Hydride transfer alcohols

The kinetics with all the substrates and isotope exchange studies are consistent with the preferred pathway mechanism described in Section II,B,4. With secondary alcohols, hydride transfer is slow, the steady-state concentration of the reactant ternary complex is large, and leak of NAD from this complex occurs thus, < a = Ak- /kki (Table I) and is different for different alcohols. With primary alcohols as substrates, hydride transfer and aldehyde dissociation are much faster than NADH dissociation. Under initial rate conditions, therefore, the ternary complex is not present in significant steady-state concentration, and dissociation of NAD from it does not occur to an appreciable extent thus, 4> = 1/ki, and like < o is the same for all primary alcohols. 

Scheme 15.5 Generation of A/-oxoammonium salts from nitroxyl radicals, and the pH-dependent mechanism of oxoammonium reactivity ith alcohols hydride transfer at pH < 5 (Path A) and adduct formation/Cope-type elimination at pH > 5 (Path B).

Dibenzo[a,j]xanthylium chloride Oxo compds. from alcohols Hydride transfer... 

Figure 1.9 Examples of functionally important intrinsic metal atoms in proteins, (a) The di-iron center of the enzyme ribonucleotide reductase. Two iron atoms form a redox center that produces a free radical in a nearby tyrosine side chain. The iron atoms are bridged by a glutamic acid residue and a negatively charged oxygen atom called a p-oxo bridge. The coordination of the iron atoms is completed by histidine, aspartic acid, and glutamic acid side chains as well as water molecules, (b) The catalytically active zinc atom in the enzyme alcohol dehydrogenase. The zinc atom is coordinated to the protein by one histidine and two cysteine side chains. During catalysis zinc binds an alcohol molecule in a suitable position for hydride transfer to the coenzyme moiety, a nicotinamide, [(a) Adapted from P. Nordlund et al., Nature 345 593-598, 1990.)...

FIGURE 18.20 NAD and NADP participate exclusively iii two-electroii transfer reactions. For example, alcohols can be oxidized to ketones or aldehydes via hydride transfer to NAD(P). ... 

The aldehyde or ketone, when treated with aluminum triisopropoxide in isopropanol as solvent, reacts via a six-membered cyclic transition state 4. The aluminum center of the Lewis-acidic reagent coordinates to the carbonyl oxygen, enhancing the polar character of the carbonyl group, and thus facilitating the hydride transfer from the isopropyl group to the carbonyl carbon center. The intermediate mixed aluminum alkoxide 5 presumably reacts with the solvent isopropanol to yield the product alcohol 3 and regenerated aluminum triisopropoxide 2 the latter thus acts as a catalyst in the overall process ... 

One suggested mechanism is that the reaction may take place by a conjugate hydride-transfer mechanism, analogous to what occurs during alcohol oxidations with NAD+. Electrons on the enolate ion might expel a (3 hydride ion, which could add to the doubly bonded NS nitrogen on FAD. Protonation of the intermediate at N1 would give the product. 

The heterocyclic derivative successfully protects the acid from attack by Grignard or hydride-transfer reagents. The carboxylic acid group can be regenerated by acidic hydrolysis or converted to an ester by acid-catalyzed reaction with the appropriate alcohol. 

The products are liberated by hydrolysis of the aluminum alkoxide at the end of the reaction. Lithium aluminum hydride reduction of esters to alcohols involves an elimination step in addition to hydride transfers. 

Thus, NaBH4-CeCl3 tends to give the more stable alcohol, but the origin of this stereoselectivity does not seem to have been established. It is thought that these reductions proceed through alkoxyborohydrides.123 It is likely that equilibration occurs by reversible hydride transfer. 

There are also reactions in which hydride is transferred from carbon. The carbon-hydrogen bond has little intrinsic tendency to act as a hydride donor, so especially favorable circumstances are required to promote this reactivity. Frequently these reactions proceed through a cyclic TS in which a new C—H bond is formed simultaneously with the C-H cleavage. Hydride transfer is facilitated by high electron density at the carbon atom. Aluminum alkoxides catalyze transfer of hydride from an alcohol to a ketone. This is generally an equilibrium process and the reaction can be driven to completion if the ketone is removed from the system, by, e.g., distillation, in a process known as the Meerwein-Pondorff-Verley reduction,189 The reverse reaction in which the ketone is used in excess is called the Oppenauer oxidation. 

On the basis of these experimental results, a possible mechanism has been proposed for the reaction of 1-215 with Sml2 (Scheme 1.52). After formation of the syn-complex A, a rearrangement occurs to give the aldehyde B, which coordinates to the added aldehyde RCHO to afford complex C. Subsequent samarium-catalyzed nucleophilic attack of the secondary alcohol to the carbonyl of RCHO generates a hemiacetal, D. There follows an irreversible intramolecular 1,5-hydride transfer via... 

The regiochemical control of Pd-catalyzed hydride transfer reaction is much more effective than that of the radical denitration, as shown in Eq. 7.98. The base-catalyzed reaction of nitroolefins with aldehydes followed by denitration provides a new synthetic method of homoallyl alcohols (Eq. 7.99).140 Exomethylene compounds are obtained by denitration of cyclic allylic nitro compounds with Pd(0), HC02H and Et3N (Eq. 7.100).140b... 

Stone CL, Bosron WF, Dunn MF. Amino acid substitutions at position 47 of human beta 1 beta 1 and beta 2 beta 2 alcohol dehydrogenases affect hydride transfer and coenzyme dissociation rate constants. J Biol Chem 1993 268 892-899... 

Rhin(bpy)3]3+ and its derivatives are able to reduce selectively NAD+ to 1,4-NADH in aqueous buffer.48-50 It is likely that a rhodium-hydride intermediate, e.g., [Rhni(bpy)2(H20)(H)]2+, acts as a hydride transfer agent in this catalytic process. This system has been coupled internally to the enzymatic reduction of carbonyl compounds using an alcohol dehydrogenase (HLADH) as an NADH-dependent enzyme (Scheme 4). The [Rhin(bpy)3]3+ derivative containing 2,2 -bipyridine-5-sulfonic acid as ligand gave the best results in terms of turnover number (46 turnovers for the metal catalyst, 101 for the cofactor), but was handicapped by slow reaction kinetics, with a maximum of five turnovers per day.50... 

A number of mechanistic pathways have been identified for the oxidation, such as O-atom transfer to sulfides, electrophilic attack on phenols, hydride transfer from alcohols, and proton-coupled electron transfer from hydroquinone. Some kinetic studies indicate that the rate-determining step involves preassociation of the substrate with the catalyst.507,508 The electrocatalytic properties of polypyridyl oxo-ruthenium complexes have been also applied with success to DNA cleavage509,5 and sugar oxidation.511... 

It is well known that strong electrophiles such as carbocations are reduced by organosilicon hydrides (Eq. 1).3,70,71 On the other hand, simple mixtures of organosilicon hydrides and compounds with weakly electrophilic carbon centers such as ketones and aldehydes are normally unreactive unless the electrophilicity of the carbon center is enhanced by complexation of the carbonyl oxygen with Brpnsted acids3,70 73 or certain Lewis acids (Eq. 2).1,70,71,74,75 Using these acids, hydride transfer from the silicon center to carbon may then occur to give either alcohol-related or hydrocarbon products. 

The pyridine-catalysed lead tetraacetate oxidation of benzyl alcohols shows a first-order dependence in Pb(OAc)4, pyridine and benzyl alcohol concentration. An even larger primary hydrogen kinetic isotope effect of 5.26 and a Hammett p value of —1.7 led Baneijee and Shanker187 to propose that benzaldehyde is formed by the two concurrent pathways shown in Schemes 40 and 41. Scheme 40 describes the hydride transfer mechanism consistent with the negative p value. In the slow step of the reaction, labilization of the Pb—O bond resulting from the coordination of pyridine occurs as the Ca—H bond is broken. The loss of Pb(OAc)2 completes the reaction with transfer of +OAc to an anion. 

Recently, Oshima et al. developed the conversion of acid chlorides into the corresponding homoallylic alcohols catalyzed by in r(/ -prepared hydridozirconium allyl reagents (Scheme 41),147 147a The proposed mechanism suggests an initial hydride transfer from the zirconocene crotyl hydride species, in equlibrium with its Cp2Zr(l-alkene),147a to the acid chloride with subsequent allylation to afford the corresponding homoallylic alcohols. 

Noyori and coworkers reported well-defined ruthenium(II) catalyst systems of the type RuH( 76-arene)(NH2CHPhCHPhNTs) for the asymmetric transfer hydrogenation of ketones and imines [94]. These also act via an outer-sphere hydride transfer mechanism shown in Scheme 3.12. The hydride transfer from ruthenium and proton transfer from the amino group to the C=0 bond of a ketone or C=N bond of an imine produces the alcohol or amine product, respectively. The amido complex that is produced is unreactive to H2 (except at high pressures), but readily reacts with iPrOH or formate to regenerate the hydride catalyst. 

No intermediate tungsten complexes were observed in this reaction. The alcohol, sec-phenethylalcohol, is consumed at a rate which is much faster than that of its formation. It was shown separately to be converted to ethylbenzene (Eq. (23)) by HOTf and [Cp(CO)3WH]. This reaction presumably proceeds through loss of water from the protonated alcohol, followed by hydride transfer from [Cp(CO)3WH] to give ethylbenzene. 

The cationic tantalum dihydride Cp2(CO)Ta(H)2]+ reacts at room temperature with acetone to generate the alcohol complex [Cp2(C0)Ta(H01Pr)]+, which was isolated and characterized [45]. The mechanism appears to involve protonation of the ketone by the dihydride, followed by hydride transfer from the neutral hydride. The OH of the coordinated alcohol in the cationic tantalum alcohol complex can be deprotonated to produce the tantalum alkoxide complex [Cp2(C0)Ta(01Pr)]. Attempts to make the reaction catalytic by carrying out the reaction under H2 at 60 °C were unsuccessful. The strong bond between oxygen and an early transition metal such as Ta appears to preclude catalytic reactivity in this example. 

Hydride transfer reactions from [Cp2MoH2] were discussed above in studies by Ito et al. [38], where this molybdenum dihydride was used in conjunction with acids for stoichiometric ionic hydrogenations of ketones. Tyler and coworkers have extensively developed the chemistry of related molybdenocene complexes in aqueous solution [52-54]. The dimeric bis-hydroxide bridged dication dissolves in water to produce the monomeric complex shown in Eq. (32) [53]. In D20 solution at 80 °C, this bimetallic complex catalyzes the H/D exchange of the a-protons of alcohols such as benzyl alcohol and ethanol [52, 54]. 

The catalytic cycle of the reaction is depicted in Scheme 20.6 [31]. After the initial ligand exchange, the ketone (10) is coordinated to the metal ion of 11 (a), yielding complex 12. A direct hydride transfer from the alkoxide to the ketone takes place via a six-membered transition state (b) in which one alkoxy group is oxidized (13). The acetone (14) and the newly formed alcohol (15) are released... 

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