行政院國家科學委員會專題研究計畫 期中進度報告
金屬有機化合物的應用(1/3)
計畫類別： 個別型計畫 計畫編號： NSC91-2113-M-002-043- 執行期間： 91 年 08 月 01 日至 92 年 07 月 31 日 執行單位： 國立臺灣大學化學系暨研究所 計畫主持人： 林英智 報告類型： 精簡報告 報告附件： 出席國際會議研究心得報告及發表論文 處理方式： 本計畫可公開查詢中 華 民 國 92 年 5 月 23 日
行政院國家科學委員會補助專題研究計畫
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金屬有機化合物的應用(1/3)
計畫類別：■ 個別型計畫 □ 整合型計畫
計畫編號：NSC91－2113－M－002－043－
執行期間： 91 年 8 月 1 日至 92 年 7 月 31 日
計畫主持人：林英智
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(二)中、英文摘要及關鍵詞(keywords)。
Abstract
This is the first mid term report for a three year project. We study the reactions of ruthenium azide (Part I) and acetylide (Part II) complexes. Previously we developed preparation of new ruthenium cyclopropenyl complexes by deprotonation of vinylidene complexes and we found a new acetylide migration and oxygen transfer reactions in ruthenium complexes containing an acetyl-substituted Cp ligand. In this report synthesis of novel ruthenium complexes with new hypervalent sulfur thiotetraazapentalenedithione ligands was readily achieved when ruthenium azide was reacted with alkyl isothiocyanate. Formation of the ligands involves three consecutive [3+2] cycloadditions mediated by the presence of Ru moiety. Reactions of ruthenium acetylide complexes with organic isothiocyanate yield a number of interesting organometallic compounds containing heterocyclic ligand with sulfur and nitrogen atoms. Subsequent alkylation at the thione sulfur of the ligand by CH2Cl2 takes place giving the new
six-membered-ring [1,3]-oxazin-2-one complex. A second alkylation at the same sulfur atom affords binuclear complex with heterocyclic six-membered ring ligands. Structures of several complexes have been determined by single-crystal X-ray diffraction analysis. 摘要 本期中報告報導釕金屬疊氮化合物以及釕金屬炔基化合物的兩個反應。以往 曾報導金屬丙二烯的脫氫反應生成環丙烯化合物，在具有-COMe 基的茂基我 們發現新的氧原子的遷移反應。釕金屬疊氮化合物與 RCH2N=C=S 的反應生 成一系列的新型有機金屬含硫與氮雙五環配位基化合物。此配位基是藉由釕 金屬的協助，以三次連續的[3+2]環加成反應而形成的。釕金屬炔基與另外的 RN=C=S 也進行一系列的環化反應，形成四環或六環的雜環化合物，六環上 的硫酮基會與二氯甲烷進行兩次烷化反應，可以形成為雙核的化合物。這些 反應的主要產物均使用單晶繞射的方法確定其固態結構。
Key words: Ruthenium, acetylide, thiotetraazapentalenedithione, heterocycles, 鑰字：釕，金屬炔基，硫四氮并環戊二烯，含氮與硫之雜環
(三)報告內容：請包括前言、研究目的、文獻探討、研究方法、結果與討 論（含結論與建議）…等。若該計畫已有論文發表者，可以 A4 紙影印， 作為成果報告內容或附錄，並請註明發表刊物名稱、卷期及出版日期。若 有與執行本計畫相關之著作、專利、技術報告、或學生畢業論文等，請在 參考文獻內註明之，俾可供進一步查考。 Part I.
Novel Thiotetraazapentalene Complexes from the Reaction of Ruthenium Azide Complex with Alkyl Isothiocyanates
The chemistry of isothiocyanates has burgeoned over the years. The attraction of isothio- cyanates as synthons is noticeably due to their diverse reactions and also due to their easy availability.1 In addition, isothiocyanates are potent and selective inhibitors of carcinogenesis induced by a variety of chemical carcinogens.2-6 Chemopreventative actions of isothiocyanates have been actively investigated.
Reactions of the ruthenium azide complex 1 with alkyl isothiocyanates RCH2NCS
give the cationic dinuclear ruthenium complex {[Ru]-NCS-[Ru]}NCS containing a bridging NCS ligand as the major product and the novel hypervalent sulfur thiotetraazapentalenedithione ruthenium complexes 3 as the minor product.7,8 The ligand, bound to the metal through the S atom, is formed from three isothiocyanate molecules and a nitrogen atom from azide. Formation of the ligands involves three consecutive [3+2] cycloadditions mediated by the presence of Ru moiety. Structural characterization of another minor product 4 isolated from the reaction mixture reveal the mechanism for the formation of the product. The X-ray structural characterization of the thiotetraazapentalene ruthenium complex is also described. As depicted in Scheme 1 (attached at the end of this report), the reaction begins with formation of the thiotetrazolate A from 1 and an isothiocyanate molecule followed by loss of a dinitrogen molecule and migration of metal from nitrogen to sulfur giving B. The major product 2 could then be derived from B. For the reaction of 1 with aryl isothiocyanate, the major product 6 could possibly be formed by loss of an aryl azide from A. This is attributed to the moderately more stable aryl azide relative to the corresponding alkyl azide. Formation of the structurally characterized S-metalated isothiourea complex 4 could be reasonably derived from hydrolysis of B as a minor product. Complex B further undergoes a second [3+2] cycloaddition9 to give C. The final product 3a is then produced by a third [3+2] cycloaddition.
References
(1) (a) Chang, C. W. J. Prog. Chem. Org. Nat. Prod., 2000, 80, 1. (b) Hartmann, A.
Methoden Org. Chem. Houben-Weyl, 1983, E4, 834.
(2) Goosen, T. C.; Kent, U. M.; Brand, L.; Hollenberg, P. F. Chem. Res. Toxicol. 2000,
13, 1349.
(3) Hecht, S. S. J. Cell. Biochem. 1995, 22, 195.
(4) Conaway, C. C.; Yang, Y.-M.; Chung, F.-L. Curr. Drug Metabolism, 2002, 3, 233. (5) Morse, M. A., Eklind, K. I., Hecht, S. S., Jordan, K. G., Choi, C.- I., Dasai, D. H.,
Amin, S. G., and Chung, F.-L. Cancer Res., 1991, 51, 1846. (6) Thornalley, P. J. Anti-Cancer Drugs, 2002, 13, 331.
(7) (a) Matsumura, N.; Tomura, M.; Tsuchiya, Y.; Yoneda, S.; Nakamura, M. Chem.
Express, 1986, 1, 487. (b) Lai, L.-L.; Reid, D. H., Heteroat. Chem., 1997, 8, 13.
(8) Iwasaki, F.; Yasui, M.; Yoshida, S.; Nishiyama, H.; Shimamoto, S.; Matsumura, N.,
Bull. Chem. Soc. Jpn., 1996, 69, 2759.
(9) L’abbé, G.; Verhelst, G.; Toppet, S. J. Org. Chem. 1977, 42, 1159.
Part II.
Reactions of Ruthenium Acetylide Complexes with EtO2CNCS: Alkylation of the
Thione with Dicholoromethane
The coordinated acetylide ligand is reactive toward electrophiles, undergoing either alkylation or protonation at C to give stable vinylidene complexes. Cycloaddition of metal acetylide with isocyanates takes place in several Ni(0) complexes.10 The other common reaction observed for the acetylide is the [2+2] cycloaddition of the triple bond with unsaturated organic substrates.11 We carry out the reactions of ruthenium acetylide complexes with EtOCONCS, a more reactive isothiocyanate. As expected, in the initial stage, two consecutive cycloadditions of isothiocyanate to the acetylide give the anticipated complexes with 2-imino-[1,3]- thiazine-4-thione ligands. However, for the product with a bidentate dppe ligand, hydrolysis of the ethoxycarbonyl group presented in the six-membered ring followed by an unusual two-step alkylation with CH2Cl2 at the thione group causes the product to transform
to a new methylene bridged dithio six-membered-ring oxo-oxazin complex.
Treatment of ruthenium acetylide complexes Cp(L)(L')RuCCPh (6a, LL' = Ph2PCH2CH2PPh2; 6b, L = PPh3, L' = P(OMe)3) with 1.1 equivalent of EtO2CN=C=S
results in a [2 + 2] cycloaddition yielding the four-membered-ring 2-imino-thiete products Cp(L)(L')Ru-C=C(Ph)C(=NCO2Et)S (7a, LL' = dppe; 7b, L = PPh3, L' =
P(OMe)3). Complexes 7a and 7b react with a 5 fold excess of EtO2CNCS to afford
the heterocyclic six-membered-ring 2-imino-[1,3]-thiazine-4-thione complexes Cp(L)(L')Ru-C=C(Ph)C(=S)N(CO2Et)C(=NCO2Et)S (8). Alkylation of complex 8a
in the presence of EtO2CNCS by CH2Cl2 takes place at the thione sulfur accompanied
with loss of an isothiocyanate molecule giving the new six-membered-ring [1,3]-oxazin-2-one complex Cp(dppe)Ru-C=C(Ph)C(SCH2Cl)NC(=O)O (9a). In
acetone complex 9a undergoes a second alkylation possibly accompanied with loss of CH2Cl2 to afford a binuclear complex with two heterocyclic six-membered rings,
[Cp(dppe)Ru-C=C(Ph)C(S-)NC(=O)O]2CH2 (10a) see Scheme 2 below. Structures
of 7b, 9a and 10a have been determined by single-crystal X-ray diffraction analysis. Ligand-based reactivity of metal-coordinated thiolates has been known in the literature and alkylation, metalation, oxygenation, and adduct formation have all been recognized.12 The strength of the coordinated thiolate’s nucleophilicity was established by the fact that even weak electrophiles, such as CH2Cl2, are prone to
attack. References
(10). Hoberg, H.; Oster, B. W. J. Organomet. Chem. 1983, 252, 359.
(11). Bruce, M. I.; Hambley, T. W.; Leddell, M. J.; Snow, M. R.; Swincer, A. G.; Tiekink, R. T. Organometallics 1990, 9, 96.
(12) (a) Constable, E. C. Metals and Ligand Reactivity: An Introduction to the
Organic Chemistry of Metal Complexes, 2nd ed.; VCH: Weinheim, Germany,
1996. (b) Musie, G.; Reibenspies, J. H.; Darensbourg, M. Y. Inorg. Chem. 1998,
37, 302. (c) Grapperhaus, C. A.; Darensbourg, M. Y. Acc. Chem. Res. 1998, 31,
451. (d) Darensbourg, M. Y.; Tuntulani, T.; Reibenspies, J. H. Inorg. Chem.
1995, 34, 6287. (e) Lyon, E. J.; Musie, G.; Reibenspies, J. H.; Darensbourg, M.
(五)附表及附圖
Scheme 1 illustrates the mechanism on the reactions of part I of this report.
N N C N N [Ru] S R - N2 metal S N N [Ru] S N R R N C N S R [Ru] N S N N N [Ru] S S R R R N S N S N NH S R R HN C NH S R [Ru] S S N N N [Ru] S N R R R migration R RCH2NCS RCH2NCS 5 4 3 RCH2NCS A B C [Ru] N3 1 Scheme 1
Ph S N Ph S N CO2Et CO2Et Ph O N SCH2Cl O S Ph N CO2Et [Ru] [Ru] [Ru] Ph O N S O [Ru] Ph O N S O [Ru] [Ru] [Ru] = (C5H5)LL'Ru EtO2CNCS EtO2CNCS 9a, LL' = dppe 6a, LL' = dppe 6b, L = PPh3, L' = P(OMe)3 Scheme 2 10a, LL' = dppe 7a, LL' = dppe 7b, L = PPh3, L' = P(OMe)3 8a, LL' = dppe 8b, L = PPh3, L' = P(OMe)3 3
(六)計畫成果自評部份，請就研究內容與原計畫相符程度、達成預期目標 情況、研究成果之學術或應用價值、是否適合在學術期刊發表或申請專 利、主要發現或其他有關價值等，作一綜合評估。
On the basis of our previous findings we anticipate that new products should be obtained from the reaction of isothiocyanate with ruthenium acetylide and azide complexes. In the reaction of these ruthenium complexes with isothiocyanate we do observed new reactivity. Some of these new products will be tested for biological activity. Novelty of these reactions deserves publication in scientific journal. This report is taken in part from two manuscripts. And manuscripts describing results of Part I and II are currently submitted to Organometallics to be considered as a communication and full paper, respectively. MANUSCRIPT NUMBER: OM0303101 and OM030341W.
