇铵为双功能有机催化剂的亲核放射性氟化反应:机理和能量学

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Abstract

We present a quantum chemical analysis of the (18)F-fluorination of 1,3-ditosylpropane, promoted by a quaternary ammonium salt (tri-(tert-butanol)-methylammonium iodide (TBMA-I) with moderate to good radiochemical yields (RCYs), experimentally observed by Shinde et al. We obtained the mechanism of the S(N)2 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 [(18)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 S(N)2 (18)F-fluorination.

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