Acid Rearrangement Research Articles

Theoretical investigation on diastereoselective [2+2] cycloaddition and Pd-catalyzed enantioselective [3+2] cycloaddition for synthesis of cis-β-lactam and exo-furobenzopyranone

The mechanism is investigated for Wolff rearrangement/Staudinger [2+2] cycloaddition cascade and Pd-catalyzed, decarboxylative, formal [3+2] cycloaddition. Wolff rearrangement of 3-diazotetramic acid is determined to be rate-limiting step generates cyclic acyl ketene. The interaction of ketene with imine firstly results in zwitterion followed by conrotatory cyclization giving major cis-β-lactam. For synthesis of s-VECs, the epoxidation−cyclization cascade and hydrolysis give precursor of better performing exocyclic derivative. The reaction with 3-cyanochromone includes decarboxylation, nucleophilic attack and subsequent ring closure yielding 5-exo-trig furobenzopyranone. Based on the comparison between possible paths, the diastereoselectivity of cis over trans and regio-divergence of 5-exo-trig over 7-endo-trig are both kinetically controlled for [2+2] and [3+2] cycloaddition in common. The positive solvation effect is suggested by decreased absolute and activation energies in chlorobenzene and chloroform solution compared with in gas. These results are supported by Multiwfn analysis on FMO composition of specific TSs, and MBO value of vital bonding, breaking.

Late-Stage Formation of a Sactionine Linkage Enabled by Lossen Rearrangement of Glycyl Hydroxamic Acid.

Late-stage formation of a sactionine thioether bond connecting a Gly α-carbon and Cys thiol was achieved by Lossen rearrangement of a glycyl hydroxamic acid (GlyHA) residue in a peptide. Lossen rearrangement allowed conversion of GlyHA within a peptide to an N-acyl iminium equivalent, which subsequently reacted with S-acetamidomethyl Cys (Cys(Acm)) in TFA in the presence of guanidine hydrochloride (Gn·HCl) to yield the desired thioether linkage in the final stage.

Interspecies hybridization between Auricularia cornea cv. Yu Muer and Auricularia heimuer cv. Bai Muer through protoplast fusion.

Color variations in cultivated edible mushrooms present novel and potentially valuable alternatives to the research and cultivation industries. We collected, identified, and domesticated a white strain of Auricularia cornea and a white strain of Auricularia heimuer from China. However, due to an unstable phenotype and stricter requirements on environment and management technology, the production and utilization of Auricularia heimuer cv. Bai Muer make slow progress. Outcrossing is an essential means to broaden the intraspecific genetic resources to expand the gene pool and compensate for the limitations of related species hybridization. In this study, interspecies hybridization between Auricularia cornea cv. Yu Muer and Auricularia heimuer cv. Bai Muer was conducted using polyethylene glycol (PEG)-induced double-inactivated protoplast fusion. Apart from the functional complementation of double-inactivated protoplasts, the hybrids were characterized by colony morphology, antagonistic test, primordial morphology, and polymerase chain reaction (PCR) fingerprinting. The results suggested that the hybrids and their parents showed significant differences in their colony morphology. Moreover, positive barrage reactions were observed between each parent and hybrid. Inter-simple sequence repeat (ISSR) and start codon targeted (SCoT) profile analysis of fusants and parents depicted that fusants contained polymorphic bands, which indicated the rearrangement and deletion of deoxyribonucleic acid (DNA) in the fusants. Yellowish-white primordia were obtained from two hybrids. Protoplast fusion may reinforce the genetic potential and provide an ideal alternative for breeding albino Auricularia.

Use of Some Metalferrites as Catalyst in Benzil-Benzilicacid Rearrangement Reaction

Magnesium ferrite was used to catalyse the Benzil-Benzilic acid rearrangement reaction of 1,2-rearrangement of 1,2-diketones to α-hydroxy carboxylic acids in presence of a base. Magnesium ferrite was prepared by hydrothermal process. It was characterized by Field Emission Scanning Electron Microscopy (FESEM), X-Ray Diffraction Spectroscopy (XRD), and Energy Dispersive X-Ray Spectroscopy (EDX). The crystalline size of magnesium ferrite was found to have 82.47nm and these are irregular in shape. It was found that the yield of the product (benzilic acid) in the presence of Mg ferrite was 81.6%, which is almost 2.3 times the yield obtained in the absence of catalyst. A comparative study was made with different metal ferrites as catalyst and it was found that the activity of metal ferrites followed the order: MgFe2O4 > Cu Fe2O4 > Ni Fe2O4 > Co Fe2O4 > Zn Fe2O4

Enantioselective [2,3]-Wittig Rearrangement of Carboxylic Acid Derived Enolates by Tetradentate Chiral Lithium Amide

AbstractA chiral lithium amide mediated enantioselective [2,3]-Wittig rearrangement of carboxylic acid enolate has been developed. The reaction proceeds through the formation of a chiral mixed aggregate that shields one enantioface of enolate anion to give a highly functionalized chiral α-hydroxycarboxylic acid.

Isomerization of 6-O-substituted glucose and fructose under neutral pH conditions and subsequent β-elimination reactions

Isomaltose (6-O-α-d-glucopyranosyl-d-glucose) and isomaltulose (palatinose; 6-O-β-d-glucopyranosyl-d-fructose) were heated to 90 °C in 100 mM sodium phosphate buffer (pH 7.5). Aldose–ketose isomerization between isomaltose, isomaltulose, and epi-isomaltulose was observed in the early stage of the reaction, alongside the release of a small amount of glucose. The total concentration of these disaccharides gradually decreased as the heating time increased. However, this decrease did not correlate with the amount of glucose or fructose released, suggesting that the releases of these monosaccharides were not caused by the hydrolysis of glycosidic linkages. A slight decrease in the pH of the reaction solution was attributed to the formation of two organic acids, 6-O-β-d-glucopyranosyl-3-deoxy-d-arabino-hexonic acid (1) and 6-O-β-d-glucopyranosyl-3-deoxy-d-ribo-hexonic acid (2). These compounds were formed from the β-elimination of the hydroxyl group at the C-3 of fructose, leaving a substituted glucose residue at the C-6 position, followed by keto–enol tautomerization and benzilic acid rearrangement. Although approximately 30% of 1 and 2 were degraded after 360 min of heating at 90 °C in 100 mM sodium phosphate, a little release of glucose was observed, indicating no hydrolysis of the glucoside bond at C-6. Besides 1 and 2, time-dependent changes in the NMR spectra of the reaction mixture in water indicated the formation of formic acid and the presence of species possibly resulting from the β-elimination of the hydroxyl group from 3- and 4-ulose. The glucose released by heating isomaltose and isomaltulose may be generated via tautomerizations of keto-enols between the C-4 and C-5 positions and cleavage of 6-O-glycosidic linkage via β-elimination.

Dibenzocyclooctendiones (DBCDOs): Arginine-Selective Chemical Labeling Reagents Obtained through Benzilic Acid Rearrangement.

We demonstrate that dibenzocyclooctendiones (DBCDOs) are efficient chemical reagents for the site-specific labeling of arginine-containing biomolecules. Unlike the commonly used probes, DBCDOs undergo an irreversible ring-contracted rearrangement with the guanidinium group on arginine residues under mild reaction conditions. The regioselective dual-labeled arginine residues were obtained in a one-pot reaction with our tested substrates. The efficiency of DBCDOs reactions and their ease of synthesis make DBCDOs an attractive choice for the site-selective bioconjugation of arginine.

Enyne diketones as substrate in asymmetric Nazarov cyclization for construction of chiral allene cyclopentenones

The Nazarov cyclization is one of the most powerful tools for the stereoselective synthesis of various cyclopentenone scaffolds. Therefore, developing the new classes substrate of Nazarov reaction is an important endeavor in synthetic chemistry. Herein, we report enyne diketones, enables diastereo- and enantioselective construction of chiral allene cyclopentenones in moderate to good yields with good enantioselectivities (up to 97% ee). Importantly, it is a typical example for asymmetric synthesis of cyclopentanones with allene moiety using Nazarov cyclisation. Mechanistic studies indicate that this metal-organo relay catalysis protocol involves a rhodium-catalyzed tandem oxonium ylide formation/[2,3]-sigmatropic rearrangement/reverse benzylic acid rearrangement, followed by organo-catalyzed asymmetric Nazarov cyclization/alkyne-to-allene isomerization to give the final chiral allene cyclopentenones.

Microfluidic fatty acid rearrangement in silkworm pupae oil with magnetically responsive lipase under continuous-flow condition

Silkworm pupae-derived structured lipids are expected to promote the absorption of unsaturated fatty acids, however, low efficiency of bioprocess and low reusability of biocatalyst limit the corresponding biocatalysis technology. Thus, a novel strategy combining magnetic response immobilized lipase and continuous-flow microchannel reactor was proposed to modify silkworm pupae oil. The lipase from Aspergillus niger was immobilized on the surface of chitosan cross-linked magnetic nanoparticles, with increased esterification activity from 151.51 to 418.10 U/g due to the hydrophobic microenvironment. In the microchannel, the enzyme activity could be increased to 2371.3 U/g because of the strengthening effect of the microfluidic field. Furthermore, the employment of chitosan cross-linked magnetic nanoparticles leads to good reusability, and the remaining activity could stay above 90% after 13 cycles. Moreover, the immobilized lipase could be removed and loaded easily due to the employment of magnetically responsive nanoparticles. In addition, 2 min was required to rearrange the unsaturated fatty acids, increasing the relative content of sn-1.3 unsaturated fatty acids from 59.91% to 74.8% and sn-2 palmitic acid from 2.69% to 18.88%, which indicated the improved nutritional value of modified silkworm pupae oil. Therefore, the combination of microfluidic field and hydrophobic microenvironment formed by the chitosan layer on the surface of the nanoparticles effectively strengthens the biocatalysis in a solvent-free system, while the developed strategy provides a convenient biocatalysis strategy for the quality improvement of edible insect oil.

Transformation of a Chiral Glycolic Acid to an Isoaurone: Stereochemical Assignment of a Benzilic Acid Rearrangment Product

AbstractThe benzilic acid rearrangement (BAR) has been exploited with great effect over the last decades, used as the key step in many cases to afford complex target structures with interesting properties. Although the reaction is inherentely stereoselective in cyclic systems, the results achieved using acylic diketone systems can be less satisfactory. This report describes a highly stereoselective BAR in an acyclic system that gives a glycolic acid product which is then transformed via an elimination reaction to an unusual isoaurone product, in fact this latter product was the key to unravelling the stereochemistry of the glycolic acid product. The elimination reaction mechanism was studied using computational approaches.

Generation of 3-deoxypentulose by the isomerization and β-elimination of 4-O-substituted glucose and fructose

Aldose–ketose isomerization is commonly used to prepare rare oligosaccharides such as maltulose (4-O-α-d-glucopyranosyl-d-fructose) and lactulose (4-O-β-d-galactopyranosyl-d-fructose). However, both sugars are degraded under alkaline conditions via β-elimination, while their subsequent benzylic acid rearrangement leads to the formation of isosaccharinic acids. Here, we investigated the behavior of maltose and maltulose upon heating in phosphate buffer solution at pH 7.5. Maltose was initially isomerized into maltulose. Maltulose was degraded via β-elimination, followed by keto–enol tautomerization, which led to the formation of a 1,3-dicarbonyl intermediate bearing an aldehyde group at the C-1 position and a ketone group at the C-3 position. Subsequent hydrolysis of this intermediate afforded formic acid and 3-deoxy-d-glycero-pent-2-ulose (1) as the major products based on HPLC and NMR data. In contrast, the formation of isosaccharinic acid via benzylic acid rearrangement, not the 3-deoxypentulose, was reported under the strongly alkaline conditions (Knill and Kennedy, 2003). The heat treatment of 1→4 linked oligo- and polysaccharides possessing glucose or fructose residue at the reducing end under neutral pH conditions could be applied for the practical preparation of a 3-deoxypentulose.

Electrosynthesis of 1,4-bis(diphenylphosphanyl) tetrasulfide via sulfur radical addition as cathode material for rechargeable lithium battery

Organic electrodes are promising as next generation energy storage materials originating from their enormous chemical diversity and electrochemical specificity. Although organic synthesis methods have been extended to a broad range, facile and selective methods are still needed to expose the corners of chemical space. Herein, we report the organopolysulfide, 1,4-bis(diphenylphosphanyl)tetrasulfide, which is synthesized by electrochemical oxidation of diphenyl dithiophosphinic acid featuring the cleavage of a P–S single bond and a sulfur radical addition reaction. Density functional theory proves that the external electric field triggers the intramolecular rearrangement of diphenyl dithiophosphinic acid through dehydrogenation and sulfur migration along the P–S bond axis. Impressively, the Li/bis(diphenylphosphanyl)tetrasulfide cell exhibits the high discharge voltage of 2.9 V and stable cycling performance of 500 cycles with the capacity retention of 74.8%. Detailed characterizations confirm the reversible lithiation/delithiation process. This work demonstrates that electrochemical synthesis offers the approach for the preparation of advanced functional materials.

Sesquiterpene Lactones from Artemisia absinthium. Biotransformation and Rearrangement of the Insect Antifeedant 3α-hydroxypelenolide.

Three new compounds, the sesquiterpenes absilactone and hansonlactone and the acetophenone derivative ajenjol, have been isolated from a cultivated variety of Artemisia absinthium. In addition, the major lactone isolated, 3α-hydroxypelenolide, was biotransformed by the fungus Mucor plumbeus affording the corresponding 1β, 10α-epoxide. A cadinane derivative was formed by an acid rearrangement produced in the culture medium, but not by the enzymatic system of the fungus. Furthermore, 3α-hydroxypelenolide showed strong antifeedant effects against Leptinotarsa decemlineata and cytotoxic activity to Sf9 insect cells, while the biotransformed compounds showed antifeedant postingestive effects against Spodoptera littoralis.

Computational Exploration of the Mechanism of Critical Steps in the Biomimetic Synthesis of Preuisolactone A, and Discovery of New Ambimodal (5 + 2)/(4 + 2) Cycloadditions.

Computational studies with ωB97X-D density functional theory of the mechanisms of the steps in Trauner's biomimetic synthesis of preuisolactone A have elaborated and refined mechanisms of several unique processes. An ambimodal transition state has been identified for the cycloaddition between an o-quinone and a hydroxy-o-quinone; this leads to both (5 + 2) (with H shift) and (4 + 2) cycloaddition products, which can in principle interconvert via α-ketol rearrangements. The origins of periselectivity of this ambimodal cycloaddition have been investigated computationally with molecular dynamics simulations and tested further by an experimental study. In the presence of bicarbonate ions, the deprotonated hydroxy-o-quinone leads to only the (5 + 2) cycloaddition adduct. A new mechanism for a benzilic acid rearrangement resulting in ring contraction is proposed.

1,3]-Claisen Rearrangement via Removable Functional Group Mediated Radical Stabilization.

A thermal O-to-C [1,3]-rearrangement of α-hydroxy acid derived enol ethers was achieved under mild conditions. The 2-aminothiophenol protection of carboxylic acids facilitates formation of the [1,3] precursor and its thermal rearrangement via stabilization of a radical intermediate. Experimental and theoretical evidence for dissociative radical pair formation, its captodative stability via aminothiophenol, and a unique solvent effect are presented. The aminothiophenol was deprotected from rearrangement products as well as after derivatization to useful synthons.

Stereoselective benzilic acid rearrangements: new advances on an old story.

The benzilic acid rearrangement (BAR) is the oldest rearrangement on record. It is a powerful synthetic tool for accessing significant biologically active molecules. The reaction is both catalytic (generally Lewis acid) and stereoselective, recently the first catalytic asymmetric version was reported with astonshing results (ees of up to 97%) to give chiral tartronic esters. In this unique highlight, we look at the progress made over the last 10 years on the stereoseletive aspects of this synthetic transformation, showing interesting examples of this rearrangment in both acyclic and cyclic systems (like for instance its importance in the stereoselective synthesis of syn and anti-hydroxy-iso-evoninic acids, α-hydroxy-α-perfluoroalkyl esters, a selective nonsteroidal mineralocorticoid receptor antagonist, Geldanamycin type polyketides and (-)-isatisine A, etc.) and the differnces in stereoselectivity encountered which culminated recently in the conquest of the first catalytic asymmetric example on record.

Synthesis, Characterization and Anti-epileptic Activity of Thiohydantoin Derivatives

A vast number of biological properties have been recognised to Thiohydantoin derivatives, have attracted continuing interest because of their various biological activities, namely anticonvulsant, hypolipidemic activity, anti-thyroidal activity, and anti-microbial actions. In this look upon, multiple numbers of Thiohydantoin derivatives are synthesised besides anti-epileptic mechanisms have been investigated. A series of 3-substituted 2-thiohydantoin Derivatives were synthesised from Benzil via Benzil-Benzilic Acid Rearrangement, characterised and evaluated for their anti-epileptic activity by Maximal Electroshock Seizure (MES) model for the anti-epileptic activity of synthesised compounds was less when compared to standard. Among the activity, synthesised compounds 1 indicated more anti-epileptic activity. With this confirmation, we revised integrated a series of innovative 3-substituted 2-thiohydantoin derivatives with a different substituent on the construction and studied the structural activity relationship. The outcomes indicated with the purpose of all the tested compounds have displayed evident anti-epileptic activity. Among the series compounds, 1 shows more anti-epileptic activity than other synthesised compounds.

Copper(II)-Assisted Ligand Fragmentation Leading to Three Families of Metallamacrocycle.

We present an unprecedented copper(II)-assisted organic ligand fragmentation process under basic conditions leading to several ligands within three families of metallamacrocycle, Cu6, Cu8, and Cu16. The sequential multistep reaction include (i) the deprotonation of the starting alcohol, 1,2-bis(3,5-dimethyl-pyrazol-1-yl)ethane-1,2-diol (H2bdped) to its diolate bdped followed by complexation through six bonds (μ6) to three copper atoms in a ring, (ii) the breaking of the ethane-pyrazole C-N bonds by the different solvent alcohols to form 1-(3,5-dimethyl-pyrazol-1-yl)-2-methoxyethane-1,2-diolate (dpmed) or 2-(3,5-dimethyl-pyrazol-1-yl)-2-hydroxyacetate (dpet), while retaining coordination to the copper centers and (iii) the final step to ethane-1,1,2,2-tetraolate, C2H2O44- (et). Importantly, the latter product, only observed on two previous occasions, occupies the core of Cu6 and Cu16 through exceptionally eight coordination bonds (μ8). Its alkyl esters, 2-alkoxyethane-1,1,2-triolate (met, eet, and pet), also occupy the central parts of Cu8 but forming six bonds (μ6) instead. The other product, 3,5-dimethylpyrazolate (dp), acts as peripheral bridges (μ2) but it is not involved in coordination if the starting salt is copper acetate, this may be a consequence of acetate being a better μ2-chelating ligand. In the presence of an oxidizing agent, K2Cr2O7, C2H2O44- (et) is oxidized to oxalate, C2O42- (ox). Thus, an additional μ3-hydroxide and μ4-oxalate in Cu16 widen the complexity of the structures, not to mention the range of coordination geometries of the copper centers, though in the present cases they can be classed in only two types: distorted square-planar and square-pyramid. In addition to single-crystal crystallography, the results from different techniques such as IR, ESI-MS, optical UV-vis, and SQUID magnetometry help in the characterization of these rare metallamacrocycles made from unexpected and in situ generated ligands. We believe the results of the organic transformations are highly relevant to von Liebig's benzil-benzilic acid rearrangement.

A Practical Approach to Ureas and Thiocarbamates: SO2F2‐Promoted Lossen Rearrangement of Hydroxamic Acid

AbstractIn this update, we report a simple, mild and practical method for the synthesis of symmetrical urea via Lossen rearrangement promoted by SO2F2, which achieves the conversion from hydroxamic acid to symmetrical urea in high selectivity and provides a new method for facile initiation of Lossen rearrangement. Meanwhile, the reaction within amine or thiol also provide the efficient synthetic strategy towards unsymmetrical urea or thiocarbamates. Significant for gram‐scale application, we afford the desired product on gram‐scale by filtration without further purification. A plausible mechanism which is supported by control experimental and spectral data is proposed.

Direct Visualization of a Mechanochemically Induced Molecular Rearrangement

AbstractRecent progress in the field of mechanochemistry has expanded the discovery of mechanically induced chemical transformations to several areas of science. However, a general fundamental understanding of how mechanochemical reactions by ball milling occur has remained unreached. For this, we have now implemented in situ monitoring of a mechanochemically induced molecular rearrangement by synchrotron X‐ray powder diffraction, Raman spectroscopy, and real‐time temperature sensing. The results of this study demonstrate that molecular rearrangements can be accomplished in the solid state by ball milling and how in situ monitoring techniques enable the visualization of changes occurring at the exact instant of a molecular migration. The mechanochemical benzil–benzilic acid rearrangement is the focal point of the study.