Highly Enantioselective Construction of Fluoroalkylated Quaternary Stereocenters via Organocatalytic Dehydrated Mannich Reaction of Unprotected Hemiaminals with Ketones

A general organocatalytic asymmetric dehydrated Mannich reaction of fluoroalkyl hemiaminals with ketones is reported. In this Mannich reaction, previously less explored aryl ketones showed great reactivity. By virtue of this efficient method, a wide range of biologically active beta-amino ketones were directly obtained. More importantly, two different intermediates involved in the reaction were detected and identified by F-19 NMR and HRMS analysis. Furthermore, the synthetic utility of the products was demonstrated by the synthesis of the biologically active fluoroalkyl beta-amino alcohols.