Proline Catalyzed anti-Selective Mannich Reaction

Significance

The authors developed a highly enantioselective Mannich reaction catalyzed by l-proline. Employing cyclic and as thus configurationally locked (Z)-imines, the reaction with various ketones furnished the anti-Mannich products in high diastereo- and excellent enantioselectivity. As cyclic substrates 5,5-disubstituted 5,6-dihydro-1,4-oxazine-2-ones were chosen, presumably ­reacting via transition state A. The obtained 1,4-morpholine-2-ones are easily converted into α-amino acids.

Review: J. M. M. Verkade, L. J. C. van Hemert, P. J. L. M. Quaedflieg, F. P. J. T. Rutjes Chem. Soc. Rev. 2008, 37, 29-41.