Multigram Synthesis of Bicyclic α- and β-Prolines via Intramolecular C(sp³)–H γ-Lactamization as a Key Step

A multigram synthesis of novel bicyclic α- and β-prolines was achieved via a C(sp³)-H amidation reaction as a key step. This step prepared seven bicyclic γ-lactams in high yield and stereoselective control. The scalable and reproducible protocol allowed the conversion of γ-lactams into α- and β-prolines in amounts up to 45 g under mild conditions, providing access to various isomeric bicyclic proline derivatives for potential use in drug design as medicinal building blocks.