Synthesis of Unprotected Spirocyclic β-Prolines and β-Homoprolines by Rh-Catalyzed C-H Insertion

A series of unprotected spirocyclic beta-prolines and beta-hornoprolines are prepared by Rh-catalyzed C-H insertion. The key intermediate, a Rh nitrenoid, is generated by the N-O bond cleavage of a substituted isoxazolidin-5-one. The reaction proceeds on a gram scale with a catalyst loading of as little as 0.1 mol %, affording spirocyclic beta-amino acids that are otherwise difficult to obtain. The building blocks prepared in this work will likely find applications in medicinal chemistry.