Aldehydes complex metal hydrides

A less powerful complex metal hydride is Na BH4 which will reduce aldehydes and ketones only, and does not attack carboxylic acid derivatives nor does it—as Li AlH4 does—attack NO2 or C=N present in the same compound. It has the great advantage of being usable in hydroxylic solvents. A wide variety of other reagents of the MH4 , MH3OR , MHjfORlj type have been developed their relative effectiveness is related to both the nucleophilicity and size of MH4 , etc. 

This complex can also transfer hydride to another molecule of the carbonyl compound in a similar manner, and the process continues until all four hydrides have been delivered. Since all four hydrogens in the complex metal hydride are capable of being used in the reduction process, 1 mol of reducing agent reduces 4 mol of aldehyde or ketone. Finally, the last complex is decomposed by the addition of water as a proton source. 

There is a rather important difference between chemical reductions using complex metal hydrides and enzymic reductions involving NADH, and this relates to stereospecificity. Thus, chemical reductions of a simple aldehyde or ketone will involve hydride addition from either face of the planar carbonyl group, and if reduction creates a new chiral centre, this will normally lead to a racemic alcohol product. Naturally, the aldehyde primary alcohol conversion does not create a chiral centre. 

We have already noted the ability of complex metal hydrides like lithium aluminium hydride and sodium borohydride to reduce the carbonyl group of aldehydes and ketones, giving alcohols (see Section 7.5). These reagents deliver hydride in such a manner that it appears to act as a nucleophile. However, as we have seen, the aluminium hydride anion is responsible for transfer of the hydride and... 

Thus, in the fine chemicals industry, reduction of ketones and aldehydes relies mainly on the use of complex metal hydrides that require time-consuming workup of reaction mixtures and produce significant amounts of inorganic and organic wastes. Similarly, the oxidation of alcohols into carbonyls is traditionally performed with stoichiometric inorganic oxidants, notably Cr(VI) reagents or a catalyst in combination with a stoichiometric oxidant [1]. 

N. C. Gaylord, Reduction with Complex Metal Hydrides , Interscience, New York, 1956 includes much of the early chemistry of hydrides including some reactions leading to aldehydes. 

Numerous methods for the reduction of ketones and aldehydes to the corresponding secondary and primary alcohols, such as the use of several complex metal hydrides, have found wide application in organic synthesis. Lithium aluminum hydride (LiAlH4) and sodium borohydride (NaBH4) are the most popular of these achiral reagents. However, since a natural product synthesis has to fulfill demands in terms of both efficiency and stereoselectivity, these methods can seldom be used with prochiral substrates. 

When Grignard reagents, organolithium compounds, or complex metal hydrides add to amides, the elimination step is slow at —78 °C, especially when the amine component is -N(Me)OMe (Weinreb amides). When the tetrahedral intermediate is sufficiently long lived, quenching of the reaction mixture with water at —78 °C gives the ketone or aldehyde rather than the alcohol. 

Aldol condensation between campholenic aldehyde (6.72) and an aldehyde or a ketone (6.73) produces an unsaturated derivative (6.74). It should be noted that this material contains an -double bond. The reason for this lies in the mechanism of the aldol condensation as described in Figure 6.4 and associated text. The carbonyl group of (6.74) can be reduced to the corresponding alcohol by, for example, a complex metal hydride such as lithium aluminium hydride or sodium boro-hydride. This produces the sandalwood material (6.75). Three typical examples are shown at the bottom of Figure 6.18. The first, (6.76), is known under various trade names such as Bangalol (Quest) and is... 

For reduction of an aldehyde using a complex metal hydride, see Section 8.3.3.1... 

Several factors affect the reactivity of the boron and aluminum hydrides, including the metal cation present and the ligands, in addition to hydride, in the complex hydride. Some of these effects can be illustrated by considering the reactivity of ketones and aldehydes toward various hydride transfer reagents. Comparison of LiAlH4 and NaAlH4 has shown the former to be more reactive,63 which is attributed to the greater... 

Molybdenum and tungsten carbonyl hydride complexes were shown (Eqs. (16), (17), (22), (23), (24) see Schemes 7.5 and 7.7) to function as hydride donors in the presence of acids. Tungsten dihydrides are capable of carrying out stoichiometric ionic hydrogenation of aldehydes and ketones (Eq. (28)). These stoichiometric reactions provided evidence that the proton and hydride transfer steps necessary for a catalytic cycle were viable, but closing of the cycle requires that the metal hydride bonds be regenerated from reaction with H2. 

The potential participation of an alternative route, involving a binuclear elimination reaction between a metal-acyl and a metal-hydride has also been probed [73]. In Rh-catalysed cydohexene hydroformylation, both [Rh4(CO)i2] and [Rh(C(0)R)(C0)4] are observed by HP IR at steady state, the duster species being a potential source of [HRh(CO)4] by reaction with syn-gas. The kinetic data for aldehyde formation indicated no statistically significant contribution from binudear elimination, with hydrogenolysis of the acyl complex dominant. For a mixed Rh-Mn system. 

The most useful reagents for reducing aldehydes and ketones are the metal hydride reagents. Complex hydrides are the source of hydride ions, and the two most commonly used reagents are NaBlTj and LiAlH4. Lithium aluminium hydride is extremely reactive with water and must be used in an anhydrous solvent, e.g. dry ether. 

Hiickel MO calculations have not revealed any intrinsic kinetic barrier to hydride migration to coordinated CO (93). Thus it is worthwhile to consider possibilities that might mask the occurrence of a metal hydride carbonylation reaction. For instance, metal hydrides have been observed to react rapidly with metal acyls reduction products such as aldehydes or bridging —CHRO— species form (94-96). Therefore, it is possible that a formyl complex might react with a metal hydride precursor at a rate competitive with its formation. Such a reaction could also complicate the decomposition chemistry of formyl complexes. Preliminary studies have in fact shown that metal hydrides can react with formyl complexes (35, 57), but a complete product analysis has not yet been done. 

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