Β-hydroxy Ketones Research Articles

Ionic Liquid Catalysed Synthesis of β-Hydroxy Ketones

Different acidic ionic liquids (ILs; namely, 1-methylimidazolium tetrafluoroborate, 1-methylimidazolium trifluoroacetate, N-methyl-2-pyrrolidone hydrogen sulfate, N,N,N-trioctyl-n-butanesulfonic acid ammonium hydrogen sulfate, 1-methyl-3-(3-sulfobutyl)imidazolium hydrogen sulfate) and basic ILs (namely, 1,1,3,3-tetramethylguanidinium lactate and choline hydroxide) were tested as catalysts for the aldol reaction. The choline hydroxide catalysed reaction gave high yield (94.3%) and selectivity of the 4-hydroxy-4-phenylbutan-2-one after a short reaction time (15 min) at 0 °C. This article demonstrates the potential of choline hydroxide, which is a derivative of choline and a naturally occurring water-soluble essential nutrient, as a highly active and selective green catalyst.

Synthesis and some transformations of functionally substituted lactones

Reactions of functionally substituted unsaturated five- and six-membered cyanolactones with α- and β-hydroxy ketones in the presence of sulfuric acid gave substituted 2-oxofuran- and 2-oxopyran-3-carboxamides. Hydrolysis of some keto amides thus obtained afforded the corresponding carboxylic acids, and reactions with hydrazines and semicarbazides led to hydrazones and semicarbazones at the side-chain oxo group.

Catalyst-Controlled Wacker-Type Oxidation of Homoallylic Alcohols in the Absence of Protecting Groups

Homoallylic alcohols are oxidized to β-hydroxy ketones using a TBHP-mediated Pd-catalyzed Wacker-type oxidation. The use of a bidentate ligand, quinoline-2-oxazoline (Quinox), and TBHP((aq)) as the terminal oxidant provides good yields of the desired products with reaction times significantly reduced as compared to the Tsuji-Wacker oxidation. Additionally, bis- and tris-homoallylic alcohols are oxidized to provide cyclic peroxyketals, presumably via nucleophilic attack of the methyl ketone product.

Titanium Tetraiodide-Promoted Reductive Enolate Formation of α-Tosyloxy Ketone Derivatives and Aldol Reaction with Aldehydes

Abstract Titanium tetraiodide-promoted reductive enolate formation from α-tosyloxy ketone derivatives and subsequent aldol reaction of the resulting enolates with aldehydes gave β-hydroxy ketones.

Role of Pseudoephedrine as Chiral Auxiliary in the “Acetate-Type” Aldol Reaction with Chiral Aldehydes; Asymmetric Synthesis of Highly Functionalized Chiral Building Blocks

We have studied in depth the aldol reaction between acetamide enolates and chiral α-heterosubstituted aldehydes using pseudoephedrine as chiral auxiliary under double stereodifferentiation conditions, showing that high diastereoselectivities can only be achieved under the matched combination of reagents and provided that the α-heteroatom-containing substituent of the chiral aldehyde is conveniently protected. Moreover, the obtained highly functionalized aldols have been employed as very useful starting materials for the stereocontrolled preparation of other interesting compounds and chiral building blocks such as pyrrolidines, indolizidines, and densely functionalized β-hydroxy and β-amino ketones using simple and high-yielding methodologies.

Effect of Substituted Groups on the Electronic Circular Dichroism of Aldols: A Combined Experimental and Time-Dependent DFT Study

A series of aldol products synthesized from the reactions of acetone and cyclohexanone with 2,3,4-substituted benzaldehydes have been studied by electronic circular dichroism (ECD) and time-dependent density functional theory (TDDFT). The influence of various functionals and basis sets on the simulated ECD properties has been tested, and the dependence of the spectra on the flexibility of the molecules has also been demonstrated. The relationship between substituents and chromophores has been discussed in detail. For aldol products of 3,4-substituted nitrobenzaldehydes, Cotton effects observed in the region of 230−400 nm lead to critical ECD pattern, with electron transfer between the nitrobenzene group and the β-hydroxy ketone moiety. The cyclohexanone group exhibits interaction with the nitrobenzene group, which results in a transition mechanism essentially different from that of acetone. The ECD pattern is also modified by the additional chirality localized at the cyclohexanone group. The most prominent effects observed in the nitro-group-substituted aldols are the electrophilic effect and conjugative effect between the nitro group and the benzene ring. These are not observed strikingly for the other substituents studied in this work.

A Two-Step, One-Pot Enzymatic Synthesis of 2-Substituted 1,3-Diols

A biocatalytic cascade reaction was designed for the stereoselective synthesis of optically pure 2-alkyl-1,3-diols employing two enzymes. The cascade process consists of two consecutive steps: a stereoselective diketone reduction and a hydroxy ketone reduction. Chiral diols were formed by the addition of ketoreductases in the same vessel, in high stereoselectivity and chemical yield, without the isolation of the intermediate β-hydroxy ketones.

Biheteroaromatic diphosphine oxides-catalyzed stereoselective direct aldol reactions

A highly stereoselective direct aldol condensation of ketones to aromatic aldehydes was realized; the trichlorosilyl enolether generated in situ in the presence of tetrachlorosilane is activated by catalytic amounts of an enantiomerically pure biheteroaromatic phosphine oxide to react with aldehydes, coordinated as well as activated by the chiral cationic hypervalent silicon species. This Lewis acid-mediated Lewis base-catalyzed transformation allowed, starting from two carbonyl compounds, to directly synthesize β-hydroxy ketones generally with high anti stereoselectivity and up to 93% ee for the anti isomer.

Diastereoselective Reductive Aldol Reaction of Enones to Ketones Catalyzed by Halogenotin Hydride

SiH2Ph2 and alcohol promoted reductive aldol reactions of the enone (I) with ketones are carried out in the presence of catalytic amounts of SnHClBu2 (SnH2Bu2/SnCl2Bu2) to give the corresponding β-hydroxy ketones in a highly chemo- and diastereoselective manner.

Evans−Tishchenko Coupling of Heteroaryl Aldehydes

The low-temperature Evans-Tishchenko coupling of a range of functionalized heteroaryl aldehydes with β-hydroxy ketones in the presence of a Sm(III) catalyst has been achieved with high yields (90-99%) and good to excellent diastereoselectivity (90:10 → 95:5 dr). However, at room temperature a retro-aldol aldol-Tishchenko reaction was found to compete with the desired Evans-Tishchenko reaction. Identification of these byproducts has allowed the corresponding aldol-Tishchenko reaction to be optimized for several heteroaryl aldehydes.

Catalytic enantioselective syn hydration of enones in water using a DNA-based catalyst

The enantioselective addition of water to olefins in an aqueous environment is a common transformation in biological systems, but was beyond the ability of synthetic chemists. Here, we present the first examples of a non-enzymatic catalytic enantioselective hydration of enones, for which we used a catalyst that comprises a copper complex, based on an achiral ligand, non-covalently bound to (deoxy)ribonucleic acid, which is the only source of chirality present under the reaction conditions. The chiral β-hydroxy ketone product was obtained in up to 82% enantiomeric excess. Deuterium-labelling studies demonstrated that the reaction is diastereospecific, with only the syn hydration product formed. So far, this diastereospecific and enantioselective reaction had no equivalent in conventional homogeneous catalysis.

A New Class of Ligands for Aqueous, Lanthanide-Catalyzed, Enantioselective Mukaiyama Aldol Reactions

The development of aqueous methods for generating enantiopure β-hydroxy carbonyl compounds is an important goal because these subunits compose many bioactive compounds and the ability to synthesize these groups in water has environmental and cost benefits. In this communication, we report a new class of ligands for aqueous, lanthanide-catalyzed, asymmetric Mukaiyama aldol reactions for the synthesis of chiral β-hydroxy ketones. Furthermore, we have used luminescence-decay measurements to unveil mechanistic information regarding the catalytic reaction via changes in water-coordination number. The precatalysts presented here yielded β-hydroxy carbonyls from aliphatic and aryl substrates with outstanding syn:anti ratios and enantiometric excesses of up to 49:1 and 97%, respectively.

Indium-mediated allylation of aldehydes, ketones and sulfonimines with 2-(alkoxy)allyl bromides

2-(Alkoxy)propenyl bromides are readily prepared from 1,3-dibromo-2-propanol in a two-step sequence involving hydroxyl protection and sodium hydride-induced dehydrobromination. Indium-mediated allylation of aldehydes, ketones, and sulfonimines with 2-(alkoxy)propenyl bromides furnishes the corresponding homoallylic alcohols and sulfonamines in good yields. The products can be easily transformed into β-hydroxy ketones and esters, as well as substituted dihydropyrans, and protected β-amino acids. Chiral 2-(alkoxy)propenyl halides, derived from (−)-menthol and d-glucal, furnish diastereomerically enriched products.

ChemInform Abstract: Diastereoselective Reduction of β-Hydroxy Ketones to 1,3-Diols with Common Hydride Reagents.

ChemInform Abstract: Diastereoselective Reduction of β-Hydroxy Ketones to 1,3-Diols with Common Hydride Reagents.

ChemInform Abstract: NiCl2(PPh3)2-Zn-Promoted Deallyloxycarbonylative Directed Aldol Reaction of Allyl β-Keto Carboxylates (I) with Aldehydes (II) to β-Hydroxy Ketones (III).

ChemInform Abstract: NiCl2(PPh3)2-Zn-Promoted Deallyloxycarbonylative Directed Aldol Reaction of Allyl β-Keto Carboxylates (I) with Aldehydes (II) to β-Hydroxy Ketones (III).

ChemInform Abstract: The Retro-Aldol Mechanism in the Pyrolysis Kinetics of Primary, Secondary, and Tertiary β-Hydroxy Ketones in the Gas Phase.

ChemInform Abstract: The Retro-Aldol Mechanism in the Pyrolysis Kinetics of Primary, Secondary, and Tertiary β-Hydroxy Ketones in the Gas Phase.

ChemInform Abstract: An Efficient Synthesis of 4-Oxo-2,5-hexadienoates via δ2- Isoxazoline Intermediates.

An efficient method for the preparation of 4-oxo-2,5-hexadienoates starting from 3,5-disubstituted Δ 2 -isoxazolines is described. The N-O bond cleavage of the isoxazoline ring, promoted by molybdenum hexacarbonyl, afforded the β-hydroxy ketone intermediates 9a-d which were smoothly dehydrated to the expected 4-oxo-2,5-hexadienoates (10a-d) in about 40% yield starting from alkyl 3-hydroxymethyl-4,5-dihydroisoxazole-5-carboxylate (6a,b)

ChemInform Abstract: Studies Directed Toward the Synthesis of Taxanes: Construction of the Tricyclo[5.3.1.01,7]undecane System.

The intramolecular nucleophilic substitution of an epoxide by the anion of a nitrile was used to construct the bicyclo[3.1.0]hexane system of 9, derived from 8, and of 14, derived from 13. The intramolecular 1,3-dipolar cycloaddition of nitrile oxide 4, obtained from 14, led to isoxazoline 3. However, it was not possible to convert 3 into the corresponding β-hydroxy ketone. Rearrangements of 3 were observed in the presence of dehydrating reagents leading to compounds 19–21, which are structurally related to 11(151)abeotaxanes.

ChemInform Abstract: Highly Diastereoselective Aldol Reactions with Camphor-Based Acetate Enolate Equivalents.

New lithium enolates of α-hydroxy ketones, derived from camphor, are evaluated for asymmetric aldol reactions in the presence of lithium chloride. The diastereoselectivity of the reactions between the lithium enolate of 3 and a variety of achiral aldehydes is strongly influenced by the lithium chloride salt. In these instances, the achieved levels of asymmetric induction, typically 95:5 dr, are in the range of those attained in aldol reactions involving the lithium enolate of the methyl ketone 4, which is sterically more demanding. The resulting aldol adducts are easily transformed into β-hydroxy carboxylic acids, ketones, and aldehydes with concomitant recovery of the camphor, the chiral controller of the process, which can be reused.

Acyclic Amino Acids Catalyzed Direct Asymmetric Aldol Reactions in Aqueous Media Assisted by 2,4-Dinitrophenol

The catalytic capabilities of acyclic amino acids for the direct asymmetric aldol reactions assisted by 2,4-dinitrophenol in aqueous media were investigated. Several acyclic amino acids catalyzed asymmetric aldol reactions with excellent stereoselectivity, and afforded the corresponding β-hydroxy ketones in high yields and up to 99% ee. Our result suggested that the L-isoleucine was the most effective one. A systematic investigation of exploring the catalytic efficiency of natural acyclic amino acids for the asymmetric aldol reactions in aqueous media assisted by 2,4-dinitrophenol was reported. The result demonstrated that the L-isoleucine was the most effective one, which catalyzed asymmetric aldol reactions to afford the corresponding β-hydroxy ketones in high yields and up to 99% ee.