Titanocene chloride

Substitution of the Cp ligands reduces the tendency to dimerize. Introduction of a cyclohexyl group is sufficient for rendering the monomer the only detectable species by CV. The substituted titanocene chlorides open epoxides slower than Cp2TiCl . However, the resulting /J-metaloxy radicals are more... 

Scheme 12.6. Synthesis of enantiomerically pure allylic alcohols with titanocene chloride.

The major obstacle to this approach is that there are few reagents capable of generating higher homologues of titanocene-methylidene. Although the procedure is not straightforward, the titanacycle 21 formed by the addition of diisobutylaluminum hydride to the double bond of (l-propenyl)titanocene chloride 22 serves as a titanocene-propylidene 23 equivalent in carbonyl olefmation (Scheme 14.12) [22]. 

Zrrconium(IV) and hafnium(IV) complexes have also been employed as catalysts for the epoxidation of olefins. The general trend is that with TBHP as oxidant, lower yields of the epoxides are obtained compared to titanium(IV) catalyst and therefore these catalysts will not be discussed iu detail. For example, zirconium(IV) alkoxide catalyzes the epoxidation of cyclohexene with TBHP yielding less than 10% of cyclohexene oxide but 60% of (fert-butylperoxo)cyclohexene °. The zirconium and hafnium alkoxides iu combiuatiou with dicyclohexyltartramide and TBHP have been reported by Yamaguchi and coworkers to catalyze the asymmetric epoxidation of homoallylic alcohols . The most active one was the zirconium catalyst (equation 43), giving the corresponding epoxides in yields of 4-38% and enantiomeric excesses of <5-77%. This catalyst showed the same sense of asymmetric induction as titanium. Also, polymer-attached zirconocene and hafnocene chlorides (polymer-Cp2MCl2, polymer-CpMCls M = Zr, Hf) have been developed and investigated for their catalytic activity in the epoxidation of cyclohexene with TBHP as oxidant, which turned out to be lower than that of the immobilized titanocene chlorides . ... 

Eisch and Piotrowski reported the preparation of gem-dizinc compounds from diiodomethane and zinc powder in the titanocene chloride mediated methylenation of ketones in 1983 (equation 5)7. In this case, it was not mentioned that they had used pyrometallurgy zinc. The Tebbe-type reagent 2 was shown as an intermediary species. Before addition of titanocene chloride, the amount of methane was measured after hydrolysis of the reaction mixture to determine the formation of gem-dizinc species7. 

Since the introduction of the titanocene chloride dimer 67a to radical chemistry, much attention has been paid to render these reactions catalytic. This field was reviewed especially thoroughly for epoxides as substrates [123, 124, 142-145] so only catalyzed reactions using non-epoxide precursors and a few very recent examples of titanium-catalyzed epoxide-based cyclization reactions, which illustrate the principle, will be discussed here. A very useful feature of these reactions is that their rate constants were determined very recently [146], The reductive catalytic radical generation using 67a is not limited to epoxides. Oxetanes can also act as suitable precursors as demonstrated by pinacol couplings and reductive dimerizations [147]. Moreover, 5 mol% of 67a can serve as a catalyst for the 1,4-reduction of a, p-un saturated carbonyl compounds to ketones using zinc in the presence of triethylamine hydrochloride to regenerate the catalyst [148]. 

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... 

Fig. 22 Hirao s titanocene chloride-catalyzed radical cyclizations...

Radical cyclizations catalyzed by 67a require the regeneration of the titanocene catalysts by a stoichiometric reductant, such as manganese. When 10 mol% of substituted cyclopentadienyltitanium complex 47e is applied instead truly catalytic cyclization sequences of epoxides 86 are possible (Fig. 25) [160]. Reductive radical generation from 86 promoted by titanocene chloride 67e and subsequent 5-exo cyclization of radical 86A generates a titanoxy cyclopentylalkyl radical 86B. Since the electron-poor titanocene chloride 67e reduces the tertiary radical 86B only sluggishly, its extended lifetime allows for a 1,5-SHi affording the bicyclic tetrahy-drofuran ring system 87. At the same time catalyst 67e is liberated. The reaction... 

Allyltitanocenes. Alkenyl chlorides, ethers, and carboxylic esters are homologated with CpjTiClj- MejAl to furnish allylic titanocene chlorides which can be used to react with carbonyl compounds. 

Aldols from a-haloketones. The Reformatsky-type reaction is readily effected at room temperature with the assistance of titanocene chloride, which is generated from Cp2TiCl2 and manganese in THF. Aromatic aldehydes are not suitable for the reaction as they tend to undergo pinacol coupling under the reaction conditions. 

The combination of Sm with titanocene chloride in t-butanol constitutes a very effective reducing system for organic azides. ... 

It has been reported recently that organotitanium compounds prepared conveniently from the corresponding Grignard reagents and titanocene chloride cyclize with an appropriately positioned internal alkene in the presence of ethylaluminium chloride (equation 119) ... 

Tebbe s reagent 8.188 is a nucleophilic carbene (Scheme 8.53). It is made by treatment of titanocene chloride with trimethyl aluminium to give a chloro-bridged complex 8.187. The reagent is released in the presence of a Lewis base, such as pyridine or DMAP, which will coordinate the aluminium. Even THE can function as an effective Lewis base. 

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