Transition states, early

When the reduction substrate can follow either of the two pathways, it is possible to obtain selectively one isomer or the other by carrying out the reduction either with an alumino- or borohydride, or with DIBAH or a borane. The first author to exploit this dichotomy was M. Midland [MKl]. The principal types of interactions to be taken into consideration are those of stereoelectronic origins, steric, torsional, and orbital interactions, and also the position of the transition state (early or late) along the reaction coordinate (see the following). 

The significance of the concept incorporated in Hammond s postulate is that, in appropriate cases, it permits discussion of transition-state structure in terms of the reactants, inteimediates, or products in a multistep reaction sequence. The postulate indicates that the cases in which such comparison is appropriate are those in which the transition state is close in energy to the reactant, intermediate, or product. Chemists sometimes speak of early or late transition states. An early transition state is reactant-like whereas a late transition state is product-like. 

The soft-nucleophile-soft-electrophile combination is also associated with a late transition state, in which the strength of the newly forming bond contributes significantly to the stability of the transition state. The hard-nucleophile-hffld-elechophile combination inqilies an early transition state with electrostatic attraction being more important than bond formation. The reaction pathway is chosen early on the reaction coordinate and primarily on the basis of charge distributiotL... 

Similarly, carboxylic acid and ester groups tend to direct chlorination to the / and v positions, because attack at the a position is electronically disfavored. The polar effect is attributed to the fact that the chlorine atom is an electrophilic species, and the relatively electron-poor carbon atom adjacent to an electron-withdrawing group is avoided. The effect of an electron-withdrawing substituent is to decrease the electron density at the potential radical site. Because the chlorine atom is highly reactive, the reaction would be expected to have a very early transition state, and this electrostatic effect predominates over the stabilizing substituent effect on the intermediate. The substituent effect dominates the kinetic selectivity of the reaction, and the relative stability of the radical intermediate has relatively little influence. 

Figure 5-6. Potential energy surface with an early transition state.

This valence bond description leads to an interesting conclusion. Because the transition state occurs at the point where the initial and final state VB configurations cross, the transition state receives equal contributions from each. This is so whether the transition state is early or late. Thus, the nucleophile Y and the leaving group X possess about equal charge densities in the transition state. This conclusion means that an early transition state is not (in this sense) reactantlike , for a reactantlike transition state should have most of the charge on Y. Similarly, a late transition state is not necessarily productlike. This view is at variance with other interpretations. 

Another possibility is that breakdown of the tetrahedral intermediate is rate determining, the transition state being very early, as in 2. 

Examine the structures of the two transition states (chlorine atom+methane and chlorine+methyI radical). For each, characterize the transition state as early (close to the geometry of the reactants) or as late (close to the geometry of the products) In Ught of the thermodynamics of the individual steps, are your results anticipated by the Hammond Postulate Explain. 

Would you describe the transition state for the Claisen rearrangement as early (like reactants), late (like products) or in between Given the overall thermodynamics of reaction, do you conclude that the Hammond Postulate applies Explain. 

The main approximation of such one-dimensional corrections is that the tunnelling is assumed to occur along the MER This may be a reasonable assumption for reactions having either early or late (close to either reactant or product) transition states. For reactions where both bond breaking and formation are significant at the TS (as is usually the case), the dominant tunnel effect is comer cutting (Figure 16.5), i.e. the favoured... 

In contrast to the open-chain and dipolar models, which are based on conformations of the carbonyl compound not representing energy minima, Karabatsos proposed a different model assuming an early, reactant-like transition state in which the most stable conformation of the free carbonyl compound is preserved1314. Thus, the C-M bond eclipses the carbonyl double bond and, in order to minimize the energy of the transition state, the nucleophile approaches close to the small substituent on the stereogenic center (Figure 5). 

With reactive aldehydes an early transition state is probably involved and therefore the steric demands of the aldehyde substituents are not highly influential. On the other hand, with less reactive ketones, the carbon-carbon bond formation is established further along the reaction coordinate, permitting the steric effects to play a greater role in the determination of the transition stale structure. 

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