Synthesis of (Arylamido)pyrrolidinone Libraries through Ritter-Type Cascade Reactions of Dihydroxylactams

The Ritter‐type reaction of arylnitriles and N‐acyliminium ions generated in situ from dihydroxy‐γ‐lactams gave tetrahydropyrrolo[2,3‐d]oxazol‐5‐ones in excellent yields. A subsequent acidic hydrolysis in EtOH/H2O/TFA (trifluoroacetic acid) yielded new (arylamido)pyrrolidinones with excellent cis diastereoselectivity. A combined one‐step Ritter–hydrolysis procedure proved to be of equal efficiency. This versatile method, which was successfully used for the construction of a screening library containing 706 molecules within the European Lead Factory consortium, provides a simple way to access new compounds incorporating an arylamido and a pyrrolidinone moiety, both of which are widely found in marketed drugs and in biologically active molecules. Ritter‐type reactions of arylnitriles and in‐situ‐generated N‐acyliminium ions gave tetrahydropyrrolo[2,3‐d]oxazol‐5‐ones in excellent yields. A subsequent acidic hydrolysis yielded new (arylamido)pyrrolidinones with excellent cis diastereoselectivity. A combined Ritter–hydrolysis cascade procedure was successfully used for the construction of a screening library containing 706 molecules.