Transition-state models

Detailed analyses of the above experiments suggest that the apparent steps in k E) may not arise from quantized transition state energy levels [110.111]. Transition state models used to interpret the ketene and acetaldehyde dissociation experiments are not consistent with the results of high-level ab initio calculations [110.111]. The steps observed for NO2 dissociation may originate from the opening of electronically excited dissociation chaimels [107.108]. It is also of interest that RRKM-like steps in k E) are not found from detailed quantum dynamical calculations of unimolecular dissociation [91.101.102.112]. More studies are needed of unimolecular reactions near tln-eshold to detennine whether tiiere are actual quantized transition states and steps in k E) and, if not, what is the origin of the apparent steps in the above measurements of k E). 

The Zimmerman-Traxler like transition state model can involve either a chair or boat geometry. 

As we have seen, the important zero energy difference which measures aromatic reactivity contains a term involving rr-electron energies, and rvith the transition state model there will also be a contribution from... 

Various structural factors have been considered in interpreting this result The most generally satisfactory approach is based on a transition>state model, advanced by Felkin and co-woricers, in which the largest group is oriented perpendiculariy to the carbonyl group. Nucleophilic addition to the carbonyl groi occurs from the opposite side. ... 

The regioselectivity of 1,3-dipolar cycloadditions can also be analyzed by MO calculations on transition-state models. For example, there are two possible regioisomers from the reaction of diazomethane and methyl vinyl ether, but only the 3-methoxy isomer is formed. 

Transition state models tliat minimize allylic. A " strain fl91 and 194) provide... 

On tlie basis of tliis Lotidusioti and on NMR studies of Lomplexes of 17b witli Lewis adds, a transition state model to explain tlie observed sdectivity was proposed. Tliis involved initial Lomplexation of a cuprate litliium ion to tlie tliree different betetoatoms in tlie substrate, followed by fotniation of a d-E complexation... 

Transition-State Model Activation Energy Diagrams... 

The idea of the activated complex was developed by, among others, Henry Eyring at Princeton in the 1930s. It forms the basis of the transition-state model for reaction rate, which assumes that the activated complex—... 

The transition-state model is generally somewhat more accurate than the collision model (at least with p = 1). Another advantage is that it explains why the activation energy is ordinarily much smaller than the bond enthalpies in the reactant molecules. Consider, for example, the reaction... 

An open-chain transition state model, based on the improved Cram model (Section A.2.), was proposed for the prediction of the stereochemical outcome1 2. Under kinetic control, if the substituent R1 in the benzylic position is of medium size, the syn-isomer is formed as the major product2. 

The results for the reaction of (S)-2-phenylpropanal and (Z)-2-butenylboronate may be reconciled with this transition state model if it is assumed that the phenyl substituent is smaller than methyl in the pair of transition states 6 and 7. analogous to 4 and 5. This is possible if the lowest energy transition state is one in which the phenyl group eclipses C(cc)-H, such that a flat, sterically undemanding surface is presented to the incoming (Z)-2-butenylboronate. Similar... 

The data reported in Table 3 for the 2-butenylborations of 2-(dibenzylamino)propanal shed additional light on this transition state model. The ( )-2-butenylboration of 2-(dibenzyl-amino)propanal evidently proceeds preferentially (90%) by way of transition state 9, suggesting that the bulky dibenzylamino substituent destabilizes transition state 8 (X = NBn2 > CH3). On the other hand, the (Z)-2-butenylboration of 2-(dibenzylamino)propanal is relatively non-selective, compared to the excellent selectivity realized in the (Z)-allylborations of a-chloro- or x-alkoxy-substituted chiral aldehydes. This result suggests that an increase in the steric requirement of X destabilizes transition state 11 such that significantly greater amounts of product are obtained from transition state 10. 

Transition state models for diastereoseleclive carbonyl additions ... 

These examples indicate that the (Z)-syn,(E)-antt correlation should be considered to be a rule with many exceptions. Two explanations may be given in order to rationalize the manifold stereochemical results in aldol additions. Firstly, it seems plausible that the many different reaction conditions and starting materials (e.g., various types of enolates, counterions, etc.) may cause the aldol addition to follow different reaction mechanisms, so that different types of transition states are involved. Secondly, in a single type of transition state model, the reactants may have different orientations to each other, so that the formation of different stereoisomers may result even for one and the same transition state model. 

The tris(diethylainino)sulfoiiium difluorotrimethylsiliconate induced aldol addition of enolsi-lancs, which delivers predominantly syw-aldols independent of the cnolate geometry (sec p 1608), calls for another mechanistic model. A.n open transition state model has been proposed which assumes that the naked" ionic oxygens are as far apart as possible28. For (Z)-enolates, one transition state is favored over the diastereomeric orientation due to the avoidance of a repulsive R /CHj interaction. 

A Zimmerman-Traxler transition state model is postulated in order to rationalize the ul topicity of this aldol addition [i.e., the (S)-enolate preferentially attacks the 7 e-face of the aldehyde]33. In the two alternative transition states 3a [ul topicity (S)jRe] and 3b [Ik topicity (S)/Si, the substituents at the stereogenic center of the enolatc are oriented in such a way that... 

Once again, desilylation and oxidative cleavage33 delivers the hydroxycarboxylic acids. A chairlike transition state model, analogous to that proposed for the corresponding boron enolate33, is postulated in order to rationalize the ul topicity of the above titanium enolate. 

Although the chiral propanoates I and 5 are similar and the reaction conditions are almost identical, the stereochemical outcomes arc explained by completely different transition state models. Predominant attack of the ketene acetal 2 to the Ai-face of 2-methylpropanal is interpreted by assuming a Zimmerman-Traxler like model, which minimizes steric hindrance in a plausible way65. 

The preference of the (5, .S )-boron cnolatc to attack almost exclusively the Si-face of an aldehyde is rationalized by assuming the Zimmerman-Traxler transition state model. It is postulated that the methyl group of the propyl residue directs the 3-elhylpenlane-3-thiol group towards the borolane moiety, the chirality of which is thus effectively transferred34. 

Cyclic and open transition state models have been used to explain syn/anti stereoselectivity in these reactions1. The possible transition states (including boat B and chair C transition states) can be deduced from the E/Z geometry of the crotyl reagent and the imine. The postulated cyclic transition states for the preferred E geometry of the imine arc shown below. 

In addition, more detailed transition state models have been proposed which account for the unusually high diastereoselectivity5,6. The suggestion is that the additional steric demands created by the axial metal ligands (L) are responsible for the energy difference between the Cram and anti-Cram transition states. 

The configurational course depends on the enolatc configuration and the metal ion which determines whether a cyclic (e.g., Zimmerman-Traxler type) or an acyclic transition state is traversed. At present the following transition state models have been proposed. 

Only true rate constants (i.e., those with no unresolved concentration dependences) can properly be treated by the Arrhenius or transition state models. Meaningful values are not obtained if pseudo-order rate constants or the rates themselves are correlated by Eq. (7-1) or Eq. (7-2). This error is found not uncommonly in the literature. The activation parameters from such calculations, A and AS in particular, are meaningless. 

Eksterowicz J. E., Houk K. N. Transition-State Modeling With Empirical Force Fields Chem. Rev. (Washington, D. C.) 1993 93 2439-2461... 

Another model can be used to predict diastereoselectivity, which assumes reactant-like transition states and that the separation of the incoming group and any electronegative substituent at the a carbon is greatest. Transition state models 45 and 46 are used to predict diastereoselectivity in what is known as the Felkin Ahn model ... 

Salahub, D. R., Chretien, S., Milet, A., Proynov, E. I., 1999, Performance of Density Functionals for Transition States in Transition State Modeling for Catalysis, Truhlar, D. G., Morokuma, K. (eds.), ACS Symp. Ser., 721, American Chemical Society, Washington, D. C. 

The selectivity of the aldol addition can be rationalized in terms of a Zimmer -man-Traxler transition-state model with TS-2-50 having the lowest energy and leading to dr-values of >95 5 for 2-51 and 2-52 [18]. The chiral copper complex, responsible for the enantioselective 1,4-addition of the dialkyl zinc derivative in the first anionic transformation, seems to have no influence on the aldol addition. To facilitate the ee-determination of the domino Michael/aldol products and to show that 2-51 and 2-52 are l -epimers, the mixture of the two compounds was oxidized to the corresponding diketones 2-53. 

Reaction of 3-ketoester 2-97 and acrolein 2-98 in presence of stoichiometric amounts of 2-103 led to the desired product 2-100 in 45 % yield. A transition-state model 2-99 may be postulated assuming an ion-pairing mechanism as reported for similar asymmetric transformations [37]. The diastereomeric mixture of 2-100 was transformed into 2-101 by mesylation and subsequent elimination. Despite the moderate 64% ee determined for 2-101, it was possible to obtain optically pure 2-101 by recrystallization from hexane. 

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