Role of Pseudoephedrine as Chiral Auxiliary in the Acetate-Type Aldol Reaction with Chiral Aldehydes; Asymmetric Synthesis of Highly Functionalized Chiral Building Blocks

We have studied in depth the aldol reaction between acetamide enolates and chiral alpha-heterosubstituted aldehydes using pseudoephedrine as chiral auxiliary under double stereodifferentiation conditions, showing that high diastereoselectivities can only be achieved under the matched combination of reagents and provided that the alpha-heteroatom-containing substituent of the chiral aldehyde is conveniently protected. Moreover, the obtained highly functionalized aldols have been employed as very useful starting materials for the stereocontrolled preparation of other interesting compounds and chiral building blocks such as pyrrolidines, indolizidines, and densely functionalized beta-hydroxy and beta-amino ketones using simple and high-yielding methodologies.