Transfer of hydride ion

LDH catalyzes the transfer of hydride ions (see p.32) from lactate to NAD"" or from NADH to pyruvate. 

Aldehyde formation during the catalytic action of the enzyme requires a net removal of two hydrogen atoms from the alcohol substrate. This dehydrogenation process is known to proceed by a mechanism of combined proton and hydride ion transfer, and it has been well established that transfer of hydride ion occurs directly between substrate and coenzyme in the productive ternary complex. 

Reduction then proceeds by successive transfers of hydride ion, H e, from aluminum to carbon. The first such transfer reduces the acid salt to the oxidation level of the aldehyde reduction does not stop at this point, however, but continues rapidly to the alcohol. Insufficient information is available to permit very specific structures to be written for the intermediates in the lithium aluminum hydride reduction of carboxylic acids. However, the product is a complex aluminum alkoxide, from which the alcohol is freed by hydrolysis ... 

NADPH is required for many biosynthetic sequences. It is generated in different kinds of cells by a variety of reactions, including an NADP+-linked oxidation of malate to pyruvate and C02 and transfer of hydride ion from NADH to NADP+ in a mitochondrial reaction that is driven by metabolic energy. However, in many cases, including in the mammalian liver, a major part of the NADPH requirement is met by oxidation of glucose-6-phosphate to ribulose-5-phosphate and C02. The four electrons that are released by the oxidation are transferred to two molecules of NADP+. 

Net transfer of a proton and two electrons may occur other than by direct transfer of hydride ion between the bonding sites. Single electron transfer followed by hydrogen atom transfer, e/H1, (3), or indeed the reverse sequence, H /e, (4), achieves the same result, as do sequential electron-proton-electron transfers, e/H + /e, (5). 

The reaction catalysed by alcohol dehydrogenases is a transfer of hydride ion from the alcohol to the 4-position of the pyridinium ring of the coenzyme NAD+ (Scheme 6), [For a review of hydride transfer in model systems, see Watt (1988).] The two hydrogen atoms at the 4-position of the dihydro-pyridine ring of NADH are diastereotopic, and over the years it has become apparent that some alcohol dehydrogenases transfer the pro-/ ... 

Mitochondria from adult H. diminuta exhibit an NADH-coupled fumarate reductase (Table 5.11). This presents a potential dilemma with respect to the utilisation of intramitochondrial reducing equivalents by this worm. As reducing equivalents are generated by the malic enzyme in the form of NADP, a mechanism for the transfer of hydride ions from NADPH to NAD to produce NADH is required so that electron-transport-associated activities can proceed and terminate with the reduction of fumarate to succinate. Such a mechanism does exist in H. diminuta as there is a non-energy-linked, membrane-associated transhydrogenase (214, 217, 221, 476). This transhydrogenase, which also occurs in H. microstoma (216) and Spirometra mansonoides (220) catalyses the reaction ... 

Polymerization of the methylenecyclanes XIII and methylcyclenes XIV, the isomers of XII, was studied independently (19). The oligomers obtained from XIII or XIV have the same structure M as those described in this paper. These results therefore confirm the hypotheses advanced for XII—i.e.y opening of the cyclopropane ring and transfer of hydride ion with formation of Xlld, the hindered intermediate which polymerizes poorly and undergoes deprotonation easily, which interrupts the polymerization process. 

Doshl and Albright, and earlier Hoffmann, Schrleshelm and this author (13) have recognized that alkylation performance Is related to the presence of oil soluble hydrocarbons, commonly called red oil or conjunct polymers. These species are usually considered to be saturated and unsaturated cations which can function as Intermediates In the transfer of hydride Ions from Isobutane to other alkyl cations. Assuming that hydride transfer Is a limiting factor, the discovery of means to augment the rate should result In Improved alkylation. This report deals with research which has led to the successful application of cationic surfactants for this purpose In commercial plants. 

This is not our first encounter with the transfer of hydride ion to an electron-deficient carbon we saw much the same thing in the 1,2-shifts accompanying the rearrangement of carbonium ions (Sec. 5.22). There, transfer was intramolecular (within a molecule) here, it is intermolecular (between molecules). We shall find hydride transfer playing an important part in the chemistry of carbonyl compounds (Chap. 19). 

Upon treatment with chloroform and aluminum chloride, alkylbenzenes give orange to red colors. These colors are due to triarylmethyl cations, Ar3C, which are probably produced by a Friedel-Crafts reaction followed by a transfer of hydride ion (Sec. 6.16) ... 

We are already familiar with the facile transfer of hydride from carbon to carbon within a single molecule (hydride shift in reanangements), and between molecules (abstraction by carbonium ion. Sec. 6.16). Later on we shall encounter a set of remarkably versatile reducing agents (hydrides like lithium aluminum hydride LiAlH4, and sodium borohydride, NaBH4) that function by transfer of hydride ion to organic molecules. 

An unusual synthesis of 3-methoxyhasubanan (81) involves an intramolecular amination. This is believed to arise by transfer of hydride ion from the benzylio-allylic position of (82) as shown in Scheme 6. The sulphate ester (84), obtained by the action of methyl sulphate on the 9-hydroxyhasuban-6-one (83), reacted with base to give the 7,14-cyclodihydrocodeine derivative (85) (Scheme 7). Further publications have appeared on the synthesis and pharmacological properties of... 

The rate constants for transfer of hydride ion from l-alkyl-3-cyano-... 

The reducing properties of 1,4-dihydropyridines are illustrated in Schemes 37 and 38. Suiphonium salts of type (99) can be reduced by transfer of hydride ion from the dihydropyridine (98). The synthetic utility of this reaction is limited... 

This reduction almost certainly proceeds via the activation of the aldehyde carbonyl both by bond polarization in the ground-state and by stabilization of bonding interactions in the transition state. Although deuterium isotope labeling experiments show that hydrogen transfer is direct, comparison of kinetic isotope effects with isotope discrimination studies (23) suggest that the transition state of this reaction may not be a simple transfer of hydride ion (see Section IV—2). 

The Wacker reaction has found most use for the oxidation of terminal alkenes to give methyl ketones. It is believed to take place by an initial trans hydroxypallada-tion of the alkene to form an unstable complex that undergoes rapid p-elimination to the enol 112 (5.112). Hydropalladation then reductive elimination completes the overall process that involves transfer of hydride ion from one carbon to the other, via the palladium atom. The hydride migration is required to explain the observation that when the reaction is conducted in deuterium oxide, no deuterium is incorporated in the aldehyde produced. 

Reactions that proceed by transfer of hydride ions are widespread in organic chemistry, and they are important also in biological systems. Reductions involving the reduced forms of coenzymes I and II, for example, are known to proceed by transfer of hydride ion from a 1,4-dihydropyridine system to the substrate. In the laboratory, the most useful reagents of this type in synthesis are aluminium isopropoxide and various metal hydride reducing agents. 

A number of metal hydrides have been employed as reducing agents in organic chemistry, but the most commonly used are lithium aluminium hydride and sodium borohydride, both of which are commercially available. These reagents are nucleophilic and as such they normally attack polarized multiple bonds such as C=0 or C=N by transfer of hydride ion to the more-positive atom. They do not usually reduce isolated carbon-carbon double or triple bonds. 

With both reagents all four hydrogen atoms may be used for reduction, being transferred in a stepwise manner (7.58). For reductions with lithium aluminium hydride, each successive transfer of hydride ion takes place more slowly than the one before, and this has been exploited for the preparation of modified reagents that are less reactive and more selective than lithium aluminium hydride itself (for example, by replacement of two or three of the hydrogen atoms of the anion by alkoxy groups). 

Dehydrogenation of Hydrocarbons. The mechanism by which quinones effect dehydrogenation is believed to involve an initial rate-determining transfer of hydride ion from the hydrocarbon followed by a rapid proton transfer leading to hydroquinone formation. Dehydrogenation is therefore dependent upon the degree of stabilization of the incipient carbocation and is enhanced by the presence of functionality capable of stabilizing the transition state. As a consequence, unactivated... 

Most of our general considerations about hydrogen isotope effects should be equally valid for the transfer of hydride ions or hydrogen atoms, and in fact these classes of reaction have provided much of the evidence for tunnel corrections. Some of it will be summarized briefly here, beginning with solution reactions. Many oxidation reactions are believed to involve hydride ion transfer, and large isotope effects have been reported in the oxidation of l-phenyI-2,2,2-trifluoroethanol by alkaline permanganate (fc //c° = 16,/c /fc = 57, both at 25 C). The activation energies for this reaction are not known accurately, but the reported values lead to — = 2.3 kcal mol A /A = 3.0. The chromic acid oxidation... 

Alkylation is often considered to include the following steps first, the formation of -C4Hg+, then reaction of olefins with these cations to produce heavier cations, and finally transfer of hydride ions to produce heavier paraffins, as indicated by equations (1, 2, 3). 

In this experiment, you will examine the reduction of 9-fluorenone (10) using sodium borohydride to give 9-fluorenol (12), as shown in Equation 17.17. This reaction is mechanistically analogous to the reduction of imines with sodium borohydride (Sec. 17.3) and involves the transfer of hydride ion (H ) from borohydride ion, BH4, to the electrophilic carbonyl carbon with concomitant transfer of the electron-deficient boron atom to the carbonyl oxygen. Theoretically, all four of the hydrogen atoms attached to boron may be transferred in this way to produce the intermediate borate salt 11, which is decomposed upon addition of water and acid to yield 9-fluorenol (12). 

Borane is a Lewis acid that is attacked by electron-rich centers. Thus, when aldehydes or ketones are treated with the BHs THF complex, the borate ester (H2B OR) is rapidly formed, which, upon hydrolysis, gives the corresponding alcohol. The reduction of the carbonyl group is believed to take place by addition of the oxygen atom to the electron-deficient boron atom, followed by irreversible transfer of hydride ion from the now anionic boron to the carbon atom of the (former) carbonyl ... 

Most reductions of carbonyl compounds, including aldehydes and ketones, are now accomplished by transfer of hydride ions from boron or aluminum hydrides. We have already seen the use of sodium borohydride to reduce the carbonyl group of aldehydes and ketones to hydroxyl groups (Section 16.11A) and the use of lithium aluminum hydride to reduce not only aldehyde and ketone carbonyl groups but also carboxyl groups to hydroxyl groups (Section 17.6A). 

The oxidation of several monohydric alcohols to the corresponding aldehydes and ketones by bis(quinuclidine)bromine(I) bromide in chloroform and in the presence of pyridinium trifluoroacetate has a two-step mechanism in which transfer of hydride ion from the substrate to the oxidant is rate-determining. The proposed mechanism is supported by the thermodynamic parameters, deuterium kinetic isotope effect, and Hammett reaction constants of the reaction. ... 

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