Titanium alkylidene

A unique approach to the requisite C-ring fragment 51 is achieved through reductive cyclization of olefinic ester 55 by way of the titanium alkylidene, as described by Rainer and Nicolaou [59]. The olefinic ester 55 is prepared in ten steps from (R)-isobutyl lactate using consecutive chelation-controlled... 

The reactions of titanium-alkylidenes prepared from thioacetals with unsymmetrical olefins generally produce complex mixtures of olefins. This complexity arises, at least in part, from the concomitant formation of the two isomeric titanacyclobutane intermediates. However, the regiochemistry of the titanacyclobutane formation is controlled when an olefin bearing a specific substituent is employed. Reactions of titanocene-alkylidenes generated from thioacetals with trialkylallylsilanes 30 afford y-substituted allylsilanes 31, along with small amounts of homoallylsilanes 32 (Scheme 14.16) [28]. 

The expected intermediate for the metathesis reaction of a metal alkylidene complex and an alkene is a metallacyclobutane complex. Grubbs studied titanium complexes and he found that biscyclopentadienyl-titanium complexes are active as metathesis catalysts, the stable resting state of the catalyst is a titanacyclobutane, rather than a titanium alkylidene complex [15], A variety of metathesis reactions are catalysed by the complex shown in Figure 16.8, although the activity is moderate. Kinetic and labelling studies were used to demonstrate that this reaction proceeds through the carbene intermediate. 

Basuli, F., Bailey, B.C., Tomaszewski, J., Huffman, J.C. and Mindiola, D.J. (2003) A terminal and four-coordinate titanium alkylidene prepared by oxidatively induced a-hydrogen abstraction. J. Am. Chem. Soc., 125, 6052. 

The metallacycle formed according to scheme (11) is in equilibrium with a small (unobservable) amount of titanium alkylidene complex formed by the opening of the titanacycle ring the alkylidene complex is then trapped by norbornene to give a new titanacycle, and thus the polymer chain is propagated [49] ... 

A plausible intermediate of this olefination is the titanium-methylene sjtecies 4, which is formed from 1 by removal of AlMe2Cl with a Lewis base, from 2 by fragmentation with elimination of isobutene, and from 3 by a-elimination and release of methane. However, none of these three routes to titanium-carbene complexes of type 4 proved to be generally applicable. Consequently, the use of these reagents in synthesis is essentially limited to the transfer of a methylene unit 18]. From a synthetic viewpoint, a general and easy route to substituted titanium-alkylidene species and their use in carbonyl olefinations would be more desirable. 

The first progress was made by Takai and Lombardo, who developed an in situ entry to titanium-alkylidene chemistry starting from the reagent combinations 5 and 6 (Scheme 4) [9]. These reactions proceed via a gem-dizinc compound 7 (its formation is catalyzed by traces of lead or lead(II) salts), which is subsequently transmetalated with TiCl4 to the titanium-alkylidene species 8, the actual olefination reagent. To date, 8 has not been characterized in detail [10]. These in situ reagents exhibit chemoselectivities similar to those of the structurally defined methylenation reagents 1-3. 

The solution to the above problem was recently found by Takeda et al., who reported on the desulfurization of dithioacetals as a general and easy entry to titanium-alkylidene chemistry [13]. Dithioacetals, which are easily accessible from carbonyl compounds, are treated with the titanocene source [Cp2Ti P(OMe)3 2] (11),... 

Scheme 6. Carbonyl olefination with titanium-alkylidene species 12 prepared from dithioacetals according to Takeda et al.

Interestingly, the subsequent reactions of the titanium-alkylidene species 12 obtained from dithioacetals are not limited to carbonyl olefina-tions. When the carbene complex is prepared in the presence of olefins, the latter are smoothly cyclopropanated (Scheme 8 13) [14]. Furthermore, the reaction of symmetrically disubstituted acetylenes with dithioacetals containing a methylene unit provides the corresponding trisubsti-tuted 1,3-dienes 14 in a stereoselective fashion 115]. 

Scheme 8. Reactions of the titanium-alkylidene species 12, prepared from dithioacetals, with olefins and acetylenes.

The synthesis of capnellene discussed earlier is an interesting example in which (3) was used to generate a new titanium alkylidene which then underwent an intramolecular reaction with an ester carbonyl. The process effectively involved carbonyl alkylidenation by a substituted titanium alkylidene (equation 14). In this case steric factors apparently account for the desired reaction selectivity. ... 

Breit, B. Dithioacetals as an entry to titanium-alkylidene chemistry a new and efficient carbonyl olefination. Angew. Chem., Int. Ed. Engl. 1998, 37, 453-456. 

The reduction of Cp2TiCl2 with Mg in the presence of P(OEt)3 affords the titanium(n) complex Cp2Ti[P(OEt)3]2 which was used as a catalyst for the carbonyl olefination of thioacetals through a titanium-alkylidene intermediate (see Section 4.05.4.2.4 alkylidene complexes).1148... 

Additional improvements in preparations of polyacetylene came from several developments. One is the use of metathesis polymerization of cyclooctatetraene, catalyzed by a titanium alkylidene complex. The product has improved conductivity, though it is still intractable and unstable. By attaching substituents it is possible to form soluble and more stable materials that can be deposited from solution on various substrates. Substitution, however, lowers the conductivity. This is attributed to steric factors introduced by the substituents that force the double bonds in the polymeric chains to twist out of coplanarity." Recently, a new family of substituted polyacetylenes was described. These polymers form from ethynylpyridines as well as from ethynyldipyridines. The polymerization reaction takes place spontaneously by a quatemization process ... 

The temperature-independence of the shifts and the small ratio of the observed isotope splitting to the estimated shift difference (100 ppm) between the averaged C-1/C-2 carbons in a titanium-alkylidene-olehn structure [36] were interpreted as being consistent with a symmetrical but easily distorted titanacyclobutane structure [35] resting at the minimum of a broad shallow potential energy surface which allows easy distortion towards a transition state for the metathesis reaction. 

Alkylidenation Several attempts have been made to prepare titanium alkylidene complex 17. The reaction of titanocene dichloride with triethylaluminum does not afford an alkylidene-bridged complex similar to the Tebbe reagent, probably due to the presence of a jS-hydrogen, and produces instead the aluminotitanium hydride... 

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