[80122-07-2]  · C15H20Ti  · Bis(cyclopentadienyl)-3,3-dimethyltitanacyclobutane  · (MW 248.20)

(methylenating agent for alkenation of carbonyl compounds, particularly esters, ketones, and aldehydes;1a,c of low basicity and functions without epimerization at a-chiral centers; catalyst precursor in living ring-opening metathesis polymerization1b)

Solubility: very sol dichloromethane, diethyl ether, and toluene; moderately sol pentane.2

Form Supplied in: red crystalline solid.

Analysis of Reagent Purity: by 1H NMR (toluene-d8, -10 °C)3 or by bromination in ether at -20 °C followed by quantitation of the 1,3-dibromo-2,2-dimethylpropane product by GC.4

Preparative Methods: most often prepared from the Tebbe reagent (1) by reaction with isobutene and 4-dimethylaminopyridine in dichloromethane.3 Alternatively, may be formed in 89% yield from Cp2TiCl2 and a 1,3-di-Grignard reagent, which is in turn obtained from 1,3-dibromo-2,2-dimethylpropane in 18% yield.4,5

Purification: may be recrystallized by slow cooling of a toluene solution from 0 °C to -78 °C under an inert atmosphere. Recrystallization from diethyl ether is also effective.

Handling, Storage, and Precautions: the title reagent (2a) may be stored indefinitely under nitrogen atmosphere, preferably in the dark. Although this titanacycle is moderately air- and water-sensitive, it may be handled in air for brief periods. In solution this complex is labile and will decompose to give the purple dimer [Cp2Ti(m-CH2)]2,6 as well as isobutene and other uncharacterized products. Solutions should be prepared at 0 °C and used immediately.2

Reactivity of Titanacyclobutanes.

A number of titanacyclobutane complexes (e.g. (2a-e)) have been efficiently prepared from Tebbe reagent (1) (m-Chlorobis(cyclopentadienyl)(dimethylaluminum)-m-methylenetitanium)1c,2,7-9 and studied in significant detail (eq 1).1 Typically pyridine bases are used; ether or tetrahydrofuran as bases give equilibrium concentrations of (1) and (2).10 Certain titanacyclobutanes may be prepared in variable yields from 1,3-di-Grignard reagents;4,5,11 a few examples are shown in eq 2. Very recently a route to titanacyclobutanes via cationic p-allyl species was demonstrated.12 Also, titanacyclobutanes may be prepared by reaction of alkenes with less stable titanacyclobutanes.3,8,9 These metallacycles cleave to afford Cp2Ti=CH2 (as the free methylidene or, more likely, an alkene complex13) as shown in the ester to vinyl ether conversion of eq 3.1a,1c,14

The titanacyclobutanes may thus serve as aluminum-free alternatives to the Tebbe reagent for methylenation of a range of carbonyl compounds. Another application which involves retro 2 + 2 cleavage of metallacycles is the ring-opening metathesis polymerization (ROMP) of strained cycloalkenes via substituted methylidene intermediates (see below).1b As methylidene sources the titanacyclobutanes offer advantages over (1); primarily in avoidance of side reactions due to acidic aluminum species, ease of workup, and lesser air sensitivity. However, titanacyclobutanes have not been as widely employed because they are not commercially available and preparation requires Schlenk line and glovebox techniques.

The titanacyclobutanes undergo a number of potentially useful reactions in which the carbon skeleton of the ring remains intact in products such as alkanes, 1,3-dibromides, cyclopropanes, and acyloins. These products may be conveniently obtained from titanacycles formed in situ from (1).1a

Titanacyclobutanes as Methylidene Precursors.

Most titanacyclobutanes, including (2a-e), thermally cleave by a retro 2 + 2 process to liberate alkene and afford the reactive methylidene species Cp2Ti=CH2, or an alkene complex thereof, as shown in eq 3.1f,13,14 Thus much of the chemistry of these metallacycles is qualitatively similar to that of the Tebbe reagent (1).1c For example, the titanium methylidene so produced affords vinyl ethers from a wide range of esters (eq 3), a conversion which is not possible using Wittig alkylidene phosphorane reagents.15 Aldehydes and ketones are likewise methylenated and reaction takes place without epimerization at a-chiral centers,1a a frequent problem when using highly basic Wittig conditions.16 Yields in these methylenations are generally good to excellent. The intermediate titanaoxacyclobutanes are not observed in these transformations, although stable analogs having b-alkylidene substitution have been characterized.17 This methylenation chemistry has been the subject of a recent comprehensive review.1c

Different reactivity is observed for the titanacycles with acid chlorides as shown in eq 4.18 The titanium enolates of methyl ketones which result do not undergo double-bond isomerization, and are useful in the aldol reaction. Although the Tebbe reagent shows similar reactivity, yields are much lower.19 Reaction of the titanacyclobutanes with sterically hindered ketones also affords titanium enolate complexes; however, these are not active in the aldol reaction.20 Reaction with anhydrides also gives enolate complexes which are not active in the aldol reaction. By contrast, unhindered imides may be methylenated in good yield with excellent selectivity in unsymmetrical cases.21

Reaction with certain alkyl halides occurs to give titanocene alkyl halides [Cp2Ti(Cl)CH2R] via a radical mechanism.22

Although a-alkyl substituted titanacyclobutanes (e.g. 2h, see eq 6) are thermally unstable,10 a-alkylidene substitution is favorable23-25 and leads to a versatile synthesis (via titanium vinylidene intermediates) of substituted allenes from ketones as shown in eq 5.26

The titanacyclobutanes have also served as precursors in the synthesis of various interesting heterobimetallic m-methylene complexes27 and other organometallic species,28 including titanium methylidene phosphine complexes.29

Choice of metallacycle is dictated by reaction conditions and ease of preparation. b-Substituted metallacycles such as (2c and 2d) are especially stable and react at 50-60 °C, whereas b,b-disubstituted titanacycles such as (2a and b) react at about 0 °C.1a,13 By contrast, the Tebbe reagent may be used at -40 °C. Titanacyclobutane (2a) is particularly convenient for NMR studies due to the simplicity of its spectrum, while (2b) is prepared by the same general method using a liquid alkene which is easier to handle than isobutene.

It should be noted that alternate methods for formation of active titanium methylidene species have been developed.1c A widely used system for methylenation of ketones30 is the still undefined mixture formed from Zn/CH2X2/TiCl4. Also, thermolysis of Cp2TiMe2 provides a clean aluminum-free source of Cp2Ti=CH2 and shows considerable synthetic promise.31 Except in the case of titanacyclobutanes prepared from strained cycloalkenes (see below), or a-alkylidene substituted cases (see above), the titanacyclobutanes are efficient precursors only for the unsubstituted methylidene species; several approaches to substituted methylidene equivalents of titanium or zirconium have been devised,1c,32 including a preparation of titanocene vinylcarbene complexes from cyclopropenes.33

Reactions Involving Substituted Alkylidene Intermediates: Ring-Opening Metathesis Polymerization (ROMP).1b

The titanacyclobutanes were the first metallacycles to demonstrate the requisite reactivity for catalysis of alkene metathesis via alkylidene complex intermediates.34 However, these species are not useful catalysts for productive metathesis of acyclic alkenes. This is due to the propensity of a-substituted titanacyclobutanes such as (2h) to cleave to the unsubstituted methylidene, as illustrated by eq 6.10

However, titanacyclobutanes formed from strained cycloalkenes will ring open to afford substituted methylidenes. This useful mode of reactivity is illustrated for complex (2i), formed from 3,3-dimethylcyclopropene, which yields titanium alkylidene phosphine complex (3), as shown in eq 7.9

Likewise, (2i) reacts with benzophenone to afford 3,3-dimethyl-1,1-diphenyl-1,4-pentadiene.9 Norbornene affords the extremely stable titanacyclobutane (2j) upon reaction with (1) or even the quite stable titanacycle (2d) under suitable conditions, and this species reacts further with norbornene (benzene solution, 65 °C) to produce ring-opened polynorbornene (cis:trans ratio 38:62) as illustrated in eq 8.35 Because rates of chain transfer and chain termination are very slow relative to initiation and propagation in this system, a living polymerization process occurs. The low polydispersity (below 1.1) of the polynorbornene and the linear increase in molecular weight with time are consistent with this. Another entry into this chemistry involves thermolysis of dimethyltitanonocene.31b The living nature of this system allows for end capping of the polymer chains by Wittig-type reactions with, for example, benzophenone36 or acetone,37 and also, by sequential addition of different monomers, for the production of block copolymers.37,38 Other monomer units employed include benzonorbornadiene, 6-methylbenzonorbornadiene, and endo- and exo-dicyclopentadiene, which have been used to synthesize diblock and triblock copolymers of low polydispersity as illustrated in eq 9.37 It has been possible to end-cap ROMP polymers with an aldehyde group and to use aldol-group-transfer polymerization to make diblock polymers with poly(vinyl alcohol) or poly(silyl vinyl ether) segments.38a ROMP chemistry using titanium methylidene sources has also been used to produce the novel cross-conjugated poly(3,4-isopropylidenecyclobutene) shown in eq 10, which becomes conducting upon oxidative doping.39

Numerous other ROMP catalysts have been developed,1d,40 some of which are stable to air and water and are active at room temperature.41

It should be noted that in situ formation of a derivative of (2j), which cleaves to give a substituted methylidene, was employed in the synthesis of D9,12-capnellene.42 Certain molybdenum alkylidenes show considerable promise for the stoichiometric43 or catalytic44 preparation of cycloalkenes, from unsaturated ketones or dienes, respectively, via metallacyclobutanes which cleave to afford substituted methylidenes.

Reactions Not Involving Methylidene Species.

Alkanes are produced upon acidolysis;34,45 for example (2a) affords neopentane.1a Titanacyclobutanes may be directly halogenated to afford 1,3-dibromides1a as shown in eq 11.2a This reaction is typically quantitative, and has been used to assay the titanacyclobutanes.4

By contrast, iodination leads to cyclopropane formation in good yield,1a as shown in eq 12, a process which was demonstrated to proceed stepwise with retention of stereochemistry at one carbon and inversion at the other.46 The titanacycles may be photolyzed, as in eq 13, to afford cyclopropanes via a 1,4-biradical intermediate.47 Reaction with chemical oxidants such as tetrakis(trifluoromethyl)cyclopentadienone or ferricinium salts also affords cyclopropanes by reductive elimination.48 Carbonylation leads to reductive coupling of two carbon monoxide units to afford a stable enediolate complex of titanocene which may be converted to a cyclic acyloin upon acidolysis; in the one-pot process of eq 14, metallacycle (2c) is generated in situ from the Tebbe reagent.1a,2a

Related Reagents.

Bis(cyclopentadienyl)dimethyltitanium; Dichlorobis(cyclopentadienyl)zirconium-Zinc-Dibromomethane; m-Chlorobis(cyclopentadienyl)(dimethylaluminum)-m-methylenetitanium; Dibromomethane-Zinc-Titanium(IV) Chloride.

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Daniel A. Straus

San Jose State University, CA, USA

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