Showing papers on "Enone published in 1999"

Novel Chemoselectivity and Stereochemical Aspects of Nickel-Catalyzed [2 + 2 + 2] Cycloadditions

Abstract: Metal-catalyzed cyclotrimerizations are well-precedented with a range of substrate classes and with a variety of metal catalysts.1,2 Features that are shared by nearly all variants include a high propensity for the incorporation of alkynes over alkenes and a high degree of stereospecificity in cases in which alkenes are incorporated. While investigating the role of organozinc structure in determining selectivities between reductive and alkylative pathways in nickel-catalyzed cyclizations of alkynyl enones,3,4 we found that an unexpected dimerization involving a formal [2 + 2 + 2] cycloaddition process was observed as a side reaction in some instances. A control experiment demonstrated that the organozinc component was not required for the [2 + 2 + 2] cycloaddition to occur, and that nearly quantitative yields of the [2 + 2 + 2] product were obtained upon exposure of alkynyl enones to Ni(COD)2 and PPh3 (Table 1). In addition to the inherent interest in a reaction that assembles two rings and four contiguous stereocenters in a completely stereoselective fashion from an acyclic, achiral substrate, several additional features were perhaps even more intriguing. First, the reaction chemoselectivity was quite unusual. The formal dimerization by a [2 + 2 + 2] reaction of an alkynyl enone requires that three unsaturated groups are incorporated while one is left unchanged, and an alkyne is the one functional group that does not participate in the cyclization. This chemoselectivity was confirmed to be quite general since treatment of alkynyl enone (E)-1 with Ni(COD)2 in the presence of 5 equiv of a variety of internal and terminal alkynes all led to efficient formation of dimer 4 without incorporation of the simple alkyne. For the alkyne unit to remain unaffected during this process goes against all expectations based on earlier investigations of related processes.5 This general trend was particularly well demonstrated in the early cobalt-catalyzed cyclotrimerizations of Vollhardt,2 and numerous related observations have been reported.6-10 The structurally distinct case of the nickel-catalyzed homo-Diels-Alder reaction of norbornadienes largely explored by Lautens is a rare example in which multiple alkene units are selectively incorporated in a metal-catalyzed [2 + 2 + 2] cycloaddition process.11 A second intriguing feature is that the initial trans stereochemistry of the starting enone (E)-1 was cleanly inverted in product 4 at the position adjacent to the ring juncture. This unexpected stereochemistry was confirmed by single-crystal X-ray analysis.12 Metal-catalyzed cycloadditions typically display high stereospecificities with alkene stereochemistry being maintained during the process. This issue has been well demonstrated in several related contexts.13-15 In a study of palladium-catalyzed [2 + 2 + 2] cycloadditions involving enyne additions to alkynes, Trost demonstrated that Z enynes underwent completely stereospecific couplings, whereas E enynes displayed moderate stereospecificity.13 In a study of nickel-catalyzed [4 + 2] cycloadditions, Wender demonstrated that both E,E-dienes and E,Z-dienes added to alkynes in a completely stereospecific fashion.14 However, we observed that treatment of enone (Z)-1 to the dimerization conditions led to the same single stereoisomer as that seen in the dimerization of enone (E)-1 (eq 1). Recovered starting material

Synthesis of Optically Active 5-(tert-Butyldimethylsiloxy)-2-cyclohexenone and Its 6-Substituted Derivatives as Useful Chiral Building Blocks for the Synthesis of Cyclohexane Rings. Syntheses of Carvone, Penienone, and Penihydrone

Abstract: Optically active 5-(tert-butyldimethylsiloxy)-2-cyclohexenone (1) and its 6-substituted derivatives 2a,b were synthesized from the readily available optically active ethyl 3-(tert-butyldimethylsiloxy)-5-hexenoate (4), where the Ti(II)-mediated intramolecular nucleophilic acyl substitution reaction and the FeCl3-mediated ring expansion reaction of a 1-hydroxybicyclo[3.1.0]hexane are the key reactions. The enone 1 reacted with higher-order cyanocuprates with excellent diastereoselectivity to afford the trans-addition products, trans-13, in excellent yields. The reaction of 1 with lower-order cyanocuprates proceeded with moderate to excellent syn-selectivity to afford cis-13. Treatment of trans- and cis-13 with DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) or catalyst p-TSA (p-toluenesulfonic acid) resulted in a β-elimination reaction to furnish the corresponding optically active 5-substituted-2-cyclohexenones 14. The 1,4-addition reaction of 2a and 2b with organocyanocuprates followed by treatment of the resulti...

Catalytic Asymmetric Conjugate Addition on Macrocyclic and Acyclic Enones. Synthesis of R-(-)-Muscone

Abstract: The asymmetric conjugate addition of diethyl zinc to acyclic enones is described. With 1% Cu(OTf)2 and 2% of a chiral phosphite ligand, the catalyst allowed ee's up to 92'% to be obtained. The addition of dimethyl zinc to a macrocyclic 15-membered ring enone lead to optically active R-(-)-muscone, in 53% yield and 79% enantiomeric excess.

A Biomimetic Approach to the Discorhabdin Alkaloids: Total Syntheses of Discorhabdins C and E and Dethiadiscorhabdin D.

Abstract: The characteristic spirodienone structure of the discorhabdin alkaloids is readily formed by reaction of the tyramine-substituted indoloquinonimines 26, 35, and 36 with cupric chloride, triethylamine, and oxygen. This cyclization provides a possibly biomimetic route to discorhabdins C and E (41 and 42). The unbrominated spirodienone 40 reacts with hydrogen over Pd/C to give enone 46. Bromination at the α position gives a mixture of bromoenones that undergo smooth conversion to dethiadiscorhabdin D (4) upon treatment with basic alumina.

A kinetic study of the reactions of NO3 with methyl vinyl ketone, methacrolein, acrolein, methyl acrylate and methyl methacrylate

Abstract: Absolute and relative-rate techniques have been used to obtain rate coefficients for the reactions: NO3+CH3C(O)CHCH2→products (1), NO3+CH2C(CH3)CHO→products (2), NO3+CH2CHCHO→ products (3), and NO3+CH2CHC(O)OCH3→products (4). The reaction NO3+CH2C(CH3)C(O)OCH3→ products (5), has been investigated by a relative-rate method only. The rate coefficients obtained by the relative-rate method at T=296±2 K and P=760 Torr are k1=(4.7±1.7)×10-16 cm3 molecule-1 s-1, k2=(3.7±1.0)×10-15 cm3 molecule-1 s-1, k3=(1.1±0.4)×10-15 cm3 molecule-1 s-1, k4=(1.0±0.6)×10-16 cm3 molecule-1 s-1 and k5=(3.6±1.3)×10-15 cm3 molecule-1 s-1. The rate coefficients determined by the discharge-flow technique at low pressure (P=1–10 Torr) and at T=293–303 K are k1=(3.2±0.6)×10-16 cm3 molecule-1 s-1, k2=(9.6±2.0)×10-15 cm3 molecule-1 s-1, k3=(8.9±2.8)×10-15 cm3 molecule-1 s-1, k4=(1.9±0.4)×10-16 cm3 molecule-1 s-1. The discrepancy between the values obtained from the relative-rate technique and the absolute technique are discussed and explained in terms of interference in the absolute study caused by secondary chemistry and fast-reacting impurities. Product studies reveal that methyl glyoxal is a product of reactions (1) and (2) along with peroxymethacryloyl nitrate (MPAN) for reaction (2) in air. A diurnally varying boundary-layer model suggests that reaction (2) is an important loss process for methacrolein and that it can lead to the generation of OH at night.

Unprecedented selectivity behaviour in the hydrogenation of an α,β-unsaturated ketone: hydrogenation of ketoisophorone over alumina-supported Pt and Pd

Abstract: The partial hydrogenation of 2,6,6-trimethyl-2-cyclohexen-1,4-dione (ketoisophorone) was studied over alumina-supported Pt and Pd catalysts. The influence of solvent, pressure, catalyst pretreatment, and Lewis acid and base additives was investigated. Chemoselectivities over 90% were achieved in the saturation of the C C or the sterically hindered C O double bonds over Pt and Pd, respectively. This seems to be the first example for the selective reduction of an α,β-unsaturated ketone to an unsaturated alcohol using dihydrogen. Enantioselective hydrogenation of the carbonyl group over cinchonidine-modified Pt afforded only 14% ee.

Julia–Colonna asymmetric epoxidation of furyl styryl ketone as a route to intermediates to naturally-occurring styryl lactones

Abstract: The enone 1 was oxidized stereoselectively using urea-hydrogen peroxide with polyeucine as the catalyst to give the epoxide 2 which was used to make (+)-goniotriol 7, (+)-goniofufurone 8, (+)-8-acetylgonitriol 9 and gonio-pypyrone 10.

Total synthesis of cytochalasin D: total synthesis and full structural assignment of cytochalasin O

Abstract: A total synthesis of cytochalasin D 3 is reported in which the key step is an intramolecular Diels–Alder reaction used to close the 11-membered ring simultaneously introducing the required stereochemistry at four of the stereogenic centres, C(4), C(5), C(8) and C(9). The precursor 21 for the Diels–Alder reaction was prepared from the aldehyde 13 by condensation with the dienyl phosphonate 14 to give the triene 15 which, after conversion into the acyl imidazole 17, was used to acylate the pyrrolidinone 18. The unstable pyrrolinone 21 was then generated from the pyrrolidinone by phenylselenation–oxidative elimination and was cyclised by heating in toluene under high dilution conditions to give the macrocyclic triene 22 (25–30%). Selective functionalisation of the double-bonds in this triene was investigated with epoxidation being selective for the 17,18-double-bond and hydroxylation using osmium tetroxide taking place selectively at the 6,7-double-bond. For completion of the synthesis of cytochalasin D 3, the 6,7-diol 26 was converted into the exocyclic alkene 30 by protection and dehydration. Further hydroxylation using osmium tetroxide gave the diol 31 which was taken through to the enone 36 by protection followed by phenylselenation, N-debenzoylation and oxidative elimination. Reduction under Luche’s conditions gave the alcohol 37 which was converted into the acetate 41 by acetylation followed by protecting group exchange. Selective deprotection of the vicinal diol and mild oxidation then gave the ketone 43. Final deprotection gave cytochalasin D 3 so completing the first total synthesis of this natural product.During the course of this work, the Diels–Alder adduct 22 was oxidised using an excess of osmium tetroxide to give the tetraol 28. After protection as its bis-acetonide 46, this was converted into the allylic acetate 51 using the chemistry developed during the synthesis of cytochalasin D 3. Selective hydrolysis of the 17,18-acetonide and oxidation under Swern conditions gave the hydroxyketone 53 which on deprotection gave cytochalasin O 54 so confirming the structure of this natural product.

Total Synthesis of Dihydroclerodin from (R)-(_)-Carvone

Abstract: The first total synthesis of the natural enantiomer of the insect-antifeedant dihydroclerodin (1) and lupulin C (40) has been achieved starting from (R)-(−)-carvone (2). In the applied strategy, the hexahydrofuro[2,3-b]furan moiety was introduced in an early stage of the synthesis. The correct configuration at C-9, C-11, C-13, and C-16 was established by application of a remarkably diastereoselective Mukaiyama reaction. The desired configuration at C-10 was obtained by catalytic reduction of the intermediate enone 21. After annulation of the second ring, the structural features at C-4, C-5, and C-6 were introduced. The successful finishing of the synthesis included a Chugaev elimination to give the exocyclic double bond at C-4 that is present in lupulin C. Oxidation of this double bond with m-CPBA afforded dihydroclerodin.

A New Entry to Enantioselective Synthesis of α-Nethylene-β-hydroxy Ketones by the Chalcogeno-Baylis-Hillman Reaciton

Abstract: Chiral hydroxy chalcogenides in the presence of TiCl4 achieved the asymmetric version of the chalcogeno-Baylis-Hillman reaction. The reaction proceeded under atmospheric pressure for 1h. 10-Methylthioisoborneol (9) achieved the best enantioselectivity. A methoxy derivative 10 of 10-methylthioisoborneol resulted in lower-selectivity than that obtained by 10-methylthioisoborneol (9). A hydroxyl group is required to perform good asymmetric induction. The asymmetric chalcogeno-Baylis-Hillman reaction with a C2 symmetric bidentate ligand-TiCl4 complex was also examined. Diol ligands gave the adduct in low to good yields with low or no enantiomeric excess. The adduct was also obtained in low to high yields with low or no enantiomeric excess using bisoxazoline ligands.

Insight into the Mechanism of the Saegusa Oxidation: Isolation of a Novel Palladium(0)–Tetraolefin Complex

Abstract: As an intermediate of the Saegusa oxidation of the silyl enol ether 1, the novel, structurally highly unusual d10 Pd0-tetraolefin complex 2 was isolated; 2 is the first complex of this type whose solid-state geometry has been fully elucidated. Apparently, the enone formed in the course of the reaction is conformationally preorganized to act as a host for the palladium atom. TMS=trimethylsilyl.

Synthesis of the C/D/E and A/B Rings of Xestobergsterol-(A)

Abstract: The A/B and the C/D/E rings of the xestobergsterol skeleton have been stereoselectively synthesized starting with testosterone and epiandrosterone, respectively. A deconjugative ketalization of the A-ring enone of testosterone provided a handle for functionalization of the B-ring. A stereoselective aldol condensation was used to incorporate the E-ring.

Electrophilic and Nucleophilic Reactivities of the Azomethine Carbon of SAMP-Hydrazones: Stereoselective Synthesis of γ-Amino Ketone Derivatives

Abstract: A novel methodology for the asymmetric synthesis of secondary N-Boc-protected γ-amino ketones is described. After the highly diastereoselective nucleophilic 1,4-addition of formaldehyde SAMP-hydrazone 1 to prochiral conjugated enones 2, the carbonyl group of the resulting 4-oxo aldehyde SAMP-hydrazones 4 was protected as ethylene ketals 5. The stereoselective (de 58−88%) addition of organometallic reagents to the CN double bond of the latter was then performed, and the unstable intermediate hydrazines obtained were either trapped as Moc-protected hydrazines 8 in good yields (65−87%) or reduced by Raney nickel-catalyzed hydrogenolysis of the N−N bond to afford the corresponding amines, which were isolated as their corresponding N-Boc derivatives 11. Noteworthy, the azomethine carbon of SAMP-hydrazones, not being essentially modified during the process, sequentially serves as a nucleophilic and an electrophilic center, acting as a nexus between the conjugated enone (electrophile) and the organometallic reag...

Nickel-Catalyzed Cyclizations of Enoate Equivalents: Application to the Synthesis of Angular Triquinanes

Abstract: Unsaturated acyloxazolidinones and α‘-silyloxy enones were found to be effective substrates in nickel-catalyzed organozinc-promoted cyclizations. Both groups served as convenient enoate equivalents, whereas methyl enoates themselves were inefficient substrates. A five-step procedure for the conversion of dimethylcyclopentenone into a highly functionalized angular triquinane was developed utilizing this observation. The key step of the procedure involves a nickel-catalyzed reductive cyclization/Dieckmann condensation sequence involving a cyclic enone tethered to an unsaturated acyloxazolidinone or α‘-silyloxy enone. The method was applied in a formal synthesis of pentalenene, pentalenic acid, and deoxypentalenic acid.

Stereoselective synthesis of β-amino alcohols: practical preparation of all four stereomers of N-PMB-protected sphingosine from l- and d-serine

Abstract: Serine was efficiently converted to the N - p -methoxybenzyl (PMB) protected α′-amino enone derivative 6 , which was reduced with Zn(BH 4 ) 2 to the corresponding anti -β-amino alcohol in >96% de. On the other hand, N -PMB- N -Boc-protected α′-amino enone derivative 8 was reduced by NaBH 4 to syn -product with a diastereoselectivity of ca. 90%.

Total Synthesis of 9-Isocyanoneopupukeanane.

Abstract: Sponges elaborate the largest number of bioactive marine natural products, which often possess fascinating structures of great varieties Our involvement in this area of chemistry has resulted in the synthesis of curcuphenol and curcudiol,1 (-)-furodysin,2 (-)-furodysinin,3 the enantiomer of herbasolide,4 and tavacpallescensin5 More recently, efforts in attaining the isocyanopupukeananes also bore fruit;6 we now describe our approach to 9-isocyanoneopupukeanane (1), which is a constituent of a Ciocalypta sp7 Besides the syntheses of 2-isocyanopupukeanane (2a, Chart 1)8 and 9-isocyanopupukeanane (2b),9,10 formal syntheses of the latter that terminated at 9-pupukeanone11-13 have also been reported On the other hand, we are not aware of 1, which possesses a rearranged skeleton, having been yielded to synthesis This work stemmed from our general interest in synthesis design related to molecular symmetry14 In a retrosynthetic analysis of isocyanoneopupukeanane, the disconnection of the isopropyl group and functional group interchange at the isocyano-substituted center led to the symmetrical ketone 10 Further tracking indicated the tricyclic olefin 8, and the cyclohexadiene 7 to be useful synthetic precursors To secure these compounds, we started from 3, which is readily available15 from a reaction sequence consisting of Birch reduction of p-cresyl methyl ether, Diels-Alder reaction with methyl acrylate (after in situ conjugation), and Grignard reaction with MeMgCl Treatment of 3 with HClO4 led to enone 4 (63%), which was epoxidized at the side chain with hydrogen peroxide-urea in acetic anhydride to give 5 in 70% yield (75% by using m-CPBA) Reduction of the epoxy enone with lithium aluminum hydride afforded the diol 6a (62%, inseparable diastereomers), which was acetylated (Ac2O, py, DMAP) to provide diacetate 6b (92%, inseparable diastereomers) Pyrolysis of 6b in a sealed tube at 450 °C for 1 h furnished directly the desired tricyclic olefin 8 (54%), indicating the generation of 7 as an intermediate With the acquisition of 8 the functionalization of its double bond was in order We expected that hydroboration-oxidation would give rise to 9 predominantly because the formation of the regioisomeric alcohol 9a is less favorable due to steric hindrance from the bridgehead methyl substituents Indeed, a separable mixture was produced in 52% and 10% yield, respectively By PCC oxidation of the major alcohol 9 to afford ketone 10 (85%) the work entered its last stage Thus, after exposure of 10 to i-PrMgBr/CeCl3 (91%) and then Me3SiCN/H2SO4, the formamide 12 was obtained in 425% yield Completion of our synthesis was attained by subjecting 12 to TsCl-py at room temperature 9-Isocyanoneopupukeanane was isolated in 83% yield The final product showed spectral data in good agreement with the reported values In conclusion, this report delineates the first total synthesis of isocyanoneopupukeanane It is interesting that we did not isolate the dimethyltwistene isomer from the pyrolysate of 6b

Synthesis of 1-amino-4-hydroxycyclohexane-1-carboxylic acids

Abstract: The synthesis of both stereoisomers of 1-amino-4-hydroxycyclohexane-1-carboxylic acid (1 and 2), a new family of constrained hydroxy-α,α-disubstituted-α-amino acids, is achieved through selective transformations of the functional groups of the corresponding enone cycloadduct provided by the Diels–Alder cycloaddition of Danishefsky’s diene to methyl 2-acetamidoacrylate The stereochemistry of intermediates 8 and 9 in the synthesis of hydroxy-α-amino acids 1 and 2 was unambiguously confirmed by X-ray structure determination

Catalyst composition, catalyst solution and process for preparing optically active epoxide

Abstract: A catalyst composition for organic a symmetric synthesis is provided, which comprises: (A) a lanthanoid element ion; (B) a binaphthol, and (C) a nitrogen and/or phosphorus compound such as lutidine-N-oxide, 1,3-dimethyl-2-imidazolldinone, hexamethyl-phosphortriamide, triphenylphosphine oxide, tri(2-methylphenyl)phosphine oxide or tri(4-methylphenyl )phosphine oxide. Asymmetric epoxidation of an enone is conducted by allowing an enone to react with an oxidizing agent in the presence of the catalyst composition or a catalyst solution containing the catalyst composition.

Metabolism of the Antimalarial Endoperoxide Ro 42-1611 (Arteflene) in the Rat: Evidence for Endoperoxide Bioactivation

Abstract: Ro 42-1611 (arteflene) is a synthetic endoperoxide antimalarial. The antimalarial activity of endoperoxides is attributed to iron(II)-mediated generation of carbon-centered radicals. An alpha, beta-unsaturated ketone (enone; 4-[2',4' bis(trifluoromethyl)phenyl]-3-buten-2-one), obtained from arteflene by reaction with iron(II), was identified previously as the stable product of a reaction that, by inference, also yields a cyclohexyl radical. The activation of arteflene in vivo has been characterized with particular reference to enone formation. [14C]Arteflene (35 micromol/kg) was given i.v. to anesthetized and cannulated male rats: 42.2 +/- 7.0% (mean +/- S.D., n = 7) of the radiolabel was recovered in bile over 5 h. In the majority of rats, the principal biliary metabolites were 8-hydroxyarteflene glucuronide (14.2 +/- 3. 9% dose, 0-3 h) and the cis and trans isomers of the enone (13.5 +/- 4.6% dose, 0-3 h). In conscious rats, 15.3 +/- 1.6% (mean +/- S.D., n = 8) of the radiolabel was recovered in urine over 24 h. The principal urinary metabolite appeared to be a glycine conjugate of a derivative of the enone. Biliary excretion of the glucuronide, but not of the enones, was inhibited by ketoconazole. 8-Hydroxyarteflene was formed extensively by rat and human liver microsomes but no enone was found. Bioactivation is a major pathway of arteflene's metabolism in the rat. Although the mechanism of in vivo bioactivation is unclear, the reaction is not catalyzed by microsomal cytochrome P-450 enzymes.

Single crystal to single crystal enantioselective [2 + 2] photodimerization of cyclohex-2-enone as an inclusion complex with (?)-1,4-bis[3-(o-chlorophenyl)-3-hydroxy-3-phenylprop-1-ynyl]benzene

Abstract: Crystals of (?)-1,4-bis[3-(o-chlorophenyl)-3-hydroxy-3-phenylprop-1-ynyl]benzene (4) with two equivalents of cyclohex-2-enone (1), forming inclusion complex 5, have been photoirradiated to give the 1 : 1 complex 6 in a single crystal to single crystal enantioselective [2 + 2] photodimerization reaction in 100% yield without collapse of the crystalline lattice of the inclusion complex. The mechanism has been elucidated by X-ray crystal structure analysis