Titanocene dimethyl

Two groups of workers have studied the reaction of p-lactams with dimethyl titanocene to give 2-methyleneazetidines <00TL1975, 00TL5607>. Reduction of P-lactams with chloroalane gave azetidines in high yield <99JOC9596>. 

Tandem carbonyl olefmation—olefm metathesis utilizing the Tebbe reagent or dimethyl-titanocene is employed for the direct conversion of olefmic esters to six- and seven-mem-bered cyclic enol ethers. Titanocene-methylidene initially reacts with the ester carbonyl of 11 to form the vinyl ether 12. The ensuing productive olefm metathesis between titano-cene methylidene and the cis-1,2 -disubstituted double bond in the same molecule produces the alkylidene-titanocene 13. Ring-closing olefin metathesis (RCM) of the latter affords the cyclic vinyl ether 14 (Scheme 14.8) [18]. This sequence of reactions is useful for the construction of the complex cyclic polyether frameworks of maitotoxin [19]. 

Table 3.8. Examples of methylenations with the Tebbe reagent and with dimethyl titanocene.

The Petasis reagent, dimethyl titanocene (4.93) can also be used for the methylenation of carbonyl compounds. The Petasis reagent (4.93) is prepared by the reaction of methyl magnesium chloride or methyllithium with titanocene dichloride (Cp2TiCl2). Carbonyl compounds on heating with 4.93 at 60-65° C in a toluene solution give the corresponding alkenes or enol ethers. 

Petasis, N. A., Lu, S.-P. Methylenations of heteroatom-substituted carbonyls with dimethyl titanocene. Tetrahedron Lett. 1995, 36, 2393-2396. 

Treatment of 18 with alkynes results in the formation of metallacyclobutenes 21 [71], which are alternatively synthesized by the reaction of dimethyl titanocene 16 with alkynes [72,73]. The latter reaction involves methane elimination from an initially formed alkenyl-methyl complex 22 giving 21. 

The process optimization centered on developing a safe, robust, and economical olefmation. An initial modification utilized MeMgCl in THF, instead of MeLi in ether, to generate dimethyl titanocene 24. In the solid state, dry 24 decomposed within minutes by turning black with gas evolution. Therefore, a process was developed that avoided isolation of intermediate 24 and resulted in the direct formation of dimethyl titanium carbene 25 stream, which converted ester 2 to desired vinyl ether 3. One additional facet was that the reaction needed to be stopped quickly once... 

Dimethyl titanocene Once again, an expensive reagent with an imperative recycle was required. 

Deoxygenative Methylenation (Witting-Type Reaction) of Selenol Ester with Dimethyl Titanocene... 

Petasis and co-worker reported that methylenation of selenol and thio esters with dimethyl titanocene led to the formation of the corresponding vinyl se-lenides and sulfides (Eq. 58) [111]. Dimethyl titanocene can be easily prepared from titanocene dichloride and methyllithium [112]. The methylenation reactions involve simply heating a mixture of dimethyl titanocene and chalcogeno esters at 60-75 °C. 

Elimination of all operational hazards encountered in first-generation route including sodium cyanide, dimethyl titanocene, and gaseons ammonia... 

The reaction to 300 is reminiscent of related work from Nicolaou s laboratory where it was demonstrated that dihydropyrans and oxepenes could be generated from olefinic esters using the Tebbe reagent or dimethyl titanocene (Scheme 3.58) [63d,ej. For example, oxepene 305 was generated from olefinic ester 304 in 45% yield when it was exposed to the Tebbe reagent. Evidence suggested that the transformation to 305 proceeded through an intermediate acyclic enol ether [64]. 

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