Hydride transfer cation effects

Several factors affect the reactivity of the boron and aluminum hydrides, including the metal cation present and the ligands, in addition to hydride, in the complex hydride. Some of these effects can be illustrated by considering the reactivity of ketones and aldehydes toward various hydride transfer reagents. Comparison of LiAlH4 and NaAlH4 has shown the former to be more reactive,63 which is attributed to the greater... 

It is necessary for the intermediate cation or complex to bear considerable car-bocationic character at the carbon center in order for effective hydride transfer to be possible. By carbocationic character it is meant that there must be a substantial deficiency of electron density at carbon or reduction will not occur. For example, the sesquixanthydryl cation l,26 dioxolenium ion 2,27 boron-complexed imines 3, and O-alkylated amide 4,28 are apparently all too stable to receive hydride from organosilicon hydrides and are reportedly not reduced (although the behavior of 1 is in dispute29). This lack of reactivity by very stable cations toward organosilicon hydrides can enhance selectivity in ionic reductions. 

The tropylium cation (274) first observed 1891 and rediscovered in 1957 is perfectly stable and isolable. Cyclopropenyl cations have been observed in solution a long time ago, but 273 remained elusive until very recently. Benzocyclo-propene (1) reacts with triphenylfluoroborate via hydride transfer some 5 times less rapidly than cycloheptatriene. The reaction of deuterated 1 exhibits a kinetic isotope effect of 7.0. However, only a low yield of benzaldehyde (277), the expected hydrolysis product of 273, could be isolated from the reaction mixture. ... 

Cracking and disproportionation in the reaction of hexane could be suppressed by the addition of cycloalkanes (cyclohexane, methylcyclopentane, cyclopentane).101 Furthermore, 3-methylpentane and methylcyclopentane also reduced the induction period. These data indicate that reactions are initiated by an oxidative formation of alkene intermediates. These maybe transformed into alkenyl cations, which undergo cracking and disproportionation. When there is intensive contact between the phases ensuring effective hydride transfer, protonated alkenes give isomerization products. 

In the phase-transfer processes discussed in Section 11.2 it is assumed that the anionic hydride source, i.e. borohydride or a hypervalent hydrosilicate, forms an ion-pair with the chiral cationic phase-transfer catalyst. As a consequence, hydride transfer becomes enantioselective. An alternative is that the nucleophilic activator needed to effect hydride transfer from a hydrosilane can act as the chiral inducer itself (Scheme 11.6). 

Inverse KIEs, which have kulkn < 1, are associated with reactions in which the transition state has a greater force constant than the reactants, as shown in Figure 8.6. Typically, this situation occurs if the transition state is late (product-like). A compelling demonstration of this phenomenon was provided in a study of hydride transfer from a series of tungsten hydrides to substituted trityl (trityl = triphenyl-methyl) cations.85 The isotope effect kWH/kWn decreased steadily from 1.8 to 0.47 as the rate constant decreased. The trend in wh wd was interpreted as arising from steadily increasing force constants of isotopically sensitive modes of the transition state. 

Substituent effects on rates and equilibria in hydride transfers between a range of NAD+ analogues have been examined. Anhydrous and aqueous acetonitrile and aqueous isopropyl alcohol have been used as reaction media, and earlier caveats as to possible complicating kinetic effects of nonproductive adduct formation apply, particularly where hydroxylic solvents are used. Data from hydride transfers have been compared with equilibria, kR +, and rates for pseudo-base formation, or for formation of cyanide adducts. The aqueous alcoholic solvent has an added disadvantage that p/fR+-values for the cations are necessarily composite. 

The utility of cationic surfactants in increasing hydride transfer would be expected to be shown by an Increased yield of octanes during butene alkylation. This follows if alkylate selectivity is decided by the ratio of the rate at which intermediate Ions are captured by hydride transfer to the rate at which they add to olefins and polymerize, and If the effect of the additives Is to selectively raise the specific rate constant for hydride transfer, kg". 

In inosine monophosphate dehydrogenase, the monovalent metal ion accelerates the hydride transfer step of the reaction with apparently few other effects on the enzyme structure. Probably the monovalent cation is involved in helping position the nicotinamide cofactor. The active site and location of the potassium ion are shown in Figure 2. Mycophenolic acid in this diagram is an inhibitor that is thought to lock inosine monophosphate into the active site, as shown. Note the large distance between the inhibitor (in the active site) and the K+. 

The nitrosonium ion (NO ), the electrophilic species formed in nitrous acid media, is also a particularly effective hydride abstracting agent. Cumene reacts with NO+ to give various condensation products that involve intermediate formation of the cumyl cation. °The formation of the cumyl cation in a nonlinear hydride transfer reaction involves a pentacoordinate carbocation [Eq. (6.45)]. 

Unsymmetrical ir-allyl-Pd complexes usually suffer attack of the hydride nucleophile at the less substituted position in an SN2-type reaction. However, the site selectivity of the process is controlled by steric and/or electronic effects. The reaction is strongly dependent on the structural features of the substrate and the reaction conditions. Opposite site selectivity is observed when the reduction occurs at the sterically more hindered position via a cationic intermediate (SN1-type). Very potent nucleophilic hydride sources, such as LiBHEt3 or LiAlH4, may rapidly attack intermediate it-ally 1 complexes at the less hindered terminal position to give the more substituted alkene, while less effective hydride-transfer reagents (NaBH3CN, NaBH4) attack the it-allyl systems at the site best able... 

In this system, planar chain-end C-H bonds in pentane radical cations from which proton donation takes place only come into close contact with secondary C-H bonds at the irmer (C5) position in decane, as well as with primary C-H bonds the latter have a much lower protonation energy than secondary C-H bonds, however, and thus cannot compete effectively as acceptor in the protonation process. Experiments show a marked predominance of 5-chlorodecane over more lateral secondary chlorodecanes, in accordance with the restricted accessibility of secondary C-H bonds in decane to planar chain-end C-H bonds in pentane radical cations. Perhaps even more importantly, no substantial preference is observed for the penultimate position relative to the C3 and C4 positions. This shows unequivocally that the preference for the penultimate position in the experiments with other systems described above is not due to the transformation of alkyl carbenium ions by hydride transfer, i.e., reactions such as... 

The reactions of various analogs of NAD H with ketones and acridinium cations gave isotope effects on the rate constants for substrate reduction (ku/k ) that were different in magnitude from the isotope effects measured by isotope abundances in products compared to reactants (Yh/Td)- For example, Yh/Yd was found to be constant at around 6 in one series of reactions, while kn/k varied with the structure of the hydride donor from about 3.3 to about 5.7. A hydride-transfer mechanism therefore appeared to be excluded. 

The same mechanistic dichotomy for HAT reactions, one-step (concerted) HAT versus sequential (stepwise) electron and proton transfer (Scheme 2.1), is applied to hydride transfer reactions, one-step (concerted) hydride transfer versus sequential (stepwise) ET followed by proton-electron (or hydrogen) transfer.13,40 64 68 Such one-step versus multistep pathways have been discussed extensively in hydride transfer reactions of dihydronicotinamide coenzyme (NADH) and analogues, particularly including the effect of metal cations and acids, 69-79 because of the essential role of acid catalysis in the enzymatic reduction of carbonyl compounds by NADH.80 In contrast to the one-step hydride transfer pathway that proceeds without an intermediate, the ET pathway would produce radical cation hydride donors as the reaction intermediates, which have rarely been observed. The ET pathway may become possible if the ET process is thermodynamically feasible. 

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