Sodium Borohydride Reduction of an Aldehyde or Ketone

Sodium Borohydride Reduction of an Aldehyde or Ketone THE OVERALL REACTION  

Step 1 Hydride (hydrogen + two electrons) is transferred from boron to the positively polarized carbon of the carbonyl group. The carbonyl oxygen bonds to boron. 

Steps 2-4 The alkoxyborohydride formed in the first step contains three more hydrogens that can be donated to carbonyl groups. It reacts with three more molecules of the starting aldehyde or ketone. 

Step 5 When the reaction is carried out in water as the solvent, the tetraalkoxy-borate undergoes hydrolysis. 

Steps 6-8 Three more hydrolysis steps convert the trialkoxyborate to three more molecules of R2CHOH and (HO)4B . 

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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... 

FIGURE 15.2 Mechanism of sodium borohydride reduction of an aldehyde or ketone. 

Sodium Borohydride Reduction of an Aldehyde or Ketone 653 Acid-Catalyzed Formation of Diethyl Ether from Ethyl Alcohol 660 Chromic Acid Oxidation of 2-Propanol 665... 

You can also catalytically reduce aldehydes and ketones to produce 1° and 2° alcohols. Reduction conditions are very similar to those used to reduce alkene double bonds. If a molecule possesses both a double bond and an aldehyde or ketone functional group, reduction of the aldehyde or ketone group is best carried out using sodium borohydride. The reduction of cyclohexanone by hydrogen gas with a platinum catalyst produces cyclohexanol in good yield. 

By far the most common laboratory reagents for reduction of the carbonyl group of an aldehyde or a ketone to a hydroxyl group are sodium borohydride, lithium aluminum hydride (LAH), and their derivatives. These compounds behave as sources of hydride ion, a powerful nucleophile, that takes part in a nucleophilic acyl addition reaction. 

Carbonyl Group Reduction. The flow of new methods for reduction of acid derivatives and aldehydes or ketones to alcohols continues unabated. The Report last year (4,134) featured the sodium borohydride reduction of carboxylic acid derivatives, originally thought to be 2-thiazoline-2-thiol esters (14), to give alcohols in good yields. Full details of the method have now appeared (Scheme 8), and it seems that the acid derivatives are in fact the 3-acyl thiazolidine-2-thiones (IS) dissappearance of their yellow colour is an easy way to monitor the reduction. Carboxylic acids or their chlorides can also be reduced to primary alcohols in good yields at room temperature using a titanium tetrachloride-sodium borohydride combination. ... 

Lithium aluminum hydride, LAH, is a stronger reducing c ent than sodium borohydride. By using some reducing agents, an aldehyde or a ketone can be reduced back to an alcohol, but in this section our emphasis is upon the reduction of a compound to form an aldehyde or a ketone. 

Enamidines (2). Lithiation of 1 followed by treatment with aldehydes or ketones results in Peterson olefination to give a mixture of isomeric enamidines (2) in good yield. These enamidines can be used to convert the carbonyl compounds used in (heir preparation to homologated amines, aldehydes, and ketones. Conversion to a mclhylaminc involves reduction with sodium borohydride (pH 6) to an aminal, which is then hydrolyzed by dilute acid. The sequence can be carried out from 1 without isolation of any intermediates (equation I). 

A variety of functional transformations occurring far from the SMA framework have been described. Acylation of a silyl ether, sodium borohydride or LAH reduction of an ester into a carbinol, oxidation of a carbinol into an aldehyde or a ketone, and the addition of Grignard reagents to a carbonyl are some examples.95,168,255... 

Sodium borohydride is selective it usually does not react with carbonyl groups that are less reactive than ketones and aldehydes. For example, carboxylic acids and esters are unreactive toward borohydride reduction. Thus, sodium borohydride can reduce a ketone or an aldehyde in the presence of an acid or an ester. 

We shall use this synthesis as a basis for discussion on chemoselectivity in reductions. In the first step, sodium borohydride leaves the black carbonyl group of the ester untouched while it reduces the ketone (in yellow) in the last step, lithium aluminium hydride reduces the ester (in black). These chemoselectivities are typical of these two most commonly used reducing agents borohydride can usually be relied upon to reduce an aldehyde or a ketone in the presence of an ester, while lithium aluminium hydride will reduce almost any carbonyl group. 

Borane reduces esters very slowly and ketones or aldehydes are selectively reduced in the presence of esters. The most widely used application of borane is for the selective reduction of carboxylic acids, even in the presence of halides, esters, nitriles, and ketones.200 since LiAlH4 reduces both acids and esters and NaBH4 does not reduce acids (and often reduces esters with difficulty), borane is the reagent of choice for selective reduction of carboxylic acids in the presence of an ester group. The reduction occurs without racemization of adjacent chiral centers, as in the borane reduction of (-)-malic acid to generate (5)-l,2,4-butanetriol in 92% yield.201 Seki and Kondo s reduction of the acid moiety in 173 to alcohol 174 (in a synthesis of orally active carbapenams), without reduction of the benzylthio or ester groups also demonstrates this selectivity.202 Borane can reduce imides to give an amine.203 Borane also reduces epoxides at the less hindered carbon when mixed with catalytic amounts of sodium borohydride.204... 

The reduction of an ajS-unsaturated aldehyde or ketone using sodium borohydride or sodium cyanoborohydride in the presence of methylamine leads to the formation of mixtures of j8-amino-alcohols and /3-diamines, the relative amounts of the two products varying with the substrate. ... 

Reductions using sodium borohydride are most commonly carried out in aqueous methanol, in pure methanol, or in ethanol. The initial product of reduction is a tetraalkyl borate, which is converted to an alcohol and sodium borate salts upon treatment with water. One mole of sodium borohydride reduces 4 moles of aldehyde or ketone ... 

Carboxylic acids are considerably less reactive than acid chlorides, aldehydes and ketones towards reduction. They cannot be reduced by catalytic hydrogenation or sodium borohydride (NaBH4) reduction. They require the use of a powerful reducing agent, e.g. LiAlH4. The reaction needs two hydrides (H ) from LiAlITj, since the reaction proceeds through an aldehyde, but it cannot be stopped at that stage. Aldehydes are more easily reduced than the carboxylic acids, and LiAltLj reduces all the way back to 1° alcohols. 

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