Paola Peluso

Homochiral metal–organic frameworks and their application in chromatography enantioseparations

The last frontier in the chiral stationary phases (CSPs) field for chromatography enantioseparations is represented by homochiral metal-organic frameworks (MOFs), a class of organic-inorganic hybrid materials built from metal-connecting nodes and organic-bridging ligands. The modular nature of these materials allows to design focused structures by combining properly metal, organic ligands and rigid polytopic spacers. Intriguingly, chiral ligands introduce molecular chirality in the MOF-network as well as homochirality in the secondary structure of materials (such as homohelicity) producing homochiral nets in a manner mimicking biopolymers (proteins, polysaccharides) which are characterized by a definite helical sense associated with the chirality of their building blocks (amino acids or sugars). Nowadays, robust and flexible materials characterized by high porosity and surface area became available by using preparative procedures typical of the so-called reticular synthesis. This review focuses on recent developments in the synthesis and applications of homochiral MOFs as supports for chromatography enantioseparations. Indeed, despite this field is in its infancy, interesting results have been produced and a critical overview of the 12 reported applications for gas chromatography (GC) and high-performance liquid chromatography (HPLC) can orient the reader approaching the field. Mechanistic aspects are shortly discussed and a view regarding future trends in this field is provided.

Selective Mono- or Dialkoxylation of 2,4,6-Trichloro-1,3,5-triazine in Solid-Liquid Phase Transfer Conditions

Abstract In solid-liquid phase transfer conditions, both the primary and the secondary alcohols react cleanly with 2,4, 6-trichloro-1,3,5-triazine to give the corresponding mono or dialkoxy derivatives depending on the reagent molar ratio.

Stereochemistry of the cyclotrimerisation of enantiopure polycyclic bromostannylalkenes: Mechanistic considerations on the coupling of alkenyl stannanes by copper(II) nitrate

The cyclotrimerisation of enantiopure 1-bromo-2-trimethylstannylbenzonorbornadiene 2. contrary to the expectations, affords predominantly the trimer anti-4. This observation suggests that the reaction proceeds mainly via a SnSn coupling to produce the dimer anti-5 and a tin-copper product that triggers halogen-metal exchange on the dimer thus allowing a second coupling with the starting reagent eventually leading to the anti- trimer. The little but consistent formation of the isomer syn-4 and meso dimer 5 can arise from a racemisation of the bromine-copper-tin intermediate possibly via an alkyne structure.

anti-Selective Heck-type cyclotrimerization of polycyclic bromoalkenes

Abstract Vinyl halides can react as both substrate and reagent in the Heck reaction. In the case of bicyclic vinyl halides, the reaction leads to cyclotrimers through an anti -selective process.

Liquid chromatography enantioseparations of halogenated compounds on polysaccharide-based chiral stationary phases: role of halogen substituents in molecular recognition.

Halogenated chiral molecules have become important in several fields of science, industry, and society as drugs, natural compounds, agrochemicals, environmental pollutants, synthetic products, and chiral supports. Meanwhile, the perception of the halogen moiety in organic compounds and its role in recognition processes changed. Indeed, the recognition of the halogen bond as an intermolecular interaction occurring when the halogen acts as a Lewis acid had a strong impact, particularly in crystal engineering and medicinal chemistry. Due to this renewed interest in the potentialities of chiral organohalogens, here we focus on selected recent applications dealing with enantioseparations of halogenated compounds on polysaccharide-based chiral stationary phases (CSPs), widely used in liquid chromatography (LC). In particular, recently the first case of halogen bonding-driven high-performance LC (HPLC) enantioseparation was reported on a cellulose-based CSP. Along with enantioseparations performed under conventional HPLC, representative applications using supercritical fluid chromatography (SFC) are reported.

Enantioselective synthesis of polycyclic ketones by desymmetrisation of bis(phenylsulfonyl)alkenes with chiral alcoholates. Control of the absolute configuration by a simple modification of the chiral auxiliary

Abstract Treatment of polycyclic bis(phenylsulfonyl)alkenes with chiral alcoholates, followed by acidic work-up, affords enantioselectively α-phenylsulfonyl ketones. The enantioselectivity is total with monomethylated hydrobenzoin and of opposite configuration with respect to that obtained with hydrobenzoin itself. Thus, starting from a bis(phenylsulfonyl)alkene, it is possible to obtain either the R or S polycyclic ketone by the use of the same chiral auxiliary (hydrobenzoin) and a simple modification (methylation of one of the hydroxy functions).

Comparative HPLC enantioseparation of thirty-six aromatic compounds on four columns of the Lux® series: impact of substituents, shapes and electronic properties.

With the aim to define a combined computational/chromatographic empirical approach useful for the high-performance liquid chromatography (HPLC) method development of new chiral compounds, 36 racemic aromatic compounds with different chemical structures were used as test probes on four polysaccharide-based chiral stationary phases (CSPs) of the Lux series, namely Lux Cellulose-1, Lux Cellulose-2, Lux Cellulose-4, and Lux Amylose-2, using classical n-hexane/2-propanol mixtures as mobile phase. Electrostatic potential surfaces (EPSs) determined using Density Functional Theory (DFT) calculations were used to derive size, shape, and electronic properties of each analyte. Then a comparative HPLC screening was carried out in order to evaluate the impact of substituents, shapes, and electronic properties of the analytes on the chromatographic behavior as the column changes. The four CSPs showed good complementary recognition ability. The elution sequence was determined in 30 cases out of 36. The success rate to afford baseline separations (R(s) ≥ 1.5) was estimated: 29 compounds out of 36 showed baseline enantioseparation on at least one of the four selected CSPs. The combined computational-chromatographic screening furnished useful collective structure-chromatographic behavior relationships and a map of the chiral discrimination abilities of the considered CSPs towards the analytes. On this basis, the chromatographic behavior of new analytes on a set of polysaccharide-based CSPs can be mapped through the qualitative correlation of chromatographic parameters (k, α, R(s)) to computed molecular properties of the analytes.

Selective Amination of Cyanuric Chloride in the Presence of 18‐Crown‐6

An interpretation of the role of 18-crown-6 in the selective di- and trialkylamination of 2,4,6-trichloro-1,3,5-triazine is reported, and the usefulness of the procedure is shown. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

Observations on the alkylation of β-acetalic carbanions: monoalkylation versus dialkylation and elimination

Abstract The reaction with methyl iodide and a base (t-BuOK) of 1,3-dioxolanes and 1,3-dithiolanes substituted at the β-position with an electron-withdrawing substituent (EWG=CO2Me, SO2Ph, SO2Ph-p-NO2, SO2Ph-o-NO2) leads to mono- or dialkylated or ring-opened products in good yield.

Li+ and Na+ switch of enantioselectivity in the desymmetrisation of polycyclic bis(phenylsulfonyl)alkenes by chiral alcohols

A complete switch of enantioselectivity is obtained in the desymmetrisation reaction of polycyclic bis(phenylsulfonyl)alkenes by the change of the base from n-BuLi to NaH, thus allowing convenient access to either enantiomer of polycyclic ketones with the same chiral auxiliary.