Catalytic Asymmetric Difunctionalization of Stable Tertiary Enamides with Salicylaldehydes: Highly Efficient, Enantioselective, and Diastereoselective Synthesis of Diverse 4‑Chromanol Derivatives

Catalyzed by a chiral BINOL–Ti­(OiPr)4 complex, various stable tertiary enamides reacted with salicylaldehydes to afford diverse cis,trans-configured 4-chromanols that contain three continuous stereogenic centers in good yields with excellent diastereoselectivity and enantioselectivity. The reaction proceeded through the addition of enamide to aldehyde followed by the intramolecular interception of the resulting iminium by the hydroxy group. Oxidation of the resulting 4-chromanols yielded almost quantitatively chroman-4-one derivatives which underwent diastereospecific reduction with NaBH4 to produce cis,cis-configured 4-chromanols.