Tebbe's reagent is the
organometallic compound with the formula (C
5H
5)
2TiCH
2ClAl(CH
3)
2. It is used in the
methylidenation of
carbonyl
In organic chemistry, a carbonyl group is a functional group with the formula , composed of a carbon atom double bond, double-bonded to an oxygen atom, and it is divalent at the C atom. It is common to several classes of organic compounds (such a ...
compounds, that is it converts organic compounds containing the R
2C=O group into the related R
2C=CH
2 derivative. It is a red solid that is
pyrophoric
A substance is pyrophoric (from , , 'fire-bearing') if it ignites spontaneously in air at or below (for gases) or within 5 minutes after coming into contact with air (for liquids and solids). Examples are organolithium compounds and triethylb ...
in the air, and thus is typically handled with
air-free technique Air-free techniques refer to a range of manipulations in the chemistry laboratory for the handling of compounds that are air-sensitive. These techniques prevent the compounds from reacting with components of air, usually water and oxygen; less com ...
s. It was originally synthesized by
Fred Tebbe at
DuPont Central Research.
Tebbe's reagent contains two
tetrahedral
In geometry, a tetrahedron (: tetrahedra or tetrahedrons), also known as a triangular pyramid, is a polyhedron composed of four triangular Face (geometry), faces, six straight Edge (geometry), edges, and four vertex (geometry), vertices. The tet ...
metal centers linked by a pair of
bridging ligands. The titanium has two
cyclopentadienyl Cyclopentadienyl can refer to
* Cyclopentadienyl anion, or cyclopentadienide,
** Cyclopentadienyl ligand
* Cyclopentadienyl radical, •
* Cyclopentadienyl cation,
See also
* Pentadienyl
{{Chemistry index ...
(, or Cp) rings and aluminium has two methyl groups. The titanium and aluminium atoms are linked together by both a
methylene bridge
In chemistry, a methylene bridge is part of a molecule with formula . The carbon atom is connected by single bonds to two other distinct atoms in the rest of the molecule. A methylene bridge is often called a methylene group or simply methylene, ...
(-CH
2-) and a chloride atom in a nearly
square-planar (Ti–CH
2–Al–Cl) geometry. The Tebbe reagent was the first reported compound where a methylene bridge connects 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
Titanocene dichloride is the organotitanium compound with the formula (hapticity, ''η''5-C5H5)2TiCl2, commonly abbreviated as Cp2TiCl2. This metallocene is a common reagent in organometallic and organic synthesis. It exists as a bright red solid t ...
and
trimethylaluminium in
toluene
Toluene (), also known as toluol (), is a substituted aromatic hydrocarbon with the chemical formula , often abbreviated as , where Ph stands for the phenyl group. It is a colorless, water
Water is an inorganic compound with the c ...
solution.
[Straus, D. A., "μ-Chlorobis(cyclopentadienyl)(dimethylaluminium)-μ-methylenetitanium": ''Encyclopedia of Reagents for Organic Synthesis.'' John Wiley, London, 2000.]
::Cp
2TiCl
2 + 2 Al(CH
3)
3 → CH
4 + Cp
2TiCH
2AlCl(CH
3)
2 + Al(CH
3)
2Cl
After about 3 days, the product is obtained after recrystallization to remove Al(CH
3)
2Cl.
Although syntheses using the isolated Tebbe reagent give a cleaner product, successful procedures using the reagent "in situ" have been reported. 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 (Petasis reagent):
::Cp
2Ti(CH
3)
2 + Al(CH
3)
2Cl → Cp
2TiCH
2AlCl(CH
3)
2 + CH
4
One drawback to this method, aside from requiring Cp
2Ti(CH
3)
2, is the difficulty of separating product from unreacted starting reagent.
Reaction mechanism
Tebbe's reagent itself does not react with carbonyl compounds, but must first be treated with a mild
Lewis base, such as
pyridine
Pyridine is a basic (chemistry), basic heterocyclic compound, heterocyclic organic compound with the chemical formula . It is structurally related to benzene, with one methine group replaced by a nitrogen atom . It is a highly flammable, weak ...
, which generates 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
In organic chemistry, an alkene, or olefin, is a hydrocarbon containing a carbon–carbon double bond. The double bond may be internal or at the terminal position. Terminal alkenes are also known as Alpha-olefin, α-olefins.
The Internationa ...
(5).
:
Scope
The Tebbe reagent is used in
organic synthesis
Organic synthesis is a branch of chemical synthesis concerned with the construction of organic compounds. Organic compounds are molecules consisting of combinations of covalently-linked hydrogen, carbon, oxygen, and nitrogen atoms. Within the gen ...
for carbonyl methylidenation.
[Pine, S. H. ''Org. React.'' 1993, ''43'', 1. (Review)][Beadham, I.; Micklefield, J. ''Curr. Org. Synth.'' 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.
Methylidenation reactions also occur for
aldehydes as well as
esters
In chemistry, an ester is a chemical compound, compound derived from an acid (either organic or inorganic) in which the hydrogen atom (H) of at least one acidic hydroxyl group () of that acid is replaced by an organyl group (R). These compounds c ...
,
lactones
Lactones are cyclic carboxylic esters. They are derived from the corresponding hydroxycarboxylic acids by esterification. They can be saturated or unsaturated.
Lactones are formed by lactonization, the intramolecular esterification of the corre ...
and
amide
In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a chemical compound, compound with the general formula , where R, R', and R″ represent any group, typically organyl functional group, groups or hydrogen at ...
s. 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 methylidenates carbonyls without racemizing a
chiral
Chirality () is a property of asymmetry important in several branches of science. The word ''chirality'' is derived from the Greek language, Greek (''kheir''), "hand", a familiar chiral object.
An object or a system is ''chiral'' if it is dist ...
α carbon. For this reason, the Tebbe reagent has found applications in reactions of sugars where maintenance of
stereochemistry
Stereochemistry, a subdiscipline of chemistry, studies the spatial arrangement of atoms that form the structure of molecules and their manipulation. The study of stereochemistry focuses on the relationships between stereoisomers, which are defined ...
can be critical.
The Tebbe reagent reacts with
acid chloride
In organic chemistry, an acyl chloride (or acid chloride) is an organic compound with the functional group . Their formula is usually written , where R is a side chain. They are reactive derivatives of carboxylic acids (). A specific example o ...
s to form titanium enolates by replacing Cl
−.
:
Modifications
It is possible to modify Tebbe's reagent through the use of different ligands. This can alter the reactivity of the complex, allowing for a broader range of reactions. For example,
cyclopropanation can be achieved using a chlorinated analogue.
:
See also
Related organotitanium reagents and reactions
*
Kulinkovich reaction
*
Petasis reagent
The Petasis reagent, named after Nicos A. Petasis, is an organotitanium compound with the formula Cp2Ti(CH3)2. It is an orange-colored solid.
Preparation and use
The Petasis reagent is prepared by the salt metathesis reaction of methylmagnesiu ...
*Lombardo reagent
[.]
*
McMurry reaction
Related methylidenation reactions
*
Nysted reagent
*
Peterson olefination
*
Wittig reaction
*
Kauffmann olefination
References
{{Aluminium compounds
Reagents for organic chemistry
Titanocenes
Organoaluminium compounds
Chloro complexes
Titanium(IV) compounds