Bifunctional Organocatalysts and Brønsted Bases in Cooperative Catalysis for the Asymmetric [4 + 2] Cycloaddition of In Situ‐Generated Dienes from Isochromane‐3,4‐Diones with Nitroalkenes

Herein, the first asymmetric Diels–Alder reaction involving in situ‐generated dienes from readily available isochromane‐3,4‐diones is reported, using nitroalkenes as dienophilic counterparts. The reaction is catalyzed by a bifunctional thiourea‐ epi ‐quinine organocatalyst, cooperatively assisted by readily available Brønsted base cocatalysts. This strategy enables highly enantio‐ and exo‐diastereo‐selective [4 + 2] cycloaddition with a wide range of nitroalkenes, leading to the formation of valuable bridged lactones, a motif found in many natural products. The method applies not only to β ‐nitrostyrenes, but also to aliphatic nitroalkenes such as (nitromethylene)cyclohexane, leading to an unusual bridged spiro lactone. The reaction proceeds with complete regioselectivity, furnishing the products in high yields and achieving enantiomeric ratios (e.r.) ranging from 90:10 to 98:2. The use of Brønsted base as a cocatalyst not only enhances the turnover and promotes diene formation by vinylogous dienolization, leading to a higher yield in shorter reaction times, but also improves the enantioselectivity. In addition, follow‐up reactivity is investigated, furnishing interesting novel bridged amino ester and tetraline motifs.