Alcohols, aryl => aldehydes

Hydrogenation of aidehydes. This complex is an effective catalyst for hydrogenation of aliphatic aldehydes to alcohols. Aryl aldehydes are reduced to benzyl alcohols. Keto and nitro groups are not reduced under the same conditions. 

Since amines, unlike alcohols, do not react with dialkylzincs but may coordinatively bind to the zinc atom, the dilithio salt of 2,5-diisopropylpiperazine is a more potent catalyst than the piperazine itself, presumably due to the greater nucleophilic power of the dianion10. Dimethylzinc reacts rather slowly with aryl aldehydes and although the product is obtained in high enantiomeric excess, the chemical yield is low10. 

CHROMIUM TRIOXIDE-PYRIDINE COMPLEX, preparation in situ, 55, 84 Chrysene, 58,15, 16 fzans-Cinnamaldehyde, 57, 85 Cinnamaldehyde dimethylacetal, 57, 84 Cinnamyl alcohol, 56,105 58, 9 2-Cinnamylthio-2-thiazoline, 56, 82 Citric acid, 58,43 Citronellal, 58, 107, 112 Cleavage of methyl ethers with iodotri-methylsilane, 59, 35 Cobalt(II) acetylacetonate, 57, 13 Conjugate addition of aryl aldehydes, 59, 53 Copper (I) bromide, 58, 52, 54, 56 59,123 COPPER CATALYZED ARYLATION OF /3-DlCARBONYL COMPOUNDS, 58, 52 Copper (I) chloride, 57, 34 Copper (II) chloride, 56, 10 Copper(I) iodide, 55, 105, 123, 124 Copper(I) oxide, 59, 206 Copper(ll) oxide, 56, 10 Copper salts of carboxylic acids, 59, 127 Copper(l) thiophenoxide, 55, 123 59, 210 Copper(l) trifluoromethanesulfonate, 59, 202... 

Organozinc reagents have been used in conjunction with a-bromovinylboranes in a tandem route to Z-trisubstituted allylic alcohols. After preparation of the vinylborane, reaction with diethylzinc effects migration of a boron substituent with inversion of configuration and exchange of zinc for boron.176 Addition of an aldehyde then gives the allylic alcohol. The reaction is applicable to formaldehyde alkyl and aryl aldehydes and to methyl, primary, and secondary boranes. 

Kitamura and Noyori have reported mechanistic studies on the highly diastere-omeric dialkylzinc addition to aryl aldehydes in the presence of (-)-i-exo-(dimethylamino)isoborneol (DAIB) [33]. They stated that DAIB (a chiral (i-amino alcohol) formed a dimeric complex 57 with dialkylzinc. The dimeric complex is not reactive toward aldehydes but a monomeric complex 58, which exists through equilibrium with the dimer 57, reacts with aldehydes via bimetallic complex 59. The initially formed adduct 60 is transformed into tetramer 61 by reaction with either dialkylzinc or aldehydes and regenerates active intermediates. The high enantiomeric excess is attributed to the facial selectivity achieved by clear steric differentiation of complex 59, as shown in Scheme 1.22. 

The 3-nitro alcohols are generally obtained in good yield by the reaction of aldehydes with nitroalkanes in the presence of a catalytic amount of base. When aryl aldehydes are used, the (3-nitro alcohols formed may undergo elimination of water to give aryl nitroalkenes. Such side reactions are not always disadvantageous, for nitroalkenes are sometimes the ultimate target for the Henry reaction. The choice of reaction conditions is important to stop the reaction at the stage of 3-nitro alcohols in aromatic cases. 

The iron slurries react readily with ethyl a-bromoacetate. The resulting organoiron species adds readily to aldehydes and ketones to produce 3 -hydroxyesters in excellent yields. Addition of a mixture of an aryl aldehyde and an allylic halide to the iron slurry produced good yields of the cross-coupled alcohol. 

Nicotinamide Adenine Dinucleotide phosphate (NADP+) Glutamate dehydrogenase, Alcohol dehydrogenase, Aryl-aldehyde dehydrogenase... 

Fluoride ion catalyzes the hydrosilylation of both alkyl and aryl aldehydes to silyl ethers that can be easily hydrolyzed to the free alcohols by treatment with 1 M hydrogen chloride in methanol.320 The most effective sources of fluoride are TBAF and tris(diethylamino)sulfonium difluorotrimethylsilicate (TASF). Somewhat less effective are CsF and KF. Solvent effects are marked. The reactions are facilitated in polar, aprotic solvents such as hexamethylphosphortriamide (HMPA) or 1,3-dimethyl-3,4,5,6-tetrahydro-2(l //)-pyrirnidinone (DMPU), go moderately well in dimethylformamide, but do not proceed well in either tetrahydrofuran or dichloromethane. The solvent effects are dramatically illustrated in the reaction of undecanal and dimethylphenylsilane to produce undecyloxyphenyldimethylsi-lane. After one hour at room temperature with TBAF as the source of fluoride and a 10 mol% excess of silane, yields of 91% in HMPA, 89% in DMPU, 56% in dimethylformamide, 9% in tetrahydrofuran, and only 1% in dichloromethane are obtained (Eq. 164).320... 

The 10-57-5-hydridosiliconate ion 62 is known in association with lithium,323 tetrabutylammonium,101 and bis(phosphoranyl)iminium93 cations. It is synthesized by hydride addition to the 8-.S7-4-silane 63, which is derived from hexafluoroacetone.101 Benzaldehyde and related aryl aldehydes are reduced by solutions of 62 in dichloromethane at room temperature101 or in tetrahydrofuran at 0°96 within two hours. The alkyl aldehyde, 1-nonanal, is also reduced by 62 in tetrahydrofuran at O0.96 Good to excellent yields of the respective alcohols are obtained following hydrolytic workup. The reactions are not accelerated by addition of excess lithium chloride,96 but neutral 63 catalyzes the reaction, apparently through complexation of its silicon center with the carbonyl oxygen prior to delivery of hydride from 62.101... 

The same laboratory has prepared three tridentate zinc chelates from chiral tertiary amino phenolic alcohols and used them for enantioselective addition of diethylzinc to aryl aldehydes in 70-87% ee. Results with the ligand 4 [from (1S,2S)-(+ )-pseudoephedrine] are typical. 

Wynberg3 has also effected stereoselective addition of (C2H5)2Zn to aryl aldehydes using cinchona alkaloids, particularly quinine and quinidine, which result in (R)- and (S)-alcohols in excess, respectively. The highest enantiomeric excess, 92% ee, was observed with o-ethoxybenzaldehyde catalyzed by quinine. 

Trimethylsilylation of enolizable carbonyl compounds and alcohols has also been accomplished by the fluoride ion promoted reaction with hexamethyldisilane and ethyl trimethylsilylacetate [48, 49], with high stereospecificity giving Z-enol ethers from ketones [50]. l-Trimethylsilyl-(l-trimethylsilyloxy)alkanes, produced from the reaction of aldehydes with hexamethyldisilane, undergo acid-catalysed hydrolysis during work up to yield the trimethylsilylcarbinols [51]. In the case of aryl aldehydes, the initially formed trimethylsiloxy carbanion produces the pinacol (Scheme 3.1). 

An intramolecular substitution of trimethylamine fix>m 17 gave a bicyclic oxetane 18 in a diastereoselective process <98MI2185>. A [2+2]cycloaddition of 2,2,4,5-tetrasubstituted 2,3-dihydrofuran to aryl aldehydes gave the bicyclic oxetane 19 <98JCS(P1)3261>. 2,2-Disubstituted-3-bromooxetane was obtained by a 4-endo-tcig cyclization process of 3,3 -disubstituted allyl alcohol in the presence of bis(collidine)bromine hexafluorophosphate <99JOC81>. 

The [Con(bipy)2 ]2+ species has also been reported to activate hydrogen peroxide and ter -butyl hydroperoxide for the selective ketonization of methylenic carbons, the oxidation of alcohols and aldehydes, and the dioxygenation of aryl olefins and acetylenes (36). Later reports (37), however, while confirming that the cobalt complexes did indeed cata-... 

Usually, after hydrolysis, the alcohol is the product, but sometimes (especially with aryl aldehydes) elimination follows directly and the product is an olefin. By the use of Bu,P along with Zn, the olefin can be made the main product,454 making this an alternative to the Wittig reaction (6-47). Since Grignard reagents cannot be formed from a-halo esters, the method is quite useful, though there are competing reactions and yields are sometimes low. A similar reaction (called the Blaise reaction) has been carried out on nitriles 455... 

Cesium fluoroxysulfate in acetonitrile medium at 35 C converts primary alcohols and alkyl and aryl aldehydes into acid fluorides in high yields.i" Hammett correlation analysis of the fluorination of various benzene-substituted aldehydes gives the reactivity constant31 q = —0.38. It has been shown that solvent polarity plays an extremely important role in the conversion of aldehydes into fluorides the conversion is almost quantitative in acetonitrile, but completely stopped in dichloromethane, hexane or tetrahydrofuran. The presence of ni-... 

The lower members of the homologous series of 1. Alcohols 2. Aldehydes 3. Ketones 4. Acids 5. Esters 6. Phenols 7. Anhydrides 8. Amines 9. Nitriles 10. Polyhydroxy phenols 1. Polybasic acids and hydro-oxy acids. 2. Glycols, poly-hydric alcohols, polyhydroxy aldehydes and ketones (sugars) 3. Some amides, ammo acids, di-and polyamino compounds, amino alcohols 4. Sulphonic acids 5. Sulphinic acids 6. Salts 1. Acids 2. Phenols 3. Imides 4. Some primary and secondary nitro compounds oximes 5. Mercaptans and thiophenols 6. Sulphonic acids, sulphinic acids, sulphuric acids, and sul-phonamides 7. Some diketones and (3-keto esters 1. Primary amines 2. Secondary aliphatic and aryl-alkyl amines 3. Aliphatic and some aryl-alkyl tertiary amines 4. Hydrazines 1. Unsaturated hydrocarbons 2. Some poly-alkylated aromatic hydrocarbons 3. Alcohols 4. Aldehydes 5. Ketones 6. Esters 7. Anhydrides 8. Ethers and acetals 9. Lactones 10. Acyl halides 1. Saturated aliphatic hydrocarbons Cyclic paraffin hydrocarbons 3. Aromatic hydrocarbons 4. Halogen derivatives of 1, 2 and 3 5. Diaryl ethers 1. Nitro compounds (tertiary) 2. Amides and derivatives of aldehydes and ketones 3. Nitriles 4. Negatively substituted amines 5. Nitroso, azo, hy-drazo, and other intermediate reduction products of nitro com-pounds 6. Sulphones, sul-phonamides of secondary amines, sulphides, sulphates and other Sulphur compounds... 

Vinyl substitution of primary or secondary allylic alcohols with aryl halides usually produces 3-aryl aldehydes or ketones, respectively. The reaction is believed to involve an addition of the intermediate arylpalladium halide to die double bond, placing the aryl group mainly on the more distant carbon from the hydroxy group, followed by palladium hydride elimination, a reverse readdition and another elimination with a hydrogen atom on the carbon bearing the hydroxy group. The product is probably a ir-com-plex of the enol which ultimately either dissociates or collapses to a a-complex with palladium on the... 

Conversion of saturated, primary alkyl and aryl alkyl alcohols into the corresponding aldehydes can be achieved by this method provided that the alcohols are entirely dissolved in the organic phase. Relatively unstable protective groups are not affected, as in the oxidation of the acetonide of 1,2,6-hexanetriol, whereas conjugated and isolated double bonds give rise to side reactions which considerably decrease selectivities and yields.4 Some examples of aldehydes synthesized with this method are reported in Table 1. Under the same conditions, secondary alcohols are oxidized to ketones. Addition of catalytic amounts of quaternary onium salts allows fast and total conversion of primary alcohols and aldehydes into carboxylic acids making this methodology very versatile 4... 

The at complex from DIB AH and butyllithium is a selective reducing agent.16 It is used tor the 1,2-reduction of acyclic and cyclic enones. Esters and lactones are reduced at room temperature to alcohols, and at -78 C to alcohols and aldehydes. Acid chlorides are rapidly reduced with excess reagent at -78 C to alcohols, but a mixture of alcohols, aldehydes, and acid chlorides results from use of an equimolar amount of reagent at -78 C. Acid anhydrides are reduced at -78 C to alcohols and carboxylic acids. Carboxylic acids and both primary and secondary amides are inert at room temperature, whereas tertiary amides (as in the present case) are reduced between 0 C and room temperature to aldehydes. The at complex rapidly reduces primary alkyl, benzylic, and allylic bromides, while tertiary alkyl and aryl halides are inert. Epoxides are reduced exclusively to the more highly substituted alcohols. Disulfides lead to thiols, but both sulfoxides and sulfones are inert. Moreover, this at complex from DIBAH and butyllithium is able to reduce ketones selectively in the presence of esters. 

Aryltrimethylstaimanes arylate aldehydes in the presence of a cationic rhodium complex, [Rh(cycloocta-l,5-diene)(MeCN)2]+, yielding secondary alcohols.114... 

Ullrich R, Niiske J, Scheibner K, Spantzel J, Hoffichter M (2004) Novel Haloperoxidase from the Agaric Basidiomycete Agrocybe aegerita Oxidizes Aryl Alcohols and Aldehydes. Appl Environ Microbiol 70 4575... 

A 2 // -2 -o x o-1,4,2-oxazaphosphi nanc (71, X = H) can be added diastereoselec-tively to alkyl- or aryl-aldehydes or the corresponding aldimines to give alcohol [X = CH (OH)R1] or amine [X = CH (NHR2)R1] products in high yield 281 Nucleophilic and electrophilic activation strategies have been investigated to maximize the de. 

In addition, the chiral titanate 2 can effect enantioselective addition of CH3Li or CH3MgBr to aryl aldehydes to provide (R)-alcohols (equation III). 

The asymmetric addition of diethyl zinc to aryl aldehydes in flow has evoked much academic interest. Supported amino alcohol 6 (Scheme 4.52) was placed in a jacketed column cooled to 0 °C and pretreated with the aldehyde. A 1 1.4 aldehyde diethyl zinc solution was then flowed through the column and collected, and after a simple aqueous workup, the desired product was obtained. In one example, 5 mmol of 6 was used to produce 90 mmol of product in 90% yield and 94% ee, and in a second example 0.7 mmol of 6 produced 58 mmol of product with 92% ee [170]. 

Asymmetric allylboration of RCHO. (S)-l reacts with aliphatic or aryl aldehydes or with a,p-enals to form homoallylic alcohols in 92-97% ee and 80-92% chemical yield. The chemical and optical yields are higher than those obtained with B-allyldiisopinocamphenylborane (14,12), with allylboronates modified with tartrates, or with B-allyltrimethylsilylboronates. The high asymmetric induction is believed to result from steric effects rather than electronic effects. 

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