HETEROCYCLES

■ Contents

■ Synthesis of Unsymmetric HetAr–X–HetAr’ Compounds by Rhodium-Catalyzed Heteroaryl Exchange Reactions

Mieko Arisawa,* Saori Tanii, Takeru Tazawa, and Masahiko Yamaguchi*

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

Abstract

Unsymmetric HetAr-X-HetAr’ compounds have flexible and chiral structures, and are expected to exhibit various biological activities by interacting with proteins and nucleic acids. Unsymmetric HetAr-X-HetAr’ compounds were efficiently synthesized by rhodium-catalyzed heteroaryl exchange reactions, which involved equilibrium control by judicious design of organic heteroaryl reagents. By using this method, unsymmetric HetAr–O–HetAr’, HetAr–S–HetAr’, and HetAr–CH2–HetAr’ compounds as well as HetAr–F compounds were obtained from heteroaryl aryl ethers and various heteroaryl reagents. The rhodium-catalyzed synthesis has a broad applicability, which gives novel unsymmetric HetAr-X-HetAr’ compounds containing five- and six-membered heteroarenes.

■ Synthesis and Crystal Structure of 45,85-Di-tert-butyl-1,3,5,7(2,5)-tetraoxadiazola-2,6(2,6)-dipyridina-4,8(1,3)-dibenzenacyclooctaphane

Katsuhiko Ono,* Satoshi Karasuda, and Masaaki Tomura

*Department of Life Science and Applied Chemistry, Nagoya Institute of Technology, Gokiso-cho, Showa-ku, Nagoya 466-8555, Japan

Abstract

The title compound (N-MC) was synthesized as a nitrogen analog of 25,45,65,85-tetra-tert-butyl-1,3,5,7(2,5)-tetraoxadiazola-2,4,6,8(1,3)-tetrabenzenacyclooctaphane (C-MC). The crystal structure of N-MC was investigated by an X-ray crystallographic analysis, and the crystal was characterized by a step-like columnar structure, which is different from the supramolecular nanotube structure of C-MC. The molecular framework and the number of tert-butyl groups affected the molecular arrangement in the crystal.

■ Synthesis of 2-Aminopyridinium Salts from 2-Iminopyridines as a Starting Material

Iwao Hachiya, Makoto Fukutomi, Naoki Kugisaki, Satoshi Shimada, and Makoto Shimizu*

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

Abstract

Synthesis of multi-substituted 2-aminopyridinium salts is developed using 2-iminopyridines as a starting material. The reactions of multi-substituted 2-iminopyridines prepared by the conjugate addition of ethyl 2-cyanopropanoate to alkynyl imines with several acids proceeded smoothly to give multi-substituted 2-aminopyridinium salts in high yields.

■ Direct β-Arylation of Furans with Aryl Iodides Catalyzed by Dinuclear Palladium Complexes

Takahiro Goto, Hayate Kato, and Naofumi Tsukada*

*Department of Chemistry, Faculty of Science, Shizuoka University, 836 Ohya, Shizuoka 422-8529, Japan

Abstract

Dinuclear palladium complexes formed by a chelate-bridging ligand showed β-selectivity in the direct arylation of furans with iodoarenes. In contrast, the arylation using PPh3 or bpy as ligands gave α-arylfurans as major products. The arylation can be applied to several furans bearing functional groups except electron-withdrawing groups.

■ Cationic Au(I)-Catalyzed Cycloisomerization of N-(2-Alkynylphenyl)indolines for the Construction of Indolobenzazepine Skeleton

Mamoru Ito, Daisuke Inoue, Ryosuke Kawasaki, Kyalo Stephen Kanyiva, and Takanori Shibata*

*Chemistry and Biochemistry, Advanced Research Center of Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 169-8555, Japan

Abstract

An intramolecular reaction of N-(2-alkynylphenyl)indolines proceeded efficiently to give indolo[1,7-ab][1]benzazepine derivatives in high to excellent yields by cationic Au(I)-catalyzed 7-endo-dig selective cycloisomerization along with DDQ oxidation. The present transformation could be used for the intramolecular reaction of N-(2-alkynylphenyl)-1,2,3,4-tetrahydroquinoline and N-(2-alkynylphenyl)-N-methylaniline, and construction of a dibenzazepine skeleton was achieved.

■ Phlenumdines A−C, New Lycopodium Alkaloids Isolated from Phlegmariurus nummulariifolius

Waka Nakayama, Orawan Monthakantirat, Kazumi Fujikawa, Santi Watthana, Susumu Kitanaka, Toshiaki Makino, and Kan'ichiro Ishiuchi*

*Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1, Tanabe-Dori, Mizuho-ku, Nagoya, Aichi, 467-8603, Japan

Abstract

Three new lycopodine-type alkaloids, phlenumdines A−C (1−3), have been isolated from the clubmoss Phlegmariurus nummulariifolius (Blume) Ching, and their structures were elucidated on the basis of spectroscopic data.

■ Synthesis of Benzo[c]thiophen-1(3H)-imine and 2,3-Dihydro-1H-isoindole-1-thione Derivatives through Cyclizations of 2-(1-Hydroxyalkyl)benzothioamides

Kazuhiro Kobayashi* and Takashi Nogi

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

Abstract

The reaction of N-alkyl-2,N-dilithiobenzothioamides, generated by treating N-alkylbenzothioamides with two equivalents of butyllithium, with aldehydes gives the corresponding 2-(1-hydroxyalkyl)benzothioamides, which undergo cyclization on treatment with methanesulfonyl chloride in the presence of triethylamine to yield 3,N-disubstituted (Z)-benzo[c]thiophen-1(3H)-imines. 2,3-Disubstituted 2,3-dihydro-1H-isoindole-1-thiones are obtained by the reaction of the above hydroxy thioamides with two equivalents of sodium hydride followed by an equivalent of phenyl chloroformate.

■ One-Pot, Diversity-Oriented Synthesis of Aryl-Substituted Benzoxacycles Including Benzofuran, Coumarin, and Benzoxazepine

Hisashi Masui, Eri Ohkawa, Rika Kitahara, Kiyofumi Wanibuchi, and Takashi Takahashi*

*Department of Pharmaceutical Sciences, Yokohama University of Pharmacy, 601 Matano-cho, Totsuka-ku, Yokohama 245-0066, Japan

Abstract

A one-pot method for the synthesis of benzoxacycles including benzofuran, coumarin, benzoxazepine, and benzoxazocine from a common synthetic intermediate was established. Benzoxacycles are privileged structures in medicinal chemistry and have featured in several clinically used drugs. The synthesis of a benzofuran containing an aryl substituent was accomplished using potassium carbonate and sodium hydride. The one-pot synthesis of coumarin was also carried out using trans-decalin as the solvent. The optimized conditions for the one-pot synthesis of benzoxazepine can also be applied to the synthesis of benzoxazocine.

■ Synthesis and Two-Photon Absorption Properties of Two Long Conjugated Asymmetric Carbazole Derivatives

Xiao-nan Liu, Wen-jie Cui, Wei-ju Zhu,* Heng Zhang, Xue Tian, Cun Li, Zhen-yu Wu, and Min Fang*

*School of Chemistry and Chemical Engineering, Anhui University and Key Laboratory of Functional Inorganic Materials Chemistry of Anhui Province, Hefei 230601, China

Abstract

Two long π conjugated asymmetric carbazole derivatives, 3-benzothiazolyl-6-(4-(4-methoxystyryl)-styryl)-9-butylcarbazole (M1) and 3-(4-(4-methoxystyryl)styryl)-9-butylcarbazole (M2), were synthesized and characterized by FT-IR, 1H NMR and elemental analyses. Their linear photophysical and two-photon absorption (TPA) properties were investigated by UV-vis absorption, fluorescence emission spectra and the two-photon excited fluorescence (TPEF) measurements in DMF, respectively. The results show that both compounds have strong fluorescence emission and the fluorescence quantum yield (Φ) of M2 (0.36) is higher than M1 (0.25), M1 exhibits larger TPA cross-section (1538 GM) than M2 (564 GM) in the femtosecond regime, indicating their potential applications as excellent optoelectronic material in optical field.

■ Regioselective DMAD-Insertion Reaction of Silyl Dienol Ether of γ-Pyrone under Catalyst- and Heating-Free Conditions

Ichiro Hayakawa,* Yuji Yamanaka, Koichi Mitsudo, Hiromi Ota, and Akira Sakakura*

*Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima-naka, Okayama 700-8530, Japan

Abstract

The reaction of silyl dienol ether of γ-pyrone with dimethyl acetylenedicarboxylate (DMAD) gives the regioselective insertion product in 66% yield. This DMAD-insertion reaction is thought to include a three-step sequence: (1) thermal [2+2]-type cycloaddition reaction of silyl dienol ether of γ-pyrone with DMAD, (2) ring-opening electrocyclic reaction of the cyclobutene skeleton, and (3) hydrolysis of the silyl dienol ether. The present reaction proceeds under mild conditions without any catalysts or heating. In addition, the [2+2]-type cycloaddition reaction proceeds regioselectively at the C3–C4 double bond in the silyl dienol ether of γ-pyrone.

■ Synthesis of 3-(Alkylsulfanyl)-1,4-benzothiazine Derivatives Based on Cyclization of 2-[(Cyanomethyl)sulfanyl]phenyl Isothiocyanate

Kazuhiro Kobayashi,* Hiroki Inouchi, Ryo Hasegawa, and Kazuki Kawano

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

Abstract

Efficient procedures for the preparation of 1,4-benzothiazine-based bicyclic and tricyclic heterocycles have been developed. The reaction of 2-[(cyanomethyl)sulfanyl]phenyl isothiocyanate, readily prepared from commercially available 2-aminobenzenethiol, with sodium hydride was found to give, after aqueous workup, 3-thioxo-3,4-dihydro-2H-1,4-benzothiazine-2-carbonitrile. Treatment with alkyl halides prior to workup yielded 3-(alkylsulfanyl)-4H-1,4-benzothiazine-2-carbonitriles. Successive treatment of these compounds with sodium hydride and alkyl halides afforded 4-alkyl-3-(alkylsulfanyl)-2H-1,4-benzothiazine-2-carbonitriles. These procedures can be applied to the synthesis of some 1,4-benzothiazine-based tricyclic heterocycles.