LiAlH4, reaction with ketones

Sodium borohydride is one of the weakest hydride donors available. The fact that it can be used in water is evidence of this as more powerful hydride donors such as lithium aluminium hydride, LiAlH4, react violently with water. Sodium borohydride reacts with both aldehydes and ketones, though the reaction with ketones is slower for example, benzaldehyde is reduced about 400 times faster than acetophenone in isopropanol. 

Alcohols are among the most versatile of all organic compounds. They occur widely in nature, are important industrial 7, and have an unusually rich chemistry. The most widely used methods of alcohol synthesis start with carbonyl compounds. Aldehydes, ketones, esters, and carboxylic acids are reduced by reaction with LiAlH4. Aldehydes, esters, and carboxylic acids yield primary alcohols (RCH2OH) on reduction ketones yield secondary alcohols (R2CHOH). 

Both aldoximes and ketoximes can be reduced to primary amines with LiAlH4. The reaction is slower than with ketones, so that, for example, PhCOCH=NOH gave 34% PhCHOHCH=NOH. Among other reducing agents that give this reduc-... 

With less hindered hydride donors, particularly NaBH4 and LiAlH4, confor-mationally biased cyclohexanones give predominantly the equatorial alcohol, which is normally the more stable of the two isomers. However, hydride reductions are exothermic reactions with low activation energies. The TS should resemble starting ketone, so product stability should not control the stereoselectivity. A major factor in the preference for the equatorial isomer is the torsional strain that develops in the formation of the axial alcohol.117... 

Preparation of sec-or t-alcohols.1 A one-pot preparation of either sec- or t-alcohols involves reaction of RMnI with an acyl chloride to form a ketone com-plexed with MnCl and stable to further reactions with RMnI. The ketone can be reduced by LiAlH4 or NaBH4 to a sec-alcohol or converted into a r-alcohol by reaction with an alkyllithium or a Grignard reagent. 

Mannich bases. A nonacidic and regioselective route to Mannich bases (3) from ketones (or esters) involves reaction with DMF dimethyl acetal (1) at 110° to form an enaminone, which is reduced by LiAlH4 to the Mannich base.1 Example ... 

This Wittig-Homer reagent is prepared from 0,N-dimethylhydroxylamine and chloroacetyl chloride and N(C2H5)3 in CH2C12 followed by reaction with triethyl-phosphite. The anion (BuLi) of 1 reacts with aldehydes or ketones to form hydrox-lmates, which are reduced to aldehydes by LiAlH4 (11, 201-202).1... 

Reduction of alkyl aryl ketones. Aromatic ketones can be reduced to the corresponding hydrocarbons by reaction with LiAlH4 and P2I4 in refluxing benzene. The ketone and the two reagents are used in equimolar amounts. Yields range from 45 to —100%. The method offers a mild alternative to Clemmensen and Wolff-Kishner reductions. 

A chiral complex of (1), LiAlH4, and 2-ethylaminopyridine (molar ratio, 1 1 2), prepared in refluxing ether for 3 h, reduces cyclic ketones to (i )-alcohols in 75-96% ee. Advantages of the enantioselective reduction of ketones with LiAlH4 modified with (1) and additives are the ready availability of (1) in either enantiomeric form and easy removal of (1) from the reaction mixture by washing with dilute acid. 

The P-hydroxy thioester products may be transformed to 1,3-diols by LiAlH4 reduction. Protection of the hydroxyl group followed by reaction with DIBAL-H leads to the corresponding P-alkoxy aldehydes.Alternatively, treatment with a cuprate reagent produces the corresponding ketone. ... 

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