Cinchona Alkaloid-Lewis Acid Catalyst Systems for Enantioselective Ketene-Aldehyde Cycloadditions

摘要

In 1982, Wynberg reported an extraordinary example of asymmetric Lewis base catalysis in the context of cinchona alkaloid-catalyzed ketene-chloral cycloadditions (Figure 1).1 Wynberg's pioneering investigations undoubtedly provided inspiration to recent reports of asymmetric alkaloid-catalyzed ketene-imine cycloadditions,2 ketene dimerizations,3 and intramolecular ketene-aldehyde cycloadditions.4 The success of these latter investigations, however, serves to emphasize the absence of a ketene-aldehyde cycloaddition based on the Wynberg model addressing the original transformation's severe substrate limitations. Successfully extending the Wynberg ketene-aldehyde cycloadditions to structurally diverse aldehydes would afford access to versatile enantioenriched β-lactones using a commercially available catalyst.5 Herein, we report asymmetric cinchona alkaloid (1 or 2)-catalyzed acid chloride-aldehyde cyclocondensation (AAC) reactions applicable to a range of structurally diverse aldehydes. These reactions are characterized by exceptionally high enantio- and diastereoselection and the operational simplicity derived from using commercially available reaction catalysts and in situ ketene generation.