Syntheses of (2 R , 4′ R , 8′ R )‐α‐Tocopherol and (2 R , 3′ E , 7′ E )‐α‐Tocotrienol

Reaction of trimethyl‐hydroquinone with methyl vinyl ketone in acidic methanol gave rac. ‐2‐methoxy‐2,5,7,8‐tetramethyl‐chroman‐6‐ol ( 8 ). This acetal was converted in four steps to rac. ‐(6‐hydroxy‐2,5,7,8‐tetramethyl‐chroman‐2‐yl)acetic acid ( 13 ). Acid 13 was readily resolved with α‐methyl‐benzylamine to give the ( S )‐enantiomer 14 . Treatment of the unwanted (2 R )‐isomer with acid regenerated 13 , thus leading to an efficient use of this compound. Employing a side chain derived from phytol, 14 was converted to (2 R , 4′ R , 8′ R )‐α‐tocopherol ( 1d , ‘natural’ vitamin E). A reaction sequence from 14 involving two highly stereoselective Claisen rearrangements has provided the first total synthesis of (2 R ,' E ,7′ E )‐α‐tocotrienol ( 2d ).