Kinetically-controlled reactions

Kinases (Section 28 3) Enzymes that catalyze the transfer of phosphate from ATP to some other molecule Kinetically controlled reaction (Section 10 10) Reaction in which the major product is the one that is formed at the fastest rate... 

The positions of substitution, orientation, and configuration of the stable form are determined by a balance between opposing steric and dipole ef-fects. There is less agreement regarding the factors influencing kinetically controlled reaction (see below). Essentially neutral conditions, such as provided by an acetate or pyridine buffer, are required to avoid isomerization. Frequently, however, bromination will not proceed under these conditions, and a compromise has been used in which a small amount of acid is added to start and maintain reaction, while the accumulation of hydrogen bromide is prevented by adding exactly one equivalent of acetate... 

When the major product of a reaction is the one that is formed at the fastest rate, we say that the reaction is governed by kinetic control. Most organic reactions fall into this category, and the electrophilic addition of hydrogen bromide to 1,3-butadiene at low temperature is a kinetically controlled reaction. 

Addition of hydrogen chloride to 2-methyl-1,3-butadiene is a kinetically controlled reaction and gives one product in much greater amounts than any isomers. What is this product ... 

Nitroolefins also offer the possibilities of 1,2 cycloaddition (37,57) or simple alkylation (57-59) products when they are allowed to react with enamines. The reaction of nitroethylene with the morpholine enamine of cyclohexanone led primarily to a cyclobutane adduct in nonpolar solvents and to a simple alkylated product in polar solvents (57). These products are evidently formed from kinetically controlled reactions since they cannot be converted to the other product under the conditions in which the other... 

Solladie and coworkers545 confirmed the earlier result of Nishihata and Nishio546 that the carbonation of the a-sulphinyl carbanion proceeds under kinetic control with retention of configuration at the metallated carbon atom. However, they also found that the stereochemical outcome of this reaction depends on other factors. They observed that 90% of asymmetric induction may be achieved under kinetic control (reaction time < 0.5 min) by using a base with low content of lithium salts, a result consistent with an electrophilic assistance by the lithium cation (equation 286)545. 

In the construction of carbocycles, five-membered ring formation has been used for preparing fused cyclic compounds, such as functionalized diquinanes. ° The reaction of 36 with (TMSlsSiH furnished the expected product 37 in 80% yield and in a or.fi ratio of 82 18, as the result of a kinetic controlled reaction (Reaction 43). 

In general, the enantioselectivity E value ) in a kinetic-control reaction is determined by the ratio of the rates of two enantiomers and defined by Equation 1 ... 

According to these equations, in kinetically controlled reactions the mean-square amplitude is about 10 V, while in reactions occurring under diffusion control it is almost an order of magnitude smaller. Thus, the size of electrochemical (thermal) equilibrium fluctuations is extremely small. 

The orbital coefficients obtained from Hiickel calculations predict the terminal position to be the most reactive one, while the AMI model predicts the Cl and C3 positions to be competitive. In polyenes, this is true for the addition of nucleophilic as well as electrophilic radicals, as HOMO and LUMO coefficients are basically identical. Both theoretical methods agree, however, in predicting the Cl position to be considerably more reactive as compared to the C2 position. It must be remembered in this context that FMO-based reactivity predictions are only relevant in kinetically controlled reactions. Under thermodynamic control, the most stable adduct will be formed which, for the case of polyenyl radicals, will most likely be the radical obtained by addition to the C1 position. 

The products are formed in kinetically controlled reactions, except in those instances, considered in the next subsection, where ethers result from the addition of a hydroxyl group to an activated alkene. The analytical method of Spurlin266 has often been used in order to evaluate relative rate-constants for reaction at the hydroxyl groups. 

MDSC is particularly useful for the study of reversible (related to the heat capacity) thermal reactions, and is less useful for non-reversing (kinetically controlled) reactions. Examples of reversible thermal events include glass transitions, heat capacity, melting, and enantiotropic phase transitions. Examples of non-reversible events include vaporization,... 

Fig. 18b.6. (a) Shape of the voltage pulses for diffusion control, mixed diffusion-kinetic control, and kinetic control, (b) concentration gradient of O showing expansion of the diffusion layer with time for complete diffusion controlled reaction, and (c) current transients show diffusion controlled, mixed kinetics and diffusion control, and complete kinetics controlled reactions corresponding to voltage pulses shown in (a). Note that the equations are derived only for the diffusion controlled case. 

Temperature plays an important contribution in kinetically controlled reactions. High temperature supplies enough energy to the system as the barrier leading to both diasteieoisomers can be surmounted, whereas a low temperature makes more probable only the surmount of the barrier corresponding to one of the diastereoisomers. 

It was recognized in early examples of nucleophilic addition to acceptor-substituted allenes that formation of the non-conjugated product 158 is a kinetically controlled reaction. On the other hand, the conjugated product 159 is the result of a thermodynamically controlled reaction [205, 215]. Apparently, after the attack of the nucleophile on the central carbon atom of the allene 155, the intermediate 156 is formed first. This has to execute a torsion of 90° to merge into the allylic carbanion 157. Whereas 156 can only yield the product 158 by proton transfer, the protonation of 157 leads to both 158 and 159. 

The attack of carbon nucleophiles such as Grignard reagents [116, 235, 236], cuprates [183, 237-242] and C-H acidic compounds [212] on allenes 155 leads generally to the non-conjugated products 158. However, it was observed early that 158 is the product of a kinetically controlled reaction also in these cases, whereas the thermodynamically more stable product 159 is formed at longer reaction times or subse-... 

The use of vinylphosphonium salts in heterocyclic synthesis continues to be exploited. The kinetically controlled reactions of the / -acylvinylphosphonium salts (143) with 2-aminopyridine lead to the salts (144) similar reactions occur with 2-aminopyrimidine and cytosine. Under conditions where thermodynamic control prevails, the salts (145) are formed predominantly, resulting from a Dimroth rearrangement of (144).136... 

Although it was not possible to verify whether this product is formed under kinetic or thermodynamic control, the authors suggest119 that if 90 arises from a kinetically controlled reaction, its formation could be rationalized on the basis of the stability of the involved intermediate. The bridged intermediate i is expected to be more stable than ii (equation 100) owing to the effect of the dimethoxymethyl substituent. 

From the independent propene pressure and residence time experiments the activation energy was calculated from Arrhenius plots to be 63.3 2.1 kj mol This value clearly indicated that the Rh-3-SlLP catalyst was operating under kinetically controlled reaction conditions and estabhshed the supposition of the homogeneous nature of the Rh-3-SlLP catalyst as confirmed by spectroscopic studies (vide supra). 

Referring to a kinetically controlled reaction in which selectivity parallels the relative thermodynamic stabilities of the products. Often in such reactions, the transition state occurs late along the reaction coordinate. 

In the latter reaction, remarkable examples of diastereoselectivity have been reported. Thus, the treatment of 7,7-dibromonorcarane 22 with n-butyllithium leads to exo-7-bromo-ewdo-7-lithiobicyclo[4.1.0]heptane23 exclusively, as shown by carboxylation (Scheme 8). It turns out that a slight excess of dibromonorcarane 22 relative to butyllithium is prerequisite to that high degree of stereoselectivity. The result is explained as follows the exo-bromine atom in 22 is exchanged first in a kinetically controlled reaction so that the ewrfo-bromo-exo-lithio-isomer 24 is formed. In a second step, an equilibration occurs by means of another bromine-lithium exchange, which takes place between 24 and the dibromonorcarane 22 (still present because used in excess). Thus, the thermodynamically... 

In 1994, Diederich and co-workers reported a very important approach for the regioselective formation of multiple adducts of Cjq by tether-directed remote functionalization [75]. This technique allows for the synthesis offullerene derivatives with addition patterns that are difficult to obtain by thermodynamically or kinetically controlled reactions with free untethered addends. This important subject has been extensively reviewed [26, 76, 77]. 

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