Carbonyl groups lithium borohydride

Neither sodium borohydride nor lithium aluminum hydride reduces isolated carbon-carbon double bonds This makes possible the selective reduction of a carbonyl group m a molecule that contains both carbon-carbon and carbon-oxygen double bonds... 

The well-known reduction of carbonyl groups to alcohols has been refined in recent studies to render the reaction more regioselective and more stereoselective Per-fluorodiketones are reduced by lithium aluminum hydride to the corresponding diols, but the use of potassium or sodium borohydride allows isolation of the ketoalcohol Similarly, a perfluoroketo acid fluonde yields diol with lithium aluminum hydnde, but the related hydroxy acid is obtainable with potassium borohydnde [i f] (equations 46 and 47)... 

The carbonyl group of carbohydrates can be reduced to an alcohol function. Typical procedures include catalytic hydrogenation and sodium borohydride reduction. Lithium aluminum hydride is not suitable, because it is not compatible with the solvents (water, alcohols) that are requited to dissolve caibohydrates. The products of caibohydrate reduction aie called alditols. Because these alditols lack a car bonyl group, they aie, of course, incapable of forming cyclic hemiacetals and exist exclusively in noncyclic forms. 

The importance of reactions with complex, metal hydrides in carbohydrate chemistry is well documented by a vast number of publications that deal mainly with reduction of carbonyl groups, N- and O-acyl functions, lactones, azides, and epoxides, as well as with reactions of sulfonic esters. With rare exceptions, lithium aluminum hydride and lithium, sodium, or potassium borohydride are the... 

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... 

Complex hydrides can be used for the selective reduction of the carbonyl group although some of them, especially lithium aluminum hydride, may reduce the a, -conjugated double bond as well. Crotonaldehyde was converted to crotyl alcohol by reduction with lithium aluminum hydride [55], magnesium aluminum hydride [577], lithium borohydride [750], sodium boro-hydride [751], sodium trimethoxyborohydride [99], diphenylstarmane [114] and 9-borabicyclo[3,3,l]nonane [764]. A dependable way to convert a, -un-saturated aldehydes to unsaturated alcohols is the Meerwein-Ponndorf reduction [765]. 

Other reagents used for the preparation of lactones from acid anhydrides are lithium borohydride [1019], lithium triethylborohydride (Superhydride ) [1019] and lithium tris sec-butyl)borohydride (L-Selectride ) [1019]. Of the three complex borohydrides the last one is most stereoselective in the reduction of 3-methylphthalic anhydride, 3-methoxyphthalic anhydride, and 1-methoxynaphthalene-2,3-dicarboxylic anhydride. It reduces the less sterically hindered carbonyl group with 85-90% stereoselectivity and is 83-91% yield [1019]. 

From carbonyl groups Sodium cyanoborohydride-Zinc iodide, 280 From thioketals Lithium aluminum hydride-Bis-(cyclopentadienyl)nickel, 158 From arenesulfonylhydrazones Sodium borohydride, 278 Sodium cyanoborohydride-Zinc iodide, 280... 

During studies on the total synthesis of Aspidosperma type alkaloids, unexpected difficulty was encountered in attempts to reduce the amide carbonyl group of the intermediate 1. Thus, many attempts to reduce 1 with lithium aluminium hydride resulted in reduction of both the amide carbonyl group and the C=C double bond. In an effort to circumvent this problem 1 was reacted with hot phosphorus oxychloride and the intermediate thus obtained treated with sodium borohydride in anhydrous methanol. The product which was isolated, however, was the pentacyclic compound 2, which was obtained in 50% yield. 

For the more reactive nucleophiles, where addition is essentially irreversible, whether 1,2-addition or 1,4-addition occurs depends on the relative rates of addition to the two electrophilic sites, the carbonyl carbon and the /3-carbon. Lithium aluminum hydride usually gives predominantly 1,2-addition and provides a useful way to reduce the carbonyl group of an a,/3-unsaturated compound. Sodium borohydride, on the other hand, often gives a mixture of 1,2-addition and the completely reduced product, where 1,4-addition followed by 1,2-addition has occurred. Thus, the reaction of 2-cyclohexenone with lithium... 

Lithium aluminum hydride (LiAlH4, abbreviated LAH) is a much stronger reagent than sodium borohydride. It easily reduces ketones and aldehydes and also the less-reactive carbonyl groups those in acids, esters, and other acid derivatives (see Chapter 21). LAH reduces ketones to secondary alcohols, and it reduces aldehydes, acids, and esters to primary alcohols. The lithium salt of the alkoxide ion is initially formed, then the (cautious ) addition of dilute acid protonates the alkoxide. For example, LAH reduces both functional groups of the keto ester in the previous example. 

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. 

Reductions of carbonyl groups with lithium aluminium hydride or sodium borohydride occur by hydride transfer to carbon from aluminium or boron, respectively. The course of reaction is subject to steric approach control and product development control [43-45]. Enzymic reactions may or may not form the epimer favoured in the chemical reduction. This has been discussed elsewhere [46]. It is quite clear that the steric course of a dehydrogenase reaction is determined by the structure of the enzyme. 

In unpublished work, Gribble and Obaza-Nutaitis (60) have adapted the Saul-nier-Gribble ellipticine synthesis (61) to the synthesis of olivacine (Scheme 14). Keto lactam 85, available from indole in four steps (71% yield) (61), was treated sequentially with methyllithium and lithium triethylborohydride to give diol 86, which, without isolation, was reduced with sodium borohydride to give 1-de-methylolivacine (87). This had been previously converted to olivacine (4) by Kutney and co-workers (62). The success of this synthesis of 87 was due to the fact that Saulnier and Gribble (63) had previously established that the ketone carbonyl of keto lactam 85 is more reactive than the lactam carbonyl group. 

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