Inverse secondary kinetic isotope

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. 

Experimental and computational studies of the pericyclic Meisenheimer rearrangement and a competitive rearrangement of A-propargyl morphol i nc N-oxide revealed a novel inverse secondary kinetic isotope effect (kn/kD 0.8) for the rate-determining cyclization step, probably occurring because of a C(sp) to C(sp2) change in hybridization at the reaction center (Scheme 3).5... 

Inverse (kn/ko< ) secondary kinetic isotope effects are seen for hybridization changes in the opposite direction (sp sp or sp sp ). One process leading to an inverse secondary kinetic isotope effect would be the protonation of an alkene, as shown for structure 81 in Figiue 6.61(b). For example, the thiocyanate-catalyzed cis-trans isomerization of maleic acid. Figure 6.61(b), has a of 0.86 at 25°C. ... 

Reactions of (ii)-l-decenyl(phenyl)iodonium salt (6a) with halide ions have been examined under various conditions. The products are those of substitution and elimination, usually (Z)-l-halodec-l-ene (6b) and dec-l-yne (6c), as well as iodobenzene (6d), but F gives exclusively elimination. In kinetic studies of secondary kinetic isotope effects, leaving-group substituent effects, and pressure effects on the rate, the results are compatible with the in-plane vinylic mechanism for substitution with inversion. The reactions of four ( )-jS-alkylvinyl(phenyl)iodonium salts with CP in MeCN and other solvents at 25 °C have been examined. Substitution with inversion is usually in competition with elimination to form the alk-l-yne. 

Much attention has been focused on defining the transition state of FTase and the structural determinants of the chemical step. For FTase, there is evidence for both an electrophilic contribution to the transition state, obtained from studies with fluoromethyl FPP analogues, and a nucleophilic contribution, obtained from the metal-substitution and pH studies [31,40,41]. These results are supported by the inability to trap a carbocation intermediate, inversion of configuration at Cl of the farnesyl group during the reaction, and an a-secondary kinetic isotope effect near unity [31,42,43]. Taken together, the available data suggest that the transition state of FTase... 

Stereochemical and kinetic analyses of the Brpnsted acid-catalysed intramolecular hydroamination/deuterioamination of the electronically non-activated cyclic alkene (13) with a neighbouring sulfonamide nucleophile have been found to proceed as an anh-addition (>90%) across the C=C bond to produce (15). No loss of the label was observed by and NMR (nuclear magnetic resonance) spectroscopies and mass spectrometry (MS). The reaction follows the second-order kinetic law rate = 2 [TfOH] [13] with the activation parameters being = 9.1 0.5 kcal moP and = -35 5 cal moP An inverse a-secondary kinetic isotope effect of d/ h = (1-15 0.03), observed for (13) deuteration at C(2), indicates a partial CN bond formation in the transition state (14). The results are consistent with a mechanism involving concerted, intermolecular proton transfer from an N-protonated sulfonamide to the alkenyl C(3) position coupled with an intramolecular anti-addition by the sulfonamide group. ... 

Diagrams showing the origin of normal (A) and inverse (B) secondary kinetic isotope effects. In A the C-H activation energy is smaller, but in B the C-D bond activation energy is smaller. 

State whether the following reactions will show a normal or inverse, primary or secondary, kinetic isotope effect. Explain your reasoning. 

The kinetics and mechanism of the aminolysis of phenyl-substituted phenyl phosphonyl chlorides (136) with anilines (135) were investigated in MeCN at 55.0 °C. Very sensitive variation of /Oy(5/Oy2>0) with the change of substituent on the nucleophile Sax) led to a large negative cross-interaction constant, pxY = Spy)/ Sox) = —1.31. The secondary kinetic isotope effects observed with deuteriated aniline nucleophiles were of the inverse type (/th/ d = 0.61-0.87), and small A// (1.6-9.7kcalmor ) and large negative A5 (—43 to —65 e.u.) values were... 

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 oxidations of formic acid by Co(III) and V(V) are straightforward, being first-order with respect to both oxidant and substrate and acid-inverse and slightly acid-catalysed respectively. The primary kinetic isotope effects are l.Sj (25°C)forCo(IU)and4.1 (61.5 C°)for V(V). The low value for Co(lII) is analogous to those for Co(IIl) oxidations of secondary alcohols, formaldehyde and m-nitrobenzaldehyde vide supra). A djo/ h20 for the Co(III) oxidation is about 1.0, which is curiously high for an acid-inverse reaction . The mechanisms clearly parallel those for oxidation of alcohols (p. 376) where Rj and R2 become doubly bonded oxygen. 

Subsequent work confirmed this apparently abnormal behaviour. Deuteriation at remote sites (the S- or e-position) induces small inverse secondary isotope effects in a-cleavages occurring in the ion source, but normal isotope effects in the decomposition of metastable ions in the field-free regions94,95. The time dependence of the isotope effect was also studied by field ionization kinetics, which permit the analysis of fragmentations occurring after lifetimes as short as 10 12 s-1. It was found that the inverse isotope effect favouring loss of the deuteriated radical operates at times shorter than 10 9 s95. 

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