Differentiation of Epoxide Enantiomers in the Confined Spaces of an Homochiral Cu(II) MOF by Kinetic Resolution

TAMOF-1, a homochiral metal-organic framework (MOF) constructed from an amino acid derivative and Cu(II), was investigated as a heterogeneous catalyst in kinetic resolutions involving the ring opening of styrene oxide with a set of anilines. The branched products generated from the ring opening of styrene oxide with anilines and the unreacted epoxide were obtained with moderately high enantiomeric excesses. The linear product arising from the attack on the non-benzylic position of styrene oxide underwent a second kinetic resolution by reacting with the epoxide, resulting in an amplification of its final enantiomeric excess and a concomitant formation of an array of isomeric aminodiols. Computational studies confirmed the experimental results, providing a deep understanding of the whole process involving the two successive kinetic resolutions. Furthermore, TAMOF-1 activity was conserved after several catalytic cycles. The ring opening of a mesoepoxide with aniline catalyzed by TAMOF-1 was also studied and moderate enantioselectivities were obtained

Separation of Volatile Organic Compounds in TAMOF-1

Separation of volatile organic compounds is one of the most studied processes in industry. TAMOF-1 is a homochiral metal-organic framework with a crystalline network of interconnected 1 nm channels and has high thermal and chemical stability. Thanks to these features, it can resolve racemic mixtures of chiral drugs as a chiral stationary phase in chromatography. Interestingly, the particular shape and size of its channels, along with the presence of metallic centers and functional groups, allow establishing weak but significant interactions with guest molecules. This opens interesting possibilities not only to resolve racemates but also to separate other organic mixtures, such as saturated/unsaturated and/or linear/branched molecules. In search of these applications, we have studied the separation of volatile organic compounds in TAMOF-1. Monte Carlo simulations in the grand-canonical ensemble have been carried out to evaluate the separation of the selected molecules. Our results predict that TAMOF-1 is able to separate xylene isomers, hexane isomers, and benzene-cyclohexane mixtures. Experimental breakthrough analysis in the gas phase and also in the liquid phase confirms these predictions. Beds of TAMOF-1 are able to recognize the substitution in xylenes and the branching in hexanes, yielding excellent separation and reproducibility, thanks to the chemical and mechanical features of this material.Universidad Pablo de Olavide. Departamento de Sistemas Físicos, Químicos y Naturale

Homochiral Metal-Organic Frameworks for Enantioselective Separations in Liquid Chromatography

Selective separation of enantiomers is a substantial challenge for the pharmaceutical industry. Chromatography on chiral stationary phases is the standard method, but at a very high cost for industrial-scale purification owing to the high cost of the chiral stationary phases. Typically, these materials are poorly robust, expensive to manufacture and often too specific for a single desired substrate, lacking desirable versatility across different chiral analytes. Here we disclose a porous, robust homochiral metal-organic framework (MOF), TAMOF-1, built from copper(II) and an affordable linker prepared from natural L-histidine. TAMOF-1 has shown to be able to separate a variety of model racemic mixtures, including drugs, in a wide range of solvents of different polarity, outperforming several commercial chiral columns for HPLC separations. Although not exploited in the present article, it is worthy to mention that the preparation of this new material is scalable to the multikilogram scale, opening unprecedented possibilities for low-energy chiral separation at the industrial scale

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

A Practical Synthesis of Rhodium Precatalysts for Enantioselective

Herein is described a practical method of preparing enantiopure rhodium(I) complexes that can be used as efficient catalysts for the asymmetric hydrogenation of functionalized alkenes, the hydrogenative kinetic resolution of vinyl sulfoxides and the desymmetrization of meso-dienes. All these rhodium precatalysts incorporate enantiopure phosphine-phosphite (POP) ligands as stereochemical directors of the hydrogenative transformations. The synthetic route starts with the ring-opening of an enantiopure Sharpless epoxy ether with a phosphorus nucleophile followed by isolation of the borane-protected phosphino alcohol derivative by crystallization. The subsequent cleavage of this borane complex, the O-phosphorylation of the resulting phosphino alcohol with the corresponding phosphorus electrophiles (chlorophosphite derivatives), and finally the complexation of the in situ generated POP ligands with [Rh(nbd)2]BF4, followed by crystallization, rendered the target precatalysts.</p

Stereoselective Catalytic Synthesis of P-Stereogenic Oxides via Hy-drogenative Kinetic Resolution

A highly stereoselective catalytic method for the preparation of structurally diverse P-stereogenic oxides has been developed. The approach relies on the ability of rhodium complexes derived from an enantiopure P–OP ligand to kinetically resolve racemic α,β-unsaturated phosphane oxides by hydrogenation of the C═C motif and formation of highly enantioenriched (or even enantiopure) P-stereogenic oxides. The practicality of the methodology has been demonstrated by the preparation of potentially functional P-chiral molecules for catalytic enantioselective synthesis

Supramolecularly Fine-regulated Enantioselective Catalysts

The use of supramolecular interactions in catalysis has undergone major growth in the last decade and has contributed to the major advances achieved in the field of enantioselective catalysis. Of the various approaches that use supramolecular interactions in enantioselective catalysis, this article highlights different supramolecular strategies to generate a set of enantiopure ligands (or enantioselectiva catalysts) that retain the majority of the backbone&rsquo;s structural features, yet at the same time incorporate subtle changes at its active site that depend on the structural characteristics of the regulation agent (RA) employed.</p

Structural Investigations on Enantiopure POP Ligands: a High- Performing POP Ligand for Rhodium-catalysed Hydrogenations

A second generation of phosphine–phosphite (P–OP) ligands, incorporating a more sterically bulky phosphite group than previous P–OP ligand designs, gave very efficient catalysts for the Rh‐catalysed asymmetric hydrogenation of a diverse array of substrates (11 examples, 93–99 % ee) containing structurally diverse substituents and chelating groups at the C=C double bond. The presence of the sterically bulky (Sa)‐3,3′‐diphenyl‐5,5′,6,6′,7,7′,8,8′‐octahydro‐[1,1′‐binaphthalene]‐2,2′‐diol‐derived phosphite fragment caused significant increases in enantioselectivity (up to Δee = 58 %), and provided improved results compared to those obtained with the first generation of P–OP‐derived rhodium catalysts {i.e., rhodium complexes incorporating phosphine–phosphite ligands with (Ra)‐ and (Sa)‐BINOL‐derived phosphite groups; BINOL = [1,1′‐binaphthalene]‐2,2′‐diol}. Overall, the optimal ligand L8 provided very high enantioselectivities for a range of structurally diverse olefins (up to 99 % ee)

Substrate Activation in the Catalytic Asymmetric Hydrogenation of N-Heteroarenes

Different methods for transforming N-heteroarenes into more reactive derivatives for catalytic asymmetric hydrogenation are highlighted. The first strategy consists of facilitating hydrogenation by the formation of positively charged derivatives of the heteroarene. Catalyst deactivation processes arising upon binding of the substrate to the metal center can thus be prevented and, additionally, hydrogenation of positively charged heteroarenes may also be more favored than that of their neutral analogues. The second strategy is based on introducing a ligating group onto the substrate to assist its coordination to the metal center and facilitate hydrogenation by chelation assistance. The last strategy involves breaking the aromaticity of the heteroarene by inducing a doublebond migration process. This microreview summarizes advances made in the above strategies, which have allowed the development of highly enantioselective catalytic hydrogenation of N-heteroarenes for the production of fully or partially saturated chiral heterocycles.</p