Inverse secondary deuterium isotope effect

The inductive effect of the donating C—D bonds to the observed large inverse secondary deuterium isotope effect has not been given proper consideration but treated as a rather minor component superimposed on the important steric component caused by larger amplitudes of vibrations of C—H bonds than those of the C—D bonds. 14C KIE have not been studied in this reaction. The C2, C V. C3 , C3, endo hydrogens are separated only by 2.11 A, substantially less than van der Waals radii (2 x 1.2 A)404. 

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. 

Another series of closely related reactions for which transition-state calculations have greatly helped in providing an understanding of the observed trends is the addition to deuterium-substituted alkenes. Szwarc and co workers (Feld et al., 1962) have determined secondary deuterium isotope effects for methyl and trifluoromethyl radicals by comparing the rate of addition to a terminal alkene with the rate for the deuterium-substituted alkene (25). Isotope effects for cyclopropyl radical addition have been measured by Stefani and coworkers (1970). For these three radicals a small inverse isotope effect (kJkK)... 

The reaction was carried in boiling benzene with 5,5-dimethylcyclopentadiene 12 selectively deuterated (X = D, Y = H or X = H, Y = D). The secondary deuterium isotope effects were measured by means of 1H and 2H NMR.65 The large and inverse (0.84) isotope effect for C5-C6 bond formation and no effect (1.00) for C1-C7 bond formation corresponds to extensive sp2->sp3 rehybridization66 of Cl atom and no rehybridization at C2 atom. At the rate-determining transition state only formation of one carbon-carbon bond is advanced in formation of [2+2] cycloadduct. 

Photooxetane formation is quite inefficient, a fact which usually points to the presence of an intermediate which can partially revert to ground state reactants. Cleavage of the diradical must be responsible for some of the inefficiency in oxetane formation 129>. However, in the past few years convincing evidence has appeared that a CT complex precedes the diradical iso.isi). The two most telling pieces of evidence are the relative reactivities of different alkenes 130> and the absence of any measurable secondary deuterium isotope effect on quenching rate constants 131>. Relative quenching rates of sterically un crowded olefins are proportional both to the ionization potentials of the donor olefins 130> and to the reduction potentials of the acceptor ketones 131>, as would be expected for a CT process. Inasmuch as n,n triplets resemble electron-deficient alkoxy radicals, such substituent effects would also be expected on direct radical addition of triplet ketone to olefin. However, radical addition would yield an inverse isotope effect (in, say, 2-butene-2,3-d2) and would be faster to 1,1-dialkylethylenes than to 1,2-dialkylethylenes, in contrast to the actual observations. 

These effects are usually much smaller than primary isotope effects (those involving rupture and/or formation of bonds to the isotopic atom). For example, secondary deuterium isotope effects are seldom greater than 30-40%, while primary deuterium isotope effects may run 700-800% or even higher. It should be noted, incidentally, that secondary isotope effects can be inverse (heavier isotopic species faster than lighter one) if bonds to the isotopic atom become stronger in the transition state than in the reactant. 

If there is only one step, the reaction has to be second order first order in the peracid and first order in the alkene. The reaction rate has very little dependence upon the solvent, supporting a concerted mechanism with little charge developing at the transition state. The small charge development is also supported by the fact that the rates correlate with a Hammett parameter a ), but the p value is only -1.1 for p-XArCH=CH2. There are only small primary kinetic isotope effects. Values of Ath/Ato around 1.1 to 1.2 are found for the peracid [ROiHfD)]. This means that the hydrogen atom transfer shown in the electron pushing of Scheme 10.5 has to be either minimal at the transition state or almost complete (see Section 8.1.2). Secondary deuterium isotope effects on the alkene carbons are inverse, as may be expected for an sp- to sp transformation. 

An unusually large inverse secondary deuterium kinetic isotope effect (1.53-2.75, depending on the reaction conditions) has been reported for bromination of the sterically congested olefin 74. This behaviour can be rationalized by decreased steric hindrance due, in particular, to the ewrfo-placement of the deuterium atoms relative to the double bond135. 

Probably the strongest support in favor of the diradical mechanism is the lack of a deuterium isotope effect in the thermal decomposition of franx-3,4-diphenyl-1,2-dioxetane. In the concerted mechanism, the ring carbon of the dioxetane changes its hybridization state from sp to sp in the activated complex (23) and an inverse secondary isotope effect k lkp) would be expected. Consequently, a diradical mechanism was argued to accommodate these results. Similarly, in the thermal decarboxylation of the dimethyl a-peroxylactone, a negligible (A ///A ) = 1.06 0.04) secondary isotope effect was observed. Presumably, in the a-peroxylactone decomposition, a diradical mechanism similar to that of dioxetanes (Eq. 66) upholds. 

The formation of the vinyl cation-silver ion complex in the slow step of the reaction is consistent with the observation of an inverse secondary deuterium kinetic isotope effect, because the terminal C—H bond undergoes a hybridization change from sp to sp in the rate-determining step of the reaction. 

Apart from a few studies (ref. 7), the use of deuterium kinetic isotope effects (kie s) appears to have had limited use in mechanistic studies of electrophilic bromination of olefins. Secondary alpha D-kie s have been reported for two cases, trans-stilbene fi and p-substituted a-d-styrenes 2, these giving relatively small inverse kie s of... 

The secondary a-deuterium KIEs calculated for the uncatalysed reaction were in the range found experimentally for other SN2 methyl transfers. The calculated KIE was also analysed in terms of the zero-point energy (ZPE), the molecular mass-moment of inertia (MMI) and the excitation (EXC) contributions to the total isotope effect. The inverse KIE was found to arise from an... 

The important observation is that all of the isotope effects are large and inverse. Therefore, the transition states in these reactions must be very crowded, i.e. the Ca—H(D) out-of-plane bending vibrations in the transition state must be high energy (Poirier et al., 1994). As a result, these workers concluded that nitrogen-a-carbon bond formation is more advanced than a-carbon-iodine bond rupture in the transition state. It is interesting, however, that in spite of the small secondary a-deuterium KIEs, these authors concluded that the N—C bond formation is only approximately 30% complete in the transition state. 

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