Synthesis of Piperidinones from β-Amino Acids by Petasis Methylenation

Significance

The authors describe a diastereoselective synthesis of 2,6-disubstituted piperidinones from substituted imines of β-amino acids via a nitrogen analogue of the Petasis-Ferrier rearrangement. Microwave-assisted Petasis methylenation followed by acid-catalyzed cyclization were the key steps in the synthesis. After methylenation, which is accelerated by microwave conditions, the precipitated titanium residue was removed by filtration and the crude residue was subjected to cyclization. The unusual combination of the polar solvent DMSO with the Lewis acid Al(i-Bu)₃ for the cyclization works very well for electron-rich imines and ketone-derived imines, rather than the use of a protic acid.