Aluminum carbonyl groups

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... 

Reduction of an azide a nitrile or a nitro compound furnishes a primary amine A method that provides access to primary secondary or tertiary amines is reduction of the carbonyl group of an amide by lithium aluminum hydride... 

The carbonyl group of carbohydrates can be reduced to an alcohol function Typi cal procedures include catalytic hydrogenation and sodium borohydnde reduction Lithium aluminum hydride is not suitable because it is not compatible with the solvents (water alcohols) that are required to dissolve carbohydrates The products of carbohydrate reduc tion are called alditols Because these alditols lack a carbonyl group they are of course incapable of forming cyclic hemiacetals and exist exclusively m noncyclic forms... 

The results of the reductions of some steroidal a,)3-unsaturated ketones have been summarized by Brown. " The carbonyl group is usually reduced to the hydrocarbon, but the behavior of the double bond depends on the structure of the compound undergoing the reduction. Cholest-4-en-3-one gives chol-est-4-ene. Addition of aluminum chloride to a solution of a 4-ene-3,6-dione followed by treatment with LiAIH4 gives the 4-ene-6-one. Steroid 4,6-dien-3-ones yield mixtures of dienes. When the ketone and double bond are in different rings the results become even more complex dienes as well as mono-enes are obtained. 

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)... 

Reduction of amides (Section 22.9) Lithium aluminum hydride reduces the carbonyl group of an amide to a methylene group. Primary, secondary, or tertiary amines may be prepared by proper choice of the starting amide. R and R may be either alkyl or aryl. 

Grignard and alkyl lithium reagents were found to add to the carbonyl group of a tricyclic vinylogous amide. However, the same compound underwent the usual vinylogous reduction with lithium aluminum hydride (712). Grignard additions to di- and trichloroenamines gave a-chloro- and dichloroketones (713). 

Vinylogous amides undergo reduction with lithium aluminum hydride, by Michael addition of hydride and formation of an enolate, which can resist further reduction. Thus -aminoketones are usually produced (309, 563,564). However, the alternative selective reduction of the carbonyl group has also been claimed (555). 

The aldehyde or ketone, when treated with aluminum triisopropoxide in isopropanol as solvent, reacts via a six-membered cyclic transition state 4. The aluminum center of the Lewis-acidic reagent coordinates to the carbonyl oxygen, enhancing the polar character of the carbonyl group, and thus facilitating the hydride transfer from the isopropyl group to the carbonyl carbon center. The intermediate mixed aluminum alkoxide 5 presumably reacts with the solvent isopropanol to yield the product alcohol 3 and regenerated aluminum triisopropoxide 2 the latter thus acts as a catalyst in the overall process ... 

Treatment of that intermediate with aluminum chloride leads to selective demethylation of that ether para to the carbonyl group (23). Cyclization by means of tosic acid gives the dihydronaphthalene nucleus (24). Alkylation of the phenol with N-(2-chloroethyl)pyrrolidine affords nafoxidine (25). ... 

Reduction of glutarimides with sodium borohydride40 or lithium aluminum hydride41 seems to occur preferentially at the less hindered carbonyl group. 

Alkylation of dianions occurs at the more basic carbon. This technique permits alkylation of 1,3-dicarbonyl compounds to be carried out cleanly at the less acidic position. Since, as discussed earlier, alkylation of the monoanion occurs at the carbon between the two carbonyl groups, the site of monoalkylation can be controlled by choice of the amount and nature of the base. A few examples of the formation and alkylation of dianions are collected in Scheme 1.7. In each case, alkylation occurs at the less stabilized anionic carbon. In Entry 3, the a-formyl substituent, which is removed after the alkylation, serves to direct the alkylation to the methyl-substituted carbon. Entry 6 is a step in the synthesis of artemisinin, an antimalarial component of a Chinese herbal medicine. The sulfoxide serves as an anion-stabilizing group and the dianion is alkylated at the less acidic a-position. Note that this reaction is also stereoselective for the trans isomer. The phenylsulfinyl group is removed reductively by aluminum. (See Section 5.6.2 for a discussion of this reaction.)... 

The mechanism by which the Group III hydrides effect reduction involves activation of the carbonyl group by coordination with a metal cation and nucleophilic transfer of hydride to the carbonyl group. Hydroxylic solvents also participate in the reaction,59 and as reduction proceeds and hydride is transferred, the Lewis acid character of boron and aluminum becomes a factor. 

These reagents generally show increased solubility in organic solvents, particularly at low temperatures, and are useful in certain selective reductions.75 Lithium tri-r-butoxyaluminum hydride and sodium Mv-(2-meLhoxyethoxy)aluminum hydride (Red-Al)76 are examples of these types of reagents that have synthetic use. Their reactivity toward carbonyl groups is summarized in Table 5.3. 

Several modifications have been made to organoaluminum-based catalysts. Methylaluminum bis(2,6-di-tert-butyl-4-alkylphenoxide) (MAD) shows high diastereofacial selectivity in carbonyl alkylation (Scheme 72).31 11 Aluminum tris(2,6-diphenylphenoxide) (ATPH) has been developed as a catalyst for conjugate addition reactions. Since a carbonyl group is stabilized by steric effect of ATPH, the 1,4-adduct is obtained selectively.312... 

The organic analogues of the reactions to be discussed here are the borane reductions of aldehydes and ketones and the addition of metal alkyls across ketonic carbonyls, equation 15. In contrast to the ease of these organic reactions, qualitative data which has accumulated in our laboratory over the last decade demonstrates that the carbonyl group in organometallies is fairly resistant to addition across CO. For example, many stable adducts of organometallie carbonyls with aluminum alkyls are known, eq. lc, but under similar conditions a ketone will quickly react by addition of the aluminum alkyl across the CO bond. A similar reactivity pattern is seen with boron halides. 

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... 

The Meerwein-Ponndorf-Verley reaction is a classic method for ketone/ aldehyde carbonyl group reduction, which involves at least 1 equivalent of aluminum alkoxide as a promoter. In this reaction, the hydrogen is transferred from isopropanol to the ketone/aldehyde substrate, so the reaction can also be referred to as a transfer hydrogenation reaction. 

Selective reduction of ketones.1 This reagent can be used to effect selective reduction of the more hindered of two ketones by DIBAH or dibromoalane. Thus treatment of a 1 1 mixture of two ketones with 1-2 equiv. of 1 results in preferential complexation of the less hindered ketone with 1 reduction of this mixture of free and complexed ketones results in preferential reduction of the free, originally more hindered, ketone. An electronic effect of substituents on a phenyl group can also play a role in the complexation. This method is not effective for discrimination between aldehydes and ketones, because MAD-complexes are easily reduced by hydrides. MAD can also serve as a protecting group for the more reactive carbonyl group of a diketone. The selectivity can be enhanced by use of a more bulky aluminum reagent such as methylaluminum bis(2-f-butyl-6-( 1,1-diethylpropyl)-4-methylphenoxide). 

Most of the substrates for these isomerizations have a tetrahedral carbon with at least one hydrogen substituent between the carbonyl group and the alkyne. Due to the comparable high acidity of this C-H bond neighboring the carbonyl group, already a weak base such as a carbonate, a tertiary amine or aluminum oxide can deprotonate this position and a subsequent protonation at the other end of the pro-pargyl/allenyl anion delivers the allene. 

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