A Photoredox Thiol-yne Reaction for the Synthesis of Vinyl Sulfide-Based Coumarins and its Effect on Fluorescence Properties.

Coumarins still remain one of the most widely explored fluorescent dyes, with a broad spectrum of applications spanning various fields, such as molecular imaging, bioorganic chemistry, materials chemistry, or medical sciences. Their fluorescence is strongly based on a push-pull mechanism involving an electron-donating group (EDG), mainly located at the C7 or C8 positions of the dye core. Unfortunately, up to now, these positions have been very limited to hydroxyl or amino groups. In this study, we present in detail the synthesis of the first series of coumarins bearing a vinyl sulfide as the EDG at the C7 position. These derivatives were prepared by thiol-yne reaction, promoted by ruthenium- or porphyrin-based photoredox catalysis, enabling rapid late-stage diversification. We also functionalized coumarins with short peptides, and BSA protein as a proof-of-concept study, in a single-step process. This strategy, capable of proceeding under aqueous conditions, overcomes the protection/deprotection steps usually required by traditional methods, which also use strong bases and organic solvents. Moreover, the photophysical properties such as absorption and emission of obtained coumarins (for 3-CF3, 3-benzothiazole, 6-8-difluoro derivatives), predominantly exhibited large Stokes shifts (up to 204 nm) and maintained intramolecular charge transfer (ICT) characteristics.

GC-FTICR mass spectrometry with dopant assisted atmospheric pressure photoionization: application to the characterization of plastic pyrolysis oil.

Pyrolysis is a promising way to convert plastic waste into valuable resources. However, for downstream upgrading processes, many undesirable species, such as conjugated diolefins or heteroatom-containing compounds, can be generated during this pyrolysis. In-depth chemical characterization is therefore required to improve conversion and valorization. Because of the high molecular diversity found in these samples, advanced analytical instrumentation is needed to provide accurate and complete characterization. Generally, direct infusion Fourier transform mass spectrometry is used to gather information at the molecular level, but it has the disadvantage of limited structural insights. To overcome this drawback, gas chromatography has been coupled to Fourier transform ion cyclotron resonance mass spectrometry. By taking advantage of soft atmospheric pressure photoionization, which preserves molecular information, and the use of different dopants (pyrrole, toluene, and benzene), selective ionization of different chemical families was achieved. Differences in the ionization energy of the dopants will only allow the ionization of the molecules of the pyrolysis oil which have lower ionization energy, or which are accessible via specific chemical ionization pathways. With a selective focus on hydrocarbon species and especially hydrocarbon species having a double bond equivalent (DBE) value of 2, pyrrole is prone to better ionize low-mass molecules with lower retention times compared to the dopant benzene, which allowed better ionization of high-mass molecules with higher retention times. The toluene dopant presented the advantage of ionizing both low and high mass molecules.

Contribution of LDI and MALDI for the Characterization of a Lignocellulosic-Based Pyrolysis Bio-Oil.

In recent years, various alternatives to fossil fuels have been developed. One of them involves the production of bio-oils from lignocellulosic-based biomass through pyrolysis. However, bio-oils present numerous heteroatoms and, in particular, oxygen atoms that need to be removed by an upgrading process. To optimize these processes, it is necessary to have good knowledge of the composition of the bio-oils at the molecular level. This work aims to establish the usefulness of laser desorption ionization (LDI) and matrix-assisted laser desorption/ionization (MALDI) techniques on lignocellulosic biomass-based bio-oils. Using a Fourier transform ion cyclotron mass spectrometer (FTICR MS), we showed that MALDI gives more information than LDI. The selectivity of a series of MALDI matrices was investigated, showing that some matrices are selective toward compound families and others ionize a wider range of compounds. In this study, nine proton-transfer matrices and three electron-transfer matrices were used and compared to results obtained in LDI. Dithranol, acetosyringone, and graphene oxide were the three promising matrices selected from all matrices, giving an overall characterization of oxygenated classes in a bio-oil. They allowed the ionization of many more species covering a wide range of polarity, aromaticity, and mass with a homogeneous relative intensity for all molecular classes such as lignin-derivative species, sugars, and lipid-derivative species.

Advances in Ultra-High-Resolution Mass Spectrometry for Pharmaceutical Analysis.

Pharmaceutical analysis refers to an area of analytical chemistry that deals with active compounds either by themselves (drug substance) or when formulated with excipients (drug product). In a less simplistic way, it can be defined as a complex science involving various disciplines, e.g., drug development, pharmacokinetics, drug metabolism, tissue distribution studies, and environmental contamination analyses. As such, the pharmaceutical analysis covers drug development to its impact on health and the environment. Moreover, due to the need for safe and effective medications, the pharmaceutical industry is one of the most heavily regulated sectors of the global economy. For this reason, powerful analytical instrumentation and efficient methods are required. In the last decades, mass spectrometry has been increasingly used in pharmaceutical analysis both for research aims and routine quality controls. Among different instrumental setups, ultra-high-resolution mass spectrometry with Fourier transform instruments, i.e., Fourier transform ion cyclotron resonance (FTICR) and Orbitrap, gives access to valuable molecular information for pharmaceutical analysis. In fact, thanks to their high resolving power, mass accuracy, and dynamic range, reliable molecular formula assignments or trace analysis in complex mixtures can be obtained. This review summarizes the principles of the two main types of Fourier transform mass spectrometers, and it highlights applications, developments, and future perspectives in pharmaceutical analysis.

Prediction of Structures of Compounds Encountered in Complex Organic Matter with Highly Flexible Alkyl Chains Using Ion Mobility-Mass Spectrometry.

The chemical structure of an organic molecule has a direct influence on its three-dimensional conformation. One way to obtain information on this conformation is to use ion mobility spectrometry. This technique allows the separation of different isomers according to their collision cross section (CCS) with an inert gas. Smaller or more compact molecules will have lower collision cross section values than larger molecules. The CCS is an intrinsic ion parameter for a specific gas and is thus predictable. Today, calculations of rigid molecules are commonly performed to obtain additional structural information on an ion. However, calculations are more complex with very flexible molecules. In particular, molecules presenting long alkyl chains can yield a high number of conformers. Each conformer is then associated with a CCS value that is specific to it. We report, here, a methodology to predict CCS of flexible molecules. The used approach is based on automatic conformers research followed by geometry optimization and CCS calculations. Determination of theoretical and experimental CCS values for a rigid polycyclic aromatic hydrocarbons (PAHs) standard was used to calibrate the Mobcal software. Then, 13 standard molecules ranging from 4 to 19 carbon alkyl chains, including three long alkyl chain isomers of C22H38, were analyzed on a TWIMS-ToF and calculated using our methodology. CCS deviations between experimental and theoretical values were found to be less than 1.5% over the whole studied CCS range. This method was finally applied for structural analysis of petroleum compounds refractory to the hydro-denitrogenation process.

Molecular Characterization of Formulated Lubricants and Additive Packages Using Kendrick Mass Defect Determined by Fourier Transform Ion Cyclotron Resonance Mass Spectrometry.

Formulated lubricants correspond to high value products used for several applications in automotive, industrial, medicinal, and agro-food sectors. They correspond to complex matrices composed of approximately 80% of base oils (mineral or synthetic) and of about 20% of additives. Additives are generally low molecular weight polymeric molecules with a great diversity of elements. To characterize such complex compositions at the molecular level, ultrahigh resolution mass spectrometers are required. Two formulated lubricants and two additive packages were analyzed by Fourier transform ion cyclotron resonance mass spectrometry in direct infusion. Atmospheric pressure chemical ionization (APCI) and electrospray ionization (ESI) sources were used to have an exhaustive characterization of the samples. The Kendrick mass defects (KMD) plot is a widespread representation to characterize polymeric molecules. Here, the terms apparent mass defect and apparent Kendrick mass defects (aKMD) values were introduced to consider the uncertainty on nominal mass determination. Several additive families including alkyldiphenylamines, trisalkylphenylthiophosphoric acid, zinc dithiophosphates, bisuccinimide dispersants, and their derivatives were observed by APCI(+). ESI(-) also presented a use for the selective ionization of acidic compounds including sulfonates, phenates, and sulfur phenate molecules. The specific aKMD values and polydispersity of many additive families have been reported to create a database of additives. Overall, this study demonstrated the great utility of the aKMD approach and the use of the ESI/APCI combination for a simple and fast characterization of formulated lubricant and additive package samples.

Speciation and Semiquantification of Nitrogen-Containing Species in Complex Mixtures: Application to Plastic Pyrolysis Oil.

Plastic pyrolysis oil is of particular interest for waste management in the current context of a circular economy. Due to their uncontrolled origin, these oils may contain significant amount of unwanted compounds such as nitrogen-containing species. These compounds are known to be catalyst poisons during refining processes. Therefore, the removal of these species is crucial, and their characterization from structural and quantification points of view is essential for this purpose. This study presents a method to specify and quantify nitrogen-containing classes in a plastic pyrolysis oil by direct infusion mass spectrometry. Two steps were used, namely structural characterization to select suitable standards and semiquantification. The structural speciation of nitrogen-containing compounds was first performed by electrospray ionization Fourier transform mass spectrometry, followed by tandem mass spectrometry using high-resolution mass isolation and infrared multiphoton dissociation fragmentation. A semiquantification is then performed by the standard addition method, which is very appropriate for such complex matrices. Aromatic cores such as quinoline and quinoxaline were evidenced for both N1 and N2 classes, allowing 2-methylquinoxaline and 2-butylquinoline to be proposed as standards for the semiquantification of N2- and N1-containing compounds, respectively. The amount of nitrogen detected from the sum of the individual species was consistent with the bulk analysis. The reported methodology can be applied to numerous other families of compounds in various other complex matrices.

Chromium Determination in Leather and Other Matrices: A Review.

Leather industry plays an essential role in the world's economy; however, it also has a negative environmental impact due to the generation of significant quantities of wastes, some of which are classified as hazardous chemicals. Chrome tanning, the most popular tanning process, employs chromium salts, acids, and some other chemicals. Some dyes can be also a source of chromium. As a result, hexavalent chromium, a known carcinogenic and mutagenic, can be found in leather products and cause allergic dermatitis or trigger other diseases. For this reason, it is important to quantify the total amount of chromium in final leather goods, as well as the oxidation state in which this element is found. This paper aims to summarize chromium contamination due to the leather production processes, and to review the analytical methods that have been used to determine chromium's most abundant species: Cr(III) and Cr(VI) in leather and other matrices (foodstuffs, cosmetic products, environmental, and pharmaceutical samples). The international and European regulations are presented as well as the last academic developments to extract and quantify chromium species. The future outlook of pretreatment and quantification techniques are also discussed in this work, with a special focus on chromium interconversions.

Cost-efficient and user-friendly 17O/18O labeling procedures of fatty acids using mechanochemistry.

Two mechanochemical procedures for 17O/18O-isotope labeling of fatty acids are reported: a carboxylic acid activation/hydrolysis approach and a saponification approach. The latter route allowed first-time enrichment of important polyunsaturated fatty acids (PUFAs) including docosahexaenoic acid (DHA). Overall, a total of 9 pure labeled products were isolated in high yields (≥80%) and with high enrichment levels (≥37% average labeling of C=O and C-OH carboxylic oxygen atoms), under mild conditions, and in short time (

Structural analysis of petroporphyrins from asphaltene by trapped ion mobility coupled with Fourier transform ion cyclotron resonance mass spectrometry.

Molecular characterization of compounds present in highly complex mixtures such as petroleum is proving to be one of the main analytical challenges. Heavy fractions, such as asphaltenes, exhibit immense molecular and isomeric complexity. Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS) with its unequalled resolving power, mass accuracy and dynamic range can address the isobaric complexity. Nevertheless, isomers remain largely inaccessible. Therefore, another dimension of separation is required. Recently, ion mobility mass spectrometry has revealed great potential for isomer description. In this study, the combination of trapped ion mobility and Fourier transform ion cyclotron resonance mass spectrometry (TIMS-FTICR) is used to obtain information on the structural features and isomeric diversity of vanadium petroporphyrins present in heavy petroleum fractions. The ion mobility spectra provided information on the isomeric diversity of the different classes of porphyrins. The determination of the collision cross section (CCS) from the peak apex allows us to hypothesize about the structural aspects of the petroleum molecules. In addition, the ion mobility signal full width at half maximum (FWHM) was used as a measure for isomeric diversity. Finally, theoretical CCS determinations were conducted first on core structures and then on alkylated petroporphyrins taking advantage of the linear correlation between the CCS and the alkylation level. This allowed the proposal of putative structures in agreement with the experimental results. The authors believe that the presented workflow will be useful for the structural prediction of real unknowns in highly complex mixtures.

Regio- and Stereo-Specific Chemical Depolymerization of High Molecular Weight Polybutadiene and Polyisoprene for Their Analysis by High-Resolution Fourier Transform Ion Cyclotron Resonance Mass Spectrometry: Comparison with Pyrolysis-Comprehensive Two-Dimensional Gas Chromatography/Mass Spectrometry, Atmospheric Solid Analysis Probe, Direct Inlet Probe-Atmospheric Pressure Chemical Ionization Mass Spectrometry, and Ion Mobility Spectrometry-Mass Spectrometry.

Polybutadiene (PB) and polyisoprene (PI), the two most common polydienes (PD), are involved in a large number of materials and used in a wide variety of applications. The characterization of these polymers by mass spectrometry (MS) continues to be very challenging due to their high insolubility and the difficulty to ionize them. In this work, a cross-metathesis reaction was used to generate end-functionalized acetoxy ionizable oligomers for the structural deciphering of different commercial PB and PI samples. A cross-metathesis reaction was carried out between polymers and the Z-1,4-diacetoxy-2-butene as a chain transfer agent in dichloromethane using a Hoveyda-Grubbs second-generation catalyst. Well-defined acetoxy telechelic structures were obtained and analyzed by Fourier transform ion cyclotron resonance (FTICR) high-resolution MS. However, after depolymerization, low molar mass polyolefins contained some units with different configurations, suggesting an olefin isomerization reaction due to the decomposition of the catalyst. The addition of an electron-deficient reagent such as 2,6-dichloro-1,4-benzoquinone suppressed this isomerization in the case of both Z- and E-PB and PI. Ion mobility spectrometry-mass spectrometry (IMS-MS) and energy-resolved tandem mass spectrometry (ERMS) analyses confirmed a successful isomerization suppression. For comparing the results obtained by depolymerization with classical methods for polymer analysis, pyrolysis-comprehensive two-dimensional gas chromatography/mass spectrometry (Py-GC × GC-MS), atmospheric solid analysis probe (ASAP), and direct inlet probe-atmospheric pressure chemical ionization (DIP-APCI) analyses were performed on the same polymers. This strategy can be applied on a variety of synthetic and natural not yet characterized polymers.

High-performance thin-layer chromatography with atmospheric solids analysis probe mass spectrometry for analysis of gasoline polymeric additives.

RATIONALE: The offline coupling of high-performance thin-layer chromatography (HPTLC) with atmospheric solids analysis probe mass spectrometry (ASAP-MS) was evaluated for the characterization of polymeric additives in gasoline. METHODS: A protocol was developed to optimize the ion signal. A glass capillary was moistened with deionized water, and then dipped into silica gel scratched from an HPTLC plate. The capillary tube was fixed to the ASAP holder and introduced into the ionization source for analysis by MS. Silica gel, reversed-phase C18 and cellulose stationary phases were evaluated. RESULTS: The effect of the stationary phase and the nature of analyte were evaluated using polypropylene glycol and polyisobutylene succinimide polyamine as analyte molecules. The optimal ionization conditions are significantly different between ASAP and HPTLC/ASAP-MS analyses. In particular, a higher desorption gas temperature was required to produce ions from the silica gel HPTLC plate. The presence of the stationary phase reduces the internal energy of the ions and limits the fragmentation. CONCLUSIONS: HPTLC/ASAP-MS is a very fast and efficient technique for the analysis of polymers in formulated fuels. Good ionization efficiency was obtained with all investigated stationary phases.

Paraffin-Inert Atmospheric Solid Analysis Probe: A Fast and Easy Approach To Characterize Extremely Air-Sensitive Organometallic Complexes by Mass Spectrometry.

Rational characterization of most organometallic compounds is hampered by their high reactivity, in particular, toward oxygen and water. Mass spectrometry experiments require physical introduction of the sample in the ionization source. So, the main challenge is to transfer air-sensitive organometallic compounds from inert atmosphere to the ionization source. In this aim, we have developed an easy technique that allows the analysis of air-sensitive compounds using the atmospheric solid analysis probe (ASAP). This method consists of a glass capillary filled with the sample (solid or liquid) and sealed by a paraffin plug to maintain the inert sample until the ionization process. It is illustrated through the structural characterization of a new highly air-sensitive dinuclear zirconium complex supported by an original switchable stilbene platform.

Structural analysis of heavy oil fractions after hydrodenitrogenation by high-resolution tandem mass spectrometry and ion mobility spectrometry.

Heavy petroleum fractions such as vacuum gas oils (VGOs) are structurally and compositionally highly complex mixtures. Nitrogen species, which have a significant impact on the subsequent refining processes, are generally removed by the hydrodenitrogenation (HDN) catalytic process. The purpose of this study was to identify and characterize compounds that are refractory to the HDN process. This may allow for the examination of the effectiveness of a vacuum distillate hydrotreatment catalytic bed in removing nitrogen-containing compounds before the cracking step. Three different VGO fractions of the same oil before and after HDN processes were analysed in ESI(+) mode by FTICR mass spectrometry and ion mobility spectrometry-mass spectrometry (IMS-MS), in particular compounds containing basic nitrogen, such as quinoline and isoquinoline. Ultra-high-resolution FTICR mass spectrometry provides a sufficiently high mass resolution power to resolve different compounds and attribute a unique molecular formula to each ion. Information on the isomeric content was obtained by use of tandem mass spectrometry (MS/MS) and IMS-MS. The evolution of the fragmentation of the N1 class of compounds as a function of collision energy allowed for the identification of the molecular nucleus raw formula. From the IMS-MS experiments, it clearly appeared that, based on the IMS peak width, a lower isomeric dispersity was obtained after the HDN process and, based on the drift time and collision cross section determination, species presenting longer alkyl branches are the molecules most refractory to the HDN process.

Diverted Natural Lossen-type Rearrangement for Bioconjugation through in Situ Myrosinase-Triggered Isothiocyanate Synthesis.

Fluorescein isothiocyanate (FITC) is one of the most extensively used fluorescent probes for the labeling of biomolecules. The isothiocyanate function reacts with lysine residues of proteins to provide a chemically stable thiourea linkage without releasing any byproduct. However, diversification of isothiocyanate-based reagents is still hampered by the lack of mild conditions to generate isothiocyanate chemical functions, as well as by their poor stability and limited solutions available to increase water solubility, restricting the use of isothiocyanate labeling to highly water-soluble fluorophores. Inspired by plant biological processes, we report a safe and biocompatible myrosinase-assisted in situ formation of isothiocyanate conjugates from a highly water-soluble and stable glucosinolate precursor. This method was applied for the fluorescence labeling of a plasmatic protein and fluorescence imaging of living cells.

Ion mobility-mass spectrometry analysis of diarylquinoline diastereomers: Drugs used for tuberculosis treatment.

Mycobacterium tuberculosis infection results in more than two million deaths per year and is the leading cause of mortality in people infected with HIV. A new structural class of antimycobacterials, the diarylquinolines, has been synthesized and is being highly effective against both M. tuberculosis and multidrug-resistant tuberculosis. As diarylquinolines are biologically active only under their ( R,S) stereoisomeric form, it is essential to differentiate the stereoisomers ( R,S) and ( R,R). To achieve this, tandem mass spectrometry and ion mobility spectrometry-mass spectrometry have been performed with 10 diarylquinoline diastereomers couples. In this study, we investigated cationization with alkali metal cations and several ion mobility drift gases in order to obtain diastereomer differentiations. We have shown that diastereomers of the diarylquinolines family can be differentiated separately by tandem mass spectrometry and in mixture by ion mobility spectrometry-mass spectrometry. However, although the structure of each diastereomer is close, several behaviors could be observed concerning the cationization and the ion mobility spectrometry separation. The ion mobility spectrometry isomer separation efficiency is not easily predictable; it was however observed for all diastereomeric couples with a significant improvement of separation using alkali adducts compared to protonated molecules. With the use of drift gas with higher polarizability only an improvement of separation was obtained in a few cases. Finally, a good correlation of the experimental collision cross section (relative to three-dimensional structure of ions) and the theoretical collision cross section has been shown.

Synthesis and Unprecedented Complexation Properties of ß-Cyclodextrin-Based Ligand for Lanthanide Ions.

Here, we report the synthesis and detailed studies on the coordination chemistry of a novel chemically modified polyaminocarboxylate (5) based on ß-cyclodextrin (CD) scaffold for lanthanides. The target ligand is prepared in a highly efficient manner (seven total steps) from ß-CD using the readily available iminodiacetic acid as a starting material. A propargyl group is attached to the iminodiacetate via N-alkylation, and the obtained derivative is efficiently conjugated to the ß-CD scaffold via the copper(I)-mediated 1,3-dipolar cycloaddition. The generated 1,2,3-triazolmethyl residues advantageously provide a competent chelating group while displacing the metal coordination center away from the primary rim of ß-CD, to afford the required conformational flexibility. The functional groups from each of the two adjacent glucopyranosyl units of ß-CD complete a uniquely created octavalent coordination sphere for lanthanides while still sparing one site for dynamic water coordination. To help study the coordination chemistry of CD ligand 5, we also design a relevant maltoside ligand 6, which faithfully represents one submetal-binding section of ligand 5. Thanks to HRMS and NMR studies, we successfully elucidate the coordination chemistries of synthesized ligands. The octavalent coordination sphere of ligand 5 shows strong binding affinity to lanthanides. By potentiometric titration experiments, ligand 5 is found to bind gadolinium(III), forming 1:1, 1:2, and 1:3 multinuclear complexes with lanthanides, thus possessing great capacity for catalyzing the dynamic water-exchange. Further NMR studies also reveal that the formed ligand 5/Gd(III) complexes show significantly better abilities to alter T1 relaxivities of coordinated water than DOTA-Gd(III) and also some of the synthetic CD probes reported in the literature.

Characterization of polyalphaolefins using halogen anion attachment in atmospheric pressure photoionization coupled with ion mobility spectrometry-mass spectrometry.

Polyalphaolefins (PAOs) are saturated alpha olefin oligomers used as a base stock oil for synthetic lubricants. The synthetic base stocks are manufactured from linear alpha olefins by catalytic oligomerization processes. The aim of this work was the characterization of different PAO grades, synthesized from different linear alpha olefins using two oligomerization processes, acid and metallocene catalyses. Negative ion atmospheric pressure photoionization (APPI) coupled with ion mobility spectrometry-mass spectrometry (IMS-MS) permitted the detection of intact PAO adducts with either chloride, bromide or iodide ions using halogenated solvents (e.g. dichloromethane, dibromomethane and diiodomethane) and toluene as the dopant. The best signal-to-noise ratio was obtained with dichloromethane. The APPI mass spectra displayed characteristic ion distributions for high viscosity PAO grades. The mass shift between two adjacent ions permitted the identification of repeating units and consequently the monomers of alpha olefins used to manufacture the PAO. For low PAO grades, the halide anion adducts were not detected as they are less stable. The IMS-MS data, as well as the correlated variables, i.e. the drift time and full width at half maximum (FWHM) of the IMS peaks, can be used to differentiate polyalphaolefins of the same grade but differently synthesized.

Atmospheric Solid Analysis Probe Coupled to Ion Mobility Spectrometry-Mass Spectrometry, a Fast and Simple Method for Polyalphaolefin Characterization.

Polyalphaolefins (PAOs) are polymers produced from linear alpha olefins through catalytic oligomerization processes. The PAOs are known as synthetic high-performance base stock fluids used to improve the efficiency of many other synthetic products. In this study, we report the direct characterization of PAOs using atmospheric solid analysis probe (ASAP) coupled with ion mobility spectrometry-mass spectrometry (IMS-MS). We studied different PAOs grades exhibiting low- and high-viscosity index. Specific adjustments of the ASAP source parameters permitted the monitoring of ionization processes as three mechanisms could occur for these compounds: hydride abstraction, nitrogen addition, and/or the formation of [M-2H]+• ions. Several series of fragment ions were obtained, which allowed the identification of the alpha olefin used to synthesize the PAO. The use of the ion mobility separation dimension provides information on isomeric species. In addition, the drift time versus m/z plots permitted rapid comparison between PAO samples and to evidence their complexity. These 2D plots appear as fingerprints of PAO samples. To conclude, the resort to ASAP-IMS-MS provides a rapid characterization of the PAO samples in a direct analysis approach, without any sample preparation. Graphical Abstract ᅟ.

A Unique (3+2) Annulation Reaction between Meldrum's Acid and Nitrones: Mechanistic Insight by ESI-IMS-MS and DFT Studies.

The fragile intermediates of the domino process leading to an isoxazolidin-5-one, triggered by unique reactivity between Meldrum's acid and an N-benzyl nitrone in the presence of a Brønsted base, were determined thanks to the softness and accuracy of electrospray ionization mass spectrometry coupled to ion mobility spectrometry (ESI-IMS-MS). The combined DFT study shed light on the overall organocatalytic sequence that starts with a stepwise (3+2) annulation reaction that is followed by a decarboxylative protonation sequence encompassing a stereoselective pathway issue.