HETEROCYCLES

■ Contents

■ Reactions of Pyridinium N-Ylides and Their Related Pyridinium Salts

Akikazu Kakehi*

*Department of Chemistry and Material Engineering, Faculty of Engineering, Shinshu University, 4-17-1 Wakasato, Nagano 380-8553, Japan

Abstract

This review describes some reactions of pyridinium N-ylides and their closely related pyridinium salts and the formation of various nitrogen-containing heterocycles which are not easily obtainable by other methods and are of high synthetical and pharmaceutical interest.

■ Synthesis of 2,2’-Bipyridines by Transition Metal-Catalyzed Alkyne/Nitrile [2 + 2 + 2] Cycloaddition Reactions

Sentaro Okamoto*

*Department of Material and Life Chemistry, Faculty of Engineering, Kanagawa University, 3-27-1 Rokkakubashi, Kanagawa-ku, Yokohama 221-8686, Japan

Abstract

2,2’-Bipyridines are of great importance in the fields of catalysis, coordination chemistry, supramolecular chemistry, macromolecular chemistry and photochemistry. Recently, the metal-catalyzed [2 + 2 + 2]-type cycloaddition reaction of alkynes and nitriles has attracted considerable interest as a straightforward, atom-economical route to substituted pyridines and methods have been extensively applied to bipyridine synthesis. Developments in the field of 2,2’-bipyridine synthesis through alkyne/nitrile [2 + 2 + 2] cycloaddition reactions catalyzed by transition metals are reviewed in this article involving two types of fully intramolecular reaction, five types of partially intramolecular reaction and fully intermolecular reactions.

■ [1,2]-Wittig Rearrangement of Aromatic Heterocycles

Jingyue Yang, Apiwat Wangweerawong, and Gregory B. Dudley*

*Department of Chemistry and Biochemistry, Florida State University, 12 Varsity Way, MC 4390, Tallahassee, U.S.A.

Abstract

Anionic rearrangement of diverse heteroaryl ethers is reported. In many cases, directed metallation followed by formal [1,2]-Wittig rearrangement provides heteroaryl carbinols in good yield.

■ Synthesis of Substituted Dihydrobenzofurans and Bis-dihydrobenzofurans

Meng-Yang Chang,* Tein-Wei Lee, and Ming-Hao Wu

*Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 807, Taiwan, R.O.C.

Abstract

Several substituted dihydrobenzofurans and bis-dihydrobenzofurans were prepared in accepted yields from 4,4'-biphenyl via a series of reasonable transformations.

■ Highly Efficient Synthesis of 3,4-Dihydro-2(1H)-quinolinone Derivatives under Microwave Heating

Xiao-Tong Zhu, Qiu-Yun Li, Bo Jiang,* and Shu-Jiang Tu*

*School of Chemistry and Chemical Engineering, Jiangsu Key Laboratory of Gree Synthetic Chemistry for Functional Materials, Jiangsu Normal University, Jiangsu 221116, China

Abstract

A sequential three-component reaction of aromatic aldehydes with aromatic amine, and Meldrum’s acid in EtOH under microwave irradiation has been developed. In this one-pot reaction, a series of 3,4-dihydro-2(1H)-quinolinone derivatives were synthesized with high chemical yields. The present green synthesis shows several advantages including operational simplicity and fast reaction rate, which makes it a useful and attractive process for library generation for drug discovery.

■ An Efficient One-Pot Three-Component Synthesis of Highly Functionalized Coumarin Fused Indenodihydropyridine and Chromeno[4,3-b]quinoline Derivatives

Naseem Ahmed,* B. Venkata Babu, Sandeep Singh, and Petar M. Mitrasinovic

*Department of Chemistry, Indian Institute of Technology, Roorkee 247 667, Uttarakhand, India

Abstract

An efficient one-pot, three-component synthesis method of highly functionalized coumarin fused 7,13-dihydro-5-oxa-13-aza-indeno[2,1-b]phenanthrene and chromeno[4,3-b]quinoline derivatives was accomplished using aromatic aldehyde, 4-aminocoumarin and cyclic 1,3-dione in acetic acid at reflux temperature. Environmental-friendly protocol has advantages of high yields, creating three new bonds and one stereocenter in single operation. Further, XRD and DFT study confirmed the molecular structure, stability and different interaction in the crystal packing.

■ Studies on the Petasis Reaction of 2-Pyridinecarbaldehyde Derivatives and Its Products

Hiroki Mandai,* Kyouta Murota, and Seiji Suga*

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

Abstract

The Petasis reaction of various 2-pyridinecarbaldehydes with secondary amines and boronic acids in refluxed acetonitrile proceeded to afford desired products up to 96% yield. The reaction proceeded under mild conditions to afford wide range of amines adjacent to heteroaromatic rings. Interestingly, the aldehyde possessing a nucleophilic moiety, 4-(dimethylamino)-2-pyridinecarbaldehyde, with (S)-(-)-N-methyl-1-phenylethylamine and 2 equivalent of trans-2-phenylvinylboronic acid afforded unexpected product, (E)-N-benzyl-3-phenyl-1-(pyridin-2-yl)prop-2-en-1-amine, in high yield. This product might be formed through the direct alkylation of aldehyde by trans-2-phenylvinylboronic acid, followed by anion/enolate isomerization. Derivatization of the Petasis products were also employed and 2-alkyl substituted pyridine derivatives can be obtained through deamination of the Petasis products under the simple hydrogenation conditions.

■ Reaction of 1-Ethoxyisoindole with Maleimide and Its Derivatives

Igor V. Levkov, Stephanie Cassel, Zoia V. Voitenko,* Gennady V. Palamarchuk, Oleg V. Shishkin, Svetlana V. Shishkina, Armand Lattes, and Isabelle Rico-Lattes

*Department of Organic Chemistry, Kiev National Taras Shevchenko University, 64 Str Volodymyrs’ka, 01033 Kiev, Ukraine

Abstract

We have reported1 the possibility of conducting the Diels-Alder [4+2]-cycloaddition reaction with isoindoles that exist predominantly in the isoindoline form, due to the Curtin-Hammet principle. Pursuing our research, we used 1-ethoxyisoindole as the most evident analog of 1-aminoisoindole. This compound is a typical simple isoindole existing chiefly as the isoindoline tautomer. We have studied the reactions of 1-ethoxyisoindoles with maleimide and its derivatives as active dienophiles. In addition, this paper describes the synthesis of a novel compound – tri-(2-methoxycarbonyl)benzylamine.

■ Synthesis and Complexation of Bis(1-azaazulen-2-yl)amines and Bis(1-azaazulen-2-yl) Sulfides

Eiko Yoshioka, Kazuya Koizumi, Kenji Nakashima, Hiroyuki Fujii, Toshihiro Murafuji, Takahiro Gunji, and Noritaka Abe*

*Department of Pure and Applied Chemistry, Faculty of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan

Abstract

Complexation of bis(3-phenyl-1-azaazulen-2-yl)amine with Zn(OAc)2 and Ni(OAc)2 was investigated, and four-coordinate bis-chelate complexes, M(II) bis[(3-phenyl-1-azaazule-2-yl)(3-phenyl-1-azaazulen-2-ylidene)aminate] (M = Zn, Ni), were obtained. Complexation of bis(1-azaazulen-2-yl) sulfide with CoCl2 gave 2 : 1 ligand-metal complex as major product and complexation of bis(3-iodo-1-azaazulen-2-yl) sulfide with CoCl2 gave 1 : 1 ligand-metal complex.

■ Determination of the Stereochemistry of C-2’ and C-3’ Positions of Taxine NA-1 (2’-Hydroxytaxine II) by the Asymmetric Synthesis of the Reductive Degradation Product of Its Side Chain Moiety

Wanxia Tang,* Hiroshi Minato, Mariko Ando, and Masayoshi Ando*

*Department of Pharmacy Engineering, College of Chemistry and Chemistry Engineering, Qiqihar University, 42 Wenhuadajie, Qiqihar, Heilongjian Shang, 161006, China

Abstract

The reductive degradation of taxine NA-1 (2'-hydroxytaxine II) with n-Bu4NBH4 gave taxinine A and (−)-3-dimethylamino-3-phenylpropane-1,2-diol (1) in addition to 11,12-dihydrotaxinine A. The relative stereochemistry of (−)-1 was identical with syn-3-dimethylamino-3-phenylpropane-1,2-diol, (±)-1b, which was synthesized from cis-2,3-epoxy-3-phenylpropan-1-ol, (±)-7. The absolute configuration of (−)-1 was certified by comparison of the specific optical rotation and the spectroscopic data of (−)-1 with those of (+)-1b and (−)-1b, which were enantioselectively synthesized by Sharpless asymmetric epoxidation reaction of cis-cinnamyl alcohol (6), respectively. As the result, the relative and absolute configuration of (−)-1 was same with that of (−)-1b possessing (2R, 3S) configuration. Thus, the absolute configuration of the side chain of taxine NA-1 (2'-hydroxytaxine II) at C-2' and C-3' positions was determined to be (2'R, 3'S).

■ A Facile Synthesis of 5,6-Dihydro-4H-pyrrolo[3,4-d]thiazole and Other Pyrrolidine-Fused Aromatic Ring Systems via One-Step Cyclization from Diols

Kenji Yoshikawa,* Tsutomu Nagata, Toshiharu Yoshino, Yumi Nakamoto, Noriyasu Haginoya, Ryo Muto, Akiyoshi Mochizuki, Hideyuki Kanno, and Toshiharu Ohta

*R & D Division, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan

Abstract

A facile synthetic method of 5,6-dihydro-4H-pyrrolo[3,4-d]thiazole, which is a subunit of a potent factor Xa (fXa) inhibitor was developed. This new approach employs one-step cyclization from a diol and can be applied to the syntheses of other pyrrolidine-fused aromatic ring sytems.

■ Convenient Synthesis of 5,7-Dichlorothiazolo[5,4-d]pyrimidine

Lianhe Shu,* Lady Mae Alabanza, and Chen Gu

*Process Research and Synthesis, Pharma Research and Early Development (pRED), Hoffmann-La Roche Inc., 340 Kingsland Street, Nutley, NJ 07110, U.S.A.

Abstract

A convenient synthesis of 5,7-dichlorothiazolo[5,4-d]pyrimidine is reported. The condensation of ethyl isocyanoacetate and ethoxycarbonyl isothiocyanate selectively gave the key 5-aminothiazole intermediate in high yield under mild conditions. This intermediate was then converted to the target product in three steps.

■ Double Intramolecular 1,3-Dipolar Cycloaddition of Diazo-terminal Dialkyne: Synthesis of a New Bis(1,2,3-triazolo-1,4-oxazine)

Mekni Husein Nejib* and Ahmed Baklouti

*Department of Chemistry, Faculty of Scince, University of Tunis, Almanar, 2092 Tunis, Tunisia

Abstract

A new bis(1,2,3-triazolo-1,4-oxazine) fused heterocyclic compound was synthesized from terminal meso-1,2,3,4-diepoxybutane via azide ring opening reaction, followed by propargylation and double 1,3-dipolar intramolecular cycloaddition. No effect on the reaction outcome was observed when Cu(I) was used as catalyst. In both cases catalyzed and uncatalyzed reactions, only the exo-tetracyclic two to two fused isomer was obtained.