Highly Efficient One-Pot Three-Component Mannich Reaction Under Solvent-Free Conditions

A mild and practically-convenient one-pot procedure for the direct Mannich reaction has been developed using a condensation of amines, aldehydes and unmodified ketones under solvent free conditions in the presence of ZnI2 with good to excellent yields. The present methodology offers several advantages, such as excellent yields, simple procedures, short reaction times and milder conditions with very small amounts of catalyst. Furthermore, it is the first time that the catalytic activity of several catalysts under solvent free conditions has been studied. It was found that both the diastereoselectivity and the rate of reaction were improved with various Lewis acids and metal oxides. However, the chiral catalysts, such as L-cystine, (-)-cinchonidine and L-proline, did not work well in terms of yield and diastereoselectivity under this condition.