Reaction modelling Diels-Alder

Tire results of a study of the effect of these catalysts on the model Diels-Alder reaction of methyl vinyl ketone (4.8) with cyclopentadiene (4.6) are summarised in Table 4.1... 

Figure 5.61 Variations of NRT C—C bond orders (triangles), 62,3 (squares), i,5 (circles), and 65,6 (plus signs) along the IRC for the model Diels-Alder reaction (see Fig. 5.59(a) for the atom numbering).

The combination of the spin-coupled formulation of modem valence bond theory with intrinsic reaction coordinate calculations provides easy-to-interpret models for the electronic rearrangements that occur along reaction pathways. We survey here the information revealed by such studies of the mechanisms of various gas-phase six-electron pericyclic reactions the Diels-Alder reaction between butadiene and ethene, the electrocyclization of cis-l,3,5-hexatriene, the 1,3-dipolar cycloaddition between fulminic acid and ethyne, and the 1,3-dipolar cycloaddition of diazomethane. The fully-variational CASVB strategy proves particularly efficient for such studies. 

Itsuno et al. explored the possibility of using polymer-supported chiral Lewis acids in a model Diels-Alder reaction of methacrolein with cyclopentadiene [23a]. By using an insoluble polymer-supported Lewis acid [23], prepared from borane with cross-linked polymers with a chiral moiety such as an A-sulfonylamino acid, the Diels-Alder adduct is obtained in good yield with almost perfect exo selectivity and moderate enantioselectivity (Eq. 23). 

A new approach to determination of partial rate constants for reactions of conformers has been developed on the basis of constituents of the Gibbs energy of activation for reactions of a series of conformationally heterogeneous substrates. The proposed model allows solving of formal kinetic tasks under conditions of thermodynamic control and in the absence of diastereoisomeric products. The p-values and partial rate constants have been determined for the chair and twist conformers of a series of 2-substituted l,3-dioxacyclohept-5-enes in the model Diels-Alder reaction with l,2,4>5-tetrazine-3,6-dicarboxylate in two solvents. In dioxane, the chair conformer reacts 3.4 times faster and, in acetone, 1.4 times faster than does the twist conformer <1996RJC477>. 

Model Diels-Alder reaction at the hexaketide stage. 

The oxazolinone 107, a new recoverable chiral auxiliary that gives a high level of asymmetric induction in model aldol reactions and Diels-Alder cycloadditions (in which the reactant is connected to the auxiliary by -acylation), has been synthesized from L-gulonic acid. The key step in its synthesis was the thermal intramolecular nitiene insertion shown in Scheme 21. The formation of oxazolinethiones on hydrolysis of isothiocyanato-sugar derivatives is covered in detail in Chapter 9, section 3.3. Base-catalysed reaction of StS-O-isopropylidene-D-xylofuranosylamine with P-isothiocyanato-alkanals led to tricyclic derivatives such as 108, considered as cyclonucleoside analogues. ... 

Continuum Solvation COSMO and COSMO-RS Peri-cyclic Reactions The Diels-Alder Reaction Reaction Path Following Solvation Modeling Transition States in Organic Chemistry Ab Initio. 

Configuration Interaction Coupled-cluster Theory Density Functional Applications Density Functional Theory (DFT), Hartree-Fock (HF), and the Self-consistent Field M0ller-Plesset Perturbation Theory Numerical Hartree-Fock Methods for Molecules Pericyclic Reactions The Diels-Alder Reaction Solvation Modeling Transition Structure Optimization Techniques. 

Solvents exert their influence on organic reactions through a complicated mixture of all possible types of noncovalent interactions. Chemists have tried to unravel this entanglement and, ideally, want to assess the relative importance of all interactions separately. In a typical approach, a property of a reaction (e.g. its rate or selectivity) is measured in a laige number of different solvents. All these solvents have unique characteristics, quantified by their physical properties (i.e. refractive index, dielectric constant) or empirical parameters (e.g. ET(30)-value, AN). Linear correlations between a reaction property and one or more of these solvent properties (Linear Free Energy Relationships - LFER) reveal which noncovalent interactions are of major importance. The major drawback of this approach lies in the fact that the solvent parameters are often not independent. Alternatively, theoretical models and computer simulations can provide valuable information. Both methods have been applied successfully in studies of the solvent effects on Diels-Alder reactions. 

We chose benzyli dene acetone (4.39, Scheme 4.11) as a model dienophile for our studies. The uncatalysed Diels-Alder reaction of this compound with cyclopentadiene is slow, justifying a catalytic approach. Reaction of 4.39 with paraformaldehyde and dimethyl amine under acidic conditions in an aqueous ethanol solution, following a literature procedure, produced the HCl salt of 4.42 (Scheme 4.11). The dienophile was liberated in situ by adding one equivalent of base. 

Careful examination of literature reporting Lewis-acid catalysis of Diels-Alder reactions in combination with kinetic investigations indicate that bidentate (or multidentate) reactants are required in order to ensure efficient catalysis in water. Moreover, studies of a number of model dienophiles revealed that a potentially chelating character is not a guarantee for coordination and subsequent catalysis. Consequently extension of the scope in this direction does not seem feasible. 

Figure 5.3 shows the dependence of the apparent second-order rate constants (koi "/[5.2]i) on the concentration of surfactant for the Diels-Alder reactions of 5.If and 5.1 g with 5.2. The results of the analysis in terms of the pseudophase model are shown in the inset in Figure 5.3 and in the first two... 

Table 5.2. Analysis using the pseudophase model partition coefficients for 5.2 over CTAB or SDS micelles and water and second-order rate constants for the Diels-Alder reaction of 5.If and 5.1g with 5.2 in CTAB and SDS micelles at 25 C.

Figure 5.6. Plots of the apparent second-order rate constant (kap-p) versus the concentration of Cu(DS )2 for the Diels-Alder reaction of S.lc ( ), 5.1 f (f ) and 5.1 g (jsC) with 5.2 at 25 C. The inset shows the treatment of the data for the reaction of 5.1g according to the pseudophase model.

In contrast to SDS, CTAB and C12E7, CufDSjz micelles catalyse the Diels-Alder reaction between 1 and 2 with enzyme-like efficiency, leading to rate enhancements up to 1.8-10 compared to the reaction in acetonitrile. This results primarily from the essentially complete complexation off to the copper ions at the micellar surface. Comparison of the partition coefficients of 2 over the water phase and the micellar pseudophase, as derived from kinetic analysis using the pseudophase model, reveals a higher affinity of 2 for Cu(DS)2 than for SDS and CTAB. The inhibitory effect resulting from spatial separation of la-g and 2 is likely to be at least less pronoimced for Cu(DS)2 than for the other surfactants. 

We have demonstrated that due to inhomogeneous distribution of both reaction partners in the micelles, the pseudophase model leads to erroneous estimates of the second-order rate Constantin the micellar pseudophase, so that conclusions regarding the medium of the reaction cannot be derived through this model. However, analysis of substituent effects and endo-exo ratios of the Diels-Alder adducts indicate that the reaction experiences a water-like medium. 

Scheme 99) (416). The 4-acetyloxy-5-ary]thiazo]e or 4-methoxy-5-arylthiazole, which are models of the protomer (174b) do not give cycloaddition products under the same experimental conditions. This rules out the possibility of a Diels-Alder reaction involving the protomer (174b) (416). 

The compound shown is quite unreactive in Diels-Alder reactions Make a space filling model of it in the conformation required for the Diels-Alder reaction to see why... 

Perfluoroalkyl groups adjacent to multiple bond systems lower the frontier molecular orbitals (FMOs) Therefore, cycloaddition reactions preferentially occur with electron-rich multiple-bond systems The preference of bis(trifluoromethyl)-substituted hetero-l,3-dienes for polar reacuons makes them excellent model compounds for developing new types of diene reactions deviating from the well documented Diels-Alder scheme (pathway 1) A systematic study of the reactions of diene (1 =2-3=4)-dienophile (5=6) combinations reveals new synthetic possibilities that have not yet been fully exploited as tools for preparative organic cherrustry (equation 25)... 

Polymer-supported BINOLs thus prepared were treated with Zr(Ot-Bu)4 to form polymer-supported zirconium 20. In the presence of 20 mol% of various zirconium 20, the model aza Diels-Alder reactions of imine Id with Danishefsky s diene (7a) were performed results from selected examples are shown in Table 5.8. Whereas the 4-t-butylphenyl group resulted in lower enantiomeric excess (ee), higher ee were obtained when 3,5-xylyl, 4-biphenyl, 4-fluorophenyl, and 3-tri-... 

Honk et al. concluded that this FMO model imply increased asynchronicity in the bond-making processes, and if first-order effects (electrostatic interactions) were also considered, a two-step mechanisms, with cationic intermediates become possible in some cases. It was stated that the model proposed here shows that the phenomena generally observed on catalysis can be explained by the concerted mechanism, and allows predictions of the effect of Lewis acid on the rates, regioselectivity, and stereoselectivity of all concerted cycloadditions, including those of ketenes, 1,3-dipoles, and Diels-Alder reactions with inverse electron-demand [2],... 

The hetero-Diels-Alder reaction of formaldehyde with 1,3-butadiene has been investigated with the formaldehyde oxygen atom coordinated to BH3 as a model for a Lewis acid [25 bj. Two transition states were located, one with BH3 exo, and one endo, relative to the diene. The former has the lowest energy and the calculated transition-state structure is much less symmetrical than for the uncatalyzed reaction shown in Fig. 8.12. The C-C bond length is calculated to be 0.42 A longer, while the C-0 bond length is 0.23 A shorter, compared to the uncatalyzed reac-... 

The reaction was studied in the absence, and presence, of (MeO)2AlMe as a model catalyst for the BINOL-AlMe system. The change in relative energy for the concerted hetero-Diels-Alder reaction, and formation of the hetero-Diels-Alder adduct 11 via a Mukaiyama aldol reaction, is shown in Fig. 8.13. The conclusion of the study was that in the absence of a catalyst the concerted reaction is the most... 

To determine the preferred pathway for the [4-r-2]-hetero-Diels-Alder reaction model reactions using formaldehyde (R =H for 12 in Scheme 8.5) as the carbonyl compound and 2-azabutadiene (R -R" = H for 13 in Scheme 8.5) for the hetero... 

Cyclopentadiene is very reactive in Diels-Alder cycloaddition reactions, but 1,3-cyclohexadiene is less reactive and 1,3-cycloheptadiene is nearly inert. Explain. (Molecular models are helpful.)... 

Cativela C., Garcia J. 1., Mayoral J. A., Salvatella L. Modeling of Solvent Effects on the Diels-Alder Reaction Chem. Soc. Rev. 1996 25 209 218... 

Dannenberg J. J. The Molecular Orbital Modeling of Free Radical and Diels-Alder Reactions Adv. Mol. Model. 1990 2 1-63... 

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