Aggregation-Induced Enantioselective Michael Addition of 1,3-Dicarbonyls to β-Nitroalkenes

A detailed understanding of the aggregation process is critical for elucidating the mechanism of aggregation-induced asymmetric catalysis. However, experimental insight into the microscopic events governing aggregation remains limited. To address this challenge, we investigate the aggregation behavior of a cinchona alkaloid-derived squaramide bifunctional organocatalyst and identify the decisive parameters governing the Michael addition of 1,3-dicarbonyl compounds to β-nitroalkenes. Spectroscopic analyses (UV-vis and photoluminescence) together with DLS measurements characterize the intrinsic nature of catalyst aggregation. Control experiments and ¹H-NMR investigations directly link aggregate structures to catalytic microsteps. Mechanistic studies uncover a distinct catalytic pathway that departs from classical homogeneous catalysis, featuring catalyst aggregation, aggregation-induced substrate activation, co-assembly, and reversible dissociation during turnover. This work establishes aggregation as a fundamental mechanistic motif in asymmetric organocatalysis and provides a unified framework for the rational design of aggregation-induced catalytic systems.