BINOL as a Chiral Solvating Agent for Sulfiniminoboronic Acids.

1H NMR spectroscopic studies using BINOL as a chiral solvating agent (CSA) for a scalemic sulfiniminoboronic acid (SIBA) have revealed concentration- and enantiopurity-dependent variations in the chemical shifts of diagnostic imine protons used to determine enantiopurity levels. 11B/15N NMR spectroscopic studies and X-ray structural investigations revealed that unlike other iminoboronate species, BINOL-SIBA assemblies do not contain N-B coordination bonds, with 1H NMR NOESY experiments indicating that intermolecular H-bonding networks between BINOL and the SIBA analyte are responsible for these variations. These effects can lead to diastereomeric signal overlap at certain er values that could potentially lead to enantiopurity/configuration misassignments. Consequently, it is recommended that hydrogen-bonding-CSA-based 1H NMR protocols should be repeated using both CSA enantiomers to ensure that any concentration- and/or er-dependent variations in diagnostic chemical shifts are accounted for when determining the enantiopurity of a scalemic analyte.

Sustainable Syntheses of Paracetamol and Ibuprofen from Biorenewable ß-pinene.

Scalable processes have been developed to convert ß-pinene into 4-isopropenylcyclohexanone, which is then used as a feedstock for the divergent synthesis of sustainable versions of the common painkillers, paracetamol and ibuprofen. Both synthetic routes use Pd0 catalysed reactions to aromatize the cyclohexenyl rings of key intermediates to produce the benzenoid ring systems of both drugs. The potential of using bioderived 4-hydroxyacetophenone as a drop-in feedstock replacement to produce sustainable aromatic products is also discussed within a terpene biorefinery context.

Discovery of a Novel Class of d-Amino Acid Oxidase Inhibitors Using the Schrödinger Computational Platform.

d-Serine is a coagonist of the N-methyl d-aspartate (NMDA) receptor, a key excitatory neurotransmitter receptor. In the brain, d-serine is synthesized from its l-isomer by serine racemase and is metabolized by the D-amino acid oxidase (DAO, DAAO). Many studies have linked decreased d-serine concentration and/or increased DAO expression and enzyme activity to NMDA dysfunction and schizophrenia. Thus, it is feasible to employ DAO inhibitors for the treatment of schizophrenia and other indications. Powered by the Schrödinger computational modeling platform, we initiated a research program to identify novel DAO inhibitors with the best-in-class properties. The program execution leveraged an hDAO FEP+ model to prospectively predict compound potency. A new class of DAO inhibitors with desirable properties has been discovered from this endeavor. Our modeling technology on this program has not only enhanced the efficiency of structure-activity relationship development but also helped to identify a previously unexplored subpocket for further optimization.

A Three-Component Derivatization Protocol for Determining the Enantiopurity of Sulfinamides by 1H and 19F NMR Spectroscopy.

A practically simple three-component chiral derivatization protocol has been developed to determine the enantiopurity of eight S-chiral sulfinamides by 1H and 19F NMR spectroscopic analysis, based on their treatment with a 2-formylphenylboronic acid template and enantiopure pinanediol to afford a mixture of diastereomeric sulfiniminoboronate esters whose diastereomeric ratio is an accurate reflection of the enantiopurity of the parent sulfinamide.

Correction: A bodipy based hydroxylamine sensor.

Correction for 'A bodipy based hydroxylamine sensor' by Adam C. Sedgwick et al., Chem. Commun., 2017, 53, 10441-10443.

A bodipy based hydroxylamine sensor.

With this research, we have developed a bodipy based system as the first "turn-on" fluorescence system for the detection hydroxylamine.

Formyloxyacetoxyphenylmethane as an N-Formylating Reagent for Amines, Amino Acids, and Peptides.

Formyloxyacetoxyphenylmethane is a stable, water-tolerant, N-formylating reagent for primary and secondary amines that can be used under solvent-free conditions at room temperature to prepare a range of N-formamides, N-formylanilines, N-formyl-α-amino acids, N-formylpeptides, and an isocyanide.

Aza-Conjugate Addition Methodology for the Synthesis of N-Hydroxy-isoindolin-1-ones.

Aryl-aldehydes containing ortho-substituted propiolate fragments react with hydroxylamine to afford carbinolamine intermediates that undergo intramolecular aza-conjugate addition reactions to afford N-hydroxy-2.3-dihydro-isoindolin-1-ones that can be reduced to their corresponding isoindolin-1-ones and isoindoles.

Effect of nanostructured ceria as support for the iron catalysed hydrogenation of CO2 into hydrocarbons.

This paper demonstrates the key role of the property-structure relationship of the support on iron/ceria catalysts on the hydrocarbon selectivity and olefin-to-paraffin ratio for the direct hydrogenation of carbon dioxide into hydrocarbons. The effect is directly related to the reducibility of the different nanostructured ceria supports and their interaction with the iron particles. Herein, we demonstrate that the iron-based catalysts can be modified not only by the addition of promoters, commonly reported in the literature, but also by careful control of the morphology of the ceria support.

Simple aza-conjugate addition methodology for the synthesis of isoindole nitrones and 3,4-dihydroisoquinoline nitrones.

Aryl-aldehydes containing ortho-substituted α,ß-unsaturated carboxylic acid derivatives react with hydroxylamine to afford reactive N-hydroxy-carbinolamine intermediates that undergo intramolecular aza-conjugate addition reactions to afford isoindole nitrones and 3,4-dihydroisoquinoline nitrones in good yield. Conditions have been developed to reduce these isoindole nitrones to their corresponding hydroxylamine, enamine, and amine derivatives. Isoindole nitrones react with dimethyl acetylenedicarboxylate (DMAD) via a [4 + 2]-cycloaddition/deamination pathway to afford substituted naphthalene derivatives, while 3,4-dihydroisoquinoline nitrones react with DMAD via a [1,3]-dipolar cycloaddition pathway to afford tricyclic heteroarenes.