Showing papers on "Methyl vinyl ketone published in 2006"

Asymmetric aza-Morita-Baylis-Hillman reaction of N-sulfonated imines with activated olefins catalyzed by chiral phosphine Lewis bases bearing multiple phenol groups phosphine; Lewis base; organocatalysts; phenol groups; N-sulfonated imines

Abstract: In the aza-Morita-Baylis-Hillman reaction of N-sulfonated imines (N-arylmethylidene-4-methylbenzenesulfonamides) with methyl vinyl ketone (MVK), ethyl vinyl ketone (EVK), and acrolein, we found that. through the use of catalytic amounts of chiral phosphine Lewis bases bearing multiple phenol groups, the corresponding adducts could be obtained in good yields with > 90% ee at -20 degrees C or at room temperature in THE The mechanism of this process was investigated by P-31 NMR spectroscopic analysis. The phenoxide or the key enolate intermediate, which is stabilized by intramolecular hydrogen bonding with phenol groups, was observed by P-31 NMR spectroscopy. Thus, the most effective bifunctional LBBA (Lewis base and Bronsted acid) phosphine-Lewis base promoter system reported to date has been identified for such catalytic, asymmetric aza-Morita-Baylis-Hillman reactions.

Enantioselective Palladium‐Catalyzed Total Synthesis of Vitamin E by Employing a Domino Wacker–Heck Reaction

Abstract: An enantioselective total synthesis of vitamin E in which a novel palladium-catalyzed domino reaction was employed as the key step is described. This reaction allows the formation of the chiral chroman framework and the concurrent introduction of part of the side chain of vitamin E. The sequence comprises an enantioselective Wacker cyclization and a subsequent Heck reaction. Accordingly, reaction of alkenylphenol 12 with methyl vinyl ketone (13) in the presence of catalytic amounts of Pd(OTFA)(2) (TFA = trifluoroacetate), the enantiopure ligand (S,S)-Bn-BOXAX (8 b; Bn = benzyl, BOXAX = 2,2'-bis(oxazolyl)-1,1'-binaphthyl, and p-benzoquinone (9) as an oxidant gives access to chiral chroman 10 with an enantioselectivity of 97 % ee in 84 % yield. Chroman 10 is then converted into 24 by an aldol condensation reaction with (3R)-3,7-dimethyloctanal (11). Subsequent 1,2-addition of methyllithium, elimination of water, and hydrogenation yields vitamin E.

Asymmetric Induction in Hydrogen-Mediated Reductive Aldol Additions to α-Amino Aldehydes Catalyzed by Rhodium: Selective Formation of syn-Stereotriads Directed by Intramolecular Hydrogen-Bonding

Abstract: Rhodium-catalyzed hydrogenation of methyl vinyl ketone and ethyl vinyl ketone in the presence of N-Boc-alpha-aminoaldehydes 3a-8a at ambient temperature and pressure results in reductive C-C coupling to furnish aldol adducts 3b-8b and 3c-8c, respectively, which incorporate stereotriads that embody high levels of syn-aldol selectivity accompanied by high levels of anti-Felkin-Anh control. The collective data are consistent with a catalytic mechanism involving addition of the Z(O)-rhodium enolate to the sterically less-encumbered aldehyde pi-face of an intramolecularly hydrogen-bonded chelate through a Zimmerman-Traxler type transition structure. Stereochemical assignments are supported by single-crystal X-ray diffraction analysis of 5b-O-3,5-dinitrobenzoate, iso-5b, N-Me-iso-5b-O-3,5-dinitrobenzoate, and 7b. As revealed by HPLC analysis, optical purity of the stereochemically labile alpha-aminoaldehydes is completely preserved under the conditions of hydrogen-mediated aldol coupling. Deletion of the intramolecular hydrogen bond, as in the case of N-methyl-N-Boc-l-leucinal N-Me-5a, inverts stereoselectivity to furnish the Felkin-Anh product N-Me-iso-5b in 17% yield. Additionally, reactions performed in the presence of tert-amyl alcohol (10 equiv) exhibit markedly lower levels of anti-Felkin-Anh control (7:1 versus > or = 20:1). The collective studies suggest that intramolecular hydrogen bonding plays a key role in both activating the alpha-aminoaldehyde toward addition and directing facial selectivity.

Structure reassignment and synthesis of Jenamidines A1/A2, synthesis of (+)-NP25302, and formal synthesis of SB-311009 analogues.

Abstract: The proposed structures of jenamidines A, B, and C (1−3) were revised to jenamidines A1/A2, B1/B2, and C (8−10). Jenamidines A1/A2 (8) were synthesized from activated proline derivative 43 by conversion to 26 in two steps and 50% overall yield. Acylation of 26 with acid chloride 38d gave 39d, which was deprotected with TFA and then mild base to give 8 in 45% yield from 26. (−)-trans-2,5-Dimethylproline ethyl ester (49) was prepared by the enantioselective Michael reaction of ethyl 2-nitropropionate (51) and methyl vinyl ketone (50) using modified dihydroquinine 60 as the catalyst. Further elaboration converted 49 to natural (+)-NP25302 (12). A Wittig reaction of proline NCA (76) with ylide 79 gave 72 as a 9/1 E/Z mixture in 27% yield, completing a one-step formal synthesis of SB-311009 analogues.

Cobalt-catalyzed reductive coupling of saturated alkyl halides with activated alkenes.

Abstract: An efficient cobalt-catalyzed reductive coupling reaction of alkyl halides with electron-withdrawing alkenes (CH2CR1EWG, EWG = electron-withdrawing group) in the presence of water and zinc powder in acetonitrile to give the corresponding Michael-type addition product (RCH2CR1EWG) was described. The methodology is versatile such that unactivated primary, secondary, and tertiary alkyl bromides and iodides and various conjugated alkenes including acrylates, acrylonitrile, methyl vinyl ketone, and vinyl sulfone all successfully participate in this coupling reaction. For the alkyl halides used in the reaction, the iodides generally gave better yields compared to those of the corresponding bromides. It is a unique method employing CoI2dppe, zinc, and alkyl halides, affording conjugate addition products in high yields. Mechanistically, the reaction appears to follow an oxidative addition driven route rather than the previously reported radical route.

Michael reactions carried out using a bench-top flow system.

Abstract: The Michael reaction between methyl 1-oxoindan-2-carboxylate and methyl vinyl ketone was achieved successfully by pumping solutions of the reactants in toluene through a fluid bed of Amberlyst A21 at 50 °C. The use of a fluid bed reactor is attractive as it allows gel-type beads, i.e. the type of bead used in most studies of polymer-supported (PS) organic reactions, to be used satisfactorily in a flow system. When polymer-supported cinchonidine was used in place of Amberlyst A21, the Michael product was obtained in high yield with an enantiomeric excess (ee) of 51%. This % ee is comparable to that achieved when the reaction was catalysed by cinchonidine itself.

Creation of monomeric La complexes on apatite surfaces and their application as heterogeneous catalysts for Michael reactions

Abstract: Using a cation-exchange method, an equimolar substitution of La3+ for Ca2+ occurred by the treatment of stoichiometric hydroxyapatite (HAP: Ca10(PO4)6(OH)2) with an aqueous solution of La(OTf)3, affording a monomeric hydroxyapatite-bound La complex (LaHAP). Physicochemical characterization by means of XRD, XPS, IR, and La K-edge XAFS analyses proved that a monomeric La3+ phosphate complex was generated on its surface. Such monomeric La3+ species function as an efficient heterogeneous catalyst for the Michael reaction of 1,3-dicarbonyls with enones under aqueous or solvent-free conditions. The work-up procedure is straightforward and the spent catalyst could be recycled without any loss of the catalytic activity. Further application to an asymmetric version was also investigated using various apatite catalysts modified with chiral organic ligands. Enantioselectivity was found to depend on the chiral ligand, solvent, and rare earth metal triflate precursor (RE(OTf)3) for the reaction of methyl 1-oxoindan-2-carboxylate with methyl vinyl ketone. Under optimized reaction conditions, a monomeric fluoroapatite-bound La complex catalyst modified with (R,R)-tartaric acid (TA-LaFAP) provided the Michael adduct quantitatively in up to 60% ee.

Traditional Morita–Baylis–Hillman reaction of aldehydes with methyl vinyl ketone co-catalyzed by triphenylphosphine and nitrophenol

Abstract: In the Morita–Baylis–Hillman reaction of aldehydes with methyl vinyl ketone (MVK), we found that in the presence of a catalytic amount of phenol, the Lewis base triphenylphosphine can effectively promote the reaction to give the corresponding normal Morita–Baylis–Hillman adducts in good yields. The mechanism has been investigated by 31P NMR spectroscopy. The solvent and substituent effects were also examined.

The uptake of methyl vinyl ketone, methacrolein, and 2-methyl-3-butene-2-ol onto sulfuric acid solutions.

Abstract: To investigate the link between molecular structure, reactivity, and partitioning of oxygenated organic compounds in acidic aerosols, the uptake of three compounds found in the atmosphere, methyl vinyl ketone (MVK), methacrolein (MACR), and 2-methyl-3-butene-2-ol (MBO), by sulfuric acid solutions has been measured using a rotated wetted-wall reactor (RWW) coupled to a chemical ionization mass spectrometer (CIMS). MVK was found to partition reversibly into 20−75 wt % H2SO4 solutions, and we report Henry's law coefficients between 20 and 7000 M atm-1 over this range. A chemical reaction for MVK was likely responsible for the uptake observed for 80−96 wt % H2SO4 solutions. We derive an upper limit to the aldol self-reaction rate coefficient for MVK in 80 wt % solution of ∼3 M-1 s-1. MACR partitioned reversibly over most of the acidity range, and in contrast to that for MVK, the Henry's law coefficient was relatively independent of H2SO4 content. These differences indicate that the increase of the coefficient...

The First Air‐Stable and Efficient Nucleophilic Trialkylphosphine Organocatalyst for the Baylis–Hillman Reaction

Abstract: 1,3,5,-Triaza-7-phosphaadamantane (PTA) is first reported to be a convenient and efficient nucleophilic trialkylphosphine organocatalyst for the Baylis–Hillman reaction. Thus, under the mediation of 15–20 mol % of PTA and practical conditions, both aromatic and aliphatic aldehydes react with the activated alkenes like acrylates and methyl vinyl ketone to afford the corresponding adducts in fair to excellent yields.

A new approach to promoting sluggish Diels-Alder reactions: dihapto-coordination of the diene.

Abstract: The cycloaddition between 1,3-cyclohexadiene and various enones and enals (methyl vinyl ketone, ethyl vinyl ketone, methacrolien) is accomplished at room temperature in yields ranging from 51 to 68% without the use of Lewis acids, high pressures, or microwave reactors. This normally sluggish cyclization is accomplished by precoordination of the diene to a π-basic molybdenum complex. The η2-bound metal is thought to promote a Michael reaction between the uncoordinated portion of the diene and the enone, and the resulting enolate then closes to form the cycloalkene product. The organic cycloadduct is removed by oxidation with air or with silver triflate in nearly quantitative yield. For more sterically hindered enones (e.g., mesityl oxide) and for methyl acrylate, the desired outcome requires the use of BF3·OEt2, and yields are significantly lower (15−35%)

One-Pot Facile Conversion of Baylis-Hillman Adducts into 1,5-Diarylpyrazoles Using Microwave Irradiation

Abstract: Several Baylis-Hillman adducts were prepared by the reaction of appropriate arylaldehydes with methyl vinyl ketone in the presence of imidazole and a catalytic amount of L-proline, in 55–90% yields. An easy transformation of these adducts into 1,5-diarylpyrazoles was achieved using microwave irradiation (400 W) with short reaction times (1–3 min) and high yields (80–91%).

Ruthenium-Catalyzed Ring Expansion Reaction of 1-Acetylenylcyclobutanols with Methyl Vinyl Ketone

Abstract: A novel type of ruthenium-catalyzed cascade ring expansion reaction is reported. A 1,2-rearrangement of acetylenylcyclobutanol followed by carbon-carbon bond formation with methyl vinyl ketone proceeds in one-pot process. This reaction enables to synthesize 2-alkylidenecyclopentanones in a stereoselective manner using appropriate ruthenium catalysts.

Palladium-catalyzed 2-phenylethenylation of codeine : 8-[(1E)-2- phenylethenyl]codeinone dimethyl ketal as the unexpected 'masked' diene for the preparation of 19-substituted Diels-alder adducts of thebaine

Abstract: In a search for starting materials for the preparation of 7,8-fused morphine alkaloid derivatives, 8-[(1E-2-phenylethenyl]codeinone dimethyl ketal (4) and 8-[(1E-2-phenylethenyl]codeine (5) were prepared. These dienes were used as substrates in the Diels–Alder reactions. Compound 5 formed the ‘normal’ adduct 12 with N-phenylmaleimide, while compound 4 behaved in reactions with dienophiles as the ‘masked’ diene 11, a 8-[(1E)-2-phenylethenyl]-substituted thebaine, yielding the corresponding 19-substituted 6,14-endo-etheno-6,7,8,14-tetrahydrothebaines. Specifically, reaction of 4 with methyl vinyl ketone gave rise to 19-[(1E)-phenylethenyl]thevinone (14) whose structure was elucidated by an X-ray diffraction analysis. The thebaine derivative 11 was also prepared from 4.

Density functional study of noncovalent catalysis of the Diels–Alder reaction by the neutral hydrogen bond donors thiourea and urea

Abstract: The Diels–Alder reaction between cyclopentadiene and methyl vinyl ketone has been investigated by density functional calculations at the B3LYP/6-31+G* level, both in the absence and presence of the hydrogen-bonding catalysts thiourea and urea. The computed transition structures are concerted, but highly asynchronous in all cases. The addition of thiourea or urea accelerates the reaction and slightly changes the endo / exo selectivity. The activation barriers are lowered by 2–3 kcal/mol, while the activation free energies show smaller reductions due to unfavorable entropic effects. The addition of BF 3 causes a more pronounced decrease in the computed barriers by 8–11 kcal/mol. Despite their lower efficiency, hydrogen-bonding catalysts such as thiourea and urea may still offer an attractive alternative to Lewis acids because they do not suffer from product inhibition and can be used in aqueous solution.

Synthesis of 2-benzylidene-7a-alkyltetrahydropyrrolizine-3,5-diones starting from baylis-hillman adducts

Abstract: Recently, 3-alkylidenedihydropyrrol-2-ones and 3-alkylidenedihydropyrrole derivatives were synthesized starting from the Baylis-Hillman adducts of methyl acrylate and methyl vinyl ketone, respectively. These compounds were prepared by the reductive cyclization of nitroalkane derivatives, which were synthesized from the Baylis-Hillman acetate by the SN2' reaction with primary nitroalkane, 1,2 as shown in Scheme 1. We reasoned that we could prepare tetrahydropyrrolizine3,5-dione skeleton by using the same nitroalkane derivative 1 as the starting material as shown in Scheme 2. A variety of compounds with tetrahydropyrrolizine-3,5-dione backbone were known and have been synthesized. The overall reaction pathway for the target compound involved sequential introduction of primary nitroalkane at the primary position of Baylis-Hillman adduct to make the starting material 1, Michael addition of 1 to appropriate Michael acceptor 2 to form 3, reduction of the nitro group of 3 and concomitant cyclization to lactam compound 4. From this lactam derivative 4 the desired tetrahydropyrrolizine-3,5dione skeleton 5 could be synthesized. Thus, we prepared 1a from the reaction of the corresponding Baylis-Hillman acetate and nitroethane as reported. The next Michael addition reaction was carried out with methyl acrylate (2a) in the presence of DBU in CH3CN to produce 3a. With this compound 3a in our hands, we examined the reduction of nitro group under Fe/AcOH conditions and obtained 4a (54%). We could not find the other possible lactam compound 4' (Scheme 2). The next cyclization reaction of 4a to the final compound 5a was performed according to method already reported in a similar system, hydrolysis of the ester group and the following lactamization under the influence of acetic anhydride at refluxing temperature. Encouraged by the successful results, we examined the

Improved Conversion and Selectivity of a Diels-Alder Cycloaddition by Use of Emulsions of Carbon Dioxide and Water

Abstract: Water and liquid carbon dioxide are mixed by power ultrasound to promote the Diels−Alder cycloaddition between cyclopentadiene and methyl vinyl ketone. Performing the reaction in emulsions of water and carbon dioxide leads to the high endo/exo selectivity and conversion that are characteristic of water but specific production rates that are greater than when either solvent is used alone. The maximum selectivity measured in this study was 16:1, which compares favorably to that obtained for the same reaction in pure water (21:1) or for a similar Diels−Alder reaction (cyclopentadiene + butyl acrylate) in supercritical carbon dioxide in the presence of Sc(OTf)3 (24:1). To interpret our results, we present a simple mathematical model in which the carbon dioxide phase acts as a carrier for water-insoluble reactants and the reaction occurs primarily in the water phase. The standoff distance between the sonic horn and the carbon dioxide/water interface is a key variable and has an optimum value of about 2.0 cm. O...

Synthesis of Cyclopropane Derivatives Starting from the Baylis-Hillman Adducts Using Sulfur Ylide Chemistry

Abstract: Cyclopropane moiety is a fundamental class of functional group that is the focus of many organic synthesis programs and performs a key structural role in a wide range of biologically active molecules. The importance of cyclopropanes is reflected in the enormous effort that has been invested in their diastereoand enantioselective synthesis. In addition, cyclopropane derivatives could be transformed to structurally diverse compounds. During the extensive studies on the chemical transformations of Baylis-Hillman adducts, we examined the introduction of cyclopropane moiety at the primary position of Baylis-Hillman adducts to form vinyl cyclopropane derivatives 2 (Scheme 1). Such vinyl cyclopropane backbone is an important entity in many naturally occurring and synthetic pyrethroidal insectides, and could be used for further chemical transformations. Our synthetic rationale is shown in Scheme 1. The starting cinnamyl bromide 1a was prepared from the Baylis-Hillman adduct and HBr according to the reported method. The reaction of 1a and dimethyl sulfide in CH3CN generated the sulfonium salt (I), which was converted into the corresponding sulfur ylide (II) by treatment with NaOH. The in situgenerated sulfur ylide (II) reacted with methyl vinyl ketone to give the desired cyclopropane derivative 2a in 45% yield as shown in Scheme 1 via the intermediate (III). The synthesis of 2a was carried out in CH3CN at room temperature within 12 h. Encouraged by the successful results we prepared other cyclopropane derivatives 2b-h and the results are summarized in Table 1. The use of Cs2CO3 instead of NaOH showed similar yield of 2a. However, the use of K2CO3 gave 2a in only trace amounts. When we used nitrogen ylide, which was made from the reaction of 1a and DABCO in the presence of NaOH, we could not observe the formation of 2a at all. Variation of the electron-withdrawing substituents (-COOMe, -COOEt, -COMe, -CN) of the starting materials 1a-f did not alter the reactivity for the formation of cyclopropanes. Ethyl vinyl ketone (entry 2) could also be used successfully as the Michael acceptor in the reaction with 1a. However, we failed to obtain the corresponding products when we replaced methyl vinyl ketone with other Michael acceptors such as methyl acrylate, acrylonitrile, and 2-cyclohexen-1one. In these cases we could not observe any major component on TLC. The reason for the failure could be explained either by the hydrolysis or low reactivity of these Michael acceptors. Fortunately, 2-chloroacrylonitrile could be used as the Michael acceptor efficiently to give 2g (entry 7) as inseparable cis-trans mixtures in 57% yield. The relative stereochemistry of the two substituents of cyclopropane was trans in all cases as reported in similar systems. We could not isolate the other stereoisomer from the reaction mixtures. Further synthetic applications of the cyclopropane products are currently underway.