Proceedings of the Symposium on Progress in Organic Reactions and Syntheses
29th Symposium on Progress in Organic Reactions and Syntheses
Displaying 1-50 of 115 articles from this issue
October 20 (Monday), 2003
Oral Presentations
  • Akito Kakuuchi, Takeo Taguchi, Yuji Hanzawa
    Pages 2-3
    Published: September 24, 2003
    Released on J-STAGE: March 16, 2004
    CONFERENCE PROCEEDINGS FREE ACCESS
    Alkenylzirconocene chlorides are readily available complexes through the hydrozirconation of alkynes with Schwartz reagent (Cp2ZrHCl). We found that Rh(I)-catalyzed various addition reactions of the alkenylzirconocene chlorides proceeded efficiently to give alkenyl adducts. Thus, the 1,2-addition of alkenylzirconocene chlorides to aldehydes and imines and conjugate 1,4-addition to α,β-unsaturated ketones, esters and amides were brought about by the use of [RhCl(cod)]2. A high diastereoselectivity (95% yield, 90% de) was obtained through the reaction of α,β-unsaturated amide derived from Oppolzer's sultam and 2-butenoyl chloride. Furthermore, alkenylzirconocene chlorides reacted with ω-alkynyl aldehyde in the presence of the Rh(I) catalyst to give a cyclization product, cyclopentanol.
  • Shinji Nagumo, Yusuke Ishii, Irie Miyoshi, Norio Kawahara, Hiroyuki Ak ...
    Pages 4-5
    Published: September 24, 2003
    Released on J-STAGE: March 16, 2004
    CONFERENCE PROCEEDINGS FREE ACCESS
    Treatment of arylpropyl vinylepoxides linked to ester with BF3•Et2O in CH2Cl2 undertook stereospecific 7-endo selective Friedel–Crafts (FC) cyclization to give seven-membered ring products in excellent yields. Di- and tri-substituted epoxides were acceptable for this new reaction. We also developed 8-endo selective FC cyclization of vinylepoxides containing alkyn-dicobalt complex moiety to give eight-membered ring products in excellent yields.
  • Mugio Nishizawa, Veejendra K. Yadav, Mariusz Skwarczynski, Hiroko Taka ...
    Pages 6-7
    Published: September 24, 2003
    Released on J-STAGE: March 16, 2004
    CONFERENCE PROCEEDINGS FREE ACCESS
    We found our original olefin cyclization agent Hg(OTf)2 exhibits remarkable catalytic activity for the hydroxylative cyclization of 1,6-enynes such to give exomethylene five-membered carbocycles in excellent yield. On the other hand Hg(OTf)2-(TMU)3 complex is effective as a catalyst for the arylyne cyclization affording dihydronaphtalens. Catalytic activity of both reactions reached up to 1,000 cycles. The reaction should involve a protodemercuration step of the vinylmercuric intermediate induced by TfOH, formed in situ, regenerating catalyst.
  • Yasuhiro Hiroki, Takayuki Goto, Kazuishi Makino, Yasumasa Hamada
    Pages 8-9
    Published: September 24, 2003
    Released on J-STAGE: March 16, 2004
    CONFERENCE PROCEEDINGS FREE ACCESS
    Catalytic asymmetric hydrogenation is one of the most efficient and useful methods to obtain a variety of chiral products with high optical purity. Generally, the asymmetric hydrogenation through dynamic kinetic resolution developed by Noyori et al can be utilized for chirally labile linear α-amino β-keto esters to afford syn β-hydroxyamino acids with high diastereo- and enantioselectivities. However it is difficult to directly obtain anti (erythro) β-hydroxy amino acids using their protocol. We report here direct anti selective hydrogenation of α-amino β-keto ester derivatives with high stereoselectivities via dynamic kinetic resolution using chiral RuCl2(binap) catalyst.
  • Hirohisa Doi, Takeo Sakai, Kiyoshi Tomioka
    Pages 10-11
    Published: September 24, 2003
    Released on J-STAGE: March 16, 2004
    CONFERENCE PROCEEDINGS FREE ACCESS
    Conjugate addition of nucleophiles to α,β-unsaturated carbonyl compounds is one of the most powerful bond forming reactions and has been widely utilized as a key reaction in organic synthesis. We have been engaged in the chiral ligand-controlled asymmetric reactions of various types of nucleophiles such as organolithiums, organocoppers, organoboranes, and arylthiols. The asymmetric conjugate addition reaction of lithium N-benzyltrimethylsilylamide 2 with tert-butyl enoates 3 bearing a variety pattern of substituents at the β-position was mediated by a chiral diether ligand 1 to afford the corresponding β-amino esters in satisfactorily high enantioselectivities. The key to success was an addition of trimethylchlorosilane together with enoates. To the best of our knowledge, this is the first success in an external chiral ligand-controlled asymmetric conjugate addition of lithium
  • Tomotaka Okino, Yasutaka Hoashi, Yoshiji Takemoto
    Pages 12-13
    Published: September 24, 2003
    Released on J-STAGE: March 16, 2004
    CONFERENCE PROCEEDINGS FREE ACCESS
    We have found that some thioureas efficiently promoted nucleophilic addition of TMSCN and ketene silyl acetals to nitrones, giving the corresponding hydroxyamines in good yield. In addition, we synthesized novel chiral thiourea derivatives with 2-dialkylamino-cylclohexyl groups. This type of thioureas could be used as non-metallic bifunctional organocatalysts. Indeed, these thioureas catalyzed asymmetric Michael reaction of malonates to nitroolefins and afforded the desired Michael adducts with high enantioselectivity (up to 93% ee).
Poster Presentations
  • Yoshihiro Matsumura, Harumi Yokota, Osamu Onomura, Toshihide Maki, Cha ...
    Pages 14-15
    Published: September 24, 2003
    Released on J-STAGE: March 16, 2004
    CONFERENCE PROCEEDINGS FREE ACCESS
    It is well known that indium (In) mediates pinacol-type reductive coupling reactions of carbonyl and imino compounds, while this method was not applicable to reductive homo-coupling reactions of N-acyliminium ion. Now, we found out that a combination of In and BrCF2CO2Et effectively mediated a reductive homo-coupling of N-acyl-β,γ-unsaturated- iminium ion generated from β,γ-unsaturated-a-methoxypiperidine derivatives in water to afford 2,2'-bipiperidine derivatives with high dl selectivity. Other solvents than water resulted in low yield of the coupling product.Active reducing species of this coupling reaction seems to be "In+" because commercially available InCl and InBr mediated this coupling reaction with low efficiency.
  • Mitsuhiro Yoshimatsu, Yasutaka Matsuura, Kohei Gotoh
    Pages 16-17
    Published: September 24, 2003
    Released on J-STAGE: March 16, 2004
    CONFERENCE PROCEEDINGS FREE ACCESS
    3,4-Dichalcogenopenta-2,4-dienylation of aldehydes proceeded in good to high yields using 4-ethoxy-1-(benzenesulfenyl)-2-(methylsulfenyl)- (1), 4-ethoxy-1,2-bis(benzenesulfenyl)but-1,3-diene (2), and 1-selenenyl derivatives 3 and 4 by a two step procedure: i) the reaction of 4-alkoxybuta-1,3-dienyl lithiums with aldehydes; ii) hydrolysis of the penta-2,4-dienyl alcohols with SOCl2/pyridine. This novel four-carbon homologation could be applied to a tandem reaction of pivaldehyde to give 3,4,7,8-tetrakis(benzenesulfenyl)-10,10-dimethylundeca- 2,4,6,8-tetraenal (15). 3,4-Bis(phenylsulfenyl)penta-2,4-dienals underwent intramolecular cyclization with a catalytic amount of p-toluenesulfonic acid to afford the 3,4-bis(phenylsulfenyl)cyclopentenones 18a,b in moderate to good yields.
  • Kazuo Yamazaki, Yoshinori Kondo
    Pages 18-19
    Published: September 24, 2003
    Released on J-STAGE: March 16, 2004
    CONFERENCE PROCEEDINGS FREE ACCESS
    Palladium-catalyzed carbonylation, which was based on a ligand exchange reaction, efficiently converted immobilized aryl halides to amides under mild reaction conditions using molybdenum hexacarbonyl [Mo(CO)6] as the carbon monoxide source. The method easily operates without irradiating with microwaves and yields a wide range of highly pure amides after cleaving from the resin. The method could also be applied to the carbonylation of immobilized amines with aryl halides and to construct heterocyclic systems via a carbonylative cyclization.
  • Minoru Kobayashi, Shinji Kitagaki, Chisato Mukai
    Pages 20-21
    Published: September 24, 2003
    Released on J-STAGE: March 16, 2004
    CONFERENCE PROCEEDINGS FREE ACCESS
    In recent years, functionalized allenes have received considerable attention due to their high and unique chemical reactivity. During the course of our studies on the development of an efficient method for the construction of oxacycles, we have recently found that the endo-mode intramolecular ring closure of allenes having a phenylsulfonyl functionality with a terminal hydroxy group proceeded very efficiently, and this protocol could be extended to the synthesis of carbocycles. Herein, we report that tandem reduction of internal azido moiety and endo-mode ring closure of sulfonylallene gives aza-heterocycles in good yields. In addition, the preliminary results on the intramolecular ring closure reaction of the allenyl sulfones with amido functionality will also be described.
  • Shimpei Sugiyama, Tsuyoshi Satoh
    Pages 22-23
    Published: September 24, 2003
    Released on J-STAGE: March 16, 2004
    CONFERENCE PROCEEDINGS FREE ACCESS
    Addition of the lithium enolate of carboxylic acid esters to 1-chlorovinyl p-tolyl sulfoxides, which were synthesized from chloromethyl p-tolyl sulfoxide and ketones or aldehydes in good yields, gave carboxylic acid esters having a tertiary or a quaternary carbon at the 3-position, and chlorine and sulfinyl groups at the 4-position in high to quantitative yields. The adducts were converted to various carboxylic esters having methyl, formyl, and hydroxycarbonyl groups at the 3-position. A novel method for the synthesis of γ-lactones, including spiro-type γ-lactones and α-methylene γ-lactones, was realized from the adducts in good overall yields.
  • Kazunori Miyamoto, Takashi Suefuji, Masahito Ochiai
    Pages 24-25
    Published: September 24, 2003
    Released on J-STAGE: March 16, 2004
    CONFERENCE PROCEEDINGS FREE ACCESS
    Ethynyl(phenyl)(tetrafluoroborato)-λ3-iodane (1) serves as an efficient Michael acceptor, but its synthetic application is limited due to the low thermal stability. We found that the λ3-iodane (1) forms the supramolecular 1:1 complex (2) with 18-crown-6 in a high yield and the complexation dramatically increased the stability of the labile λ3-iodane (1). Solid state structure with pentacoordinated iodine(III) was determined by X-ray analysis and solution structure was examined by 1H NMR and CSI–MS, and binding constant was measured. The complex (2) holds for the high reactivity toward attack of nucleophiles and serves as a direct ethynylation agent for enolate anions, sulfinates, and phosphites. The 18-crown-6 ligand in (2) makes it possible to synthesize the highly labile (Z)-(β-alkoxyvinyl)phenyl-λ3-iodanes, which have never been synthesized, as a crown ether complex.
  • Keisuke Nishioka, Shigemitsu Takeda, Masatsugu Arai, Hitoshi Abe, Taka ...
    Pages 26-27
    Published: September 24, 2003
    Released on J-STAGE: March 16, 2004
    CONFERENCE PROCEEDINGS FREE ACCESS
    Aryl–aryl couplings are very important reactions because they have been utilized as key reactions for the syntheses of various natural products. Recently, we reported an intramolecular cyclization of aryl benzoate derivatives with a novel palladium reagent system. In this report, we examined cyclizations of phenyl benzoate derivatives possesing various substituent patterns, in order to investigate the substituent effects to the reactivity and the regioselectivity. Syntheses of graphislactones, which were isolated from graphis prunicola, were also carried out using the intramolecular cyclization of phenyl benzoate derivatives.
  • Masayuki Kirihara, Akihiro Shimajiri, Makoto Tsunooka, Kumiko Okubo, T ...
    Pages 28-29
    Published: September 24, 2003
    Released on J-STAGE: March 16, 2004
    CONFERENCE PROCEEDINGS FREE ACCESS
    The reaction of tertiary cyclopropanol silyl ethers with diethylaminosulfur trifluoride usually causes ring opening to produce allylic fluorides. However, cyclopropyl silyl ethers bearing a strong electron-donating substituent at C1 or an electron-withdrawing substituent at C2 do not afford allylic fluorides but fluorocyclopropanes. It has also been proved that an electron-donating substituent at C2 of the tertiary cyclopropanol silyl ethers promotes ring opening in the reaction with diethylaminosulfur trifluoride.Tertiary cyclopropanol systems react with a catalytic amount of vanadyl acetylacetonate under an oxygen atmosphere to afford β-hydroxy ketones and β-diketones. This reaction proceeds through peroxides. The peroxides could be effectively obtained from the reaction in 2,2,2-trifluoroethanol.
  • Kazunori Tsubaki, Daisuke Tanima, Tomokazu Kusumoto, Takeo Kawabata, K ...
    Pages 30-31
    Published: September 24, 2003
    Released on J-STAGE: March 16, 2004
    CONFERENCE PROCEEDINGS FREE ACCESS
    Recently, we reported an artificial receptor 1, which is a hybrid molecule consist of phenolphthalein and two crown ethers. In this system, the length of α,ω-diamines could be recognized by developing purple color. In addition, the coloration was so sensitive to temperature that receptor 1 could visualize "temperature". We found that the variable temperature coloration of receptor 1 with alkali metal ions significantly depends on the metal. As the temperature rises, the coloration of receptor 1 with NaOH becomes weaker, in contrast with KOH becomes more intense. Based on the variable temperature UV, NMR, and IR spectra, we propose that equilibrium between colored and colorless complex of receptor 1 with alkali metal ions is responsible for the observed phenomena.
  • Mitsuru Shindo, Keiko Ohtsuki, Chinatsu Tsuchiya, Kotaro Itoh, Kozo Sh ...
    Pages 32-33
    Published: September 24, 2003
    Released on J-STAGE: March 16, 2004
    CONFERENCE PROCEEDINGS FREE ACCESS
    The inverse electron-demand 1,3-dipolar cycloaddition of nitrones with ynolate anions, followed by quenching with t-BuOH, produced substituted 5-isoxazolidinones with good trans-selectivity. These products were easily converted into β-amino acids via hydrogenation. Asymmetric 1,3-dipolar cycloaddition of ynolates with chiral nitrones derived from D-mannitol also successfully afforded the chiral products with high diastereoselectivity. These products, after separation of the minor isomers, were led to optically pure β-amino acids. These results show the first 1,3-dipolar cycloaddition and the first asymmetric reaction using ynolates.
  • Lisa Araki, Maho Yamaguchi, Sumi Yonezawa, Natsumi Taniguchi, Shinya H ...
    Pages 34-35
    Published: September 24, 2003
    Released on J-STAGE: March 16, 2004
    CONFERENCE PROCEEDINGS FREE ACCESS
    To investigate the direct role of imidazole in RNA catalysis, we designed and synthesized an imidazole C-ribonucleoside phosphoramidite from tribenzylribofuranosylimidazole1) . This phosphoramidite can be readily used in conventional DNA/RNA synthesizer to incorporate imidazole into normal base position of RNA sequence. In the synthetic study, we demonstrate that pivaloyloxymethyl (POM) group is suitable as N-protecting group of imidazole in the synthesis of oligonucleosides. Use of POM group as a protecting group of imidazole was first reported in RNA synthesis.
  • Takashi Ikawa, Hironao Sajiki, Kosaku Hirota
    Pages 36-37
    Published: September 24, 2003
    Released on J-STAGE: March 16, 2004
    CONFERENCE PROCEEDINGS FREE ACCESS
    Despite numerous literature precedents, selective mono-alkylation of primary amines for the synthesis of secondary amines remains a challenging in organic synthesis. Reported synthetic methods of secondary amines mainly include direct N-alkylation of primary amines using alkyl halides, amide reduction and reductive alkylation protocols although those methods possess serious limitations such as the concomitant overalkylation. The reductive alkylation of amines using aldehydes is one of the most important methods while the aldehyde is one of the environmentally-unfriendly reagents. We have found an environmentally-benign mono-alkylation method of aromatic amines under Pd/C-catalyzed hydrogenation conditions using nitriles as alkylating agents. The present method could be applied to the direct synthesis of secondary amines from aromatic nitro compounds.
  • Hironao Sajiki, Takanori Kurita, Hiroyoshi Esaki, Fumiyo Aoki, Tomohir ...
    Pages 38-39
    Published: September 24, 2003
    Released on J-STAGE: March 16, 2004
    CONFERENCE PROCEEDINGS FREE ACCESS
    Replacement of hydrogen atoms on alkyl carbons by deuterium has been the focus of much research of late. During the last several decades, development of a new synthetic method of deuterium-labeled compounds has been extensively studied. Many of the existing techniques are mainly used deuterium gas as the deuterium source although deuterium gas is quite expensive. Some studies of hydrogen-deuterium isotope exchange between D2 and H2O or H2 and D2O in strongly acidic conditions has been reported. However, the reactions were found to be very slow, with only a few turnovers of the catalyst. Herein we report that heterogeneous 10% Pd/C catalyze the H–D isotope exchange reaction between H2–D2O under quite mild conditions (neutral and room temperature) with unprecedented efficiency.
  • Akinori Mori, Takashi Ikawa, Hironao Sajiki, Kosaku Hirota
    Pages 40-41
    Published: September 24, 2003
    Released on J-STAGE: March 16, 2004
    CONFERENCE PROCEEDINGS FREE ACCESS
    Deoxygenation method of phenolic hydroxyl groups appears to be an important synthetic tool in the field of organic synthesis. Palladium-catalyzed reduction of perfluoroalkane sulfonates has arisen as an important method although the synthesis of perfluoroalkane sulfonates from the corresponding phenols can frequently be a major problem in terms of selectivity, stability and cost. Meanwhile we have recently reported Pd/C-Et3N system smoothly catalyzes the hydrogenolysis of aryl halides. According to these results, the similar catalyst system should catalyze the hydrogenolysis of aryl mesylates. So we investigated the optimezed reaction conditions for the hydrogenolysis of the mesylate. The Pd/C–Et2NH–H2 system was found as an optimum catalyst for the hydrogenolysis.
  • Tatsuya Matsumoto, Kei Takeda
    Pages 42-43
    Published: September 24, 2003
    Released on J-STAGE: March 16, 2004
    CONFERENCE PROCEEDINGS FREE ACCESS
    We have recently reported that O-silyl cyanohydrins of β-silyl-α,β-epoxyaldehyde (1) can function as a highly functionalized homoenolate equivalent via the tandem sequence involving base-promoted ring opening, Brook rearrangement, and alkylation of the resulting allylic anion. During our investigation of the mechanism of the reaction, we observed that treatment of γ-(t-butyldimethylsilyl)-β,γ-epoxybutyronitrile (2), lacking the siloxy group, with a base in the presence of MeI afforded dimethylated products in addition to monomethylated products. The fact promted us to examine the reaction of 2 with substrates bearing two electrophilic centers in the molecule. When 2 was treated with NaN(SiMe3)2 in the presence of 1,ω-dihaloalkanes, ω-halo-α,β-unsaturated esters, or bis enoates, two cyclization modes were observed depending upon the electrophile and the number of carbon atoms connecting the two electrophilic sites.
  • Tasuku Ishida, Ryo Akiyama, Shu Kobayashi
    Pages 44-45
    Published: September 24, 2003
    Released on J-STAGE: March 16, 2004
    CONFERENCE PROCEEDINGS FREE ACCESS
    We have already developed a recoverable and reusable osmium-catalyst that can be used in asymmetric dihydroxylation of olefins based on a microencapsulation technique. In the presence of a new osmium catalyst (PEM-MC OsO4), two-phase asymmetric dihydroxylation has been successfully performed, and complete recover and reuse of the catalyst have been achieved. PEM-MC OsO4 allows asymmetric dihydroxylation of olefins in water as the sole solvent. Furthermore, we have developed a new type of polymer-supported osmium catalyst based on the cross-linked polystyrene. The catalyst was also effective for asymmetric dihydroxylation of olefins in water as the sole solvent.
  • Tatsushi Imahori, Chieko Hori, Yohei Yamaguchi, Yoshiyuki Tanaka, Yosh ...
    Pages 46-47
    Published: September 24, 2003
    Released on J-STAGE: March 16, 2004
    CONFERENCE PROCEEDINGS FREE ACCESS
    ransformations of alkynes using catalytic amount of t-Bu–P4 base were accomplished. Additions of alcohols and an amine to alkynes were promoted by cat. t-Bu–P4 base under relatively mild reaction conditions, and desired vinyl ethers and an enamine were obtained in good yields. A dimerization of terminal alkynes via C–H activation proceeded with cat. t-Bu–P4 base and an amine as additive, and a conjugated enyne product was obtained. The first catalytic enyne synthesis via alkyne dimerization catalyzed by organic catalyst was performed. NMR studies on reaction species of C–H activation of terminal alkynes with t-Bu–P4 base were also carried out.
  • Takumichi Sugihara, Kimiko Kuwahara, Akihito Wakabayashi, Chieko Taniy ...
    Pages 48-49
    Published: September 24, 2003
    Released on J-STAGE: March 16, 2004
    CONFERENCE PROCEEDINGS FREE ACCESS
    Nitric oxide is stable paramagnetic gas, is considered as air-pollutant, and is also known to play fundamental role in biochemical processes. While a number of approaches to fix nitric oxide into organic molecules have been investigated for one and half centuries, yields of nitrogen containing products and reproducibility of the reaction were usually low to moderate. We solved these problems and reported herein a practical method to fix nitric oxide into organic molecules. A key feature of the reaction was use of alkynyllithium as substrate. Reaction of nitric oxide with alkynyllithiums cleanly proceeded for a short period to produce 5-substituted 1,2,3-oxadiazole 3-oxides in good yields after quenching with water. When deuterium oxide and chlorotrimethylsilane were used as quenching agent, 4-deuteriated and silylated products were produced, respectively.
  • Takehiro Yamagishi, Takanori Kusano, Kazuyoshi Kurosawa, Tsutomu Yokom ...
    Pages 50-51
    Published: September 24, 2003
    Released on J-STAGE: March 16, 2004
    CONFERENCE PROCEEDINGS FREE ACCESS
    The diastereoselective synthesis of α,β-functionalized phosphinates was examined through hydrophosphinylation of α-oxy aldehydes and α-amino aldehydes. When reactions of phosphinic nucleophile with α-oxy aldehydes or α-amino aldehydes were carried out in the presence of catalytic amount of PhOLi or AlLibis(binaphthoxide) (ALB), anti-β-substituted α-hydroxyphosphinates were formed with high diastereoselectivity. The product was transformed into β-amino-α-hydroxy(methoxycarbonylmethyl)phosphinic acid, which would be applicable as a building block for peptidic transition state analogue inhibitors of protease. The hydrophosphinylation product was also converted into N-Boc-aziridine phosphinate.
  • Atsushi Ohigashi, Atsushi Kanda, Hiroyuki Tsuboi, Norio Hashimoto
    Pages 52-53
    Published: September 24, 2003
    Released on J-STAGE: March 16, 2004
    CONFERENCE PROCEEDINGS FREE ACCESS
    Fujisawa Pharmaceutical Co. launched Funguard, a novel antifungal agent on December 6, 2002. The clinical studies of Funguard have shown its significant activity for the treatment of systemic Candidiasis and Aspergillosis without safety concerns. The original synthesis of Funguard involved expensive reagents, environmentally unfriendly metals and low yield. We investigated practical synthesis of Funguard amenable to a large scale synthesis to eliminate these problems. New synthetic methods established by these studies use a regioselective conversion of FR179342 to isoxazole following recrystallization to obtain FR203042. In addition, the isolated isomer is recovered as FR179342 after hydrolysis. The reported methods are advantageous over the original methods from the viewpoints of large scale manufactureability, and thus applied to industrial scale synthesis of Funguard.
  • Junko Nobuhiro, Maho Hirayama, Shigeo Tohyama, Tominari Choshi, Satosh ...
    Pages 54-55
    Published: September 24, 2003
    Released on J-STAGE: March 16, 2004
    CONFERENCE PROCEEDINGS FREE ACCESS
    Veiutamine, a new type of marine indroiminoquinone alkaloid, was isolated from the Fijian sponge Zyzzya fuliginosa by Ireland group in 1997. Veiutamine exhibits a potential antitumor activity (IC50 0.3μg/ml).We are currently developing the synthesis of bioactive condensed heterocyclic compounds based on the electrocyclic reaction of either 6π-electron system or aza 6π-electron system incorporating the aromatic one double bond. We planned the total synthesis of veiutamine by an application of this methodology. In the present work, we here describe the synthesis of deoxyveiutamine through the construction of the poly-functional indole framework based on a thermal electrocyclic reaction of 3-allenyl-2-alkenylpyrrole intermediate derived from 3-propargylpyrrole. The indole was converted into indolequinone in several steps. A conversion of indolequinone to deoxyveiutamine are now in progress.
  • Ikuo Kawasaki, Toshiharu Morimoto, Norihiro Sakaguchi, Michiko Watanab ...
    Pages 56-57
    Published: September 24, 2003
    Released on J-STAGE: March 16, 2004
    CONFERENCE PROCEEDINGS FREE ACCESS
    Ageliferins 13 were isolated from a Caribbean marine sponge, Agelas coniferin, by Rinehart et al. in 1989, and Kobayashi reported that these alkaloids had several interesting biological properties such as actomyosin ATPase and antiviral activities. 1-Benzyl-5-[(2-methoxycarbonyl)ethenyl]-2-phenylsulfanyl-1H-imidazole (10) was prepared in 46 % yield by regioselective N-alkylation of 4-formyl-2-phenylsulfanyl-1H-imidazole (7e) with benzyl bromide in the presence of ZnCl2 and DBU. Diels–Alder dimerization at 140°C of 10 stereoselectively gave the dimer (8e). The dimer (8e) reduced by LiAlH4 followed by NaBH4/NiCl2 to the diol (13) (R = H), which was an important intermediate for ageliferins 13. Herein, we are going to report the above-mentioned chemistry and recent progress of the investigation.
  • Takashi Nagamine, Kiminori Ohta, Yasuyuki Endo, Adam Januszko, Piotr K ...
    Pages 58-59
    Published: September 24, 2003
    Released on J-STAGE: March 16, 2004
    CONFERENCE PROCEEDINGS FREE ACCESS
    Several series of esters containing p-carborane rings were synthesized. The series contain ring structures, which are p-carborane, benzene, bicyclo[2.2.2]octane and cyclohexane. These ring structures are linked by ester group. Their mesogenic properties investigated using thermal analysis (DCS) and optical microscopy. These carborane derivatives show nematic phases.
  • Atom Transfer Radical Annulation Approach
    Takehiko Yoshimitsu, Hideyuki Nakajima, Yuki Shinohara, Hiroto Nagaoka
    Pages 60-61
    Published: September 24, 2003
    Released on J-STAGE: March 16, 2004
    CONFERENCE PROCEEDINGS FREE ACCESS
    The atom-transfer radical reaction has been found quite useful for functionalizing unsaturated organic molecules. The addition of various halocarbons to olefins in the presence of radical initiators is particularly effective for this purpose. Poly-halogenated compounds obtained by this reaction have been used as versatile intermediates for organic synthesis owing to their compatibility with numerous transformations. In the present study, the ACD ring system of paclitaxel (Taxol) has been synthesized from a readily available glucose derivative via radical reactions involving carbon tetrachloride-transfer annulation and photochemical cyclobutanone rearrangement. This synthesis provides a novel route to the chiral ACD ring system that would serve as a key intermediate in the total synthesis of paclitaxel.
  • Akimori Wada, Koji Ishida, Kaori Wakabayashi, Masayoshi Ito
    Pages 62-63
    Published: September 24, 2003
    Released on J-STAGE: March 16, 2004
    CONFERENCE PROCEEDINGS FREE ACCESS
    As an extension of our study on the sysnthesis of retinoic acid analogs, we developed a novel synthesis of analogs containing the ring systems such as indene, benzofurane and indole in place of 2,6,6-trimethylcyclohexene ring including 7–8 double bond in retinoic acid. Enol triflates derived from 2-indanone, 2-chromanone and N-methyl oxindole are smoothly reacted with E- and Z-3-tributylstannyl-2-butenols in the presence of a palladium catalysis to afford the corresponding coupling products. After oxidation with MnO2, the resulting aldehydes were converted into the retinoic acid analogs via Emmons-Horner reaction of C5 phosphonate and subsequent basic hydrolysis.
  • Masashi Ohba, Itaru Natsutani, Takashi Sakuma
    Pages 64-65
    Published: September 24, 2003
    Released on J-STAGE: March 16, 2004
    CONFERENCE PROCEEDINGS FREE ACCESS
    Suaveoline (1) and norsuaveoline (2), Rauwolfia alkaloids possessing a 9-azabicyclo[3.3.1]nonane skeleton fused by indole and pyridine rings, have been synthesized through a route starting from L-tryptophan methyl ester (3) and exploiting an intramolecular oxazole-olefin Diels–Alder reaction. On treatment with α-lithiated methyl isocyanide −78°C, the ester 3 protected by the Boc group was converted into the oxazole 4. The stereoselective formation of the 1,3-cis-tetrahydro-β-carboline moiety from 4 via Bischler–Napieralski cyclization followed by catalytic hydrogenation and subsequent introduction of the olefinic dienophile afforded the oxazole-olefin 5. The intramolecular Diels–Alder reaction of 5 proceeded smoothly in boiling xylene in the presence of DBN to provide the pyridine 6, which was then converted into 1 and 2 by the conventional method.
  • Hiromichi Fujioka, Yusuke Ohba, Junko Futamura, Yasuyuki Kita
    Pages 66-67
    Published: September 24, 2003
    Released on J-STAGE: March 16, 2004
    CONFERENCE PROCEEDINGS FREE ACCESS
    The rearrangements of epoxy alcohol derivatives having electron-withdrawing functional groups such as 2,3-epoxy acylates and 2,3-epoxy sulfonates provide a useful method for synthesizing many kinds of chiral compounds having a chiral quaternary carbon center. Epoxides with 2,3-dialkyl substituents react through cleavage of oxirane ring at the C3-position due to the electron-withdrawing nature of the functional groups. A similar reaction course is observed for epoxides with C3-aryl substituents. On the other hand, the reaction of epoxides with C2-aryl substituents occurs through cleavage of oxirane ring at the C2-position due to the cation-stabilizing ability of the aromatic ring.The methods were successfully applied to the asymmetric formal synthesis of (−)-aphanorphine and total syntheses of (+)-(S)-sporochnol, (−)-α-herbertenol and (−)-herbertenediol.
  • Yasuyoshi Miki, Yasuhiko Tsuzaki, Yoshiyuki Aoki, Hajime Hibino
    Pages 68-69
    Published: September 24, 2003
    Released on J-STAGE: March 16, 2004
    CONFERENCE PROCEEDINGS FREE ACCESS
    Indole-2,3-dicarboxylic anhydride is an attractive intermediate in a synthesis of natural products. We have shown the synthesis of ellipticine by the reaction of 1-benzylindole-2,3-dicarboxylic anhydride (1) with 3-bromo-4-lithiopyridine. Recently, reaction of 1-benzylindole-2,3-dicarboxylic anhydride (1) with anisoles in the presence of titanium chloride (IV) gave 3-(4-methoxybenzoyl)indole-2-carboxylic acids as sole products in high yields. However, in a similar manner, reaction of 1-benzenesulfoylindole-2,3-dicarboxylic anhydride with anisoles afforded 2-(4-methoxybenzoyl)indole-3-carboxylic acids, exclusively. In this report, we would like to show a synthesis of pyridocarbazole alkaloids, ellipticine and olivacine, by the reaction of the anhydride with 2,4,6-trimethoxypyridine in the presence of titanium chloride (IV).
  • Rie Namme, Hideyo Takahashi, Shiro Ikegami
    Pages 70-71
    Published: September 24, 2003
    Released on J-STAGE: March 16, 2004
    CONFERENCE PROCEEDINGS FREE ACCESS
    We have recently reported that the acid-catalyzed O-glycosidation of 1-exo-methylenesugars afforded 1-C-methyl-α-glycosides in a highly α-stereoselective manner. Applying this method to the oligosaccharide-synthesis, we envisioned the synthesis of 1-C-methyl-substituted analogue of PI-88, which is a potent heparanase inhibitor. After a survey of several catalysts, it was found that methanesulfonic acid promoted the reaction without the cleavage of acid sensitive MPM ether existing in the sugar unit. Therefore, we succeeded in the synthesis of O-protected pentasaccharide by the sequence of O-glycosidation/MPM-deprotection processes.
  • Tsuyoshi Satoh, Yuta Fukuda
    Pages 72-73
    Published: September 24, 2003
    Released on J-STAGE: March 16, 2004
    CONFERENCE PROCEEDINGS FREE ACCESS
    Optically active sulfinylaziridines having 4-methoxyphenyl group on their nitrogen atom were synthesized from optically active 1-chloroalkyl p-tolyl sulfoxide and an imine, which was derived from benzaldehyde and p-anisidine, stereoselectively in good overall yields. The sulfinylaziridines were treated with ethylmagnesium bromide or tert-butyllithium to afford the aziridinylmagnesiums or aziridinyllithiums, respectively, in quantitative yields. Cross-coupling of the aziridinylmagnesiums with iodoalkanes in the presence of Cu(I) iodide gave tetra-substituted aziridines in high yields; from which enantiomerically pure β,β-disubstituted β-amino acid derivatives were synthesized. On the other hand, from the aziridinyllithium, enantiomerically pure quaternary phenylalanine and quaternary aspartic acid derivatives were synthesized.
  • Etsuko Sekino, Takuya Kumamoto, Tsutomu Ishikawa
    Pages 74-75
    Published: September 24, 2003
    Released on J-STAGE: March 16, 2004
    CONFERENCE PROCEEDINGS FREE ACCESS
    Calophyllum coumarins (Guttiferae) are strongly active against HIV-1, in which (+)-calaonolide A (1) and (+)-inophyllum B (2) are candidates for AIDS drugs. We had succeeded in the enantioselective total synthesis of (+)-1 through (−)-quinine-catalyzed intramolecular oxo-Michael-type addition (IMA) reaction as a key step; however, utilization of protecting (TIPS) group was necessary. Now we established enantioselective short-course synthesis of (+)-1 and (+)-2 without any additional protecting groups. Demethylation and thermodynamic isomerization of optically active cis-methoxypyranocoumarin with MgI2 gave a 1:1 mixture of cis- and trans-hydroxypyranocoumarins without loss of optical purity. After separation, trans-derivative was subjected to chromene formation followed by stereoselective reduction to give a desired coumarin. Thus, (+)-2 and (+)-1 were obtained in total 5.1% and 15.2% yield, respectively, with 8 steps.
  • Shuji Yasuike, Shin-ichiro Kawara, Satoru Okajima, Kentaro Yamaguchi, ...
    Pages 76-77
    Published: September 24, 2003
    Released on J-STAGE: March 16, 2004
    CONFERENCE PROCEEDINGS FREE ACCESS
    We are interested in the synthesis and utilization of optically active organoantimony compounds for asymmetric reaction as chiral ligands. We have recently reported that optically active 2,2'-bis[di-(p-tolyl)stibano-1,1'-binaphthyls (BINASb), is an useful ligand in palladium-catalyzed asymmetric allylic alkylation of racemic 1,3-diphenyl-2-propen-1-yl acetate. We present here the synthesis of enantiomerically pure 2-dimethylamino-2'-di(p-tolyl)stibano-1,1'-binaphthyl (MASb) and 2-diphenylphosphino-2'-di(p-tolyl)stibano-1,1'-binaphthyl (BINAPSb), and propose that they can be used as effective chiral ligands for palladium-catalyzed asymmetric reactions. Such as the allylic alkylation asymmetric hydrosilylation of stylene derivatives.
  • Kiyoharu Nishide, Minoru Ozeki, Hideaki Kunishige, Hiroaki Shiraki, Ma ...
    Pages 78-79
    Published: September 24, 2003
    Released on J-STAGE: March 16, 2004
    CONFERENCE PROCEEDINGS FREE ACCESS
    We have found that pentafluorobenzoic acid (PFBA) was the most effective additive in the tandem Michael addition – Meerwein–Ponndrof–Verley (MPV) reduction of α,β-disubstituted α,β-unsaturated ketones 3 (R2 = alkyl) with mercapto alcohol 1 as a chiral auxiliary to improve both yield and diastereoselectivity of the products 4. The tuning effect of additives depended on the pH value. In addition, we have done asymmetric synthesis of 1,3-mercapto alcohols bearing contiguous three stereogenic centers and total synthesis of Whisky lactone and Cognac lactone, utilizing the above tandem reaction as a key reaction.
  • Takashi Osamura, Hironori Kinoshita, Sayaka Kinoshita, Kazumi Mizuno, ...
    Pages 80-81
    Published: September 24, 2003
    Released on J-STAGE: March 16, 2004
    CONFERENCE PROCEEDINGS FREE ACCESS
    We developed tandem intramolecular Michael–aldol reactions of chalcogenide-enones with aldehydes. Reaction of N-cinnamoyl-1,3-thiazolidine-2-thione with p-chlorobenzaldehyde gave products which have tricyclic ring system with a bridgehead carbon bound to four heteroatoms. When an enone with a chiral auxiliary was used, products with three consecutive chiral carbons and a chiral bridgehead were formed. This reaction induced four chiral centers at the same time. The products were stable to the alkaline hydrolysis. The acid hydrolysis β-mercaptopropionylamides.
  • Ryosuke Munakata, Hironori Katakai, Tatsuo Ueki, Jun Kurosaka, Ken-ich ...
    Pages 82-83
    Published: September 24, 2003
    Released on J-STAGE: March 16, 2004
    CONFERENCE PROCEEDINGS FREE ACCESS
    The first total synthesis and determination of the absolute configuration of (+)-macquarimicin A (1), a novel inhibitor of neutral sphingomyelinase (N-SMase) possessing an anti-inflammatory activity, have been accomplished. The present total synthesis features the construction of the unique tetracyclic framework via a stereoselective transannular Diels–Alder reaction, which is based on a plausible biosynthetic pathway to 1.
  • Tomoya Fujiwara, Kenji Omata, Kuninobu Kabuto
    Pages 84-85
    Published: September 24, 2003
    Released on J-STAGE: March 16, 2004
    CONFERENCE PROCEEDINGS FREE ACCESS
    The modified Mosher's method has often been employed to determine the absolute configurations of chiral substrates such as secondary alcohols and primary amines. In this method, the absolute configuration is assigned using the correlation model. The validity of the correlation model can be judged by examining the chemical shift differences between diastereomeric MTPA derivatives for as many protons as possible. Therefore, if a substrate has only few protons, the validity cannot be verified. We here report that the reversal of the relative position of 1H NMR signals observed for the diastereomers upon addition of La(hfaa)3 can be used for verification of the validity of the correlation model. This verification extends the scope of the determination of absolute configurations using the Mosher's method to substrates having only few probes.
  • Masayuki Yamashita, Takashi Shimizu, Ai Takada, Yoshiharu Fujii, Ikuo ...
    Pages 86-87
    Published: September 24, 2003
    Released on J-STAGE: March 16, 2004
    CONFERENCE PROCEEDINGS FREE ACCESS
    (−)-Linderol A [(−)-1; 5aR*,6R*,9R*,9aS*-4-cinnamoyl-3,6-dihydroxy-1-methoxy-6-methyl-9-(1-methylethyl)- 5a,6,7,8,9,9a-hexahydrodibenzofuran], a constituent of Lindera umbellata (Lauraceae), shows the potent inhibitory activity on the melanin biosynthesis of cultured B-16 melanoma cells. Its structure was determined by Sashida et al. except for its absolute configuration. We already reported the first total synthesis of (±)-1. An acetate [(±)-2] of the intermediate [(±)-3] in the total synthesis of (±)-1 separated to (+)- and (−)-2 by using HPLC with a chiral column. (−)-Camphanyl ester [(−)-4] of the triol [(−)-3] was subjected to X-ray crystallographic analysis, and the absolute configuration could be determined. The triol [(−)-3] was derived to (−)-1 according to the previous total synthesis of (±)-1. From these facts, the absolute configuration of (−)-1 should be 5aR,6R,9R,9aS
  • Shin-ichi Shirokawa, Masato Kamiyama, Tomoaki Nakamura, Masakazu Okada ...
    Pages 88-89
    Published: September 24, 2003
    Released on J-STAGE: March 16, 2004
    CONFERENCE PROCEEDINGS FREE ACCESS
    We found that the chiral ketene-N,O-acetal (1), prepared from α,β-unsaturated chiral imide, underwent a highly regio- and diastereoselective TiCl4-mediated vinylogous Mukaiyama aldol reaction with carbonyl compounds. The stereochemical sense of these reactions can be regarded as a formal 1,6- and 1,6,7-asymmetric induction, and high selectivity in such a remote asymmetric inductions are quite unusual. From a synthetic point of view, this methodology can provide a one-step construction of δ-hydroxy-αγ-dimethyl-α,β-unsaturated carbonyl unit that can be seen in many natural products. We would like to report the scope, limitation, and application of this methodology.
  • Fumiko Kato, Toshiya Takizawa, Kazuhiro Watanabe, Kunio Hiroi
    Pages 90-91
    Published: September 24, 2003
    Released on J-STAGE: March 16, 2004
    CONFERENCE PROCEEDINGS FREE ACCESS
    Asymmetric functionalization of allenes via carbopalladation with chiral phosphine ligands was demonstrated and the stereochemical reaction path is discussed. Upon treatment with a palladium catalyst, allenes bearing o-iodoaryl groups and nucleophilic sites undergo intramolecular carbopalladation at the allene function, followed by intramolecular nucleophilic substitution reactions, to provide a facile and direct entry to heterocycles or carbocycles in one-pot reactions. Use of chiral phosphine ligands in the above reactions provided optically active heterocycles such as tricyclic indoles with considerably high e.e.. The highest e.e. was obtained with (S)-Tol-BINAP as a ligand. The mechanism of the asymmetric induction is discussed.
  • Hideo Horibe, Kazuhiro Kondo, Hiroaki Okuno, Yasuoki Murakami, Toyohik ...
    Pages 92-93
    Published: September 24, 2003
    Released on J-STAGE: March 16, 2004
    CONFERENCE PROCEEDINGS FREE ACCESS
    A novel chiral ligand mimicking N–Ar axial chirality, (S)-N-[2-(diphenylphosphanyl)naphthalene-1-yl]-2-(piperidinylmethyl)piperidine, was found to exhibit good enantioselectivity (up to 80% ee) in the asymmetric cross-coupling reaction of 1-phenylethylmagnesium chloride with β-bromostyrene derivatives. To the best of our knowledge, the results are the third best enantioselectivity in the reported literature. Additionally, this type ligand is appealing, because it allows the synthesis of a wide variety of analogues.
Oral Presentations
  • Studies toward General Catalytic Enantioselective Synthesis of Tetrasubstituted Carbons
    Motomu Kanai, Reiko Wada, Yutaka Suto, Kounosuke Oisaki, Masakatsu Shi ...
    Pages 94-95
    Published: September 24, 2003
    Released on J-STAGE: March 16, 2004
    CONFERENCE PROCEEDINGS FREE ACCESS
    New catalytic methods for allylation, aldol reaction, and cyanoalkylation are described, using copper fluoride as a catalyst and silylated reagents (allyltrimethoxysilanes, ketene silyl acetals, and TMSCH2CN) as nucleophiles. These reactions proceed under very mild conditions with broad substrate generality. The mechanistic studies suggested that an allylcopper, copper enolates, and copper N-ketene imides, which are generated through dynamic ligand exchange between silicon and copper atoms, are the actual nucleophiles. These reactions can be extended to catalytic enantioselective reactions with ketones using chiral phosphine ligands. Conceptually more advanced direct catalytic cyanoalkylation of aldehydes, using unactivated alkylnitriles as a prenucleophile, is also described.
  • Masahiro Anada, Takuya Washio, Naoyuki Shimada, Shunichi Hashimoto
    Pages 96-97
    Published: September 24, 2003
    Released on J-STAGE: March 16, 2004
    CONFERENCE PROCEEDINGS FREE ACCESS
    The enantioselectivity in dirhodium(II) complexes-catalyzed hetero-Diels–Alder reaction of 1-methoxy-3-triethylsiloxy-1,3-butadiene with various aldehydes was investigated. The use of Rh2(S-BPTPI)4, a new dirhodium(II) carboxamidate incorporating (S)-3-(benzene-fused-phthalimido)-2-piperidonate as the bridging ligand, was found to produce 2-substituted-2,3-dihydropyran-4-ones in up to 96% ee. It is noteworthy that the present protocol was also successful for enantio- and endo-selective hetero-Diels–Alder reactions between 1,3-dienes activated by one oxygen atom and substituted propargylaldehydes. Formyl C–H hydrogen-bonding model proposed by Corey coupled with the solid-state structure of Rh2(S-PTPI)4, the parent complex of Rh2(S-BPTPI)4, confirms the observed stereochemical preferences.
  • Toshikatsu Takanami, Taketoshi Kikkawa, Shin-ichiro Nakajima, Kohji Su ...
    Pages 98-99
    Published: September 24, 2003
    Released on J-STAGE: March 16, 2004
    CONFERENCE PROCEEDINGS FREE ACCESS
    Catalytic and regio- and stereoselective rearrangement of epoxides to aldehydes via an alkyl migration can easily be achieved with a high valent metalloporphyrin complex, Cr(tpp)OTf, at a low catalyst loading (1–20 mol%). The yield and regio- and stereoselectivity of the catalytic process are generally good to high, and almost fully comparable to those of the corresponding reactions done stoichiometrically in a bulky organoaluminum reagent MABR. Since we have previously reported that Fe(tpp)X (X = OTf or ClO4) catalyzes the rearrangement of epoxides to ketones via a hydrogen mygration, ketones and aldehydes can selectively be prepared from epoxides in a highly controlled manner by the simple choice of Fe(III) and Cr(III) as a central metal ion of the porphyrin catalysts.
  • Akira Otaka, Junko Watanabe, Akira Yukimasa, Hideaki Watanabe, Hirokaz ...
    Pages 100-101
    Published: September 24, 2003
    Released on J-STAGE: March 16, 2004
    CONFERENCE PROCEEDINGS FREE ACCESS
    (Z)-Fluoroalkene-type dipeptide isosteres have served as potential dipeptide mimetics, where the peptide bond within a parent dipeptide is replaced by fluoroolefin units. Previously, we found that γ-phosphono-γ,γ-difluoro-α,β-enoate was reduced to the corresponding γ-phosphono-γ-fluoro-β,γ-enoate with organocopper reagent. This organocopper-mediated reduction has been successfully applied to the synthesis of the fluoroalkene isosteres. Mechanistic investigation of the organocopper-mediated reduction led us to envision that single electron transfer is responsible for the reduction and SmI2, a powerful one-electron reducing agent, should be applicable to the synthesis of the isosteres. Reduction with SmI2 proceeded via formation of the Sm-dienolate which upon kinetically controlled trapping with t-BuOH or a carbonyl compound yielded Xaa-Gly-type or α-substituted isosteres, respectively.
feedback
Top