Here we report on inroads concerning increased substrate breadth via the picolylamine organocatalyst template, a vicinal chiral diamine based on a pyridine-primary amine motif. The addition of cyclohexanone to β-nitrostyrene has many catalyst solutions, but cyclopentanone and isobutyraldehyde additions continue to be challenging. PicAm-3 (10 mol%) readily allows the Michael addition of cyclopentanone or isobutyraldehyde (5.0 equiv.) to β-nitrostyrene derivatives. By contrast, PicAm-1 (7.0 mol%) is optimal for catalyzing the aldol reaction of cyclohexanone or cycloheptanone (3.3 equiv.) with aromatic aldehydes. Eighteen products are reported and for each reaction type new products are reported (4b-d, 9c). Very good yields and stereoselectivities are generally noted. The reactions, which require an acid additive, proceed via a transient chiral enamine and a mechanistic case is put forth for a bifunctional catalysis model.

In contrast to Diels−Alder reactions involving heteroatom-containing substrates, the endo dimerization of cyclopentadiene responds only very weakly to changes in the microenvironment or the presence of potential catalysts (less than a factor of 10 variations). This pure hydrocarbon reaction has been used as an early model to predict the maximum possible catalytic effect (k cat /k uncat ca. 10 6 M) due to entropic contributions of transition-state confinement [

Chiral Picolylamines for Michael and Aldol Reactions: Probing Substrate Boundaries. -A new primary-tertiary bifunctional organocatalyst, which can be further fine-tuned, is developed for the title reactions. -(NUGENT*, T. C.; BIBI, A.; SADIQ, A.; SHOAIB, M.; UMAR, M. N.; TEHRANI, F. N.; Org. Biomol. Chem. 10 (2012) 46, 9287-9294, http://dx.

In contrast to Diels-Alder reactions involving heteroatom-containing substrates, the endo dimerization of cyclopentadiene responds only very weakly to changes in microenvironment or the presence of potential catalysts (less than factor of 10 variation), although this pure hydrocarbon reaction has been used as an early model to predict the maximum possible catalytic effect (kcat/kuncat ca. 10 6 M) due to entropic contributions of a transition-state confinement (Page,

In contrast to Diels-Alder reactions involving heteroatom-containing substrates, the endo dimerization of cyclopentadiene responds only very weakly to changes in microenvironment or the presence of potential catalysts (less than factor of 10 variation), although this pure hydrocarbon reaction has been used as an early model to predict the maximum possible catalytic effect (kcat/kuncat ca. 106 M) due to entropic contributions of a transition-state confinement (Page, M. I.; Jencks, W. P. Proc. Natl. Acad. Sci. USA 1971, 68, 1678). In the presence of cucurbit[n]uril homologues the reaction is selectively and almost maximally (kcat/kuncat ca. 4 × 105 M) accelerated by the intermediary sized cucurbit[7]uril in aqueous solution, while the other macrocyclic homologues display no acceleration or an inhibitory effect. The expected product inhibition due to the strong binding of the dicyclopentadiene reaction product can be overcome by addition of 10% methanol, which affords catalytic turnover numbers above 10. The reaction was monitored using 1H NMR spectroscopy as well as UV spectrophotometry. The analysis of the kinetic data, combined with packing coefficient considerations, modelling of Lennard-Jones potentials, and dispersion-corrected DFT calculations, suggest that the catalysis is due to an entropy-dominated transition-state stabilization in the tightly packed ternary complex.