Synthesis of Atropisomeric Hydrazides by One-Pot Sequential Enantio- and Diastereoselective Catalysis

The first catalytic enantioselective and diastereoselective synthesis of atropisomeric hydrazides was achieved using a sequential catalysis protocol. This strategy is based on a one-pot sequence of two organocatalytic cycles featuring the enamine amination of branched aldehydes followed by nitrogen alkylation under phase-transfer conditions. The resulting axially chiral hydrazides were obtained directly from commercially available reagents in high yields and with good stereocontrol. The permutation of organocatalysts allowed easy access to all stereoisomers, enabling a stereodivergent approach to enantioenriched atropisomeric hydrazides

Solving the Puzzling Absolute Configuration Determination of a Flexible Molecule by Vibrational and Electronic Circular Dichroism Spectroscopies and DFT Calculations: The Case Study of a Chiral 2,2_-Dinitro-2,2_-biaziridine

The absolute configuration of a recently synthesized racemate of 2,2-dinitro-2,2-biaziridine (2a), a possible catalyst for asymmetric synthesis, has been determined by vibrational circular dichroism (VCD) spectroscopy in the mid-IR region and DFT calculations. Electronic circular dichroism (ECD) spectra have been obtained and Time-Dependent DFT (TDDFT) calculations have been performed and found to be inagreement with the conclusions from VCD and DFT. A detailed conformational analysis, for approximately 300 geometries, has been carried out, allowing us to find evidence for the most populated conformers chiefly contributing to VCD and ECD spectra. The proposed absolute configuration and prevalent conformers are in correspondence with an equal configuration of the nitrogen atoms of the two aziridine rings

On the Nature of the Rotational Energy Barrier of Atropisomeric Hydrazides

N-N atropisomers represent a useful class of compounds that has recently received important attention from many research groups. This article presents an in-depth analysis of the energy barrier needed for the racemization process of atropoisomeric hydrazides, combining an experimental and computational approach. The focus is on examining how electronic and steric factors impact the racemization process. The results obtained indicate that the barrier observed during the racemization process mainly arises from an increase in the p-orbital character of the nitrogen atoms

Primary Amine Catalyzed Activation of Carbonyl Compounds: A Study on Reaction Pathways and Reactive Intermediates by Mass Spectrometry

The field of organocatalysis is expanding at a fast pace. Its growth is sustained by major stimuli, such as the effort toward an understanding of the mechanisms of reaction and catalytic processes in general, the elucidation of basic properties leading to stereocontrol and the search for broad applicability and scalability of the synthetic methodology. This paper reports a thorough study based on ESI-MS spectrometry of amino-organocatalyzed model reactions under different experimental conditions. Off-line reaction monitoring of mixtures containing different catalytic systems, by ESI-MSn showed the presence of several putative intermediate species, either in their protonated or sodiated forms. In addition, enantioselective chromatography of crude reactions provides the stereochemical outcome of asymmetric reactions. The bulk of the data collected offers a clue of the intricate pathways occurring in solution for the studied reactions

Valorization of By-Products from Biofuel Biorefineries: Extraction and Purification of Bioactive Molecules from Post-Fermentation Corn Oil

The aim of this work was to develop innovative and sustainable extraction, concentration, and purification technologies aimed to recover target substances from corn oil, obtained as side stream product of biomass refineries. Residues of bioactive compounds such as carotenoids, phytosterols, tocopherols, and polyphenols could be extracted from this matrix and applied as ingredients for food and feeds, nutraceuticals, pharmaceuticals, and cosmetic products. These molecules are well known for their antioxidant and antiradical capacity, besides other specific biological activities, generically involved in the prevention of chronic and degenerative diseases. The project involved the development of methods for the selective extraction of these minor components, using as suitable extraction technique solid phase extraction. All the extracted and purified fractions were evaluated by NMR spectroscopic analyses and UV–Vis spectrophotometric techniques and characterized by quali-quantitative HPLC analyses. TPC (total phenolic content) and TFC (total flavonoid content) were also determined. DPPH and ABTS radical were used to evaluate radical quenching abilities. Acetylcholinesterase (AChE), amylase, glucosidase, and tyrosinase were selected as enzymes in the enzyme inhibitory assays. The obtained results showed the presence of a complex group of interesting molecules with strong potential in market applications according to circular economy principles

Tetrasubstituted cyclopentadienones as suitable enantiopure ligands with axial chirality.

A series of thermally stable atropisomeric phencyclone ligands (ΔG‡ rac > 35 kcal mol−1), bearing two chiral axes, has been successfully synthesized, taking into account the results of DFT calculations on model systems. The absolute configurations of the novel atropisomers have been assigned using TD-DFT simulation of ECD spectra. Atropisomeric phencyclones herein presented pave the way towards new ruthenium- based enantioselective hydrogenation catalyst

Atropisomers of arylmaleimides: stereodynamics and absolute configuration

4-Aryl-3-bromo-N-benzylmaleimides and 3,4- biaryl-N-benzylmaleimides have been synthesized by a modified Suzuki cross-coupling reaction from 3,4-dibromo-Nbenzylmaleimide. The conformational studies by dynamic NMR and DFT calculations showed that the interconversion barrier between the two available skewed conformations is under steric control. When the aryl group was a 2- methylnaphthyl, thermally stable atropisomers were isolated by enantioselective HPLC and their absolute configurations were assigned by TD-DFT simulations of the ECD spectr

A Compendium of the Principal Stationary Phases Used in Hydrophilic Interaction Chromatography: Where Have We Arrived?

Hydrophilic interaction liquid chromatography (HILIC) today is a well-known and largely applied technique to analyse polar compounds such as pharmaceuticals, metabolites, proteins, peptides, amino acids, oligonucleotides, and carbohydrates. Due to the large number of stationary phases employed for HILIC applications, this review aims to help the reader in choosing a proper stationary phase, which often represents the critical point for the success of a separation. A great offer is present for achiral applications in contrast to the chiral phases developed for HILIC enantioseparations. In the last case, up-to-date solutions are presented

Separation of complex sugar mixtures on a hydrolytically stable bidentate urea-type stationary phase for hydrophilic interaction near ultra high performance liquid chromatography

A stationary phase bearing both bridged bis-ureido and free amino groups (USP-HILICNH2–2.5SP) for high-speed hydrophilic interaction liquid chromatography separations was prepared using a one-pot two-step procedure starting from 2.5 m totally porous silica particles. Highly polar compounds, such as polyols, hydroxybenzoic acids, and sugars, were successfully analyzed in shorter times and with higher peak efficiency, when compared to results obtained with a bidentate urea-type column packed with 5 m particles. Increased sugarophilicity and better peak shape were attested for the USP-HILIC-NH2–2.5SP column (100 × 3.2 mm id) when compared with two commercially available UHPLC columns, namely an acquity BEH amide packed with totally porous 1.7 m microparticles and a HILIC Kinetex column packed with core–shell 2.6 m particles. Finally, the new column was employed in the separation of complex mixture of sugars (mono-, di-, and oligosaccharides) and in the analysis of beer samples. The resulting chromatograms showed good selectivity and overall resolution, while the catalyzing effect of the free amino moieties resulted in excellent peak shapes and in the absence of split peaks due to sugar anomerization phenomen

A perspective on enantioselective chromatography by comparing ultra-high performance supercritical fluid chromatography and normal-phase liquid chromatography through the use of a Pirkle-type stationary phase

Since their discovery, the Pirkle-type chiral stationary phases, and in particular the Whelk-O1, have been used in a large number of applications and theoretical studies. Although they can be used in many elution modes, their main field of application is in normal phase liquid chromatography and more recently in supercritical fluid chromatography. In this review, we tried to compare the two techniques using the Whelk-O1 stationary phase as a trait d'union. The main milestones obtained in the last decades of research in enantioselective chromatography and possible lights and shadows of the two techniques have been described. There is still a long way to go to achieve the full potential in the field of enantioselective separations, and especially ultra-high supercritical fluid chromatography, given its great potential, is a technique still to be improved