Preorganized Hydrogen Bond Donor Catalysts: Acidities and Reactivities

Abstract

Measured DMSO pKa values for a series of rigid tricyclic adamantane-like triols containing 0-3 trifluoromethyl groups (i.e., 3(0)-3(3)) are reported. The three compounds with CF3 substituents are similar or more acidic than acetic acid (pKa = 13.5 (3(1)), 9.5 (3(2)), 7.3 (3(3)) vs 12.6 (HOAc)), and the resulting hydrogen bond network enables a remote γ-trifluoromethyl group to enhance the acidity as well as one located at the α-position. Catalytic abilities of 3(0)-3(3) were also examined. In a nonpolar environment a rate enhancement of up to 100-fold over flexible acyclic analogs was observed presumably due to an entropic advantage of the locked-in structure. Gas-phase acidities are found to correlate with the catalytic activity better than DMSO pKa values and appear to be a better measure of acidities in low dielectric constant media. These trends are reduced or reversed in polar solvents highlighting the importance of the reaction environment.

Predicting pKa Values of Quinols and Related Aromatic Compounds with Multiple OH Groups

“…This deviation is similar to that achieved using the best existing theoretical methods; moreover, it is not uncommon to observe differences greater than 0.5 units between experimental values reported for a single compound. For example, significant variations have been noted for 2,2′- and 4,4′-dihydroxybiphenyl, − BINOL, − and various catechols, and in certain cases, the differences have provoked controversies in the literature. This underscores the importance of developing theoretical methods for assessing the reliability of experimental values.…”

Anion Binding of One-, Two-, and Three-Armed Thiourea Receptors Examined via Photoelectron Spectroscopy and Quantum Computations

“…These values indicate that all three compounds are more acidic than acetic acid, hydrochloric acid, and phosphoric acid, and that the larger two derivatives are also stronger than sulfuric acid (Δ H ° acid = 309.6 kcal mol –1 ) . This is undoubtedly due to the presence of two and four intramolecular hydrogen bonds in 2a and 3a , respectively, as interactions of this sort previously have been shown to be capable of providing very large stabilizations. − The predicted gas-phase acidity of 3 appears to explain why it protonates OAc – in DMSO and helps rationalize why monohydrogen phosphate (HPO 4 2– ) is extracted into chloroform from an aqueous solution of dihydrogen phosphate (eq ). Both the adiabatic and vertical detachment energies increase sequentially with the number of arms in the thiourea for all three series of cluster ions.…”

Electrostatically Enhanced Thioureas

“…To evaluate the catalytic activity of electrostatically enhanced thioureas 3 and 4 , the Friedel–Crafts alkylation of trans -β-nitrostyrene with N -methylindole was examined in CDCl 3 at room temperature (eq ). This transformation was chosen because the reaction rate has been observed to correlate with the acidity of hydrogen bond catalysts, whereas acetic acid does not promote this process. , Second-order rate constants were determined by monitoring the reaction via 1 H NMR spectroscopy, and the data are summarized in Table . Diphenylthiourea 1 is a poor catalyst in that it only speeds up the uncatalyzed process by a factor of 1.4, and more than a month is needed for half of the starting material to be converted to product.…”