HETEROCYCLES

■ Contents

■ Preface
Steven M. Weinreb/ Heterocycles

Richard W. Franck

*Hunter College of CUNY

■ Biographical Data

Steven M. Weinreb*

*Department of Chemistry, The Pennsylvania State University, University Park, PA 16802, U.S.A.

■ Publications

Steven M. Weinreb*

*Department of Chemistry, The Pennsylvania State University, University Park, PA 16802, U.S.A.

■ Chapters and Books

Steven M. Weinreb*

*Department of Chemistry, The Pennsylvania State University, University Park, PA 16802, U.S.A.

■ Graduate Students Supervised

Steven M. Weinreb*

*Department of Chemistry, The Pennsylvania State University, University Park, PA 16802, U.S.A.

■ Invited and Plenary Lectures

Steven M. Weinreb*

*Department of Chemistry, The Pennsylvania State University, University Park, PA 16802, U.S.A.

■ Brominative Indolization of an Unsaturated Bridgehead Sultam with Extrusion of Sulfur Dioxide

Adam J. Preston and Leo A. Paquette*

*Department of Chemistry, The Ohio State University, 100 West 18th Avenue Columbus, Ohio 43210, U.S.A.

Abstract

The dissolution of an unsaturated bridgehead sultam in liquid bromine at room temperature results in the formation of a pentabromo indole derivative in an unusual desulfonylative process.

■ Synthesis of Substituted 4-Arylpiperidin-2-ones by a 6-exo-Trig Radical Cyclization

Xavier Vila and Samir Z. Zard*

*Laboratoire de Synthèse Organique Associé au C.N.R.S., Ecole Polytechnique, F-91128 Palaiseau, France

Abstract

A series of 5-substituted-4-arylpiperidin-2-ones have been synthesized in a 4 step sequence involving a radical 6-exo-trig cyclization as the key step.

■ Convenient Synthesis of Masked Aminoindoles by Indium Mediated Ont-Pot Reductive Acylation of 3- and 2-Nitroindoles

Sujata Roy and Gordon W. Gribble*

*Department of Chemistry, Dartmouth College, 6128 Burke Laboratory, Hanover, New Hampshire 03755, U.S.A.

Abstract

Unstable 3- and 2-aminoindoles are generated in situ by indium mediated reduction of 3- and 2-nitroindoles and capped as the stable amides (or carbamate) in moderate to high yields under mild conditions in a one-pot procedure.

■ Titanium Tetraiodide Mediated Reductive Opening of Aziridines, Leading to the Aldol and Mannich-Type Reactions

Makoto Shimizu,* Hiroshi Kurokawa, Shuji Nishiura, and Iwao Hachiya

*Department of Chemistry for Materials, Faculty of Engineering, Mie University, 1577 Tsu, Mie 514-8507, Japan

Abstract

Reductive ring-opening of N-tosylazirindes was readily carried out with titanium tetraiodide to form the titanium enolates, which in turn were subjected to addition reaction with aldehydes or imines to give aldol or Mannich-type products in good yields.

■ Total Synthesis of Cytostatin

Brian G. Lawhorn, Sobhana B. Boga, Scott E. Wolkenberg, and Dale L. Boger*

*Department of Chemistry and The Skaggs Institute for Chemcial Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, U.S.A.

Abstract

The total synthesis of cytostatin, an antitumor agent belonging to the fostriecin family of natural products, is disclosed. The convergent route features a key epoxide opening reaction to join the two stereotriad units and a single-step late stage, stereoselective installation of the sensitive triene through a β-chelation controlled nucleophilic addition. The synthesis provides rapid access to the C4-C6 and C10-C11 stereoisomers of cytostatin and additional analogues to define the substituent role in PP2A binding.

■ Synthesis of Novel Silacyclobutene Derivatives Utilizing Zirconocene- and Titanocene-Ethylene Complexes

Chung Keun Jin, Tinh Van Dang, Yoshifumi Ikee, Toshiaki Yamada, Shigeki Sano, Motoo Shiro, and Yoshimitsu Nagao*

*Graduate School of Pharmaceutical Sciences, University of Tokushima, Sho-machi, Tokushima 770-8505, Japan

Abstract

New types of silacyclobutene derivatives were synthesized by zirconocene- and titanocene-ethylene complexes-promoted reactions of some rac-dialkynyldiarylsilanes.

■ Investigations of Pd-Catalyzed Aryl Substitution Reactions. A Case Study towards Zoanthenol

David R. Williams,* David C. Ihle, Todd A. Brugel, and Samarjit Patnaik

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

Abstract

Synthesis studies feature results for variations of Heck reaction strategies utilized for aryl substitution processes toward construction of the fully functionalized AB ring system of zoanthenol. A novel intramolecular Michael reaction is described, and the deployment of sensitive allylation reactions are reported.

■ Crystal Structures of N,N’-Bis(1-naphthylmethyl)-1,4,10,13-tetraoxa-7,16-diazacyclooctadecane Complexed with Lithium and Zinc Thiocyanates

Kanji Kubo,* Tadamitsu Sakurai, Hajime Takahashi, and Haruko Takechi

*School of Dentistry, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan

Abstract

The crystal structures of N,N‘-bis(1-naphthylmethyl)- 4,13-diaza-18-crown-6 (1) complexed with LiNCS and Zn(NCS)₂ were analyzed by X-Ray crystallography. Diazacrown (1) formed a unique 1:2 complex with LiNCS, while Zn(NCS)₂ complex of 1 consisted of an ion pair with [Zn(NCS)₄]^2- and 1·2H⁺. The two naphthalene rings in the crystals adopt an anti conformation with respect to each other.

■ The 1,3-Dipolar Cycloaddition of Methyl Acrylate to Hindered 3-Oxidopyraziniums

Madeleine Helliwell, Yun You, and John A. Joule*

*The School of Chemistry, The University of Manchester, Oxford Road, Manchester, M13 9PL, U.K.

Abstract

Methyl acrylate adds to 1,2,5,6-tetramethyl-3-oxidopyrazinium to give a standard 1,3-dipolar cycloadduct — a 3,8-diazabicyclo[3.2.1]octan-2-one — however from the more hindered 5,6-diethyl-1,2-dimethyl-3-oxidopyrazinium, a 4,7-dioxo-3,6-diazabicyclo[3.2.1]octane, the result of extensive rearrangement of the initial 1,3-dipolar cycloadduct, was obtained and its structure determined by X-Ray crystallographic analysis.

■ Diastereoselective Synthesis of Atropisomeric 3-(2-Substituted Aryl)quinazolin-4-ones and Their Stereochemical Properties

Takashi Tokitoh, Toshitake Kobayashi, Eisuke Nakada, Tohru Inoue, Satoshi Yokoshima, Hideyo Takahashi, and Hideaki Natsugari*

*Faculty of Pharmaceutical Sciences, Teikyo University, 1091-1 Suarashi, Sagamiko-machi, Tsukui-gun, Kanagawa 199-0195, Japan

Abstract

Atropisomeric {1-[(2-substituted-aryl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl and -2-phenylethyl}carbamic acid t-butyl ester (9a-c) were diastereoselectively synthesized by acid-catalyzed cyclization of {2-[(2-substituted-arylcarbamoyl)phenylimino]-1-methyl- and -1-benzyl-2-piperidin-1-yl}carbamic acid t-butyl ester (8a-c). Investigation of the stereochemical properties of 9 revealed that both atropisomers have high stereochemical stability and the (aR*, S*)-form (9R*) is stereochemically more stable than the isomeric (aS*, S*)-form (9S*).

■ Concise and Short Synthesis of Functionalized 5,6-Dihydropyridin-2-ones by Means of Palladium(0)-Catalyzed Cross-Coupling of Ketene Aminal Phosphates

Haruhiko Fuwa,* Akane Kaneko, Yasuaki Sugimoto, Taisuke Tomita, Takeshi Iwatsubo, and Makoto Sasaki*

*Laboratory of Biostructural Chemistry, Graduate School of Life Sciences, Tohoku University, 1-1 Tsutsumidori-amamiya, Aoba-ku, Sendai 981-8555, Japan

Abstract

A concise and short synthetic entry to 5,6-dihydropyridin-2-one derivatives has been developed by means of palladium(0)-catalyzed cross-coupling of cyclic ketene aminal phosphates.

■ Regioselective Oxidation of Isoxazolidines to Ketonitrones

Osamu Iwamoto, Miyuki Sekine, Hiroyuki Koshino, and Kazuo Nagasawa*

*Division of Biotechnology and Life Science, Institute of Symbiotic Science and Technology, Tokyo University of Agriculture and Technology, 2-24-16 Nakamachi, Koganei, Tokyo 184-8588, Japan

Abstract

Mild and neutral conditions of m-CPBA-induced regioselective ring opening reaction of isoxazolidine into ketonitrone was described.

■ Synthetic Studies toward Cribrostatin IV: An Intriguing Epimerization

Collin Chan and Samuel J. Danishefsky*

*Department of Chemistry, MSKCC, Columbia University, Box 106, 1275 York Ave., New York, NY 10021, U.S.A.

Abstract

Surprising effects of remote substituents on the relative rates of vinylogous Pictet-Spengler reaction versus epimerization through a Grigg like progression have been encountered (contrast cyclizations of 3 and 7). Deuterium labeling experiments have been used to clarify mechanisms of epimerization, thereby allowing for the assignment of absolute configuration.

■ Substituent Effects on the Regiochemical and Stereochemical Course of the Nussbaumer-Frater Variation of the Prins Cyclization

Chad E. Bennett, Ruth Figueroa, David J. Hart,* and Dexi Yang

*Department of Chemistry, The Ohio State University, 100 West 18th Avenue Columbus, Ohio 43210, U.S.A.

Abstract

Eleven vinylogous carbonates were examined in the Nussbaumer-Frater variation of the Prins cyclization to provide 2,3,4,6-tetrasubstituted tetrahydropyrans. Results indicate that substrate olefin geometry is a more reliable control element than preset substrate vicinal stereochemistry for establishing C₂-C₃ vicinal stereochemistry in tetrahydropyran products.

■ Investigation of the Bromination of Tetrahydrobenzimidazoles

Carl J. Lovely,* Yong He, Heather M. Fenton, and H. V. Rasika Dias*

*Department of Chemistry, The University of Texas at Arlington, 502 Yates Street, Arlington, TX 76019, U.S.A.

Abstract

During an investigation of the bromination of tetrahydrobenzimidazoles, an interesting dimerization reaction was observed. This dimerization pathway can be attenuated by conducting the reaction in the presence of silica gel.

■ Synthetic Studies toward Clavilactone A: A Concise Access to α,γ-Substituted γ-Butenolides by Metathesis

Hiroyuki Yasui, Shun Yamamoto, Ken-ichi Takao, and Kin-ichi Tadano*

*Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Hiyoshi, Kohoku-ku Yokohama 223-8522, Japan

Abstract

Synthetic studies toward clavilactone A (1), using olefin metathesis as key steps, have been described. The ring-opening/ring-closing metathesis of 3- bromo-2-[1-(1-cyclobutenyl)carboxyl-2-propenyl]-1,4-dimethoxybenzene (9) constructed a γ-arylated butenolide (11). The ring-opening/ring-closing/cross metathesis of 2-[1-(1-cyclobutenyl)carboxyl-2-propenyl-1,4-dimethoxybenzene (19) in the presence of methallyl acetate (20) provided 2-[4-((E)-5-acetoxy- 4-methyl-3-pentenyl)-5-oxo-2,5-dihydrofuran-2-yl]-1,4-dimethoxybenzene (21). The π-allyl palladium complex-mediated intramolecular cyclization of 21 for construction of the 11-membered lactone moiety in the clavilactones was also explored.

■ An Approach to Cyclic α-Amino Acids by a Novel Hetero Diels-Alder/Intramolecular Hydantoin Enolate Alkylation Strategy: An Approach to Halichlorine

Hyoungsu Kim, Jae Hong Seo, Kye Jung Shin, Dong Jin Kim, and Deukjoon Kim*

*College of Pharmacy, Seoul National University, Shillim-Dong, San 56-1, Kwanak-Gu, Seoul 151-742, Korea

Abstract

An efficient, novel synthetic strategy has been developed for preparation of cyclic α-amino acid employing an intermolecular hetero Diels-Alder reaction and an intramolecular hydantoin enolate alkylation as key steps. Application of the present hetero Diels-Alder/intramolecular hydantoin alkylation methodology to synthesis of halichlorine was explored.

■ Cytochrome c Oxidase Active Site Mimics: New Ligands for Copper and an Unexpected Oxidative C-C Bond Formation

Yakira R. Landaverry, Kimberly N. White, Marilyn M. Olmstead, Ólöf Einarsdóttir, and Joseph P. Konopelski*

*Department of Chemistry, University of California, Santa Cruz, CA 95064, U.S.A.

Abstract

Ligands that mimic the unusual active site polypeptide of cytochrome c oxidase have been prepared in overall good yield; structures of the corresponding Cu(II) complexes are secured by single crystal x-ray analysis. The key step in the synthesis of the ligands is the coupling of a suitable organolead(IV) phenol derivative with the ε-N of the histidine imidazole ring. In the process of preparing crystals of a tridentate ester ligand an unusual oxidative C-C bond-forming reaction occurs that affords the imidazotetrahydropyridine ring system.

■ Total Synthesis of (-)-Dihydrocorynantheol Using Bicyclo[3.2.1]octenone Chiral Building Block

Ayako Tosaka, Shinichiro Ito, Norio Miyazawa, Masatoshi Shibuya, Kunio Ogasawara,* and Yoshiharu Iwabuchi*

*Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Aobayama, Sendai 980-8578, Japan

Abstract

The diastereocontrolled synthesis of (-)-dihydrocorynantheol from a bicyclo[3.2.1]octane chiral building block has been achieved by employing a tandem retro-aldol-Pictet-Spengler reaction-C-3 epimerization sequence as the key step.

■ Synthesis of Artificial Ladder-Shaped Polyethers Containing a 6/7 cis-Fused Ring System

Kohei Torikai, Hiroshi Yari, MIchio Murata, and Tohru Oishi*

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

Abstract

Ladder-shaped tetracyclic and heptacyclic ethers containing a 6/7 cis-fused ring system have been synthesized. The synthesis features convergent coupling of monocyclic building blocks through esterification, ring-closing reaction using a low-valent titanium complex, and hydroxy dithioacetal cyclization. The double reaction strategy enabled expeditious synthesis of the heptacyclic ether in only thirteen steps from the building blocks.

■ Investigation of Vinylcyclopropane Monoradical Cyclization-Fragmentation as a Possible Route towards Eight-Membered Rings

James A. Miranda* and R. Daniel Little

*Department of Chemistry, California State University, 6000 J Street, Sacramento, CA 95819-6057, U.S.A.

Abstract

A monoradical vinylcyclopropane cyclization-fragmentation route to eight-membered rings was investigated. 6-Exo-trig cyclization was preferred over the alternative 7-endo-trig cyclization, due to entropic factors and the position of a radical stabilizing electron withdrawing group. Changing position of the electron withdrawing group was not enough to entice 7-endo-trig cyclization.

■ Synthesis of Cyclic Ether via Intramolecular Acyloin Condensation

Tatsuo Saito, Atsushi Kimishima, and Tadashi Nakata*

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

Abstract

Polycyclic ether was synthesized via intramolecular acyloin condensation and Lewis acid-promoted silane reduction.

■ A Convenient Synthesis of 2-Functionalized Pyrrolo[2,3-d]pyrido[1,2-a]pyrimidines

Yuchi Zhang, Keisuke Kawashima, and Michihiko Noguchi*

*Department of Industrial Chemistry, Faculty of Engineering, Yamaguchi University, 2-16-1 Tokiwadai, Ube, Yamaguchi 755-8611, Japan

Abstract

The thermal reaction of N-benzyl-N-{3-formyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yl}amino esters (1) provides 2-substituted pyrrolo[2.3-d]pyrido[1,2-a]pyrimidin-4(1H)-ones (2) effectively. Therein, the lactonization and consecutive decarboxylation of the initially formed methyl 2-substituted 1,2,3,4-dihydro-3-hydroxy-4-oxopyrrolo[2.3-d]pyrido[1,2-a]pyrimidine-2-carboxylates (4) is proposed for the formation of 2.