Asymmetric Synthesis Of ?-Tocopherol Benzodihydropyran Core

Vitamin E family consists of eight naturally occurring compounds, which covers all Tocopherols and Tocotrienols. Vitamin E was discovered by Evans and co-workers in 1922 as a dietary factor essential for reproduction. Its isolation from wheat germ oil enabled its structural elucidation by Fernholz. ?-Tocopherol, which is the most important lipid-soluble antioxidant in biological systems, functions as a chain-breaking antioxidant that protects polyunsaturated fatty acids in membranes and plasma lipoproteins against the propagation of free-radical reactions. ?-Tocopherol also plays an important role in cell signaling, gene expression and regulation of other cell functions. As its prominent biological activity, considerable efforts have been directed during the recent decades at the development of stereoselective synthesis of ?-Tocopherol and of corresponding building blocks. However, the construction of the quaternary center of ?-Tocopherol with efficient strategy still remains a great challenge. This thesis is mainly focused on the enantioselective construction of the quaternary center and efficient synthesis of ?-Tocopherol benzodihydropyran core.Trimethylhydroquinone 10 was chosen as the initial material for the preparing of phenol 57. Using Pd catalyzed asymmetric allylic alkylation, homoallylic alcohol 56 was provided via the coupling of 57 with isoprene monoxide 51. After scanning the reaction conditions(temperature, solvent, ligand, acid and additives), the key intermediate 56 was generated in 90% yield with high enantioselectivity(92% ee). With 56 in hand, protection of the hydroxyl, hydroboration, oxidization with Dess-Martin periodinane, followed by cyclization under acid condition yielded alkene 67 in high overall yield. At last, bicyclic target 54 could be readily delivered by hydrogenation from alkene 67.In conclusion, we obtained ?-Tocopherol benzodihydropyran core 54 in 8 steps with 21% yield. This strategy is suitable for the efficient asymmetric synthesis of ?-Tocopherol, and paves the way for the syntheses of the other Vitamin E members.