Kinetic isotope effect Diels-Alder reaction

Beno, B. R., Houk, K. N., Singleton, D. A., 1996, Synchronous or Asynchronous An Experimental Transition State from a Direct Comparison of Experimental and Theoretical Kinetic Isotope Effects for a Diels-Alder Reaction , J. Am. Chem. Soc., 118, 9984. 

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. 

As measured by the criteria of stereospecificity, regioselectivity, kinetic isotope effects, and solvent effects [117-120, 541-543], 1,3-dipolar cycloaddition reactions represent orbital symmetry-allowed [n + n s] cycloadditions, which usually follow concerted pathways Diels-Alder reactions and 1,3-dipolar cycloadditions resemble each other, as demonstrated by the small solvent effects on their bimolecular rate constants. In going from nonpolar to polar solvents, the rate constants of 1,3-dipolar cycloadditions change only by a factor of 2... 10 [120, 131-134]. 

Gajewski, J. J. Peterson, K. B. Kagel, J. R. Huang, Y. C. J. Transition-statestructure variation in the Diels-Alder reaction from secondary deuterium kinetic isotope effects. The reaction of nearly symmetrical dienes and dienophUes is nearly synchronous, 7. Am. Chem. Soc. 1989, 111, 9078-9081. 

Storer JW, Raimondi L, Houk KN. Theoretical secondary kinetic isotope effects and the interpretation of transition state geometries. 2. The Diels-Alder reaction transition state geometry. J Am Chem Soc 1994 116 9675-9683. 

For every Diels-Alder reaction the H/D a kinetic isotope effect of which has been measured, the qualitative findings are the same, i.e. (W h) is larger than unity. The magnitude of the effect is also of the expected order, both when values per D atom are calculated assuming one-step addition and when attack at a single site is assumed to be rate-controlling (for symmetrical deuteration, the former assumption attributes the observed effect to twice as many atoms as the latter). A few typical examples are listed below (isotope effects per D atom, as calculated for one-step addition, are given). 

Using this method, the kinetic isotope effects of H and - C at each atom in isoprene for the Diels-Alder reaction with maleic anhydride were determined. NMR spec-... 

The [4-1-2] cycloaddition of dienes to double bonds, the Diels-Alder reaction (see Pericycttc Reactions The Diels-Alder Reaction), is one of the most useful synthetic reactions in organic chemistry. The mechanism of the Diels-Alder reaction has been the subject of intensive study using a large number of different methods. This is at least in part due to the fact that, based on thermochemical estimates, there is a reasonable possibility for a stepwise mechanism. The energy of concert , i.e., the difference between the concerted and a diradicaloid mechanism, is small enough to be potentially overcome in some cases. The comparison of the results for the two different pathways suffers, however, from the difficulties of comparing closed-shell specie.s and diradicals within a single-determinant MO approach. Only recently, the use of multireference and DFT methods in combination with experimental kinetic isotope effect studies allow an unequivocal assessment of the reaction mechanism of the Diels-Alder reaction. ... 

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