Cycloaddition reactions of 5-deutero-1-phenyl-4-vinylpyrazole. Stereoselectivecis “ene” reaction and simplification of NMR spectra of mixtures of cycloadducts

Summary The reaction of methyl propiolate (MP) with 1-phenyl-4-vinylpyrazole deuterated in the five position has clarified the¹H NMR spectrum of the mixture of the adducts 1:2 which are obtained as a result of a Diels-Alder cycloaddition followed by a non-regioselective ene reaction. The deuterated substrate allowed at the same time to establish the stereochemistry of the ene reaction as a concertedcis process.

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Cycloadditionsreaktionen von 5-Deutero-1-phenyl-4-vinylpyrazol. Stereoselektivecis-en-Reaktion und Vereinfachung von NMR-Spektren von Mischungen der Cycloaddukte (Kurze Mitt.)

Zusammenfassung Die Reaktion von Methylpropiolat (MP) mit an der 5-Stellung deuteriertem 1-Phenyl-4-vinylpyrazol wurde zur vereinfachten Interpretation der¹H-NMR-Spektren einer 1:2 Mischung von Addukten aus der Diels-Alder-Cycloaddition mit nachfolgender nicht-regioselektiver en-Reaktion eingesetzt. Das deuterierte Substrat erlaubte zugleich auch die Bestimmung der Stereochemie der en-Reaktion als einen konzertiertencis-Prozeß.

     

Sparsely substituted chlorins as core constructs in chlorophyll analogue chemistry. II. Derivatization

Stable chlorins bearing few or no substituents have been subjected to a variety of reactions including demetalation, magnesium insertion, oxochlorin formation, and bromination followed by Suzuki coupling. The kinetics of deuteration also have been determined for two oxochlorins and a series of chlorins bearing 0, 1, 2, or 3 meso-aryl substituents.     

Preferential Uniplanar Orientation of Cellulose Microfibrils Reinvestigated by the FTIR Technique

A simple detection method to observe the uniplanar orientation behavior of native cellulose microfibrils to the cell wall surface by using Fourier transform infrared (FTIR) spectroscopy in the transmission mode is reported. Four bands at 1372, 1355, 1337, and 1317 cm⁻¹ (the latter two have been mentioned previously by Liang and Marchessault (1960, J. Polym. Sci. 43: 85–100)) were found to be sensitive to such orientation: the two middle bands at 1355 and 1337 cm⁻¹ increase remarkably when the 0.60–61 nm lattice planes lie parallel to the cell wall surfaces. The reverse was true when the 0.53–54 nm lattice planes oriented preferentially. Polarization of the two bands at 1372 and 1355 cm⁻¹ was parallel, while that of the other two bands at lower wavenumbers, i.e., at 1337 and 1317 cm⁻¹, was perpendicular to the molecular axis of cellulose. These bands were assigned to OH-related motion, probably to in-plane OH bending, as reported by Maréchal and Chanzy (2000, J. Mol. Spectrosc. 523: 183–196).     

Deuterated Digoxin

Abstract

A method for preparing [21,21,22-²H₃] digoxin by proton exchange with D₂O under high temperature and basic conditions is described. Loss of signal for the protons at C₂₁ and C₂₂ upon deuteration, with retention of structural integrity for the remainder of the parent compound, is established with high resolution proton NMR spectroscopy. Confirmation of the site of deuterium exchange and relative abundance of the species ²H₀:²H₁:²H₂:²H₃ is demonstrated by capillary gas chromatography - mass spectrometry (GC-MS) of the trimethylsilyl derivative of the steroidal component of digoxin, digoxigenin.     

双功能MoNi4电极实现水参与的氮杂环化合物转移氢化与脱氢

氮杂环的催化氢化在有机合成、药物研发、石油化工等领域有着重要应用.尽管发展了一系列均相和非均相催化加氢体系,但由于通常使用易燃易爆的氢气或价格昂贵且毒性较高的试剂(如:水合肼和硼氢化钠)为氢源,给安全生产及生态环境带来了严重的问题.此外,由于动力学同位素效应,氘代药物具有重要应用.氮杂环结构作为生物医药的构筑单元与关键中间体,现有的策略由于没有合适的氘源难以用于氘代氮杂环化合物的合成.因此,急需开发一种基于非贵金属催化剂和安全易得氢(氘)源的氮杂环催化氢(氘)化策略.水相中的电化学氢化可利用水电解原位产生的活性氢替代传统的氢气裂解实现有机氢化产物的合成,已成为一种理想氢化策略,被广泛应用于二氧化碳还原、硝酸根还原和生物质氢解等.本课题组前期研究已经实现了以氘水为氘源的氘代分子的高效电化学合成(Angew.Chem.Int.Ed.,2020,59,18527–18531;Angew.Chem.Int.Ed.,2020,59,21170–21175;CCS Chem.,2021,3,507–515).然而,要开发一种电化学的杂环氢化方法,一方面要克服氮杂环化合物对催化剂的毒化,另一方面要在电极表面产生大量的活性氢.因此,开发具有较好的水离解性能的非贵金属电极材料是实现氮杂芳烃电化学氢化和氘代的关键.基于上述要求,MoNi4(目前用于碱性电催化水分解制氢的活性较高的非贵金属材料)成为理想的电极材料.本文以喹喔啉(1,2,3,4-四氢喹喔啉骨架作为重要的结构单元存在于许多生物活性化合物中)作为模板底物,设计并制备了三维自支撑的MoNi4多孔纳米片为双功能电极,以水和氘水为氢源和氘源,实现了喹喔啉及其他氮杂环分子的氢化与氢化,同时实现了四氢喹喔啉的电化学氧化脱氢.制备了MoNi4纳米片阵列,利用扫描电子显微镜、透射电子显微镜、X射线衍射和X光电子能谱等手段进行表征,评估了其在碱性电解液中用于喹喔啉电化学转移氢化的性能.结果表明,MoNi4电极加速了动力学缓慢的Volmer步骤,在仅50 mV的过电势下以80％的法拉第效率实现了喹喔啉的电化学氢化.电子顺磁共振等证实水电解生成了H*,并与喹喔啉自由基阴离子偶联实现喹喔啉的氢化.同时,该电化学转移氢化方法可很好地应用于一系列喹喔啉衍生物和其他氮杂芳烃化合物.克级合成体现了该电化学转移氢化方法的潜在应用性.原位拉曼实验结果表明,在MoNi4表面形成的NiOOH是实现1,2,3,4-四氢喹喔啉氧化脱氢的重要物种.此外,以D2O代替H2O,可以较好的收率和高达99％的氘化率实现氘代氮杂环的合成.与传统的氮杂环氢化方法相比,本文的电化学转移氢化策略具有绿色、温和、高效的特点,同时拓宽了电化学氢化在合成化学中的应用.     

Use of very long-distance NOEs in a fully deuterated protein: an approach for rapid protein fold determination

The high sensitivity of modern NMR instrumentation, in combination with full deuteration, enabled the measurement of long-range NOEs between amide protons in a fully deuterated protein corresponding to distances up to 8A. These are beyond the limit normally observed in protonated samples. Such long-distance NOEs could be observed using long mixing times, which became possible due to reduced spin diffusion and T1 relaxation of the amide protons in the fully deuterated sample. This information was used in combination with secondary structure restraints derived from secondary chemical shifts for structure calculations. With these backbone amide proton NOEs only, a unique fold could be obtained with positional root mean square deviations from the average of 1.30 and 2.25 A for backbone and heavy atoms, respectively. Despite the low density of restraints, no mirror image problems were observed. Addition of sidechain NOE information increased the precision of the ensemble and in particular of the core packing. The structures obtained in this way were close to the published crystal structure. NOE completeness analysis revealed that the cumulative completeness is still more than 80% for an 8.0 A cut-off distance.     

Deuteration-induced structural phase transition versus quantum paraelectric behavior: Quantum chemical modeling of H/D bonded materials

On the examples of the K₃(H/D)(SO₄)₂ family (I), the derivatives of 9-hydroxyphenalenone (II) and chromous acids α-(H/D)CrO₂ (III) the problem of the deuteration-induced structural phase transition (SPT) is considered using pseudospin dynamic Ising model formalism. The pseudospin Hamiltonian parameters – tunneling integrals Ω(H/D) and Ising model coupling parameters J_ij(H/D) along with molecular field parameters J₀(H/D) have been evaluated on the base of quantum chemical models and various computational techniques. The crystal-chemistry factors that influence on the values of these parameters are discussed. For I and II solids zero-dimensional character of the H-bond network is believed to be the main reason of the deuteration-induced SPT, although the pronounced geometrical (H/D) isotope effect (0.04 Å) also may play a noticeable role for I. Meanwhile for III such SPT is due to the giant (0.1 Å) geometrical (H/D) isotope effect.     

Accessibility and size of <Emphasis Type="Italic">Valonia</Emphasis> cellulose microfibril studied by combined deuteration/rehydrogenation and FTIR technique

We report an FTIR method to measure the accessibility and the size of cellulose microfibrils from the cell wall of Valonia ventricosa. This method is similar to the conventional deuteration technique for measuring the accessibility of cellulosic materials; however, the difference in our method is that the hydroxyl groups O2H, O3H, and O6H in the crystalline region were initially completely deuterated. The sample was then rehydrogenated by soaking in water at 25 °C, so that the OD groups on the surface were rehydrogenated. The ratio of OH to OD absorbance was used to calculate the number of surface vs. core cellulose chains in a microfibril. The obtained experimental ratio of 0.934 was consistent with the value calculated for a previously published 33 × 38 chain Valonia model (Sugiyama et al. 1984). The rehydrogenation process was further investigated by immersing the sample in water at elevated temperatures. At temperatures above 120 °C, rehydrogenation was more efficient, and the efficiency plots vs. rehydrogenation temperature showed two inflection. These points may correspond to the temperature where the cleavage of inter-chain hydrogen bonds and/or crystalline-phase transition would have been occurred.     

Palladium-catalyzed site-selective hydrogen isotope exchange (HIE) reaction of arylsulfonamides using amino acid auxiliary

Hydrogen isotope exchange (HIE) is a versatile method for the introduction of deuterium to organic compounds. Herein, regioselective deuteration of sulfonamides is achieved by palladium-Catalyzed HIE reaction. By using amino acid as weakly coordination-directing auxiliary, a variety of sulfonamides are efficiently deuterated at the ortho-position. Placing competing directing groups on the aromatic ring does not affect the site-selectivity.     

A highly efficient cobalt-catalyzed deuterogenolysis of diboron: Synthesis of deuterated pinacolborane and vinylboronates

Highly efficient hydrogenolysis and deuterogenolysis of diboron compounds have been realized by the use of a cobalt catalyst, affording TON up to 48201. Furthermore, a one-pot two-step procedure comprising sequential deuterogenolysis of diboron and deuteroboration of alkynes under the same cobalt catalyst has been developed for the efficient, atom-economical synthesis of deuterated vinylboronates with high deuterium incorporation and excellent regio- and stereoselectivity.