Tebbe's reagent

Chembox new
Name = Tebbe's reagent
ImageFile = TebbeRgt.png ImageName = Structure of Tebbe's reagent
ImageFile1 = Tebbe's-reagent-3D-balls.png ImageName1 = Ball-and-stick model of Tebbe's reagent
OtherNames = Tebbe Reagent
Section1 = Chembox Identifiers
CASNo = 67719-69-1
Section2 = Chembox Properties
Formula = C₁₃H₁₈AlClTi
MolarMass = 284.60 g/mol
Solvent = other solvents
SolubleOther = toluene, benzene, dichloromethane,
THF (low temperatures only)The Tebbe reagent is (C₅H₅)₂TiCH₂ClAl(CH₃)₂, an organometallic compound used in the methylenation of carbonyl compounds. [cite journal | author = F. N. Tebbe, G. W. Parshall and G. S. Reddy | title = Olefin homologation with titanium methylene compounds | year = 1978 | journal = J. Am. Chem. Soc. | volume = 100 | issue = 11 | pages = 3611–3613 | doi = 10.1021/ja00479a061] It is a red solid that is pyrophoric in the air, and thus is typically used under nitrogen (N₂) or argon (Ar) gas.

The Tebbe reagent contains two cyclopentadienyl (C₅H₅^-, Cp) rings bonded to titanium. The titanium and aluminium atoms are bridged by both CH₂ and chloride ligands. Aluminium is also bonded to two methyl groups. This compound exhibits a nearly square (Ti-CH₂-Al-Cl) bridge. [Wells, A.F., "Structural Inorganic Chemistry" Fifth Ed., Oxford University Press, New York, p. 976.]

The Tebbe reagent is the first reported compound where a methylene group bridges a transition metal (Ti) and a main group metal (Al).Herrmann, W.A., "The Methylene Bridge" "Advances in Organometallic Chemistry" 1982, "20", 195-197.]

Preparation

The Tebbe reagent is synthesized from titanocene dichloride and trimethylaluminium in toluene solution.Straus, D. A., "μ-Chlorobis(cyclopentadienyl)(dimethylaluminium)-μ-methylenetitanium": "Encyclopedia of Reagents for Organic Synthesis." John Wiley & Sons, Ltd, 2000.]

::Cp₂TiCl₂ + 2 Al(CH₃)₃ → CH₄ + Cp₂TiCH₂AlCl(CH₃)₂ + Al(CH₃)₂Cl

After stirring for about 3 days at 25 °C, the product is recrystallized to remove Al(CH₃)₂Cl. This procedure gives 80-90% yield of the Tebbe reagent. Although syntheses using the isolated Tebbe reagent give a cleaner product, successful procedures using the reagent "in situ" have been reported. [Pine, S. H.; Kim, G.; Lee, V. "Org. Syn.", Coll. Vol. 8, p.512 (1993); Vol. 69, p.72 (1990). ( [http://www.orgsyn.org/orgsyn/prep.asp?prep=cv8p0512 Article] )] [cite journal | author = L. F. Cannizzo and R. H. Grubbs | title = In situ preparation of (μ-chloro)(μ-methylene)bis(cyclopentadienyl)(dimethylaluminum)titanium (Tebbe's reagent) | year = 1985 | journal = J. Org. Chem. | volume = 50 | issue = 13 | pages = 2386–2387 | doi = 10.1021/jo00213a040 ] Instead of isolating the Tebbe reagent, the solution is merely cooled in an ice bath or dry ice bath before adding the starting material.

An alternative but less convenient synthesis entails the use of dimethyltitanocene:Payack, J. F.; Hughes, D. L.; Cai, D.; Cottrell, I. F.; Verhoeven, T. R. "Org. Syn.", Coll. Vol. 10, p.355 (2004); Vol. 79, p.19 (2002). ( [http://www.orgsyn.org/orgsyn/prep.asp?prep=v79p0019 Article] )]

::Cp₂Ti(CH₃)₂ + Al(CH₃)₂Cl → Cp₂TiCH₂AlCl(CH₃)₂ + CH₄

One drawback to this method, aside from requiring Cp₂Ti(CH₃)₂, is the difficulty of separating product from unreacted Cp₂Ti(CH₃)₂.

Reaction mechanism

The Tebbe reagent itself does not react with carbonyl compounds, but must first be treated with a mild Lewis base, such as pyridine, to form the active Schrock carbene.

Also analogous to the Wittig reagent, the reactivity appears to be driven by the high oxophilicity of Ti(IV). The Schrock carbene (1) reacts with carbonyl compounds (2) to give a postulated oxatitanacyclobutane intermediate (3). This cyclic intermediate has never been directly isolated, presumably because it breaks down immediately to the produce the desired alkene (5).

cope

The Tebbe reagent is used in organic synthesis for carbonyl methylenation.Pine, S. H. "Org. React." 1993, "43", 1. (Review)] Beadham, I.; Micklefield, J. "Curr. Org. Syn." 2005, "2", 231-250. (Review)] This conversion can also be effected using the Wittig reaction, although the Tebbe reagent is more efficient especially for sterically encumbered carbonyls. Furthermore, the Tebbe reagent is less basic than the Wittig reagent and does not give the β-elimination products.

Methylenation reactions also occur for aldehydes as well as esters, lactones and amides. The Tebbe reagent converts esters and lactones to enol ethers and amides to enamines. In compounds containing both ketone and ester groups, the ketone selectively reacts in the presence of one equivalent of the Tebbe reagent.

The Tebbe reagent methylenates carbonyls without racemizing a chiral α carbon. For this reason, the Tebbe reagent has found applications in reactions of sugars where maintenance of stereochemistry can be critical. [cite journal | author = A. Marra, J. Esnault, A. Veyrieres and P. Sinay | title = Isopropenyl glycosides and congeners as novel classes of glycosyl donors: theme and variations | year = 1992 | journal = J. Am. Chem. Soc. | volume = 114 | issue = 16 | pages = 6354–6360 | doi = 10.1021/ja00042a010]

The Tebbe reagent reacts with acid chlorides or other compounds with the same functionality. As in the above reactions, the Tebbe reagent converts the carbonyl group to a methylene group, but the intermediate Cp₂TiO reacts further to form a titanium enolate by replacing Cl^-.

ee also

*Petasis reagent
*Peterson olefination
*Titanocene dichloride
*Wittig reaction

References