Reductive elimination kinetic isotope effects

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... 

A very recent report moves forward significantly understanding the mechanism of reductive elimination reactions to form carbon-carbon bonds from platinum(IV) complexes.245 This report described the kinetics of reductive elimination from a cationic platinum(IV) complex as a function of solvent, of substituent character in a leaving group, of the potential effect of different spectator ligands and addressed whether there was a kinetic isotope effect. The reactions were studied also as a... 

Kinetic Isotope Effects for H2 Oxidative Addition and Reductive Elimination... 

Parkin and Bercaw reported that Cp 2W(Me)(H) eliminates methane to form Cp (ri5,ri1-C5Me4CH2)WH.26 For the mixed isotopomer, Cp 2W(CH3)(D), H/D scrambling to give Cp 2W(CH2D)(H) is competitive with the methane elimination process (Scheme 11.7). Although the authors point out that the H/D exchange process could occur by pathways other than formation of a methane-coordinated intermediate, the observation of an inverse kinetic isotope effect (KIE) for the methane reductive elimination (see bottom of Scheme 11.7) provides additional support for the reversible formation of coordinated alkane (see below for a more detailed discussion of KIEs for reductive elimination of C—H bonds). Furthermore, at relatively low concentrations, heating a mixture of Cp 2W(CH3)(H) and Cp 2W(CD3)(D) produces only CH4 and CD4 with no observation of H/D crossover, which is consistent with intramolecular C—H(D) processes. Similar results have been obtained for... 

SCHEME 11.19 Two scenarios that lead to inverse kinetic isotope effect for overall C—H reductive elimination (HE = inverse isotope effect NIE = normal isotope effect). 

OA of C-H bonds, the microscopic reverse of reductive elimination of C-H, must also proceed via a a complex. There are abundant data to show that, as for H2 additions, the kinetic isotope effects are normal for alkane OA. For example, reaction of Cp Rh(PMe3)(neopentyl )H with hexane versus hexane-d14 gives kH/kD= 1.2 0.1 at 213 K,111 and photolysis of Cp Ir(PMe3)H2 gives kH/kD — 1.38 upon reaction with cyclohexane to form Cp Ir(PMe3Xcyclohexyl)H.119... 

A few processes reported in the literature have been interpreted as binuclear H2 reductive elimination Irom 17-electron hydride complexes. This process requires, of course, the formation of 16-electron products or intermediates, unless it is preceded by coordination of a 2-electron donor to afford 19-electron complexes which then undergoes the reductive elimination process. In most cases, however, mechanistic studies e.g. rate law determinations, kinetic isotope effects, use of different solvents, etc.) in support of this proposal have not been carried out. In particular, in no case can the observed process be unambiguously distinguished from a disproportionation process. Proof of the viability of a truly bimolecular one-electron reductive elimination process from 17-electron hydride complexes requires, in our opinion, additional investigations. 

In the literature [25, 26a,c-g], inverse kinetic isotope effects for the reductive elimination of alkanes from metal centers, which is the miaoscopic reverse of alkane activation by oxidative addition, have been explained by the presence of an a alkane intermediate. Recently, thermolysis of the diastereomerically pure complexes (R5),(5R)-[2,2-dimethylcyclopropyl) (Cp )-(PMe3)lrH] and (/ / ),(5 5)-[2,2-dimethylcyclopropyl)(Cp )(PMe3)IrH] (see Scheme VI.5) in CaDs has been shown [26h] to result in its interconversion to the other diastereomer. The analogous reaction of the deuterium-labeled complexes resulted additionally in scrambling of the deuterium from the a-position of the dimethylcyclopropyl ring to the metal hydride position. Diastereomer interconversion and isotopic scrambling occurred at similar rates and have been discussed in terms of a common intermediate mechanism involving a metal alkane complex (Scheme VI.5). 

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