Derivatives of Titanocene

While the replacement of carbon monoxide by a tertiary phosphine ligand represents one of the most fundamental substitution reactions in metal carbonyl chemistry, it was not until 1975, some 16 years after the 

Bond Distances (A) and Angles (°) for the Group 4B Metallocene Dicarbonyls 

Complexes 41 and 42 were characterized by their IR and H-NMR spectra, and 41 also by elemental analysis. Table III contains the pertinent spectral data. Noteworthy are the very low energy terminal carbonyl bands for 41 and 42 at 1864 cm-1 (hexane). The weak 7r-accepting abilities of PR3 (R = Et, Ph) allow the lone CO ligand to 77-backbond to the Ti(II) center to a much greater degree. The -NMR spectrum of 41 exhibited a doublet (/H-p = 1.5 Hz) at 8 4.75 due to the coupling of the cyclo-pentadienyl protons with the 31P nucleus, while complex 42 exhibited a broad cyclopentadienyl singlet at 8 4.67. 

Atwood and Rogers have determined the structure of 41 via an X-ray diffraction study (50). The Ti-P and Ti-CO bond distances were found to be 2.585(1) and 2.009(4) A, respectively. An ORTEP drawing of CpTi(CO)(PEt3) (41) appears in Fig. 4. 

The thermal and photochemical reactions of Cp2Ti(CO)2 (1) with the strongly 7r-accepting phosphines PF2N(Me)PF2 and PF3 were also investigated by Rausch and Sikora (49-51). Methylaminobis(difluorophosphine), PF2N(Me)PF2, has received much attention of late in organotransition 

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The chiral complex EBTHI—Ti is an excellent chiral catalyst [40]. This complex is a derivative of titanocene and used as the Kaminsky catalyst, which has brought epoch-making progress in polypropylene production. The chiral bridged titanocene complex is used for the production of optically active polypropylene arising from the helical structure of the polymer chain. The chiral complex also behaves as an excellent... 

We have recently prepared some new and very thermolabile CO- and N2 comPlexes derived from titanocene [1] or decamethyltitanocene [2], and have characterized them by their vibrational spectra. As well as "classical" matrix spectroscopy, we have used spectroscopy in liquid xenon (LXe). The application of chemistry and methodology indicates the decamethylsilicocene structure, which represents the first example of a stable jt-complex of divalent silicon [3]. Reaction with CO or N2 leads to the two title complexes [4] ... 

Although the reaction of a titanium carbene complex with an olefin generally affords the olefin metathesis product, in certain cases the intermediate titanacyclobutane may decompose through reductive elimination to give a cyclopropane. A small amount of the cyclopropane derivative is produced by the reaction of titanocene-methylidene with isobutene or ethene in the presence of triethylamine or THF [8], In order to accelerate the reductive elimination from titanacyclobutane to form the cyclopropane, oxidation with iodine is required (Scheme 14.21) [36], The stereochemistry obtained indicates that this reaction proceeds through the formation of y-iodoalkyltitanium species 46 and 47. A subsequent intramolecular SN2 reaction produces the cyclopropane. 

The reactions of titanocene derivatives TiX(C CsCR)Cp 2 (X = C1, C= CC=CR R = SiMe3, Et) or of cis-Pt(C=CC=CR)2(PR 3)2 with mononuclear metal complexes have given numerous products in which the diynyl ligand(s) are chelated to a low-valent metal via the internal C=C fragment(s). These cis-bis(diynyl) complexes are often referred to as molecular tweezers. 

Gansauer and coworkers studied very thoroughly titanocene chloride-catalyzed radical cyclizations using epoxides as starting materials [142-145]. More recently the applicability of 10 mol% of titanocene chloride complexes 47a-d in radical 4-exo cyclizations of 6,7-epoxy-2-heptenoate derivatives 79 was demonstrated... 

Although the progress of titanocene into the clinic has been hampered by the complicated characterisation of its metabolites [17, 20], the discovery of its cytotoxic activity has triggered the search for titanocene derivatives and other metallocenes ([M(Cp)2Cl2], where M is, e.g. V, Mo) that show similar or better antineoplastic activity [23-26] whilst controlling aqueous activity [3, 20, 27]. 

Although hydrolysis may play an important role in the activation of titanocene derivatives as tumour inhibitors, few studies as yet support this postulate. 

Mokdsi G, Harding MM (1998) Water soluble, hydrolytically stable derivatives of the antitumor drug titanocene dichloride and binding studies with nucleotides. J Organomet Chem 565 29-35... 

Unfortunately, the presence of stereoisomers does not allow this class of compounds to proceed directly into clinical trials. There is hope that future synthesis using chiral bases like sparteine may allow enantioselective preparation of titanocene dichloride derivatives and not only ferrocenes [30]. Additionally, further reaction pathways leading to achiral titanocenes have to be explored. 

Allyl propargyl ethers are easily cyclized to tetrahydrofuran derivatives by titanocene- and zirconocene-mediated reactions. Thus, these compounds are convenient starting materials for the stereoselective synthesis of highly substituted 3-alkylidenetetrahydrofurans (Scheme 72) <1996TL9059>. It is noteworthy that the titanocene- and zirconocene-mediated reactions show opposite (Z)/( )-selectivities. 

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