Toward the Robust Synthesis of [18F]F‐DOPA: Quantum Chemical Analysis of SNAr Cold Fluorination of Diaryl Iodonium Salt by 19F−

Abstract

Quantum chemical analysis is presented for S NAr cold fluorination of diaryliodonium salts by 19F− observed by Wirth et al. [Eur. J. Org. Chem. 2015, 625]. We examine the origin of experimentally obtained low yields (0–5%) of fluorination by calculating and comparing the relative Gibbs free energies of pre‐reaction complexes and the Gibbs free energies of activation for fluorination, bromination, and intramolecular cyclization. Focusing on the counter‐anion in diaryliodonium salt, we propose that S NAr bromination would be the predominant process rather than fluorination, resulting in very small amount of fluorinated product. Discussions are made for possible means of improving the yields in cold fluorination.