Concerted reactions, transition states

Equation 1.7). A concerted synchronous transition state [15] (the formation of new bonds occurs simultaneously) and a concerted asynchronous transition state [16] (the formation of one reaction depends on the nature of the reagents and the experimental conditions [17]. 

Most Diels-Alder reactions, particularly the thermal ones and those involving apolar dienes and dienophiles, are described by a concerted mechanism [17]. The reaction between 1,3-butadiene and ethene is a prototype of concerted synchronous reactions that have been investigated both experimentally and theoretically [18]. A concerted unsymmetrical transition state has been invoked to justify the stereochemistry of AICI3-catalyzed cycloadditions of alkylcyclohexenones with methyl-butadienes [12]. The high syn stereospecificity of the reaction, the low solvent effect on the reaction rate, and the large negative values of both activation entropy and activation volume comprise the chemical evidence usually given in favor of a pericyclic Diels-Alder reaction. 

We have just discussed several common strategies that enzymes can use to stabilize the transition state of chemical reactions. These strategies are most often used in concert with one another to lead to optimal stabilization of the binary enzyme-transition state complex. What is most critical to our discussion is the fact that the structures of enzyme active sites have evolved to best stabilize the reaction transition state over other structural forms of the reactant and product molecules. That is, the active-site structure (in terms of shape and electronics) is most complementary to the structure of the substrate in its transition state, as opposed to its ground state structure. One would thus expect that enzyme active sites would bind substrate transition state species with much greater affinity than the ground state substrate molecule. This expectation is consistent with transition state theory as applied to enzymatic catalysis. 

The retro-Diels-Alder reaction has been reviewed.A fully concerted cyclic transition state has been proposed for conrotatory opening of cyclobutenes, in order to account for the low activation entropy and unexpected activation volume of ca —2 to —3cm mol . ... 

Generally, only a single stepwise or concerted pathway for aliphatic nucleophihc substitution is detected by experiment because of the very different activation barriers for formation of the respective reaction transition states for these reactions. The description of the borderline between stepwise and concerted nucleophilic substitution reactions presented in this chapter has been obtained through a search for those rare substrates that show comparable barriers to these two reactions and through the characterization of the barrier for nucleophile addition to the putative carbocation intermediate of the stepwise reaction in the region of this change in mechanism. 

Theoretical calculations (B3LYP) gave predicted isotope effects consistent with experimental effects. Modelled reaction pathway involves complexation of the diazoesters to rhodium, loss of N2 and rhodium carbenoid formation and formation of asynchronous but concerted cyclopropanation transition state. 

High-valent oxo-complexes, isolated or in situ-generated, interact most often with electron-rich n -systems 1 or suitable C-H bonds with low bond dissociation energy (BDE) in substrates 3 (Fig. 2). These reactions may occur concerted via transition states 1A or 3A leading to epoxides 2 or alcohols 4. On the other hand, a number of epoxidation reactions, such as the Jacobsen-Katsuki epoxidation, is known to proceed by a stepwise pathway via transition state IB to radical intermediate 1C [39]. Similarly, hydrocarbon oxidation to 4 can proceed by a hydrogen abstraction/S ... 

An ene reaction involves the formation and cleavage of unequal numbers of o-bonds in a concerted cyclic transition state. 

This chapter is concerned with a group of thermally induced elimination reactions widely used for the introduction of carbon-carbon double Irands into complex molecules. These reactions form a discrete group of elimination reactions in that they proceed with syn stereochemistry via concerted cyclic transition states. Related syn elimination processes are believed to be involved in other elimination reactions, e.g. alcohol dehydration using the Burgess reagent, but are not discussed here. One of the advantages of the syn elimination reactions discussed in this chapter is that they do not require the use of... 

Enzyme catalyzed mechanisms represent fundamentally familiar reactions from organic chemistry (Figure 2.17). Acid-base catalysis is associated with the donation or subtraction of protons. Acid catalysis is a process in which partial proton transfer from an acid lowers the free energy of the reaction transition state, while base catalysis is a process in which partial proton subtraction by a base lowers the free energy of the reaction transition state. Concerted acid-base catalysis, where both processes occur simultaneously, is a common enzymatic mechanism. 

The other method to determine reactivity for reactions with synchronous concerted cyclic transition state structures is evaluation of the transition state ring aromaticity through bond order deviation. The results of the exo cyclopropene addition to the heterocycles and to cyclopentadiene are presented in Table 33. The higher the sum of bond order deviation from average bond order (x) is, the lower aromatic character the transition state structure has. The most reactive dienophile was cyclopentadiene, followed by furan, and then heterocycles. The most reactive heterocycle with heteroatoms in 1,3-position was 1,3-oxazole as was predicted on the basis of the FMO energy changes (Table 32). The least reactive was 1,3-diazole, as one would expect on the basis of experimental observations. It is very difficult to rely on the transition state structure bond order deviation to determine the experimental feasibility of a reaction but, because SBOD for furan and 1,3-oxadiazole were very similar, one can conclude that the cycloaddition with 1,3-oxadiazole is also experimentally feasible. 

The 3,3-shift of 1,2,6-heptatriene was found to occur at 300°C with log A = 9.97 - 30 470/2.While a concerted, cyclic transition state was proposed for the reaction, the possibility that a cyclohexane-1,4-diyl intermediate stabilized by the additional double bond was examined. Extensive calorimetric and kinetic studies as well as oxygen trapping experiments led to the enthalpy surface of Scheme 8.49, which also includes data on the conversion of 2-methylenebicyclo[2.2.0]hexane to 3-methylene-l,5-hexadiene, back to itself with bridgehead double inversion, and to 1,2,6-heptatriene. " ... 

The mechanism of tetrahydroquinoline formation by the Povarov reaction has been debated. A stepwise mechanism involves ionic intermediate 13, followed by an intramolecular electrophilic substitution. A concerted hetero Diels-Alder reaction was proposed where a concerted asynchronous transition state 14 was suggested. 

MO studies have shown that the Diels-Alder reaction of substituted selenocar-bonyl compounds with buta-1,3-diene or 2-methoxybuta-1,3-diene proceeds through a concerted, asynchronous transition state. Q ,jS-Unsaturated seleno ketones and seleno aldehydes readily undergo 4 - - 2-cycloaddition with alkenes and 4 - - 2-dimerization. The reaction of phosphaacetylene (138) with buta-1,3-diene produces triphosphatri-cyclooctenes (139) through a sequence involving Diels-Alder, ene, and intramolecular 4 -I- 2-cycloadditions (Scheme 53). The 4 + 2-cycloaddition of phosphaalkynes with 5,8-bis(trimethylsilyl)cycloocta-l,3,6-triene (140) readily yields the tricyclodecadiene (142) via the bicyclic intermediate (141) (Scheme 54). "... 

Mechanistic studies have been designed to determine if the concerted cyclic transition state is a good representation of the mechanism. The reaction is only moderately sensitive to electronic effects. The p value for a series of 1-arycyclopentenes is —1.2, which would indicate that there is little charge development in the transition state. The reaction shows a primary kinetic isotope effect indicative of C—H bond breaking in the rate-determining step. These observations are consistent with a concerted... 

Back to the starting point there is e qierimental data that has not yet been commented. Until now we have been dealing with a mechanism involving polar transition states that should have been affected to some extent by a change in the polarity of the medium. However, the fact is that the reactions of cinnamate 1 and hydroxylamine derivatives show no difference (either in stereochemistry or yields) when the solvent was changed from THF ( t 0.207) to EtOH 0.654). The laek of sensitivity to a change in the solvent polarity is a characteristic of the reactions involving concerted (isopolar) transition states. 

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