Article pubs.acs.org/JACS
Alternating Sequence Controlled Copolymer Synthesis of α‑Hydroxy Acids via Syndioselective Ring-Opening Polymerization of O‑Carboxyanhydrides Using Zirconium/Hafnium Alkoxide Initiators Yangyang Sun,† Zhaowei Jia,† Changjuan Chen,†,‡ Yong Cong,† Xiaoyang Mao,† and Jincai Wu*,† †
State Key Laboratory of Applied Organic Chemistry, Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, People’s Republic of China ‡ College of Chemistry and Pharmaceutical Engineering, Huanghuai University, Zhumadian 463000, People’s Republic of China S Supporting Information *
ABSTRACT: The ring-opening polymerization (ROP) of Ocarboxyanhydrides (OCAs) can give diverse poly(α-hydroxy acid)s (PAHAs) with different functional groups because of easy modification of the side group of OCAs, which can extend applications of PAHAs widely. The stereoselective polymerization of O-carboxyanhydrides and further sequence controlled alternating copolymerization of OCAs were still big challenges until now for lack of suitable catalysts/initiators. In this work, a highly syndioselective ROP of OCAs system as the first stereoselective example in this area is reported using zirconium/hafnium alkoxides as initiators with the highest Pr value up to 0.95. Furthermore, these initiators were successfully applied in the precisely alternating sequence controlled copolymerization of PheOCA and Tyr(Bn)OCA, and alternating copolymerization of LacOCA and PheOCA was also achieved.
■
INTRODUCTION Precisely controlling the microstructures of synthetic polymers including tacticity, region-regularity, and monomer sequence is still a central challenge in polymer chemistry so far, especially in living polymerization processes. Because sequence controlled polymers such as natural DNA and polypeptides may have some functions and properties that are inaccessible from sequence unregulated polymers, in recent decades tremendous efforts have been devoted to the synthesis of sequence controlled copolymers, and many pieces of excellent work have been reported.1 Alternating copolymers as the simplest sequence controlled artificial copolymers can be synthesized facilely; normally, the living alternating copolymerization methods are efficient for different types of monomers which have high rates of cross-propagation, for example, copolymerization of epoxides and CO2/CO, 2,3 epoxides and anhydrides,4 aziridines and CO,5 alkenes and CO,6 and so on. For different monomers which belong to the same type, like different olefins or cyclic esters, the viable living approaches are still significantly fewer. In the challenging living radical polymerizations, successful alternating copolymerizations of some special olefin monomer pairs have been reported, for example, olefin pairs of electron-donor and -acceptor7 and olefin pairs preassembled via coordination chemistry,8 supramolecular chemistry,9 or a cleavable covalent bond.10 The monomers of ethylene and α-olefin can be alternatingly copolymerized with some metallocene catalysts possessing heterotopic active sites.11 Alternating ring-opening metathesis polymerizations (AROMP) of some olefins based on catalyst © 2017 American Chemical Society
and monomer designs also have been successfully reported in the past decade.12 Although various living alternating copolymerization examples for the same type of monomer have been reported, the monomers mostly focus on olefins.1 The living alternating copolymerization method for monomers derived from hydroxy acids has rarely been explored. In 2009 and 2014, Thomas and Coates,13 Guillaume and Carpentier, 14 and co-workers succeeded in the alternating polymerization of β-alkyllactones and alkyl-β-malolactonates giving different alternating copolymers of poly(β-hydroxy acid)s via syndioselective catalysts, respectively. This stereospecifc alternating copolymerization method seems to be feasible for two similar but different chiral monomers of opposite absolute configuration. Irrespective of this, the monomers as successful examples have only focused on four-membered ring β-lactones thus far. To the best of our knowledge, the living alternating copolymerization approach for the synthesis of poly(α-hydroxy acid)s (PAHAs) has not been investigated (except syndiotactic homopolymer obtained from a racemic mixture of monomers). α-Hydroxy acids (AHAs) are typically derived from food products including glycolic acid, lactic acid, malic acid, and so on. The related PAHAs have wide applications from biomedical devices to packaging materials because of their biocompatibility, biodegradability, and ability to partially replace petrochemicalbased thermoplastics.15 However, most conventional PAHAs, Received: May 8, 2017 Published: July 17, 2017 10723
DOI: 10.1021/jacs.7b04712 J. Am. Chem. Soc. 2017, 139, 10723−10732
Article
Journal of the American Chemical Society
Scheme 1. Synthesis of Syndiotactic Poly(α-hydroxy acid)s and Alternating Copolymers of α-Hydroxy Acids by Zirconium and Hafnium Complexes
initiators.21 However, regardless of whether they are organocatalysts or metal complexes, no example of the stereoselective polymerization of OCAs has been reported until now. Stereoselective polymerization of OCAs is still a challenging goal in the ROP of OCAs and undoubtedly it is also a valuable research issue because the physical and chemical properties of PAHAs, such as polylactide,22 are highly dependent on their stereo microstructures. In addition, a highly stereoselective polymerization of different OCAs can be used to synthesize alternating sequence controlled poly(α-hydroxy acid)s when catalysts/initiators are highly syndioselective, which can further enrich the diversity of PAHAs with optimized properties for applications. Thus, in this work we reported the first example of syndioselective ring-opening polymerization of OCAs using zirconium and hafnium alkoxide initiators. Furthermore, these initiators were successfully applied in alternating sequence controlled synthesis of poly(α-hydroxy acid)s using OCA monomers.
for instance, polylactide (PLA), poly(glycolic acid) (PGA), and poly(lactic-co-glycolic acid) (PLGA), are short of side-chain functionalities, and thus it is difficult to alter their structures for modulating their physicochemical properties and the applications of PAHAs are somewhat restricted. Actually, in order to enhance the physical and mechanical properties of PAHAs, some analogues of ploylactide have been reported via the ringopening polymerization (ROP) of various substituted 1,4dioxane-2,5-dione derivatives.16 However, the syntheses of these types of monomers and the control of ROP progress is sometimes not easy. For example, replacing the methyl group of polylactide with phenyl, Baker et al. reported that the polymer of mandelide can possess a high glass-tranistion temperature (Tg, 95−100 °C) compared to a low Tg of polylactide (30−60 °C).16c However, the synthesis of stereoregular poly(mandelic acid) (PMA) is difficult because of unavoidable racemization of mandelide under polymerization conditions; the monomer synthesis of mandelide also requires long reaction time and high-boiling solvents, which just gives a mixture of rac and meso diastereomers. Davidson and Carbery,17 and Chen and Tong et al.18 changed mandelide to an activated O-carboxyanhydride (OCA) type mandelic acid monomer of L-ManOCA, the racemization of the monomer does not happen in the ROP progress of L-ManOCA and the Tg of stereoregular isotatic PMA can reach as high as 105 °C.17 In fact, inspired by the successfully controlled synthesis of polylactide from the OCA activated monomer of L-LacOCA reported by Bourrisou, Dove, and others,19 great efforts have been devoted to synthesizing PAHAs via the ROP of various OCAs in the past decades with the aim to enrich the diversity of PAHAs and enhance their properties, because OCAs derived from natural α-hydroxy acid or amino acids possess rich sidechain functionalities. Some examples demonstrated that the controllable ROP of OCAs, including LacOCA, L-PheOCA, LGluOCA, L-Thry(alkynyl)OCA, L-Ser(Bn)OCA, L-ManOCA, LLys(Cbz)OCA, and so on, can be efficiently achieved via organocatalysts17−20 and very few metal complex catalysts/
■
RESULTS AND DISCUSSION Syndioselective ROP of OCAs. In order to achieve a highly syndioselective system for the ROP of OCAs, a lot of excellent catalysts/initiators for the ROP of chiral cyclic esters, like rac-lactide, were screened by us. Among these tremendous stereoselective catalysts/initiators, amine tris(phenolate) Zr/ Hf/Ge alkoxide complexes attract our attention because of the special C3-symmetry of ligands23 and their excellent stereoselectivities toward the ROP of rac-lactide reported by Davidson and co-workers.24 It is fortunate that amine tris(phenolate) Zr/Hf alkoxides 1−2 also can show high syndioselectivies for the ROP of OCAs (Scheme 1A). First, racLacOCA was chosen as a typical monomer of OCAs. The ROP of rac-LacOCA at a 100:1 ratio of [monomer]0/[initiator]0 with zirconium complex 1a and hafnium complex 2a as an initiator can be completed with a 99% conversion at room temperature in 24 and 1.5 h, respectively. However, the number-average 10724
DOI: 10.1021/jacs.7b04712 J. Am. Chem. Soc. 2017, 139, 10723−10732
Article
Journal of the American Chemical Society Table 1. Syndioselective ROP of rac-OCAs Initiated by Zirconium/Hafnium Complexes 1−2a Entry
Cat.
rac-OCA
[I]0/[OCA]0
t
Conversionb(%)
Mn,obsdc (g/mol)
Mn,NMRd (g/mol)
Mn,calcde(g/mol)
Đ
Prf
1 2 3 4 5g 6h
1a 2a 1b 2b 2b 2b
LacOCA LacOCA LacOCA LacOCA PheOCA Tyr(Bn)OCA
1:100 1:100 1:100 1:100 1:50 1:50
24 h 1.5 h 20 min 20 min 14 h 50 h
99 99 99 99 81 90
10600 12400 6600 6700 5000 10500
9000 10000 6700 7500 5700 12000
7200 7200 7200 7200 6100 11500
1.57 1.63 1.23 1.12 1.11 1.18
0.80 0.83 0.80 0.84 0.93 0.95
a
Conditions: Reactions were carried out under a dry nitrogen atmosphere, 0.01 mmol of initiator, 2 mL of toluene, at room temperature in addition to the noted conditions. bDetermined by 1H NMR spectrum. cExperimental Mn and Đ determined by GPC in THF against polystyrene standards, and corrected using the factor 0.58 for poly(LacOCA);26 poly(PheOCA) and poly(Tyr(Bn)OCA) are not corrected. dDetermined from the relative integration of the signals for the main-chain methine units and chain ends. eCalculated from the equation (molar mass of OCA − molar mass of CO2) × [OCA]0/[I]0 × Conversion % + the molar mass of the initiators. fDetermined by analyses of all of the tetrad signals in the methine region of the 13C NMR spectrum. gIn 5 mL toluene. hIn 20 mL toluene.
Figure 1. (A) Plots of Mn and molecular weight distribution Đ of poly(rac-LacOCA) versus [rac-LacOCA]0/[2b]0 ratio. (B) Representative gel permeation chromatography (GPC) traces of the poly(rac-LacOCA) prepared by 2b. (C) Methine region of 1H NMR spectrum (left) and homonuclear-decoupled 1H NMR spectrum (right) of poly(rac-LacOCA) (Table 1, entry 4). (D) Detail of the methine region of 13C NMR spectra (100 MHz, CDCl3) of poly(rac-LacOCA) synthesized from ROP of rac-LacOCA in the presence of (a) 2b (Pr = 0.84; Table 1, entry 4), (b) 1b (Pr = 0.80; Table 1, entry 3), (c) the DMAP/iPrOH system (Pr = 0.5), and (d) D-LacOCA in the presence of 1b (Pm = 1; Table S1, entry 10). (E) Pr values determined for all tetrads on the basis of first-order Markov statistics (Table 1, entry 4, Pr = 0.84). (F) The MALDI-TOF mass spectrum of poly(rac-LacOCA) prepared by initiator 2b (Table S1, entry 6); the minor population stands for [C4H7O2(C3H4O2)nOH] + K+ polymer chains.
molecular weight (Mn) of gel permeation chromatography (GPC) values are higher than expected and the molecular weight distributions Đ = 1.57/1.63 are broad (Table 1, entries 1−2, Figure S1A). After replacing isopropanolate Zr complex 1a with L-methyl lactate Zr complex 1b, the polymerization rate sharply increases offering a 99% conversion of monomer within 20 min under the same conditions (Table 1, entry 3). The Mn also becomes controllable and a slightly low molecular weight distribution Đ = 1.23 can be obtained. Considering the same
ligand and metal ion but different alkoxy group in 1a and 1b, the different catalytic performance of 1a and 1b may result from different initiation rates at the beginning of ROP of LacOCA. The similar phenomena also appeared in the BDI-Zn catalyst system for ROP of OCAs reported by Cheng, Tong, and co-workers, where the uncontrollable molecular weights and low activities were ascribed to the existence of predominant inactive dimeric isomer of isopropanolate BDI-Zn compared to monomeric L-methyl lactate BDI-Zn complex,18 while in our 10725
DOI: 10.1021/jacs.7b04712 J. Am. Chem. Soc. 2017, 139, 10723−10732
Article
Journal of the American Chemical Society
Figure 2. (A) Details of the methine region of the 13C NMR spectra (150 MHz, CDCl3) of atactic, isotactic-enriched, isotactic, and sydiotactic poly(PheOCA)s synthesized via the ROP of (a) rac-PheOCA, (b) L-PheOCA/D-PheOCA = 5/1, (c) L-PheOCA in the presence of DMAP/iPrOH catalyst system, and (d) rac-PheOCA in the presence of 2b (Pr = 0.92, Table 1, entry 5). (B) Detail of the methine region of the 13C NMR spectra (150 MHz, CDCl3) of atactic, isotactic-enriched, isotactic, and syndiotactic poly(Tyr(Bn)OCA)s synthesized via ROP of (a) rac-Tyr(Bn)OCA, (b) i L-Tyr(Bn)OCA/D-Tyr(Bn)OCA = 9/1, (c) L-Tyr(Bn)OCA with DMAP/ PrOH as a catalyst, and (d) rac-Tyr(Bn)OCA with 2b as an initiator (Pr = 0.95, Table 1, entry 6). (C) Pr values of poly(rac-PheOCA) determined for all tetrads on the basis of first-order Markov statistics29 (Table 1, entry 5, Pr = 0.92). (D) Pr values of poly(rac-Tyr(Bn)OCA) determined for all tetrads on the basis of first-order Markov statistics29 (Table 1, entry 6, Pr = 0.95). (E) The MALDI-TOF spectrum of poly(rac-PheOCA) prepared by initiator 2b (Table S1, entry 15). (F) The MALDI-TOF spectrum of poly(rac-Tyr(Bn)OCA) prepared by inititor 2b (Table S1, entry 21).
system, only single set signals of 1b in 1H and 13C NMR spectra cannot show the existence of some isomers (see Supporting Information). The 1H NMR spectrum of a mixture of same equivalents of 1a and 1b in toluene-d8 under same condition of polymerization did not produce new signals belonging to a new compound (Figure S2), which may rule out the existence of dimers and other possible oligomers.25 When a 1:1 ratio of complex 1a and D-LacOCA was mixed for about 30 min in CDCl3, 1H NMR spectrum of this mixture exhibits that most molecules of 1a remain unchanged (Figure S3). Only a small amount of new signals appear at 1.27, 1.35, and 6.95 ppm, which are similar to the related signals in 1b. At the same time most D-LacOCA monomers were converted to polymers evidenced by the obvious quartet peak at 5.16 ppm and doublet peak at 1.58 ppm. These results suggest that the initiation of the ROP of D-LacOCA using complex 1a is slower than the propagation, which also can be confirmed by the fact that the resulting molecular weight distributions are broad and even bimodal at high conversions, and the ROP of rac-LacOCA initiated by 2a is similar (Table 1 entries 1 and 2; Table S2, entries 1−4; Figure S1A). However, the mixture 1H NMR spectrum of 1:1 ratio of complex 1b and D-LacOCA does not produce polymers because no obvious quartet peak at 5.16 ppm occurs, which hints that complex 1b can quickly initiate the ROP of LacOCA (Figure S4). Therefore, the difference between these two complexes mostly results from the initiation step, which possibly originates from the different coordination environments around the metal center of complexes 1a and 1b; we failed to obtain the crystals of 1b and 2b many times, the real reason for this phenomenon evidenced by structures is still under investigation now. The analogue Hf complex 2b displays
a similar activity and a better control compared with 1b giving polymers with a narrower Đ of 1.12 (Table 1, entry 4). The Mn values of obtained poly(rac-LacOCA)s increased linearly with [rac-LacOCA]0/[2b]0 ratios arranging from 30 to 200, and the Đ values remain narrow at about 1.10 (Table 1, entry 4; Table S1, entries 6−8; Figure 1A,B; see Figure S1B for Mn and Đ vs conversion). The clear identification of the methoxy group at δ ∼ 3.7 ppm in the 1H NMR spectrum showed the presence of the end-capped group of methoxy in the polymer (Figure S5), which can be further confirmed by a series of +1 charge peaks of 72n + 104 + 23 (n(LacOCA − CO2) + HOCH(CH3)COOCH3) + Na+) in MALDI-TOF spectrum (Figure 1F). Therefore, this ROP of OCA was initiated by the alkoxy group of methyl lactate in complexes. Stereomicrostructural analysis of the resulting poly(rac-LacOCA) was analyzed by 1H NMR and 13C NMR spectra. The methine regions of 1H NMR and homonuclear-decoupled 1H NMR spectra of poly(rac-LacOCA) obtained with 2b as an initiator (Figure 1C, Table 1, entry 4) are similar to those of syndiotactic poly(meso-lactide) obtained from meso-lactide via a heteroselective catalyst of [(BDI)ZnOiPr]2 reported by Coates and co-workers,27 but the statistical distributions of tetrads for different stereosequences are different because of using different types of monomers. There is a serious overlap at the methine region between tetrad signals of rrr, rrm, mrr, and mrm in decoupled 1H NMR spectra; thus the 13C NMR spectrum was analyzed for the methine region and the distinct tetrads were assigned based on previous work on poly(meso-lactide) and poly(rac-lactide).28 Atactic, isotactic, and syndiotactic-enriched poly(rac-LacOCA) were also deliberately synthesized for comparison via the ROP of racLacOCA and L-LacOCA with DMAP/iPrOH24 and 1b/2b as 10726
DOI: 10.1021/jacs.7b04712 J. Am. Chem. Soc. 2017, 139, 10723−10732
Article
Journal of the American Chemical Society
values of different multiads (triads and tetrads) of atactic, isotactic, and isotactic enriched poly(OCA)s, which were deliberately synthesized via the ROP of rac-OCA, L-OCA, and a mixture of L-OCA and D-OCA with DMAP/iPrOH as a catalyst19b (Figure 2A,B; see more details of assignment via statistical analyses in Supporting Information and Figures S19− S24). The methylene regions of poly(rac-PheOCA) and poly(rac-Tyr(Bn)OCA) in 13C NMR show single main peaks corresponding to rr triad (Figures S21 and S24), which indicates that the syndioselectivity of this system is very high. The methine region of poly(rac-PheOCA) in 13C NMR shows three peaks which can be ascribed to tetrads of rrm, rrr/mrr, and rmr in the predominant stereoerror sequence of -rrrmrrr(−RSRSSRSR−/−SRSRRSRS−). The Pr value of the final polymer was 0.92, which was calculated from the tetrads at the methine region by a first-order chain end stereocontrol statistics (Table 1, entry 5; Figure 2C).29 This high syndioselectivity also can be confirmed by the following alternating copolymerization experiments (vide infra). A consistently high syndioselectivity of Pr = 0.95 was also achieved for the ROP of rac-Tyr(Bn)OCA with 2b as an initiator (Table 1, entry 6; Figure 2D). It is noted above that MALDI-TOF spectra also can indirectly confirm the high selectivities of this system for the ROP of (rac-PheOCA) and poly(rac-Tyr(Bn)OCA). As shown in Figure 2E,F, the intensities of an even number of degrees of polymerization (DP) are stronger than that of an odd number which does not happen in the slightly lower syndioselective ROP of racLacOCA (for more spectra, see Figures S25−27). Because the very good alternating sequence of D-OCA and L-OCA and Lmethyl lactate is used in complex 2b, the starting monomer mostly is D-OCA; then as a statistical result the chain end monomer mostly should be L-OCA to agree with the racemic mixture of OCA when conversion is close to 100% (Figure S25). When increasing the amount of D-OCA, it is reasonable for the polymers with an odd number of DP, which are endcapped with D-OCA, to become stronger (Figure S25). It is also noted here that when D-methyl lactate was used in complex 2b, the syndioselective results are similar for the three racemic monomers above (Table S3, entries 1−3). In this system, trying to synthesize high molecular weight polymers of poly(racPheOCA) and poly(rac-Tyr(Bn)OCA) with the ratio of [monomer]0/[2b]0 greater than 50:1 was not successful, even when changing reaction solvent to THF; attempts to synthesize syndiotactically enriched and high molecular weight poly(OCA)s are still in progress in our lab. It is interesting that when we decrease the temperature of reaction for the ROP of rac-LacOCA using 2b as an initiator, the Pr value of syndioselectivity decreases from 0.83 at 25 °C, to 0.75 at −40 °C, and further decreases to 0.72 at −60 °C (Figure 3, Table S4, entries 1−4). A stereoselective mechanism in which only chirality of the growing chain end controls the configuration of the next monomer cannot explain this kind of decrease of syndioselectivity, while a mechanism termed “enhanced” chain end control seems to be suitable, which was suggested by Davidson and co-workers24 for heteroselective ROP of rac-lactide. In this mechanism, both the growing chain end and the chiral center of metal are important for the highly syndioselective system. As shown in Scheme 2, there are two diastereoisomers of (S)-(M)-Hf and (S)-(P)-Hf for complex 2b (L-methyl lactate was used in 2b) which can invert to each other via the inversion of the axial chirality (P or M) of the metal center. Actually, this inversion for complex 2b is quick at room temperature because the energy barrier is just
initiators, respectively (Figure 1D and Figure S8). After a careful comparison, the signals from downfield to upfield in the methine region can be assigned to the rmr, rrr, rrm, and mrr tetrads, respectively. The resulting poly(rac-LacOCA)s show a strong contribution correlating to rrr tetrad at 69.25 ppm which indicates that syndiotactic-enriched poly(rac-LacOCA) was achieved; and the predominant stereoerror sequence can be ascribed to -rrrmrrr- (−RSRSSRSR−/−SRSRRSRS−). The Pr value of the final polymer was assessed by fitting the tetrad resonances observed in the 13C NMR spectrum with the values predicted via a first-order chain-end stereo control (or a Markov first-order chain-end control, Mk1) (Figure 1E).29 As shown in Table 1, highly syndioselective Pr values ranging from 0.79 to 0.84 for complexes 1a, 1b, 2a, and 2b can be achieved at room temperature in toluene, and the syndioselectivities of Hf complexes (2a and 2b) are better than that of Zr complexes (1a and 1b) possibly due to somewhat different subtle environments around Hf and Zr metal ions (Table 1, entries 3 and 4), which also was discovered in some stereoselective olefin polymerization systems.30 When the solvent was changed to THF, the syndioselectivity using 2b does not increase with a Pr value of 0.80 (Table S1, entry 5). We then expanded the monomer scope to other OCAs with side groups of benzyl (rac-PheOCA) and benzyl protected cresyl (rac-Tyr(Bn)OCA). The polymerization of 50 equiv racPheOCA is somewhat slow with complex 1b as an initiator at room temperature in toluene (conversion 80% in 24 h, Table S1, entry 13); when increasing temperature to 80 °C, the polymerization can almost be completed within 14 h but with a lower experimental Mn value than calculated and a relatively broad molecular weight distribution (Table S1, entry 14), which may result from decomposition and partial direct oligomerizaton of PheOCA at this high temperature (Figure S10).31 The polymerization of rac-PheOCA and rac-Tyr(Bn)OCA with 2b as an initiator proceeded slightly rapidly at room temperature; the experimental NMR Mn values agreed well with the calculated Mn and the Đ values of 1.11 and 1.18 are narrow (Table 1, entries 5 and 6). The large steric side groups of rac-PheOCA and rac-Tyr(Bn)OCA can hinder the transport of OCA to the active metal center; thus the ROP activities of rac-PheOCA and rac-Tyr(Bn)OCA were significantly lower compared to rac-LacOCA with a small side group of methyl. The clear identification of the methoxy group at δ ∼ 3.7 ppm in the 1H NMR spectrum of the resulting poly(rac-PheOCA)s and poly(rac-Tyr(Bn)OCA)s confirmed that the methyl lactate is the chain end group of polymers (Figures S11 and S15). The MALDI-TOF MS of low molecular weight poly(OCA)s demonstrated a series of peaks at 148m + 104 + 23 (poly(rac-PheOCA)) and 254m + 104 + 23 (poly(racTyr(Bn)OCA)) with a charge of +1 (Figure 2E,F), which can be assigned to m(PheOCA − CO2) + HOCH(CH3)COOCH3) + Na+ and m(Tyr(Bn)OCA − CO2) + HOCH(CH3)COOCH3) + Na+, respectively. Thus, MALDI-TOF MS proved again that the methyl lactate of initiator 2b initiated the ROP reaction. Stereomicrostructural analyses of the resulting poly(rac-PheOCA) and poly(rac-Tyr(Bn)OCA) were performed by 13C NMR spectrum, which were more challenging than that of poly(rac-LacOCA) due to the lack of clear stereosequence assignment reported in the literature. Assignments at the tetrad level of resolution for the methine region and the triad level of resolution for the methylene region were made after carefully comparing Bernoullian statistically predicted values with those 13C NMR experimentally integrated 10727
DOI: 10.1021/jacs.7b04712 J. Am. Chem. Soc. 2017, 139, 10723−10732
Article
Journal of the American Chemical Society
syndioselectivity decrease. The above “enhanced” chain end control mechanism is possible, but the interplays between chiral metal center, the end group of growing chain, and monomers are complicated, the stereoregulating mechanism for the ROP of OCAs may be somewhat different from that in the ROP of rac-lactide. Therefore, more reliable details of mechanism are under investigation now in our lab. Alternating Polymerization of OCAs. It is also interesting that the ROP reactions initiated by 2b are very slow (conversion
