Titanocene derivatives

The best results were obtained with the Brintzinger indenyl zirconene and titanocene derivatives [(EBTHI)MX2], developed earlier for the stereocontrolled po-... 

Early transition-metal complexes have been some of the first well-defined catalyst precursors used in the homogeneous hydrogenation of alkenes. Of the various systems developed, the biscyclopentadienyl Group IV metal complexes are probably the most effective, especially those based on Ti. The most recent development in this field has shown that enantiomerically pure ansa zirconene and titanocene derivatives are highly effective enantioselective hydrogenation catalysts for alkenes, imines, and enamines (up to 99% ee in all cases), whilst in some cases TON of up to 1000 have been achieved. 

Whilst hydrogenation catalysts based on early transition metals are as active and selective as those based on late transition metals, they are usually not as compatible with functional groups, and this represents the major difficulty for their use in organic synthesis. Nonetheless, titanocene derivatives have been used in industry to hydrogenate unsaturated polymers. 

In addition to phosphine ligands, a variety of other monodentate and chelating ligands have been introduced to functionalized polymers [1-5]. For example, cyclo-pentadiene was immobilized to Merrifield resins to obtain titanocene complexes (Fig. 42.13) [102]. The immobilization of anionic cyclopentadiene ligands represents a transition between chemisorption and the presently discussed coordinative attachment of ligands. The depicted immobilization method can also be adopted for other metallocenes. The titanocene derivatives are mostly known for their high hydrogenation and isomerization activity (see also Section 42.3.6.1) [103]. 

Several titanocene derivatives containing silsesquioxane ligands have also been prepared and characterized. It soon turned out that reactions of 3 or its mono-silylated derivative 12 with titanocene dihalides are not straightforward and usually lead to the formation of product mixtures. A common feature appears to be the formation of p-oxo species despite the use of carefully dried solvents. Although at this stage the occurrence of partial hydrolysis cannot completely be ruled out, we... 

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. 

Titanocene derivatives undergo substitution reactions at the mclal atom ... 

Titanocene dichloride (8) is readily reduced to the [(ir-C5H5)2Ti(III)]+ species which in turn can be converted into alkyl and hydrido derivatives (18-20). These titanocene derivatives have been found to be active catalysts in the low-pressure polymerization of ethylene (21, 22) and the... 

The titanocene derivative 85 condensed with benzene-iV,iV-dichlorosulfonamide to afford iV-phenylsulfonyl-1,3,2-dithiazole 86 (Equation 25) <1998JA352>. 

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. 

Fig. 14 The five most cytotoxic titanocene derivatives synthesised from fulvenes...

H. Schnutenhaus, and H. H. Brintzinger, 1, r-Trimethylene-bis(r 5-3-/t>/-/-butylcyclo-pentadienyl)titanium(IV) Dichloride, a Chiral mwa-Titanocene Derivative, Angew. Chem. Int. Ed. Engl. 18, 777-778 (1979). 

F. R. W. P. Wild, L. Zsolnai, G. Huttner, and H. H. Brintzinger, Synthesis and Molecular Structures of Chiral ausa-Titanocene Derivatives with Bridged Tetrahydroin-denyl Ligands, J. Organomet. Chem. 232, 233-247 (1982). 

Fridkin et al. made use of the possibility of bringing about an effective site isolation in resin-bound substrates, a situation approaching infinite dilution of reactants, to effect an intramolecular peptide eyclization for the synthesis of cyclic peptides (see sect. 3.4) 109 110). Several other attempts have been made to exploit the phenomenon of diminished site-site interactions in polymeric matrices relative to those in solutions the results are often difficult to interpret or contradictingly interpretted137). The titanocene derivative 19 which is bound to 20% cross-linked polystyrene shows catalytic activity, whereas its solution counter part dimerizes to the catalytically inactive 20 138). 

Scheme 11 Titanocene derivatives as catalysts in PK-type reactions...

On the other hand, the transition metal-catalyzed isomerization of terminal olefins into internal olefins has been extensively studied, and in general a mixture of 1-alkenes and E- and Z-2-alkenes, reflecting the thermodynamic equilibrium, is obtained [67]. Some low-valent titanocene derivatives are highly effective and stereoselective in favor of the E-2 isomer [68]. When non-conjugated dienes such as 92, containing one or two substituted vinyl groups, are treated with the zirconocene 21, a regioisomerization of the less-substituted... 

TiCl3(THF)3] cat., Zn, TMSCl, t-BuOH [10], or [Cp2Ti(Ph)Cl] cat., Zn, chlorosilane [11]. The use of Cp2TiCl2 in this context deserves particular emphasis, because titanium sources of this type open up new vistas for stereocontrol if ansfl-titanocene derivatives are used to transfer chiral information from the ligand to the diol [12]. 

C4Me4P)2ZrCl2] can be reduced by magnesium in THF and further with 2-butyne to yield the zirconacyclopentadiene 181 <20020M259>. Zirconacyclopentadiene 182 has been prepared as an intermediate in the reaction of bis(l-phenylboratabenzene)bis(trimethylphosphine) zirconium(ll) with acetylene <1997AGE2014>. A similar reaction has been noted for a titanocene derivative <1998ZFA919>. 

CpTiCls is conveniently prepared by treatment of TiCLi with CpSiMes (eqnation 23)7 The synthesis and reactivity bis(cyclopentadienyl)titanium throngh the mid- 90s has been extensively reviewed by Bechaus np7 The synthesis of chiral titanocene derivatives has been reviewed by Halterman. ... 

Other Reactions of Chiral Titanocene Derivatives. Buch-wald has recently reported the catalytic asymmetric hydrogenation of imines and unfunctionalized alkenes using chiral titanocene catalysts. 

Chiral titanocene derivatives can also be used as catalysts in asymmetric Diels-Alder reactions (Sch. 56 and 57). Collins reported that the asymmetric Diels-Alder reaction of oxazolidine derivatives and cyclopentadiene was effectively catalyzed by... 

The PMR spectra of certain related titanocene derivatives have been similarly studied and analyzed for transmission effects. For the para-substituted diaryltitanocenes (VIII), 21% of the effect from the substituent was estimated to be transmitted through the metal atom to the cyclo-pentadienyl ring (3, 11). It is interesting that this value is higher than that obtained for the arylferrocenes (14%). This is not, however, unexpected since the aryl group of titanocene is directly bonded to the metal. 

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