Turning Spiroketals Inside Out: A Rearrangement Triggered by an Enol Ether Epoxidation

Spiroketals organize small molecule structures into well-defined, three-dimensional configurations that make them good ligands of proteins. We recently discovered a tandem cycloisomerization–dimerization reaction of alkynyl hemiketals that delivered polycyclic, enol-ether-containing spiroketals. Here we describe rearrangements of those compounds, triggered by epoxidation of their enol ethers that completely remodel their structures, essentially turning them “inside out”. Due to the high level of substitution on the carbon skeletons of the substrates and products, characterization resorted to X-ray crystallography and advanced computation and NMR techniques to solve the structures of representative compounds. In particular, a new proton-detected ADEQUATE NMR experiment (1,1-HD-ADEQUATE) enabled the unequivocal assignment of the carbon skeleton of one of the new compounds. Solution of the structures of the representative compounds allowed for the assignment of product structures for the other compounds in two separate series. Both the rearrangement and the methods used for structural determination of the products are valuable tools for the preparation of characterization of new small molecule compounds.     

Cover Picture: A Practical One-Pot Synthesis of Positron Emission Tomography (PET) Tracers via Nickel-Mediated Radiofluorination (ChemistryOpen 4/2015)

Invited for this months cover picture is the group of Professor Bernd Neumaier at the Institute of Radiochemistry and Experimental Molecular Imaging at the University Clinic of Cologne. The cover picture shows the differences in brain metabolism of a healthy young and a healthy old subject, as well as a patient suffering from Parkinsons disease (left to right) uncovered by 6-[¹⁸F]FDOPA-positron emission tomography (PET). Morbus Parkinson occurs when nerve cells that produce dopamine begin to die. The shortage of dopamine leads to movement problems in affected individuals. 6-[¹⁸F]FDOPA is extensively used to evaluate the progression of Parkinsons disease. Bold stick projections of this PET tracer, as well as a neuronal network, are seen in the background. Unfortunately, conventional procedures to produce 6-[¹⁸F]FDOPA are cumbersome. Thus, several recent developments aim at the simplification of this radiosynthesis. In our work, we studied the applicability of the recently reported Ni-mediated radiofluorination approach for daily routine production of 6-[¹⁸F]FDOPA. For more details, see the Full Paper on p. 457 ff.     

Thermal decomposition of p-methyl-p'-nitrobenzoyl and bis-p-nitrobenzoyl peroxides

Differential enthalpic analysis was carried out below the melting point as well as at regular increases of temperature over the melting point of peroxides. From these measurements it follows that the thermal stabilities of peroxides in the solid state increase with their melting points. The rise in the melting point of the peroxide due to changed chemical structure is accompanied by a rise in the melting points of products which in turn affects the isothermal autocatalytic decomposition. The common feature of the thermal decomposition of the peroxides studied below their melting points is a very high apparent activation energy of the initiation of a chain decomposition reaction which is several times higher than that of a spontaneous thermal decomposition of peroxide in solution or in a melt of peroxide. p]From the study of the decomposition of nitro derivatives of benzoyl peroxide in solution it is known¹ that the electron attracting nitro-substituents have a retarding effect on the spontaneous decomposition of peroxides. The introduction which accompanies its thermal decomposition in solution². However not only the substitution of nitro groups in the molecule but also the presence of nitro compounds accelerates the decomposition of benzoyl peroxide³. This indicates that the decomposition reaction may be influenced not only by an intramolecular rearrangement of electrons but also by an intermolecular interaction of nitro compounds with the peroxidic compounds or radicals generated by them. The substitution of methyl groups for hydrogen in aromatic rings does not produce any marked changes in the decomposition reactions of benzoyl peroxide². p]Among other changes produced by substitution, the physical changes—in particular, the changes in the melting points of investigated substances—are of importance to out study of the thermal decomposition of nitro derivatives of nitro derivatives of benzoyl peroxide. These data are interesting mainly because the decomposition of peroxides is influenced by the state of aggregation of the decomposing substances.     

The base-catalyzed transformation of polyacrylonitrile

In an effort to produce high-molecular-weight, linear ladder polymer by linking the nitrile groups within the molecule of polyacrylonitrile, polyacrylonitrile homopolymers were heat treated in N,N-dimethylformamide and N,N-dimethylacetamide solutions, in the presence of tertiary alkylamine catalysts. The products were soluble in formic acid, had relatively low molecular weight, and could be cast into brittle films. The infrared spectra indicated that the polymerization of the nitrile groups is initiated by a self-initiation mechanism based on the active methine groups in polyacrylonitrile, as proposed by Grassie and Hay, and that the reaction is complicated by molecular weight degradation via reverse Michael addition, as proposed by Hamada and Takahashi. The inherent viscosities of the products increase with increasing catalyst concentration, and further increases can be achieved by the addition of anionic chain coinitiators of phenolic nature. Density measurements indicated that the ladder structures undergo rearrangement into a more stereoregular form after formation, and that some aromatization occurs when the reaction is carried out in the presence of air.     

Synthesis of poly condensed oxygen-containing helical heterocycles via rearrangement of benzofused-2,2′-diphenoquinone derivatives

The thermal rearrangement reaction of helical-shaped quinone (benzofused-2,2′-diphenoquinone derivative) afforded three types of poly-condensed oxygen-containing heterocyclic compounds. One type of them was spiro compound which is consisting of cyclopentadiene and γ-butyrolactone. The other two compounds were helically condensed compounds, one of them containing as cyclopentadiene and pyranone ring and the other consists of fused furan and oxepin ring. These products were could be selectively synthesized by the choosing modification of reaction conditions. Moreover, the mechanistic aspects of these reactions are also discussed.     

Stuffed Graphite‐like vs. Stuffed Diamond‐like Structures of the 18 Valence Electron Compounds REAuSn (RE = Sc,Y, La‐Nd,Sm, Gd‐Lu)

18‐electron compounds REML (RE = rare earth metal; M = Cu, Ag, Au; L = Ge, Sn) can adopt either the stuffed graphite‐like (P6₃mc) or the stuffed diamond‐like ( ) structure. To understand why one structure is favored over the other, we carried out density functional theory electronic structure calculations for a number of REAuSn compounds. The stuffed graphite‐like and stuffed diamond‐like structures of an 18‐electron compound REAuSn are quite similar in their electronic structures with the Au atoms best described as existing as anions. The diamond‐like REML becomes possible only when the RE³⁺ ion is small and the M‐L bond is long.     

含P_H键苯并磷杂环化合物与醛反应的研究

利用含P_H键苯并磷杂环化合物与醛的反应,设计合成了新的A2羟基膦酸衍生化喹唑啉酮含磷类似物2或Ò,并研究了含P_C_O结构的2或Ò转化为含P_O_C结构的3或Ó的重排反应,目标化合物的结构经NMR,IR,MS和元素分析证实.结合NMR数据,探讨了化合物2因具有C^*和P^*两个手性中心而产生的非对映异构现象及其氢谱特征.对所合成的化合物进行了初步生物活性测试,发现部分化合物具有很好的抗植物病原真菌(苹果斑点落叶病菌)作用和一定的人体疱疹病毒抑制活性.     

Carboxylphosphanes and Carboxyphosphane Chalcogenides

Abstract

Low temperature reactions of organo chloro phosphanes with carboxylic acids and their salts allow the preparation of carboxyphosphanes - mixed anhydrides of carboxylic acids with phosphinic acids. These are subject to thermal rearrangement reaction of the Michaelis-Arbusov type. Molecular oxygen converts them into carboxy-phosphorane oxides. These compounds are also obtainable by reacting organochlorophosphane oxides with carboxylates. Their thermal stability is higher than that of the P(III)compounds. Analoguous reactions of P-sulfides and selenides give the corresponding thio and seleno phosphoranes with higher thermal stability. At elevated temperatures a number of rearrangement reactions occur, thus producing phosphane oxides and phosphinic acid phosphinyl alkaryl ester. The reaction products of the following reaction sequences are discusses with regard to their NMR-, IR-, MS-spectra and hydrolytic and thermal properties:     

Synthesis and Aza-[2,3]-Wittig Rearrangements of Vinylaziridines: Scope and Limitations

cis- and trans-2,3-Trisubstituted vinylaziridines have been prepared from cis- and trans-epoxy alcohols, respectively, and used as substrates in the aza-[2,3]-Wittig rearrangement. Five different anion-stabilizing groups have been investigated for their efficiency to promote the rearrangement, and it was found that N-tert-butyl acetyl vinylaziridines were superior in this reaction, affording the corresponding cis-2,6-tetrahydropyridines (>90%) as single isomers when treated with LDA. Similarly, the corresponding (Z)-propenylaziridines gave trans,trans-2,3,6-trisubstituted tetrahydropyridines as the sole products while the (E)-propenylaziridines afforded the cis,cis-2,3,6-derivatives with equally high selectivity. The scope and limitations of the process have been investigated by varying the structure of the substrate, and the mechanism of the rearrangement has been probed to some extent; the mechanistic picture is more complex than assumed previously.     

Reaction of a complexed phosphinidene with 2,4,6-tri-tert-butyl-1,3,5-triphosphabenzene

The terminal phosphinidene complex PhPW(CO)5 reacts with 2,4,6-tri-tert-butyl-1,3,5-triphosphabenzene to give two unexpected multicyclic organophosphorus compounds. One of them results from an initial 1,2-addition, followed by an intramolecular rearrangement. B3LYP/6-31G* calculations on simplified parent systems suggest that the reaction follows a unique concerted reaction pathway. The second, and major, product is a tetraphosphaquadricyclane derivative, which presumably results from an intramolecular [2+2] cycloaddition of an intermediate tetraphosphanorbornadiene complex. Single-crystal X-ray structures are presented for both products.     

De Mayo光环加成和桥(螺)环倍半萜基本碳架的构建

通过烃单萜3-甲基-6-异丙亚甲基环己烯(1)和2,6-二氧代戊酸甲酯(2)的de Mayo反应, 得到[2＋2]环加成产物、开环产物和游离基复合产物3～10. 经retro-aldol重排, 环加成产物3开环生成取代环己烯4, 在酸和碱性介质中对开环产物进行再环合, 经分子内Claisen缩合反应形成螺环和桥环化合物11～14. 讨论了可能的反应机理, 对所得新化合物的结构经IR, ¹H NMR, ¹³C NMR及元素分析予以确定.     

New Polycyclic Compounds from Photochemical Rearrangements of Some Substituted 2-Azatricyclo[5.2.2.01,5]undeca-4,8,10-trien-3-ones

The products formed on UV irradiation of several tricyclic compounds (i.e. 3 , 6 , 8 , 15 , and 17 , Schemes 2-4) were studied in detail. A marked dependence of the reaction course on the type and site of substitution was found. Among the several light-induced transformations, a novel rearrangement, i.e. 11 to 9 (Scheme 3) was identified. The formation of the polycyclic compound 13 on irradiation of 8a (Scheme 3) resulted from an unexpected skeletal rearrangement with dearomatization of one benzene ring. The structures of compounds 10 , 11 , and 13 were established by X-ray crystallography (Figs. 1-3). An attempt was made to give a general mechanistic picture of all observed photochemical results (Schemes 4-6).     

Electron ionization-induced fragmentation of N- and O-alkoxymethylated carbostyril and phenanthridinone

Unimolecular fragmentation patterns of N-alkoxymethylated carbostyril and phenanthridinone and their O-alkoxymethyl isomers were studied. The main fragmentation reaction observed for the studied compounds is the elimination of an aldehyde molecule. The main products of this reaction are the appropriate N-methyl derivatives, but ions with other structures are also formed. This reaction is supposed to proceed via 1,3-H shift in the alkoxymethyl group in the case of the N-alkoxymethyl derivatives and by a multi-step mechanism for O-alkoxymethylated compounds. Another important fragmentation common for all studied compounds is the loss of an alkyl radical from N- and O-alkoxymethyl groups, yielding the appropriate stable isomeric cations, which, according to the results of the further fragmentation, undergo fast equilibration reaction via an ion–neutral complex. This process is accompanied by the unusually high kinetic energy release value. Copyright © 2004 John Wiley & Sons, Ltd.     

Conformational Dynamics of DNA G-Quadruplex in Solution Studied by Kinetic Capillary Electrophoresis Coupled On-line with Mass Spectrometry

Invited for this months cover is the group of Prof. Maxim V. Berezovski. The cover picture shows the two-dimensional separation of unfolded (green) and folded (red) forms of G-quadruplex (GQ) DNA. The first dimension is kinetic capillary electrophoresis (KCE) separation of unfolded and folded DNA with different K⁺ concentrations in solution; the second dimension is ion mobility mass spectrometry separation of DNA conformers in the gas phase. DNA folding into a compact GQ structure is mediated by K⁺ ions. For more details, see the Full Paper on p. 58 ff.     

Chiral Iodotriptycenes: Synthesis and Catalytic Applications

Invited for this month′s cover picture is the group of Thomas Wirth at Cardiff University (UK). The cover picture shows two structures of triptycenes. In each of these molecules all three aromatic rings are different with the rigid structure of the molecules making them chiral. The two sp³-carbons shown in red and green are the stereocentres with defined configuration. These molecules contain the crucial iodine functionality which are utilised to generate hypervalent iodine(III)-catalysts in situ . The authors acknowledge Dr. Yu Wang for the creation of the cover image. Read the full text of their Research Article at 10.1002/open.202200145 .     

水相介质中碳酸钾/硫脲联合促进邻位氨基溴转变成α,β-脱氢氨的研究

建立了在水相介质中, 在碳酸钾/硫脲联合促进下, 具有邻位氨基溴的酯和邻位氨基溴的酮在室温下发生溴化氢消除反应, 高收率地制备α,β-脱氢氨(功能化烯胺)的新方法. 共考察了23种不同结构α,β-邻位氨基溴的酯和α,β-邻位氨基溴的酮的反应情况, 证明该方法具有广泛的适应性. 实验发现, 无论底物为α-氨基-β-溴结构还是α-溴-β-氨基结构, 反应过程中都要经过一个氮丙啶过程, 而氮丙啶的开环是区域专一的, 因此产物具有区域专一性(烯键上的氨基均处在羰基的α-位). 所有产物的结构均经过核磁共振波谱及高分辩率质谱确证. 克量级放大实验结果表明, 该方法具有一定的用于工业化生产的可行性.     

Single versus double proton transfer in the photochromic Schiff bases. Electronic spectroscopy and synthesis of model compounds

Symmetric, photochromic Schiff bases were studied. Their photophysics, experimental and calculated dipole moments (molecular mechanics and INDO/S) were compared with model compounds representing “one half” of the parent molecule. The photochromic transients were identified as monoketotautomers of a zwitterionic character — products of a one-proton transfer reaction along the internal H bond. It was found unexpectedly that the same molecule in the S_o state reveals a strong tendency to remain symmetric, opposite to its behaviour on the S₁ level.     

The Role of Aromaticity,Hybridization, Electrostatics,and Covalency in Resonance-Assisted Hydrogen Bonds of Adenine–Thymine (AT) Base Pairs and Their Mimics

Invited for this issues cover are Dr. Célia Fonseca Guerra from the VU University of Amsterdam and her collaborators at the University of Girona. The cover picture shows H-bonds in the adenine–thymine Watson–Crick base pair. An essential part of these H-bonds is their covalent component arising from donor–acceptor interactions between N or O lone pairs and the N−H antibonding σ* acceptor orbital. This charge-transfer interaction is represented by green figures walking on the pedestrian crossing, connecting the bases. This covalent component is the reason why H-bonds between DNA and/or unsaturated model bases are significantly stronger than those between analogous saturated bases. This contrasts sharply with the classical picture of predominantly electrostatic H-bonds which is not only incomplete in terms of a proper bonding mechanism, but also fails to explain the trend in stability. For more details, see the Full Paper on p. 318 ff.     

Mass-spectrometric study of the cyclization reactions of diazoketones. 8. 1-Diazo-3,4-epoxy-4-arylbutan-2-ones

An analysis of the mass spectra of 1-diazo-3,4-epoxy-4-arylbutanones has shown that the molecular ions of these compounds lose a molecule of nitrogen and that the [M — N₂]⁺ ions formed cyclize to form hydroxyfuran structures, whose further fragmentation determines the whole picture of the dissociative ionization of the compounds investigated under electron impact. The majority of the [M — N₂]⁺ ions have the form of the cyclic intermediate formed in the first step of the cyclization process. It cannot, however, be ruled out that a certain portion of the [M — N₂]⁺ ions are stabilized as a result of a Wolff rearrangement and do not cyclize at all.For report 7 see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 17–22, January, 1986.     

The structure of intermediate products of ‘fragmentation’ of 10-bromodihydrocinchonine

10-Bromodihydrocinchonine 1d, similarly to analogical derivatives of other main cinchona alkaloids, transforms into nicinquine and isonicinquine 2d formally loosing its C2 carbon atom in a form of formaldehyde. This reaction was found to proceed via the so-far unstudied intermediate compounds (5a) 4-S-(Z-propenyl)- and (5 4-S-(E-propenyl)-6-R-7-S-(quinolyl-4)-8-oxa-1-R-azabicyclo[4.3.0]nonane which at the same time are products of a novel rearrangement of the parent cinchonine. The stereostructure of these compounds was determined using, mainly, NMR techniques. The energy minima of conformers 5 and 5a were supported by molecular mechanics calculations. The mechanisms for the 1d → 5 → 2d sequence have been discussed. The alkaloid 5 is sterically preferred to its Z-isomer. The accompanying nucleophilic substitution (1d → 6) and elimination (1d → 7) are also stereospecific.