Controlled stereoselective polymerization of lactide monomers by group 4 metal initiators that contain an (OSSO)-type tetradentate bis(phenolate) ligand

Abstract

Group 4 metal complexes Zr-1 to Zr-4, Ti-4 and Ti-4a that contain an (OSSO)-type tetradentate bis(phenolate) ligand were found to initiate the ring-opening polymerization of meso-, rac-, and L-lactides in toluene solution. The polymerizations were controlled with initiator efficiency values around one and gave polymers with low polydispersity (M_w/M_n < 1.2). The polylactides were atactic when rac-lactide was used as the monomer and heterotactic biased when meso-lactide was used. Kinetic measurements showed that meso-lactide was polymerized generally faster than rac- and L-lactide.

---

Introduction

Poly(lactic acids) (PLAs) have been studied intensively during the past few decades because of their biodegradability and biocompatibility.^1,2PLA possesses versatile physical properties and has been used in medical applications and tissue engineering such as media for the controlled drug release.³Ring-opening polymerization (ROP) of lactide (LA) by single-site initiators is the most efficient route to PLAs with controlled molecular weight and narrow molecular weight distribution. The two stereogenic centers in one lactide molecule result in three distinct configurational isomers (S,S)-LA, (L-LA), (R,R)-LA, (D-LA) and (R,S)-LA, meso-LA. The 1 : 1 mixture of (S,S)-LA and (R,R)-LA is referred to as rac-LA (Scheme 1).

Scheme 1 Lactide monomers.

Group 4 metal complexes are widely used as single-site catalysts for the polymerization of olefins.⁴ Currently, there is interest in the so-called post-metallocene complexes which may serve as new types of single-site polymerization catalysts.⁵ Polydentate ligands for metal complexation are crucial for structurally well-defined initiators for lactide polymerization as well: Davidson et al.^6a and Eisen et al.^6b recently reported titanium(IV) and zirconium(IV) complexes with two bidentate ligands, whilst Harada et al.^7a and Mountford et al.^7b introduced tridentate ligands. Recently, Ishii et al. reviewed group 4 metal complexes with (OSSO)-type bis(phenolato) ligands and their use as polymerization catalysts for olefins.⁸Kolet al. used an (OSSO)-type ligand that is analogous to the (ONNO)-Salan type ligand, containing a methylene group between the sulfur atoms and the phenol groups. The resulting group 4 metal complexes polymerized 1-hexene, affording stereoirregular poly(1-hexene).⁹ Furthermore, group 4 metal complexes containing an (OSSO)-type dithiobis(phenolate) ligand polymerized rac- and L-lactide efficiently, but with a low level of control.¹⁰ In contrast, initiators based on group 4 metal bis(phenolate) complexes catalyze the syndioselective polymerization of meso-lactide efficiently and in a controlled fashion.¹¹

We report here the use of further group 4 metal complexes with an (OSSO)-type ligand framework as initiators for the polymerization of lactide monomers. The complexes reported are structurally classified according to their chelate ring size (5-5-5, 5-6-5 and 6-5-6) at the metal center.^8,9

Results and discussion

Synthesis and characterization of complexes

To explore the steric and possible electronic influence of substituents on the phenolate rings on the stereoselective ROP of lactide, a set of proligands with and without a methylene group between the sulfur atoms and the phenol groups in the backbone were prepared. The proligands were selected to allow direct comparison with each other (Scheme 2).

Scheme 2 Group 4 metal complexes.

Complexes Zr-1 to Zr-4 were synthesized by the reaction of [Zr(O^tBu)₄] with one equivalent of proligand H₂-1 to H₂-4, respectively, in n-pentane at 25 °C for 18 h. Complexes Ti-4 and Ti-4a were synthesized by the reaction of [Ti(OⁱPr)₄] or [Ti(OⁱPr)₃Cl] with one equivalent of H₂-4 in toluene at 25 °C for 18 h. Complexes Zr-1 and Zr-3 were isolated as colorless solids after crystallization from a cold n-pentane solution (Fig. S1–S4†). Complexes Zr-1 and Zr-3 were obtained in 57% and 30% yields, respectively. The ¹H NMR spectrum for complex Zr-1 shows a diagnostic doublet of doublets at 2.5 ppm for the bridging CH₂ protons. In addition, a singlet at 1.85 ppm represents the methyl protons from the tert-butoxy group.

Stoichiometric reaction of proligand H₂-4 with [Ti(OⁱPr)₃Cl] at 25 °C in n-pentane afforded complex Ti-4a, as orange crystals in 78% yield after crystallization from a cold n-pentane solution (Fig. S11–S12†). A diagnostic multiplet signal is found at 5.10 ppm (1H) which corresponds to OCH(CH₃)₂. The bridging protons corresponding to SCH₂CH₂S and SCH₂Ph are shifted downfield from 3.76 to 3.50 ppm and 2.57 to 1.92 ppm, respectively, upon complexation.

Polymerization of meso-lactide

Complexes Zr1 to Zr4, Ti-4 and Ti-4a were tested in the polymerization of meso-lactide in toluene at 100 °C (Scheme 3). The results are shown in Table 1.

Scheme 3 Stereoselective polymerization of meso-lactide to afford syndio- or hetero-tactic PLAs including their respective microstructures.

Table 1 Data for the polymerization of meso-lactide^a

Entry	Init.	Time/h	Conv.^b (%)	M n,exp ^c/g mol^−1	f ^d	M w/Mn^c	P s ^e
a Polymerization conditions: [LA]0/[init]0 = 100, [LA]0 = 0.520 M, T = 100 °C, toluene, 2 mL. b Conversion of monomer (([LA]0 − [LA]t)/[LA]0). c Measured by GPC with PS standards in THF, corrected by multiplication by 0.58.^12 d Efficiency calculated using f = Mn,exp/Mn,theo with Mn,theo = [LA]0/[init]0 × 144.13 × conv. e P s is the probability of a new s dyad.^13 f M n,theo = [LA]0/2[init]0 × 144.13 × conv.
1	Zr-1	0.5	29	6500	1.29	1.03	0.18
2	Zr-1	1	55	9800	1.24	1.02	0.16
3	Zr-1	4	95	19 800	1.23	1.07	0.20
4	Zr-2	4	67	9200	0.95	1.06	0.24
5	Zr-3	48	84	15 100	1.05	1.16	0.36
6	Zr-4	24	47	8100	1.19	1.03	0.50
7	Ti-4	72	55	4800	1.21^f	1.14	0.42
8	Ti-4a	72	48	4500	0.65	1.08	0.44

---

The polymerization of meso-lactide by complex Zr-1, based on 5-5-5 (OSSO)-type ligand 1, proceeded with efficiency values f of around 1.2. The efficiency value decreased with an increase in the steric bulk of the ligand's ortho- and para-substituents from tert-butyl, Zr-1 (f = 1.23), to cumyl (CMe₂Ph), Zr-2 (f = 0.95). Complex Zr-3, based on flexible (OSSO)-type ligand 3 with a 5-6-5 chelate array, polymerized meso-lactide the fastest with efficiency value f = 1.05. However, complex Zr-4, based on (OSSO)-type ligand 4 with a 6-5-6 chelate array, polymerized meso-lactide the slowest with less control over the polymerization (f = 1.19). The poly(meso-lactides) synthesized by group 4 metal complexes with an (OSSO)-type ligand showed low polydispersity (1.02 < M_w/M_n < 1.16).

Poly(meso-lactides) produced using complexes Zr-1 and Zr-2 with the 5-5-5 chelate based on (OSSO)-type ligands 1 and 2 showed heterotactic biased PLAs (0.18 < P_s < 0.24). Heterotacticity decreased from a P_s of 0.20 to 0.50 when initiators 3 and 4 with more flexible ligands were used. When the metal is changed from Zr-4 to Ti-4, complexes with the 6-5-6 chelate based on the (OSSO)-type ligand, the heterotacticity did not change (P_s of 0.50 and 0.42, respectively). Previously, we reported that the group 4 metal bis(phenolate) complex with 5-5-5 and 5-6-5 (OSSO)-chelates led to syndiotactic biased PLAs.¹¹ The somewhat unexpected formation of heterotactic PLA from meso-lactide is ascribed to site epimerization (Λ–Δ inversion) or to chain transfer after each ring-opening step, triggered by traces of acids.^17c

In Fig. 1, ¹³C{¹H} NMR spectra of the methine region are shown which indicate the decrease of heterotacticity with increasing flexibility of the ligand.

Fig. 1 ¹³C{¹H} NMR spectra of the methine region of poly(meso-lactides) obtained at 100 °C with an initiator : monomer ratio of 1 : 100 in toluene initiated by (a) Zr-1 and (b) Zr-4.

Polymerization of rac-lactide

Complexes Zr1, Zr4, Ti-4 and Ti-4a were tested in the polymerization of rac-lactide in toluene at 100 °C (Scheme 4). The results of the polymerization are shown in Table 2.

Scheme 4 Stereoselective polymerization of rac-lactide to afford atactic PLAs including its respective microstructure.

Table 2 Data for the polymerization of rac-lactide^a

Entry	Init.	Time/h	Conv.^b (%)	M n,exp ^c/g mol^−1	f ^d	M w/Mn^c	P s ^e
a Polymerization conditions: [LA]0/[init]0 = 100, [LA]0 = 0.520 M, T = 100 °C, C6D6, 0.5 mL. b Conversion of monomer (([LA]0 − [LA]t)/[LA]0). c Measured by GPC with PS standards in THF, corrected by multiplication by 0.58.^12 d Efficiency calculated using f = Mn,exp/Mn,theo with Mn,theo = [LA]0/[init]0 × 144.13 × conv. e P s is the probability of a new s dyad.^13 f M n,theo = [LA]0/2[init]0 × 144.13 × conv.
1	Zr-1	15	87	21 200	1.65	1.15	0.48
2	Zr-4	141	90	8150	0.63	1.11	0.49
3	Ti-4	255	69	4430	0.71^f	1.18	0.54
4	Ti-4a	255	86	5740	0.58	1.08	0.54

---

The polymerization of rac-lactide by complex Zr-1 led to a high efficiency value of PLA, indicating the possible occurrence of transesterification reactions (f = 1.65). The introduction of the flexible linker in complex Zr-4 decreased the efficiency of the polymerization of rac-lactide (f = 0.63). This mirrors the results found with meso-lactide. The polymerization of rac-lactide showed a slightly higher efficiency value when the metal was changed from Zr-4 to Ti-4 (f = 0.71). However, on going from the two isopropoxide groups to one (Ti-4a), the poly(rac-lactides) produced after 255 h but at a lower conversion level showed the lowest efficiency value (f = 0.58), indicating that the presence of the chloro ligand has a strong effect over the polymerization. Similar efficiency values for the ROP of rac-lactide were reported in the literature.^7b,14 All the poly(rac-lactides) exhibited low polydispersities (1.08 < M_w/M_n < 1.18).

The ROP of rac-lactide using complexes Zr1, Zr4, Ti-4 and Ti-4a give an essentially atactic microstructure of poly(rac-lactides). The introduction of a methylene linker, change in the metal from zirconium to titanium, or in the number of initiating groups did not influence the microstructure (Fig. S17–S20†). The poly(rac-lactides) synthesized by using group 4 metal complexes have been shown in the literature to give isotactic,¹⁵ heterotactic,^6a,14b,e or atactic polymers.^6a,14c

Polymerization of L-lactide

The polymerizations of L-lactide by complexes Zr-1 and Zr-4 proceeded with high values of efficiency but low polydispersities (M_w/M_n of 1.06, f of 1.59 for Zr-1) and (M_w/M_n of 1.11, f of 1.40 for Zr-4). Kolet al. reported similar results for group 4 metal complexes in polymerizing L-lactide.¹⁶ Analysis of the microstructures by ¹H{¹H} and ¹H NMR spectroscopy showed that the polymers produced from L-lactide exhibited high isotacticity, P_i > 0.95 (Fig. S21–S24†).

Kinetic studies of the meso-lactide polymerization

Pseudo-first order kinetic data of the polymerization of meso-lactide at 100 °C in benzene-d₆, with an initiator : monomer ratio of 1 : 100 using complexes Zr-1 to Zr-4, Ti-4 and Ti-4a are shown in Fig. 2 and Table S1–S6†.

Fig. 2 Semilogarithmic plots of meso-lactide conversion vs. time, [LA]₀/[init]₀ = 100, [LA]₀ = 0.520 M, T = 100 °C, benzene-d₆ (0.5 mL): (a) using zirconium complexes: Zr-1 (k_obs = 423 × 10⁻³ h⁻¹), Zr-2 (k_obs = 271 × 10⁻³ h⁻¹), Zr-3 (k_obs = 535 × 10⁻³ h⁻¹), and Zr-4 (k_obs = 38 × 10⁻³ h⁻¹); and (b) using the flexible ligand 4: Ti-4 (k_obs = 16 × 10⁻³ h⁻¹) and Ti-4a (k_obs = 10 × 10⁻³ h⁻¹).

The C₃ bridged complex, Zr-3, based on the 5-6-5 (OSSO)-type ligand, showed the highest activity in the ROP of meso-lactide (k_obs = 535 × 10⁻³ h⁻¹), followed by the C₂ bridged complex, Zr-1, based on the 5-5-5 (OSSO)-type ligand (k_obs = 423 × 10⁻³ h⁻¹). This is in agreement with our previous observation that the slowest among all of the titanium complexes tested was the one that possessed a rigid trans-1,2-cyclohexanediyl backbone and the fastest was the titanium complex with a C₃ bridged backbone.¹¹

Higher activity is observed with the complexes containing tert-butyl substituents, Zr-1 (k_obs = 423 × 10⁻³ h⁻¹), rather than cumyl (CMe₂Ph), Zr-2 (k_obs = 271 × 10⁻³ h⁻¹). This is to be expected as coordination of the monomer to the Zr-1 complex with tert-butyl substituents is less sterically hindered, allowing easier monomer addition.

The introduction of a flexible linker (SCH₂Ph) between the phenol ring and the sulfur bridge of the ligand has a significant effect on the polymerization rates of meso-lactide. Complex Zr-1, based on the 5-5-5 (OSSO)-type ligand, has 11 times higher activity (k_obs = 423 × 10⁻³ h⁻¹) than Zr-4, based on the 6-5-6 chelate array (k_obs = 38 × 10⁻³ h⁻¹).

This slow rate with the flexible ligand can also be observed by changing the metal center to titanium using complex Ti-4 (k_obs = 16 × 10⁻³ h⁻¹) which has twice as many initiating OⁱPr groups than Ti-4a which showed ca. 1.6 times faster rate for the polymerization of meso-lactide (k_obs = 10 × 10⁻³ h⁻¹). This is attributed to a combination of steric and strong electronic effects of the chloro ligand in comparison with those from a second growing chain (i.e. starting from the bis(isopropoxide) titanium initiator Ti-4).

The polymerization of meso-lactide using Zr-1 in toluene (k_obs = 1360 × 10⁻³ h⁻¹) showed a faster rate than in benzene-d₆ (k_obs = 423 × 10⁻³ h⁻¹) (Fig. S25†). This rate for the polymerization of meso-lactide in toluene is comparable to the fastest rate reported in the literature by Feijen et al. with salan aluminium complexes.^17c The polymerization rates for the polymerization of meso-lactide in benzene-d₆ are the highest for group 4 metal initiators,¹¹ but lower than those of other initiator metals reported in the literature.¹⁷

Kinetic studies of the polymerization of rac- and L-lactides

Kinetic studies of the polymerization of rac-lactide at 100 °C in benzene-d₆ with an initiator : monomer ratio of 1 : 100 using complex Zr-1 and complexes bearing the flexible linkers Zr-4, Ti-4, and Ti-4a are shown in Fig. S26 and Table S7–S10†.

As with the ROP of meso-lactide, Zr-1 is faster than Zr-4 towards the ROP of rac-lactide (k_obs = 142 × 10⁻³ h⁻¹ and k_obs = 21 × 10⁻³ h⁻¹ respectively). Likewise, Zr-4 is faster than Ti-4. However, the rate of the polymerization of rac-lactide using Ti-4 showed an initiation period with a higher rate constant (k_obs = 14 × 10⁻³ h⁻¹) followed by a slower period after around 50% conversion (k_obs = 5 × 10⁻³ h⁻¹). Interestingly, the rate for the slower second phase was equal to that of propagation using Ti-4a (k_obs = 5 × 10⁻³ h⁻¹). This could be due to the growing polymer chains becoming too large for initiation by both isopropoxide groups. A rate similar to that of the mono(isopropoxide) complex Ti-4a may result. The titanium and zirconium complexes polymerized rac-lactide more slowly than other group 4 metal complexes reported in the literature.^6a,7b,14b

Kinetic studies of the polymerization of L-lactide at 100 °C in benzene-d₆ with an initiator : monomer ratio of 1 : 100 using Zr-1 and Zr-4 are shown in Fig. S27 and Table S11–S14†. As was the case for meso- and rac-lactides, Zr-1 polymerizes L-lactide faster (k_obs = 164 × 10⁻³ h⁻¹) than does Zr-4 (k_obs = 24 × 10⁻³ h⁻¹). In addition, zirconium initiators polymerized L-lactide faster than the titanium homologs (k_obs = 3 × 10⁻³ h⁻¹ for Ti-4, k_obs = 7 × 10⁻³ h⁻¹ for Ti-4a) (Fig. S28–S29†).

The kinetic results of the polymerization of meso-, rac- and L-lactides using Zr-1 and Zr-4 are given in Fig. 3. meso-Lactide is polymerized faster than rac- and L-lactides, when using Zr-1 and Zr-4 (Table 3). This can be attributed to the fact that the RS configuration of meso-lactide is more strained in comparison to the RR and SS configuration found in rac-lactide.¹⁸ Furthermore, rac- and L-lactide are polymerized with similar propagation rates relative to each other (Table 3).

Fig. 3 Semilogarithmic plots of lactide monomer conversion vs. time, [LA]₀/[init]₀ = 100, [LA]₀ = 0.520 M, T = 100 °C, benzene-d₆ (0.5 mL): (a) Zr-1meso-lactide (k_obs = 423 × 10⁻³ h⁻¹), L-lactide (k_obs = 164 × 10⁻³ h⁻¹), and rac-lactide (k_obs = 142 × 10⁻³ h⁻¹); and (b) Zr-4meso-lactide (k_obs = 38 × 10⁻³ h⁻¹), L-lactide (k_obs = 24 × 10⁻³ h⁻¹), and rac-lactide (k_obs = 21 × 10⁻³ h⁻¹).

Table 3 Rate constants for the polymerization of lactide monomers^a

Entry	Initiator	Monomer	Solvent	k obs/×10^−3 h^−1
a Polymerization conditions: [LA]0/[init]0 = 100, [LA]0 = 0.520 M, T = 100 °C.
1	Zr-1	meso	C6D6	423
2	Zr-2	meso	C6D6	271
3	Zr-3	meso	C6D6	535
4	Zr-4	meso	C6D6	38
5	Ti-4	meso	C6D6	16
6	Ti-4a	meso	C6D6	10
7	Zr-1	meso	Toluene	1360
8	Zr-1	rac	C6D6	142
9	Zr-4	rac	C6D6	21
10	Ti-4	rac	C6D6	5
11	Ti-4a	rac	C6D6	5
12	Zr-1	L	C6D6	164
13	Zr-4	L	C6D6	24
14	Ti-4	L	C6D6	3
13	Ti-4a	L	C6D6	7

---

Conclusions

Structurally defined initiators based on group 4 metal bis(phenolate) complexes with an (OSSO)-type ligand catalyzed the polymerization of lactide monomers with initiator efficiency values f of around 1 to give polymers with low polydispersity (M_w/M_n < 1.2). All zirconium complexes used during this study led to heterotactic poly(meso-lactides). The titanium complexes with a flexible CH₂ linker between the phenolate ring and the sulfur-containing bridge gave heterotactic biased PLAs. In contrast, those without the methylene linker gave syndiotactic biased poly(meso-lactides).¹¹

Complexes with the 5-6-5 chelate derived from the C₃-bridged (OSSO)-type ligand 3 led to higher rates of the polymerization of the lactide monomers than those based on C₂ bridged ligands 1 and 2 with the 5-5-5 chelate array. The introduction of the methylene linker between the sulfur donor and the phenolate group in the complexes based on C₂ bridged ligand 4 with the 6-5-6 chelate resulted in lower polymerization rates.

Experimental

General details

All operations were performed under an inert atmosphere of argon using standard Schlenk-line or glove box techniques. Toluene, n-hexane and THF were distilled under argon from sodium/benzophenone ketyl prior to use. n-Pentane was purified by distillation from sodium/triglyme benzophenone ketyl. Benzene-d₆, chloroform-d₁ and other reagents were carefully dried and stored in a glove box. [Ti(OⁱPr)₄] (Sigma Aldrich), [Zr(O^tBu)₄] (ABCR), and [Ti(OⁱPr)₃Cl] (Sigma Aldrich) were purchased and used as received. meso-Lactide was recrystallized from isopropanol at −30 °C, washed with diethylether and dried under vacuum. L-Lactide and rac-lactide were purchased from Sigma-Aldrich and purified as meso-lactide. Glassware and vials used in the polymerization were dried overnight in an oven at 120 °C and exposed to a vacuum–argon cycle three times. Ligands were synthesized following the procedures in the literature.^4c,d,9,19,20

Chemical shifts for ¹H and ¹³C{¹H} NMR spectra were recorded on a Bruker Avance 400 MHz spectrometer or a Varian NMR 200 MHz spectrometer at room temperature in 5 mm NMR tubes. Chemical shifts were reported in parts per million and referenced against TMS using the residual proton signal of the solvent (¹H: benzene-d₆, δ = 7.16 ppm; chloroform-d₁, δ = 7.26 ppm), (¹³C{¹H}: benzene-d₆, δ = 128.06 ppm; chloroform-d₁, δ = 77.00 ppm).

Molecular weights and polydispersities were determined by size exclusion chromatography (SEC) in THF at 35 °C, at a flow rate of 1 mL min⁻¹ utilizing an Agilent 1100 Series HPLC, a G1310A isocratic pump, an Agilent 1100 Series refractive index detector and 8 × 600 mm, 8 × 300 mm, 8 × 50 mm PSS SDV linear M columns. Calibration standards were commercially available narrowly distributed linear polystyrene samples that cover a broad range of molar masses (10³ < M < 2 × 10⁶ g mol⁻¹). The molecular weights were multiplied by 0.58 according to a method in the literature.¹²

Polymerization procedure

A solution of a certain amount of the initiator Zr-1 in 0.5 mL of toluene (according to table entry) was added to a solution of 150 mg of meso-lactide which was dissolved in 1.5 mL of toluene. After the desired time the polymerization mixture was quenched with drops of moist hexanes and was added slowly to a cooled, quickly stirred hexanes solution. The polymer was filtered using a Büchner funnel, washed with diethyl ether, and dried in vacuo. The polymer was dissolved in a minimum quantity of CH₂Cl₂ and ran through a flash silica gel column (in a Pasteur pipette) to afford a colorless solution, which was added slowly to a cooled, quickly stirred hexanes solution. The colorless polymer was filtered and dried under vacuum.

Kinetic measurement of polymerization

From a stock solution of complex Zr-1 in benzene-d₆, a certain amount was added to a solution of lactide monomer in benzene-d₆ and was monitored regularly using ¹H NMR spectroscopy. Finally, after the desired time of the polymerization, the polylactide was worked-up as previously.

Synthesis and characterization of Zr-2, Zr-4 and Ti-4

These complexes were synthesized following literature procedures.^9,11

Synthesis and characterization of complex Zr-1

To a solution of 1 equivalent of [Zr(O^tBu)₄] (270 mg, 0.70 mmol) in n-pentane (2 mL) was added one equivalent of a solution of H₂-1 (350 mg, 0.70 mmol) in n-pentane (2 mL) and the reaction mixture was stirred overnight at room temperature. The solvent was removed in vacuo to afford an off-white solid that was dissolved in the minimum amount of n-pentane, filtered and left overnight at −30 °C. The solvent was removed to afford a white solid which was dried in vacuo to give a yield of 305 mg (59%). ¹H NMR (400 MHz, C₆D₆, 25 °C): δ (ppm) 7.52 (d, 2H, ⁴J_HH = 2.5 Hz, 3-H), 7.23 (d, 2H, ⁴J_HH = 2.5 Hz, 5-H), 2.40 (dd, 4H, ²J_HH = 10.8 Hz, SCH₂), 1.70 (s, 18H, OC(CH₃)₃), 1.36 (s, 18H, Ph–C(CH₃)₃), 1.20 (s, 18H, C(CH₃)₃). ¹³C{¹H} NMR (100.1 MHz, C₆D₆, 25 °C): δ (ppm) 163.88 (C-1), 140.63 (C-2), 137.64 (ipso, C-6), 127.16 (C-3), 125.44 (C-5), 121.46 (ipso, C-4), 77.57 (O–C(CH₃)₃), 36.64 (SCH₂), 35.79 (Ph–C(CH₃)₃), 34.37 (Ph–C(CH₃)₃), 32.61 (Ph–C(CH₃)₃), 31.71 (Ph–C(CH₃)₃), 29.69 (O–C(CH₃)₃). Elemental analysis, calculated for C₃₈H₆₂S₂O₄Zr (738.25 g mol⁻¹): C 61.82%, H: 8.46%; found: C 61.13%, H 8.8%.

Synthesis and characterization of complex Zr-3

To a solution of [Zr(O^tBu)₄] (190 mg, 0.49 mmol) in n-pentane (2 mL) was added one equivalent of H₂-3 (250 mg, 0.49 mmol) and the reaction mixture was stirred overnight at room temperature. The solvent was removed in vacuo to afford a white solid which was not soluble in n-pentane; this was dissolved in the minimum amount of n-pentane with a few drops of tetrahydrofuran, filtered and then left overnight at −30 °C. The solvent was then removed, washed with n-pentane and dried in vacuo which afforded a white solid in a yield of 110 mg (30%). ¹H NMR (400 MHz, C₆D₆, 25 °C): δ (ppm) 7.51 (d, 2H, ⁴J_HH = 4.0 Hz, 3-H), 7.31 (d, 2H, ⁴J_HH = 4.0 Hz, 5-H), 2.43 (t, 4H, ³J_HH = 8.0 Hz, SCH₂), 1.72 (s, 18H, OC(CH₃)₃), 1.34 (s, 18H, C(CH₃)₃), 1.29 (m, 2H, SCH₂), 1.26 (s, 18H, C(CH₃)₃). ¹³C{¹H} NMR (100.1 MHz, C₆D₆, 25 °C): δ (ppm) 163.90 (C-1), 140.65 (C-2), 137.66 (ipso, C-6), 127.16 (C-3), 125.44 (C-5), 121.46 (ipso, C-4), 77.60 (O–C(CH₃)₃), 36.67 (Ph–C(CH₃)₃), 35.73 (Ph–C(CH₃)₃), 34.33 (SCH₂), 32.61 (Ph–C(CH₃)₃), 31.71 (Ph–C(CH₃)₃), 29.69 (O–C(CH₃)₃), 23.43 (SCH₂). Elemental analysis, calculated for C₃₉H₆₄S₂O₄Zr (766.3 g mol⁻¹), C 62.27%, H 8.58%; found: C: 61.55%, H 6.35%.

Synthesis and characterization of complex Ti-4a

To a solution of one equivalent of [Ti(OⁱPr)₃Cl] (98 mg, 0.38 mmol) in n-pentane (2 mL) was added a solution of 1 equivalent of H₂-4 (200 mg, 0.38 mmol) in n-pentane (2 mL) and the solution instantly turned a dark orange colour at room temperature. The solvent was removed in vacuo to afford an orange solid, which was dissolved in the minimum amount of n-pentane, filtered and then left over the weekend at −30 °C. The solvent was removed to afford an orange solid which was dried in vacuo to give a yield of 196 mg (78%). ¹H NMR (400 MHz, C₆D₆, 25 °C): δ (ppm) 7.55 (br d, 2H, 3-H), 6.64 (br d, 2H, 4-H), 5.20 (m, CH(CH₃)₂), 4.41 (br s, 1H, SCH₂CH₂S), 3.66 (br s, 1H, SCH₂CH₂S), 3.12 (br s, 2H, SCH₂CH₂S), 1.89 (br s, 6H, Ph–C(CH₃)₃), 1.87 (br s, 18H, Ph–C(CH₃)₃), 1.45 (br s, 4H, SCH₂Ph), 1.30 (s, 18H, Ph–C(CH₃)₃). ¹³C{¹H} NMR (100.1 MHz, C₆D₆, 25 °C): δ (ppm) 161.00 (C-1), 142.27 (C-2), 138.50 (ipso, C-6), 129.04 (C-3), 125.78 (C-5), 121.46 (ipso, C-4), 83.98 (O–C(CH₃)₂), 36.84 (Ph–C(CH₃)₃), 36.17 (Ph–C(CH₃)₃), 34.78 (SCH₂CH₂CH₂S), 32.18 (Ph–C(CH₃)₃), 31.15 (Ph–C(CH₃)₃), 25.53 (O–C(CH₃)₃), 23.06 (SCH₂CH₂CH₂S), 14.61 (SCH₂Ph). Elemental analysis, calculated for C₃₅H₅₅ClS₂O₃Ti (671.26 g mol⁻¹): C 62.62%, H 8.26%; found: C 63.19%, H 7.28%.

Acknowledgements

We thank the German-Israeli Foundation, Deutsche Forschungsgemeinschaft, the Fonds der Chemischen Industrie for financial support and Uhde Inventa-Fischer for the generous gift of meso-lactide.

Notes and references

1. (a) R. E. Drumright, P. R. Gruber and D. E. Henton, Adv. Mater., 2000, 12, 1841; (b) S. Inkinen, M. Hakkarainen, A.-C. Albertsson and A. Södergard, Biomacromolecules, 2011, 12, 523.
2. (a) P. J. Dijkstra, H. Du and J. Feijen, Polym. Chem., 2011, 2, 520; (b) C. M. Thomas, Chem. Soc. Rev., 2010, 39, 165; (c) M. J. Stanford and A. P. Dove, Chem. Soc. Rev., 2010, 39, 486; (d) C. A. Wheaton, P. G. Hayes and B. J. Ireland, Dalton Trans., 2009, 4832; (e) R. H. Platel, L. M. Hodgson and C. K. Williams, Polym. Rev., 2008, 48, 11; (f) A. Amgoune, C. M. Thomas and J.-F. Carpentier, Pure Appl. Chem., 2007, 79, 2013; (g) J. Wu, T.-.L. Yu, C.-T. Chen and C.-C. Lin, Coord. Chem. Rev., 2006, 250, 602; (h) O. Dechy-Cabaret, B. Martin-Vaca and D. Bourissou, Chem. Rev., 2004, 104, 6147; (i) B. J. O'Keefe, M. A. Hillmyer and W. B. Tolman, J. Chem. Soc., Dalton Trans., 2001, 2215.
3. (a) L. Huang, X. Zhuang, J. Hu, L. Lang, P. Zhang, Y. Wang, X. Chen, Y. Wei and X. Jing, Biomacromolecules, 2008, 9, 850; (b) E. T. H. Vink, K. R. Rábago, D. A. Glassner and P. R. Gruber, Polym. Degrad. Stab., 2003, 80, 403; (c) J. Park, M. Ye and K. Park, Molecules, 2005, 10, 146.
4. (a) Z. Janas, Coord. Chem. Rev., 2010, 254, 2227; (b) M. Lamberti, M. Mazzeo, D. Pappalardo and C. Pellecchia, Coord. Chem. Rev., 2009, 253, 2082; (c) C. Capacchione, R. Manivannan, M. Barone, K. Beckerle, R. Centore, L. Oliva, A. Proto, A. Tuzi, T. P. Spaniol and J. Okuda, Organometallics, 2005, 24, 2971; (d) C. Capacchione, A. Proto, H. Ebeling, R. Mülhaupt, K. Möller, T. P. Spaniol and J. Okuda, J. Am. Chem. Soc., 2003, 125, 4964.
5. (a) L. S. Baugh and J. A. M. Canich, Stereoselective Polymerization with Single-Site Catalysts, CRC Press, Boca Raton, FL, 2008; (b) V. C. Gibson and S. K. Spitzmesser, Chem. Rev., 2003, 103, 283.
6. (a) A. J. Chmura, D. M. Cousins, M. G. Davidson, M. D. Jones, M. D. Lunn and M. F. Mahon, Dalton Trans., 2008, 1437; (b) F. Gornshtein, M. Kapon, M. Botoshansky and M. S. Eisen, Organometallics, 2007, 26, 497.
7. (a) Y. Takashima, Y. Nakayama, K. Watanabe, T. Itono, N. Ueyama, A. Nakamura, H. Yasuda and A. Harada, Macromolecules, 2002, 35, 7538; (b) A. D. Schwarz, K. R. Herbert, C. Paniagua and P. Mountford, Organometallics, 2010, 29, 4171.
8. N. Nakata, T. Toda and A. Ishii, Polym. Chem., 2011, 2, 1597.
9. A. Cohen, A. Yeori, I. Goldberg and M. Kol, Inorg. Chem., 2007, 46, 8114.
10. E. Sergeeva, J. Kopilov, I. Goldberg and M. Kol, Inorg. Chem., 2010, 49, 3977.
11. J.-C. Buffet and J. Okuda, Chem. Commun., 2011, 47, 4796.
12. M. Save, M. Schappacher and A. Soum, Macromol. Chem. Phys., 2002, 203, 889.
13. Probability of tetrad sequences in PLA based on Bernoullian statistics: [sss] = P_s² + P_sP_i/2, [sis] = (P_i² + P_iP_s)/2, [ssi] = [iss] = (P_sP_i)/2 and [isi] = P_i²/2.
14. (a) S. L. Hancock, M. F. Mahon and M. D. Jones, Dalton Trans., 2011, 40, 2033; (b) E. L. Whitelaw, M. D. Jones and M. F. Mahon, Inorg. Chem., 2010, 49, 7176; (c) E. L. Whitelaw, M. D. Jones, M. F. Mahon and G. Kociok-Köhn, Dalton Trans., 2009, 9020; (d) A. D. Schwarz, A. L. Thompson and P. Mountford, Inorg. Chem., 2009, 48, 10442; (e) A. J. Chmura, M. G. Davidson, C. J. Frankis, M. D. Jones and M. D. Lunn, Chem. Commun., 2008, 1293; (f) S. K. Russell, C. L. Gamble, K. J. Gibbins, K. C. S. Juhl, W. S. Mitchell, A. J. Tumas and G. E. Hofmeister, Macromolecules, 2005, 38, 10336.
15. (a) M. Hu, M. Wang, H. Zhu, L. Zhang, H. Zhang and L. Sun, Dalton Trans., 2010, 39, 4440; (b) F. Zhang, H. Song and G. Zi, J. Organomet. Chem., 2010, 695, 1993.
16. S. Gendler, S. Segal, I. Goldberg, Z. Goldschmidt and M. Kol, Inorg. Chem., 2006, 45, 4783.
17. For kinetic studies on the polymerization of meso-lactide see: (a) J.-C. Buffet and J. Okuda, Polym. Chem.,  10.1039/c1py00206f; (b) A. Pietrangelo, S. C. Knight, A. K. Gupta, L. J. Yao, M. A. Hillmyer and W. B. Tolman, J. Am. Chem. Soc., 2010, 132, 11649; (c) H. Du, A. H. Velders, P. J. Dijkstra, J. Sun, Z. Zhong, X. Chen and J. Feijen, Chem.–Eur. J., 2009, 15, 9836; (d) T. M. Ovitt and G. W. Coates, J. Am. Chem. Soc., 2002, 124, 1316; (e) B. M. Chamberlain, M. Cheng, D. R. Moore, T. M. Ovitt, E. B. Lobkovsky and G. W. Coates, J. Am. Chem. Soc., 2001, 123, 3229; (f) H. Du, A. H. Velders, P. J. Dijkstra, Z. Zhong, X. Chen and J. Feijen, Macromolecules, 2009, 42, 1058.
18. (a) M. H. Chisholm, N. W. Eilerts, J. C. Huffman, S. S. Iyer, M. Pacold and K. Phomphrai, J. Am. Chem. Soc., 2000, 122, 11845; (b) I. A. Shuklov, H. Jiao, J. Schulze, W. Tietz, K. Kühlein and A. Börner, Tetrahedron Lett., 2011, 52, 1027.
19. Y.-L. Wong, C.-Y. Mak, H. S. Kwan and H. K. Lee, Inorg. Chim. Acta, 2010, 363, 1246.
20. J. Klosin, L. Ackerman, X. Bei, G. M. Diamond, J. Longmire, V. Murphy, V. Nava-Salgado and J. A. W. Shoemaker, WO. Pat., 200707529, 2007.

---

Footnote

† Electronic supplementary information (ESI) available: NMR data of complexes Zr-1 to Zr4, Ti-4 and Ti-4a; NMR of the microstructures of polylactides and tables for the kinetic of polymerization data. See DOI: 10.1039/c1py00266j

---