The polystyrene-supported N-alkylimidazole-based dendritic catalysts for the Baylis-Hillman reaction exhibit one of the strongest beneficial effects of multivalent architecture ever reported for an organocatalyst. The yields in the model reaction of methyl vinyl ketone with p-nitrobenzaldehyde are more than tripled when a non-dendritic catalyst is replaced by a second- or third-generation analogue. Moreover, the reaction of the less active substrates will not occur with the non-dendritic catalyst and will proceed to a significant extent only with the analogous catalysts of higher generations. A substantial additional enhancement of the reaction yield could be achieved by increasing the content of water in the reaction solvent. The plausible cause of the dendritic effect is the assistance of the second, nearby imidazole moiety in the presumably rate-determining proton transfer in the intermediate adduct, after the first imidazole unit induced the formation of the new carbon-carbon bond.

Among the several variants of the highly useful and versatile Robinson annulation, a particular variation that involves ketones reacting with nonenolizable enones, while the α-carbons of the ketones act as nucleophiles at both steps of this cascade process, remains largely unexplored. Moreover, such a catalytic enantioselective reaction is exceptionally rare. While pursuing catalysis of this transformation, we developed two fluorogenic assays that, in combination with other analytic techniques, enabled rapid screening of several sets of catalysts. The first set of polymer-bound aminourea bifunctional organocatalysts was screened using a two-step fluorogenic protocol, designed for slower (e.g., heterogeneous) catalysts. Robinson annulation of acetone with 4′-nitrochalcone formed 3-(4-nitrophenyl)-5-phenyl-2-cyclohexenone, which, after a “developing” reductive treatment, was converted into the corresponding amino derivative, serving as a fluorescent reporter. On the other hand, a range of potentially faster homogeneous catalyst–cocatalyst systems were examined using a direct assay, where 4′-dimethylaminochalcone is converted into the corresponding cyclohexanone fluorescent reporter already upon annulation with acetone. In both cases, the combination of the fluorogenic protocols with high-performance liquid chromatography-based enantiomeric excess estimation enabled identification of lead catalysts, which promoted the enantioselective version of this variant of the annulation.