Syntheses and Applications of (Thio)Urea-Containing Chiral Quaternary Ammonium Salt Catalysts

We herein report our efforts to obtain a new class of systematically modified bifunctional (thio)urea-containing quaternary ammonium salts based on easily obtainable chiral backbones. Among the different classes of catalysts that were successfully synthesized, those based on trans-1,2-cyclohexane diamine were found to be the most powerful for the asymmetric α-fluorination of β-keto esters. Selectivities up to 93:7 could be obtained by using only 2 mol-% of the optimized catalyst. The importance of the bifunctional nature of these catalysts was demonstrated by control experiments using simplified monofunctional catalyst analogues, which gave almost racemic product only.