Iridium-Catalyzed Asymmetric Hydrogenation of 2,3-Diarylallyl Amines with a Threonine-Derived P-Stereogenic Ligand for the Synthesis of Tetrahydroquinolines and Tetrahydroisoquinolines.

Chiral compounds containing nitrogen heteroatoms are fundamental substances for the chemical, pharmaceutical and agrochemical industries. However, the preparation of some of these interesting scaffolds is still underdeveloped. Herein we present the synthesis of a new family of P-stereogenic phosphinooxazoline iridium catalysts from L-threonine methyl ester and its use in the asymmetric hydrogenation of N -Boc-2,3-diarylallyl amines, achieving very high enantioselectivity. Furthermore, the synthetic utility of the 2,3-diarylpropyl amines obtained is demonstrated by their transformation to 3-aryl-tetrahydroquinolines and 4-benzyl-tetrahydroisoquinolines, which are not reported in an enantioselective manner by direct reduction of the corresponding aromatic heterocycles. This strategy allows the preparation of these types of alkaloids with the highest enantioselectivity reported up to date.

Although trifluoromethylthiolated compounds have privileged applications in pharmaceuticals and agrochemicals, efficient strategies for the asymmetric construction of Csp3–SCF3 bonds are limited. S...

Chiral nitrogen-containing compounds are crucial for the chemical, pharmaceutical, and agrochemical industries. Nevertheless, the synthesis of certain valuable scaffolds remains underdeveloped due to the vast chemical space available. In this work, we present a diastereoselective methodology for synthesizing 3,3-diarylallyl phthalimides, which, following iridium-catalyzed asymmetric hydrogenation using Ir-UbaPHOX, yield 3,3-diarylpropyl amines with high enantioselectivity (98-99% ee). The importance of alkene purity to achieve high enantioselectivity is discussed. The synthetic utility of the chiral propylamines obtained is demonstrated through the preparation of medicinally useful bioactive compounds like the drugs tolterodine and tolpropamine and 4-aryl tetrahydroquinolines. This strategy enables the synthesis of these compounds with the highest enantioselectivity reported to date.

Chiral hydroxyl compounds have been widely used in pharmaceutical, agrochemical, fine chemicals, and functional materials industries, due to their unique physical and chemical properties. Stereoselective carbonyl reductases can be efficiently applied to catalyze asymmetric synthesis of chiral hydroxyl compounds with high optical purity from directed reduction of prochiral carbonyl group of the corresponding keto substrates. Based on the diversity of substrates, single enantiomers of various chiral hydroxyl compounds, including chiral alcohols, hydroxyl esters, and hydroxyl amino acids, can be prepared through carbonyl reductase-catalyzed asymmetric reduction in a high efficiency. However, most of the available carbonyl reductases only exhibit low activity towards the substrates involving bulky groups. This review summarizes the basic traits and principles of biocatalytic asymmetric oxidoreductions, and the key characteristics and structure-function relationship of stereoselective carbonyl reductases. In addition, the carbonyl reductases and their systems for asymmetric synthesis of bulky chiral hydroxyl compounds are also addressed, and the potential strategies targeting the critical issue are further discussed.

A Modular Strategy for the Direct Catalytic Asymmetric α-Amination of Carbonyl Compounds

Aromatic heterocycles are ubiquitous building blocks in bioactive natural products, pharmaceutical and agrochemical industries. Accordingly, the carborane-fused heterocycles would be potential candidates in drug discovery, nanomaterials, metallacarboranes, as well as photoluminescent materials. In recent years, the transition metal catalyzed B-H activation has been proved to be an effective protocol for selective functionalization of B-H bond of o-carboranes, which has been further extended for the synthesis of polyhedral borane cluster-fused heterocycles via cascade B-H functionalization/annulation process. This article summarizes the recent progress in construction of polyhedral borane cluster-fused heterocycles via B-H activation.

Methods for synthesis of chiral organic compounds bearing trifluoromethyl-substituted stereocenters are of great interest for agrochemical and pharmaceutical labs and industries in their search for new bioactive materials. We report on employment of bisfunctionalized electrophiles, bearing both a trifluoromethyl and a functional group as direct substituents of the reactive center, in cross-coupling reactions. We exemplify this concept in the asymmetric synthesis of enantioenriched α-trifluoromethyl- and perfluoroalkyl-containing benzylic and allylic ethers and alcohols by nickel-catalyzed stereoconvergent Hiyama cross-coupling reaction. Substrate electrophiles are conveniently prepared in few steps from trifluoroacetic acid. The method represents a conceptually different approach to chiral CF3-substituted alcohols and ethers and allows for a rapid catalytic preparation of a wide range of these valuable compounds in high yields and enantioselectivity.

Reactions catalyzed by transition metal complexes almost always entail binding of one or more reactants to the metal center, and nearly every corner of the "chiral pool" has been picked over in efforts to develop enantioselective catalysts. As reported by Alfred Werner in 1911-1912, salts of the formally D3-symmetric [Co(en)3]3+ trication (en = ethylenediamine) were among the first chiral inorganic compounds to be resolved into enantiomers. These air- and water-stable complexes are substitution-inert, so for 100 years they languished without application in organic synthesis. We then showed that when they are rendered soluble in organic media by lipophilic anions such as fluorinated tetraarylborates BArf-, they become potent catalysts for a variety of carbon-carbon and carbon-heteroatom bond forming reactions.These involve substrate activation by hydrogen bonding to the coordinated NH2 units (pKa ca. 15), a "second coordination sphere" mechanism. Only modest enantioselectivities are obtained with [Co(en)3]3+ 3BArf- or related chromium, rhodium, iridium, and platinum salts. However, high enantioselectivities are achieved when the three en ligands are replaced by the 1,2-diphenyl analogues (S,S)- or (R,R)-H2NCHPhCHPhNH2. Here only one BArf- anion is required to solubilize the trication, so a number of mixed-salt catalysts (2X-BArf-) have been evaluated. Alternatively, a dimethylamino group can be tethered to the backbone of one en ligand, providing bifunctional catalysts that obviate any need for an external base. Interestingly, the counteranions modulate the enantioselectivities somewhat. However, catalysts with chiral anions do not significantly outperform benchmark catalysts with achiral anions. Cagelike chiral hexaaminecobalt(III) complexes known as sepulchrates and sarcophagines, which feature secondary NH donor atoms, can also serve as catalysts, but the enantioselectivities are very low.In a spinoff application, certain salts are found to be superb "chiral solvating agents", leading to distinct sets of NMR signals for enantiomers of chiral analytes with Lewis basic functional groups. Loadings of 10-25 mol % generally suffice, providing the best way of assaying the enantiomeric purities of a host of compounds. Also, mixtures of several chiral compounds can be simultaneously analyzed. It is not surprising that complexes that perform well in chiral recognition phenomena also excel as enantioselective catalysts.In this Account, the stereochemical properties of the preceding complexes are treated, as well as arcana generally known only to specialists in the field. These include the use of charcoal for equilibrating configurations of the cobalt stereocenter and Sephadex for separating enantiomers and diastereomers. Other types of metal-containing hydrogen-bond-donor catalysts are briefly surveyed (noncoordinating NH units can also be effective), including several developed by other groups. However, the mechanisms of enantioselection in all of these transformations remain obscure. The optimum diastereomer and anion set varies from reaction to reaction, suggesting a "phenotypic plasticity" that allows adaption to a variety of processes.

Chiral analysis is central for scientific advancement in the fields of chemistry, biology, and medicine. It is also indispensable in the development and quality control of chiral compounds in the chemical and pharmaceutical industries. Current methods for chiral analysis, namely optical polarimetry, mass spectrometry and nuclear magnetic resonance, are either insensitive, have low time resolution, or require preparation steps, and so are unsuited for monitoring chiral dynamics within complex environments: the current need of both research and industry. Here we present the concept of absolute optical chiral analysis, as enabled by cavity-enhanced polarimetry, which allows for accurate unambiguous enantiomeric characterization and enantiomeric-excess determination of chiral compounds within complex mixtures at trace levels, without the need for calibration, even in the gas phase. The utility of this approach is demonstrated by post chromatographic analysis of complex gaseous mixtures, the rapid quality control of perfume mixtures containing chiral volatile compounds, and the online in-situ observation of chiral volatile emissions from a plant under stress. Our approach and technology offer a step change in chiral compound determination, enabling online quality control of complex chemical mixtures, identification of counterfeit goods, detection of pests on plants, and assessment of chiral emission processes from climate relevant ecosystems.

Chirality, the absence of mirror symmetry, governs behavior in most biologically important molecules, thus making the chiral recognition of great importance in the pharmaceutical and agrochemical industries, as well as medicine. Chiral molecules can be characterized by means of optical experiments based on chiro-optical excitation of molecules. Specifically, chiral absorptive materials differently absorb left- and right-circular polarized light, i.e., they possess circular dichroism (CD). Unfortunately, the natural CD of most molecules is very low and lies in the ultraviolet range. Fluorescence-detected CD is a fast and sensitive tool for investigation of chiral molecules which emit light; ultralow CD in absorption can be detected as the difference in emission. In this work, we perform fluorescence-detected CD on novel chiral amide compounds, designed specifically for visible green emission; we synthesize two enantiomeric fluorescent compounds using low-cost starting compounds and easy purification. We investigate different solutions of the enantiomers at different concentrations, and we show that the fluorescence of the intrinsically chiral compounds depends on the polarization state of the penetrating light, which is absorbed at 400 nm and emits across the green wavelength range. We believe that these compounds can be coupled with plasmonic nanostructures, which further shows promise in applications regarding chiral sensing or chiral emission.

Chirality has increasingly nurtured scientific interests because, beyond the concepts related with the emergence and evolution of Life, it has remarkable implications in practical fields, where chiral materials, coupled with nanotechnology, can be exploited in chiral sensing, optical displays, information storage, asymmetric catalysis and so on.Porphyrins have been extensively used as building blocks to assembling organized systems featuring chirality at supramolecular level, mostly in solution. Indeed, the fine tuning of the properties of these chiral systems, is made possible by a florilegium of either internal or external stimuli, such as solvent polarity, pH, ionic strength, and templates.1 Although the achievement in solution is now well-established, the transfer of the chiral assemblies from solution to thin-film onto inorganic surfaces is not so obvious. Indeed, outside factors as hydrophilic/hydrophobic character of the substrates or the solvent evaporation process can deeply influence film formation and, consequently, its chirality. Furthermore, multiple limitations concerning, among others, robustness and versatility of the chiral nanostructures has still to be overcome for their efficient real-life implementation in a device.Over the years, we investigated the construction of chiral aggregates based on prolinated porphyrin derivatives in hydroalcoholic mixtures, whose formation was steered by hydrophobic effect. We demonstrated the influence of structural parameters (metal coordinated, charge/stereochemistry of the proline moiety) as well as solvent bulk properties (composition, concentration, ionic strength, presence of co-solutes) on both the overall aggregation process and the final morphologies observed.2-4 The implementation on a device often requires the fabrication of solid film by varied controlled deposition techniques able to maintain/amplify the chiral features of the aggregates formed in solution or to create ordered chiral layers by symmetry breaking events (i.e. Langmuir Blodgett or Langmuir-Schaefer techniques). Porphyrin derivatives bearing an appended (L)- or (D)- functionality on a meso phenyl position offered multiple options for realizing chiral surfaces, which are illustrated in Figure 1. Indeed, chiral films can be obtained by drop casting the aggregates formed in EtOH/H2O mixtures on glass, as well as a toluene solution of the porphyrin monomers. Alternatively, the carboxylic group placed on the proline unit can be exploited to anchor the macrocycle onto different inorganic nanostructures, as ZnO or silica nanoparticles, giving chiral layers on glass or quartz slides. In this regard, we also recently found that hybrid systems constituted by chiral Zn-porphyrin capped ZnO nanostructures are able to selectively detect the different enantiomers of chiral analytes, such as limonene vapours, when layered on quartz microbalance surface.5 The potential use of these chiral systems as sensitive materials in stereoselective sensors is indeed particularly appealing, since the most of new emergent pollutants released into the environment by pharmaceutical or agrochemical industries are chiral compounds, whose biological impact strictly depends on the specific enantiomer.In this contribution, an overview of the different preparation protocols of chiral porphyrin-based films will be provided, thoroughly illustrating the characterization of the obtained surfaces by several microscopies and spectroscopic investigations. Furthermore, studies on the chiral discrimination potential featured by the developed surfaces will be also presented. Figure 1

Multifunctional graphene oxide nanocomposites simultaneously possessing high enantioselectivity, excellent thermosensitivity, and magnetism demonstrate great application potentials in direct enantioseparation. We herein report one novel smart graphene oxide nanocomposite (MGO@PNG-CD) with high enantioselectivity, excellent thermosensitivity, and magnetism for highly efficient chiral identification and enantioseparation of tryptophan enantiomers. The MGO@PNG-CD is composed of graphene oxide nanosheets with immobilized superparamagnetic Fe3O4 nanoparticles and grafted PNG-CD smart polymer brushes. The PNG-CD is made up of poly(N-isopropylacrylamide-co-glycidyl methacrylate) (PNG) chains with numerous appended β-cyclodextrin (β-CD) units, which play a significant role in effective chiral discrimination and resolution of DL-tryptophan (DL-Trp). The β-CD units serve as chiral selectors capable of selectively recognizing and binding L-tryptophan (L-Trp) into their cavities to form stable host-guest inclusion complexes of β-CD/L-Trp. The PNIPAM chains in PNG act as a microenvironmental adjustor for the inclusion constants of β-CD/L-Trp complexes. The resulted MGO@PNG-CD demonstrates high thermosensitive enantioselectivity toward L-Trp over D-Trp based on the chiral discrimination ability of β-CD toward L-Trp and the thermosensitive volume phase transition of PNIPAM chains. Operating temperature and initial concentrations of DL-Trp are two significant factors affecting the separation efficiency of DL-Trp enantiomers. Moreover, the MGO@PNG-CD also displays satisfactory recycling and convenient magnetic separability from enantiomeric solution. Such a multifunctional graphene oxide nanocomposite developed in this study can serve as a high-performance nanoselector for highly efficient chiral recognition and enantioseparation of various chiral compounds.

Historical development of the chemical industry.- Chemical process safety: Safe practices and accident prevention.- Managing an emergency preparedness program.- Applied statistical methods.- Green engineering: Integration of green chemistry, pollution prevention, and risk based considerations.- Industrial catalysis: A practical guide.- Environmental chemical determinations.- Nanotechnology: Principles and applications.- Nanostructured materials: Industrial Applications.- Synthetic organic chemicals.- Chemistry in the pharmaceutical industry.- Manufactured textile fibers.- Dye application, manufacture of dyes and dye intermediates.- Chemistry of structural adhesives: Epoxy, urethane, and acrylic adhesives.- Synthetic resins and plastics.- Rubber.- The agrochemical industry.- Petroleum and its products.- Coal technology for power, liquid fuels and chemicals.- Natural gas.- The nuclear industry.- Synthetic nitrogen products.- Phosphorus and phosphates.- Fertilizers.- Sulfur and sulfuric acid.- Salt, chlor-alkali, and related heavy chemicals.- Industrial gases.- Wood and wood products.- Pigments, paints, polymer coatings, lacquers and printing inks.- Industrial biotechnology: Discovery to delivery.- Industrial enzymes and biocatalysis.- Industrial production of therapeutic proteins: Cell lines, cell culture and purification.- Biomass utilization.- Animal and vegetable fats, oils and waxes.- Sugar and other sweeteners.- Soap, fatty acids, and synthetic detergents.- Chemical explosives.- Electrochemical energy storage: Applications, processes, and trends.

Chirality is crucial for life. The preparation of enantiopure chiral compounds is highly desirable in the chemical industry, especially in the pharmaceutical sector. In this context, the design of chiral solids able to discriminate between enantiomers of chiral compounds, either during adsorption or asymmetric catalytic processes, is one of the greatest challenges nowadays in chemical research. Zeolite-type materials represent ideal candidates to achieve enantioselective chiral solids since they could combine their high stability, surface area, and shape-selectivity with a potential enantioselectivity that could be enhanced by the confinement effect. Despite the occurrence of chiral zeolite frameworks and the strong interest in preparing these chiral solids, very little success has been met in preparing these in homochiral form. The main strategy to induce chirality in zeolite materials has been the use of chiral structure-directing agents, in an attempt to transfer their chiral feature into the nascent zeolite structure. However, although many chiral organic species have directed the crystallization of zeolite frameworks, some of them even being chiral, there is only one unique very recent example of success in transferring the chirality from the organic structure-directing agent into an enantioenriched chiral zeolite material. Chiral coordination compounds have been very successful in transferring their chirality onto inorganic frameworks through the development of extensive H-bond host–guest interactions, but these chiral materials usually collapse upon removal of the guest species. In this chapter we report the different types of chiral molecules, both organic and organometallic compounds, used so far as structure-directing agents in an attempt to promote the crystallization of homochiral zeolites; we analyze in detail the possible reasons for the general failure in transferring their chirality, and we propose approaches to prepare known chiral zeolite frameworks in homochiral form. Furthermore, we also review a different approach we have followed in our group in order to induce chirality in zeolite materials, consisting in the development of chiral spatial distributions of dopants embedded in otherwise achiral zeolite frameworks.

Heterocyclic aromatic compounds containing nitrogen, sulfur, or oxygen heteroatoms (NSO-HET) have been detected in air, soil, marine, and freshwater systems. However, only few publications are available investigating NSO-HET using in vitro bioassays. To support better characterization of environmental samples, selected NSO-HET were screened for dioxin-like activity in two bioassays. The present study focuses on the identification and quantification of dioxin-like effects of 12 NSO-HET using the DR-CALUX assay, and the 7-ethoxyresorufin-O-deethylase (EROD) assay with the permanent fish liver cell line RTL-W1. Changes of the total medium compound concentrations during the test procedure due to, e.g., sorption or volatilization were quantified using GC/MS. The NSO-HET benzofuran, 2,3-dimethylbenzofuran, dibenzofuran, dibenzothiophen, acridine, xanthene, and carbazole caused a response in the DR-CALUX assay. Only benzofuran and 2,3-dimethylbenzofuran were also positive in the EROD assay. All other compounds were inactive in the EROD assay. Relative potency (REP) values ranged from (2.80 ± 1.32) · 10(-8) to (3.26 ± 2.03) · 10(-6) in the DR-CALUX and from (3.26 ± 0.91) · 10(-7) to (4.87 ± 1.97) · 10(-7) in the EROD assay. The REP values were comparable to those of larger polycyclic aromatic hydrocarbons, e.g., fluoranthene and pyrene. Thus, and because of the ubiquitous distribution of heterocyclic aromatic compounds in the environment, the provided data will further facilitate the bioanalytical and analytical characterization of environmental samples towards these toxicants.