Reductive elimination isotope effects

Isotope effects indicate that the collapse of the adduct by reductive elimination is the rate-determining step.54 Theoretical treatments of the mechanism suggest similar intermediates. (See Section 8.1.2.7 for further discussion of the computational results.)55... 

The existence of tr-complex intermediates in C-H activation chemistry has been suggested to explain inverse kinetic isotope effects in reductive elimination processes whereby alkanes are formed from alkyl metal hydrides (Scheme 3).9... 

According to isotope studies the rate-determining step of this sequence is the reductive elimination, and all other reactions (C-H activation, insertion of alkene) are reversible. The first indication of this behaviour was the H/D exchange of the ortho proton of acetophenone. Secondly, and perhaps useful for many other systems, was the kinetic isotope effect observed for 13C natural... 

The reaction pathways of conjugate addition of Me2CuLi and Me2CuLi LiCl have been studied for acrolein [79] and cydohexenone [80] with the aid of density functional methods, and fit favorably with the NMR properties of intermediates, kinetic isotope effects [81], and the diastereofacial selectivity. A similar mechanism also operates in this reaction, as summarized in Scheme 10.5. The rate-determining step of the reaction (TScc) is the C-C bond formation caused by reductive elimination from Cu " to give Cu. ... 

The mechanism of conjugate addition of lithium dialkylcuprates to enones has been explored by the determination of 13C kinetic isotope effects by an NMR method reductive elimination from Cu is implicated as the rate-determining step.109... 

A complete set of 13C kinetic isotope effects determined (by a natural abundance CMR method) for addition of lithium dibutylcuprate to cyclohexenone, in THF at —78°C, have been shown to be consistent with those calculated theoretically for ratedetermining reductive elimination from an intermediate square-planar copper complex.120 Thus, die KIE (12k/13k) = 1.020-1.026 at C(3) is indicative of substantial bonding change, and partial alkyl transfer can explain the significant low KIE = 1.011-1.016 for Ca of die butyl group. 

Various mechanisms for the aerobic oxidation of alcohols catalysed by (NHC)Pd (carboxylate)2(H20) complexes [NHC = l,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene] were investigated using DFT combined with a solvent model. Of these, reductive j3-hydride elimination, in which the -hydrogen of a palladium-bound alkoxide is transferred directly to the free oxygen of the bound carboxylate, provided the lowest-energy route and explained the published kinetic isotope effect, activation enthalpy, reaction orders, and dependence of rate on carboxylate pKa.26S... 

Both normal and inverse KIEs have played a major role in unraveling the mechanisms of alkane activation with transition metal complexes. Alkyl hydride complexes are typical intermediates in such reactions. The loss of alkane in well-defined alkyl hydrides frequently exhibits an inverse KIE and involves a O-alkane complex.86 87 As a result, an inverse isotope effect is now taken as evidence for the intermediacy of o-alkane complexes in reductive eliminations (Scheme 8.14). 

C isotope effect at C3 (1.025) corresponds to the bonding change at this atom in the rate-determining step. Smaller but significant 13C KIE at Ca atom is indicative for the butyl group transfer in the same step. Such results are consistent with reductive elimination process in the rate-determining step. 

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