Highly stereoselective construction of the C2 stereocentre of α-tocopherol (vitamin E) by asymmetric addition of Grignard reagents to ketones.

ABSTRACT

Tertiary alcohol precursors of both C2 diastereoisomers of α-tocopherol were prepared in three ways by our recently reported asymmetric Grignard synthesis. The versatility of Grignard chemistry inherent in its three-way disconnection was exploited to allow the synthesis of three product grades 77 23 dr (5 steps), 81 19 dr (5 steps) and 96 4 dr (7 steps, one gram scale) from readily available and abundant starting materials. The products were converted to their respective α-tocopherols in 3 steps, which allowed a definitive re-assignment of their absolute configurations.