Direct Organocatalytic Asymmetric Mannich Addition of 3-Substituted-2H-1,4-Benzoxazines: Access to Tetrasubstituted Carbon Stereocenters

3-Substituted-2H-1,4-benzoxazines undergo a highly enantioselective direct Mannich reaction with acetone in the presence of an L-proline catalyst at room temperature. The corresponding N-heterocycles with -tetrasubstituted carbon stereocenters were obtained in good yields (48-92%) and excellent enantioselectivity (up to >99% ee). Furthermore, a novel modification involving the diastereoselective reduction of the Mannich adduct was carried out leading to the formation of a 1,3-amino alcohol with a chiral tetrasubstituted carbon stereocenter in high yield.