Transition state conjugative stabilization

Streitwieser and Boerth studied the kinetic acidities of cycloalkenes with lithium cyclo-hexylamide (LiCHA) in cyclohexylamine for comparison with those of benzene and toluene66. The relative rates of deprotonation and the corresponding equilibrium pK values are tabulated in Table 12. These proton transfer transition states are stabilized by conjugation of the reacting C—H bond with the double bond. 

The stereoselectivity of the second and key Michael-type conjugate addition reaction can be rationalized as follows. The conformation of 63 will be restricted to 63-A due to A(l 3) strain between the N-methoxycarbonyl and w-propyl groups in 63-B. Attack of the vinyl anion from the stereoelectronically favored a-axial direction provides the adduct 64 exclusively. It is noteworthy that the stereochemical course of the above reaction is controlled by the stereoelectronic effect in spite of severe 1,3-diaxial steric repulsion between the axial ethyl group at the 5-position and the incoming vinyl anion. This remarkable stereoselectivity can be also explained by Cieplak s hypothesis[31]. On the preferred conformation 63-A, the developing a of the transition state is stabilized by the antiperiplanar donor Gc-h at the C-4 position. 

The double bond stabilizes the S 2 transition state by conjugation with the p orbital at the carbon atom under attack. This full p orbital (shown in yellow in the diagram below) forms a partial bond with the nucleophile and with the leaving group in the transition state. Any stabilization of the transition state will, of course, accelerate the reaction by lowering the energy barrier. 

The fact that suitably sterically biased cif-alkylvinylcyclopropanes participate in these types of reactions attests to the ability of the cyclopropane ring to transfer conjugative properties and to act as a pseudo ene unit. Competing pathways of higher order may become dominant in those cases where the transition state is stabilized by extended conjugation, as in the case of (18) and its predominant [1,7] hydrogen shift (Scheme 2). ... 

The situation is exactly analogous to the one discussed for addition to conjugated dienes (Sec. 8.24). Both reactant and transition state arc stabilized by resonance whether reaction is faster or slower than for simple alkenes depends upon which is stabilized more (see Fig. 8.9, p. 275). 

The first reaction offers a choice between an Sn2 reaction at a tertiary carbon or an SnI reaction next to a carbonyl group. Neither looks very good but experiments have shown that these reactions go with inversion of configuration and they are about the only examples of Sn2 reactions at tertiary carbon. They work because the p orbital in the transition state is stabilized by conjugation with the carbonyl group Sn2 reactions adjacent to C=0 groups are usually fast. 

Conjugated substituents at C-2, C-3, C-4, or C-5 accelerate the rearrangement. Donor substituents at C-2 and C-3 have an accelerating effect. The effect of substituents can be rationalized in terms of the stabilization of the transition state by depicting their effect on two interacting allyl systems. 

In the brosylate acetolysis sets, conjugative stabilization of the transition state is geometrically excluded in the syn form, but is anticipated in the anti form (13). That is, on structural grounds, is expected to be the parameter of choice for the syn set and for the anti set. The available data (for the OMe, Me, Cl and NO2 substituents) do indeed conform to this expectation ... 

This result, associated with those on substituent effects, supports previous conclusions to the effect that the position of the transition state depends on the reactivity in agreement with RSP. In particular, stabilization of the intermediate as a result of conjugation, such as that in the reaction of enol ethers, makes the transition state very early. The few available KSIEs also suggest that the transition states for aromatic series are earlier than those for alkenes. 

With push-pull ethylenes in which the donor part is a cyclic conjugated system with An + 2 ir electrons and/or the acceptor part is one with An tt electrons, the possibility exists for aromatic stabilization of the transition state to C=C rotation. Several such systems with both carbocylic and heterocyclic ring components have been studied. 

R was varied. Since the mechanism for the methyl ester is certainly A-1 and since intramolecular general acid catalysis should give a different transition state structure and therefore a different p value, it was concluded that the mechanism was A-1 in both cases. The rate enhancement provided by the carboxyl group substituent was ascribed to electrostatic catalysis whereby a proton is stabilized on the acetal oxygen, thus lowering the dissociation constant of the conjugate acid. Complete protonation of methoxymethoxybenzoic acids might be required because of the unstable carbonium ion intermediate. 

Treatment of Zr(/r--Cl)Cp 2(At-Fv) with LiC CR (R = Ph, SiMes) gave orange Zr(/r-r j -C2R)Cp 2(/r-Fv). The SiMcs complex is fluxional by exchange of the bonds on the Zr centers. Comparison of kinetic parameters with the phenylethynyl complex showed no bond breaking occurs the transition state for the latter is stabilized by conjugation with the Ph -electrons. 

Scheme 26 Aldol and conjugate addition reactions require different types of stabilization for the transition state...

---