Selective Reduction of Functional Groups

Selective reduction of functional groups can be achieved by chemical modification of the LiALH4 for example, lithium tri(t-butoxy)aluminium hydride [LiAIH(t-OBu)3] is a more selective reagent, and reduces aldehydes and ketones, but slowly reduces esters and epoxides. Nitriles and nitro groups are not reduced by this reagent. Carboxylic acids can be converted into the aldehyde via acid chloride with lithium tri(tert-butoxy) aluminium hydride at a low temperature (—78°C). The nitro compounds are not reduced under this condition. Thus, selective reduction of 3,5-dinitrobenzoic acid (6.45) to 3,5-dinitrobenzaldehyde (6.47) can be achieved in two steps. First, 6.45 is converted into 3,5-dinitrobenzoyl chloride (6.46) and then LiAlH(t-OBu)3 reduction of 6.46 gives 6.47. 

The selective reduction of functional groups in the pyridine series over ring hydrogenation is probably due to the effect of the nitrogen atom. It is conceivable that this selectivity could be changed, particularly... 

In a series of papers, Caubere and co-workers have described their continued exploration of the use of complex reducing agents in the selective reduction of functional groups. For example, the readily prepared NaH-Bu ONa-FeCls reduces oct-l-ene to n-octane in 90—95% yield, and shows selectivity towards exocyclic double bonds. Aliphatic and aromatic halides are reduced to hydrocarbons in high yield by the same reagent, but ketones are unaffected. 

Figure 10, Selective reductions of functional groups in benzonitriles.

Electrochemical studies are usually performed with compounds which are reactive at potentials within the potential window of the chosen medium i.e. a system is selected so that the compound can be reduced at potentials where the electrolyte, solvent and electrode are inert. The reactions described here are distinctive in that they occur at very negative potentials at the limit of the cathodic potential window . We have focused here on preparative reductions at mercury cathodes in media containing tetraalkylammonium (TAA+) electrolytes. Using these conditions the cathodic reduction of functional groups which are electroinactive within the accessible potential window has been achieved and several simple, but selective organic syntheses were performed. Quite a number of functional groups are reduced at this limit of the cathodic potential window . They include a variety of benzenoid aromatic compounds, heteroaromatics, alkynes, 1,3-dienes, certain alkyl halides, and aliphatic ketones. It seems likely that the list will be increased to include examples of other aliphatic functional groups. 

For such a modular configuration, it is claimed that a large number of heterogeneously catalyzed reactions can be performed, e.g. Heck and Suzuki coupling, acid-catalyzed esterifications and reductions of functional groups [83], However, for the mentioned process, the catalyst and reactants are not named and no reaction conditions or experimental results, e.g. yield, selectivity or nature of side products, are given. 

Some selected results are collected in Table 13.1. Entries 1 and 2 refer to the selective reduction of carbonyl groups in the presence of unconjugated C=C double bonds. Both the ketones can be converted into the corresponding alcohols with excellent yields, leaving the other functionalities unaffected. 

The lithium aluminium hydride reductions often proceed at room temperature or below and are usually rapid and free from side reactions. The compound to be reduced is added slowly to an excess of the reagent suspended or dissolved in ether (normal addition). Selective reduction of polar groups in the presence of other reducible functions can frequently be achieved by an inverse addition method the reagent is added slowly to the substance to be reduced, so that the reagent is never present in excess. Thus, by inverse addition cinnamaldehyde (6.44) is reduced to cinnamyl alcohol (6.3). Normal addition gives dihydrocinnamyl alcohol (6.4). 

The reduction of functional groups with sulfurated horohydrides has been reviewed by Lalancette et al. The reagent is particularly useful for selective reductions. Thus selective reduction of a nitro, an oxime, or a nitrile group in the presence of an ester group is possible. In the case of steroidal ketones, the carbonyl group at C is the most reactive site selective reduction of a C -carbonyl group in the presence of other carbonyls at C, I, C,2, C,7, or Cjo is possible. The alcohol obtained is the equatorial isomer. Aldehydes can be reduced selectively in the presence of a carhonyl group if the molar ratio of NaBHjS, is kept at a suitable value. 

Lithium aluminium hydride LiAlH is a useful and conveuient reagent for the selective reduction of the carbonyl group and of various other polar functional groups. It is obtained by treatment of finely powdered lithium hydride with an ethereal solution of anhydrous aluminium chloride ... 

The reduction of a benzenoid ring, except in benzoic acid derivatives, occurs only in the presence of a proton donor having a pKa of 19 or less (pKa of ammonia is about 33). With the exception of the vinyl group, the other functional groups listed above do not require a proton donor of this acidity in order to be reduced, although the course of reduction may then be complex, e.g. as with esters. " Consequently, a variety of functional groups should be capable of selective reduction in the presence of a benzenoid ring if the reaction medium does not contain an acid of pKa <19. A few examples of such selective reductions have been reported in the steroid literature. 

Selective reduction of acetylenes containing carbonyl functions seems to present no difficulties if the groups are not conjugated. 

For a review of selective reduction of aliphatic nitro compounds without disturbance of other functional groups, see Ioffe, S.L. Tartakovskii, V.A. Novikov, S.S. Russ. Chem. Rev., 1966, 35, 19. 

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