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Macromolecules 2001, 34, 3863-3868

3863

A Novel and Versatile Calcium-Based Initiator System for the Ring-Opening Polymerization of Cyclic Esters
Zhiyuan Zhong,† Pieter J. Dijkstra,† Christin Birg,‡ Matthias Westerhausen,‡ and Jan Feijen*,†
Department of Chemical Technology and Institute for Biomedical Technology, University of Twente, P. O.Box 217, 7500 AE Enschede, The Netherlands, and Department Chemie der Ludwig-Maximilians-Universita ¨ t, Butenandtstr. 9 (Haus D), D-81377 Mu ¨ nchen, Germany Received November 15, 2000

ABSTRACT: A novel and efficient calcium alkoxide initiating system, generated in situ from bis(tetrahydrofuran)calcium bis[bis(trimethylsilyl)amide] and an alcohol, for the ring-opening polymerization of cyclic esters has been developed. The solution polymerization in THF using mild conditions is living, yielding polyesters of controlled molecular weight and tailored macromolecular architecture. The polymerizations initiated with the 2-propanol-Ca[N(SiMe3)2]2(THF)2 system are first-order in monomer with no induction period. At high 2-propanol/Ca[N(SiMe3)2]2(THF)2 ratios, complete conversion of 2-propanol occurs due to fast and reversible transfer between dormant and active species.

Introduction Biodegradable and biocompatible aliphatic polyesters have received much interest for their medical, pharmaceutical, and environmental applications.1-3 Many of these polyesters can be synthesized by the ring-opening polymerization of cyclic esters, for which various effective initiating systems have been developed.4-9 However, in practice, complete removal of the catalyst residues from the polymer is not possible, and therefore a biocompatible catalyst should be used. Ca-, Fe-, and Mg-based catalysts/initiators are the most favored, since these metals participate in the human metabolism.10-12 Recently, the ring-opening polymerization of L-lactide and/or -caprolactone with catalysts based on these metals has been described.13-17 However, racemization is generally observed for L-lactide polymerization as a result of the high temperature and long polymerization time necessary to reach high conversion.18 In-situ generated yttrium alkoxides, based on fast exchange between yttrium 2,6-di-tert-butylphenoxides and different alcohols, have unprecedented activity in the ring-opening polymerization of lactides and lactones under very mild conditions, allowing excellent control over the polymerization process.19,20 Very recently, the ring-opening polymerization of -caprolactone with [tris(hexamethyldisilyl)amide]yttrium in the presence of an excess of 2-propanol, which gave polymers with controlled molecular parameters, was also reported.21 We describe here a novel and efficient calcium alkoxide initiating system, generated in situ from bis(tetrahydrofuran)calcium bis[bis(trimethylsilyl)amide] and an alcohol, for the ring-opening polymerization of cyclic esters. Experimental Section
Materials. L-Lactide (Purac Biochem b.v., The Netherlands) was purified by recrystallization from dried toluene. -Caprolactone (Merck-Schuchardt, Darmstadt, Germany), 2-propanol,
University of Twente. Ludwig-Maximilians-Universita ¨ t. * Corresponding author. Fax +31-53-4893823, E-mail j.feijen@ ct.utwente.nl.
‡ †

and methanol were dried over CaH2 and distilled prior to use. Poly(ethylene glycol) with Mn ) 2.0 × 103 g/mol (SigmaAldrich, Steinheim, Germany) was purified by dissolution in CHCl3 and precipitation from diethyl ether followed by drying under reduced pressure (∼8.0 mmHg) for more than 1 week. Bis(tetrahydrofuran)calcium bis[bis(trimethylsilyl)amide] [Ca[N(SiMe3)2]2(THF)2] was prepared by the transmetalation of bis[bis(trimethylsilyl)amido]tin(II) with calcium metal in THF and crystallized from n-hexane at 0 °C, as described previously.22 Ca[N(SiMe3)2]2(THF)2 is sensitive toward moisture and air and readily soluble in common organic solvents (e.g., toluene, benzene, THF). Toluene and benzene-d6 were dried by refluxing over a Na/K alloy. THF was dried by refluxing and distillation over sodium wire. All glassware for the polymerization was dried in an oven before use. Polymerizations. All polymerizations were carried out at room temperature with THF as the solvent in a glovebox under a nitrogen atmosphere. In a typical procedure, a THF (1.0 mL) solution of Ca[N(SiMe3)2]2(THF)2 (0.069 mmol) was added under vigorous stirring to a mixture of L-lactide (1.0 g, 6.9 mmol) and 2-propanol (0.138 mmol, added as 5 wt % stock solution in THF) in THF (6.0 mL) ([M]0/[2-PrOH]0/[Ca]0 ) 100/ 2/1). After the desired reaction time (35 min), polymerization was terminated by introducing acetic acid. A sample was taken for conversion determination using 1H NMR. The poly(Llactide) was isolated by precipitation from excess methanol followed by filtration and drying at 40 °C in vacuo. Monomer conversion: 100%; yield: 0.91 g; Mn,GPC ) 6.9 × 103, PDI ) 1.05. 1H NMR (CDCl3): δ 0.05 (s, HN(Si(CH3)3)2), 1.24 (t, (CH3)2CHOC(O)-), 1.56 (d, -C(O)CH(CH3)O-), 2.66 (broad, -C(O)CH(CH3)OH), 4.34 (q, -C(O)CH(CH3)OH), 5.06 (m, (CH3)2CHOC(O)-), 5.16 (q, -C(O)CH(CH3)O-). An Mn of 6.9 × 103 was calculated based on the relative intensities of the 1H NMR (CDCl ) signals at δ 5.16 and 1.24. Polymerization 3 of -caprolactone ( -CL) was performed as described above to afford poly( -caprolactone). Monomer conversion: 100%, Mn,GPC ) 6.2 × 103, PDI ) 1.24. 1H NMR (CDCl3): δ 0.05 (s, HN(Si(CH3)3)2), 1.22 (d, (CH3)2CHOC(O)-), 1.37 (m, -C(O)CH2CH2CH2CH2CH2O-), 1.66 (m, -C(O)CH2CH2CH2CH2CH2O-), 2.30 (t, -C(O)CH2CH2CH2CH2CH2O-), 3.63 (t, -C(O)CH2CH2CH2CH2CH2OH), 4.04 (t, -C(O)CH2CH2CH2CH2CH2O-), 4.98 (m, (CH3)2CHOC(O)-). Synthesis of Poly(E-caprolactone)-b-(L-lactide). A living poly( -caprolactone) prepolymer was prepared similarly as described above. To a mixture of -CL (1.54 g, 13.5 mmol) and 2-propanol (0.27 mmol, added as 5 wt % stock solution in THF) in THF (16.0 mL) ([ -CL]0/[2-PrOH]0/[Ca]0 ) 100/2/1) was

10.1021/ma0019510 CCC: $20.00 © 2001 American Chemical Society Published on Web 05/02/2001

CDCl3). 4.9 6. The sample was heated from 20 to 185 °C at a rate of 10 °C/min. the polymer had a low polydispersity index (PDI) of 1. The poly(L-LA) isolated had a narrow molecular weight distribution.0 0.GPC ) 12.18.0 mL) of Ca[N(SiMe3)2]2(THF)2 (0. Differential scanning calorimetry (DSC) was carried out with a Perkin-Elmer DSC-7 apparatus calibrated with pure indium. part of the reaction mixture (ca. 3. The -CL polymerization afforded polymers of somewhat broader polydispersity index (PDI). -OCH(CH3)C(O)OCH2CH2O. e Determined by GPC analysis.0 mL) was removed.138 g.05. -OH). the conversion was complete within 35 min. 6. were assignable to the methyl protons of the isopropoxycarbonyl end group and the methine proton neighboring the hydroxyl end group.8 11. and elution was performed at 25 °C at a flow rate of 1. Mn. The Mn calculated from the relative intensities . The two doublets appearing as a triplet at δ 1.7 7.29 ROH [M]0 (mol/L) 1.8 6. f Calculated based on the following formula: M n.23.0 0. 1H NMR analysis revealed complete monomer conversion. The 300 MHz 1H NMR spectrum (CDCl3) of poly(L-LA) obtained with 2-PrOH-Ca[N(SiMe3)2]2(THF)2 (molar ratio: 2/1) (entry 4.68 (broad. 2. Experimental values obtained from 1H NMR end group analysis (300 MHz. Results and Discussion Attempts to homopolymerize L-lactide (L-LA) or caprolactone ( -CL) with Ca[N(SiMe3)2]2(THF)2 in THF at room temperature (∼18 °C) revealed a slow L-LA but fast -CL polymerization (Table 1. Because the end groups could not be detected by 1H NMR.9 × 103 (entry 4).28-4. A trace signal appearing at δ 0. The 1H NMR spectrum as well as detailed peak assignments of the obtained poly(L-LA) is shown in Figure 1.5 × 103. Mn.5 a All polymerizations were carried out under N atmosphere at room temperature (∼18 °C) with THF as the solvent. 10.24 In the presence of Ca[N(SiMe3)2]2(THF)2 and 2propanol.07 1. PDI ) 1.26 MHz) NMR spectra were recorded on a Varian Inova spectrometer with chemical shifts relative to the solvent peak.65 (s.16 (q.7 9. Polymerization of L-LA and E-CL Initiated with Alcohol-Ca[N(SiMe3)2]2(THF)2 Systems ([M]0/[Ca]0 ) 100/1)a Mn × 10-3 entry 1 2b 3 4 5 6 7 8 mon L-LA PDI theof 5. 2.1 10.) for absolute molecular weight determinations. The molecular weight as determined by GPC deviated largely from the theoretical value. The polyester isolated by precipitation from methanol had an Mn of 6. and then a second heating scan at a rate of 10 °C/min was recorded..2 5.24 and the quartet at δ 4.8 1. [I]0 refers to [ROH]0 or 2[Ca]0 (in the absence of alcohol. the reaction was quenched by adding excess acetic acid. Synthesis of Poly(L-lactide)-b-(ethylene glycol)-b-(Llactide). respectively.9 mmol) was added a THF solution (1. b Toluene as solvent. Polymers were dissolved in chloroform (1. and the polymer was isolated using the procedures described above.95 2. kept at 185 °C for 2 min. alcohol + Mw. yield: 0. 34.7 15. The GPC measurements were conducted with a Waters 6000A GPC apparatus equipped with a series of standard Waters Styragel HR columns and a H502 viscometer detector (Viscotek Corp.0 wt %). 12. 0. the others with [ROH]0/[Ca]0 ) 2/1 (molar ratio). PDI ) 1. -OCH2CH2O-).0 mL) solution of Ca[N(SiMe3)2]2(THF)2 (0. i.3864 Zhong et al.50 g. l-LA conversion: 100%. 1H (300 or 400 MHz) and 13C (75.4 22. entries 1-3).1 5.0 mL) of poly(ethylene glycol) with Mn ) 2.6 × 103.5 0.2 15. After 18 min.24 1.56 (d. L-LA (1.069 mmol) and l-LA (1. Measurements.2 15.and -C(O)CH(CH3)OH). -C(O)CH(CH3)O-). and the polymer was isolated using the procedures described above. Analogous observations have been reported for yttrium and samarium amides in -CL polymerization.96 g. Macromolecules.5 7.0 g.8 time (min) 35 1 8 35 6 18 18 10 convc (%) 71 100 100 100 100 100 97 100 NMRd GPCe 8. and cooled to 20 °C at a rate of 40 °C/min. No.135 mmol) under vigorous stirring.39 1.0 0. monomer × [M]0/[I]0 × conversion. Entries 1-3 2 without alcohol.5 12. entries 1-3). the reaction was quenched by adding excess acetic acid. Vol. c Estimated from 1H NMR spectra (300 MHz.05 1.theor ) Mw.0 1. To a vigorously stirred THF solution (6. A rapid increase in viscosity was observed.05 was attributed to the free HN(Si(CH3)3)2 residues originating from the alcoholysis of Ca[N(SiMe3)2]2(THF)2.03. d CDCl3) of the crude polymerization mixtures.16 3.0 × 103 g/mol (0.03 1. when a THF solution of Ca[N(SiMe3)2]2(THF)2 was added to a mixture of 2propanol and L-LA at a molar ratio [L-LA]0/[2-PrOH]0/ [Ca]0 of 100/2/1. 1H NMR (CDCl3): δ 1. After 6 min prepolymerization. Figure 1. L-LA conversion: 93%.4 mmol) in 8 mL of THF was added.7 GPCe 1. with an integral ratio close to 6:1 within the limits of the NMR experimental errors. the polymerization of L-LA and -CL proceeded smoothly to afford the corresponding polyester with a narrow molecular weight distribution (entries 4 and 5). 2001 Table 1.0 -CL -CL L-LA -CL L-LA L-LA -CL 2-PrOH 2-PrOH PEG2000 MeOH MeOH 6. close to the theoretical value (7.GPC ) 15. The maximum of the endothermic peak was taken as the melting temperature. added a THF (1. For example.0 5. -C(O)CH(CH3)O-). no accurate Mn value could be calculated.9 6. 5.21.069 mmol). Table 1).34 (m.34.3 8. To the remaining mixture containing the living poly( -caprolactone) prepolymer. and the polymerization was terminated by the addition of acetic acid.5 1.2 × 103) calculated from the monomer-to-alcohol molar ratio.5 mL/min using chloroform as eluent. Moreover. After another 80 min.e.7 5.

0 × 103. Poly(L-LA) molecular weight and polydispersity index (PDI) vs conversion with [M]0/[2-PrOH]0/[Ca]0 ) 150/2/ 1. a quantitative crossover from the living poly( -CL) end to the living poly(L-LA) end. indicates that no random sequences due to transesterification were formed.16 (main chain methine proton) and at δ 1. Interestingly. Figure 2. No. as shown in Figure 6. affording after 6 min polymerization 100% monomer conversion. both yielding exclusively poly(L-LA) homopolymer.4 and 169. Similar results were also observed for the -CL polymerization (entry 5). A THF solution of Ca[N(SiMe3)2]2(THF)2 was added to a mixture of PEG2000 and L-LA at a molar ratio [L-LA]0/ [OH]0/[Ca]0 ) 100/2/1. PEG2000) was used in the present system. with isolated poly( -CL) chains bearing an isopropoxycarbonyl group at one end and a hydroxyl group at the other end as revealed by the 1H NMR analysis (Figure 2). were clearly detected.6 × 103 (Mn. In the first stage.63 completely disappeared. Moreover. The polymerization of L-LA ensued to give at 93% conversion after 80 min a block copolymer with Mn ) 12. The ratio of the degree of polymerization (DP) of poly(L-LA) and monomer conversion increased proportionally with the initial monomer-to-alcohol ratio (Figure 3).25-27 The absence of resonances between the two carbonyl signals at δ 173.NMR ) 2. THF. with the carbonyl signals proven to be the most sensitive to sequence effects. yielding poly(L-lactide)- . with the PDI becoming lower during the polymerization course (Figure 4).03.24 (methyl protons of the isopropoxycarbonyl end group) was 6. poly(ethylene glycol) (Mn. The 300 MHz 1H NMR spectrum (CDCl3) of poly( -CL) obtained with 2-PrOH-Ca[N(SiMe3)2]2(THF)2 (molar ratio: 2/1) (entry 5. 34. Dependence of the ratio of degree of polymerization (DP) of poly(L-LA) and monomer conversion on the initial monomer/2-PrOH molar ratio. The good agreement between the theoretical value of Mn and that determined by GPC or 1H NMR end group analysis unambiguously showed that the 2-propanol groups and not the bis(trimethylsilyl)amide ligands were incorporated during the initiation and that the polymerization proceeded exclusively by acyl-oxygen cleavage of the monomer. such as aluminum alkoxides28 and yttrium alkoxides. the same phenomena were observed for analogous initiator systems. Conversion (%) is noted in parentheses. Vol. corresponding to poly( CL) block and poly(L-LA) block. room temperature. 2001 Ca-Based Initiator System for ROP of Cyclic Esters 3865 Figure 3. The perfect control over molecular weight and low PDI indicate that the polymerization has a living nature. theory ) 12. 12.25-27 In contrast. The triplet assignable to R-methylene protons of hydroxyl-capped poly( -CL) at δ 3.19 The alcohol used determines the end functionalities and/or macromolecular architectures. These results indicate Figure 4. Besides resonances from the main chain. [M]0 ) 0. the signals at δ 1. 13C NMR analysis of the copolymers of -caprolactone and L-lactide affords distinct information on the sequence distribution of -oxycaproyl and lactyl units. To exemplify this.Macromolecules. respectively.4. a solution of L-LA (44 equiv with respect to 2-propanol) in THF was added.4 × 103) and PDI ) 1. a THF solution of Ca[N(SiMe3)2]2(THF)2 was added to a mixture of -CL and 2-propanol ([ -CL]0/[2-PrOH]0/[Ca]0 ) 100/2/1. The DP was determined by 1H NMR end group analysis. THF. the molecular weight also followed a linear relationship in monomer conversion. PDI ) 1. [ -CL]0 ) 0. Table 1). This was further confirmed by the sequential copolymerization of -CL and L-LA. Polymerization conditions: [2-PrOH]0/ [Ca]0 ) 2/1. The polymerization proceeded to 100% conversion within 18 min. attempts to prepare the block copolymer in the reverse order or to synthesize random copolymers by simultaneously polymerizing an -CL and L-LA mixture failed.22 (doublet) and 4.8 mol/L).8 mol/L. To this reaction mixture.9 × 103. The 1H NMR spectrum of the block copolymer is shown in Figure 5. room temperature. respectively.18. of signals at δ 5.34 (quartet) characteristic of the methyl protons of the isopropyl ester end group and the lactyl methine proton neighboring the hydroxyl group.

NMR ) 3. This implies that the alcoholCa[N(SiMe3)2]2(THF)2 initiator system promotes living ring-opening polymerization of cyclic esters with fast reversible transfer between dormant species and active species (“immortal” polymerization8. such as 2-propanol and poly(ethylene glycol).5 × 103 and 1. -OEt. supporting the rapid and reversible exchange between coordinated alkoxides and free alcohols. 2001 Figure 5.36. This is in close agreement with the melting behavior of optically pure poly(L-LA) reported by Prud’homme et al.5 h. Table 1). DSC of a poly(L-LA) sample revealed a crystallization exotherm at 106 °C and a single melting peak at 165 °C (Figure 8).5 × 103.34 The introduction of stereochemical defects into poly(L-LA) chains as a result of racemization would dramatically alter the thermal behavior such as a decrease of melting point and the degree of crystallinity.26 MHz.26 MHz 13C NMR spectrum (CDCl3) of poly(L-LA) obtained with 2-PrOH-Ca[N(SiMe3)2]2(THF)2 (molar ratio: 2/1) (entry 4.30 The alcohol used in this catalyst/initiator system apparently plays an important role.3866 Zhong et al. 34. After 1. the characteristic thermal properties are good indexes for the structural perfectness.39 or commercial yttrium isopropoxides40 .theory ) 3.32-35 13C NMR spectra (Figure 7) of all poly(LLA)s obtained in this study showed only three sharp signals corresponding to the carbonyl. Figure 6. This is in sharp contrast to polymerizations with aluminum alkoxides38. The combination of Ca[N(SiMe3)2]2(THF)2 and methanol in the homopolymerizations of L-LA or -CL yielded polyesters having a much higher Mn than expected (entries 7 and 8). CDCl3) of poly( -CL)-b-(L-LA) block copolymer prepared by sequential ring-opening polymerization of -CL and L-LA employing 2-PrOH-Ca[N(SiMe3)2]2(THF)2 (molar ratio: 2/1). the polymerization is first-order in monomer. etc. Another important issue for L-LA polymerization is the possible racemization during the reaction. No. indicating the formation of isotactic poly(L-LA) and no base-promoted epimerization of the L-LA monomer or poly(L-LA). Sterically more crowded alcohols.9 × 103.29. Macromolecules. Mn. a 1H NMR spectrum of the crude polymerization mixture showed that conversion was complete and all 2-propanol molecules had taken part in the polymerization (Mn. respectively. and methine carbons.03. methyl. This may result from the aggregation of in-situ generated calcium methoxide and/or growing species. respectively (entry 6). can sufficiently suppress the formation of coordinative aggregates and thus lead to good control over the polymerization.37 Kinetics of -CL polymerization in THF initiated with a low concentration of Ca[N(SiMe3)2]2(THF)2 was investigated at room temperature and monitored by manual sampling followed by 1H NMR analysis (CDCl3) to determine the monomer conversion. since calcium alkoxides containing sterically compact groups (-OMe. The 75. polymerization of L-LA was carried out with a large excess of 2-propanol relative to Ca[N(SiMe3)2]2(THF)2 ([L-LA]0/[2-PrOH]0/[Ca]0 ) 192/ 8/1). Figure 7. 12.37 Therefore. PDI ) 1. and no induction period is observed (Figure 9). In the presence of 2 equiv of 2-propanol with respect to Ca[N(SiMe3)2]2(THF)2. A 1H NMR spectrum of a 2-propanol-Ca[N(SiMe3)2]2(THF)2 mixture (10/1) in C6D6 at room temperature revealed that the isopropyl groups are in a single average environment. In another experiment. Carbonyl region of 13C NMR spectrum (75. The 300 MHz 1H NMR spectrum (CDCl3) of poly( -CL)-b-(L-LA) block copolymer prepared by sequential ringopening polymerization of -CL and L-LA employing 2-PrOHCa[N(SiMe3)2]2(THF)2 (molar ratio: 2/1).) are oligomeric or polymeric. b-(ethylene glycol)-b-(L-lactide) triblock copolymer capped with hydroxyl groups at both ends and with a Mn and PDI of 15.31). 13C NMR spectroscopy has been established as a useful method to identify the stereosequence distribution in poly(lactide). Vol.13).

[Ca]0 ) 1.41. 2001 Ca-Based Initiator System for ROP of Cyclic Esters 3867 Scheme 1. No. These features are in line with the absence of termination reactions and the conclusion that fast exchange of the free 2-propanol with bis(trimethylsilyl)amide ligands occurs and that the initiation is fast compared to propagation. In-situ formed calcium alkoxides are highly active. No . 12. initiating a fast living ring-opening polymerization of both -caprolactone and L-lactide under mild conditions. Polymerization Reactions Figure 8. 34. In the case of excess alcohol with regard to bis(trimethylsilyl)amide ligands.35 mmol/L. in the absence of alcohol (0). calculated according to ln([M]0/[M]t) ) kpapp[2PrOH]0t. Vol.0 mmol/L. The apparent propagation rate constants (kpapp).42 In contrast. which are lower than that determined for the yttrium isopropoxide polymerization of -CL using CH2Cl2 as the solvent40 but comparable to those of aluminum alkoxides in THF.6di-tert-butylphenoxides and 2-propanol. Kinetic profiles with first-order propagation in monomer and no induction period were established for -caprolactone polymerization with a 2-PrOH-Ca[N(SiMe3)2]2(THF)2 initiating system. DSC thermogram (second scan) of a poly(L-LA) sample recorded at a heating rate of 10 °C/min under N2 flow. This feature ensures that more than two polymer chains can be produced by each Ca[N(SiMe3)2]2(THF)2 molecule.40 It appears that in-situ generated initiators have superior polymerization kinetics in that the polymerization reaction starts immediately upon mixing catalyst and monomer.43 an initiation mechanism in which the bis(trimethylsilyl)amide ligands in Ca[N(SiMe3)2]2(THF)2 are irreversibly exchanged for the alcohol and the in-situ formed calcium alkoxides subsequently promote the ring-opening polymerization of cyclic esters through exclusive acyl-oxygen cleavage of the monomer and insertion into the calcium-alkoxide bond (Scheme 1) is proposed. The ring-opening process involves selective acyl-oxygen rupture of the monomer and insertion into the calciumalkoxide bond initially obtained after the alcoholysis of calcium amides. Kinetics of -CL ([ -CL]0 ) 200 mmol/L) polymerization initiated with Ca[N(SiMe3)2]2(THF)2 in THF at room temperature: [Ca]0 ) 1.70 mmol/L (2). which leads to the formation of the hydroxyl end group.4. [2-PrOH]0 ) 2.7 mmol/L).20. Interestingly. Conclusions Aggregation and/or insolubility of calcium alkoxide derivatives was circumvented by generating them in situ from Ca[N(SiMe3)2]2(THF)2 precursor and an adequate alcohol using THF as the solvent. The living species can be hydrolytically deactivated by adding an acid. A rapid initiation and early propagation is followed by a very slow first-order propagation. the active species (coordinated alkoxides and/or growing polymer ends) exchange rapidly and reversibly with the dormant species (free alcohol molecules and/or hydroxyl-capped polymers). [2-PrOH]0 ) 2. Polyesters and block copolyesters of expected molecular weight and tailored chain structure can be readily prepared. in the absence of 2-propanol. respectively.0 mmol/L. where a pronounced induction time to rearrange the ligands of the initiator thereby allowing the monomer to access the coordination sphere of the metal is present.40.0 mmol/L (b).0 mmol/ L) and 0. [Ca]0 ) 1.041 L mol-1 s-1 ([2-PrOH]0 ) 2.38. the polymerization appears to proceed in two stages. On the basis of the results and by analogy with the mechanisms accepted for the ring-opening polymeriza- tion of cyclic esters mediated with other metal alkoxides. Figure 9. are 0.Macromolecules.33 L mol-1 s-1([2-PrOH]0 ) 2. no retardation was observed for either -caprolactone or L-lactide polymerization with the insitu yttrium isopropoxides generated from yttrium 2.

. J. J. J. Kasperczyk. Chem. K. B.. M. Appl. 432-446. Kasperczyk. Teyssie. 30. 1990. 1995. (17) Kricheldorf... Siepmann.. J.. 1999.. P. 305-313.. 1993. J. B.. 11583-11584. J. M. 2581-2590. P. (32) Chabot. B.. Jerome.. Dijkstra. R. 1992. Chem. Prud’homme.. 29. H. Acknowledgment.. R. P. 300-305. S. Sci.. 20. J. Greiner. Macromolecules 1996.. J. Makromol. Macromolecules 1996. A. Bero. Polymer 1983.. G. Z. Makromol. Phys. 3332-3333. Nutr. J.. K. S. H. K. Soc. Polym.. R. J.. Sci. T. Jerome. 29. J. Ropson.. P. 1653-1664. I. W. Kean. W.. H. 144. W. Vol. Huffman.. Nutr. 8296-8303.. Jerome. 6412-6417. Ankone.. N.. 1998. Inoue. 24. Makromol. Makromol. S.. Macromol. Dijkstra. E. N. P. P. M. Symp. Chem. R. N. 1530-1535. Polymerization by Metalloporphyrin and Related Complexes. 3027-3034. Spenlehauer. Macromolecules 1996.. J. 2422-2428. Teyssie. MA0019510 . N. D. Chem. as revealed by NMR and DSC analyses. (25) Kasperczyk. Chem. Macromolecules 1995. O. S. 191. Chem. Hanusa.. A35. H. 31. Karl. 1991. A. A. Massa. R. A. J. P.. Li. (38) Duda. Am. Bero. Adv. Macromol. 121. 73. R.. Chem. (3) Puelacher. (43) Dubois. Jerome. Teyssie. M. Am. J.. 29.. A. R.. 474486.. Huffman. 30. Ankone. Phys. Dubois. H. 913-925. Feijen. Kolstad. Anorg. Munson.. 96-101.. 32. J.. W. K. Phys. A. P. P. Springer-Verlag: Berlin: 1999. 29. Katsumata. Macromolecules 1996.. 197. T. J. 10. Aida. Aida. 7589-7598. 194. E... 5981-5992. W. H. M. 33. R. 103-116. E. D. (30) Tesh.. Wisniewski. (37) Sarasua. Ankone. M. Tsang. 2001. Feijen. W. Bero. Boettcher. Mast.. 1999. T. Chem. D. 28. O. (26) Bero. Chem. Dehnicke. I. P. 1999. R. 28. pp 39-119.. (27) Kasperczyk. Macromol. (19) Stevels. Phys. Mater. 21. J. Inorg. Lobkovsky.. M. 1996. 1992.. Guerin. J. Teyssie. Upton. B. Macromolecules 1994. M. Coates. (36) Tsuji. Macromol. Med. W. Mater. R. R. R. Soc. (33) Kricheldorf. (41) Ropson. 1320-1322. C. Russell. Doscotch. Macromol... 29. G. P. M. 57-62. Chapelle. J. Jerome. Manolova. Macromolecules 2000. Macromolecules 1998. 24. Spassky.. 2000. 339340. No. P.. 200. S. Phys. (11) Turnlund. 3251-3258. J. Am. M. M. Espartero. 207.. A. P... (40) Stevels. (14) Dobrzynski. (8) Mecerreyes. (2) Chiellini. Vol. 31. Makromol.. This study was financially supported by the Netherlands Foundation for Chemical Research. 4735-4737. Sci. C. 1965-1975. 1993.. (12) Koo. J.. Y... Tolman. racemization was observed in L-LA polymerization. Monnier. 1999. Inoue. Dubois.. F. Macromol. Granger. (39) Dubois. (13) Li. A. J. (28) Jacobs. Sodergard.. (5) Sugimoto.. Symp. J.. (29) Lutz.. 29822988. P. Dubois. 29. Vert. Inoue. Kretsch. Macromolecules 1995. Langer. 905-910. Damrau. 6132-6138.. R. (21) Martin.. Feijen. 493-505. W. 1875-1887... Mater..3868 Zhong et al. Vert. 27. Jerome. Damrau. R.. R. (24) Agarwal. H. Dehnicke. J. K. 62. Chem. 1996. P... 5. J. 123... (16) Kricheldorf. Macromol. J. (6) Cheng. J. M. The high catalytic activity of the calcium-oxygen bond of alkoxide in the polymerization of cyclic ester substrates as demonstrated by the present study offers great potential of calcium-based initiators in the synthesis of biomedical and pharmaceutical polyesters.. 194. 1669-1674. A. M. J. M. (22) Westerhausen. Chem. J. M. (42) Duda. Phys. Clin. S. 1399-1406. Hillmyer. 195-212. Dijkstra. T. 1967.. 1992. W. Macromolecules. G. P. 56. E. Kasperczyk. Kreiser-Saunders. A. Macromolecules 1999. Macromol. 34833499. 197.. C. Hall. 146. 42-3. M. Macromolecules 1999. Macromolecules 1987. (7) Stevels. 32. Am. W. Jedlinski. Macromol. J. M. (35) Thakur. S. H.. C. 15. 28.. J. D. Dijkstra. Chem. A. M. (15) Stolt.. R. Chem. Sci. P. Rashkov. C. W. J.. (23) Evans. (4) Akatsuka. Le Borgne. Sauberlich. Macromolecules 1997. R. M. M. M. (9) Agarwal. M. Macromolecules 1996. Chem. 192. M. Chem. Lindgren. M. Attygalle. K.. (31) Endo. Solaro. E. Vacanti. Z. I. M.. S. M. 34. (20) Stevels. Ikada. 53-59. M. M. Macromolecules 1996. a rapid and controlled lactide polymerization with two different iron alkoxides was reported. Vacanti. J. Macromolecules 1991. Greiner. Detailed mechanistic and kinetic investigations for L-lactide polymerization as well as the development of structurally well-defined single-site calcium alkoxide with a formula Ln*-CaOR (Ln* refers to a bulky ligand set) are currently in progress. J.. Chem. Inorg. M. Seybert. P. 2001 (18) After the submission of this manuscript. 3.. 1991. 23302332.. L. J. Chem.. 1996.. Liebman. 1997. 8. 1777-1787. Macromol. Rapid Commun. A. K... 2287-2296. C. C. J. References and Notes (1) Vert. Betschart. R. J.. M. Pure Appl. F.. Macromolecules 1995. Nutr. Clin. Feijen.. A. Chem. J.. T.. 1991.. 38953905. S. Macromol.. 269-276. 1991. A. K. C. 12. S. O’Keefe. M. Allg. Suter. J. (10) Wood... Trends Polym.. E. M. E. (34) Bero.. J... P. 353. Biomaterials 1994. 774-778. Coll.. Am. Mooney. Penczek. S. 5572-5579. Phys.. D.