Cycloaddition reactions isotope effects

The intramolecular and intermolecular deuterium isotope effects in the cycloaddition of acrylonitrile to allene (equation 98) have been studied by Dolbier and Dai231,232. The intramolecular KIEs in the allene-acrylonitrile system were found to be 1.21 0.02 at 206°C and 1.14 0.02 at 225°C. A negligible intermolecular SKIE was found in the reaction of the mixture of tetradeuteriated and undeuteriated allene using a limited amount of acrylonitrile (ku/ku) = 1.04 0.05 at 190-210 °C for D0/D4 allene. An equilibrium deuterium IE of 0.92 0.01 was found at 280-287 5°C (15-45 h reaction time). 

A very remote secondary H/D isotope effect has been measured for the 2 + 2-cycloaddition of TCNE to 2,7-dimethylocta-2,fran -4,6-triene. The reaction of nitric oxide with iV-benzylidene-4-methoxyaniline to produce 4-methoxybenzenediazonium nitrate and benzaldehyde is thought to proceed via a 2 + 2-cycloaddition between nitric oxide and the imine double bond. A novel mechanism for the stepwise dimerization of the parent silaethylene to 1,3-disilacyclobutane involves a low-barrier [1,2]-sigmatropic shift. Density functional, correlated ab initio calculations, and frontier MO analysis support a concerted 2 + 2-pathway for the addition of SO3 to alkenes. " The enone cycloaddition reactions of dienones and quinones have been reviewed. The 2 + 2-photocycloadditions of homochiral 2(5H)-furanones to vinylene carbonate are highly diastereoisomeric. ... 

Deuterium substitution on the four carbon atoms changing from trigonal to tetrahedral as the reaction proceeds, gives rise to inverse secondary kinetic isotope effects, small but measurable, both for the diene and the dienophile 3.1. If both bonds are forming at the same time, the isotope effect when both ends are deuterated is geometrically related to the isotope effects at each end. If the bonds are being formed one at a time, the isotope effects are arithmetically related. It is a close call, but the experimental results, both for cycloadditions and for cycloreversions, suggest that they are concerted. 

Disilenes react with ketones, aldehydes, esters and acid chlorides by formal [2 + 21-cycloaddition to yield the corresponding disiloxetanes (equation 73)8,16. The reaction is non-concerted and proceeds through the initial formation of a 1,4-biradical intermediate, as has been shown by the products of reaction of tetramesityldisilene (110) with the cyclopropyl aldehyde 117 (equation 90)163. The absolute rate constants listed in Table 19 indicate there to be a significant difference in reactivity between the monophenyl-substituted disilene 103 and the 1,2-diphenyl-substituted derivatives 104, consistent with a steric effect on the rate of formation of the biradical intermediate. As would be expected, no kinetic deuterium isotope effect is discernible from the relative rates of addition of acetone and acetone- to these compounds. 

These results are compatible with stereochemical predictions derived through orbital symmetry theory, assuming a one-step n2s - -n2a addition. But secondary deuterium kinetic isotope effects on the allene plus allene thermal (2+2) cycloaddition seem to require a two-step mechanism with formation of an intermediate 44>, and as Moore and coworkers fully realized 83> stereoselective formation and reactions of 2,2 -biallylene intermediates will equally well account for the product ratios. In their rationale, two allenes approach and distort through simultaneous conrotatory twistings to give the perpendicular 2,2 -biallylene intermediate, which closes to form products in a disrotatory fashion. The experimentally observed stereochemical selectivity is equally compatible with a reversed order of rotatory motions disrotatory joining of two allenic reactants followed by conrotatory closure to create the 1,2-dimethylenecyclobutane products 83>. 

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]. 

Some years ago Cornelisse reported that deuteration of alkyl benzenes results in a deuterium isotope effect upon the quantum yield of the meta photocycloaddition reaction with alkenes. In a new report the same group has published an analysis describing how the observed isotope effect upon the reaction quantvun yield can be ascribed to a kinetic deuterium isotope effect on the excited state reaction and distinguished from an effect upon the unimolecular photophysical modes of decay of the excited state. In addition, it is reported that when the quantum yield of meta photocycloaddition of cyclopentene to alkyl benzenes is measured using a mixture of deuterated and non-deuterated benzenes, the quantum yield is arene concentration dependent.The authors argue that this arises from competition between cycloaddition and the formation of mixed excimers between deuterated and non-deuterated alkyl benzenes which dissociate to yield excited deuterated alkyl benzene and ground state non-deuterated alkyl benzene preferentially. 

Absolute rate coefficients and Arrhenius parameters have been obtained for the cycloaddition reaction of S( F2,1,0) atoms with a representative series of olefins and acetylenes. The activation energies are small, and they exhibit a trend with molecular structure which is expected for an electro-philic reagent The A-factors show a definite trend which can be attributed to steric repulsions and a generalized secondary a-isotope effect explained by activated complex theory. Secondary a-H/D kinetic isotope effects have been measured and their origin discussed. Hartree-Fock type MO calculations indicate that the primary product of the S( F) + olefin reaction is a ring-distorted, triplet state thi-irane, with a considerable energy barrier with respect to rotation around the C-C bond. 

Stereochemistry, substituent effects and activation parameters of most ketene reactions are consistent with a one-step cycloaddition polar effects of substituents and solvents, as well as the isotope effect, often require, however, that a fair amount of charge separation (that is, unequal bond formation) characterises the transition state. It has been kinetically proved that cycloadditions of enamines to ketenes can also proceed through a dipolar intermediate this is so for the reaction between dimethylketene and N-isobutenylpyrrolidine . In the latter case, the rate coefficient for the formation of the intermediate strongly depends on solvent polarity itacetonuriie/ cyclohexane = 560. Use of the Same criteria used for ketenes (as far as experimental data allow it) in the case of the 1,2-cycloadditions of fluorinated olefins results, instead, in the conclusion that a two-step biradical mechanism is operating. Results for 1,2-cycloaddition of sulfonyl isocyanates to olefins, cases (g) and (h) in Table 17, give indications of dipolar intermediates during the course of these reactions. 

An intramolecular secondary isotope effect has been measured by analysing the product of 1,2-cycloaddition of l,l-c(2-allene to acrylonitrile in benzene at 210-225°C. The result is (Ah/Ad)2s°c 1-18 per D atom it has the opposite direction of that found for a Diels-Alder reaction of M-r/j-allene, and is consistent with a two-step mechanism (see Section 4.1.5). A diradical intermediate seems probable. A similar result was obtained from the study of isotope effects for the dimerisation of allene. Since the reaction of / (-)-... 

Cyclobutanones.— These are frequently prepared by the cycloaddition of a keten or its formal derivative to an olefin. The secondary detuerium isotope effect, for the reaction of [a- H]styrene with dimethylketen is 0.8, indicating that the reaction is concerted, by analogy with other concerted cycloadditions which exhibit inverse isotope effects. ... 

The authors found just such an effect in the presumably concerted H- 2]-cycloaddition of allene to hexachlorocyclopentadiene, but not in its [ 2 H- 2]-cycloaddition to acrylonitrile. There, athough no isotope effect was observed on the rate of reaction, there was a substantial direct isotope effect ( h > d) on product formation protium was preferentially incorporated in the ring. The authors therefore concluded that the reaction takes place in two steps. 

The confusion was compounded when Isaacs and Hatcher [54] reported an inverse isotope effect (fcn/A D 0.8) at Ci of styrene in its cycloaddition to dimethylketene and cited it as further evidence for a concerted reaction. Finally, Holder et al [55] measured the isotope effect for the reaction of DPK with 5,5-dimethylcyclopentadiene. 

Although the interpretation offered above for the isotope effect is consistent with the solvent and substituent effects, as well as with secondary isotope effects on other reactions, it will probably be resisted as counterintuitive unless its predictive power is established experimentally. A finding that the isotope effect at Cl is inverse in the cycloaddition of DPK to relatively unhindered alkyl vinyl ethers and reversed as the steric requirements of the substituents on Ci increase will go a long way towards its confirmation. Such an investigation was undertaken by the late Professor E.A. Koerner von Gustorf but discontinued on his untimely death in September 1975. ... 

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