Enolate addition, carbocation

Chapter 13. Enzymatic Addition, Elimination, Condensation, and Isomerization Roles for Enolate and Carbocation Intermediates... 

Alternatively one can make use of No Barrier Theory (NBT), which allows calculation of the free energy of activation for such reactions with no need for an empirical intrinsic barrier. This approach treats a real chemical reaction as a result of several simple processes for each of which the energy would be a quadratic function of a suitable reaction coordinate. This allows interpolation of the reaction hypersurface a search for the lowest saddle point gives the free energy of activation. This method has been applied to enolate formation, ketene hydration, carbonyl hydration, decarboxylation, and the addition of water to carbocations. ... 

The very small p- and m-values observed for the fast bromination of a-methoxystyrenes deserve comment since they are the smallest found for this electrophilic addition. The rates, almost but not quite diffusion-controlled, are amongst the highest. The sensitivity to polar effects of ring substituents is very attenuated but still significant that to resonance is nil. These unusually low p-values for a reaction leading to a benzylic carbocation are accompanied by a very small sensitivity to the solvent. All these data support a very early transition state for this olefin series. Accordingly, for the still more reactive acetophenone enols, the bromination of which is diffusion-controlled, the usual sensitivity to substituents is annulled. 

Alkenes are scavengers that are able to differentiate between carbenes (cycloaddition) and carbocations (electrophilic addition). The reactions of phenyl-carbene (117) with equimolar mixtures of methanol and alkenes afforded phenylcyclopropanes (120) and benzyl methyl ether (121) as the major products (Scheme 24).51 Electrophilic addition of the benzyl cation (118) to alkenes, leading to 122 and 123 by way of 119, was a minor route (ca. 6%). Isobutene and enol ethers gave similar results. The overall contribution of 118 must be more than 6% as (part of) the ether 121 also originates from 118. Alcohols and enol ethers react with diarylcarbenium ions at about the same rates (ca. 109 M-1 s-1), somewhat faster than alkenes (ca. 108 M-1 s-1).52 By extrapolation, diffusion-controlled rates and indiscriminate reactions are expected for the free (solvated) benzyl cation (118). In support of this notion, the product distributions in Scheme 24 only respond slightly to the nature of the n bond (alkene vs. enol ether). The formation of free benzyl cations from phenylcarbene and methanol is thus estimated to be in the range of 10-15%. However, the major route to the benzyl ether 121, whether by ion-pair collapse or by way of an ylide, cannot be identified. 

C4 is nucleophilic (enol ether), and CIO is electrophilic. The Lewis acid makes CIO more electrophilic by coordinating to 013. After conjugate addition, 08 traps the C3 carbocation. Proton-Li+ exchange gives the product. 

The first step is protonation. Because both C3 and C4 need to pick up protons, we protonate on C4. At this point, there s not much we can do except allow H20 to add to the carbocation, even though this is not a bond that is in our list of bonds that need to be made we will need to cleave it later. Addition of 08 to C5, H+ transfer from 08 to 06, and cleavage of the C5-06 bond follow. At this point we still need to make the C1-C5 bond. C5 is clearly electrophilic, so Cl needs to be made nucleophilic. Proton transfer from 08 to C3 and another H+ transfer from Cl to 08 gives the Cl enol, which attacks the C5 carbocation. Another H+ transfer from Cl to 08 is followed by cleavage of the 08-C5 bond, and loss of H+ gives the product. 

Again, this produces a favourable tertiary carbocation. Loss of a proton gives the required alkene. Note that potentially three different carbons could lose a proton. The reaction shown generates the most stable product this has the maximum number of alkyl substituents and also benefits from extended conjugation. We then get another aldol-type reaction. The enolate anion is produced from the ethyl chloroacetate, and simple addition yields an anion that is subsequently protonated. 

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