Isotope effects, secondary , steric

Support for hyperconjugation as the major cause of p isotope effects is the fact that the effect is greatest when D is anti to the leaving group (because of the requirement that all atoms in a resonance system be coplanar, planarity of the D—C—C—X system would most greatly increase the hyperconjugation), and the fact that secondary isotope effects can be transmitted through unsaturated systems. There is evidence that at least some p isotope effects are steric in... 

Solvolytic experiments specifically designed to test Bartell s theory were carried out by Karabatsos et al. (1967), who were primarily interested in an assessment of the relative contributions of hyperconjugation and non-bonded interactions to secondary kinetic isotope effects. Model calculations of the (steric) isotope effect in the reaction 2- 3 were performed, as well as that in the solvolyses of acetyl chloride... 

Brown and McDonald (1966) provided another type of kinetic evidence for these size relationships by determining secondary kinetic isotope effects in reactions of pyridine-4-pyridines with alkyl iodides. For example, the isotopic rate ratio in the reaction between 4-(methyl-d3)-pyridine and methyl iodide at 25-0 C in nitrobenzene solution was determined to be kjyfk = l-OOl, while that in the corresponding reaction with 2,6-(dimethyl-d6)-pyridine was 1-095. (Brown and McDonald (1966) estimate an uncertainty of 1% in the k jk values.) Furthermore, the isotopic rate ratio in the case of the 2-(methyl-d3)-compound increased from 1 030 to 1-073 as the alkyl group in the alkyl iodide was changed from methyl to isopropyl, i.e. the isotope effect increased with increasing steric requirements of the alkyl iodide. 

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. 

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. 

Felder, T., Schalley, C.A. Secondary isotope effects on the deslipping reaction of rotaxanes high-precision measurement of steric size, Angew. Chem. 115 (2003), 2360-2363 Angew.Chem. Int. Ed. 42, (2003), 2258-2260. 

The kinetic isotope effect can be used to direct the steric course of the deprotonation at a chiral deuteromethylene group and form a secondary organolithium 370 with retention of stereochemistry.162-163... 

Later, Balaban et al. showed that the accelerating secondary isotope effect obtained on replacing two a-CH3 groups by two CD3 groups consists approximately of equal amounts of steric and electronic components (82JCR(M)559, 82JCR(S)44). 

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. 

Let us now consider Scheppele s discussion of the solvolysis of 2-d-exo- and -endo-bicyclo[2.2.1] hept-2-yl p-nitrobenzoates and p-toluenesulfonates. A maximum a isotope effect of 1 22 is suggested for kH/kD for the limiting solvolysis of simple secondary sulphonates (solvolyses where the rate is not affected by the nucleophilicity of the medium). The endo-esters yield a similar value which might be taken to imply the absence of steric hindrance in their reaction. However, whereas the maximum isotope effect for the simple sulphonates is believed to arise partly from an activated complex in the conversion of the internal ion pair into a solvent-separated ion pair, B - C, the effect in the endo-norbomyl compounds is suggested to arise during the transition state involved in the formation of the intimate ion pair, A - B. The latter is deduced from the fact that polarimetric and titrimetric rate constants are the same in acetic acid, aqueous acetone and ethanol (Winstein and Trifan, 1949 and 1952). If this is the case, the endo-effect of 1-20 should be... 

The role of steric factors has been examined in the opening of polyfluorinated oxiranes. Accounts have been given of the alcoholysis of steroid oxiranes and their transformation with phenol.The kinetics of the reactions of oxiranes with alcohols and phenols have been reported in a number of publications. The catalytic influence of transition metals has been examined. A secondary deuterium isotope effect has been studied in the course of methanolysis, and the solvent effect has been considered in reactions with phenols. ... 

The secondary -deuterium kinetic isotope effects in reactions of -perdeuterated ethyl-, isopropyl- and rm-butylmagnesium halides with four different ketones were described [24] and were found to be small (within 5%). There, too, hyperconjugative stabilization was supposed to play a role, but this effect was opposed by the steric effects. The role of hyperconjugation in reactions of Grignard reagents, therefore, seems complicated and requires further studies. 

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