Unusual Reaction Mechanism Research Articles

Rh(II)-Catalyzed C-N Bond Formation Using Enynones and N-H Imines: An Approach to Diarylmethylamines.

A Rh(II)-catalyzed furyl carbene N-H insertion reaction involving an N-sp2-hybridized imine is described, which represents an atom-economical route by which to access diarylmethylamine derivatives with high efficiency and broad substrate scope. An unusual reaction mechanism is proposed, in which the rhodium catalyst plays a dual role in facilitating enynone cyclization via activation and enhancement of the nucleophilicity of the NH imine.

Evidence for Iron‐Catalyzed α‐Phosphinidene Elimination with Phenylphosphine

The ubiquitous half-sandwich iron complex [CpFe(CO)2 Me] (Cp=η5 -C5 H5 ) appears to be a catalyst for α-phosphinidene elimination from primary phosphines. Dehydrocoupling reactions provided initial insight into this unusual reaction mechanism, and trapping reactions with organic substrates gave products consistent with an α elimination mechanism, including a rare example of a three-component reaction. The substrate scope of this reaction is consistent with generation of a triplet phosphinidene. In all, this study presents catalytic phosphinidene transfer to unsaturated organic substrates.

Electronic Structure Analysis of the Dinuclear Metal Center in the Bioremediator Glycerophosphodiesterase (GpdQ) from Enterobacter aerogenes

The glycerophosphodiesterase (GpdQ) from Enterobacter aerogenes is a promiscuous, dinuclear metallohydrolase that has potential application in the remediation of organophosphate nerve agents and pesticides. GpdQ employs an unusual reaction mechanism in which the enzyme is predominantly mononuclear in the resting state, and substrate binding induces the formation of the catalytically competent dinuclear center (Hadler et al. J. Am. Chem. Soc. 2008, 130, 14129). Reactivity is further modulated by the coordination flexibility of Asn80, a ligand that binds to the second, loosely bound metal ion (Hadler et al. J. Am. Chem. Soc. 2009, 131, 11900). It is proposed that hydrolysis is initiated by a terminal, metal-bound hydroxide molecule which is activated at unusually low pH by electrostatic/hydrogen bonding interactions with a bridging hydroxide species. In this study, electronic structure analysis of the dinuclear center is employed to study the coordination environment of the dinuclear center at the resting and product-bound stage of catalysis. This is achieved through the use of variable temperature, variable field magnetic circular dichroism experiments involving the Co(II)-substituted wild type enzyme and its Asn80Asp variant. The data support the above model for the catalytic mechanism whereby the metal ion-bridging hydroxide molecule activates a terminally bound hydroxide nucleophile. Replacement of Asn80 by an aspartate residue does prevent coordination flexibility but also leads to cleavage of the mu-hydroxide bridge and reduced reactivity. This is the first study to investigate the electronic structure of an enzyme with a mu-1,1-carboxylate bridged dicobalt(II) center.

Formation of a stalled early intermediate of pseudouridine synthesis monitored by real-time FRET

Pseudouridine is the most abundant of more than 100 chemically distinct natural ribonucleotide modifications. Its synthesis consists of an isomerization reaction of a uridine residue in the RNA chain and is catalyzed by pseudouridine synthases. The unusual reaction mechanism has become the object of renewed research effort, frequently involving replacement of the substrate uridines with 5-fluorouracil (f(5)U). f(5)U is known to be a potent inhibitor of pseudouridine synthase activity, but the effect varies among the target pseudouridine synthases. Derivatives of f(5)U have previously been detected, which are thought to be either hydrolysis products of covalent enzyme-RNA adducts, or isomerization intermediates. Here we describe the interaction of pseudouridine synthase 1 (Pus1p) with f(5)U-containing tRNA. The interaction described is specific to Pus1p and position 27 in the tRNA anticodon stem, but the enzyme neither forms a covalent adduct nor stalls at a previously identified reaction intermediate of f(5)U. The f(5)U27 residue, as analyzed by a DNAzyme-based assay using TLC and mass spectrometry, displayed physicochemical properties unaltered by the reversible interaction with Pus1p. Thus, Pus1p binds an f(5)U-containing substrate, but, in contrast to other pseudouridine synthases, leaves the chemical structure of f(5)U unchanged. The specific, but nonproductive, interaction demonstrated here thus constitutes an intermediate of Pus turnover, stalled by the presence of f(5)U in an early state of catalysis. Observation of the interaction of Pus1p with fluorescence-labeled tRNA by a real-time readout of fluorescence anisotropy and FRET revealed significant structural distortion of f(5)U-tRNA structure in the stalled intermediate state of pseudouridine catalysis.

1,2-α-l-Fucosynthase: A glycosynthase derived from an inverting α-glycosidase with an unusual reaction mechanism

Fucosyloligosaccharides have great therapeutic potential. Here we present a new route for synthesizing a Fucα1,2Gal linkage by introducing glycosynthase technology into 1,2-α-l-fucosidase. The enzyme adopts a unique reaction mechanism, in which asparagine-423 activated by aspartic acid-766 acts as a base while asparagine-421 fixes both a catalytic water and glutamic acid-566 (an acid) in the proper orientations. Glycosynthase activity of N421G, N423G, and D766G mutants was examined using β-fucosyl fluoride and lactose, and among them, the D766G mutant most effectively synthesized 2′-fucosyllactose. 1,2-α-l-Fucosynthase is the first glycosynthase derived from an inverting α-glycosidase and from a glycosidase with an unusual reaction mechanism.

Au‐ and Pt‐Catalyzed Cycloisomerizations of 1,5‐Enynes to Cyclohexadienes with a Broad Alkyne Scope.

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Au- and Pt-Catalyzed Cycloisomerizations of 1,5-Enynes to Cyclohexadienes with a Broad Alkyne Scope

We describe the development of gold- and platinum-catalyzed cycloisomerizations of 1,5-enynes. This catalytic process displays a wide alkyne scope and furnishes a range of highly functionalized 1,4- and 1,3-cyclohexadienes. In the case of 1-siloxy-1-yne-5-enes, the reactions are efficiently catalyzed by AuCl (1 mol %) at ambient temperature to afford siloxy cyclohexadienes or the corresponding 1,2- and 1,3-cyclohexenones upon subsequent protodesilylation. We propose that the reaction proceeds via a novel mechanism involving a series of 1,2-alkyl shifts. Elucidation of this unusual reaction mechanism enabled us, in turn, to significantly expand the scope of the cycloisomerization by incorporation of a quaternary center at the C(3) position of the enyne. Indeed, we established that PtCl(2) (5 mol %) efficiently catalyzed the cycloisomerizations of 1,5-enynes containing terminal, internal, and arene-conjugated alkynes. Since a variety of 1,5-enynes are readily accessible, the cycloisomerization provides a rapid approach to a wide range of highy substituted cyclohexadienes for many subsequent synthetic applications.

A new color of the synthetic chameleon methoxyallene: synthesis of trifluoromethyl-substituted pyridinol derivatives: an unusual reaction mechanism, a remarkable crystal packing, and first palladium-catalyzed coupling reactions.

Addition of lithiated methoxyallene to pivalonitrile afforded after aqueous workup the expected iminoallene 1 in excellent yield. Treatment of this intermediate with silver nitrate accomplished the desired cyclization to the electron-rich pyrrole derivative 2 in moderate yield. Surprisingly, trifluoroacetic acid converted iminoallene 1 to a mixture of enamide 3 and trifluoromethyl-substituted pyridinol 4 (together with its tautomer 5). A plausible mechanism proposed for this intriguing transformation involves addition of trifluoroacetate to the central allene carbon atom of an allenyl iminium intermediate as crucial step. Enamide 3 is converted to pyridinol 4 by an intramolecular aldol-type process. A practical direct synthesis of trifluoromethyl-substituted pyridinols 4, 10, 11, and 12 starting from typical nitriles and methoxyallene was established. Pyridinol 10 shows an interesting crystal packing with three molecules in the elementary cell and a remarkable helical supramolecular arrangement. Trifluoromethyl-substituted pyridinol 4 was converted to the corresponding pyridyl nonaflate 13, which is an excellent precursor for palladium-catalyzed reactions leading to pyridine derivatives 14-16 in good to excellent yields. The new synthesis of trifluoromethyl-substituted pyridines disclosed here demonstrates a novel reactivity pattern of lithiated methoxyallene which is incorporated into the products as the unusual tripolar synthon B.

A combined crossed beam and theoretical investigation of O(3P) + C3H3 --> C3H2 + OH.

The radical-radical reaction dynamics of ground-state atomic oxygen [O(3P)] with propargyl radicals (C3H3) has first been investigated in a crossed beam configuration. The radical reactants O(3P) and C3H3 were produced by the photodissociation of NO2 and the supersonic flash pyrolysis of precursor propargyl bromide, respectively. A new exothermic channel of O(3P) + C3H3 --> C3H2 + OH was identified and the nascent distributions of the product OH in the ground vibrational state (X 2Pi:nu" = 0) showed bimodal rotational excitations composed of the low- and high-N" components without spin-orbit propensities. The averaged ratios of Pi(A')/Pi(A") were determined to be 0.60 +/- 0.28. With the aid of ab initio theory it is predicted that on the lowest doublet potential energy surface, the reaction proceeds via the addition complexes formed through the barrierless addition of O(3P) to C3H3. The common direct abstraction pathway through a collinear geometry does not occur due to the high entrance barrier in our low collision energy regime. In addition, the major reaction channel is calculated to be the formation of propynal (CHCCHO) + H, and the counterpart C3H2 of the probed OH product in the title reaction is cyclopropenylidene (1c-C3H2) after considering the factors of barrier height, reaction enthalpy and structural features of the intermediates formed along the reaction coordinate. On the basis of the statistical prior and rotational surprisal analyses, the ratio of population partitioning for the low- and high-N" is found to be about 1:2, and the reaction is described in terms of two competing addition-complex mechanisms: a major short-lived dynamic complex and a minor long-lived statistical complex. The observed unusual reaction mechanism stands in sharp contrast with the reaction of O(3P) with allyl radical (C3H5), a second significant conjugated hydrocarbon radical, which shows totally dynamic processes [J. Chem. Phys. 117, 2017 (2002)], and should be understood based upon the characteristic electronic structures and reactivity of the intermediates on the potential energy surface.

Keto–enol/enolate equilibria in the 2-acetylcyclopentanone system. An unusual reaction mechanism in enol nitrosation

The keto–enol equilibrium of 2-acetylcyclopentanone (ACPE) was studied in water by analysing the effect that aqueous micellar solutions produce in the UV absorption spectrum of this compound. Aqueous solutions of anionic, cationic, or nonionic surfactants forming micelles have been used. The quantitative treatment of absorbance changes measured at the maximum absorption wavelength as a function of surfactant concentration gave the keto–enol equilibrium constant, KE. In the same sense, the analysis of spectral changes measured as a function of pH in aqueous basic media allowed us to determine the acidity equilibrium constant, Ka. The combination of both equilibrium constants gives the acidity constant of the enol ionizing as an oxygen acid, pKEa=7.72 and the acidity constant of the ketone ionizing as a carbon acid, pKKa=8.12. The kinetic study of the nitrosation reaction of ACPE has been realized in aqueous strong acid media under several experimental conditions. As expected, the reaction is first-order with respect to ACPE concentration, but in sharp contrast to other β-dicarbonyl compounds, the dependence of both [H+] or [X−] (X−=Cl−, Br−, or SCN−) is not simple first-order; instead a fractional order which varied from 1 to 0 was observed. The kinetic interpretation of these experimental facts has been done on the basis of a reaction mechanism that considers the formation of an intermediate in steady-state, which has been postulated as a chelate-nitrosyl complex. The quantitative treatment of the experimental data gave the values of every rate constant appearing in the proposed reaction mechanism.

Liquid Crystalline Bispropargyl Thermosets

A series of rigid-rod bispropargyl thermoset monomers have been synthesized. These monomers were examined by differential scanning calorimetry (DSC) and hot stage polarized optical microscopy. Enantiotropic or monotropic nematic liquid crystalline phases were observed for all but two monomers. Partial curing of these reactive liquid crystalline monomers resulted in the formation of stable liquid crystalline phases with broad nematic phase ranges. In one example, a monomer that was neither enantiotropic nor monotropic exhibited a stable nematic phase after partial curing. DSC investigations indicated that the onset temperature of thermally induced cross-linking was approximately 260 °C and insensitive to the phase type. The rate of cure was insensitive to the phase in which the cure occurred due to the unusual reaction mechanism for the propargyl end group.