Silver-Catalyzed Asymmetric Desymmetrization of Cyclopentenediones via [3 + 2] Cycloaddition with α‑Substituted Isocyanoacetates

A highly selective and practical asymmetric Ag­(I) catalyst system has been developed for the [3 + 2] cycloaddition reactions between isocyanoacetates and cyclopentenediones. The current Ag­(I) catalyst system tolerates moisture and air and readily utilizes class III solvents such as EtOAc and acetone. The development of <i>on demand</i> generation of an active chiral catalyst in the presence of isocyanides paves a way to the efficient asymmetric preparation of bicyclic pyrrolidines with four stereogenic centers, including two quaternary centers in 80–97% ee

Substituted Pyrrololactams via Ring Expansion of Spiro‑2<i>H</i>‑pyrroles from Intermolecular Alkyne–Isocyanide Click Reactions

The facile synthesis of 6- to 8-membered pyrrololactams has been developed using a ring expansion of spiro-2<i>H</i>-pyrroles, the products of intermolecular alkyne–isocyanide click reactions. The key to successful ring expansion of spiro-2<i>H</i>-pyrroles to pyrrololactams is the enforced orbital overlap between the internal alkene and the amide carbonyl group through the conformationally locked bicyclic structures. The newly disclosed α-isocyano lactams, substrates for click reactions, should find their utility in the synthesis of pharmaceutically important heterocyclic compounds