Methylenation Tebbe reagent

CPv. / Ti Al Tebbe reagent methylenation of aldehydes, ketones, esters, thioesters, amides, carbonates can also induce olefin metathesis in situ preparation [711-713]... 

The Tebbe reagent [//-chloro-bis(cyclopentadienylXdimethylalumin-ium)-/r-methylenetitanium] in its pure, crystalline (70,71) or crude (72) forms has been employed for the methylenation of aldonolactones. Thus, D-ribono- 1,4-lactone derivatives 71a and 71b reacted with Tebbe s reagent to give (70,71) the exo-methylene compounds 72a and 72b. 

Elaborate organic substrates and dicarbonyl compounds can also be methylenated in high yields with the Tebbe reagent (Table 3.8) [699-702]. Acid chlorides or... 

Most experimental data suggest that the actual methylenating agent derived from the Tebbe reagent upon treatment with a weak base, is the highly reactive carbene complex Cp2Ti=CH2 [709]. This complex is a typical Schrock-type carbene, because it is high-valent [Ti(IV)], electron-deficient (16 valence electrons) and nucleophilic at carbon. 

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

Experimental Procedure 3.2.4. Methylenation of an Ester with Tebbe Reagent 1 -Phenoxy-1 phenylethene [712,713]... 

Petasis, et al. have discovered that dimethyltitanocene is an excellent substitute for the Tebbe reagent" for the methylenation of heteroatom-substituted carbonyl compounds. ... 

Tebbe reagent as well as Zn-CH2X2-TiCl4 did not give satisfactory results. However, the combination of 3 and /9-TiCl3 gave fully methylenated products without racemization. 

The Tebbe reagent functions as a nucleophilic carbenoid in its reactions with carbonyl groups. The carbenoid is activated in the presence of a Lewis base which presumably complexes with the aluminum atom. Tetrahydrofuran is the Lewis base in the reactions described above. If the reaction is performed in the absence of added tetrahydrofuran, the carbonyl oxygen atom can function as a weak Lewis base, although the methylenation process is considerably slower. 

Methylidene-rare earth complexes (27) have been synthesized and fully characterized.32 In these complexes, the methylene should be seen as a doubly charged negative ligand. Nevertheless, these methylidene complexes react as Schrock-type nucleophilic carbenes, (27) therefore being analogous to the Tebbe reagent. 

While this approach to ring expansion yielded the desired product 252 in an overall yield of 47%, photochemical (room lights) and thermal sensitivity (room temperature) of the dibromomethyl intermediates inspired the development of an alternate approach. As shown in Scheme 21, decalenone 249 could be smoothly methylenated with Tebbe reagent to provide diene 255 in excellent yield. Clean and reproducible oxidative ring expansion could then be effected with thallium trinitrate to furnish enone 252 in 62% overall yield (unoptimized). 

The Tebbe Reagent is a metal carbenoid prepared from the dimetallomethylene species derived by the reaction of trimethyl aluminium with titanocene dichloride this reagent exhibits carbenoid behaviour after the addition of a catalytic amount of pyridine. The Tebbe Reagent reacts with various carbonyl partners to give the product of methylenation ... 

The introduction of a methylene acetal tether needs some further discussion. The 2-propenyl ether is prepared by reaction of a C(2) acetyl group with Tebbe reagent, (C5H5)2TiMe2. Treatment of the resulting enol ether with p-toluenesulfonic acid results in the formation of an oxocarbenium ion, which upon reaction with an alcohol provides an acetal. As can be seen in the reaction scheme, the acid is regenerated, thus only a catalytic amount is required. 

Methylenation of ketones. The Tebbe reagent (1) or the unstable 3,pdisubstituted titanacyclobutane 2 methylenate even easily enolizable ketones rapidly at room temperature. Yields are generally high except in reactions with a very hindered ketone. 

Titanocene methylene-Zinc iodide complex, CpjTiCHj ZnI, (1). The reagent is prepared by reaction of CpjTiCE with CHjfZnl), in THF. It is related to the Tebbe reagent (8, 83-84 10, 87-88), but is easier to prepare. 

The Tebbe reagent (4.85) is used for methylenation of carbonyl compounds. ... 

The Tebbe reagent (4.85) has found applications in reactions of sugars because it methyle-nates carbonyls without racemizing a chiral a-carbon. Thus, methylenation of the formyl functions of 1-0-formylglycoside 4.91 with 4.85 produced 1-0-vinyl glycosides 4.92. 

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