Claisen rearrangement kinetics

The differences in the rate constant for the water reaction and the catalyzed reactions reside in the mole fraction of substrate present as near attack conformers (NACs).171 These results and knowledge of the importance of transition-state stabilization in other cases support a proposal that enzymes utilize both NAC and transition-state stabilization in the mix required for the most efficient catalysis. Using a combined QM/MM Monte Carlo/free-energy perturbation (MC/FEP) method, 82%, 57%, and 1% of chorismate conformers were found to be NAC structures (NACs) in water, methanol, and the gas phase, respectively.172 The fact that the reaction occurred faster in water than in methanol was attributed to greater stabilization of the TS in water by specific interactions with first-shell solvent molecules. The Claisen rearrangements of chorismate in water and at the active site of E. coli chorismate mutase have been compared.173 It follows that the efficiency of formation of NAC (7.8 kcal/mol) at the active site provides approximately 90% of the kinetic advantage of the enzymatic reaction as compared with the water reaction. 

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.). 

The metastable byproduct of [4+2] cycloaddition was detected when the reaction of cyclopentadiene with diphenylketene was (Equation (38)) was examined by low-temperature NMR experiment at — 30°C.67 The [4+2] cycloadduct was not observed at elevated temperature because easily isomerizes to [2+2] cycloaddition product via [3,3] sigmatropic (Claisen) rearrangement. This observation was supported by kinetic measurements NMR) and isolation of [4+2] cycloadduct.68 Mechanism proposed by Machiguchi and Yamabe was re-examined by Singleton.69... 

Claisen rearrangements, in 2-allyloxythia-zole, kinetic siudy. 410 stereochemistry. 410 Qeavage. of 2-acetylimino-4-thjazolines. 

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. 

Later work showed that such displacements can be effected with a BusSnCu reagent [83], With this reagent secondary mesylates afford allenylstannanes as the exclusive kinetic products (Eq. 68). The configuration of the allenic products was confirmed by an independent synthesis involving an orthoester Claisen rearrangement (Eq. 69). 

The kinetics in solution pertaining to ethers is relegated primarily to the Claisen rearrangement. An excellent review of the kinetics of this rearrangement appeared in 1963. Discussion of this topic will be abbreviated for this reason. The reaction scheme for the ortho- and para-Claisen rearrangement is illustrated below with allyl phenyl ether... 

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