Hydride pathway

Dihydrogen evolves from vanadium(II)-cysteine at pH6.0-9.5. This reduction is first order in V11 and independent of pH in the range 7.5-8.5. If cysteamine or cysteine methyl ester is used, dihydrogen is still evolved. The reaction with serine is 1000 times slower than with cysteine even though the half wave potentials are comparable.156 This reaction may be explained by a hydride pathway similar to that proposed for catechol complexes or alternatively Scheme 8. 

Transfer Hydrogenations. Transition metal-catalyzed transfer hydrogenation is thought to occur via two different intermediates, monohydrides or dihydrides, depending on the transition metal species employed. For Wilkinson s catalyst the mono-hydridic pathway was shown to be operative with the aid of deuterium labeling experiments (eq 59). ... 

These considerations are illustrated by an ad initio study of cationic palladium amine complexes. Experimentally, it is found that methylpalladium complexes of chelating terdentate nitrogen ligands insert CO readily. Calculations of the model reaction [PdMe(NH3)3] + CO [Pd(COMe)(NH3)3] showed that a purely five-coordinate pathway (with five ligands firmly coordinated to palladium) could be ruled out. Similarly, a purely dissociative route in which an NH3 ligand dissociates completely was high in energy. The most favorable route was found to be a hydrid pathway in which a five-coordinate intermediate is a transition state, first to partial NH3 dissociation. In the subsequent... 

Compounds with a Ln-As bond (Table Vn.2) have been obtained like the P-analogues via the interaction of LiAs(Bu-t)2 with REM trichlorides in THE medium [13] or via the hydride pathway [7]. The last method has been used for the synthesis of the bimetallic complex with diphenylarsino-bridges [14]. 

To fully elucidate the mechanism of the reaction a computational study using the M06 functional was undertaken. Most of the overall mechanism, such as the involvement of a P-hydride elimination, a migratory insertion, and some details on the structure of the active catalyst, had been determined experimentally. Therefore, the main challenge to be solved by this computational study was to confirm the mechanistic proposal and clarify the fine details such as the distinction between the two pathways in which either the hydride (pathway a) or the amine (pathway b) are located trans to the alkoxide. The full calculated, catalytic cycle is shown in Scheme 8.12. 

In the acid catalyzed dehydration of 2 methyl 1 propanol what carbocation would be formed if a hydride shift accompanied cleavage of the carbon-oxygen bond in the alkyloxonium lon" What ion would be formed as a result of a methyl shift" Which pathway do you think will predominate a hydnde shift or a methyl shift" ... 

Nicotinamide is an essential part of two important coenzymes nicotinamide adenine dinucleotide (NAD ) and nicotinamide adenine dinucleotide phosphate (NADP ) (Figure 18.19). The reduced forms of these coenzymes are NADH and NADPH. The nieotinamide eoenzymes (also known as pyridine nucleotides) are electron carriers. They play vital roles in a variety of enzyme-catalyzed oxidation-reduction reactions. (NAD is an electron acceptor in oxidative (catabolic) pathways and NADPH is an electron donor in reductive (biosynthetic) pathways.) These reactions involve direct transfer of hydride anion either to NAD(P) or from NAD(P)H. The enzymes that facilitate such... 

Tire 2-dimethylamino derivatives 147 were prepared by a three-step reaction pathway that comprised (a) methylation of the 2-acetamido derivative 144 with methyl iodide and sodium hydride to 145, (b) mild acid-catalyzed N-deacetylation of 145 to 146, and (c) further methylation of 146 to the 2-dimethylamino compound 147 (90JMC1230) (Scheme 57). 

A similar reaction pathway is even described for an aliphatic nitro group nucleophilic displacement. Nitrohydrazones 126 with sodium hydride provide acceptable yields (40-60%) of tricyclic [l,2,4]triazolo[5,l-c][l,4]benzoxazines 128... 

A third method of aldehyde synthesis is one that we ll mention here just briefly and then return to in Section 21.6. Certain carboxylic acid derivatives can be partially reduced to yield aldehydes. The partial reduction of an ester by dhsobutylaluminum hydride (DIBAH), for instance, is an important laboratory-scale method of aldehyde synthesis, and mechanistically related processes also occur in biological pathways. The reaction is normally carried out at —78 °C (dry-ice temperature) in toluene solution. 

The aldehyde intermediate can be isolated if 1 equivalent of diisobutvl-aluminum hydride (D1BAH) is used as the reducing agent instead of LiAlH4. The reaction has to be carried out at -78 °C to avoid further reduction to the alcohol. Such partial reductions of carboxylic acid derivatives to aldehydes also occur in numerous biological pathways, although the substrate is either a thioester or acyl phosphate rather than an ester. 

Reductive animations also occur in various biological pathways, fn the biosynthesis of the amino acid proline, for instance, glutamate 5-semjaldehyde undergoes internal imine formation to give 1-pyrrolinium 5-carboxylate, which is then reduced by nucleophilic addition of hydride ion to the C=N bond. 

We now tum our attention to the C21-C28 fragment 158. Our retrosynthetic analysis of 158 (see Scheme 42) identifies an expedient synthetic pathway that features the union of two chiral pool derived building blocks (161+162) through an Evans asymmetric aldol reaction. Aldehyde 162, the projected electrophile for the aldol reaction, can be crafted in enantiomerically pure form from commercially available 1,3,4,6-di-O-benzylidene-D-mannitol (183) (see Scheme 45). As anticipated, the two free hydroxyls in the latter substance are methylated smoothly upon exposure to several equivalents each of sodium hydride and methyl iodide. Tetraol 184 can then be revealed after hydrogenolysis of both benzylidene acetals. With four free hydroxyl groups, compound 184 could conceivably present differentiation problems nevertheless, it is possible to selectively protect the two primary hydroxyl groups in 184 in... 

In a more general sense, this reduction method provides a convenient pathway for converting an aromatic carboxyl group to a methyl group (see Table I).7 Previously, this transformation has been achieved by reduction of the acid to the alcohol with lithium aluminum hydride, conversion of the alcohol to the tosylate, and a second reduction either with lithium aluminum hydride [Aluminate(l —), tetrahydro, lithium,... 

We similarly attempted to remove the hydride in the sandwich series and room-temperature experiments faced the same steric problem. Reactions occurred by an ET pathway followed by cleavage of the C-C bond in the 17e cation [39]. 

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