Special Issue

Barry M. Trost's Special Issues, Vol. 67, No. 2, 2006

38 data found. 1 - 30 listed Next Last
Communication | Special issue | Vol 67, No. 2, 2006, pp. 489 - 494
Published online: 28th October, 2005
DOI: 10.3987/COM-05-S(T)17
Synthesis of 5-Heterocyclic Substituted Quinazolin-4-ones via 2-Aminobenzonitrile Derivatives

M. Jonathan Fray,* Paul Allen, Paul R. Bradley, Clare E. Challenger, Michael Closier, Tim J. Evans, Mark L. Lewis, John P. Mathias, Carly L. Nichols, Yvonne M. Po-Ba, Hayley Snow, Mark H. Stefaniak, and Hannah V. Vuong

*Department of Discovery Chemistry, Pfizer Global Research and Development, Sandwich, Kent, CT13 9NJ, U.K.


Two routes to prepare a series of six 5-heterocyclic substituted 2-chloro-7-methoxyquinazolin-4-ones are described, where the heterocycle is a substituted or unsubstituted 1-pyrazolyl, 5-pyrazolyl or 2-thiazolyl group. Both routes proceeded via key 2-aminobenzonitrile intermediates.

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Communication | Special issue | Vol 67, No. 2, 2006, pp. 495 - 501
Published online: 18th November, 2005
DOI: 10.3987/COM-05-S(T)41
Catalytic Asymmetric Michael Reaction under Phase-transfer Catalysis: Construction of Chiral Tetrasubstituted Carbon and Its Application to the Synthesis of a Chiral Pyrrolidone

Shigeru Arai,* Fumie Takahashi, Riichiro Tsuji, and Atsushi Nishida*

*Graduate School of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan


A catalytic asymmetric Michael reaction using Schiff bases promoted by D2-symmetrical ammonium salts as phase-transfer catalysts is described. The reaction of glycine Schiff base (1a) gave the Michael adduct with up to 91% ee and tetrasubstituted carbons was also constructed using alanine Schiff base (3a) with up to 63% ee.

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Communication | Special issue | Vol 67, No. 2, 2006, pp. 503 - 506
Published online: 16th September, 2005
DOI: 10.3987/COM-05-S(T)43
Tin(II) Iodide-catalyzed Selective Aziridination or 1,2-Diamination of Alkenes with Chloramine-T

Yoshiro Masuyama,* Masaru Ohtsuka, Masaru Harima, and Yasuhiko Kurusu

*Department of Chemistry, Faculty of Science and Technology, Sophia University, Kioi-cho 7-1, Chiyoda-ku, Tokyo 102-8554, Japan


Tin(II) iodide selectively catalyzes reactions of alkenes in acetonitrile to afford the corresponding aziridines by the use of one equimolar amount of Chloramine-T [Ts(Cl)N-] at room temperature and to afford the corresponding 1,2-diamines by the use of excess Chloramine-T at 50 °C.

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Communication | Special issue | Vol 67, No. 2, 2006, pp. 507 - 510
Published online: 30th September, 2005
DOI: 10.3987/COM-05-S(T)46
Group 14 Hetero- Mono- and Bicyclosilanes

Jelena Fischer, Walter Gaderbauer, Judith Baumgartner, and Christoph Marschner*

*Institut für Anorganische Chemie, Technische Universität Graz, Stremayrgasse 16, A-8010 Graz, Austria


Sila-, germa- and stannacyclopentasilanes could be obtained by reaction of a 1,4-dianionic polysilane with the dimethyl dichlorides of silicon, germanium and tin. With potassium tert-butoxide the cyclopentasilanes could be transformed into dianions, which were converted to bicyclic compounds by reaction with ethylene glycol ditosylate.

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Communication | Special issue | Vol 67, No. 2, 2006, pp. 511 - 518
Published online: 6th December, 2005
DOI: 10.3987/COM-05-S(T)47
Solid-phase Pyrrolidine Synthesis via 1,3-Dipolar Cycloaddition of Azomethine Ylides Generated by the Decarboxylative Route

Batia Ben-Aroya Bar-Nir and Moshe Portnoy*

*School of Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv, 69978, Israel


Although solid-phase pyrrolidine synthesis via dipolar cycloaddition of ester-stabilized azomethine ylides has been demonstrated on several occasions, this reaction with nonstabilized azomethine ylides, generated on solid support by a decarboxylative pathway, has never been reported. Herein we present the first solid-phase synthesis of pyrrolidines via this route and demonstrate that the reacting azomethine ylide can be generated both from a resin-bound aldehyde or amino acid. Using cyclic and acyclic dipolarophiles, bi- and monocyclic resin-bound pyrrolidines were obtained. The modest to high degree of regio- and diastereoselectivity observed in the reaction can be tuned by the substituents of the partners of this three-component process.

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Communication | Special issue | Vol 67, No. 2, 2006, pp. 519 - 522
Published online: 30th September, 2005
DOI: 10.3987/COM-05-S(T)52
Synthesis of Bicyclic Cyclopropylamines from Amino Acid Derivatives

Catherine A. Faler, Bin Cao, and Madeleine M. Joullié*

*Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, PA 19104-6323, U.S.A.


The synthesis of novel [3.1.0] bicyclic cyclopropylamines from differently substituted amino acids using Ti(II)-mediated coupling and the extension of this methodology to provide [4.1.0] systems is described.

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Communication | Special issue | Vol 67, No. 2, 2006, pp. 523 - 528
Published online: 30th September, 2005
DOI: 10.3987/COM-05-S(T)54
Synthesis of Bicyclic Compounds Containing a 2-Pyridone Structure by Addition Reactions of Malonic Esters to Alkynylpyridines, Pyrimidine, and Thiazoles

Iwao Hachiya, Masaki Atarashi, and Makoto Shimizu*

*Department of Chemistry for Materials, Faculty of Engineering, Mie University, 1515 Uehama-cho, Tsu, Mie 514-8507, Japan


4H-Quinolizin-4-ones, 6H-pyrido[1,2-a]pyrimidin-6-ones, and 5H-thiazolo[3,2-a]pyridin-5-ones were prepared by addition reactions of malonic esters to 2-alkynylpyridines, pyrimidine, and thiazoles.

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Communication | Special issue | Vol 67, No. 2, 2006, pp. 529 - 533
Published online: 16th September, 2005
DOI: 10.3987/COM-05-S(T)58
Synthesis of Chiral Tropopodands Having L-Amino Acid Moieties and Ability of Their Metal Complexes as an Asymmetric Catalyst

Ohki Sato,* Yusuke Koshiba, Satoshi Sagara, and Katsuyoshi Okada

*Department of Chemistry, Faculty of Science, Saitama University, Urawa, Saitama 338-8570, Japan


Optical active tropopodands (10 and 11) having neutral L-amino acids and L-histidine moieties were synthesized. Within their metal complexes, Pd complexes of histidine-tropopodands (11b and 11c) bearing bulky amide moieties showed good ability as an asymmetric catalyst in conjugate addition.

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Communication | Special issue | Vol 67, No. 2, 2006, pp. 535 - 542
Published online: 28th October, 2005
DOI: 10.3987/COM-05-S(T)63
Pd-catalyzed Allylic Alkylation of Pyrroles with Allyl Alcohols Promoted by Triethylborane

Masanari Kimura, Miki Fukasaka, and Yoshinao Tamaru*

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


Triethylborane promotes the Pd-catalyzed allylic alkylation of pyrroles with a variety of allylic alcohols to provide either C2 allylation products (α,α-, γ,γ-dimethylallyl alcohol and geraniol) or C2,C5 diallylation products (allyl alcohol, α-, β-, γ-methyl-, and α-, γ-phenylallyl alcohols) in good to excellent yields under mild conditions.

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Communication | Special issue | Vol 67, No. 2, 2006, pp. 543 - 547
Published online: 18th November, 2005
DOI: 10.3987/COM-05-S(T)64
Pyridine Metallations in the Synthesis of Triazole Based NK-1 Antagonists

K. Jeff Thrasher, Erik J. Hembre, Kevin M. Gardinier, Kenneth A. Savin, Jian Eric Hong, and Louis N. Jungheim*

*Lilly Reserach Laboratories, Lilly Corporate Center, Eli Lilly & Company, Indianapolis, IN 46285-4813, U.S.A.


Regioselective pyridine metallation chemistry was used to produce N-(3-chloropyridin-4-ylmethyl)-N-methyl-1-(3,5-bis-trifluoromethylbenzyl)-5-phenyl-1H-[1,2,3]triazole-4-carboxamide (9a) and [1-(3,5-bis-trifluoromethylbenzyl)-5-morpholin-4-yl-1H-[1,2,3]triazol-4-yl]-[3-(3-chloropyridin-4-yl)-5-hydroxymethylisoxazol-4-yl]methanone (16a), which exhibit NK-1 antagonist activity.

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Communication | Special issue | Vol 67, No. 2, 2006, pp. 549 - 554
Published online: 14th October, 2005
DOI: 10.3987/COM-05-S(T)65
Synthesis of 3-Oxoazacyclohept-4-enes by Ring-closing Metathesis. Application to the Synthesis of an Inhibitor of Cathepsin K

Catherine Taillier, Thomas Hameury, Véronique Bellosta,* and Janine Cossy*

*Laboratoire de Chemie Organique, Ecole Supérieure de Physique & Chemie Industrielle, 10 rue Vauquelin, 75231 Paris Cedex 05, France


The ring-closing metathesis allows the formation of 3-oxoazacyclohept-4-enes from but-3-enamine. By using this methodology, the synthesis of an inhibitor of cathepsin K was achieved in 10 steps from but-3-enamine.

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Communication | Special issue | Vol 67, No. 2, 2006, pp. 555 - 559
Published online: 30th September, 2005
DOI: 10.3987/COM-05-S(T)70
An Enantiocontrolled Approach for the Synthesis of Chiral 3,5-Disubstituted 2(1H)-pyridinones

David R. Williams,* David C. Kammler, and William R. F. Goundry

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


An enantioselective route for the convergent synthesis of chiral, nonracemic 5-substituted 3-acyl-2(1H)-pyridinones is reported. Claisen rearrangement provides direct access to the α-branched 2-[4-(tert-butyldimethylsilanoxy)cyclohex-2-enyl]-3-hydroxypropionaldehyde as a key intermediate. The application of mild oxidation conditions facilitates the preparation of a series of 3,5-disubstituted 2(1H)-pyridinones.

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Communication | Special issue | Vol 67, No. 2, 2006, pp. 561 - 566
Published online: 11th November, 2005
DOI: 10.3987/COM-05-S(T)73
Novel Series of Highly Potent Non-peptide Growth Hormone Secretagogues with Improved Bioavailability

Hirohide Ishige,* Nobuo Ishiyama, Mitsuo Mimura, Mitsuo Hayashida, Tadashi Okuno, Kiyoharu Ukai, Takeshi Kiyofuji, Yasuo Yoneda, Shinji Tauchi, Akinori Aoyama, and Kiyoshi Inoguchi

*Central Research Institute, Kaken Pharmaceutical Co., Ltd., Shinomiya, Minamikawara-cho, Yamashina-ku, Kyoto 607-8042, Japan


The discovery and the SAR of acylproline derivatives as highly potent growth hormone secretagogues (GHSs) with good oral bioavailability are described. One representative compound, N-[3-(2,2-dimethylpropylamino)-2- hydroxypropyl]-2(R)-[1-(2,2-dimethylpropionyl)pyrrolidine-2(S)-carbonylamino]-3-naphthalen-2-ylpropionamide (4e), showed potent GHS activity (ED50=1 nM) and good oral bioavailability (BA=33.2%). Moreover, the optically pure N-[3-(2,2-dimethylpropylamino)-2(S)-hydroxypropyl]-2(R)-[1-(2,2-dimethylpropionyl)pyrrolidine-2(S)-carbonylamino]-3-naphthalen-2-ylpropionamide ((2S)-4e) showed a good metabolic stability against in vitro clearance (human liver microsome) with potent GHS activity.

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Communication | Special issue | Vol 67, No. 2, 2006, pp. 567 - 574
Published online: 11th November, 2005
DOI: 10.3987/COM-05-S(T)74
Extending the Concept of Mixtures of Chiral Monodentate P-Ligands in Asymmetric Rh-Catalyzed Olefin-hydrogenation: Use of Oxazaphospholidines

Manfred T. Reetz* and Marek Surowiec

*Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, D-45470 Mülheim / Ruhr, Germany


The previously described combinatorial concept of using mixtures of monodentate BINOL-derived phosphites, phosphonites or phosphoramidites as superior ligand systems in Rh-catalyzed asymmetric olefin-hydrogenation has been extended to include chiral oxazaphospholidines. Specifically, the latter were prepared from ephedrine and pseudo-ephedrine according to literature procedures. Mixtures of these P-ligands among themselves or in combination with a BINOL-derived phosphonite lead to enhanced enantioselectivity in the Rh-catalyzed hydrogenation of itaconic acid dimethyl ester (ee up to 89%).

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Communication | Special issue | Vol 67, No. 2, 2006, pp. 575 - 583
Published online: 27th September, 2005
DOI: 10.3987/COM-05-S(T)75
Self-assembling Cyclic α,γ-Tetrapeptides

Manuel Amorín, Roberto J. Brea, Luis Castedo, and Juan R. Granja*

*Departamento de Química Orgánica, Facultad de Química, Universidad de Santiago de Compostela, E-15706 Santiago de Compostela, Spain


Cyclic α,γ-tetrapeptide self-assembled into dimers by formation of only 4-hydrogen-bonded interactions of amide groups of the two α-amino acids of a cyclic tetrapeptides.

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Communication | Special issue | Vol 67, No. 2, 2006, pp. 585 - 588
Published online: 18th October, 2005
DOI: 10.3987/COM-05-S(T)76
Synthesis of Dihydroquinolinones Angularly-fused to Tetrahydrobenzazepinone Rings

Larry E. Overman* and Emily A. Peterson

*Department of Chemistry, University of California, Irvine, Irvine, California 92717, U.S.A.


Acylation of the dimethylaluminum derivative of a hindered secondary amine with N-Boc isatin, and sequential intramolecular aldol condensation-lactamization, are key steps in the first synthesis of tetrahydro-4bH-6,12-diazabenzo[3,4]cyclohepta[1,2-a]naphthalene-5,11-diones.

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Communication | Special issue | Vol 67, No. 2, 2006, pp. 589 - 595
Published online: 21st October, 2005
DOI: 10.3987/COM-05-S(T)80
Stereoselective Synthesis of γ- and δ-Sultams by Intramolecular Diels-Alder Reaction of Vinylsulfonamides Possessing an Acyclic or Carbocyclic 1,3-Diene Moiety

Victor O. Rogachev, Victor D. Filimonov, Roland Fröhlich, Olga Kataeva, and Peter Metz*

*Institut of Organic Chemistry, Technical University Dresden, Bergstrasse 66, D-01069 Dresden, Germany


A range of novel γ- and enantiopure δ-sultams was prepared by intramolecular [4+2] cycloaddition of vinylsulfonamides with purely thermal activation and under high pressure.

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Paper | Special issue | Vol 67, No. 2, 2006, pp. 597 - 619
Published online: 8th November, 2005
DOI: 10.3987/COM-05-S(T)18
Improved Syntheses of the FR900482 and Mitomycin Benzazocine Ring Core via Mitsunobu Cyclization

Pascal Ducept, Daniel A. Gubler, and Robert M. Williams*

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


An asymmetric synthesis of a highly functionalized benzazocine core of FR900482 and the mitomycins has been achieved in 20 and 19 steps, respectively. Key features of the synthesis include a highly chemoselective reduction of a nitro group and a Mitsunobu cyclization using either sulfonamides or carbamates. Removal of the protecting groups afforded the free benzazocine.

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Paper | Special issue | Vol 67, No. 2, 2006, pp. 621 - 628
Published online: 14th October, 2005
DOI: 10.3987/COM-05-S(T)29
Oxidative Cyclizations and the Synthesis of Lactones: A Streamlined Synthesis of epi-Crobarbatic Acid

John D. Brandt and Kevin D. Moeller*

*Department of Chemistry, Washington University, St. Louis, Missouri 63130, U.S.A.


While anodic cyclizations have been shown to be compatible with the synthesis of lactones, the previous synthetic route to the starting materials was cumbersome and limited the overall utility of the approach. In this manuscript, a new strategy is reported that allows for very rapid synthesis of the electrolysis substrates. In addition, an efficient conversion of the ortho ester product obtained from the oxidative cyclization to a lactone acid is reported. The result is a dramatically improved synthetic strategy for the synthesis of functionalized tetrahydrofuranones.

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Paper | Special issue | Vol 67, No. 2, 2006, pp. 629 - 641
Published online: 16th September, 2005
DOI: 10.3987/COM-05-S(T)31
A Convenient Method for the Synthesis of Carboxamides and Thioesters by Using Tetrakis(2-methylimidazol-1-yl)silane

Takashi Tozawa, Yoshinobu Yamane, and Teruaki Mukaiyama*

*Center for Basic Research, The Kitasato Institute, 6-15-5 (TCI), Toshima, Kita-ku, Tokyo 114-0003, Japan


Tetrakis(2-methylimidazol-1-yl)silane [Si(2-Me-Im)4], a new dehydrating reagent having silicon–imidazole linkage, reacted readily with carboxylic acids at room temperature to form the corresponding 1-acyl-2-methylimidazole intermediates, which smoothly underwent subsequent condensation with nucleophiles such as amines or thiols to afford the corresponding carboxamides or thioesters in good to excellent yields, respectively.

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Paper | Special issue | Vol 67, No. 2, 2006, pp. 643 - 653
Published online: 27th September, 2005
DOI: 10.3987/COM-05-S(T)38
Synthesis of Highly Substituted Indole Alkaloid Species via [4+1] Cyclization of Nucleophilic Carbenes and Indole Isocyanates

James H. Rigby* and Patrick J. Burke

*Department of Chemistry, Wayne State University, Detroit, MI 49202-3489, U.S.A.


Thermally induced [4 + 1] cyclization between indole isocyanates and dimethoxycarbene or bis(propylthio)carbene has been achieved with good chemical efficiency. The methodology provides rapid access to fused pyrroloindole substructures commonly found in a variety of indole alkaloid natural products.

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Paper | Special issue | Vol 67, No. 2, 2006, pp. 655 - 663
Published online: 30th September, 2005
DOI: 10.3987/COM-05-S(T)48
Synthesis and Properties of Ethylenethiotetraselenafulvalene (ET-TSF) and Its Conductive Radical Cation Salts

Kazuo Takimiya,* Mie Kodani, Satoshi Murakami, Tetsuo Otsubo, and Yoshio Aso

*Department of Applied Chemistry, Faculty of Engineering, Hiroshima University, 1-4-1 Kagamiyama, Higashi-hiroshima, Hiroshima 739-8527, Japan


The title heterocycle-fused tetraselenafulvalene derivative, ET-TSF (ethylenethiotetraselenafulvalene) has been synthesized as a novel electron donor. Electrocrystallization of ET-TSF gave highly conductive radical cation salts with I3-, Cl-, Br-, and AuI2- counter anions. Among them, the AuI2 salt isostructural with the organic superconductor (MDT-TSF)-AuI2 (MDT-TSF = methylenedithiotetraselenafulvalene) was highly conductive (1600 S cm-1) and metallic down to 1.8 K with no superconducting transition.

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Paper | Special issue | Vol 67, No. 2, 2006, pp. 665 - 678
Published online: 16th September, 2005
DOI: 10.3987/COM-05-S(T)55
Novel 9,10-Bis(1,3-dithiol-2-ylidene)-9,10-dihydroanthracene Derivatives Bridged by a Crown Ether Unit at the 1,8-Positions: A New Type of Redox-switchable Hosts Undergoing Reversible Structural Changes

Akira Ohta,* Taeko Numae, Yoshiro Yamashita, and Kunihide Fujimori*

*Department of Chemistry, Faculty of Science, Shinshu University, Asahi, Matsumoto 390-8621, Japan


Novel redox-switchable host molecules (2) composed of a 9,10-bis(1,3-dithiol-2-ylidene)-9,10-dihydroanthracene unit and a crown ether moiety bridging the 1,8-positions have been synthesized. Cyclic voltammetry and X-Ray analyses revealed that the molecules undergo a significant structural change upon oxidation. 1H-NMR titration experiments on the neutral and dication states show that the binding abilities of the dication states for alkali metal cations (Li+, Na+, K+) are considerably lower than those of the neutral molecules. The binding properties of 2 were also investigated by cyclic voltammetry.

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Paper | Special issue | Vol 67, No. 2, 2006, pp. 679 - 694
Published online: 18th November, 2005
DOI: 10.3987/COM-05-S(T)56
The Effect of Substituents on the Pyridine Ring in the Diastereoselective Cyclopropanation Reaction of Pyridinium Ylides Bearing an 8-Phenylmenthyl Ester Group

Satoshi Kojima,* Kouji Fujitomo, Yoshiaki Itoh, Kyoko Hiroike, Masaaki Murakami, and Katsuo Ohkata

*Department of Chemistry, Graduate School of Science, Hiroshima University, 1-3-1 Kagamiyama, Higashi-hiroshima, Hiroshima 739-8526, Japan


The reaction between β-substituted methylidenemalononitriles and the ylide from (-)-8-phenylmenthyl α-pyridiniumacetate, which affords activated cyclopropanes bearing two cyano groups and one carboxylic ester group, was examined. The trans isomer was obtained in up to 91:9 diastereoselectivity under optimized solvent conditions for the t-butyl substituted substrate. The selectivity increased to 96:4 upon using 4-methoxypyridine in the place of pyridine, whereas selectivities were generally lower for N,N-diethylnicotinamide. The major 4-pyridyl substituted cyclopropane was determined to be trans-1R by X-Ray structural analysis.

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Paper | Special issue | Vol 67, No. 2, 2006, pp. 695 - 704
Published online: 16th September, 2005
DOI: 10.3987/COM-05-S(T)61
Construction of Optically Active Spiroketal by Direct Aldol Reaction

Hisanaka Ito,* Chie Kawabe, and Kazuo Iguchi*

*Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan


Novel preparation of symmetric spiroketal was developed by the use of direct aldol reaction of α-hydroxyacetophenone catalyzed by chiral dinuclear zinc catalyst. The spiroketal was obtained in excellent enantiomeric excess.

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Paper | Special issue | Vol 67, No. 2, 2006, pp. 705 - 720
Published online: 27th September, 2005
DOI: 10.3987/COM-05-S(T)67
A Versatile Stereoselective Approach to Paraconic Acids

Marta Amador, Xavier Ariza,* and Jordi Garcia*

*Department of Organic Chemistry, University of Barcelona, Av. Diagonal 647, 08028 Barcelona, Spain


A versatile methodology has been developed for the independent stereochemical control in the construction of all the stereocenters of the γ-butyrolactone skeleton that are present in paraconic acids (1 and 2). The configuration of the γ-carbon came from an enantiopure alk-2-yne-1,4-diol. Stereoselective partial reduction to a (Z)- or (E)-alk-2-ene-1,4-diol (10) controlled the stereochemistry of the β-carbon whereas the α-carbon stereochemistry in 1 was partially selected by a (Z)- or (E)-enolate formation of the 1,4-dipropanoate derived from diol (10).

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Paper | Special issue | Vol 67, No. 2, 2006, pp. 721 - 730
Published online: 18th October, 2005
DOI: 10.3987/COM-05-S(T)69
A Diastereoselective Silver(I) Promoted gem-Dibromocyclopropane Ring Opening Reaction via an Anchimeric Assisted Transannular Benzoate Migration

Matt S. Mortensen, Aaron C. Schmitt, Catherine M. Smith, Eric A. Voight, and George A. O’Doherty*

*Department of Chemistry, West Virginia University, Morgantown, WV 26506-6045, U.S.A.


A highly diastereoselective synthesis of a protected 4-amino-5,7-dihydroxy-1-bromocyclohept-1-ene was achieved by a silver tosylate promoted gem-dibromocyclopropane ring opening reaction. The target molecule was prepared in only six steps from benzene or four steps from 7,7-dibromo-3-norcarene. The key to this approach was the discovery of a stereoselective transannular benzoate migration, which occurred via tandem anchimeric assistance in a silver(I) promoted gem-dibromocyclopropane ring opening reaction.

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Paper | Special issue | Vol 67, No. 2, 2006, pp. 731 - 748
Published online: 16th September, 2005
DOI: 10.3987/COM-05-S(T)71
Synthesis of Dioxabicyclo[3.2.1]octane Core of the Zaragozic Acids

Masayoshi Tsubuki,* Hiroyuki Okita, and Toshio Honda*

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


Synthesis of the bicyclic core of zaragozic acids employing chiral furylglycerol (6) is described. Key steps are stereoselective construction of the C4 to C6 carbon centers by syn-dihydroxylation of alkene followed by reduction of carbonyl group in pyranone (8), introduction of ethynyl moiety as a carboxylic acid synthon at C3 by nucleophilic addition of lithium trimethylsilylacetylide to aldehyde (19), and bicyclic formation of dihydroxy ketone by ketalization, providing the 2,8-dioxabicyclo[3.2.1]octane core of zaragozic acids.

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Paper | Special issue | Vol 67, No. 2, 2006, pp. 749 - 762
Published online: 30th September, 2005
DOI: 10.3987/COM-05-S(T)77
Synthesis of 5-Selenoxo-1,2,4-triazole-1-carboxylates from Isoselenocyanates and Azodicarboxylates

Francesco Favero, Geoffroy L. Sommen, Anthony Linden, and Heinz Heimgartner*

*Institute of Organic Chemistry, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland


A mixture of an azodicarboxylate and triphenylphosphine in dichloromethane reacted with aryl isoselenocyanates (1) at room temperature to give 4,5-dihydro-5-selenoxo-1H-1,2,4-triazole-1-carboxylates (4a-f) in a one-pot reaction in good to excellent yields. The isoselenocyanates (1) have been prepared conveniently from formamides by treatment with elemental selenium and phosgene according to Barton’s procedure.

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Note | Special issue | Vol 67, No. 2, 2006, pp. 763 - 768
Published online: 14th October, 2005
DOI: 10.3987/COM-05-S(T)40
Palladium-catalyzed Arylation of Diisopropyl Malonate Applied to the Efficient Synthesis of the Selective MMP Inhibitor 5-(4-Phenoxyphenyl)-5-[4-(2-pyrimidinyl)-1-piperazinyl]barbituric Acid

Stanley Hutchings, Wen Liu, and Roumen Radinov*

*Chemical Synthesis Department, Hoffmann - La Roche Inc., Building 66, 340 Kingsland Street, Nutley, NJ 07110-1199, U.S.A.


An efficient synthesis of the highly selective MMP inhibitor 5-(4-phenoxyphenyl)-5-[4-(2-pyrimidinyl)-1-piperazinyl]barbituric acid is reported. The title compound was prepared in three steps and 72% overall yield from 4-bromophenyl phenyl ether via an improved arylation of diisopropyl malonate.

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38 data found. 1 - 30 listed Next Last