Asymmetric Synthesis of (S)-metoprolol via Sharpless Asymmetric Dihydroxylation Induced by A Recoverable Polymer Ligand QN-AQNOPEG- OMe

The catalytic asymmetric dihydroxylation (AD) discovered by Sharpless, a Nobel Prize winner in 2001, has rapidly become an invaluable synthetic tool in the possibility of converting prochiral olefins to chiral vicinal diols. After our long-running investigation of optimized methodology for the production of stereo-defined diols based on the AD reaction, an efficient and environmentally friendly approach for the synthesis of (S)-metoprolol via AD reaction was reported. The synthetic route proceeded in four-step reactions of nucleophilic substitution, AD reaction, cyclization, and nucleophilic ring opening. The key step, AD reaction, proceeded effectively in homogeneous catalysis by using a soluble polymer chiral ligand QN-AQN-OPEG-OMe, which can be easily separated from the reaction system and reused at least four times while maintaining its high catalytic activity and enantioselectivity. This protocol has been demonstrated to produce kilogram quantities of (S)-metoprolol on scale.