Concise Total Synthesis\nof (−)-Codeine

Codeine\nand morphine are among the few natural products that are\nused directly as drugs for medical treatment. However, the availability\nof these is widely dependent on natural resources. Herein, we report\nan efficient enantioselective seven-step synthesis of (−)-codeine\nstarting from simpler starting materials. The key steps involve microwave-assisted\nintramolecular cascade double heck cyclization to access the ABCE\nring of opium alkaloids with the required stereocenters in one pot.\nA photoinduced intramolecular hydroamination of carboxamide forms\nthe D ring and completes the pentacyclic core of the morphinans. Following\nthat, an oxidation followed by global reduction leads to the formation\nof (−)-codeine. Our synthesis relies on simple and classical\nreactions to address the opium alkaloids and will serve as an efficient\nroute to access the other morphinans.