A new route to Vitamin E key-intermediates by olefin cross-metathesis

The ruthenium-catalyzed olefin cross-metathesis has been successfully applied to the synthesis of derivatives of phytyltrimethylhydroquinone. These products, containing a trisubstituted olefinic double bond, are useful intermediates for an alternative route to α-tocopheryl acetate (Vitamin E acetate). Using the second generation Grubbs’ catalyst RuCl2(C21H26N2)(CHPh)PCy3 (Cy = cyclohexyl) and Hoveyda–Grubbs’ catalyst RuCl2(C21H26N2){CH-C6H4(O-iPr)-2}, the reactions were performed with various C-allylated and O-allylated derivatives of trimethylhydroquinone-1-acetate as substrates. 2,6,10,14-Tetramethylpentadec-1-ene and derivatives of phytol were employed as olefin partners for the cross-metathesis reactions. The Vitamin E precursors could be prepared in up to 83% isolated yields as mixtures of E and Z stereoisomers.