NMR Kinetic Experiments Research Articles

Rapid hydrolysis of tertiary isoprene nitrate efficiently removes NOx from the atmosphere

The formation of a suite of isoprene-derived hydroxy nitrate (IHN) isomers during the OH-initiated oxidation of isoprene affects both the concentration and distribution of nitrogen oxide free radicals (NOx). Experiments performed in an atmospheric simulation chamber suggest that the lifetime of the most abundant isomer, 1,2-IHN, is shortened significantly by a water-mediated process (leading to nitric acid formation), while the lifetime of a similar isomer, 4,3-IHN, is not. Consistent with these chamber studies, NMR kinetic experiments constrain the 1,2-IHN hydrolysis lifetime to less than 10 s in deuterium oxide (D2O) at 298 K, whereas the 4,3-IHN isomer has been observed to hydrolyze much less efficiently. These laboratory findings are used to interpret observations of the IHN isomer distribution in ambient air. The IHN isomer ratio (1,2-IHN to 4,3-IHN) in a high NOx environment decreases rapidly in the afternoon, which is not explained using known gas-phase chemistry. When simulated with an observationally constrained model, we find that an additional loss process for the 1,2-IHN isomer with a time constant of about 6 h best explains our atmospheric measurements. Using estimates for 1,2-IHN Henry's law constant and atmospheric liquid water volume, we show that condensed-phase hydrolysis of 1,2-IHN can account for this loss process. Simulations from a global chemistry transport model show that the hydrolysis of 1,2-IHN accounts for a substantial fraction of NOx lost (and HNO3 produced), resulting in large impacts on oxidant formation, especially over forested regions.

Direct C–S Bond Functionalization of Benzyl Mercaptan

Cleavage of a C–S bond of benzyl mercaptan led to formation of a new C–C bond during (Z)‐selective alkenylation of nitriles using 1,10‐phenanthroline as organocatalyst and tBuOK as a base. Furthermore, we have shown that the cascaded functionalization of benzylic C–S and aryl–halide bonds could be done in one pot. 1H NMR study and kinetic experiments also helped to establish the mechanism of the reaction.

Water Networks and Allosteric Scaffolds ‐ What Does Water Have to do with Protein Dynamics?

The thermophilic enzyme Fluoroacetate Dehalogenase (FAcD) has been well characterized by crystallography and NMR. FAcD (RPA1163) is a homodimer alpha/beta hydrolase that breaks down haloacetates (including fluoroacetate, iodoacetate, and chloroacetate) into glycolate and a halogen ion. FAcD achieves this by half‐of‐sites activity, where the homodimer adopts a rare asymmetric state that is primed to capture substrate which must then diffuse along an 11 Å cavity before engaging the active site and adopting the Michaelis intermediate. This triggers release of ~30 bound water molecules, thereby entropically favouring the forward reaction. FAcD is thus an ideal model system to pursue paradigm shifting questions regarding allostery, interprotomer communication, and the role of hydrogen bonded water networks in catalysis ‐ all from an ensemble perspective. Here we examine how deuterium water (D2O) changes the dynamic and allosteric mechanisms of this system. Compared to water, D2O results in an increase in viscosity and has stronger hydrogen bonds. Through 19F NMR kinetic experiments we determine that despite the higher viscosity enzyme activity is increased in the D2O environment. Additionally, 19F NMR experiments reveal increased dynamics in D2O. This provides key insight into discrete hydrogen‐bonded water networks that are key to stabilization of allosteric processes associated with the reaction coordinate.Support or Funding InformationNatural Sciences and Engineering Research Council (NSERC)

Reactivity of Re2O7 in aromatic solvents – Cleavage of a β-O-4 lignin model substrate by Lewis-acidic rhenium oxide nanoparticles

The nature of the active species in a dehydration reaction using the “catalyst” Re2O7 is investigated. During studies on the cleavage of the β-O-4 bond of a lignin model substrate, apparent “TOFs” of 240 h−1 and good selectivities of up to 73% for the sensitive product phenylacetaldehyde (compared to other applied (Lewis) acids) are observed. However, divergent kinetic data during the studies led to an in-depth investigation on the activation mechanism of Re2O7 in the applied apolar, aprotic medium. Here, it is shown, that, in fact, Re2O7 itself is completely inactive in the dehydration reaction, but forms even at low temperatures mixed valence rhenium nanoparticles, which promote the desired reaction. The nanoparticles are characterized by XPS, DLS and TEM. In order to discriminate whether either dissolved rhenium compounds or nanoparticles are the active species, 17O NMR studies and kinetic experiments are performed. An activation mechanism of rhenium heptoxide is suggested based on a careful analysis of byproducts under catalytic conditions and application of selected potential catalysts. Furthermore, an outlook is given, as these nanoparticles might participate in numerous other catalytic reactions.

Thermally and Photochemically Induced Dethreading of Fumaramide‐Based Kinetically Stable Pseudo[2]rotaxanes

The thermally and photochemically induced dethreading of a series of pseudo[2]rotaxanes bearing tetraalkyl‐substituted fumaramide axles and polyamide macrocycles is reported herein. The length of the alkyl chains at the ends of the thread, the void size, and flexibility of the macrocycle and the intercomponent interactions are critical for a satisfactory dethreading process. 1H NMR kinetic experiments were carried out in order to calculate the rate constants of the thermal dethreading processes and stabilities of the rotaxanes, by comparing with the similar data for the deslipping of the succinamide surrogates. The deslipping reaction occurs faster with the fumaramide systems than succinamide ones. The incorporation of adamantane moieties into the polyamide macrocycle drastically slowed down the disconnecting process. Furthermore, interlocked systems with dipropylamino groups as stoppers experienced a rapid dethreading when irradiated under UV‐light, a process triggered by the fumaramide–maleamide isomerization. In this case, the n‐propyl groups are not bulky enough to keep together both components as the number of hydrogen bonds between thread and macrocycle is halved in the maleamide systems.

Reactivity of Two-Electron-Reduced Boron Formazanate Compounds with Electrophiles: Facile N-H/N-C Bond Homolysis Due to the Formation of Stable Ligand Radicals.

The reactivity of a boron complex with a redox-active formazanate ligand, LBPh2 [L = PhNNC(p-tol)NNPh], was studied. Two-electron reduction of this main-group complex generates the stable, nucleophilic dianion [LBPh2]2–, which reacts with the electrophiles BnBr and H2O to form products that derive from ligand benzylation and protonation, respectively. The resulting complexes are anionic boron analogues of leucoverdazyls. N–C and N–H bond homolysis of these compounds was studied by exchange NMR spectroscopy and kinetic experiments. The weak N–C and N–H bonds in these systems derive from the stability of the resulting borataverdazyl radical, in which the unpaired electron is delocalized over the four N atoms in the ligand backbone. We thus demonstrate the ability of this system to take up two electrons and an electrophile (E+ = Bn+, H+) in a process that takes place on the organic ligand. In addition, we show that the [2e–/E+] stored on the ligand can be converted to E• radicals, reactivity that has implications in energy storage applications such as hydrogen evolution.

Aminopyridine-Borane Complexes as Hydrogen Atom Donor Reagents: Reaction Mechanism and Substrate Selectivity.

Lewis base-borane complexes are shown to be potent hydrogen atom donors in radical chain reduction reactions. Results obtained in 1 H, 11 B, and 13 C NMR measurements and kinetic experiments support a complex reaction mechanism involving the parent borane as well as its initial reaction products as active hydrogen atom donors. Efficient reduction reactions of iodides, bromides, and xanthates in apolar solvents rely on initiator systems generating oxygen-centered radicals under thermal conditions and pyridine-borane complexes carrying solubilizing substituents. In contrast to tin hydride reagents, the pyridine-boranes reduce xanthates faster than the corresponding iodides.

Supramolecular Agent–Simulant Correlations for the Luminescence Based Detection of V‐Series Chemical Warfare Agents with Trivalent Lanthanide Complexes

AbstractSolution spectroscopic investigations into the interactions of eight potential bidentate V‐series organophosphorus chemical warfare agent (OP CWA) simulants with [Eu(phen)2(NO3)3]·2H2O demonstrated that the chemical and structural composition of the secondary binding site within the simulant was of paramount importance. Only simulants containing both phosphoryl/phosphonyl and amine moieties generated analogous spectroscopic behaviours to V‐series OP CWAs seen in previous studies. The results demonstrated that the bidentate chelation mechanism was driven by the phosphoryl/phosphonyl moieties and that the presence of the amine moieties induced a significant secondary dynamic luminescence quenching mechanism. The binding modes of the simulants VO and TEEP to trivalent lanthanides (Eu and La) were further investigated using 1H and 31P NMR spectroscopic titrations and kinetic IR experiments. VO, with both the phosphonyl and amine binding sites was found to be the most appropriate simulant for V‐series OP CWAs in supramolecular studies with trivalent lanthanide ions and we recommend VO for use in supramolecular studies of this type.

Dethreading of Tetraalkylsuccinamide-Based [2]Rotaxanes for Preparing Benzylic Amide Macrocycles.

The dethreading of a series of succinamide-based [2]rotaxanes bearing benzylic amide macrocycles is reported herein. These transformations proceeded quantitatively either under flash vacuum pyrolysis, conventional heating, or microwave irradiation. Studying the size complementarity of the stoppers at the ends of the thread and the cavity of the macrocycle allowed us to set up the best substituents for implementing the extrusion of the thread from the interlocked precursors. A variety of (1)H NMR kinetic experiments were carried out in order to evaluate the rate constants of the dethreading process, the half-life times of the rotaxanes, and the influence of temperature and solvents on these processes. The use of dibutylamino groups as stoppers yielded the rotaxane precursor in a reasonable yield and allowed the quantitative deslipping of the rotaxane. The overall process, including the rotaxane formation and its further dethreading, has been exploited for preparing benzylic amide macrocycles enhancing, in most cases, the results of the classical (2 + 2) condensation and other reported stepwise syntheses. The kinetics of the dethreading process is fairly sensitive to the electronic effects of the substituents on the isophthalamide unit or to the electronic nature of the pyridine rings through a conformational equilibrium expanding or contracting the cavity of the interlocked precursor.

Mechanism of Brønsted acid-catalyzed glucose dehydration.

We present the first DFT-based microkinetic model for the Brønsted acid-catalyzed conversion of glucose to 5-hydroxylmethylfurfural (HMF), levulinic acid (LA), and formic acid (FA) and perform kinetic and isotopic tracing NMR spectroscopy mainly at low conversions. We reveal that glucose dehydrates through a cyclic path. Our modeling results are in excellent agreement with kinetic data and indicate that the rate-limiting step is the first dehydration of protonated glucose and that the majority of glucose is consumed through the HMF intermediate. We introduce a combination of 1) automatic mechanism generation with isotopic tracing experiments and 2) elementary reaction flux analysis of important paths with NMR spectroscopy and kinetic experiments to assess mechanisms. We find that the excess formic acid, which appears at high temperatures and glucose conversions, originates from retro-aldol chemistry that involves the C6 carbon atom of glucose.

The Glaser–Hay Reaction: Optimization and Scope Based on 13C NMR Kinetics Experiments

AbstractThe oxidative Glaser–Hay coupling of two terminal alkynes to furnish a butadiyne is a key reaction for acetylenic scaffolding. Although the reaction is performed under rather simple conditions [CuCl/TMEDA/O2 (air)], the mechanism is still under debate. Herein we present detailed studies on the scope of this reaction by using both 13C NMR and UV/Vis spectroscopic methods. The former method was used to study the kinetics of the coupling of aryl‐substituted alkynes as the aryl carbon resonances of the reactants and products have similar NOEs and relaxation times. The reaction was found to be zero‐order with respect to the terminal alkyne reactant under standard preparative conditions. Moreover, as the reaction proceeded, a clear change to slower reaction kinetics was observed, but it was still apparently zero‐order. The onset of this change was found to depend on the catalyst loading. This unfavorable change in reaction profile could be avoided by adding molecular sieves to the reaction mixture, thereby removing the water that is accumulated from the air and produced in the reaction in which dioxygen acts as the oxidizing agent. Not unexpectedly, the stirring rate, and hence uptake of air (O2), was found to have a significant effect on the rate of the reaction: The percentage of alkyne remaining after a certain time decreased linearly with the rate of stirring. On the basis of systematic studies, the optimized conditions for the coupling reaction using CuCl/TMEDA as the catalyst system are presented. Finally, we investigated the effect of different ligands and found that piperidine can also be conveniently employed as a ligand, albeit monodentate, in accord with related studies.

Synthesis, structure, and kinetic studies on [RuCl2(NCCH3)2(cod)

[RuCl2(NCCH3)2(cod)], an alternative starting material to [RuCl2(cod)] n for the preparation of ruthenium(II) complexes, has been prepared from the polymer compound and isolated in yields up to 87% using a new work-up procedure. The compound has been obtained as a yellow solid without water of crystallization. The complexes [RuCl2(NCR)2(cod)] spontaneously transform into dimers [Ru2Cl(μ-Cl)3(cod)2(NCR)] (R = Me, Ph). 1H NMR kinetic experiments for these transformations evidenced first-order behavior. [RuCl2(NCPh)2(cod)] dimerizes slower by a factor of ten than [RuCl2(NCCH3)2(cod)]. The following activation parameters, ΔH # = 114 ± 3 kJ mol−1 and ΔS # = 66 ± 9 J K−1 mol−1 for R = CH3CN (ΔG # = 94 ± 5 kJ mol−1, 298.15 K) and ΔH # = 122 ± 2 kJ mol−1 and ΔS # = 75 ± 6 J K−1 mol−1 for R = Ph (ΔG # = 100 ± 4 kJ mol−1, 298.15 K), have been calculated from the first-order rate constants in the temperature range 294–323 K. The kinetic parameters are in agreement with a two-step mechanism with dissociation of acetonitrile as the rate-determining step. The molecular structures of [Ru2Cl(μ-Cl)3(cod)2(NCR)] (R = Me, Ph) have been determined by X-ray diffraction.

Ligand Recognition of Lipocalin-Type Prostaglandin D Synthase

Lipocalin-type prostaglandin (PG) D synthase (L-PGDS) is a multi functional protein that functions as a PGD2 synthesizing enzyme, a scavenger of various lipophilic ligands, and an amyloid β chaperone in the brain. L-PGDS is a member of the lipocalin superfamily and has the ability to bind various lipophilic molecules, such as prostanoid, retinoid, bile pigment, and amyloid β peptide. However, the molecular mechanism for this wide variety of ligand binding is not fully understood. In this study, we determined the NMR structures of recombinant mouse L-PGDS and a L-PGDS/PGH2 analog. L-PGDS has a typical lipocalin fold, consisting of an eight-stranded β-barrel and a single α-helix. The interior of the barrel forms a hydrophobic cavity and the upper end of the barrel is open. The size of the barrel was found to be larger than those of other lipocalins and the cavity contained two pockets. The results of NMR titration, kinetic and molecular docking experiments revealed that PGH2 and retinoic acid occupied the hydrophilic pockets 1 and 2, respectively. A structural comparison of the L-PGDS/PGH2 analog complex with apo-L-PGDS showed that the H2-helix, CD-loop, and EF-loop located at the upper end of the β-barrel undergo a conformational change and cover the entrance of the cavity upon U-46619 binding. These results indicate that the two binding sites in the large cavity are responsible for the broad ligand specificity of L-PGDS in its induced-fit mechanism.

Free‐radical homo‐ and copolymerization of vinyl acetate and n‐butyl acrylate: Kinetic studies by online 1H NMR kinetic experiments

AbstractFree‐radical homo‐ and copolymerization of vinyl acetate (VAc) and n‐butyl acrylate (BA) in benzene‐d6 were performed by using benzoyl peroxide as an initiator at 70°C. Polymerization kinetic was followed by online 1H NMR kinetic experiments. Significant drift in the comonomer mixture composition with reaction progress was observed. Reactivity ratios of VAc and BA were calculated by terminal unit model (TUM) as well as by simplified penultimate unit model (PUM) with rVAc = 0. It was found that copolymer composition can be described well by the TUM. “Lumped” kinetic parameter ( $ k_p .k_t^{ - 0.5} $) was estimated from experimental data. A good fitting between the theoretical and experimental drifts in the comonomer mixture and copolymer compositions with reaction progress was observed. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011

On the Synthesis and Chemical Behaviour of the Elusive Bis(hydrosulfido)-Bridged Dinuclear Rhodium(I) Complexes [{Rh(μ-SH)(CO)(PR3)}2

Several bis(hydrosulfido)-bridged dinuclear rhodium(I) compounds, [{Rh(mu-SH)(L)(2)}(2)], have been prepared from rhodium(I) acetylacetonato complexes, [Rh(acac)(L)(2)], and H(2)S(g). Reaction of [Rh(acac){P(OPh)(3)}(2)] with H(2)S(g) affords the dinuclear bis(hydrosulfido)-bridged compound [{Rh(mu-SH){P(OPh)(3)}(2)}(2)] (1). However, reaction of complexes [Rh(acac)(CO)(PR(3))] with H(2)S(g) gives the dinuclear compound [{Rh(mu-SH)(CO)(PR(3))}(2)] (R=Cy, 2; R=Ph, 4) and the trinuclear cluster [Rh(3)(mu-H)(mu(3)-S)(2)(CO)(3)(PR(3))(3)] (R=Cy, 3; R=Ph, 5). The selective synthesis of both type of compounds has been carried out by control of the H(2)S(g) concentration in the reaction media. The trinuclear hydrido-sulfido cluster [Rh(3)(mu-H)(mu(3)-S)(2)(CO)(3)(PPh(3))(3)] (5) has been also obtained by reaction of [{Rh(mu-SH)(CO)(PPh(3))}(2)] (4) with [Rh(acac)(CO)(PPh(3))], proceeding through the trinuclear hydrosulfido-sulfido intermediate [Rh(3)(mu(3)-SH)(mu(3)-S)(CO)(3)(PPh(3))(3)]. The molecular structures of complexes 1 and 3 have been determined by X-ray diffraction methods. Compound 1 is stable in solution, but complexes 2 and 4 slowly transform in solution into the trinuclear hydrido-sulfido clusters 3 and 5, respectively, with the release of H(2)S(g) in a reversible way. (1)H NMR kinetic experiments for the transformation of 4 into 5 have revealed that this transformation follows second-order-type kinetic. The following activation parameters, DeltaH( not equal)=24+/-3 kJ mol(-1) and of DeltaS( not equal)=-223+/-8 J K(-1) mol(-1), have been calculated from the determination of the second-order rate constants in the temperature range 30-45 degrees C. The large negative value of the activation entropy is consistent with an associative character of the rate-determining step. A plausible multistep mechanism based on the chemical behaviour of hydrosulfido-metal complexes and compatible with the kinetic behaviour has been proposed.

Calorimetric, Spectroscopic, and Model Studies Provide Insight into the Transport of Ti(IV) by Human Serum Transferrin

Evidence suggests that transferrin can bind Ti(IV) in an unhydrolyzed form (without bound hydroxide or oxide) or in a hydrolyzed form. Ti(IV) coordination by N,N'-di(o-hydroxybenzyl)ethylenediamine-N,N'-diacetic acid (HBED) at different pH values models the two forms of Ti(IV)-loaded transferrin spectrally and structurally. 13C NMR and stopped-flow kinetic experiments reveal that when the metal is delivered to the protein using an unhydrolyzed source, Ti(IV) can coordinate in the typical distorted octahedral environment with a bound synergistic anion. The crystal structure of TiHBED obtained at low pH models this type of coordination. The solution structure of the complex compares favorably with the solid state from pH 3.0 to 4.0, and the complex can be reduced with E1/2 = -641 mV vs NHE. Kinetic and thermodynamic competition studies at pH 3.0 reveal that Ti(citrate)3 reacts with HBED via a dissociative mechanism and that the stability of TiHBED (log beta = 34.024) is weaker than that of the Fe(III) complex. pH stability studies show that Ti(IV) hydrolyzes ligand waters at higher pH but still remains bound to HBED until pH 9.5. Similarly, at a pH greater than 8.0 the synergistic anion that binds Ti(IV) in transferrin is readily displaced by irreversible metal hydrolysis although the metal remains bound to the protein until pH 9.5. Thermal denaturation studies conducted optically and by differential scanning calorimetry reveal that Ti(IV)-bound transferrin experiences only minimal enhanced thermal stability unlike when Fe(III) is bound. The C- and N-lobe transition Tm values shift to a few degrees higher. The stability, competition, and redox studies performed provide insight into the possible mechanism of Ti2-Tf transport in cells.

A new simple procedure to calculate monomer reactivity ratios by using on-line 1H NMR kinetic experiments: Copolymerization system with greater difference between the monomer reactivity ratios

Free radical copolymerization reaction of vinyl acetate (VA) and methyl acrylate (MA) in solution of benzene-d6 using benzoyl peroxide (BPO) as the initiator was studied with on-line 1H NMR kinetic experiments at 60°C. It was observed that composition drifts in the comonomer mixture with reaction progress is significant. Hence, the monomer reactivity ratios of VA/MA system could be calculated by the data collected only from one sample via on-line following the comonomer mixture and copolymer compositions at different reaction time intervals up to medium overall monomer conversions. The results were in good agreement with the literature data reported for this system. The good fitting between theoretical and experimental changes in the comonomer mixture compositions as a function of reaction progress was observed, indicating the accuracy of the monomer reactivity ratios calculated by the new procedure presented here.

Solution NMR Study of Methyltin(IV)-Cupferronates: Analysis of a Unique Dismutation Reaction and Preorganization Process

Multinuclear multidimensional 1 H, 1 3 C, and 1 1 9 Sn NMR data indicated that both the cyclic tetrameric [Me 3 Sn(ON(NO)Ph)] 4 (1 t ) and dimeric [Me 2 Sn(ON(NO)Ph) 2 ] 2 (2 d ) supramolecules are predominantly monomeric [Me 3 Sn(ON(NO)Ph)] 1 (1 m ) and [Me 2 Sn(ON(NO)Ph) 2 ] 1 (2 m ) in noncoordinating solvents (CDCl 3 , CD 2 Cl 2 ) at room temperature. This has been proven by the concerted interpretation of (1) Me-Sn-Me angles calculated from J-coupling data; (2) tin coordination numbers deduced from 1 1 9 Sn chemical shift data; and (3) molecular hydrodynamic radii calculated from the measurement of translational diffusion constants. Both 1 m and 2 m monomers underwent a cis-trans conformational exchange that is fast on the chemical shift time scales. In noncoordinating solvents the dominance of the cis-TBP and cis-O h conformations was characteristic for 1 m and 2 m , respectively. In coordinating solvents (DMSO, pyridine, methanol), the trans-conformers dominated and the formation of specific solute-solvent 1 m * and 2 m * coordination complexes was confirmed. The solvent-induced cis-trans conformational exchange was held responsible for the demethylation reaction of 1 m , which yielded 2 m and the byproduct Me 4 Sn. 1 H NMR kinetic experiments have proven that the dismutation process followed a second-order 2 A → B + C type kinetics. In Lewis base solvents, the dismutation product 2 m was stabilized by the formation of a heptacoordinated solute-solvent complex 2 m *, which then underwent no further dismutation. The stability constant of the pyridine complex of 2 m was determined from the analysis of NMR titration data. The mechanism of the methyl-migrational process was proposed on the basis of solvent-induced 1 m (cis) ⇄ 1 m * (trans) conformational equilibrium. Low-temperature 1 H and 1 1 9 Sn NMR experiments in noncoordinating solvents revealed the first example of a 1 m ⇄ 1 t preorganization process leading to the re-formation of a solvated 20-membered macrocycle (1 t ).

Orientational isomers of α-cyclodextrin [2]semi-rotaxanes with asymmetric dicationic threads

Two series of novel dicationic threading molecules [Quin(CH2)10R]2+ and [3,5-Lut(CH2)10R]2+, where Quin+ = quinuclidinium, 3,5-Lut+ = 3,5-lutidinium, and R+ = N(CH3)3+ and N(CH3)2CH2CH3+, form [2]semi-rotaxanes with [small alpha]-cyclodextrin (alpha-CD) in aqueous solution. The quinuclidinium and 3,5-lutidinium are sufficiently bulky to prevent threading while the R+ groups allow for slow threading by alpha-CD at 25 degrees C. The resulting [2]semi-rotaxanes exist in two orientational isomers owing to the asymmetry of both the alpha-CD cavity and the threading molecules. Two-dimensional 1H NMR spectroscopy and kinetics experiments reveal that the isomer in which the narrower rim (primary OHs) is positioned near the R+ group is the kinetically preferred isomer, while the other isomer is the thermodynamically preferred product. The kinetics and mechanism of the formation, dissociation, and interconversion of the two isomers have been determined at 25 degrees C.

Mechanistic studies of the biomimetic epoxy ester-orthoester and orthoester-cyclic ether rearrangements.

The relative rates of acid-catalyzed rearrangements of epoxy esters to [3.2.1]bicyclic orthoesters, the subsequent rearrangements of these ortho esters to substituted tetrahydrofurans, and the rates of orthoester hydrolysis at pH 4.75 were measured in NMR kinetics experiments. The ease of formation and stabilities of these orthoesters compared favorably with the OBO-type [2.2.2]bicyclic orthoesters typically used as protecting groups of carboxylic acids. Studies with 13C NMR-detected 18O-labeling show that epoxy ester rearrangement takes place preferentially via 6-exo cyclization, although the 7-endo process competes when the distal center of the epoxide is disubstituted. The ortho ester-cyclic ether rearrangement was shown by 18O-labeling to occur exclusively via intermediacy of a five-membered dioxonium ion. The structures of the hydrolysis products also indicate the intermediacy of a dioxolanium ion during hydrolysis. The implications for a hypothetical biosynthesis of marine polyether toxins are discussed.