Ketones hydride reduction

The mechanism of lithium aluminum hydride reduction of aldehydes and ketones IS analogous to that of sodium borohydride except that the reduction and hydrolysis... 

Hydride reduction (with L1AIH4 or NaBH4) of each of the following ketones has been... 

The introduction of tritium into molecules is most commonly achieved by reductive methods, including catalytic reduction by tritium gas, PH2], of olefins, catalytic reductive replacement of halogen (Cl, Br, or I) by H2, and metal pH] hydride reduction of carbonyl compounds, eg, ketones (qv) and some esters, to tritium-labeled alcohols (5). The use of tritium-labeled building blocks, eg, pH] methyl iodide and pH]-acetic anhydride, is an alternative route to the preparation of high specific activity, tritium-labeled compounds. The use of these techniques for the synthesis of radiolabeled receptor ligands, ie, dmgs and dmg analogues, has been described ia detail ia the Hterature (6,7). 

The introduction of the l/, 2j5-methylene function into cortical hormones is best carried out by starting with the A -3)S-aIcohols (7) which are prepared by lithium aluminum hydride or lithium tri-t-butoxyaluminum hydride reduction of the corresponding A -3-ketones. 

A-ring conjugated ketones do not normally interfere with the epoxidation reaction, but hydride reduction will reduce any ketone groups to alcohols. These can be reoxidized by conventional means. 

An alternate method of producing the 21-hydroxy-20-ketone consists in lithium aluminum hydride reduction of the dimethyl acetal, hydrolysis to the 20-hydroxy-21-aldehyde and rearrangement, preferably via the bisulfite addition product... 

Hydride reduction (with LiAlH4 or NaBH4) of each of the following ketones has been reported in the chemical literature and gives a mixture of two diastereomeric alcohols in each case. Give the structures or build molecular models of both alcohol products for each ketone. 

The chemical reduction of enamines by hydride again depends upon the prior generation of an imonium salt (111,225). Thus an equivalent of acid, such as perchloric acid, must be added to the enamine in reductions with lithium aluminum hydride. Studies of the steric course (537) of lithium aluminum hydride reductions of imonium salts indicate less stereoselectivity in comparison with the analogous carbonyl compounds, where an equatorial alcohol usually predominates in the reduction products of six-membered ring ketones. 

Formation of C—Nu The second mode of nucleophilic addition, which often occurs with amine nucleophiles, involves elimination of oxygen and formation of a C=Nu bond. For example, aldehydes and ketones react with primary amines, RNH2, to form imines, R2C=NR. These reactions proceed through exactly the same kind of tetrahedral intermediate as that formed during hydride reduction and Grignard reaction, but the initially formed alkoxide ion is not isolated. Instead, it is protonated and then loses water to form an imine, as shown in Figure 3. 

Butylcyclohexanol has been prepared from />-/-butylphenol by reduction under a variety of conditions.3 4 Winstein and Holness5 prepared the pure trans alcohol from the commercial alcohol by repeated crystallization of the acid phthalate followed by saponification of the pure trans ester. Eliel and Ro 6 obtained 4-f-butylcyclohexanol containing 91% of the trans isomer by lithium aluminum hydride reduction of the ketone. Iliickel and Kurz 7 reduced />-/-butylphenol with platinum oxide in acetic acid and then separated the isomers by column chromatography. 

The homology between 22 and 21 is obviously very close. After lithium aluminum hydride reduction of the ethoxycarbonyl function in 22, oxidation of the resultant primary alcohol with PCC furnishes aldehyde 34. Subjection of 34 to sequential carbonyl addition, oxidation, and deprotection reactions then provides ketone 21 (31% overall yield from (—)-33). By virtue of its symmetry, the dextrorotatory monobenzyl ether, (/ )-(+)-33, can also be converted to compound 21, with the same absolute configuration as that derived from (S)-(-)-33, by using a synthetic route that differs only slightly from the one already described. 

By studying the NMR spectra of the products, Jensen and co-workers were able to establish that the alkylation of (the presumed) [Co (DMG)2py] in methanol by cyclohexene oxide and by various substituted cyclohexyl bromides and tosylates occurred primarily with inversion of configuration at carbon i.e., by an 8 2 mechanism. A small amount of a second isomer, which must have been formed by another minor pathway, was observed in one case (95). Both the alkylation of [Co (DMG)2py] by asymmetric epoxides 129, 142) and the reduction of epoxides to alcohols by cobalt cyanide complexes 105, 103) show preferential formation of one isomer. In addition, the ratio of ketone to alcohol obtained in the reaction of epoxides with [Co(CN)5H] increases with pH and this has been ascribed to differing reactions with the hydride (reduction to alcohol) and Co(I) (isomerization to ketone) 103) (see also Section VII,C). 

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... 

Another fruitful investigation was based upon the cyanohydrin of ketone 60. This substance (75) undergoes hydride reduction to the corresponding aminoalcohol, which forms cyclic carbamate 76 on... 

Tributyltin hydride reduction of carbonyl compounds. The reduction of carbonyl compounds with metal hydrides can also proceed via an electron-transfer activation in analogy to the metal hydride insertion into TCNE.188 Such a notion is further supported by the following observations (a) the reaction rates are enhanced by light as well as heat 189 (b) the rate of the reduction depends strongly on the reduction potentials of ketones. For example, trifluoroacetophenone ( re<1 = —1.38 V versus SCE) is quantitatively reduced by Bu3SnH in propionitrile within 5 min, whereas the reduction of cyclohexanone (Erea — 2.4 V versus SCE) to cyclohexanol (under identical... 

Deuterium-labeled organosilicon hydride alkene to alkane reductions, 34 disubstituted alkenes, 37-38 alkyl halide reduction, 29-31 Diastereoselectivity, ketone-alcohol reduction, 76-79... 

The stereoselective total synthesis of both ( )-corynantheidine (61) (170,171) (alio stereoisomer) and ( )-dihydrocorynantheine (172) (normal stereoisomer) has been elaborated by Szdntay and co-workers. The key intermediate leading to both alkaloids was the alio cyanoacetic ester derivative 315, which was obtained from the previously prepared ketone 312 (173) by the Knoevenagel condensation accompanied by complete epimerization at C-20 and by subsequent stereoselective sodium borohydride reduction. ( )-Corynantheidine was prepared by modification of the cyanoacetate side chain esterification furnished diester 316, which underwent selective lithium aluminum hydride reduction. The resulting sodium enolate of the a-formyl ester was finally methylated to racemic corynantheidine (171). 

Several early reports of high asymmetric induction during the hydride reduction of ketones under the influence of chiral catalysts [e.g. 1,2] have been discredited [3-6]. 

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