Practical Catalytic Asymmetric Synthesis of Gem-Dimethyl Bicyclic [3.1.0] Proline: A Valuable Building Block for Antiviral Agents

We report a practical catalytic asymmetric synthesis of gem-dimethyl bicyclic [3.1.0] proline, a valuable noncanonical amino acid scaffold widely found in antiviral protease inhibitors. The strategy features a catalytic enantioselective bromocyclization (95% ee ) followed by a substrate-controlled, diastereoselective dibromocyclopropanation (trans only). This approach avoids both chiral resolution and cyanide-based transformations, delivering the target in 11% overall yield over nine steps. The concise and scalable nature of this route provides efficient access to this pharmaceutically relevant building block.