Secondary isotope effects inductive effect

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 . 

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 ... 

The a-secondary IE of two deuteriums on the rate of base-catalyzed CD exchange of toluene, 3A ( PhC112D)/k(PhCD is 1.31, and the [3-secondary D IE on the rate of base-catalyzed a-C-D exchange of ethylbenzene, k(PhCHDCH3)//t(PhCHDCD3), is 1.11 0.03.58 Similarly, from the rates of base-catalyzed a-C-D exchange of tolucne-a,4-r/2, -a,2,4,6-c/4, and -a,2,3,4,5,6-d6 and with an assumption of linearity of IEs, the contributions of ortho, meta, and para deuteration lead to rate retardations of 2.4, 0.4, and 1.8%, respectively.59 These are all kinetic IEs, but to the extent that the transition state resembles closely the carbanion, or to the extent that the reverse reprotonation is encounter-controlled and independent of isotopic substitution, these kinetic IEs represent equilibrium IEs on acidity. The IEs were interpreted in terms of an electron-donating inductive effect of D relative to H. 

The relevant question regarding secondary IEs on acidity is the extent to which IEs affect the electronic distribution. How can an inductive effect be reconciled with the Born-Oppenheimer approximation Although the potential-energy function and the electronic wave function are independent of nuclear mass, an anharmonic potential leads to different vibrational wave functions for different masses. Averaging over the ground-state wave function leads to different positions for the nuclei and thus averaged electron densities that vary with isotope. This certainly leads to NMR isotope shifts (IEs on chemical shifts), because nuclear shielding is sensitive to electron density.16... 

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. 

Secondary /7-deuterium isotope effects are associated with the interaction of the empty p-orbital of the carbenium ion centre with the adjacent tr-carbon-hydrogen/deuterium bond. Small inductive effects are operating in the opposite direction. Release of steric strain is not considered to be associated with isotope effects in these reactions. 

Deuterium ( H) is more electropositive than protium ( H) and thus some isotope effects can be discussed in terms of inductive effects. This has been clearly demonstrated in the measurement of the secondary isotope effect on ionization equilibria of some deuterated carboxylic acids and protonated amines as shown in Table 1. 

Dilsopinocampheylborane derivatives continue to be attractive as reagents for enantloselective processes. Studies on the secondary kinetic isotope effect of deuterium on enantioselective hydroborations with (+)(Ipc)2BH have provided significant experimental evidence which provides a test for any detailed explanation of the process. The reagent has been used in a systematic study with representative heterocycles bearing an endocycllc double bond in order to establish the asymmetric induction achieved. It turns out that the reaction provides a simple and efficient method of synthesising heterocyclic boronates... 

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