HETEROCYCLES
An International Journal for Reviews and Communications in Heterocyclic ChemistryWeb Edition ISSN: 1881-0942
Published online by The Japan Institute of Heterocyclic Chemistry
Special Issue
Victor Snieckus's Special Issues, Vol. 88, No. 2, 2014
Published online: 4th October, 2013
■ Polyfluoroalkylation of Carbonyl Compounds by Polyfluoroalkyl Anions Generated from Polyfluorcarboxamides
Natshumi Wakita and Shoji Hara*
*Graduate School of Engineering, Hokkaido University, Kita 13 Nishi 8, Kita-ku, Sapporo, Hokkaido 060-8628, Japan
Abstract
Polyfluoroalkyl anions, generated by reduction of (polyfluoroalkanoyl)piperidines with Et3BHK, were used for the polyfluoroalkylation of carbonyl compounds. Trifluoromethylation of aromatic aldehydes proceeded in good yields, and that of aliphatic aldehydes afforded a moderate yield. In contrast, the yield was low when the reaction involved benzophenone. Pentafluoroethylation and octafluorobutylation of aldehydes were also carried out by using the corresponding (polyfluoroalkanoyl)piperidines, which were prepared from commercially available polyfluorocompounds. The (polyfluoroalkanoyl)piperidines were also prepared through polyfluorination, and were used in the polyfluoroalkylation of aldehydes.
Published online: 14th August, 2013
■ Synthesis of Macrobicycles Comprising 2,7-Diaminonaphthalene Moiety via Palladium-Catalyzed Amination Reaction
Alexei N. Uglov, Georgii A. Zubrienko, Anton S. Abel, Alexei D. Averin, Olga A. Maloshitskaya, Alla Bessmertnykh-Lemeune, Franck Denat, and Irina P. Beletskaya*
*Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory 1-3, 119991, Moscow, Russia
Abstract
An original synthetic approach to bismacrocyclic ligands bearing naphthalene moiety was developed. First, the macrocycles comprising 2,7-diaminonaphthalene fragment were reacted with 2,7-dibromonaphthalene, 4,4’-dibromobiphenyl or bromobenzyl bromide affording corresponding N,N’-bis(bromoaryl) or N,N’-bis(bromobenzyl) substituted macrocycles. Pd-catalyzed macrocyclization of these compounds with a wide range of di- and polyamines led to a series of new macrobicyclic ligands. The yields of the macrobicycles are strongly dependent on the nature of starting compounds, reaching 35% in some cases.
Published online: 7th October, 2013
■ Synthesis of de novo Chiral γ-Amino-ynamides Using Lithiated Ynamides. Observation of a Unique 5-endo-dig Cyclization with an Inversion of S-Center
Xiao-Na Wang, Richard P. Hsung,* Sierra K. Fox, Ming-Can Lv, and Rui Qi
*Department of Chemistry, School of Pharmacy, University of Wisconsin, 777 Highland Aenue, Madison, WI 53705, U.S.A.
Abstract
We describe herein details of our efforts in developing a highly stereoselective synthesis of de novo chiral γ-amino-ynamides through additions of lithiated ynamides to Ellman–Davis chiral N-tert-butanesulfinyl imines. While additions of ynamides could be highly stereoselective even without Lewis acids, the use of BF3-OEt2 completely reversed the stereoselectivity. On the other hand, additions of oxazolidinone-substituted, oxazinanone-substituted and tetrahydropyrimidinone-substituted ynamides behaved quite differently and functioned better with BF3-OEt2. The chirality of the oxazolidinone ring exerts no impact on the selectivity. This work also features a unique 5-endo-dig cyclization of oxazolidinone-substituted γ-amino-ynamides that could be promoted with acid, leading to isothiazoles and 2,3-dihydro-isothiazole S-oxides.
Published online: 27th August, 2013
■ Chemoenzymatic Approach to Synthesis of Hydroxylated Pyrrolidines from Benzoic Acid
David R. Adams, Johannes van Kempen, Jason R. Hudlicky, and Tomas Hudlicky*
*Department of Chemistry, Brock University, 500 Glenridge Ave., St. Catharines, Ontario, L2R 3K4, Canada
Abstract
The fermentation of benzoic acid with R. eutrophus B9 provides the corresponding ipso-diol that serves as a convenient homochiral starting material for the synthesis of oxygenated compounds. In this paper we report the conversion of the ipso-diol to a hydroxylated pyrrolidine, which is found as a subunit in biologically active compounds. The key steps involve the enzymatic oxidation of benzoic acid, the subsequent hetero-Diels-Alder cycloaddition, and the oxidative cleavage, reductive cyclization to form the pyrrolizidine. Experimental and spectral data are provided for all new compounds.
Published online: 7th August, 2013
■ Regioselective Bromination: An Approach to the D-Ring of the Gilvocarcins
Ehesan U. Sharif and George A. O'Doherty*
*Department of Chemistry and Chemical Biology, Northeastern University, 360 Huntington Avenue, Boston, MA 02115-5096, U.S.A.
Abstract
A method for the regioselective ortho-bromination of unsymmetrically protected 3,5-dihydroxybenzoic acid esters has been developed. The route involves protecting group optimization studies to attain high regioselectivity for the ortho-bromination. Pd-catalyzed stannation and boration were performed to construct the D-ring coupling partners for the synthesis of gilvocarcin analogs.
Published online: 28th August, 2013
■ Synthesis of Macrocyclic Dimer of Cyclic Hexaoxazole and Examination of Its Interaction with Telomeric Oligonucleotide
Keisuke Iida, Gen Tsubouchi, Takahiro Nakamura, and Kazuo Nagasawa*
*Biotechnology and Life Science, Graduate School of Engineering, Tokyo University of Agriculture and Technology, 2-24-16, Naka-cho, Koganei, Tokyo 184-8588, Japan
Abstract
A telomestatin-type macrocyclic dimer of cyclic hexaoxazole, termed 6OTD-dimer (5), was synthesized as a new G-quadruplex (G4) ligand by incorporating a second linker into L2H2-6OTD-dimer (3). This macrocyclic-type G4 ligand (5) was found to interact with telomeric oligonucleotide, and stabilized telomeric G4 structure more effectively than did the corresponding non-macrocyclic L2H2-6OTD analog 4.
Published online: 19th September, 2013
■ Synthesis of Functionalized 1-Azabicyclo[3.1.0]hexanes: Studies towards Ficellomycin and Its Analogs
Gang Chen, Zhi He, and Andrei K. Yudin*
*Davenport Research Laboratories, Department of Chemistry, University of Toronto, 80 St. George Street., Toronto, Ontario, M5S 3H6, Canada
Abstract
The molecule of antibiotic agent ficellomycin contains an intriguing array of functional groups assembled around a bicyclic aziridine core. To address the challenges of constructing ficellomycin derivatives, we have developed cycloamination methodology for the stereocontrolled transformation of unprotected aziridine-containing olefins. The present paper discusses application of this process towards synthesis of ficellomycin.
Published online: 20th August, 2013
■ Total Synthesis of 8-epi-Javaberine A and Javaberine A
Yasutomo Yamamoto,* Yuri Tabuchi, Ayana Baba, Kumiko Hideshima, Mai Nakano, Akari Miyawaki, and Kiyoshi Tomioka*
*Faculty of Pharmaceutical Sciences, Department of Medicinal Chemistry, Doshisha Women’s College of Liberal Arts, Kodo, Kyotanabe, Kyoto 610-0395, Japan
Abstract
The total synthesis of berberine alkaloid javaberine A was examined. The B/C ring of berberine was successfully constructed by sequential Bischler–Napieralski cyclization–reduction protocols, and final demethylation afforded both javaberine A and its epimer.
Published online: 28th August, 2013
■ Selective Formation of trans/threo/cis and cis/threo/cis Bis-Tetrahydrofurans from the Same Diene Diols
Hiromichi Fujioka,* Tomohiro Oki, Tatsuya Hayashi, Maki Yamakawa, Takeshi Kurachi, Kenji Nakahara, Ryota Maehata, Tomohito Hamada, Kenichi Murai, and Yasuyuki Kita
*Graduate School of Pharmaceutical Science, Osaka University, 1-6 Yamadaoka, Suita, Osaka 560-0871, Japan
Abstract
Double intramolecular iodoetherification reactions of cyclic acetals and ketals, prepared from the same C2-symmetric diene diol with aldehydes or ketones, stereoselectively afford trans/threo/cis or cis/threo/cis bis-THF ring systems.
Published online: 27th September, 2013
■ Highly Efficient Preparation of Both Enantiomers of Versatile Chiral Synthon for 1,2-Diamines via the Fe(III)-Catalyzed Oxidation of 2-Imidazolone
Hirofumi Matsunaga,* Iori Eshita, Shoichi Tsunoda, Naoko Ishimoto, Shin Ando, and Tadao Ishizuka*
*Department of Pharmaceutical Sciences, Graduate School of Life Sciences, Kumamoto University, 5-1 Oe-hon-machi, Kumamoto 862-0973, Japan
Abstract
A new method was established for the preparation of both of the enantiomers of trans-4,5-dimethoxy-2-imidazolidinone (DMIm) via the Fe(III)-catalyzed oxidation of 2-imidazolone by H2O2-urea, which allowed the subsequent achievement of optical resolution via the introduction of a MAC moiety and a 2-mesitylenesulfonyl group at the two nitrogen positions of DMIm, which then were easily removed. The two enantiomers are useful as versatile chiral synthons for 1,2-diamines.
Published online: 11th September, 2013
■ Enantioselective Synthesis of Planar-Chiral Phosphines with 1,N-Dioxa[N]paracyclophane Scaffold and Their Application as Chiral Ligands
Kazumasa Kanda, Shoya Oshima, Tsubasa Shizuno, Risa Hamanaka, Miku Fukai, and Takanori Shibata*
*Chemistry and Biochemistry, Advanced Research Center of Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 169-8555, Japan
Abstract
A new family of chiral phosphines based on planar-chiral 1,n-dioxa[n]paracyclophane scaffold was created. They were synthesized with excellent enantioselectivity via asymmetric ortho-lithiation using sec-butyllithium and (-)-sparteine. These phosphines were used as chiral ligands in three reactions: Ag-catalyzed allylation of imines, Pd-catalyzed asymmetric Sonogashira coupling of diiodoparacyclophanes, and Pd-catalyzed asymmetric Suzuki-Miyaura coupling of tricarbonyl(η6-ortho-dichlorobenzene)chromium.
Published online: 18th September, 2013
■ Synthetic Studies of Fisetin, Myricetin and Nobiletin Analogs and Related Probe Molecules
Aiki Hiza, Yuta Tsukaguchi, Takahiro Ogawa, Makoto Inai, Tomohiro Asakawa, Yoshitaka Hamashima, and Toshiyuki Kan*
*Synthetic Organic ＆ Medicinal Chemistry, School of Pharmaceutical Science, University of Shizuoka, 52-1 Yada, Suruga, Shizuoka 422-8526, Japan
Abstract
We synthesized a series of analogs of fisetin, myricetin and nobiletin, as well as related fluorescein- and biotin-based flavone-probe molecules, on a suitable scale for biological and structure-activity relationship studies.
Published online: 11th November, 2013
■ Synthesis and Reactions of 1,3,4-Selenadiazines
Wolf-Diethard Pfeiffer,* Harald Roßberg, Nazken Kelzhanova, Amanzhan T. Saginayev, Alexander Villinger, and Peter Langer*
*Institute of Chemistry, University of Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany
Abstract
Various 1,3,4-selenadiazines were prepared by cyclization of selenosemicarbazides with phenacyl bromides. The compounds generally exist in their 6H-tautomeric form and contain an exocyclic imino group in the solid state. 1,3,4-4H-Selenadiazines, available from 1,2-dimethylated selenosemicarbazides, cannot be isolated because they rapidly undergo a deselenation reaction under the conditions of their formation. Deselenation can be induced for 1,3,4-6H-selenadiazines under forcing conditions by reflux of a solution in glacial acetic acid. On the other hand, a ring contraction is observed when concentrated HCl or HBr is used.
Published online: 17th September, 2013
■ Formation of Xanthone Oxime and Related Compounds Using a Combination of tert-Butyl Nitrite and Potassium Hexamethyldisilazide
Yusuke Iwama, Takahiro Noro, Kentaro Okano, Hidetsura Cho,* and Hidetoshi Tokuyama*
*Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Aramaki, Aoba-ku, Sendai 980-8578, Japan
Abstract
Synthesis of xanthone oxime and related compounds via nitrosation of the dibenzylic position using a combination of tert-butyl nitrite and potassium hexamethyldisilazide is described. The reaction conditions are effective for the synthesis of xanthone oxime as well as thioxanthone, acridone, and anthrone oximes, which have been difficult to synthesize from the corresponding ketones by conventional dehydrative condensation with hydroxylamine.
Published online: 16th October, 2013
■ Synthesis of Pyrrolidine 3,4-Diol Derivatives with Anticancer Activity on Pancreatic Tumor Cells
Frederic Steimer, Ana T. Carmona, Antonio J. Moreno-Vargas, Irene Caffa, Michele Cea, Fabrizio Montecucco, Alessio Nencioni, Pierre Vogel, and Inmaculada Robina*
*Department of Organic Chemistry, University of Seville, Prof. Garcia Gonzalez, 1 Seville-41012, Spain
Abstract
Novel pyrrolidine 3,4-diol derivatives of the type (2R and 2S,3R,4S)-{[((1R)-1-methoxycarbonyl and hydroxylmethyl)-1-arylmethyl)amino]ethyl}-pyrrolidine-3,4-diol have been prepared and evaluated as α-mannosidase inhibitors and assayed for their anticancer activity in vitro. They all exhibit specific but moderate activity as inhibitors towards α-mannosidase from Jack beans. Compounds 7 and 8b bearing hydroxymethyl and trifluoromethylbiphenyl groups show the best antiproliferative effect in two pancreatic cancer cell lines.
Published online: 20th November, 2013
■ Advances in Siloxane-Based Coupling Reactions: Novel 16-Electron Palladium(0) Tri-alkene Catalysts for Allyl-Aryl Coupling in Precursors to Amaryllidaceae Alkaloids
Frederick E. Nytko, III, Krupa H. Shukla, and Philip DeShong*
*Department of Chemistry and Biochemistry, University of Maryland, 7950 Baltimore Avenue, College Park, MD 20742, U.S.A.
Abstract
A new class of 16-electron Pd(0) catalysts are surveyed for applications in siloxane based allyl-aryl coupling protocols. The ability to "tune" the catalysts' activity by varying either the cone angle or the electronic characteristics of the alkene ligands attached to palladium was demonstrated. Attempts to prepare chiral adducts in the coupling reaction utilizing chiral bicyclooctadiene derivatives as a ligand for palladium provided no significant enantioenrichment in the coupled product.
Published online: 24th October, 2013
■ Bi(OTf)3 as a Dual Role Catalyst. Synthesis of Substituted Morpholine Derivatives via Catalytic O-Allylation
Ryuji Hayashi, Jin-A Park, and Gregory R. Cook*
*Department of Chemistry and Biochemistry, North Dakota State University, Fargo, North Dakota 58108, U.S.A.
Abstract
The diastereoselective synthesis of cis-1,4-disubstituted morpholines has been accomplished in good to excellent yields via Bi(OTf)3 catalyzed ring-closing O-allylation under mild conditions without the need for added base. The bismuth Lewis acid catalyst appeared to play two roles; the mild deprotection of a silyl ether and the Lewis acid activation of an allylic halide for mild nucelophilic cyclization. Substituted morpholines were obtained with diastereoselectivity ranging from 2:1 to >99:1.
Published online: 19th August, 2013
■ Selective Preparation of 6- and 7-(Polyhydroxypropyl)pterins from Pentos-2-uloses
Tadashi Hanaya* and Kasumi Ito
*Department of Chemistry, Faculty of Science, Okayama University, 3-1-1 Tsushima-naka, Okayama 700-8530, Japan
Abstract
The Gabriel-Isay condensation of three types of pentos-2-uloses with 2,5,6-triaminopyrimidin-4(3H)-one (3) was examined under both acidic and basic conditions. The condensation of 5-deoxy- and 5-O-protected pentofuranos-2-uloses with 3 at pH 8 afforded 6-substituted pterins as major isomers, whereas the same reaction at pH 3 yielded the 7-substituted pterins predominantly.
Published online: 4th September, 2013
■ Constituents from the Rhizomes of Curcuma comosa and Their Wnt Signal Inhibitory Activities
Rolly G. Fuentes, Kazufumi Toume, Midori A. Arai, Takashi Koyano, Thaworn Kowithayakorn, and Masami Ishibashi*
*Department of Natural Products Chemistry, Graduate School of Pharmaceutical Science, Chiba University, 1-8-1 Inohana, Chuo, Chiba, Japan
Abstract
Activity-guided fractionation of the Curcuma comosa rhizome MeOH extract that inhibited Wnt signal activity led to the characterization of two new diarylheptanoids (1 and 2) together with six known diarylheptanoids (3-8) and two known sesquiterpenoids (9 and 10). Their structures were identified by 1D and 2D NMR, HRESIMS, optical rotation, and chemical evidences. Compounds 1 and 8 exhibited dose-dependent inhibitory activity against β-catenin/TCF transcriptional activity.
Published online: 28th August, 2013
■ Synthesis of 1,4-Disubstituted-1,2,3-trizazoles via Click Reaction in Micro Flow Reactor
Ming Lei,* Ruijun Hu, Yanguang Wang, and Hong Zhang
*Department of Chemistry, Zhejiang University , 38 Zheda Road, Hangzhou, 310027, China
Abstract
A Cu (I)-catalyzed three-component click reaction of alkyl bromide, terminal alkyne and sodium azide was developed in micro flow reactor. Sodium ascorbate was added as additive to prevent the oxidative coupling of desired product with terminal alkyne. Under optimized condition, various 1,4-disubstituted-1,2,3-triazoles were obtained in 85-95% yield with exclusive 1,4-regioisomeric selectivity. The present smooth procedure greatly accelerated the reaction due to the excellent mixing and mass transfer in micro flow system.
Published online: 21st August, 2013
■ Iodoetherification of Conformationally Restricted Dienyl Alcohols: Unexpected Formation of Oxocenes by 8-endo-mode Oxacyclizations
Kristen L. Stoltz, Andrea-Nekane R. Alba, Frank E. McDonald,* Marika B. Wieliczko, and John Bacsa
*Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, GA 30322, U.S.A.
Abstract
Iodine-promoted oxacyclizations of a family of conformationally restricted dienyl alcohols consistently afford oxocenes, arising from 8-endo-mode cyclizations.
Published online: 21st August, 2013
■ Synthetic Studies on Furanosteroids. Functionalization of Ring A of the Viridin Core Skeleton
Kristen C. Mascall and Peter A. Jacobi*
*6128 Burke Laboratory, Department of Chemistry, Dartmouth College, Hanover, New Hampshire 03755, U.S.A.
Abstract
The late-stage installation of an important carbonyl group on ring A of the viridin core skeleton is reported, via a two-step process consisting of benzylic bromination and Kornblum oxidation. The synthetic route described also provides access to several other interesting furanosteroid congeners.
Published online: 26th September, 2013
■ Facile Formation of Imidazolinium Salt by Reaction of Corresponding Diamine and Trimethyl Orthoformate in 1,1,1,3,3,3-Hexafluoroisopropanol
Kensuke Usui and Masahisa Nakada*
*Department of Chemistry and Biochemistry, School of Advanced Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 169-8555, Japan
Abstract
The preparation of imidazolinium salts, which can be used as precursors of pincer-type N-heterocyclic carbene ligands, is described. The formation of imidazolinium salts under standard conditions is difficult, but they have been successfully synthesized by reaction of the corresponding diamines and trimethyl orthoformate in 1,1,1,3,3,3-hexafluoroisopropanol. The synthesis of new chiral C2 symmetric imidazolinium salts is also described.
Published online: 24th September, 2013
■ Yb(OTf)3-Mediated Ring Opening of Functionalized Cyclopentane Epoxides with Aniline: Aspects of Regiochemistry and Stereochemistry
Stephen Hanessian* and Changwei Mu
*Department of Chemistry, University of Montreal, C.P. 6128, Succ. Centre-ville, Montréal, Québec H3C 3J7, Canada
Abstract
The ring-opening reaction of cyclopentan-1-ol 2,3-epoxides bearing alkoxy and hydroxyl groups with aniline was studied in the presence of Yb(OTf)3 in refluxing toluene. The syn- and anti- relationship of the alkoxy group has an influence on the regioselectivity of attack affording aniline adducts at the secondary or tertiary position.
Published online: 9th September, 2013
■ o-Directed Lithiation of Acylated Hydroxythiophenes
Ineta Vendina, Anete Parkova, and Peteris Trapencieris*
*Dept. Organic Chemistry, Latvian Institute of Organic Synthesis, Aizkraukles 21, Riga, Latvia
Abstract
O-Carbamates derived from 2-hydroxy- and 3-hydroxy-thiophenes generated o-directed carbanions, which were transformed to the corresponding methyl sulfides and methyl and trimethylsilyl substituted thiophenes.
Published online: 22nd August, 2013
■ Preparation of New Heptafulvenes and the Related Compounds Derived from 2H-Cyclohepta[d]thiazol-2-one and -2-thione
Ohki Sato,* Nobuhiro Ando, and Tatsuro Toma
*Department of Chemistry, Graduate School of Science and Engineering, Saitama University, 255 Shimo-okubo, Sakura-ku, Saitama 338-8570 , Japan
Abstract
2H-Cyclohepta[d]thiazol-2-one reacted with dimethyl malonate in the presence of sodium hydride to generate the 6- and 4-adducts, which were oxidized by DDQ to afford a 2-thiazolone-fuzed heptafulvene and a tricyclic compound, respectively. The reaction of 2H-cyclohepta[d]thiazol-2-thione under the same addition conditions gave the similar 6- and 4-adducts. Oxidation of each separated adducts afforded the corresponding regioisomeric heptafulvene disulfides with thiazole rings, respectively.
Published online: 27th August, 2013
■ Rare Earth Triflates/Chlorotrimethylsilane-Promoted One-Pot Synthesis of Enals
Natsuko Kagawa, Yoshiko Sasaki, Shoko Sakaguchi, Ayumi Nagatomo, Hideo Kojima, and Masahiro Toyota*
*Team TOYOTA, Graduate School of Science, Osaka Prefecture University, 1-2 Gakuencho, Sakai, Osaka 593-8531, Japan
Abstract
Some heteroaromatic aldehydes were subjected to conditions promoting the rare earth triflates/chlorotrimethylsilane-promoted one-pot synthesis of enals. As a result, diverse α,β-unsaturated aldehydes were obtained in moderate yields.
Published online: 30th September, 2013
■ Glycosidation Reactions of Benzyl-Type Selenoglycoside Donors
Masanori Menjo, Hideki Tamai, Hiromune Ando,* Hideharu Ishida, Mamoru Koketsu, and Makoto Kiso*
*Faculty of Applied Biological Sciences, Gifu University , 1-1 Yanagido, Gifu, Gifu 501-1193, Japan
Abstract
p-Methoxybenzyl (PMB), and p-nitrobenzyl (PNB) selenoglycosides of glucose were synthesized, and their glycosidation reactions were investigated. The Bn and PNB derivatives were successfully activated with IBr-AgClO4 to provide the glycosylated products in high yields. The glycosidation with the PMB derivatives required promotion with a metal triflate, such as (CuOTf)2·PhMe or In(OTf)3, and afforded the glycosylated products in medium to high yields.
Published online: 15th October, 2013
■ Development of a New Synthetic Strategy for Procyanidin Dimer Condensation Using Peracetylated Electrophiles
Sayaka Ishihara, Syoma Doi, Kota Harui, Taisuke Okamoto, Shuhei Okamoto, Joji Uenishi, Takashi Kawasaki, Noriyuki Nakajima,* and Akiko Saito*
*Department of Biotechnology, Faculty of Engineering, Toyama Prefectural University, 5180 Kurokawa, Kosugi, Toyama 939-0398, Japan
Abstract
Proanthocyanidins, also known as condensed tannins and/or oligomeric flavonoids, are found in many edible plants and show interesting various biological activities. We report a simple new proanthocyanidin synthesis strategy in which an electrophile derived from a flavan-3-ol peracetate is condensed with 1.5 eq. of a benzylated nucleophile. We demonstrate here the synthesis of procyanidin B1, a (−)-epicatechin-(4β-8)-(+)-catechin dimer, to demonstrate the utility of this method. This strategy is applicable for the synthesis of various commercially available flavan-3-ol and various oligomeric flavonoids.
Published online: 12th November, 2013
■ Introducing the Diels-Alder Reactivity of 2-Furanmethanethiol with Selected Maleic Acid Derivatives
Mohanad Gh. Shkoor, Irena Nikoloska, and Adrian L. Schwan*
*Department of Chemistry, University of Guelph, Guelph, Ontario, N1G 2W1, Canada
Abstract
Surprising chemoselectivity is demonstrated in the reaction of 2-furanmethanethiol with maleic anhydride and with N-phenylmaleimide. These maleic acid derivatives demonstrate a predilection for Diels-Alder cycloaddition, forgoing both conjugate addition and initial carbonyl attack. N-Ethylmaleimide showed a preference for conjugate addition, whereas diethyl fumarate or dimethyl maleate proved unreactive. The cycloadduct of 2-furanmethanethiol and maleic anhydride was subjected to dehydration/aromatization conditions to create benzo[c]thiophen-1(3H)-one-7-carboxylic acid. An alkylation attempt also led to the formation of a thiolester.