Pericyclic Mechanism Research Articles

Mechanism and Plasticity of Isochorismate Pyruvate Lyase: A Computational Study

The isochorismate pyruvate lyase (IPL) from Pseudomonas aeruginosa, designated as PchB, catalyzes the transformation of isochorismate into pyruvate and salicylate, but it also catalyzes the rearrangement of chorismate into prephenate, suggesting that both reactions may proceed by a pericyclic mechanism. In this work, molecular dynamics simulations employing hybrid quantum mechanics/molecular mechanics methods have been carried out to get a detailed knowledge of the reaction mechanism of PchB. The results provide a theoretical rate constant enhancement by comparison with the reaction in solution, in agreement with the experimental data, and confirm the pericyclic nature of the reaction mechanism. The robustness of this promiscuous enzyme has been checked by considering the impact of Ala37Ile mutation, previously proposed by us to improve the secondary chorismate mutase (CM) activity. The effect of this mutation, which was shown to increase the rate constant for the CM activity by a factor of 10(3), also increases the IPL catalytic efficiency, although only by a factor of 6.

Diels–Alder reactions of 5,6-dihydrothiazolo[3,2-d][1,4,2]diazaphospholes: A DFT investigation

The density functional theory level (B3LYP/6-311G**) computations of the Diels–Alder (DA) reactions of 5,6-dihydrothiazolo[3,2-d][1,4,2]-diazaphospholes with 1,3-butadiene and with isoprene confirm pericyclic mechanism via asynchronous transition states. The aromatic character of the transition states is established by negative nucleus independent chemical shift (NICS) values falling in the range from −14 to −16. Integration of the dienophilic >CP functionality in the 6π aromatic azaphosphole ring raises the activation energy barrier (B3LYP/6-311++G**//B3LYP/6-311G**) compared to that for the DA reaction of the acyclic phosphaethene, but it is lower than the activation energy barrier for the DA reaction of the corresponding 10π aromatic system, thiazolo[3,2-d][1,4,2]diazaphospholes. The experimentally observed stereo- and regioselectivities in the reactions can be accounted on the basis of secondary molecular orbital (SMO) interactions detected in the respective transition structures. The attachment of an electron-withdrawing group to the dienophilic moiety enhances both stereo- and regio- selectivities which agree well with the experimental values. Solvent (toluene) effect studied with polarizable continuum model (PCM) indicates that the stereo- and regioselectivities are not affected by the solvent. © 2006 Wiley Periodicals, Inc. Heteroatom Chem 17:402–410, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20196

Isochorismate Pyruvate Lyase: A Pericyclic Reaction Mechanism?

Isochorismate pyruvate lyase (IPL) catalyzes the cleavage of isochorismate to give salicylate and pyruvate, a key step in bacterial siderophore biosynthesis. We investigated the enzyme from Pseudomonas aeruginosa using isochorismate selectively deuterated at C2 as a substrate. Monitoring the reaction by 2H NMR spectroscopy revealed that the label is quantitatively transferred from C2 to C9, producing stoichiometric amounts of [3-2H]pyruvate as product. Moreover, the deuterium kinetic isotope effect of 2.34 +/- 0.08 on kcat indicates that C-H cleavage is significantly rate limiting. Consistent with these data, hybrid density functional theory (HDFT) calculations at the Becke3LYP/DZ+(2d,p) level of theory predict a concerted but highly asynchronous pericyclic transition structure, in which carbon-oxygen bond cleavage is more advanced than hydrogen atom transfer from C2 to C9; the calculated 2H isotope effect of 2.22 at C2 is in excellent accord with the experimental value. Together, these findings indicate that IPL should be added to the small set of proteins that are known to catalyze pericyclic reactions. They also raise the possibility that enzymes, such as chorismate pyruvate lyase, salicylate synthase, 4-amino-4-deoxychorismate lyase, and anthranilate synthase, which accelerate formally similar reaction steps, may also exploit pericyclic mechanisms.

Acetylene Coupling on Cu(111): Formation of Butadiene, Benzene, and Cyclooctatetraene

Acetylene trimerizes to benzene on the (111) face of copper, as it does on the (100) and (110) planes. However, Cu(111) also yields butadiene and cyclooctatetraene, the latter never previously found with Cu or any other material. No coverage threshold is observed for the onset of these coupling reactions, implying high adsorbate mobility: gaseous benzene is formed by a surface reaction rate-limited process, whereas butadiene and cyclooctatetraene are formed by desorption rate-limited processes. H/D isotope tracing shows that benzene formation proceeds via a statistically random associative mechanism, whereas butadiene formation is associated with strong kinetic isotope effects, probably associated with C-H cleavage. A pericyclic mechanism involving dimerization of C4H4 metallocycles is proposed to account for the formation of cyclooctatetraene. We also found that approximately 45 nm alpha-alumina supported copper particles operated under catalytic conditions at atmospheric pressure yield the same principal reaction products as those found with Cu(111) under vacuum conditions. It therefore seems likely that the elementary reaction steps that describe the surface chemistry of the model system are also important under practical conditions. Comparison of the structure, bonding, and reactivity of acetylene on Cu(111) and Pd(111) indicates that the effectiveness of copper in promoting C-H cleavage in adsorbed acetylene is associated with greater rehybridization of the C-C bond with concomitant weakening of the C-H bond.

4,5‐Dihydro‐3H‐benzo[c]azepines from 1,7‐Electrocyclization Reactions of 2‐Aza‐4,5‐benzoheptatrienyllithium Compounds

AbstractVarious differently substituted (2‐alkenylbenzylidene)amines 4b−d gave, upon deprotonation with amide bases and addition of an electrophile, the respective 4,5‐dihydro‐3H‐benzo[c]azepines 6a−k in moderate to good yields. The imines 4 are easily accessible from 2‐bromobenzaldehyde (1) by Wittig olefination, formylation with DMF, and subsequent condensation with benzylamine. The ring‐closure reaction is interpreted as an anionic 1,7‐electrocyclization reaction involving benzo‐annulated 2‐azaheptatrienyllithium compounds. This reaction, and the subsequent addition of the electrophiles, proceed with excellent diastereoselectivity, determined by the (E) or (Z) configuration of the imines 4b−d. The corresponding allylimines 4e,f do not give ninemembered heterocycles 7, but rather the corresponding 3‐vinyl‐4,5‐dihydro‐3H‐benzo[c]azepines 6l,m. Molecular structures of several compounds 6 in the solid state were determined by X‐ray crystallography, including the structure of a 14‐membered ring dimer 8. High‐level quantum chemical calculations on model anions concerning structures and relative energies of possible intermediates and transition states support the pericyclic mechanism suggested for the ring‐closure reaction. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

Pericyclic and Heteroelectrocyclic Mechanisms for the Cyclization of 1,3,5-Hexatrien-1-one and Its 6-Aza Analog

The cyclization of 1,3,5-hexatrien-1-one, 1, and the Z- and E-isomers of 1-aza-1,3-butadienylketene 3 were studied using the semiempirical AM1 and PM3 methods. Cyclizations of compounds 1 and Z-3 are shown to occur via a mono-rotation mechanism with barriers of 15.49 and 32.85 kcal/mol respectively. The reactions proceed via non-planar transition states which result from rotation of the methylene group for compound 1 and the imino group for compound Z-3. Cyclization of E-3 proceeds via a non-rotatory mechanism through a planar transition state. The activation barrier is 4.83 kcal/mol (AM1). The electronic structures of the initial and final states, and of some intermediate structures, including the transition states for the cyclization of compounds 1 and 3, were analyzed by the natural orbital method using HF/6-31G*//AM1 calculations. Energetic, structural, and orbital criteria indicate the heteroelectric mechanism for the cyclization of compound E-3 and the pericyclic mechanism for the cyclization of compounds 1 and Z-3.

10 Reaction mechanisms : Part (iii) Pericyclic reactions

Computational studies of pericyclic reaction mechanisms have greatly enhanced our understanding of, and predictions regarding, reaction mechanisms. In recent years, the importance of non-statistical effects in pericyclic reactions, as studied using dynamics trajectory calculations, has been recognized. Some examples are the electrocyclic ring opening of the cyclopropyl radical, the Cope rearrangement of hepta-1,2,6-triene, and the rearrangement of bicyclo[n.1.0]polyenes. High quality mechanistic studies, though becoming less common, were also carried out. For example, two studies were published on vinylcyclobutane derivatives, one focusing on the thermal stereomutations and cycloreversions, and the other on the [1,3] sigmatropic reactions. The strength of the interplay between experiment and theory is demonstrated in studies of the intramolecular [4+2] cycloaddition of cyclobutadiene with tethered alkenes, in the use of isotope effects to determine the mechanism of an electron-transfer catalyzed Diels–Alder reaction, and in the degenerate interconversions of bicyclo[3.1.0]hex-2-ene.

Directed sequential synthesis of conjugated linoleic acid isomers from Δ7, 9 to Δ12, 14

AbstractPosition and configuration isomers of conjugated linoleic acid (CLA), from 7, 9‐ through 12, 14‐C18:2, were synthesized by directed sequential isomerizations of a mixture of rumenic (cis‐9, trans‐11 C18:2) and trans‐10, cis‐12 C18:2 acids. Indeed, the synthesized conjugated fatty acids cover the range of unsaturated systems as found in milk fat CLA. The two‐step sequence consisted in initial sigmatropic rearrangement of cis/trans CLA isomers at 200 °C for 13 h under inert atmosphere (Helium, He), followed by selenium‐catalyzed geometrical isomerization of double bonds at 120 °C for 20 h under He. Product analysis was achieved by gas‐liquid chromatography using a 120 m polar capillary column coated with 70% cyanoalkylpolysiloxane equivalent polymer. Migration of conjugated systems was geometrically controlled as follows: the cis‐Cn, trans‐Cn+2 double bond system was rearranged through a pericyclic [1, 5] sigmatropic mechanism into a trans‐Cn‐1, cis‐Cn+1 unsaturated system, while the trans‐Cn, cis‐Cn+2 double bond system was rearranged through a similar pericyclic mechanism into a cis‐Cn+1, trans‐Cn+3 unsaturated system. Selenium‐catalyzed geometrical isomerization under mild conditions then allowed cis/trans double bond configuration transitions, resulting in the formation of all cis, all trans, cis‐trans and trans‐cis isomers. A sequential combination of the two reactions resulted in a facile controlled synthesis of CLA isomers, useful for the chromatographic identification of milk fat CLA, as well as for the preparation of CLA standard mixture.

The iconoclastic dynamics of the 1,2,6-heptatriene rearrangement.

CASSCF(8,8)/6-31G* and AM1-SRP direct dynamics trajectory calculations have been run on the rearrangement of 1,2,6-heptatriene to 3-methylene-1,5-hexadiene. They show that the experimental results of Roth et al. on this reaction can be explained without the need to invoke a concerted, pericyclic mechanism. Instead, bifurcation occurs at the transition state for conversion of the reactant to 2-methylenecyclohexane-1,4-diyl. Some trajectories leaving the transition state do enter the PES local minimum for the intermediate, but others, differing only in the phases of the real-frequency vibrational modes, bypass the intermediate and proceed over a second transition state to the product. A significant fraction of the trajectories that do enter the biradical local minimum proceed on to the product in <500 fs, despite the fact that the minimum is some 12 kcal/mol deep at the CASSCF level. This nonstatistical behavior seems to be due in part to a resonance between key C-H bending and C-C stretching vibrations in the intermediate.

σ Bond Activation by Cooperative Interaction with ns2 Atoms: Be + nH2, n = 1−3

Ab initio investigations at the MP2, CCSD(T), and MRCISD levels of theory with augmented triple-ζ basis sets have identified and characterized various stationary points on the Be/(H2)n, n = 1−3, hypersurfaces. The van der Waals complexes, Be(H2)n, are very weakly bound (De = 0.08−0.32 kcal/mol with respect to H2 loss) with H2/H2 interactions playing an important role in determining equilibrium structures which can be understood in terms of the various relevant long-range potentials. The covalent molecule, BeH2, is found to have a linear, centrosymmetric structure and to be strongly bound with respect to Be + H2, in agreement with previous calculations. BeH2 interacts weakly with additional H2 molecules (De < 0.75 kcal/mol) which are positioned parallel to the near-linear BeH2 moiety in the equilibrium structures of the BeH2(H2)n-1 complexes. Of particular interest is the dramatic change in the nature of the transition state for BeH2 production depending on the number of H2 molecules present. For n = 1, the reaction proceeds stepwise: first breaking the H2 bond and forming one BeH bond followed by forming the second BeH bond. This process has an activation energy of about 56 kcal/mol. For n = 2, the reaction proceeds via a pericyclic mechanism through a planar cyclic transition state where two H2 bonds are broken while simultaneously two BeH bonds and one new H2 bond are formed. The activation energy for this process decreases from the n = 1 value to about 38 kcal/mol. For n = 3, the reaction proceeds through a true insertion mechanism with the addition of the third H2 molecule, decreasing the activation energy to about 33 kcal/mol. The results are discussed in comparison to the isoelectronic B+/nH2 systems where significant σ bond activation through a cooperative interaction mechanism has been identified.

Ab initio investigations of Li−+nH2→LiH2−(H2)n−1,n=1–3

Ab initio investigations at the coupled-cluster single double (triple) [CCSD(T)] and MRCISD level with augmented triple and quadruple zeta basis sets have identified various stationary points on the Li−/(H2)n,n=1–3, hypersurfaces. The electrostatic complexes, Li−(H2)n, are very weakly bound (De&amp;lt;0.25 kcal/mol with respect to H2 loss) and H2/H2 interactions play a contributing role in determining the equilibrium structures within the electrostatic constraint of a linear or near-linear Li−–H–H orientation. The covalent molecular ion, LiH2−, is found to have a linear centrosymmetric structure and to be bound with respect to Li−+H2 in agreement with previous calculations. The interaction of LiH2− with additional H2 is purely electrostatic but with a De larger than those of the Li−(H2)n complexes. LiH2−(H2) is found to have a linear equilibrium structure and LiH2−(H2)2 is found to have two almost isoenergetic structures: linear with an H2 on either end of the LiH2−, and C2v with both H2 on the same end of the LiH2−. Of particular interest is the dramatic change in the nature of the transition state for LiH2− production depending on the number of H2 molecules present. For n=1, the reaction proceeds through a conical intersection between the lowest energy B21 and A11 electronic surfaces in C2v symmetry. For n=2, the reaction occurs on a single surface in a pericyclic mechanism through a transition state consisting of a planar five-member ring where simultaneously two H2 bonds are broken while two LiH bonds and one new H2 bond are formed. For n=3, the reaction proceeds by direct insertion of Li− into one of the H2 molecules with the two additional H2 molecules providing substantial stabilization of the transition state by taking on part of the negative charge in a weakly covalent interaction. The results are discussed in comparison to the isoelectronic B+/(H2)n systems where significant sigma bond activation through a cooperative interaction mechanism has been identified recently.

Sigma Bond Activation by Cooperative Interaction with ns2 Atoms: B+ + nH2

The reactions of B+ + nH2 to produce BH2+(H2)n-1 have been studied by high-level ab initio techniques. The reaction mechanism and associated activation energy is found to depend dramatically on the number of H2 molecules present. For n = 1, the reaction proceeds stepwise: first breaking the H2 bond and forming one BH bond followed by forming the second BH bond. This process has an activation energy of about 57 kcal/mol. For n = 2, the reaction proceeds via a pericyclic mechanism though a planar cyclic transition state where two H2 bonds are broken while simultaneously two BH bonds and one new H2 bond are formed. The activation energy for this process decreases dramatically from the n =1 value to only about 11 kcal/mol. For n = 3, the reaction proceeds through a true insertion mechanism; however, the actual insertion occurs late in the reaction after over 75% of the exothermicity has been realized. The addition of the third H2 molecule decreases the activation energy to only about 3.4 kcal/mol. For n = 4,...

Cyclobutene photochemistry. Substituent effects on the photochemistry of 1-phenylcyclobutene

The photochemistry and photophysics of 1-phenylcyclobutene and five aryl-substituted derivatives have been studied in various solvents at room temperature. All six compounds fluoresce with quantum yields in the 0.2–0.3 range in cyclohexane and acetonitrile solution. 1-Phenylcyclobutene undergoes [2+2]-cycloreversion [Formula: see text] to yield phenylacetylene upon photolysis in either hydrocarbon or acetonitrile solution, and undergoes (Markovnikov) solvent addition upon irradiation in methanol solution [Formula: see text] in addition to cycloreversion. Triplet sensitization and quenching experiments indicate that cycloreversion and methanol addition are both excited singlet state processes. None of the six compounds studied undergo ring opening to the corresponding 2-aryl-1,3-butadiene in detectable yield. Quantum yields for cycloreversion in cyclohexane, acetonitrile, and methanol solution and methanol addition have been determined for the six compounds, along with excited singlet state lifetimes. The quantum yields and rate constants for cycloreversion and methanol addition are both enhanced by substitution with electron-donating groups. The variation in the rate constant for [2+2]-cycloreversion with substituent indicates that there is substantial dipolar character developed in the cyclobutenyl σ-bond framework during the reaction, in almost exact correspondence with that developed in the π system during photoprotonation. No deuterium scrambling is observed in 1-phenylcyclobutene-2,4,4-d3 after photolysis in pentane solution to ca. 80% conversion, indicating that skeletal rearrangements leading to cyclopropyl carbenes do not occur in the direct photolysis of arylcyclobutene derivatives. A pericyclic mechanism for the photocycloreversion reaction is suggested. Triplet–triplet absorption spectra and triplet lifetimes of 1-phenyl-, 1-(para-methylphenyl)-, and 1-(para-trifluoromethylphenyl)cyclobutene in hydrocarbon solution are also reported. Keywords: photochemistry, cyclobutene, fluorescence, [2+2]-cycloreversion, substituent effects, nanosecond laser flash photolysis, lifetime, triplet state, styrene, photoaddition

Kinetically deduced existence of CO .....C close contacts. Pericyclic rearrangement of 1,2-diacetyl-1,2-dihydro-3 [formula omitted]-indazol-3-one

First-order kinetics of the title rearrangement to 3-acetoxy-1-acetylindazole (2a), complete exchange of O-acyl groups in cross-experiments, insensitivity to change in reaction medium, lack of electronic substituent effects and activation parameters are considered as evidence in favour of a pericyclic mechanism through CO .....C close contacts.

The Monofunctional Chorismate Mutase from Bacillus subtilis: Structure Determination of Chorismate Mutase and Its Complexes with a Transition State Analog and Prephenate, and Implications for the Mechanism of the Enzymatic Reaction

Structures have been determined for chorismate mutase from Bacillus subtilis and of complexes of this enzyme with product and an endo -oxabicyclic transition state analog using multiple isomorphous replacement plus partial structure phase combination and non-crystallographic averaging. In addition to 522 water molecules, the model includes 1380 of the 1524 amino acid residues of the four trimers (each containing 3 × 127 amino acid residues) in the asymmetric unit. Refinement to 1·9 Å resolution yields 0·194 for R and r.m.s. deviations from ideal values of 0·014 Å for bond lengths and 2·92° for bond angles. The trimer resembles a β-barrel structure in which a core β-sheet is surrounding by helices.The structures of the two complexes locate the active sites which are at the interfaces of adjacent pairs of monomers in the trimer. These structures have been refined a 2·2 Å to a crystallographic R value of 0·18 and show r.m.s. deviations from ideal values of 0·013 Å for bond lengths and 2·84° or 3·05° for bond angles, respectively. The final models have 1398 amino acid residues, nine prephenate molecules and 503 water molecules in the product complex, and 1403 amino acid residues, 12 inhibitor molecules and 530 water molecules in the transition state complex.The active sites of all three of these structures are very similar and provide a structural basis for the biochemical studies that indicate a pericyclic mechanism for conversion of chorismate to prephenate. The absence of reactive catalytic residues on the enzyme, the selective binding of the single reactive conformation of chorismate, the stabilization of the polar transition state, and the possible role of the C-terminal region in "capping" the active site are factors which relate these structures to the million-fold rate enhancement of this reaction.

A Theoretical Study of the Stevens Rearrangement of Methylammonium Methylide and Methylammonium Formylmethylide

Ab initio and semi-empirical molecular orbital theory has been used to study the reaction pathways of the Stevens rearrangement of the prototype methylammonium methylide and methylammonium formylmethylide . For both reactions, the stepwise (free radical) process is predicted to require less energy than the concerted rearrangement (in accordance with experimental suggestions). With inclusion of electron correlation, the energy difference between these pathways is reduced; however, for the smaller system at the CCSD/6-31G(d) level of theory, the free radical process is still favoured by over 180 kJ mol-1. For both systems, the concerted transition structures for the pericyclic mechanisms reveal that some amount of bonding is retained in these formally symmetry-forbidden processes.

Unimolecular loss of molecular nitrogen from metastable dicyanoacetylene radical cation (NCCCN + [rad

In contrast with neutral dicyanoacetylene 1 and highly energized 1 +&.zrad;, the slow dissociations (metastable ion) of 1 + are dominated by the extrusion of molecular nitrogen. This process is completely absent in the MI spectrum of ionized dicyanodiacetylene 2 + , thus pointing to the possible operation of a pericyclic mechanism in the reaction 1 + → C + 4 + N 2.

Stereoselective 1,4-hydroboration of acyclic (E)-α,β-unsaturated ketones with dialkylboranes. Synthesis of (Z)-vinyloxyboranes.

Dialkylboranes add to acyclic disubstituted (E)-α,β-unsaturated ketones in a 1,4-fashion affording (Z)-vinyloxyboranes as major or sole products. The stereochemical outcome of the hydroboration reaction is consistent with a concerted pericyclic mechanism. The intermediate vinyloxyboranes can be trapped with aldehydes to give virtually pure syn β-hydroxyketones.

A remarkable pericyclic mechanism for enzyme-catalyzed phosphorus-carbon bond formation [Erratum to document cited in CA112(11):94492t

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA remarkable pericyclic mechanism for enzyme-catalyzed phosphorus-carbon bond formation [Erratum to document cited in CA112(11):94492t]Michael S. McQueney, Sheng Lian Lee, Elise Bowman, Patrick S. Mariano, and Debra Dunaway-MarianoCite this: J. Am. Chem. Soc. 1989, 111, 26, 9280Publication Date (Print):December 1, 1989Publication History Published online1 May 2002Published inissue 1 December 1989https://doi.org/10.1021/ja00208a050RIGHTS & PERMISSIONSArticle Views81Altmetric-Citations3LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (135 KB) Get e-Alerts Get e-Alerts

A remarkable pericyclic mechanism for enzyme-catalyzed phosphorus-carbon bond formation

A remarkable pericyclic mechanism for enzyme-catalyzed phosphorus-carbon bond formation