Showing papers on "Enone published in 2003"
241 citations
TL;DR: Upon exposure of mono-enone mono-allylic carbonates to tributylphosphine and 1 mol % Pd(Ph3P)4, efficient conversion to the corresponding cycloallylated products is achieved.
Abstract: Upon exposure of mono-enone mono-allylic carbonates to tributylphosphine and 1 mol % Pd(Ph3P)4, efficient conversion to the corresponding cycloallylated products is achieved. This transformation combines the nucleophilic features of the Morita−Baylis−Hillman reaction with the electrophilic features of the Trost−Tsuji reaction.
189 citations
188 citations
TL;DR: In this article, the effects of ligands and bases in the rhodium(I)-catalyzed 1,4-addition of arylboronic acids to α,β-unsaturated carbonyl compounds were reinvestigated to carry out the reaction under mild conditions.
Abstract: The effects of ligands and bases in the rhodium(I)-catalyzed 1,4-addition of arylboronic acids to α,β-unsaturated carbonyl compounds were reinvestigated to carry out the reaction under mild conditions. Rhodium(I) complexes possessing a 1,5-cyclooctadiene (cod) and a hydroxo ligand such as [RhOH(cod)]2 exhibited excellent catalyst activities compared to those of the corresponding rhodium−acac or −chloro complexes and their phosphine derivatives. The reaction was further accelerated in the presence of KOH, thus allowing the 1,4-addition even at 0 °C. A cationic rhodium(I)−(R)-binap complex, [Rh(R-binap)(nbd)]BF4, catalyzed the reaction at 25−50 °C in the presence of Et3N with high enantioselectivities of up to 99% ee for α,β-unsaturated ketones, 92% for aldehydes, 94% for esters, and 92% for amides.
181 citations
161 citations
TL;DR: It has been found that the chiral amines catalyze the formation of optically active substituted 5-keto aldehydes in good yields and enantioselectivities, using aldeHydes and, e.g., methyl vinyl ketone as starting compounds.
Abstract: Chiral amines such as (S)-2-[bis(3,5-dimethylphenyl)methyl]pyrrolidine and the C2-symmetric (2S,5S)-2,5-diphenylpyrrolidine can catalyze the direct enantioselective Michael addition of simple aldehydes to vinyl ketones. The conditions for this organocatalytic reaction have been optimized and it has been found that the chiral amines catalyze the formation of optically active substituted 5-keto aldehydes in good yields and enantioselectivities, using aldehydes and, e.g., methyl vinyl ketone as starting compounds. Taking into account that the chiral amine can activate the aldehyde and/or the enone, the mechanism for the reaction has been investigated. On the basis of intermediate synthesis, nonlinear effect, and theoretical investigations, the mechanism for the catalytic direct enantioselective Michael addition of aldehydes to vinyl ketones is discussed.
145 citations
144 citations
TL;DR: Temperature-dependent studies show that monodentate phosphoramidites form stable complexes with metals and can induce high enantioselectivities even at high temperatures in polar solvents.
Abstract: A very fast reaction and enantioselectivities >98% have been reached in the rhodium-catalyzed arylboronic acid addition to enones using a monodentate phosphoramidite ligand. Temperature-dependent studies show that monodentate phosphoramidites form stable complexes with metals and can induce high enantioselectivities even at high temperatures in polar solvents.
111 citations
TL;DR: In this paper, a GaCl3-catalyzed reaction of α,β-unsaturated ketones with isocyanides leading to the formation of unsaturated lactone derivatives is described.
Abstract: A GaCl3-catalyzed reaction of α,β-unsaturated ketones with isocyanides leading to the formation of unsaturated lactone derivatives is described. This is the first example of the catalytic [4+1] cycloaddition of α,β-unsaturated ketones and isocyanides. GaCl3 is an excellent catalyst due to its lower oxophilicity, which is desirable for all of the key steps, such as E/Z isomerization, cyclization, and deattachment from the products.
105 citations
TL;DR: In this paper, the K2CO3 (10 mol %)-catalyzed 1,4-addition reaction of diethyl malonate with various substituted 1,2-allenic ketones leading to polyfunctionalized β,γ-unsaturated enones 3 or 4 was studied.
Abstract: The K2CO3 (10 mol %)-catalyzed 1,4-addition reaction of diethyl malonate with various substituted 1,2-allenic ketones leading to polyfunctionalized β,γ-unsaturated enones 3 or 4 was studied. With 3-unsubstituted 1-substituted-1,2-allenyl ketones, the highly selective formation of β,γ-unsaturated enones 4 was observed; with 1,2-allenyl ketones bearing one or two 3-substituents in the allenyl group, only β,γ-unsaturated enones 3 with an unmigrated carbon−carbon double bond were produced; with 3-monosubstituted-1,2-allenyl ketones Z-β,γ-unsaturated enones 3 were formed with excellent stereoselectivity (E:Z > 96:4); with propadienyl ketones, mixtures of β,γ-unsaturated enones 3 and 4 were formed. α-Pyrone derivatives were synthesized via the K2CO3-catalyzed or -promoted reaction of 1,2-allenic ketones with diethyl malonate via a sequential Michael addition−carbon-carbon double bond migration−lactonization process.
85 citations
TL;DR: This contribution describes a synthetic approach to alkaloid GB 13, previously isolated from the North Australian and Papua New Guinean rain forest tree Galbulimima belgraveana, which was discovered that a Birch reduction of the aromatic ring also present in the molecule could be performed at the same time to give the enone 15.
Abstract: This contribution describes a synthetic approach to alkaloid GB 13, previously isolated from the North Australian and Papua New Guinean rain forest tree Galbulimima belgraveana. A Birch reductive alkylation of 2,5-dimethoxybenzoic acid by 3-methoxybenzyl bromide, followed by an acid-catalyzed cyclization was used to synthesize the [3.3.1]bicyclononane 8. A ring contraction performed on the diazo derivative 9 of the [3.3.1]bicyclononane led to [3.2.1]bicyclooctane 10. This [3.2.1]bicyclooctane was converted into a dienophile and subjected to a Diels−Alder reaction to generate a pentacyclic intermediate 13 with a carbon skeleton closely resembling the target alkaloid. The surplus substituent, required for activation and regioselectivity in the Diels−Alder reaction, was removed using Birch reductive conditions to effect a decyanation. It was discovered that a Birch reduction of the aromatic ring also present in the molecule could be performed at the same time to give the enone 15, which was cleaved by means ...
TL;DR: An efficient stereoselective synthesis of two 3,5-dialkyl-substituted indolizidine alkaloids is reported, presenting one of a few examples of a highly selective CM reaction in the synthesis of a natural product.
Abstract: An efficient stereoselective synthesis of two 3,5-dialkyl-substituted indolizidine alkaloids is reported. The convergent syntheses are based on a novel sequence of a cross-metathesis (CM) reaction of an α,β-unsaturated ketone and a chiral homoallylic amine followed by a domino reaction involving hydrogenation, N-deprotection, and two diastereoselective reductive aminations. Our concept presents one of a few examples of a highly selective CM reaction in the synthesis of a natural product.
TL;DR: In this paper, high-intensity ultrasound (HIU) was used to investigate the aldol reaction in water and a library of polyols was obtained starting from a series of acetophenones and excess formaldehyde.
TL;DR: Asymmetric 1,4-addition of 9-phenyl-9-borabicyclo[3.3.1]nonane (2m) to 2-cyclohexenone (1a) proceeded with high enantioselectivity in toluene at 80 °C in the presence of 3 mol % of a rhodium catalyst generated from [Rh(OMe)(cod)]2 and (S)-binap, which was 98% enantiomerically pure as discussed by the authors.
Abstract: Asymmetric 1,4-addition of 9-phenyl-9-borabicyclo[3.3.1]nonane (2m) to 2-cyclohexenone (1a) proceeded with high enantioselectivity in toluene at 80 °C in the presence of 3 mol % of a rhodium catalyst generated from [Rh(OMe)(cod)]2 and (S)-binap to give a high yield of boron enolate (S)-3am, which is 98% enantiomerically pure. Reaction of the boron enolate 3am with electrophiles, methanol-d, propanal, and allyl bromide, gave the corresponding 2-substituted (3S)-3-phenylcyclohexanones with perfect regio- and diastereoselectivity.
TL;DR: In this paper, a catalytic asymmetric epoxidation of an enone was effectively promoted by the novel multifunctional asymmetric catalyst generated from La(O- i -Pr) 3, BINOL, and Ph 3 AsO in a 1:1:1 ratio to afford epoxide in 94% yield and 96% ee, which was recrystallized to give optically pure epoxide.
TL;DR: The titanium tetrachloride mediated reaction of alpha-keto esters with 5,5-dimethylcyclohex-2-enone provides the corresponding Baylis-Hillman adducts exclusively, thus clearly demonstrating the role of the steric factors in directing the reaction pathway.
Abstract: The titanium tetrachloride mediated reaction of α-keto esters with 5,5-dimethylcyclohex-2-enone provides the corresponding Baylis−Hillman adducts exclusively whereas a similar reaction of α-keto esters with cyclohex-2-enone furnishes the corresponding aldol adducts (with high syn-diasteroeselectivity) as the major product (along with the Baylis−Hillman adducts as the minor product), thus clearly demonstrating the role of the steric factors in directing the reaction pathway.
TL;DR: The highly functionalized tricyclic framework resident in jatrophatrione and citlalitrione has been synthesized and undergoes remarkably efficient, fully regiocontrolled Treibs reaction to generate 54.
Abstract: The highly functionalized [5.9.5] tricyclic framework resident in jatrophatrione (1) and citlalitrione (2) has been synthesized. The route begins with the tandem anionic oxy-Cope rearrangement/methylation/transannular ene cyclization of 21 and subsequent introduction of a conjugated enone double bond. Hydroxyl-directed 1,4-reduction of this functionality in 25 with LiAlH4/CuI/hexamethylphosphoramide/tetrahydrofuran sets the stage for the implementation of a Grob fragmentation and expedited generation of 27. Stereocontrolled intramolecular hydrosilylation allows for the subsequent introduction of a cyclic carbonate as in 53. This intermediate undergoes remarkably efficient, fully regiocontrolled Treibs reaction to generate 54, with this maneuver serving as a pivotal step for making 1 available five steps later. Treatment of 1 with m-chloroperbenzoic acid leads to 2, with attack occurring preferentially on a α-face of the double bond more remote to the carbonyl.
TL;DR: Molecular docking studies indicate that in hGSTP1-1, the hydroxyl group of Tyr108 might serve as a general acid catalyst during substrate turnover and the possible significance of these observations with respect to the metabolism of COMC derivatives in multidrug resistant tumors is discussed.
Abstract: Human glutathione (GSH) transferase (hGSTP1-1) processes with similar kinetic efficiencies the antitumor agents 2-crotonyloxymethyl-2-cyclohexenone (COMC-6), 2-crotonyloxymethyl-2-cycloheptenone (COMC-7), and 2-crotonyloxymethyl-2-cyclopentenone (COMC-5) to 2-glutathionylmethyl-2-cyclohexenone, 2-glutathionylmethyl-3-glutathionyl-2-cycloheptenone, and 2-glutathionylmethyl-2-cyclopentenone, respectively. This process likely involves initial enzyme-catalyzed Michael addition of GSH to the COMC derivative to give a glutathionylated enol(ate), which undergoes nonstereospecific ketonization, either while bound to the active site or free in solution, to a glutathionylated exocyclic enone. Free in solution, GSH reacts at the exomethylene carbon of the exocyclic enone, displacing the first GSH to give the final product. This mechanism is supported by the observation of multiphasic kinetics in the presence of high concentrations of hGSTP1-1 and the ability to trap kinetically competent exocyclic enones in aqueous ...
TL;DR: In this paper, the mass transfer model for the epoxidation of α,β-unsaturated carbonyl compounds in the 1-butyl-3-methylimidazolium hexafluorophosphate ([C 4 MIm][PF 6 ])/water biphasic system has been proposed.
Abstract: The epoxidation reactions of electron-deficient α,β-unsaturated carbonyl compounds were investigated in ionic liquid (IL)/water biphasic system using hydrogen peroxide as an oxidant at room temperature. By optimizing the reaction conditions, including reaction time, temperature, the amount of oxidant and sodium hydroxide, 100% conversion and 98% selectivity could be achieved in the epoxidation of mesityl oxide. The mass transfer model for the epoxidation of α,β-unsaturated carbonyl compounds in the 1-butyl-3-methylimidazolium hexafluorophosphate ([C 4 MIm][PF 6 ])/water biphasic system has been proposed.
TL;DR: The procedure was successful with ketene silyl acetals giving in a single step a good yield of alpha-(4-aminophenyl)propionic(acetic) esters, known intermediates for the preparation of analgesic compounds.
Abstract: 4-Aminophenyl cations (expediently generated by photolysis of 4-chloroaniline and its N,N-dimethyl derivative by photolysis in MeCN) added to enamines and gave the corresponding α-(4-aminophenyl) ketones in satisfactory yields. The yields of the same ketones were increased when silyl enol ethers were used in the place of enamines. The α-arylation of silyl enol ethers of aldehydes occurred with lower yields and only with the N,N-dimethyl derivative. The procedure was successful with ketene silyl acetals giving in a single step a good yield of α-(4-aminophenyl)propionic(acetic) esters, known intermediates for the preparation of analgesic compounds. The reaction of the aryl cation with Danishefsky's diene gave the arylated β-methoxy enone. The method is complementary to the recently developed palladium-catalyzed α-arylation and occurs under neutral conditions.
TL;DR: An asymmetric synthesis of fused bicyclic amino acids having a hexahydro-cyclopenta[c]pyridine skeleton and carrying besides an enone structural element a substituent at the beta-position and a propargyl group at the N-atom is described.
Abstract: An asymmetric synthesis of fused bicyclic amino acids having a hexahydro-cyclopenta[c]pyridine skeleton and carrying besides an enone structural element a substituent at the β-position is described. The key steps of the synthesis are a highly selective allylation of N-tert-butylsulfonyl imino ester with bis(allylsulfoximine)titanium complexes and a highly diastereoselective Pauson−Khand cycloaddition of sulfonimidoyl-substituted γ,δ-unsaturated α-amino acid esters carrying a substituent at the β-position and a propargyl group at the N-atom. The cyclization is accompanied by a reductive cleavage of the sulfoximine group of the primary cyclization product. Surprisingly, the removal of the sulfoximine group proceeds with inversion of the configuration at the S-atom and gives N-methyl-phenylsulfinamide with ≥98% ee. Deprotection of the bicyclic N-tert-butylsulfonyl-protected amino acid ester was accomplished through treatment with CF3SO3H under anhydrous conditions. The enantio- and diastereomerically pure su...
TL;DR: A (-)-quinic acid-derived enone, with the trans-1,2-diol protected as a 2,3-dimethoxybutanediyldioxy ketal, provides an excellent template for further highly stereoselective elaboration as exemplified by its conversion into the core of scyphostatin, a potent inhibitor of neutral sphingomyelinase.
TL;DR: In this paper, a novel enantioenriched Ca complex was generated using low cost commercially available CaCl 2 and the potassium salt of (S )-6,6′-diphenylBINOL and its application to α,β-unsaturated enone epoxidation is described.
Abstract: A novel enantioenriched-Ca complex was generated using low cost commercially available CaCl 2 and the potassium salt of ( S )-6,6′-diphenylBINOL and its application to α,β-unsaturated enone epoxidation is described Furthermore the absolute stereochemistry of ( S )-6,6′-diphenylBINOL has been corrected and unequivocally established by single crystal X-ray analysis, 500 MHz NMR spectroscopy and mass spectra The enantiomeric excess (ee) was determined by 1 H NMR spectroscopy of its corresponding MTPA ester and was found to be >98%
TL;DR: The aza-Baylis-Hillman reaction of N-sulfonated imine with phenyl vinyl ketone gave the double aza, Baylis, Hillman adduct in good yields with excellent stereoselectivities in the presence of Lewis base 1,4-diazabicyclo[2.2]octane.
Abstract: The aza-Baylis-Hillman reaction of N-sulfonated imine with phenyl vinyl ketone gave the double aza--Baylis-Hillman adduct in good yields with excellent stereoselectivities in the presence of lewis base 1,4-diazabicyclo[222]octane
TL;DR: A working model for asymmetric induction is proposed based on correlation between catalyst structures and enantioselectivities and the use of 2,6-diisopropylphenol and tert-butyl methyl ether as additives is found to be essential to achieve high enantiOSElectivity in these reactions.
Abstract: allo-Threonine-derived O-aroyl-B-phenyl-N-tosyl-1,3,2-oxazaborolidin-5-ones 1g,n catalyze the asymmetric Mukaiyama−Michael reaction of acyclic enones with a trimethylsilyl ketene S,O-acetal in high enantioselectivity. A range of alkenyl methyl ketones is successfully employed as Michael acceptors affording ee values of 85−90% by using 10 mol % of the catalyst. The use of 2,6-diisopropylphenol and tert-butyl methyl ether as additives is found to be essential to achieve high enantioselectivity in these reactions. The effects of the additives are discussed in terms of the retardation of an Si+-catalyzed racemic pathway, which seriously deteriorates the enantioselectivity of asymmetric Mukaiyama−Michael reactions. A working model for asymmetric induction is proposed based on correlation between catalyst structures and enantioselectivities.
TL;DR: In this paper, the Meerwein-Ponndorf-Verley (MPV) reduction of unsaturated ketones with alcohols as reductants was investigated.
Abstract: Zr and Hf catalysts were immobilized in mesoporous materials such as MCM-41 or MCM-48; in comparison with the homogeneous catalysts, the resulting materials display strongly increased activity in the Meerwein–Ponndorf–Verley (MPV) reduction of ketones with alcohols as reductants. In the reduction of unsaturated ketones, a very high selectivity for the allylic alcohol is obtained. For efficient reduction, an excess of the reducing alcohol with respect to the enone is required. For the model reduction of benzalacetone with cyclopentanol, the adsorption of reagents and products on the catalytic material is studied. Even complex substrates such as prostaglandin enone precursors can be reduced; in certain cases a substantial diastereomeric excess is observed.
TL;DR: In this paper, the authors show that α-hydroxy enones react with dienes in the presence of (S,S)-[Cu(tBu-box)](OTf)2 or (S S −[Cu (tBu)-box](SbF6)2 (2 to 10 mol %) to afford the corresponding Diels−Alder adducts in high yield and selectivity.
Abstract: α‘-Hydroxy enones react with dienes in the presence of (S,S)-[Cu(tBu-box)](OTf)2 or (S,S)-[Cu(tBu-box)](SbF6)2 (2 to 10 mol %) to afford the corresponding Diels−Alder adducts in high yield and selectivity. Isomeric ratios (regioselectivity, endo/exo or cis/trans) of up to >99:1 and ee values of up to >99% are obtained. Significantly, difficult dienes such as isoprene, 2,3-dimethyl butadiene and piperylene behave satisfactorily. Subsequent oxidative cleavage of the ketol in the resulting cycloadducts by treatment with cerium ammonium nitrate (CAN) yields the corresponding enantiopure carboxylic acids. Alternatively, carbonyl addition and subsequent diol cleavage with CAN produces the corresponding ketone adducts.
TL;DR: Results are reported that deal with the synthesis of two new bicyclic Nazarov reagents and their cycloaddition with two cyclohexenones (1 and 4) and constitute an important improvement concerning the versatility of the strategy.
Abstract: We published recently our results on a new and convergent synthesis of natural steroids. The strategy was based on a cycloaddition reaction of Nazarov reagents 2 and 5 with cyclohexenones 1 and 4. In this paper we report results that deal with the synthesis of two new bicyclic Nazarov reagents (13 and 19) and their cycloaddition with two cyclohexenones (1 and 4). These new results constitute an important improvement concerning the versatility of the strategy since tetracycles having the stereochemistry found in natural steroids are now available.
TL;DR: R-5-Methylcyclohex-2-enone 1 reacts successively with the phenyldimethylsilylzincate reagent and acetaldehyde to give with regiocontrol the aldols 7, dehydration of which creates the E-exocyclic double bond of the alpha,beta-unsaturated ketone 2.
Abstract: R-5-Methylcyclohex-2-enone 1 reacts successively with the phenyldimethylsilylzincate reagent and acetaldehyde to give with regiocontrol the aldols 7, dehydration of which creates the E-exocyclic double bond of the α,β-unsaturated ketone 2. Conjugate addition of the ethylcuprate reagent to this compound takes place with high (96 ∶ 4) selectivity in favour of the R stereoisomer 12, hydrolysis of which gives (2R,3R,5S,2′R)-2-(but-2′-yl)-3-dimethyl(phenyl)silyl-5-methylcyclohexanone 3. The oxime acetate of this ketone undergoes fragmentation in the presence of trimethylsilyl trifluoromethanesulfonate to give 3R,7R,5E-3,7-dimethylnon-5-enonitrile 4, in which an open-chain 1,5-stereochemical relationship is set up with a high level of stereocontrol. A similar sequence adding 4-methylpentylcuprate to the enone 2, and fragmentation gives 3R,7R,5E-3,7,11-trimethyldodec-5-enonitrile 20. Reduction and hydrogenation of this nitrile gives 3R,7R-3,7,11-trimethyldodecanal 22, which can be converted into phytol 25. The ketoaldehyde 29 reacts with samarium iodide to give only the alcohol 30, in which the radical anion has attacked from the top surface, just like the cuprate reagents in their reactions with the ketone 2.
TL;DR: In this article, a key feature of the last part of the synthesis is the use of t -BuMe 2 Si-groups (as in intermediate 24 ) both to direct hydrogenation from the appropriate face and to protect the benzylic CO bond from hydrogenolysis.