Direct organocatalytic asymmetric α-oxidation of ketones with iodosobenzene and N-sulfonyloxaziridines

The novel, direct amino acid-catalyzed α-oxidation of ketones with iodosobenzene and N-sulfonyloxaziridines is presented. A screen of several synthetically common oxidants revealed that iodosobenzene and N-sulfonyloxaziridines act as electrophiles in the direct organocatalytic asymmetric α-hydroxylation of ketones. The direct proline-catalyzed asymmetric α-oxidation of ketones with iodosobenzene yielded the corresponding α-hydroxylated ketones with up to 77% ee. Furthermore, several amino acid derivatives catalyze the stereoselective α-oxidation of ketones with N-sulfonyloxaziridines. For example, the direct diamine-catalyzed enantioselective α-hydroxylation of ketones with N-sulfonyloxaziridines furnished the corresponding α-hydroxylated products in moderate yield with up to 63% ee.     

Metal-free base-promoted sulfenylation for the synthesis of α-arylthio-α,β-unsaturated ketones

A new sulfenylation reaction has been established, stereoselectively affording 37 examples of α-arylthio-α,β-unsaturated ketones with generally good yields via a metal-free three-component reaction of α-thiocyanate ketones with diaryliodonium salts and 1,2-dicarbonyls. The reaction enabled multiple bond-forming events including C(sp²)–S formation to provide a high-efficient and practical method toward α-arylthio-α,β-unsaturated ketones. The reasonable mechanism for forming α-arylthio-α,β-unsaturated ketones was proposed.     

Bismuth trichloride-catalyzed oxy-Michael addition of water and alcohol to α,β-unsaturated ketones

An efficient method was developed for the conjugate addition of water to various α,β-unsaturated ketones by using bismuth(III) chloride as a catalyst. The reactions proceeded smoothly in the presence of a catalytic amount of BiCl₃ (20 mol%) in aqueous media to furnish a variety of synthetically useful β-hydroxyl ketones in moderate to good yields. Apart from water molecule, various alcohols could also be employed as nucleophiles to react with α,β-unsaturated ketones, leading to β-alkoxyl ketones in modest to high yields. In addition, the mild reaction conditions also entailed the conjugate addition reactions to proceed with the tolerance to a range of functional groups.     

Enantioselective one-pot synthesis of β-sulfonyl ketones and trisubstituted tetrahydrothiophenes via β-elimination/cycloaddition sequence

A mild and efficient enantioselective one-pot synthesis of β-sulfonyl ketones and trisubstituted tetrahydrothiophenes via introducing 1,4-dithiane-2,5-diol to the simple kinetic resolution of β-sulfonyl ketones has been described herein. The one-pot reaction sequence including kinetic resolution and cascade sulfa-Michael/Aldol reaction proceeded successively to afford corresponding sulfonyl ketones and tetrahydrothiophenes with high enantioselectivities (85%–98% ee and 84%–95% ee, respectively).     

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.     

A new finding in selective Baeyer-Villiger oxidation of α-fluorinated ketones; a new and practical route for the synthesis of α-fluorinated esters

α-Fluorinated esters were effectively prepared by the Baeyer-Villiger oxidation of α-fluorinated ketones with m-chloroperbenzoic acid (m-CPBA) under mild conditions. The yield of the esters was influenced by the choice of solvent, base, and substituent on the aryl group of the ketones. 4-Methoxyphenyl substituted fluoroketones were oxidized almost quantitatively with m-CPBA within 10 min to 12 h at room temperature using 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) as a cosolvent with CH₂Cl₂ (1:1, v/v) and aqueous buffer (KH₂PO₄-NaOH, pH 7.6) as an additive base. The oxidation reaction rates of α-fluorinated ketones were higher than those of the corresponding non-fluorinated ketones. The fluorine atom at α-position of fluoromethyl aryl ketones enhanced the reactivity in the Baeyer-Villiger oxidation.     

Highly enantioselective aldol reactions using a tropos dibenz[c,e]azepine organocatalyst

The four-step synthesis of a chiral primary tertiary diamine salt, possessing a tropos dibenz[c,e]azepine ring is described. It is shown that 3.5-5 mol % of this salt is capable of promoting highly enantioselective crossed-aldol reactions between cyclohexanone and a series of aromatic aldehydes. In all cases, the aldol reactions proceed with high diastereoselectivity for the anti-aldol product. The outcome of crossed-aldol reactions involving other cyclic ketones and acyclic ketones are also described. All examples involving cyclic ketones result in selectivity for the anti-aldol products, whereas acyclic ketones were found to favour the syn-aldol products. A discussion on the role of the chiral primary tertiary diamine salt in the catalysis of the aldol reactions is also presented.     

Direct catalytic diastereoselective Mannich reactions: the synthesis of protected α-hydroxy-β-aminoketones

The combination of Mg(ClO₄)₂, 2,2′-bipyridine and N-methylmorpholine generates an effective catalyst system for the direct addition of α-carbonate-substituted ketones to aryl N-Ts imines. Methyl-carbonate-substituted ketones deliver acyclic α-hydroxy-β-aminoketone derivates, while ketones substituted with α-iso-propenyl-carbonates furnish cyclic carbamate adducts. In both cases the anti-configured Mannich products dominate.     

Hetero-Diels-Alder reaction of photochemically generated α-hydroxy-o-quinodimethanes with trifluoromethyl ketones

Hetero-Diels-Alder reaction of α-hydroxy-o-quinodimethanes photochemically generated from o-tolualdehydes with trifluoromethyl ketones gave a mixture of hemiacetals and hydroxyaldehydes in fairly good yields. Their subsequent oxidation with PCC provided 1-isochromanones as formal oxidative [4+2] cycloaddition products. In contrast, similar reaction of aromatic ketones such as o-methylbenzophenone, 1-indanone, and α-tetralone gave exclusively the corresponding ketones having (trifluoromethyl)methylol groups at the o-position.     

Synthesis of sterically hindered ketones from aldehydes via O-silyl oximes

A mild and efficient method to synthesize sterically hindered ketones from aldehydes via O-silyl oximes was developed. Treatment of O-triphenylsilylated oximes with alkyl iodides in the presence of triethyl borane afforded the corresponding ketones.     

Synthesis of β-disubstituted β-amino isoxazolyl ketones by addition of ketimines with isoxazolyl methyl ketone enolates

A series of β-disubstituted N-sulfinyl β-amino isoxazolyl ketones has been prepared by addition of tert-butanesulfinyl ketimines with the n-BuLi-generated enolates of isoxazolyl methyl ketones.     

An efficient one-pot synthesis of β-enamino ketones from endo glucal via hypervalent iodine

β-Enamino ketones were successfully synthesized by reaction of endo glycals with primary or secondary amines in the presence of hypervalent iodine reagent in one pot. After the oxidation and protonation taking place on hypervalent iodine agent in acidic condition, endo glucals were effectively converted into the uncyclic β-alkoxyvinyl ketones. Further substitution of β-alkoxyvinyl ketones with primary or secondary amines provided the corresponding β-enamino ketone derivatives in 57-67% yields.     

Lentinus strigellus: a new versatile stereoselective biocatalyst for the bioreduction of prochiral ketones

Growing cells of the basiodiomycete Lentinus strigellus in potato-dextrose broth have been used for the first time as a biocatalyst in the stereoselective reduction of aromatic and aliphatic ketones. Most of the aromatic ketones were converted into the corresponding optically active alcohols in up to >99% enantiomeric excess under very mild reaction conditions. Among the aliphatic ketones tested, 2-octanone was enzymatically reduced by this microorganism to enantiopure (S)-2-octanol with almost complete conversion.     

A new useful entry of IBX: the synthesis and structure of α-(2-iodobenzoyloxy)ketones

α-Functionalized ketones can be conveniently prepared in one step by the reaction of ketones possessing α-methene with o-iodoxybenzoic acid (IBX) in the presence of potassium iodide. Methyl aryl ketones produced bi-substituted products, whereas the others gave mono-substituted ones.     

New reactions of alkynes with ketones in superbasic media

The present work reviews new reactions of alkynes with ketones in the superbasic media MOH—DMSO (M = Na, K, Cs) and KOBu^t—DMSO: the stereoselective nucleophilic addition of deprotonated ketones to the triple bond to form the E-isomers of β,γ-enones; vinylation of tertiary acetylenic alcohols that formed in situ from acetylene and ketones; the direct synthesis of vinyl ethers of tertiary acetylenic alcohols from acetylene and ketones; the stereoselective synthesis of dispirocyclic ketals containing the Z-ethylene fragment from arylalkynes and two molecules of a cyclic ketone; the stereoselective cascade synthesis of hexahydroazulenones from two arylalkyne molecules and 2-alkylcyclohexanones; the stereoselective cascade assembly of 7-methylidene-6,8-dioxabicyclo[3.2.1]octanes from two acetylene molecules and two ketone molecules; the stereoselective cascade synthesis of 7-methylidene-6,8-dioxabicyclo[3.2.1]octanes from acetylenes and 1,5-diketones; and the three-component cascade reaction of acetylene, ketones, and oximes to afford 4-methylidene-3-oxa-1-azabicyclo-[3.1.0]hexanes.     

The application of a structurally simple,recyclable, and large-scale l-prolinamide catalyst for asymmetric aldol reactions

A highly efficient, bifunctional prolinamide catalyst, which consists of chiral proline and trans-cyclohexanediamine moieties, was prepared and evaluated in the direct asymmetric aldol reactions of various ketones and aldehydes. The catalyst displayed impressive catalytic activity toward heterocyclic ketones containing oxygen, sulfur, or nitrogen, which have not been sufficiently explored. The substrate scope also covered cyclic and acyclic ketones. With heterocyclic ketones or cyclohexanone, the aldol reactions gave products in high yields and with respectable enantioselectivities (87–99% ee) and diastereoselectivities (up to >99:1 anti/syn). The catalyst could be recycled and reused up to seven times resulting in good yields and with good selectivities. This catalyst is also efficient in large-scale reactions with the enantioselectivities remaining at the same level as in the experimental scale reactions.     

Synthesis of threo- and erythro-configured trihydroxy open chain lipophilic ketones as possible anti-mycobacterial agents

A series of threo- and erythro-configured open-chain trihydroxy ketones was synthesized starting from l- and d-ascorbic acid respectively as the starting material, through the use of Grignard reactions for the requisite CC bond formations. The lipophilic ketones were screened against Mycobacteriumtuberculosis for anti-proliferative activity. The lipophilic ketones with tetradecyl alkyl side chains were found to be moderately active against cell proliferation.     

Application of directed metalation in synthesis. Part 8: Interesting example of chemoselectivity in the synthesis of thioaurones and hydroxy ketones and a novel anionic ortho-Fries rearrangement used as a tool in the synthesis of thienopyranones and thiafluorenones

Chemoselective synthesis of thioaurones or 3-hydroxy benzo[b]thiophen-2-aryl ketones, 1-hydroxy naphtho[2,1-b]thiophen-2-aryl ketones and chalcones from N,N-diethyl-ortho-methyl sulfanyl aryl amides were described. (Benzo[b]thiophen-2-yl) alkylates and (naphtho[2,1-b]thiophen-2-yl) alkylates undergo a novel anionic ortho-Fries rearrangement leading to (3-hydroxy benzo[b]thiophen-2-yl) and (1-hydroxy naphtho[2,1-b]thiophen-2-yl) alkyl ketones. The hydroxy ketones were used as intermediates in the synthesis of wide range of benzothienopyranones and thiafluorenones.     

Facile Access to Sterically Hindered Aryl Ketones via Carbonylative Cross-Coupling: Application to the Total Synthesis of Luteolin

A general and mild protocol for achieving the carbonylative cross-coupling of sterically hindered, ortho-disubstituted aryl ketones is reported. The commercially available PEPPSI-IPr catalyst is shown to efficiently promote the carbonylative cross-coupling of hindered ortho-disubstituted aryl iodides to give diaryl ketones; traditional phosphine catalysts are less effective. Carbonylative Suzuki-Miyaura cross-couplings provide a diverse array of biaryl ketones in good to excellent yields. The same catalyst is also shown to catalyze a carbonylative Negishi cross-coupling reaction, utilizing a variety of alkynyl-zinc reagents to give the corresponding alkynyl aryl ketones. Application of this new methodology to the synthesis of the natural product luteolin is reported.     

Carbenoid type base induced ring expansion of the adducts of cyclic ketones with bis(phenylthio)methyllithium

In another application of the principle that metallo derivatives of bis(phenylthio)acetals behave as carbenoids when present in the same molecule with another anionic group, the adducts of cyclic ketones with bis(phenylthio)methyllithium react with an alkyllithium to yield the ring expanded α-(phenylthio) ketones.