Sharpless asymmetric epoxidation Propranolol synthesis

The Sharpless asymmetric epoxidation of allyl alcohol gives the glycidol derivative 61 in 90% ee after in situ tosylation of 60 [63]. This process is working on a multiton-a-year scale (Arco Co., USA), facilitating the synthesis of a variety of /0-blockers. Asymmetric dihydroxylation of the allyl ether 63 catalyzed by a combined system of OSO4 and the cinchona alkaloid-based ligand 65 allows the commercial synthesis of the propranolol intermediate 64 in 91 % (Sepracor Co., USA) [64]. 

Introduction Catalytic methods of asymmetric induction Part I - Sharpless Asymmetric Epoxidation The AE Method The ligands The catalyst Catalyst structure The mnemonic device The synthesis of propranolol Modification after Sharpless Epoxidation Oxidation after Sharpless epoxidation The Payne rearrangement... 

Besides the more common reactions such as hydrogenation, isomerization, alkylation, and the Diels-Alder reaction. Sharpless epoxidation and dihydroxylation by asymmetrical catalysis are rapidly emerging as reactions with immense industrial potential. Table 9.7 lists some important syntheses based on asymmetric catalysis. These include processes for the pharmaceutical drugs (S)-naproxen, (S)-ibuprofen, (,S)-propranolol, L-dopa, and cilastatin, a fragrance chemical, L-menthol, and an insecticide (/ )-disparlure. Deltamethrin, an insecticide, is another very good example of industrial asymmetric synthesis. The total synthetic scheme is also given for each product. In general, the asymmetric step is the key step in the total synthesis, but this is not always so, as in the production of ibuprofen. Many of the processes listed in the table are in industrial production. 

Perhaps the most important recent development in the field of asymmetric synthesis has been the famous Sharpless epoxidation. It is appropriate that this chapter includes the asymmetric synthesis of the beta-adrenergic blocker (S)-(-)-propranolol, reported by Sharpless himself. 

---