Chemoselective reduction of aldehyd

Sodium cyanoborohydride is remarkably chemoselective. Reduction of aldehydes and ketones are, unlike those with NaBH pH-dependent, and practical reduction rates are achieved at pH 3 to 4. At pH 5—7, imines (>C=N—) are reduced more rapidly than carbonyls. This reactivity permits reductive amination of aldehydes and ketones under very mild conditions (42). 

Chemoselective reduction of aldehydes.1 Aldehydes can be reduced in the presence of ketones by 1 with 98-100% chemoselectivity. This chemoselectivity is the highest reported for this reduction. 

Reductions. Carbonyl group reduction is achieved with Mg-FeCl3-6H20 in aq DMF at room temperature. For chemoselective reduction of aldehydes, the combination of Mg-SnCl2 2H20 in THF suffices. ... 

Reductions. Chemoselective reduction of aldehydes in the presence of ketones is quite general, except for very highly hindered aldehydes. 

Cyclohexenone is reduced to cyclohexanone, whereas excess reagent leads to the formation of cyclohexanol. Cyclohexanone is preferentially reduced in the presence of benzyl chloride. Under the reaction conditions, methyl benzoate and benzylcyanide do not undergo reduction. Consequently, the lithium di-n-butyl ate complex of 9-BBN permits [33] the chemoselective reduction of aldehydes in the presence of ketones, esters, and nitriles. 

Chemoselective reduction of aldehydes in the presence of ketones has been performed with lithium borohydride adsorbed on molecular sieve zeolites of types A and X. Although it is tempting to postulate that only aldehydes can penetrate into the pores containing the borohydride, preliminary evidence does not seem to support this idea. The more unusual reverse chemoselectivity, that is reduction of only the ketones in ketone-aldehyde mixtures, has been demonstrated for sodium borohydride in the presence of lanthanoid cations (Ln ) such as Ce (Scheme 7). Lanthanoid salts are known to catalyse the... 

These reaction conditions also permit the chemoselective quantitative reduction of benzaldehyde to benzyl alcohol without any concomitant reduction of either acetophenone or 3,3-dimethylbutan-2-one present in the same reaction mixture.83 Additionally, this useful method permits the reduction of aldehyde functions in polyfunctional compounds without affecting amide, anhydride, eth-ylenic, bromo, chloro, or nitro groups.79,80,319... 

Reduction to Alcohols. The organosilane-mediated reduction of ketones to secondary alcohols has been shown to occur under a wide variety of conditions. Only those reactions that are of high yield and of a more practical nature are mentioned here. As with aldehydes, ketones do not normally react spontaneously with organosilicon hydrides to form alcohols. The exceptional behavior of some organocobalt cluster complex carbonyl compounds was noted previously. Introduction of acids or other electrophilic species that are capable of coordination with the carbonyl oxygen enables reduction to occur by transfer of silyl hydride to the polarized carbonyl carbon (Eq. 2). This permits facile, chemoselective reduction of many ketones to alcohols. 

The second synthetic approach to oidiolactone C (61) is summarized in Scheme 20. This route also commences with the ozonolysis of trans-communic acid 180. Now, when this compound was exposed to ozone in excess, keto aldehyde 187 was obtained in 76% yield. The key step in this approach was the y-lactone closure via chemoselective reduction of the lactone moiety on compound 189 through a SN2 mechanism. Compound 189 could be prepared by saponification of the corresponding methyl ester with sodium propanethiolate. Once the primary alcohol is oxidized, the completion of the synthesis of key lactone 103 only requires the allylic oxidation of the C-17 methyl with concomitant closure of the 8-lactone. This conversion was achieved with Se02 in refluxing acetic acid to give 103 in 51% yield. 

Chemoselective reduction of methyl ester 7 to aldehyde 2 is possible with DIB AH. The metallatcd hemiacetal that results from addition of DIBAII to the carbonyl group of ail ester usually decomposes rapidly in polar solvents like THF to an intermediate aldehyde This then competes with the ester and, as a result of its higher clcctrophilicity. js reduced by DIBAH to an alcohol. However, ester 7 bears a methoxymethyl residue in its a-position, which stabilizes the metallated hemiacetal by chelate formation. Chelate complex 22 is protolytically cleaved by way of the hemiacetal only in the course of aqueous workup, so in this case the DIBAH reaction produces only aldehyde 2, not the alcohol (see also Chapter 3), DIBAH, THF, -78 C 100. ... 

Chemoselective reduction of the conjugated double bond of a, /f-unsaturated aldehydes such as citral (556) to give citronellal (577) is possible by Pd-catalysed hydrostannation in the presence of AcOH [213],... 

The relatively inexpensive and safe sodium borohydride (NaBH4) has been extensively used as a reducing agent because of its compatibility with protic solvents. Varma and coworkers reported a method for the expeditious reduction of aldehydes and ketones that used alumina-supported NaBH4 and proceeded in the solid state accelerated by microwave irradiation (Scheme 7) [50]. The chemoselectivity was apparent from the reduction of frarcs-cinnamaldehyde to afford cinnamyl alcohol. 

Fig. 6.42. Preparation of Weinreb amides through SN reactions at the carboxyl carbon. Chemoselective reduction of Weinreb amides to aldehydes.

Fig. 6.43. Chemoselective reduction of carboxylic acid chloride to furnish an aldehyde the keto group of the substrate is compatible with these reaction conditions, too.

Fig. 6.34. Chemoselective reduction of free carboxylic acids to aldehydes. Intermediate B yields, upon hydrolysis, initially an aldehyde hydrate, which dehydrates to the aldehyde spontaneously (mechanism Section 7.2.1).

Fig. 8.2. Chemoselective carbonyl group reductions I. On the left side a chemoselective reduction of the aldehyde takes place, whereas on the right side a chemoselective reduction of the ketone is shown.

Table 3 Comparison of Chemoselectivity in Reductions of Aldehydes in the Presence of Reactive Ketones...

A comparison of four tri-f-alkoxyaluminum hydrides revealed that lithium tris[(3-ethyl-3-pen-tyl)oxy]aluminum hydride, prepared from LAH and 3-ethyl-3-pentanol, was the most selective for reduction of aldehydes over ketones of all types. Even the less reactive benzaldehyde was reduced in THE at -78 C faster than cyclohexanone (97.7 2.3). A good correlation between the steric demands of the reducing agent and the observed chemoselectivity was observed. 

Hydrostannation of carbonyl compounds with tributyltin hydride is promoted by radical initiation and Lewis or protic acid catalysis.The activation of the carbonyl group by the acidic species allows the weakly nucleophilic tin hydride to react via a polar mechanism. Silica gel was a suitable catalyst allowing chemoselective reduction of carbonyl groups under conditions that left many functional groups unchanged. Tributyltin triflate generated in situ from the tin hydride and triflic acid was a particularly efficient catalyst for the reduction of aldehydes and ketones with tributyltin hydride in benzene or 1,2-di-chloromethane at room temperature. Esters and ketals were not affected under these conditions and certain aldehydes were reduced selectively in preference to ketones. 

Alane (AIH3) and its derivatives have also been utilized in the reduction of carboxylic acids to primary alcohols. It rapidly reduces aldehydes, ketones, acid chlorides, lactones, esters, carboxylic acids and salts, tertiary amides, nitriles and epoxides. In contrast, nitro compounds and alkenes are slow to react. AIH3 is particularly useful for the chemoselective reduction of carboxylic acids containing halogen or nitro substituents, to produce the corresponding primary alcohols. DIBAL-H reduces aliphatic or aromatic carboxylic acids to produce either aldehydes (-75 °C) or primary alcohols (25 C) Aminoalu-minum hydrides are less reactive reagents and are superior for aldehyde synthesis. ... 

The facile reduction of the -COOH group by BHj THF or BH3 SMej has been employed for chemoselective reductions of the carboxyl group in the presence of ester or lactone functionalities using a stoichiometric quantity of the borane. The carbonyl group in triacylboranes resembles the reactivity of an aldehyde or a ketone more than of an ester (ester resonance) due to electron delocalization from the acyl oxygen into the p orbital of boron. 

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