Geometries Of Transition Structures Research Articles

Stereoelectronic constraints in the aryl radical cylization of phenethylenamides

The 7-endo-trig and 6-exo-trig cyclizations of the N-formylphenethylenamide radicals have been computationally studied at the UM062X/6–31 + G** and UPW6B95-D3 DFT levels of theory. Computations show a regioselectivity preference for the 7-endo process over the 6-exo in agreement with known experimental results. This 7-endo process takes place preferentially through a transition structure of half-boat geometry which fully retains enamide planarity. On the other hand, the 6-exo-trig cyclization prefers a chair transition structure geometry which places the N-vinyl group in a pseudo-equatorial position. Computations also show that conformational locking in cyclic enamides greatly increases the preference for the 7-endo path in agreement with experimentally observed outcomes.

Ionic liquid supported acid additive stabilizes the transition structure of organocatalytic asymmetric direct aldol reaction by proton donation: A quantum mechanical study

ONIOM studies were performed on the transition structure (TS) of organocatalytic direct aldol reaction by using ionic liquid supported benzoic acid (ILS-PhCO2H) as an additive. Results obtained from this computation suggest direct involvement of ILS-PhCO2H in the TS as a proton donor. It has also come out from the present study that, the counter ion of the ILS-acid additive may also play significant role to maintain the proper TS geometry by holding the organocatalyst and the acid additive close together during the course of reaction.

CASSCF Computational Study of Pseudopericyclic Character in Electrocyclic Rearrangements Involving Heteroatoms.

The Complete Active Space Self-Consistent Field (CASSCF) computational method, with the 6-31G* basis set, was used to examine six electrocyclic rearrangements, each involving a 1,2,4,6-heptatetraene skeleton with two variously located oxygen and/or nitrogen heteroatoms, as a way to determine which, if any, are pseudopericyclic as opposed to pericyclic. Primarily through the close examination of the active space orbitals, but also considering transition structure geometries and activation energies, it was concluded that rearrangements 3 → 4, 5 → 6, 7 → 8, and 9 → 10 are pseudopericyclic with two orbital disconnections each, whereas the 13 → 14 and 15 → 16 rearrangements are pericyclic. Our conclusions agreed with those of others in two of the four cases that had been studied previously by density functional theory (3 → 4 and 7 → 8) but ran contrary to the previous conclusions that the 5 → 6 rearrangement is pericyclic and that the 15 → 16 rearrangement is pseudopericyclic. Our results are also compared and contrasted to previous similar ones of ours involving the 3 → 4 electrocyclization (essentially pericyclic), the 11 → 12 [3,3] sigmatropic rearrangement (pseudopericyclic), and similar [3,3] sigmatropic rearrangements (all pericyclic), and detailed rationales for these latest results are provided.

5]Radialene.

The [n]radialenes are a unique family of fundamental [n]-membered carbocyclic structures with radiating alkenes, which have attracted significant synthetic and theoretical attention. Whereas [3]-, [4]-, and [6]radialenes have been prepared and studied, all efforts to synthesize the five-membered ring compound have thus far met with failure. Here we describe the first synthesis of the fundamental hydrocarbon [5]radialene, C10H10. Our approach was a departure from previous radialene syntheses in that it utilized a low-temperature decomplexation of a stable organometallic compound, rather than high-temperature elimination or rearrangement. Our strategy was guided by analysis of previous radialene syntheses, which indicated rapid decomposition in oxygen, and ab initio calculations, which revealed an extraordinary susceptibility of [5]radialene to undergo Diels-Alder dimerization/polymerization. The origin of this susceptibility was traced to a small distortion energy associated with the formation of the transition structure geometry from the relaxed reactant monomers and to a narrow HOMO-LUMO gap.

Metal-Mediated Dihydrogen Activation. What Determines the Transition-State Geometry?

Density functional theory and absolutely localized molecular orbital energy decomposition analysis calculations were used to calculate and analyze dihydrogen activation transition states and reaction pathways. Analysis of a variety of transition-metal complexes with d(0), d(6), d(8), and d(10) orbital occupation with a diverse range of metal ligands reveals that for transition states, akin to dihydrogen σ complexes, there is a continuum of activated H-H bond lengths that can be classified as "dihydrogen" (0.8-1.0 Å), "stretched or elongated" (1.0-1.2 Å), and "compressed dihydride" (1.2-1.6 Å). These calculations also quantitatively for the first time reveal that the extent to which H(2) is activated in the transition-structure geometry depends on back-bonding orbital interactions and not forward-bonding orbital interactions. This is true regardless of the mechanism or whether the metal ligand complex acts as an electrophile, ambiphile, or nucleophile toward dihydrogen.

Computation of Accurate Activation Barriers for Methyl-Transfer Reactions of Sulfonium and Ammonium Salts in Aqueous Solution.

The energetics of methyl-transfer reactions from dimethylammonium, tetramethylammonium, and trimethylsulfonium to dimethylamine were computed with density functional theory, MP2, CBS-QB3, and quantum mechanics/molecular mechanics (QM/MM) Monte Carlo methods. At the CBS-QB3 level, the gas-phase activation enthalpies are computed to be 9.9, 15.3, and 7.9 kcal/mol, respectively. MP2/6-31+G(d,p) activation enthalpies are in best agreement with the CBS-QB3 results. The effects of aqueous solvation on these reactions were studied with polarizable continuum model, generalized Born/surface area (GB/SA), and QM/MM Monte Carlo simulations utilizing free-energy perturbation theory in which the PDDG/PM3 semiempirical Hamiltonian for the QM and explicit TIP4P water molecules in the MM region were used. In the aqueous phase, all of these reactions proceed more slowly when compared to the gas phase, since the charged reactants are stabilized more than the transition structure geometries with delocalized positive charges. In order to obtain the aqueous-phase activation free energies, the gas-phase activation free energies were corrected with the solvation free energies obtained from single-point conductor-like polarizable continuum model and GB/SA calculations for the stationary points along the reaction coordinate.

Novel Diborane-Analogue Transition Structures for Borane Reactions with Alkyl Halides

Ab initio and DFT calculations were performed to examine the mechanisms of reduction of alkyl halides and formaldehyde by borane. With alkyl halides, the optimized transition structure geometry resembled diborane, with a pair of hydrogen atoms bridging the boron and carbon atoms by three-center-two-electron bonds. A similar transition structure was found for the reduction of formaldehyde, although it was not the lowest-energy transition structure. Solvation by dimethyl ether or dimethyl sulfide disrupted this bridging with chloromethane, while both ligands dissociated from borane during the reduction of formaldehyde. The high calculated activation free energies of alkyl halide reduction are consistent with their observed lack of reactivity with borane.

Isotope Effects and the Nature of Enantioselectivity in the Shi Epoxidation. The Importance of Asynchronicity

The epoxidation of beta-methylstyrene catalyzed by the Shi fructose-derived ketone is studied using experimental kinetic isotope effects and DFT calculations. The observation of a large beta olefinic (13)C isotope effect and small alpha carbon isotope effect is indicative of an asynchronous transition state with more advanced formation of the C-O bond to the beta olefinic carbon. By varying the catalyst conformation and alkene orientation, diverse transition structure geometries were located calculationally, and the lowest-energy structure leads to an accurate prediction of the isotope effects. Given this support for the accuracy of the calculations employed, the nature of enantioselectivity in this and related epoxidations is considered. The lowest-energy transition structures are generally those in which the differential formation of the incipient C-O bonds, the "asynchronicity," resembles that of an unhindered model, and the imposition of greater or less asynchronicity leads to higher barriers. In reactions of cis-disubstituted and terminal alkenes using Shi's oxazolidinone catalyst, the asynchronicity of the epoxidation transition state leads to increased steric interaction with the oxazolidinone when a pi-conjugating substituent is distal to the oxazolidinone but decreased steric interaction when the pi-conjugating substituent is proximal to the oxazolidinone. Overall, the asynchronicity of the transition state must be considered carefully to understand the enantioselectivity.

A B3LYP study of the effects of phenyl substituents on 1,5-hydrogen shifts in 3-(Z)-1,3-pentadiene provides evidence against a chameleonic transition structure.

The effects of one or two phenyl substituents on the activation enthalpy for a 1,5-hydrogen shift in 3-(Z)-1,3-pentadiene (1) and on the geometry of the transition structure (TS) have been investigated by B3LYP/6-31G calculations. The phenyl-substituent effects on the experimentally measured activation enthalpies are predicted to be sizable, spanning a range of nearly 10 kcal/mol. However, if differences between steric effects in the transoid isomers of the reactants are factored out by comparing the activation enthalpies in the cisoid conformers, the electronic components of the phenyl-substituent effects on both the barrier heights and the TS geometries are found to be quite modest in size. Unlike the TS in the Cope rearrangement, the TS for a 1,5-hydrogen shift in 1 is not highly variable in nature, and the reason the 1,5-hydrogen shift TS is not chameleonic is discussed.

A Standard Set of Pericyclic Reactions of Hydrocarbons for the Benchmarking of Computational Methods: The Performance of ab Initio, Density Functional, CASSCF, CASPT2, and CBS-QB3 Methods for the Prediction of Activation Barriers, Reaction Energetics, and Transition State Geometries

Experimental and theoretical data are provided for a set of 11 pericyclic reactions of unsaturated hydrocarbons. Literature experimental data are evaluated and standardized to ΔH⧧0K for comparison to theory. Hartree−Fock, MP2, CASSCF, CASPT2, density functional theory (B3LYP, BPW91, MPW1K, and KMLYP functionals), and CBS-QB3 transition-structure geometries, activation enthalpies and entropies, and reaction enthalpies and entropies for these reactions are reported and are compared to experimental results. For activation enthalpies, several density functionals rival CASPT2 and CBS-QB3 for closest agreement with experiment, while CASPT2 and CBS-QB3 provide the most accurate heats of reaction. Transition-structure geometries are reproduced well by all methods with the exception of the Cope rearrangement and cyclopentadiene dimerization transition structures.

Modern Valence-Bond Description of Chemical Reaction Mechanisms: The 1,3-Dipolar Addition of Methyl Azide to Ethene

Spin-coupled [SC(8)/6-31G(d,p)] calculations on top of the MP2/6-31G(d,p) intrinsic reaction coordinate are used in order to obtain a model for the electronic mechanism of the gas-phase concerted 1,3-dipolar cycloaddition (13DC) reaction between methyl azide (CH3N3) and ethene (C2H4). It is shown that this reaction follows a homolytic mechanism characterized by an almost simultaneous breaking of the two coplanar π bonds in methyl azide and of the π bond in ethene, and the subsequent reengagement of the valence orbitals initially responsible for these bonds into two new bonds, closing the triazole ring, and a lone pair on the central nitrogen in the product. This is in contrast to previous SC research which established heterolytic mechanisms, realized through the movement of electron pairs, for 13DC reactions involving 1,3-dipoles with more polar coplanar π bonds, such as fulminic acid (HCNO) and diazomethane (CH2N2). We find that neither the homolytic nor heterolytic mechanisms for 13DC reactions involve aromatic transition states. Other aspects of the gas-phase concerted 13DC reaction of methyl azide with ethene, including optimized transition structure geometry, electronic activation energy, activation barrier corrected for zero-point energies, and standard enthalpy, entropy, and Gibbs free energy of activation, have been calculated at the HF/6-31G(d), HF/6-31G(d,p), B3LYP/6-31G(d), B3LYP/6-31G(d,p), MP2/6-31G(d), MP2/6-31G(d,p), QCISD/6-31G(d), and CCD/6-31G(d) levels of theory. The paper includes a critical survey of recently published research on the electronic mechanisms of 13DC reactions and reveals the limitations of approaches relying on closed-shell wave functions and/or on hand-crafted valence-bond constructions.

The effect of solvent on a Lewis acid catalyzed Diels-Alder reaction, using computed and experimental kinetic isotope effects.

A new transition structure for the Diels-Alder reaction between isoprene and acrolein catalyzed by Et(2)AlCl is found to reconcile reported discrepancies between computed and observed secondary kinetic isotope effects (KIEs). Including the effect of solvent realigns the computed results with experiment demonstrating the importance of nonbond interactions at transition structures. Comparison of experimental and newly predicted KIE data reaffirms the ability of theory and experiment to probe the mechanism and transition structure geometry of organic reactions.

Structure and reactivity of the vinylcyclopropane radical cation

The [C5H8]+ potential energy hypersurface was investigated at the UCCSD(T)/DZP//UMP2(fc)/DZP+ZPE and B3LYP/DZP+ZPE levels of theory. The vinylcyclopropane radical cation 2A″ electronic ground state, with two elongated cyclopropyl C–C bonds, is 14.8 and 17.4kcalmol−1 less stable in its s-anti (2) and s-syn (1) conformation, respectively, than the cyclopentene radical cation, 5. The 21.6kcalmol−1 barrier for syn/anti-isomerization is due to a strong interaction of vinyl-π and cyclopropyl-σ MOs. The preferred rearrangement of the vinylcyclopropane radical cation is stepwise: ring opening to a distonic radical cation intermediate followed by a subsequent [1,2] H-shift to the open-chain 1,3-pentadiene radical cation (barrier of 21.0kcalmol−1 vs. 2). Disfavored by only 2.8kcalmol−1 is a concerted [1,3] alkyl shift rearrangement which preferentially proceeds with a suprafacial/inversion stereochemistry to ring expand to the cyclopentene radical cation, 5. The neutral concerted reaction has a 30kcalmol−1 higher barrier. Transition structure geometries are similar for the neutral and radical cation reaction. However, concerted and stepwise rearrangements to 5 have essentially the same activation barriers (21.3 and 21.2kcalmol−1, respectively). An activation of 23.2kcalmol−1 allows one cyclopropyl methylene group to insert into the C–C bond linking vinyl and cyclopropyl units (leading to the 1,4-pentadiene radical cation). This process is competitive with the ring expansion reactions. A H-shift initiated cyclopropyl ring opening was found to require a higher activation (32.4kcalmol−1 for 2). Experimentally, vinylcyclopropane radical cations, generated with an excess energy of 30.0kcalmol−1, have been reported to isomerize to 1,3-pentadiene radical cations.

Modern valence-bond description of chemical reaction mechanisms: the 1,3-dipolar addition of diazomethane to ethene.

The electronic mechanism for the gas-phase concerted 1,3-dipolar cycloaddition of diazomethane (CH2N2) to ethene (C2H4) is described through spin-coupled (SC) calculations at a sequence of geometries along the intrinsic reaction coordinate obtained at the MP2/6-31G(d) level of theory. It is shown that the bonding rearrangements occurring during the course of this reaction follow a heterolytic pattern, characterized by the movement of three well-identifiable orbital pairs, which are initially responsible for the pi bond in ethene and the C-N pi bond and one of the N-N pi bonds in diazomethane and are retained throughout the entire reaction path from reactants to product. Taken together with our previous SC study of the electronic mechanism of the 1,3-dipolar cycloaddition of fulminic acid (HCNO) to ethyne (C2H2) (Theor. Chim. Acc. 1998, 100, 222), the results of the present work suggest strongly that most gas-phase concerted 1,3-dipolar cycloaddition reactions can be expected to follow a heterolytic mechanism of this type, which does not involve an aromatic transition state. The more conventional aspects of the gas-phase concerted 1,3-dipolar cycloaddition of diazomethane to ethene, including optimized transition structure geometry, electronic activation energy, activation barrier corrected for zero-point energies, standard enthalpy, entropy and Gibbs free energy of activation, have been calculated at the HF/6-31G(d), B3LYP/6-31G(d), MP2/6-31G(d), MP2/6-31G(d,p), QCISD/6-31G(d) and CCD/6-31G(d) levels of theory. We also report the CCD/6-311++G(2d, 2p)//CCD/6-31G(d), MP4(SDTQ)/6-311++G(2d,2p)//CCD/6-31G(d) and CCSD(T)/6-311++G(2d, 2p)//CCD/6-31G(d) electronic activation energies.

Electrocyclic Ring Openings of 2-Furylcarbene and Related Carbenes: A Comparison between Pseudopericyclic and Coarctate Reactions

Ring openings of 2-furylcarbene (5a), 2-pyrrolylcarbene (5b), 1-cyclopenta-1,3-dienylcarbene (5c), and of 11, as well as of the 3- and five-membered ring vinylogs (7a, 7c, 9a, 9c) were investigated at the B3LYP/6-31G(d,p) level of theory. The reactions of 5a, 5c, and 11 were also studied at the G2(MP2) level. This work provides the first comparison of pseudopericyclic and coarctate orbital topologies in concerted reactions. The ring openings of 5a, 5b, 11 and their vinylogs have pseudopericyclic (but not coarctate) topologies, while the ring openings of 5c and vinylogs are pericyclic and can be described as coarctate. The transition structure geometry for the ring opening of 5c is not well described by MP2 theory. The G2(MP2) barrier for this ring opening is estimated to be 6.4 kcal/mol, significantly higher than that calculated by Sun and Wong. The ring opening is an eight-electron, Möbius, conrotatory process, not the six-electron, Huckel process described by Herges in his original work describing coarctate orbital topology. The vinylogous reactions of 7c and 9c are disrotatory. The triplet photochemistry of 3a and 3b, as studied by Nakatani et al., was modeled by 6a and 12, respectively. The difference between the two is attributed to the greater stability of the triplet carbene 311 as compared to 3syn-5.

Transition States for the Carboalumination of Alkenes and Alkynes

Ab initio molecular orbital theory was used to characterize stationary points on the potential energy surface for the carboalumination of alkenes and alkynes. Activation energies and entropies of activation were calculated and found to be in good agreement with experimental values. A π-complex between the alkyl aluminum and the substrate is a stable precursor to the transition structure. The transition structures are four-centered. Substituent effects on the transition structure geometries are small and predictable, suggesting that standard values for geometrical parameters for this and related reactions are reasonable. The anomalous relative reactivities of substrates can be explained by considering the reaction to essentially be a nucleophilic attack, rather than an electrophilic one.

Transition Structure Geometries for Transfers of Neutral and Anionic Nitrogen to Lithiated Carbanions.

The geometries of nucleophilic substitutions at neutral and anionic nitrogen by organolithium species have been investigated. The demonstration of an intramolecular conversion of 9 to 10 provides an endocyclic restriction test which supports a trigonal bipyramidal transition structure for nitrogen transfer. A lack of isotopic scrambling of 12a-18O during nitrogen transfer is taken to rule out reaction via an oriented ion pair. Attempted endocyclic restriction tests for transfers of formally anionic nitrogen with 32 and 33 were not successful. Reactions of n-butyl, s-butyl and tert-butyllithium reagents with 16, 23, 30, 31, and 36-38 generally afford higher yields with increasing substitution at the carbon of the organolithium reagent and with decreasing substitution adjacent to the nitrogen of the aminating reagent. These results are consistent with trigonal bipyramidal transition states for nucleophilic displacements of oxygen by carbon at neutral and anionic nitrogen.

On Transition Structures for Hydride Transfer Step: A Theoretical Study of the Reaction Catalyzed by Dihydrofolate Reductase Enzyme

A theoretical study is presented of the catalytic mechanism of dihydrofolate reductase (DHFR) enzyme based upon the characterization of the transition structure (TS) for the hydride transfer step. Analytical gradients at AM1 and PM3 semiempirical levels have been used to characterize the saddle point of index one (SPi-1) on global energy hypersurface for the hydride transfer in the active site of DHFR enzyme. The geometry, stereochemistry, electronic structure, and transition vector (TV) components associated to SPi-1 are qualitatively computational level independent. The TV amplitudes show primary and secondary isotope effects to be strongly coupled. The geometrical arrangement of the TS results in optimal frontier orbital interaction. Comparison of the TS geometry with the X-ray coordinates shows that the TS can be fitted without any stress at the active site. By comparison of the TS for the hydride transfer step in models of related enzymes, the geometries and the components of TV for TSs in hydride transfer steps are transferable and invariant. The results of this study suggest that the primary function of the enzyme is to constrain the reactants in the endo configuration, situating the system in a neighborhood of a SPi-1. This fact is in accordance with Pauling's postulate for enzyme catalysis.

AM1 semiempirical study of benzopyrroles as dienes for Diels-Alder reaction

A qualitative approach for quick evaluation of the reactivity of dienes such as cyclopentadiene, furan, pyrrole, indole, and isoindole for Diels–Alder reactions was applied. As qualitative methods, the frontier molecular orbital (FMO) energy gap and the Hammond postulate through bond orders and energy of the reaction were evaluated for such dienophiles as ethylene, 1,3-dioxa-4-cyclopentene, and maleic anhydride. It was demonstrated that pyrrole and benzopyrroles are poor dienes in comparison with cyclopentadiene and furan. Because the reaction is controlled by the HOMO of the diene there are special cases when isoindole can react as a diene, while the loss of indole aromaticity in the course of the reaction precludes the cycloaddition. Geometries of transition structures and the accompanying activation energies were calculated for pyrrole, indole, and isoindole as dienes. The stereoselectivity of the reaction is discussed and compared with experimental results. Key words: benzopyrroles as dienes, Diels–Alder cycloaddition, Hammond postulate.

Geometrical preferences for general acid-catalysed hydride transfer: comparative theoretical study of transition structures for reduction of formaldehyde

The geometries of transition structures (TSs) for acid-catalysed hydride reduction of formaldehyde have been determined using several different theoretical methods. In each case hydride transfer (HT) and proton transfer (PT) occur in roughly perpendicular planes. The TS for the simplest system, with methylamine as the hydride donor and ammonium as the proton donor, exists in three conformations differing in the orientation of methylamine about the axis for HT; the preferred conformer has been studied using the AM1, PM3, HF/3-21G, HF/6-31G** and MP2/6-31G** methods. TSs with dihydropyridine as the hydride donor and with imidazolium as the proton donor have been studied using the AM1, PM3 and HF/3-21G methods, and show very similar overall structural features. Most of the TSs are for concerted HT and PT, but the PM3 method predicts some reactions to be stepwise with rate-determining HT. All the TSs show PT to be very much more advanced than HT. The preferred distance between the donor and acceptor carbon atoms for HT is about 2.6 Å for a system bearing an overall positive charge in the HT moiety. As compared with more sophisticated models for the mechanism of reduction by lactate dehydrogenase, the use of very simple models does not materially alter the nature of the TS, which seems to be a rather structurally robust entity.