Total Synthesis of (S,S)-Tetramethylmagnolamine via Aerobic Desymmetrization

We describe a concise synthesis of the pseudo dimeric tetrahydroisoqunoline alkaloid (S,S)−tetramethylmagnolamine by a catalytic aerobic desymmetrization of phenols. Desymmetrization reactions increase molecular complexity with high levels of efficiency, but those that do so by aerobic oxidation are uncommon. Our conditions employ molecular oxygen as an oxygen atom transfer agent and a formal acceptor of hydrogen, enabling two, mechanistically distinct aromatic C-H oxygenation reactions with high degrees of selectivity.