Preassociation complexes

As mentioned above, an aspect that complicates mechanistic studies is when mnltiple pathways result in similar reaction kinetics, rendering pathways difficult to distinguish from each other. One such complication is when a rapid equilibrium occurs between the incoming ligand and the 6-coordinate reactant to form an ion pair or preassociation complex. This species then reacts to form product and release the initial ligand. 

The relative magnitudes of these rate constants lead to different scenarios. If and are both large with respect to ki, the first step can be considered an equilibrium (with = ki/k-i) that can be treated independently from the second step. The intermediate preassociation complex may be detectable on the basis of the relative magnitudes of k and k-i. Detection of this intermediate provides supporting evidence for this substitution mechanism, and may allow calculation of K.  

In the event that the intermediate is undetectable ( 2 is comparable in magnitude to and k-i), but the rapid preequilibrium still holds, applying the steady-state approximation to [ML5X Y] affords the relationship 

Substitution into the steady-state approximation equation above provides 

The final rate equation after rearrangement and substitution of = — becomes 

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The yield of the nucleophilic substitution product from the stepwise preassociation mechanism k[ = k. Scheme 2.4) is small, because of the low concentration of the preassociation complex (Xas 0.7 M for the reaction of X-2-Y). Formally, the stepwise preassociation reaction is kinetically bimolecular, because both the nucleophile and the substrate are present in the rate-determining step ( j). In fact, these reactions are borderline between S l and Sn2 because the kinetic order with respect to the nucleophile cannot be rigorously determined. A small rate increase may be due to either formation of nucleophile adduct by bimolecular nucleophilic substitution or a positive specific salt effect, whUe a formally bhnole-cular reaction may appear unimolecular due to an offsetting negative specific salt effect on the reaction rate. 

The change from a stepwise preassociation mechanism through a triple ion intermediate to an uncoupled concerted reaction occurs as the triple ion becomes too unstable to exist in an energy well for the time of a bond vibration ( 10 s). The borderline between these two reaction mechanisms is poorly marked, and there are no clear experimental protocols for its detection. These two reaction mechanisms cannot be distinguished by experiments designed to characterize their transition states, which lie at essentially the same position in the inner upper right hand corner of Figure 2.3. Only low yields of the nucleophilic substitution product are obtained from both stepwise preassociation and uncoupled concerted reactions, because for formation of the preassociation complex in water is small... 

An important question is whether nucleophilic substitution at tertiary carbon proceeds though a carbocation intermediate that shows a significant chemical barrier to the addition of solvent and other nucleophiles. The yield of the azide ion substitution product from the reaction of 5-Cl is similar to that observed for the reactions of X-2-Y when this product forms exclusively by conversion of the preassociation complex to product. Therefore the carbocation 5 is too unstable to escape from an aqueous solvation shell and undergo diffusion-controlled trapping by azide ion. This result sets a lower limit of w fcj > -d 1.6 x 10 ° s (Scheme 2.4) " for addition of solvent to the ion pair intermediate 5" C1 . 

Fig. 3. Reaction coordinate diagram showing how a reaction will proceed through a preassociation complex (R.C.) when the associated intermediate and catalyst (I.C.) breaks down to reactants faster than it dissociates to separated I and C. Additional stabilisation of I.C. may occur through hydrogen-bonding.

While an ion pair is relatively straightforward to imagine between oppositely charged species, the driving force for the formation of a preassociation complex involving neutral species can be dipole-dipole interactions. 

A number of mechanistic pathways have been identified for the oxidation, such as O-atom transfer to sulfides, electrophilic attack on phenols, hydride transfer from alcohols, and proton-coupled electron transfer from hydroquinone. Some kinetic studies indicate that the rate-determining step involves preassociation of the substrate with the catalyst.507,508 The electrocatalytic properties of polypyridyl oxo-ruthenium complexes have been also applied with success to DNA cleavage509,5 and sugar oxidation.511... 

In conclusion, this extreme importance of preassociation of reagents appears to be peculiar to the cobaltammine systems and may very well arise from some property of the N-H bond (27). Recent work on the substitution reactions of [Co diars2 Cl2]+ (diars = o-phenylenebis(dimethylarsine)) in methanol shows that, even in the case of the cis complex, there is absolutely no kinetic effect in isomerization, in... 

X 10-3 sec.-1, was found for the dissociation of water. However, when ClOr was replaced by NO3 " as the inert anion the rates were up to 30% slower and the curvature of the k0b vs. (Cl ) plot was considerably lessened. A dependence on the nature of the inert anion would not be expected for this mechanism. The curvature cannot be explained by preassociation of chloride and complex ions. This would have to be much larger than is expected for 2 1 electrolytes of this type and no spectrophotometric evidence for it was obtained. 

To make the task more manageable this chapter will focus specifically on the interaction between the nucleophile and a double bond and not consider in any depth subsequent steps. We will also only briefly consider reactions in which there is a preassociation or complexation of the double bond with a Lewis acid prior to nucleophilic attack. Finally we shall concentrate on conventional nucleophilic attack and not discuss mechanisms involving single electron processes. In Section II we shall examine the types of double bonds that undergo nucleophilic attack, in particular examining relative reactivity, where available, and models for explaining this order. In Section III we shall review the orbital interactions that control the approach of a nucleophile to the double bond and the associated geometrical constraints. Then in Section IV we shall consider the implications of these constraints on selective reactions. 

The preassociation mechanism is more efficient than the trapping mechanism because it generates an intermediate which immediately reacts by an ultrafast proton transfer (in the pre-association complex, Int) and thus avoids the diffusion-controlled step bringing the catalyst and intermediate together. This mechanism is sometimes called a spectator mechanism because, although the catalyst is present in the transition structure, it is not undergoing any transformation [10]. 

Rebek and his co-workers have shown that replication - autocatalysis based on molecular recognition - best accommodates the facts observed in the reaction of 42 with 43, and that under the published conditions 44 is responsible for the autocatalysis. The results indicated template-catalyzed replication as the source of autocatalysis, where recognition surfaces and functional groups interact to form a productive termolecular complex. The mechanism demands that catalysis would be absent with esters that lack hydrogen-bonding sites. One complication of this system is that the initial product of this bimolecular preassociative mechanism is postulated to be a cw-amide, which isomerized to the frani-amide, the active form of template. This appears to be one major background reaction for product formation (Scheme 14). 

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