Mechanism of Hydride Transfer

As early as 1957, it was reported that ternary complexes including 

In the reduction of pyruvate to lactate, isoenzymes of lactate dehydrogenase from pig heart and pig muscle exerted no kinetic deuterium isotope effect (Holbrook and Stinson, 1973). The results reveal that the process involving the movement of the hydrogen nucleus does not constitute the rate-determining step. Here, the isomerization of the substrate-NADH-enzyme ternary complex to an active complex is suggested to be the rate-determining step. The question of whether the active complex corresponds to a charge transfer complex or to a conformationally distorted complex remains unsolved. 

In addition to physical organic techniques mentioned above, product analyses have been done from the viewpoint of reaction mechanism diagnosis. Namely, the reaction with HLADH was investigated by means of several chemically detectable radical probes such as nortricyclanone (NTC), 2,2-dimethyl-5-hexenal (DMHA), and Z-3- 

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The kinetics and mechanism of hydride transfer between Michler s hydride and 2,3,5,6-tetrabromo-/3-benzoquinone have been investigated spectrophotometrically, examining both solvent and pressure effects.330... 

N. Bodor, M. E. Brewster, and J. J. Kaminski, Reactivity of biologically important reduced pyridines. Part III. Energetics and mechanism of hydride transfer between l-methyl-l,4-dihydronicotinamide and the 1-methylnicotinamide cation, a theoretical study, J. Mol. Struct. (Theochem.) 206 315 (1990). 

With all reagents generated by addition of chiral materials to L1A1H4, their exact structure must be determined before facial and orientation preferences can be determined for a given substrate. As illustrated by Alpine borane , the mechanism of hydride transfer must also be known. When these parameters are known, careful examination of models (Dreiding models or computer generated modeling) should determine the actual steric interactions. A casual inspection is usually insufficient for accurate predictions however. 

Scheme 7.4 Mechanism of hydride transfer via Li2TiH-imine complex...

The mechanism of hydride transfer reactions is of special biochemical interest due to the enzymatic significance of the cofactor NAD(P)H (see 3.2). In case of a stepwise PCET reaction, short-lived radical intermediates are expec-ted44 46 existence of unpaired electrons may be probed by analysing the... 

The mechanism of hydride transfer has proved to be controversial. However, it has been demonstrated that hydride transfer reactions can take place in either one or two steps, E. 8.20 - 8.21 ... 

Since the first use of catalyzed hydrogen transfer, speculations about, and studies on, the mechanism(s) involved have been extensively published. Especially in recent years, several investigations have been conducted to elucidate the reaction pathways, and with better analytical methods and computational chemistry the catalytic cycles of many systems have now been clarified. The mechanism of transfer hydrogenations depends on the metal used and on the substrate. Here, attention is focused on the mechanisms of hydrogen transfer reactions with the most frequently used catalysts. Two main mechanisms can be distinguished (i) a direct transfer mechanism by which a hydride is transferred directly from the donor to the acceptor molecule and (ii) an indirect mechanism by which the hydride is transferred from the donor to the acceptor molecule via a metal hydride intermediate (Scheme 20.3). 

The greater lability of complex 146.C (compared to 145.c), as evinced by the much shorter reaction time, is typical of those that bear a carbomethoxy or acetyl substituent at the central carbon of an i73-allylic ligand. The temperature required for complete decarbonylation of complexes of type 146 and 148 increases with the size of the R-substituent, which suggests a mechanism involving hydride transfer.111 This would also explain the observed activating effect of the centrally located carbomethoxy group in 146.C, which would clearly labilize the methyl proton shown explicitly in 146. 

There are two mechanistic possibilities left, either hydride transfer precedes decarboxylation, or vice versa. These two possibilities can be distinguished using Equations 11.51 and 11.53. Within experimental error only Equation 11.51 is consistent with the isotope effect data collected in Table 11.1, thus confirming that the reaction proceeds via a stepwise mechanism with hydride transfer to triphosphate nucleotide (NADP+) and intermediate formation of oxalacetate preceding decarboxylation ... 

In the aldol-Tishchenko reaction, a lithium enolate reacts with 2 mol of aldehyde, ultimately giving, via an intramolecular hydride transfer, a hydroxy ester (51) with up to three chiral centres (R, derived from rYhIO). The kinetics of the reaction of the lithium enolate of p-(phenylsulfonyl)isobutyrophenone with benzaldehyde have been measured in THF. ° A kinetic isotope effect of fee/ o = 2.0 was found, using benzaldehyde-fil. The results and proposed mechanism, with hydride transfer rate limiting, are supported by ab initio MO calculations. 

The mechanism of proton transfer to hydridic hydrogens depends strongly on the strengths of proton-donor and proton-acceptor sites, the nature of the element, bonding to a hydridic hydrogen, and also on the aggregate states (the solid state, the gas phase, or solution) and medium polarity. 

Other methods are also available for generation of boron enolates. Dialkylboranes react with acyclic enones to give Z-enolates by a 1,4-reduction.19 The preferred Z-stereochemistry is attributed to a cyclic mechanism for hydride transfer ... 

The mechanism of 1,4-dihydropyridine reductions is actively being pursued (B-78MI20702). A mechanism involving hydride transfer is attractive because of its simplicity (80JA4198). However, many workers in the area prefer an electron transfer as the first step (79JA7402). The hydride mechanism can be completed by the transfer of a proton followed by an electron or by the transfer of a hydrogen atom (Scheme 29). It is unlikely that the mechanistic question will be resolved in the near future. It may be that the mechanistic pathway that these reactions follow is very sensitive to both the structure of the dihydropyridine and the compound being reduced. 

Clearly, this is a different system in detail, and the only feature that I want to carry over is the possibility of hydride transfer to the copper, which we know to be a strong hydride acceptor. One could, of course, accommodate this feature of the mechanism by a variety of detailed schemes, including one involving chelation. 

The catalyst precursors 112 and 114, the true catalysts 113 and 115, and the reactive intermediate 116 in the transfer hydrogenation were isolated and the mechanism of the transfer hydrogenation has been clearly established [69]. The catalyst precursor 114, the 18-electron complex, was prepared by reacting [RuCbO/Vvcymcnc), (S,S)-TsDPEN and KOH (1 1 1) as orange crystals. Elimination of HC1 from 114 by treatment with one equivalent of KOH produces the true catalyst 115 as the 16-electron, neutral Ru(II) complex. The complex 115 shows distinct dehydrogenative activity for 2-propanol. Rapid formation of acetone occurs to produce the Ru-hydride species 116 as yellow needles when 115 is treated with 2-propanol at room... 

In the 1,4-dihydropyridine series, there has been much discussion on detailed mechanism. In a study of reduction of-cyanocinnamates with a 4,4-dideutero Hantzsch dihydropyridine, a product that was singly deuterated at only the benzylic position together with the oxidized pyridine product 503 was obtained. This seems to show that the mechanism involves hydride transfer from the 4-position of the 1,4-dihydropyridine followed by proton extraction from the nitrogen of the dihydropyridine <2000J(P2)1857>. 

Three reaction mechanisms were considered a radical chain mechanism, a hydride transfer mechanism and an electron transfer reaction from Bu3SnH to the disilane followed by H transfer. The first mechanism should lead to high yields of BugSn2, but this was not observed. We thus assume the last mechanism, which is also in agreement with other investigated reactions of trialkylstaimanes [5-7]. 

Hydrides of tin and germanium also reduce quinones, ultimately to the hydroquinones. The detailed mechanism of hydrogen transfer between four stannanes and four quinones has been studied which suggested a radical mechanism in which hydrogen transfer was the first step. ... 

Promise is held in MPV reactions carried out under catalytic conditions. Instead of, for example, stoichiometric amounts of aluminum as the metal ion activator, catalytic quantities of complexes of rhodium and iridium can sometimes be used to bring about the same reactions. Although the catalytic mechanisms have not been established, postulation of the usual six-membered transition state in the critical step of hydride transfer appears reasonable. The strongly basic conditions of the MPV reaction are avoided. Reductions of aryl ketones (69 equation 30) using (excess) isopropyl alcohol as hydrogen donor and at partial conversions have led to the formation of alcohol (70) in modest enantiomeric excesses with various chiral ligands. " ... 

The additional stereochemical control available in carbanions relative to alkoxides arises both from the extra ligation about carbon and the contributions of the metal. The stereochemistry of hydride transfer from organostannanes has been particularly well investigated. Coordinatively saturated metals like tin function less well as Lewis acids in a cyclic mechanism, and tend to induce hydride loss through an anti-... 

Metal catalysis of olefin and arene hydrogenation is critically dependent on the reactive hydridometal intermediates. However, little is known about the mechanism of hydrogen transfer and hydrometallation and the reactive intermediates involved. The observation of transient charge-transfer absorption during hydrogenation and hydrometallation of olefins with tungsten or molybdenum hydrides [185], opens up the question of a possible electron-transfer mechanism in which the overall hydrogen-atom transfer is the result of a two-step electron-transfer-proton-transfer (ET-PT) process (Eq. 58). 

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