Ketone reaction with LiAlH

Notice in the previous reaction that the ketone carbonyl group has been reduced to an alcohol by reaction with LiAlH. The protected aldehyde group has not been reduced. Hydrolysis of the reduction product recreates the original aldehyde group in the final product. 

Commercially, pure ozonides generally are not isolated or handled because of the explosive nature of lower molecular weight species. Ozonides can be hydrolyzed or reduced (eg, by Zn/CH COOH) to aldehydes and/or ketones. Hydrolysis of the cycHc bisperoxide (8) gives similar products. Catalytic (Pt/excess H2) or hydride (eg, LiAlH reduction of (7) provides alcohols. Oxidation (O2, H2O2, peracids) leads to ketones and/or carboxyUc acids. Ozonides also can be catalyticaHy converted to amines by NH and H2. Reaction with an alcohol and anhydrous HCl gives carboxyUc esters. 

Stereoselectivity in the reaction of acyclic ketone 270 is different from that of the cyclic ketone 256. The acetate in 271, prepared by reduction of the ketone 270 to alcohol with LiAlH and acetylation, was displaced with Me A1 from the exo side to give 272 with retention of the stereochemistry. No racemization of benzyl cation was observed. However, reaction of 270 with MeLi gave 274. The OH group of 274 was removed with hydride from the less hindered side as shown by 275 to give 276 with... 

Treatment of a ketone or aldehyde with LiAlH or NaBH4 reduces the carbonyl group and yields an alcohol (Section 17.5). Although the exact details of carbonyl-group reduction are complex, LLAIH4 and NaBH act as if they were donors of hydride ion, H , and the key step is a nucleophilic addition reaction (Figure 19.7). Addition of water or aqueous acid after the hydride addition step protonates the tetrahedral alkoxide intermediate and gives the alcohol product. 

The reduction-hydroboration of alkyldihalogenoboranes provides a more general approach to unsymmetrical dialkylboranes. The reduction of RBX2 (X = Br, Cl) with LiAlH followed by the addition of a terminal olefin gives RR BX. Redistribution does not occur, as proved by clean conversion of these dialkylhalogenoboranes into ketones via DCME reaction. However, if the olefin is present in the reaction mixture prior to the reduction, redistributed products are formed ... 

Asymmetric reduction of prochiral ketones, A chiral hydride reagent formed by treating the chiral diamine 1 with LiAlH was postulated to assume a cis-fused five-membered bicyclic ring structure Highly enantiomerically pure alcohols were obtained when the reaction was carried out in ether at low temperature (-100 C) by employing diamines 1 having 2,6-xylyl or phenyl substituents on nitrogen, ... 

The reduction of ketone 559 by LiAlH results mainly in the endo alcohol 556. The thermodynamic equilibrium of exo and endo alcohols leads mainly to exo alcohol 560. Hence, the formation of endo alcohol 556 upon solvolysis of tosylate 558 cannot be due to steric factors — the endo-side attack is sterically less favourable than the exo-side one the resulting alcohol 556 is not a thermodynamically controllable product. Consequently, the data obtained cannot be used to assume a classical structure of the intermediate cation 561. At the same time the participation of the C —C bond and the intermediate non-classical ion are quite compatible with these facts. The acetolysis of the optically active tosylate 558 is accompanied by complete racemization, the rate of the latter being 3 times as high as that of acid elimination (internal return). The completeness of racemization shows the reaction to proceed via a symmetrical trishomocyclopropenyl ion or rapid equilibration of unsymmetrical cations 561 or to be accompanied by a 1,3-hydride shift from to C . 

Thiophen Analogues of Tropylium Ions and Related Compounds.—Condensation of 3,4-diformyl-2,5-dimethylthiophen with acetone or diethyl ketone yields the tropone (496). The reaction with acetone differs from that of phthalaldehyde, which only yields indanones." The reduction of (496) with LiAlH, and also the reaction with Grignard reagents, gave ethereal solutions of alcohols, which with HCIO4 gave the deep-blue tropylium-type perchlorates (497), which are stable in acetic acid." " The carbonium ion (497 R = Me) is less stable than the tropylium ion itself, as a mixture of (498 R = Me) and (499 R = Me) is obtained upon reaction with cyclo-... 

The disproportionation of tertiary and primary alkoxy species 4 has been reported. The NMR spectrum of an equivalent molar mixture of LiAlH3(OBu ) and LiAlH(OBu )3 was the same as that of LiAlH2(OBu )2, suggesting disproportionation of the nonsymmetrical compounds (37). Kinetics of the reduction of several aromatic ketones in ether with reagents formed by the reaction of LAH with Bu OH were consistent with partial disproportionation of species 4 (38) ... 

LiAlH(OBu )3 does not undergo disproportionation to the tetraalkoxy species. Reduction of the aromatic ketones studied involved either monomeric LAH or both this species and the monoalkoxy species, depending on the steric hindrance of the substrate. In a similar study of the reduction of camphor in THF (39), the kinetic results were also consistent with disproportionation of r-butoxy species (eqs. [6] and [7]), active reducing species being LAH and LiAl(OBu )H3. In the reduction of camphor with a series of reagents prepared by the reaction of LAH... 

The reaction of 2-acetylphenothiazine with ethyl magnesium bromide led to 2-(but-2-enyl)phenothiazine (156) A-substituted ketones gave ethynyl derivatives (157) on treatment with acetylene. Reduction of 2-acyl derivatives to alcohols has been performed by the Meerwein-Ponndorf reaction and by using LiAlH. - - Polarographic one-electron reduction of the keto group in 10-acetyl-2-()3-piperidinopropionyl)phenothiazine has been reported. ... 

Asymmetric reduction of ketones. A complex hydride reagent (2) is prepared in I HF by reaction of equimolar amounts of LiAlH, optically active S)-l, and ethanol. This reagent effects asymmetric reduction of aryl and alkenyl ketones with high enantioselectivity. Reductions of dialkyl ketones are less selective (e.g., 13% ec for benzyl methyl ketone). This method has also been applied to ketones that are intermediates in prostaglandin synthesis. ... 

The reduction of unsaturated carbonyl compounds by metal hydrides, and the reaction of organometallic nucleophiles with them, is a complicated story.87 It is more common than not, in each case, to get direct attack at the carbonyl group, but reaction in the conjugate position is well known. Conjugate reduction of a/i-unsaturated ketones by metal hydrides increases88 in the sequences Bu2iAlH < LiAlH4 < LiAlH(OMe)3 < LiAlH(OBu )3 and... 

Lithium aluminum hydride (8) reacts with ketones and aldehydes in the same way as sodium borohydride, except that LiAlH is a more powerful reducing agent. In one experiment, reaction of heptanal (13) with LiAlH4 in diethyl ether, followed by aqueous acid workup, gave 1-heptanol (16) in 86% yield. The mechanism is identical to that of borohydride in that heptanal reacts with the negatively polarized hydrogen of the Al-H unit in 8 via the four-centered transition state 14, This leads to an alkoxyalmninate product, 15, and subsequent treatment with dilute acid... 

Treating an aldehyde or a ketone with NaBU, or LiAlH, followed by water or some other proton source, affords an alcohol. This is an addition reaction because the elanents of H2 are added across the n bond, but it is also a reduction because the product alcohol has fewer C-O bonds than the starting carbonyl compound. 

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