HETEROCYCLES

■ Contents

■ Curriculum Vitae

Albert I. Meyers*

*Department of Chemistry, Colorado State University, Fort Collins, CO 80523-1872, U.S.A.

■ Preface

Peter Beak

*Urbana, Illinois

■ Tribute to Professor Albert I. Meyers

Kiyoshi Tomioka

*Graduate School of Pharmaceutical Sciences, Kyoto University

■ Publications

Albert I. Meyers*

*Department of Chemistry, Colorado State University, Fort Collins, CO 80523-1872, U.S.A.

■ Highly Functionalized Pyrans Designed for Multipoint Side Chain Attachment to the F-Ring Sector of Spongistatin 1 (Altohyrtin A)

Il Hwan Cho and Leo A. Paquette*

*Evans Chemical Laboratories, The Ohio State University, 120 W. 18th Avenue, Columbus, Ohio 43210, U.S.A.

Abstract

The synthesis of three potential F-ring components, variably functionalized for attachment to the chlorodiene side chain by differing chemical means, has been accomplished from D-(+)-mannose as the generic precursor.

■ Selective Synthesis of β-Amino Esters and β-Lactams by Rhodium-catalyzed Reformatsky-Type Reaction

Kazuo Kanai, Hitoshi Wakabayashi, and Toshio Honda*

*Faculty of Pharmaceutical Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan

Abstract

β-Amino esters and β-lactams are synthesized selectively from aldimines and ethyl bromoacetate by applying a simply modified rhodium-catalyzed Reformatsky-type reaction.

■ Nucleophilic Substitution Reactions of 1-Methoxy-6-nitroindole-3-carbaldehyde

Koji Yamada, Fumio Yamada, Takei Shiraishi, Saori Tomioka, and Masanori Somei*

*Faculty of Pharmaceutical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-0934, Japan

Abstract

1-Methoxy-6-nitroindole-3-carbaldehyde is proved to be a versatile substrate for the nucleophilic substitution reactions providing 2,3,6-trisubstituted indole derivatives. Preparation of a novel pyrimido[1,2-a]indole derivative is also reported.

■ Stereocontrolled Synthesis of a Highly Functionalized 1,7-Dioxaspiro[4.4]nonane Derivative Related to Antibiotic Pseurotins

Shin-ya Aoki, Takahiro Ohi, Kazuya Shimizu, Ryota Shiraki, Ken-ichi Takao, and Kin-ichi Tadano*

*Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Hiyoshi, Kohoku-ku Yokohama 223-8522, Japan

Abstract

For a total synthesis of pseurotins, unusual heterospirocyclic antibiotics, a key intermediate (5), having a highly functionalized 1,7-dioxaspiro-[4.4]nonane structure, has been synthesized from diacetone D-glucose.

■ Electrochemical Oxidations of 1,3-Dihydro-1,3-diazaazulanones and Effects of Reaction Temperature

Katsuhiro Saito,* Yosuke Ueda, Ayako Kawamura, Akiyoshi Kajita, Hiroyuki Ishiguro, Takayasu Ido, Katsuhiko Ono, and Yasutaka Awadu

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

Abstract

Electrochemical oxidations of 1-tosyl-3-aryl-1,3-dihydro- 1,3-diazaazulanones at 0 °C afforded 3-aryl-6-tosyl-1,3-dihydro-1,3- diazaazulanones via migrations of the tosyl group. However, the same type of electrochemical oxidations at an elevated temperature (25 °C) gave another type of product, i.e., double bond isomers, 1-tosyl-3-aryl-1,3-dihydro-1,3-diazaazulanones via 1,5-hydrogen migration, together with 3-aryl-6-tosyl-1,3-dihydro-1,3-diazaazulanones.

■ Chiral Ligand-controlled Catalytic Asymmetric Epoxidation of Enone with Hydroperoxide

Yoshihito Tanaka, Katsumi Nishimura, and Kiyoshi Tomioka*

*Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-shimoadachi-machi, Sakyo-ku, Kyoto 606-8501, Japan

Abstract

Conjugate addition-type asymmetric epoxidation of an enone with lithium cumene hydroperoxide was mediated by a chiral ligand. The catalytic process was realized under conditions of a slow addition of cumene hydroperoxide.

■ Regioselective Synthesis of 2,3,5-Trisubstituted Indoles from p-Sulfinylaniline by Dual Use of the Sulfinyl Group

Shuji Akai, Norihito Kawashita, Nobuyoshi Morita, Yuka Nakamura, Kiyosei Iio, and Yasuyuki Kita*

*Graduate School of Pharmaceutical Science, Osaka University, 1-6 Yamadaoka, Toyonaka, Osaka 560-0043, Japan

Abstract

A novel and convergent synthesis of 2,3,5-trisubstituted indoles (6) from p-sulfinylaniline (1) is described. The single p-sulfinyl group was repeatedly employed in two ways; viz., the construction of the 2,3-disubstituted indole/indoline skeleton and the introduction of a carbon substituent at the C-5 position.

■ Solid-Phase Synthesis of 2-(4-Carbamoylpyrazolyl)-4-alkylamino-6-aminopyrimidine Derivatives

Makoto Haruta, Akio Ejima, Hiroshi Tanaka, and Takashi Takahashi*

*Department of Applied Chemistry, Graduate School of Science and Technology, Tokyo Instituteof Technology, Meguro-ku, Tokyo 152-8552, Japan

Abstract

A solid-phase synthesis of 2-(1-pyrazolyl)pyrimidine derivatives is described. The developed methodology allows the construction of a library of 2-(1-pyrazolyl)pyrimidine.

■ Facile Asymmetric Synthesis of Aziridine Derivatives via the Diastereoselective Reaction of Chiral Imines with Dimethylsulfonium Methylide

Kimio Higashiyama,* Masataka Matsumura, Ayako Shiogama, Takayasu Yamauchi, and Sigeru Ohmiya

*Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan

Abstract

A simple method for the synthesis of chiral 2-substituted aziridine derivatives is described. The reaction pathway consists of the diastereoselective addition of dimethylsulfonium methylide to chiral imines derived from (R)-phenylglycinol and various aldehydes.

■ Synthesis of Substituted Pyrroles from N-Vinylic Phosphazenes Derived from β-Amino Acids and α-Bromo Ketones

Francisco Palacios,* Esther Herrán, and Gloria Rubiales

*Departamento de Química Orgánica, Facultad de Farmacia, Universidad del País Vasco, Apartado 450, 01080 Vitoria-Gasteiz, Spain

Abstract

Synthesis of di-, tri- and tetrasubstituted pyrroles by reaction of N-vinylic phosphazenes derived from β-amino acids with α-bromo ketones is described.

■ Cationic Copper(II)-Oxazoline-Sulfoxide Catalysts: Application to Asymmetric Diels-Alder Reactions

Kazuhiro Watanabe, Takashi Hirasawa, and Kunio Hiroi*

*Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan

Abstract

New chiral sulfoxides bearing a chiral 1,3-oxazoline ring were prepared and used as chiral ligands in copper(II)-catalyzed Diels-Alder reactions. The copper(II)-catalyzed cycloaddition reactions using the new chiral ligands were carried out at –78°C to afford adducts with rather high (up to 75 %) enantiomeric excess. Introduction of a counterion (triflate or hexafluoroantimonate) into the catalysts represented higher degree of asymmetric induction; namely, the more cationic copper(II)-oxazoline sulfoxide catalysts improved the enantioselectivity in the cycloaddition reaction.

■ Total Synthesis of (—)-Halicholactone

Taichi Takahashi, Hidenori Watanabe, and Takeshi Kitahara*

*Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan

Abstract

A convergent total synthesis of halicholactone (1), 5-lipoxygenase inhibitor, using (1S, 5S, 6R)-5-hydroxybicyclo[4.1.0]heptan-2-one (7) as a chiral building block is described. Z-Selective RCM reaction was the key step to construct the nine-membered unsaturated lactone linkage of 1.

■ Mechanistic Studies on the Reactions of Bis(alkylthio)carbenes with Vinyl Isocyanates

James H. Rigby,* Nancy A. Neale, and H. Bernhard Schlegel

*Department of Chemistry, Wayne State University, Detroit, MI 48202-3489, U.S.A.

Abstract

Nucleophilic bis(alkylthio)carbenes demonstrate unique reactivity in their reactions with vinyl isocyanates. When a rapid addition of an excess amount of the oxadiazoline precursor (1) is reacted with vinyl isocyanate (2), a highly functionalized 2-pyridone (3) is produced. In an effort to further understand the mechanistic pathway followed by this reaction, ab initio methods are employed and experimental results support the proposed thermally induced [4+2] pathway of this reaction.

■ Concise Syntheses of Harmicine and a Pyrrolidinoisoquinoline Derivative Using Chiral 1-Allyl Adducts of β-Carboline and Isoquinoline as Starting Materials

Takashi Itoh, Michiko Miyazaki, Kazuhiro Nagata, Masashi Yokoya, Shigeru Nakamura, and Akio Ohsawa*

*School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan

Abstract

Total syntheses of (S)-harmicine and (R)-1,2,3,5,6,10b-hexahydropyrrolo[2,1-a]isoquinoline were carried out using chiral 1-allyl-1,2,3,4-tetrahydro-β-carboline and 1-allyl-1,2-dihydroisoquinoline as starting materials, respectively.

■ An Asymmetric Synthesis of 3-Aryl-1,4-oxazin-2-ones: Synthesis of a Key Intermediate of an NK₁ Receptor Antagonist

Paul N. Devine,* Bruce S. Foster, Edward J. J. Grabowski, and Paul J. Reider

*Department of Process Reseach, Merck Research Laboratories, Division of Merck & Co., Inc., P. O. Box 200,0, Rahway, New Jersey 07065, U.S.A.

Abstract

Pyrrolidine derived (S)-lactamide auxiliaries mediate a highly diastereoselective coupling reaction between racemic α-halo acids and N-benzylethanolamine. The adducts are readily cyclized upon treatment with a catalytic amount of TsOH giving the above titled compounds in >90% ee. The 4-fluorophenyl substituted oxazinone thus formed is the key intermediate in the synthesis of a potent NK₁ receptor antagonist.

■ A Practical Synthesis of (+)-Biotin through Palladium Hydroxide on Charcoal-catalyzed Fukuyama Coupling Reaction

Yoshikazu Mori and Masahiko Seki*

*CMC Research Laboratory, Tanabe Seiyaku Co. Ltd.,, 3-16-89, Kashima, Yodogawa-ku, Osaka 532-8505, Japan

Abstract

The Fukuyama coupling reaction of thiolactone (2) with 5-ethoxy-5-oxopentylzinc iodide (4) in the presence of 0.65 mol% of non pyrophoric palladium hydroxide on charcoal (Pearlman’s catalyst) provided a vinyl sulfide (3) carrying a C-4 side chain of (+)-biotin (1) in 87% yield.

■ Inter- and Intramolecular [4+2] Cycloaddition of Nitroalkenes with Allenylsilanes. A Case of Unexpected Regioselectivity

Scott E. Denmark* and Laurent Gomez

*245 Roger Adams Laboratory, Box 18; Department of Chemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, U.S.A.

Abstract

A conjugated nitroalkene tethered to an allenylsilane undergoes formal [4+2] cycloaddition in the presence of tin tetrachloride to afford a bicyclic nitronate. The stereo- and regiochemical course of the reaction was established by a subsequent dipolar cycloaddition with 4-bromophenyl acrylate to generate a crystalline nitroso acetal. Single crystal X-Ray crystallographic analysis of the nitroso acetal revealed an unexpected stereostructure which arose from attack of the nitroalkene on the central carbon of the allenylsilane and closure of the oxygen atom on the terminal carbon. This outcome is interpreted as arising from a stepwise reaction via a silicon-stabilized carbocation which can undergo rotation to an allylic cation prior to ring closure. An intermolecular example of this same process was also documented.

■ Studies on a Chirality of Orellanine. Spectral Nonequivalence of Atropisomers of Tetra-O-methylorellanine and Related Compounds Induced by Chiral Solvating Agents

Róza Antkowiak, Wieslaw Z. Antkowiak,* and Barbara Nowak-Wydra

*Facluty of Chemistry, Adam Mickiewicz University, ul. Grunwaldzka 6, 60-780 Poznan, Poland

Abstract

The precise carbon-hydrogen correlations of orellanine tetramethyl ether were established by NMR techniques and the methylated alkaloid, as well as some of its structural analogues, was subjected to ¹H NMR experiments with the use of (R)-(+)-t-butylphenylphosphinothioic acid, BINOL or TADDOL as the chiral solvating agents. It was found that tetramethylorellanine, as well as 3,3’-dimethoxy-2,2’-bipyridine-N,N’-dioxide, and some other model compounds gave, in such conditions, proton spectra being composed of separated patterns, each of which corresponds to the individual enantiomer.

■ An Efficient Multicomponent Reaction Involving the Interception of the Zwitterionic Intermediate between DMAD and Isocyanides with Some Active Methylene Compounds

Vijay Nair,* A. U. Vinod, R. Ramesh, Rajeev S. Menon, Luxmi Varma, Saumini Mathew, and Angele Chiaroni

*Organic Chemistry Division, Regional Research Laboratory, Council of Scientific and Industrial Research (CSIR), Trivandrum-695 019, India

Abstract

The 1:1 zwitterionic intermediate generated from dimethyl acetylenedicarboxylate and isocyanide is intercepted with 2-hydroxy-1,4-naphthoquinone, 4-hydroxycoumarin, 4-hydroxy-1-methylquinolinone, 4-hydroxy-6-methylpyrone, and 1-naphthol in one-pot to give novel pyran annulated heterocyclic systems in good yields.

■ Extension of the SAR in the 1,2-Diaminocyclohexane Phenylacetamide Template

Shikai Zhao, Stephen A. Mizsak, Jeremiah P. Freeman, and Jacob Szmuszkovicz*

*Department of Chemistry and Biochemistry, University of Notre Dame, 251 Nieuwland Science Hall, Notre Dame, IN 46556, U.S.A.

Abstract

Rigid analogs of 3,4-dichloro-N-methyl-N-[(1-methyl-2-piperidinyl)phenylmethyl]-benzeneacetamide (3), were prepared and allowed to extend the SAR of the U-50,488 template.

■ Aryl-Aryl Coupling Reaction Catalyzed by a Palladium Reagent Prepared from Pd(OAc)₂ and n-Bu₃P

Takashi Harayama,* Akihiro Hori, Yuichiro Nakano, Toshihiko Akiyama, Hitoshi Abe, and Yasuo Takeuchi

*Faculty of Pharmaceutical Science, Okayama University, 1-1-1 Tsushima-naka, Okayama 700-8530, Japan

Abstract

A palladium reagent prepared from Pd (OAc)₂ (0.2 eq) and n-Bu₃P (0.6 eq) catalyzed an aryl-aryl coupling reaction. This procedure is effective for coupling reactions of aryl triflate possessing no oxygen groups with arene, and of aryl iodide with arene.

■ Synthesis and Fluorescence Properties of 4,5-, 4,6- and 5,6-Disubstituted Benzofurazan (2,1,3-Benzoxadiazole) Compounds

Natsuko Okiyama, Seiichi Uchiyama, Maki Onoda, Kazuhiro Imai, and Tomofumi Santa*

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

Abstract

New 4,5-, 4,6- and 5,6-disubstituted benzofurazan (2,1,3-benzoxadiazole) compounds having various substituent groups were synthesized. Their fluorescence properties were obtained and the discussions were made to develop new sensitive and selective fluorescent reagents.

■ Studies on the Selective Intramolecular Biaryl Coupling Reaction of 2-Tryflyloxy-6-halobenzanilides Using a Palladium Reagent

Takashi Harayama,* Hiroko Toko, Kyoko Kubota, Hiromi Nishioka, Hitoshi Abe, and Yasuo Takeuchi

*Faculty of Pharmaceutical Science, Okayama University, 1-1-1 Tsushima-naka, Okayama 700-8530, Japan

Abstract

The aryl-aryl coupling reaction of 2-triflyloxy-6-halobenzanilides using a palladium reagent under several reaction conditions was examined. The 6-iodo compound gave triflyloxyphenanthridone selectively in excellent yield under the conditions for the ordinary Heck reaction.

■ Diels-Alder Cycloaddition of Highly Substituted Pyran-2-ones with Maleic Anhydride

Kristof Kranjc, Ivan Leban, Slovenko Polanc, and Marijan Kočevar*

*Faculty of Chemistry and Chemical Technology, University of Ljubljana, Askerceva 5, P.O. Box 537, SLO-1000 Ljubljana, Slovenia

Abstract

The Diels-Alder cycloaddition reaction of substituted 3-benzoylamino-pyran-2-ones (1) with maleic anhydride (2) in 1,2,3,4-tetrahydronaphthalene yielding representatives of bicyclo[2.2.2]oct-7-ene-2,3,5,6-tetra-carboxylic acid 2,3;5,6-dianhydride (5) has been investigated. The emphasis was given both on the study of the influence of substituents on the reaction and development of the synthesis of derivatives with unprecedented substituent patterns. Structures of products were determined by the X-Ray study and by the spectroscopic analyses.

■ Diastereoselective Reactions of a Homoenolate Generated from (S)-N-(1-Phenylethyl)-3-(trimethylsilyl)propanamide: Enantioselective Synthesis of (+)-Massoialactone

Naoko Sadayori, Asako Kawatoh, Ryoko Sakurazawa, Tomoko Utsumi, Miharu Inagaki, and Morio Asaoka*

*Department of Chemical and Biological Sciences, Faculty of Science, Japan Women's University, 2-8-1 Mejirodai, Bunkyoku, Tokyo 112-0015, Japan

Abstract

Alkylation of the homoenolate generated from (S)-N-(1-phenylethyl)-3-(trimethylsilyl)propanamide gave the corresponding products with good diastereoselectivity. Starting with one of the alkylated products, enantioselective synthesis of (+)-massoialactone [(+)-13] was carried out.