Tebbe's reagent
| Template:Chembox header | Tebbe's reagent | |
|---|---|
| Structure of Tebbe's reagent Ball-and-stick model of Tebbe's reagent | |
| Systematic name | μ-Chlorobis(cyclopentadienyl)- (dimethylaluminium)- μ-methylenetitanium |
| Other names | Tebbe Reagent |
| Molecular formula | C13H18AlClTi |
| Molar mass | 284.60 g/mol |
| CAS number | Template:CASREF |
| Solubility | toluene, benzene, dichloromethane, THF (low temperatures only) |
| Template:Chembox header |Disclaimer and references | |
The Tebbe reagent is (C5H5)2TiCH2ClAl(CH3)2, an organometallic compound used in the methylenation of carbonyl compounds.[1] 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 aluminum 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.[2]
The Tebbe reagent is the first reported compound where a methylene group bridges a transition metal (Ti) and a main group metal (Al).[3]
Preparation
The Tebbe reagent is synthesized from titanocene dichloride and trimethylaluminium in toluene solution.[3][4]
- 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.[3] Although syntheses using the isolated Tebbe reagent give a cleaner product, successful procedures using the reagent "in situ" have been reported.[5][6] 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:[7]
- 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).
Scope
The Tebbe reagent is used in organic synthesis for carbonyl methylenation.[8][9] 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.[10]
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-.
See also
References
- ↑ F. N. Tebbe, G. W. Parshall and G. S. Reddy (1978). "Olefin homologation with titanium methylene compounds". J. Am. Chem. Soc. 100 (11): 3611–3613. doi:10.1021/ja00479a061.
- ↑ Wells, A.F., Structural Inorganic Chemistry Fifth Ed., Oxford University Press, New York, p. 976.
- ↑ 3.0 3.1 3.2 Herrmann, W.A., "The Methylene Bridge" Advances in Organometallic Chemistry 1982, 20, 195-197.
- ↑ Straus, D. A., "μ-Chlorobis(cyclopentadienyl)(dimethylaluminium)-μ-methylenetitanium": Encyclopedia of Reagents for Organic Synthesis. John Wiley & Sons, Ltd, 2000.
- ↑ Pine, S. H.; Kim, G.; Lee, V. Org. Syn., Coll. Vol. 8, p.512 (1993); Vol. 69, p.72 (1990). (Article)
- ↑ L. F. Cannizzo and R. H. Grubbs (1985). "In situ preparation of (μ-chloro)(μ-methylene)bis(cyclopentadienyl)(dimethylaluminum)titanium (Tebbe's reagent)". J. Org. Chem. 50 (13): 2386–2387. doi:10.1021/jo00213a040.
- ↑ 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). (Article)
- ↑ Pine, S. H. Org. React. 1993, 43, 1. (Review)
- ↑ Beadham, I.; Micklefield, J. Curr. Org. Syn. 2005, 2, 231-250. (Review)
- ↑ A. Marra, J. Esnault, A. Veyrieres and P. Sinay (1992). "Isopropenyl glycosides and congeners as novel classes of glycosyl donors: theme and variations". J. Am. Chem. Soc. 114 (16): 6354–6360. doi:10.1021/ja00042a010.