The synthesis of α-tocopherol via 2-(sulphinylmethyl)chromans

Abstract

2,5,7,8-Tetramethyl-2-[(phenylthio)methyl]chroman-6-ol, (6) was synthesized from trimethylhydroquinone (1) and 3-methyl-4-(phenylthio)buten-3-ol (12). Acetylation of (6) and subsequent oxidation gave 6-acetoxy2,5,7,8-tetramethyl-2-[(phenylsufphinyl)methyl]chroman (9). This was converted to the known α-tocopherol precprsor 6-acetoxy-2.5, 7.8-tetramethylchroman-2-carbaldehyde (4) by Pummerer reaction, hydrolysis, and reacetylation. An attempted more direct synthesis of α-tocopherol via alkylation of 6-(methoxymethoxy)-2,5,7,8-tetramethyl-2-[(phenylsulphonyl)methyl]chroman (12) with hexahydrofarnesyl bromide led to ring opening and subsequent O-alkylation.