Total Synthesis of (R, R, R)-α-Tocopherol Through Asymmetric Cu-Catalyzed 1,4-Addition

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 CuI-phosphoramidite complex as a catalyst. This paved the way for an efficient and conceptually novel synthesis of (R, R, R)-alpha-tocopherol from readily available starting materials.