Stereodivergent Synthesis of Spiroaminals via Chiral Bifunctional Hydrogen Bonding Organocatalysis

Abstract Spiroaminals represent novel structural motifs prevalent in diverse natural products and biologically active molecules. Achieving their enantioselective synthesis is a highly desirable and challenging task in synthetic endeavors due to their intricate molecular frameworks. Herein, we accomplished the first stereodivergent construction of spiroaminals using chiral bifunctional organocatalyzed intramolecular 1,2‐addition followed by an oxa‐Michael addition cascade in a high atom and step economical pathway. A proper modulation of the cinchona‐derived squaramide catalysts efficiently provided access to all the possible stereoisomers with high yield, diastereoselectivity, and excellent enantioselectivity while displaying a broad substrate tolerance. Additionally, we validated the scalability of the reaction and demonstrated the synthesis of variable spiroaminal scaffolds, confirming the viability of our protocol.