WO2021176213A1 - Process for the preparation of cyclopentadienide-based ansa ligands - Google Patents

Abstract

A method for preparing a compound comprising a cyclopentadienyl moiety is described. The method comprises: (a) deprotonating a cyclopentadienyl moiety in a solution comprising an alkali hydroxide and a reducing agent; and (b) reacting the deprotonated cyclopentadienyl moiety with a compound having an electrophilic site. Also described is a method of separating a rac-ansa-bridged bis-indenyl transition metal compound of formula (rac-M1) from its meso isomer.

Description

PROCESS FOR THE PREPARATION OF CYCLOPENTADIENIDE-BASED ANSA

LIGANDS

FIELD OF THE INVENTION

[0001] The invention relates to a method for preparing a compound comprising a cyclopentadienyl moiety, such as a compound comprising ansa-cyclopentadienyl moieties, particularly of substituted cyclopentadienyl moieties. The invention also provides a method of separating a rac-ansa-bridged b/s-indenyl Group 4 transition metal from a mixture of isomers.

BACKGROUND

[0002] Metallocene compounds for use as polymerization catalysts are known in the art. There is a sub-class of metallocene compounds known as ansa- metallocenes where the cyclopentadienyl moieties are linked by a bridging group. This bridging group is often referred to as an ansa-bridge. Ansa- metallocenes have been used as olefin polymerization catalysts, where the ansa-bridge can have advantageous effects on the activity of the catalyst and can influence the properties of the resulting polymer, such as the polymer’s molecular weight and its tacticity.

[0003] To prepare an ansa- metallocene, a ligand precursor containing an ansa-bridge linking the cyclopentadienyl moieties is normally synthesised for reaction with a suitable metallic compound. The synthesis of the ligand precursor typically involves deprotonating a cyclopentadienyl moiety with an organolithium reagent to generate a moiety comprising a cyclopentadienide anion. The resulting anion is then used to perform a nucleophilic substitution or a nucleophilic addition reaction with a compound having an electrophilic site for forming the ansa-bridge.

[0004] Organolithium reagents, such as te/f-butyllithium, are highly pyrophoric and are often provided as a solution in an alkane solvent (e.g. pentane or hexane) or an ether solvent (e.g. diethyl ether). Such solutions and their vapor are extremely flammable and should only be used in relatively small quantities to minimise the risk of a fire. It is therefore difficult to produce significant quantities of the ligand precursor on an industrial scale using a single preparative process. This increases the cost of the ansa-bridged precursor and is a bottleneck in the manufacture of industrial quantities of ansa- metallocenes for use as polymerization catalysts. [0005] The presence of the ansa-bridge in ansa- metallocenes restricts the rotation of the cyclopentadienyl moiety about its h⁵ tt-bond to the metal (e.g. its C5 axis). When the cyclopentadienyl moiety is substituted, then these substituents are fixed in position and stereoisomers of the associated ansa- metallocene may exist. When preparing ansa- metallocenes with such ligands, an isomeric mixture of the metallocene is typically produced and it can be difficult to obtain a single isomer from this mixture.

SUMMARY OF THE INVENTION

[0006] The invention provides, in a first aspect, a method for preparing a compound comprising a cyclopentadienyl moiety. The method comprises:

(a) deprotonating a cyclopentadienyl moiety represented by formula (A1) or an isomer thereof in a solution comprising an alkali hydroxide and a reducing agent:

wherein each of R¹, R², R³ and R⁴ is independently selected from hydrogen, optionally substituted Ci-20-alkyl, optionally substituted C2-2o-alkenyl, optionally substituted C3-2o-cycloalkyl, optionally substituted C6-2o-aryl and a silyl group, or at least two adjacent R¹, R², R³ and R⁴ substituents form an optionally substituted ring having a total of 6 to 9 ring carbon atoms; and (b) reacting the deprotonated cyclopentadienyl moiety with a compound having an electrophilic site.

[0007] The invention provides a method for manufacturing an ansa-bridged ligand precursor comprising a cyclopentadienyl moiety that can be used on an industrial scale. The method does not require the use of an organolithium reagent in the synthesis of the ligand precursor (e.g. to deprotonate the cyclopentadienyl moiety). Besides avoiding the risks associated with the use of organolithium reagents, the method can also be performed under comparatively mild reaction conditions. The method of the invention therefore provides a cheaper and safer route to a range of ansa-ligand precursors for metallocenes, such as polymerisation catalysts. [0008] In a second aspect, the invention also provides a method of separating a rac- ansa-bridged b/s-indenyl transition metal compound of formula (rac-M1) from a mixture of its isomers, particular from its meso isomer. The method comprises:

(a) washing a first solid product with dichloromethane to obtain a first extraction liquid comprising a rac isomer and a meso isomer of an ansa-bridged b/s-indenyl transition metal compound as represented by the formula (rac-M1) and the formula (meso-M1) respectively;

(rac-M1) (meso-M1) wherein:

M is selected from Zr and Hf;

Y is selected from chloro or bromo; and n is an integer selected from 1 and 2;

(b) evaporating the dichloromethane from the first extraction liquid to obtain a second solid product; and

(c) washing the second solid product with a solvent to remove the meso isomer (e.g. to leave the rac isomer), wherein the solvent is toluene or ethanol.

[0009] Specific isomers of Group 4 transition metal metallocene catalysts, such as rac- ethylenebis(indenyl)zirconium(IV) dichloride, can be difficult, dangerous and costly to synthesize on industrial scale using current methods.

[0010] The method of the second aspect relates directly to the manufacture of an ansa- metallocene polymerization catalyst for the industrial production of, for example, isotactic polypropylene. The invention facilitates much easier and quicker separation of the rac- isomers of the metal compounds that are used as catalysts. It is not, for example, necessary to perform a crystallisation step to obtain the rac-isomer. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] The invention is further described hereinafter with reference to the accompanying drawings.

[0012] Figure 1 is a ¹H NMR spectrum of 1,2-bis(3-indenyl)ethane.

[0013] Figure 2 is a ¹H NMR spectrum of bis(3-indenyl)methane.

[0014] Figure 3 is a ¹H NMR spectrum of rac-ethylenebis(indenyl)zirconium(IV) dichloride.

DEFINITIONS

[0015] The term “alkyl” as used herein refers to a straight or branched hydrocarbon radical consisting of carbon and hydrogen atoms, and containing no unsaturation. A “Ci-2o-alkyl” group contains one to twenty carbon atoms. In general, it is preferred that the alkyl group is a Ci-₆-alkyl group. Unless stated otherwise specifically in the specification, an alkyl group is unsubstituted or may be substituted by one or more substituents (e.g. one or more unsubstituted substituents) selected from Ci-₆-alkoxy, C3-8-cycloalkyl and C₆-io-aryl. It is generally preferred that the alkyl group is unsubstituted.

[0016] The term “alkenyl” as used herein refers to a straight or branched hydrocarbon radical group consisting of carbon and hydrogen atoms, and containing at least one carbon-carbon double bond. A “C2-20 alkenyl” group contains two to twenty carbon atoms and at least one double bond. The alkenyl group may contain two or more double bonds, which may or may not be (a) conjugated or (b) an allene (e.g. adjacent to one another). Typically, the alkenyl group is a C2-6-alkenyl group. In general, it is preferred that each alkenyl group is straight (e.g. unbranched). Unless stated otherwise specifically in the specification, an alkenyl group is unsubstituted or may be substituted by one or more substituents (e.g. one or more unsubstituted substituents) selected from Ci-₆-alkoxy, C3-8-cycloalkyl and C₆-io-aryl. It is generally preferred that the alkenyl group is unsubstituted.

[0017] The term “alkoxy” as used herein refers to a radical bonded through an oxygen atom of the formula -O-alkyl, where the alkyl group is defined above.

[0018] The term “aryl” as used herein refers to a radical derived from an aromatic monocyclic or polycyclic hydrocarbon ring system by removing a hydrogen atom from a ring carbon atom. The aromatic monocyclic or polycyclic hydrocarbon ring system contains only hydrogen atoms and carbon atoms, where at least one of the rings in the ring system is fully unsaturated (i.e. it contains a cyclic, delocalized (4n+2) tt-electron system in accordance with the Huckel theory). The ring system from which aryl groups may be derived include, for example, benzene, indane, indene, tetralin and naphthalene.

It is generally preferred that the aryl group is a phenyl group. Unless stated otherwise specifically in the specification, an aryl group is unsubstituted or may be substituted by one or more substituents (e.g. one or more unsubstituted substituents) selected from Ci-₆-alkyl, C2-6 alkenyl, Ci-₆-alkoxy and C3-8-cycloalkyl, preferably one or more substituents selected from Ci-₆-alkyl and Ci-₆-alkoxy. It is generally preferred that the aryl group is unsubstituted.

[0019] The term “aryloxy” as used herein refers to a radical bonded through an oxygen atom of the formula -O-aryl, where the aryl group is defined above.

[0020] The term “cycloalkyl” as used herein refers to a straight or branched hydrocarbon radical consisting of carbon and hydrogen atoms, and containing no unsaturation. A “C3-20 cycloalkyl” group contains three to twenty carbon atoms. In general, it is preferred that the cycloalkyl group is a C3-8-cycloalkyl group, particularly a C5-6-cycloalkyl group. Unless stated otherwise specifically in the specification, a cycloalkyl group is unsubstituted or may be substituted by one or more substituents (e.g. one or more unsubstituted substituents) selected from Ci-₆-alkoxy, Ci-₆-alkyl and C₆-io-aryl, preferably one or more substituents selected from Ci-₆-alkoxy and Ci-₆-alkyl. It is generally preferred that the cycloalkyl group is unsubstituted.

[0021] The term “cyclopentadienyl moiety” as used herein refers to a ring system comprising at least 5 ring carbon atoms and two conjugated carbon-carbon double bonds, such as, for example, shown in any one of formulae (A1) to (A3) herein. The cyclopentadienyl moiety may be monocyclic or polycyclic. When the cyclopentadienyl moiety is polycyclic, the cyclopentadienyl moiety may be fused polycyclic (e.g. the cyclopentadienyl moiety comprises two or more fused rings), preferably ortho-fused polycyclic (i.e. two rings have two, and only two, carbon atoms in common). Examples of cyclopentadienyl moieties that are fused polycyclic, particularly ortho-fused polycyclic, are indane, indene, octahydrofluorene (specifically, 1,2,3,4,5,6,7,8-octahydrofluorene) and fluorene. The term “cyclopentadienyl moiety” therefore embraces the terms “indenyl moiety” and “fluorenyl moiety”, unless it is clear from the context that the cyclopentadienyl moiety is not fused polycyclic. It is preferred that the cyclopentadienyl moiety is fused polycyclic and is an indenyl moiety or a fluorenyl moiety. Unless stated otherwise specifically in the specification, the cyclopentadienyl moiety is unsubstituted or may be substituted by one or more substituents (e.g. one or more unsubstituted substituents) selected from Ci-₆-alkyl, C2-6-alkenyl, C3-8-cycloalkyl, C₆-io-aryl and a silyl group, preferably substituted by one or more substituents selected from Ci-₆-alkyl, C₆-io-aryl and a silyl group, particularly Ci-₆-alkyl. It may be preferred that the cyclopentadienyl moiety is unsubstituted.

[0022] The term “isomer” as used herein in the context of a cyclopentadienyl moiety refers to the conjugate acid or acids of the cyclopentadienide moiety (i.e. the cyclopentadienyl moiety can be deprotonated to form a cyclopentadienide moiety). Thus, the term “isomer” in the context of a cyclopentadienyl moiety refers to a tautomer (e.g. a tautomer resulting from a [1 ,5]-sigmatropic shift of a hydrogen atom), such as any one of the tautomers of (A1) shown in (A1p) to (A1s) below for a cyclopentadienyl moiety and the conjugated double bond isomer of (A2) shown in (A2p) for an indenyl moiety. In principle, any one (or all) of the tautomers shown in (A1p) to (A1s) could replace the structural formula of (A1). Similarly, the tautomer shown in (A2p) could replace the structural formula of (A2).

[0023] In general, the cyclopentadienyl moiety may form part of a ligand precursor for a metallocene. The term “ligand” normally refers to the species that is coordinated to the metal in a metallocene. The term “ligand precursor” as used herein refers to an uncoordinated species that may be used to form the ligand, such as by a deprotonation step. The metallocene is typically prepared by a salt metathesis reaction between an alkali metal cyclopentadienide moiety in the ligand precursor and a transition metal halide.

[0024] The term “cyclopentadienide moiety” is synonymous with the term “moiety comprising a cyclopentadienide anion”. These terms refer to the anion formed from a cyclopentadienyl moiety by deprotonation (e.g. removal of a proton from a ring carbon atom of the cyclopentadienyl moiety). The cyclopentadienide moiety may be monocyclic or polycyclic, such as described above for the cyclopentadienyl moiety. Thus, the terms “cyclopentadienide moiety” and “moiety comprising a cyclopentadienide anion” embrace the terms “indenide moiety” and “fluorenide moiety”, unless the context indicates otherwise. The cyclopentadienide moiety has an aromatic ring because at least one of the rings in the ring system is fully unsaturated (i.e. it contains a cyclic, delocalized (4n+2) TT-electron system in accordance with the Huckel theory).

[0025] The term "indenyl moiety" as used herein refers to a ring system comprising at least 9 ring carbon atoms, where a benzene ring is fused with a cyclopentene ring, such as, for example, shown in formula (A2) herein. It is preferred that the indenyl moiety is bicyclic. Thus, the term “indenyl moiety” does not preferably embrace the term “fluorenyl moiety”. Unless stated otherwise specifically in the specification, the indenyl moiety is unsubstituted or may be substituted by one or more substituents (e.g. one or more unsubstituted substituents) selected from Ci-₆-alkyl, C2-6-alkenyl, C3-8-cycloalkyl, C₆-io-aryl and a silyl group, preferably substituted by one or more substituents selected from Ci-₆-alkyl, C₆-io-aryl and a silyl, particularly Ci-₆-alkyl. It may be preferred that the indenyl moiety is unsubstituted.

[0026] The term “fluorenyl moiety” as used herein refers to a ring system comprising at least 13 ring carbon atoms in which a cyclopentane ring is fused to two, separate benzene rings, such as, for example, shown in formula (A3) herein. It is preferred that the fluorenyl moiety is tricyclic. Unless stated otherwise specifically in the specification, the indenyl moiety is unsubstituted or may be substituted by one or more substituents (e.g. one or more unsubstituted substituents) selected from Ci-₆-alkyl, C2-6-alkenyl, C3-8-cycloalkyl, C₆-io-aryl and a silyl group, preferably substituted by one or more substituents selected from Ci-₆-alkyl, C₆-io-aryl and a silyl group, particularly Ci-₆-alkyl. It may be preferred that the indenyl moiety is unsubstituted. [0027] The terms “indenide moiety” and “fluorenide moiety” refer to the anion formed from a indenyl moiety and fluorenyl moiety respectively by deprotonation (e.g. removal of a proton from a ring carbon atom, particularly the cyclopentene ring of the indenyl moiety or the cyclopentane ring of the fluorenyl moiety). It is preferred that the term “indenide moiety” does not embrace the term “fluorenide moiety”.

[0028] Reference is made herein to an “optionally substituted ring” having a specified number of ring carbon atoms, such as, for example, a total of 6 to 9 ring carbon atoms. The ring may be unsubstituted or substituted, such as by one or more substituents selected from Ci-₆-alkyl, C2-6-alkenyl, optionally substituted C3-8-cycloalkyl, optionally substituted C₆-io-aryl and a silyl group. It is preferred that the substituents are unsubstituted substituents. More generally, it is preferred that the ring is unsubstituted.

[0029] The term “silyl” as used herein refers to a group comprising a silicon radical. The silicon atom may be substituted with one to three substituents, preferably unsubstituted substituents. Each substituent may be independently selected from hydrogen, Ci-₆-alkyl, C2-6-alkenyl, C3-8-cycloalkyl, C₆-io-aryl, Ci-₆-alkoxy and C₆-io-aryloxy. For example, the silyl group may be -SiH3, -SiHMe2, -SiMe2Ph or -Si(OEt)3. It is preferred that each substituent is independently selected from hydrogen, Ci-₆-alkyl and C₆-io-aryl, more preferably each substituent is selected from Ci-₆-alkyl and C₆-io-aryl. Thus, the silyl group may be (Ci-₆-alkyl)₃silyl, (Ci-₆-alkyl)₂(C₆-io-aryl)silyl or (Ci-₆-alkyl)(C₆-io-aryl)₂silyl. More preferably, the silyl group is (Ci-6-alkyl)3Silyl.

[0030] It should be understood that the term “catalyst” as referred to herein is used in a general sense and is not strictly limited to the actual catalytic species that participates in a chemical reaction. The term “catalyst” typically includes a “precatalyst”, which is a compound that is converted into the actual catalyst during the course of a reaction, particularly a catalysed reaction.

[0031] For the avoidance of doubt, the expression “consists essentially of’ as used herein limits the scope of a feature to include the specified materials, and any other materials or steps that do not materially affect the basic and novel characteristics of that feature, such as, for example, minor impurities. The expression “consists essentially of embraces the expression “consisting of”.

DETAILED DESCRIPTION

[0032] The invention provides a method for preparing or manufacturing a compound comprising a cyclopentadienyl moiety. The method is typically an industrial method. [0033] The compound comprising a cyclopentadienyl moiety is typically a ligand precursor, such as a ligand precursor for a metallocene (e.g. the preparation of a metallocene).

[0034] In general, the method is for preparing or manufacturing a compound comprising an ansa-bridged cyclopentadienyl moiety, preferably a compound comprising ansa- bridged cyclopentadienyl moieties, particularly a compound comprising two cyclopentadienyl moieties linked by an ansa-bridge.

[0035] The term “ansa” or “ansa-bridge” is normally used when the compound comprising a cyclopentadienyl moiety is coordinated to a metal as a ligand and refers to the moiety linking two coordinated cyclopentadienyl moieties. For the uncoordinated ligand precursor, the ansa-bridge may refer to the moiety that links the cyclopentadienyl moieties of the compound, such as -E¹- or -E¹-Q-E²- described below.

[0036] The method of the invention includes a step of deprotonating a cyclopentadienyl moiety represented by formula (A1) or an isomer thereof with an alkali hydroxide in a solution comprising a reducing agent.

(A1).

[0037] Cyclopentadienyl moieties of formula (A1) are commercially available or methods for their preparation are known in the art.

[0038] In formula (A1), each of R¹, R², R³ and R⁴ is independently selected from hydrogen, optionally substituted Ci-20-alkyl, optionally substituted C2-2o-alkenyl, optionally substituted C3-2o-cycloalkyl, optionally substituted C6-2o-aryl and a silyl group, or at least two adjacent R¹, R², R³ and R⁴ substituents form an optionally substituted ring having a total of 6 to 9 ring carbon atoms.

[0039] In general, the optionally substituted Ci-20-alkyl may be optionally substituted Ci-io-alkyl, preferably optionally substituted Ci-₆-alkyl, more preferably unsubstituted Ci-₆-alkyl, such as methyl, ethyl, propyl, butyl, pentyl or hexyl. [0040] The optionally substituted C_2-2o-alkenyl is typically an optionally substituted C₂-io-alkenyl, preferably optionally substituted C_2-6-alkenyl, more preferably unsubstituted C_2-6-alkenyl, such as vinyl, propenyl or butenyl.

[0041] Typically, the optionally substituted C_3-2o-cycloalkyl may be optionally substituted C_3-8-cycloalkyl, preferably optionally substituted C_3-6-cycloalkyl, more preferably unsubstituted C_3-6-cycloalkyl, such as cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

[0042] In general, the optionally substituted C_6-2o-aryl may be optionally substituted C₆-i₂-aryl, preferably optionally substituted C₆-io-aryl, more preferably unsubstituted C₆-io-aryl, such as phenyl or naphthyl. Even more preferably, the optionally substituted C_6-2o-aryl is optionally substituted phenyl, particularly unsubstituted phenyl.

[0043] The silyl group is typically substituted with three substituents, where each substituent is independently selected from hydrogen, Ci-₆-alkyl and C₆-io-aryl, more preferably each substituent is selected from Ci-₆-alkyl and C₆-io-aryl. It is preferred that the silyl group is (Ci-₆-alkyl)₃silyl, (Ci-₆-alkyl)₂(C₆-io-aryl)silyl or (Ci-₆-alkyl)(C₆-io-aryl)₂silyl. More, the silyl group is (Ci-₆-alkyl)_3Silyl, such as trimethylsilyl or triethylsilyl.

[0044] At least two adjacent R¹, R², R³ and R⁴ substituents form an optionally substituted ring having a total of 6 to 9 ring carbon atoms. Thus, in formula (A1):

(i) R¹ and R² form an optionally substituted ring having a total of 6 to 9 ring carbon atoms, and each of R³ and R⁴ is independently selected from hydrogen, optionally substituted Ci-₂₀-alkyl, optionally substituted C_2-2o-alkenyl, optionally substituted C_3-2o-cycloalkyl, optionally substituted C_6-2o-aryl and a silyl group; or

(ii) R¹ and R⁴ form an optionally substituted ring having a total of 6 to 9 ring carbon atoms, and each of R² and R³ is independently selected from hydrogen, optionally substituted Ci-₂₀-alkyl, optionally substituted C_2-2o-alkenyl, optionally substituted C_3-2o-cycloalkyl, optionally substituted C_6-2o-aryl and a silyl group; or

(ii) R³ and R⁴ form an optionally substituted ring having a total of 6 to 9 ring carbon atoms, and each of R¹ and R² is independently selected from hydrogen, optionally substituted Ci-₂₀-alkyl, optionally substituted C_2-2o-alkenyl, optionally substituted C_3-2o-cycloalkyl, optionally substituted C_6-2o-aryl and a silyl group; or (iv) R¹ and R² form an optionally substituted ring having a total of 6 to 9 ring carbon atoms, and R³ and R⁴ form an optionally substituted ring having a total of 6 to 9 ring carbon atoms.

[0045] When two adjacent R¹, R², R³ and R⁴ substituents form an optionally substituted ring, the cyclopentadienyl ring provides two carbon atoms of the 6 to 9 ring carbon atoms. [0046] In general, when at least two adjacent R¹, R², R³ and R⁴ substituents form an optionally substituted ring, then preferably the optionally substituted ring has a total of 6 to 8 ring carbon atoms, more preferably the optionally substituted ring has total of 6 ring carbon atoms. The optionally substituted ring having a total of 6 ring atoms may be a benzene ring or a cyclohexene ring, preferably a benzene ring. One of the unsaturated carbon-carbon double bonds in the benzene ring or the unsaturated carbon-carbon double bond in the cyclohexene ring is from the cyclopentadienyl ring, as shown in formula (A1).

[0047] In the method of the invention, step (a) of deprotonating a cyclopentadienyl moiety or an isomer thereof is to prepare a compound comprising a deprotonated cyclopentadienyl moiety (e.g. a compound comprising a cyclopentadienide moiety), such as a compound of formula (A1a):

wherein each of R¹, R², R³ and R⁴ is as defined herein.

[0048] It has surprisingly been found that the combination of an alkali hydroxide base and a reducing agent can deprotonate the cyclopentadienyl moiety to produce a cyclopentadienide moiety. Using this combination, the most acidic proton in a cyclopentadienyl moiety can be removed. In comparison to the use of organolithium reagents as bases, the alkali hydroxide base can be used under considerably milder reaction conditions and can be used on an industrial scale.

[0049] An alkali hydroxide is the hydroxide of an alkali metal (e.g. metal from Group 1 of the Period Table) or an alkaline earth metal (e.g. metal from Group 2 of the Periodic Table). It is preferred that the alkali hydroxide is a hydroxide of an alkali metal (e.g. Group 1 metal).

[0050] When the alkali hydroxide is a hydroxide of an alkali metal, then the alkali hydroxide is sodium hydroxide (NaOH), potassium hydroxide (KOH), rubidium hydroxide (RbOH) or caesium hydroxide (CsOH), preferably sodium hydroxide or potassium hydroxide. The alkali hydroxide may be sodium hydroxide. The alkali hydroxide may be potassium hydroxide. [0051] When the alkali hydroxide is a hydroxide of an alkaline earth metal, then the alkali hydroxide is calcium hydroxide (Ca(OH)2).

[0052] Step (a) of the method involves the use of a reducing agent. Without wishing to be bound by theory, it is believed that the reducing agent safeguards the presence of the cyclopentadienide moiety and can prevent the formation of undesirable radical intermediates, particularly when it is reacted with a compound having an electrophilic site. Poor yields of the desired product are usually obtained when the method is performed without the reducing agent.

[0053] The reducing agent may be selected from a hydride reducing agent and an alkaline earth metal. It is preferred that the reducing agent is an alkaline earth metal.

[0054] When the reducing agent is a hydride reducing agent, then the hydride reducing agent may be a borohydride reducing agent or an aluminium hydride reducing agent.

[0055] The borohydride reducing agent may, for example, be selected from a tetrahydroborate (BhU , e.g. MBhU, where M is an alkali metal, preferably Na, Li or K), a trihydrocyanoborate (BH3CN , e.g. MBH3CN, where M is an alkali metal, preferably Na), a trialkyl hydroborate, such as a triethyl hydroborate (BH(Et)3 , e.g. MBH(Et)3, where M is an alkali metal, preferably lithium) or a tributyl hydroborate (e.g. BH(^sBu)3 , such as MBH(^SBU)3, where M is an alkali metal, preferably Li), and a triacetoxyborohydride (BH(OAC)₃-, e.g. MBH(OAc)₃, where M is Na).

[0056] The aluminium hydride reducing agent may, for example, be selected from a tetrahydroaluminate (AIH₄ , such as MAIH₄, where M is an alkali metal, preferably Li) and a trialkoxyhydroaluminate, such as a tributyl hydroaluminate (e.g. AIH(0‘Bu)₃ , such as MAIH(0‘BU)₃, where M is alkali metal, preferably Li).

[0057] When the reducing agent is a hydride reducing agent, then it is preferred that the reducing agent is a borohydride reducing agent, more preferably a tetrahydroborate, such as sodium borohydride. Borohydride reducing agents can, in general, be used under milder reaction conditions and are less pyrophoric than aluminium hydride reducing agents.

[0058] The reducing agent may be an alkaline earth metal, such as calcium or magnesium (i.e. calcium or magnesium in elemental, metallic form). When the reducing agent is an alkaline earth metal, then it is preferred that the alkaline earth metal is calcium. It has been found that excellent yields of the product can be obtained when calcium is used as the reducing agent. [0059] For the avoidance of doubt, the method of the first aspect of the invention, particularly the step of deprotonating a cyclopentadienyl moiety as described herein, does not involve the use or addition of an organolithium reagent. Examples of organolithium reagents include, but are not limited to, methyllithium, ethyllithium, isopropyllithium, phenyllithium, n-butyllithium and f-butyllithium.

[0060] Typically, in step (a) of the method, the solution comprising an alkali hydroxide and a reducing agent does not comprise an organolithium reagent.

[0061] In step (a) of the method, the solution may further comprise an aprotic solvent, preferably a dipolar aprotic solvent. The dipolar aprotic solvent may be dimethyl sulfoxide (DMSO), acetonitrile, hexamethylphosphoramide (HMPA), dimethoxyethane (DME) or an amide-type solvent, such as L/,L/’-dimethylpropyleneurea (DMPU), dimethylformamide (DMF), 1,3-dimethyl-2-imidazolidinone (DMI), dimethylacetamide (DMA) or A/-methyl-2- pyrrolidone (NMP). It is preferred that the dipolar aprotic solvent is dimethyl sulfoxide.

[0062] The step of (a) deprotonating the cyclopentadienyl moiety or an isomer thereof may include stirring the cyclopentadienyl moiety or the isomer in the solution comprising an alkali hydroxide and the reducing agent. Thus, the solution for stirring typically comprises the cyclopentadienyl moiety, the alkali hydroxide and the reducing agent.

[0063] The solution may be stirred at a temperature of ³ 0°C. The solution may be stirred at a temperature from 5°C to 50°C, preferably 10°C to 35°C, more preferably 15°C to 25°C or at least at room temperature (e.g. 20°C). As mentioned above, it is not necessary to use low temperatures to perform the deprotonation step, unlike when organolithium reagents are used as a base. This avoids the practical inconvenience, hazards and cost of having to cool the reaction solution.

[0064] The solution should be stirred at a temperature that is greater than the melting point of the solvent.

[0065] The solution may be stirred for at least 3 hours, preferably at least 6 hours, such as at least 12 hours. The stirring time will depend on the scale of the reaction (e.g. the molar quantities of reactants), the composition of the cyclopentadienyl moiety, the reaction temperature and the solvent.

[0066] Step (a) of the method may include adding the cyclopentadienyl moiety or an isomer thereof to, or admixing the cyclopentadienyl moiety or an isomer thereof with, the solution comprising an alkali hydroxide and a reducing agent. Alternatively, the solution comprising the alkali hydroxide and the reducing agent may be added to, or admixed with, the cyclopentadienyl moiety or an isomer thereof.

[0067] In step (a) of the method, the molar ratio of the alkali hydroxide to the cyclopentadienyl moiety (e.g. when the alkali hydroxide is monobasic) may be ³ 1.1:1.

The molar ratio of the alkali hydroxide to the cyclopentadienyl moiety or an isomer thereof is typically 1.1:1 to 2.5: 1 , such as 1.2:1 to 2.0: 1 , preferably 1.3: 1 to 1.8: 1 (e.g. about 1.5:1). The base should be present in a molar excess to the cyclopentadienyl moiety or the isomer thereof to ensure complete deprotonation.

[0068] When the alkali hydroxide is dibasic (e.g. Ca(OH)2), then the molar ratio of the alkali hydroxide to the cyclopentadienyl moiety may be ³ 0.6:1. The molar ratio of the alkali hydroxide to the cyclopentadienyl moiety is typically 0.6:1 to 1.3:1, such as 0.7:1 to 1.1:1, preferably 0.7:1 to 0.9:1 (e.g. about 0.8:1).

[0069] In step (a) of the method, the molar ratio of the cyclopentadienyl moiety or an isomer thereof to the reducing agent may be 25:1 to 2.5:1, such as 20:1 to 5:1, preferably 15:1 to 7.5:1 (e.g. about 10:1). The molar ratio that is used when the reducing agent is an alkaline earth metal is typically same as the molar ratio that is used when the reducing agent is a hydride reducing agent.

[0070] In the method of the invention, step (a) may be performed under an inert gas.

The inert gas may, for example, be nitrogen (N2) or argon (Ar). It is preferred that the inert gas is nitrogen (N2).

[0071] The inert gas may be substantially free of oxygen, preferably oxygen and water. The term “substantially free” in this context refers to the purity of the inert gas, which is typically at least 99.9% (e.g. total impurities £ 1000 ppm), preferably at least 99.99% (e.g. total impurities £ 100 vpm).

[0072] The solvent may be a degassed solvent, preferably degassed for the removal or reduction of oxygen and/or water in the solvent. The solvent may have been degassed in the presence of an inert gas, such as the inert gas described above.

[0073] In general, it is preferred that the cyclopentadienyl moiety represented by formula (A1) or an isomer thereof is substituted. Thus, at least one of R¹, R², R³ and R⁴ is not hydrogen.

[0074] Typically, at least one of R¹, R², R³ and R⁴ is independently selected from optionally substituted Ci-20-alkyl, optionally substituted C2-2o-alkenyl, optionally substituted C3-2o-cycloalkyl, optionally substituted C6-2o-aryl and a silyl group, or two adjacent R¹, R², R³ and R⁴ substituents form an optionally substituted ring having a total of 6 to 9 ring carbon atoms. It is preferred that at least one of R¹, R², R³ and R⁴ is independently selected from optionally substituted Ci-20-alkyl, optionally substituted C6-2o-aryl and a silyl group, or at least two adjacent R¹, R², R³ and R⁴ substituents form an optionally substituted ring having a total of 6 to 9 ring carbon atoms.

[0075] In a first embodiment of the invention, in formula (A1), each of R¹, R², R³ and R⁴ is independently selected from hydrogen, optionally substituted Ci-20-alkyl, optionally substituted C2-2o-alkenyl, optionally substituted C3-2o-cycloalkyl, optionally substituted C6-2o-aryl and a silyl group. Thus, the cyclopentadienyl moiety of formula (A1) or an isomer thereof is monocyclic or is non-fused polycyclic (e.g. when one of R¹, R², R³ or R⁴ is optionally substituted C6-2o-aryl).

[0076] Generally, it is preferred that at least one of R¹, R², R³ and R⁴ is not hydrogen. Thus, at least one of R¹, R², R³ and R⁴ is independently selected from optionally substituted Ci-20-alkyl, optionally substituted C2-2o-alkenyl, optionally substituted C3-2o-cycloalkyl, optionally substituted C6-2o-aryl and a silyl group. It is preferred that at least one of R¹, R², R³ and R⁴ is independently selected from optionally substituted Ci-2o-alkyl, optionally substituted C6-2o-aryl and a silyl group.

[0077] In the first embodiment, the cyclopentadienyl moiety of formula (A1) or an isomer thereof may be monocyclic (e.g. not polycyclic). Thus, R¹, R², R³ and R⁴ are not optionally substituted C6-2o-aryl.

[0078] When the cyclopentadienyl moiety of formula (A1) or an isomer thereof is monocyclic, then each of R¹, R², R³ and R⁴ is independently selected from hydrogen, optionally substituted Ci-20-alkyl, optionally substituted C2-2o-alkenyl, optionally substituted C3-2o-cycloalkyl and a silyl group. It is preferred that each of R¹, R², R³ and R⁴ is independently selected from hydrogen, optionally substituted Ci-20-alkyl and a silyl group.

[0079] The monocyclic cyclopentadienyl moiety of formula (A1) or an isomer thereof may be unsubstituted (e.g. R¹, R², R³ and R⁴ are hydrogen).

[0080] Before step (a), the method may include a step of cracking a dimer (e.g. of the cyclopentadienyl moiety represented by formula (A1)) to form a monomer of the cyclopentadienyl moiety. For example, it may be necessary to crack a dicyclopentadiene dimer before deprotonating the cyclopentadiene monomer.

[0081] Alternatively, in the first embodiment, at least one of R¹, R², R³ and R⁴ may be independently selected from optionally substituted Ci-20-alkyl, optionally substituted C2-2o-alkenyl, optionally substituted C3-2o-cycloalkyl and a silyl group. More preferably, at least one of R¹, R², R³ and R⁴ is independently selected from optionally substituted Ci-2o-alkyl and a silyl group. Thus, the monocyclic cyclopentadienyl moiety of formula (A1) or an isomer thereof is a substituted monocyclic cyclopentadienyl moiety.

[0082] Generally, it is preferred that the cyclopentadienyl moiety is either substituted when monocyclic or is polycyclic. This can reduce the likelihood of the moiety dimerising during deprotonation.

[0083] The monocyclic cyclopentadienyl moiety of formula (A1) or an isomer thereof may, for example, be 1,2,3,4-tetramethyl-1,3-cyclopentadiene (e.g. R¹, R², R³ and R⁴ are methyl), trimethylsilyl-cyclopentadiene (one of R¹, R², R³ and R⁴ is trimethylsilyl and the others are hydrogen) or 1,2,3,4-tetraphenyl-1,3-cyclopentadiene (e.g. R¹, R², R³ and R⁴ are phenyl).

[0084] In a second embodiment, in formula (A1), two adjacent R¹, R², R³ and R⁴ substituents (e.g. only two adjacent R¹, R², R³ and R⁴ substituents) form an optionally substituted ring having a total of 6 to 9 ring carbon atoms. Thus, either:

(i) R¹ and R² form an optionally substituted ring having a total of 6 to 9 ring carbon atoms, and each of R³ and R⁴ is independently selected from hydrogen, optionally substituted Ci-20-alkyl, optionally substituted C2-2o-alkenyl, optionally substituted C3-2o-cycloalkyl, optionally substituted C6-2o-aryl and a silyl group; or

(ii) R¹ and R⁴ form an optionally substituted ring having a total of 6 to 9 ring carbon atoms, and each of R² and R³ is independently selected from hydrogen, optionally substituted Ci-20-alkyl, optionally substituted C2-2o-alkenyl, optionally substituted C3-2o-cycloalkyl, optionally substituted C6-2o-aryl and a silyl group; or

(iii) R³ and R⁴ form an optionally substituted ring having a total of 6 to 9 ring carbon atoms, and each of R¹ and R² is independently selected from hydrogen, optionally substituted Ci-20-alkyl, optionally substituted C2-2o-alkenyl, optionally substituted C3-2o-cycloalkyl, optionally substituted C6-2o-aryl and a silyl group; or

[0085] In the second embodiment, the optionally substituted ring may have a total of 6 to 8 ring carbon atoms, preferably the optionally substituted ring has total of 6 ring carbon atoms. The optionally substituted ring having a total of 6 ring atoms may be a benzene ring or a cyclohexene ring, preferably a benzene ring.

[0086] It is preferred that R³ and R⁴ form an optionally substituted ring having a total of 6 ring carbon atoms. [0087] When R³ and R⁴ form an optionally substituted ring having a total of 6 ring carbon atoms, the resulting cyclopentadienyl moiety or indenyl moiety may be represented by formula (A2):

wherein: each of R¹ and R² is independently selected from hydrogen, optionally substituted Ci-2o-alkyl, optionally substituted C2-2o-alkenyl, optionally substituted C3-2o-cycloalkyl, optionally substituted C6-2o-aryl and a silyl group, or R¹ and R² form an optionally substituted ring having a total of 6 to 9 ring carbon atoms; and each of R^3A, R^3B, R^4A and R^4B is independently selected from hydrogen, optionally substituted Ci-₆-alkyl, optionally substituted C2-6-alkenyl, optionally substituted C3-8-cycloalkyl, optionally substituted C₆-io-aryl and a silyl group, or at least two adjacent R^3A, R^3B, R^4A and R^4B substituents form an optionally substituted ring having a total of 6 to 8 ring carbon atoms.

[0088] Each of R¹ and R² may be independently selected from hydrogen, optionally substituted Ci-20-alkyl, optionally substituted C2-2o-alkenyl, optionally substituted C3-2o-cycloalkyl, optionally substituted C6-2o-aryl and a silyl group. It is preferred that each of R¹ and R² is independently selected from hydrogen, optionally substituted Ci-20-alkyl, optionally substituted C6-2o-aryl and a silyl group. More preferably, that each of R¹ and R² is independently selected from hydrogen, optionally substituted Ci-20-alkyl and a silyl group. Even more preferably each of R¹ and R² is independently selected from hydrogen and optionally substituted Ci-20-alkyl. Still more preferably, R¹ is hydrogen and R² is hydrogen.

[0089] In a third embodiment, in formula (A2), R¹ and R² may form an optionally substituted ring having a total of 6 to 9 ring carbon atoms. The optionally substituted ring may have a total of 6 to 8 ring carbon atoms, preferably the optionally substituted ring has total of 6 ring carbon atoms. The optionally substituted ring having a total of 6 ring atoms may be a benzene ring or a cyclohexene ring, preferably a benzene ring. [0090] When R¹ and R² form an optionally substituted ring having a total of 6 ring carbon atoms, then the resulting cyclopentadienyl moiety or fluorenyl moiety may be represented by formula (A3):

wherein: each of R^1A, R^1B, R^2A and R^2B is independently selected from hydrogen, optionally substituted Ci-₆-alkyl, optionally substituted C2-6-alkenyl, optionally substituted C3-8-cycloalkyl, optionally substituted C₆-io-aryl and a silyl group, or at least two adjacent

R^IA, R^1B, R^2A and R^2B substituents form an optionally substituted ring having a total of 6 to 8 ring carbon atoms, and wherein R^3A, R^3B, R^4A and R^4B are as defined above for formula (A2).

[0091] When at least two adjacent R^1A, R^1B, R^2A and R^2B substituents and/or at least two adjacent R^3A, R^3B, R^4A and R^4B substituents form an optionally substituted ring, then it is preferred that each optionally substituted ring has a total of 6 to 8 ring carbon atoms, preferably each optionally substituted ring has total of 6 ring carbon atoms. More preferably, the ring is unsubstituted.

[0092] When each substituted or unsubstituted ring has a total of 6 ring atoms, then the ring may be a benzene ring or a cyclohexene ring, preferably a benzene ring.

[0093] In the second and third embodiments, it is generally preferred that each of R^1A,

R^IB, R^2A and R^2B is independently selected from hydrogen, optionally substituted Ci-₆-alkyl, optionally substituted C2-6-alkenyl, optionally substituted C3-8-cycloalkyl, optionally substituted C₆-io-aryl and a silyl group. More preferably, each of R^1A, R^1B, R^2A and R^2B is independently selected from hydrogen, optionally substituted Ci-₆-alkyl, optionally substituted C₆-io-aryl and a silyl group. It is further preferred that each of R^1A, R^1B, R^2A and R^2B is independently selected from hydrogen, optionally substituted Ci-20-alkyl and a silyl group. Even more preferably each of R^1A, R^1B, R^2A and R^2B is independently selected from hydrogen and optionally substituted Ci-20-alkyl. Still more preferably, each of R^1A, R^1B, R^2A and R^2B is hydrogen. [0094] In the third embodiment, it is generally preferred that each of R^3A, R^3B, R^4A and R^4B is independently selected from hydrogen, optionally substituted Ci-₆-alkyl, optionally substituted C2-6-alkenyl, optionally substituted C3-8-cycloalkyl, optionally substituted C₆-io-aryl and a silyl group. More preferably, each of R^3A, R^3B, R^4A and R^4B is independently selected from hydrogen, optionally substituted Ci-₆-alkyl, optionally substituted C₆-io-aryl and a silyl group. It is further preferred that each of R^3A, R^3B, R^4A and R^4B is independently selected from hydrogen, optionally substituted Ci-20-alkyl and a silyl group. Even more preferably each of R^3A, R^3B, R^4A and R^4B is independently selected from hydrogen and optionally substituted Ci-20-alkyl. Still more preferably, each of R^3A, R^3B, R^4A and R^4B is hydrogen.

[0095] In the third embodiment, each of R^1A, R^1B, R^2A, R^2B, R^3A, R^3B, R^4A and R^4B may be hydrogen.

[0096] The method of the invention includes a step (b) of reacting the deprotonated cyclopentadienyl moiety with a compound having an electrophilic site.

[0097] In principle, the cyclopentadienide moiety formed from the deprotonation step can be reacted with any type of compound having an electrophilic site. Generally, it is preferred that the compound having an electrophilic site is an organic compound for forming a ligand precursor.

[0098] It is preferred that the compound having an electrophilic site is not a transition metal compound.

[0099] Typically, the electrophilic site is a carbon atom or a silicon atom, such as either (a) a carbon atom or the silicon atom bonded to a leaving group or (b) a carbon atom in carbon-carbon double bond. There are several classes of compound that may be a compound having an electrophilic site for use in the method of the invention.

[0100] The compound having an electrophilic site may be selected from (i) a compound having a least one carbon atom bonded to a leaving group, (ii) a compound having at least one silicon atom bonded to a leaving group, and (iii) a fulvene (e.g. an optionally substituted fulvene).

[0101] The compound having an electrophilic site may be represented by formula (L1):

wherein:

E¹ is selected from a carbon atom and a silicon atom; each of X¹ and X² is a leaving group; each of R⁵ and R⁶ is independently selected from hydrogen, optionally substituted Ci-2o-alkyl, optionally substituted C2-2o-alkenyl, optionally substituted C3-2o-cycloalkyl, optionally substituted C6-2o-aryl and a silyl group, or R⁵ and R⁶ form an optionally substituted ring having a total of 3 to 9 ring carbon atoms.

[0102] The compound of formula (L1) is an example of a compound having a least one carbon atom or silicon atom bonded to a leaving group.

[0103] The deprotonated cyclopentadienyl moiety may react with the compound of formula (L1) to perform a nucleophilic substitution at E¹ of X¹ and/or X². X¹ and X² are leaving groups, such as halides or sulfonate anions.

[0104] Each of X¹ and X² may be independently selected from a halogen atom or a sulfonate ester (e.g. -OSO2-R).

[0105] The halogen atom may be chlorine, bromine or iodine, preferably chlorine or bromine. The sulfonate ester may be tosylate, mesylate, brosylate, triflate or nosylate.

[0106] It is preferred that each of X¹ and X² is independently selected from a halogen atom. More preferably, each of X¹ and X² is chlorine or bromine.

[0107] When E¹ is a carbon atom, then preferably X¹ and X² are bromine.

[0108] X¹ and X² may be the same or different. It is preferred that X¹ and X² are the same.

[0109] It may be preferable that E¹ is a silicon atom. Thus, the compound having an electrophilic site may be represented by formula (L1 a):

wherein X¹, X², R⁵ and R⁶ are as defined above.

[0110] In formula (L1) or formula (L1a), R⁵ and R⁶ may be the same or different. It is preferred that R⁵ and R⁶ are the same.

[0111] Preferably, each of R⁵ and R⁶ is independently selected from hydrogen, optionally substituted Ci-20-alkyl, optionally substituted C2-2o-alkenyl, optionally substituted C_3-2o-cycloalkyl, optionally substituted C_6-2o-aryl and a silyl group. More preferably, each of R⁵ and R⁶ is independently selected from hydrogen, optionally substituted Ci-₂₀-alkyl, optionally substituted C_6-2o-aryl and a silyl group. It is further preferred that each of R⁵ and R⁶ is independently selected from hydrogen, optionally substituted Ci-₂₀-alkyl and optionally substituted C_6-2o-aryl. Even more preferably, each of R⁵ and R⁶ is independently selected from optionally substituted Ci-₂₀-alkyl, preferably unsubstituted Ci-₂o-alkyl, such as methyl or ethyl.

[0112] When a compound of formula (L1) is used, then the method of the invention may be a method for preparing a compound comprising a cyclopentadienyl moiety represented by formula (C1) or an isomer thereof:

wherein:

E¹, R⁵ and R⁶ are as defined above for formula (L1) or formula (L1a);

R¹, R², R³ and R⁴ are as defined above for formula (A1), formula (A2) or formula (A3); and each of R⁹, R¹⁰, R¹¹ and R¹² is independently selected from hydrogen, optionally substituted Ci-₂₀-alkyl, optionally substituted C_2-2o-alkenyl, optionally substituted C_3-2o-cycloalkyl, optionally substituted C_6-2o-aryl and a silyl group, or at least two adjacent R⁹, R¹⁰, R¹¹ and R¹² substituents form an optionally substituted ring having a total of 6 to 9 ring carbon atoms.

[0113] When the compound having an electrophilic site is represented by formula (L1a) above, then the method of the invention may be a method for preparing a compound comprising a cyclopentadienyl moiety represented by formula (C1a) or an isomer thereof:

wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁹, R¹⁰, R¹¹ and R¹² are as defined herein.

[0114] In general, it is preferred that the cyclopentadienyl moieties in each of formula (C1) and formula (C1a) are the same.

[0115] Typically, R⁹ is the same as R¹, R¹⁰ is the same as R², R¹¹ is the same as R³, and R¹² is the same as R⁴. Thus, the method of the invention relates to a method of preparing a compound comprising a cyclopentadienyl moiety as represented by formula (C1c), formula (C1d) or an isomer thereof.

[0116] When the cyclopentadienyl moiety in step (a) of the method (e.g. is deprotonated in the solution) is an indenyl moiety represented by formula (A2), then the method of the invention relates to a method of preparing a compound comprising a cyclopentadienyl moiety or an indenyl moiety as represented by formula (C1e), formula (C1f) or an isomer thereof:

wherein E¹, R¹, R², R^3A, R^3B, R^4A, R^4B, R⁵ and R⁶ are as defined above.

[0117] When the cyclopentadienyl moiety in step (a) of the method (e.g. is deprotonated in the solution) is a fluorenyl moiety represented by formula (A3), then the method of the invention relates to a method of preparing a compound comprising a cyclopentadienyl moiety or a fluorenyl moiety as represented by formula (C1g), formula (C1h) or an isomer thereof:

[0118] Alternatively, the compound having an electrophilic site may be represented by formula (L2):

wherein:

E¹ and E² is each independently selected from a carbon atom and a silicon atom; each of X¹ and X² is a leaving group;

Q is a single bond or is a chain of 1 to 5 atoms in length, wherein each atom is a carbon atom or a silicon atom; each of R⁵, R⁶, R⁷ and R⁸ is independently selected from hydrogen, optionally substituted Ci-20-alkyl, optionally substituted C2-2o-alkenyl, optionally substituted C3-2o-cycloalkyl, optionally substituted C6-2o-aryl and a silyl group, or two geminal or vicinal substituents from R⁵, R⁶, R⁷, R⁸ or a substituent of Q form an optionally substituted ring having a total of 5 to 9 ring carbon atoms.

[0119] The compound of formula (L2) is also an example of a compound having a least one carbon atom bonded to a leaving group.

[0120] The deprotonated cyclopentadienyl moiety may react with the compound of formula (L2) to perform a nucleophilic substitution at E¹ of X¹ and/or a nucleophilic substitution at E³ of X². X¹ and X² are leaving groups, such as halides or sulfonate anions.

[0121] Each of X¹ and X² may be independently selected from a halogen atom or a sulfonate ester (e.g. -OSO2-R).

[0122] The halogen atom may be chlorine, bromine or iodine, preferably chlorine or bromine. The sulfonate ester may be tosylate, mesylate, brosylate, triflate or nosylate.

[0123] It is preferred that each of X¹ and X² is independently selected from a halogen atom. More preferably, each of X¹ and X² is chlorine or bromine.

[0124] X¹ and X² may be the same or different. It is preferred that X¹ and X² are the same.

[0125] Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independently selected from hydrogen, optionally substituted Ci-20-alkyl, optionally substituted C2-2o-alkenyl, optionally substituted C3-2o-cycloalkyl, optionally substituted C6-2o-aryl and a silyl group. More preferably, each of R⁵, R⁶, R⁷ and R⁸ is independently selected from hydrogen, optionally substituted Ci-2o-alkyl, optionally substituted C6-2o-aryl and a silyl group. It is further preferred that each of R⁵, R⁶, R⁷ and R⁸ is independently selected from hydrogen and optionally substituted Ci-20-alkyl, such as unsubstituted Ci-20-alkyl, particularly methyl or ethyl. Even more preferably, each of R⁵, R⁶, R⁷ and R⁸ is hydrogen.

[0126] R⁵ and R⁶ may be the same or different. It is preferred that R⁵ and R⁶ are the same (i.e. R⁵ = R⁶).

[0127] R⁷ and R⁸ may be the same or different. It is preferred that R⁷ and R⁸ are the same (i.e. R⁷ = R⁸). More preferably, R⁵, R⁶, R⁷ and R⁸ are the same (i.e. R⁵ = R⁶ = R⁷ = R⁸).

[0128] Q is a single bond or is a chain of 1 to 5 atoms in length, wherein each atom is a carbon atom or a silicon atom. The chain of 1 to 5 atoms in length is preferably a hydrocarbon chain (e.g. each atom is a carbon atom). More preferably, Q is a single bond, methylene (e.g. -CH2-), or ethylene (e.g. -CH2-CH2-). Even more preferably, Q is a single bond or methylene (e.g. -CH2-). Most preferably, Q is a single bond.

[0129] When Q is a single bond, then the compound having an electrophilic site may be represented by formula (L2a):

(L2a).

[0130] In formula (L2) or formula (L2a), E¹ and E² may be the same or different. It is preferred that E¹ and E² are the same.

[0131] E¹ may be a silicon atom and E² may be a selected from a carbon atom and a silicon atom.

[0132] It is preferred that E¹ and E² are carbon atoms. The compound having an electrophilic site may therefore be represented by formula (L2b) or (L2c):

(L2b) (L2c) where Q, X¹, X², R⁵, R⁶, R⁷ and R⁸ are as defined above. [0133] The compound of formula (L2b) may, for example, be 1,3-dichloropropane; 1,3- dibromopropane; 1,4-dichlorobutane; 1,4-dibromobutane; or bis(chloromethyl)- dimethylsilane.

[0134] The compound of formula (L2c) may be 1 ,2-dichloroethane or 1 ,2-bromoethane.

[0135] When a compound of formula (L2) is used, then the method of the invention may be a method for preparing a compound comprising a cyclopentadienyl moiety represented by formula (C2) or an isomer thereof:

wherein:

E¹, E², Q, R⁵, R⁶, R⁷ and R⁸ are as defined above for formula (L2), formula (L2a), formula (L2b) or formula (L2c);

R¹, R², R³ and R⁴ are as defined above for formula (A1), formula (A2) or formula (A3); and each of R⁹, R¹⁰, R¹¹ and R¹² is independently selected from hydrogen, optionally substituted Ci-20-alkyl, optionally substituted C2-2o-alkenyl, optionally substituted C3-2o-cycloalkyl, optionally substituted C6-2o-aryl and a silyl group, or at least two adjacent R⁹, R¹⁰, R¹¹ and R¹² substituents form an optionally substituted ring having a total of 6 to 9 ring carbon atoms.

[0136] When the compound having an electrophilic site is represented by formula (L2a) above, then the method of the invention may be a method for preparing a compound comprising a cyclopentadienyl moiety represented by formula (C2a) or an isomer thereof:

wherein E¹, E² are as defined above, and R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹ and R¹² are as defined herein.

[0137] The method of the invention may be a method for preparing a compound comprising a cyclopentadienyl moiety represented by formula (C2b) or an isomer thereof, when the compound having an electrophilic site is represented by formula (L2b) above.

[0138] The method of the invention may be a method for preparing a compound comprising a cyclopentadienyl moiety represented by formula (C2c) or an isomer thereof, when the compound having an electrophilic site is represented by formula (L2c) above.

[0139] In general, it is preferred that the cyclopentadienyl moieties in each of formula (C2), formula (C2a), formula (C2b) and formula (C2c) are the same. [0140] Typically, R⁹ is the same as R¹, R¹⁰ is the same as R², R¹¹ is the same as R³, and R¹² is the same as R⁴. Thus, the method of the invention relates to a method of preparing a compound comprising a cyclopentadienyl moiety as represented by formula (C2d), formula (C2e) or an isomer thereof.

[0141] When the cyclopentadienyl moiety in step (a) of the method (e.g. is deprotonated in the solution) is an indenyl moiety represented by formula (A2), then the method of the invention relates to a method of preparing a compound comprising a cyclopentadienyl moiety or an indenyl moiety as represented by formula (C2f), formula (C2g) or an isomer thereof:

wherein

as defined above. [0142] When each of E¹ and E² is a carbon atom, then the method of the invention relates to a method of preparing a compound comprising a cyclopentadienyl moiety or an indenyl moiety as represented by formula (C2h), formula (C2i) or an isomer thereof.

[0143] It is preferred that the method of the invention is a method of preparing 1 ,2-bis(3- indenyl)ethane. [0144] When the cyclopentadienyl moiety in step (a) of the method (e.g. is deprotonated in the solution) is a fluorenyl moiety represented by formula (A3), then the method of the invention relates to a method of preparing a compound comprising a cyclopentadienyl moiety or a fluorenyl moiety as represented by formula (C2j), formula (C2k) or an isomer thereof:

wherein

are as defined above.

[0145] When each of E¹ and E² is a carbon atom, then the method of the invention relates to a method of preparing a compound comprising a cyclopentadienyl moiety or an indenyl moiety as represented by formula (C2I), formula (C2m) or an isomer thereof.

[0146] It is preferred that the method of the invention is a method of preparing 1 ,2-bis(3- indenyl)ethane.

[0147] In another example of the invention, the compound having an electrophilic site may be represented by formula (L3):

wherein: each of R⁵ and R⁶ is independently selected from hydrogen, optionally substituted Ci-2o-alkyl, optionally substituted C2-2o-alkenyl, optionally substituted C3-2o-cycloalkyl, optionally substituted C6-2o-aryl, and a silyl group, or R⁵ and R⁶ form an optionally substituted ring having a total of 5 to 9 ring carbon atoms; and each of R⁹, R¹⁰, R¹¹ and R¹² is independently selected from hydrogen, optionally substituted Ci-20-alkyl, optionally substituted C2-2o-alkenyl, optionally substituted C3-2o-cycloalkyl, optionally substituted C6-2o-aryl and a silyl group, or at least two adjacent R⁹, R¹⁰, R¹¹ and R¹² substituents form an optionally substituted ring having a total of 6 to 9 ring carbon atoms.

[0148] The deprotonated cyclopentadienyl moiety may react with the compound of formula (L3) to perform a nucleophilic addition reaction at the carbon atom with the R⁵ and R⁶ substituents. As a result of the nucleophilic addition reaction, a cyclopentadienide anion may be generated in the cyclopentadienyl moiety of the compound of formula (L3).

[0149] The compound of formula (L3) is a fulvene. Such compounds are known in the art. It is also known that some fulvenes dimerise at room temperature.

[0150] Typically, the compound of formula (L3) is a monomer or is monomeric (i.e. it is not a dimer, such as a fulvene dimer), preferably at room temperature (e.g. 20°C).

[0151] It is preferred that each of R⁵ and R⁶ is independently selected from hydrogen, optionally substituted Ci-20-alkyl, optionally substituted C6-2o-aryl, and a silyl group, or R⁵ and R⁶ form an optionally substituted ring having a total of 5 to 9 ring carbon atoms, preferably 5 or 6 ring carbon atoms.

[0152] In general, for a compound for formula (L3), it is preferred that each of R⁵ and R⁶ is not hydrogen. Thus, each of R⁵ and R⁶ is independently selected from optionally substituted Ci-20-alkyl, optionally substituted C6-2o-aryl and a silyl group, or R⁵ and R⁶ form an optionally substituted ring having a total of 5 to 9 ring carbon atoms, preferably 5 or 6 ring carbon atoms. More preferably, each of R⁵ and R⁶ is independently selected from optionally substituted Ci-20-alkyl and optionally substituted C6-2o-aryl. Even more preferably, each of R⁵ and R⁶ is independently selected from methyl, ethyl and phenyl.

[0153] Typically, each of R⁹, R¹⁰, R¹¹ and R¹² is independently selected from hydrogen, optionally substituted Ci-20-alkyl, optionally substituted C6-2o-aryl and a silyl group, or at least two adjacent R⁹, R¹⁰, R¹¹ and R¹² substituents form an optionally substituted ring having a total of 6 to 9 ring carbon atoms, preferably a total of 6 ring carbon atoms. It is preferred that each of R⁹, R¹⁰, R¹¹ and R¹² is independently selected from hydrogen, optionally substituted Ci-20-alkyl, optionally substituted C6-2o-aryl and a silyl group. More preferably, each of R⁹, R¹⁰, R¹¹ and R¹² is independently selected from hydrogen, and optionally substituted Ci-20-alkyl, such as unsubstituted Ci-₆-alkyl.

[0154] When a compound of formula (L3) is used, then the method of the invention may be a method for preparing a compound comprising a cyclopentadienyl moiety represented by formula (C1b) or an isomer thereof:

wherein:

R¹, R², R³ and R⁴ are as defined above for formula (A1), formula (A2) or formula (A3); and

R⁵, R⁶, R⁹, R¹⁰, R¹¹ and R¹² are as defined above for formula (L3).

[0155] When the cyclopentadienyl moiety is an indenyl moiety as represented by formula (A2), then the method of the invention may be a method for preparing a compound comprising a cyclopentadienyl moiety or an indenyl moiety represented by formula (C1i) or an isomer thereof:

wherein:

R¹, R², R^3A, R^3B, R^4A are as defined above formula (A2); and R⁵, R⁶, R⁹, R¹⁰, R¹¹ and R¹² are as defined above for formula (L3).

[0156] When the cyclopentadienyl moiety is a fluorenyl moiety as represented by formula (A3), then the method of the invention may be a method for preparing a compound comprising a cyclopentadienyl moiety or a fluorenyl moiety represented by formula (C1j) or an isomer thereof:

wherein:

R^1A, R^1B, R^2A, R^2B, R^3A, R^3B, R^4A are as defined above formula (A3); and R⁵, R⁶, R⁹, R¹⁰, R¹¹ and R¹² are as defined above for formula (L3).

[0157] In general, it is preferred that the cyclopentadienyl moieties in each of formula (C1) and formula (C1a) are the same.

[0158] Typically, R⁹ is the same as R¹, R¹⁰ is the same as R², R¹¹ is the same as R³, and R¹² is the same as R⁴. Thus, the method of the invention relates to a method of preparing a compound comprising a cyclopentadienyl moiety as represented by formula (C1c) or formula (C1d).

[0159] The method of the invention includes a step (b) of reacting the deprotonated cyclopentadienyl moiety with a compound having an electrophilic site, such as a compound of any one of formula (L1), (L1a), (L2), (L2a), (L2b), (L2c) or (L3). Step (b) is to prepare a ligand precursor or a compound comprising a cyclopentadienyl moiety as represented in any one of formulae (C1), (C1a), (C1b), (C1c), (C1d), (C1e), (C1f), (C1g), (C1h), (C1i), (C1j), (C2a), (C2b), (C2c), (C2d), (C2e), (C2f), (C2g), (C2h), (C2i), (C2j), (C2k), (C2I) or (C2m).

[0160] Without wishing to be bound by theory, it is believed that the reducing agent present from step (a) prevents the formation of undesirable cyclic intermediates during the reaction with the compound having an electrophilic site. Poor yields of the desired ligand precursor product are usually obtained when the method is performed without the reducing agent.

[0161] In step (b), the deprotonated cyclopentadienyl moiety is a cyclopentadienide moiety, which is a conjugate base of the cyclopentadienyl moiety as, for example represented by formula (A1), (A2) or (A3). [0162] Step (b) of the method may include stirring the deprotonated cyclopentadienyl moiety with the compound having an electrophilic site. The deprotonated cyclopentadienyl moiety and the compound having an electrophilic site may be stirred in the reaction solution obtained from step (a) of the method, such as described above.

Thus, the solution in step (b) may comprise the deprotonated cyclopentadienyl moiety, the compound having an electrophilic site and the solvent as described above.

[0163] Typically, in (b), the deprotonated cyclopentadienyl moiety and the compound having an electrophilic site may be admixed at a temperature from 10°C to 30°C, preferably at room temperature (e.g. 20°C), particularly when the compound having an electrophilic site has at least one carbon atom or at least one silicon atom bonded to a leaving group, such as in formula (L1), (L1a), (L2), (L2a), (L2b) or (L2c). The reaction is typically exothermic and it may be necessary to maintain the reaction solution at room temperature when the reactants are admixed. It is possible to maintain the reaction solution at room temperature by immersing the reaction vessel in a water bath. This avoids the need to use expensive and potentially hazardous cooling systems, such as dry ice cooling baths, when performing this step of the reaction.

[0164] In general, step (b) may be performed under an inert gas. The inert gas may, for example, be nitrogen (N2) or argon (Ar). It is preferred that the inert gas is nitrogen (N2).

[0165] The order in which the deprotonated cyclopentadienyl moiety and the compound having an electrophilic site are added to one another may depend on the ligand precursor that is desired.

[0166] When the ligand precursor or the compound comprising a cyclopentadienyl moiety has two cyclopentadienyl moieties that are the same, such as shown in any one of formulae (C1c) to (C1h) or (C2d) to (C2m), then it is desirable for the deprotonated cyclopentadienyl moiety to be present in an excess and for the compound having an electrophilic site to be added thereto.

[0167] In step (b) of the method, the deprotonated cyclopentadienyl moiety and the compound having an electrophilic site may be admixed, such as at temperature described above, by adding the compound having an electrophilic site to the deprotonated cyclopentadienyl moiety and mixing (e.g. stirring) the compound having an electrophilic site with the deprotonated cyclopentadienyl moiety. The compound having an electrophilic site may be a compound of formula (L1), (L1a), (L2), (L2a), (L2b) or (L2c).

[0168] The compound having an electrophilic site may be added dropwise to the deprotonated cyclopentadienyl moiety. [0169] Step (b) of the method may include stirring a reaction solution comprising the deprotonated cyclopentadienyl moiety and the compound having an electrophilic site for at least 3 hours, preferably at least 6 hours, more preferably at least 12 hours.

[0170] The reaction solution comprising the deprotonated cyclopentadienyl moiety and the compound having an electrophilic site may be stirred at room temperature (e.g. 20°C) or at a temperature of ³ 30°C, such as a temperature from 30°C to 100°C. It is preferred that the reaction solution is stirred at a temperature from 50°C to 90°C, more preferably 60°C to 80°C.

[0171] Thus, step (b) of the method may include heating a reaction solution comprising the deprotonated cyclopentadienyl moiety and the compound having an electrophilic site to a temperature as described above.

[0172] When the ligand precursor or the compound comprising a cyclopentadienyl moiety has two cyclopentadienyl moieties that are the same, then the molar ratio of the cyclopentadienyl moiety (e.g. the deprotonated cyclopentadienyl moiety) to the compound having an electrophilic site is about 2:1 (e.g. 1.9:1 to 2.1:1).

[0173] When the ligand precursor or the compound comprising a cyclopentadienyl moiety has two cyclopentadienyl moieties that are different, then it is desirable for the compound having an electrophilic site to be present in an excess and for a first deprotonated cyclopentadienyl moiety to be added thereto.

[0174] In step (b) of the method, a first deprotonated cyclopentadienyl moiety and the compound having an electrophilic site may be admixed, such as at temperature described above, by adding the first deprotonated cyclopentadienyl moiety to the compound having an electrophilic site and mixing (e.g. stirring) the first deprotonated cyclopentadienyl moiety with the compound having an electrophilic site. The compound having an electrophilic site may be a compound of formula (L1), (L1a), (L2), (L2a), (L2b) or (L2c).

[0175] The solution comprising the first deprotonated cyclopentadienyl moiety from step (a) of the method may be added to the compound having an electrophilic site, preferably a solution of the compound having an electrophilic site.

[0176] The first deprotonated cyclopentadienyl moiety may be added dropwise to the compound having an electrophilic site.

[0177] When the ligand precursor or the compound comprising a cyclopentadienyl moiety has two cyclopentadienyl moieties that are different, then the molar ratio of the first cyclopentadienyl moiety (e.g. the first deprotonated cyclopentadienyl moiety) to the compound having an electrophilic site is about 1:1 (e.g. 0.9:1 to 1.1:1).

[0178] Step (b) of the method may include stirring a reaction solution comprising the first deprotonated cyclopentadienyl moiety and the compound having an electrophilic site for at least 3 hours, preferably at least 6 hours, more preferably at least 12 hours.

[0179] The reaction solution comprising the first deprotonated cyclopentadienyl moiety and the compound having an electrophilic site may be stirred at room temperature (e.g. 20°C) or at a temperature of ³ 30°C, such as a temperature from 30°C to 100°C. It is preferred that the reaction solution is stirred at a temperature from 50°C to 90°C, more preferably 60°C to 80°C.

[0180] Thus, step (b) of the method may include heating a reaction solution comprising the first deprotonated cyclopentadienyl moiety and the compound having an electrophilic site to a temperature as described above.

[0181] After admixing the first deprotonated cyclopentadienyl moiety with the compound having an electrophilic site, a second deprotonated cyclopentadienyl moiety may be admixed with the reaction solution. Typically, the second deprotonated cyclopentadienyl moiety has a different structure to the structure of the first deprotonated cyclopentadienyl moiety. It may be desirable for the first deprotonated cyclopentadienyl moiety to have lower reactivity (e.g. to be more sterically hindered) than the second deprotonated cyclopentadienyl to ensure that better yields of the desired ligand precursor are obtained.

[0182] The second deprotonated cyclopentadienyl moiety may be added dropwise to the reaction solution.

[0183] Typically, the molar ratio of the second cyclopentadienyl moiety (e.g. the second deprotonated cyclopentadienyl moiety) to the compound having an electrophilic site is about 1:1 (e.g. 0.9:1 to 1.1:1).

[0184] Step (b) of the method may further include stirring the reaction solution (e.g. which comprises the second deprotonated cyclopentadienyl moiety) for at least 3 hours, preferably at least 6 hours, more preferably at least 12 hours.

[0185] The reaction solution comprising the second deprotonated cyclopentadienyl moiety may be stirred at room temperature (e.g. 20°C) or at a temperature of ³ 30°C, such as a temperature from 30°C to 100°C. It is preferred that the reaction solution is stirred at a temperature from 50°C to 90°C, more preferably 60°C to 80°C. [0186] Thus, step (b) of the method may include heating a reaction solution comprising the second deprotonated cyclopentadienyl moiety to a temperature as described above.

[0187] When the compound having an electrophilic site is a fulvene, such as in formula (L3) above, then the way in which the deprotonated cyclopentadiene moiety and the fulvene are added to one another may not be important.

[0188] In step (b) of the method, the deprotonated cyclopentadienyl moiety and the compound having an electrophilic site of formula (L3) may be admixed, such as at temperature described above, by either (a) adding the compound having an electrophilic site of formula (L3) to the deprotonated cyclopentadienyl moiety and mixing (e.g. stirring) the compound having an electrophilic site of formula (L3) with the deprotonated cyclopentadienyl moiety or (b) adding the deprotonated cyclopentadienyl moiety to the compound having an electrophilic site of formula (L3) and mixing (e.g. stirring) the deprotonated cyclopentadienyl moiety with the compound having an electrophilic site of formula (L3).

[0189] The compound having an electrophilic site of formula (L3) may be added dropwise to the deprotonated cyclopentadienyl moiety or vice-versa.

[0190] Step (b) of the method may include stirring a reaction solution comprising the deprotonated cyclopentadienyl moiety and the compound having an electrophilic site of formula (L3) for at least 3 hours, preferably at least 6 hours, more preferably at least 12 hours.

[0191] The reaction solution comprising the deprotonated cyclopentadienyl moiety and the compound having an electrophilic site of formula (L3) may be stirred at room temperature (e.g. 20°C) or at a temperature of ³ 30°C, such as a temperature from 30°C to 100°C. It is preferred that the reaction solution is stirred at a temperature from 50°C to 90°C, more preferably 60°C to 80°C.

[0192] Thus, step (b) of the method may include heating a reaction solution comprising the deprotonated cyclopentadienyl moiety and the compound having an electrophilic site of formula (L3) to a temperature as described above.

[0193] Typically, the molar ratio of the cyclopentadienyl moiety (e.g. the deprotonated cyclopentadienyl moiety) to the compound having an electrophilic site of formula (L3) is about 1:1 (e.g. 0.9:1 to 1.1:1).

[0194] After performing step (b) of the method, the ligand precursor or a compound comprising a cyclopentadienyl moiety as represented in any one of formulae (C1), (C1a), (C1b), (C1c), (C1d), (C1e), (C1f), (C1g), (C1h), (C1i), (C1j), (C2a), (C2b), (C2c), (C2d), (C2e), (C2f), (C2g), (C2h), (C2i), (C2j), (C2k), (C2I) or (C2m) can be isolated and purified using conventional techniques.

[0195] The molar amount of the compound having an electrophilic site is typically at least 0.5 moles, preferably at least 1.0 moles, such as at least 5.0 moles, more preferably at least 10.0 moles.

[0196] The invention also provides a method of separating a rac-ansa-bridged bis- indenyl transition metal compound of formula (rac-M1) from its meso isomer.

[0197] The rac- form of an ansa-bridged b/s-indenyl transition metal compound can be present as two enantiomers (e.g. when the substituents on the transition metal, represented by Y, are the same), as shown below.

(rac-M1)

[0198] The meso form of the ansa-bridged b/s-indenyl transition metal compound is optically inactive and is shown below. In the meso form the indenyl rings “point” in the same direction.

(meso-M1)

[0199] The method of the invention is a method of separating the enantiomers of a rac- ansa-bridged b/s-indenyl transition metal compound of formula (rac-M1) (e.g. as a racemic mixture) from a meso-ansa-bridged b/s-indenyl transition metal compound of formula (meso-M1).

[0200] In the formulae (rac-M1) and (meso-M1), M represents a transition metal. Typically, M is selected from Zr and Hf. It is preferred that M is Zr. [0201] In the formulae (rac-M1) and (meso-M1), Y represents a halogen. Typically, Y is selected from chloro or bromo. It is preferred that Y is chloro.

[0202] In the formulae (rac-M1) and (meso-M1), n is an integer selected from 1 and 2. It is preferred that n is 2.

[0203] The method involves (a) washing a first solid product with dichloromethane to obtain a first extraction liquid comprising a rac isomer (e.g. as represented by formula (rac-M1)) and a meso isomer (e.g. as represented by formula (meso-M1), preferably the first extraction liquid comprises both rac enantiomers and the meso isomer. Thus, step (a) is for extracting the ansa-bridged b/s-indenyl transition metal compound (e.g. in all its isomeric forms) from the first solid product.

[0204] The step of washing the first solid product with dichloromethane may comprise stirring the first solid product in dichloromethane.

[0205] Before washing, the first solid product is the product that is obtained from the reaction mixture. In addition to the ansa-bridged b/s-indenyl transition metal compound, the first solid product may further comprise one or more by-products and/or unreacted starting materials, such as the ligand, the ligand precursor and/or the compound of formula MY₄ described below.

[0206] Before washing, the first solid product is typically a residue obtained after removing the solvent from a reaction mixture for preparing the ansa-bridged b/s-indenyl transition metal compound. The solvent may have been removed under reduced pressure (e.g. in vacuo ) to, for example, leave the first solid product.

[0207] The first solid product may be washed with a plurality of portions of dichloromethane, and the first extraction liquid may comprise the combined portions of the dichloromethane. Typically, washing with dichloromethane preferentially extracts the ansa-bridged b/s-indenyl transition metal compound (e.g. the rac isomers and the meso isomer) from the first solid product.

[0208] After washing the first solid product, the method may further comprise filtering the first extraction liquid, such as to produce a first extraction liquid filtrate. Filtration is performed to remove solids from the first extract liquid.

[0209] Step (b) involves evaporating the dichloromethane from the first extraction liquid or from the first extraction liquid filtrate (e.g. when the first extraction liquid is filtered) to obtain a second solid product. Typically, the evaporating is performed to dryness. The second solid product may be in the form of a powder.

[0210] The second solid product may comprise a rac isomer, preferably both rac enantiomers, and the meso isomer of the ansa-bridged b/s-indenyl transition metal compound. Typically, the second solid product comprises the rac enantiomers as a racemic mixture.

[0211] The method of the invention further comprises (c) washing the second solid product with a solvent to remove the meso isomer (e.g. the meso isomer of the ansa- bridged b/s-indenyl transition metal compound, as represented by the formula ( meso - M1)). The second solid product is washed with the solvent to leave the rac isomer (e.g. the rac isomer of the ansa-bridged b/s-indenyl transition metal compound, as represented by the formula (rac-M1)).

[0212] Typically, the solvent is toluene or ethanol. It is preferred that the solvent is toluene. When toluene is used as the solvent, it provides better yields of the rac isomer than when other solvents, such as ethanol, are used.

[0213] The step of washing the second solid product with the solvent may comprise stirring the second solid product in the solvent.

[0214] This second washing step preferentially extracts or removes the meso isomer from the second solid product, such that the rac isomer remains, typically as a remaining solid.

[0215] After the second washing step, the remaining solid comprises, or consists essentially of, the rac isomer of the ansa-bridged b/s-indenyl transition metal compound. The second washing step is performed to obtain a remaining solid where £ 10 wt. % of the weight of the solid, preferably £ 5 wt. %, more preferably £ 1 wt. %, is the meso isomer of the ansa-bridged b/s-indenyl transition metal compound. The remaining solid may not comprise the meso isomer of the ansa-bridged b/s-indenyl transition metal compound. [0216] The second solid product may be washed with a plurality of portions of the solvent.

[0217] The second extraction liquid therefore comprises the meso isomer of the ansa- bridged b/s-indenyl transition metal compound represented by the formula (meso-M1).

The second extraction liquid may consist essentially of the meso isomer of the ansa- bridged b/s-indenyl transition metal compound and the solvent. The second extraction liquid may not comprise the rac isomer of the ansa-bridged b/s-indenyl transition metal compound, as represented by the formula (rac-M1).

[0218] After washing the second solid product, the method may further comprise separating and collecting the solid rac isomer from the solvent. For example, a wash mixture of the second solid product and the solvent can be filtered to collect the solid rac isomer. The meso isomer is dissolved in the solvent (e.g. second extraction liquid).

[0219] The solid rac isomer is typically a racemic mixture of the rac enantiomers. [0220] The method may further comprise (d) washing the solid rac isomer with pentane and/or drying the solid rac isomer, such as to obtain powder.

[0221] Before the step of washing the first solid product in (a), the method of the invention may include a step of preparing ansa-bridged b/s-indenyl transition metal compound in solution.

[0222] The method of the invention may further comprise:

(a)(i) reacting a compound of formula MY₄ with an anion of a compound comprising a cyclopentadienyl moiety represented by formula (C3) in a solvent:

(a)(ii) removing the solvent to obtain a solid product.

[0223] In formula MY₄, M is selected from Zr and Hf, Y is selected from Cl or Br, and n is an integer selected from 1 and 2.

[0224] After (a)(ii), the step of washing the solid product in (a) above may be performed as step (a)(iii).

[0225] Typically, the anion of compound comprising a cyclopentadienyl moiety represented by formula (C3) is a lithium anion.

[0226] The anion is typically a di-anion, such as di-lithium anion. There are two indenyl rings in formula (C3) above that can be deprotonated.

[0227] The compound comprising a cyclopentadienyl moiety as represented by formula (C3) may be obtained from a method of the invention, such as a method of preparing a compound comprising a cyclopentadienyl moiety or an indenyl moiety as represented by formula (C1e), (C2i) or an isomer thereof.

Examples

[0228] The present disclosure will now be illustrated by the following non-limiting examples. Example 1

Method of preparing 1 ,2-bis(3-indenyl)ethane

[0229] A Schlenk flask containing a stirred solution of indene (5.0 g, 43 mmol, 1 eq.), NaOH (2.6 g, 65 mmol, 1.5 eq.) and Ca granules (170 mg, 4.3 mmol, 0.1 eq.) in 5 ml DMSO was thoroughly degassed of atmospheric oxygen by repeated cycles of vacuum and refilling with nitrogen gas. The mixture was stirred at room temperature overnight to give a green solution. The flask was surrounded by a water bath at room temperature to act as a heat sink whilst 1,2-dichloroethane (2.1 g, 1.7 ml, 22 mmol, 0.5 eq.) was added in one portion (exothermic reaction). The reaction was stirred at room temperature for 1h then heated to 70°C overnight. The mixture was cooled to room temperature and approximately 30 ml water were added and stirred for 0.5h. The resulting precipitate was collected by suction filtration and stirred with 20 ml dilute HCI (aq.) to dissolve residual Ca. The precipitate was again collected, washed well with water, EtOH and hexane and dried in vacuo to give pure 1,2-bis(1H-inden-3-yl)ethane as a white microcrystalline solid. Yield 3.35 g (60%).

[0230] A ¹H NMR spectrum of the product using CDCh as the solvent is shown in Figure 1. The NMR spectrum confirms that 1,2-bis(3-indenyl)ethane has been prepared.

Example 2

Method of preparing bis(3-indenyl)methane

[0231] A Schlenk flask containing a stirred solution of indene (1.0 g, 8.6 mmol, 1 eq.), NaOH (0.52 g, 12.9 mmol, 1.5 eq.), dibromomethane (0.75 g, 4.3 mmol, 0.5 eq.) and Ca granules (40 mg, 0.9 mmol, 0.1 eq.) in 5 ml DMSO was thoroughly degassed of atmospheric oxygen by repeated cycles of vacuum and refilling with nitrogen gas. The mixture was stirred at room temperature overnight and poured into approximately 30 ml water and stirred for 0.5 h to give an oily solid. The oily material was washed with 20 ml EtOH then dissolved in 20 ml hexane. The hexane solution was filtered and the solvent removed in vacuo to give an oily product. Yield 400 mg (38 %). [0232] A ¹H NMR spectrum of the product using CDC as the solvent is shown in Figure 2. The NMR spectrum confirms that bis(3-indenyl)methane has been prepared.

Example 3

Method of preparing rac-ethylenebis(indenyl)zirconium(IV) dichloride

[0233] A solution of n-BuLi 1 6M in hexanes (4.8 ml, 7.74 mmol, 2.0 eq.) was added dropwise to a solution of 1,2-b/s(3-indenyl)ethane (0.5 g, 1.94 mmol, 1 eq.) in 10 ml THF at 0°C to give a thick, cream-coloured precipitate. The reaction mixture was then warmed to dissolve the precipitate to ensure complete reaction, then once again cooled to 0°C. To this stirred solution was added dropwise a solution of ZrCU (450 mg, 1.94 mmol, 1 eq.) in 20 ml THF over a period of several hours (the ZrCU solution was prepared by adding ZrCU to cooled (0°C) THF, then heated to dissolve the solid). The reaction mixture was slowly allowed to warm to room temperature and stirred overnight resulting in an orange solution and precipitate.

[0234] The solvent was removed in vacuo and the residue washed with pentane and once again dried to ensure complete removal of THF. The crude product was then extracted by repeated stirring with portions of dichloromethane and filtering through a glass sinter until the washings were colourless (approx. 60 ml total required). The solvent was removed in vacuo and the crude product was stirred vigorously with 5 ml toluene for 30 min. The mixture was filtered and the yellow precipitate collected, which was washed further with n-pentane. The product was dried by heating to 60°C under vacuum for 30 min to give pure rac isomer. Yield 0.41 g (51 %).

[0235] A ¹H NMR spectrum of the product using CDCb as the solvent is shown in Figure 3. The NMR spectrum confirms that rac-ethylenebis(indenyl)zirconium(IV) dichloride has been prepared.

Claims

1. A method for preparing a compound comprising a cyclopentadienyl moiety, wherein the method comprises:

(a) deprotonating a cyclopentadienyl moiety represented by formula (A1) or an isomer thereof in a solution comprising an alkali hydroxide and a reducing agent:

wherein each of R¹, R², R³ and R⁴ is independently selected from hydrogen, optionally substituted Ci-20-alkyl, optionally substituted C2-2o-alkenyl, optionally substituted C3-2o-cycloalkyl, optionally substituted C6-2o-aryl and a silyl group, or at least two adjacent R¹, R², R³ and R⁴ substituents form an optionally substituted ring having a total of 6 to 9 ring carbon atoms; and (b) reacting the deprotonated cyclopentadienyl moiety with a compound having an electrophilic site.

2. The method according to claim 1 , wherein the alkali hydroxide is sodium hydroxide or potassium hydroxide, preferably sodium hydroxide.

3. The method according to claim 1 or claim 2, wherein the reducing agent is selected from an alkaline earth metal and a hydride reducing agent.

4. The method according to claim 3, wherein the reducing agent is an alkaline earth metal, preferably the alkaline earth metal is calcium or magnesium.

5. The method according to claim 3, wherein the reducing agent is a hydride reducing agent selected from a borohydride reducing agent and an aluminium hydride reducing agent.

6. The method according to any one of the preceding claims, wherein the solution further comprises a dipolar, aprotic solvent, preferably a dipolar, aprotic solvent, which is dimethyl sulfoxide, L/,L/’-dimethylpropyleneurea, acetonitrile or hexamethyl- phosphoramide, more preferably dimethyl sulfoxide.

7. The method according to any one of the preceding claims, wherein step (a) and/or step (b) is performed under an inert gas.

8. The method according to any one of the preceding claims, wherein R³ and R⁴ form an optionally substituted ring having a total of 6 ring carbon atoms, such that the cyclopentadienyl moiety is represented by formula (A2):

wherein: each of R¹ and R² is independently selected from hydrogen, optionally substituted Ci-₂o-alkyl, optionally substituted C_2-2o-alkenyl, optionally substituted C_3-2o-cycloalkyl, optionally substituted C_6-2o-aryl and a silyl group, or R¹ and R² form an optionally substituted ring having a total of 6 to 9 ring carbon atoms; and each of R^3A, R^3B, R^4A and R^4B is independently selected from hydrogen, optionally substituted Ci-₆-alkyl, optionally substituted C_2-6-alkenyl, optionally substituted C_3-8-cycloalkyl, optionally substituted C₆-io-aryl and a silyl group, or at least two adjacent R^3A, R^3B, R^4A and R^4B substituents form an optionally substituted ring having a total of 6 to 8 ring carbon atoms.

9. The method of claim 8, wherein each of R¹ and R² is independently selected from hydrogen, optionally substituted Ci-₂₀-alkyl, optionally substituted C_2-2o-alkenyl, optionally substituted C_3-2o-cycloalkyl, optionally substituted C_6-2o-aryl and a silyl group.

10. The method according to any one of the preceding claims, wherein the compound having an electrophilic site is selected from (i) a compound having a least one carbon atom bonded to a leaving group, (ii) a compound having at least one silicon atom bonded to a leaving group, and (iii) an optionally substituted fulvene.

11. The method according to any one of the preceding claims, which is a method for preparing a compound comprising a cyclopentadienyl moiety represented by formula (C2) or an isomer thereof:

wherein step (b) comprises reacting the deprotonated cyclopentadienyl moiety with a compound having an electrophilic site represented by formula (L2):

wherein: each of E¹ and E² is independently selected from a carbon atom and a silicon atom; each of X¹ and X² is a leaving group;

Q is a single bond or is a chain of 1 to 5 atoms in length, wherein each atom is a carbon atom or a silicon atom; each of R⁵, R⁶, R⁷ and R⁸ is independently selected from hydrogen, optionally substituted Ci-20-alkyl, optionally substituted C2-2o-alkenyl, optionally substituted C3-2o-cycloalkyl, optionally substituted C6-2o-aryl and a silyl group, or two geminal or vicinal substituents from R⁵, R⁶, R⁷, R⁸ or a substituent of Q form an optionally substituted ring having a total of 5 to 9 ring carbon atoms; each of R⁹, R¹⁰, R¹¹ and R¹² is independently selected from hydrogen, optionally substituted Ci-20-alkyl, optionally substituted C2-2o-alkenyl, optionally substituted C3-2o-cycloalkyl, optionally substituted C6-2o-aryl and a silyl group, or at least two adjacent R⁹, R¹⁰, R¹¹ and R¹² substituents form an optionally substituted ring having a total of 6 to 9 ring carbon atoms.

12. The method according to claim 11 , which is a method of preparing a compound comprising a cyclopentadienyl moiety as represented by formula (C2f) or an isomer thereof:

wherein: each of R^3A, R^3B, R^4A and R^4B is independently selected from hydrogen, optionally substituted Ci-₆-alkyl, optionally substituted C2-6-alkenyl, optionally substituted C3-8-cycloalkyl, optionally substituted C₆-io-aryl and a silyl group, or at least two adjacent R^3A, R^3B, R^4A and R^4B substituents form an optionally substituted ring having a total of 6 to 8 ring carbon atoms.

13. The method according to claim 11 or claim 12, wherein step (b) comprises (i) admixing the deprotonated cyclopentadienyl moiety and the compound having an electrophilic site at a temperature from 10°C to 30°C.

14. The method according to claim 13, wherein step (b) further comprises (ii) stirring a reaction solution comprising the deprotonated cyclopentadienyl moiety and the compound having an electrophilic site for at least 3 hours.

15. The method according to claim 13 or claim 14, wherein step (b) further comprises (ii) stirring a reaction solution comprising the deprotonated cyclopentadienyl moiety and the compound having an electrophilic site at a temperature of ³ 30°C.

16. The method according to any one of claims 1 to 10, which is a method of preparing a compound comprising a cyclopentadienyl moiety represented by formula (C1) or an isomer thereof:

wherein step (b) comprises reacting the deprotonated cyclopentadienyl moiety with a compound having an electrophilic site represented by formula (L1):

wherein:

E¹ is selected from a carbon atom and a silicon atom; each of X¹ and X² is a leaving group; and each of R⁹, R¹⁰, R¹¹ and R¹² is independently selected from hydrogen, optionally substituted Ci-20-alkyl, optionally substituted C2-2o-alkenyl, optionally substituted C3-2o-cycloalkyl, optionally substituted C6-2o-aryl and a silyl group, or at least two adjacent R⁹, R¹⁰, R¹¹ and R¹² substituents form an optionally substituted ring having a total of 6 to 9 ring carbon atoms.

17. The method according to any one of claims 1 to 10, which is a method of preparing a compound comprising a cyclopentadienyl moiety represented by formula (C1b) or an isomer thereof:

wherein step (b) comprises reacting the cyclopentadienyl moiety with a compound having an electrophilic site represented by formula (L3):

wherein: each of R⁵ and R⁶ is independently selected from hydrogen, optionally substituted Ci-₂o-alkyl, optionally substituted C_2-2o-alkenyl, optionally substituted C_3-2o-cycloalkyl, optionally substituted C_6-2o-aryl and a silyl group, or R⁵ and R⁶ form an optionally substituted ring having a total of 5 to 9 ring carbon atoms; and each of R⁹, R¹⁰, R^{1 1} and R¹² is independently selected from hydrogen, optionally substituted Ci-₂₀-alkyl, optionally substituted C_2-2o-alkenyl, optionally substituted C_3-2o-cycloalkyl, optionally substituted C_6-2o-aryl and a silyl group, or two adjacent R⁹, R¹⁰, R^{1 1} and R¹² substituents form an optionally substituted ring having a total of 6 to 9 ring carbon atoms.

18. The method according to any one of the preceding claims, wherein each silyl group has a silicon atom substituted with one to three substituents, wherein each substituent is independently selected from hydrogen, Ci-6-alkyl, C_2-6-alkenyl, C_3-8-cycloalkyl, C6-io-aryl, Ci-6-alkoxy and C6-io-aryloxy.

19. A method of separating a rac-ansa-bridged b/s-indenyl transition metal compound of formula (rac-M1) from its meso isomer, wherein the method comprises:

(a) washing a first solid product with dichloromethane to obtain a first extraction liquid containing a rac isomer and a meso isomer of an ansa-bridged bis- indenyl transition metal compound as represented by the formula (rac-M1) and the formula (meso-M1) respectively;

wherein:

M is selected from Zr and Hf;

Y is selected from chloro or bromo; and n is an integer selected from 1 and 2;

(b) evaporating the dichloromethane from the first extraction liquid to obtain a second solid product; and

(c) washing the second solid product with a solvent to remove the meso isomer, wherein the solvent is toluene or ethanol.

20. The method of claim 19, further comprising:

(a)(i) reacting a compound of formula MY₄, wherein M is selected from Zr and Hf, and Y is selected from Cl or Br, with an anion of a compound represented by formula (C1d) in a solvent:

wherein n is an integer selected from 1 and 2; (a)(N) removing the solvent to obtain a first solid product; and

(a)(iii) performing step (a) in the method of claim 19 as step (a)(iii).