Organocatalytic Asymmetric Oxa‐[3+3]‐annulation for Chiral Tricyclic Chromans with Contiguous Stereocenters

Comprehensive Summary A bifunctional squaramide‐catalyzed asymmetric synthesis of chiral tricyclic chromans featuring three contiguous stereocenters has been successfully developed. This innovative strategy relies on the synergistic activation of 3‐aminophenol derivatives and 4‐benzylidenepyrrolidine‐2,3‐diones by the chiral catalyst, enabling an efficient asymmetric oxa‐[3+3]‐annulation reaction. The protocol exhibits a broad substrate scope with 34 diverse examples, delivering moderate‐to‐good yields ranging from 64% to 81%, excellent enantioselectivity (up to 99% ee), and tunable diastereoselectivity ( dr up to 15 : 1). Notably, halogen substitution plays a pivotal role in dramatically enhancing stereocontrol, further optimizing the diastereoselectivity of the target products. To validate its practical utility, gram‐scale synthesis was successfully conducted without compromising yield or stereoselectivity, and subsequent derivatization reactions confirmed the versatility of the obtained chiral tricyclic chromans. This metal‐free, mild reaction system not only enriches the synthetic toolbox for constructing complex chroman architectures, but also provides a versatile platform for the asymmetric synthesis of bioactive molecules containing the chiral tricyclic chroman skeleton, highlighting the significance of enantioselectivity and diastereoselectivity in accessing functionalized heterocyclic compounds.