NOVEL TOTAL SYNTHESIS OF (2R,4'R,8'R)-ALPHA-TOCOPHEROL (VITAMIN-E) - CONSTRUCTION OF CHIRAL CHROMANS FROM AN OPTICALLY-ACTIVE, NON-AROMATIC PRECURSOR

A new approach to the total synthesis of (2R,4′R,8′R)-α-tocopherol (vitamin E, 1) is described in which the chro-man synthoh (S)-(+)-6-benzylpxy-3,4-dihydro-2,5,7,8-tetramethyl-2H-l-benzppyran-2-carboxaldehyde (6) is prepared starting from (S)-(-)-2-methyl-5-oxotetrahydro-2-furoic acid (TT). By a seven-stage sequence, 11 was elaborated to (5)-(-f-)-2,3,6-trimethyl-5-(2,2,4-trimethyl-1,3-dioxolane-4-ethyl)phenol (20), further transformations of which provided the optically active intermediates 21, 22, 24, and 26-28. The key processes involve reductive aromatization of the bridged, tricyclic qui-none monoketal 24 and acid-catalyzed cyclodehydrations of hydroquinpnes 22 and 28, all of which proceed with 95-100% retention of configuration generating (S)-((+)-3,4-dihydro-6-hydroxy-2,5,7,8-tetramethyl-2H-l-benzopyran-2-methanol (25). The total synthesis was completed by Wittig coupling of 6 (obtained in two steps from 25) with the known (3R,7R)-3,7,1 1-trimethyl-2-dodecyltriphenylphosphonium bromide (7), followed by catalytic hydrogenation, giving 1, characterized as its acetate 2. © 1979, American Chemical Society. All rights reserved.