Enantioselective Mannich Reactions with the Practical Proline Mimetic N-(p-Dodecylphenylsulfonyl)-2-pyrrolidinecarboxamide

A highly enantioselective and diastereoselective protocol for performing Mannich reactions has been developed by using a p-dodecylphenylsulfonamide-based proline catalyst. This catalyst facilitates the use of common, nonpolar solvents and increased concentrations as compared to alternative methods. A series of syn-selective Mannich reactions is reported, including the rapid access of alpha- and beta-amino acids surrogates. The use of the industrially attractive nonpolar solvents, such as 2-methyl-tetrahydrofuran, is also demonstrated.