Enantioselective Michael addition catalyzed by cinchona alkaloids

Enantioselective Michael additions of cyclic beta -ketoesters to methyl vinyl ketone catalyzed by cinchona alkaloids were studied. The results revealed that the induced enantioselectivity was significantly influenced by both the structure of the catalyst and that of the substrate. Interesting differences in the effect of the structure of the alkaloid on the enantioselectivity of this reaction in the case of three beta -ketoesters were discovered. High enantioselectivities were obtained in the reaction of ethyl 2-oxocyclopentanecarboxylate and ethyl 2-oxocyclohexanecarboxylate (up to 83 and 80%, respectively) at a low cinchona:reactant ratio of 1:500. As the specific rotations of the product enantiomers, were unknown, they were determined by optical rotation and chiral GC measurements and verified by NMR experiments. (C) 2001 Wiley-Liss, Inc.