四氟乙烯齐聚体的反应VII:多氟烷基硫醚的分子内重排及其动力学的研究

本文通过交叉反应、溶剂效应、反应物浓度、截捕实验、动力学参数研究了多氟烷基硫醚的分子内热重排过程.确认并根据Arrhenius方程计算出在四氯化碳溶液中反应的活化能.多氟烷基硫醚分子内重排系经分子内亲核协同过程进行.     

(四甲基二硅撑)二(3-三甲硅基环戊二烯基)四羰基二铁及其相关化合物的合成及结构

1,2-二(三甲硅基环戊二烯基)四甲基二硅烷与Fe(CO)5在二甲苯中于105～110℃反应除分离到少量标题化合物(Me2SiSiMe2)[η-(3-Me3SiC5H3Fe(CO)]2(μ-CO)2(5)外,主要是生成了脱Me3Si基的产物(Me2SiSiMe2)[η-C5H4Fe(CO)]2(μ-CO)2(1)及1的热重排异构体[Me2SiC5H4-Fe(CO)2]2(2).将5的二甲苯溶液加热回流18h,则转化为其异构体[Me2Si(Me3SiC5H3)Fe(CO)2]2(6).脱硅基发生在由相应反应物制备5的过程中。且脱硅基是与反应物中(Me2SiSiMe2)桥的存在有关。5的晶体结构经X射线衍射测定属单斜晶系,P21/m空间群,晶体学数据:a=0.6780(1)nm,b=2.2303(9)nm,c=0.9988(1)nn,;β=98.96(1)°,V=1.4960nm3.Z=2,Dc=1.36g/cm3.     

Biologically Active 1-Aminodeoxy and 1-O-Alkyl Derivatives of The Powerful D-Glucosidase Inhibitor 2,5-Dideoxy-2,5-Imino-D-Mannitol

ABSTRACT

By an Amadori rearrangement of easily available 5-azido-5-deoxy-D-glucofuranose with dibenzylamine and subsequent catalytic hydrogenation of the resulting 5-azido-1-(N,N-dibenzyl)amino-1,5-dideoxy-D-fructopyranose, 1-amino-1,2,5-trideoxy-2,5-imino-D-mannitol was obtained in only two steps and in excellent overall yield. Likewise, other amines were employed to introduce extended side chains ultimately suitable for attachment of the inhibitor to solid supports. The reported rearrangement reaction is a high yielding, convenient and apparently general entry to 1-aminodeoxyketopyranoses modified at C-5, facilitated by the ring enlargement of the aldofuranose to the ketopyranose as an additional driving force. A range of selected chain extended analogues was prepared by acylation of N-1. Inhibitors obtained exhibit K _i-values with D-glucosidases in the micromolar range. Interestingly, 1-N-acylation resulted in superior inhibitory activities, as did the addition of a hexyl chain.     

Acyclic forms of [1-(13)C]aldohexoses in aqueous solution: quantitation by (13)C NMR and deuterium isotope effects on tautomeric equilibria

High-resolution (13)C NMR spectra (150 MHz) have been obtained on the complete series of D-aldohexoses (D-allose 1, D-altrose 2, D-galactose 3, D-glucose 4, D-gulose 5, D-idose 6, D-mannose 7, D-talose 8) selectively labeled with (13)C at C1 in order to detect and quantify the percentages of acyclic forms, and to measure and/or confirm percentages of furanoses and pyranoses, in aqueous solution. Aldehyde and hydrate signals were detected for all aldohexoses, and percentages of these forms at 30 degrees C ranged from 0.006 to 0.7% (hydrate) and 0.0032 to 0.09% (aldehyde). Aldehyde percentages are largest for the altro, ido, and talo configurations, ranging from 0.01 to 0.09%; the ido configuration yielded the most hydrate (0.74%). Hydrate/aldehyde ratios vary with aldohexose configuration, ranging from 1.5 to 13, with gluco exhibiting the smallest ratio and gulo the largest. (2)H Equilibrium isotope effects (EIEs) on aldohexose anomerization were measured in D-galactose 3 and D-talose 8 selectively (13)C- and (2)H-labeled at C1 and H1. The (2)H isotope effect on (13)C chemical shift, and broadband (1)H- and (2)H-decoupling, were exploited to permit simultaneous observation and quantitation of the protonated and deuterated molecules in NMR samples containing equimolar mixtures of D-[1-(13)C]aldose and D-[1-(13)C; 1-(2)H]aldose. Small (2)H EIEs were observed for 8, but were undetectable for 3. These results suggest that configuration at C2 influences the magnitude of the (2)H isotope effect at H1 and/or that the observed effect cannot be reliably interpreted due to complications arising from the involvement of acyclic aldehyde forms as intermediates in the interconversion of cyclic forms. The observed (2)H isotope effects on aldohexose tautomeric equilibria provide new insights into the important question of whether (2)H substitutions can alter aldofuranose ring conformation, and lead to the identification of an optimal (2)H- and (13)C-substituted 2-deoxyribofuranose isotopomer on which to investigate this potential effect.     

Synthesis and Characterization of a Novel Galactosylated Cholesterol

Mammalian hepatocytes (parenchymal cells) exclusively possess large number ofasialoglycoprotein receptors (ASGPr), which can recognize terminal D-galactose orN-acetylgalactosamine residues. Lactobionic acid 1, bearing a galactosyl group, isusually used as…     

Structural characterization of oligosaccharides in recombinant soluble human interferon receptor 2 using fluorophore-assisted carbohydrate electrophoresis

The N-linked oligosaccharide profiles (banding patterns in gels) and structures of recombinant soluble human interferon receptor 2 (r-shIFNAR2) were determined using fluorophore-assisted carbohydrate electrophoresis (FACE, Glyko, Novato, CA). The method involves releasing N-linked oligosaccharide moieties from a glycoprotein by digestion with peptide-N glycanase (PNGase F), labeling the released oligosaccharides with the fluorescent dye 8-aminonaphthalene-1,3,6-trisulfonate (ANTS), and separating the labeled oligosaccharides by gel electrophoresis. The isolated oligosaccharides in the bands from the profiling gels can then be sequenced using exoglycosidases to reveal the oligosaccharide structures. The oligosaccharide profile of r-shIFNAR2 consists of at least nine oligosaccharide bands. The relative amount of oligosaccharide in each band can vary, depending on the culture conditions of the source cells. FACE structural analysis shows that r-shIFNAR2 contains only core-fucosylated N-linked oligosaccharides, most of which are fully sialylated (approximately 92%). The major types and relative amounts of the oligosaccharides from a representative sample are: disialylated, galactosylated, biantennary (15%); trisialylated, galactosylated, triantennary (19%), tetrasialylated, galactosylated, tetraantennary (30%), and N-acetyllactosamine-containing higher-order oligosaccharides including tri-, tetra-, and pentaantennary (28%). The remaining oligosaccharides are not fully sialylated and/or not fully galactosylated di-, tri-, and tetraantennary structures (approximately 5%) and unidentified structures (approximately 3%). A method for determining the types and structures of the N-acetyllactosamine containing oligosaccharides is also reported in this study.     

Asymmetric induction in the Neber rearrangement of simple ketoxime sulfonates under phase-transfer conditions: experimental evidence for the participation of an anionic pathway

Phase-transfer catalysis has been successfully utilized for the Neber rearrangement of simple ketoxime sulfonates. For instance, treatment of (Z)-1a with p-toluenesulfonyl chloride (1.2 equiv), tetrabutylammonium bromide (5 mol %) and MeOH (10 equiv) in toluene-50% KOH aqueous solution (volume ratio = 3:1) at 0 degrees C for 2 h, and subsequent benzoylation followed by acidic hydrolysis afforded the protected alpha-amino ketone 2a in 80% isolated yield. On the basis of this finding, asymmetric Neber rearrangement with ketoxime (Z)-1a was examined under phase-transfer conditions using structurally rigid, C(2)-symmetric chiral quaternary ammonium bromide 3 as catalyst. The desired 2a was obtained in 80% yield and 51% ee. This represents the first experimental demonstration of the substantial involvement of anion pathway in the Neber rearrangement of simple ketoxime sulfonates. Importantly, the reaction with (E)-1a under otherwise similar conditions afforded racemic 2a in 61% yield. Moreover, enhanced enantioselectivity (63% ee) was observed in the rearrangement of the oxime sulfonate derived from (Z)-1b, and notably, use of mesitylene in place of toluene further increased the enantioselectivity to 70% ee. Our approach provides not only a new mechanistic insight but also an opportunity for extending the full synthetic utility of this classical yet useful rearrangement.     

环丙基卡宾重排为环丁烯机理的密度泛函研究

采用 B3LYP 方法,用 6-311G(d)基组计算了环丙基卡宾重排为环丁烯的反应物、过渡态和产物的能量和振动频率,并用 IRC 计算验证了过渡态。结果表明环丙基卡宾的重排机理不同于通常碳正离子重排采用的亲核重排机理,而是一个亲电重排机理。     

Vapor-phase Beckmann rearrangement of oxime molecules over H-Faujasite zeolite.

The Beckmann rearrangement (BR) plays an important role in a variety of industries. The mechanism of this reaction rearrangement of oximes with different molecular sizes, specifically, the oximes of formaldehyde (H₂C?NOH), Z‐acetaldehyde (CH₃HC?NOH), E‐acetaldehyde (CH₃HC?NOH) and acetone (CH₃)₂C?NOH, catalyzed by the Faujasite zeolite is investigated by both the quantum cluster and embedded cluster approaches at the B3LYP level of theory using the 6‐31G (d,p) basis set. To enhance the energetic properties, single point calculations are undertaken at MP2/6‐311G(d,p). The rearrangement step, using the bare cluster model, is the rate determining step of the entire reaction of these oxime molecules of which the energy barrier is between 50–70 kcal mol^?1. The more accurate embedded cluster model, in which the effect of the zeolitic framework is included, yields as the rate determining step, the formaldehyde oxime reaction rearrangement with an energy barrier of 50.4 kcal mol^?1. With the inclusion of the methyl substitution at the carbon‐end of formaldehyde oxime, the rate determining step of the reaction becomes the 1,2 H‐shift step for Z‐acetaldehyde oxime (30.5 kcal mol^?1) and acetone oxime (31.2 kcal mol^?1), while, in the E‐acetaldehyde oxime, the rate determining step is either the 1,2 H‐shift (26.2 kcal mol^?1) or the rearrangement step (26.6 kcal mol^?1). These results signify the important role that the effect of the zeolite framework plays in lowering the activation energy by stabilizing all of the ionic species in the process. It should, however, be noted that the sizeable turnover of a reaction catalyzed by the Brønsted acid site might be delayed by the quantitatively high desorption energy of the product and readsorption of the reactant at the active center.     

Unimolecular dissociation reactions of methyl benzoate radical cation

The blackbody infrared radiation induced dissociation of methyl benzoate (C8H8O2(+*)) radical cation was investigated by using a Fourier transfer ion cyclotron resonance mass spectrometer equipped with a resistively heated (wire temperatures of 400-1070 K) wire ion guide. We observed product ion branching ratios that are strongly dependent upon wire temperature. At low temperatures (670-890 K) the major product ion C7H8 (+*) (m/z 92), which is formed by loss of CO2, and at higher temperatures (above 900 K), loss of methoxy radical ((*)OCH3) competes with loss of CO2. The energies of the various reactant ions and transition states for product ion formation were estimated by using density functional theory molecular orbital calculations, and a proposed mechanism for the dissociation chemistry of C8H8O2 (+*) involving a multistep rearrangement reaction is tested using the Master Equation formalism.     

Excited- and ground-state versions of the tri-pi-methane rearrangement: mechanistic and exploratory organic photochemistry

The di-pi-methane rearrangement with two pi-groups bonded to a single carbon leading to pi-substituted cyclopropanes is now well established. The present research had as its goal the exploration of molecular systems having three pi-moieties attached to an sp(3)-hybridized atom in a search for a tri-pi-methane rearrangement. Indeed, it was found that such systems do rearrange photochemically to afford cyclopentenes. However, it was also established that vinylcyclopropanes ring-expand to cyclopentenes on direct irradiation. Since both three-ring and five-ring photoproducts often are found to be produced, it was important to establish that the observed photochemistry was really the result of a true single-step tri-pi-methane rearrangement and not the consequence of two sequential rearrangements, first to form a vinyl cyclopropane which subsequently ring expanded to the cyclopentene. The general situation has three species-A, B, and C-corresponding to tri-pi-methane reactant A, vinylcyclopropane photoproduct B, and cyclopentene photoproduct C. Three rate constants are involved, k(1) for A --> B, k(2) for A --> C, and k(3) for B --> C. The kinetics were applied to two examples with provision to avoid differential light absorption; this utilized singlet sensitization. It was determined that direct formation of the cyclopentene photoproduct proceeds more rapidly than the ring-expansion route. In contrast to the di-pi-methane rearrangement, the tri-pi-methane reaction was found to be preferred by the singlet, while in these sterically congested systems, the triplet led to di-pi-methane reactivity. Finally, a ground-state counterpart of the reaction was obtained.     

3-Aza-cope rearrangement of quaternary N-allyl enammonium salts. Stereospecific 1,3 allyl migration from nitrogen to carbon on a tricyclic template

N-Allyl enamines can undergo a [3,3] sigmatropic rearrangement known as a 3-aza-Cope (or amino-Claisen) reaction. We explored a 3-aza-Cope reaction involving 1,3 allylic migration from nitrogen to carbon in N-allyl enammonium quaternary salts, exemplified by benzo[a]quinolizine 8 and pyrrolo[2,1-a]isoquinoline 13, with an interest in stereochemistry and mechanism. Salts 8 and 13 were accessed, respectively, through stereospecific allylation of hydroxy amines 4 and 11a/11b to give 7 and 12a/12b, which were dehydrated with trifluoroacetic acid. Allylic migration in these tricyclic tetrahydroisoquinolines occurred with high stereospecificity, with the major products 9 (from 8) and 15a (from 13) apparently deriving from a concerted suprafacial [3,3] rearrangement. The rearrangement of 8 to 9 was facile at 23 degrees C (t(1/2) = ca. 5 h) and was >98% stereospecific, whereas the rearrangement of 13 to 15a/15b required heating between 50 and 100 degrees C, with ca. 90-95% stereospecificity (t(1/2) = ca. 0.3 h at 100 degrees C). A deuterium-labeling experiment with 21 ((2)H-13) confirmed that allylic inversion accompanies the 1,3 migration en route to major isomer 22a ((2)H-15a), supporting the predominance of a concerted [3, 3] sigmatropic mechanism. However, the 5-10% loss of stereospecificity in the rearrangements of the pyrroloisoquinolines 13 and 21, reflected by formation of minor isomers 15b and 22b, respectively, indicates a minor nonconcerted reaction pathway.     

Active site reactant center geometry in the Co(II)-product radical pair state of coenzyme B12-dependent ethanolamine deaminase determined by using orientation-selection electron spin-echo envelope modulation spectroscopy

The distances and orientations among reactant centers in the active site of coenzyme B12-dependent ethanolamine deaminase from Salmonella typhimurium have been characterized in the Co(II)-product radical pair state by using X-band electron paramagnetic resonance (EPR) and two-pulse electron spin-echo envelope modulation (ESEEM) spectroscopies in the disordered solid state. The unpaired electron spin in the product radical is localized on C2. Our approach is based on the orientation-selection created in the EPR spectrum of the biradical by the axial electron-electron dipolar interaction. Simulation of the EPR line shape yielded a best-fit Co(II)-C2 distance of 9.3 A. ESEEM spectroscopy performed at four magnetic field values addressed the hyperfine coupling of the unpaired electron spin on C2 with 2H in the C5' methyl group of 5'-deoxyadenosine and in the beta-2H position at C1 of the radical. Global ESEEM simulations (over the four magnetic fields) were weighted by the orientation dependence of the EPR line shape. A Nelder-Mead direct search fitting algorithm was used to optimize the simulations. The results lead to a partial model of the active site, in which C5' is located a perpendicular distance of 1.6 A from the Co(II)-C2 axis, at distances of 6.3 and 3.5 A from Co(II) and C2, respectively. The van der Waals contact of the C5'-methyl group and C2 indicates that C5' remains close to the radical species during the rearrangement step. The C2-Hs-C5' angle including the strongly coupled hydrogen, Hs, and the C5'-Hs orientation relative to the C1-C2 axis are consistent with a linear hydrogen atom transfer coordinate and an in-line acceptor p-orbital orientation. The trigonal plane of the C2 atom defines sub-spaces within the active site for C5' radical migration and hydrogen atom transfers (side of the plane facing Co(II)) and amine migration (side of the plane facing away from Co(II)).     

Rutheniun-catalyzed cycloisomerization of o-(ethynyl)phenylalkenes to diene derivatives via skeletal rearrangement

Treatment of a series of 2',2'-disubstituted (o-ethynyl)styrenes with TpRu(PPh(3))(CH(3)CN)(2)PF(6) (10 mol %) in benzene (80 degrees C, 12-18 h) efficiently gave 2-alkenyl-1H-indene derivatives. This catalytic reaction represents an atypical enyne cycloisomerization with skeletal rearrangement of starting enyne, where the C=C bond is completely cleaved and inserted by the terminal alkynyl carbon. The reaction mechanism was elucidated by a series of deuterium and (13)C labeling experiments, as well as by changing the substituents at the phenyl moieties. The mechanism is proposed to involve the following key steps: 5-endo-dig cyclization of ruthenium-vinylidene intermediate, a nonclassical ion formation, and the "methylenecyclopropane-trimethylenemethane" rearrangement.     

How important is bishomoaromatic stabilization in determining the relative barrier heights for the degenerate Cope rearrangements of semibullvalene, barbaralane, bullvalene, and dihydrobullvalene?

[structure: see text] B3LYP/6-31G* calculations have been used to investigate the origins of the relative barrier heights for the degenerate Cope rearrangements of semibullvalene (1), barbaralane (2), bullvalene (3), and dihydrobullvalene (4). We conclude from our calculations that, of the four transition structures (TSs), that for rearrangement of 1 has the smallest amount of interallylic bonding. Nevertheless, relief of strain in the reactant confers on 1 the lowest barrier to Cope rearrangement. Conjugation between the cyclopropane ring and the pi bond of the etheno bridge in 3 makes the barrier for its Cope rearrangement higher than that for 4 and also contributes to making the barrier for 3 higher than that for 2. However, the relatively low barrier to the Cope rearrangement of 2 is largely due to the TS for this reaction having the largest amount of interallylic bonding of all four TSs.     

Thermal [1,3] sigmatropic rearrangements of bicyclic and tricyclic vinylcyclobutanes: a gray zone between the concerted and stepwise extremes

Four typical thermal [1,3] sigmatropic rearrangements of bicyclic and tricyclic vinylcyclobutanes and one fancied analogous reaction (R2 in Scheme 1) were examined using CASSCF, CASPT2 and CAS+1+2 methods to discern the reaction mechanisms. Computed results indicate that it is difficult to simply designate these reactions as traditional single-step concerted or stepwise mechanisms, but a situation locating between these two extremes seems to be reasonable. The extent the reaction exhibits as a single-step concerted or stepwise path is much dependent on the geometrical constraints of reactant. For example, the system with three-member ring will tend to behave like a single-step concerted process, where only one rotation movement around C–C bond could be found when the bridged C–C is broken. However, the species with four-member ring will be much closer to the stepwise mechanism involving diradical varieties, because there are two different rotation movements exist when the bridged C–C is broken. Our calculation will also rationalize that only suprafacial retention product could be yielded for the thermal [1,3] sigmatropic rearrangement of tricyclic vinylcyclobutane.     

Making a difference on excited-state chemistry by controlling free space within a nanocapsule: photochemistry of 1-(4-alkylphenyl)-3-phenylpropan-2-ones

The free space within a reaction cavity plays a determining role during the excited-state reaction of 1-(4-alkylphenyl)-3-phenylpropan-2-ones included within a capsule formed by two molecules of a deep cavity cavitand. By controlling the free space within the reaction cavity through remote alkyl substitution on the reactant ketone it is possible to control the yield of the rearrangement product shown above.     

Chiral recognition by resorcin[4]arene receptors: intrinsic kinetics and dynamics

Molecular recognition of representative amino acids (A) by a chiral amido[4]resorcinarene receptor (1(L)) was investigated in the gas phase by ESI-FT-ICR mass spectrometry. The ligand displacement reaction between noncovalent diastereomeric [1(L).H.A](+) complexes and the 2-aminobutane enantiomers (B) exhibits a distinct enantioselectivity with regard to both the leaving amino acid A and the amine reactant B. The emerging selectivity picture, discussed in the light of molecular mechanics and molecular dynamics calculations, points to chiral recognition by 1(L), as determined by the effects of the host asymmetric frame on the structure, stability, and rearrangement dynamics of the diastereomeric [1(L).H.A](+) complexes and the orientation of the amine reactant B in encounters with [1(L).H.A](+). The results contribute to the development of a dynamic model of chiral recognition of biomolecules by enzyme mimics in the unsolvated state.     

Total Synthesis of the Antiviral Natural Product Houttuynoid B

The first total synthesis of houttuynoid B, a powerful antiviral flavonoid glycoside from the Chinese plant Houttuynia cordata, is described. In a key step, a Baker–Venkataraman rearrangement employing an already glycosylated substrate was used to efficiently set up the fully functionalized carbon skeleton. The required benzofuran building block was prepared through a domino Sonogashira coupling/5‐endo‐dig cyclization and converted into a stable 1‐hydroxybenzotriazole‐derived active ester prior to linking with a galactosylated hydroxyacetophenone unit. The elaborated synthesis requires only nine steps (11 % overall yield) along the longest linear sequence and paves the way for the preparation of structurally related compounds for further biological evaluation.     

Asymmetric synthesis of dihydrofurans via a formal retro-Claisen photorearrangement

Solution-phase irradiation of a series of syn-7-benzoylnorbornene derivatives is shown to lead to cis-fused dihydrofuran derivatives in low quantum but excellent chemical yields in what is formally a retro-Claisen rearrangement. In analogy to the well-known Paterno-Buchi reaction, the first step of the rearrangement is suggested to involve (n,pi)(3)-mediated addition of the carbonyl oxygen to the norbornene double bond, producing a triplet 1,4-biradical. This intermediate, rather than closing to the oxetane, undergoes cleavage accompanied by intersystem crossing to form the dihydrofuran. To determine whether the retro-Claisen photorearrangement could be carried out enantioselectively, the 7-benzoylnorbornene reactant was equipped with a para-carboxylic acid substituent to which a series of optically pure amines was attached ionically via salt bridges. Irradiation of these salts in the crystalline state followed by diazomethane workup (the solid-state ionic chiral auxiliary method) was shown to afford the corresponding dihydrofuran in optical yields as high as 93% at 95% conversion. X-ray crystallography revealed that the enantioselectivity arises from crystallization of the reactant in a conformation in which the carbonyl oxygen is more favorably oriented for bond formation to one end of the norbornene double bond than the other, thus leading to a predominance of a single enantiomer.