Mechanism aldehyde reduction

Strong reducing agents like sodium borohydride and lithium aluminum hydride are capable of reducing aldehydes to primary alcohols and ketones to secondary alcohols. The general reaction is the reverse of the reactions used to form aldehydes and ketones by the oxidation of primary and secondary alcohols, respectively (to review, see the earlier section Oxidation reactions ). However, the mechanisms for reduction are different. 

DFT has been used to explore the mechanism of reductive etherification of aromatic aldehydes by alcohols, using BH3 as catalyst and reductant.312 The reaction is suggested to proceed by addition (rate controlling), followed by reduction, and is expected to be feasible in polar solvents such as acetonitrile. 

The mechanism of reductive elimination of a hydrido alkyl complex is therefore often approached in an indirect manner. The hydrido-alkyl complex is made not by oxidative addition of the alkane but by some other route. The decomposition of the hydrido-alkyl complex to give alkane is then studied for mechanistic information. Reductive eliminations of an aldehyde from an acyl-hydrido complex, Reaction 2.7, and acetyl iodide from an iodo-acyl complex,... 

Other rhodium complex also catalyzed the addition of the C-H bond in aldehyde to olefins [115-117]. The use of paraformaldehyde results in the formation of aldehydes [115]. Marder et al. proposed the reaction mechanism of CpRh(eth-ylene)2-catalyzed addition of C-H bond in aldehyde to ethylene by the use of isotope-labeling experiments [117]. They suggested that insertion of ethylene to the Rh-H bond must take place rapidly and reversibly, and this equilibrium must be established significantly faster than either aldehyde reductive elimination or product formation (Scheme 4). 

LADH catalyzes the dismutation of different aldehydes to alcohol and acid in the presence of NAD+ at high aldehyde concentrations (53,347,348). Dalziel and Dickinson (349) found that this reaction did not influence the kinetic parameters of normal aldehyde reduction, provided reasonable substrate concentrations were used. They also suggested a mechanism for the dismutase reaction based on a catalytic role of NAD+. Using acetyl pyridine AD+ instead of NAD+ it could, however, be demonstrated (350) that a net reduction of coenzyme occurs during this reaction. Later studies (351) have shown a stoichiometry of one mole NAD+ reduced per mole acid formed. It was also shown that with octanal as a substrate the reaction exhibits a much higher maximal velocity than with acetaldehyde. The isomerase activity of LADH previously reported (260,352) was later shown to result from impurities in the LADH preparations (353). 

In the Heck-Breslow mechanism, formal reductive cleavage of the acyl-Co complex 8 with molecular hydrogen or HCo(CO)4 (2) is proposed. However, it is more than likely that the actual acyl-Co complex that reacts with molecular hydrogen is the coordinatively unsaturated (16-electron) acyl-Co(CO)3 7, and the oxidative adduct 10 is formed from 7, which then reductively eliminates to give aldehyde and HCo(CO)3 (3) (Scheme... 

Another catalytic cycle studied by Matsubara, Morokuma, and coworkers [77] is the hydroformylation of olefin by an Rh(I) complex. Hydroformylation of olefin by the rhodium complex [78-80] is one of the most well known homogeneous catalytic reactions. Despite extensive studies made for this industrially worthwhile reaction [81, 82], the mechanism is still a point of issue. The active catalyst is considered to be RhH(CO)(PPh3)2, 47, as presented in Fig. 25. The most probable reaction cycle undergoes CO addition and phosphine dissociation to generate an active intermediate 41. The intramolecular ethylene insertion, CO insertion, H2 oxidative addition, and aldehyde reductive elimination are followed as shown with the surrounding dashed line. Authors have optimized the structures of nearly all the relevant transition states as well as the intermediates to determine the full potential-... 

Reduction of ethylenic carboxylic acids, esters, and amides on low H2 overvoltage cathodes gives rise to high yields of the respective dihydro compounds, as in the catalytic process, although on metals of high H2 overvoltage reductive dimerization occurs. a,/3-Unsaturated aldehydes and ketones are reduced to a number of products due to the mechanism of reduction. ... 

Note that this mechanism postulates that the iimer sphere water molecule is displaced by substrate during ternary complex formation, and that the substrate oxygen atom occupies the site vacated by the water molecule. This arrangement provides a facile pathway for proton donation to, or abstraction from, the substrate as demanded by the overall course of the reaction. This mechanism accommodates most, but not all, of the steady-state and transient-state kinetic information on pH effects (see, for example. Ref. 65, 67, 68, 85). Both the pre-steady-state kinetic experiments of Shore et al. [85) on the time-course of proton release during alcohol oxidation, and the transient-state kinetic experiments of Dunn (68) on the time-course of proton uptake during aldehyde reduction are in qualitative agreement with this proposal. Both studies show that proton transfer occurs in a step which is different from the oxidoreduction step. Shore et al. (85)... 

NADP+ (Figure 1.40). The mechanism of reduction of imines to amines as well as of carboxylate to aldehyde is similar to that of the reduction of ketones. 

Foreign compounds may be metabolized by non-microsomal enzyme systems. These reactions include deamination of amines, oxidation of alcohols and aldehydes, reduction of aldehydes and ketones, hydrolysis of some esters and amides and may occur in the mitochondria, or the cell supernatant fraction, or in the circulating plasma. A thorough discussion of these non-microsomal mechanisms has been presented by Parke [20], These reactions are confined to Phase I oxidations, reductions, and hydrolyses (see Fig. 1). 

Similar to the reduction of aldehydes, reduction of ketones with Alpine-Borane also involves two competing reaction pathways, a bimolecular -hydride elimination process (cyclic mechanism) affording optically active product [6], and a dehydroboration-reduction sequence yielding racemic product [2] (Scheme 26.1). 

SCHEME 5.65 Proposed mechanism in reductive couplings of alkynes, aldehydes, and silanes. 

For the mechanism of reduction of aldehydes and ketones using NaBHt, see Section 8.3.3.1... 

This mechanism is directly analogous to the mechanism for reduction of an acid chloride with LAH. The first equivalent of LAH reduces the ester to an aldehyde, and the second equivalent of lAH reduces the aldehyde to an alcohol. Treating an ester with only one equivalent of LAH is not an efficient method for preparing an aldehyde, because aldehydes are more reactive than esters and will react with LAH immediately after being formed. If the desired product is an aldehyde, then DIBAH is used as a reducing agent instead of LAH. The reaction is performed at low temperature to prevent further reduction of the aldehyde. 

Propose a mechanism that accounts for the second and third equivalents of hydride in these aldehyde reductions. Hint. Remember the Meerwein-Ponndorf-Verley-Oppenauer equilibration. 

Alkylation of ketones by organic halides If one considers the reaction mechanisms described in sections 4.3.1. and 4.3.2. it appears that radicals and carbanions could be involved in reactions between aldehydes or alkyl halides and Smij. It was hypothesized by Namy et al. (1977) that it could be possible to trap one of the intermediates of the aldehyde reduction by replacing methanol by an electrophile such as CHjI. C-C bond formation was indeed observed but the reaction mixture is quite complicated ... 

Fig. 16 Mechanism for reduction of carboxylic acid into aldehyde by using H-zincate...

From these facts, a mechanism of the Rosenmund reduction has been proposed, in which the formation of the acylpalladium species 893 is the first step of the aldehyde formation and also the decarbonylation, although the Rosenmund reduction proceeds under heterogeneous conditions[744]. 

Sodium borohydride and lithium aluminum hydride react with carbonyl compounds in much the same way that Grignard reagents do except that they function as hydride donors rather than as carbanion sources Figure 15 2 outlines the general mechanism for the sodium borohydride reduction of an aldehyde or ketone (R2C=0) Two points are especially important about this process... 

The mechanism of lithium aluminum hydride reduction of aldehydes and ketones IS analogous to that of sodium borohydride except that the reduction and hydrolysis... 

FIGURE 15 2 Mechanism of sodium borohydnde reduction of an aldehyde or ketone... 

The amount of a particular component in a sample can be monitored by examining the height of a spectral absorption peak The reduction of an aldehyde to an alcohol would show up as a decrease in line intensity for the carbonyl and an increase for the hydroxyl peaks in the spectrum. Changes in the relative importance of different relaxation modes in a polymer can also be followed by the corresponding changes in a mechanical spectrum. 

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