Mechanistic Studies and Radiofluorination of Structurally Diverse Pharmaceuticals with Spirocyclic Iodonium(III) Ylides.

ABSTRACT: Synthesis of non-activated electron-rich and sterically hindered ¹⁸F-arenes remains a major challenge due to limitations of existing radiofluorination methodologies. Herein, we report on our mechanistic investigations of spirocyclic iodonium(III) ylide precursors for arene radiofluorination, including their reactivity, selectivity, and stability with no-carrier-added [¹⁸F]fluoride. Benchmark calculations at the G2[ECP] level indicate that pseudorotation and reductive elimination at iodine(III) can be modeled well by appropriately selected dispersion-corrected density functional methods. Modeling of the reaction pathways show that fluoride-iodonium(III) adduct intermediates are strongly activated and highly regioselective for reductive elimination of the desired [

SUBMITTER: Rotstein BH 

PROVIDER: S-EPMC4987086 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature