Hydrogen-Bonding Phase-Transfer Catalyst Enabled Asymmetric Fluorination
17 September 2018 (online)
Following publication of Synfacts 2018, 14, 861, we recognized that our comment may be vulnerable to misinterpretations which undermine the novelty of the highlighted work (Science 2018, 360, 638) and we would like to clarify the intention of our statement. Gouverneur and co-workers reported a chiral bis-urea catalyzed asymmetric nucleophilic fluorination of in situ formed episulfonium salts. The novelty of this method lies in the catalyst’s ability to bind and subsequently exchange a halide anion with CsF, an organic solvent insoluble metal salt, to form a supramolecular chiral, non-racemic anion, which is consequently used as the asymmetric fluoride delivery source. The success of this strategy is owed to the increased thermodynamic stability of the fluoride-bound catalyst over the bromide-bound catalyst, underlying the crucial role of the hydrogen bonding network in the phase-transfer catalyst. This approach is therefore fundamentally different from the phase-transfer catalysis manifolds known to date, such as that mentioned in our original comment (Org. Lett. 2014, 16, 6432). The approach of Gouverneur et al. is distinct and highly innovative as it relies exclusively on the use of a hydrogen bond donor catalyst to enable effective phase transfer.here is an error in the structure of the starting material in the batch synthesis.