WO2019166783A1

WO2019166783A1 - Polymerisation of cyclic esters and cyclic amides

Info

Publication number: WO2019166783A1
Application number: PCT/GB2019/050492
Authority: WO
Inventors: Dermot O'hare; Jean-Charles BUFFET; Zoe R. TURNER; Thomas Robinson
Original assignee: Scg Chemicals Co., Ltd.
Priority date: 2018-02-27
Filing date: 2019-02-22
Publication date: 2019-09-06
Also published as: GB201803210D0

Abstract

A process for the polymerisation of cyclic esters or cyclic amides is described, using catalytic compounds based on Group IV metals bound to permethylpentalene and amidinate ligands.

Description

POLYMERISATION OF CYCLIC ESTERS AND CYCLIC AMIDES

INTRODUCTION

[0001] The present invention relates to a process for the polymerisation of cyclic esters and cyclic amides. More specifically, the present invention relates to a process for the polymerisation of cyclic esters (e.g. lactones and lactides) and cyclic amides using catalytic compounds based on group IV metals having permethylpentalene and amidinate ligands.

BACKGROUND OF THE INVENTION

[0002] Poly(lactic acids) (PLAs) have been studied intensively over the past few decades due to the promise they have shown as potential alternatives to petroleum-based polymers for uses a plastics, fibres and coatings. Moreover, since PLAs are both biodegradable and biocompatible, they are of equal value to the field of medicine, wherein their versatile physical properties make them suitable for in vivo applications (e.g. as media for controlled drug delivery devices).

[0003] Lactic acid forms PLA upon polycondensation. However, the fact that this reaction is in equilibrium, and the difficulties in completely removing water, makes it difficult to obtain PLAs of high molecular weight. With this in mind, ring opening polymerisation (ROP) of lactides is the most efficient route to PLAs with controlled molecular weights and narrow molecular weight distributions.

[0004] Metal complexes useful for initiating ring opening polymerisation of lactides are known.

[0005] Wenshan Ren et al, Inorganic Chemistry Communications, 30, (2013), 26-28 report that benzyl thorium metallocenes [q⁵-1 ,3-(Me3C)2C5H3]2 Th(CH2Ph)2 (1) and [q⁵-1 ,2,4-(Me3C)3C5H2]2 Th(CH2Ph)2 (2) can initiate the ring opening polymerisation of racemic-lactide (rac-LA) under mild conditions. Complete conversion of 500 equiv of lactide occurs within 5h at 40°C in dichloromethane at [rac-LA]=1.0 mol L ¹ , and the molecular weight distribution is very narrow (ca.1.15) over the entire monomer-to-initiator range, indicating a single-site catalyst system.

[0006] Yalan Ning et al, Organometallics 2008, 27, 5632-5640 report four neutral zirconocene bis(ester enolate) and non-zirconocene bis(alkoxy) complexes employed for ring-opening polymerisations and chain transfer polymerisations of L-lactide ( -LA) and e-caprolactone (e- CL). [0007] In spite of the above, due to the high value that industry places on such materials, there remains a need for catalysts/initiators capable of effectively polymerising cyclic esters (such as lactides and lactones) and cyclic amides.

The present invention was devised with the foregoing in mind.

SUMMARY OF THE INVENTION

[0008] According to a first aspect of the present invention there is provided a process for the polymerisation (e.g. ring-opening polymerisation) of a cyclic ester or a cyclic amide, the process comprising the step of:

a) contacting a compound having a structure according to formula (I) defined

herein with one or more cyclic esters or cyclic amides.

[0009] According to a second aspect of the present invention there is provided a use of a compound having a structure according to formula (I) defined herein in the polymerisation (e.g. ring-opening polymerisation) of one or more cyclic esters or cyclic amides

DETAILED DESCRIPTION OF THE INVENTION

Definitions

[0010] The term "(m-nC)" or "(m-nC) group" used alone or as a prefix, refers to any group having m to n carbon atoms.

[0011] 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.

[0012] 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.

[0013] 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 (CºC). This term includes reference to groups such as ethynyl, propynyl, butynyl, pentynyl and hexynyl. [0014] 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- ch loro pentyl, as well as perfluoroalkyl groups, such as perfluoromethyl.

[0015] 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.

[0016] 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.

[0017] 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.

[0018] 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.

[0019] 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 O and aryl groups.

[0020] The term "halogen" or“halo” as used herein refers to F, Cl, Br or I. In a particular, halogen may be F or Cl, of which Cl is more common.

[0021] 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.

[0022] 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 formula (I)

[0023] As discussed above, the first aspect of the invention provides a process for the polymerisation of a cyclic ester or a cyclic amide, the process comprising the step of:

a) contacting a compound having a structure according to formula (I) shown below with one or more cyclic esters or cyclic amides.

wherein

X is selected from zirconium or hafnium;

Y is selected from:

i) halo, hydrogen, a phosphonate, sulfonate or borate anion,

ii) (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, (1-6C)alkoxy, -C(0)NR_aR_b, - NR_aR_b, aryl and aryloxy, any of which is optionally substituted with one or more groups selected from halo, (1-4C)alkyl, nitro, -NR_aR_b, aryl, (1- 6C)alkoxy, -C(0)NR_aR_b, and Si[(1-4C)alkyl]₃, or

iii) a ligand having a structure according to formula A below:

A wherein

each R^x is independently selected from (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl and aryl, any of which is optionally substituted with one or more groups selected from halo, (1-6C)alkyl, (2-6C)alkenyl, (2- 6C)alkynyl, -NR_aR_b, (1-6C)alkoxy, -C(0)NR_aR_b, (1-3C)fluoroalkyl, aryl and aryloxy, and

R^y is selected from hydrogen, (1-6C)alkyl, (2-6C)alkenyl, (2- 6C)alkynyl, -NR_aR_b and aryl, any of which is optionally substituted with one or more groups selected from halo, (1-6C)alkyl, (2-6C)alkenyl, (2- 6C)alkynyl, -NR_aR_b, (1-6C)alkoxy, -C(0)NR_aR_b, (1-3C)fluoroalkyl, aryl and aryloxy;

each R¹ is independently selected from (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl and aryl, any of which is optionally substituted with one or more groups selected from halo, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, -NR_aR_b, (1-6C)alkoxy, -C(0)NR_aR_b, (1- 3C)fluoroalkyl, aryl and aryloxy; and

R² is selected from hydrogen, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, -NR_aR_b and aryl, any of which is optionally substituted with one or more groups selected from halo, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, -NR_aR_b, (1-6C)alkoxy, -C(0)NR_aR_b, (1- 3C)fluoroalkyl, aryl and aryloxy;

and wherein R_a and R_b are independently hydrogen or (1-4C)alkyl.

[0024] Through intensive investigations, the inventors have developed new compounds that exhibit activity in catalysing the polymerisation (i.e. ring-opening polymerisation) of cyclic ester and cyclic amides. The new compounds, which contain a permethylpentalene (“Pn*”) ligands and an amidinate ligand, are particularly active in the polymerisation of lactides and lactones (e.g. e-caprolactone). [0025] It will be appreciated that the compounds of formula (I) exist in a number of isomeric forms. For example, the exact nature of the bonding between metal X and the amidinate ligand may give rise to various isomeric forms, as illustrated below:

[0026] It will be appreciated that, depending on the nature of ligand Y, the compound of formula (I) may exist as a dimer. It will be understood that such dimeric forms of the compound of formula (I) are within the scope of the present invention. Dimeric forms of the compound of formula (I) may adopt the general structure:

[0027] In an embodiment, X is zirconium.

[0028] In embodiments of first aspect of the invention, X may also be titanium.

[0029] In an embodiment, each R¹ group is independently selected from (1-6C)alkyl, (2- 4C)alkenyl, (2-4C)alkynyl and aryl, any of which is optionally substituted with one or more groups selected from halo, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, -NR_aR_b, (1-6C)alkoxy, - C(0)NR_aR_b, (1-3C)fluoroalkyl, aryl and aryloxy.

[0030] Suitably, each R¹ group is independently selected from (1-6C)alkyl, (2-4C)alkenyl, (2- 4C)alkynyl and aryl, any of which is optionally substituted with one or more groups selected from halo, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, (1-6C)alkoxy, (1-3C)fluoroalkyl, aryl and aryloxy.

[0031] More suitably, each R¹ group is independently selected from (1-6C)alkyl and aryl, either of which is optionally substituted with one or more groups selected from halo, (1-6C)alkyl, (1- 6C)alkoxy, aryl and aryloxy.

[0032] Even more suitably, each R¹ group is independently selected from (1-4C)alkyl and phenyl, either of which is optionally substituted with one or more groups selected from halo, (1- 4C)alkyl, (1-2C)alkoxy, phenyl and phenoxy.

[0033] Yet more suitably, each R¹ group is independently selected from (1-4C)alkyl and phenyl, either of which is optionally substituted with 1-3 groups selected from halo, (1-4C)alkyl and (1- 2C)alkoxy.

[0034] In a particularly suitable embodiment, each R¹ group is independently selected from methyl, ethyl, isopropyl and tertbutyl, or each R¹ group is independently a phenyl group that is optionally substituted with 1-3 groups selected from methyl, ethyl, isopropyl and tertbutyl.

[0035] Both R¹ groups are suitably identical to one another.

[0036] In an embodiment, R² is selected from hydrogen, (1-6C)alkyl, (2-6C)alkenyl, (2- 6C)alkynyl, -NR_aR_b and aryl, any of which is optionally substituted with one or more groups selected from halo, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, (1-6C)alkoxy, (1-3C)fluoroalkyl, aryl and aryloxy.

[0037] Suitably, R² is selected from hydrogen, (1-6C)alkyl, -N'Pr'Pr and aryl, any of which is optionally substituted with one or more groups selected from halo, (1-6C)alkyl, (1-6C)alkoxy, (1- 3C)fluoroalkyl, aryl and aryloxy.

[0038] More suitably, R² is selected from hydrogen, (1-4C)alkyl and aryl, any of which is optionally substituted with one or more groups selected from halo, (1-4C)alkyl, (1-2C)alkoxy, aryl and aryloxy.

[0039] Even more suitably, R² is selected from hydrogen, (1-4C)alkyl and phenyl, any of which is optionally substituted with one or more groups selected from halo, (1-4C)alkyl, (1-2C)alkoxy, phenyl and phenoxy.

[0040] Yet more suitably, R² is selected from hydrogen, (1-4C)alkyl and phenyl, any of which is optionally substituted with one or more groups selected from halo and (1-4C)alkyl.

[0041] In a particularly suitable embodiment, R² is selected from hydrogen, (1-4C)alkyl and phenyl, any of which is optionally substituted with one or more groups selected from halo and (1-4C)alkyl. [0042] In an embodiment, R_a and R_b are independently selected from methyl, ethyl, iso-propyl and tert-butyl.

[0043] Suitably, R_a and R_b are independently selected from methyl, ethyl and iso-propyl.

[0044] More suitably, R_a and R_b are identical.

[0045] When taken in combination with the group -N-C(R²)H-N-, the groups R¹ and R² form an amidinate ligand -(R¹)N-C(R²)H-N(R¹)-. Exemplary amidinate ligands useful in the context of the present invention are as follows:

[0046] In an embodiment, Y is

i) halo, hydrogen, a phosphonate, sulfonate or borate anion, ii) (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, (1-6C)alkoxy, -C(0)NR_aR_b, -NR_aR_b, aryl and aryloxy, any of which is optionally substituted with one or more groups selected from halo, (1- 4C)alkyl, nitro, -NR_aR_b, aryl, (1-6C)alkoxy, -C(0)NR_aR_b, and Si[(1-4C)alkyl]₃, or iii) a ligand having a structure according to formula A, wherein each R^x has any of the definitions discussed hereinbefore in relation to R¹ , and R^y has any of the definitions discussed hereinbefore in relation to R².

[0047] Suitably, Y is

i) halo, hydrogen, a phosphonate, sulfonate or borate anion, ii) (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, (1-6C)alkoxy, -C(0)NR_aR , -NR_aR , aryl and aryloxy, any of which is optionally substituted with one or more groups selected from halo, (1- 4C)alkyl, nitro, -NR_aR_b, aryl, (1-6C)alkoxy, -C(0)NR_aR_b, and Si[(1-4C)alkyl]₃, or iii) a ligand having a structure according to formula A, wherein both R¹ groups are identical, each R^x is identical to R¹, and R^y is identical to R².

[0048] More suitably, Y is

i) halo, or ii) (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, (1-6C)alkoxy, aryl and aryloxy, any of which is optionally substituted with one or more groups selected from halo, (1-4C)alkyl, -NR_aR_b, aryl, (1- 6C)alkoxy, -C(0)NR_aR , and Si[(1-4C)alkyl]₃.

[0049] Even more suitably, Y is

i) halo, or ii) (1-6C)alkyl, (1-6C)alkoxy, aryl and aryloxy, any of which is optionally substituted with one or more groups selected from halo, (1-4C)alkyl, aryl and (1-6C)alkoxy.

[0050] Yet more suitably, Y is

i) halo, or ii) (1-4C)alkyl, (1-4C)alkoxy, aryl and aryloxy, any of which is optionally substituted with one or more groups selected from halo and (1-4C)alkyl.

[0051] Yet even more suitably, Y is

i) chloro or bromo, or ii) (1-4C)alkoxy, phenyl and phenoxy, any of which is optionally substituted with one or more groups selected from halo and (1-4C)alkyl.

[0052] In a particularly suitable embodiment, Y is

i) chloro, or ii) (1-4C)alkoxy, phenyl and phenoxy, any of which is optionally substituted with 1-3 groups selected from halo and (1-4C)alkyl.

[0053] In another particularly suitable embodiment, Y is

i) chloro, or ii) (1-4C)alkoxy (e.g. f-butoxy) or a phenoxy group that is optionally substituted (e.g. at the ortho position) with 1 or 2 (1-4C)alkyl groups (e.g. methyl or isopropyl).

[0054] In an embodiment, the compound of formula (I) has a structure according to formula (la) shown below:

wherein

X, Y and R² have any of the definitions discussed hereinbefore in respect of formula (I); each R³ is independently selected from (1-4C)alkyl and (1-3C)fluoroalkyl; and each n is independently 0, 1 , 2 or 3. [0055] Suitably, the compound of formula (I) has a structure according to formula (la), wherein

X, Y and R² have any of the definitions discussed hereinbefore in respect of formula (I);

each R³ is independently an ortho or para substituent selected from (1-4C)alkyl and (1- 3C)fluoroalkyl; and

each n is independently 0, 1 , 2 or 3.

[0056] More suitably, the compound of formula (I) has a structure according to formula (la), wherein

X is zirconium;

R² is selected from hydrogen, (1-6C)alkyl and aryl, any of which is optionally substituted with one or more groups selected from halo, (1-6C)alkyl, (1-6C)alkoxy, aryl and aryloxy

Y is: i) halo, hydrogen, a phosphonate, sulfonate or borate anion, ii) (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, (1-6C)alkoxy, -C(0)NR_aR_b, -NR_aR_b, aryl and aryloxy, any of which is optionally substituted with one or more groups selected from halo, (1- 4C)alkyl, nitro, -NR_aR_b, aryl, (1-6C)alkoxy, -C(0)NR_aR_b, and Si[(1-4C)alkyl]₃, or iii) an amidinate ligand identical to that depicted in formula (la) (i.e. that comprising groups R¹ and R²); each R³ is independently an ortho or para substituent selected from (1-4C)alkyl and (1- 3C)fluoroalkyl; and

each n is independently 0, 1 , 2 or 3.

[0057] Even more suitably, the compound of formula (I) has a structure according to formula (la), wherein

X is zirconium;

R² is selected from hydrogen, (1-4C)alkyl and phenyl, any of which is optionally substituted with one or more groups selected from halo and (1-4C)alkyl;

Y is: i) halo, or ii) (1-6C)alkyl, (1-6C)alkoxy, aryl and aryloxy, any of which is optionally substituted with one or more groups selected from halo, (1-4C)alkyl, aryl and (1-6C)alkoxy; each R³ is independently an ortho or para substituent selected from (1-4C)alkyl and (1- 3C)fluoroalkyl; and

each n is independently 0, 1 , 2 or 3.

[0058] Yet more suitably, the compound of formula (I) has a structure according to formula (la), wherein

X is zirconium;

Y is: i) chloro, or ii) (1-4C)alkoxy or a phenoxy group that is optionally substituted with 1 or 2 (1-4C)alkyl groups; each R³ is independently an ortho or para substituent selected from methyl, iso-propyl and trifluoromethyl; and

each n is independently 0, 1 , 2 or 3.

[0059] In an embodiment, the compound of formula (I) has a structure according to formula (lb) shown below:

wherein

X, Y and R² have any of the definitions discussed hereinbefore in respect of formula (I).

[0060] Suitably, the compound of formula (I) has a structure according to formula (lb), wherein X is zirconium;

R² is selected from hydrogen, (1-6C)alkyl, -NR_aR_b and aryl, any of which is optionally substituted with one or more groups selected from halo, (1-6C)alkyl, (1-6C)alkoxy, (1- 3C)fluoroalkyl, aryl and aryloxy;

Y is: i) halo, hydrogen, a phosphonate, sulfonate or borate anion, ii) (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, (1-6C)alkoxy, -C(0)NR_aR_b, -NR_aR_b, aryl and aryloxy, any of which is optionally substituted with one or more groups selected from halo, (1- 4C)alkyl, nitro, -NR_aR_b, aryl, (1-6C)alkoxy, -C(0)NR_aR_b, and Si[(1-4C)alkyl]₃, or iii) an amidinate ligand identical to that depicted in formula (la) (i.e. that comprising groups R¹ and R²).

[0061] More suitably, the compound of formula (I) has a structure according to formula (lb), wherein

X is zirconium;

R² is selected from hydrogen, (1-4C)alkyl, -N'Pr'Pr and phenyl, any of which is optionally substituted with one or more groups selected from halo, (1-4C)alkyl, (1-2C)alkoxy and (1- 3C)fluoroalkyl;

Y is: i) halo, or ii) (1-6C)alkyl, (1-6C)alkoxy, aryl and aryloxy, any of which is optionally substituted with one or more groups selected from halo, (1-4C)alkyl, aryl and (1-6C)alkoxy.

[0062] Even more suitably, the compound of formula (I) has a structure according to formula (lb), wherein

X is zirconium;

R² is selected from hydrogen, (1-4C)alkyl, -N'Pr'Pr and phenyl, any of which is optionally substituted with one or more groups selected from halo, (1-4C)alkyl, (1-2C)alkoxy and trifluoromethyl;

Y is: i) chloro, or ii) (1-4C)alkoxy or a phenoxy group that is optionally substituted with 1 or 2 (1-4C)alkyl groups.

[0063] In an embodiment, the compound of formula (I) has a structure according to formula (lc) shown below:

wherein

X, R¹ and R² have any of the definitions discussed hereinbefore in respect of formula (I).

[0064] In an embodiment, the compound of formula (I) has a structure according to formula (lc) wherein

X is zirconium;

each R¹ group is independently selected from (1-6C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl and aryl, any of which is optionally substituted with one or more groups selected from halo, (1- 6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, (1-6C)alkoxy, (1-3C)fluoroalkyl, aryl and aryloxy; and

R² is selected from hydrogen, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, -NR_aR_b and aryl, any of which is optionally substituted with one or more groups selected from halo, (1-6C)alkyl, (2- 6C)alkenyl, (2-6C)alkynyl, (1-6C)alkoxy, (1-3C)fluoroalkyl, aryl and aryloxy.

[0065] In an embodiment, the compound of formula (I) has a structure according to formula (lc) wherein

X is zirconium;

each R¹ group is independently selected from (1-6C)alkyl and aryl, either of which is optionally substituted with one or more groups selected from halo, (1-6C)alkyl, (1-6C)alkoxy, (1- 3C)haloalkyl, aryl and aryloxy; and R² is selected from hydrogen, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, -N'Pr 'Pr and aryl, any of which is optionally substituted with one or more groups selected from halo, (1-6C)alkyl, (2- 6C)alkenyl, (2-6C)alkynyl, (1-6C)alkoxy, (1-3C)fluoroalkyl, aryl and aryloxy.

[0066] In an embodiment, the compound of formula (I) has a structure according to formula (lc) wherein

X is zirconium;

each R¹ group is independently selected from (1-4C)alkyl and phenyl, either of which is optionally substituted with one or more groups selected from halo, (1-4C)alkyl, (1-2C)alkoxy, phenyl and phenoxy; and

R² is selected from hydrogen, (1-4C)alkyl and phenyl, any of which is optionally substituted with one or more groups selected from halo, (1-4C)alkyl, (1-2C)alkoxy, phenyl and phenoxy.

[0067] In an embodiment, the compound of formula (I) has a structure according to formula (lc) wherein

X is zirconium;

R¹ group is selected from methyl, ethyl, isopropyl and tertbutyl, or R¹ group is a phenyl group that is optionally substituted with 1-3 groups selected from methyl, ethyl, isopropyl and tertbutyl; and

R² is selected from hydrogen, (1-4C)alkyl and phenyl, any of which is optionally substituted with one or more groups selected from halo and (1-4C)alkyl.

[0068] In an embodiment, the compound of formula (I) has a structure according to formula (Id) shown below:

wherein X, R¹ and R² have any of the definitions discussed hereinbefore in respect of formula (I); and

R⁴ is selected from (1-4C)alkyl and aryl, either or which is optionally substituted with one or more substituents selected from (1-4C)alkyl and (1-3C)fluoroalkyl.

[0069] In an embodiment, the compound of formula (I) has a structure according to formula (Id) wherein

X is zirconium;

each R¹ group is independently selected from (1-6C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl and aryl, any of which is optionally substituted with one or more groups selected from halo, (1- 6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, (1-6C)alkoxy, (1-3C)fluoroalkyl, aryl and aryloxy;

R² is selected from hydrogen, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, -NR_aR_b and aryl, any of which is optionally substituted with one or more groups selected from halo, (1-6C)alkyl, (2- 6C)alkenyl, (2-6C)alkynyl, (1-6C)alkoxy, (1-3C)fluoroalkyl, aryl and aryloxy; and

R⁴ is selected from (1-4C)alkyl and phenyl, either or which is optionally substituted with one or more substituents selected from (1-4C)alkyl and (1-3C)fluoroalkyl.

[0070] In an embodiment, the compound of formula (I) has a structure according to formula (Id) wherein

X is zirconium;

each R¹ group is independently selected from (1-6C)alkyl and aryl, either of which is optionally substituted with one or more groups selected from halo, (1-6C)alkyl, (1-6C)alkoxy, (1- 3C)haloalkyl, aryl and aryloxy; and

R² is selected from hydrogen, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, -N'Pr 'Pr and aryl, any of which is optionally substituted with one or more groups selected from halo, (1-6C)alkyl, (2- 6C)alkenyl, (2-6C)alkynyl, (1-6C)alkoxy, (1-3C)fluoroalkyl, aryl and aryloxy.

[0071] In an embodiment, the compound of formula (I) has a structure according to formula (Id) wherein

X is zirconium;

each R¹ group is independently selected from (1-4C)alkyl and phenyl, either of which is optionally substituted with one or more groups selected from halo, (1-4C)alkyl, (1-2C)alkoxy, phenyl and phenoxy;

R² is selected from hydrogen, (1-4C)alkyl and phenyl, any of which is optionally substituted with one or more groups selected from halo, (1-4C)alkyl, (1-2C)alkoxy, phenyl and phenoxy; and R⁴ is selected from methyl, iso-propyl, tert-butyl and phenyl, either or which is optionally substituted with one or more substituents selected from methyl, iso-propyl, tert-butyl and trifluoromethyl.

[0072] In an embodiment, the compound of formula (I) has a structure according to formula (Id) wherein

X is zirconium;

R¹ group is selected from methyl, ethyl, isopropyl and tertbutyl, or R¹ group is a phenyl group that is optionally substituted with 1-3 groups selected from methyl, ethyl, isopropyl and tertbutyl;

R² is selected from hydrogen, (1-4C)alkyl and phenyl, any of which is optionally substituted with one or more groups selected from halo and (1-4C)alkyl; and

R⁴ is selected from tert-butyl, 2,6-dimethyl phenyl and 2,6-diisopropyl phenyl.

[0073] In an embodiment, the compound of formula (I) has any of the following structures:

[0074] In an embodiment, the compound of formula (I) has any of the following structures:

[0075] Suitably, the compound of formula (I) has any of the following structures:

[0076] In an embodiment, the compound of formula (I) has any of the following structures:

Synthesis of compounds of formula (I)

[0077] The compounds of formula (I) may be synthesised by any suitable process known in the art. Particular examples of processes for the preparation of the compounds are set out in the accompanying examples.

[0078] Suitably, the compounds of formula (I) are prepared according to a process comprising the steps of:

a) reacting a compound of formula (II) shown below:

wherein X is as defined in formula (I), M is a metal (such as Li, Na or K) and Q is halo (e.g. chloro);

with a compound of formula (III) shown below:

wherein R¹ and R² are as defined in formula (I) and M⁺ is a metal cation (such as Li⁺, Na⁺ or K⁺); and optionally thereafter

b) reacting the resulting product with a compound of formula (IV) shown below:

M(Y)

(iv) wherein Y is as defined in formula (I) and M is a metal (such as Li, Na or K). [0079] If a compound of formula (I) is required in which Y is other than halo, then step b) is typically implemented.

[0080] Suitably, M is Li in step a).

[0081] Any suitable solvent may be used for steps a) and b) of the process defined above. A particularly suitable solvent may be, for example, diethyl ether, toluene, THF, dichloromethane, chloroform, hexane DMF, benzene etc.

[0082] Within step a), the compound of formula (III) is typically added dropwise to the compound of formula (II) in order to prevent double ligand substitution (unless this is desired).

[0083] A person of skill in the art will be able to select suitable reaction conditions (e.g. temperature, pressures, reaction times, agitation etc.) for such a synthesis.

Polymerisation of cyclic esters and cyclic amides

[0084] As discussed above, the first aspect of the invention provides a process for the polymerisation of a cyclic ester or a cyclic amide, the process comprising the step of:

[0085] In an embodiment, the one or more cyclic esters or cyclic amides has a structure according to formula (V) shown below:

wherein

Z is selected from O or NR⁵, wherein R⁵ is selected from hydrogen, (1-6C)alkyl, (2-6C)alkenyl and (2-6C)alkynyl; and

ring A is a 3-23 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.

[0086] 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.

[0087] In an embodiment, Z is selected from O or NR⁵, wherein R⁵is selected from hydrogen, (1-3C)alkyl, (2-3C)alkenyl or (2-3C)alkynyl.

[0088] In an embodiment, Z is selected from O or NR⁵, wherein R⁵ is selected from hydrogen and (1-3C)alkyl.

[0089] In an embodiment, Z is selected from O or NR⁵, wherein R⁵ is hydrogen.

[0090] In an embodiment, Z is O.

[0091] In an embodiment, ring A is a 4-23 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.

[0092] 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.

[0093] 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.

[0094] 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.

[0095] 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.

[0096] 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.

[0097] 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.

[0098] 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. [0099] In an embodiment, ring A does not contain any N heteroatoms.

[00100] In an embodiment, the one or more cyclic esters or cyclic amides is a lactone. Non limiting examples of lactones include b-propiolactone, g-butyrolactone, g-valerolactone, e- caprolactone and w-pentadecalactone. Suitably, the lactone is e-caprolactone.

[00101] 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:

D-lactide {R,R) L-lactide (S,S) meso- 1 acti d e (R,S)

Suitably, the lactide is L-lactide.

[00102] In an embodiment, the one or more cyclic esters or cyclic amides is a lactam. Non limiting examples of lactams include b-lactams (4 ring members), y-lactams (5 ring members), d-lactams (6 ring members) and e-lactams (7 ring members).

[00103] In an embodiment, the one or more cyclic esters or cyclic amides are selected from e- caprolactone and L-lactide.

[00104] In an embodiment, in step a), the mole ratio of the compound of formula (I) to the cyclic ester or cyclic amide is 1 :5 to 1 :10,000. Suitably, in step a), the mole ratio of the compound of formula (I) to the cyclic ester or cyclic amide is 1 :25 to 1 :1000. More suitably, in step a), the mole ratio of the compound of formula (I) to the cyclic ester or cyclic amide is 1 :50 to 1 :500.

[00105] 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 benzene, toluene, tetrahydrofuran and methylene chloride.

[00106] 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). [00107] In an embodiment, step a) is conducted at a temperature of 15 to 180°C. Suitably, step a) is conducted at a temperature of 15 to 100°C. In one particular embodiment, step a) is conducted at a temperature of 15 to 40°C (e.g. room temperature). In another particular embodiment, step a) is conducted at a temperature of 60 to 100°C (e.g. at 80°C). In another embodiment, when step a) is conducted in the melt (i.e. without solvent), it is conducted at a temperature sufficient to melt the cyclic ester or cyclic amide (e.g. 120 to 180°C for lactide poylmerisation).

[00108] 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.

[00109] 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.

[00110] According to a second aspect of the present invention, there is provided a use of a compound having a structure according to formula (I) in the ring opening polymerisation (ROP) of one or more cyclic esters or cyclic amides.

[00111] It will be appreciated that, in the context of the second aspect of the invention, the one or more cyclic esters or cyclic amides may have any of those definitions outlined in respect of the first aspect of the invention.

[00112] It will be appreciated that, in the context of the second aspect of the invention, the use of the compound having a structure according to formula (I) 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 first aspect of the invention.

[00113] The following numbered statements 1 to 44 are not claims, but instead serve to define particular aspects and embodiments of the claimed invention:

1. A process for the polymerisation of a cyclic ester or a cyclic amide, the process

comprising the step of:

a) contacting a compound having a structure according to formula (I) shown below with one or more cyclic esters or cyclic amides

wherein

X is selected from zirconium, hafnium and titanium;

Y is selected from:

i) halo, hydrogen, a phosphonate, sulfonate or borate anion, ii) (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, (1-6C)alkoxy, -C(0)NR_aR_b, - NR_aR_b, aryl and aryloxy, any of which is optionally substituted with one or more groups selected from halo, (1-4C)alkyl, nitro, -NR_aR_b, aryl, (1- 6C)alkoxy, -C(0)NR_aR_b, and Si[(1-4C)alkyl]₃, or

iii) a ligand having a structure according to formula A below:

A wherein

and wherein R_a and R_b are independently hydrogen or (1-4C)alkyl. The process of statement 1 , wherein X is zirconium. The process of statement 1 or 2, wherein each R¹ group is independently selected from (1-6C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl and aryl, any of which is optionally substituted with one or more groups selected from halo, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, - NR_aR_b, (1-6C)alkoxy, -C(0)NR_aR_b, (1-3C)fluoroalkyl, aryl and aryloxy. The process of any one of statements 1 , 2 or 3, wherein each R¹ group is independently selected from (1-6C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl and aryl, any of which is optionally substituted with one or more groups selected from halo, (1-6C)alkyl, (2- 6C)alkenyl, (2-6C)alkynyl, (1-6C)alkoxy, (1-3C)fluoroalkyl, aryl and aryloxy. The process of any preceding statement, wherein each R¹ group is independently selected from (1-6C)alkyl and aryl, either of which is optionally substituted with one or more groups selected from halo, (1-6C)alkyl, (1-6C)alkoxy, aryl and aryloxy. The process of any preceding statement, wherein each R¹ group is independently selected from (1-4C)alkyl and phenyl, either of which is optionally substituted with one or more groups selected from halo, (1-4C)alkyl, (1-2C)alkoxy, phenyl and phenoxy. The process of any preceding statement, wherein each R¹ group is independently selected from (1-4C)alkyl and phenyl, either of which is optionally substituted with 1-3 groups selected from halo, (1-4C)alkyl and (1-2C)alkoxy. The process of any preceding statement, wherein each R¹ group is independently selected from methyl, ethyl, isopropyl and tertbutyl, or each R¹ group is independently a phenyl group that is optionally substituted with 1-3 groups selected from methyl, ethyl, isopropyl and tertbutyl. The process of any preceding statement, wherein both R¹ groups are identical The process of any preceding statement, wherein R² is selected from hydrogen, (1- 6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, -NR_aR_b and aryl, any of which is optionally substituted with one or more groups selected from halo, (1-6C)alkyl, (2-6C)alkenyl, (2- 6C)alkynyl, (1-6C)alkoxy, (1-3C)fluoroalkyl, aryl and aryloxy. The process of any preceding statement, wherein R² is selected from hydrogen, (1- 6C)alkyl and aryl, any of which is optionally substituted with one or more groups selected from halo, (1-6C)alkyl, (1-6C)alkoxy, aryl and aryloxy. The process of any preceding statement, wherein R² is selected from hydrogen, (1- 4C)alkyl and aryl, any of which is optionally substituted with one or more groups selected from halo, (1-4C)alkyl, (1-2C)alkoxy, aryl and aryloxy. The process of any preceding statement, wherein R² is selected from hydrogen, (1- 4C)alkyl and phenyl, any of which is optionally substituted with one or more groups selected from halo, (1-4C)alkyl, (1-2C)alkoxy, phenyl and phenoxy. The process of any preceding statement, wherein R² is selected from hydrogen, (1- 4C)alkyl and phenyl, any of which is optionally substituted with one or more groups selected from halo and (1-4C)alkyl. The process of any preceding statement, wherein R² is selected from hydrogen, (1- 4C)alkyl and phenyl, any of which is optionally substituted with one or more groups selected from halo and (1-4C)alkyl. The process of any preceding statement, wherein the group -(R¹)N-CH(R²)-N(R¹)- is an amidinate ligand having any one of the following structures:

The process of any preceding statement, wherein Y is

i) halo, hydrogen, a phosphonate, sulfonate or borate anion,

ii) (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, (1-6C)alkoxy, -C(0)NR_aR_b, -NR_aR_b, aryl and aryloxy, any of which is optionally substituted with one or more groups selected from halo, (1-4C)alkyl, nitro, -NR_aR_b, aryl, (1-6C)alkoxy, -C(0)NR_aR_b, and Si[(1-4C)alkyl]₃, or iii) a ligand having a structure according to formula A, wherein each R^x has any of the definitions appearing in any preceding statement in relation to R¹, and R^y has any of the definitions appearing in any preceding statement in relation to R². The process of any preceding statement, wherein Y is

i) halo, hydrogen, a phosphonate, sulfonate or borate anion,

ii) (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, (1-6C)alkoxy, -C(0)NR_aR , -NR_aR , aryl and aryloxy, any of which is optionally substituted with one or more groups selected from halo, (1-4C)alkyl, nitro, -NR_aR_b, aryl, (1-6C)alkoxy, -C(0)NR_aR_b, and Si[(1-4C)alkyl]₃, or iii) a ligand having a structure according to formula A, wherein each R^x is identical to R¹ , and R^y is identical to R². The process of any preceding statement, wherein Y is

i) halo, or

ii) (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, (1-6C)alkoxy, aryl and aryloxy, any of which is optionally substituted with one or more groups selected from halo, (1-4C)alkyl, - NRaRb, aryl, (1-6C)alkoxy, -C(0)NR_aR_b, and Si[(1-4C)alkyl]₃. The process of any preceding statement, wherein Y is

i) halo, or

ii) (1-6C)alkyl, (1-6C)alkoxy, aryl and aryloxy, any of which is optionally substituted with one or more groups selected from halo, (1-4C)alkyl, aryl and (1-6C)alkoxy. The process of any preceding statement, wherein Y is

i) halo, or

ii) (1-4C)alkyl, (1-4C)alkoxy, aryl and aryloxy, any of which is optionally substituted with one or more groups selected from halo and (1-4C)alkyl. The process of any preceding statement, wherein Y is

i) chloro or bromo, or

ii) (1-4C)alkoxy, phenyl and phenoxy, any of which is optionally substituted with one or more groups selected from halo and (1-4C)alkyl. The process of any preceding statement, wherein Y is

i) chloro, or

ii) (1-4C)alkoxy, phenyl and phenoxy, any of which is optionally substituted with 1-3 groups selected from halo and (1-4C)alkyl. The process of any preceding statement, wherein Y is

i) chloro, or

ii) (1-4C)alkoxy or a phenoxy group that is optionally substituted with 1 or 2 (1-4C)alkyl groups. The process of any preceding statement, wherein the compound of formula (I) has a structure according to formula (la) shown below:

wherein

X, Y and R² are as defined in any preceding statement; each R³ is independently selected from (1-4C)alkyl and (1-3C)fluoroalkyl; and each n is independently 0, 1 , 2 or 3. The process of any one of statements 1 to 24, wherein the compound of formula (I) has a structure according to formula (lb) shown below:

wherein

X, Y and R² are as defined in any preceding statement; The process of any one of statements 1 to 24, wherein the compound of formula (I) has a structure according to formula (lc) shown below:

wherein

X, R¹ and R² are as defined in any preceding statement. The process of any one of statements 1 to 24, wherein the compound of formula (I) has a structure according to formula (Id) shown below:

wherein

X, R¹ and R² are as defined in any preceding statement; and

R⁴ is selected from (1-4C)alkyl and aryl, either or which is optionally substituted with one or more substituents selected from (1-4C)alkyl and (1-3C)fluoroalkyl. The process of statement 1 , wherein the compound has any of the following structures:

ess of statement 1 , wherein the compound has any of the following structures:

30. The process of statement 1, wherein the compound has any of the following structures:

The process of statement 1 , wherein the compound has any of the following structures:

The process of any preceding statement, wherein the one or more cyclic esters or cyclic amides has a structure according to formula (V) shown below:

wherein

ring A is a 3-23 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. The process of statement 32, wherein Z is selected from O or NR⁵, wherein R⁵ is hydrogen. The process of statement 32, wherein Z is O. The process of statement 32, 33 or 34, wherein ring A is a 4-23 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. The process of any one of statements 32 to 35, wherein 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. The process of any one of statements 32 to 36, wherein 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 The process of any preceding statement, wherein the one or more cyclic esters or cyclic amides is a lactone or a lactide. The process of statement 38, wherein the lactone is e-caprolactone. The process of statement 38 or 39, wherein the lactide is L-lactide. The process of any preceding statement, wherein in step a), the mole ratio of the compound of formula (I) to the cyclic ester or cyclic amide is 1 :5 to 1 :10,000. The process of any preceding statement, wherein step a) is conducted in a solvent selected from benzene, toluene, tetrahydrofuran and methylene chloride. 43. The process of any preceding statement, wherein step a) is conducted in the presence of a chain transfer agent suitable for use in the ring opening polymerisation of a cyclic ester or cyclic amide.

44. The process of any preceding statement, wherein step a) is conducted at a temperature of 15 to 180°C.

EXAMPLES

[00114] Examples of the invention will now be described, for the purpose of illustration only, with reference to the accompanying figures, in which:

Fig. 1 shows the ¹H NMR spectrum of Pn^*Zr(CI)(HC(N-2,6-'Pr-C₆H₃)₂) recorded at 298 K in CD2CI2. ^*denotes NMR solvent residue.

Fig. 2 shows the molecular structure of Pn^*Zr(CI)(HC(N-2,6-'Pr-C₆H₃)₂), shown with thermal ellipsoids at 50% probability and hydrogen atoms removed for clarity.

Fig. 3 shows the ¹H NMR spectrum of Pn^*Zr(CI)(MeC(N'Pr)2) recorded at 298 K in Obϋ_d. *denotes NMR solvent residue.

Fig. 4 shows the molecular structure of dimeric [Pn^*Zr(CI)(MeC(N'Pr)2)]2, shown with thermal ellipsoids at 50% probability and hydrogen atoms removed for clarity.

Fig. 5 shows the ¹H NMR spectrum of Pn^*Zr(CI)(PhC(N'Pr)2) recorded at 298 K in O_dϋ_d. *denotes NMR solvent residue and residual THF.

Fig. 6 shows the molecular structure of Pn^*Zr(CI)(PhC(N'Pr)2), shown with thermal ellipsoids at 50% probability and hydrogen atoms removed for clarity. An additional symmetry inequivalent molecule composes the asymmetric unit and is also omitted for clarity.

Fig. 7 shows the ¹H NMR spectrum of Pn^*Zr(CI)(HC(N-4-Me-C₆H₄)₂) recorded at 298 K in CD2CI2. ^*denotes NMR solvent residue and residual hexane.

Fig. 8 shows the molecular structure of dimeric [Pn^*Zr(CI)(HC(N-4-Me-C₆H₄)₂)]₂, shown with thermal ellipsoids at 50% probability and hydrogen atoms removed for clarity.

Fig. 9 shows the ¹H NMR spectrum of Pn^*Zr(0-2,6-Me-C₆H₃)(PhC(N'Pr)₂) recorded at 298 K in O_dϋ_d. *denotes NMR solvent residue.

Fig. 10 shows the molecular structure of Pn^*Zr(0-2,6-Me-C₆H₃))(PhC(N'Pr)₂), shown with thermal ellipsoids at 50% probability and hydrogen atoms removed for clarity. An additional symmetry inequivalent molecule composes the asymmetric unit and is also omitted for clarity. Fig. 11 is a plot showing conversion of L-lactide to Polylactide as a function of time using the compounds of Example 1. Reactions catalysed by the series of permethylpentalene zirconium catalysts. Polymerisations were performed in a 0.5M L-lactide solution in CeD₆ at 80 °C with 2 mol% [Zr]

Fig. 12 is a plot showing concentration of e-caprolactone monomer as a function of polymerisation time using Pn^*Zr(0-2,6-Me-C₆H₃)(PhC(N'Pr)₂), with the reaction following a zero order rate law. Polymerisations were performed in a 0.5M e-caprolactone solution in CeD₆ at room temperature with 2 mol% Pn^*Zr(0-2,6-Me-C6H3)(PhC(N'Pr)2).

Fig. 13 shows the ¹ H NMR spectrum of Pn*Zr{('PrN)₂C(4-OMe-C₆H₄)}CI recorded at 298K in C₆D₆. *denotes NMR solvent residue and # denotes residual thf.

Fig. 14 shows the ¹ H NMR spectrum of Pn*Zr{('PrN)₂C(4-CF₃-C₆H₄)}CI recorded at 298K in C₆D₆. *denotes NMR solvent residue and # denotes residual thf.

Fig. 15 shows the ¹ H NMR spectrum of Pn*Ti{(2,6-'PrC₆H₃N)₂CH}CI recorded at 298K in CeD₆. *denotes NMR solvent residue.

Fig. 16 shows the ¹ H NMR spectrum of Pn*Ti{('PrN)2C(C6H5)}CI recorded at 298K in CeD₆. *denotes NMR solvent residue and # denotes residual pentane.

PART I

Example 1 - Synthesis of compounds

1.1. General procedure for the synthesis of Pn*Zr(CI)L (L = HC(N-2.6-^lPr- MeC/N'Prl?

and PhCfN'Prl?

[00115] [Pn*ZrCl2]2LiCI THF_x (0.114 mmol) and a metal salt of the desired ligand (M-L*, 0.229 mmol) were combined as solids in a Schlenk tube and toluene (3 ml_) was added at room temperature. When L = MeC(N'Pr)2 or PhC(N'Pr)2 solutions were stirred for 2 hours at room temperature and when L = HC(N-2,6-'Pr-C₆H₃)₂ the solution was stirred at 60 °C for 15 h. In all cases all volatiles were removed in vacuo and the residues extracted into toluene and filtered through celite. Toluene was removed in vacuo and the products extracted into hexane and filtered to remove remaining LiCI. Crystals of each product were obtained by cooling concentrated hexane solutions to -30 °C. Crystals were isolated by filtration. [*Lithium salts were used for MeC(N'Pr)2 and PhC(N'Pr)2 whilst a potassium salt of HC(N-2,6-'Pr-C6H3)2 was used.]

[00116] Fig. 1 shows the ¹ H NMR spectrum of Pn^*Zr(CI)(HC(N-2,6-'Pr-C₆H₃)₂) recorded at 298 K in CD2CI2. The molecular structure is depicted in Fig. 2. [00117] Fig. 3 shows the ¹ H NMR spectrum of Pn^*Zr(CI)(MeC(N'Pr)2) recorded at 298 K in C₆D₆. The molecular dimeric structure is depicted in Fig. 4.

[00118] Fig. 5 shows the ¹ H NMR spectrum of Pn^*Zr(CI)(PhC(N'Pr)2) recorded at 298 K in C₆D₆. The molecular structure is depicted in Fig. 6.

1.2. Procedure for the synthesis of Pn^*Zr(CI)(HC(N-4-Me-C6H₄)₂)

[00119] [P^ZrC kLiCI THF_x (0.114 mmol) and K[HC(N-4-Me-C₆H₄)₂] (0.229 mmol) were added to separate Schlenk tubes and each dissolved in toluene (2 ml_). The solution of the ligand was then added dropwise to that of [Pn*ZrCl2]2LiCI THF_x at -20 °C to prevent double ligand substitution. The reaction was returned to room temperature and stirred for 1 h after which all volatiles volatiles were removed in vacuo. The residue was extracted into toluene and filtered (multiple times if required) to remove LiCI. Toluene was removed in vacuo and hexane added to precipitate the product.

[00120] Fig. 7 shows the ¹ H NMR spectrum of Pn^*Zr(CI)(HC(N-4-Me-C₆H₄)₂) recorded at 298 K in CD2CI2. The molecular dimeric structure is depicted in Fig. 8.

1.3. Procedure for the synthesis of

[00121] [Pn^*ZrCI₂]₂LiCI TH F_x (0.1 14 mmol) and K[PhC(N'Pr)₂] (0.229 mmol) were combined in a schlenk tube and toluene (3 mL) was added and the solution stirred for 1 h. The reaction mixture was then transferred to a flask containing K[0-2,6-Me-C₆H₃] (0.229 mmol) and stirred for a further 1 hour. All volatiles were removed in vacuo and the residues extracted into toluene and filtered through celite. Toluene was removed in vacuo and the product was extracted into hexane and filtered to remove remaining LiCI. Crystals were obtained by cooling concentrated hexane solutions to -30 °C. Crystals were isolated by filtration.

[00122] Fig. 9 shows the ¹ H NMR spectrum of Pn^*Zr(0-2,6-Me-C₆H₃)(PhC(N'Pr)₂) recorded at 298 K in CeD₆. The molecular structure is depicted in Fig. 10.

Example 2 - Polymerisation studies

2.1. L-lactide polymerisation

[00123] The ability of the compounds of Example 1 to catalyse the polymerisation of L-lactide was assessed. Polymerisation experiments were conducted in a 0.5M L-lactide solution in Obϋ_d at 80 °C with 2 mol% [Zr] [00124] Fig. 11 shows that all of the Example 1 compounds are potent catalysts for L-lactide polymerisation.

2.2. e-caprolactone polymerisation

[00125] The ability of Pn^*Zr(0-2,6-Me-C₆H₃)(PhC(N'Pr)₂) to catalyse the polymerisation of e- caprolactone was assessed. Polymerisation experiments were conducted in a 0.5M e- caprolactone solution in Obϋ_d at room temperature with 2 mol% Pn*Zr(0-2,6-Me- C6H₃)(PhC(N'Pr)2).

[00126] Fig. 12 shows that Pn^*Zr(0-2,6-Me-C₆H₃)(PhC(N'Pr)₂) is a potent catalyst for e- caprolactone polymerisation.

PART II

Example 3 - Synthesis of further compounds

3.1. Procedure for the synthesis of Pn^*Zr{('PrN)₂C(4-R-C6H₄))CI (R=OMe, CF3)

[00127] Pn^*Zr{('PrN)₂C(4-R-C₆H₄)}CI (R=OMe, CF3) was prepared by the reaction of 1 eq. [Pn^*ZrCI₂]₂· LiCI-thf₂ with 2 eq. (l\TPr)₂C(PhR) (R = OMe, CF₃) in a NMR tube. The ¹ H NMR spectra are shown in Figs. 13 and 14.

3.2. Procedure for the synthesis of Pn*Tif(2.6-'PrC_fsH3N)₂CH>CI

[00128] Pn*Ti{(2,6-'PrC₆H₃N)₂CH}CI was synthesised by reaction of 1 eq. [Pn*TiCl2]2with 2 eq. K{(2,6-'PrC₆H₃N)₂CH}in a NMR tube. The ¹ H NMR spectrum is shown in Fig. 15.

3.3. Procedure for the synthesis of Pn*Tif('PrN)₂C

[00129] Pn*Ti{('PrN)2C(C6H5)}CI was synthesised by reaction of 1 eq. [Pn*TiCl2]₂ with 2 eq. Li{( 'PrN)2C(C6H5)}in a NMR tube. The ¹ H NMR spectrum is shown in Fig. 16.

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.

Claims

comprising the step of:

wherein

X is selected from zirconium, hafnium and titanium;

Y is selected from:

i) halo, hydrogen, a phosphonate, sulfonate or borate anion,

iii) a ligand having a structure according to formula A below:

A wherein

and wherein R_a and R_b are independently hydrogen or (1-4C)alkyl.

2. The process of claim 1 , wherein X is zirconium.

3. The process of claim 1 or 2, wherein each R¹ group is independently selected from (1- 6C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl and aryl, any of which is optionally substituted with one or more groups selected from halo, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, - NR_aR_b, (1-6C)alkoxy, -C(0)NR_aR_b, (1-3C)fluoroalkyl, aryl and aryloxy.

4. The process of any preceding claim, wherein each R¹ group is independently selected from (1-6C)alkyl and aryl, either of which is optionally substituted with one or more groups selected from halo, (1-6C)alkyl, (1-6C)alkoxy, aryl and aryloxy.

5. The process of any preceding claim, wherein each R¹ group is independently selected from methyl, ethyl, isopropyl and tertbutyl, or each R¹ group is independently a phenyl group that is optionally substituted with 1-3 groups selected from methyl, ethyl, isopropyl and tertbutyl.

6. The process of any preceding claim, wherein both R¹ groups are identical

7. The process of any preceding claim, wherein R² is selected from hydrogen, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, -NR_aR_b and aryl, any of which is optionally substituted with one or more groups selected from halo, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, (1- 6C)alkoxy, (1-3C)fluoroalkyl, aryl and aryloxy.

8. The process of any preceding claim, wherein R² is selected from hydrogen, (1-4C)alkyl and aryl, any of which is optionally substituted with one or more groups selected from halo, (1-4C)alkyl, (1-2C)alkoxy, aryl and aryloxy.

9. The process of any preceding claim, wherein R² is selected from hydrogen, (1-4C)alkyl and phenyl, any of which is optionally substituted with one or more groups selected from halo and (1-4C)alkyl.

10. The process of any preceding claim, wherein Y is

i) halo, hydrogen, a phosphonate, sulfonate or borate anion,

ii) (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, (1-6C)alkoxy, -C(0)NR_aR_b, -NR_aR_b, aryl and aryloxy, any of which is optionally substituted with one or more groups selected from halo, (1-4C)alkyl, nitro, -NR_aR_b, aryl, (1-6C)alkoxy, -C(0)NR_aR_b, and Si[(1-4C)alkyl]₃, or iii) a ligand having a structure according to formula A, wherein each R^x has any of the definitions appearing in any preceding claim in relation to R¹, and R^y has any of the definitions appearing in any preceding claim in relation to R².

11. The process of any preceding claim, wherein Y is

i) halo, or

ii) (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, (1-6C)alkoxy, aryl and aryloxy, any of which is optionally substituted with one or more groups selected from halo, (1-4C)alkyl, - NR_aR_b, aryl, (1-6C)alkoxy, -C(0)NR_aR_b, and Si[(1-4C)alkyl]₃.

12. The process of any preceding claim, wherein Y is

i) halo, or

ii) (1-4C)alkyl, (1-4C)alkoxy, aryl and aryloxy, any of which is optionally substituted with one or more groups selected from halo and (1-4C)alkyl.

13. The process of any preceding claim, wherein Y is i) chloro, or

ii) (1-4C)alkoxy or a phenoxy group that is optionally substituted with 1 or 2 (1-4C)alkyl groups.

14. The process of claim 1 , wherein the compound has any of the following structures:

15. The process of claim 1 , wherein the compound has any of the following structures:

16. The process of claim 1 , wherein the compound has any of the following structures:

17. The process of claim 1 , wherein the compound has any of the following structures

18. The process of any preceding claim, wherein the one or more cyclic esters or cyclic amides has a structure according to formula (V) shown below:

wherein

19. The process of claim 18, wherein Z is O.

20. The process of claim 18 or 19, wherein ring A is a 4-23 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.

21. The process of any preceding claim, wherein the one or more cyclic esters or cyclic amides is a lactone or a lactide.

22. The process of any preceding claim , wherein the one or more cyclic esters or cyclic amides is e-caprolactone or L-lactide.

23. The process of any preceding claim, wherein in step a), the mole ratio of the compound of formula (I) to the cyclic ester or cyclic amide is 1 :5 to 1 :10,000.

24. The process of any preceding claim, wherein step a) is conducted in the presence of a chain transfer agent suitable for use in the ring opening polymerisation of a cyclic ester or cyclic amide.