HETEROCYCLES

■ Rolf Huisgen’s Contribution to Organic Chemistry, Emphasizing 1,3-Dipolar Cycloadditions

Reiner Sustmann

*Institut fur Organische Chemie, Universität Essen, D-45117 Essen, Germany

■ References in Chronological Order

Rolf Huisgen*

*Department of Chemistry, University of Munich, Butenandtstr. 5-13 (Haus F), D-81377, Muenchen, Germany

■ Synthesis of Annulated 7-Aza-indolizines by Intramolecular [3+2]Cycloaddition with Pyrazinium Dicyanomethylides

Martin Engelbach, Peter Imming, Gunther Seitz*, and Ralph Tegethoff

*Institut für Pharmazeutische Chemie, Philipps-Universität, Marbacher Weg 6 D-35032 Marburg/Lahn, Germany

Abstract

Thermally induced intramolecular [3+2] cycloaddition reactions of the pyrazinium dicyanomethylides (2, 9, and 15), carrying different side chains with terminal alkynes as dipolarophiles, lead lo the novel fused 7-aza-indolizines (6, 11, 12, and 18) in high yields. In a combined inter/intramolecular cycloaddition the dicyanomethylide (15b) surprisingly furnishes the bimolecular adduct (20) besides the desired tricycle (19).

■ One Pot exo-endo Isomerization in Bicyclic Adducts Arising from 1,3-Dipolar Cycloaddition Reactions of 7-oxanorbornene Derivatives

Odón Arjona, Araceli Mallo, and Joaqín Plumet

*Department of Organic Chemistry, Faculty of Chemistry, Complutense University, 28040 Madrid, Spain

Abstract

A new, one pot methodology to carry out the exo-endo isomerization of some tricyclic adducts derived from the cycloaddition of 7-oxabicyclo[2.2.1]hept-5-ene derivatives and nitrile oxides is described.

■ N-carboethoxypiperidine, a Convenient Reagent for the Preparation of Symmetrical Ketones from Organolithiums

G. K. Surya Prakash, Chentao York, Qimu Liao, Kirtivan Kotian, and George A. Olah

*Donald P. and Katherine B. Loker Hydrocarbon, Research Institute and Department of Chemistry, University of Southern California, Los Angeles California 90089-1661, U.S.A.

Abstract

N-Carboethoxypiperidine on reaction with organolithium reagents, RLi, followed by acidic work-up gave excellent yields of the corresponding symmetrical ketones, R₂CO.

■ Reaction of Metal Cyclopentadienides with 1,3-Bis(methylthio)-1,2-dithiolium Salts

Klaus Hartke* and Xue-Ping Popp

*Institut für Pharmazeutische Chemie, Universität Marburg, Marbacher Weg 6, D-35032 Marburg/Lahn, Germany

Abstract

Thallium and lithium cyclopentadienides (3) cleave the S,S-bond of 1,2-dithiolium salts (2) giving rise to intramolecular Diels-Alder adducts such as 6, 7, 8, and 9 or to intramolecular condensation products such as 10. Substitution of a methylthio group in 2 leads to the 2,3-dithiafulvalenes (11).

■ Reductions of 3-(N-Arylaminomethylene)succinimides

Rudolph A. Abramovitch* and Andrew V. Chapman

*Department of Chemistry, Clemson University, Clemson, SC 29634-1905, U. S. A.

Abstract

The reduction Z-N-methylanilinomethylene-N’-phenylsuccinimide reported and, depending on the conditions, a variety of products may be formed in reasonable yield. For example, the regioselectivity of the NaBH₄/EtOH reduction is different from that predicted in the literature, and LAH reduction under mild conditions gives N-phenylpyrrole-3-carboxaldehyde.

■ A 1,2-O-O-Silyl-Migration-Claisen-Rearrangement-S_N2'-Displacement Sequence in the Stereoselective Synthesis of 5-Oxaprostanoid Derivatives

Johann Mulzer* and Stefan Greifenberg

*Institut fur Organische Chemie, Freien Universitat Berlin, Takustrasse 3 D-14195 Berlin, Germany

Abstract

A novel stereocontrolled route to 5-oxaprostaglandin and PGF intermediates is described, which starts from the ene-diols (6/7) and uses a sequence of Claisen rearrangement, 1,2-O-O-silyl migration and S_N2’-cyclization reactions (9b → 10a/b via 11a/b).

■ Unexpected Stereoselectivity of Intramolecular 1,3-Dipolar Cycloaddition Caused by the Presence of Fluorine Atom

Masataka Ihara, Tatsuo Kawabuchi, Yuji Tokunaga, and Keiichiro Fukumoto

*Pharnaceutical Institute, Tohoku University, Aramaki, Aoba-ku, sendai 980-8578, Japan

Abstract

Intramolecular 1,3-dipolar cycloaddition of nitrones (11; R = Me, Et, and Bn) bearing one fluorine atom at the quaternary α-position produced two diastereoisomers of bicyclic isoxazolidines (12) and (13). It was revealed that the stereochemical outcome was considerably influenced by the presence of fluorine atom.

■ Isomerizations of 1,7-Diheteradispiro[4.0.4.4]tetradeca-11,13-dienes in the Presence of Tetracyanoethylene

Leo A. Paquette and Bruce M. Branan

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

Abstract

TCNE is shown to be capable of promoting the isomerization of the title compounds to a new class of unsaturated [4.4.4]propellanes and aromatic isomers thereof.

■ 1,3-Dipolar Cycloadditoin Reaction of 2-[(Trimethylsilylmethylamino)(methylthio)]methylene-1,3-indandione: Synthetic Equivalent of Cyclic Dicarbonyl Alkylidene-azomethine Ylide as a Novel 1,3-Dipolar Reagent

Yoshinori Tominaga, Satoshi Takada, and Shinya Kohra

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

Abstract

2-[(Trimethylsilylmethylamino)(methylthio)]methylene-1,3-indandione (1), readily prepared by reaction of the corresponding 2-bis(methylthio)methylene-1,3-indandione (7) with trimethylsilylmethylamine (8), was found to be a synthetic equivalent of carbonyl alkylidene-azomethine ylide. Reaction of 1 with reactive hetero-dipolarophiles such as aldehydes and ketones and reactive alkenes in the presence of cesium fluoride gave 1,3-dipolar cycloadducts, 2-(1,3-dioxoindan-2-ylidene)-1,3-oxazolidines (5a-i) and 2-(1,3-dioxoindan-2-ylidene)pyrrolidines (6a-c).

■ 5H-Dibenz[b,f]azepines, Part 5. Comparative Study of 10,11-Dihydro-5H-dibenz[b,f]azepine and Its Analogues in the Hydrogen Transfer Dehydrogenation Reaction

Imre Köhegyi and Vilmos Galamb

*Department of Research, Alkaloida Chemical Co. Ltd., H-4440 Tiszavasvári, POB 1, Hungary

Abstract

Improved hydrogen transfer reaction of 10,11-dihydro-5H-dibenz[b,f]azepine ( 1 ) was elaborated and generalized to 1,2-diphenylethane ( 10 ) and 9,10-dihydroanthracene ( 20 ) analogues Kinetic constants and activation parameters were determined. Stereomutation of ( Z )-stilbene ( 11 ) was achieved by supported palladium catalyst.

■ Silymethyl Radical Cyclization in Theopederins Synthesis — A New Access to Pederic Acid

Masahiro Toyota, Noriko Yamamoto, Youichi Nishikawa, and Keiichiro Fukumoto

*Pharnaceutical Institute, Tohoku University, Aramaki, Aoba-ku, sendai 980-8578, Japan

Abstract

Silylmethyl radical cyclization of the silyl ether (6) provided the 2-silatetrahydropyran derivative (7) possessing the correct C2, C3 and C7 stereochemistries of theopederins (1) and functionalities suitable for further elaboration.

■ Simple Syntheses of Lespedamine and 5-Bromo-N,N-dimethyltryptamine Based on 1-Hydroxyindole Chemistry

Masanori Somei, Kensuke Kobayashi, Keiko Tanii, Toshihiko Mochizuki, Yumiko Kawada, and Yashikazu Fukui

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

Abstract

Various types of 1-hydroxyindoles were prepared for the first time. Through methylation or acid catalyzed nucleophilic bromination of N,N-dimethyl-1-hydroxytryptamine, simple syntheses of lespedamine and 5-bromo-N,N-dimethyltryptamine were achieved, respectively.

■ Preparation and Properties of Tris(1,3-dithiole) Donors Containing Thiophene Spacer Units

Akira Ohta and Yoshiro Yamashita

*Department of Structural Molecular Science, The Graduate University for Advanced Studies, Institute for Molecular Science, Myodaiji, Okazaki 444-8585, Japan

Abstract

Novel tris(1,3-dithiole) donors (4) and (5) containing thiophene spacer units have been prepared. The cyclic voltammograms indicate that 4 and 5 are oxidized to trication radicals and tetracations, respectively, and on-site Coulombic repulsion in the dication state is reduced. An electroactive polymer was formed from 4c. The donors (4) and (5) gave conducting charge-transfer complexes with iodine.

■ Thermal Retrocycloaddition of 1,2,4,3-Trithiagermolanes: A New Method for Generation of Germanethiones

Norihiro Tokitoh, Tsuyoshi Matsumoto, and Renji Okazaki*

*Department of Chemistry, Graduate School of Science, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8567, Japan

Abstract

Thermolysis of 5,5-diphenyl-1,2,4,3-trithiagermolanes bearing bulky aromatic substituents on germanium atom resulted in the formation of novel germanium-sulfur double bond compounds, diarylgermanethiones, which were found to undergo ready [2+2] and [2+4] cycloaddition reactions with dimethyl acetylenedicarboxylate and 2,3-dimethyl-1,3-butadiene to give a new class of germanium-containing heterocycles.

■ Syntheses of Regiospecifically Meso Functionalized Dipyrromethanes, Porphyrins, and Diphenylethane-linked Bisporphyrins

David A. Lee, Jean M. Brisson, and Kevin M. Smith*

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

Abstract

Acid catalyzed condensation of 2-unsubstituted pyrroles with diethyl acetals permits preparation, in good yields, of a variety of meso-functionalized dipyrromethanes. Subsequent use in the so-called MacDonald “2+2” condensation provides 5-functionalized porphyrins and, eventually, benzochlorin derivatives. A novel application of a reductive coupling scheme, utilizing Ni(0), provides diphenylethane-linked bisporphyrins, which are potential models for electron transfer studies.

■ Asymmetric Synthesis of Methyl N,O-Diacetylspicigerinate

Takefumi Momose and Naoki Toyooka

*Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama, Toyama 930-0194, Japan

Abstract

The first asymmetric synthesis of methyl N,O-diacetylspicigerinate (1) has been achieved, and the absolute configuration of the parent alkaloid (2) was determined to be 2S, 3S, 6R.

■ Active Receptors in the Nucleophilic Addition of Pyrrolidine to Acrylamide

Mercedes Crego, César Raposo, M^a Luisa Mussons, Amanda Berrocal, M^a Cruz Caballero, and Joaquín R. Morán

*Departamento de Química Orgánica, Universidad de Salamanca, Plaza de los Caídos, 37008 Salamanca, Spain

Abstract

Three amide receptors which show significant catalytic activity in the nucleophilic addition of pyrrolidine to acrylamide have been prepared. Additional hydrogen bonds and charge-transfer in the transition state are invoked to explain the catalytic effect.

■ An Effective Method for Formylation of Weakly Nucleophilic Anilines and Indole

Isamu Shiina, Mitsutomo Miyashita, Masashi Nagai, and Teruaki Mukaiyama

*Department of Applied Chemistry, Faculty of Science, Science University of Tokyo, Kagurazaka 1-3, Shinjuku-ku, Tokyo 162-8601, Japan

Abstract

In the presence of a catalytic amount of active titanium(IV) salt or Yb(OTf)₃, weakly nucleophilic anilines and indole react under mild conditions with formic acid or aqueous formic acid to afford respectively the corresponding formanilides and indole-3-carboxaldehyde in excellent yields using 4-trifluoromethylbenzoic anhydride as a coreagent.

■ Formation of 2-Alkylaminooxazoles by the Rh₂(OAc)₄-Catalyzed Reaction of α-Diazocarbonyl Compounds in the Presence of Cyanamides

Kazuaki Fukushima and Toshikazu Ibata*

*Department of Chemistry, Faculty of Science, Osaka University, Toyonaka, Osaka 560-8531, Japan

Abstract

The Rh₂(OAc)₄-catalyzed reaction of α-diazoacetophenones with N,N-dialkylcyanamides gave the corresponding 2-(N,N-dialkyIamino)-5-aryloxazoles in high yields. Although para-substituents of the diazoacetophenone and the N-alkyl groups of cyanamide did not affect the yields of the oxazole, unsubstituted and monosubstituted cyanamides gave the corresponding 2-aminooxazoles in low yields. 2-(N,N-Dialkylamino)-5-alkoxyoxazoles formed by the similar reaction of diazoacetates with N,N-dialkylcyanamides were found to be unstable upon isolation.

■ Formation of a New Ring System via Addition of Acrylonitrile to Benzoquinolizines

Lajos Szabó, György Kalaus, Alajos Kálmán, Pál Kolonits, and Csaba Szántay

*Institute for Organic Chemistry, Technical University Budapest, H-1521 Budapest, P.O. Box 91Gellért tér 4, Hungary

Abstract

The reaction of enamine (4) with acrylonitrile gave rise to compound (6) in addition to four (7-10) stereoisomeric derivatives of a new ring system.

■ Syntheses of New Heterocycles Starting from Dicyanoacetates

Richard Neidlein and Peter Meffert

*Pharmazeutisch-Chemishces Institut, Ruprecht-Karls-Universität Heidelberg, Im Neuenheimer Feld 364, D-69120 Heidelberg, Germany

Abstract

The reactions of 4-chloro-2-dialkylamino-6-oxo-6H-1,3-oxazine-5-carbonitriles (3) with C-, N- and S-nucleophiles are reported. The chloro atom can also be substituted in a Michaelis-Arbuzov reaction giving the corresponding 1,3-oxazinyl phosphinates and phosphinoxides.

■ The Conformation of Trispyrazolylmethanes: An Experimental and Theoretical Study

Rosa María Claramunt, Concepción López, Carles Jaime, Albert Virgili, Carlos Marco, and José Elguero

*Departamento de Química Orgánica y Biologiá, Faclutade de Ciencias, UNED, Senda del Rey 9, E-28040 Madrid, Spain

Abstract

A combination of methods which include MM2 and MNDO calculations, nmr spectroscopy in the solid state (CPMAS) and in solution (¹H, ¹³C, LSR, chiral solvents and NOE experiments), DSC and X-ray powder diffraction has been used to study the conformation of tris(pyrazol-1-yl)methanes and ethanes. It has been shown that tris(3,5-dimethylpyrazol-1-yl)methane (4) exists in two isolable isomers, the ABB and the BBB, whose interconversion by melting, crystallization and sublimation has been studied.

■ Conversion of 1-(o-Nitroaryl)alkyl p-Tolylsulfones into Isoxazoles

Zbigniew Wróbel and Mieczyslaw Makosza

*Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-244 Warsaw, Poland

Abstract

Partial reduction of o-nitrobenzyl p-tolylsulfones in alkaline medium results in the formation of the nitrosobenzylsulfone carbanions which cyclize to isoxazoles.

■ 1,3-Dipolar Cycloaddition Chemistry of 2,3-Bis(phenylsulfonyl)-1,3-diene with Diazoalkanes

Albert Padwa, Michael Meske, and Augusto Rodoriguez

*Department of Chemistry, Emory University, 1515 Pierce Drive Atlanta, Georgia 30322, U.S.A.

Abstract

2,3-Bis(phenylsulfonyl)-1,3-butadiene was found to react smoothly with diazomethane and diazopropane to give a mixture of 1:1- and 2:1-cycloadducts. Heating the 1:1-cycloadduct at 110°C resulted in loss of nitrogen and formation of mainly phenylsulfonyl-substituted 1,3-dienes. Cycloaddition of 2-phenylsulfinyl-3-phenylsulfonyl-1,3-butadiene with the same diazoalkanes gave only 1:1-cycloadducts which readily extruded nitrogen producing related 1,3-dienes. The regiochemistry of the dipolar cycloaddition is compatible with FMO considerations.

■ Stereoselective Epoxidation of 5(10)-Ene of 11β-Functionated Steroids and Effect of 5(10)-Epoxy Group on Reaction of 11β-Substitute

Yang Suming, Yang Zhengyu, Xia Yi, and Xia Peng

*Department of Organic Chemistry, School of Pharmacy, Shanghai Medical University, 138 Yi Yuan Road Shanghai 200032, China

Abstract

A route for synthesis of steroidal 5(10)α-epoxy-9(11)-ene from 11β-functionalized estr-5(10)-ene via epoxidation of 5(10)-ene and then introduction of 9(11)-ene was reported. The effect of 11β-hydroxy and acyloxy groups on stereoselective epoxidation of 5(10)-ene as well as the effect of 5(10)-epoxide configuration on some reactions of corresponding 11β-substitutes were described. A 11β-phenyl-4,9-estradiene compound has been synthesized from the 9(11)-ene-5(10)α-epoxide intermediate obtained by this route.

■ Biorational Design of Herbicides: Synthesis of Inhibitors of the PFP Enzyme

Mukund S. Chorghade* and Csaba T. Cseke

*Abbott Laboratories, Abbott Park, N. Chicago, IL60064, U.S.A.

Abstract

Transition state and reaction coordinate analog inhibitors of the PFP enzyme were synthesized for the biorational design of herbicides. Some of the promising ones were scaled up and tested on whole plants. Open chain, aza and phosphonated analogs of fructose showed significant PFP inhibitory activity.

■ Studies of Schmidt-Type Rearrangements of Pentacyclo[5.4.0.0^2,6.0^3,10.0^5,9]undecan-8-one. Unexpected Incursion of the Huisgen Rearrangement

Alan P. Marchand*, Viktor D. Sorokin, D. Rajagopal, and Simon G. Bott

*Department of Chemistry, University of North Texas, NT Station, P.O. Box 305070, Denton, TX 76203-0068, U.S.A.

Abstract

Reaction of pentacyclo[5.4.0.0_2,6.0_3.10.0_5.9]undecan-8-one (1) with H₂NOSO₃H-HCO₂H affords two pentacyclic lactams (2a) (15%) and (2b) (30%). Reaction of 1 with HN₃-Tf₂O results in the formation of a pentacyclic urea (3) (16%) and a tricyclic azidonitrile (4) (18%). The unusual “double Schmidt rearrangement” that results in the formation of 3 is rationalized via formation of an intermediate tetrazole (5) which undergoes subsequent acylation with concomitant Huisgen rearrangement.

■ Imidoylbenzotriazoles: Stable Alternatives to Imidoyl Chlorides

Alan R. Katritzky*, Christian V. Stevens, Gui-Fen Zhang, Jinlong Jiang, and Norbert De' Kimpe

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

Abstract

Imidoylbenzotriazoles were prepared from the corresponding amides and 1,1’-sulfinyldibenzotriazole, generated in situ from 1-trimethylsilylbenzotriazole and thionyl chloride. The imidoylbenzotriazoles are stable precursors for the synthesis of imidates and thioimidates.