Charge-enhanced Brønsted acid organocatalysts with electron-withdrawing substituents were synthesized, and their relative acidities were characterized by computations, 1:1 binding equilibrium constants (K 1:1 ) with a UV−vis active sensor, 31 P NMR shifts upon coordination with triethylphosphine oxide, and in one case by infrared spectroscopy. Pseudo-first-order rate constants were determined for the Friedel−Crafts alkylations of Nmethylindole with trans-β-nitrostyrene and 2,2,2-trifluoroacetophenone and the Diels−Alder reaction of cyclopentadiene with methyl vinyl ketone. These results along with kinetic isotope effect determinations revealed that the rate-determining step in the Friedel−Crafts transformations can shift from carbon−carbon bond formation to proton transfer to the catalyst's conjugate base. This leads to an inverted parabolic reaction rate profile and slower reactions with more acidic catalysts in some cases. Electronwithdrawing groups placed on the N-vinyl and N-aryl substituents of hydroxypyridinium ion salts lead to enhanced acidities, more acidic catalysts than trifluoroacetic acid, and a linear correlation between the logarithms of the Diels−Alder rate constants and measured K 1:1 values.

Several charge-containing TADDOL salts were synthesized and used as organocatalysts in asymmetric Diels-Alder and hetero-Diels-Alder reactions.Their catalytic activity was found to exceed that of a noncharged analog while maintaining or improving upon the enantioselectivity. The enhanced activities of the TADDOL salts enabled them to act as presumed hydrogen bond donor catalysts in the Diels-Alder and hetero-Diels-Alder reactions of 1,3-cyclohexadiene with methyl vinyl ketone at 40 C and 2-phenoxy-1,3-butadiene with ethyl glyoxylate at room temperature, respectively. Given the ionic nature of these charge-activated catalysts, it also proved possible to recycle and reuse the TADDOL without chromatography or the need for a recrystallization.

Charge-enhanced chiral thioureas were used in the organocatalysis of the Friedel-Crafts alkylation of indole with trans-β-nitrostyrene and the oxa-Pictet-Spengler reaction of tryptophol and benzaldehyde. The effects of substoichiometric Brønsted acidic additives on the reaction conversions and enantiomeric ratios of these transformations were examined, and the role of these species in the mechanism of the latter reaction was explored using variable time normalization kinetics to elucidate the reaction order of the catalyst, cocatalyst, and reagents. A proposed pathway for the oxa-Pictet-Spengler cyclization that involves matched and mismatched catalyst and cocatalyst pairs and an off-cycle racemization of the latter species is provided.