Felkin-Anh stereoselectivity in cycloadditions of acetylketene: evidence for a concerted, pseudopericyclic pathway

The cycloadditions of acetylketene with alpha-chiral aldehydes and ketones are shown to be diastereoselective, forming a tertiary or quaternary chiral center at an acetal or ketal carbon with good stereocontrol. X-ray crystallography of a minor product (5b) shows that the major products (e.g., 4b) are those predicted by the Felkin-Anh model. Transition states are reported at the MP2/6-31G level for the addition of ethanal to formylketene and at the B3LYP/6-31G level for the addition of 2-phenylpropanal. The ground-state conformations of the reactants and products are used to rationalize the relative energies and geometries of the transition states without the need to invoke the Cieplak hypothesis. However, chiral substituents on the alpha-oxoketene show no diastereoselectivity. These experimental and computational results are only consistent with the nearly planar, pseudopericyclic transition state previously proposed.     

On the 6-exo atom transfer radical cyclization reactions of 3-butenyl 2-iodoalkanoates

Bis(tributyltin)-initiated atom transfer cyclization reactions of 3-butenyl iodoalkanoates in the presence of BF3.OEt2 as the catalyst afforded the 6-exo cyclization products as a mixture of 3,4-cis- and trans-substituted tetrahydro-2H-pyran-2-ones in 53-71% yield with the major isomers being the cis ones. Ab initio calculations at the B3LYP/6-31G level on the transition states of the radical cyclization and on the cyclized products revealed that the reactions are kinetically controlled and the transition states for the 6-exo radical cyclization are in boat conformations. Moreover, the cis-oriented transition states are of lower energy than the corresponding trans-oriented ones, which are in excellent agreement with experimental results.     

Acid‐Catalyzed Cyclization of Terpenes Under Homogeneous and Heterogeneous Conditions as Probed Through Stereoisotopic Studies: A Concerted Process with Competing Preorganized Chair and Boat Transition States

Based on stereoisotopic studies and β‐secondary isotope effects, we propose that the acid‐catalyzed cyclization of geranyl acetate proceeds through a concerted mechanism. Under heterogeneous conditions (zeolite Y confinement), a preorganized chairlike transition state predominates, whereas under homogeneous conditions the boat‐ and chairlike transition states are almost isoenergetic. For the case of farnesyl acetate, we propose that under homogeneous conditions a concerted dicyclization occurs with a preorganized boat–chair transition state competing with the chair–chair transition state. Under zeolite confinement conditions, the chair–chairlike dicyclization transition state is highly favorable. The preference of chairlike transition states within the cavities of zeolite Y is attributed to a transition state shape selectivity effect.     

Conformational preference and cis-trans isomerization of 4(R)-substituted proline residues

We report here the conformational preference and prolyl cis-trans isomerization of 4(R)-substituted proline dipeptides, N-acetyl-N'-methylamides of 4(R)-hydroxy-L-proline and 4(R)-fluoro-L-proline (Ac-Hyp-NHMe and Ac-Flp-NHMe, respectively), studied at the HF/6-31+G(d), B3LYP/6-31+G(d), and B3LYP/6-311++G(d,p) levels of theory. The 4(R)-substitution by electron-withdrawing groups did not result in significant changes in backbone torsion angles as well as endocyclic torsion angles of the prolyl ring. However, the small changes in backbone torsion angles phi and psi and the decrease of bond lengths r(Cbeta-Cgamma) or r(Cgamma-Cdelta) appear to induce the increase of the relative stability of the trans up-puckered conformation and to alter the relative stabilities of transition states for prolyl cis-trans isomerization. Solvation free energies of local minima and transition states in chloroform and water were calculated using the conductor-like polarizable continuum model at the HF/6-31+G(d) level of theory. The population of trans up-puckered conformations increases in the order Ac-Pro-NHMe < Ac-Hyp-NHMe < Ac-Flp-NHMe in chloroform and water. The increase in population for trans up-puckered conformations in solution is attributed to the increase in population for the polyproline-II-like conformations with up puckering. The barriers DeltaGct++ to prolyl cis-to-trans isomerization for Ac-Hyp-NHMe and Ac-Flp-NHMe increase as the solvent polarity increases, as seen for Ac-Pro-NHMe. In particular, it was identified that the cis-trans isomerization proceeds through the clockwise rotation about the prolyl peptide bond for Ac-Hyp-NHMe and Ac-Flp-NHMe in chloroform and water, as seen for Ac-Pro-NHMe.     

Conformational analysis of a cyclopropane analogue of phenylalanine with two geminal phenyl substituents

Quantum mechanical methods have been used to investigate the intrinsic conformational preferences of 1-amino-2,2-diphenylcyclopropanecarboxylic acid (c(3)Dip), a cyclopropane analogue of phenylalanine bearing two phenyl substituents on the same beta-carbon. Geometries, energies, and frequencies were calculated on the N-acetyl-N'-methylamide derivative at the HF and B3LYP levels using the 6-31G(d), 6-311G(d), and 6-31+G(d,p) basis sets. Four minimum energy conformations were characterized: axial C(7), equatorial C(7), right-handed helix, and polyproline II. Analysis of the whole results, which are fully consistent with available experimental data, indicates that c(3)Dip tends to promote gamma-turn conformations.     

Tautomerizations of 2-, 3-, and 4-formylpyridine semicarbazone conformers in gas and aqueous phases

The search for possible conformations of 2-formylpyridine (H2FoPyS), 3-formylpyridine (H3FoPyS), and 4-formylpyridine (H4FoPyS) semicarbazones was carried out using potential energy surface method at the B3LYP/6-31G(d) level of theory. Thermodynamic quantities of amino-imino tautomerizations of the most stable conformers for H2FoPyS (o-Atctcc), H3FoPyS (m-Acttcc), and H4FoPyS (p-Atttcc) determined via the transition states with and without water-assisted proton transfers, derived from the frequencies calculations at the B3LYP/6-311++G(d,p) level in gas and aqueous phases are reported.     

Transition states for the dimerization of 1,3-cyclohexadiene: a DFT, CASPT2, and CBS-QB3 quantum mechanical investigation

Quantum mechanical calculations using restricted and unrestricted B3LYP density functional theory, CASPT2, and CBS-QB3 methods for the dimerization of 1,3-cyclohexadiene (1) reveal several highly competitive concerted and stepwise reaction pathways leading to [4 + 2] and [2 + 2] cycloadducts, as well as a novel [6 + 4] ene product. The transition state for endo-[4 + 2] cycloaddition (endo-2TS, DeltaH(double dagger)(B3LYP(0K)) = 28.7 kcal/mol and DeltaH(double dagger)(CBS-QB3(0K)) = 19.0 kcal/mol) is not bis-pericyclic, leading to nondegenerate primary and secondary orbital interactions. However, the C(s) symmetric second-order saddle point on the B3LYP energy surface is only 0.3 kcal/mol above endo-2TS. The activation enthalpy for the concerted exo-[4 + 2] cycloaddition (exo-2TS, DeltaH(double dagger)(B3LYP(0K)) = 30.1 kcal/mol and DeltaH(double dagger)(CBS-QB3(0K)) = 21.1 kcal/mol) is 1.4 kcal/mol higher than that of the endo transition state. Stepwise pathways involving diallyl radicals are formed via two different C-C forming transition states (rac-5TS and meso-5TS) and are predicted to be competitive with the concerted cycloaddition. Transition states were located for cyclization from intermediate rac-5 leading to the endo-[4 + 2] (endo-2) and exo-[2 + 2] (anti-3) cycloadducts. Only the endo-[2 + 2] (syn-3) transition state was located for cyclization of intermediate meso-5. The novel [6 + 4] "concerted" ene transition state (threo-4TS, DeltaH(double dagger)(UB3LYP(0K)) = 28.3 kcal/mol) is found to be unstable with respect to an unrestricted calculation. This diradicaloid transition state closely resembles the cyclohexadiallyl radical rather than the linked cyclohexadienyl radical. Several [3,3] sigmatropic rearrangement transition states were also located and have activation enthalpies between 27 and 31 kcal/mol.     

Ab initio computational studies of conformationally restricted cope rearrangements. First examples of fully concerted allenyl cope rearrangements

Results of (8,8)CASPT2/6-31G//(8,8)CASSCF/6-31G level calculations on the potential surface for the conformationally restricted allenyl Cope rearrangements of syn-5-propadienylbicylco[2.1.0]pent-2-ene (14) and syn-6-propadienylbicyclo[2.1.1]hex-2-ene (15) are reported. Both are found to proceed through concerted pathways. Also included are the results of (6,6)CASPT2/6-31G//(6,6)CASSCF/6-31G level calculations on the Cope rearrangements of syn-5-ethenylbicyclo[2.1. 0]pent-2-ene (18), syn-6-ethenylbicyclo[2.1.1]hex-2-ene (19), and syn-7-vinylnorborene (20), which are found to involve diallylic diradical intermediates 26, 30, and 36, respectively. Previous studies have shown that the allenyl Cope rearrangement of 1,2, 6-heptatriene (1) to 3-methylene-1,5-hexadiene (2) involves a single transition structure that either proceeds to the monoallylic cyclohexane-1,4-diyl derivative 3 or bypasses 3 to form 2 directly. (4) More recently, the conformationally restricted allenyl Cope rearrangement of syn-7-allenylnorbornene (7) has also been found to involve tricyclic monoallylic cyclohexane-1,4-diyl intermediate 11. (7) The rearrangements of 14 and 15 appear to represent the first reported examples of fully concerted allenyl Cope rearrangements. Concertedness in these cases is ascribed to two parallel factors: (1) the relative instability of possible tricyclic diradical intermediates 16 and 17, compared to diradical intermediates 3 and 11 formed in the rearrangements of 1 and 7, respectively; and (2) the opportunity that exists to form sp-sp(2) sigma bonds in transition structures 21 and 23 that lead, respectively, to products 22 and 24. By contrast, only weaker sp(2)-sp(2) sigma bonds could form in unobserved concerted transition structures leading to products 28 and 32, formed in the nonconcerted rearrangements of 18 and 19.     

Conformational analysis of azepane, oxepane, silepane, phosphepane, thiepane and the azepanium cation by high level quantum mechanics

A complete conformational analysis of the title compounds was performed by quantum mechanics at the B3LYP and the CCSD(T) levels of theory with the triple-zeta quality basis set 6-311+G(d,p). The results are compared with the well-established results of cycloheptane. Without exception, twist-chair conformations are found to be stable conformations with the chair forms as transition states. Second row hetero atoms lower the relative energy of the boat conformations relative to the chair forms. The barrier of interconversion between the chair and boat families of conformations is found to be around 8 kcal/mol, except for phosphepane where it is 2 kcal/mol lower and for silepane, where the barrier is only 2.7 kcal/mol.     

Imidoylketene-alpha-oxoketenimine and alpha-oxoketene-alpha-oxoketene rearrangements. 1,3-shifts of substituted phenyl groups

1,3-phenyl shifts interconvert imidoylketenes 1 and alpha-oxoketenimines 2 and, likewise, alpha-oxoketenes 3 automerize by this 1,3-shift. These rearrangements usually take place in the gas phase under conditions of flash vacuum thermolysis. Energy profiles calculated at the B3LYP/6-31G(d,p) and B3LYP/6311 + G(3df,2p)//B3LYP/6-31G(d,p) levels demonstrate that electron donating substituents (D) in the migrating phenyl group and electron withdrawing ones (W) in the non-migrating phenyl group, can stabilise the transition states TS1 and TS2 to the extent that activation barriers of ca. 100 kJ mol(-1) or less are obtained; i.e. enough to make these reactions potentially observable in solution at ordinary temperatures. The calculated transition state energies DeltaG(TS1) show an excellent correlation with the Hammett constants sigma(p)(W) and sigma(p+)(D).     

Origins of boat or chair preferences in the Ireland-Claisen rearrangements of cyclohexenyl esters: a theoretical study

The relative energies of the chair and boat transition states of a variety of Ireland-Claisen rearrangements were obtained by B3LYP/6-31G calculations. Theoretical results are in good agreement with experimental data and provide a quantitative analysis of the origins of boat preferences that are observed in some of these reactions.     

A computational study of conformational interconversions in 1,4-dithiacyclohexane (1,4-dithiane)

Ab initio molecular orbital theory with the 6-31G(d), 6-31G(d,p), 6-31+G(d), 6-31+G(d,p), 6-31+G(2d,p), 6-311G(d), 6-311G(d,p), and 6-311+G(2d,p) basis sets and density functional theory (BLYP, B3LYP, B3P86, B3PW91) have been used to locate transition states involved in the conformational interconversions of 1,4-dithiacyclohexane (1,4-dithiane) and to calculate the geometry optimized structures, relative energies, enthalpies, entropies, and free energies of the chair and twist conformers. In the chair and 1,4-twist conformers the C-Hax and C-Heq bond lengths are equal at each carbon, which suggest an absence of stereoelectronic hyperconjugative interactions involving carbon-hydrogen bonds. The 1,4-boat transition state structure was 9.53 to 10.5 kcal/mol higher in energy than the chair conformer and 4.75 to 5.82 kcal/mol higher in energy than the 1,4-twist conformer. Intrinsic reaction coordinate (IRC) calculations showed that the 1,4-boat transition state structure was the energy maximum in the interconversion of the enantiomers of the 1,4-twist conformer. The energy difference between the chair conformer and the 1,4-twist conformer was 4.85 kcal/mol and the chair-1,4-twist free energy difference (deltaG degrees (c-t)) was 4.93 kcal/mol at 298.15 K. Intrinsic reaction coordinate (IRC) calculations connected the transition state between the chair conformer and the 1,4-twist conformer. This transition state is 11.7 kcal/mol higher in energy than the chair conformer. The effects of basis sets on the 1,4-dithiane calculations and the relative energies of saturated and unsaturated six-membered dithianes and dioxanes are also discussed.     

Retro [2 + 2 + 2] ring opening in tricyclobutabenzene derivatives. Thermochemistry and reaction barriers. A theoretical hybrid density functional study

The starting materials, transition states, and products of the concerted retro [2 + 2 + 2] ring-opening reactions of several tricyclobutabenzene derivatives substituted by double-bonded substituents were calculated at the B3LYP/6-31G theoretical level. It was found that the geometries of the products (cyclododecatriyne derivatives) are governed by the electronegativity of the substituents and hyperconjugation effects. The transition-state geometries of all the derivatives are similar. It was found that the retro [2 + 2 + 2] ring-opening reactions are endothermic (ca. 30-85 kcal mol(-1), depending on the substituents) with high barriers, ranging between ca. 95 and 115 kcal mol(-1). It is predicted that the tricyclobutabenzene derivatives under study will be stable when prepared and that they can be made by [2 + 2 + 2] intramolecular ring closure of the respective cyclododecatriyne derivative, especially with the use of transition metals as mediators or catalysts.     

二氯亚甲基锗烯与乙烯环加成反应机理的理论研究

The mechanism of a cycloaddition reaction between singlet dichloromethylene germylene and ethylene has been investigated with B3LYP/6-31G＊ method, including geometry optimization and vibrational analysis for the involved stationary points on the potential energy surface. Energies for the involved conformations were calculated by CCSD（T）//B3LYP/6-31G＊ method. On the basis of the surface energy profile obtained with CCSD（T）// B3LYP/6-31G＊ method for the cycloaddition reaction between singlet dichloromethylene germylene and ethylene, it can be predicted that the dominant reaction pathway is that an intermediate INT1 is firstly formed between the two reactants through a barrier-free exothermic reaction of 61.7 kJ/mol, and the intermediate INT1 then isomerizes to an active four-membered ring product P2.1 via a transition state TS2, an intermediate INT2 and a transition state TS2.1, in which energy barriers are 57.7 and 42.2 kJ/mol, respectively.     

Origins of stereoselectivity in intramolecular Diels-Alder cycloadditions of dienes and dienophiles linked by ester and amide tethers

B3LYP/6-31+G(d) calculations of structures and relative energies for competing transition states for intramolecular Diels-Alder reactions of substituted 3,5-hexadienyl acrylates and acrylamides show that boatlike conformations are sometimes favored in the forming ring that includes the tether.     

The first density functional study on the

The hetero-Diels-Alder reactions of 1,2-diaza-1,3-butadiene with ethylene, methyl vinyl ether, and methyl acrylate have been investigated theoretically with the aid of density functional theory using the Becke3LYP/6-31G(d) computational level. In the reactions with substituted alkenes, the transition states are concerted but asynchronous; the shortest bond-forming distance involves the nonsubstituted carbon of the alkene. In agreement with the experimental results, the reaction with methyl vinyl ether proceeds with high endo stereoselectivity and with complete regioselectivity to form the 6-methoxy cycloadduct. The conformational study of the transition states shows a sharp s-trans preference. In contrast, the [4 + 2]-cycloaddition of 1,2-diaza-1,3-butadiene with methyl acrylate have been found to occur with low regio- and stereoselectivity but with a s-cis preference in the transition structures.     

Competition between diradical stepwise and concerted mechanisms in chalcogeno-Diels-Alder reactions: a density functional study

The chalcogeno-Diels-Alder reactions of H(2)C=X (X = S, Se, Te) with butadiene, with trans,trans- and cis,trans-2,4-hexadiene, as well as of ethylene with thio-, seleno-, and telluroacrolein and reactions of thioformaldehyde with thioacrolein are examined theoretically. The B3LYP exchange-correlation functional with the 6-31G(d) and LanL2DZ(d) basis sets is employed. Stepwise diradical and concerted pathways are considered for all reactants. A modified concerted mechanism via a pre-reaction complex followed by a concerted transition state is studied for thioformaldehyde reacting with thioacrolein. The stepwise diradical pathways are predicted to be energetically less favorable than the concerted pathways for all cases considered. Even the sterically hindered reaction between selenoformaldehyde and cis,trans-2,4-hexadiene prefers a concerted path. It is a considerable challenge to reverse this energy preference for the concerted reaction given that both electronic and steric factors act to increase or decrease the activation energies of the concerted and diradical stepwise paths in the same way. A modified concerted mechanism operates for reagents with very small HOMO-LUMO gaps such as thioformaldehyde and thioacrolein. This mechanism is completely synchronous, with a vanishingly small barrier.