Claisen rate enhancement

Chorismate Mutase catalyzed Claisen Rearrangement- 10 rate enhancement over non-enzymatic reaction... 

For the ort/io-Claisen rearrangement of allyl p-io y ether shown in Eq. (5-50), the rate enhancement with increasing solvent polarity is modest, in agreement with a cyclic process involving concerted bond-making and -breaking on activation [153]. 

The rate enhancement observed with polar solvents corresponds well with a dipolar transition state in the Claisen rearrangement see Section 7.2.2.12. 

The aqueous rate-enhanced Claisen rearrangement of glycoorganic compounds was shown to proceed in excellent yields [57]. The water solubility of the reactants was induced by grafting a free sugar onto the allyl vinyl ether moiety moreover, the sugar functioned as a chiral template and gave highly crystalline diastereomers which were easily separable to yield pure enantiomers after enzymic hydrolysis. This method allows the preparation of either enantiomerically pure (R)- or (S)-l,3-diol (Scheme 1). 

Rate enhancements of Claisen rearrangements can be achieved by the formation of anions a to C-2 (which can formally be considered as strong n-donors in position 2). Ester enolatcs of lithium87 88 91. sodium92-95, magnesium96-98 and zinc" have been widely used to effect chargc-accelerated rearrangements. 

The catalytic influence of ammonium chloride on the rate of the reaction was discussed by Claisen in his first report19. Since then, numerous catalysts have been introduced to affect rate enhancements of Claisen rearrangements, e.g., Bronsted and Lewis acids, bases or transition metal complexes. The literature concerning catalytic effects in the Claisen rearrangement has been thoroughly covered until 1984 0,122. 

Enantloselectivity Rate enhanced Claisen Enolate trapping ... 

Chorismic acid is the key branch point intermediate in the biosynthesis of aromatic amino acids in microorganisms and plants (Scheme 1.1a) [1]. In the branch that leads to the production of tyrosine and phenylalanine, chorismate mutase (CM, chorismate-pyruvate mutase, EC 5.4.99.5) is a key enzyme that catalyzes the isomerization of chorismate to prephenate (Scheme 1.1b) with a rate enhancement of about lO -lO -fold. This reaction is one of few pericyclic processes in biology and provides a rare opportunity for understanding how Nature promotes such unusual transformations. The biological importance of the conversion from chorismate to prephenate and the synthetic value of the Claisen rearrangement have led to extensive experimental investigations [2-43]. 

As mentioned in the solvent effect section, protic solvents accelerate the Claisen rearrangement. In particular the reaction rate enhances by increasing the acidity of the protic solvent used and trifluoroacetic acid (pKj=0.2) is one of the most effective catalysts. It was reported that in trifluoroacetic acid the Claisen rearrangement of allyl phenyl ether proceeds at room temperature to afford the ortho-rearrangement product 3 and 2-methylcoumaran 25 along with a small amount of phenol and unreacted starting ether [28, 29],... 

The course of other types of reactions which are also accelerated in aqueous solutions can help for a better understanding. For instance, in the Mukaiyama reaction between a silylenol ether and a carbonyl compound we obtained, in water, without any catalyst and in a similar yield, the same stereoselectivity than under 1(XX)0 atmospheres in dichloromethane that is the reverse of the normal stereoselectivity obtained by TiC catalysis(22,25). We and others have also described such a rate enhancement in the Claisen rearrangement (24 5), All these reactions, including the Diels Alder reaction have in common their negative activation volume. We anticipate that a reaction under kinetic control, between two small hydrophobic molecules (or between the hydrophobic moieties of amphiphilic molecules) for which the activation volume AVt is negative must be accelerated in water as it is under pressure. When several transition states are possible, the more compact should be favored. Actually, this hypothesis is verified for all our aqueous reactions, especially the Diels-Alder reactions which give virtually pure endo transition state which is also the transition state favored under external pressure. 

PROBLEM 20.45 We saw on page 1063 that chorismate undergoes a [3,3] sigmatropic shift (Claisen rearrangement) to prephenate catalyzed by the enzyme chorismate mutase. This enzyme-catalyzed reaction occurs more than 1 million times faster than the corresponding nonenzymatic reaction. How does the enzyme effect rate enhancement Both enzymatic and nonenzymatic reactions proceed through a chairlike transition state. However, the predominant conformer of chorismate in solution, as determined by H NMR spectroscopy, is the pseudodiequatorial conformer 2, which cannot undergo the reaction. 

The studies of such closely related structures also ruled out any possible steric effects and the driving influence for reaction rate enhancement has to be seen in the oxygen atom in the y-allylic position (C6 of the Claisen system. Scheme 14). In previous reports [23], Carpenter and Burrows had developed a model to predict the influence of substituents on various pericyclic reactions based on Hiickel orbital energy calculations. According to this approach, a n-... 

Scheme 27. Water-promoted Claisen rearrangement in the aglycone moiety Rate enhancement and stereochemical induction [59]...

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