HETEROCYCLES

■ Contents

■ Preface to Heterocycles Issue
Honoring the 77th Birthday of Professor Isao Kuwajima

Eiichi Nakamura*

*Department of Chemistry, Graduate School of Science, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8567, Japan

■ Preface to Heterocycles Issue
Honoring the 77th Birthday of Professor Isao Kuwajima

Keiji Tanino*

*Department of Chemistry, Graduate School of Science, Hokkaido University, Kita 10 Nishi 8, Kita-ku, Sapporo, Hokkaido 060-0810, Japan

■ Curriculum Vitae

Isao Kuwajima*

*

■ List of Publication (Isao Kuwajima)

Isao Kuwajima*

*

■ Prenylated Acylphloroglucinols and Meroterpenoids from Hypericum Plants

Naonobu Tanaka and Jun'ichi Kobayashi*

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

Abstract

Hypericum plants {family Clusiaceae (APG: Hypericaceae)} are known to be a rich source of prenylated acylphloroglucinols (PAPs), some of which have attracted attention as new drug leads as well as challenging targets for total synthesis. This review covers the researches of the isolation and structure elucidation of PAPs from Hypericum plants from 2006 to 2013. Several meroterpenoids with interesting chemical structures isolated from this genus are also summarized.

■ Light Absorption Spectral Patterns of Intact Garden Flowers in Relation to the Flower Colors and Anthocyanin Pigments

Norio Saito, Fumi Tatsuzawa,* and Toshio Honda

*Laboratory of Olericultural and Floricultural Science, Faculty of Agriculture, Iwate University, 3-18-8 Ueda, Morioka, Iwate 020-8550, Japan

Abstract

Spectrophotometric studies were made on fresh flower petals of 139 species and/or cultivars in forty families on the basis of their absorption peaks in the visible light wavelength region. The absorption spectra measured were classified into mainly four flower groups according to the types of aglycones (anthocyanidins) and their absorption spectral patterns. The relationships between flower colors, absorption spectra and structures of anthocyanins were investigated for the above mentioned four flower groups. These investigations may give a clue to the chemical basis of color variation in the flowers.

■ Synthesis of 2,6-Diaminoazulenes by the SNAr Reaction with Cyclic Amines

Taku Shoji,* Yuki Fujiwara, Akifumi Maruyama, Mitsuhisa Maruyama, Shunji Ito, Masafumi Yasunami, Ryuji Yokoyama, and Noboru Morita

*Department of Chemistry, Faculty of Science, Shinshu University, Asahi, Matsumoto 390-8621, Japan

Abstract

2-Amino-6-bromoazulene derivatives reacted with cyclic amines (pyrrolidine, piperidine and morpholine) under the sealed-tube conditions to afford the corresponding 2,6-diaminoazulenes in excellent yields.

■ Cobalt-Catalyzed C5-Selective C-H Functionalization of 4-Me-Quinolines with Styrenes: An Approach to 5,6-Dihydro-4H-benzo[de]quinolines

Shohei Yamamoto, Shigeki Matsunaga,* and Motomu Kanai*

*Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan

Abstract

Cobalt-catalyzed C5-selective C-H functionalization of 4-Me-quinolines is described. A postulated cobalt-hydride catalyst, generated from 2 mol % of CoI2, promoted the reaction of 4-Me-quinolines with styrenes, giving 5,6-dihydro-4H-benzo[de]quinolines (34-55% yield) in one-pot. A plausible reaction mechanism is also described.

■ 2-Aryl-4-quinolone Synthesis Using the Thermal Rearrangement of Iminocyclobutenones

Iwao Hachiya, Keiichi Yokoyama, Akinori Ito, and Makoto Shimizu*

*Department of Chemistry for Materials, Graduate School of Engineering, Mie University, 1577 Kurimamachiya-cho Tsu, Mie 514-8507, Japan

Abstract

2-Aryl-4-quinolone synthesis is developed using the thermal rearrangement of iminocyclobutenones formed by a conjugate addition reaction of ketene silyl acetals to alkynyl imines.

■ Crystal Structures of 3-Methylpyrrolo[2,3-b]tropone and Its Copper(II) Complex

Kanji Kubo,* Taisuke Matsumoto, Keiko Ideta, and Akira Mori

*Department of Life Science and Technology, Faculty of Engineering, Hokkai-Gakuen Univiersity, Sapporo, Hokkaido 062-8605, Japan

Abstract

The crystal structures of 3-methylpyrrolo[2,3-b]tropone (1) and its Cu(II) complex (12∙Cu) were analyzed by X-ray crystallography. The structure of 1 exists in the crystal in its keto form rathar than in the enol form (1’). Pyrrolotropone (1) formed a 2:1 complex with Cu(II). The Cu(II) ion has a tetragonal environment formed by two tropone O atoms and two pyrrole N atoms.

■ Three-Component Synthesis of Indolizines from Azaaromatic-Acetylenedicarboxylate Zwitterions with Acylzirconocene Chloride Complexes

Akio Saito,* Naoki Yamashita, Kohei Sudo, and Yuji Hanzawa

*Division of Applied Chemistry, Graduate School of Engineering, Tokyo University of Agriculture and Technology, 2-24-16 Nakamachi, Koganei, Tokyo 184-8588, Japan

Abstract

Acylzirconocene chloride complexes worked well as a reaction partner of azaaromatic-acetylenedicarboxylate zwitterions derived from isoquinolines or pyridines with diethyl acetylenedicarboxylate to afford the corresponding indolizine derivatives.

■ Facile Synthesis of Guaiazulene-Heterocycle Hybrids via Ugi Multicomponent Reactions

Naoko Takenaga,* Koh Fukazawa, Miki Maruko, and Koichi Sato*

*Laboratory of Medicinal Chemistry, Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, Japan

Abstract

The Ugi reaction with isocyanoazulene 1 afforded a variety of azulene-heterocycle hybrids. The described approach could be applied to combinatorial synthesis of biologically active compounds of the azulene series.

■ Synthesis and Structural Characterization of a Novel Organotellurium Compound: Dinaphtho[2,3-b;2’,3’-d]tellurophene

Mio Matsumura, Atsuya Muranaka, Naoki Kakusawa, Jyoji Kurita, Daisuke Hashizume, Masanobu Uchiyama,* and Shuji Yasuike*

*Faculty of Pharmaceutical Sciences, Aichi Gakuin University, 1-100 Kusumoto-cho Chikusa-ku Nagoya city 464-8650, Japan

Abstract

The first example of dinaphtho[2,3-b;2’,3’-d]tellurophene (1d) has been synthesized by the condensation of tellurium with 3,3’-dilithio-2,2’-binaphthalene. Single crystal X-ray analysis of 1d revealed that naphthalene and tellurophene rings are almost coplanar. A linear relationship (R2 = 0.971) between the atomic radius of Group 16 elements and the HOMO-LUMO gap energies of 1a–d was found by density functional theory (DFT) calculations.

■ Three-Way Output Molecular Response System Based on Tetrakis(3,4-dialkoxyphenyl)-3,4-dihydro[5]helicenes: Perturbation of Properties by Long Alkyl Chains

Yusuke Ishigaki, Satoshige Yoshida, Hidetoshi Kawai, Ryo Katoono, Kenshu Fujiwara, Takanori Fukushima, and Takanori Suzuki*

*Division of Chemistry, Graduate School of Science, Hokkaido University, Kita 10 Nishi 8, Kita-ku, Sapporo, Hokkaido 060-0810, Japan

Abstract

Starting from (S)-dimethyl 1,1'-binaphthyl-2,2'-dicarboxylate, optically pure (P)-3,3,4,4-tetrakis(3,4-dialkoxyphenyl)-3,4-dihydro[5]helicenes (P)-1 were prepared via bis(diarylhydroxymethyl)binaphthyl and/or tetraaryldinaphthodihydroxepin as key intermediates. Upon electrochemical oxidation to the corresponding (S)-1,1'-binaphthyl-2,2'-diylbis(diarylcarbenium)s (S)-22+, three kinds of spectral changes (UV-Vis, circular dichroism, fluorescence) were successfully observed. Compared to the methoxy compound, the octyloxy and hexadecyloxy derivatives exhibit a redshifted emission maxima in the dihydro[5]helicenes. The long alkyl chains induce step-by-step two-electron reduction of the binaphthyldiyl(dicarbenium)s whereas the dication with methoxy groups exhibits one-wave two-electron process.

■ Bis(diarylethenyl)thiophene, -bithiophene, and -terthiophene: A New Series of Violene-Cyanine Hybrid-Type Electron Donors

Yusuke Ishigaki, Hidetoshi Kawai, Ryo Katoono, Kenshu Fujiwara, and Takanori Suzuki*

*Division of Chemistry, Graduate School of Science, Hokkaido University, Kita 10 Nishi 8, Kita-ku, Sapporo, Hokkaido 060-0810, Japan

Abstract

The title fluorescent (oligo)thiophenes 1-3 were designed as new violene/cyanine-hybrid-type electron donors, which have two 4-methoxyphenyl groups each on the two cyanine parts. Voltammetric analyses showed that they all undergo reversible two-stage one-electron oxidation. The intramolecular short S(thiophene) -- Cipso(Ar) contacts were commonly present in their X-ray structures, and the coplanarily extended geometries are suitable for π-delocalization. Electrochemical oxidation of 1-3 caused continuous changes in their UV-Vis-NIR and fluorescence spectra although the oxidized species are too labile to be isolated.

■ Palladium(0)-Mediated C−S and O−H Bonds Cleavage Reaction in 2-Hydroxybenzyl Phenyl Sulfide: Formations of Oxyphosphorane and 1,2-Oxapalladacycle

Norio Nakata, Noriyuki Furukawa, Hiroki Kobayashi, Izuru Suzuki, and Akihiko Ishii*

*Department of Chemistry, Faculty of Science, Saitama University, Urawa, Saitama 338-8570, Japan

Abstract

Treatment of 2-hydroxybenzyl phenyl sulfide 3 with 1.5 equiv. of [Pd(PPh3)4] in toluene led to the unanticipated formation of oxyphosphorane 4 in 30% isolated yield. In contrast, the reaction of 3 with Pd(0) complex bearing PMe3 ligands in toluene afforded the corresponding 1,2-oxapalladacycle 7 and oxyphosphorane 9 in addition to dithiolato complex trans-[Pd(SPh)2(PMe3)2] 8.

■ Total Syntheses of Zwitterionic Indole Alkaloids, Flavocarpine and Dihydrovincarpine, by Extended Method for Substituted Pyridine Synthesis through Azaelectrocyclization

Yoshikatsu Hirose, Hiroshi Tsuchikawa, Toyoharu Kobayashi,* and Shigeo Katsumura*

*School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda, Hyogo 669-1337, Japan

Abstract

The total syntheses of flavocarpine (1) and dihydrovincarpine (2) have been accomplished through the common intermediate, 2,4,5-trisubstituted pyridine compound 3 which was prepared by the accelerated 6π-azaelectrocyclization of 4-alkoxycarbonylazatriene 4 followed by aromatization of the resulting dihydropyridine derivative.

■ Tandem [4+2] Cycloaddition/Aromatization Sequence of Allenyl 2-Bromo-3-vinylcyclohex-2-enyl Thioether to Naphtho[1,8-bc]thiophene

Noriyuki Hatae,* Aiichirou Kaji, Chiaki Okada, and Eiko Toyota

*Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan

Abstract

A concise synthetic route of tetrahydro-3H-naphtho[1,8-bc]thiophene was developed. Allenyl 2-bromo-3-vinylcyclohex-2-enyl thioether underwent a tandem [4+2] cycloaddition/aromatization sequence to produce the naphthothiophene with high yield. A density functional study for the transition and reaction enthalpies was performed to elucidate the details of the reaction.

■ Synthesis of α-Halobutenolides Using the Nucleophilicity of Magnesium Alkylidene Carbenoids

Tsutomu Kimura,* Kazuki Fukuda, Gaku Kashiwamura, and Tsuyoshi Satoh*

*Tokyo University of Science, Kagurazaka 1-3, Shinjuku-ku, Tokyo 165-0035, Japan

Abstract

α-Halobutenolides were synthesized from halomethyl p-tolyl sulfoxides, α-bromoketones, and phenyl chloroformate in three steps using the nucleophilicity of magnesium alkylidene carbenoids. The reaction of α-bromoketones with [halo(p-tolylsulfinyl)methyl]lithiums and the subsequent basification of the reaction mixture using an aqueous NaOH solution afforded 1-chloro-3-hydroxyprop-1-enyl p-tolyl sulfoxides in 83–99% yield. A phenoxycarbonyl group was then introduced to the hydroxyl group of the sulfoxides by reacting with phenyl chloroformate in the presence of pyridine. The sulfoxide/magnesium exchange reaction of the cyclization precursors with i-PrMgCl•LiCl led to the formation of α-halobutenolides in moderate to good yields.

■ Halichonadins M-Q, Sesquiterpenes from an Okinawan Marine Sponge Halichondria sp.

Naonobu Tanaka, Shohei Suto, Miki Asai, Taishi Kusama, Azusa Takahashi-Nakaguchi, Tohru Gonoi, Jane Fromont, and Jun'ichi Kobayashi*

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

Abstract

Four new dimeric sesquiterpenes, halichonadins M–P (1–4), and one new sesquiterpene, halichonadin Q (5), were isolated from an Okinawan marine sponge Halichondria sp. The sesquiterpenes have eudesmane skeleton in common. Halichonadin M (1) is a symmetrical dimer linked to a nitrilotriacetic acid fragment through amide bonds. Halichonadin N (2) is a structurally unique dimeric sesquiterpene connected via a pyrrolidine unit, while halichonadins O (3) and P (4) have linker moieties consisting of a piperidine unit. Halichonadin Q (5) is a sesquiterpene possessing a pyrrolidine unit. The structures of 1–5 were elucidated by spectroscopic analysis. Halichonadin O (3) showed antimicrobial activity against Staphylococcus aureus, Micrococcus luteus, and Trichophyton mentagrophytes.

■ Pd/C-Catalyzed Hydrodechlorination of Dioxins from Fly Ash under Ambient Pressure and Temperature

Yasunari Monguchi,* Akiko Ido, Miki Niikawa, Nobuharu Nagatsu, Ryosuke Mizukoshi, Hisamitsu Nagase, and Hironao Sajiki*

*Laboratory of Organic Chemistry, Department of Pharmaceutical Sciences, Gifu Pharmaceutical University, 1-25-4 Daigakunishi, Gifu 501-1196, Japan

Abstract

Dioxins, such as polychlorinated dibenzodioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs), which could be efficiently extracted from fly ash based on the method approved by the Japanese Industrial Standard, were degraded by the palladium on carbon (Pd/C)-catalyzed hydrodechlorination in the presence of triethylamine at room temperature under ordinary pressure with a greater than 97% efficiency. The distinct features of the present degradation method of dioxins are its mildness, simplicity, safety, and efficiency without any expensive facilities.

■ Formation of 2-Acetamido-2-deoxy-D-glucopyranosidic Linkages via Glycosidation Using a Combination of Two Lewis Acids

Yoshiki Oda, Masanobu Midorikawa, and Takashi Yamanoi*

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

Abstract

A mixed activation system composed of ytterbium(III) triflate and a catalytic boron trifluoride diethyl etherate complex efficiently promotes the glycosylation of various alcohol acceptors using 2-acetamido-3,4,6-tri-O-benzyl-2-deoxy-α-D-glucopyranosyl acetate in dichloromethane at room temperature to afford 2-acetamido-2-deoxy-D-glucopyranosides in good yields with significant formation of the α-isomers. Notably, stereoselective glycosylations of phenol derivatives as the acceptors afforded aryl 1,2-cis-α-glycosides without the formation of any β-isomers. This highly stereocontrolled 1,2-cis-α-glycosidation was applied to the synthesis of a novel hydroquinone α-glycoside.

■ Synthesis of 7-Alkyl-6-amino-7H-pyrrolo[2,3-d]pyrimidine-6-carbonitriles by the Copper-Catalyzed Reaction of 4-(Alkylamino)-5-iodopyrimidines with Propanedinitrile

Kazuhiro Kobayashi,* Kazuya Nakazawa, Shohei Yuba, Hidetaka Hiyoshi, and Kazuto Umezu

*Division of Applied Chemistry, Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori University, 4-101 Koyama-minami, Tottori 680-8552, Japan

Abstract

A convenient sequence for the first general preparation of 6-aminopyrrolo[2,3-d]pyrimidine-5-carbonitrile derivatives has been developed. Thus, treatment of 4-chloro-6-methoxypyrimidines with lithium diisopropylamide in THF at –78 °C lithiated the 5-position to generate 4-chloro-5-lithio-6-methoxypyrimidines, which were allowed to react with iodine to give 4-chloro-5-iodo-6-methoxypyrimidines in good yields. Substitution of the 4-chloro group of these compounds with primary amines in the presence of triethylamine in refluxing THF afforded 4-(alkylamino)-5-iodo-6-methoxypyrimidines. The reaction of these aminated compounds with propanedinitrile (malononitrile) in the presence of a catalytic amount of copper(I) iodide and excess potassium carbonate in dimethyl sulfoxide at 100 °C provided 7-alkyl-6-amino-4-methoxypyrrolo[2,3-d]pyrimidine-5-carbonitriles in moderate yields.

■ Diversity Oriented Approach to Phenylalanine Derivatives via the Diels-Alder Reaction Involving Sulfolene Intermediates

Sambasivarao Kotha* and Vijayalakshmi Bandi

*Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai - 400076, India

Abstract

We report a new synthetic approach to highly functionalized phenylalanine derivatives via sulfolenes as latent diene equivalents. Here, the Diels−Alder reaction has been used as a key step to assemble diverse unusual amino acid derivatives.

■ Unusually Efficient Deformylative Synthesis of 1,2,8,9-Tetrasubstituted Dipyrrins from 4,5-Disubstituted Pyrrole-2-carbaldehydes

Mitsunori Oda,* Yurie Fujiwara, Yoshimitsu Kumai, Akira Ohta, and Ryuta Miyatake

*Department of Chemistry, Faculty of Science, Shinshu University, Asahi 3-1-1, Matsumoto, Nagano 390-8621, Japan

Abstract

Upon heating in a mixture of hydrobromic acid and acetic acid, 4-arylmethyl-5-(4-methoxyphenyl)pyrrole-2-carbaldehydes (9a–c) react to give 2,8-bis(arylmethyl)-1,9-bis(4-methoxyphenyl)dipyrrins (10a–c) in high yields, demonstrating the first example of an unusually efficient deformylative transformation of pyrrole-2-carbaldehyde to dipyrrin. Dipyrrins 10 show a clear color change from red to blue, when exposed to Brønsted acid. Structure of 10a·H+ was determined by X-ray crystallographic analysis. The absorption change of 10a in the presence of a metal ion was also studied.

■ Palladium-Catalyzed [3+2] Annulation of meso-Bromoporphyrin with Silylacetylenes and Desilylation of 8a-Silyl-7,8-dehydropurpurin

Norihito Fukui, Seiji Arai, Hiroshi Shinokubo, Hideki Yorimitsu,* and Atsuhiro Osuka*

*Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo, Kyoto 606-8502, Japan

Abstract

Palladium-catalyzed [3+2] annulation of meso-bromoporphyrins with trimethylsilyl-, tert-butyldimethylsilyl-, and triisopropylsilylacetylenes afforded 8a-silyl-7,8-dehydropurpurins. Protodesilylation of 8a-trimethylsilyl-7,8-de- hydropurpurin resulted in the first synthesis of an 8a,8b-unsubstituted 7,8-de hydropurpurin.

■ Hexaaryl-benzodipyrroles: Properties and Application as Amorphous Carrier-Transporting Materials

Hayato Tsuji,* Yuki Yokoi, Shunsuke Furukawa, and Eiichi Nakamura*

*Department of Chemistry, Graduate School of Science, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8567, Japan

Abstract

We have newly synthesized 1,2,3,5,6,7-hexaarylbenzo[1,2-b:4,5-b′]dipyrroles (HABDPs) and studied their properties. The HABDPs showed UV absorption maxima at 377–390 nm, indicating their extended π-conjugation system. They were also found to serve as efficient amorphous materials, featuring high electrochemical and thermal stability with high carrier mobility of up to 10–3 cm2/Vs using the time-of-flight technique. Application of the HABDPs to organic light-emitting diodes resulted in significantly improved performance in driving voltage and efficiency compared with α-NPD, a commonly used hole-transporting material.

■ Copper Mediated Formation of Carbon-Heteroatom Bonds Using Organoboron Reagents and Ultrasound

Bryan J. Musolino and George W. Kabalka*

*Chemistry Department, University of Tennessee, Knoxville, Tennessee, 37996-1600, U.S.A.

Abstract

This report summarizes research efforts focused on copper acetate mediated reactions to form new carbon-heteroatom bonds using organoboron reagents under ultrasound irradiation. The method involves the application of ultrasound irradiation to the Chan-Evans-Lam reaction to achieve O-arylation of phenols, N-arylation of anilines and indoles, and S-arylation of thiols. Ultrasound irradiation was found to decrease reaction times from 72 hours to 4 hours while improving the product yields an average of 20%.1 Representative C-O, C-N, and C-S coupling reactions were successfully scaled-up from the milligram to gram levels while maintaining good product yields offering potential applications in industrial processes.

■ ABC → ABCE/D Based Approaches to the Pentacyclic Ring System of the Vinca Alkaloids Using Intramolecular Hetero-[2+2]cycloaddition and Gold(I)-Catalyzed 6-endo-dig Cyclisation Protocols

Lorenzo V. White, Martin G. Banwell,* and Anthony C. Willis

*Research School of Chemistry, Australian National University, Canberra, ACT 0200, Australia

Abstract

The angularly substituted tetrahydrocarbazole 13, which is readily obtained from cyclohexane-1,4-dione monoethylene ketal (6) using Fischer indole chemistry, has been converted into the isothiocyanate 16. Photolysis of this last compound affords, via an intramolecular hetero-[2+2]cycloaddition reaction, the pentacyclic β-thiolactam 17 that incorporates the ABCE ring substructure of natural products 1–3. Attempts to effect a two-carbon homologation of the four-membered ring within compound 17, and thereby establish the D-ring, failed. The azide 20, also obtained from compound 13, forms the cyclic imine 21 on thermolysis in refluxing toluene and the readily derived enamide 23 engages in a Au(I)-catalysed 6-endo-dig cyclisation reaction to give compound 24 embodying the ABCDE ring system of the title alkaloids.