Total synthesis of (R,R,R)-α-tocopherol through asymmetric Cu-catalyzed 1,4-addition

Abstract

By introducing a disposable activating substituent at C-3, the asymmetric 1,4-addition to a notoriously unreactive 2-substituted chromenone was achieved with high levels of (2R)-stereoselectivity in the presence of a chiral Cu(I)-phosphoramidite complex as a catalyst. This paved the way for an efficient and conceptually novel synthesis of (R,R,R)-α-tocopherol from readily available starting materials.

Keywords: asymmetric conjugate addition; chiral ligands; chromenones; copper catalysis; vitamin E.