Tebbe's reagent is the

organometallic compound Organometallic chemistry is the study of organometallic compounds, chemical compounds containing at least one chemical bond between a carbon atom of an organic molecule and a metal, including alkali, alkaline earth, and transition metals, and s ...

with the formula (C₅H₅)₂TiCH₂ClAl(CH₃)₂. It is used in the methylenation of

carbonyl In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom: C=O. It is common to several classes of organic compounds, as part of many larger functional groups. A compound containi ...

compounds, that is it converts organic compounds containing the R₂C=O group into the related R₂C=CH₂ derivative. It is a red solid that is

pyrophoric A substance is pyrophoric (from grc-gre, πυροφόρος, , '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 organolith ...

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 ...

s. It was originally synthesized by Fred Tebbe at DuPont Central Research. Tebbe's reagent contains two

tetrahedral In geometry, a tetrahedron (plural: tetrahedra or tetrahedrons), also known as a triangular pyramid, is a polyhedron composed of four triangular faces, six straight edges, and four vertex corners. The tetrahedron is the simplest of all the ...

metal centers linked by a pair of

bridging ligand In coordination chemistry, a bridging ligand is a ligand that connects two or more atoms, usually metal ions. The ligand may be atomic or polyatomic. Virtually all complex organic compounds can serve as bridging ligands, so the term is usually ...

s. 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 (-CH₂-) and a chloride atom in a nearly

square-planar The square planar molecular geometry in chemistry describes the stereochemistry (spatial arrangement of atoms) that is adopted by certain chemical compounds. As the name suggests, molecules of this geometry have their atoms positioned at the corn ...

(Ti–CH₂–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 ( ''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 that slowl ...

and

trimethylaluminium Trimethylaluminium is one of the simplest examples of an organoaluminium compound. Despite its name it has the formula Al2( CH3)6 (abbreviated as Al2Me6 or TMA), as it exists as a dimer. This colorless liquid is pyrophoric. It is an industriall ...

toluene Toluene (), also known as toluol (), is a substituted aromatic hydrocarbon. It is a colorless, water-insoluble liquid with the smell associated with paint thinners. It is a mono-substituted benzene derivative, consisting of a methyl group (CH3) ...

solution.Straus, D. A., "μ-Chlorobis(cyclopentadienyl)(dimethylaluminium)-μ-methylenetitanium": ''Encyclopedia of Reagents for Organic Synthesis.'' John Wiley, London, 2000. ::Cp₂TiCl₂ + 2 Al(CH₃)₃ → CH₄ + Cp₂TiCH₂AlCl(CH₃)₂ + Al(CH₃)₂Cl After about 3 days, the product is obtained after recrystallization to remove Al(CH₃)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): ::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 starting reagent.

Reaction mechanism

Tebbe's reagent itself does not react with carbonyl compounds, but must first be treated with a mild

Lewis base A Lewis acid (named for the American physical chemist Gilbert N. Lewis) is a chemical species that contains an empty orbital which is capable of accepting an electron pair from a Lewis base to form a Lewis adduct. A Lewis base, then, is any sp ...

, such as

pyridine Pyridine is a basic 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, weakly alkaline, water-miscible liquid w ...

, which generates the active

Schrock carbene A transition metal carbene complex is an organometallic compound featuring a divalent organic ligand. The divalent organic ligand coordinated to the metal center is called a carbene. Carbene complexes for almost all transition metals have been rep ...

. : 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 is a hydrocarbon containing a carbon–carbon double bond. Alkene is often used as synonym of olefin, that is, any hydrocarbon containing one or more double bonds.H. Stephen Stoker (2015): General, Organic ...

(5). :

Scope

The Tebbe reagent is used in

organic synthesis Organic synthesis is a special branch of chemical synthesis and is concerned with the intentional construction of organic compounds. Organic molecules are often more complex than inorganic compounds, and their synthesis has developed into one o ...

for carbonyl methylenation. 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 The Wittig reaction or Wittig olefination is a chemical reaction of an aldehyde or ketone with a triphenyl phosphonium ylide called a Wittig reagent. Wittig reactions are most commonly used to convert aldehydes and ketones to alkenes. Mos ...

, 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 In organic chemistry, an aldehyde () is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred to as an aldehyde but can also be classified as a formyl grou ...

as well as

esters In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ar ...

lactones Lactones are cyclic carboxylic esters, containing a 1-oxacycloalkan-2-one structure (), or analogues having unsaturation or heteroatoms replacing one or more carbon atoms of the ring. Lactones are formed by intramolecular esterification of the c ...

and

amide In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula , where R, R', and R″ represent organic groups or hydrogen atoms. The amide group is called a peptide bond when it i ...

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 methylenates 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 (''kheir''), "hand", a familiar chiral object. An object or a system is ''chiral'' if it is distinguishable from i ...

α carbon. For this reason, the Tebbe reagent has found applications in reactions of sugars where maintenance of

stereochemistry Stereochemistry, a subdiscipline of chemistry, involves the study of the relative spatial arrangement of atoms that form the structure of molecules and their manipulation. The study of stereochemistry focuses on the relationships between stereoi ...

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. :

References

{{Aluminium compounds Reagents for organic chemistry Titanocenes Organoaluminium compounds Chloro complexes Titanium(IV) compounds

Preparation

Reaction mechanism

Scope

Modifications

See also

Related organotitanium reagents and reactions

Related methylenation reactions

References