Unsymmetrical Ketones Research Articles

Syntheses and regiochemistry of enol addition to 9-phenyl-9 H-xanthen-9-ol

Regioselective C–C bond formation of 9-phenyl-9 H-xanthen-9-ol 1 with various enolizable ketones I– X in an acidic (HBr) medium, obtained by the reaction of 1,1′-(ethane-1,2-diyl)dipyridinium bistribromide (EDPBT) with ketone is observed. Except for ketone, 4-methyl-pentan-2-one VII in all other cases examined the attack to xanthenyl carbocation is from the thermodynamically stable enolizable side of the unsymmetrical ketones. In the case of 3-methyl-butan-2-one VIII the equilibrium is in favor of the more stable enolizable ketone, which has large steric factor, hence no reaction was observed during its addition to alcohol 1.

Tetranuclear BINOL−Titanium Complex in Selective Direct Aldol Additions

The extremely robust and water-stable tetranuclear complex Ti(4)(micro-BINOLato)(6)(micro(3)-OH)(4) (1) catalyzes the direct aldol addition with high degrees of regioselectivity at the sterically more encumbered alpha-side of unsymmetrical ketones. The formation of quaternary stereocenters is described. Oxygen-containing ene components can also be used as starting material in these reactions. When used with aliphatic aldehydes, acetals 18 or acetals of aldol adducts 20 were observed. As few as 0.2 mol % loadings with this catalyst 1 were enough to complete the reactions. Mechanistical aspects of the reactions are discussed.

Intermolecular Asymmetric Reductive Aldol Reaction

This is a valuable report on the reductive aldol reaction of conjugated esters with ketones. Tertiary alcohols are generated in this reaction with up to 98% ee when acetone is used as the ketone. The rhodium (Phebox) complex is the catalyst used to obtain high selectivities. A variety of reductants were screened with MePh2SiH giving the best results. Various esters can be used and reasonable diastereoselectivities accompany the high ee values when unsymmetrical ketones are used.

Highly efficient N‐Heterocyclic carbene–palladium complex‐catalyzed multicomponent carbonylative Suzuki reaction: novel practical synthesis of unsymmetric aryl ketones

AbstractHighly efficient and chemoselective N‐heterocyclic carbene palladium complexes‐catalyzed multicomponent carbonyltive Suzuki reaction with sodium tetraphenylborate used as phenylating reagent has been demonstrated in this article. Both electron‐rich and electron‐deficient aryl iodides gave unsymmetric aryl ketones in excellent yields. Copyright © 2007 John Wiley & Sons, Ltd.

Regioselective α-alkylation of ketones with alkyl chlorides and fluorides via highly nucleophilic magnesium enamides

A magnesium enamide derived from N-2-( N′, N′-dimethylamino)ethyl imine reacts with primary and secondary alkyl chlorides and fluorides to give an α-alkylated ketone in good to excellent yields upon hydrolysis of the imine moiety. Reactions of the highly nucleophilic magnesium enamide derived from an unsymmetrical ketone take place regioselectively. In addition, the C–C bond formation is stereospecific: a substantial inversion of stereochemistry at the electrophilic carbon center (Walden inversion) was observed, proving its potential utility for the production of optically active compounds.

The first example of regiospecific magnesium carbenoid 1,3-CH insertion: its mechanism and stereochemistry

Addition reaction of two geometrical isomers of 1-chlorovinyl p-tolyl sulfoxides, derived from unsymmetrical ketones and chloromethyl p-tolyl sulfoxide, with lithium enolate of tert-butyl acetate gave single isomers of the adduct, respectively. Treatment of each diastereomer with i-PrMgCl resulted in the formation of magnesium carbenoids. Highly regiospecific 1,3-CH insertion reaction was found to take place from the magnesium carbenoids to afford cyclopropanes in high yields. Stereochemistry of the adducts, reaction mechanism, and origin of the regiospecificity are discussed.

Fischer Indole Synthesis in Brønsted Acidic Ionic Liquids: A Green, Mild, and Regiospecific Reaction System

AbstractA novel one‐pot Fischer indole synthesis approach has been developed by using Brønsted acidic ionic liquids as dual solvent‐catalysts. Yields of 83–97 % were obtained after reaction in BMImHSO4 at 70–110 °C in 0.5–6 h, and exclusive formation of 2,3‐disubstituted indoles was observed in the reaction of alkyl methyl unsymmetrical ketones. The indoles produced could be conveniently separated from the reaction mixture without any volatile organic solvents, and the BMImHSO4 could be readily reused without efficiency loss after simple treatment involving only 1 equiv. of HCl for neutralization followed by filtration.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Multinuclear enantiopure titanium self‐assembly complexes—synthesis, characterization and application to organic synthesis

AbstractHexa‐ and nonanuclear titanium complexes were obtained by self‐assembly of titanium(IV)‐tert‐butoxide and D‐mandelic acid. Suitable single crystals of these complexes were characterized by X‐ray structure analysis. When used with these complexes, aldol adducts were isolated with a high degree of regioselectivity in direct aldol additions of aromatic and aliphatic aldehydes to functionalized unsymmetrical ketones. High syn‐diastereoselectivities were obtained in aldol additions of enolizable aldehydes with hydroxyacetone and methoxyacetone. Copyright © 2007 John Wiley & Sons, Ltd.

Carbon-carbon bond formation via palladium catalyzed reactions of organomercurials with acylhalides

The palladium catalyzed acyldemetallation reactions of methyl mercury iodide provide a mild, selective and general method for the construction of new C-C bond i.e. for the synthesis of unsymmetrical ketone. The reaction proceeds in acetone, in the presence of a nucleophilic catalyst (iodide ion), at room temperature. The catalytic cycle involved in the reaction consists of a sequence of oxidative addition, transmetallation and reductive elimination steps. The role played by the iodide ion as a nucleophilic catalyst is discussed.

Microwave-promoted cross-coupling of acid chlorides with arylboronic acids: a convenient method for preparing aromatic ketones

Simple catalytic systems for cross-coupling reactions of acyl chlorides with arylboronic acids under microwave conditions were tested. Microwave irradiation facilitated the reaction course. Mild reaction conditions afford the symmetrical and unsymmetrical aryl ketones in reasonable to high yields within a short time. A wide range of substrates bearing an electron-donating or an electron-withdrawing substituent on aryl ring of acid chloride as well as on boronic acid were examined and high yields of ketones were produced.

Triethylgallium as a Nonnucleophilic Base to Generate Enolates from Ketones

Triethylgallium deprotonated cyclic and acyclic ketones at 125-175 degrees C without forming carbonyl addition products, and the resulting gallium enolates underwent facile C-benzoylation and an aldol reaction. Unsymmetrical ketones were preferentially enolized at the methylene moiety, which was under kinetic control. [reaction: see text]

Direct and Efficient One-Pot Preparation of Ketones from Aldehydes Using N-tert-Butylphenylsulfinimidoyl Chloride

A general, one-pot process has been established to prepare ketones from aldehydes using N-tert-butylphenylsulfinimidoyl chloride. By employing the developed protocol, a range of unsymmetrical ketones has been prepared in good yields from aldehydes in one simple synthetic operation. [reaction: see text]

Palladium‐Catalyzed Suzuki Cross‐Coupling of 2‐Haloselenophenes: Synthesis of 2‐Arylselenophenes, 2,5‐Diarylselenophenes, and 2‐Arylselenophenyl Ketones.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Carbonylation of Organic Halides with Carbon Monoxide Mediated by Samarium Diiodide. Improvement and Mechanistic Investigations

Abstract Under an atmospheric pressure of carbon monoxide, photoinduced reductive carbonylation of organic halides (RX) with samarium diiodide (SmI2) occurs to afford the corresponding unsymmetrical ketones (RC(O)CH2R) in good yields. Mechanistic insight into this carbonylation, especially the pathway for the generation of an acylsamarium species (RC(O)SmI2) as a key intermediate, is also investigated in detail.

Catalytic Enantioselective Addition of Silyl Ketene Acetals to Ketones

Using a CuF/TaniaPhos/PhBF3K catalyst system with added (EtO)3SiF, a variety of unsymmetrical ketones and silyl ketene acetals were transformed to the corresponding chiral 3° alcohol with high levels of enantio- and diastereo­selectivity. For β-substituted silyl ketene acetals, the diastereomeric ratio is independent of the E/Z ratio of the starting material; thus this is the first example of catalytic and enantioselective addition of silyl ketene acetals to ketones.

A versatile synthesis, including asymmetric synthesis, of bicyclo[ n.1.0]alkanes from cyclic ketones via the magnesium carbenoid 1,3-CH insertion as a key reaction

Treatment of 1-chlorovinyl p-tolyl sulfoxides, which were synthesized from various cyclic ketones and chloromethyl p-tolyl sulfoxide in three steps, in high yields, with lithium enolate of tert-butyl acetate or its homologues gave the adducts in quantitative yields. The adducts were treated with isopropylmagnesium chloride in ether in dry toluene as the reaction solvent to afford bicyclo[ n.1.0]alkanes in high to quantitative yields via magnesium carbenoid 1,3-CH insertion. When this method was carried out starting from unsymmetrical cyclic ketones and ( R)-chloromethyl p-tolyl sulfoxide, an asymmetric synthesis of bicyclo[ n.1.0]alkane was realized.

A synthesis of optically active α-quaternary α-amino acids and esters by assembling three components, ketones, ( R)-chloromethyl p-tolyl sulfoxide, and sodium azide, via sulfinyloxiranes

Treatment of lithium α-sulfinyl carbanion of chloromethyl p-tolyl sulfoxides with ketones at low temperature afforded adducts in almost quantitative yields, which were exposed to t-BuOK to give sulfinyloxiranes in high yields. The sulfinyloxirane was reacted with benzylamine to give α-amino aldehyde, which was oxidized with iodine in methanol to afford α-amino carboxylic ester in moderate yield. The sulfinyloxiranes were treated with sodium azide to afford α-azido aldehydes in good yields. Oxidation with NaClO 2 followed by catalytic hydrogenation of the azido group of the α-azido aldehydes gave α-quaternary α-amino acids in good overall yields. The oxidation of the azido aldehydes with iodine in methanol in the presence of KOH followed by the catalytic hydrogenation resulted in α-quaternary α-amino acid methyl esters in good yields. When these reactions were carried out starting from unsymmetrical ketones and optically pure ( R)-chloromethyl p-tolyl sulfoxide, a new method for a synthesis of optically active α-quaternary α-amino acids and esters in good overall yields was realized.

Design of a Binaphthyl‐Based Axially Chiral Amino Acid as an Organocatalyst for Direct Asymmetric Aldol Reactions

A novel and robust binaphthyl-based amino acid was designed and successfully applied to the direct asymmetric aldol reaction. In some cases, this catalyst leads to higher yields and selectivities than the well-known proline catalyst. For instance, the direct asymmetric aldol reaction of acetone with 4-nitrobenzaldehyde in the presence of the binaphthyl-based amino acid catalyst proceeded smoothly to give the aldol adduct in 82% yield with 95% ee. This catalyst was also found to catalyze effectively the reactions of cyclic or unsymmetrical ketones to give the corresponding aldol adducts with excellent diastereo- and enantioselectivities.

Palladium-Catalyzed Suzuki Cross-Coupling of 2-Haloselenophenes: Synthesis of 2-Arylselenophenes, 2,5-Diarylselenophenes, and 2-Arylselenophenyl Ketones

We present herein our results on the Suzuki coupling reaction of 2-haloselenophenes with boronic acids catalyzed by palladium salt and describe a new route established to prepare 2-arylselenophenes and 2,5-diarylselenophenes in good yields. The reaction proceeded cleanly under mild conditions and was performed with aryl boronic acids bearing electron-withdrawing, electron-donating, and neutral substituents, in the presence of Pd(OAc)2, K2CO3/H2O in DME. In addition, by this protocol unsymmetrical aryl ketones were also obtained from 2-iodoselenophene and boronic acids via a carbonylative process.

Room‐Temperature Palladium‐Catalyzed and Copper(I)‐Mediated Coupling Reactions of Acid Chlorides with Boronic Acids under Neutral Conditions.

The palladium-catalyzed cross-coupling reactions of acid chlorides with arylboronic acids in the presence of copper(I) thiophene-2-carboxylate (CuTC) as an activator under strictly non-basic and mild reaction conditions afford the unsymmetrical ketones in moderate to excellent yields. A wide range of substrates bearing an electron-donating or an electron-withdrawing substituent on the aromatic ring is compatible.