Addition reactions transition state calculations

A deeper understanding of carbenic philicity requires a more detailed representation of the addition reaction transition state than that afforded by structure 4. Early MO calculations furnished structure 6 as representative of the transition state for addition of a singlet carbene to an alkene (Fig. 7.6). " ... 

Ab initio calculation of Diels-Alder reactions of a series of 5-heteroatom substituted cyclopentadienes Cp-X (65 X = NH, 50 X = NH, 64 X = NH3, 67 X = O", 54 X = OH, 68 X = OH3% 69 X = PH, 51 X = PH, 70 X = PH3% 71 X = S, 55 X = SH, 72 X = SH/) with ethylene at HF/6-31++G(d)//HF/6-31-i i-G(d) level by BumeU and coworkers [37] provided counterexamples of the Cieplak effect. The calculation showed that ionization of substituents has a profound effect on the n facial selectivity deprotonation enhances syn addition and protonation enhances anti addition. The transition states for syn addition to the deprotonated dienes are stabilized relative to those of the neutral dienes, while those for anti addition are destabilized relative to those of the neutral dienes. On the other hand, activation energies for syn addition to the protonated dienes are similar to those of the neutral dienes, but those for anti addition are very much lowered relative to neutral dienes (Table 6). 

One feature of the correlations is the scatter in the points for unsubstituted alkyl radicals, and this is particularly serious for the reaction of methyl radicals with ethylene. The experimental A-factor of this process is probably the most accurately known of any radical addition, and AS°9S is also very well established yet the point lies well away from the line through the other data. A possible explanation may be that in methyl radical, and other nucleophilic alkyl radical additions, the transition state is more like the reactants, so that the correlation with /15°98, a quantity calculated from product properties, is less likely. The early nature of the transition state in methyl radical reactions is... 

Another series of closely related reactions for which transition-state calculations have greatly helped in providing an understanding of the observed trends is the addition to deuterium-substituted alkenes. Szwarc and co workers (Feld et al., 1962) have determined secondary deuterium isotope effects for methyl and trifluoromethyl radicals by comparing the rate of addition to a terminal alkene with the rate for the deuterium-substituted alkene (25). Isotope effects for cyclopropyl radical addition have been measured by Stefani and coworkers (1970). For these three radicals a small inverse isotope effect (kJkK)... 

This is a question of reaction prediction. In fact, this is a deterministic system. If we knew the rules of chemistry completely, and understood chemical reactivity fully, we should be able to answer this question and to predict the outcome of a reaction. Thus, we might use quantum mechanical calculations for exploring the structure and energetics of various transition states in order to find out which reaction pathway is followed. This requires calculations of quite a high degree of sophistication. In addition, modeling the influence of solvents on... 

Transition state theory calculations present slightly fewer technical difficulties. However, the accuracy of these calculations varies with the type of reaction. With the addition of an empirically determined correction factor, these calculations can be the most readily obtained for a given class of reactions. 

Calculate activation barriers for bromide addition t( methyl bromide, ethyl bromide, 2-propyl bromide an( 2-methyl-2-propyl bromide using energies for Sn transition states bromide+methyI bromide, bromide- ethyl bromide, bromide+2-propyl bromide and bromides 2-methyl-2-propyl bromide) and Br (at left). Whicl reaction is fastest Slowest ... 

Obtain the energies of propene, dimethylborane, and 1-propyldimethyl borane, and calculate AH n for dimethylborane addition. Is this reaction exothermic or endothermic Use this result and the Hammond Postulate to predict whether the transition state will be more reactant like or more product like . Compare the geometry of the transition state to that of the reactants and products. Does the Hammond Postulate correctly anticipate the structure of the transition state Explain. 

Dimethylborane+propene C2 and 2-propyldimethyl borane depict the regioisomeric transition state and addition product. Calculate the energies of these species relative to those of the alternative transition state and product. Given these energy differences, and the experimental observation that this addition is almost completely selective for the anti-Markovnikov product, does it appear that this reaction is under kinetic or thermodynamic control Explain. 

Calculate activation energies for the preferred addition mode of each reagent. (Data for borane, 9-BBN and cis-4-methylpent-2-ene are available.) Which reaction will be faster Is the faster reaction more or less regioselective than the slower reaction Compare the structures of the two transition states and identify specific interactions that can account for differences in regioselectivity and reactivity. Use space-filling models. 

The validity of the model was demonstrated by reacting 35 under the same reaction conditions as expected, only one diastereoisomer 41 was formed, the structure of which was confirmed by X-ray analysis. When the vinylation was carried out on the isothiazolinone 42 followed by oxidation to 40, the dimeric compound 43 was obtained, showing that the endo-anti transition state is the preferred one. To confirm the result, the vinyl derivative 42 was oxidized and the intermediate 40 trapped in situ with N-phenylmaleimide. The reaction appeared to be completely diastereoselective and a single diastereomer endo-anti 44 was obtained. In addition, calculations modelling the reactivity of the dienes indicated that the stereochemistry of the cycloaddition may be altered by variation of the reaction solvent. 

Both experimental [7] and theoretical [8] investigations have shown that the anti complexes of acrolein and boranes are the most stable and the transition states were located only for these four anti complexes. The most stable transition-state structure was calculated (RHF/3-21G) to be NC, while XT is the least stable of the four located. The activation energy has been calculated to be 21.6 kcal mol for the catalyzed reaction, which is substantially above the experimental value of 10.4 1.9 kcal mol for the AlCl3-catalyzed addition of methyl acrylate to butadiene [4a]. The transition-state structure NC is shown in Fig. 8.5. 

Various ab initio and scmi-cmpirical molecular orbital calculations have been carried out on the reaction of radicals with simple alkenes with the aim of defining the nature of the transition state (Section 1.2.7).2I>,j , 6 These calculations all predict an unsymmetrical transition state for radical addition (i.e. Figure 1.1) though they differ in other aspects. Most calculations also indicate a degree of charge development in the transition state. 

In contrast with exo (top) facial selectivity in the additions to norbomene 80 [41], Diels-Alder reaction between isodicyclopentadiene 79 takes place from the bottom [40] (see Scheme 32). To solve this problem, Honk and Brown calculated the transition state of the parent Diels-Alder reaction of butadiene with ethylene [47], They pointed ont that of particular note for isodicyclopentadiene selectivity issue is the 14.9° out-of-plane bending of the hydrogens at C2 and C3 of butadiene. The bending is derived from Cl and C4 pyramidalization and rotation inwardly to achieve overlap of p-orbitals on these carbons with the ethylene termini. To keep the tr-bonding between C1-C2 and C3-C4, the p-orbitals at C2 and C3 rotate inwardly on the side of the diene nearest to ethylene. This is necessarily accompanied by C2 and C3 hydrogen movanent toward the attacking dienophile. They proposed that when norbomene is fused at C2 and C3, the tendency of endo bending of the norbomene framework will be manifested in the preference for bottom attack in Diels-Alder reactions (Schane 38). 

Table 10.4 lists the rate parameters for the elementary steps of the CO + NO reaction in the limit of zero coverage. Parameters such as those listed in Tab. 10.4 form the highly desirable input for modeling overall reaction mechanisms. In addition, elementary rate parameters can be compared to calculations on the basis of the theories outlined in Chapters 3 and 6. In this way the kinetic parameters of elementary reaction steps provide, through spectroscopy and computational chemistry, a link between the intramolecular properties of adsorbed reactants and their reactivity Statistical thermodynamics furnishes the theoretical framework to describe how equilibrium constants and reaction rate constants depend on the partition functions of vibration and rotation. Thus, spectroscopy studies of adsorbed reactants and intermediates provide the input for computing equilibrium constants, while calculations on the transition states of reaction pathways, starting from structurally, electronically and vibrationally well-characterized ground states, enable the prediction of kinetic parameters. 

An ab initio MO calculation by Jorgensen revealed enhanced hydrogen bonding of a water molecule to the transition states for the Diels-Alder reactions of cyclopentadiene with methyl vinyl ketone and acrylonitrile, which indicates that the observed rate accelerations for Diels-Alder reactions in aqueous solution arise from the hydrogenbonding effect in addition to a relatively constant hydrophobic term.7,76 Ab initio calculation using a self-consistent reaction field continuum model shows that electronic and nuclear polarization effects in solution are crucial to explain the stereoselectivity of nonsymmetrical... 

In the end, what is unique about computational methods is their ability to describe transition states and intermediates. This is why the calculation of reaction mechanisms has achieved such a prominent position in quantum biochemistry. We will therefore spend a considerable amount of time to describe when improved active-site geometries can be expected to give important beneficial effects on reaction energies. In addition, we will try to describe how the non-bonded interactions between active site and surrounding protein affect relative energies. 

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