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Nucleophilic Radiofluorination Using Tri-tert-Butanol Ammonium as a Bifunctional Organocatalyst: Mechanism and
Young-Ho Oh1, Sandip S Shinde2, Sungyul Lee1
1Department of Applied Chemistry, Kyung Hee University, Deogyeong-daero 1732, Yongin-si 17104, Gyeonggi-do, Korea.
Abstract:
We present a quantum chemical analysis of the 18F-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 SN2 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 [18F]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 SN2 18F-fluorination.
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