Ligand transition-state structure

In the last 20 years a great deal of effort has been focused towards the immobilization of chiral catalysts [2] and disparate results have been obtained. In order to ensure the retention of the valuable chiral hgand, the most commonly used immobihzation method has been the creation of a covalent bond between the ligand and the support, which is usually a solid, hi many cases this strategy requires additional functionalization of the chiral hgand, and this change - together with the presence of the very bulky support - may produce unpredictable effects on the conformational preferences of the catalytic complex. This in turn affects the transition-state structures and thus the enantioselectivity of the process. 

Based on this feature, aggregation states of transition-state structures for base-promoted isomerization of oxiranes have been established by kinetic studies of LDA-mediated isomerizations of selected oxiranes in nonpolar media in the presence of variable concentrations of coordinating solvents (ligands). Results reported provide the idealized rate law V = [ligand]" [base] [oxtrane] for a-deprotonation and v = fc[ligand]°[base] / [oxirane]... 

Furukawa and co-workers (368,369) succeeded in applying the softer dicationic Pd-BINAP 260 as a catalyst for the 1,3-dipolar cycloaddition between 225 and 241a (Scheme 12.82). In most cases, mixtures of endo-243 and exo-243 were obtained, however, enantioselectives of up to 93% ee were observed for reactions of some derivatives of 225. A transition state structure has been proposed to account for the high selectivities obtained for some of the substrates (368). In the structure shown in Scheme 12.82, the two phosphorous atoms of the Tol-BINAP ligand and the two carbonyl oxygens of the crotonoyl oxazolidinone are arranged in a square-planar fashion around the palladium center. This leaves the ii-face of the alkene available for the cycloaddition reaction, while the re-face is shielded by one of the Tol-BINAP tolyl groups. 

Direct observation of complex in the a-deprotonation of N,N-dimethylbenzamide and kinetic studies are interpreted in terms of a tetrameric cube-like transition state structure typical of solid-state RLi structures in which ligands bound to the Li centers facilitate the release of the a-carbanion species. The continuing existence of the RLi tetramer on addition of TMEDA contrasts with the dogma that this additive breaks up aggregates and is rationalized by TMEDA advancing the formation of the a-carbanion in the transition state analogous to the effect of the R carbanion character in the tetramer. 

It should be remembered that the classification criterion used above has nothing to do with the fact that the composition of the products may indicate that an atom or group has been transferred between the two metal centers. An inner-sphere mechanism may or may not be accompanied by atom or group transfer, and this may either occur as a consequence of the transition state structure or trivially be due to the fact that the complexes involved are substitution labile, i.e. exchange of ligands between themselves or the environment takes place at a rate faster than that of electron transfer. 

The interaction of a prochiral molecule with a chiral homogeneous catalyst results in the formation of diastereomeric intermediates and transition states. High enantioselectivity is obtained if for the rate-determining step out of the many possible diastereomeric transition states, one is energetically favored. In such a situation the reaction follows mainly this path. Other possible pathways that cause dilution of optical purity are avoided. A fundamental point to note is that diastereomers, unlike enantiomers, need not have identical energies. The presence of a C2 axis of symmetry in these ligands makes some of the possible diastereomeric transition states structurally and energetically equivalent. As the... 

A comparison of the computed transition state structures for reactions in the presence and absence of basic ligand shows no large structural differences (Figs. 3 and 4). Table 1 shows that the differences in the enthalpy of activation for these reactions are less than 1 kcal/mol and that the [3 + 2] pathway is significantly lower in energy compared to the [2 + 2] pathway. 

Structure correlation to map reaction pathways might become important in the field of the monoclonal catalytic antibodies [145, 146]. These proteins are produced by the immune system to bind molecules which resemble the transition state of a chemical reaction. They show catalytic properties with high substrate specificity. Reactions can be imagined for which a biochemical catalyst is not yet known (e.g. the Diels-Alder reaction). The rational design of catalysts for these reactions requires detailed information about possible transition-state structures, geometrical and energetic aspects of the ligand/receptor interface and results from structure/reactivity relationships which are available from structure correlation. 

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