Hyperconjugative secondary isotope effects

The intensity of the bending mode also bears out the contention of Streitwieser et al. (54) that this motion, rather than the CH stretching motion, is of primary importance in hyperconjugative secondary isotope effects in electron deficient systems but the proviso must be added that its effect is felt through coupling with other displacements, and not directly through a decrease of the CH bending frequency itself. 

Secondary isotope effects at the position have been especially thoroughly studied in nucleophilic substitution reactions. When carbocations are involved as intermediates, substantial /9-isotope effects are observed. This is because the hyperconjugative stabliliza-... 

When reactions were run with substrate deuterated in the ortho position, isotope effects of about 1.22 were obtained.23 It is difficult to account for such high secondary isotope effects in any other way except that an incipient phenyl cation is stabilized by hyperconjugation,24 which is reduced when hydrogen is replaced by deuterium. 

Solvolysis of 15 in 97% trifluoroethanol gave a secondary isotope effect of 1.17, which indicates a vertically stabilized transition state. Thus the highly unsymmetrical dihedral dependence of silicon participation can almost entirely be attributed to the hyperconjugation model with little non-vertical involvement of the silicon nucleophile. 

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... 

The beta-tritium secondary isotope effect for elimination from the propyl-trimethylammonium ion (8, Table 7) seems most probably explained in terms of reduced acidity of the beta hydrogen caused by the greater inductive effect of the bond to the heavier isotope. A hyperconjugative effect also fits the observed data as in the transition state the developing double bond would be more effectively stabilised by the methyl than the monotritiomethyl group. However, the latter explanation seems less likely as the elimination from the propyl compound is slightly slower than that from the ethyl derivative . 

Secondary isotope effects are also observed with isotopic substitution at carbon atoms relatively remote from the reaction site. These effects have been studied especially thoroughly in the case of nucleophilic substitution reactions. When deuterium is introduced at the carbon two atoms down the chain (the p carbon), significant secondary isotope effects are observed when carbonium ions are formed as intermediates. It is generally believed that hyperconjugative interactions with the carbonium ion site are responsible for the changes in vibrational force constants... 

It is a sad commentary on the state of the art with regard to secondary isotope effects that hyperconjugation—the factor most intimately associated with the effects in the earlier researches and much of the later work—is now an area of profound disagreement. The writer is reluctant to take sides in this controversy, which was thoroughly aired in the University of Indiana symposium several years ago (74), and more recently in an epistolog published in Tetrahedron to which some reference has already been made (69,70,73). Still, in order to discuss secondary isotope effects in terms of hypercon-... 

The first serious challenge to hyperconjugation as a factor in secondary isotope effects was presented by Swain et al. (173). They showed that nitration of toluene was not affected by side-chain tritia-tion to within a few tenths of a percent. Neither was any isotope effect observed within 3% on mercuration of toluene-ads with mer-... 

The correlation of selectivity with hyperconjugation has been made many times in the past, and is the basis of the recent attempt of Knowles et al. (179) at a parametric separation of the polarization and polarizability effects of alkyl substituents. Still, the simple induction-hyperconjugation balance interpretation of secondary isotope effects—or of the relative effects of methyl vs. terf-butyl—in aromatic substitution does not hold up well under scrutiny ... 

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... 

This corresponds to an isotope effect of approximately 3.5% per deuterium. In comparison, the secondary /3-deuterium KIEs in SN1 reactions are all normal and range from 5% to 15% per deuterium. Because the normal KIEs in SN1 reactions result from the weakening of the C,—L bond by a hyperconjugative interaction with the incipient carbocation in the transition state, the authors concluded that hyperconjugative interactions are present also in the transition state for the insertion reaction. The normal secondary /3-deuterium KIE observed for the insertion reaction is consistent with the dipolar three-centre transition state structure [15] proposed by Seyferth et al. (1970a,b) because the partial positive charge on the a-carbon is stabilized by hyperconjugation. 

Similar conclusions attend the insertions of CCI2 (from the thermolysis of ClsCCOONa at 120 °C) into a-deuteriocumene and cumene in which the primary fen/feo = 2.6, similar to Seyferth s finding with 32, and the p-secondary kinetic isotope effect is 1.20-1.25 for six deuteriums. Here, hyperconjugation at the p-CH (CD) bonds is thought to stabilize the partial cationic charge at the reaction center in transition state 33. 

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