Lowest energy transition state

The mechanism of the carbo-Diels-Alder reaction has been a subject of controversy with respect to synchronicity or asynchronicity. With acrolein as the dieno-phile complexed to a Lewis acid, one would not expect a synchronous reaction. The C1-C6 and C4—C5 bond lengths in the NC-transition-state structure for the BF3-catalyzed reaction of acrolein with butadiene are calculated to be 2.96 A and 1.932 A, respectively [6]. The asynchronicity of the BF3-catalyzed carbo-Diels-Alder reaction is also apparent from the pyramidalization of the reacting centers C4 and C5 of NC (the short C-C bond) is pyramidalized by 11°, while Cl and C6 (the long C-C bond) are nearly planar. The lowest energy transition-state structure (NC) has the most pronounced asynchronicity, while the highest energy transition-state structure (XT) is more synchronous. 

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... 

Fig. 19 Lowest energy transition states for the addition of pyrrole and indole to iminium ions...

The syn and the anti conformations leading to (R,R)-29, and illustrated in Tab. 16.3, are calculated (Mechanics) to be the two lowest energy transition states for the cyclization of 27. Of the two, the anti conformation (rhodium carbene and carbonyl co-planar, but pointing in opposite directions) is the more stable by 3.37 kcal moh. If steric factors alone governed the outcome of these cyclizations, we would expect that the anti transition state leading to R,R)-29 would compete with the syn transition state leading to (S,S)-29, with the former being favored by 4.35 kcalmor. We have found that if the... 

The product formed in greatest amount in a kinetically-controlled reaction (the kinetic product) is that proceeding via the lowest-energy transition state, irrespective of whatever or not this is lowest-energy product (the thermodynamic product). 

A different type of stereoelectronic control has been found in the breakdown in solution of tetrahedral addition intermediates that arise in ester and amide hydrolysis and other reactions of carboxyl and carbonyl groups. In the case of an intermediate such as structure 8.47, in which there are two atoms with non-bonded electrons (generally O or N), the lowest-energy transition state for breakdown is a conformation in which nonbonded electrons of each are anti to the group being expelled (structures 8.48).50... 

In general, reactions that aren t easily reversible are kinetically controlled because equilibrium is rarely established. In kinetically controlled reactions, the product with the lowest-energy transition state predominates. Reactions that are easily reversible are thermody namically controlled, unless something occurs that prevents equilibrium. In thermodynamically controlled reactions, the lowest-energy product predominates. 

In summary, our photophysical studies indicate that the thermally activated relaxation pathways of (2E)Cr(III) very likely involve 2E-to- (intermediate) surface crossing. These (intermediates) can be associated with some, not necessarily the lowest energy, transition state (or transition states) for ground state substitution. The Arrhenius activation barriers for thermally activated relaxation are remarkably similar from complex to complex, but they can be altered in systems with highly strained ligands. Some of this work indicates that the steric and electronic perturbations of the ligands dictate the choice among possible relaxation channels. 

One approach of use in ground state organic chemistry is a static one. This assumes that one can predict the reactivity of a molecule from a description of the starting material itself. Thus, very electron rich centers are subject to electrophilic attack, electron poor sites in the molecules are expected to be susceptible to facile nucleophilic attack, weak bonds are subject to scission, etc. This approach is imperfect, in that a reaction course is really determined by a preference for the lowest energy transition state. Nevertheless, this starting state reasoning is quite useful, since most often it is, indeed, the predicted site of attack which affords the preferred transition state. 

The principle of microscopic reversibility states that a forward reaction and a reverse reaction taking place under the same conditions (as in an equilibrium) must follow the same reaction pathway in microscopic detail. The hydration and dehydration reactions are the two complementary reactions in an equilibrium therefore, they must follow the same reaction pathway. It makes sense that the lowest-energy transition states and intermediates for the reverse reaction are the same as those for the forward reaction, except in reverse order. 

Reaction barriers ( ) are determined by calculating the energy differences between the most stable initial and the lowest energy transition states. 

The lowest energy transition state obtained in this way is appropriate to the gas phase reaction, and does not necessarily correspond to the transient species for the reaction in solution. Similarly, there is no valid justification for assuming that the pathway catalyzed by the enzyme is the calculated minimum energy reaction pathway. There is, however, good reason to suppose that one of the calculated low energy reaction pathways will be that catalyzed by the enzyme. The calculations may thus provide two or more alternative reference reactions with their corresponding transition states, one of which will be selectively stabilized at the active site of the enzyme. 

The inside alkoxy effect is useful for predicting the stereoselectivity of nitrile oxide cycloaddition reactions with chiral lylic ethers. The hypothesis states that allylic ethers adopt the inside position and alkyl substituents prefer the sterically less-crowded anti conformation in transition states for these electrophilic cycloadditions . The terms inside and outside are defined in (17) for a hypothetical nitrile oxide cycloaddition transition state. Both ab initio (Gaussian 80 with 3-2IG basis set) and molecular mechanics calculations agree, each predicting the lowest-energy transition state to be the one described, i.e. (18 H outside) just above it lies one where the alkyl group is anti, OR outside and H inside (19 ). As illustrated, the former leads to a product wherein OR and the nitrile oxide oxygen are anti, the latter to one with them syn (Scheme 19). 

In an effort to understand the origin of the selectivity, we developed a model that views the cycloaddition as a kinetically controlled process, where the lowest energy transition state corresponds to the extended pseudochair formulation, 26, illustrated below [7]. 

The product ratio is therefore not determined by AG, but by the relative energy of the two transition states A and B. The conclusion that the ratio of products formed from conformational isomers is not determined by the conformational equilibrium ratio is known as the Curtin-Hammett principled Although the rate of the formation of the products is dependent upon the relative concentration of the two conformers, because AGb is decreased relative to AG to the extent of the difference in the two conformational energies, the conformational preequilibrium is established rapidly, relative to the two competing product-forming steps. " The position of the conformational equilibrium cannot control the product ratio. The reaction can proceed through a minor conformation if it is the one that provides access to the lowest-energy transition state. 

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