Unexpected Isomerization Research Articles

Direct synthesis of N-functionalized indoles through isomerization of azomethine ylides.

An unexpected isomerization of azomethine ylides generated in situ from isatin with indoline-2-carboxylic acid has been disclosed, providing direct access to N-functionalized indole scaffolds. This protocol has good functional group tolerance and provides various 3-(1H-indol-1-yl)indolin-2-one derivatives in moderate to high yields simply by using alcohol as the solvent, with no additional additive being required.

Atmospheric Chemistry of NH2SO3H in Polluted Areas: An Unexpected Isomerization of NH2SO3H in Acid-Polluted Regions.

NH2SO3H is an effective nucleation agent for the formation of atmospheric aerosols and cloud particles. So, the ammonolysis of SO3 to form NH2SO3H without and with neutral (H2O) and basic (NH3) trace gases has been extensively investigated. However, the acidic trace gas X (X = H2SO4 and CH3SO3H)-assisted ammonolysis of SO3 is still up for debate. In this work, a comprehensive theoretical investigation of X-assisted ammonolysis of SO3 and its reverse reaction (the isomerization of NH2SO3H to form SO3-···NH3+) was carried out in the gas phase and at the air-water interface. The gas-phase results show that X-assisted isomerization of NH2SO3H to form SO3-···NH3+ is more energetically and kinetically favorable than its reverse reaction and the isomerization of NH2SO3H in the presence of H2O and NH3. Such unexpected findings revealed that gas-phase NH2SO3H is highly reactive in the presence of acidic trace gas in contrast to the high stability of NH2SO3H in neutral and basic conditions. At the air-water interface, the X-assisted isomerization reaction of NH2SO3H involves multiple water molecules. The loop structure of the reaction center (X···NH2SO3H···3H2O) promotes the transfer of protons in the water molecules to form the SO3-···NH3+ ion pair, which can then interact with several interfacial water molecules to form ammonium bisulfate. These interfacial reaction channels follow a stepwise mechanism and proceed at the picosecond time-scale. The findings of this study will contribute to a better understanding of the atmospheric behavior of NH2SO3H in polluted acidic trace gases.

Toward a Formyl-to-Phenyl Conversion: An Unexpected Photochemical Fulvene Rearrangement.

Toward a conversion of aldehydes into arenes, we designed a sequence involving the initial reaction of an aldehyde to give a fulvene, followed by photochemical and platinum-catalyzed rearrangements into a Dewar benzene derivative, which finally isomerizes into the targeted arene. While computational studies support the plausibility of this route, we found that fulvene irradiation resulted in an unexpected isomerization into a spiro[2.4]heptadiene. This unusual photorearrangement has been investigated mechanistically and provides access to a variety of spiro[2.4]heptadienes with different substituents.

Auf dem Weg zu einer Formyl‐zu‐Phenyl‐Reaktion: Eine unerwartete photochemische Fulven‐Umlagerung

AbstractUm Aldehyde in Arene zu überführen, haben wir eine Sequenz entworfen, bei der ein Aldehyd zunächst zu einem Fulven umgesetzt wird. Daraufhin folgen photochemische und platinkatalysierte Umlagerungen zu einem Dewar‐Benzol‐Derivat, welches schließlich in das gewünschte Aren isomerisiert. Obwohl theoretische Berechnungen die Plausibilität dieses Weges nahelegen, stellten wir experimentell fest, dass die Fulven‐Bestrahlung zu einer unerwarteten Isomerisierung in ein Spiro[2.4]heptadien führt. Diese ungewöhnliche Photoumlagerung wurde mechanistisch untersucht und ermöglicht den Zugang zu verschiedenen Spiro[2.4]heptadienen mit unterschiedlichen Substituenten.

Unexpected Isomerization of Oxetane-Carboxylic Acids.

Many oxetane-carboxylic acids were found to be unstable. They easily isomerized into new (hetero)cyclic lactones while being stored at room temperature or slightly heated. Chemists should keep in mind the high instability of these molecules, as this could dramatically affect the reaction yields and lead to negative results (especially in those reactions that require heating).

Synergistic roles of B/L acids and hierarchical micro-mesoporous structures for the unexpected isomerization of β-pinene over dual-modified MOR zeolite by inorganic/organic bases

The isomerization of β -pinene is an important reaction to synthesize spices, such as camphene, limonene, terpinene, and terpinolene, among which terpinene and terpinolene are particularly difficult to be obtained. Herein, MOR zeolite modified by both inorganic base (NaOH) and organic base (TEAOH) was conducted, which showed high catalytic activity for the isomerization of β -pinene to high-added value spices of terpinene and terpinolene. Different from the zeolite catalyst modified by solely inorganic base or organic base, both high conversion of β -pinene and high selectivity for terpinene and terpinolene could be achieved over the dual-modified zeolite catalyst. Based on the various characterizations, catalytic reaction results and comparison studies, the roles of inorganic base and organic base were revealed and possible reaction mechanism was described. The modification by inorganic base was mainly to introduce additional mesopores in the MOR zeolite, which had important influence on the conversion of β -pinene through accelerating the diffusion and mass transfer of various bulky organic molecules in the reaction system. The modification by organic base was mainly to tune the Brønsted/Lewis (B/L) acid property, which had important impact on the selectivity of products. In contrast, the zeolite modified by solely inorganic base mainly showed Lewis acidity, which led to camphene and limonene as the main products; the zeolite modified by solely organic base mainly showed Brønsted acidity, which produced camphene, terpinene and terpinolene as the main products. The dual-modified zeolite catalyst by inorganic/organic bases could achieve 99.5% conversion of β -pinene with the total selectivity for terpinene and terpinolene as high as 70.9%. In addition, the catalyst showed high reaction-recycling stability, which could maintain the catalytic performance up to 10 recycles. • Synergistic roles of B/L acids and hierarchical structures. • Catalytic synthesis terpinene and terpinolene by β -pinene isomerization. • Inorganic/organic bases dual-modified MOR zeolite catalyst. • Efficient heterogeneous catalyst with excellent recycling stability.

Three‐Component Castagnoli‐Cushman Reaction of 3‐Arylglutaconic Acid Anhydrides, Carbonyl Compounds, and Ammonium Acetate: a Quick and Flexible Way to Assemble Polysubstituted NH‐δ‐lactams

AbstractA practical straightforward synthesis of medicinally important NH‐δ‐lactams through the three‐component Castagnoli‐Cushman reaction of 3‐arylglutaconic anhydrides with carbonyl compound and ammonium acetate has been developed. The scope of the protocol has been thoroughly explored paying particular attention to the carbonyl component using wide array of aliphatic and aromatic aldehydes as well as rarely involved cyclic and acyclic ketones. Synthetic potential of prepared compounds was demonstrated by a series of post‐modifications, including unexpected isomerization.

Trans-3-Methylglutaconyl CoA isomerization-dependent protein acylation

3-methylglutaconic (3MGC) aciduria is associated with a growing number of discrete inborn errors of metabolism. Herein, an antibody-based approach to detection/quantitation of 3MGC acid has been pursued. When trans-3MGC acid conjugated keyhole limpet hemocyanin (KLH) was inoculated into rabbits a strong immune response was elicited. Western blot analysis provided evidence that immune serum, but not pre-immune serum, recognized 3MGC-conjugated bovine serum albumin (BSA). In competition ELISAs using isolated immune IgG, the limit of detection for free trans-3MGC acid was compared to that for cis-3MGC acid and four structurally related short-chain dicarboxylic acids. Surprisingly, cis-3MGC acid yielded a much lower limit of detection (∼0.1 mg/ml) than trans-3MGC acid (∼1.0 mg/ml) while all other dicarboxylic acids tested were poor competitors. The data suggest trans-3MGC- isomerized during, or after, conjugation to KLH such that the immunogen was actually comprised of KLH harboring a mixture of cis- and trans-3MGC haptens. To investigate this unexpected isomerization reaction, trans-3MGC CoA was prepared and incubated at 37 °C in the presence of BSA. Evidence was obtained that non-enzymatic isomerization of trans-3MGC CoA to cis-3MGC CoA precedes intramolecular catalysis to form cis-3MGC anhydride plus CoASH. Anhydride-dependent acylation of BSA generated 3MGCylated BSA, as detected by anti-3MGC immunoblot. The results presented provide an explanation for the unanticipated detection of 3MGCylated proteins in a murine model of primary 3MGC aciduria. Furthermore, non-enzymatic hydrolysis of cis-3MGC anhydride represents a potential source of cis-3MGC acid found in urine of subjects with 3MGC aciduria.

Unexpected Isomerization of Hexa-tert-butyl-octaphosphane.

Octaphosphane {cyclo‐(P4 tBu3)}2 (1) undergoes an unexpected isomerization reaction to the constitutional isomer 2,2′,2′′,2′′′,3,3′‐hexa‐tert‐butyl‐bicyclo[3.3.0]octaphosphane (2) in the presence of Lewis acidic metal salts. The mechanism of this reaction is discussed and elucidated with DFT calculations. The results underline the fascinating similarity between phosphorus‐rich and isolobal carbon compounds. The new bicyclic octaphosphane 2 shows a dynamic behavior in solution and reacts with [AuCl(tht)] (tht=tetrahydrothiophene) to give a mono‐ ([AuCl(2‐κP 3)], 3) and a dinuclear complex ([(AuCl)2(2‐κP 3,κP 3′)], 4). With cis‐[PdCl2(cod)] (cod=1,5‐cyclooctadiene), the chelate complex ([PdCl2(2‐κ2 P 2,P 2′)], 5) with a different coordination mode of the ligand was obtained.

Cover Feature: Unexpected Isomerization of Hexa‐tert‐butyl‐octaphosphane (Chem. Eur. J. 5/2020)

The vitruvian phosphane is presented! Just as da Vinci's drawing, it shows two superimposed phosphane molecules and thus a conflation of both phosphorus frameworks. Similar to their isolobal organic relatives, these isomers of hexa-tert-butyl-octaphosphane interconvert, which is represented herein by a rotation of 90°, keeping the two central P atoms fixed. The new phosphorus-rich molecule with pentalane structure coordinates to gold(I) or palladium(II) with different coordination modes. The beauty that lies in these structures is a reminder of da Vinci's masterpiece. More information can be found in the Communication by E. Hey-Hawkins and T. Grell on page 1008.

Synthesis and Properties of Energetic Hydrazinium 5-Nitro-3-dinitromethyl-2H-pyrazole by Unexpected Isomerization of N-Nitropyrazole.

A new energetic salt, hydrazinium 5-nitro-3-dinitromethyl-2H-pyrazole, was synthesized using 1-nitro-3-trinitromethylpyrazole and hydrazine as raw materials and fully characterized by IR and NMR spectroscopy, elemental analysis, and X-ray crystallography. The isomerization of N-nitropyrazole in the reaction condition was first reported and the possible mechanism was explained by the density functional theory method. The salt has good density, high positive enthalpy of formation superior to those of the RDX and HMX, and good detonation properties comparable to those of RDX. By denitration and isomerization reactions, the salt gains a better thermal stability and lower sensitivity toward impact and friction compared with its parent compound. Based on an overall energetic evaluation, the salt has a promising future as an alternative explosive. The research also contributes to the synthesis and application of polynitro-substituted N-heterocyclic compounds as energetic materials.

Bastimolide B, an Antimalarial 24-Membered Marine Macrolide Possessing a tert-Butyl Group.

We reported previously the discovery of the potent antimalarial 40-membered macrolide bastimolide A (1) from the tropical marine cyanobacterium Okeania hirsute. Continued investigation has led to the discovery of a new analogue, bastimolide B (2), a 24-membered polyhydroxy macrolide with a long aliphatic chain and unique terminal tert-butyl group. Its complete structure was determined by a combination of extensive spectroscopic methods and comparative analysis of its methanolysis products with those of bastimolide A. A methanolysis mechanism for bastimolide A is proposed, and one unexpected isomerization product of the C2-C3 double bond, 2-(E)-bastimolide A (3), was obtained. Bastimolide B (2) showed strong antimalarial activity against chloroquine-sensitive Plasmodium falciparum strain HB3. A preliminary investigation of the structure-activity relationship based on six analogues revealed the importance of the double bond as well as the 1,3-diol and 1,3,5-triol functionalities.

Phosphenium Hydride Reduction of [(cod)MX2] (M = Pd, Pt; X = Cl, Br): Snapshots on the Way to Phosphenium Metal(0) Halides and Synthesis of Metal Nanoparticles

The outcome of the reduction of [(cod)PtX2] (X = Cl, Br; cod = 1,5-cyclooctadiene) with N-heterocyclic phosphenium hydrides RNHP-H depends strongly on the steric demand of the N-aryl group R and the nature of X. Reaction of [(cod)PtCl2] with DippNHP-H featuring bulky N-Dipp groups produced an unprecedented monomeric phosphenium metal(0) halide [(DippNHP)(DippNHP-H)PtCl] stabilized by a single phosphine ligand. The phosphenium unit exhibits a pyramidal coordination geometry at the phosphorus atom and may according to DFT calculations be classified as a Z-type ligand. In contrast, reaction of [(cod)PtBr2] with the sterically less protected MesNHP-H afforded a mixture of donor-ligand free oligonuclear complexes [{(MesNHP)PtBr}n] (n = 2, 3), which are structural analogues of known palladium complexes with μ2-bridging phosphenium units. All reductions studied proceed via spectroscopically detectable intermediates, several of which could be unambiguously identified by means of multinuclear (1H, 31P, 195Pt) NMR spectroscopy and computational studies. The experimental findings reveal that the phosphenium hydrides in these multistep processes adopt a dual function as ligands and hydride transfer reagents. The preference for the observed intricate pathways over seemingly simpler ligand exchange processes is presumably due to kinetic reasons. The attempt to exchange the bulky phosphine ligand in [(DippNHP)(DippNHP-H)PtCl] by Me3P resulted in an unexpected isomerization to a platinum(0) chlorophosphine complex via a formal chloride migration from platinum to phosphorus, which accentuates the electrophilic nature of the phosphenium ligand. Phosphenium metal(0) halides of platinum further show a surprising thermal stability, whereas the palladium complexes easily disintegrate upon gentle heating in dimethyl sulfoxide to yield metal nanoparticles, which were characterized by TEM and XRD studies.

ChemInform Abstract: Stereocontrolled Synthesis of Benzo[k]fluoranthenes — An Unexpected Isomerization Mediated by Rhodacyclopentadiene.

AbstractHerein, a RhIII‐catalyzed stereocontrolled synthesis of benzo[k]fluoranthenes is reported.

Facile Rearrangement of a Bis(N‐heterocyclic carbene)borate Chelate Ligand and Access to [:GeX]+ Complexes (X = H, Cl)

AbstractThe unexpected isomerization of the potassium bis(N‐heterocyclic carbene)borate [BPh2(tBuNHC)2]K (2′) (tBuNHC = 3‐tert‐butylimidazole‐2‐ylidene) in toluene, affording the unique potassium imidazolyl–NHC–borate [BPh2(tBuIm)(tBuNHC)]K (2) (tBuIm = 3‐tert‐butyl‐2‐imidazolyl), is reported. The latter crystallizes as the centrosymmetric dimer 22. According to the results of DFT calculations, the rearrangement of 2′ is basically triggered by the solvation of the K+ ion: while 2′ is most stable in THF solutions, the formation of 2 is feasible in least coordinating toluene and drastically favored through dimerization to give 22. The latter reacts with GeCl2·dioxane to form solely the unprecedented chlorogermyliumylideneborate [BPh2(tBuIm)(tBuNHC)]GeCl (3). Treatment of 3 with KHB(sBu)3 furnishes the corresponding hydridogermyliumylideneborate complex [BPh2(tBuIm)(tBuNHC)]GeH (4) in 66 % yield.

Unexpected Isomerisation of a Fragment Analogue During Fragment-Based Screening of HIV Integrase Catalytic Core Domain

Fragment-based screening of human immunodeficiency virus type 1 (HIV) integrase revealed several aromatic carboxylic acid fragment hits, some of which bound weakly at the site on the HIV-integrase catalytic core domain that binds the lens epithelium-derived growth factor (LEDGF). Virtual screening of an internal database identified an analogue that bound with higher affinity and in an isomerised form to the LEDGF binding site. The starting lactone was stable in CDCl3; however, an unexpected isomerisation process occurred in [D6]DMSO to give the same isomer found in the LEDGF binding site. This hit led directly to a series of low-micromolar LEDGF inhibitors and, via a scaffold hop, to a series of allosteric binding site inhibitors.

Rhodium-catalyzed hydroformylation of ketal-masked β-isophorone: computational explanation for the unexpected reaction evolution of the tertiary Rh-alkyl via an exocyclic β-elimination derivative.

Ketal-masked β-isophorone (7,9,9-trimethyl-1,4-dioxaspiro[4.5]dec-7-ene) is an interesting case study of Rh-catalyzed hydroformylations not only for the competition between secondary and tertiary rhodium alkyls but also for the unexpected isomerization of the tertiary Rh-alkyl to the exocyclic olefin which undergoes hydroformylation, yielding the acetaldehyde derivative (2) of 7,9,9-trimethyl-1,4-dioxaspiro[4.5]decane. Although experimental results at 100 °C pointed to reaction reversibility, the reason for this kind of behavior was however obscure. A thorough density functional theory (DFT) computational investigation of the various transition states (TS) and intermediates along the reaction pathways making use of B3P86 hybrid functionals and the 6-31G* basis set, coupled to effective core potentials for Rh in the LanL2DZ valence basis set, has been carried out to shed some light on the reaction mechanism. The TS barrier heights, based on alkyl-Rh TS free energies, computed under the hypothesis of nonreversibility were in favor of a normal hydroformylation reaction (III:II = 70:30). While the endocyclic olefins produced skew or twisted arrangements of the six-membered ring similarly to the CO insertion TS that can be even higher than the alkyl-Rh ones, grid-point calculations during the potential energy surface (PES) scan produced the much more stable chair conformation for the exocyclic olefin complex. The relevant TS were found to be very favorable as well, thus explaining the preference for the exocyclic arrangement of the tertiary intermediate, for which the reaction is therefore entirely reversible and invariably proceeds to the acetaldehyde derivative (2). Conversely for the secondary isomers, the reaction is only partially reversible, thus enriching the tertiary fraction and producing the secondary aldehyde (3) in a very limited amount.

Frontispiece: Stereocontrolled Synthesis of Benzo[k]fluoranthenes-An Unexpected Isomerization Mediated by Rhodacyclopentadiene

Frontispiece: Stereocontrolled Synthesis of Benzo[<i>k</i>]fluoranthenes-An Unexpected Isomerization Mediated by Rhodacyclopentadiene

Stereocontrolled synthesis of benzo[k]fluoranthenes--an unexpected isomerization mediated by rhodacyclopentadiene.

Herein, a Rh(III) -catalyzed stereocontrolled synthesis of benzo[k]fluoranthenes is reported. It was found that the unexpected E/Z isomerization was highly sensitive to the electronic effects of the substituents on the aryl groups. Theoretical calculations revealed that this controllable stereochemistry originates from the mediation of rhodacyclopentadiene intermediates during the isomerization. The fact that similar stereochemistry was observed when using an Ir(III) catalyst further suggests a certain generality of this discovery toward some other transition metals.

Efficient procedure for the preparation of 2-bromo-5-ethylfuran and its unexpected isomerization

Efficient procedure for the preparation of 2-bromo-5-ethylfuran and its unexpected isomerization