Thorsten Lauterbach

Unlikeliness of Pd-free gold(I)-catalyzed Sonogashira coupling reactions.

The Sonogashira coupling reaction is not catalyzed by AuI/dppe in the absence of Pd complexes. However, addition of 0.1 mol % of Pd(0) led to efficient cross-coupling reactions. The most plausible catalytic cycles for the Au-catalyzed cross-coupling reactions have been examined and are unlikely in the absence of Pd contamination.

A Catalytic Enantioselective Electron Transfer Reaction: Titanocene-Catalyzed Enantioselective Formation of Radicals from meso-Epoxides.

A rationally designed titanium(III) catalyst allows the opening of epoxides with high enantioselectivity. This reaction [Eq. (1)] constitutes the first example of an enantioselective transition metal catalyzed radical reaction that proceeds by electron transfer.

Titanocene-Catalysed Enantioselective Opening ofmeso-Epoxides

A comparison of different titanium catalysts in the enantioselective opening of meso-epoxides has been carried out. The best catalyst is readily available in both enantiomers from menthol and allows for a highly enantioselective reaction.

Eine katalytische enantioselektive Elektronentransfer-Reaktion: Titanocen-katalysierte enantioselektive Bildung von Radikalen ausmeso-Epoxiden

Ein rational entworfener Titan(III)-Katalysator ermoglicht die Ringoffnung von Epoxiden mit hoher Enantioselektivitat. Diese Reaktion [Gl. (1)] stellt das erste Beispiel einer hochenantioselektiven Metall-katalysierten Radikalreaktion durch Elektronentransfer dar.

Carbonyl-Substituted Titanocenes: A Novel Class of Cytostatic Compounds with High Antitumor and Antileukemic Activity

The outstanding success of cisplatin [cis-Pt ACHTUNGTRENNUNG(NH3)2Cl2], one of the most broadly used chemotherapeutic agents, has sparked tremendous interest in the development of related metal compounds with similar properties. Currently, complexes of platinum, iron, ruthenium and titanium are in the center of attention. Of the titanium compounds derivatives of titanocene dichloride [Cp2TiCl2] have emerged as the most promising candidates for further investigations. However, the progress of this fascinating field of research has been severely hampered by the lack of a general approach to structurally and functionally diverse complexes. Thus, the highly desirable screening of wide regions of chemical space could not be realized. Recently, we have described the first modular approach to exactly these compounds, that relies on the use of titanocenes with pending carboxylic acid chlorides. In this manner oxygen and nitrogen nucleophiles could be acylated to yield a large number of structurally and functionally diverse titanocene complexes possessing ester and amide functionality. Besides the possibility to vary the nucleophile another crucial issue for the biological activity of the titanocenes can be addressed. Due to coordination of the carbonyl group, the amide complexes are soluble and stable in water or DMSO. Here, we report on the first synthesis of ketonesubstituted titanocenes and the activity of our complexes against a variety of malignant cells. As in the case of the amides our synthetic targets were cationic and water soluble complexes. However, ketones are noticeably weaker ligands than amides. Thus, we looked for a synthetic sequence that allows the conversion of the carboxylic acid chloride to electron-rich ketones as well as the abstraction of one chloride ligand of titanium. Thus, a general access to a large number of cationic complexes can be envisioned. All complexes discussed here were obtained as racemates, only one enantiomer is shown. Friedel–Crafts acylations of donor-substituted arenes in the presence of ZnCl2 emerged as especially well-suited for our purposes. The desired complexes could be isolated in satisfactory to high yields as the tetrachloro zincates (Table 1). An example of the coordination of the ketone at the cationic titanium center is depicted in Figure 1. In addition to the variation of the aryl substituents and the straightforward modification of the gem-dialkyl group attached to the upper cyclopentadienyl ligand our synthesis of the carboxylates allows the alteration of the distance of the keto group from this ligand and the introduction of the substituents at the lower cyclopentadienyl ligand. A single additional methylene group prevents coordination of the ketone in 2 f as the result of the highly unfavorable formation of a strained ring. The structural modifications (Table 1, Scheme 1) should be essential for the biological activity of the complexes for three reasons. First, the polarity of the compounds can be tailored. Second, the electronic and steric properties of all substituents will have an influence on the exact coordination geometry of titanium. Third, the overall three-dimensional shape of the titanocenes can be varied in a straightforward manner. This can turn out to be crucial regarding the binding ability to enzymes and receptors. To understand the biological activity of our titanocenes, we investigated a broad spectrum of both solid tumors and leukemia cell lines. These include BJAB cells (lymphoma), [a] Prof. Dr. A. Gans;uer, I. Winkler, D. Worgull, Dr. T. Lauterbach, Dr. D. Franke Kekul?-Institut f@r Organische Chemie und Biochemie Universit;t Bonn, Gerhard-Domagk-Str. 1 53121 Bonn (Germany) Fax: (+49)228-734760 E-mail : andreas.gansaeuer@uni-bonn.de [b] A. Selig, L. Wagner, Dr. A. Prokop Department of Pediatric Oncology/Hematology University Medical Center Charit? Berlin, 13353 Berlin (Germany) Fax: (+49)450-559999 E-mail : aram.prokop@charite.de Supporting information for this article is available on the WWW under http://www.chemistry.org or from the author.