Synthesis of cis-2,6-tetrahydropyran-4-one via diastereoselectively intramolecular cyclization of β-hydroxy allyl ketone

A series of cis-2,6-tetrahydropyran-4-ones was synthesized from the intramolecular cyclization reaction of β-hydroxy allyl ketones in the presence of Me₃SiOTf as catalyst. The β-hydroxy allyl ketone was prepared from allylation reaction with β-hydroxynitrile without protection of hydroxy functionality under the Barbier-type reaction condition.     

Palladium(O) Catalysed Isomerisation of 2,3-Epoxy Alcohols to α and β-Hydroxy Ketones

Isomerisation of 2,3-epoxy alcohols possessing an arylgroupat1 and/or 3 position, with Pd(PPh₃)₄ leads to formation of α and β-hydroxy ketones.     

Chiral propionate enolate equivalent for stereoselective additions to symmetrical ketones

The copper enolate derived from (η⁵-C₅H₅)Fe(CO)(PPh₃)COCH₂CH₃ reacts stereoselectively with symmetrical ketones to generate RR,SS-α-methyl-β-hydroxy acyl complexes which on decomplexation liberate the corresponding β-hydroxy acids.     

Mo(CO)6-mediated synthesis of calix[4]arenes carrying β-hydroxy ketones or α,β-unsaturated-β-amino ketones

Mo(CO)₆-mediated ring opening reactions of calix[4]arene isoxazolines/isoxazoles provide a new synthetic methodology for calix[4]arenes carrying bifunctional β-hydroxy ketones or α,β-unsaturated-β-amino ketones. Mo(CO)₆ is a highly selective and convenient reagent for the ring opening process of these supramolecular isoxazolines/isoxazoles.     

Practically useful Reformatsky Type Reactions of Chlorodifluoroacetate and Bromodifluoroacetate Induced by Samarium(II) Diiodide

Treatment of XCF₂COOEt (X = Cl and Br) with SmI₂ in THF gave efficiently β,β-difluorinated enolate equivalent, which was used for Reformatsky type reaction with aldehydes and ketones to give 2,2-difluoro-3-hydroxy ester.     

Revisiting the Corey-Chaykovsky reaction: the solvent effect and the formation of β-hydroxy methylthioethers

The classical Corey-Chaykovsky (CC) reaction of ketones in ethereal solvents (i.e., THF or Et₂O) resulted in the production of a significant amount of β-hydroxy methylthioether 2 along with normal epoxide product 1. Some interesting and synthetically useful transformations of the CC reaction product of cyclopropyl ketones were also described.     

An efficient synthesis of (E)-α,β-unsaturated ketones and esters with total stereoselectivity by using chromium dichloride

(E)-α,β-Unsaturated ketones 1 or esters 2 can be obtained with complete stereoselectivity by reaction of different 2-chloro-3-hydroxy ketones 3 or esters 4 and CrCl₂. A comparative study of the results of synthesis of ketones 1 with CrCl₂ or samarium is performed. A mechanism to explain both β-elimination reactions has been proposed.     

Chiral bifunctional thiourea-catalyzed enantioselective aldol reaction of trifluoroacetaldehyde hemiacetal with aromatic ketones

In the presence of saccharide-derived bifunctional amine-thiourea catalysts, the direct aldol condensation of trifluoroacetaldehyde methyl hemiacetal with aromatic ketones proceeds to produce (R)-β-hydroxy β-trifluoroalkyl ketones in low to moderate yields with good enantioselectivities.     

Tributyltin Hydride-Induced Free Radical Deoxygenation of the Cyclic Thionocarbonates of Threo-2,3-Dihydroxy Esters and Ketones

Abstract: A practical and enantiospecific method for the synthesis of optically pure β-hydroxy esters and ketones is described. The key reaction is free radical deoxygenation of the cyclic thionocarbonates of threo-2,3-dihydroxy esters and ketones with tributyltin hydride.     

Organocatalytic Enantioselective Acyloin Rearrangement of α-Hydroxy Acetals to α-Alkoxy Ketones

We report an unprecedented organocatalytic enantioselective acyloin rearrangement of α,α-disubstituted α-hydroxy acetals. In the presence of a catalytic amount of chiral binol-derived N-triflyl phosphoramide, α-hydroxy acetals rearranged to α-alkoxy ketones in good to high yields with high enantioselectivities. Formation of an ion pair between the in situ generated oxocarbenium ion and the chiral phosphoramide anion was proposed to be responsible for the highly efficient transfer of chirality. Conditions for removal of cyclohexyl and cyclopentyl groups from the corresponding α-alkoxy ketones were uncovered underpinning their potential general utility as hydroxy protecting groups. Conversion of the rearranged products to the enantioenriched α-hydroxy ketone, 1,2-diol, β-amino alcohol and 1,4-dioxane was also documented.     

A general copper-BINAP-catalyzed asymmetric propargylation of ketones with propargyl boronates

An operationally simple copper-BINAP-catalyzed, highly enantioselective propargylation of ketones is presented. The methodology was developed as an enantioselective process for methyl ethyl ketone and shown to be applicable to a wide variety of prochiral ketones. The resulting homopropargyl adducts are versatile latent carbonyls from which γ-butyrolactones, β-hydroxy methyl ketones, and β-hydroxycarboxylates are readily obtained.     

Synthesis and Rhizopus oryzae mediated enantioselective hydrolysis of α-acetoxy aryl alkyl ketones

Mn(OAc)₃ oxidation of aromatic ketones afforded the α-acetoxy ketones in good yield. Selective hydrolysis of the acetoxy ketones by the fungus Rhizopus oryzae yields (R)-hydroxy ketones in high enantiomeric excess.     

Enantioselective reduction of α-substituted ketones mediated by the boronate ester TarB-NO2

A facile and mild reduction procedure is reported for the preparation of chiral secondary alcohols prepared from α-substituted ketones using sodium borohydride and the chiral boronate ester (l)-TarB-NO₂. Direct reduction of substituted ketones bearing Lewis basic heteroatoms generally provided secondary alcohols of only modest enantiomeric excess likely due to either competition between the target carbonyl and the functionalized sidechains at the Lewis acidic boron atom in TarB-NO₂ or the added steric bulk of the α-sidechain. As an alternative method, these substrates were synthesized using TarB-NO₂ via a two-step procedure involving the reduction of an α-halo ketone to a chiral terminal epoxide, followed by regioselective/regiospecific epoxide opening by various nucleophiles. This procedure provides access to a variety of functionalized secondary alcohols including β-hydroxy ethers, thioethers, nitriles, and amines with enantiomeric excesses of 94% and yields up to 98%.     

An efficient procedure for the synthesis of 2-N-Boc-amino-3,5-diols

We wish to describe here the diastereoselective reaction between chiral N-Boc-α-amino aldehydes with both achiral allyltrichlorostannanes leading to 1,2-syn-N-Boc-α-amino alcohols, which are easily converted to the corresponding 4-N-Boc-amino-3-hydroxy ketones after treatment with catalytic amounts of OsO₄ in the presence of NaIO₄. After reduction of the carbonyl function, these 4-N-Boc-amino-3-hydroxy ketones were converted to 1-deoxy-5-hydroxy sphingosine analogues.     

Aerobic oxidation of organic compounds catalyzed by vanadium compounds

Aerobic oxidation of α-hydroxy ketones catalyzed by dichloroethoxyoxovanadium in ethanol causes a carbon–carbon bond cleavage that produces diesters or diketones. This reaction is highly chemoselective, and disecondary glycols do not react at all. However, ditertiary glycols effectively react with dichloroethoxyoxovanadium or trichlorooxovanadium to provide the corresponding ketones. Aerobic oxidation of α-hydroxy ketones catalyzed by dichloroethoxyoxovanadium or trichlorooxovanadium in aprotic solvents almost quantitatively affords the corresponding α-diketones. The reaction of tertiary cyclopropanol compounds with vanadyl acetylacetonate under an oxygen atmosphere causes fragmentation of the cyclopropane moiety to produce β-hydroxy ketones and β-diketones. For the 6-substituted bicyclo[4.1.0]heptanol derivatives, the endoperoxides are also obtained together with β-hydroxy ketones. Conversely, 2-ethoxycarbonylcyclopropyl silyl ethers produce γ-oxocarboxylate derivatives given the same reaction conditions. Monothioacetals are easily deprotected into carbonyls using a catalytic amount of trichlorooxovanadium in 2,2,2-trifluoroethanol under an oxygen atmosphere. Thiols are converted into the corresponding disulfides by the aerobic oxidation catalyzed by trichlorooxovanadium in the presence of molecular sieves 3A. Polymer-supported vanadium compounds are synthesized by the reaction of vanadium oxytrichloride with polymers bearing hydroxyl moieties. The catalyst prepared from TentaGel S OH was highly active and reusable for the aerobic oxidations.     

Stereoselective acyclic ketone reduction: Synthesis of the synthons having three consecutive chiral centers

Four possible diastereomers of a functionalized 1,3-dimethyl-2-hydroxy unit were synthesized based on the stereoselective reduction of various acyclic ketones (i.e. reduction of β-keto ester, β-hydroxy ketone, α-hydroxy ketone, and α-silyloxy ketone) and the regioselective ring opening of epoxide by 1,3-dithiane anion.     

A new synthesis of 1,3-aminols from direct double reduction of β-enamino ketones formed in situ by reaction of β-dicarbonyl compounds with anilines

A new one-pot synthesis of 1,3-aminols by direct reduction of β-enamino ketones, formed in situ by reaction of easily available β-dicarbonyl compounds, with anilines were described. In the case of aliphatic amines such as benzyl amine, n-butyl amine and β-hydroxy ethyl amine, the corresponding 1,3-minols were not obtained. In fact, the β-enamino ketone formed was failed to accomplish further reduction to 1,3-aminol. This approach is the most direct available method for the synthesis of 1,3-aminols.     

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.     

Etude des petits cycles—XXXVI. Photo-oxygenation d'alkylidenecyclopropanes. Syntheses specifiques d'alkenylcyclopropanols,de β′-hydroxy α-enones et d'α,α′-dienones

The dye-sensitized photo-oxygenation of alkylidenecyclopropanes 1a–4a at –50°C gives the hydroperoxydes 1b–4b, which were reduced in situ by PPh₃ into 1-alkenylcyclopropanols 1c–4c in high yield. At higher temperatures, 1b–4b rearranged exclusively into β′-hydroxy α-enones 1d–4d if pyridine was added (α,α′-dienones 1e–4e are also formed competitively in absence of pyridine). At 3°C the photosensitised oxygenation of alkylidenecyclopropanes 1a–4a gives ketones 1k–4k, cyclobutanones 1i–4i and β′-hydroxy α-enones 1d–4d. The origin of products is discussed.     

Efficient synthesis of β-acetamido ketones using BF3/Et2O: a fertile approach toward avoiding usage of acetyl chloride

Abstract

A simple and efficient one pot synthesis of β-acetamido ketones from reaction of aldehydes, enolizable ketones, alkyl/aryl nitriles, and BF₃/Et₂O catalyst under microwave irradiations is described. This method allows synthesis of β-acetamido ketones without using corrosive and hazardous acetyl chloride. It is applicable for diversified aldehydes and active methylene ketones supported by synthesizing varieties of β-acetamido ketones. As per literature, majority of synthetic methods of β-acetamido ketones are restricted to use of acetonitrile lonely, as a nitrile component. This method is found to be equally effective for range of nitriles, also. Key features of reported method are simple reaction protocol, better yields, shorter reaction time, and nonhazardous reaction conditions which support the “Green Chemistry approach.”