HETEROCYCLES

■ Contents

■ Preface to Heterocycles Issue
Honoring the 75th Birthday of Prof. Dr. h.c. Lutz F. Tietze

Daniel B. Werz*

*Institut für Organische Chemie, Technische Universität Braunschweig, Hagenring 30, D-38106 Braunschweig, Germany

■ Curriculum Vitae

Lutz F. Tietze*

*

■ List of Publications (Prof. Dr. Dr. h.c. Lutz F. Tietze)

Lutz F. Tietze*

*

■ Synthesis of (S)- and (R)-Sporochnol by Using the Allylic Substitution of the Secondary Allylic Picolinate

Yuichi Kobayashi,* Yusuke Sugihara, Toshifumi Tojo, and Takuri Ozaki

*Department of Biomolecular Engineering, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Box B52, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan

Abstract

The allylic substitution of secondary allylic picolinates and copper reagents for the construction of a quaternary carbon was applied to synthesis of sporochnol. The enantiomerically enriched allylic picolinate (R)-5 was synthesized through the asymmetric hydrogen transfer of acetylene ketone 11 and the Pd-catalyzed methylation of the iodoallylic alcohol 16a. The key allylic substitution of the allylic picolinate (R)-5 with 4-MeOC6H4MgBr/Cu(acac)2 (2:1) proceeded with 95% chirality transfer with 98% regioselectivity to afford anti SN2' product 6 in 89% yield, which was converted to the methyl ether of unnatural (R)-sporochnol. Similarly, the methyl ether of (S)-sporochnol (the natural form) was synthesized.

■ Stereoselectivity of D-Psicofuranosylation Influenced by Protecting Groups of Psicofuranosyl Donors

Takashi Yamanoi,* Yoshiki Oda, Toshiaki Ishiyama, and Mikio Watanabe

*Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan

Abstract

We synthesized several types of novel D-psicofuranosyl acetate derivatives, and investigated their use as glycosyl donors in scandium triflate-catalyzed D-psicofuranosylation reactions. Psicofuranosylation demonstrated unique stereoselectivities depending on the protecting groups of psicofuranosyl donors. The donor having a 3,4-isopropylidene group afforded β-psicofuranosides with high stereoselectivities. Donors having a C3 benzoyloxy group demonstrated low stereoselectivities with no neighboring group participation. This study also discusses the stereoselectivities of psicofuranosylation based on the conformers of the glycosyl oxocarbenium ion intermediates as influenced by the protecting groups of the psicofuranosyl donors. We also compared the neighboring group participation of the glycosyl donors bearing a C3 benzoyloxy group during D-psicofuranosylation and D-fructofuranosylation.

■ Synthesis of 3,4-Dihydro-2H-1,3-benzoxazine-2-thiones via Cyclization of 2-(1-Isothiocyanatoalkyl)phenols

Kazuhiro Kobayashi,* Hiroki Inouchi, Naoki Matsumoto, and Yuuki Chikazawa

*Division of Applied Chemistry, Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori University, 4-101 Koyama-minami, Tottori 680-8552, Japan

Abstract

Convenient sequences for the preparation of 3,4-dihydro-2H-1,3-benzoxazine-2-thiones from 2-hydroxybenzaldehyde and 2-hydroxyphenyl ketones or 2-methylphenols have been developed, which both employ cyclization of 2-(1-isothiocyanatoalkyl)phenols generated in situ under mild conditions.

■ Synthesis of 2-Arylquinoxalines: Triarylstibane-Catalyzed Oxidative Cyclization of α-Hydroxy Ketones with 1,2-Diamines under Aerobic Conditions

Mio Matsumura, Rie Takada, Yuu Ukai, Mizuki Yamada, Yuki Murata, Naoki Kakusawa, and Shuji Yasuike*

*Faculty of Pharmaceutical Sciences, Aichi Gakuin University, 1-100 Kusumoto-cho Chikusa-ku Nagoya city 464-8650, Japan

Abstract

The reaction of -hydroxy ketones with 1,2-diamines in the presence of triphenylstibane (10 mol%) as catalyst led to the formation of 2-arylquinoxalines in moderate to good yield under aerobic conditions. This reaction is the first example of oxidative cyclization catalyzed by organoantimony compounds.

■ Total Synthesis of Carbazole-1,4-quinone Alkaloid Koeniginequinones A and B Based on a One-Pot Cyclocarbonylation Procedure from 2-Alkenyl-3-iodoiodoindole

Takashi Nishiyama, Nanase Satsuki, Satoshi Hibino,* Mami Fujii, Takumi Abe, Minoru Ishikura, and Tominari Choshi*

*Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Fukuyama, Hiroshima 729-0292, Japan

Abstract

Total syntheses of koeniginequinones A and B, isolated from Murraya koenigii, were newly achieved by constructing of carbazole-1,4-quinone using a one-pot Pd-catalyzed cyclocarbonylation method with 2-(but-2-en-1-yl)-3-iodoindoles derived from known methyl 6-methoxyindole-2-carboxylate and methyl 5,6-dimethoxyindole-2-carboxylate, followed by desilylation, and an oxidation sequence.

■ Practical and Facile Route to a Functional Intermadiate from Stigmasterol for the Synthesis of 1α-Hydroxyvitamin D5 and Related Compounds

Michiyasu Takahashi, Seiya Hosokawa, Yuuya Ono, and Noboru Kubodera*

*International Institute of Active Vitamin D Analogs, 35-6, Sankeidai, Mishima, Shizuoka 411-0017, Japan

Abstract

As a functional and versatile intermediate for the synthesis of 1α-hydroxyvitamin D5 and related compounds, 1α,2α-epoxy-3β-hydroxystigmasta- 5,7-diene was synthesized by a practical and facile 17-step route from stigmasterol in 17% overall yield.

■ Access to Apoerysopine and Pratosine Skeletons via Intramolecular Carbolithiation and Palladium-Catalyzed Alkenylation Reactions

Estíbaliz Coya, Esther Lete, and Nuria Sotomayor*

*Departamento de Química Orgánica, Facultad de Ciencia y Tecnologia, Universidad del País Vasco, Barrio Sarriena s/n. Leioa (Bizkaia) Bilbao 48940, Spain

Abstract

(Pyrrolo[1,2-a]benzazepinyl)acetamides, obtained through carbolithiation reactions, have been used as intermediates in the access to Apoerysopine skeleton. Derivatization implies reduction to the correponding aldehyde using the Snieckus procedure for in situ generation of the Schwartz reagent, followed by Wittig reaction and intramolecular Pd(II)-catalyzed C-H alkenylation. The same sequence has been applied for the obtention of Pratosine from a pyrroloisoquinoline intermediate.

■ New Applications of Hetaryl Thioketones for the Synthesis of Hetaryl-Substituted Ethenes via ‘Two-Fold Extrusion Reaction’

Grzegorz Mlostoń, Katarzyna Urbaniak, Aneta Pawlak, and Heinz Heimgartner*

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

Abstract

A series of aryl/hetaryl thioketones was applied for the reactions with aryl/hetaryldiazomethanes yielding, after elimination of N2, the corresponding thiiranes. The relatively unstable dihetaryldiazomethanes were generated in situ from the corresponding hydrazones by oxidation with DMSO. The obtained thiiranes were converted into tetraaryl/hetaryl-substituted ethenes in good yields by desulfurization performed with tris(diethylamino)phosphine ((Et2N)3P).

■ Synthesis of Furan-Oxazole Conjugated Fluorescent Materials from Biomass-Derived Furfural through Cross-Coupling Reactions

Yuki Murase, Kana Ashida, Shota Tanaka, Kentaro Okano, and Atsunori Mori*

*Chemical Science & Technology, Graduate School of Engineering, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan

Abstract

Synthesis of furyloxazole was performed from biomass-derived furfural and serine methyl ester through dehydrative condensation and oxidation in one pot. Bromination and subsequent palladium-catalyzed arylation with arylboronates proceeded smoothly at the furan ring to provide arylated furylthiazoles. Arylation of C–H bond at the 5 position of the oxazole ring under Fagnou’s conditions led to formation of diarylated furyloxazoles, which exhibit higher quantum yields over those of the related furylthiazole derivatives.

■ Conversion of 2-Thioxo-2,3-dihydroquinazolin-4(1H)-ones to N(3)-Unsubstituted 2-(Het)Arylquinazolin-4(3H)-ones by Copper-Mediated Pd-Catalysed Cross-Coupling Reactions

Vilija Kriščiūnienė, Gita Matulevičiūtė, Osvaldas Paliulis, Patrick Rollin, and Algirdas Šačkus*

*Institute of Synthetic Chemistry, Kaunas University of Technology, Radvilėnų Rd. 19, LT-50270 Kaunas, Lithuania

Abstract

With the purpose of searching for new heterocyclic building blocks, a new method to access N(3)-unsubstituted 2-(het)arylquinazolin-4(3H)-ones from 2-thioxo-2,3-dihydroquinazolin-4(1H)-one derivatives was developed. The synthetic protocol was based on the copper-mediated palladium-catalysed cross-coupling reactions of 2-thioxo-2,3-dihydroquinazolin-4(1H)-ones with (het)arylstannanes or their S-benzylated derivatives with (het)arylboronic acids, using CuBr·Me2S and CuMeSal as promoters, respectively. A similar transformation was applied for the preparation of 2-aryl[1]benzothieno[3,2-d]pyrimidin-4(3H)-ones.

■ New Gas-Phase Domino Processes Leading to Benzopyranones and Benzofurans

R. Alan Aitken* and Da Chang

*School of Chemistry, University of St. Andrews, North Haugh, St Andrews, Fife KY 16 9ST, U.K.

Abstract

A new domino approach to flavones by gas phase pyrolysis of β,γ-dioxophosphonium ylides containing a 2-methoxyphenyl group is frustrated by unexpected and novel decarbonylation of the intermediate flavon-3-yl radical leading to 2-phenylbenzofuran. Alternative approaches based on dioxolane protection of one carbonyl, or selective elimination in β,β'-dioxo or β-oxo-β'-thioxo ylides were not successful, but pyrolysis of a β-oxo-β'-phenylimino ylide did give the required domino reaction leading to a protected benzopyranone in moderate yield.

■ Diversity-Oriented Approach to 1,2,3,4-Tetrahydroisoquinoline-3-carboxylic Acid (Tic) Derivatives

Sambasivarao Kotha,* Shilpi Misra, Nimita Gopal Krishna, Vijayalakshmi Bandi, Mohammad Saifuddin, and Nagaraju Devunuri

*Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai - 400076, India

Abstract

A convenient method is reported for synthesizing various 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives and bis-armed -amino acid derivatives by treating dibromo-o-xylylenes precursor with diethyl acetamidomalonate under basic conditions. Suzuki coupling reaction has been used to expand this methodology. One of the structure revision of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid into bis-armed amino acid is also reported.

■ Synthesis of Functionalized Fullerenes by Photoaddition of N-α-Trimethylsilyl-N-carboxymethyl-N-benzylamines to C60

Suk Hyun Lim, Dae Won Cho,* and Patrick S. Mariano*

*Department of Chemistry and Chemical Biology, University of New Mexico, Albuequerque, NM 87131, U.S.A.

Abstract

Photoaddition reactions of fullerene C60 with N-α- trimethylsilyl-N-carboxymethyl-N-benzylamines, which contain various para-substituents, were explored in order to evaluate factors governing efficiencies of this potentially useful method for preparing functionalized fullerene derivatives. Observations made in this study show that two reaction pathways are followed in these photoreactions. The first involves initial formation of α-trimethylsilyl-aminium radicals and the C60 anion radical by SET from the amines to the triplet excited state of C60. This step is followed by desilylation to produce α-amino radicals. Coupling of these radicals with the anion radical of C60 followed by protonation or with the hydrofullerene radical generated by protonation of the anion radical of C60 then produces aminomethyl- 1,2-dihydrofullerenes. When limited amounts of 3O2 are present in the reaction medium, fulleropyrrolidines are generated in low yields by a competitive pathway involving formation of singlet oxygen, which undergoes sequential H-atom abstractions from the N-α-trimethylsilyl-N-carboxymethyl-N-benzylamines to produce azomethine ylide intermediates. Dipolar cyloaddition of the ylides to C60 then produces fulleropyrrolidines. Photoreactions of the C60 and the amines in the presence of high 3O2 concentrations exclusively produce fulleropyrrolidine. In addition, the results show that photoreactions of non-silicon substituted, N-methyl-N-carboxymethyl-N-benzylamines with C60 form fulleropyrrolidines independent of the concentration of 3O2 present in the media.

■ Synthesis of Chemical-Biology Tools Enabling in vivo Imaging and Analysis of Epigallocatechin Gallate

Tomohiro Asakawa,* Atsushi Yoshida, Yasuo Hirooka, Takashi Suzuki, Kunihiko Itoh, Kosuke Shimizu, Naoto Oku, Takumi Furuta, Toshiyuki Wakimoto, Makoto Inai, and Toshiyuki Kan

*Synthetic Organic ＆ Medicinal Chemistry, School of Pharmaceutical Science, University of Shizuoka, 52-1 Yada, Suruga, Shizuoka 422-8526, Japan

Abstract

(–)-Epigallocatechin gallate (EGCg) has multiple bioactivities, and imaging/analytical tools are required for drug development studies. Here we present full details of our synthetic studies aimed at providing building blocks for development of such tools, including a concise synthesis of model compound 5,7-dideoxyEGCg (DOEGCg, 2) and an asymmetric synthesis of 6-(5-aminopentyl)-5,7-deoxyepigallocatechin gallate (APDOEGCg, 4), which contains a reactive terminal amino group. To demonstrate its utility, APDOEGCg (4) was efficiently converted to a fluorescent probe 53 by linking it to a fluorescein derivative, Tokyo Green, via the amino group. We confirmed that 53 is suitable for in vivo imaging studies. We also prepared an immunogen 56 by conjugation of 4 to human serum albumin carrier protein via a glutaraldehyde linker, and we used 56 to raise anti-EGCg antiserum in mice. The fluorescent probe and antiserum should be useful tools for biochemical investigations of the localization and target sites of EGCg. APDOEGCg should also be available for developing other novel tools for biochemical studies of catechins.

■ Computational Study for 1,5-Sigmatropic Hydrogen Shift on Trifluoromethylazadiene Derivatives - The Key Step in the Synthesis of Fluorine-Containing Oxazines -

Norio Ota, Yasuhiro Kamitori,* Takashi Okuda, and Etsuji Okada

*Department of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan

Abstract

1,5-Sigmatropic hydrogen shifts on two types of azadiene systems, O-protonated β-trifluoroacetylenamines 9 and 3,3,3-trifluoro-1- alkylideneaminopropen-2-ols 10, are elucidated on the basis of DFT calculations to develop new synthetic methodologies accessing novel fluorine-containing heterocycles. These results suggest that the 1,5-hydrogen shift on 9 and 10 requires slightly further enhanced conditions compared with the corresponding step on diazadiene systems, O-protonated 1,1,1-trifluoro-3-hydrazono-2- alkanones 3, which results in the derivation of oxadiazines 2.

■ A DFT Investigation of the anti- and syn-Fused Isomers of Difuropyridines, Difuropyrazines, and Their Dithieno Analogues

Naoto Hayashi,* Naoki Okamoto, Naho Sasaki, Miho Ito, Junro Yoshino, and Hiroyuki Higuchi

*Department of Chemistry, Graduate School of Science and Engineering, Toyama University, Gofuku 3190, Toyama 930-8555, Japan

Abstract

Density functional theory calculations have been performed on the anti- and syn-isomers of a series of difuropyridines and difuropyrazines, as well as their dithieno analogues, and the results compared with those of the corresponding benzodifurans and benzodithiophenes. When the central ring in these systems was changed from benzene to pyridine and finally to pyrazine, the difference in the energy levels of the lowest unoccupied molecular orbitals (ELUMO) of the anti- and syn-isomer became smaller, irrespective of the fused rings. Furthermore, the difference in the ELUMO values of the furan- and thiophene-fused systems decreased as the central ring became increasingly electron deficient. In contrast, rather complicated trends were observed between the energy levels of the highest occupied molecular orbitals.

■ Simple Synthetic Method for 1,2,3,3a,8,8a-Hehahydropyrrolo[2,3-b]indoles Having a Halogen or an Oxygen Functional Group at the 3a-Position

Takako Iwaki, Yoshikazu Fukui, Masaki Okigawa, Fumio Yamada, Yoshiyuki Nagahama, Sachiko Ogasawara, Satomi Tanaka, Shiho Funaki, and Masanori Somei*

*Noto Marine Laboratory, Institute of Nature and Environmental Technology, Faculty of Pharmaceutical Sciences, Graduate School of Natural Science and Technology, Kanazawa University, 56-7 Matsuhidai, Matsudo-shi, Chiba 270-2214, Japan

Abstract

1-Methoxy-Nb-methoxycarbonyltryptamine derivatives are successfully converted by either halogenating reagents or iodine/morpholine to 1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indoles having a halogen or an oxygen functional group at the 3a-position. Synthesis of the corresponding methyl 1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indole-2-carboxylates is also reported.

■ New Synthesis of Tetrahydrobenzodifurans by Iterative Coupling of Quinone Monoacetals with Alkene Nucleophiles

Tohru Kamitanaka, Hitoho Takamuro, Kazuyuki Shimizu, Yudai Aramaki, Toshifumi Dohi, and Yasuyuki Kita*

*College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga, 525-8577, Japan

Abstract

A new efficient synthetic strategy of tetrahydrobenzodifurans has been developed by the repetitive [3+2] couplings of quinone monoacetals with alkene nucleophiles. Both the symmetrical and unsymmetrical tetrahydrobenzodifurans can be easily synthesized by this continuous method by altering the type of alkenes. These tetrahydrobenzodifurans have also become a useful precursor of highly-substituted benzofurans by dehydrogenation.

■ Formal Total Synthesis of Artocarpin

Isao Mizota, Kana Taniguchi, and Makoto Shimizu*

*Department of Chemistry for Materials, Graduate School of Engineering, Mie University, 1577 Kurimamachiya-cho Tsu, Mie 514-8507, Japan

Abstract

A formal total synthesis of artocarpin was achieved via selective demethylation, iodination, followed by Suzuki-Miyaura coupling reaction of the key flavone derivative. It took only 7 steps in the overall yield of 55% starting from commercially available 3,5-dimethoxyphenol.

■ Crystal Structures of Intermediates in a New Synthesis of Antitumor Drug Cabozantinib

Gerhard Laus, Erwin Schreiner, Sven Nerdinger,* Volker Kahlenberg, Klaus Wurst, Stefan Vergeiner, and Herwig Schottenberger

*Sandoz GmbH, Biochemiestrasse 10, 6250 Kundl , Austria

Abstract

The heterocyclic antitumor drug cabozantinib was synthesized by condensation of 4-(6,7-dimethoxyquinolin-4-yloxy)aniline and methyl 1-(4-fluorophenylcarbamoyl)cyclopropanecarboxylate in the presence of two equivalents of sodium methoxide and azeotropic removal of methanol. In turn, the intermediate methyl 1-(4-fluorophenylcarbamoyl)cyclopropanecarboxylate was prepared from 4-fluoroaniline and dimethyl 1,1-cyclopropanedicarboxylate in the presence of one equivalent of sodium methoxide. Four crystal structures of intermediates and a byproduct were determined.

■ Synthesis of 7,7′-Linked-bis-Indoles via 7-Tryptamines

Hakan Kandemir, Ibrahim F. Sengul, Christopher R. Gardner, Eryn L. Werry, Melissa L. Barron, Michael Kassiou, Naresh Kumar, and David StC. Black*

*School of Chemistry, The University of New South Wales, Sydney 2052, Australia

Abstract

The synthesis of 7-tryptamines was accomplished via the reduction of 7-nitrovinylindoles which were developed by the condensation of indole-7-carbaldehydes with nitromethane and ammonium acetate. 7-Tryptamines were subsequently used for the construction of 2,3-disubstituted and 3-substituted 7,7′-linked-bis-indoles.

■ Crystal Structures of N,N’-bis(5-Dodecyloxytropon-2-yl)piperazine and N,N’-bis(4-Butoxyphenyl)piperazine

Kanji Kubo,* Emi Yamamoto, Taisuke Matsumoto, Seiji Ujiie, and Akira Mori

*Department of Life Science and Technology, Faculty of Engineering, Hokkai-Gakuen Univiersity, Sapporo, Hokkaido 062-8605, Japan

Abstract

The crystal structures of N,N’-bis(5-dodecyloxytropon-2-yl)piperazine (1) and N,N’-bis(4-butoxyphenyl)piperazine (2) were analyzed by X-ray crystallography. The molecules of 1 and 2 sits on a center of symmetry such that the two aromatic rings are in an anti conformation with respect to one another across the piperazine ring. The molecules (1, 2) forms a tilted layer structure via intermolecular C-H∙∙∙O and C-H∙∙∙π interactions in 1 and intermolecular C-H∙∙∙O, C-H∙∙∙N, and C-H∙∙∙π interactions in 2.

■ Synthesis of Benzophenone and Phenylazide Derivatives of Salicin for Functional Analysis of the Bitter Taste Receptor Using Photoaffinity Labeling

Takuma Yoshida, Yasuyuki Hashidoko, and Makoto Hashimoto*

*Graduate School of Agriculture, Hokkaido University, Kita 9 Nishi 9, Kita-ku, Sapporo, Hokkaido 060-0589, Japan

Abstract

Salicin is a substance that is well known for its bitter taste. Photoreactive benzophenone and phenylazide derivatives of salicin are for the functional analysis of interactions between the bitter taste receptor and salicin. First synthesis of these derivatives was prepared from acetobromo-α-D-glucose via glucosidation with salicylaldehyde derivatives followed by reduction of aldehyde to form salicin skeleton.

■ Chemical Reactivity and Application of 4-Alkylidene-3H-pyrazol-3-ones: Synthesis and Antifungal Activity of Polysubstituted Pyrazoles

Hiroshi Maruoka,* Masataka Hokao, Nobuhiro Kashige, Eiichi Masumoto, Fumi Okabe, Reiko Tanaka, Fumio Miake, Toshihiro Fujioka, and Kenji Yamagata

*Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan

Abstract

Chemical reactivity and application of 4-alkylidene-3H-pyrazol-3-ones are described. Furthermore, twelve of the newly synthesized O-substituted pyrazoles were evaluated for their antifungal activity in vitro against Candida albicans and Saccharomyces cerevisiae.

■ A Short Synthesis of 2,3,5-Trisubstituted Pyrroles by an Alkylation/Dehydrocyanation Sequence

Murat Kucukdisli, Marco M. Nebe, Solveig M. Bartelt, and Till Opatz*

*Institute of Organic Chemistry, Johannes Gutenberg-University, Duesbergweg 10-14, 55128 Mainz, Germany

Abstract

2,3,5-Trisubstituted pyrroles were prepared in a one-pot procedure from readily available 3,5-disubstituted 3,4-dihydro-2H-pyrrole-2-carbonitriles by an alkylation/dehydrocyanation sequence. The method was also applied to α,ω-dihaloalkanes to furnish dipyrroles tethered with an alkyl spacer.

■ Asymmetric Synthesis of cis-4a,5,8,8a-Tetrahydrophthalazin-1(2H)-one Derivatives Based on Organocatalytic Alcoholysis of Cyclic Dicarboxylic Anhydride

Shigeki Sano,* Masanori Kamura, Akihito Nakamura, Syuji Kitaike, and Michiyasu Nakao

*Molecular Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokushima, 1-78 Sho-machi, Tokushima 770-8505, Japan

Abstract

Asymmetric synthesis of optically active cis-4-phenyl-4a,5,8,8a- tetrahydrophthalazin-1(2H)-one and its N-alkylated derivatives based on an organocatalytic enantioselective alcoholysis of cyclic dicarboxylic anhydride was described.