An improved procedure for the Beckmann rearrangement of cyclobutanones

γ-Lactams are important building blocks for the synthesis of biologically active molecules and can easily be accessed via Beckmann rearrangement of cyclobutanones. However, Beckmann fragmentation is often a competing reaction for these strained ketones. We found that performing the Beckmann rearrangement with Tamura’s reagent in the presence of aqueous HCl suppresses the undesired fragmentation reaction. This improved procedure was applied to a broad scope of substrates affording monocyclic, bicyclic, tricyclic or spirocyclic lactams.Our experimental results and DFT calculations suggest that the mechanism of the rearrangement probably involves a tetrahedral intermediate and doesn’t proceed via oxime fragmentation as in a classical Beckmann rearrangement.     

Access to 3-aminobenzothiophenes and 3-aminothiophenes fused to 5-membered heteroaromatic rings through 6π-electrocyclization reaction of keteniminium salts

We described a general approach to 3-aminobenzothiophenes and 3-aminothiophenes fused to 5-membered heteroaromatic rings as thiophenes, furans and pyrroles through a 6π-elctrocyclization reaction of keteniminium salts. We investigated various substituents not only on the aromatic rings, but also at C-2 and on the nitrogen atom of the keteniminium salt. In particular, we have determined the electronic requirements of the nitrogen substitution to secure the efficient formation of the corresponding keteniminium salt. A clear relation between the pK_a of the amine leading to the formation of the keteniminium salt and the yield obtained for benzothiophene is established and should find broad application to other reactions involving these intermediates. Additional insight on the ease of this 6π-electrocyclization reaction was gained through competition reactions and DFT calculations.     

Kernel principal component analysis residual diagnosis (KPCARD): An automated method for cosmic ray artifact removal in Raman spectra

A new, fully automated, rapid method, referred to as kernel principal component analysis residual diagnosis (KPCARD), is proposed for removing cosmic ray artifacts (CRAs) in Raman spectra, and in particular for large Raman imaging datasets. KPCARD identifies CRAs via a statistical analysis of the residuals obtained at each wavenumber in the spectra. The method utilizes the stochastic nature of CRAs; therefore, the most significant components in principal component analysis (PCA) of large numbers of Raman spectra should not contain any CRAs. The process worked by first implementing kernel PCA (kPCA) on all the Raman mapping data and second accurately estimating the inter- and intra-spectrum noise to generate two threshold values. CRA identification was then achieved by using the threshold values to evaluate the residuals for each spectrum and assess if a CRA was present.     

First Total Syntheses of Novel Non-Enzymatic Polyunsaturated Fatty Acid Metabolites and Their Identification in Edible Oils

Oxidative stress (OS) is an in vivo process leading to free radical overproduction, which triggers polyunsaturated fatty acid (PUFA) peroxidation resulting in the formation of racemic non-enzymatic oxygenated metabolites. As potential biomarkers of OS, their in vivo quantification is of great interest. However, since a large number of isomeric metabolites is formed in parallel, their quantification remains difficult without primary standards. Three new PUFA-metabolites, namely 18-F_3t-isoprostane (IsoP) from eicosapentaenoic acid (EPA), 20-F_4t-neuroprostane (NeuroP) from docosahexaenoic acid (DHA) and 20-F_3t-NeuroP from docosapentaenoic acid (DPA_n-3) were synthesized by two complementary synthetic strategies. The first one relied on a racemic approach to 18(RS)-18-F_3t-IsoP using an oxidative radical anion cyclization as a key step, whereas the second used an enzymatic deracemization of a bicyclo[3.3.0]octene intermediate obtained from cyclooctadiene to pursue an asymmetric synthesis. The synthesized metabolites were applied in targeted lipidomics to prove lipid peroxidation in edible oils of commercial nutraceuticals.     

Reduced energy functionals for a three-dimensional fast rotating Bose Einstein condensates

We prove that in the fast rotating regime, the three-dimensional Gross–Pitaevskii energy describing the state of a Bose Einstein condensate can be reduced to a two-dimensional problem and that the vortex lines are almost straight. Additionally, we prove that the minimum of this two-dimensional problem can be sought in a reduced space corresponding to the first eigenspace of an elliptic operator. This space is called the Lowest Landau level and is of infinite dimension     

Extension du domaine de définition d'une série de Dirichlet multiplicative

We prove a general theorem which allows to approach a multiplicative Dirichlet series with two variables by a known series.     

Wavelength-tunable ultraviolet photodissociation (UVPD) of heparin-derived disaccharides in a linear ion trap

A set of three heparin-derived disaccharide deprotonated ions was isolated in a linear ion trap and subjected to UV laser irradiation in the 220–290 nm wavelength range. The dissociation yields of the deprotonated molecular ions were recorded as a function of laser wavelength. They revealed maximum absorption at 220 nm for the nonsulfated disaccharide, but centered at 240 nm for the sulfated species. The comparison of the fragmentation patterns between ultraviolet photodissociation (UVPD) at 240 nm and CID modes showed roughly the same distribution of fragment ions resulting from glycosidic bond cleavages. Interestingly, UVPD favored additional cross ring cleavages of A and X type ion series enabling easier sulfate group location. It also reduced small neutral losses (H₂O).     

Mechanistic analysis of the transition metal-catalyzed hydrogenation of imines and functionalized enamines

The asymmetric hydrogenation of prochiral imines has been mainly studied on cationic rhodium or iridium complexes and involves the coordination of the nitrogen atom on the metal centre. Oxidative addition of dihydrogen followed by one hydride transfer onto the carbon atom produces a σ-bonded nitrogen-metal intermediate from which reductive elimination occurs with the second hydride to produce the amine. From all these reactivity studies we propose that in an early step a hydrogen atom transfer could occur on the nitrogen atom to generate an iminium species which coordinates the metal centre through the CN double bond. The Shvo catalyst, an active neutral ruthenium(II) complex, presents the particularity to transfer almost simultaneously a proton from the hydroxycyclopentadienyl ligand and a hydride bonded to the metal center. In this case too, we suggest the first proton transfer generates an iminium species.Morever, a few titanium complexes have been shown to catalyze the hydrogenation of imines.Concerning enamines, literature is rather scarce on catalytic success. On the contrary, many studies focused on hydrogenation of enamides, which represent functionalized enamines, and enantiomeric excesses very close to 100% have been obtained. Extensive studies of the effect of the (chiraldiphosphine)Rh⁺ framework on the asymmetric induction have shown that several reversible steps can occur related to the oxidative addition of dihydrogen before or after the coordination of the enamide; the irreversible step directly connected to the asymmetric induction is the formation of the chiral alkyl-rhodium species.     

Photoinduced dissociation of heparin-derived oligosaccharides controlled by charge location

The development of strategies based on mass spectrometry to help for deep structural analysis of acidic oligosaccharides remains topical. We thus examined the dissociation behavior of deprotonated ions of heparin-derived di- to tetra-saccharides under UV irradiation at 220 nm. Depending on the ionization state of the carboxylic groups, an oxidized species issued from electron photodetachment was observed in complement to photoinduced fragmentation of precursor ions. The influence of the charge location in the oligosaccharide dianions on the balance between photodissociation and electron photodetachment is examined and a way to direct the relaxation pathways, (i.e., dissociation versus electron detachment), is proposed using sodium adducts. The oxidized species was subjected to activated-electron photodetachment (activated-EPD) leading to complementary informative fragment ions to those issued from photodissociation. Directed photoinduced dissociation at 220 nm and activated-EPD should complement the more conventional CAD and IRMPD activation modes for deeper structural analysis of acidic oligosaccharides-derived anions.     

SMARTER crystallography of the fluorinated inorganic-organic compound Zn3Al2F12·[HAmTAZ]6

We present in this paper the structure resolution of a fluorinated inorganic-organic compound--Zn(3)Al(2)F(12)·[HAmTAZ](6)--by SMARTER crystallography, i.e. by combining powder X-ray diffraction crystallography, NMR crystallography and chemical modelling of crystal (structure optimization and NMR parameter calculations). Such an approach is of particular interest for this class of fluorinated inorganic-organic compound materials since all the atoms have NMR accessible isotopes ((1)H, (13)C, (15)N, (19)F, (27)Al, (67)Zn). In Zn(3)Al(2)F(12)·[HAmTAZ](6), (27)Al and high-field (19)F and (67)Zn NMR give access to the inorganic framework while (1)H, (13)C and (15)N NMR yield insights into the organic linkers. From these NMR experiments, parts of the integrant unit are determined and used as input data for the search of a structural model from the powder diffraction data. The optimization of the atomic positions and the calculations of NMR parameters ((27)Al and (67)Zn quadrupolar parameters and (19)F, (1)H, (13)C and (15)N isotropic chemical shifts) are then performed using a density functional theory (DFT) based code. The good agreement between experimental and DFT-calculated NMR parameters validates the proposed optimized structure. The example of Zn(3)Al(2)F(12)·[HAmTAZ](6) shows that structural models can be obtained in fluorinated hybrids by SMARTER crystallography on a polycrystalline powder with an accuracy similar to those obtained from single-crystal X-ray diffraction data.