HETEROCYCLES

■ Contents

■ Curriculum Vitae

Shô Itô*

*Department of Chemistry, Graduate School of Science, Tohoku University, Aramaki, Aoba-ku, Sendai 980-8578, Japan

■ Preface

Koji Nakanishi

*Department of Chemistry, Columbia University, U.S.A.

■ Contributions of Professor Sho Ito in Organic Chemistry

Masahiro Hirama

*Department of Chemistry, Graduate School of Science, Tohoku University, Sendai 980-8578, Japan

■ List of Publications

Shô Itô*

*Department of Chemistry, Graduate School of Science, Tohoku University, Aramaki, Aoba-ku, Sendai 980-8578, Japan

■ Cascading Single-step Stereoselective Construction of the α-Alloyohimbine Framework: A New Synthesis of (-)-Nitraraine

Hideki Sakagami and Kunio Ogasawara*

*Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980-8578, Japan

Abstract

(—)-Nitraraine and its 10-methoxy -analogue having an α-alloyohimbine framework have been constructed stereoselectively in a cascading single step sequence from chiral mono-substituted N-2-(3-indolyl)ethyltetrahydro-pyridine precursors under the Heck reaction conditions.

■ Resolution and Absolute Configurational Assignments to 1-Oxa- and 1-Thia-6-ketospiro[4.4]nonanyl Platforms

Leo A. Paquette,* James C. Lanter, Dafydd R. Owen, Fabrizio Fabris, Richard Todd Bibart, and Miriam Alvarez

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

Abstract

A convenient chiral sulfoxide mediated protocol for resolving the heterocyclic spiro[4.4]nonanes (3, 7, and 10) is described, along with crystallographic substantiation of their absolute configuration.

■ Solvent Effects on Relative Stability of Meridine and Its Tautomer: MO Calculations

Tsuguo Sato* and Masahiro Kataoka

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

Abstract

The solvent effect on the ground-state energy difference of meridine (enol form) and meridin-12(13H)-one (keto form) is examined by use of AM1 and COSMO methods. The results show that solvents stabilize the keto form more than the enol form. In apolar solvents, the enol form is the predominant species, whereas in polar solvents, the enol and keto forms are present in an almost equal amount.

■ Photochemistry of Pyrazino- and Quinoxalino-fused Naphthobarrelenes

Chuan-Hung Chou, Rama Krishna Peddinti, and Chun-Chen Liao*

*Department of Chemistry, National Tsing Hua University, Hsinchu, Taiwan 30043, Taiwan, R.O.C.

Abstract

Irradiation of the title compounds afforded the corresponding semibullvalenes via aza-di-π-methane rearrangement. No naphtho-vinyl bridged products were observed.

■ Photochemical Synthesis and Characterization of the Tautomers of 1,3,5,7,9- and 1,3,6,8,10-Pentamethylcyclooctapyrimidine-2,4-diones

Kazue Ohkura, Ken-ichi Nishijima, Shun Uchiyama, Akiyo Sakushima, and Koh-ichi Seki*

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

Abstract

UV-irradiation of 1,3,6,8,10- and 1,3,5,7,9-pentamethylcyclooctapyrimidine-2,4-diones (3, 5) effected bond-switching to produce their tautomeric isomers (4, 6). Upon heated in the dark, the former (4) reverted to 3, while the latter (6) transformed itself into cyclobutaquinazoline (7) through intramolecular Diels-Alder reaction.

■ Concise Synthesis of (3R,4S)-3-hydroxy-4-methyl-γ-butyrolactone

Takashi Nishiyama, Toshiko Nishioka, Tomoyuki Esumi, Yoshiharu Iwabuchi, and Susumi Hatakeyama*

*Faculty of Pharmaceutical Sciences, Nagasaki 852-8521, Japan

Abstract

A three-step sequence involving highly stereoselective deconjugation of ethyl (E)-2-pentenoate, osmylation, and resolution by lipase-catalyzed enzymatic acetylation allowed an extremely expeditious synthesis of (3R,4S)-3-hydroxy-4-methyl-γ-butyrolactone with 90% ee, from which (—)-blastmycinolactol and (+)-blastmycinone were synthesized.

■ Asymmetric Pauson-khand Reactions of Chiral Sulfinamides:Å@Asymmetric Synthesis of 3-Azabicyclo[3.3.0]oct-5-en-7-one Derivatives

Kunio Hiroi* and Takashi Watanabe

*Department of Synthetic Organic Chemistry, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan

Abstract

Unprecedented asymmetric Pauson-Khand reactions of chiral sulfinamides are described. Cobalt-catalyzed reactions of chiral N-allyl-N-propargyl-N-arylsulfinamide derivatives were carried out in dichloromethane at -20°C~room temperature under carbon monoxide atmosphere in the presence of Co₂(CO)₈ to give chiral 3-azabicyclo[3.3.0]oct-5-en-7-one with moderate or low enantioselectivity.

■ Synthesis of N-Boc-3-amino-1,2-epoxy-4-phenylbutane from (3S)-Hydroxy-γ-butyrolactone by Means of the Hofmann Rearrangement

Masahiro Murakami, Kazumasa Hinoue, Kazuya Nakagawa, Yoshiko Monden, Yoshiro Furukawa, and Shigeo Katsumura*

*School of Science, Kwansei Gakuin University, Gakuen, Sanda-shi 662-8501, Japan

Abstract

The stereocontrolled synthesis of the title alkylaminoepoxide was achieved starting from (3S)-hydroxy-γ-butyrolactone by efficient utilization of the Hofmann rearrangement followed by intramolecular oxazolidinone ring formation as a key step.

■ Efficient and Stereoselective β-Epoxidation of the 16(17)-Double Bond of Gibberellic Acid Derivatives with an Acylperoxy Radical Generated by Irradiation of α-Diketones and Oxygen

Hideharu Seto,* Mikio Hoshino, Shozo Fujioka, Toshiro Suenaga, Takeshi Shimizu, and Shigeo Yoshida

*The Institute of Physical and Chemical Research, Wako-shi, Saitama 351-0198, Japan

Abstract

Irradiation of gibberellic acid derivatives in the presence of α-diketones in an oxygen saturated solution led to efficient epoxidation of the 16(17)-double bond to give the 16β,17-epoxides predominantly. The observed stereoselectivity of α- to β-epoxidation ranging from 0:100 on 3,13-di-O-acetylgibberellic acid methyl ester (7) through 11:89 on its 3,13-di-O-methoxymethyl congener, i.e., β-selectivity, was in contrast to the α-selectivity of 74:26 resulted from a peracid epoxidation on 7. This clearly illustrates the radical reaction mechanism involving an acylperoxy radical as a one-oxygen transfer species, in which the stability of the diastereomeric transition states of the intermediary α-acylperoxy carbon radical determines the stereochemical course.

■ Syntheses and Properties of Tetraazaazulenocoronands and Octaazaazulenocryptand¹

Hidetsugu Wakabayashi,* Teruo Kurihara, and Tetsuo Nozoe

*Department of Chemistry, Faculty of Science, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan

Abstract

Treatment of 1,3-diformylazulene (1) with 1.2 equiv. of α,ω-alkanediamines (3 and 4) and tris(2-aminoethyl)amine (5a) in ethanol for 24 h at room temperature gave tetaraazaazulenocoronands (2 and 9) and octaazaazulenocryptand (10) in one-pot procedure in good yields.

■ Convergent Strategy for Synthesizing Polycyclic Ether Marine Toxins: Synthesis of the ABCDE Ring Fragment of Ciguatoxin CTX3C

Megumi Maruyama, Kenji Maeda, Tohru Oishi, Hiroki Oguri, and Masahiro Hirama*

*Department of Chemistry, Graduate School of Science, Tohoku University, Aobayama, Sendai 980-8578, Japan

Abstract

The ABCDE ring fragment of CTX3C, the most important member of the ciguatoxin family, was concisely synthesized by extensive use of ring-closing olefin metathesis.

■ Samarium(II) Iodide-mediated Intramolecular Aldol-type Cyclization

Masakazu Sono, Yasuyo Nakashiba, Katsuyuki Nakashima, Shigeru Takaoka, and Motoo Tori*

*Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-machi, Tokushima, 770-8514, Japan

Abstract

The α-substituted α,β-epoxy ketone having a formyl group in the molecule reacted with samarium(II) iodide to afford cyclized spiro ketones formed by an intramolecular aldol-type reaction. However, in the presence of proton source the ratio of spiro products decreased and the yield of hydrindanone increased. The α-substituted α,β-unsaturated cyclopentenone derivative smoothly cyclized into the same hydrindanone.

■ A Practical Route to Quinolines from Anilines

Hidetoshi Tokuyama, Masashi Sato, Toshihiro Ueda, and Tohru Fukuyama*

*Graduate School of Pharmaceutical Sciences, University of Tokyo, CREST, The japan Science and Technology Corporation (JST), 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan

Abstract

A practical route to quinoline from anilines through acid-mediated cyclization of 3-(N-aryl-N-sulfonylamino)propionaldehydes has been developed. Treatment of the cyclization products, dihydroquinoline intermediates with KOH in DMSO leads to substituted quinolines.

■ Benzyloxymethyl Group as a Convertible Internal Ligand for La(OTf)₃-Catalyzed 7-endo Ring-openig of Hydroxy Epoxide

Kenshu Fujiwara,* Hiroshi Morishita, Tetsuo Tokiwano, and Akio Murai*

*Division of Chemistry, Graduate School of Science, Hokkaido University, Sapporo 060-0810, Japan

Abstract

The benzyloxymethyl group at C5 of cis-5,6-epoxyheptanol promoted 7-endo selective ring-opening of the hydroxy epoxide under La(OTf)₃-catalyzed conditions to give r-2-methyl-c-3-benzyloxymethyl-t-3-hydroxyoxepane, whose benzyloxymetyl group was transformable to a methyl group.

■ Synthesis of Azanaphthoquinone Annelated Pyrroles

Helmut Spreitzer,* Andrea Pichler, Wolfgang Holzer, Martin Kratzel, Rita Slanz, Alexandra Koulouri, Petra Krenn, Ulrike Parrer, and Petra Szieber

*Institute of Pharmaceutical Chemistry, University of Vienna, Pharmaziezentrum, Althanstraβe 14, A-1090 Vienna, Austria

Abstract

The synthesis of azanaphthoquinone annelated pyrrole derivatives is described. The [c]-annelated derivative was synthesized by reaction of an azanaphthoquinone monoketal with tosylmethyl isocyanide. The synthesis of each of the two isomeric [b]-annelated pyrrole derivatives was realized by selective acylation reactions with pyrrole. Furthermore detailed NMR spectroscopic studies (¹H, ¹³C) are published.

■ Synthesis of Pyridinocrownophanes Exhibiting High Ag⁺-Affinity

Seiichi Inokuma, Koichi Kimura, Takashi Funaki, and Jun Nishimura*

*Department of Chemistry, Gunma University, 1-5-1 Tenjin-cho, Kiryu 376-8515, Japan

Abstract

Crownophanes possessing a pyridine moiety were prepared by means of intramolecular [2 + 2] photocycloaddition of the styrene derivatives. The crown compounds having six to ten ethereal oxygens selectively extracted Ag⁺ with high efficiency in the liquid-liquid extraction. The high extractability and efficiency were maintained even at low pH region of the extraction system. From ESI-MS analysis, it was found that the crownophanes formed some kinds of complexes having 1:1 and 2:1 stoichiometry (host/guest) with Ag⁺ and Pb²⁺ in MeCN-H₂O homogeneous system.

■ An Efficient Synthesis of Optical Isomers of Vasopressin V₂ Receptor Antagonist OPC-41061 by Lipase-catalyzed Enantioselective Transesterification

Jun Matsubara,* Seiji Morita, Hiroshi Yamashita, Kenji Otsubo, Kazuyoshi Kitano, Tadaaki Ohtani, Yoshikazu Kawano, Masahiko Bando, Masaru Kido, Minoru Uchida, and Fujio Tabusa

*Medical Chemistry Research Institute, Otsuka Pharmaceutical Co., Ltd., Kagasuno 463-10, Kawauchi-cho, Tokushima, Tokushima 771-0192, Japan

Abstract

The optically active enantiomers of 7-chloro-5-hydroxy-1-[2-methyl-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-1-benzazepine (OPC-41061, 1) were enantioselectively synthesized. The chiral acetate ((R)-(–)-3) and the chiral alcohol ((S)-(+)-2) were prepared via the resolution of the racemic alcohol ((±)-2) using the lipase-mediated transesterification with vinyl acetate. Compounds ((R)-(–)-3) and ((S)-(+)-2) were converted to optically active 1.

■ Synthesis and Properties of Novel Medium-sized Heterocyclic Compounds Containing Two Sulfur Atoms in the Ring and Synthetic Approaches to Conjugated Cyclic Disulfonium Ylides

Hiroshi Shimizu,* Hiroyoshi Watanabe, Masahiro Mizuno, Tadashi Kataoka, and Mikio Hori

*Gifu Pharmaceutical University, 6-1 Mitahora-higashi 5-chome, Gifu 502-8585, Japan

Abstract

Tribenzo[b,f,h][1,4]dithiecin (8) was prepared by coupling 2,2’-bis(bromomethyl)biphenyl (10) with 1,2-benzenedithiol (11) in the presence of NaH in acetonitrile. Another novel dithiecin derivative, 1,8-dihydro-2,7-benzodithiecin (9) was synthesized by coupling of 1,4-dimercapto-2,3-O-isopropylidene-Lg-threitol (13a) with α,α’-dibromo-o-xylene (12), followed by hydrolysis and subsequent dehydration via the mesylate derivative (16). The benzodithiecin (9) was also prepared by treatment of dithiol (18) with butadiyne along with α,α’-bis(1-buten-3-ynylthio)-o-xylene (19) as a byproduct. Compound (19) was subjected to an intramolecular coupling reaction using CuCl-pyridine-O₂ in benzene to yield the 12-membered ring compound (23). We also describe our effort to prepare the corresponding cyclic diylide compounds from the above new dithiecins (8) and (9), and known dithiecin (7).

■ Synthesis and Alkali Metal Picrate Extraction Studies of an Unusual Cage-functionalized Cryptand

Alan P. Marchand,* H. K. Hariprakasha, Hyun-Soon Chong, and Mohamed Takhi

*Department of Chemistry, University of North Texas, NT Station, Denton, TX 76203, U.S.A.

Abstract

Novel cage-functionalized cryptand (4) which contains two formaldehyde acetal linkages was synthesized. The structure of 4 was estabilished unequivocally via application of X-Ray crystallographic techniques. Alkali metal picrate extractions were performed by using 4 as the host complexant, and the results thereby obtained were compared with the corresponding extraction efficiencies of two model crown ethers, i.e., (8 and 9) at the same concentraction. Host system (4) proved to be considerably more efficient than either 8 or 9 as an alkali metal picrate extractant. In addition, 4 displayed moderatly high selectivity toward extraction of Li⁺ and Na⁺ picrates.

■ Synthesis and Properties of anti-6,15-Epithia-8,13-methanobenzo[e][14]annulene-7,14-dione, anti-5,14-Epithia-7,12-methanofuro[3,4-e][14]annulene-5,13-diones, and Their Ionic Species

Shengli Zuo, Shigeyasu Kuroda,* Mitsunori Oda,* Shin-ya Kuramoto, Yoshihiro Mizukami, Atsushi Fukuta, Yukiyasu Hirano, Teruhiko Nishikawa, Shinji Furuta, Ryuta Miyatake, Sha. I. Shaheen, Takanori Kajioka, and Mayumi Kyogoku

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

Abstract

The sulfur bridged annulene diones fused with benzene and furan were synthesized, and their ¹H and ¹³C NMR spectra in strong acid media indicated formation of dicationic species in which the positive charges localized on the carbonyl carbons, mainly due to the unfavorable p-orbital overlap.

■ Convenient Construction of Hexahydrobenzo[b]furan Skeleton Containing Heteroatoms. Choice of Mn(III)- and Ce(IV)-based Radical Cyclization

Shougo Kajikawa, Hiroshi Nishino,* and Kazu Kurosawa

*Institute for Fundamental Research of Organic Chemistry, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan

Abstract

Hexahydrobenzo[b]furan derivatives were efficiently synthesized by the radical cyclization of 1-arylcyclohexenes, 1-phenylcycloheptene, and 1,1-diarylethenes with barbituric acid derivatives or 5,5-dimethyl-1,3-cyclohexanedione (dimedone) using manganese(III) acetate or cerium(IV) ammonium nitrate (CAN).

■ Preparation of New Nitrogen-bridged Heterocycles. 50.¹ Syntheses of Some Heterocyclic Compounds Starting from Pyridinium 1-(Ethoxycarbonylacetyl)methylides

Akikazu Kakehi,* Suketaka Ito, Hiroyuki Suga, and Katsuaki Yasuraoka

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

Abstract

The reactions of the title methylides with dialkyl acetylenedicarboxylates gave the corresponding 3-(ethoxycarbonylacetyl)indolizine derivatives, whose 3-substituent was smoothly converted to a coumarin skeleton by Knoevenagel reaction with salicylaldehyde. The reactions of the methylides with carbon disulfide and alkylating agent in the presence of a base afforded pyridinium 1-[alkylthio(thiocarbonyl)](ethoxycarbonylacetyl)methylides, and the S-alkylations of these ylides with phenacyl bromides and subsequent alkaline treatment of the resulting pyridinium salts gave ethyl 3-alkylthio-1-(arylcarbonyl)thieno[3,4-b]indolizine-9-carboxylates.

■ Thionation of N-Acylthreonine and Its Methyl Ester with Lawesson's Reagent: Synthesis of 5-Oxazolones, 5-Thiazolones and Thiazolines

Mayuko Ori and Takehiko Nishio*

*Department of Chemistry, University of Tsukuba, Ten-nodai, Tsukuba-shi, Ibaraki, 305-8571, Japan

Abstract

The treatment of N-acylthreonine (1) with Lawesson’s reagent [LR: 2,4-bis(p-methoxyphenyl)-1,3,2,4-dithiaphosphetane 2,4-disulfide] afforded 5-oxazolones (2) in moderate yields, along with 5-thiazolones (3). On the other hand, N-acylthreonine methyl ester (5) reacted with LR to give 5-thiazolones (3) and 4-methoxycarbonylthiazolines (6).

■ Cycloaddition Reactions of Trimethylsilylketene with 8-Azaheptafulvenes and 6-Amino-1-azafulvenes

Kiyo Takaoka, Toyohiko Aoyama,* and Takayuki Shioiri*

*Faculty of Pharmaceutical Sciences, Nagoya City University, Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan

Abstract

Trimethylsilylketene smoothly reacts with 8-azaheptafulvenes to give 3,3a-dihydro-3-trimethylsilyl-1-azaazulen-2(1H)-ones, the [8+2] cycloadducts, in excellent yields. Furthermore, trimethylsilylketene also undergoes the [6+2] cycloaddition reaction with 6-amino-1-azafulvenes to afford 1H-pyrrolizin-3(2H)-ones.

■ Synthesis of α,α'-Asymmetric Nitroxide Radicals by C- or O-Acylation of Radical-enolate Intermediates Generated by Reduction of Homoallylic Nitro Enones with Samarium(II) Iodide

Rui Tamura,* Satoshi Shimono, Kasuke Fujita, and Ken-ichi Hirao

*Graduate School of Human and Environmental Studies, Kyoto University, Kyoto 606-8501, Japan

Abstract

A new synthetic method to form two structurally different α, α’-asymmetric bicyclic nitroxides from the same substrate is described. Reduction of certain homoallylic nitro enones bearing a long alkyl chain with 3.0 equiv of SmI₂ in THF at -78°C gave a nitroxide radical-anion species of type A, while the same reduction followed by addition of HMPA at -78°C resulted in the isomerization of the double bond to afford a different nitroxide radical anion species of type C. The former radical-anion undergoes O-acylation by the reaction with acyl chlorides to give α, α’-asymmetric bicyclic ester-nitroxides of type B, while the latter one does C-acylation to produce α, α’-asymmetric bicyclic β-diketonitroxides of type D.