Dimethyltitanium dichloride

The first system to be studied was 2-methyl-2-tolyl-cyclopentanone 168. In early 1979 we attempted to perform direct geminal dimethylation of this compound using dimethyltitanium dichloride 17114 in hope of obtaining curparene (Sect. F.II). Initial attempts were unsuccessful, since the product turned out to be the Grignard-type adducts 169 and 170 (Equation 57). 

Relative to tertiary alkyl halides, secondary derivatives react considerably slower. At room temperature and long reaction periods ( 24h) cyclohexyl chloride is almost quantitatively methylated with dimethyltitanium dichloride (prepared in situ from dimethylzinc and catalytic amounts of TiQ4)137>, but other cyclic or acyclic halides tend to undergo competing rearrangements prior to C—C bond formation 77). The same applies to 1,2-dihalides such as 1,2-dibromocyclohexane which affords 1,1-dimethylcyclohexane instead of the 1,2-dimethyl derivative137. In complete contrast, activated secondary chlorides behave much like tertiary derivatives, i.e., methylation is fast and position specific at low temperatures. Examples are shown in Equation 86137>. It should be noted that in such cases cuprate chemistry affords less than 40 % of methylation products138). 

Methyltitanium trichloride, CH3TiCl3 Dimethyltitanium dichloride, (CH3),TiCl2. These alkyltitanium compounds are prepared from (CHi),Zn and TiCl4. 

The direct geminal dimethylation of ketones using dimethyltitanium dichloride has provided an extremely simple synthesis of cuparene (120) from the ketone (121).77 This efficient procedure should prove useful in other sesquiterpenoid syntheses in view of the fact that the gem-dimethyl group is a common feature in a number of such compounds. A new sesquiterpene, (—)-herbertene (122), has been... 

Iwasaki, F., Maki, T., Onomura, O., Naka.shima, W Matsumura, Y. JOC65, 996 (2000). Dimethyltitanium dichloride. 

The use of titanium species in organic synthesis is increasing notably. Ketones react with dimethyltitanium dichloride under mild conditions leading directly to the corresponding geminal dimethyl-substituted compounds (Scheme 12). As the geminal dimethyl substituent occurs in many natural products, this procedure could find many applications. 

Like homopropargylic alcohols, homoallylic alcohols undergo with dimethyltitanium dichloride carbotitanation followed by elimination of titanium hydride. As a consequence of the yw-addition/syw-elimination mode, the configiuation of internal double bonds (as in 21 or 22) is inverted whereas terminal substrates (20) minimize steric repulsion and afford tra 5-3-penten-l-ols (Scheme 1-17). The optimum medium is a mixture of pentanes and the slowly evaporating dimethyl ether. Obviously the titanium species has to be coordinatively unsaturated to accomplish the critical carbometalation step. ° ... 

Scheme 1-17. Stereocontrolled homologation of homoallylic alcohols e.g., 20-22) using dimethyltitanium dichloride.

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