Synthesis of α-Tocopherol for The Next Century

Studies on the synthesis of α-tocopherol have been carried out using the following two routes. First, the reaction between trimethylhydroquinone and 7, 11, 15-trimethyl-3-methylene-1, 6-hexadecadiene was examined in the presence of various Lewis acids and/or Brøonsted acids. In a model reaction using myrcene, (+) -10-camphorsulfonic acid and an aluminium chloride-tetraalkylammonium halide system were found to catalyze the Friedel-Crafts reaction between myrcene and trimethylhydroquinone to provide the desired chroman compound in good yields, while Lewis acids, such as BF3·Et2O or SnCl4, gave predominantly spiro compounds. Next, the condensation reaction of trimethylhydroquinone with isophytol was examined in the presence of several kinds of Lanthanides triflates, Sc (OTf) 3, or montmorillonite. Of these, Sc (OTf) 3 and metal ion-exchanged montmorillonite were found to be effective catalysts giving α-tocopherol in excellent yields and purity. These catalysts worked well in various solvents and could be easily recovered and reused. These systems would be friendly to the environment and amenable to industrial-scale synthesis.