LiAlH4, reaction with alcohols

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). 

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... 

Lithium mesitylhydroborate was prepared by reaction of mesitylmagnesium bromide with trimethoxyborane and subsequent reduction with LiAlH4. The polymerization was performed by adding a THF solution containing a slight excess of lithium mesitylhydroborate to oligo(ethylene oxide) in THF. After treatment with alcohol, the lithium borate polymers were obtained as transparent soft solids soluble in methanol, THF, and chloroform. 

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. 

In 1963, an asymmetric synthesis of chloroallenes was reported by the SNi reaction of propargyl alcohols with thionyl chloride [34]. Since then, rearrangement of pro-pargylic precursors has been one of the most useful methodologies for the synthesis of allenes [35]. Treatment of 84, obtained by asymmetric reduction with LiAlH4-Dar-von alcohol complex, with thionyl bromide gave 86 as the major product via 85 (Scheme 4.21) [36],... 

LiAlH4 usually reduces open-chain anhydrides to give 2 moles of alcohol, With cyclic anhydrides the reaction with LiAIH4 can be controlled to give either diols or lactones572 (see 9-41). NaBH4 in THF, with dropwise addition of methanol, reduces open-chain anhydrides to one mole of primary alcohol and one mole of carboxylic acid.573 OS VI, 482. 

Reaction with LiAlH4 at -78 °C selectively reduces the keto-function from the face opposite to the angular methyl group. Subsequently, the resulting alcohol is protected as TMS ether 58. 

But it is important that multistriatin be made in enantiomerically pure form as well as one diastereomer. Looking back over the synthesis, the first chiral intermediate is 42 and, after some failures, reaction with the isocyanate (+)-(/ )-46 gave a mixture of the urethanes 47 that could be separated by crystallisation. Removal of the urethane by reduction with LiAlH4 gave enantiomerically pure alcohol 42 from which enantiomerically pure (>99%) multistriatin 3 could be made by the methods above. 

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. 

With milder reducing agents such as DIBAL-H and LiAlH[OC(CH3)3]3, the process stops after reaction with one equivalent of Hr and the aldehyde is formed as product. With a stronger reducing agent like LiAlH4, two equivalents of H are added and a 1° alcohol is formed. 

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