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.