Claisen rearrangement comparisons

Claisen rearrangement, 1194-1195 dehydration, 622 elimination reactions, 393 oxidation, 625-626 radical reactions, 243-244 characteristics of, 162-164 comparison with laboratory reactions, 162-164 conventions for writing, 162. 190 energy diagram of, 161 reduction, 723-725 reductive animation, 932 substitution reactions, 381-383 Biological reduction, NADH and, 610-611... 

For example /-butyl phenyl ether with aluminium chloride forms para-t-butyl phenol155. Often the de-alkylated phenol is also formed in considerable quantity. The reaction formally resembles the Fries and Claisen rearrangements. Like the Fries rearrangement the question of inter- or intramolecularity has not been settled, although may experiments based on cross-over studies156, the use of optically active ethers157 and comparison with product distribution from Friedel-Crafts alkylation of phenols158 have been carried out with this purpose in view. 

Several comparative procedures are included. The formation of 1-BENZYLINDOLE and GERANYL CHLORIDE by two different procedures are representative. An interesting comparison of three of the recent adaptations of the Claisen rearrangement on the same substrate is presented in the preparations of N.N-DIMETHYL-5/ -CHOLEST-3-ENE-5-ACETAMIDE, ETHYL-5/S-CHOLEST-3-ENE-5-ACETATE, and 5/9-CHOLEST-3-ENE-5-ACETALDEHYDE. For the utility of the procedure itself as well as for comparison with previously presented syntheses, the preparation and use of triflates in the synthesis of CYCLOBUTANONE is included. 

A kinetic study of the Cope rearrangement of 2-(trifluoromethyl)oeta-l.5-diene [(Z)-7] showed no rate acceleration in comparison with the rearrangement of unsubsliluled hexa-1,5-diene. Equilibrium was reached after 7 days at 207 C (K = 3.46 favoring the is-isomer). at which stage no intermediate 4-ethylhcxa-l,5-diene 8 was observed.6 In contrast, a trifluoromethyl group at position 2 does accelerate the Claisen rearrangement (sec Section 5.1.5.2.). 

Hur S, TC Bruice (2003a) Comparison of formation of reactive conformers (NACs) for the Claisen rearrangement of chorismate to prephenate in water and in the E-coli mutase The efficiency of the enzyme catalysis. J. Am. Chem. Soc. 125 (19) 5964-5972... 

Another series of publications from Ken s group compared kinetic isotope effects, computed for different possible transition structures for a variety of reactions, with the experimental values, either obtained from the literature or measured by Singleton s group at Texas A M. These comparisons established the most important features of the transition states for several classic organic reactions — Diels-Alder cycloadditions, Cope and Claisen rearrangements, peracid epoxidations, carbene and triazolinedione cycloadditions and, most recently, osmium tetroxide bis-hydroxylations. Due to Ken s research, the three-dimensional structures of many transition states have become nearly as well-understood as the structures of stable molecules. 

Chorismate mutase provides an example of an enzyme where QM/MM calculations have identified an important catalytic principle at work [8], This enzyme catalyses the Claisen rearrangement of chorismate to prephenate. The reaction within the enzyme is not believed to involve chemical catalysis, and this pericylic reaction also occurs readily in solution. Lyne et al. [8] investigated the reaction in chorismate mutase in QM/MM calculations, at the AMI QM level (AMI was found to perform acceptably well for this reaction in comparisons with ab initio results for the reaction in the gas phase [8]). Different sizes of QM system were tested in the QM/MM studies (e.g. including the substrate and no, or up to three, protein side chains), and similar results found in all cases. The reaction was modelled by minimization along an approximate reaction coordinate, defined as the ratio of the forming C-C and breaking C-0 bonds. Values of the reaction coordinate were taken from the AMI intrinsic reaction coordinate for the gas-phase reaction. 

Overall rate coefficients and activation parameters for the Claisen rearrangement of predominantly ort/io-substituted allyl aryl ethers are given in Table 26. There are some changes in the solvent medium for these rearrangements, but as seen later this should not greatly affect the comparisons. 

Aromatic Claisen rearrangements in 2,3-unsaturated sugar systems are useful for the stereo-controlled synthesis of aryl-branched sugars [87] (O Scheme 20). The a-anomer 97 is much less reactive in comparison to the /3-anomer 99. This thermal rearrangement is carried out by refluxing in iV,iV-diethylaniline. The efficiency of the reaction is almost independent of the nature of the p-substituent in the phenyl group. 

Figure 1 In a QM/MM calculation, a small region is treated by a quantum mechanical (QM) electronic structure method, and the surroundings treated by simpler, empirical, molecular mechanics. In treating an enzyme-catalysed reaction, the QM region includes the reactive groups, with the bulk of the protein and solvent environment included by molecular mechanics. Here, the approximate transition state for the Claisen rearrangement of chorismate to prephenate (catalysed by the enzyme chorismate mutase) is shown. This was calculated at the RHF(6-31G(d)-CHARMM QM-MM level. The QM region here (the substrate only) is shown by thick tubes, with some important active site residues (treated by MM) also shown. The whole model was based on a 25 A sphere around the active site, and contained 4211 protein atoms, 24 atoms of the substrate and 947 water molecules (including 144 water molecules observed by X-ray crystallography), a total of 7076 atoms. The results showed specific transition state stabilization by the enzyme. Comparison with the same reaction in solution showed that transition state stabilization is important in catalysis by chorismate mutase78.

The Claisen rearrangement of disubstituted allyl vinyl ether 24 was expected to proceed via to a chair-like transition state D because of favorable less-hindered geometry (Eq. 3.1.28) [35]. The importance of the favorable steric control elements found in D to the excellent stereochemical complementary can best be emphasized by comparison with the rearrangement of 26 bearing the E allyl ether under the same reaction conditions as that of 24 (Eq. 3.1.29). In this case, 25% of the aldehydic product mixture arises by way of boat-like transition state E because it is rather less crowded than F. 

Extensive theoretical studies have been reported for the parent Claisen rearrangement and for allyl vinyl ethers related to the chorismate to prephenate Claisen rearrangement catalyzed by chorismate mutase [16]. There has been, by comparison, much less study of the Ireland-Claisen rearrangement. 

A quantification of substituent effects on the rate of the Ireland-Claisen rearrangement was undertaken by Ireland et al. [19] and Curran and Suh [20]. The comparison of the rate constants for three acyclic allyl vinyl ether containing different substituents at C-6 illustrated a significant accelerating effect of the methoxy substituent (Scheme 11.12). The comparison of the rate constant for the parent allyl vinyl ether 1 (Table 1) and 3a (Scheme 11.12) indicates the immense accelerating effect of the siloxy group at the 2-position of an aUyl vinyl ether. 

The comparison of experimental and theoretically predicted kinetic isotope effects (KIEs) can be used to probe the accuracy of the computationally predicted transition structure provided that the experimental KIEs have been determined accurately. A comparison of predicted and experimental KIEs by Meyer et al. [55] led to the conclusion that, There is a firm disagreement in about half the cases between predicted and literature experimental heavy atom KIEs for both the aliphatic and aromatic Claisen rearrangements . Therefore, they reinvestigated the experimental KIEs for the Claisen rearrangement of aUyl phenyl and allyl vinyl ether and compared the determined values (solution) with the calculated data (gas phase). Eor the Claisen rearrangement of allyl vinyl ether, the transition structure was calculated on the MP4(SDQ)/6-31G level of theory and the predicted KIEs were in excellent agreement with the new experimental KIEs. The authors collected and compared previously reported data for the calculated distance between C- l/C-6 and O/C-4 and added their own predicted data (Scheme 11.40). 

Claisen rearrangement of Merrifield resin derivatized with O-allyl phenolic ethers into ortho-allylic phenols under microwave irradiation was performed by Kumar et al. [ 135]. The reactions were carried out in a household microwave oven, in which samples were irradiated in an open Erlenmeyer flask for 4-6 min (600 W) to afford products in 84-92% yield. In comparison, under thermal conditions, similar yields were obtained after 10-16 h at 140 °C (Fig. 39). 

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