Substituent, Solvent and Isotope Effects

As long as excessive steric compression of OR and L does not reduce k2 below the relative rates of formation, dissociation and collapse of the zwitterionic intermediate are irrelevant to the stereochemistry of the product cyclobutanone. In contrast, the substituent, solvent and isotope effects cannot be understood unless the timing of the various steps is taken into account. 

An elementary steady state analysis of the stepwise mechanism illustrated in Fig. 6.8, on the assumption that kr k2, leads to the following expression for the rate of formation of the contrathermodynamic cyclobutanone  

This reduces to two familiar limiting forms when 2 and A i are very unequal Case 1 [k2 k-i) k xp 1 zwitterion formation is rate-limiting. 

Case 2 k2 k-i) k xp (fci/ -i) 2 ring-closure occurs from a low concentration of zwitterion maintained in a pre-equilibrium with the reactants. 

Stabilization of the zwitterion by polar substituents decreases both A i and /u2, but is not expected to have a dominant effect on their ratio. Bulky substituents on the ketene and on Ci of the olefin should therefore favor Case 2 by reducing 2, provided that it is not reduced so drastically that k2 K, in which case rotation and closure to the thermodynamically more stable isomer will become competitive. A kinetic probe into the timing of the successive steps that should avoid the latter possibility would therefore be a series of reactions in which R =H and the steric requirements of one or both ketene substituents are varied. As the bulk of these substituents (L and S in Fig. 6.8) is increased, the reaction should shift from Case 1 towards Case 2 the change nianifesting itself in a gradual reduction in the sensitivity to polar substituent effects and to solvent polarity. Pending such an investigation, the published evidence is supportive of the proposed mechanism  

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In comparison, the level of detail in the understanding of radical ion reaction mechanisms is much lower for a number of reasons. Due to the inherently complex nature of the electron transfer-chemical reaction-electron transfer (ECE) mechanism, measurement of substituent, solvent and isotope effects will usually provide a combination of effects on all the steps involved. Introducing a donor substituent on a substrate will, for example, not only change the relative stability of the transition structures and intermediates with localized charges, but will also affect the rate constant of electron transfer and self-exchange between two substrates as well as the rate of back electron transfer. 

The generally contrathermodynamic stereochemistry, as well as the disparate substituent, solvent and isotope effects, are consistent with the zwitterionic mechanism illustrated in Fig. 6.8 [56], in which the orbital symmetry analysis plays a small but essential role. It is assumed that substitutional desymmetriza-tion is insufficient to destroy the essential symmetry of the tt orbitals, which sets the reactants on a path in which the four interacting C atoms are initially coplanar, but are induced by orbital symmetry conservation to bond along the diagonal. The preferred direction of approach and the stereochemical consequences then follow directly. 

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