HETEROCYCLES

■ Contents

■ Congratulations to Professor Albert Padwa on his 75th Birthday

C. Oliver Kappe*

*Institute for Organic Chemistry, Karl-Franzens-University Graz, Heinrichstrasse 28, A-8010 Graz, Austria

■ Resume

Albert Padwa*

*Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, GA 30322, U.S.A.

■ Publications

Albert Padwa*

*Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, GA 30322, U.S.A.

■ Albert Padwa: A Renaissance Man of Great Passion and Grit

Jeffrey I. Seeman*

*Department of Chemistry, University of Richmond, Richmond, VA 23173, U.S.A.

Abstract

A brief personal tribute to Professor Albert Padwa is presented. This essay describes Padwa’s energy and passion in four fundamentally different areas of activity: his science, his contributions to the chemistry profession, his devotion to physical activities including trekking and mountaineering, and his creativity and artistry in the form of his mobiles and ‘rust art.’ A number of photographs highlight and document Padwa’s varied talents, experiences and achievements.

■ Recent Advances on the Synthesis of Piperidines through Ruthenium-Catalyzed Ring-Closing Metathesis (RCM) Reactions

Pedro Merino,* Tomas Tejero, Graziella Greco, Eduardo Marca, Ignacio Delso, Asier Gómez-SanJuan, and Rosa Matute

*Department of Organic Chemistry, University of Zaragoza, E-50009 Zaragoza, Aragon, Spain

Abstract

Ring-closing metathesis reactions of dialkenyl amines, amides and carbamates catalyzed by Ru-catalysts provide efficient approaches to six-membered nitrogen heterocyclic compounds, which are precursors of a variety of natural products and related compounds.

■ Absolute Configurational Elucidation of Monoterpene Indole Alkaloids by Circular Dichroism

Alfarius Eko Nugroho and Hiroshi Morita*

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

Abstract

Monoterpene indole alkaloids comprise a group of naturally occurring compounds, exhibiting a range of biological activities. These compounds have attracted great attention because of their interesting biosynthetic route and also as a challenging target for total synthesis. For such synthetic approach and structure – activity relationship studies, the knowledge about their absolute stereostructures is essential. This review summarizes the presently available results of studies on the determination of the absolute configuration of indole alkaloids by the use of circular dichroism (CD).

■ Practically Usable C3 Building Blocks for the Syntheses of Nitro Heterocycles

Nagatoshi Nishiwaki,* Shotaro Hirao, Jun Sawayama, and Kazuhiko Saigo

*School of Science and Technology, Kochi University of Technology, Tosayamada-cho, Kochi, 782-8502, Japan

Abstract

Nitromalonaldehyde (NMA-H) is one of useful synthons for synthesizing nitro compounds. However, NMA-H itself cannot be practically employed because of its unstable property. Therefore, sodium salt of NMA-H (NMA-Na) has been used as its synthetic equivalent from old time, and NMA-Na is still important even now albeit several restrictions with regard to safety and treatability. On the other hand, dinitropyridone, nitropyrimidinone and dinitropyrazole can be employed in place of NMA-Na for the same purpose, and furthermore azadienamines, formylnitroenamines and dinitropyrazole also serve as the synthetic equivalents of NMA-H, which are usable in common organic solvents with safety. These reagents condense with dinucleophiles to afford various kinds of nitro compounds.

■ Truncated Aspidosperma Alkaloid-Like Scaffolds: Unique Structures for the Discovery of New, Bioactive Compounds

Scott C. Benson, Lily Lee, Wanguo Wei, Feng Ni, Julian David Janna Olmos, Kyle R. Strom, Aaron B. Beeler, Ken Chih-Chien Cheng, James Inglese, Smitha Kota, Virginia Takahashi, A. Donny Strosberg, John H. Connor, G. Guy Bushkin, and John K. Snyder*

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

Abstract

Exploration into the dienophilicity of indole in inverse electron demand Diels-Alder reactions has led to the development of the triazatetracyclo[7.7.0.01,13.02,7]hexadeca-2,4,6,10,12-pentaene and related scaffolds for diversification in the search for new, biologically active compounds. The libraries constructed from these core structures have lead to the discovery of new anti-viral and anti-malarial compounds.

■ Recently Discovered Naturally Occurring Heterocyclic Organohalogen Compounds

Gordon W. Gribble*

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

Abstract

Amongst the more than 5,000 naturally occurring organohalogen compounds, both biotic and abiotic, are a diverse collection of structurally novel heterocycles. The present review covers this fascinating area of natural products as presented over the past three years.

■ Copper-Catalyzed Domino Reaction of Heteroallenes towards Benzo-Heterocycle Compounds

Fei Wang, Peng Zhao, and Chanjuan Xi*

*Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, China

Abstract

The present review summarizes information on the copper-catalyzed reaction of heteroallenes, including carbodiimides, isothiocyanates, and carbon disulfide, with o-halobenzenamines or o-halophenols or o-halobenzamides for constructing benzo-heterocycle compounds via domino nucleophilic addition/cyclization reactions.

■ Preparation and Synthetic Applications of Azetidines

Tina M. Bott and F. G. West*

*Gunning/Lemieux Chemistry Center, Department of Chemistry, University of Alberta, Edmonton, Alberta T6G 2G2, Canada

Abstract

Azetidines (four-membered saturated nitrogen heterocycles) are found in a diverse range of natural products, and also serve as valuable building blocks for other structural classes. The ring-strain inherent in these compounds poses challenges in their preparation, and a number of creative methods for the synthesis of substituted azetidines are presented. The application of azetidines in the construction of acyclic products or other heterocyclic systems is also described. Finally, recent examples of the use of chiral, enantiomerically pure azetidines in asymmetric catalysis are detailed.

■ Mechanistic Investigations of the Cyclocondensation Step of the Knorr Pyrrole Synthesis

Scott A. Snyder,* Ferenc Kontes, and Adel M. ElSohly

*Department of Chemistry, Columbia University, 3000 Broadway, New York, NY 10027, U.S.A.

Abstract

A mechanistic investigation of the cyclocondensation step of the Knorr pyrrole synthesis of pyrrolo[2,1,5-cd]indolizidines is reported. Kinetic isotope effect measurements suggest the participation of two protic solvent molecules in a rate-determining ketone protonation prior to cyclization and dehydration.

■ Synthesis and Spectroscopic Properties of 1,6-Methano[10]annulene-Fused and 2,4-Dimethyl-7,12-methano-3H-cyclohepta[10]annulen-3-one-Fused 10H-Pyrrolo[1,2-a]perimidin-10-ones

Shigeyasu Kuroda,* Naoko Matsumoto, Yanmei Zhang, Takako Abe, Yoshikazu Horino, Yurie Fujiwara, and Mitsunori Oda*

*Department of Environmental Applied Chemistry, Faculty of Engineering, Toyama University, Gofuku 3190, Toyama 930-8555, Japan

Abstract

The title 1,6-methano[10]annulene-fused and 2,4-dimethyl-7,12-methano-3H-cyclohepta[10]annulen-3-one-fused 10H-pyrrolo[1,2-a]perimidin-10-ones, denoted by 2 and 3, respectively, were synthesized. A novel and efficient synthetic method involving tandem [4 + 3] cycloaddition and 10π-electrocyclization was developed for constructing the 2,4-dimethyl-7,12-methano- 3H-cyclohepta[10]annulen-3-one skeleton toward the synthesis of 3 from 6H-cyclohepta[c]furan-5,7-dicarbaldehyde (5). Spectroscopic properties of 2 and 3 were also described in relation to the tropone-fusion.

■ Chemo-Enzymatic Synthesis of 1’-Photoreactive Sucrose Derivatives via Ether Linkage

Yuka Tsunekawa, Katsuyoshi Masuda, Miho Muto, Yasuyuki Muto, Yuta Murai, Yasuyuki Hashidoko, Yoshitake Orikasa, Yuji Oda, Yasumaru Hatanaka, and Makoto Hashimoto*

*Graduate School of Agriculture, Hokkaido University, Kita 9 Nishi 9, Kita-ku, Sapporo, Hokkaido 060-8589, Japan

Abstract

As the 1’-hydroxyl group of sucrose is well known to be less reactive than other primary alcohols, there are no reports on the substitution of a phenoxy group at this position. Chemo-enzymatic synthesis of photoreactive 1’-phenoxy-substituted sucrose was examined to elucidate the functional analysis of sweet receptors.

■ A Flexible Convergent Route to Azaoxindoles, Azaindolines, Azaindoles, and Tetrahydroazaquinolones

Eric Bacqué, Myriem El Qacémi, and Samir Z. Zard*

*Department of Chemistry, Ecole Polytechnique, CNRS UMR 7652, 91128 Palaiseau, France

Abstract

A variety of azaoxindoles, azaindolines, azaindoles, and tetrahydroazaquinolones can be readily prepared by cyclisation onto pyridine rings of radicals derived from xanthates. The xanthate precursors may themselves be produced by intermolecular radical addition-transfer to allylamino- or butenoylamide side-chains.

■ Regioselective Ring-Opening Reaction of 2-Mono-Substituted Azetidin-3-ones Promoted by the Combined Use of Titanium Tetraiodide and Its Chloro or Bromo Counterpart

Shingo Hata, Daisuke Fukuda, Iwao Hachiya, and Makoto Shimizu*

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

Abstract

The ring-opening reaction of 2-mono-substituted azetidin-3-ones at the more substituted bond occurred with the combined use of TiI4 and TiCl4 to give the corresponding ketones in moderate to high yields with high regioselectivity. The reductive aldol reaction of the enolate thus prepared proceeded with chloral in the presence of Pd(O2CCF3)2 to give the syn-aldol adduct in moderate yield.

■ Chemistry of Renieramycins. Part 10: Structure of Renieramycin V, a Novel Renieramycin Marine Natural Product Having a Sterol Ether at C-14 Position

Naoki Saito,* Miho Yoshino, Kornvika Charupant, and Khanit Suwanborirux

*Meiji College of Pharmacy, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan

Abstract

A new renieramycin-type marine natural product, renieramycin V, was isolated from the low polar fraction obtained from the Thai blue sponge Xestospongia sp., and its structure was elucidated by comparing its spectral data with those of renieramycin O and cholesterol. This is the first example of renieramycin that has a sterol moiety attached to it. It is interesting that renieramycin V does not show any cytotoxicity to several human cancer cell lines.

■ Solid-State Fluorescence Properties and Crystal Structures of 7-(Diethylamino)coumarin Derivatives

Kanji Kubo,* Taisuke Matsumoto, Keiko Ideta, Haruko Takechi, and Hajime Takahashi

*School of Dentistry, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan

Abstract

7-(Diethylamino)-3-phenylcoumarin (1) gave strong emission band at 477 nm in the solid state when excited at 400 nm, but ethyl 2-[7-(diethylamino)-2-oxo-2H-1-benzopyran-3-yl]-4-thiazolecarboxylate (2) had no fluorescence in solid state. The crystal structures of 1 and 2 were analyzed by X-ray crystallography. The crystal of 1 had intermolecular C-H···O, C-H···N and C-H···π interactions and that of 2 had intermolecular C-H···O, π···π, and S···π interactions.

■ Highly Regioselective Intramolecular Biaryl Coupling Reaction of a Phenyl Benzoate Derivative for the Synthesis of Graphislactone G

Hitoshi Abe,* Takuya Matsukihira, Tomoko Fukumoto, Yoshikazu Horino, Yasuo Takeuchi,* and Takashi Harayama

*Department of Applied Chemistry, Faculty of Engineering, Toyama University, Gofuku 3190, Toyama 930-8555, Japan

Abstract

The 6H-dibenzo[b,d]pyran-6-one type natural product graphislactone G was synthesized using a palladium-mediated aryl-aryl coupling reaction of the phenyl benzoate derivative. The regioselectivity in the coupling step was also investigated.

■ Formal Synthesis of Sceletium Alkaloids, (±)-Mesembrine and (±)-Mesembranol

Toshio Honda,* Hironobu Arai, Naoshi Yamamoto, and Kazunori Takahashi

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

Abstract

An intramolecular Mizoroki-Heck reaction was exploited for construction of a benzylic quaternary carbon center. The product obtained was further converted into the key intermediate for the synthesis of (±)-mesembrine and (±)-mesembranol.

■ Preparation and Optical and Electrochemical Properties of Unsymmetrical Phthalocyanines with One or Two TTF Units

Takeshi Kimura,* Nobuhiro Takahashi, Tomoyuki Tajima, and Yutaka Takaguchi

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

Abstract

Unsymmetrical phthalocyanines with one or two TTF units were obtained by treating mixed 3,6-dioctyltetrathiafluvalenophthalonitrile and 4,5-dioctoxyphthalonitrile with Li in n-hexanol. Their optical and electrochemical properties were examined by UV-vis spectroscopy and cyclic voltammetry.

■ Ni-Catalyzed Multi-Component Coupling Reaction of Norbornene, Dimethylzinc, Butadiene, and Aldimine

Toshiyuki Nakamura, Takamichi Mori, Mariko Togawa, and Masanari Kimura*

*Department of Applied Chemistry, Faculty of Engineering, Nagasaki University, 1-14, Bunkyo-machi, Nagasaki 852-8521, Japan

Abstract

In the presence of a Ni catalyst and dimethylzinc, aldimines, which are prepared from aldehydes and primary amines, undergo a multi-component coupling reaction with 1,3-butadiene and norbornene to provide homoallylamines in good to excellent yields. Under similar conditions, the reaction can be successfully extended to the N,O-acetals prepared from lactols and amines, giving rise to ω-hydroxyhomoallylamines.

■ Condensation of Catechin and Epicatechin Incorporating a TBS-Protecting Group

Noriyuki Nakajima,* Keiko Horikawa, Norimasa Takekawa, Masahiro Hamada, and Takao Kishimoto

*Biotechnology Research Center, Toyama Prefectural University, 5180 Kurokawa, Kosugi, Toyama 939-0398, Japan

Abstract

Stereoselective synthesis of catechin and epicatechin dimers incorporating a tert-butyldimethylsilyl (TBS)-protecting group under intermolecular condensation is achieved using SnCl4 as the Lewis acid. Four TBS-protected dimers were successfully converted to the deca-acetates of procyanidin B1, B2, B3, and B4 easily via the TBS-deprotection process. This procedure offers an advantage for dimmer synthesis in large-scale over existing benzyl-protecting methods.

■ Palladium-Catalyzed Selective and Sequential Functionalization of 2,4,6-Trihalopyridine Rings: Synthesis of Ethynylpyridine Polymers Directly Joined with Aza-Crown Ethers

Shunsuke Takashima, Tsuyoshi Yamamoto, Hajime Abe,* and Masahiko Inouye*

*Graduate School of Pharmaceutical Sciences, University of Toyama, Sugitani 2630, Toyama, 930-0194, Japan

Abstract

meta-Ethynylpyridine polymer directly joined with 1-aza-18-crown-6 ether was synthesized by applying 2,4,6-trihalopyridines as a starting material. By using a Pd(OAc)2-BINAP combination with an excess of Cs2CO3, 2,6-dichloro-4-iodopyridine could be condensed with 1-aza-18-crown-6 ether to afford 4-azacrown-substituted 2,6-dichloropyridine selectively. The two chlorine atoms of this product were replaced with ethynyl groups by copper-free Sonogashira reaction with tert-butyldimethylsilylacetylene followed by protiodesilylation. Subsequent steps involving Sonogashira reactions gave diiodo- and diethynyl- substituted tripyridine units, and their co-polymerization yielded the targeted polymer.

■ Optimized Syntheses of the Furan Fatty Acids F5 and F6 Featuring Convertion of a β-Iodofuran into a β-Methylfuran in a Single Operation

David W. Knight* and Andrew W. T. Smith

*School of Chemistry, Cardiff University, Main Building, Park Place, Cardiff, CF10 3AT, U.K.

Abstract

Optimized syntheses of the furan fatty acids F5 1a and F6 1b are described, which give >60% overall yields over 7 or 8 steps respectively starting from 10-undecenal 6. The F6 approach also features a conversion of a β-iodofuran into the corresponding β-methyl derivative in a single operation.

■ Highly Efficient Condensation of Glycerol to Cyclic Acetals Catalyzed by Titanium-Exchanged Montmorillonite

Takato Mitsudome, Tsuyoshi Matsuno, Shoichiro Sueoka, Tomoo Mizugaki, Koichiro Jitsukawa, and Kiyotomi Kaneda*

*Research Center for Solar Energy Chemistry, Graduate School of Engineering Science, Osaka University, 1-3 Machikaneyama, Toyonaka, Osaka 560-8531, Japan

Abstract

Titanium cation-exchanged montmorillonite (Ti4+-mont) showed high catalytic activity for the condensation reaction of glycerol with ketones or aldehydes to provide cyclic acetals under mild conditions. The solid Ti4+-mont catalyst could be easily separated after the reaction and reused without any loss of activity.

■ Asymmetric Synthesis of Isoquinuclidine by Diels-Alder Reaction of 1,2-Dihydropyridine and Chiral Dienophile Utilizing a Chiral Lewis Acid

Masafumi Hirama, Chonticha Suttibut, N. D. M. Romauli Hutabarat, Chigusa Seki,* Noritaka Sakuta, Takefumi Tsuchiya, Yoshihito Kohari, Hiroto Nakano, Koji Uwai, Nobuhiro Takano, Mitsukuni Yasui, Yuko Okuyama, Kenichi Osone, Mitsuhiro Takeshita, and Haruo Matsuyama*

*Department of Applied Chemistry, Graduate School of Engineering, Muroran Institute of Technology, 27-1 Mizumoto, Muroran, Hokkaido 050-8585, Japan

Abstract

The asymmetric Diels-Alder reaction of 1-phenoxycarbonyl-1,2-dihydropyridine 1 with 3-acryloyl (4S)-4-benzyl-1,3-oxazolidin-2-one (4S)-2 {or (4R)-2} in the presence of Ti-TADDOLate 4 as a chiral Lewis acid afforded the chiral isoquinuclidine derivative endo-(4’S)-3 in high yield (99%) with high diastereoselectivity (up to 92% d.e.). The reaction exhibits a strong match-mismatch effect. The stereochemistry of endo-(4’S)-3 was established to be (1R, 4S, 7R) and a reaction mechanism is proposed.

■ Enantioenriched Formation of Synthons of 1,5-Hexadiene Bis-epoxides for Construction of Nonracemic cis- and trans-2,5-Disubstituted Tetrahydrofurans

David R. Williams* and Ramkrishna De

*Department of Chemistry, Indiana University, 800 East Kirkwood Avenue, Bloomington, IN 47405-7102, U.S.A.

Abstract

A pathway for the synthesis of enantioenriched bis-epoxides derived from 2,6-heptadien-1-ol is described. Use of the Katsuki titanium salalen catalyst affords high asymmetric induction for mild epoxidation of the monosubstituted alkene as the key step. Regioselective nucleophilic additions to these chiral bis-epoxides lead to a stereocontrolled preparation of nonracemic cis- and trans-2,5-disubstituted tetrahydrofurans.

■ [3+2] Cycloaddition of Seleno- and Thioaldehydes with Cyclic Azomethine Imines

Hajime Maeda, Yusuke Takamizawa, and Masahito Segi*

*Chemistry Course, College of Science and Engineering, School of Chemistry, Kanazawa University, Kakuma, Kanazawa, Ishikawa 920-1192, Japan

Abstract

Reaction of seleno- and thioaldehydes with cyclic azomethine imines in refluxing toluene gave [3+2] cycloadducts as a diastereomeric pure form in high yields. Thermal cycloreversion of the [3+2] cycloadducts regioselectively occurred to regenerate seleno- and thioaldehydes which can be trapped in situ by 2,3-dimethyl-1,3-butadiene.