Enantioselective 1,3-Dipolar Cycloadditions of a-Methylene Lactams to Construct Spirocycles

Spirocyclic scaffolds are important motifs due to their potential to bestow favorable effects on pharmaceutical compounds. However, there is a need for efficient methods for their enantioselective construction. We report a method for the asymmetric 1,3-dipolar cycloaddition of diazoacetates or nitrile oxides with a-methylene lactams to prepare chiral spirocyclic heterocycles. The methodology is high yielding (up to 91% yield) and enantioselective (up to 89% ee) for a wide range of N-substituents and 6- and 7-membered ring lactam substrates.

Automated summary

Spirocyclic scaffolds are important motifs that can have favorable effects on pharmaceutical compounds. This study reports a high-yielding and enantioselective method for synthesizing chiral spirocyclic heterocycles.