Stereoselective Coupling of N-tert-Butanesulfinyl Aldimines and β-Keto Acids: Access to β-Amino Ketones

Abstract

The reaction of chiral N-tert-butanesulfinyl aldimines with β-keto acids under basic conditions at room temperature proceeds with high levels of diastereocontrol, leading to β-amino ketones in high yields. Based on DFT calculations, an eight-membered cyclic transition state involving coordination of the lithium atom to the oxygens of carboxylate and sulfinyl units was proposed, being in agreement with the observed experimental diastereomeric ratios. The synthesis of the piperidine alkaloid (−)-pelletierine was successfully undertaken in order to demonstrate the utility of this methodology.