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. An efficient and diastereoselective protocol for synthesizing highly substituted γ‐lactams is presented. The process involves an initial Ugi reaction, which is followed by an intramolecular Michael addition. This approach demonstrates excellent diastereoselectivity and shows a high tolerance for various isonitriles and carbonyl compounds. As a result, the desired γ‐lactams are obtained in moderate to good overall yields.