CATALYSTS SUITABLE FOR THE RING-OPENING POLYMERISATION OF CYCLIC ESTERS AND CYCLIC AMIDES

A new family of Group IV transition metal catalytic compounds are provided, which are capable of catalysing the ROP of cyclic esters and cyclic amides to yield polymers of high molecular weight and narrow PDI. The new family of catalysts are surprisingly active not only in catalysing the ROP of lactones such as caprolactone, but also macrolactones (e.g. ω-pentadecalactone, PDL), where the reduced amount of ring strain would typically compromise efficient polymerisation. Also provided is a process for the ring opening polymerisation (ROP) of a cyclic ester or a cyclic amide employing the new catalytic compounds.

INTRODUCTION

The present invention relates to catalytic compounds, in particular those that are suitable for catalysing the ring-opening polymerisation (ROP) of cyclic esters (e.g. lactones) and cyclic amides (e.g. lactams). The present invention also relates to a process of polymerising cyclic esters and cyclic amides.

BACKGROUND OF THE INVENTION

Poly(olefins), such as poly(ethylene) and poly(propylene), are derived almost entirely from non-renewable fossil fuel feedstocks. These materials, consisting of kinetically inert C—C and C—H bonds, also lack a viable biodegradation pathways, thus they will persist in the environment unless recycled. The desirable thermal and mechanical properties gained from poly(olefins) stem from regions of crystallinity, or semi-crystallinity, between overlapping aliphatic chains. These properties can be closely mimicked by poly(esters) derived from the ring-opening polymerisation (ROP) of macrolactones, which contain long sequences of aliphatic chains between ester functionalities.1Materials of this kind will retain the attractive properties of polyolefins while allowing for biodecomposition through hydrolysis.

The first detailed report of the ROP of macrolactones by Endo et al. showed how the addition of various group I methoxides at elevated temperature can afford low molecular weight poly(macrolactones) comprised of 12- and 13-membered rings.2More recently, detailed kinetic studies of Al-salen catalysts have shown that polymerizations of lactones larger than caprolactone proceed at similar rates.4-5

There is therefore a need for new compounds that exhibit high catalytic activity in catalysing the ROP of cyclic esters, such as lactones—across the range of ring sizes—to high molecular weight.

The present invention was devised with the foregoing in mind.

SUMMARY OF THE INVENTION

According to a first aspect of the present invention there is provided a compound having a structure according to formula (I-A), (I-B) or (I-C) defined herein.

According to a second aspect of the present invention there is provided a process for the ring opening polymerisation (ROP) of a cyclic ester or a cyclic amide, the process comprising the step of:a) contacting a compound according to the first aspect of the invention with one or more cyclic esters or cyclic amides.

According to a third aspect of the present invention there is provided a use of a compound according to the first aspect of the invention in the ring opening polymerisation (ROP) of one or more cyclic esters or cyclic amides.

DETAILED DESCRIPTION OF THE INVENTION

Definitions

The term “(m-nC)” or “(m-nC) group” used alone or as a prefix, refers to any group having m to n carbon atoms.

The term “alkyl” as used herein refers to straight or branched chain alkyl moieties, typically having 1, 2, 3, 4, 5 or 6 carbon atoms. This term includes reference to groups such as methyl, ethyl, propyl (n-propyl or isopropyl), butyl (n-butyl, sec-butyl or tert-butyl), pentyl, hexyl and the like. In particular, an alkyl may have 1, 2, 3 or 4 carbon atoms.

The term “alkenyl” as used herein refers to straight or branched chain alkenyl moieties, typically having 1, 2, 3, 4, 5 or 6 carbon atoms. The term includes reference to alkenyl moieties containing 1, 2 or 3 carbon-carbon double bonds (C═C). This term includes reference to groups such as ethenyl (vinyl), propenyl (allyl), butenyl, pentenyl and hexenyl, as well as both the cis and trans isomers thereof.

The term “alkynyl” as used herein refers to straight or branched chain alkynyl moieties, typically having 1, 2, 3, 4, 5 or 6 carbon atoms. The term includes reference to alkynyl moieties containing 1, 2 or 3 carbon-carbon triple bonds (C═C). This term includes reference to groups such as ethynyl, propynyl, butynyl, pentynyl and hexynyl.

The term “haloalkyl” as used herein refers to alkyl groups being substituted with one or more halogens (e.g. F, Cl, Br or I). This term includes reference to groups such as 2-fluoropropyl, 3-chloropentyl, as well as perfluoroalkyl groups, such as perfluoromethyl.

The term “alkoxy” as used herein refers to —O-alkyl, wherein alkyl is straight or branched chain and comprises 1, 2, 3, 4, 5 or 6 carbon atoms. In one class of embodiments, alkoxy has 1, 2, 3 or 4 carbon atoms. This term includes reference to groups such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, pentoxy, hexoxy and the like.

The term “dialkylamino” as used herein means a group —N(RA)(RB), wherein RAand RBare alkyl groups.

The term “aryl” or “aromatic” as used herein means an aromatic ring system comprising 6, 7, 8, 9 or 10 ring carbon atoms. Aryl is often phenyl but may be a polycyclic ring system, having two or more rings, at least one of which is aromatic. This term includes reference to groups such as phenyl, naphthyl and the like. Unless otherwise specification, aryl groups may be substituted by one or more substituents. A particularly suitable aryl group is phenyl.

The term “aryloxy” as used herein refers to —O-aryl, wherein aryl has any of the definitions discussed herein. Also encompassed by this term are aryloxy groups in having an alkylene chain situated between the 0 and aryl groups.

The term “heteroaryl” or “heteroaromatic” means an aromatic mono-, bi-, or polycyclic ring incorporating one or more (for example 1-4, particularly 1, 2 or 3) heteroatoms selected from nitrogen, oxygen or sulfur. Examples of heteroaryl groups are monocyclic and bicyclic groups containing from five to twelve ring members, and more usually from five to ten ring members. The heteroaryl group can be, for example, a 5- or 6-membered monocyclic ring or a 9- or 10-membered bicyclic ring, for example a bicyclic structure formed from fused five and six membered rings or two fused six membered rings. Each ring may contain up to about four heteroatoms typically selected from nitrogen, sulfur and oxygen. Typically the heteroaryl ring will contain up to 3 heteroatoms, more usually up to 2, for example a single heteroatom.

The term “heteroaryloxy” as used herein refers to —O-heteroaryl, wherein heteroaryl has any of the definitions discussed herein. Also encompassed by this term are heteroaryloxy groups in having an alkylene chain situated between the 0 and heteroaryl groups.

The term “carbocyclyl”, “carbocyclic” or “carbocycle” means a non-aromatic saturated or partially saturated monocyclic, or a fused, bridged, or spiro bicyclic carbocyclic ring system(s). Monocyclic carbocyclic rings contain from about 3 to 12 (suitably from 3 to 7) ring atoms. Bicyclic carbocycles contain from 7 to 17 carbon atoms in the rings, suitably 7 to 12 carbon atoms, in the rings. Bicyclic carbocyclic rings may be fused, spiro, or bridged ring systems. A particularly suitable carbocyclic group is adamantyl.

The term “heterocyclyl”, “heterocyclic” or “heterocycle” means a non-aromatic saturated or partially saturated monocyclic, fused, bridged, or spiro bicyclic heterocyclic ring system(s). Monocyclic heterocyclic rings contain from about 3 to 12 (suitably from 3 to 7) ring atoms, with from 1 to 5 (suitably 1, 2 or 3) heteroatoms selected from nitrogen, oxygen or sulfur in the ring. Bicyclic heterocycles contain from 7 to 17 member atoms, suitably 7 to 12 member atoms, in the ring. Bicyclic heterocyclic(s) rings may be fused, spiro, or bridged ring systems.

The term “halogen” or “halo” as used herein refers to F, Cl, Br or I. In a particular, halogen may be F or CI, of which CI is more common.

The term “substituted” as used herein in reference to a moiety means that one or more, especially up to 5, more especially 1, 2 or 3, of the hydrogen atoms in said moiety are replaced independently of each other by the corresponding number of the described substituents. The term “optionally substituted” as used herein means substituted or unsubstituted.

It will, of course, be understood that substituents are only at positions where they are chemically possible, the person skilled in the art being able to decide (either experimentally or theoretically) without inappropriate effort whether a particular substitution is possible.

The terms “cyclic esters” and “cyclic amides” as used herein refer to heterocycles containing at least one ester or amide moiety. It will be understood that lactides, lactones and lactams are encompassed by these terms.

Compounds of the Invention

According to a first aspect of the present invention there is provided a compound having a structure according to formula (I-A), (I-B) or (I-C) shown below:

wherein

M is a Group IV transition metal,

each X is independently selected from halo, hydrogen, a phosphonate, sulfonate or boronate group, (1-4C)dialkylamino, (1-6C)alkyl, (1-6C)alkoxy, aryl, and aryloxy, any of which may be optionally substituted one of more groups selected from halo, oxo, hydroxy, amino, nitro, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, (1-6C)haloalkyl, (1-6C)alkoxy, aryl and Si[(1-4C)alkyl]3,

R2is absent or is selected from hydrogen, halo, oxo, hydroxy, amino, nitro, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, (1-6C)haloalkyl, (1-6C)alkoxy, aryl, aryloxy, heteroaryl, heteroaryloxy, carbocyclyl and heterocyclyl, any of which may be optionally substituted with one or more substituents selected from halo, oxo, hydroxy, amino, nitro, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, (1-6C)haloalkyl and (1-6C)alkoxy, bond a is a carbon-nitrogen single bond (C—N) or a carbon-nitrogen double bond (C═N), with the proviso that when R2is absent, bond a is a carbon-nitrogen double bond (C═N), and when R2is other than absent, bond a is a carbon-nitrogen single bond (C—N),

R1is a group having the formula (II) shown below:

Through detailed investigations, the inventors have developed a new family of Group IV transition metal-based catalysts capable of catalysing the ROP of cyclic esters and cyclic amides to yield polymers of high molecular weight and narrow PDI. The new family of catalysts are surprisingly active not only in catalysing the ROP of lactones such as caprolactone, but also macrolactones (e.g. ω-pentadecalactone, PDL), where the reduced amount of ring strain would typically compromise efficient polymerisation.

The new family of catalysts encompasses three different coordination chemistry, embodied by formulae (I-A), (I-B) and (I-C). As depicted below, in formula (I-A), both bidentate phenyl-containing ligands are bound to M via two oxygen atoms (O,O:O,O coordination), thereby forming two 5-membered rings. In formula (I-B), one of the phenyl-containing ligands is bound to M via two oxygen atoms, whereas the other phenyl-containing ligand is bound to M via one oxygen atom and one nitrogen atom (O,O:N,O coordination), thereby forming one 5-membered ring and one 6-membered ring. In formula (I-C), both bidentate phenyl-containing ligands are bound to M via one oxygen atom and one nitrogen atom (N,O:N,O coordination), thereby forming two 6-membered rings.

It will be appreciated that the compounds of the invention may exist in a number of structurally isomeric forms. For example, compound of formula (I-C) may exist in either of the following structural isomeric forms:

The compounds of the invention are suitable for catalysing the ROP of cyclic esters and cyclic amides.

In an embodiment, the compound has a structure according to formula (I-A) or (I-B). The particular coordination type depicted in formulae (I-A) and (I-B) is preferred.

In an embodiment, the compound has a structure according to formula (I-A). The particular coordination type depicted in formula (I-A) is most preferred.

In an embodiment, the compound has a structure according to formula (I-B).

In an embodiment, the compound has a structure according to formula (I-C).

In an embodiment, the compound has a structure according to formula (I-A), (I-B) or (I-C), whereinM is a Group IV transition metal,each X is independently selected from halo, hydrogen, a phosphonate, sulfonate or boronate group, (1-6C)alkyl, (1-6C)alkoxy, aryl, and aryloxy, any of which may be optionally substituted one of more groups selected from halo, oxo, hydroxy, amino, nitro, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, (1-6C)haloalkyl, (1-6C)alkoxy, aryl and Si[(1-4C)alkyl]3,R2is absent or is selected from hydrogen, halo, oxo, hydroxy, amino, nitro, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, (1-6C)haloalkyl, (1-6C)alkoxy, aryl, aryloxy, heteroaryl, heteroaryloxy, carbocyclyl and heterocyclyl, any of which may be optionally substituted with one or more substituents selected from halo, oxo, hydroxy, amino, nitro, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, (1-6C)haloalkyl and (1-6C)alkoxy,bond a is a carbon-nitrogen single bond (C—N) or a carbon-nitrogen double bond (C═N), with the proviso that when R2is absent, bond a is a carbon-nitrogen double bond (C═N), and when R2is other than absent, bond a is a carbon-nitrogen single bond (C—N),R3, R4, R5and R6are each independently selected from hydrogen, halo, oxo, hydroxy, amino, nitro, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, (1-6C)haloalkyl, (1-6C)alkoxy, aryl, aryloxy, heteroaryl, heteroaryloxy, carbocyclyl and heterocyclyl, any of which may be optionally substituted with one or more substituents selected from halo, oxo, hydroxy, amino, nitro, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, (1-6C)haloalkyl and (1-6C)alkoxy,R7is selected from (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, (1-6C)haloalkyl, aryl, heteroaryl, carbocyclyl and heterocyclyl, any of which may be optionally substituted with one or more substituents selected from halo, oxo, hydroxy, amino, nitro, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, (1-6C)haloalkyl and (1-6C)alkoxy,R1is a group having the formula (II) shown below:

In an embodiment, M is selected from titanium, zirconium and hafnium. Suitably, M is selected from titanium and zirconium. More suitably, M is titanium.

In an embodiment, each X is independently selected from halo, hydrogen, (1-4C)dialkylamino, (1-6C)alkoxy, and aryloxy, any of which may be optionally substituted one of more groups selected from halo, oxo, hydroxy, amino, nitro, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, (1-6C)haloalkyl, (1-6C)alkoxy, aryl and Si[(1-4C)alkyl]3.

In an embodiment, each X is independently selected from halo, hydrogen, (1-6C)alkoxy, and aryloxy, any of which may be optionally substituted one of more groups selected from halo, oxo, hydroxy, amino, nitro, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, (1-6C)haloalkyl, (1-6C)alkoxy, aryl and Si[(1-4C)alkyl]3.

In an embodiment, each X is independently selected from halo, hydrogen, (1-6C)alkoxy, and aryloxy, any of which may be optionally substituted one of more groups selected from halo, oxo, hydroxy, amino, nitro, (1-6C)alkyl, (1-6C)haloalkyl, (1-6C)alkoxy and aryl.

In an embodiment, each X is independently selected from halo, hydrogen, (1-4C)alkoxy, and phenoxy, any of which may be optionally substituted one of more groups selected from halo, oxo, hydroxy, amino, nitro, (1-4C)alkyl, (1-4C)haloalkyl, (1-4C)alkoxy and phenyl.

In an embodiment, each X is independently selected from halo, hydrogen, —N(CH3)2, —N(CH2CH3)2and (1-4C)alkoxy, any of which may be optionally substituted one of more groups selected from halo, hydroxy, amino, (1-4C)alkyl and (1-4C)alkoxy.

In an embodiment, each X is independently selected from halo, hydrogen, and (1-4C)alkoxy, any of which may be optionally substituted one of more groups selected from halo, hydroxy, amino, (1-4C)alkyl and (1-4C)alkoxy.

In an embodiment, each X is independently selected from chloro, bromo, —N(CH3)2, —N(CH2CH3)2and (1-4C)alkoxy.

In an embodiment, each X is independently selected from chloro, bromo and (1-4C)alkoxy.

In an embodiment, each X is independently (1-4C)alkoxy.

In an embodiment, each X is isopropoxy.

In an embodiment, each X is independently (1-4C)dialkylamino. Suitably, X is independently —N(CH3)2or —N(CH2CH3)2.

In an embodiment, R2is absent or is selected from hydrogen, hydroxy, (1-4C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, (1-4C)haloalkyl, (1-4C)alkoxy, aryl and heteroaryl, any of which may be optionally substituted with one or more substituents selected from halo, oxo, hydroxy, amino, nitro, (1-4C)alkyl, (1-4C)haloalkyl and (1-4C)alkoxy.

In an embodiment, R2is absent or is selected from hydrogen, (1-4C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl and aryl, any of which may be optionally substituted with one or more substituents selected from halo, hydroxy, amino, (1-4C)alkyl and (1-4C)alkoxy.

In an embodiment, R2is absent or is selected from hydrogen, (1-4C)alkyl and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, hydroxy, amino, (1-4C)alkyl and (1-4C)alkoxy.

In an embodiment, R2is absent or is selected from hydrogen, (1-4C)alkyl and phenyl.

In an embodiment, R2is absent or is selected from hydrogen and (1-4C)alkyl.

In an embodiment, R2is absent or hydrogen.

In an embodiment, bond a is a carbon-nitrogen double bond (C═N).

In an embodiment, R3, R4, R5and R6are each independently selected from hydrogen, halo, amino, nitro, (1-4C)alkyl, (1-4C)haloalkyl, (1-4C)alkoxy, aryl and heteroaryl, any of which may be optionally substituted with one or more substituents selected from halo and (1-4C)alkyl.

In an embodiment, R3, R4, R5and R6are each independently selected from hydrogen, halo, amino, (1-4C)alkyl, (1-4C)haloalkyl, (1-4C)alkoxy and phenyl, any of which may be optionally substituted with one or more substituents selected from halo and (1-4C)alkyl.

In an embodiment, R3, R4, R5and R6are each independently selected from hydrogen, halo, amino, (1-4C)alkyl and phenyl, any of which may be optionally substituted with one or more substituents selected from halo and (1-4C)alkyl.

In an embodiment, R7is selected from (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, (1-6C)haloalkyl, aryl and heteroaryl, any of which may be optionally substituted with one or more substituents selected from halo, oxo, hydroxy, amino, nitro, (1-6C)alkyl, (1-6C)haloalkyl and (1-6C)alkoxy.

In an embodiment, R7is selected from (1-4C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, (1-4C)haloalkyl, aryl and heteroaryl, any of which may be optionally substituted with one or more substituents selected from halo, oxo, hydroxy, amino, nitro, (1-4C)alkyl, (1-4C)haloalkyl and (1-4C)alkoxy.

In an embodiment, R7is selected from (1-4C)alkyl, (1-4C)haloalkyl, aryl and heteroaryl, any of which may be optionally substituted with one or more substituents selected from halo, hydroxy, amino, (1-4C)alkyl and (1-4C)alkoxy.

In an embodiment, R7is selected from (1-4C)alkyl and aryl, any of which may be optionally substituted with one or more substituents selected from halo, hydroxy, amino, (1-4C)alkyl and (1-4C)alkoxy.

In an embodiment, R7is selected from (1-2C)alkyl and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, hydroxy, amino and (1-4C)alkyl. Suitably, the one or more optional substituents is halo (e.g. fluoro).

In an embodiment, R7is (1-2C)alkyl, optionally substituted with one or more substituents selected from halo.

In an embodiment, R7is methyl, optionally substituted with one or more fluoro substituents.

In an embodiment, R7is methyl or trifluoromethyl.

In a particularly suitable embodiment, R7is methyl.

In an embodiment, Rais selected from aryl, aryloxy, heteroaryl, heteroaryloxy, carbocyclyl and heterocyclyl, any of which (for example the aryl group) may be optionally substituted with one or more substituents selected from halo, oxo, hydroxy, amino, nitro, (1-6C)alkyl, (1-6C)haloalkyl, aryl, aryloxy, heteroaryl and heteroaryloxy.

In an embodiment, Rais selected from phenyl, 5-7 membered heteroaryl and 5-12 membered carbocyclyl, any of which (for example the phenyl group) may be optionally substituted with one or more substituents selected from halo, oxo, hydroxy, amino, nitro, (1-5C)alkyl, (1-5C)haloalkyl, phenyl, and heteroaryl.

In an embodiment, Rais selected from phenyl and 5-12 membered carbocyclyl, any of which (for example the phenyl group) may be optionally substituted with one or more substituents selected from halo, hydroxy, amino, (1-5C)alkyl, (1-5C)haloalkyl, phenyl, and heteroaryl.

In an embodiment, Rais selected from phenyl, cyclohexyl and adamantyl, any of which (for example the phenyl group) may be optionally substituted with one or more substituents selected from halo, (1-5C)alkyl, phenyl, and heteroaryl.

In an embodiment, Rais not unsubstituted phenyl or unsubstituted cyclohexyl.

In an embodiment, Rais not unsubstituted phenyl.

In an embodiment, Rais not unsubstituted cyclohexyl.

In an embodiment, Rxis independently selected from hydrogen, (1-6C)alkyl, (1-6C)alkoxy and aryl, any of which may be optionally substituted with one or more substituents selected from halo, oxo, hydroxy, amino, nitro, (1-6C)alkyl and (1-6C)haloalkyl.

In an embodiment, Rxis independently selected from hydrogen, (1-4C)alkyl, (1-4C)alkoxy and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, amino and (1-6C)alkyl.

In an embodiment, Rxis independently selected from hydrogen, (1-4C)alkyl, and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, amino and (1-3C)alkyl.

In an embodiment, each Rxis phenyl.

In an embodiment, n is 0, 1 or 2.

In an embodiment, n is 0 or 1.

In an embodiment, n is 0 (in which case Rais bonded directly to N).

In an embodiment, the compound has a structure according to formula (I-A), (I-B) or (I-C), wherein

M is selected from titanium, zirconium and hafnium;
each X is independently selected from halo, hydrogen, (1-6C)alkoxy, and aryloxy, any of which may be optionally substituted one of more groups selected from halo, oxo, hydroxy, amino, nitro, (1-6C)alkyl, (1-6C)haloalkyl, (1-6C)alkoxy and aryl;
R2is absent or is selected from hydrogen, (1-4C)alkyl and phenyl;
R3, R4, R5and R6are each independently selected from hydrogen, halo, oxo, hydroxy, amino, nitro, (1-4C)alkyl, (1-4C)haloalkyl, (1-4C)alkoxy, aryl and heteroaryl, any of which may be optionally substituted with one or more substituents selected from halo, oxo, hydroxy, amino, nitro, (1-4C)alkyl, (1-4C)haloalkyl and (1-4C)alkoxy;
R7is selected from (1-4C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, (1-4C)haloalkyl, aryl and heteroaryl, any of which may be optionally substituted with one or more substituents selected from halo, oxo, hydroxy, amino, nitro, (1-4C)alkyl, (1-4C)haloalkyl and (1-4C)alkoxy;
R1is a group of formula (II) defined herein, wherein
Rais selected from (1-4C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, (1-4C)haloalkyl, (1-4C)alkoxy, aryl, aryloxy, heteroaryl, heteroaryloxy, carbocyclyl and heterocyclyl, any of which (for example the aryl group) may be optionally substituted with one or more substituents selected from halo, oxo, hydroxy, amino, nitro, (1-6C)alkyl, (1-6C)haloalkyl, aryl, aryloxy, heteroaryl and heteroaryloxy;
Rxis independently selected from hydrogen, (1-4C)alkyl, (1-4C)alkoxy and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, amino and (1-6C)alkyl; and
n is 0, 1 or 2.

In an embodiment, the compound has a structure according to formula (I-A), (I-B) or (I-C), wherein

M is selected from titanium and zirconium;
each X is independently selected from halo, hydrogen, and (1-4C)alkoxy, any of which may be optionally substituted one of more groups selected from halo, hydroxy, amino, (1-4C)alkyl and (1-4C)alkoxy;
R2is absent or is selected from hydrogen, (1-4C)alkyl and phenyl;
R3, R4, R5and R6are each independently selected from hydrogen, halo, amino, (1-4C)alkyl, (1-4C)haloalkyl, (1-4C)alkoxy and phenyl, any of which may be optionally substituted with one or more substituents selected from halo and (1-4C)alkyl;
R7is selected from (1-4C)alkyl and aryl, any of which may be optionally substituted with one or more substituents selected from halo, hydroxy, amino, (1-4C)alkyl and (1-4C)alkoxy;
R1is a group of formula (II) defined herein, wherein
Rais selected from aryl, aryloxy, heteroaryl, heteroaryloxy, carbocyclyl and heterocyclyl, any of which (for example the aryl group) may be optionally substituted with one or more substituents selected from halo, oxo, hydroxy, amino, nitro, (1-6C)alkyl, (1-6C)haloalkyl, aryl, aryloxy, heteroaryl and heteroaryloxy;
Rxis independently selected from hydrogen, (1-4C)alkyl, and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, amino and (1-3C)alkyl; and
n is 0 or 1.

In an embodiment, the compound has a structure according to formula (I-A), (I-B) or (I-C), wherein

M is selected from titanium and zirconium;
each X is independently selected from chloro, bromo and (1-4C)alkoxy;
R2is absent or is selected from hydrogen and (1-4C)alkyl;
R3, R4, R5and R6are each independently selected from hydrogen, halo, amino, (1-4C)alkyl and phenyl, any of which may be optionally substituted with one or more substituents selected from halo and (1-4C)alkyl;
R7is selected from (1-2C)alkyl and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, hydroxy, amino and (1-4C)alkyl;
R1is a group of formula (II) defined herein, wherein
Rais selected from phenyl and 5-12 membered carbocyclyl, any of which (for example the phenyl group) may be optionally substituted with one or more substituents selected from halo, hydroxy, amino, (1-5C)alkyl, (1-5C)haloalkyl, phenyl, and heteroaryl;
Rxis independently selected from hydrogen, (1-4C)alkyl, and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, amino and (1-3C)alkyl; and
n is 0 or 1.

In an embodiment, the compound has a structure according to formula (I-A), (I-B) or (I-C), wherein

R1is a group of formula (II) defined herein, wherein
Rais selected from phenyl, cyclohexyl and adamantyl, any of which (for example the phenyl group group) may be optionally substituted with one or more substituents selected from halo, (1-5C)alkyl, phenyl, and heteroaryl;
each Rxis phenyl; and
n is 0 or 1.

In an embodiment, the compound has a structure according to formula (I-A-1), (I-B-1) or (I-C-1) shown below:

wherein M, X, R1and R3-R7have any of the definitions discussed hereinbefore in respect of formulae (I-A), (I-B) and (I-C).

In an embodiment, the compound having a structure according to formula (I-A-1), (I-B-1) or (I-C-1) has a structure according to formula (I-A-1) or (I-B-1).

In an embodiment, the compound having a structure according to formula (I-A-1), (I-B-1) or (I-C-1) has a structure according to formula (I-A-1).

In an embodiment, the compound having a structure according to formula (I-A-1), (I-B-1) or (I-C-1) has a structure according to formula (I-B-1).

In an embodiment, the compound having a structure according to formula (I-A-1), (I-B-1) or (I-C-1) has a structure according to formula (I-C-1).

In an embodiment, the compound has a structure according to formula (I-A-1), (I-B-1) or (I-C-1), wherein

M is selected from titanium, zirconium and hafnium;
each X is independently selected from halo, hydrogen, (1-6C)alkoxy, and aryloxy, any of which may be optionally substituted one of more groups selected from halo, oxo, hydroxy, amino, nitro, (1-6C)alkyl, (1-6C)haloalkyl, (1-6C)alkoxy and aryl;
R3, R4, R5and R6are each independently selected from hydrogen, halo, oxo, hydroxy, amino, nitro, (1-4C)alkyl, (1-4C)haloalkyl, (1-4C)alkoxy, aryl and heteroaryl, any of which may be optionally substituted with one or more substituents selected from halo, oxo, hydroxy, amino, nitro, (1-4C)alkyl, (1-4C)haloalkyl and (1-4C)alkoxy;
R7is selected from (1-4C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, (1-4C)haloalkyl, aryl and heteroaryl, any of which may be optionally substituted with one or more substituents selected from halo, oxo, hydroxy, amino, nitro, (1-4C)alkyl, (1-4C)haloalkyl and (1-4C)alkoxy;
R1is a group of formula (II) defined herein, wherein
Rais selected from (1-4C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, (1-4C)haloalkyl, (1-4C)alkoxy, aryl, aryloxy, heteroaryl, heteroaryloxy, carbocyclyl and heterocyclyl, any of which (for example the aryl group) may be optionally substituted with one or more substituents selected from halo, oxo, hydroxy, amino, nitro, (1-6C)alkyl, (1-6C)haloalkyl, aryl, aryloxy, heteroaryl and heteroaryloxy;
Rxis independently selected from hydrogen, (1-4C)alkyl, (1-4C)alkoxy and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, amino and (1-6C)alkyl; and
n is 0, 1 or 2.

In an embodiment, the compound has a structure according to formula (I-A-1), (I-B-1) or (I-C-1), wherein

M is selected from titanium and zirconium;
each X is independently selected from halo, hydrogen, and (1-4C)alkoxy, any of which may be optionally substituted one of more groups selected from halo, hydroxy, amino, (1-4C)alkyl and (1-4C)alkoxy;
R3, R4, R5and R6are each independently selected from hydrogen, halo, amino, (1-4C)alkyl, (1-4C)haloalkyl, (1-4C)alkoxy and phenyl, any of which may be optionally substituted with one or more substituents selected from halo and (1-4C)alkyl;
R7is selected from (1-4C)alkyl and aryl, any of which may be optionally substituted with one or more substituents selected from halo, hydroxy, amino, (1-4C)alkyl and (1-4C)alkoxy;
R1is a group of formula (II) defined herein, wherein
Rais selected from aryl, aryloxy, heteroaryl, heteroaryloxy, carbocyclyl and heterocyclyl, any of which (for example the aryl group) may be optionally substituted with one or more substituents selected from halo, oxo, hydroxy, amino, nitro, (1-6C)alkyl, (1-6C)haloalkyl, aryl, aryloxy, heteroaryl and heteroaryloxy;
Rxis independently selected from hydrogen, (1-4C)alkyl, and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, amino and (1-3C)alkyl; and
n is 0 or 1.

In an embodiment, the compound has a structure according to formula (I-A-1), (I-B-1) or (I-C-1), wherein

M is selected from titanium and zirconium;
each X is independently selected from chloro, bromo and (1-4C)alkoxy;
R3, R4, R5and R6are each independently selected from hydrogen, halo, amino, (1-4C)alkyl and phenyl, any of which may be optionally substituted with one or more substituents selected from halo and (1-4C)alkyl;
R7is selected from (1-2C)alkyl and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, hydroxy, amino and (1-4C)alkyl;
R1is a group of formula (II) defined herein, wherein
Rais selected from phenyl and 5-12 membered carbocyclyl, any of which may (for example the phenyl group) be optionally substituted with one or more substituents selected from halo, hydroxy, amino, (1-5C)alkyl, (1-5C)haloalkyl, phenyl, and heteroaryl;
Rxis independently selected from hydrogen, (1-4C)alkyl, and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, amino and (1-3C)alkyl; and
n is 0 or 1.

In an embodiment, the compound has a structure according to formula (I-A-1), (I-B-1) or (I-C-1), wherein

M is titanium;
each X is independently (1-4C)alkoxy;
R3, R4, R5and R6are each independently selected from hydrogen, (1-4C)alkyl and phenyl;

R1is a group of formula (II) defined herein, wherein
Rais selected from phenyl, cyclohexyl and adamantyl, any of which (for example the phenyl group) may be optionally substituted with one or more substituents selected from halo, (1-5C)alkyl, phenyl, and heteroaryl;
each Rxis phenyl; and
n is 0 or 1.

In an embodiment, the compound has a structure according to formula (I-A-2), (I-B-2) or (I-C-2) shown below:

wherein M, X and R1-R6have any of the definitions discussed hereinbefore in respect of formulae (I-A), (I-B) and (I-C).

In an embodiment, the compound having a structure according to formula (I-A-2), (I-B-2) or (I-C-2) has a structure according to formula (I-A-2) or (I-B-2).

In an embodiment, the compound having a structure according to formula (I-A-2), (I-B-2) or (I-C-2) has a structure according to formula (I-A-2).

In an embodiment, the compound having a structure according to formula (I-A-2), (I-B-2) or (I-C-2) has a structure according to formula (I-B-2).

In an embodiment, the compound having a structure according to formula (I-A-2), (I-B-2) or (I-C-2) has a structure according to formula (I-C-2).

In an embodiment, the compound has a structure according to formula (I-A-2), (I-B-2) or (I-C-2), wherein

M is selected from titanium, zirconium and hafnium;
each X is independently selected from halo, hydrogen, (1-6C)alkoxy, and aryloxy, any of which may be optionally substituted one of more groups selected from halo, oxo, hydroxy, amino, nitro, (1-6C)alkyl, (1-6C)haloalkyl, (1-6C)alkoxy and aryl;
R2is absent or is selected from hydrogen, (1-4C)alkyl and phenyl;
R3, R4, R5and R6are each independently selected from hydrogen, halo, oxo, hydroxy, amino, nitro, (1-4C)alkyl, (1-4C)haloalkyl, (1-4C)alkoxy, aryl and heteroaryl, any of which may be optionally substituted with one or more substituents selected from halo, oxo, hydroxy, amino, nitro, (1-4C)alkyl, (1-4C)haloalkyl and (1-4C)alkoxy;
R1is a group of formula (II) defined herein, wherein
Rais selected from (1-4C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, (1-4C)haloalkyl, (1-4C)alkoxy, aryl, aryloxy, heteroaryl, heteroaryloxy, carbocyclyl and heterocyclyl, any of which (for example the aryl group) may be optionally substituted with one or more substituents selected from halo, oxo, hydroxy, amino, nitro, (1-6C)alkyl, (1-6C)haloalkyl, aryl, aryloxy, heteroaryl and heteroaryloxy;
Rxis independently selected from hydrogen, (1-4C)alkyl, (1-4C)alkoxy and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, amino and (1-6C)alkyl; and
n is 0, 1 or 2.

In an embodiment, the compound has a structure according to formula (I-A-2), (I-B-2) or (I-C-2), wherein

M is selected from titanium and zirconium;
each X is independently selected from halo, hydrogen, and (1-4C)alkoxy, any of which may be optionally substituted one of more groups selected from halo, hydroxy, amino, (1-4C)alkyl and (1-4C)alkoxy;
R2is absent or is selected from hydrogen, (1-4C)alkyl and phenyl;
R3, R4, R5and R6are each independently selected from hydrogen, halo, amino, (1-4C)alkyl, (1-4C)haloalkyl, (1-4C)alkoxy and phenyl, any of which may be optionally substituted with one or more substituents selected from halo and (1-4C)alkyl;
R1is a group of formula (II) defined herein, wherein
Rais selected from aryl, aryloxy, heteroaryl, heteroaryloxy, carbocyclyl and heterocyclyl, any of which (for example the aryl group) may be optionally substituted with one or more substituents selected from halo, oxo, hydroxy, amino, nitro, (1-6C)alkyl, (1-6C)haloalkyl, aryl, aryloxy, heteroaryl and heteroaryloxy;
Rxis independently selected from hydrogen, (1-4C)alkyl, and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, amino and (1-3C)alkyl; and
n is 0 or 1.

In an embodiment, the compound has a structure according to formula (I-A-2), (I-B-2) or (I-C-2), wherein

M is selected from titanium and zirconium;
each X is independently selected from chloro, bromo and (1-4C)alkoxy;
R2is absent or hydrogen;
R3, R4, R5and R6are each independently selected from hydrogen, halo, amino, (1-4C)alkyl and phenyl, any of which may be optionally substituted with one or more substituents selected from halo and (1-4C)alkyl;
R1is a group of formula (II) defined herein, wherein
Rais selected from phenyl and 5-12 membered carbocyclyl, any of which (for example the phenyl group) may be optionally substituted with one or more substituents selected from halo, hydroxy, amino, (1-5C)alkyl, (1-5C)haloalkyl, phenyl, and heteroaryl;
Rxis independently selected from hydrogen, (1-4C)alkyl, and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, amino and (1-3C)alkyl; and
n is 0 or 1.

In an embodiment, the compound has a structure according to formula (I-A-2), (I-B-2) or (I-C-2), wherein

M is titanium;
each X is independently (1-4C)alkoxy;
R2is absent or hydrogen;
R3, R4, R5and R6are each independently selected from hydrogen, (1-4C)alkyl and phenyl;
R1is a group of formula (II) defined herein, wherein
Rais selected from phenyl, cyclohexyl and adamantyl, any of which (for example the phenyl group) may be optionally substituted with one or more substituents selected from halo, (1-5C)alkyl, phenyl, and heteroaryl;
each Rxis phenyl; and
n is 0 or 1.

In an embodiment, the compound has a structure according to formula (I-A-2), (I-B-2) or (I-C-2), wherein

M is selected from titanium and zirconium;
each X is independently selected from chloro, bromo and (1-4C)alkoxy;
R2is absent;
R3, R4, R5and R6are each independently selected from hydrogen, halo, amino, (1-4C)alkyl and phenyl, any of which may be optionally substituted with one or more substituents selected from halo and (1-4C)alkyl;
R1is a group of formula (II) defined herein, wherein
Rais selected from phenyl and 5-12 membered carbocyclyl, any of which (for example the phenyl group) may be optionally substituted with one or more substituents selected from halo, hydroxy, amino, (1-5C)alkyl, (1-5C)haloalkyl, phenyl, and heteroaryl;
Rxis independently selected from hydrogen, (1-4C)alkyl, and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, amino and (1-3C)alkyl; and
n is 0 or 1.

In an embodiment, the compound has a structure according to formula (I-A-2), (I-B-2) or (I-C-2), wherein

M is titanium;
each X is independently (1-4C)alkoxy;
R2is absent or hydrogen;
R3, R4, R5and R6are each independently selected from hydrogen, (1-4C)alkyl and phenyl;
R1is a group of formula (II) defined herein, wherein
Rais selected from phenyl, cyclohexyl and adamantyl, any of which (for example the phenyl group) may be optionally substituted with one or more substituents selected from halo, (1-5C)alkyl, phenyl, and heteroaryl;
each Rxis phenyl; and
n is 0 or 1.

In an embodiment, the compound has a structure according to formula (I-A-3), (I-B-3) or (I-C-3) shown below:

wherein M, X, R1-R3and R7have any of the definitions discussed hereinbefore in respect of formulae (I-A), (I-B) and (I-C).

In an embodiment, the compound having a structure according to formula (I-A-3), (I-B-3) or (I-C-3) has a structure according to formula (I-A-3) or (I-B-3).

In an embodiment, the compound having a structure according to formula (I-A-3), (I-B-3) or (I-C-3) has a structure according to formula (I-A-3).

In an embodiment, the compound having a structure according to formula (I-A-3), (I-B-3) or (I-C-3) has a structure according to formula (I-B-3).

In an embodiment, the compound having a structure according to formula (I-A-3), (I-B-3) or (I-C-3) has a structure according to formula (I-C-3).

In an embodiment, the compound has a structure according to formula (I-A-3), (I-B-3) or (I-C-3), wherein

M is selected from titanium, zirconium and hafnium;
each X is independently selected from halo, hydrogen, (1-6C)alkoxy, and aryloxy, any of which may be optionally substituted one of more groups selected from halo, oxo, hydroxy, amino, nitro, (1-6C)alkyl, (1-6C)haloalkyl, (1-6C)alkoxy and aryl;
R2is absent or is selected from hydrogen, (1-4C)alkyl and phenyl;
R7is selected from (1-4C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, (1-4C)haloalkyl, aryl and heteroaryl, any of which may be optionally substituted with one or more substituents selected from halo, oxo, hydroxy, amino, nitro, (1-4C)alkyl, (1-4C)haloalkyl and (1-4C)alkoxy;
R1is a group of formula (II) defined herein, wherein
Rais selected from (1-4C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, (1-4C)haloalkyl, (1-4C)alkoxy, aryl, aryloxy, heteroaryl, heteroaryloxy, carbocyclyl and heterocyclyl, any of which (for example the aryl group) may be optionally substituted with one or more substituents selected from halo, oxo, hydroxy, amino, nitro, (1-6C)alkyl, (1-6C)haloalkyl, aryl, aryloxy, heteroaryl and heteroaryloxy;
Rxis independently selected from hydrogen, (1-4C)alkyl, (1-4C)alkoxy and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, amino and (1-6C)alkyl; and
n is 0, 1 or 2.

In an embodiment, the compound has a structure according to formula (I-A-3), (I-B-3) or (I-C-3), wherein

M is selected from titanium and zirconium;
each X is independently selected from halo, hydrogen, and (1-4C)alkoxy, any of which may be optionally substituted one of more groups selected from halo, hydroxy, amino, (1-4C)alkyl and (1-4C)alkoxy;
R2is absent or is selected from hydrogen, (1-4C)alkyl and phenyl;
R7is selected from (1-2C)alkyl and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, hydroxy, amino and (1-4C)alkyl;
R1is a group of formula (II) defined herein, wherein
Rais selected from aryl, aryloxy, heteroaryl, heteroaryloxy, carbocyclyl and heterocyclyl, any of which (for example the aryl group) may be optionally substituted with one or more substituents selected from halo, oxo, hydroxy, amino, nitro, (1-6C)alkyl, (1-6C)haloalkyl, aryl, aryloxy, heteroaryl and heteroaryloxy;
Rxis independently selected from hydrogen, (1-4C)alkyl, and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, amino and (1-3C)alkyl; and
n is 0 or 1.

In an embodiment, the compound has a structure according to formula (I-A-3), (I-B-3) or (I-C-3), wherein

M is selected from titanium and zirconium;
each X is independently selected from chloro, bromo and (1-4C)alkoxy;
R2is absent or hydrogen;
R7is selected from (1-2C)alkyl and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, hydroxy, amino and (1-4C)alkyl;
R1is a group of formula (II) defined herein, wherein
Rais selected from phenyl and 5-12 membered carbocyclyl, any of which (for example the phenyl group) may be optionally substituted with one or more substituents selected from halo, hydroxy, amino, (1-5C)alkyl, (1-5C)haloalkyl, phenyl, and heteroaryl;
Rxis independently selected from hydrogen, (1-4C)alkyl, and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, amino and (1-3C)alkyl; and
n is 0 or 1.

In an embodiment, the compound has a structure according to formula (I-A-3), (I-B-3) or (I-C-3), wherein

M is selected from titanium and zirconium;
each X is independently selected from chloro, bromo and (1-4C)alkoxy;
R2is absent;
R7is selected from (1-2C)alkyl and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, hydroxy, amino and (1-4C)alkyl;
R1is a group of formula (II) defined herein, wherein
Rais selected from phenyl and 5-12 membered carbocyclyl, any of which (for example the phenyl group) may be optionally substituted with one or more substituents selected from halo, hydroxy, amino, (1-5C)alkyl, (1-5C)haloalkyl, phenyl, and heteroaryl;
Rxis independently selected from hydrogen, (1-4C)alkyl, and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, amino and (1-3C)alkyl; and
n is 0 or 1.

In an embodiment, the compound has a structure according to formula (I-A-3), (I-B-3) or (I-C-3), wherein

M is titanium;
each X is independently (1-4C)alkoxy;
R2is absent or hydrogen;

R1is a group of formula (II) defined herein, wherein
Rais selected from phenyl, cyclohexyl and adamantyl, any of which (for example the phenyl group) may be optionally substituted with one or more substituents selected from halo, (1-5C)alkyl, phenyl, and heteroaryl;
each Rxis phenyl; and
n is 0 or 1.

In an embodiment, the compound has a structure according to formula (I-A-3), (I-B-3) or (I-C-3), wherein

M is titanium;
each X is independently (1-4C)alkoxy;
R2is absent;

R1is a group of formula (II) defined herein, wherein
Rais selected from phenyl, cyclohexyl and adamantyl, any of which (for example the phenyl group) may be optionally substituted with one or more substituents selected from halo, (1-5C)alkyl, phenyl, and heteroaryl;
each Rxis phenyl; and
n is 0 or 1.

In an embodiment, the compound has a structure according to formula (I-A) or (I-B), wherein

M is selected from titanium, zirconium and hafnium;
each X is independently selected from halo, hydrogen, (1-6C)alkoxy, and aryloxy, any of which may be optionally substituted one of more groups selected from halo, oxo, hydroxy, amino, nitro, (1-6C)alkyl, (1-6C)haloalkyl, (1-6C)alkoxy and aryl;
R2is absent or is selected from hydrogen, (1-4C)alkyl and phenyl;
R3, R4, R5and R6are each independently selected from hydrogen, halo, oxo, hydroxy, amino, nitro, (1-4C)alkyl, (1-4C)haloalkyl, (1-4C)alkoxy, aryl and heteroaryl, any of which may be optionally substituted with one or more substituents selected from halo, oxo, hydroxy, amino, nitro, (1-4C)alkyl, (1-4C)haloalkyl and (1-4C)alkoxy;
R7is selected from (1-4C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, (1-4C)haloalkyl, aryl and heteroaryl, any of which may be optionally substituted with one or more substituents selected from halo, oxo, hydroxy, amino, nitro, (1-4C)alkyl, (1-4C)haloalkyl and (1-4C)alkoxy;
R1is a group of formula (II) defined herein, wherein
Rais selected from (1-4C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, (1-4C)haloalkyl, (1-4C)alkoxy, aryl, aryloxy, heteroaryl, heteroaryloxy, carbocyclyl and heterocyclyl, any of which (for example the aryl group) may be optionally substituted with one or more substituents selected from halo, oxo, hydroxy, amino, nitro, (1-6C)alkyl, (1-6C)alkoxy, (1-6C)haloalkyl, aryl, aryloxy, heteroaryl and heteroaryloxy;
Rxis independently selected from hydrogen, (1-4C)alkyl, (1-4C)alkoxy and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, amino and (1-6C)alkyl; and
n is 0, 1 or 2.

In an embodiment, the compound has a structure according to formula (I-A) or (I-B), wherein

M is selected from titanium and zirconium;
each X is independently selected from halo, hydrogen, and (1-4C)alkoxy, any of which may be optionally substituted one of more groups selected from halo, hydroxy, amino, (1-4C)alkyl and (1-4C)alkoxy;
R2is absent or is selected from hydrogen, (1-4C)alkyl and phenyl;
R3, R4, R5and R6are each independently selected from hydrogen, halo, amino, (1-4C)alkyl, (1-4C)haloalkyl, (1-4C)alkoxy and phenyl, any of which may be optionally substituted with one or more substituents selected from halo and (1-4C)alkyl;
R7is selected from (1-4C)alkyl and aryl, any of which may be optionally substituted with one or more substituents selected from halo, hydroxy, amino, (1-4C)alkyl and (1-4C)alkoxy;
R1is a group of formula (II) defined herein, wherein
Rais selected from aryl, aryloxy, heteroaryl, heteroaryloxy, carbocyclyl and heterocyclyl, any of which (for example the aryl group) may be optionally substituted with one or more substituents selected from halo, oxo, hydroxy, amino, nitro, (1-6C)alkyl, (1-6C)alkoxy, (1-6C)haloalkyl, aryl, aryloxy, heteroaryl and heteroaryloxy;
Rxis independently selected from hydrogen, (1-4C)alkyl, and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, amino and (1-3C)alkyl; and
n is 0 or 1.

In an embodiment, the compound has a structure according to formula (I-A) or (I-B), wherein

M is selected from titanium and zirconium;
each X is independently selected from chloro, bromo and (1-4C)alkoxy;
R2is absent or is selected from hydrogen and (1-4C)alkyl;
R3, R4, R5and R6are each independently selected from hydrogen, halo, amino, (1-4C)alkyl and phenyl, any of which may be optionally substituted with one or more substituents selected from halo and (1-4C)alkyl;
R7is selected from (1-2C)alkyl and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, hydroxy, amino and (1-4C)alkyl;
R1is a group of formula (II) defined herein, wherein
Rais selected from phenyl and 5-12 membered carbocyclyl, any of which (for example the phenyl group) may be optionally substituted with one or more substituents selected from halo, hydroxy, amino, (1-5C)alkyl, (1-3C)alkoxy, (1-5C)haloalkyl, phenyl, and heteroaryl;
Rxis independently selected from hydrogen, (1-4C)alkyl, and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, amino and (1-3C)alkyl; and
n is 0 or 1.

In an embodiment, the compound has a structure according to formula (I-A) or (I-B), wherein

R1is a group of formula (II) defined herein, wherein
Rais selected from phenyl, cyclohexyl and adamantyl, any of which (for example the phenyl group) may be optionally substituted with one or more substituents selected from halo, (1-5C)alkyl, phenyl, and heteroaryl;
each Rxis phenyl; and
n is 0 or 1.

In an embodiment, the compound has a structure according to formula (I-A) or (I-B), wherein

M is selected from titanium, zirconium and hafnium;
each X is independently selected from halo, hydrogen, (1-6C)alkoxy, (1-4C)dialkylamino and aryloxy, any of which may be optionally substituted one of more groups selected from halo, oxo, hydroxy, amino, nitro, (1-6C)alkyl, (1-6C)haloalkyl, (1-6C)alkoxy and aryl;
R2is absent or is selected from hydrogen, (1-4C)alkyl and phenyl;
R3, R4, R5and R6are each independently selected from hydrogen, halo, oxo, hydroxy, amino, nitro, (1-4C)alkyl, (1-4C)haloalkyl, (1-4C)alkoxy, aryl and heteroaryl, any of which may be optionally substituted with one or more substituents selected from halo, oxo, hydroxy, amino, nitro, (1-4C)alkyl, (1-4C)haloalkyl and (1-4C)alkoxy;
R7is selected from (1-4C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, (1-4C)haloalkyl, aryl and heteroaryl, any of which may be optionally substituted with one or more substituents selected from halo, oxo, hydroxy, amino, nitro, (1-4C)alkyl, (1-4C)haloalkyl and (1-4C)alkoxy;
R1is a group of formula (II) defined herein, wherein
Rais selected from (1-4C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, (1-4C)haloalkyl, (1-4C)alkoxy, aryl, aryloxy, heteroaryl, heteroaryloxy, carbocyclyl and heterocyclyl, any of which (for example the aryl group) may be optionally substituted with one or more substituents selected from halo, oxo, hydroxy, amino, nitro, (1-6C)alkyl, (1-6C)alkoxy, (1-6C)haloalkyl, aryl, aryloxy, heteroaryl and heteroaryloxy;
Rxis independently selected from hydrogen, (1-4C)alkyl, (1-4C)alkoxy and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, amino and (1-6C)alkyl; and
n is 0, 1 or 2.

In an embodiment, the compound has a structure according to formula (I-A) or (I-B), wherein

M is selected from titanium and zirconium;
each X is independently selected from halo, hydrogen, (1-4C)dialkylamino and (1-4C)alkoxy, any of which may be optionally substituted one of more groups selected from halo, hydroxy, amino, (1-4C)alkyl and (1-4C)alkoxy;
R2is absent or is selected from hydrogen, (1-4C)alkyl and phenyl;
R3, R4, R5and R6are each independently selected from hydrogen, halo, amino, (1-4C)alkyl, (1-4C)haloalkyl, (1-4C)alkoxy and phenyl, any of which may be optionally substituted with one or more substituents selected from halo and (1-4C)alkyl;
R7is selected from (1-4C)alkyl and aryl, any of which may be optionally substituted with one or more substituents selected from halo, hydroxy, amino, (1-4C)alkyl and (1-4C)alkoxy;
R1is a group of formula (II) defined herein, wherein
Rais selected from aryl, aryloxy, heteroaryl, heteroaryloxy, carbocyclyl and heterocyclyl, any of which (for example the aryl group) may be optionally substituted with one or more substituents selected from halo, oxo, hydroxy, amino, nitro, (1-6C)alkyl, (1-6C)alkoxy, (1-6C)haloalkyl, aryl, aryloxy, heteroaryl and heteroaryloxy;
Rxis independently selected from hydrogen, (1-4C)alkyl, and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, amino and (1-3C)alkyl; and
n is 0 or 1.

In an embodiment, the compound has a structure according to formula (I-A) or (I-B), wherein

M is selected from titanium and zirconium;
each X is independently selected from chloro, bromo, (1-2C)dialkylamino and (1-4C)alkoxy;
R2is absent or is selected from hydrogen and (1-4C)alkyl;
R3, R4, R5and R6are each independently selected from hydrogen, halo, amino, (1-4C)alkyl and phenyl, any of which may be optionally substituted with one or more substituents selected from halo and (1-4C)alkyl;
R7is selected from (1-2C)alkyl and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, hydroxy, amino and (1-4C)alkyl;
R1is a group of formula (II) defined herein, wherein
Rais selected from phenyl and 5-12 membered carbocyclyl, any of which (for example the phenyl group) may be optionally substituted with one or more substituents selected from halo, hydroxy, amino, (1-5C)alkyl, (1-3C)alkoxy, (1-5C)haloalkyl, phenyl, and heteroaryl;
Rxis independently selected from hydrogen, (1-4C)alkyl, and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, amino and (1-3C)alkyl; and
n is 0 or 1.

In an embodiment, the compound has a structure according to formula (I-A) or (I-B), wherein

R1is a group of formula (II) defined herein, wherein
Rais selected from phenyl, cyclohexyl and adamantyl, any of which (for example the phenyl group) may be optionally substituted with one or more substituents selected from halo, (1-5C)alkyl, phenyl, and heteroaryl;
each Rxis phenyl; and
n is 0 or 1.

In an embodiment, the compound has a structure according to formula (I-A-1) or (I-B-1), wherein

M is selected from titanium, zirconium and hafnium;
each X is independently selected from halo, hydrogen, (1-6C)alkoxy, and aryloxy, any of which may be optionally substituted one of more groups selected from halo, oxo, hydroxy, amino, nitro, (1-6C)alkyl, (1-6C)haloalkyl, (1-6C)alkoxy and aryl;
R3, R4, R5and R6are each independently selected from hydrogen, halo, oxo, hydroxy, amino, nitro, (1-4C)alkyl, (1-4C)haloalkyl, (1-4C)alkoxy, aryl and heteroaryl, any of which may be optionally substituted with one or more substituents selected from halo, oxo, hydroxy, amino, nitro, (1-4C)alkyl, (1-4C)haloalkyl and (1-4C)alkoxy;
R7is selected from (1-4C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, (1-4C)haloalkyl, aryl and heteroaryl, any of which may be optionally substituted with one or more substituents selected from halo, oxo, hydroxy, amino, nitro, (1-4C)alkyl, (1-4C)haloalkyl and (1-4C)alkoxy;
R1is a group of formula (II) defined herein, wherein
Rais selected from (1-4C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, (1-4C)haloalkyl, (1-4C)alkoxy, aryl, aryloxy, heteroaryl, heteroaryloxy, carbocyclyl and heterocyclyl, any of which (for example the aryl group) may be optionally substituted with one or more substituents selected from halo, oxo, hydroxy, amino, nitro, (1-6C)alkyl, (1-6C)alkoxy, (1-6C)haloalkyl, aryl, aryloxy, heteroaryl and heteroaryloxy;
Rxis independently selected from hydrogen, (1-4C)alkyl, (1-4C)alkoxy and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, amino and (1-6C)alkyl; and
n is 0, 1 or 2.

In an embodiment, the compound has a structure according to formula (I-A-1) or (I-B-1), wherein

M is selected from titanium and zirconium;
each X is independently selected from halo, hydrogen, and (1-4C)alkoxy, any of which may be optionally substituted one of more groups selected from halo, hydroxy, amino, (1-4C)alkyl and (1-4C)alkoxy;
R3, R4, R5and R6are each independently selected from hydrogen, halo, amino, (1-4C)alkyl, (1-4C)haloalkyl, (1-4C)alkoxy and phenyl, any of which may be optionally substituted with one or more substituents selected from halo and (1-4C)alkyl;
R7is selected from (1-4C)alkyl and aryl, any of which may be optionally substituted with one or more substituents selected from halo, hydroxy, amino, (1-4C)alkyl and (1-4C)alkoxy;
R1is a group of formula (II) defined herein, wherein
Rais selected from aryl, aryloxy, heteroaryl, heteroaryloxy, carbocyclyl and heterocyclyl, any of which (for example the aryl group) may be optionally substituted with one or more substituents selected from halo, oxo, hydroxy, amino, nitro, (1-6C)alkyl, (1-6C)alkoxy, (1-6C)haloalkyl, aryl, aryloxy, heteroaryl and heteroaryloxy;
Rxis independently selected from hydrogen, (1-4C)alkyl, and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, amino and (1-3C)alkyl; and
n is 0 or 1.

In an embodiment, the compound has a structure according to formula (I-A-1) or (I-B-1), wherein

M is selected from titanium and zirconium;
each X is independently selected from chloro, bromo and (1-4C)alkoxy;
R3, R4, R5and R6are each independently selected from hydrogen, halo, amino, (1-4C)alkyl and phenyl, any of which may be optionally substituted with one or more substituents selected from halo and (1-4C)alkyl;
R7is selected from (1-2C)alkyl and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, hydroxy, amino and (1-4C)alkyl;
R1is a group of formula (II) defined herein, wherein
Rais selected from phenyl and 5-12 membered carbocyclyl, any of which (for example the phenyl group) may be optionally substituted with one or more substituents selected from halo, hydroxy, amino, (1-5C)alkyl, (1-3C)alkoxy, (1-5C)haloalkyl, phenyl, and heteroaryl;
Rxis independently selected from hydrogen, (1-4C)alkyl, and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, amino and (1-3C)alkyl; and
n is 0 or 1.

In an embodiment, the compound has a structure according to formula (I-A-1) or (I-B-1), wherein

M is titanium;
each X is independently (1-4C)alkoxy;
R3, R4, R5and R6are each independently selected from hydrogen, (1-4C)alkyl and phenyl;

R1is a group of formula (II) defined herein, wherein
Rais selected from phenyl, cyclohexyl and adamantyl, any of which (for example the phenyl group) may be optionally substituted with one or more substituents selected from halo, (1-5C)alkyl, phenyl, and heteroaryl;
each Rxis phenyl; and
n is 0 or 1.

In an embodiment, the compound has a structure according to formula (I-A-1) or (I-B-1), wherein

M is selected from titanium, zirconium and hafnium;
each X is independently selected from halo, hydrogen, (1-6C)alkoxy, (1-4C)dialkylamino and aryloxy, any of which may be optionally substituted one of more groups selected from halo, oxo, hydroxy, amino, nitro, (1-6C)alkyl, (1-6C)haloalkyl, (1-6C)alkoxy and aryl;
R3, R4, R5and R6are each independently selected from hydrogen, halo, oxo, hydroxy, amino, nitro, (1-4C)alkyl, (1-4C)haloalkyl, (1-4C)alkoxy, aryl and heteroaryl, any of which may be optionally substituted with one or more substituents selected from halo, oxo, hydroxy, amino, nitro, (1-4C)alkyl, (1-4C)haloalkyl and (1-4C)alkoxy;
R7is selected from (1-4C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, (1-4C)haloalkyl, aryl and heteroaryl, any of which may be optionally substituted with one or more substituents selected from halo, oxo, hydroxy, amino, nitro, (1-4C)alkyl, (1-4C)haloalkyl and (1-4C)alkoxy;
R1is a group of formula (II) defined herein, wherein
Rais selected from (1-4C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, (1-4C)haloalkyl, (1-4C)alkoxy, aryl, aryloxy, heteroaryl, heteroaryloxy, carbocyclyl and heterocyclyl, any of which (for example the aryl group) may be optionally substituted with one or more substituents selected from halo, oxo, hydroxy, amino, nitro, (1-6C)alkyl, (1-6C)alkoxy, (1-6C)haloalkyl, aryl, aryloxy, heteroaryl and heteroaryloxy;
Rxis independently selected from hydrogen, (1-4C)alkyl, (1-4C)alkoxy and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, amino and (1-6C)alkyl; and
n is 0, 1 or 2.

In an embodiment, the compound has a structure according to formula (I-A-1) or (I-B-1), wherein

M is selected from titanium and zirconium;
each X is independently selected from halo, hydrogen, (1-4C)dialkylamino and (1-4C)alkoxy, any of which may be optionally substituted one of more groups selected from halo, hydroxy, amino, (1-4C)alkyl and (1-4C)alkoxy;
R3, R4, R5and R6are each independently selected from hydrogen, halo, amino, (1-4C)alkyl, (1-4C)haloalkyl, (1-4C)alkoxy and phenyl, any of which may be optionally substituted with one or more substituents selected from halo and (1-4C)alkyl;
R7is selected from (1-4C)alkyl and aryl, any of which may be optionally substituted with one or more substituents selected from halo, hydroxy, amino, (1-4C)alkyl and (1-4C)alkoxy;
R1is a group of formula (II) defined herein, wherein
Rais selected from aryl, aryloxy, heteroaryl, heteroaryloxy, carbocyclyl and heterocyclyl, any of which (for example the aryl group) may be optionally substituted with one or more substituents selected from halo, oxo, hydroxy, amino, nitro, (1-6C)alkyl, (1-6C)alkoxy, (1-6C)haloalkyl, aryl, aryloxy, heteroaryl and heteroaryloxy;
Rxis independently selected from hydrogen, (1-4C)alkyl, and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, amino and (1-3C)alkyl; and
n is 0 or 1.

In an embodiment, the compound has a structure according to formula (I-A-1) or (I-B-1), wherein

M is selected from titanium and zirconium;
each X is independently selected from chloro, bromo, (1-2C)dialkylamino and (1-4C)alkoxy;
R3, R4, R5and R6are each independently selected from hydrogen, halo, amino, (1-4C)alkyl and phenyl, any of which may be optionally substituted with one or more substituents selected from halo and (1-4C)alkyl;
R7is selected from (1-2C)alkyl and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, hydroxy, amino and (1-4C)alkyl;
R1is a group of formula (II) defined herein, wherein
Rais selected from phenyl and 5-12 membered carbocyclyl, any of which (for example the phenyl group) may be optionally substituted with one or more substituents selected from halo, hydroxy, amino, (1-5C)alkyl, (1-3C)alkoxy, (1-5C)haloalkyl, phenyl, and heteroaryl;
Rxis independently selected from hydrogen, (1-4C)alkyl, and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, amino and (1-3C)alkyl; and
n is 0 or 1.

In an embodiment, the compound has a structure according to formula (I-A-1) or (I-B-1), wherein

M is titanium;
each X is independently (1-2C)dialkylamino or (1-4C)alkoxy;
R3, R4, R5and R6are each independently selected from hydrogen, (1-4C)alkyl and phenyl;

R1is a group of formula (II) defined herein, wherein
Rais selected from phenyl, cyclohexyl and adamantyl, any of which (for example the phenyl group) may be optionally substituted with one or more substituents selected from halo, (1-5C)alkyl, phenyl, and heteroaryl;
each Rxis phenyl; and
n is 0 or 1.

In an embodiment, the compound has a structure according to formula (I-A-2) or (I-B-2), wherein

M is selected from titanium, zirconium and hafnium;
each X is independently selected from halo, hydrogen, (1-6C)alkoxy, and aryloxy, any of which may be optionally substituted one of more groups selected from halo, oxo, hydroxy, amino, nitro, (1-6C)alkyl, (1-6C)haloalkyl, (1-6C)alkoxy and aryl;
R2is absent or is selected from hydrogen, (1-4C)alkyl and phenyl;
R3, R4, R5and R6are each independently selected from hydrogen, halo, oxo, hydroxy, amino, nitro, (1-4C)alkyl, (1-4C)haloalkyl, (1-4C)alkoxy, aryl and heteroaryl, any of which may be optionally substituted with one or more substituents selected from halo, oxo, hydroxy, amino, nitro, (1-4C)alkyl, (1-4C)haloalkyl and (1-4C)alkoxy;
R1is a group of formula (II) defined herein, wherein
Rais selected from (1-4C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, (1-4C)haloalkyl, (1-4C)alkoxy, aryl, aryloxy, heteroaryl, heteroaryloxy, carbocyclyl and heterocyclyl, any of which (for example the aryl group) may be optionally substituted with one or more substituents selected from halo, oxo, hydroxy, amino, nitro, (1-6C)alkyl, (1-6C)alkoxy, (1-6C)haloalkyl, aryl, aryloxy, heteroaryl and heteroaryloxy;
Rxis independently selected from hydrogen, (1-4C)alkyl, (1-4C)alkoxy and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, amino and (1-6C)alkyl; and
n is 0, 1 or 2.

In an embodiment, the compound has a structure according to formula (I-A-2) or (I-B-2), wherein

M is selected from titanium and zirconium;
each X is independently selected from halo, hydrogen, and (1-4C)alkoxy, any of which may be optionally substituted one of more groups selected from halo, hydroxy, amino, (1-4C)alkyl and (1-4C)alkoxy;
R2is absent or is selected from hydrogen, (1-4C)alkyl and phenyl;
R3, R4, R5and R6are each independently selected from hydrogen, halo, amino, (1-4C)alkyl, (1-4C)haloalkyl, (1-4C)alkoxy and phenyl, any of which may be optionally substituted with one or more substituents selected from halo and (1-4C)alkyl;
R1is a group of formula (II) defined herein, wherein
Rais selected from aryl, aryloxy, heteroaryl, heteroaryloxy, carbocyclyl and heterocyclyl, any of which (for example the aryl group) may be optionally substituted with one or more substituents selected from halo, oxo, hydroxy, amino, nitro, (1-6C)alkyl, (1-6C)alkoxy, (1-6C)haloalkyl, aryl, aryloxy, heteroaryl and heteroaryloxy;
Rxis independently selected from hydrogen, (1-4C)alkyl, and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, amino and (1-3C)alkyl; and
n is 0 or 1.

In an embodiment, the compound has a structure according to formula (I-A-2) or (I-B-2), wherein

M is selected from titanium and zirconium;
each X is independently selected from chloro, bromo and (1-4C)alkoxy;
R2is absent;
R3, R4, R5and R6are each independently selected from hydrogen, halo, amino, (1-4C)alkyl and phenyl, any of which may be optionally substituted with one or more substituents selected from halo and (1-4C)alkyl;
R1is a group of formula (II) defined herein, wherein
Rais selected from phenyl and 5-12 membered carbocyclyl, any of which (for example the phenyl group) may be optionally substituted with one or more substituents selected from halo, hydroxy, amino, (1-5C)alkyl, (1-3C)alkoxy, (1-5C)haloalkyl, phenyl, and heteroaryl;
Rxis independently selected from hydrogen, (1-4C)alkyl, and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, amino and (1-3C)alkyl; and
n is 0 or 1.

In an embodiment, the compound has a structure according to formula (I-A-2) or (I-B-2), wherein

M is titanium;
each X is independently (1-4C)alkoxy;
R2is absent;
R3, R4, R5and R6are each independently selected from hydrogen, (1-4C)alkyl and phenyl;
R1is a group of formula (II) defined herein, wherein
Rais selected from phenyl, cyclohexyl and adamantyl, any of which (for example the phenyl group) may be optionally substituted with one or more substituents selected from halo, (1-5C)alkyl, phenyl, and heteroaryl;
each Rxis phenyl; and
n is 0 or 1.

In an embodiment, the compound has a structure according to formula (I-A-2) or (I-B-2), wherein

M is selected from titanium, zirconium and hafnium;
each X is independently selected from halo, hydrogen, (1-6C)alkoxy, (1-4C)dialkylamino and aryloxy, any of which may be optionally substituted one of more groups selected from halo, oxo, hydroxy, amino, nitro, (1-6C)alkyl, (1-6C)haloalkyl, (1-6C)alkoxy and aryl;
R2is absent or is selected from hydrogen, (1-4C)alkyl and phenyl;
R3, R4, R5and R6are each independently selected from hydrogen, halo, oxo, hydroxy, amino, nitro, (1-4C)alkyl, (1-4C)haloalkyl, (1-4C)alkoxy, aryl and heteroaryl, any of which may be optionally substituted with one or more substituents selected from halo, oxo, hydroxy, amino, nitro, (1-4C)alkyl, (1-4C)haloalkyl and (1-4C)alkoxy;
R1is a group of formula (II) defined herein, wherein
Rais selected from (1-4C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, (1-4C)haloalkyl, (1-4C)alkoxy, aryl, aryloxy, heteroaryl, heteroaryloxy, carbocyclyl and heterocyclyl, any of which (for example the aryl group) may be optionally substituted with one or more substituents selected from halo, oxo, hydroxy, amino, nitro, (1-6C)alkyl, (1-6C)alkoxy, (1-6C)haloalkyl, aryl, aryloxy, heteroaryl and heteroaryloxy;
Rxis independently selected from hydrogen, (1-4C)alkyl, (1-4C)alkoxy and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, amino and (1-6C)alkyl; and
n is 0, 1 or 2.

In an embodiment, the compound has a structure according to formula (I-A-2) or (I-B-2), wherein

M is selected from titanium and zirconium;
each X is independently selected from halo, hydrogen, (1-4C)dialkylamino and (1-4C)alkoxy, any of which may be optionally substituted one of more groups selected from halo, hydroxy, amino, (1-4C)alkyl and (1-4C)alkoxy;
R2is absent or is selected from hydrogen, (1-4C)alkyl and phenyl;
R3, R4, R5and R6are each independently selected from hydrogen, halo, amino, (1-4C)alkyl, (1-4C)haloalkyl, (1-4C)alkoxy and phenyl, any of which may be optionally substituted with one or more substituents selected from halo and (1-4C)alkyl;
R1is a group of formula (II) defined herein, wherein
Rais selected from aryl, aryloxy, heteroaryl, heteroaryloxy, carbocyclyl and heterocyclyl, any of which (for example the aryl group) may be optionally substituted with one or more substituents selected from halo, oxo, hydroxy, amino, nitro, (1-6C)alkyl, (1-6C)alkoxy, (1-6C)haloalkyl, aryl, aryloxy, heteroaryl and heteroaryloxy;
Rxis independently selected from hydrogen, (1-4C)alkyl, and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, amino and (1-3C)alkyl; and
n is 0 or 1.

In an embodiment, the compound has a structure according to formula (I-A-2) or (I-B-2), wherein

M is selected from titanium and zirconium;
each X is independently selected from chloro, bromo, (1-2C)dialkylamino and (1-4C)alkoxy;
R2is absent;
R3, R4, R5and R6are each independently selected from hydrogen, halo, amino, (1-4C)alkyl and phenyl, any of which may be optionally substituted with one or more substituents selected from halo and (1-4C)alkyl;
R1is a group of formula (II) defined herein, wherein
Rais selected from phenyl and 5-12 membered carbocyclyl, any of which (for example the phenyl group) may be optionally substituted with one or more substituents selected from halo, hydroxy, amino, (1-5C)alkyl, (1-3C)alkoxy, (1-5C)haloalkyl, phenyl, and heteroaryl;
Rxis independently selected from hydrogen, (1-4C)alkyl, and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, amino and (1-3C)alkyl; and
n is 0 or 1.

In an embodiment, the compound has a structure according to formula (I-A-2) or (I-B-2), wherein

M is titanium;
each X is independently (1-2C)dialkylamino or (1-4C)alkoxy;
R2is absent;
R3, R4, R5and R6are each independently selected from hydrogen, (1-4C)alkyl and phenyl;
R1is a group of formula (II) defined herein, wherein
Rais selected from phenyl, cyclohexyl and adamantyl, any of which (for example the phenyl group) may be optionally substituted with one or more substituents selected from halo, (1-5C)alkyl, phenyl, and heteroaryl;
each Rxis phenyl; and
n is 0 or 1.

In an embodiment, the compound has a structure according to formula (I-A-3) or (I-B-3), wherein

M is selected from titanium, zirconium and hafnium;
each X is independently selected from halo, hydrogen, (1-6C)alkoxy, and aryloxy, any of which may be optionally substituted one of more groups selected from halo, oxo, hydroxy, amino, nitro, (1-6C)alkyl, (1-6C)haloalkyl, (1-6C)alkoxy and aryl;
R2is absent or is selected from hydrogen, (1-4C)alkyl and phenyl;
R7is selected from (1-4C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, (1-4C)haloalkyl, aryl and heteroaryl, any of which may be optionally substituted with one or more substituents selected from halo, oxo, hydroxy, amino, nitro, (1-4C)alkyl, (1-4C)haloalkyl and (1-4C)alkoxy;
R1is a group of formula (II) defined herein, wherein
Rais selected from (1-4C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, (1-4C)haloalkyl, (1-4C)alkoxy, aryl, aryloxy, heteroaryl, heteroaryloxy, carbocyclyl and heterocyclyl, any of which (for example the aryl group) may be optionally substituted with one or more substituents selected from halo, oxo, hydroxy, amino, nitro, (1-6C)alkyl, (1-6C)alkoxy, (1-6C)haloalkyl, aryl, aryloxy, heteroaryl and heteroaryloxy;
Rxis independently selected from hydrogen, (1-4C)alkyl, (1-4C)alkoxy and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, amino and (1-6C)alkyl; and
n is 0, 1 or 2.

In an embodiment, the compound has a structure according to formula (I-A-3) or (I-B-3), wherein

M is selected from titanium and zirconium;
each X is independently selected from halo, hydrogen, and (1-4C)alkoxy, any of which may be optionally substituted one of more groups selected from halo, hydroxy, amino, (1-4C)alkyl and (1-4C)alkoxy;
R2is absent or is selected from hydrogen, (1-4C)alkyl and phenyl;
R7is selected from (1-2C)alkyl and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, hydroxy, amino and (1-4C)alkyl;
R1is a group of formula (II) defined herein, wherein
Rais selected from aryl, aryloxy, heteroaryl, heteroaryloxy, carbocyclyl and heterocyclyl, any of which (for example the aryl group) may be optionally substituted with one or more substituents selected from halo, oxo, hydroxy, amino, nitro, (1-6C)alkyl, (1-6C)alkoxy, (1-6C)haloalkyl, aryl, aryloxy, heteroaryl and heteroaryloxy;
Rxis independently selected from hydrogen, (1-4C)alkyl, and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, amino and (1-3C)alkyl; and
n is 0 or 1.

In an embodiment, the compound has a structure according to formula (I-A-3) or (I-B-3), wherein

M is selected from titanium and zirconium;
each X is independently selected from chloro, bromo and (1-4C)alkoxy;
R2is absent;
R7is selected from (1-2C)alkyl and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, hydroxy, amino and (1-4C)alkyl;
R1is a group of formula (II) defined herein, wherein
Rais selected from phenyl and 5-12 membered carbocyclyl, any of which (for example the phenyl group) may be optionally substituted with one or more substituents selected from halo, hydroxy, amino, (1-5C)alkyl, (1-3C)alkoxy, (1-5C)haloalkyl, phenyl, and heteroaryl;
Rxis independently selected from hydrogen, (1-4C)alkyl, and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, amino and (1-3C)alkyl; and
n is 0 or 1.

In an embodiment, the compound has a structure according to formula (I-A-3) or (I-B-3), wherein

M is titanium;
each X is independently (1-4C)alkoxy;
R2is absent;

R1is a group of formula (II) defined herein, wherein
Rais selected from phenyl, cyclohexyl and adamantyl, any of which (for example the phenyl group) may be optionally substituted with one or more substituents selected from halo, (1-5C)alkyl, phenyl, and heteroaryl;
each Rxis phenyl; and
n is 0 or 1.

In an embodiment, the compound has a structure according to formula (I-A-3) or (I-B-3), wherein

M is selected from titanium, zirconium and hafnium;
each X is independently selected from halo, hydrogen, (1-6C)alkoxy, (1-4C)dialkylamino and aryloxy, any of which may be optionally substituted one of more groups selected from halo, oxo, hydroxy, amino, nitro, (1-6C)alkyl, (1-6C)haloalkyl, (1-6C)alkoxy and aryl;
R2is absent or is selected from hydrogen, (1-4C)alkyl and phenyl;
R7is selected from (1-4C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, (1-4C)haloalkyl, aryl and heteroaryl, any of which may be optionally substituted with one or more substituents selected from halo, oxo, hydroxy, amino, nitro, (1-4C)alkyl, (1-4C)haloalkyl and (1-4C)alkoxy;
R1is a group of formula (II) defined herein, wherein
Rais selected from (1-4C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, (1-4C)haloalkyl, (1-4C)alkoxy, aryl, aryloxy, heteroaryl, heteroaryloxy, carbocyclyl and heterocyclyl, any of which (for example the aryl group) may be optionally substituted with one or more substituents selected from halo, oxo, hydroxy, amino, nitro, (1-6C)alkyl, (1-6C)alkoxy, (1-6C)haloalkyl, aryl, aryloxy, heteroaryl and heteroaryloxy;
Rxis independently selected from hydrogen, (1-4C)alkyl, (1-4C)alkoxy and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, amino and (1-6C)alkyl; and
n is 0, 1 or 2.

In an embodiment, the compound has a structure according to formula (I-A-3) or (I-B-3), wherein

M is selected from titanium and zirconium;
each X is independently selected from halo, hydrogen, (1-4C)dialkylamino and (1-4C)alkoxy, any of which may be optionally substituted one of more groups selected from halo, hydroxy, amino, (1-4C)alkyl and (1-4C)alkoxy;
R2is absent or is selected from hydrogen, (1-4C)alkyl and phenyl;
R7is selected from (1-2C)alkyl and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, hydroxy, amino and (1-4C)alkyl;
R1is a group of formula (II) defined herein, wherein
Rais selected from aryl, aryloxy, heteroaryl, heteroaryloxy, carbocyclyl and heterocyclyl, any of which (for example the aryl group) may be optionally substituted with one or more substituents selected from halo, oxo, hydroxy, amino, nitro, (1-6C)alkyl, (1-6C)alkoxy, (1-6C)haloalkyl, aryl, aryloxy, heteroaryl and heteroaryloxy;
Rxis independently selected from hydrogen, (1-4C)alkyl, and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, amino and (1-3C)alkyl; and
n is 0 or 1.

In an embodiment, the compound has a structure according to formula (I-A-3) or (I-B-3), wherein

M is selected from titanium and zirconium;
each X is independently selected from chloro, bromo, (1-2C)dialkylamino and (1-4C)alkoxy;
R2is absent;
R7is selected from (1-2C)alkyl and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, hydroxy, amino and (1-4C)alkyl;
R1is a group of formula (II) defined herein, wherein
Rais selected from phenyl and 5-12 membered carbocyclyl, any of which (for example the phenyl group) may be optionally substituted with one or more substituents selected from halo, hydroxy, amino, (1-5C)alkyl, (1-3C)alkoxy, (1-5C)haloalkyl, phenyl, and heteroaryl;
Rxis independently selected from hydrogen, (1-4C)alkyl, and phenyl, any of which may be optionally substituted with one or more substituents selected from halo, amino and (1-3C)alkyl; and
n is 0 or 1.

In an embodiment, the compound has a structure according to formula (I-A-3) or (I-B-3), wherein

M is titanium;
each X is independently (1-2C)dialkylamino or (1-4C)alkoxy;
R2is absent;

R1is a group of formula (II) defined herein, wherein
Rais selected from phenyl, cyclohexyl and adamantyl, any of which (for example the phenyl group) may be optionally substituted with one or more substituents selected from halo, (1-5C)alkyl, phenyl, and heteroaryl;
each Rxis phenyl; and
n is 0 or 1.

In an embodiment, the compound has a structure according to formula (I-A-4a), (I-B-4a) or (I-C-4a) shown below:

whereinM is titanium or zirconium,each X is independently isopropoxide, ethoxide, N(CH3)2or N(CH2CH3)2;R2is absent (in which case bond a is a double bond) or hydrogen (in which case bond a is a single bond); andRais selected from perfluorophenyl, cyclohexyl, 2,6-dimethylphenyl, 2,6-diisopropylphenyl, biphenyl, adamantyl, 2,4,6-tritertbutylphenyl and trityl.

In an embodiment, the compound has a structure according to formula (I-A-4a), (I-B-4a) or (I-C-4a), wherein R2is absent.

In an embodiment, the compound has a structure according to formula (I-A-4a), (I-B-4a) or (I-C-4a), wherein M is titanium and Rais selected from 2,6-diisopropylphenyl, biphenyl, adamantyl, 2,4,6-tritertbutylphenyl and trityl.

In an embodiment, the compound has a structure according to formula (I-A-4a), (I-B-4a) or (I-C-4a), wherein M is titanium and Rais selected from adamantyl, 2,4,6-tritertbutylphenyl and trityl.

In an embodiment, the compound has a structure according to formula (I-A-4b), (I-B-4b) or (I-C-4b) shown below:

In an embodiment, the compound has a structure according to formula (I-A-4b), (I-B-4b) or (I-C-4b), wherein M is titanium and Rais selected from 2,6-diisopropylphenyl, biphenyl, adamantyl, 2,4,6-tritertbutylphenyl and trityl.

In an embodiment, the compound has a structure according to formula (I-A-4b), (I-B-4b) or (I-C-4b), wherein M is titanium and Rais selected from adamantyl, 2,4,6-tritertbutylphenyl and trityl.

In an embodiment, the compound has a structure according to formula (I-A-4c), (I-B-4c) or (I-C-4c) shown below:

whereinM is titanium or zirconium,Rvand Rware each independently methyl or ethyl;R2is absent (in which case bond a is a double bond) or hydrogen (in which case bond a is a single bond); andRais selected from perfluorophenyl, cyclohexyl, 2,6-dimethylphenyl, 2,6-diisopropylphenyl, biphenyl, adamantyl, 2,4,6-tritertbutylphenyl and trityl.

In an embodiment, the compound has a structure according to formula (I-A-4c), (I-B-4c) or (I-C-4c), wherein R2is absent.

In an embodiment, the compound has a structure according to formula (I-A-4c), (I-B-4c) or (I-C-4c), wherein M is titanium and Rais selected from 2,6-diisopropylphenyl, biphenyl, adamantyl, 2,4,6-tritertbutylphenyl and trityl.

In an embodiment, the compound has a structure according to formula (I-A-4c), (I-B-4c) or (I-C-4c), wherein M is titanium and Rais selected from adamantyl, 2,4,6-tritertbutylphenyl and trityl.

In an embodiment, the compound is immobilised on a supporting substrate. Suitably, the supporting substrate is a solid. It will be appreciated that the compound may be immobilised on the supporting substrate by one or more covalent or ionic interactions, either directly, or via a suitable linking moiety. It will be appreciated that minor structural modifications resulting from the immobilisation of the compound of the supporting substrate (e.g. loss of one or both groups, X) are nonetheless within the scope of the invention. Suitably, the supporting substrate is selected from silica, alumina, zeolite and layered double hydroxide. Most suitably, the supporting substrate is silica.

Preparation of the Compounds

The compounds of the present invention may be formed by any suitable process known in the art. Particular examples of processes for the preparation of compounds of the present invention are set out in the accompanying examples.

Generally, the processes of preparing a compound of the present invention as defined herein comprises:(i) Reacting two equivalents of compound of formula A shown below:

wherein R1-R7and bond a have any of the definitions appearing hereinbefore, with one equivalent of a compound of formula B shown below:

M(X)4Bwherein M and X have any of the definitions appearing hereinbeforein the presence of a suitable solvent.

Any suitable solvent may be used for step (i) of the process defined above. A particularly suitable solvent is dry toluene.

It will be appreciated that the compound of formula B may be used in a solvated form (e.g. M(X)4.(THF)2).

It will be appreciated that for certain identities of X, it may be necessary to treat the compound of formula A with a strong, non-nucleophilic base (such as potassium bis(trimethylsilyl)amide) prior to reaction with the compound of formula B. For example, when X is chloro, the compound of formula A may be treated with potassium bis(trimethylsilyl)amide prior to reaction with MCl4.(THF)2.

Step (i) is suitably conducted at low temperature (e.g. <0° C.). More suitably, step (i) is conducted at a temperature of −80 to 0° C. Other reaction conditions (e.g. pressures, reaction times, agitation, etc.) could be readily selected by one of ordinary skill in the art.

Compounds of formula A may be generally prepared by a process comprising the step of:(i) Reacting, in a suitable solvent (such as acidic ethanol), a compound of formula C shown below:

wherein R3-R7have any of the definitions appearing hereinbefore, with a compound of formula D shown below:

wherein R1and R2have any of the definitions appearing hereinbefore.

Step (i) is suitably conducted under refluxing conditions. Other reaction conditions (e.g. pressures, reaction times, agitation, etc.) could be readily selected by one of ordinary skill in the art.

Polymerisation of Cyclic Esters and Cyclic Amides

According to a second aspect of the present invention there is provided a process for the ring opening polymerisation (ROP) of a cyclic ester or a cyclic amide, the process comprising the step of:a) contacting a compound according to the first aspect of the invention with one or more cyclic esters or cyclic amides.

As discussed hereinbefore, the new family of Group IV transition metal-based catalysts are capable of catalysing the ROP of cyclic esters and cyclic amides to yield polymers of high molecular weight and narrow PDI. The new family of catalysts are surprisingly active not only in catalysing the ROP of lactones such as caprolactone, but also macrolactones (e.g. w-pentadecalactone, PDL), where the reduced amount of ring strain would typically compromise efficient polymerisation.

In an embodiment, the one or more cyclic esters or cyclic amides has a structure according to formula (III) shown below:

whereinQ is selected from O or NRy, wherein Ryis selected from hydrogen, (1-6C)alkyl, (2-6C)alkenyl and (2-6C)alkynyl; andring A is a 4-23 membered heterocycle containing 1 to 4 O or N ring heteroatoms in total, wherein the heterocycle is optionally substituted with one or more substituents selected from oxo, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, (1-6C)alkoxy, aryl and heteroaryl.

It will be understood that the one or more cyclic esters and cyclic amides may be identical (e.g. all caprolactone) or different (e.g. a mixture of different cyclic esters and/or cyclic amides). Accordingly, the compounds of the invention may be used for the homopolymerisation or copolymerisation of cyclic esters and cyclic amides.

In an embodiment, Q is selected from O or NRy, wherein Ryis selected from hydrogen, (1-3C)alkyl, (2-3C)alkenyl or (2-3C)alkynyl.

In an embodiment, Q is selected from O or NRy, wherein Ryis selected from hydrogen and (1-3C)alkyl.

In an embodiment, Q is selected from O or NRy, wherein Ryhydrogen.

In an embodiment, Q is O.

In an embodiment, ring A is a 6-23 membered heterocycle containing 1 to 3 O or N ring heteroatoms in total, wherein the heterocycle is optionally substituted with one or more substituents selected from oxo, (1-6C)alkyl, (1-6C)alkoxy and aryl.

In an embodiment, ring A is a 6-18 membered heterocycle containing 1 to 3 O or N ring heteroatoms in total, wherein the heterocycle is optionally substituted with one or more substituents selected from oxo, (1-6C)alkyl, (1-6C)alkoxy and aryl.

In an embodiment, ring A is a 6-16 membered heterocycle containing 1 to 2 O or N ring heteroatoms in total, wherein the heterocycle is optionally substituted with one or more substituents selected from oxo, (1-6C)alkyl, (1-6C)alkoxy and aryl.

In an embodiment, ring A is a 4-18 membered heterocycle containing 1 to 3 O or N ring heteroatoms in total, wherein the heterocycle is optionally substituted with one or more substituents selected from oxo, (1-6C)alkyl, (1-6C)alkoxy and aryl.

In an embodiment, ring A is a 4-16 membered heterocycle containing 1 to 2 O or N ring heteroatoms in total, wherein the heterocycle is optionally substituted with one or more substituents selected from oxo, (1-6C)alkyl, (1-6C)alkoxy and aryl.

In an embodiment, ring A is a 4, 6, 7 or 16 membered heterocycle containing 1 to 3 O or N ring heteroatoms in total, wherein the heterocycle is optionally substituted with one or more substituents selected from oxo, (1-6C)alkyl, (1-6C)alkoxy and aryl.

In an embodiment, ring A is a 4, 6, 7 or 16 membered heterocycle containing 1 to 2 O or N ring heteroatoms in total, wherein the heterocycle is optionally substituted with one or more substituents selected from oxo, (1-6C)alkyl, (1-6C)alkoxy and aryl.

In an embodiment, ring A does not contain any N heteroatoms.

In an embodiment, the one or more cyclic esters or cyclic amides is a lactone. Non-limiting examples of lactones include β-propiolactone, γ-butyrolactone, γ-valerolactone, ε-caprolactone and ω-pentadecalactone.

In an embodiment, the one or more cyclic esters or cyclic amides is a lactide. It will be appreciated by one of skill in the art that there are three stereoisomers of lactide, shown below, all of which are encompassed by the invention:

Suitably, the lactide is L-lactide.

In an embodiment, the one or more cyclic esters or cyclic amides is a lactam. Non-limiting examples of lactams include β-lactams (4 ring members), γ-lactams (5 ring members), δ-lactams (6 ring members) and ε-lactams (7 ring members).

In a particular embodiment, the one or more cyclic esters or cyclic amides is ε-caprolactone and rac-lactide, which are copolymerised during step a).

In an embodiment, in step a), the mole ratio of the compound of formula (I-A), (I-B) or (I-C) to the cyclic ester or cyclic amide is 1:50 to 1:10,000. Suitably, in step a), the mole ratio of the compound of formula (I-A), (I-B) or (I-C) to the cyclic ester or cyclic amide is 1:150 to 1:5000. More suitably, in step a), the mole ratio of the compound of formula (I-A), (I-B) or (I-C) to the cyclic ester or cyclic amide is 1:200 to 1:1000.

Step a) may be conducted in a solvent, or in the absence of a solvent (i.e. using neat reactants). When a solvent is used, any suitable solvent may be selected, including toluene, tetrahydrofuran and methylene chloride. Most suitably, step a) is conducted in the absence of a solvent.

Step a) may be conducted in the presence of a chain transfer agent suitable for use in the ring opening polymerisation of a cyclic ester or cyclic amide. In an embodiment, the chain transfer agent is a hydroxy-functional compound (e.g. an alcohol, diol or polyol). Suitably, the chain transfer agent is used in an excess with respect to the compound of formula (I-A), (I-B) or (I-C).

In an embodiment, step a) is conducted at a temperature of 15 to 150° C. Suitably, step a) is conducted at a temperature of 40 to 150° C. More suitably, step a) is conducted at a temperature of 50 to 120° C. Most suitably, step a) is conducted at a temperature of 60 to 120° C. (e.g. 80° C. or 100° C.).

Those of skill in the art, will be capable of selecting a suitable pressure at which to carry out step a). For example, step a) may be conducted at a pressure of 0.9 to 5 bar or 0.2 to 2 bar. Suitably, step a) is conducted at atmospheric pressure.

In an embodiment, step a) is conducted from a period of 1 minute to 96 hours. Suitably, step a) is conducted for a period of 5 minutes to 72 hours. Alternatively, step a) is conducted for a period of 15 minutes to 72 hours. Alternatively still, step a) is conducted for a period of 30 minutes to 72 hours.

According to a third aspect of the present invention, there is provided a use of a compound according to the first aspect of the invention in the ring opening polymerisation (ROP) of one or more cyclic esters or cyclic amides.

It will be appreciated that, in the context of the third aspect of the invention, the one or more cyclic esters or cyclic amides may have any of those definitions outlined in respect of the second aspect of the invention.

It will be appreciated that, in the context of the third aspect of the invention, the use of the compound according to the first aspect of the invention in the ring opening polymerisation (ROP) of one or more cyclic esters or cyclic amides may proceed according to any of those variables (quantities, temperatures, pressures, times, additives, etc) outlined in respect of the second aspect of the invention.

MATERIALS AND METHODS

All metal complexes were synthesized under anhydrous conditions, using MBraun gloveboxes and standard Schlenk techniques. Solvents and reagents were obtained from Sigma Aldrich or Strem and were used as received unless stated otherwise. THF and toluene were dried by refluxing over sodium and benzophenone and stored under nitrogen. ε-caprolactone and ω-pentadecalactone were dried over CaH2and fractionally distilled under nitrogen before use. All dry solvents were stored under nitrogen and degassed by several freeze-pump-thaw cycles. NMR spectra were recorded using a Bruker AV 400 or 500 MHz spectrometer. Correlation between proton and carbon atoms were obtained by COSY, HSQC, and HMBC spectroscopic methods and subsequently assigned. MALDI-ToF analysis was carried out on a Waters MALDI Micro MX instrument in positive ion mode. Samples were prepared by dissolving the desired molecule (10 mg/ml) and matrix (dithranol, 10 mg/ml) in THF. This mixture was spotted onto the MALDI plate and allowed to dry. Due to a high degree of fragmentation and the formation of clusters, only the M+-OiPr value is reported for metal complexes. Elemental analysis was carried out by Mr. Stephen Boyer of the London Metropolitan University.

Crystals suitable for single crystal x-ray diffraction were grown either through slow evaporation of hexanes into THF or through low temperature crystallization in concentrated THF at −30° C. Samples were isolated in a glovebox under a pool of fluorinated oil and mounted on MiTeGen MicroMounts. The crystal was then cooled to 150 K with an Oxford Cryosystems Cryostream nitrogen cooling device. Data collection was carried out with an Oxford Diffraction Supernova diffractometer using Cu Kα (λ=1.5417 Å) or Mo Kα (λ=0.7107 Å) radiation. The resulting raw data was processed using CrysAlisPro. Structures were solved by SHELXT and Full-matrix least-squares refinements based on F2were performed in SHELXL-146, as incorporated in the WinGX package.7For each methyl group, the hydrogen atoms were added at calculated positions using a riding model with U(H)=1.5 Ueq (bonded carbon atom). The rest of the hydrogen atoms were included in the model at calculated positions using a riding model with U(H)=1.2 Ueq (bonded atom). Neutral atom scattering factors were used and include terms for anomalous dispersion.8

Part A

Example 1—Ligand Synthesis

A variety of ligands, HL1-HL8, were prepared according to the general synthesis depicted in Scheme 1 shown below:

Synthesis of HL1

o-Vanillin (5 g, 32.9 mmol) was added to a round bottom flask and dissolved in ethanol (60 mL). 2,3,4,5,6-pentafluoroaniline (6.02 g, 32.9 mmol) was added into the stirring solution along with several drops of formic acid. This reaction mixture was refluxed for 72 hours resulting in a bright orange precipitate and a pale yellow solution. Precipitate was filtered, washed with ethanol (20 mL) and pentane (3×20 mL) and dried under vacuum. Crude product was then washed with hot ethanol (30 mL) and dried. Yield: 3.67 g (35%)1H NMR (400 MHz, CDCl3) δ (ppm): 12.58 (s, 1H), 8.85 (s, 1H), 7.05 (m, 2H), 6.93 (t, 1H), 3.94 (s, 3H).

Synthesis of HL2

Synthesis of HL3

Synthesis of HL4

Synthesis of HL5

Synthesis of HL6

Synthesis of HL7

Synthesis of HL8

Example 2—Complex Synthesis

Using ligands HL1-HL8prepared in Example 1, a variety of complexes, (L1)2Ti(OiPr)2-(L8)2Ti(OiPr)2, were prepared according to the general synthesis depicted in Scheme 2 shown below:

The o-vanillin derived ligands were found to possess two separate modes of coordination to the metal: 6-membered N,O coordination, and 5-membered O,O coordination. These two coordination modes were found to be independent of one another, thus the eight catalysts synthesized each exhibit one of three basic types of coordination chemistries found to be possible in these systems. Type A: N,O:N,O coordination, Type B: N,O:O,O coordination, Type C: O,O:O,O coordination. Within each type there are also additional isomers that are theoretically possible. Upon increasing steric bulk, coordination around the metal centre rearranges from: Type A-I to Type A-II, then to Type B followed by Type C. (Scheme 3).

Synthesis of (L1)2Ti(OiPr)2

FIG. 11shows the ORTEP representation of (L1)2Ti(OiPr)2. (L1)2Ti(OiPr)2crystallize in the centrosymmetric space group P-1 and adopt Type A-I coordination, with imine nitrogens in a cis arrangement. Due to the low steric pressure exerted around the titanium metal centre by R1=C6F5this complex prefers the coordination mode typically seen in salicylaldehyde derivatives. The coordination is reinforced by the electron deficient C6F5substituent 7ε-stacking with the adjacent Ph-OMe substituent, with an average difference between rings of 3.10 Å.

Synthesis of (L2)2Ti(OiPr)2

FIG. 13shows the ORTEP representation of (L2)2Ti(OiPr)2. (L2)2Ti(OiPr)2crystallize in the centrosymmetric space group P-1 and adopt Type A-I coordination, with imine nitrogens in a cis arrangement. Due to the low steric pressure exerted around the titanium metal centre by R1=Cy this complex prefers the coordination mode typically seen in salicylaldehyde derivatives.

Synthesis of (L3)2Ti(OiPr)

FIG. 16shows the ORTEP representation of (L3)2Ti(OiPr)2. Upon increasing steric hindrance to form (L3)2Ti(OiPr)2a rearrangement is observed from Type A-I to Type A-II where imine nitrogens prefer a trans geometry. In this arrangement, steric pressure is relieved by creating space between R groups while still maintaining O,N:O,N coordination. As a result of this rearrangement, the Ti—N bond distances shorten and Ti—O distances elongate by ˜0.08 Å compared to (L2)2Ti(OiPr)2.

Synthesis of (L4)2Ti(OiPr)

FIG. 19shows the ORTEP representation of (L4)2Ti(OiPr)2. (L4)2Ti(OiPr)2crystallizes in the chiral orthorhombic space group Pna21and adopts Type B coordination with one nitrogen trans to OiPr and one detached, in favour of O—O coordination through the o-methoxy group. Due to the formation of a five-membered ring, the O(1)-Ti—O(2) bite angle is far more acute, at 72.92(8°), than the O(3)-Ti—N(2) bite angle, which is similar to that seen in (L2)2Ti(OiPr)2, at 80.72(9°). Additionally, Ti—OiPr distances are significantly shorter than in Type A by ca. 0.05 Å, and the bound imine moiety is 0.02 Å shorter than the unbound imine, which is expected.

Synthesis of (L5)2Ti(OiPr)

FIG. 20shows the ORTEP representation of (L5)2Ti(OiPr)2. (L5)2Ti(OiPr)2crystallizes in the centrosymmetric space group P21/n and adopts Type B coordination with one nitrogen trans to OiPr and one detached, in favour of O—O coordination through the o-methoxy group. Due to the formation of a five-membered ring, the O(1)-Ti—O(2) bite angle is far more acute, at 72.92(8°), than the O(3)-Ti—N(2) bite angle, which is similar to that seen in (L2)2Ti(OiPr)2, at 80.72(9°). Additionally, Ti—OiPr distances are significantly shorter than in Type A by ca. 0.05 Å, and the bound imine moiety is 0.02 Å shorter than the unbound imine, which is expected.

Synthesis of (L6)2Ti(OiPr)

FIG. 23shows the ORTEP representation of (L6)2Ti(OiPr)2. (L6)2Ti(OiPr)2crystallizes in a centrosymmetric space group and adopts Type C coordination, where steric bulk forces O,O chelation of both ligands. (L6)2Ti(OiPr)2shows O—Ti—O bite angles similar to those found in (L4)2Ti(OiPr)2at 73.67(5)° [O(1)-Ti—O(2)] and 73.99(5)° [O(3)-Ti—O(4)]. OiPr moieties arrange trans to the neutral OMe groups and Ti—OiPr distances are shorter than those found Type A and B complexes. (Table 1) Both Imine C═N bonds are ca. 1.27 Å as expected.

Synthesis of (L7)2Ti(OiPr)

FIG. 26shows the ORTEP representation of (L7)2Ti(OiPr)2. (L7)2Ti(OiPr)2crystallizes in a centrosymmetric space group and adopts Type C coordination, where steric bulk forces O,O chelation of both ligands. OiPr moieties arrange trans to the neutral OMe groups and Ti—OiPr distances are shorter than those found Type A and B complexes. (Table 1) Both Imine C═N bonds are ca. 1.27 Å as expected.

Synthesis of (L8)2Ti(OiPr)

FIG. 29shows the ORTEP representation of (L8)2Ti(OiPr)2. (L8)2Ti(OiPr)2crystallizes in a centrosymmetric space group and adopts Type C coordination, where steric bulk forces O,O chelation of both ligands. OiPr moieties arrange trans to the neutral OMe groups and Ti—OiPr distances are shorter than those found Type A and B complexes. (Table 1) Both Imine C═N bonds are ca. 1.27 Å as expected.

Using ligands HL2and HL3prepared in Example 1, complexes (L2)2ZrCl2and (L3)2ZrCl2were prepared according to the general synthesis depicted in Scheme 4 shown below

Synthesis of (L2)2ZrCl2

Synthesis of (L3)2ZrCl2

HL3(0.246 g, 0.964 mmol) and K[N(SiMe3)2] (0.192 g, 0.964 mmol) were dissolved separately in THF (5 mL and 3 mL, respectively). The K[N(SiMe3)2] solution was then added dropwise to the stirring solution of ligand and allowed to react for 24 hours. ZrCl4(THF)2(0.182 g, 0.482 mmol) was dissolved in THF (5 mL) and added to the deprotonated ligand. After stirring for 24 hours the resulting cloudy yellow solution was centrifuged and the solution was decanted. Volatiles were removed in vacuo and hexane (10 mL) was added to the resulting yellow wax. This hexane was removed under vacuum to provide a light powder, which could be recrystallized by layering of hexanes and THF. Yield: 0.282 mg, 87.3%. MALDI-TOF MS (m/z): 633.1627 (calc. for [M+-Cl=633.1098])1H NMR (400 MHz, CDCl3) δ (ppm): 8.33 (s, 2H), 7.09 (m, 6H), 7.06 (d, 2H), 7.0 (d, 2H), 6.90 (t, 2H), 3.78 (s, 6H), 2.45 (s, 12H).

Example 3—Crystallographic Studies

Table 1 below provides a summary of the T-O distances in complexes (L1)2Ti(OiPr)2-(L8)2Ti(OiPr)2.

TABLE 1Summary of T-O distances in complexes(L1)2Ti(OiPr)2—(L8)2Ti(OiPr)2Ti—OiPr(1)Ti—OiPr(2)CoordinationCompoundDist. (Å)Dist. (Å)Type(L1)2Ti(OiPr)21.847(2)1.834(2)A-I(L2)2Ti(OiPr)2*1.771.81A-I(L3)2Ti(OiPr)21.795(1)1.803(1)A-II(L4)2Ti(OiPr)21.771.786(2)B(L5)2Ti(OiPr)21.787(1)1.800(1)B(L6)2Ti(OiPr)21.760(2)1.785(2)C(L5)2Ti(OiPr)21.758(2)1.776(2)C(L8)2Ti(OiPr)21.774(2)1.780(2)C*An average is given between the two enantiomers in the asymmetric unit

Table 2 below provides select crystallographic details for (L1)2Ti(OiPr)2-(L4)2Ti(OiPr)2.

Table 3 below select crystallographic details for (L5)2Ti(OiPr)2-(L8)2Ti(OiPr)2.

Example 4—NMR Studies

Evidence of different isomers in solution can be seen by following the1H NMR spectra of each type. For (L1)2Ti(OiPr)2, which has Type A-I coordination, the imine CH resonance shifts up field by 0.67 ppm, relative to the parent ligand, and broadens significantly. (FIG. 32) (L4)2Ti(OiPr)2which adopts Type B coordination shows a single CH imine peak shifted 0.25 ppm downfield from the parent ligand, along with a slight broadening. (FIG. 33) Broadening is likely due to the rapid conversion between Δ and Λ enantiomers, along with fluxionality between the two asymmetrically bound ligands, vida infra. This rapid conversion has been seen previously in similar systems and can be frozen out by variable temperature NMR. Broadening can also be seen in the aryliPr resonance at ˜3 ppm which suggests restricted rotation of these groups in solution. (L6-L8)2Ti(OiPr)2adopt the third conformation, Type C, where both ligands are O—O chelated, and they all display the same gross features in their1H NMR. In each case the imine CH resonance shifts significantly down field by ca. 0.5 ppm, while the OMe resonance shifts up field from the parent ligand. (FIG. 34)

Example 5—Variable Temperature NMR

To better understand the nature of intermediate case of Type B catalysts, variable temperature NMR experiments were undertaken on (L4)2Ti(OiPr)2. As Type B coordination shows both N,O and O,O chelation, but only shows a single imine resonance, it was necessary to confirm that the asymmetry observed in the solid state structure remains in solution. (FIG. 35) Upon cooling (L4)2Ti(OiPr)2from room temperature to −80° C. the imine resonance at ˜8.6 ppm broadened and split into two peaks at ˜8.75 and 8.3 ppm. These two peaks correlate to the individual imine resonance on the O,N and O,O bound ligands. Additionally, the ppm value of the O,N imine resonance correlates closely with that seen in Type A complexes, ˜8.3 ppm, while the ppm value of the O,O resonance correlates to that seen in Type C complexes, ˜8.7 ppm. This indicates that the Type B coordination is retained in solution, and at room temperature signals are averaged due to dynamic exchange between ligands.

Upon heating (L4)2Ti(OiPr)2in d2-1,1,2,2-tetrachloroethane (TCE) incrementally from room temperature to 100° C., peaks sharpened slightly but did not shift (FIG. 36). Additionally, after being held at this temperature for 24 hours, the1H NMR of (L4)2Ti(OiPr)2showed no discernible change. There was also no change in the1H NMR after heating at 70° C. in d8-THF for five hours. This resilience at high temperature indicates that the molecule retains its structure under reaction conditions in both coordinating and non-coordinating solvent.

Example 6—Polymerisation Studies

The general polymerisation conditions were as follows: In a glovebox, catalyst was weighed (˜7 mg) into a vial, dissolved in ε-caprolactone and, in cases where the reaction was not run neat, enough toluene to produce a 1 M solution in lactone. The vial was sealed and the stirring solution was immersed in an oil bath preheated to 80° C. After the desired time samples were cooled to 0° C., exposed to air and aliquots of the crude reaction mixture were taken for analysis by1H NMR in CDCl3. Volatiles were removed under vacuum and a 10 mg/mL THF solution was prepared for GPC. The conversion of ε-CL to PCL was determined by integration of the methylene proton peaks of the1H NMR spectra, δ 4.30-3.95.

ε-caprolactone was chosen to initially test the newly synthesized family of catalysts towards the ROP of lactones. Polymerizations were conducted both in toluene solution (1:200 [I]:[ε-CL], 1 M [ε-CL]; Table 4) and under neat conditions (1:200 [I]:[ε-CL] or 1:1000 [I]:[ε-CL]; Table 5). Catalysts (L1)2Ti(OiPr)2and (L2)2Ti(OiPr)2were capable of polymerization under both conditions. After 24 hours, however both (L1)2Ti(OiPr)2and (L2)2Ti(OiPr)2had reached full conversion, indicating a significant initiation period.

(L4-8)2Ti(OiPr)2are all active initiators and are, in some cases, several times faster than (L1,2)2Ti(OiPr)2. (L4)2Ti(OiPr)2reached full conversion to PCL within four hours, while (L6-8)2Ti(OiPr)2reached full conversion in just two. In each case the resulting PCL shows a monomodal distribution in the GPC trace with narrow PDIs. Experimental Mnwere in good agreement with calculated values when accounting for two growing PCL chains per Ti centre. All catalysts polymerize CL in a living manner, with Mnincreasing with reaction time while maintaining narrow PDI.

Interestingly, the order of reactivity follows the trend (L8)2Ti(OiPr)2˜(L7)2Ti(OiPr)2˜(L6)2Ti(OiPr)2>(L5)2Ti(OiPr)2˜(L4)2Ti(OiPr)2>(L3)2Ti(OiPr)2>(L2)2Ti(OiPr)2˜(L1)2Ti(OiPr)2or, written in terms of coordination chemistry, Type C>Type B>Type A-II>Type A-I. The reasons for this trend can be explained by examining the crowding around the metal centre. Type C complexes possess bulkier R groups, however this bulk is pushed distal to the metal centre and actually results in less steric crowding around the Ti than Type A-I. This more open coordination environment causes an increase in rate through the coordination insertion mechanism.

Caprolactone Kinetic Studies

The general polymerisation conditions for analysing the ε-caprolactone kinetics were as follows: In a glovebox, catalyst was weighed (0.025 mmol, ˜20 mg) into a volumetric flask (5 mL), and dissolved with dry toluene. ε-caprolactone was then added to the solution (5 mmol, 0.554 mL), mixed thoroughly, and divided into individual vials. Vials were sealed with isolation tape and added simultaneously to a pre-heated oil bath set to 80° C. Vials were removed at set time intervals and immediately submerged in an ice bath. The solution was then exposed to air and a portion of the crude mixture was dissolved in wet CDCl3to determine conversion via NMR. Pentane/Hexane was added to the remaining aliquot to precipitate the resulting polymer followed by the removal of all volatiles under high vacuum. A 10 mg/mL THF solution of the polymer was then prepared for GPC analysis.

To better understand the effect coordination type has on the rate of polymerization, kinetic studies were conducted in toluene (0.9 M solution of ε-CL in toluene, 200:1 monomer:catalyst) at 80° C. All polymerizations showed expected increases in Mnand narrow PDI values which implies a well-controlled, living-polymerization. Calculated and experimental Mnvalues were in good agreement for 2 growing polymer chains per metal center throughout the duration of each experiment indicating that the two chains grow at a similar rate with similar initiation times. (FIGS. 40a,b,c) The three catalysts studied (L3)2Ti(iOPr)2, (L4)2Ti(OiPr)2, and (L8)2Ti(OiPr)2show first order kinetics in monomer and the trend in reactivity confirms what was observed in the bulk polymerizations where Type C>Type B>Type A. From this data we can see that generally, Type C is twice as fast as Type B, which is three times faster than Type A-II. (FIG. 41) The coordination insertion mechanism with OiPr as an initiator was confirmed through MALDI-ToF analysis of low molecular weight PCL produced from each catalyst. (FIG. 42-45) In each case a distribution of (iPrO)(PCL)n(H) was identified. This data, taken together, indicates that despite the drastic change in coordination environment in this family of catalysts, the mechanism remains the same.

Polymerization reactions conducted in neat ε-CL show similar trends to those in toluene, however, they are hampered by an increase in viscosity with increasing conversion. As such, several reactions show experimental Mnhigher than calculated values at high conversion. This may be due to chain coupling at the metal centre. Additionally, PDI values remained narrow for all catalysts (1.05-1.37). Several catalysts were also tested in the melt at lower catalyst loading (1:1000, [1]:[ε-CL]) and all maintain their activity.

The general polymerisation conditions were as follows: In a glovebox, catalyst was weighed (˜7 mg) into a vial, along with ω-pentadecalactone and, in cases where the reaction was not run neat, enough toluene to produce a 1 M solution in lactone. The vial was sealed and the stirring solution was immersed in an oil bath preheated to 100° C. After the desired time aliquots of the crude reaction mixture were taken for analysis by1H NMR in CDCl3. Samples were then cooled to 0° C., exposed to air and quenched with wet hexanes. Volatiles were removed under vacuum and a 25 mg/mL CHCl3solution was prepared for GPC. The conversion of ω-PDL to PPDL was determined by integration of the methylene proton peaks of the1H NMR spectra, δ 4.30-3.95.

Following the successful formation of PCL, the ROP of PDL was screened with the new family of catalysts. Polymerizations were conducted under similar conditions, in toluene solution at 100° C. (1:100 [I]:[ω-PDL], 1 M [ω-PDL]; Table 6) and in the melt (1:100 [I]:[ω-PDL] Table 6). As expected, the ROP of PDL is universally slower than CL. The order in catalyst, however, remains the same with Type C>Type B>Type A-II>Type A-I.

Molecular weights are considerably higher than anticipated for two growing chains. Advantageous water in the reaction may serve to deactivate a portion of catalyst causing an increase in Mn, however PPDL produced from (L8)2Ti(OiPr)2with freshly distilled PDL and unpurified PDL gave very similar conversion and Mnafter 5 hours. This suggests that even at high temperature (L)2Ti(OiPr)2catalysts are relatively tolerant to impurities, such as water.

Part B

Example 7—Ligand Synthesis

Amine Ligands

Following the formation of imine ligands previously described (L1-8) a reduction with excess NaBH4could be performed to yield amine ligands (L4-8′). These ligands were characterized through1H and13C{1H} NMR.

Synthesis of HL4′

Synthesis of HL5′

Synthesis of HL6′

Synthesis of HL7′

Synthesis of HL6′

Synthesis of HL4F

Example 8—Complex Synthesis

Using Imine Ligands

Synthesis of [(L4F)2Ti(OiPr)2]

Synthesis of [(L4)2Ti(OEt)2]

Synthesis of [(L4)2Ti(NMe2)2]

HL4(2 eq.) and Ti(NMe2)4(1 eq) were dissolved separately in toluene (10 mL and 10 mL, respectively), and cooled to −30° C. in a glovebox freezer. The two solutions were then mixed and allowed to stir for 24 hours. Volatiles were removed in vacuo and hexane (10 mL) was added to the resulting red solid. Hexane was removed under vacuum to provide the final complex as a dark red powder. Crystals suitable for XRD were grown from slow evaporation of CDCl3.1H NMR was inconclusive, most likely due to fluxionality in the catalyst.

Using Amine Ligands

General Synthesis

The appropriate amine ligand and Ti(OiPr)4in a 2:1 molar ratio, were dissolved separately in toluene (20 mL and 5 mL, respectively), and cooled in a glovebox freezer to −30° C. The dissolved ligand was added slowly to the Ti(OiPr)4solution in a Schlenk flask. After stirring for 24 hours, volatiles were removed under vacuum, and the resulting solid was twice dissolved in hexane and dried under vacuum to yield a coloured solid.

Synthesis of [(L4)2Ti(OiPr)2]

Synthesis of [(L5)2Ti(OiPr)2]

Synthesis of [(L6)2Ti(OiPr)2]

Synthesis of [(L7)2Ti(OiPr)2]

Example 9—Crystallographic Studies

The structure of the complexes prepared from amine ligands could in some cases be confirmed by X-ray crystallography and are shown to adopt Type C coordination (O,O/O,O coordination, Scheme 3).FIG. 65shows the X-ray crystal structures of (L412Ti(OiP02 (top) and (L7′)2Ti(OiPr)2(bottom) showing Type C coordination.

Having regard toFIGS. 66 to 68, the1H NMR spectra of (L4-6′)2Ti(OiPr)2remain virtually unchanged upon cooling (R.T. to −80° C.) or heating (R.T. to 80° C.) confirming (based on the assignment of the R.T.1H NMR and the solid state structures of (L4-6′)2Ti(OiPr)2) that 1) all of these catalysts contain Type C coordination 2) and these catalysts retain this coordination chemistry from −80° C. to 80° C.

The initiating group on the titanium could be changed from isopropoxide to ethoxide or dimethylamide by changing the titanium precursor to Ti(OEt)4or Ti(NMe2)4, thus yielding (L4)2Ti(OEt)2and (L4)2Ti(NMe2)2respectively. The structures of these compounds were confirmed using x-ray crystallography.FIG. 69suggests that changing the steric bulk of the initiating group has an effect on the observed coordination type.

Example 10—Polymerisation Studies

Catalysts prepared from phenoxy-amine ligands were tested for the ROP of ε-caprolactone, and in the case of (L5′)2Ti(OiPO2, ε-decalactone, ω-pentadecalactone, and rac-lactide. The general conditions used in each ROP polymerisation experiment are outlined below:

ε-caprolactone ROP polymerisation: In a glovebox, the catalyst was weighed (˜7 mg) into a vial, dissolved in ε-caprolactone and, in cases where solvent was used, sufficient toluene was added to form a 1 M solution in lactone. The vial was sealed and the stirring solution was immersed in an oil bath preheated to 80° C. After the desired time, samples were cooled to 0° C., exposed to air and aliquots of the crude reaction mixture were evaporated to dryness. The crude PCL was characterized as a 10 mg/mL THF solution for GPC and in CHCl3 for1H NMR spectroscopy.
ω-pentadecalactone ROP polymerisation: In a glovebox, the catalyst was weighed (˜7 mg) into a vial, along with ω-pentadecalactone and, in cases where solvent was used, sufficient toluene was added to form a 1 M solution in lactone. The vial was sealed and the stirring solution was immersed in an oil bath preheated to 100° C. After the desired time aliquots of the crude reaction mixture were taken for analysis by1H NMR in CDCl3. Samples were then cooled to 0° C., exposed to air and quenched with wet hexanes. Volatiles were removed under vacuum and a 25 mg/mL CHCl3solution was prepared for GPC. The conversion of PDL to PPDL was determined by integration of the methylene proton peaks of the1H NMR spectra, δ 4.30-3.95.
ε-decalactone ROP polymerisation: The catalyst (0.012 g, 0.015 mmol) was dissolved in a 1 M solution of toluene (1.5 mL) and monomer (1.500 mmol: 0.255 g ε-DL), to yield a 100:1 monomer:catalyst ratio. The reaction solution was divided up into 4 separate vials, which were sealed, removed from the glovebox, and placed in a pre-heated aluminum block to stir at 100° C. At each time point, the vials were aliquoted and quenched as in the ε-CL polymerisations.
rac-lactide ROP polymerisation: LA (0.058 g, 4.0×10−4mmol) was added to each of 4 vials along with dry toluene to give a 1M solution. The catalyst was then added to each vial, to give a 200:1 monomer:catalyst ratio. After sealing, the vials were removed from the glovebox and placed in a pre-heated aluminum block to stir at 100° C. Aliquots were taken and reactions were quenched as in the e-caprolactone polymerisations.

Reaction Kinetics

The kinetics of the ROP of ε-caprolactone using catalysts prepared from phenoxy-amine ligands were studied (FIG. 70) and, in conjunction with MALDI-ToF analysis of the polymer, confirm a coordination-insertion mechanism. The general conditions used for this experiment are outlined below:

In a glovebox, catalyst was weighed (0.025 mmol, ˜20 mg) into a volumetric flask (5 mL), and dissolved with dry toluene. ε-Caprolactone was then added to the solution (0.55 mL, 5 mmol), mixed thoroughly, and divided into individual vials. Vials were sealed with isolation tape and added simultaneously to a pre-heated oil bath set to 80° C. Vials were removed at set time intervals and immediately submerged in an ice bath. The solution was then exposed to air and a portion of the crude mixture was dissolved in wet CDCl3to determine conversion via NMR. Pentane/Hexane was added to the remaining aliquot to precipitate the resulting polymer followed by the removal of all volatiles under high vacuum. A 10 mg/mL THF solution of the polymer was then prepared for GPC analysis.

Copolymerization of ε-caprolactone and rac-lactide was also achieved using (L5′)2Ti(OiPr)2through subsequent addition of one monomer after full conversion of the first to yield poly(PLA-b-CL) or poly(CL-b-LA) depending on the order of addition. The general conditions used for this experiment are outlined below:

Into one vial LA (0.216 g, 1.500 mmol), toluene (1.5 mL) and the catalyst (0.012 g, 0.015 mmol) were added, giving a 100:1 monomer:catalyst ratio. This was taped, removed from the glovebox, and placed on a pre-heated aluminium block stir at 100° C. After 4 hours, the vial was taken into the glove box, an aliquot of the reaction mixture was added to C6D6, and ε-CL (0.270 g, 2.37 mmol) was added. The vial was retaped, removed from the glovebox and placed on a pre-heated aluminium block to stir for a further 3 hours at 80° C., after which the vial was opened, another aliquot was taken in C6D6, and the reaction was quenched as in previous polymerisations.
Into a second vial ε-CL (0.171 g, 1.500 mmol), toluene (1.5 mL) and the catalyst (0.012 g, 0.015 mmol) were added (100:1 monomer:catalyst ratio). This was taped, removed from the glovebox, and placed on a pre-heated metal adaptor to stir at 80° C. After 3 hours, the vial was taken into the glove box, an aliquot of the reaction mixture was added to C6D6, and LA (0.216 g, 1.500 mmol) was added. The vial was retaped, removed from the glovebox and placed on a pre-heated aluminium block to stir for a further 4 hours at 100° C., after which the vial was opened, another aliquot was taken in C6D6, and the reaction was quenched as in previous polymerisations.
1H{1H} NMR spectra for the block polymers were taken in CDCl3after the aliquots in C6D6were evaporated and re-dissolved. These samples were then dried under a stream of nitrogen gas and dissolved in THF for GPC analysis.
The polymers were purified by adding a solution of polymer in a small amount of DCM dropwise into stirring methanol (100 mL) to precipitate the polymer. The solid was then filtered and washed with pentane to be used for13C{1H} NMR spectra and GPC analysis of the final product.

Additionally, a one pot copolymerization of ε-caprolactone and ω-pentadecalactone with (L6)2Ti(OiPr)2yielded a statistical copolymer of poly(CL-co-PDL). The general conditions used for this experiment are outlined below:

In a glovebox, catalyst (˜7 mg, 0.010 mmol) was weighed into a vial, along with w-pentadecalactone, ε-caprolactone and enough toluene to produce a 1 M solution. The vial was then sealed and the stirring solution was immersed in an oil bath preheated to 100° C. Aliquots were removed at 2.5 h and 24 h for analysis by1H NMR in CDCl3. Samples were then cooled to 0° C., exposed to air and quenched with wet hexanes.

While specific embodiments of the invention have been described herein for the purpose of reference and illustration, various modifications will be apparent to a person skilled in the art without departing from the scope of the invention as defined by the appended claims.

REFERENCES