Brønsted Acid-Catalyzed, Highly Enantioselective Addition of Enamides to In Situ-Generated ortho-Quinone Methides: A Domino Approach to Complex Acetamidotetrahydroxanthenes

The highly enantioselective conjugate addition of enamides and enecarbamates to in situ‐generated ortho‐quinone methides, upon subsequent N,O‐acetalization, gives rise to acetamido‐substituted tetrahydroxanthenes with generally excellent enantio‐ and diastereoselectivities. A chiral BINOL‐based phosphoric acid catalyst controls the enantioselectivity of the carbon–carbon bond‐forming event. The products are readily converted into other xanthene‐based heterocycles. With excellent enantio‐ and diastereoselectivity, acetamido‐substituted tetrahydrobenzoxanthenes and related heterocycles are obtained in one synthetic operation. A specifically optimized chiral phosphoric acid converts ortho‐hydroxy benzhydryl alcohols and enamides into highly functionalized target compounds carrying three contiguous chiral centers with typically good overall yields.