Claisen rearrangements chair transition structure

The results of a computational study of the transition structures of the Claisen rearrangement were published by Vance et al. in 1988 [30]. The authors provided an analysis of the geometrical and electronic properties of the boat and chair transition structures for the Claisen rearrangement of the parent (unsubstituted) aUyl vinyl ether. The results were based on calculations on the RHF level of theory with correlation-corrected energies obtained by MP2/6-31G frequency analysis. It was found that larger basis sets in combination with polarization functions and... 

Discussing the stereochemical outcome of the Claisen rearrangements, two aspects had to be considered. On the one hand, the relative configuration of the new stereogenic centers was found to be exclusively syn in 201 and 202, pointing out the passing of a chair-like transition state c-a and c-jS, respectively, including a Z-acylammonium enolate structure (complete simple diastereo-selectivity/internal asymmetric induction). 

This conclusion has been applied in the Ireland-Claisen rearrangement 5.56 —> 5.58, which is one of the most frequently used [3,3] sigmatropic rearrangements, because it sets up two usefully substituted stereogenic centres with high levels of predictability, stemming from the chair-like transition structure 5.57. 

Structure B corresponds to the most stable transition state of the Ireland-Claisen rearrangement of Figure 14.49. In this transition state, the substituent at the allylic stereocenter is in a pseudo-equatorial orientation with respect to the chair-shaped skeleton. This is the same preferred geometry as in the case of the most stable transition state B of the Claisen rearrangement of Figure 14.48. The reason for this preference is as before that is, an allylic substituent that is oriented in this way experiences the smallest possible interaction with the chair skeleton. The obvious similarity of the preferred transition state structures of the Ireland-Claisen rearrangements of Figures 14.49 and 14.48 causes the same trans-selectivity. 

In cyclic systems, however, conformational constraints can override the inherent preference for chairlike transition states in Cope as well as Claisen rearrangements and lead to a partial involvement if not a dominance of boat-like TS structures. In the Ireland rearrangement of lactones of type (247), for example, chair-like transition state (249) is accessible only when the diaxial bridging methylene chain becomes sufficient in length (n = 7, Scheme 44). The preference of boat-like transition state (250) over (251) is due to a serious A - -type interaction between the endocyclic oxygen atom and pseudoaxial substituent R in (251). 

Claisen rearrangement of chorismic acid 1 to prephenic acid 2 (Scheme 1), which is catalyzed by the enzyme chorismate mutase, can be considered as the key step in the biosynthesis of aromatic compounds, that is the so-called shikimic acid pathway. The chair-like transition state geometry 3 was proved by double isotope-labeling experiments [2]. However, in the laboratory this particular reaction can be accelerated not only by enzymes but also by catalytic antibodies [3]. For the generation of such antibodies haptenes such as 4 were used, that is, molecules whose structure is very similar to the transition state of the particular reaction and which are tightly bound by the antibody. 

The loss of rotational freedom when the cyclic transition state is formed from the acyclic starting material accounts for the observed negative entropies and volumes of activation. It has been established that the transition state of the closely related Cope rearrangement (see below) resembles the chair conformation of cyclohexane. An analogous transition state structure for the Claisen rearrangement would account for the fact that isomerization of vinyl a-methylallyl ether yields 97% trans 4-hexQm and 3% cw-4-hexenal, since there should be a preference for an equatorial orientation of the methyl group in a cyclohexane chair-like transition state . 

Besides the question of the relative extents of bond making and breaking, the overall structure of the transition state in the Ireland-Claisen rearrangement is a chair-like structure. Included in Scheme 7.94 is the aromatic Claisen transition state whose SDKIEs were first determined by McMichael. " It is significant that this... 

Long before the development of the enolate Claisen rearrangement, it was established theoretically [31] and with sufficient experimental precedence [6, 32] that, lacking the structural constraints in the allyl vinyl ether system, the chair-like transition state is preferred for the rearrangement. This is understandable since between the two possible transition states A and B, the transition state A is of lower energy due to the equatorial disposition of the R group. 

Similar discussion is possible with respect to the transition state of the Claisen and Cope rearrangements i ). These can be treated similarly. Fig. 7.29a indicates that the symmetry of SO MO suggests ds-cis interaction with the six-membered structure for the transition state, but the chair-boat selectivity is not determined by the SO-SO interaction. The overlapping of LU and HO plays a secondary role. Fig. 7.29 shows that the boat form is unfavourable in comparison with chair form on account of the different signs of LU and HO at the central carbons. Similar consideration is possible with respect to the extended Cope rearrangement (Fig. 7.29.b). The predominance of thechair-form transition state is known both in the Claisen i f and the Cope rearrangements... 

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