HETEROCYCLES

■ Preface

Masatomo Hamana*

*Faculty of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan

■ Summary of Katritzky Research Group Scientific Results (1954-1993)

Alan R. Katritzky

*Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, P. O. Box 117200, Gainesville, FL 32611-7200, U.S.A.

■ References in Chronological Order (This list covers books, reviews, and original publications — conference proceedings and abstracts are not included)

Alan R. Katritzky*

*Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, P. O. Box 117200, Gainesville, FL 32611-7200, U.S.A.

■ Synthesis of 5,5-Dimethyl-7-methoxy-4-oxatricyclo[4,3,1,0^3,7]decan-2-ones

Sadagopan Raghavan and G. S. R. Subba Rao*

*Department of Organic Chemistry, Indian Institute of Science, Bangalore-560 012, India

Abstract

Two new synthetic routes for the preparation of the title compound and its 3-substituted derivatives, a novel ring system present in morellin and other related natural products, are reported from the readily available dihydroanisoles.

■ Reaction of 2,6-Diaryl-3,7-dioxabicyclo[3.3.0]octane Lignans

Andrew Pelter* and Robert S. Ward

*Chemistry Department, University of Swansea, Singleton park, Swansea SA2 8PP, U.K.

Abstract

Reactions of 2,6-diaryl-3,7-dioxabicyclo[3.3.0]octane lignans (furofurans) have been rationalised in terms of the production of stabilised carbocations. These may be produced by acid catalysed or oxidative reactions dependant on the constitution of the lignan substrate. The carbocations may then undergo rearrangements in the case of acid catalysed reactions or the reanangement products may themselves be funher oxidised. In the presence of hiethylsiie the carbocations are reduced prior to rearrangement.

■ Indoline Formation by Regioselective Aryl Radical Cyclization to Azomethine Bond

Seiichi Takano,* Mahito Suzuki, and Kunio Ogasawara

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

Abstract

Aryl radical-initiated cyclization of the ketimines derived from acetophenone and benzophenone occurred exclusively at the nitrogen end of the azomethine bond in an exo-5 mode to yield the corresponding indoline derivatives.

■ Convenient Synthetic Methods for 5-Trifluoromethyloxazoles and 5-Trifluoromethylthiazoles

Yasuhiro Kamitori, Masaru Hojo, Ryoichi Masuda,* Masaaki Wada, and Toshiya Takahashi

*Department of Industrial Chemistry, Faculty of Engineering, Kobe University, Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan

Abstract

5-(Trifluoromethyl)oxazoles (3) and 5-(trifluoromethyl)thiazoles (4) were conveniently as well as effectively synthesized from 3-(N-tert-butyl-N-methylhydrazono)-1,1,1-trifluoroalkan-2-ones (1) via 5-(trifiuoromethyl)-3-oxazoline (2). One-pot conversion of 1 to 4 also proceeded successfully.

■ A Convenient Synthetic Method for Fluorine-containing Naphtho[1,2-d][1,3]thiazines from N, N-Dialkyl-2,4-bis(trifluoroacetyl)-1-naphthylamines

Etsuji Okada, Ryoichi Masuda,* Masaru Hojo, Hiroshi Tone, and Takeshi Tomifuji

*Department of Industrial Chemistry, Faculty of Engineering, Kobe University, Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan

Abstract

The reaction of N,N-dialkyl-2,4-bis(trifluoroacetyl)-1-naphthylamines with Lawesson’s reagent proceeded in refluxing toluene to give fluorine-containing naphtho[1,2-d][1,3]thiazines in satisfactory yields. The regioselectivity in this cyclization was also investigated.

■ Synthesis of Bis(trifluoromethyl)chromanols

Mayumi Koyama, Toshiyuki Takagi, Akira Ando, and Itsumaro Kumadaki*

*Faculty of Pharmaceutical Sciences, Setsunan University, 45-1, Nagaotoge-cho, Hirakata-shi, Osaka 573-0101, Japan

Abstract

Dimethylhydroquinones (1a-c) were treated with 6-chloro-3-methyl-2-hexen-1-ol in the presence of zinc chloride to give 2-(3-chloropropyl)chromanol derivatives (2a-c), which were methoxymethylated and condensed with trifluoroacetone through the corresponding phosphonium salts (4a-c) to 5,5,5-trifluoro-4-methyl-3-pentenylchromanols (5a-c). 2,5,7-Trimethyl compound (5a) was iodinated and treated with trifluoromethyl iodide and copper powder followed by deprotection and hydrogenation to give 4’,8-bis(trifluoromethyl) compound (9a). 4’,5-And 4’,7-bis(trifluoromethyl) compounds (9b and 9c) were derived from 5b and 5c through bromine compounds.

■ Novel Lactam Synthesis via Enol Lactone

Shin-ichi Hamaoka, Mami Kawaguchi, and Miwako Mori*

*Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan

Abstract

The lactams (11) and (13) were synthesized by the reaction of mine with the enol lactones (12), which were prepared from the enol triflates (5) using palladium catalyzed carbonylation.

■ Efficient and Facile Syntheses of [4,5]-Annelated Pyridazines from 4-Pyridazinecarbaldehydes

Péter Mátyus,* Kaoru Fuji, and Kiyoshi Tanaka*

*Institute for Chemistry, Kyoto University, Uji, Kyoto 611-0011, Japan

Abstract

New synthetic approaches to novel [4,5]-annelated pyridazine derivatives through the closely related intermediates, are described. These include derivatives of two angularly oriented ring systems (4) and (5), as well as those of pyrano[2,3-d]- and pyrazolo[3,4-d]pyridazines (6) and (8). The tertiary amino effect was successfully applied to the construction of the former compounds, whereas the latter compounds were formed by the cyclization based on additionelimination sequences.

■ The Reaction of Indolyl Grignard and Related Organometallic Reagents with 2-Phenylsulphonylbuta-1,3-diene and 2,3-Diphenylsulphonylbuta-1,3-diene

Neil Barnwell, Roy L. Beddoes, Michael B. Mitchell, and John A. Joule*

*Department of Chemistry, University of Manchester, Oxford Road, Manchester, M13 9PL, U.K.

Abstract

Indolyl Grignard reagents, and some related organometallic species, react with 2,3-diphenylsulfonylbuta-1,3-diene producing RCH₂C(SO₂Ph)=C=CH₂, where R is derived from the organometallic reagent.

■ A Facile Synthesis of 4-Aryl-5-hydroxy-(2E)-pentenoate Derivatives and Its Applications to the First Synthesis of (±)-Curucudiol, (±)-Curcuhydroquinone and (±)-Curcuquinone

Machiko Ono,* Yasuo Yamamoto, Reiko Todoriki, and Hiroyuki Akita*

*Faculty of Pharmaceutical Sciences, Toho University, 2-2-1, Miyama, Funabashi, Chiba 274-8510, Japan

Abstract

The tirst syntheses of three kinds of bisabolane sesquiterpenes, (±)-curcudiol (29), (±)-curcuhydroquinone (40) and (±)-curcuquinone (41) were achieved based on the BF₃·Et₂O catalyzed reaction of (±) methyl 4,5-epoxy-(2E)-pentenoate (1) and polymethoxytoluene.

■ Thionium Ion-activated Pinacol Rearrangements. Generality and Scope

Leo. A. Paquette,* Uta Dullweber, and Bruce M. Branan

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

Abstract

The acid-catalyzed rearrangement of tertialy allylic alcohols produced by the addition of 5-lithio-2,3-dihydrothiophene to cyclic ketones of various ring size has been probed.

■ The Reaction of Furazano[3,4-b]quinoxaline 1-Oxide with Cyclopentadiene: Trapping of the 2,3-Dinitrosoquinoxaline Intermediate

John K. Gallos* and Elizabeth Malamidou-Xenikaki

*Department of Chemistry, Aristotle University of Thessaloniki, Thessaloniki 540 06, Greece

Abstract

The trapping of the 2,3-dinitrosoquinoxaline by reaction of furazano[3,4-b]quinoxaline 1-oxide with cyclopentadiene is reported.

■ Synthesis of Enantiomerically Pure (5S)-4-Aza-2-oxa-6,6-dimethyl-7,10-methylene-5-spiro[4.5]-decan-3-one, a Novel Chiral Oxazolidin-2-one from (-)-Camphene for Use as a Recyclable Chiral Auxiliary in Asymmetric Transformations

Malcolm R. Banks, J. I. G. Cadogan, Ian Gosney,* Keith J. Grant, Philip K. G. Hodgson, and Paul Thorburn

*Department of Chemistry, The University of Edinburgh, King's Buildings, West Mains Road Edinburgh, EH9 3JJ, U.K.

Abstract

By an intramolecular nitreno-mediated route (-)-camphene is transformed into a novel spiro-oxazolidin-2-one whose efficiency as a chiral auxiliary is highlighted by the excellent levels of chiral induction attained in an array of asymmetric transformations such as the Diels -Alder, conjugate addition, aldol condensation, alkylation and acylation reactions.

■ Kinetic vs Thermodynamic Product Distributions of Macrocyclic Tetrapyrrole Cyclization Products from 1,19-Disubstituted A,C-Biladiene Salts

Kevin R. Gerzevske, Jack J. Lin, and Kevin M. Smith*

*Department of Chemistry, University of California, Davis, One Shields Avenue, Davis, CA 95616-5295, U.S.A.

Abstract

Chromium(III) promoted oxidative cyclization reactions of a,c-biladiene hydrobromides bearing bulky 1- and 19-substituents to give macrocyclic products are partially reversible; depending upon the reaction temperature, kinetic or thermodynamic products are formed and identified.

■ Some New Porphodimethene Chemistry: Synthesis of meso-Formylporphyrins

José A. S. Cavaleiro, M. Graça, P. M. Neves, Craig J. Medforth, and Kevin M. Smith*

*Department of Chemistry, University of California, Davis, One Shields Avenue, Davis, CA 95616-5295, U.S.A.

Abstract

Treatment of dipyrromethane-1,9-dicarboxylic acids with triethyl orthoformate and trifluoroacetic acid gives the expected symmetrically substituted porphyrin, along with small amounts of meso-formyl and meso-diformyl-porphyrins. The 5,15 regioselectivity of the formyl groups in the disuhstituted product and NOE experiments suggest that serendipitous formylation takes place at the intermediate porphodimethene stage.

■ Oxidation of N⁶-Benzyladenine with m-Chloroperoxybenzoic Acid: Formation of the N(1)-Oxide

Tozo Fujii,* Kazuo Ogawa, and Taisuke Itaya

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

Abstract

Oxidation of N⁶-benzyladenine (2) with m-chloroperoxybenzoic acid in MeQH has been found to give N⁶-benzyladenine 1-oxide (1) as the main product. The structure of 1 has been established by leading it to N⁶-methoxyadenine (4) through O-methylation, Dimroth rearrangement, and nonreductive debenzylation.

■ Synthesis of Furans from Epoxypropargyl Esters

José M. Aurrecoechea* and Mónica Solay-Ispizua

*Departamento de Química Orgánica, Facultad de Ciencias, Universidad del País Vasco, Apartado 644, 48080 Bilbao, Spain

Abstract

Treatment of 1-(1,2-epoxyalkyl)-2-alkynyl esters with samarium diiodide/Pd° affords E/Z mixtures of 2-alken-4-yn-1-ols where the Z-isomers can be directly transformed into substituted furans. The method is useful for the synthesis of tetrahydroisobenzofurans. A different substitution pattern in the furan nucleus is obtained by application of the same reaction to a regioisomeric 4-(1,2-epoxyalkyl)- 2-alkynyl ester via a cumulene alcohol intermediate.

■ Structure and Spectral Properties of β-Carbolines, Part 6. Regiooooselectivity of Cyclocondensation of Spiro[piperidine-m',1-(1,2,3,4-tetrahydro-β-carbolines)] with Aldehydes

Maria J. Mokrosz,* Maria H. Paluchowska, Stanislaw Misztal, and Jerzy L. Mokrosz

*Department of Mmedical Chemistry, Institute of Pharmacology, Polish Acadeamy of Sciences, 12 Smetna Street, 31-343 Kraków, Poland

Abstract

Cyclocondensation of spiro derivatives of 1,2,3,4-tetrahydro-β-carbolines (1) and (5) with aldehydes was found to be a regioselective process. The structure of individual new ring systems. i.e. N-3,7 (2-4), N-2,7 (6) and N-2,14 (7-9) cyclocondensation products, was determined using ¹H nmr techniques.

■ Synthesis of the Novel Tricyclic Heterocycle, 1H-1,4,7-Triazaphenalene, Pyridine-containing Ring System: Hexamethyl 1H-1,4,7-Triazaphenalene-2,3,5,6,8,9-hexacarboxylate

Yoshinori Tominaga* and Kenichi Nomoto

*Faculty of Pharmaceutical Sciences, Nagasaki University, 1-14, Bunkyo-machi, Nagasaki 852-8521, Japan

Abstract

The reaction of 3-amino-3-methylthio-2-cyanoacrylonitrile (1) with excess dimethyl acetylenedicarboxylate(DMAD) in the presence of potassium carbonate in dimethyl sulfoxide gave a novel tricyclic heterocycle, hexamethyl IH-1,4,7-triazaphenalene-2,3,5,6,8,9-hexacarboxylate (5). When one equivalent of DMAD was used in this reaction, dimethyl 4-amino-3-cyano-2-methylthiopyridine-5,6-dicarboxylate(3), a key intermediate of 5, was obtained.

■ Synthesis of 4,6-Dihydro-4-oxopyrido[2,1-a]isoindoles and 4,6-Dihydro-6-oxothieno[2',3',:3,4]pyrrolo[1,2-a]pyridines

Serge Burner, Rolf Canesso, and Ulrich Widmer*

*Pharma Division, Preclinical Research, F.Hoffmann-La Roche Ltd., CH-4002 Basel, Switzerland

Abstract

Tricyclic pyridones (3) which are important intermediates for the preparation of potent benzodiazepine receptor ligands were obtained by different chemical routes. Key reaction in the so far optimal synthesis of 3a is the base catalyzed ring contraction reaction of 2 to intermediate (13). Under similar reaction conditions, however, thiophene derivative (14) yielded instead of the analogous acid (16), the nitrile (15). In two additional steps the final product (3b) was obtained in good yield.

■ Synthesis of 7-Azabicyclo[2.2.1]heptane and 8-Azabicyclo[3.2.1]octane Systems Using Radical Cyclization

Tatsunori Sato, Tomiyo Mori, Tadakatsu Sugiyama, Hiroyuki Ishibashi, and Masazumi Ikeda*

*Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607-8414, Japan

Abstract

A new method for the synthesis of the titled systems using cyclization of the α-acylamino radicals generated from methyl N-(o-bromobenzoyl)-2-(prop-2-enyl)pyrrolidine-2-carboxylates and the piperidine congener by Bu₃SnH-mediated radical translocation reaction is described.

■ Heteroaromaticity. 9. The Role of Zwitterions in the Tautomerism of Hydroxy- and Mercaptoheterocycles

Clive W. Bird*

*Department of Chemistry, King’ s College London, The Strand, London WC2R 2LS, U.K.

Abstract

The application of the Aromaticity Index, I_A, shows that the zwitterions derived from a variety of hydroxy or mercaptoheterocycles have comparable aromaticities to their precursors, thus emphasising the potential role of zwitterionic species in tautomeric equilibria.

■ Reaction of Aromatic N-Oxides with Dipolarophiles XIX. PM3 Analysis of Sequential Pericyclic Reactions between Pyridine N-Oxides and Allenes

Toshikazu Matsuoka, Kazunobu Harano, and Takuzo Hisano*

*Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-hon-machi, Kumamoto 862-0973, Japan

Abstract

Sequential pericyclic reactions between pyridine N-oxides and allenes were evaluated in terms of PM3 calculation. Structures corresponding to the perturbating system were calculated by varying the distance of the addends. The cycloaddition occurs via Π-complex. In the transition structure TS1 of primary cycloaddition, the lengths of the newly created bonds of O-C and C-C are 1.864 and 2.204 A, respectively. The bond between the O atom of pyridine N-oxide and the central carbon of allene is ca. 35 % formed at TS1, slightly advanced than the other (ca. 30 %). The PM3 calculation at the UHF level predicts that [1,5]-sigmatropic rearrangement of the primary cycloadduct proceeds via a transition state with a biradical character.

■ Structure and Spectral Properties of β-Carbolines. Part 7. The Pictet-Spengler Reaction of Tryptamines with N-Benzyl-4-piperidone

Maria J. Mokrosz, Piotr Kowalski, Andrzej J. Bojarski, and Jerzy L. Mokrosz*

*Department of Mmedical Chemistry, Institute of Pharmacology, Polish Acadeamy of Sciences, 12 Smetna Street, 31-343 Kraków, Poland

Abstract

The Pictet-Spengler reaction of substituted tryptamines (1b-1g) with N-benzyl-4-piperidone afforded spiro derivatives (3b-3g) with a yield of 11-76%. A charge sensitivity analysis (CSA) of the protonated form of Schiff bases (8) indicated that the intramolecular electrophilic attack at position 3 is favorable in relation to that at position 2.

■ Transition-Metal Binding Site of Bleomycin. Significance of the β-Aminoalaninamide Appendage in Regulating Oxygen Activation

Toru Sugiyama, Masaji Ohno, Masakatsu Shibasaki, Masami Otsuka,* Yukio Sugiura, Susumu Kobayashi, and Kenji Maeda

*Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan

Abstract

A synthetic model study on the iron-binding site of bleomycin demonstrated that the dioxygen-activating properties of ligands largely depend on the characteristics of functional groups contained in the β-aminoalaninamide moiety.

■ Photoinduced Molecular Transformations. part 147. [2+2]Photoaddition of Protected 4-Hydroxy-1(2H)-isoquinolinone with an Electrondeficient Alkene and the Formation of a 3,6-Epoxy-3,4,5,6-tetrahydro-2-benzazocin-1(2H)-one via a β-Scission of Cyclobutanoxyl Radicals Generated from the Resulting photoadduct

Hiroshi Suginome,* Yoshinori Kajizuka, Masayoshi Suzuki, Hisanori Senboku, and Kazuhiro Kobayashi

*Organic Synthesis Division, Faculty of Engineering, Hokkaido University, Sapporo 060, Japan

Abstract

The direct irradiation of 4-benzyloxycarbonyloxy-2-methyl-1-(2H)-isoquinolinone gave a 1 to 1 ratio of two stereoisomers of [2+2] photoadducts in 97% yield. Removal of the protecting group from the adducts by hydrogenolysis gave the corresponding cyclobutanols, (1α, 2aα, 8bα)-(±)-1-cyano-1,2a,3,8b-tetrahydro-8b-hydroxy-3-methylcyclobut[c]-isoquinolin-4(2H)-one and its (1a, 2aβ, 8bβ)- isomer in 78 and 67% yields. The photolysis of the hypoiodite generated in situ from the (1α, 2aα, 8bα)-(±)-cyclobutanol with mercury(II) oxide - iodine in benzene induced a regioselective β-scission at the ring fusion bond of the cyclobutanoxyl radical to give 5-cyano-3,6-epoxy-3,4,5,6-tetrahydro-6-hydroxy-2-methyl-2-benzazocin-1(2H)-one in 76% yield. The cyano substituent and the amide nitrogen play a decisive role in directing the bond to be cleaved.

■ A Total Synthesis of (±)-Tacamonine (Pseudovincamone I) through Radical Cyclization

Masataka Ihara, Fumihito Setsu, Miyuki Shohda, Nobuaki Taniguchi, and Keiichiro Fukumoto:

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

Abstract

The radical cyclization of the bromo ester (11), prepared from 2-hydroxymethylbutan-1-ol (7), giving the diastereoisomeric mixture of lactones (12) was examined under various conditions. Treatment of the bromo ester (17), derived from 7, with tris(trimethylsilyl)silane in the presence of 2,2-azoisobutyronitrile provided the epimeric mixture of lactams (18), convertible to (±)-tacamonine (pseudovincamone I) (1) in three steps.