Subject transition state geometry

One may wish a more precise approximation to the transition state geometry than is represented by an intermediate or a compound somewhat resembling the transition state. This can sometimes be achieved by optimizing to a minimum, subject to the constraint that the bonds being made and broken have lengths... 

Conformational considerations restrict the number of possible transition state geometries in intramolecular cyclopropanations, which are quite selective, as shown by the examples from Doyle, Martin, and Muller illustrated in Scheme 6.38a [140,141]. Intramolecular cyclopropanation of diazo esters of chiral allylic alcohols are subject to double asymmetric induction, as shown by the series of examples in Scheme 6.38b. For all of these substrates, the exo product is slightly preferred when cyclopropanation is mediated by an achiral catalyst [142], but this selectivity is reversed dramatically when the S ester is allowed to react with the 5-S-MEPY catalyst. This pronounced endo selectivity persists for both the E and the Z-alkenes, although it is higher for the Z alkenes. Note also that when the chirality sense of the substrate and the catalyst are mismatched (5 substrate and R catalyst), the endo selectivities are low, unless R1/R2 are trimethylsilyl. For the matched case of double asymmetric induction, the same features that cause the endo selectivity can be used... 

Theoretical studies of several classes of the title heterocycles have appeared. Although the majority of these studies have focused on the conformational preferences of partially to completely reduced derivatives or on transition state geometries for intramolecular rearrangement reactions, several have addressed the stability and potential aromaticity of the parent fully unsaturated derivatives as well. Beyond the brief mention of these theoretical studies provided in this section, further details are more appropriately reported in the sections dealing with the structural and thermodynamic aspects of the subject heterocycles. 

Ito and coworkers discovered a nniqne Trnce-Smiles rearrangement of the substituted anilide intermediate 16 upon exposure to LDA. When 16 was subjected to an oxidative process (LDA, THE, Oj, -70°C), the rearranged product 17 was obtained in 75% yield instead of the desired oxidation product. Their proposed transition state geometry (18) is depicted in the box in Figure 18.2 [11]. 

It is interesting that the molecular structure in the transition state is also subject to a solvent effect. Compared to the gas phase, the solute molecular geometry at the transition state shifts toward the reactant side in aqueous solution the C—N and C—Cl distances... 

The practice of considering the catalyst as a featureless surface or a planar array of atomic centers deprives theory of an adequate concern for the geometry of the transition from reactants to products. Balandin (23) recognized the importance of the concept of a transition state to the development of a mechanistic theory of catalysis, and in his hands the multiplet theory proved fruitful. However the directional properties of binding orbitals, a subject of more recent development, apparently has not been incorporated into his theory. 

Equilibrium structure (geometry) may be determined from experiment, given that the molecule can be prepared and is sufficiently long-lived to be subject to measurement. On the other hand, the geometry of a transition state may not be established from measurement. This is simply because it does not exist in terms of a population of molecules on which measurements may be performed. 

Transition states for a number of simple reactions can be located simply by geometry optimization subject to an overall symmetry constraint. 

Gas-phase decarboxylation of /i-ketocarboxylic acids XCOCH2COOH (X = H, OH, and CH3) has also been the subject of theoretical studies.42 Ah initio calculations reveal that decarboxylation via a six-membered (rather than four-membered) ring transition state is favoured. Activation barriers of 23.8, 23.3 and 28.5 kcal mol-1 have been calculated for decarboxylation of 3-oxopropanoic acid, acetoacetic acid, and malonic acid, respectively. Only marginal effects of solvent on the energy barriers and on the geometries of the reactants and transition structures are predicted. The activation energy predicted for reaction of malonic acid agrees well with the experimental value and rate constants have been predicted for decarboxylation of 3-oxopropanoic acid and acetoacetic acid in the gas phase. 

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