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
Tohru Fukuyama's Special Issues, Vol. 99, No. 2, 2019
Published online: 8th January, 2019
■ Further Studies on the Gold-Catalyzed Oxidative Domino Cyclization/Cycloaddition to Give Polyfunctional Tetracycles
Tobias Groß, Korany A. Ali, Anne Jäger, and Peter Metz*
*Faculty of Chemistry and Food Chemistry, Organic Chemistry I, Technische Universität Dresden, Bergstraße 66, 01069 Dresden, Germany
Abstract
Enyne aldehydes and ketones with ester and ether functions in the tether between the reactive functional groups were subjected to a gold(III)-catalyzed domino process in the presence of a pyridine N-oxide as external oxygen donor. The resulting tetracyclic ketoethers were formed in high yields under mild conditions and with excellent induced diastereoselectivity for substrates featuring a stereogenic center within the enyne tether.
Published online: 15th February, 2019
■ Synthesis of a Poly-Heterocyclic Tetra-Substituted Alkene via a Palladium-Catalyzed Four-Fold Domino Reaction for the Design of Polymeric Molecular Switches
Taukeer A. Khan and Lutz F. Tietze*
*Institute of Organic and Biomolecular Chemistry, University of Goettingen, Tammannstrasse 2, 37077 Goettingen, Germany
Abstract
A facile synthesis of a complex poly-heterocyclic tetrasubstituted alkene 4 with intrinsic helical chirality containing two acrylate moieties suitable for polymerization is described. Compound 4 can act as a molecular switch and was prepared via a palladium-catalyzed four-fold domino reaction including two Sonogashira reactions and two domino-carbopalladation/C‒H-activation reactions.
Published online: 20th February, 2019
■ Construction of Pinpoint-Fluorinated Benzothiophene Frameworks Using Palladium-Catalyzed Cyclization of o-(Fluorovinyl)phenyl-Substituted Thiophenes
Kohei Fuchibe, Nobushige Tsuda, Kento Shigeno, and Junji Ichikawa*
*Division of Chemistry, Faculty of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Ten-nodai, Tsukuba-shi, Ibaraki 305-8571, Japan
Abstract
o-(2,2-Difluorovinyl)phenyl- or o-(1,2,2-trifluorovinyl)phenyl-substituted thiophenes underwent palladium(II)-catalyzed Friedel–Crafts-type cyclization on the fluorovinyl moieties to construct regioselectively monofluorinated or difluorinated benzothiophene frameworks (pinpoint-fluorinated naphtho[b]thiophenes). The cyclization of less nucleophilic 2-substituted thiophenes was effectively promoted by the addition of a CuOTf complex. Cyclization was also conducted in a tandem process, which facilitated the rapid synthesis of higher-order pinpoint-fluorinated PAHs (polycyclic aromatic hydrocarbons) bearing thiophene rings. Furthermore, cyclization was applied to the corresponding furan systems, which led to pinpoint-fluorinated naphtho[b]furans.
Published online: 22nd January, 2019
■ A De Novo Asymmetric Synthesis of Phomopsolide E: A Practical Conversion from Phomopsolide D
Joel M. Harris, Miaosheng Li, and George A. O'Doherty*
*Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115, USA.
Abstract
A practical three-step synthesis of phomopsolide E has been developed from a synthetic sample of phomopsolide D in three steps at 62% yield. A de novo asymmetric synthesis of phomopsolide D was accomplished in 8 steps from an achiral dienone in 47% yield. The initial asymmetry of phomopsolide E was installed by a Sharpless asymmetric dihydroxylation, whereas, a highly diastereoselective reagent control iterative asymmetric hydrogenation reaction was used to diastereoselectively install the pyranone stereochemistry. The net synthetic effort of phomopsolide E was accomplished in a total 11 steps in 40% overall yield. The route as devised provided for the first-time access to synthetic material for biological analysis and established both the absolute and relative stereochemistry for this natural product.
Published online: 15th February, 2019
■ Optimized Synthesis and Solid State Investigations on the Drug Candidate Encenicline Hydrochloride
Gerhard Laus, Sandro Neuner, Ramona Metz, Thomas Müller, Volker Kahlenberg, Thomas Gelbrich, Sven Nerdinger,* Erwin Schreiner, Verena Adamer, Klaus Wurst, and Herwig Schottenberger
*Global Portfolio, Sandoz GmbH, Biochemiestrasse 10, 6250 Kundl, Austria
Abstract
For the production of drug substances a robust, scalable process delivering the active pharmaceutical ingredient (API) in excellent chemical and polymorphic purity is required. For this purpose we developed a novel imidazole-mediated one-pot procedure for the preparation of encenicline hydrochloride monohydrate, which crystallizes directly from the reaction mixture as pure non-hygroscopic polymorph (Form I). Solid state studies revealed a series of additional new physical forms for which crystal structures have been determined by single crystal X-ray diffraction.
Published online: 1st February, 2019
■ Stereospecific Ring-Expanding Skeletal Rearrangement of Isoindoline to Tetrahydroisoquinoline via a Sequential Aziridine Ring Formation/Opening
Kenichi Kobayashi,* Ryusei Endo, Yusuke Honma, Emi Kasahara, Haruka Saito, Kosaku Tanaka III, Momoko Suzuki, and Hiroshi Kogen*
*Graduate School of Pharmaceutical Sciences, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan
Abstract
A stereospecific skeletal rearrangement of isoindoline to tetrahydroisoquinoline was developed under Appel reaction conditions using a combination of PPh3 and CCl4. This reaction involves a sequential ring formation/opening of a labile aziridine and enables the construction of a quaternary carbon center, offering a highly useful method for accessing 3,3,4-trisubstituted tetrahydroisoquinolines.
Published online: 27th February, 2019
■ Diastereo–/Enantioselective Diels–Alder Synthesis of 14β-Hydroxysteroid Scaffolds: A Combined Experimental and DFT Study
Clovis Peter, Philippe Geoffroy, Takatsugu Murata, Takayuki Tonoi, Isamu Shiina,* and Michel Miesch*
*Department of Applied Chemistry, Faculty of Science, Tokyo University of Science, 1-3 Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan
Abstract
Natural, non-natural and ent-14β-hydroxyandrostane derivatives closely related to the cardenolide and bufadienolide skeletons were readily available through highly diastereo-/enantioselective Diels–Alder reactions calling for high pressure or Lewis acid activation. Moreover, in the presence of (R)- or (S)-carvone as chiral dienophile, the Diels–Alder reaction took place under chemodivergent parallel kinetic resolution control. Based on experimental and DFT studies, reasonable mechanism insights were postulated to explain the concave/convex and endo/exo selectivities observed for the formation of the different Diels–Alder and Diels–Alder–Michael adducts.
Published online: 14th February, 2019
■ Preparation of Tricyclic Analog as CDE Ring Model of Renieramycin Marine Natural Product by Novel Photo-Induced Transformation of 6-Methoxy-1,2,3,4-tetrahydroisoquinoline-5,8-dione
Masashi Yokoya, Shohei Takahashi, and Naoki Saito*
*Graduate School of Pharmaceutical Sciences, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo, 204-8588, Japan
Abstract
2-Acetyl-6-[(benzyloxy)methyl]-9-methoxy-8-methyl-11,11a- dihydro-2H-pyrazino[1,2-b]isoquinoline-1,4,7,10(3H,6H)-tetraone (11a) was prepared as the CDE ring model of renieramycins, and its novel photo-induced transformation was demonstrated to construct a 1,3-dioxol ring.
Published online: 20th February, 2019
■ 1,2-cis-Selective Formation of a Unique Amino-Containing Amino Glycoside by Endocyclic Cleavage Strategy
Shino Manabe* and Yukishige Ito*
*Synthetic Cellular Chemistry Laboratory, RIKEN, Hirosawa, Wako, Saitama 351-0198, Japan
Abstract
2-Acetamido-4-amino-2,4,6-trideoxy-α-D-galactopyranoside (AAT), a unique aminated sugar unit, is often found in zwitterionic polysaccharides. Stereoselective formation of the 1,2-cis linkage of these unique sugar derivatives was achieved by an anomerization reaction based on an endocyclic cleavage process.
Published online: 17th December, 2018
■ Palladium Acetate-Catalyzed One-Pot Synthesis of Mono- and Disubstitued Pyridines
Shunya Mikami and Masahiro Toyota*
*Department of Chemistry, Graduate School of Science, Osaka Prefecture University, 1-1 Gakuencho, Sakai, Osaka 599-8531, Japan
Abstract
A Pd-catalyzed one-pot synthesis of mono- and disubstituted pyridines was developed. The substituted pyridines were obtained from ketones or an aldehyde and 1,3-diaminopropane using a combination of catalytic Pd(OAc)2 and Cu(OAc)2. High-concentration reaction conditions enabled this catalytic reaction to be acid-free.
Published online: 26th October, 2018
■ Formation of an Aluminum Complex of 5-O-Caffeoylquinic Acid with Chiral Molecular Stacking under Vacuolar Condition
Kumi Yoshida,* Daisuke Ito, and Tadao Kondo
*Graduate School of Informatics, Nagoya University, Chikusa, Nagoya 464-8601, Japan
Abstract
5-O-Caffeoylquinic acid (neochlorogenic acid, 5CQ) is an essential co-pigment for blue coloration of hydrangea. 5CQ solubilizes a water insoluble aluminum complex of 3-O-glucosyldelphinidin (Dp3G) to give a water-soluble blue complex, in which both Dp3G and 5CQ chelate a single Al3+ ion. However, its isomer, 3-O-caffeoylquinic acid (chlorogenic acid, 3CQ), has no such effect and does not give blue complex. It was clarified that 5CQ was complexed with Al3+ with a chiral molecular stacking under physiological vacuolar condition as aq. solution at pH 4.0. However, 3CQ did not give such complex with Al3+. The difference in aluminum complexation between the isomers may result from the difference configuration of 5-OH and 3-OH group in quinic acid.
Published online: 16th November, 2018
■ Bimetallic Lewis Acid Template-Mediated Enantioselective Hetero-Diels-Alder Reactions of 4-Siloxy-2,4-pentadienols
Jun Ishihara,* Yuka Ohzono, Kengo Oka, Yasuhiro Urayama, and Susumi Hatakeyama
*Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, 852-8521, Japan
Abstract
Enantioselective hetero-Diels-Alder reactions catalyzed by a bimetallic Lewis acid template are described. The hetero-Diels-Alder reactions of 4-siloxy-2,4-pentadienols and various dienophiles by the chiral H8-BINOL template provide a general entry into the substituted dihydropyrans with good enantioselectivities. This protocol is also applicable to a dihydropirazine formation.
Published online: 25th January, 2019
■ Problem of Regioselectivity in the Amination of 2-Fluoro-5-iodopyridine with Adamantylalkyl Amines
Anton S. Abel, Yury N. Kotovshchikov, Alexei D. Averin,* Olga A. Maloshitskaya, Evgenii N. Savelyev, Boris S. Orlinson, Ivan A. Novakov, and Irina P. Beletskaya
*Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory 1-3, 119991, Moscow, Russia
Abstract
Cu(I)-Catalyzed and catalyst-free amination of 2-fluoro-5-iodopyridine with adamantylalkyl amines possessing different steric hindrances at amino group was investigated to obtain corresponding 5-amino-2-fluoro- and 2-amino-5-iodopyridines. The competition between catalytic substitution of iodine and non-catalytic substitution of fluorine was shown to take place. The catalytic system CuI/2-(isobutyryl)cyclohexanone in DMF provided yields of 5-amino-2-fluoropyridines up to 58% with stoichiometric ratio of the reagents and up to 98% with two equiv. of amines. The non-catalytic amination of 2-fluoro-5-iodopyridine provided the yields of 2-amino-5-iodopyridines up to 97%.
Published online: 17th December, 2018
■ Preparation and Optical and Electrochemical Properties of Phthalocyanine with Four Bis(carbomethoxy)tetrathiafulvalene Units
Takeshi Kimura* and Tadafumi Chiba
*Center for Instrumental Analysis, Iwate University, 4-3-5 Ueda, Morioka, Iwate 020-8551, Japan
Abstract
α-Octaoctylphthalocyaninato Ni(II) with four bis(carbomethoxy)tetrathiafulvalene units was prepared from β-tetrakis(o-xylylenedithio)-α-octaoctyl-phthalocyaninato Ni(II) via C-S bond cleavage, carbonylation, and condensation with 4,5-bis(carbomethoxy)-1,3-dithiol-2-one. The structure of the product was determined by NMR and MALDI-TOF-MS and the electrochemical and optical properties were examined by cyclic voltammetry, UV-vis spectra, and ESR spectrum.
Published online: 18th December, 2018
■ Efficient Synthesis of Benzofuran Fused 1-Azaazulene
Hiroyuki Fujii,* Yusuke Hironaka, and Noritaka Abe
*Science Research Center, Yamaguchi University, Yamaguchi 753-8512, Japan
Abstract
The synthesis of benzofuran fused 1-azaazulene (cyclohepta[d]benzo[4,5]furano[2,3-b]pyrrole) (4) was achieved by one pot reaction of 2-chloro-1-azaazulene (1) with 2-iodophenol (2) under the conditions in the presence of Pd(OAc)2 and without using a ligand.
Published online: 3rd December, 2018
■ Divergent Synthesis of Photoaffinity Probe Candidates by Click Reactions of Azido-Substituted Aryltrifluoromethyldiazirines
Kenji Watanabe, Junpei Tsuda, Hidenori Ochiai, Takashi Niwa, and Takamitsu Hosoya*
*Laboratory of Chemical Bioscience, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University (TMDU), 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan
Abstract
Two types of azido-substituted aryltrifluoromethyldiazirine units have been designed and prepared for the divergent synthesis of photoaffinity probe (PAP) candidates. Using these azides, various aryltrifluoromethyldiazirine derivatives have been rendered easily synthesizable by several click reactions, as well as the Staudinger reduction affording the corresponding aniline. The triazole-conjugated aryltrifluoromethyldiazirine derivatives prepared in this study showed normal photoreactivity compared with those reported previously. These results indicate the utility of these azido-substituted aryltrifluoromethyldiazirine units for development of PAPs for target identification of bioactive compounds.
Published online: 25th February, 2019
■ Study toward an Asymmetric and Catalytic Synthesis of Koumine
David Reyes Loya, Jacques Maddaluno, and Michaël De Paolis*
*Normandie Université, UNIROUEN, INSA de Rouen, CNRS, Laboratoire COBRA (UMR 6014 & FR 3038), 76000 Rouen, France
Abstract
A synthetic study of koumine, a natural product with a densely functionalized and inspiring heterocyclic skeleton, was conducted by exploring a strategy of desymmetrization of 1,3-cyclohexanedione by an intramolecular vinylation reaction of an enolate under palladium catalysis to give a strained bridgehead 1,3-cyclohexanedione scaffold. In the course of the study, a domino ring expansion was discovered and developed.
Published online: 13th February, 2019
■ Asymmetric Synthesis of t-Butyl 3-Alkyl-oxindole-3-carboxylates via Chiral Phosphoric Acid-Catalyzed Desymmetrization of Di-t-butyl 2-Alkyl-2-(2-aminophenyl)malonates
Kyoji Ishida, Masahiro Shimizu, Yu-suke Yamai, Itaru Natsutani, Shinichi Uesato, Yasuo Nagaoka, and Takaaki Sumiyoshi*
*Department of Life Science and Biotechnology, Faculty of Chemistry, Materials and Bioengineering, Kansai University, Yamate-cho 3-3-35, Suita, Osaka, 564-8680, Japan
Abstract
We describe the asymmetric desymmetrization of di-t-butyl 2-alkyl-2-(2-aminophenyl)malonates to prepare enantioenriched t-butyl 3-alkyl-oxindole-3-carboxylates using (S)-TRIP, a chiral phosphoric acid. Optimization study increased the enantioselectivity up to 66% ee.
Published online: 7th January, 2019
■ Synthesis of Indolo[1,2-a]indole Derivatives by Cationic Au(I)-Catalyzed exo-Selective Cycloisomerization and Their Photophysical Properties
Madhurima Hazra, Daisuke Inoue, Mamoru Ito, Kyalo Stephen Kanyiva, and Takanori Shibata*
*Department of Chemistry and Biochemistry, School of Advanced Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku, Tokyo 169-8555, Japan
Abstract
Cationic Au(I)-catalyzed intramolecular cycloisomerization of N-(2-alkynylphenyl)indoles proceeded efficiently in exo-selective manner, and (Z)-10-(arylidene)indolo[1,2-a]indole derivatives were obtained in moderate to high yields. Their photophysical properties were also measured.
Published online: 5th February, 2019
■ A Novel Route to (R)-2-(3-Chlorophenyl)propan-1-amine, a Key Intermediate for the Synthesis of Lorcaserin
Ivana Gazic Smilovic, Sven Nerdinger,* Sandro Neuner, Herwig Schottenberger, Thomas Gelbrich, and Klaus Wurst
*Global Portfolio, Sandoz GmbH, Biochemiestrasse 10, 6250 Kundl, Austria
Abstract
A new and efficient three-step synthesis of (R)-2-(3-chlorophenyl)propan-1-amine is reported, which serves as an intermediate in the synthesis of the antiobesity drug lorcaserin. The key step is a chiral resolution due to the formation of a salt with l-(-)-3-phenyllactic acid. The structure of the relevant salt phase is reported.
Published online: 18th February, 2019
■ Synthesis of Di(3-thienyl)benzoporphyrin
Tetsuo Okujima,* Kota Muramatsu, Shigeki Mori, Masayoshi Takase, and Hidemitsu Uno
*Graduate School of Science and Engineering, Ehime University, Matsuyama 790-8577, Japan
Abstract
We have successfully synthesized 2,3-di(3-thienyl)benzo[b]porphyrin based on retro Diels–Alder reaction of bicyclo[2.2.2]octadiene(BCOD)-fused porphyrin and investigated its photoisomerization reaction.
Published online: 14th February, 2019
■ Synthesis of Furan-Fused Silole and Phosphole by One-Pot Halogen Dance/Homocoupling of Bromofurfural Derivative
Kentaro Okano,* Yuki Murase, and Atsunori Mori
*Department of Chemical Science and Engineering, Kobe University, 1-1 Rokkodai, Nada, Kobe 657-8501, Japan
Abstract
Synthesis of a furan-fused silole and phosphole was achieved through a one-pot halogen dance/homocoupling of a bromofurfural derivative followed by the formation of the silole and phosphole skeleton.