Preparation of Titanocene-Methylidene

An improved procedure for the preparation of the Tebbe reagent 3 and the in situ preparation of 3 for large-scale reactions has been developed, requiring neither vacuum line nor Schlenk techniques [9] the crude reaction mixture formed by the combination of titanocene dichloride and two equivalents of trimethylaluminum can be employed for further reactions [10]. 

Methylenation of carboxylic acid derivatives The Tebbe reagent 3 is extremely valuable as a reagent for the methylenation of carboxylic acid derivatives, which is generally unsuccessful using phosphorus ylides. Esters and lactones are readily transformed into enol ethers (Table 4.3), especially when a Lewis base such as THE is present in the reaction mixture. In the methylenation of a,j8-unsaturated esters, the internal olefin is not involved in the reaction, and the configuration of the double bond is maintained (entry 4). When carbonyl compounds bearing a terminal double bond are subjected to the methylenation, significantly lower yields are observed (entries 6 and 11), which may be attributable to competitive formation of a titanacycle from titanocene-methylidene 4 and the terminal olefin. 

Similar methylenation of amides, imides, and thiol esters produces the corresponding heteroatom-substituted olefins (Table 4.4). Since the olefination of imides is greatly affected by steric hindrance, an unsymmetrical imide is monomethyl-enated at the sterically less hindered carbonyl group when treated with 3 (entry 3). The low basicity of 3 allows the transformation of a thiol ester to the corresponding alkenyl sulfide without racemization (entry 4). 

As the representative examples in Table 4.5 indicate, the titanocene-methylidene precursors 11 transform various carbonyl compounds, including imides [30], in yields comparable to those obtained with the Tebbe reagent 3. Kinetic studies indicate that the reaction of 11 with carbonyl compounds proceeds via the titanium carbene 4 [llbj. 

3 Zinc and Magnesium Analogues oTthe Tebbe Reagent 

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As noted in the previous section, one drawback of the Tebbe reagent 3 is that an acidic aluminum compound is produced when it is converted into titanocene-methylidene 4. The instabUity of 3 toward air and water necessitates special techniques for its preparation and is also an obstacle to its use in organic synthesis. In this sense, dimethyltitanocene 30 is a convenient precursor for the preparation of titanocene-methylidene 4 (Scheme 4.22). 

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