Asymmetric Synthesis of Cyclohexenone-Fused Isochromans via Quinidine-Catalyzed Domino Peroxyhemiacetalization/Oxa-Michael Addition/Desymmetrization Sequence

A highly enantio- and diastereoselective synthesis of highly functionalized isochromans was achieved through an organocatalyzed domino reaction. Quinidine as the catalyst initiates a peroxyhemiacetalization/oxa-Michael/desymmetrization domino sequence between various 2,5-cyclohexadienone-tethered aryl aldehydes with hydroperoxides to generate the single diastereomers of isochromans appended with a cyclohexenone ring bearing three vicinal stereocenters in good yields and high enantioselectivities under ambient reaction conditions.

Automated summary

A highly functionalized isochroman was synthesized with high enantio- and diastereoselectivity through an organocatalyzed domino reaction. Quinidine catalyzed the peroxyhemiacetalization/oxa-Michael/desymmetrization domino sequence between 2,5-cyclohexadienone-tethered aryl aldehydes and hydroperoxides, resulting in isochromans with a cyclohexenone ring and three vicinal stereocenters in good yields and high enantioselectivities under ambient reaction conditions.