HETEROCYCLES

■ Contents

■ Portrait

Victor Snieckus*

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

■ Preface – Honoring the 77th Birthday of Professor Victor Snieckus

Gordon W. Gribble*

*6128 Burke Laboratory, Department of Chemistry, Dartmouth College, Hanover, New Hampshire 03755, U.S.A.

■ Curriculum Vitae – Victor Algirdas Snieckus

Victor Snieckus*

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

■ Publications

Victor Snieckus*

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

■ Synthesis of Heterocycles via Nucleophilic Substitution of Hydrogen in Nitroarenes

Mieczysław Mąkosza* and Krzysztof Wojciechowski

*Institute of Organic Chemistry, Polish Academy of Sciences, ul. Kasprzaka 44/52, P.O.Box 58, PL-01-224 Warszawa 42, Poland

Abstract

The main message of this review is that nucleophilic substitution of hydrogen in nitroarenes and other electron-deficient arenes is primary general process of wide scope and great value in organic synthesis, whereas conventional nucleophilic substitution of halogens, SNAr reaction, is just a secondary process. Nucleophilic substitution of hydrogen in electron-deficient arenes is a powerful tool in organic synthesis, effectively applicable to the synthesis of heteroaromatic compounds.

■ Additive Effects on Asymmetric Hydrogenation of N-Heteroaromatics

Takuto Nagano, Atsuhiro Iimuro, Kenta Yamaji, Yusuke Kita, and Kazushi Mashima*

*Graduate School of Engineering Science, Osaka University, 1-3 Machikaneyama, Toyonaka, Osaka 560-8531, Japan

Abstract

The multiplication of chiral information is one of the most important tasks in organic chemistry. Chiral catalysis is the most elegant way to achieve this and organic chemists developed a variety of catalytic asymmetric reaction systems, in which the addition of some chemicals effectively improves the performance of transition-metal-catalysis. In this review, we summarize development of additive effects in the asymmetric hydrogenation of N-heteroaromatic compounds based on interactions of additives with catalysts and substrates.

■ Hydrazines and Azo-Compounds in the Synthesis of Heterocycles Comprising N-N Bond

Svetlana Tšupova and Uno Mäeorg*

*TBD-Biodiscovery, Tiigi 61b, 50410 Tartu, Estonia

Abstract

The synthesis of nitrogen containing heterocycles is of great importance in modern science, owing to their valuable biological properties, and endocyclic hydrazinocycles are no exception. There are methods that enable the transformation of amines to hydrazines, however the use of hydrazine derivatives and azo-compounds as starting materials is both logical and straightforward. In this review we aimed to summarize the methods that use simple hydrazines and azo-compounds for the synthesis of these heterocycles. We begin with simple stoichiometric alkylation of hydrazines and later on move to catalytic systems. Finally, we provide an overview of the advances in the field of azomethine imines chemistry.

■ Synthesis and Characterization of Nickel Complex of 4-Amino-3-pyridinethiolate

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

A Ni(Hapt)2 complex, apt = 4-amino-3-pyridinethiolate, is isolated and characterized by X-ray crystallography, cyclic voltammetry, and UV-Vis spectroscopy.

■ N,N-Bond Formation in Intramolecular Cobalt-Catalyzed [2+2+2] Cyclizations of Alkynyl-Linked Bisnitriles, and the Preparation of Annulated Pyridazines

Cuifang Cai, Megan A. Audet, and John K. Snyder*

*Department of Chemistry, Boston University, 590 Commonwealth Ave RM 474, Boston, MA 02215, U.S.A.

Abstract

Cobalt(I) catalyzed intramolecular [2 + 2 + 2] cyclization of bisnitriles linked through a central alkyne has led to a facile route to annulated pyridazines. Ring closure through N,N-bond formation allows the construction of annulated pyridazine scaffolds that can be utilized in further small molecule library syntheses.

■ One-Pot Access to 3,3’-Bisindolylmethanes through the Intermolecular Pummerer Reaction

Takumi Abe, Toshiaki Ikeda, Tomoki Itoh, Noriyuki Hatae, Eiko Toyota, and Minoru Ishikura*

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

Abstract

A one-pot synthesis of 3,3’-bisindolylmethanes was developed through the intermolecular Pummerer reaction using indole as a nucleophile.

■ Palladium-Catalyzed Borylation of Aryl Iodides with 2,3-Dihydro-1H-benzo[d][1,3,2]diazaboroles

Miki Murata,* Nobuyoshi Hirai, Michihiro Okuyama, Takeshi Namikoshi, and Shinji Watanabe

*Department of Materials Science and Engineering, Kitami Institute of Technology, Koen-cho 165, Kitami, Hokkaido 090-8507, Japan

Abstract

The palladium-catalyzed borylation of aryl iodides with 2,3-dihydro-1H-benzo[d][1,3,2]diazaboroles was achieved. The mild reaction conditions employed allowed for the inclusion of a wide variety of functional groups in aryl iodides to be tolerated. Additionally, the borylated products can be transformed into the corresponding boronic acids or their esters under acidic conditions.

■ Formation of 1,2-cis-α-Aryl-glycosidic Linkages Directly from 2-Acetamido-2-deoxy-D-glucopyranosyl Acetate by the Mixed Activating System Using Ytterbium(III) Triflate and Catalytic Boron Trifluoride Diethyl Etherate Complex

Takashi Yamanoi,* Masanobu Midorikawa, and Yoshiki Oda

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

Abstract

We found that a mixed activating system using ytterbium(III) triflate and a catalytic boron trifluoride diethyl etherate complex efficiently promoted glycosidation of the 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 along with the formation of a considerable amount of α-isomers. Glycosylations of the aryl alcohols as the acceptors stereoselectively afforded aryl α-glycosides without producing any β-isomers.

■ Preparation and Electrochemical Property of Octaethylphthalocyanine Fused with Four Diselenadithiafulvalene Units

Takeshi Kimura*

*Center for Instrumental Analysis, Iwate University, 4-3-5 Ueda, Morioka, Iwate 020-8551, Japan

Abstract

3,6-Diethylphthalonitrile (3) fused with diselenadithiafulvalene (DSDTF) was prepared from 5,6-dibromo-4,7-diethylbenzotriselenole (1) and treated with lithium alkoxide to produce octaethylphthalocyanine (6) with four DSDTF units. The structure of the product was determined by 1H NMR and MALDI-TOF-MS. Electrochemical and optical properties of 6 and its nickel complex (6-Ni) were examined by cyclic voltammetry and UV-vis spectroscopy.

■ Introduction of Heteroarene Functionality on the Bipedal-Thiol-Capped Gold Nanoparticle by Deprotonative C-H Coupling with Palladium Complex

Atsushi Sugie, Hiroki Yamauchi, Kei Miyamura, Kenta Kumazawa, Shota Tanaka, Kiyoshi Kanie, Atsushi Muramatsu, and Atsunori Mori*

*Chemical Science & Technology, Graduate School of Engineering, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan

Abstract

Gold nanoparticle stabilized by adsorption of bipedal thiol whose end is modified with bromoarene is prepared to undergo palladium-mediated deprotonative C-H arylation reaction. Heteroarenes are introduced onto the organic moiety of the nanoparticle.

■ Palladium-Catalyzed Tetraarylation of 5,15-Dialkylporphyrins with Aryl Bromides

Yutaro Yamamoto, Sumito Tokuji, Takayuki Tanaka, Hideki Yorimitsu,* and Atsuhiro Osuka*

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

Abstract

Nickel complexes of 5,15-dialkylporphyrins are subjected to palladium-catalyzed direct arylation under the modified Fagnou conditions. The arylation takes place still exclusively at the four less hindered β positions although the meso-nonyl, hexyl, and propyl groups are considered to impose less steric hindrance than the meso-3,5-di-tert-butylphenyl group in the previous report.

■ Cu/HP20-Catalyzed Solvent-Free Huisgen Cycloaddition at Ordinary Temperatures

Yoshiaki Kitamura, Kazumi Taniguchi, Tomohiro Maegawa, Yasunari Monguchi, Yukio Kitade, and Hironao Sajiki*

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

Abstract

We have developed an environmentally friendly and highly efficient solvent-free Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction using a polymer-supported copper catalyst (Cu/HP20). Substrates poorly soluble in common organic solvents are also applicable to the present cycloaddition reaction without any solvents and provide the corresponding 1,4-triazole in high yields.

■ Efficient Oxidative Spirolactamization by μ-Oxo Bridged Heterocyclic Hypervalent Iodine Compound

Toshifumi Dohi, Eisuke Mochizuki, Daisuke Yamashita, Keitaro Miyazaki, and Yasuyuki Kita*

*College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga, 525-8577, Japan

Abstract

In this report, the authors have clarified that the μ-oxo bridged heterocyclic hypervalent iodine compound 1 shows a more effective reactivity in the oxidative dearomatizing spirolactamization compared to conventional PIDA (phenyliodine(III) diacetate). Besides the high reactivity, a new selectivity during the oxidations based on the steric discrimination of the nitrogen groups of the pre-spirocyclic substrates is demonstrated for the heterocyclic hypervalent iodine compound 1.

■ Synthesis and Optical Properties of 2,2'-Biimidazole and Benzo[d]imidazole Derivatives: Changing π-Conjugation by Photoexcitation

Shoji Matsumoto,* Yu Zhao, and Motohiro Akazome

*Department of Applied Chemistry and Biotechnology, Graduate School and Faculty of Engineering, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan

Abstract

1,1′,5,5′-Tetraaryl-2,2′-biimidazole and benzo[d]imidazole derivatives were synthesized. Symmetrical and unsymmetrical benzo[d]imidazole derivatives could be obtained by the Pd-catalyzed coupling reaction between 2-iodo-benzo[d]imidazole and the corresponding (benzo)imidazole anion. Hypsochromic shifts in absorption and fluorescence spectra of 1,1′,5,5′-tetraaryl-2,2′-biazole were observed by switching pyrrole rings for imidazole and benzo[d]imidazole rings, resulting in compounds with various Stokes shifts. Based on the (TD)DFT calculation, it was reasoned that changing the conformation of each single bond from a twisted to planar structure by photoexcitation led to larger Stokes shifts.

■ Palladium-Catalyzed Direct Arylation and Alkenylation of 3-(Indol-3-yl)propionic Acids through C–H Bond Cleavage

Daisuke Takeda, Koji Hirano, Tetsuya Satoh,* and Masahiro Miura*

*Department of Applied Chemistry, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan

Abstract

The palladium-catalyzed direct arylation of 3-(indol-3-yl)propionic acids with aryl bromides proceeds through C–H bond cleavages to give C2-arylated product in good yields. The C2-alkenylation of the substrates can also be performed smoothly under appropriate oxidative conditions.

■ New, Lithiation-Based Synthesis of Tofisopam, a 2,3-Benzodiazepine Type Anxiolytic Drug

Erika Molnárné Samu,* Gyula Lukács, Balázs Volk, and Gyula Simig

*Chemical Research Deivision, EGIS Pharmaceuticals PLC, 1106 Hungary, Budapest,
Keresztúri út 30-38, Hungary

Abstract

The classical, widely-used synthesis of the anxiolytic drug tofisopam applies chromium(VI) oxide reagent for the synthesis of the diketone key intermediate. The chromium salts formed in the course of the reaction are strongly toxic compounds. In order to reduce the reagents contributing to the pollution of the environment, an alternative manufacturing process has been elaborated at our laboratory. Starting compound (3,4-dimethoxyphenyl)acetone was transformed to the ethylene ketal of (2-bromo-4,5-dimethoxyphenyl)acetone. Bromine-lithium exchange and introduction of a 3,4-dimethoxybenzoyl moiety resulted in the new key intermediate. Removal of the ketal protecting group and ring closure with hydrazine was carried out in one pot affording drug substance tofisopam.

■ Total Synthesis of the Benzo[c]phenanthridine Alkaloids, Terihanine and Isoterihanine, and Their Antitumor Activity

Yuhki Kurata, Tominari Choshi,* Yuhsuke Ishihara, Noriyuki Hatae, Takashi Nishiyama, and Satoshi Hibino*

*Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Fukuyama, Hiroshima 729-0292, Japan

Abstract

A new total synthesis of terihanine (2a) and isoterihanine (2b) was established by our new bond formation between the C4b and N5 positions of the benzo[c]phenanthridine ring based on a microwave-assisted thermal electrocyclic reaction of 2-cycloalkenylbenzaldoxime as an aza 6π-electron system. In addition, the antitumor activity of these synthesized compounds, including nitidine and nornitidine was evaluated in HCT-116 cells.

■ Synthetic Approaches to 3,3’-Biindolyl and 3,3’-Biindazolyl Derivatives

Azadeh Nakhai and Jan Bergman*

*Department of Biosciences and Nutrition, Unit for Organic Chemistry, Karolinska Institute, Novum Research Park, SE-141 57 Huddinge, Sweden

Abstract

In this paper new syntheses of 3,3’-biindolyl and 3,3’-biindazolyl derivatives are described. Formation of 3,3’-biindolyl derivatives by oxidative coupling of N-acetylindole with TeCl4 gave a good yield, while attempt to use the same reaction conditions for synthesis of 3,3’-biindazolyl derivatives failed. However, conversion of 3-haloindazole derivatives to its trimethylstannane derivative, followed by palladium-catalyzed Stille cross-coupling reaction, resulted in formation of 3,3’-biindazolyl derivatives.

■ Synthesis, Properties, and Crystal Structure of DDQ-Adducts of Ethynylated 2H-Cyclohepta[b]furan-2-ones

Taku Shoji,* Mitsuhisa Maruyama, Erika Shimomura, Akifumi Maruyama, Shunji Ito, Masafumi Yasunami, Junya Higashi, Kozo Toyota, and Noboru Morita*

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

Abstract

Ethynylated 2H-cyclohepta[b]furan-2-ones reacted with 2,3-dichrolo-5,6-dicyano-1,4-benzoquinone (DDQ) in a formal [2+2] cycloaddition reaction to afford the corresponding DDQ-adducts in good yields. The electronic properties of the DDQ-adducts were investigated by UV/Vis spectroscopy. One of the DDQ-adducts was revealed the molecular structure by X-ray crystallographic analysis. The redox behavior of the new compounds was examined by cyclic voltammetry (CV) and differential pulse voltammetry (DPV).

■ Diastereoselective Synthesis of 3-Fluoro-2-substituted Piperidines and Pyrrolidines

Paul N. Gichuhi, Masami Kuriyama, and Osamu Onomura*

*Department of Natural Product Chemistry, Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan

Abstract

A facile procedure for synthesis of trans-3-fluoro-2-substituted piperidines by utilizing electrophilic fluorination of cyclic enamines and Lewis acid mediated nucleophilic substitution has been developed. Also, optically active trans-2-allyl-3-fluorinated pyrrolidines have been prepared by utilizing nucleophilic fluorination of hydroxyl group of trans-hydroxy-L-proline and Lewis acid mediated diastereoselective allylation as key steps.

■ Diastereoselective Lithiation of N-Silyl-Protected (S)-Tetrahydro-1H-pyrrolo[1,2-c]imidazol-3(2H)-one

Costa Metallinos,* Seyed Iraj Sadraei, and Nadezda Zhukovskaya

*Department of Chemistry, Brock University, 500 Glenridge Ave., St. Catharines, Ontario, L2R 3K4, Canada

Abstract

An L-proline-derived imidazolone protected with an N-triethylsilyl (N-TES) group undergoes diastereoselective lithiation–electrophile quench to give C5-substituted products with syn stereochemistry. Unlike the previous N-t-Bu analogues, the N-TES derivatives may be easily N-desilylated to give secondary ureas that serve as precursors to N-phenyl chiral bicyclic guanidines.

■ Isolation, Structure Characterization, and Synthesis of Stabilized 1,2,3,4-Tetrahydroisoquinoline Marine Natural Product from Potassium Cyanide Pretreated Thai Tunicate, Ecteinascidia thurstoni

Shinya Kimura, Waree Pangkruang, Masashi Yokoya, Amane Honda, Ploenthip Puthongking, Khanit Suwanborirux,* and Naoki Saito*

*Department of Medicinal Chemistry, Pharmaceutical Chemistry, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan

Abstract

A simple 1,2,3,4-tetrahydroisoquinoline marine natural product (2a) together with two known compounds (3 and 4) was isolated from a low polar fraction of the crude extract of KCN pretreated Thai tunicate Ecteinascidia thurstoni. The structure of 2a was determined by X-ray crystallographic analysis. We also reported an eight-step large-scale preparation of 2a from isovanillin (9).

■ The Ability of 1-Aryltriazole-Containing Nucleobases to Recognize a TA Base Pair in Triplex DNA

Yoshiyuki Hari,* Motoi Nakahara, Shin Ijitsu, and Satoshi Obika*

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

Abstract

Phosphoramidites bearing propargyl and (N-propargylcarbamoyl)methyl groups at the C1-position of deoxyribose were synthesized and introduced into oligonucleotides by using an automated DNA synthesizer. Copper-catalyzed alkyne-azide 1,3-dipolar cycloaddition of the oligonucleotides with various aryl azides led to triplex-forming oligonucleotides (TFOs) possessing the corresponding aryltriazole-containing nucleobases. The triplex-forming ability of TFOs with double-stranded DNA (dsDNA) was evaluated through UV-melting experiments, and it was demonstrated that m-hydroxy or m-ureido derivatives in the (1-aryltriazol-4-yl)methyl nucleobases likely interacted with a TA base pair in dsDNA.

■ Exploration of Fluoral Hydrazones Derived from Carbohydrazides for the Synthesis of Trifluoromethylated Heterocycles

Grzegorz Mlostoń,* Katarzyna Urbaniak, Natalia Jacaszek, Anthony Linden, and Heinz Heimgartner*

*Institute of Organic Chemistry, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland

Abstract

The reaction of fluoral hydrate with carbohydrazides in methanol in the presence of molecular sieves (4 Å) gave the desired N-acylated fluoral hydrazones (3a–f) in fair yields. Treatment of the latter with mercaptoacetic acid in benzene led to the corresponding 2-trifluoromethyl-1,3-thiazolidinone derivatives (4a–f), whereas the reaction with acetic anhydride gave 3-acetyl-2,3-dihydro-2-trifluoromethyl-1,3,4-oxadiazoles (5a–f). The structures of each type of product have been established by X-ray crystallography.

■ Hydrogen Bond Organocatalysis of Benzotriazole in Transamidation of Carboxamides with Amines

Thanh Binh Nguyen,* Ludmila Ermolenko, Marie-Elise Tran Huu Dau, and Ali Al-Mourabit

*Department of Chemistry, Institut de Chimie des Substances Naturelles, CNRS, 1, Avenue de la Terrasse, 91190 Gif-sur-Yvette, France

Abstract

A new method of transamidation of carboxamides with amines catalyzed by benzotriazole has been developed.