Diastereoselective Synthesis of Highly Functionalized γ‐Lactams via Ugi Reaction/Michael Addition

The γ-lactam ring is a prominent feature in medicinal chemistry, and its synthesis has garnered significant interest due to its valuable properties. Among the γ-lactams, 2-oxopyrrolidine-3-carbonitrile derivatives stand out as versatile synthons that can be readily transformed into a variety of other functional groups. In this work, we successfully synthesized highly functionalized 3-cyano-2-pyrrolidinones with moderate to good overall yields using the Ugi reaction followed by intramolecular Michael addition. The process demonstrated excellent diastereoselectivity and showed good tolerance to a range of isonitriles and carbonyl compounds.