Investigating Substituent Interactions with Cationic Catalysts.

Rates of isothiourea catalyzed silylation and acylation reactions were measured for substrates with various electronic substituents at the aryl group. Through these measurements, the intermolecular interactions between cationic catalyst intermediates and different aryl groups were explored. These studies were performed to understand how changes in the catalyst structure affected electrostatic intermolecular interactions.

Cycloaddition/Electrocyclic Ring Opening Sequence between Alkynyl Sulfides and Azodicarboxylates To Provide ,-Dicarbamoyl 2-Iminothioimidates.

The α-oxidized thioimidates are useful bidentate ligands and are important motifs in pharmaceuticals, pesticides, and fungicides. Despite their broad utility, a direct route for their synthesis has been elusive. Herein, we describe a one-step synthesis of ,-dicarbamoyl 2-iminothioimidates from easily accessible thioacetylenes and commercially available azodicarboxylates (20 examples, ≤99% yield).

Understanding Internal Chirality Induction of Triarylsilyl Ethers Formed from Enantiopure Alcohols.

Chirality transmission from point chirality to helical chirality was explored using triarylsilyl ethers. Circular dichroism (CD) spectroscopy was employed to show that the alcohol stereocenter of silylated, enantiopure secondary alcohols can transmit chirality to the aryl groups on the silicon resulting in a higher population of one helical conformation over another. Cotton effects characteristic of the aryl groups organized into one preferred conformation were observed for all of the compounds examined, which included both triphenyl- and trinaphthylsilyl groups.

Diastereoselective and enantioselective silylation of 2-arylcyclohexanols.

The silylation-based kinetic resolution of trans 2-arylcyclohexanols was accomplished by employing a triaryl silyl chloride as the derivatizing reagent with a commercially available isothiourea catalyst. The methodology is selective for the trans diastereomer over the cis, which provides an opportunity to selectively derivatize one stereoisomer out of a mixture of four. By employing this technology, a facile, convenient method to form a highly enantiomerically enriched silylated alcohol was accomplished through a one-pot reduction-silylation sequence that started with a 2-aryl-substituted ketone.

Linear free-energy relationship and rate study on a silylation-based kinetic resolution: mechanistic insights.

The substituent effect of different p-substituted triphenylsilyl chlorides on silylation-based kinetic resolutions was explored. Electron-donating groups slow down the reaction rate and improve the selectivity, while electron-withdrawing groups increase the reaction rate and decrease the selectivity. Linear free-energy relationships were found correlating both selectivity factors and initial rates to the σ(para) Hammett parameters.

Silylation-based kinetic resolution of α-hydroxy lactones and lactams.

A silylation-based kinetic resolution has been developed for α-hydroxy lactones and lactams employing the chiral isothiourea catalyst (-)-benzotetramisole and triphenylsilyl chloride as the silyl source. The system is more selective for lactones than lactams, and selectivity factors up to 100 can be achieved utilizing commercially available reagents.

Obtaining enriched compounds via a tandem enantioselective reaction and kinetic resolution polishing sequence.

Herein we describe a tandem method of coupling an enantioselective reaction with a nonenzymatic kinetic resolution to prepare highly enantioenriched compounds. The procedure employs a moderately selective enantioselective reaction on a ketone or aldehyde to form an enriched alcohol followed by a kinetic resolution of the alcohol to generate ee's of >99% in yields greater than what is possible with a kinetic resolution. This method highlights an avenue to quickly acquire highly enriched compounds without developing and optimizing a new methodology.

Silylation-based kinetic resolution of monofunctional secondary alcohols.

The nucleophilic small molecule catalyst (-)-tetramisole was found to catalyze the kinetic resolution of monofunctional secondary alcohols via enantioselective silylation. Optimization of this new methodology allows for selectivity factors up to 25 utilizing commercially available reagents and mild reaction conditions.

Catalytic asymmetric synthesis of esters from ketenes.

By building on elementary principles of Brønsted acid-base chemistry, a nucleophile-catalyzed method for the asymmetric synthesis of esters from ketenes has been transformed into a much more versatile and effective Brønsted acid-catalyzed process. The product aryl esters can be converted into useful derivatives, such as enantioenriched alcohols and carboxylic acids.

Tuning the specificity of a synthetic receptor using a selected nucleic acid receptor.

Because of their relative simplicity, synthetic receptors often lack the selectivity observed for biopolymer receptors, such as aptamers. However, aptamer recognition of ligands is limited by the chemistries inherent in the four canonical nucleotides. Here, we report the design and selection of a ternary complex in which the specificity of a bis-boronic acid synthetic host (1) that binds to various carboxylic acids is tuned by a surrounding aptamer.

Thermodynamic analysis of receptors based on guanidinium/boronic acid groups for the complexation of carboxylates, alpha-hydroxycarboxylates, and diols: driving force for binding and cooperativity.

The thermodynamics of guanidinium and boronic acid interactions with carboxylates, alpha-hydroxycarboxylates, and diols were studied by determination of the binding constants of a variety of different guests to four different hosts (7-10). Each host contains a different combination of guanidinium groups and boronic acids. The guests included molecules with carboxylate and/or diol moieties, such as citrate, tartrate, and fructose, among others.

Using indicator-displacement assays in test strips and to follow reaction kinetics.

[structure: see text] An indicator-displacement assay was used to study the kinetics of reactions that produce tartrate. The same assay was also found to be useful in developing tartrate test strips, by coating filter paper with the same receptor and indicator.

Threshold detection using indicator-displacement assays: an application in the analysis of malate in Pinot Noir grapes.

The mathematics for modeling indicator-displacement assay isotherms is presented and contrasted to the classical host-guest binding isotherm. It is shown that the signal response can be tuned to occur closer to 1 equiv of guest relative to a standard binding algorithm. This delay in response leads to a better triggering protocol for threshold detection schemes.

Cross-couplings of alkyl electrophiles under "ligandless" conditions: Negishi reactions of organozirconium reagents.

This report establishes that simple, "ligandless" palladium complexes can catalyze the first zirconium-Negishi reactions of alkyl electrophiles. In view of the attractiveness of ligandless catalysts (cost, simplicity, and ease of purification), these observations add a significant and intriguing new dimension to the development of effective palladium-based processes for coupling alkyl electrophiles.

Teaching old indicators new tricks.

Most synthetic sensors are designed with covalent attachment between a receptor and a reporter moiety. In this report, we describe the current progress of our use of noncovalently attached indicators to signal binding of analytes. With these systems, analyte binding leads to indicator displacement from the binding cavity, which in turn yields an optical signal modulation.

pK(a) values and geometries of secondary and tertiary amines complexed to boronic acids-implications for sensor design.

[structure in text] The pK(a) values and the geometries of secondary and tertiary amines adjacent to boronic acids were determined using potentiometric and (11)B NMR titrations. The studies showed that the secondary ammonium ion has a pK(a) similar to that of the tertiary ammonium species, which leads to the formation of tetrahedral boron centers at pH values above approximately 5.5.