Addition reactions kinetic versus thermodynamic

Formation of a highly electrophilic iodonium species, transiently formed by treatment of an alkene with iodine, followed by intramolecular quenching with a nucleophile leads to iodocyclization. The use of iodine to form lactones has been elegantly developed. Bartlett and co-workers216 reported on what they described as thermodynamic versus kinetic control in the formation of lactones. Treatment of the alkenoic acid 158 (Scheme 46) with iodine in the presence of base afforded a preponderance of the kinetic product 159, whereas the same reaction in the absence of base afforded the thermodynamic product 160. This approach was used in the synthesis of serricorin. The idea of kinetic versus thermodynamic control of the reaction was first discussed in a paper by Bartlett and Myerson217 from 1978. It was reasoned that in the absence of base, thermodynamic control could be achieved in that a proton was available to allow equilibration to the most stable ester. In the absence of such a proton, for example by addition of base, this equilibration is not possible, and the kinetic product is favored. 

Further studies by Brown and coworkers lent additional support to this mechanism and the absence of a free alkyl cation. Olah and coworkers have applied the concept of competitive alkylation to the case of naphthalene in order to study both positional and substrate selectivities, and to clarify the nature of kinetically versus thermodynamically controlled product composition. They explained the observed results by suggesting that a ir-complex, such as (1), was the intermediate involved when highly electrophilic catalysts or strongly basic aromatics were employed, and a o-complex (as proposed earlier by Brown) was involved in reactions with weakly electrophilic catalysts or less basic aromatics. 

Before commencing this discussion, it is appropriate to consider briefly the issue of kinetic versus thermodynamic control in the reactions of preformed Group I and Group II enolates and to summarize the structure-stereoselectivity generalizations that have emerged to date. It is now welt established that preformed lithium, sodium, potassium and magnesium enolates react with aldehydes in ethereal solvents at low temperatures (typically -78 °C) with a very low activation barrier. For example, reactions can often be quenched within seconds of the addition of an aldehyde to a solution of a lithium enolate. ... 

Kinetic versus thermodynamic control. A plot of Gibbs free energy versus reaction coordinate for Step 2 in the electrophilic addition of HBr to 1,3-butadiene. The resonance-stabilized allylic carbocation intermediate reacts with bromide ion by way of the transition state on the left to give the 1,2-addition product. It reacts with bromide ion by way of the alternative transition state on the right to give the 1,4-addition product. 

A large number of workers have examined the effects of temperature, solvent and reaction times on the ratio of the products of 1,4-addition versus 1,2-addition of dithiane and other a-thioalkyl carb-anions.34 Their results show that in general 1,2-addition is kinetically favored and therefore predominates at low temperatures and in less polar solvents,34 34 5 whereas 1,4-addition is thermodynamically favored... 

The difference was attributed to the operation of kinetic control in the aqueous system versus thermodynamic control in DMSO or dioxane, though, probably, there may be another explanation, as the reactions in organic solvents were run without the addition of base, while the reactions in the aqueous system were run with DBU, and thus, in the latter case, the nucleophiles were actually the anions of uracils. For ambident nucleophiles, the influence of the counter-ion and other factors associated with the ionic... 

The electrophilic addition of HBr to 1,3-butadiene is a good example of how a change in experimental conditions can change the product of a reaction. The concept of thermodynamic control versus kinetic control is a useful one that we can sometimes take advantage of in the laboratory. 

Figure 13.10 A schematic free-energy versus reaction coordinate diagram for the 1,2 and 1,4 addition of hbr to 1,3-butadiene. An allylic carbocation is common to both pathways. The energy barrier for attack of bromide on the allylic cation to form the 1,2-addition product is less than that to form the 1,4-addition product. The 1,2-addition product is kinetically favored. The 1,4-addition product is more stable, and so it is the thermodynamically favored product.

Careful product and kinetic studies for selected electron-deficient alkenes, electron-rich dienes and vinyl-substituted aromatic systems have provided some clarification of the [2 + 2] versus [2 + 2] cycloaddition issue. The thermodynamically favored product can often be anticipated on structural grounds. Reactions of TCNE with vinyl-substituted benzenoid aromatics, protoporphorins or heteroaromaticsgive [2 + 2] products, but for some styrenes the [2 + 4] addition may be kinetically favored. p-Methoxystyrene and TCNE react to form a charge-transfer complex which leads reversibly to the Diels-Alder product, and eventually to the finally isolated [2 + 2] adduct. An isomer of di-cyclopentadiene shows the same pattern, with the initially formed Diels-Alder adduct giving rise to a [2 + 2] adduct. 

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