HETEROCYCLES

■ Contents

■ CROSS-COUPLING REACTIONS FOR THE SYNTHESIS OF C-GLYCOSIDES AND RELATED COMPOUNDS

Pedro Merino,* Tomas Tejero, Eduardo Marca, Fernando Gomollón-Bel, Ignacio Delso, and Rosa Matute

*Department of Organic Chemistry, University of Zaragoza, E-50009 Zaragoza, Aragon, Spain

Abstract

Cross-coupling reactions provide versatile strategies for preparing hydrolytically stable C-glycosides and C-nucleoside analogues, which are of interest in the search for new biologically active molecules. Several types of cross-coupling reactions have been studied, including Heck, Suzuki, Stille and Negishi couplings. The aim of this work is to review the state-of-the-art in that sort of reactions applied to the synthesis of C-glycosides and related compounds.

■ Asymmetric Reactions of a Series of Aromatic Azines with Nucleophiles

Ilya N. Egorov,* Tatyana A. Tseitler, Grigory V. Zyryanov, Vladimir L. Rusinov, and Oleg N. Chupakhin

*Department of Organic Chemistry, Ural Federal University, Mira St. 19, Ekaterinburg 620002 , Russia

Abstract

Current review is devoted to the reactions of nucleophilic addition in azine series, leading to the stereoselective formation of optically active products. Three types of reactions are reviewed: the reactions of achiral nucleophiles with chiral azines; the reactions of chiral nucleophiles with achiral azines; reactions of achiral nucleophiles with achiral azines in the presence of chiral catalysts.

■ Distribution of Cyclic and Acyclic Bis-bibenzyls in the Marchantiophyta (Liverworts), Ferns and Higher Plants and Their Biological Activities, Biosynthesis, and Total Synthesis

Yoshinori Asakawa* and Agnieszka Ludwiczuk

*Faculty of Pharmaceutical Sciences, Tokushima Bunri University, 180 Nishihamabouji, Yamashiro-machi, Tokushima, 770-8514, Japan

Abstract

The Marchantiophyta (liverworts) are rich sources of cyclic and acyclic bis-bibenzyls which are very rare natural products in the plant kingdom. At present more than 70 of bis-bibenzyls have been found in liverworts. The structurally unique cyclic and acyclic bis-bibenzyls shows various biological activities such as antimicrobial, antifungal, cytotoxicity, antiobesitic, muscle relaxation, antitripanosomal activity, among others. They are biosynthesized from dimerization of lunularic acid via dihydrocoumaric acid and prelunularin. The present paper deals with the distribution of bis-bibenzyls in liverworts, fern and higher plants and their biological activity, biosynthesis, and total synthesis.

■ SCANDIUM TRIFLATE-CATALYZED D-FRUCTOFURANOSYLATION REACTIONS USING DISACCHARIDE UNITS

Takashi Yamanoi,* Noriko Misawa, Sho Matsuda, Mikio Watanabe, and Yoshiki Oda

*Research Department, The Noguchi Institute, 1-8-1, Kaga, Itabashi-ku, Tokyo 173-0003, Japan

Abstract

This paper describes efficient D-fructofuranosylation reactions catalyzed by scandium triflate. The reactions used several benzoylated or benzylated glycosyl acylate derivatives from disaccharides containing the D-fructofuranose moiety at the reducing ends. Only 5 - 10 mol% scandium triflate effectively promoted the D-fructofuranosylation reactions using the disaccharide derivatives as the glycosyl donors. The structures and protecting groups of the disaccharide donors and alcohol acceptor species influenced the stereoselectivity and reactivity of the fructofuranosylation reactions. The fructofuranosylation reactions could be applied to synthesize several non-reducing trisaccharides containing a sucrose-like disaccharide unit.

■ Selective Cross-Dehydrogenative Coupling of N-Phenyltetrahydroisoquinolines in Aqueous Media Using Poly(Aniline Sulfonic Acid)/Gold Nanoparticles

Toru Amaya, Tsubasa Ito, and Toshikazu Hirao*

*Department of Applied Chemistry, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 560-0871, Japan

Abstract

Selective cross-dehydrogenative coupling of N-phenyltetrahydroisoquinoline with carbon nucleophiles such as dimethyl malonate, ethyl acetoacetate, and nitromethane was demonstrated in complete aqueous media using poly(2-methoxyaniline-5-sulfonic acid)/gold nanoparticles under molecular oxygen.

■ A NOVEL THREE-COMPONENT COUPLING REACTION OF ARYNES, ISOCYANIDES, AND CYANOFORMATES: A STRAIGHTFORWARD ACCESS TO CYANO-SUBSTITUTED IMINOISOBENZOFURANS

Jing Li, Shintaro Noyori, Masayuki Iwasaki, Kiyohiko Nakajima, and Yasushi Nishihara*

*Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University, 1-1-1 Tsushima-naka, Okayama 700-8530, Japan

Abstract

Iminoisobenzofuran derivatives have been prepared by the palladium-catalyzed three-component coupling reaction of arynes, isocyanides, and cyanoformates in moderate yields.

■ Syntheses of Novel Dibenzo[d,f]heteronins Incorporating Group 15 and 16 Heavier Elements

Shuji Yasuike,* Satoshi Tsukada, Naoki Kakusawa, Takashi Tsuchiya, and Jyoji Kurita*

*Faculty of Pharmaceutical Sciences, Hokuriku University, 3-Ho, Kanagawa machi, Kanazawa 920-1181, Japan

Abstract

Fully unsaturated dibenzo[d,f]heteronins incorporating Group 15 (P, As, Sb) and Group 16 (S, Se, Te) heavier elements have been prepared via a common 1,8-dilithium intermediate. These heteronins, except for dibenzothionin, are the first examples of fused nine-membered heterocyclic ring.　Proton NMR spectra of the heteronins revealed that two olefinic bonds in the heteronin ring have the cis configurations and the nine-membered rings exist in a buckled, non-planar conformation.

■ INTRAMOLECULAR CYCLIZATION OF γ-ACETYLENIC ACIDS USING DENDRIMER-ENCAPSULATED Pd2+ CATALYSTS

Zen Maeno, Takato Mitsudome, Tomoo Mizugaki, Koichiro Jitsukawa, and Kiyotomi Kaneda*

*GSC Lab, Research Center for Solar Energy Chemistry, Osaka University, 1-3 Machikaneyama, Toyonaka, Japan

Abstract

Polyamine dendrimer-encapsulated Pd2+ catalysts were prepared by complexation of PdCl2 with internal tertiary amino groups of the dendrimer. The fifth-generation Pd2+ dendrimer catalyst showed cooperative catalysis between Pd2+ species and the internal nanocavity consisting of regularly arranged tertiary amino groups to promote the intramolecular cyclization of γ-acetylenic acids efficiently.

■ IMPROVEMENT OF HELIX-FORMING ABILITY OF MANNOSIDE-LINKED ETHYNYLPYRIDINE OLIGOMERS CONSTRUCTED BY CONVERGENT SYNTHESIS

Hajime Abe,* Hiroki Makida, and Masahiko Inouye*

*Graduate School of Pharmaceutical Sciences, University of Toyama, Sugitani 2630, Toyama, 930-0194, Japan

Abstract

The improvement of helix-forming ability of α-D-mannoside-linked 2,6-pyridylene ethynylene "ethynylpyridine" oligomers was made by modification of the linker between the ethynylpyridine and mannoside moieties in the oligomers. The linker involves a triazole ring because the preparation utilizes Huisgen reaction, and the proper distance between the triazole ring and the ethynylpyridine moiety was found to be important to show strong Cotton effects.

■ RAPID ASSEMBLY OF POLYCYCLIC STRUCTURES VIA SIGMATROPIC REARRANGEMENT OF S-PROPARGYL XANTHATES

Ryan M. Harrington, David Wright, and Samir Z. Zard*

*Department of Chemistry, Ecole Polytechnique, CNRS UMR 7652, 91128 Palaiseau, France

Abstract

Upon heating in chlorobenzene, propargyl xanthates yield the corresponding 4,5-bis(alkylidene)-1,3-dithiolan-2-ones which are trapped by unactivated olefins in an intramolecular Diels-Alder cycloaddition yielding interesting polycyclic structures.

■ A NEW MAGNETIC NANOPEAPOD: ENCAPSULATION OF MAGNETITE NANOPARTICLES IN POLYTHIOPHENE NANOTUBES

Tsukasa Nakahodo, Katsuya Yamamoto, and Hisashi Fujihara*

*Department of Applied Chemistry, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashi-Osaka 577-8502, Japan

Abstract

Template-based electropolymerization of cyclohexanedioxythiophene (CDOT) gave the corresponding polythiophene nanotubes (PNTs). A new hybrid polymer nanopeapod was constructed by introducing magnetite nanoparticles into the CDOT PNTs.

■ Rapid Trifluoromethylation of Indole Derivatives

Ayako Miyazaki, Ryo Shimizu, Hiromichi Egami, and Mikiko Sodeoka*

*Synthetic Organic Chemistry Laboratory, The Institute of Physical and Chemical Research, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan

Abstract

Rapid trifluoromethylation of indole derivatives was achieved using trimethylsilyltriflate as the catalyst. Good to high yields were observed within only 5 min at room temperature. This reaction system is able to provide not only the mono-trifluoromethylated products, but also the di-trifluoromethylated derivatives, because of its high reaction efficiency.

■ A NEW ENTRY TO THE SYNTHESIS OF PRIMIN VIA A B-ALKYL SUZUKI–MIYAURA CROSS-COUPLING REACTION

Kazuhiro Watanabe, Tomohiro Sugizaki, Yumi Tozawa, and Tadashi Katoh*

*Laboratory of Synthetic and Medicinal Chemistry, Department of Pharmaceutical Sciences, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan

Abstract

Primin, a biologically active benzoquinone natural product, was efficiently synthesized in 57% overall yield in six steps starting from commercially available 5-iodovanillin. The synthetic method involves crucial steps, including a B-alkyl Suzuki–Miyaura cross-coupling reaction to directly install an alkyl side chain in an aromatic ring and elaboration of quinone functionality by degradative oxidation using Fremy’s salt to yield the target primin.

■ ISOLATION AND FIRST X-RAY STRUCTURES OF NICKEL COMPLEXES OF 1,2,5-THIADIAZOLE-3,4-DITHIOLATE (TDAS) IN PROTONATED FORMS

Kouzou Matsumoto,* Maho Nishizawa, Yasukazu Hirao, Hiroyuki Kurata, and Takashi Kubo*

*Department of Chemistry, Graduate School of Science, Osaka University, Toyonaka, Osaka 560-8531, Japan

Abstract

Protonated Ni(tdas)2 complexes, tdas = 1,2,5-thiadiazole-3,4-dithiolate, are isolated and characterized by X-ray crystallography. pH-dependent absorption measurements reveal high proton donor ability of Ni(Htdas)2.

■ Synthesis of the E Ring Segment of Ciguatoxin CTX3C via the Negishi Coupling of Cyclic Ketene Acetal Triflate

Kengo Shiroma, Hiroyoshi Takamura, and Isao Kadota*

*Graduate School of Natural Sciences and Technology, Okayama University, 3-1-1 Tsushima-naka, Okayama 700-8530, Japan

Abstract

Stereocontrolled synthesis of the E ring segment of ciguatoxin CTX3C was performed via the Negishi coupling of cyclic ketene acetal triflates. Transformation of 8-membered lactones to the corresponding ketene acetal triflates was found to be affected by the protective groups of the substrates.

■ Rapid and Convergent Synthesis of a 2,4’-Linked Tri-oxazole in an Approach to Poly-oxazoles

Daniel D. Caspi, Haiming Zhang, Scott C. Virgil, Fabian M. Piller, and Brian M. Stoltz*

*CCE, California Institute of Technology, 1200 E. California Blvd, Pasadena, CA 91125, U.S.A.

Abstract

A rapid and convergent synthesis of a 2,4’-linked tri-oxazole using a Negishi coupling is described.

■ First Total Synthesis and Absolute Configuration of Keramamine C

Haruaki Ishiyama, Yuta Mori, Takashi Matsumoto, and Jun'ichi Kobayashi*

*Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita 12 Nishi 6, Kita-ku, Sapporo, Hokkaido 060-0812, Japan

Abstract

Asymmetric first total synthesis of keramamine C, a tetrahydro-β-carboline alkaloid from an Okinawan marine sponge Amphimedon sp., has been accomplished with the Bischler–Napieralski reaction and the Noyori catalytic asymmetric hydrogen-transfer reaction. The absolute configuration of keramamine C was elucidated to be 1R from comparison of the 1H and 13C NMR, CD spectral data and [α]D values of synthetic and natural keramamine C, respectively.

■ DEHYDROGENATIVE N-HETEROCYCLIZATION OF 2-(2-AmINOARYL)ETHYL ALCOHOLS TO INDOLE DERIVATIVES CATALYZED BY (μ-OXO)TETRARUTHENIUM CLUSTER/1,2-BIS(DIPHENYLPHOSPHINO)BENZENE

Teruyuki Kondo,* Takashi Kanda, Daisuke Takagi, Kenji Wada, Yu Kimura, and Akio Toshimitsu

*Advanced Biomedical Engineering Research Unit, Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan

Abstract

A novel catalyst system of (μ-oxo)tetraruthenium cluster (2) combined with 1,2-bis(diphenylphosphino)benzene (dppbz) realized a simple, selective, and practical synthesis of indole and its derivatives from 2-(2-aminoaryl)ethyl alcohols via dehydrogenative N-heterocyclization reaction. Spontaneous formation of a stoichiometric amount of hydrogen (H2) was observed, and the present reaction proceeded smoothly under an argon atmosphere without oxidants and/or hydrogen acceptors.

■ Ligand Modified CuFe2O4 Nanoparticles as Magnetically Recoverable and Reusable Catalyst for Azide-Alkyne Click Condensation

Shingo Ishikawa, Reuben Hudson, Audrey Moores,* and Chao-Jun Li*

*Department of Chemistry, McGill University, 801 Sherbrooke St. West, Montreal, Quebec H3A 2K6, Canada

Abstract

A ligand can make the trick: 2,2’-bipyridine was found to promote the activity of copper ferrite nanoparticles as catalysts for the azide-alkyne “click” coupling reaction. The reaction proceeded in excellent yields at room temperature, and the catalyst could be magnetically separated and recycled. Phosphorus and nitrogen containing ligands were tested and 2,2’-bipyridine proved to be the most efficient for this reaction.

■ DIRECT OXIDATION OF 4-METHYLPYRROLE-2-CARBOXYLATES WITH DDQ IN THE PRESENCE OF A GLYCOL

Kana Takahashi, Ryoji Iwamoto, Ryo Sakata, Takahiro Soeta, Katsuhiko Inomata, and Yutaka Ukaji*

*Chemistry Course, Graduate School of Natural Science and Technology, Kanazawa University, Kakuma, Kanazawa, Ishikawa 920-1192, Japan

Abstract

Oxidation of 4-methylpyrrole-2-carboxylates with DDQ in the presence of a glycol proceeded smoothly on the methyl group at the C4 position regioselectively to afford the corresponding pyrrole-2,4-dicarboxylates directly. Direct oxidation of a methyl group of 2,4,6-trimethylphenol and 3-methyl-9H-carbazole into carboxylates was also demonstrated.

■ Reaction of 1,2,3-Oxadiazole 3-Oxides

Takumichi Sugihara,* Akira Murakawa, Chiemi Sawanaka, Megumi Seki, Natsuki Iio, Ayano Iizuka, Takuya Oohora, and Shinobu Honzawa

*Niigata University of Pharmacy and Applied Life Sciences, 265-1, Higashi-jima, Niigata 956-8603, Japan

Abstract

1,2,3-Oxadiazole 3-oxides with an alkoxymethyl group at the 5-position were reduced by reacting them with sodium borohydride to produce 4,5-dihydro-1,2,3-oxadiazole 3-oxides in good yields, which were further transformed into substituted diazene N-oxides by reacting with Grignard reagents.

■ Combined Directed Metalation – Suzuki-Miyaura Cross Coupling Strategies. Synthesis of Isomeric Chromenopyridinones and Related Annulated Analogues

Ricarda E. Miller,* Roman Sommer, Hope Fan, Victor Snieckus,* and Ulrich Groth

*Department of Chemistry, Queen's University, 90 Bader Lane K7L 3N6, Canada

Abstract

A general strategy encompassing a Directed ortho Metalation (DoM) – Suzuki-Miyaura cross coupling and Directed remote Metalation (DreM) sequence for the synthesis of 5H-chromeno[4,3-c]pyridin-5-ones 5a-j, 5H-chromeno[3,4-b]pyridin-5-ones 6a-j, 5H-chromeno[3,4-c]pyridin-5-ones 13a-d, 12H-benzo[7,8]chromenopyridin-12-ones 16a-c, 17a-c, and pyrido[3',4':4,5]pyrano[2,3-e]indazol-5(1H)-one analogues 18, 28 is reported. Thus, using the powerful directed metalation group properties of aryl O-carbamates 9a-h, 14a-c metalation-boronation followed by Suzuki-Miyaura coupling with 3-bromopyridine affords a variety of azabiaryls 7a-i, 8a-b, 12a-c, 15a-c which, upon DreM reaction leads to several series of chromenopyridinones 5a-j, 6a-j, 13a-d and pyridonaphthopyrones 16a-c, 17a-c. The synthesis of an unusual pyridopyranoindazolone 18 is also described.

■ Advances in Siloxane-Based Coupling Reactions: Application of Palladium-Mediated Allyl-Aryl Coupling to the Synthesis of Pancratistatin Derivatives. The Formal Total Synthesis of (±)-7-Deoxypancratistatin

Krupa H. Shukla and Philip DeShong*

*Department of Chemistry and Biochemistry, University of Maryland, 7950 Baltimore Avenue, College Park, MD 20742, U.S.A.

Abstract

Palladium-mediated coupling of an allylic carbonate and an aryl siloxane has been applied to the formal total synthesis of 7-deoxypancratistatin and pancratistatin analogues. The key coupling reaction involved the use of a novel palladium olefin complex resulting in regio- and stereoselective arylation yielding a tetracyclic A-C ring intermediate. The observed regioselectivity of the coupling reaction was consistent with a model in which an unsymmetrical π-allyl palladium complex was formed. Coupling of a variety of substituted phenyl siloxane derivatives was achieved using the new Pd(0) system to provide access to novel pancratistatin derivatives.

■ STEREOCONTROLLED TOTAL SYNTHESIS OF (−)-FR901483

Shigeru Ieda, Akitaka Masuda, Mami Kariyama, Toshiyuki Wakimoto, Tomohiro Asakawa, Tohru Fukuyama,* and Toshiyuki Kan*

*Synthetic Organic ＆ Medicinal Chemistry, School of Pharmaceutical Science, University of Shizuoka, 52-1 Yada, Suruga, Shizuoka 422-8526, Japan

Abstract

The total synthesis of a potent immunosuppressant (–)-FR901483 is accomplished. The skeleton itself is constructed by the Ugi 4CC reaction, subsequent intramolecular Dieckmann condensation, and a diastereoselective intramolecular aldol reaction. However, the remarkable feature is the stereoselective incorporation of the p-methoxybenzyl and methylamino groups within the tricyclic core skeleton.

■ THE FIRST TOTAL SYNTHESES OF SCHOLAREINS A, C, AND D EMPLOYING 2ND GENARATION PALLADIUM-CATALYZED CYCLOALKENYLATION

Yasufumi Kawai, Megumi Saeki, and Masahiro Toyota*

*Department of Chemistry, Graduate School of Science, Osaka Prefecture University, 1-1 Gakuencho, Sakai, Osaka 593-8531, Japan

Abstract

(±)-Scholareins A (1), C (3), and D (4) have been synthesized for the first time by a 2nd generation palladium-catalyzed cycloalkenylation. In addition, total synthesis of (±)-boonein (5) has also been achieved by applying the same catalytic cyclization as the key step.

■ RHODIUM-CATALYZED SYNTHESIS OF BENZOFURANS BY THE REACTION OF KETONES AND o-DIFLUOROBENZENES

Mieko Arisawa,* Soichiro Nakane, Manabu Kuwajima, and Masahiko Yamaguchi*

*Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Aramaki, Aoba-ku, sendai 980-8578, Japan

Abstract

In the presence of catalytic amounts of RhH(PPh3)4 and 1,2-bis(diphenylphosphino)ethane (dppe), ketones reacted with o-difluorobenzenes giving benzofurans in high yields. The α-arylation of ketones and furan cyclization proceeded without in the absence of a base. Benzofuran cyclization was applied to substituted pentafluorobenzenes to give 6-substituted-4,5,7-trifluorobenzofuranes.

■ Synthesis of Calycotomine and N-Methylcalycotomine Using a Petasis Reaction — Pomeranz-Fritsch-Bobbitt Cyclization Sequence

Maria Chrzanowska, Agnieszka Grajewska, and Maria D. Rozwadowska*

*Faculty of Chemistry, Adam Mickiewicz University, ul. Grunwaldzka 6, 60-780 Poznań, Poland

Abstract

The use of aminoacetaldehyde acetals as the amine components in the one-step, three-component Petasis reaction followed by the Pomeranz-Fritsch-Bobbitt cyclization has been shown to be a convenient and simple method for the synthesis of tetrahydroisoquinoline alkaloids. Using this method two alkaloids, calycotomine and N-methylcalycotomine hydrochlorides, have been prepared in 61% overall yield.

■ Hydrogen Bonding Induced Highly Selective Isomerization of an Olefin Having Heteroaromatic Rings

Takuya Kobayashi and Tatsuo Arai*

*Department of Chemistry, Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Ten-nodai, Tsukuba-shi, Ibaraki 305-0006, Japan

Abstract

Heteroaromatic compounds having two different isomerization parts in the molecule containing nitrogen at the aromatic ring have been synthesized and their photoisomerization and fluorescence properties have been examined.

■ A 2-AMINO-6-METHYLPYRIDIN-5-YL NUCLEOBASE FOR GC BASE PAIR RECOGNITION IN THE PARALLEL TRIPLEX DNA

Motoi Nakahara, Yoshiyuki Hari,* and Satoshi Obika

*Graduate School of Pharmaceutical Science, Osaka University, 1-6 Yamadaoka, Suita, Osaka 560-0871, Japan

Abstract

DNA triple helices containing consecutive C+H•GC triplets are unstable at physiological pH because protonations of cytosines into the third strand are necessary. Previously, a 2-aminopyridin-5-yl nucleobase (P) was developed and has been widely used as a substitute for the cytosine nucleobase. In this work, we designed a 2-amino-6-methylpyridin-5-yl nucleobase (PMe), which could preferentially adopt an anti-orientation by the 6-methyl group. This might lead to formation of a stable base triplet with a GC base pair compared to P. We also synthesized 15-mer triplex-forming oligonucleotides (TFOs) containing PMe by the standard solid-phase method and evaluated the triplex stability of the TFOs at physiological pH by UV melting experiments.