A New Route to Vitamin E Key‐Intermediates by Olefin Cross‐Metathesis

Ru‐Catalyzed olefin cross‐metathesis (CM) has been successfully applied to the synthesis of several phytyl derivatives ( 2b, 2d – f, 3b ) with a trisubstituted CC bond, as useful intermediates for an alternative route to α ‐tocopheryl acetate (vitamin E acetate; 1b ) ( Scheme 1 ). Using the second‐generation Grubbs catalyst RuCl 2 (C 21 H 26 N 2 )(CHPh)PCy 3 (Cy = cyclohexyl; 4a ) and Hoveyda–Grubbs catalyst RuCl 2 (C 21 H 26 N 2 ){CH‐C 6 H 4 (O‐ i Pr)‐2} ( 4b ), the reactions were performed with various C ‐allyl ( 5a – f, 7a,b ) and O ‐allyl ( 8a – d ) derivatives of trimethylhydroquinone‐1‐acetate as substrates. 2,6,10,14‐Tetramethylpentadec‐1‐ene ( 6a ) and derivatives 6c – e of phytol ( 6b ) as well as phytal ( 6f ) were employed as olefin partners for the CM reactions ( Schemes 2 and 5 ). The vitamin E precursors could be prepared in up to 83% isolated yield as ( E / Z )‐mixtures.