1.5- hydride transfer

The hydride ion is a very strong base (pAT of hydrogen 40) and hydride transfer to electrophihc centres in non-enzyme-catalysed reactions usually requires H either to be pushed off , as in metal hydride reductions or the Cannizzaro reaction, or to be pulled off by strong electrophiles, such as carbonium ions or bromine. The Cannizzaro reaction is another good example of how reaction at one centre in a molecule may completely modify the properties of an adjacent potential reaction site. Hydride transfer from an aldehyde group is thermodynamically unfavourable 

Possibly, glyoxylase, which catalyses the conversion of j8-keto aldehydes to -hydroxy thiol esters, acts by an analogous sort of intramolecular hydride transfer. 

However, the mechanism is not unambiguous and an alternative pathway involves proton abstraction to give an enediolate which can then be reprotonated at the adjacent carbon. 

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The formation of 1-and 2-aIkenes can be understood by the following mechanism. In the presence of formate anion, the 7r-allylpalladium complex 572 is converted into the 7r-allylpalladium formate 573. The most interesting feature is the attack of the hydride from formate to the more substituted side of the (T-allylic system by the cyclic mechanism shown by 574 to form the 1-alkene 575[367]. The decarboxylation and hydride transfer should be a concerted... 

The same regioselective and stereospecific reactions are observed in decalin systems. The 3/3-formate 605 is converted into the a-oriented (j-allylpalladium complex 606, and the hydride transfer generates the fra .s-decalin 607, while the cis junction in 610 is generated from the 3tt-formate 608 by attack of the hydride from the /3-side (609). An active catalyst for the reaction is prepared by mixing Pd(OAc)2 and BU3P in a 1 I ratio with this catalyst the reaction proceeds at room temperature. The reaction proceeded in boiling dioxane when a catalyst prepared from Pd(OAc)2 and BujP in a 1 4 ratio was used[390]. 

The regioselective and stereospecific construction of C-20 stereochemistry is explained by the following mechanism. The Pd(0) species attacks the ( )-/3-carbonate 616 from the a-side by inversion to form the Tr-allylpalladium species 620, which has a stable syn structure[392]. Then concerted decarboxylation-hydride transfer as in 621 takes place from the a-side to give the unnatural configuration in 617. On the other hand, the Tr-allylpalladium complex 622... 

Approach of borohydnde to the top face of the carbonyl group is sterically hindered by one of the methyl groups The bottom face of the carbonyl group is less congested and the major product is formed by hydride transfer from this direction... 

Although the alkylation of paraffins can be carried out thermally (3), catalytic alkylation is the basis of all processes in commercial use. Early studies of catalytic alkylation led to the formulation of a proposed mechanism based on a chain of ionic reactions (4—6). The reaction steps include the formation of a light tertiary cation, the addition of the cation to an olefin to form a heavier cation, and the production of a heavier paraffin (alkylate) by a hydride transfer from a light isoparaffin. This last step generates another light tertiary cation to continue the chain. 

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.)...

It should be noted that compounds of this type " have been of interest as models for hydride transfer reductions in biological systems. Van Bergen and Kellogg state clearly their hope, if not expectation, that when ions such as H, Zn , Mg, etc. are com-plexed in the vicinity of the donor, beneficial catalytic effects might be forthcoming . ... 

That the reduction with formic acid proceeds by a hydride transfer reaction was proposed by Lukes and Ji2ba 100) and finally proven by Leonard and Sauers 63). The use of variously deuterated formic acid allowed Leonard and Sauers to determine that (1) protonation or... 

As shown in Figure 16.10, this reaction mechanism involves nucleophilic attack by —SH on the substrate glyceraldehyde-3-P to form a covalent acylcysteine (or hemithioaeetal) intermediate. Hydride transfer to NAD generates a thioester intermediate. Nucleophilic attack by phosphate yields the desired mixed carboxylic-phosphoric anhydride product, 1,3-bisphosphoglycerate. Several examples of covalent catalysis will be discussed in detail in later chapters. 

FIGURE 16.10 Formation of a covalent intermediate in the glyceraldehyde-3-phos-phate dehydrogenase reaction. Nucleophilic attack by a cysteine —SH group forms a covalent acylcysteine intermediate. Following hydride transfer to NAD, nucleophilic attack by phosphate yields the product, 1,3-bisphosphoglycerate. 

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 NAD- and NADP-dependent dehydrogenases catalyze at least six different types of reactions simple hydride transfer, deamination of an amino acid to form an a-keto acid, oxidation of /3-hydroxy acids followed by decarboxylation of the /3-keto acid intermediate, oxidation of aldehydes, reduction of isolated double bonds, and the oxidation of carbon-nitrogen bonds (as with dihydrofolate reductase). 

The stereospecificity of hydride transfer in dehydrogenases is a consequence of the asymmetric nature of die acUve site. 

FIGURE 24.12 The mechanism of acyl-CoA dehydrogenase. Removal of a proton from the u-C is followed by hydride transfer from the /3-carbon to FAD. 

It is known that tropylium may be prepared from tropylidene via hydride abstraction by PhgC or MegC carbonium ions therefore, it is very likely that here too the dehydrogenation is a hydride transfer from the 1,5-dione to an acceptor. A similar dehydrogenation of chromanones to chromones, with triphenylmethyl perchlorate was reported. A study of the electrooxidation of 1,5-diones on a rotating platinum electrode showed that 1,5-diaryl-substituted diones afford pyrylium salts in these conditions and that the half-wave potentials correlate with yields in chemical dehydrogenations. 

Boron trifluoride etherate, is also a good catalyst for this hydride transfer to chalcone. Unlike triphenylmethyl perchlorate, however, chalcone is able to enter Michael additions with the 1,5-diketone followed by eliminations leading to unexpected products, e.g., 3-benzyl-2,4,6-triphenylpyrylium from 2-carbethoxy-l,3,5-tri-phenylpentane-l,5-dione and chalcone the benzyl group originates from chalcone, the elimination product being ethyl benzoylacetate. ... 

Aldehydes can react through a hydride transfer as in the Cannizzaro reaction. 

The key step of the Cannizzaro reaction is a hydride transfer. The reaction is initiated by the nucleophilic addition of a hydroxide anion to the carbonyl group of an aldehyde molecule 1 to give the anion 4. In a strongly basic medium, the anion 4 can be deprotonated to give the dianionic species 5 ... 

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 ... 

Hydrogen transfer is more correctly called hydride transfer. It is a bimolecular reaction in which one reactant is an olefin. Two examples are the reaction of two olefins and the reaction of an olefin and a naphthene. 

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. 

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