Totalsynthese von natürlichem α‐Tocopherol. 2. Mitteilung. Aufbau der Seitenkette aus (−)‐(<i>S</i>)‐3‐Methyl‐γ‐butyrolacton

Abstract

Total Synthesis of Natural α‐Tocopherol A short and efficient route to optically pure (+)‐(3 R , 7 R )‐trimethyldodecanol ( 14 ) is demonstrated, 14 serving as side chain unit in the preparation of natural vitamin E. The synthesis of 14 is based on the concept of using a single optically active C 5 ‐synthon of suitable configuration and functionalization to introduce both asymmetric centres in 14 . (−)‐( S )‐3‐Methyl‐γ‐butyrolacton ( 1 ) and ethyl (−)‐( S )‐4‐bromo‐3‐methylbutyrate ( 2 ), respectively, is used in a sequence of either two Grignard C,C‐coupling reactions 5 → 8 and 12 → 13 or two Wittig reactions 17a → 18 and 20 → 21 to achieve this goal. 14 is converted to (2 R , 4′ R , 8′ R )‐α‐tocopherol (= vitamin E) by coupling with a chroman unit in known manner. Optical purity of products and intermediates is established.