Single-site catalysts for ring-opening polymerization: Synthesis of heterotactic poly(lactic acid) from rac-lactide [9]

Full text of DOI:10.1021/ja992678o

J. Am. Chem. Soc. 1999, 121, 11583-11584
11583
Scheme 1
Single-Site Catalysts for Ring-Opening
Polymerization: Synthesis of Heterotactic Poly(lactic
acid) from rac-Lactide
Ming Cheng, Athula B. Attygalle, Emil B. Lobkovsky, and
Geoffrey W. Coates*
Department of Chemistry and Chemical Biology
Baker Laboratory, Cornell UniVersity
Ithaca, New York 14853-1301
ReceiVed July 29, 1999
Single-site catalysts are revolutionizing polymer synthesis.
These homogeneous, molecular compounds have the general
formula LnMR, where Ln is a ligand set that remains attached to
and thus modifies the reactivity of the active metal center (M)
during the entire chemical reaction, and R is a group that can
initiate polymerization. Through ligand design, homogeneous
catalysts are now available that can control polymer molecular
weights, molecular weight distributions, comonomer incorpora-
tion, and stereochemistry in ways that are impossible using
conventional hetereogeneous catalysts. Although remarkable
advances have been reported concerning the development of
molecular catalysts for olefin polymerization,1,2 comparatively few
single-site metal catalysts are available for the ring-opening
polymerization of heterocycles such as epoxides and lactones.3
Herein we report the synthesis of a zinc alkoxide complex that
acts as a single-site catalyst for the synthesis of heterotactic poly-
(lactic acid).
Poly(lactic acid)s (PLAs) have many potential medical, agri-
cultural, and packaging applications due to their biocompatibility
and biodegradability.4 A convenient synthetic route to these
polymers is the ring-opening polymerization of lactide, the cyclic
diester of lactic acid.5 A range of metal alkoxide initiators has
been reported to polymerize lactide with retention of configura-
tion.6 For example, the polymerization of optically active (R,R)-
lactide yields isotactic PLA, while polymerization of meso-lactide
using an optically active initiator can produce syndiotactic PLA.3a
Polymerization of rac-lactide (1) typically produces amorphous,
atactic polymers. We have recently reported the synthesis of
single-site â-diiminate zinc complexes that are highly active for
the copolymerization of epoxides and carbon dioxide,3b as well
as the polymerization of optically active lactides.7 Due to the
significant steric bulk of the ligands, we anticipated that these
initiators might be capable of stereochemical control in the
polymerization of rac-lactide via a chain-end control mechanism.8
In such a reaction, the bulky ligands increase the influence of
the stereogenic center of the last inserted monomer, which in turn
determines whether (R,R)- or (S,S)-lactide is enchained. Therefore
two scenarios are possible: if a chain end of R stereochemistry
selects (R,R)-lactide (meso enchainment; kR/RR . kR/SS), then
isotactic PLA forms; if this chain end selects (S,S)-lactide (racemic
enchainment; kR/SS . kR/RR), then heterotactic9 PLA forms (Scheme
1). Although stereocontrol of this type is conceptually very simple,
only a modest degree of chain-end control during lactide
polymerization has previously been reported.10,11
Reaction of Zn(N(TMS)2)2 with the 2,6-diisopropylphenyl-
substituted â-diimine ligand ((BDI)H) produces the zinc complex
[(BDI)ZnN(TMS)2] in quantitative yield. Although this complex
slowly initiates the polymerization of lactide, we decided to
transform the sterically bulky amido group of this complex into
an isopropoxide group that would be a more suitable mimic of
the putative propagating alkoxide species (Scheme 1). Reaction
of [(BDI)ZnN(TMS)2] with 2-propanol produces the desired
complex [(BDI)ZnOiPr] (2) in 54% isolated yield following
crystallization. The molecular structure of 2, determined by X-ray
diffraction, reveals a dimeric species in the solid state where
isopropoxide ligands bridge distorted tetrahedral zinc centers
(Figure 1).12
Compound 2 is highly active for the polymerization of rac-
lactide (1); in 20 min at 20 °C, 2 polymerized 1 to 95% conversion
([2] ) 2.1 × 10-3 M, [1]/[2] ) 200). Gel-permeation chroma-
tography (GPC, versus polystyrene standards) revealed a Mn of
37900 g/mol and a molecular weight distribution (MWD) of 1.10.
This narrow polydispersity and the experimentally determined
linear correlation between Mn and percent conversion are indica-
(8) For some recent examples of polymerization catalysts with bulky ligands
that control stereochemistry by a chain-end control mechanism, see: (a) Small,
B. L.; Brookhart, M. Macromolecules 1999, 32, 2120-2130. (b) Resconi, L.;
Abis, L.; Franciscono, G. Macromolecules 1992, 25, 6814-6817.
(9) Heterotactic macromolecules are a rare type of polymer that have
alternating pairs of stereogenic centers in the main chain (i.e. only mr/rm
dyads are present). For some recent examples, see: (a) Hirano, T.; Yamaguchi,
H.; Kitayama, T.; Hatada, K. Polym. J. 1998, 30, 767-769. (b) Yamada, K.;
Nakano, T.; Okamoto, Y. Macromolecules 1998, 31, 7598-7605. (c)
Kitayama, T.; Hirano, T.; Hatada, K. Tetrahedron 1997, 53, 15263-15279.
(d) Nakahama, S.; Kobayashi, M.; Ishizone, T.; Hirao, A. J. Macromol. Sci.,
Pure Appl. Chem. 1997, A34, 1845-1855. (e) Fossum, E.; Matyjaszewski,
K. Macromolecules 1995, 28, 1618-1625.
(1) Brintzinger, H. H.; Fischer, D.; Mulhaupt, R.; Rieger, B.; Waymouth,
R. M. Angew. Chem., Int. Ed. Engl. 1995, 34, 1143-1170.
(2) Ivin, K. J.; Mol, J. C. Olefin Metathesis and Metathesis Polymerization;
Academic Press: San Diego, 1997.
(3) For some notable exceptions, see: (a) Ovitt, T. M.; Coates, G. W. J.
Am. Chem. Soc. 1999, 121, 4072-4073. (b) Cheng, M.; Lobkovsky, E. B.;
Coates, G. W. J. Am. Chem. Soc. 1998, 120, 11018-11019. (c) Chamberlain,
B. M.; Sun, Y. P.; Hagadorn, J. R.; Hemmesch, E. W.; Young, V. G.; Pink,
R.; Hillmyer, M. A.; Tolman, W. B. Macromolecules 1999, 32, 2400-2402.
(d) Spassky, N.; Wisniewski, M.; Pluta, C.; Le Borgne, A. Macromol. Chem.
Phys. 1996, 197, 2627-2637. (e) Chisholm, M. H.; Eilerts, N. W. Chem.
Commun. 1996, 853-854. (f) Kruper, W. J.; Dellar, D. V. J. Org. Chem.
1995, 60, 725-727. (g) Aida, T.; Inoue, S. Acc. Chem. Res. 1996, 29, 39-
48.
(4) Chiellini, E.; Solaro, R. AdV. Mater. 1996, 8, 305-313.
(5) These polymers are therefore formally poly(lactide)s, but to simplify
the stereochemical nomenclature they will be referred to poly(lactic acid)s in
this paper.
(6) For examples of Al, Mg, Sn, and Y-based alkoxide initiators, see: (a)
Dubois, P.; Jacobs, C.; Je´roˆme, R.; Tessie´, P. Macromolecules 1991, 24, 2266-
2270. (b) Reference 3e. (c) Kricheldorf, H. R.; Lee, S. R.; Bush, S.
Macromolecules 1996, 29, 1375-1381. (d) Stevels, W. M.; Dijkstra, P. J.;
Feijen, J. Trends Polym. Sci. 1997, 5, 300-305.
(7) Cheng, M.; Ovitt, T. M.; Hustad, P. D.; Coates, G. W. Polym. Prepr.
1999, 40 (1), 542-543.
(10) Kasperczyk has reported that LiOtBu polymerizes rac-lactide to PLA
that is enriched in heterotactic sequences: Kasperczyk, J. E. Macromolecules
1995, 28, 3937-3939.
(11) (a) Thakur, K. A. M.; Kean, R. T.; Hall, E. S.; Kolstad, J. J.; Lindgren,
T. A.; Doscotch, M. A.; Siepmann, J. I.; Munson, E. J. Macromolecules 1997,
30, 2422-2428. (b) Thakur, K. A. M.; Kean, R. T.; Hall, E. S.; Kolstad, J. J.;
Munson, E. J. Macromolecules 1998, 31, 1487-1494. (c) Wisniewski, M.;
Le Borgne, A.; Spassky, N. Macromol. Chem. Phys. 1997, 198, 1227-1238.
(d) Coudane, J.; Ustariz-Peyret, C.; Schwach, G.; Vert, M. J. Polym. Sci.,
Polym. Chem. Ed. 1997, 35, 1651-1658.
(12) Crystal data of 2: orthorhombic, Pbca, colorless; a ) 21.4727(4) Å,
b ) 19.5105(3) Å, c ) 33.3509(3) Å; V ) 13972.1(4); Z ) 8; R ) 0.0540;
GOF ) 1.033.
10.1021/ja992678o CCC: $18.00 © 1999 American Chemical Society
Published on Web 11/24/1999

11584 J. Am. Chem. Soc., Vol. 121, No. 49, 1999
Communications to the Editor
1
Figure 2. Homonuclear decoupled H NMR spectrum of the methine
region of heterotactic PLA prepared with 2 at 0 °C (500 MHz, CDCl3).
1
The reaction of 1 with 2 (9:1) was monitored by H NMR; in 5
Figure 1. Molecular structure of [2]2. Selected bond distances (Å) and
angles (deg): Zn(1)-N(1), 2.074(4); Zn(1)-N(2), 2.054(4); Zn(1)-O(1),
1.983(3); N(1)-Zn(1)-N(2), 94.8(2); N(1)-Zn(1)-O(1), 122.95(15);
N(2)-Zn(1)-O(1), 126.08(14); O(1)-Zn(1)-O(2), 78.50(12); Zn(1)-
O(1)-Zn(2), 101.72(13).
min, 1 was completely consumed. The reaction was quenched
by adding methanol, then the crude material was analyzed by
electrospray-ionization mass spectrometry. Molecular ions cor-
responding to (BDI)H2+ (m/z 419) and oligomers of the formula
+
H(OCHMeCO)2nOiPr‚NH4 (n ) 3 to 12) were found. This
tive of a living polymerization, as well as a single type of reaction
site. Microstructural analysis of the polymer by 1H NMR revealed
that 2 exerts a significant influence on the tacticity of the polymer
formed, as the microstructure is highly heterotactic. On the basis
of the spectrum, the probability of a racemic enchainment in the
polymer (Pr )13 is 0.90; in other words, 90% of the linkages formed
are between lactide units of opposite stereochemistry. To further
increase the stereoregularity of the heterotactic PLA, we per-
formed the polymerization using 2 at 0 °C. The reaction reached
95% conversion after 2 h. GPC revealed a Mn of 38800 g/mol
and a MWD of 1.09. Shown in Figure 2 is the homonuclear
decoupled 1H NMR spectrum of the methine region of the PLA.
The shifts at 5.22 and 5.14 ppm are the heterotactic rmr and mrm
tetrads, respectively. From the intensities of these peaks and those
attributed to the mmm, mmr, and rmm impurities,14 a Pr of 0.94
can be calculated.13 Despite the stereoregularity of the polymer,
it is an amorphous material with a Tg of 49 °C.
strongly supports our hypothesis that the â-diiminate ligand does
not react with lactide, but instead it remains bound to the zinc
center while the isopropoxide group initiates polymerization. We
propose that the bulky ligand serves to increase the stereochemical
influence of the polymer chain-end on stereocontrol, thus forming
the highly heterotactic microstructure.
In conclusion, we report a zinc alkoxide complex that acts as
a single-site, living initiator for the polymerization of rac-lactide
to heterotactic PLA. Mass spectrometry experiments revealed that
the isopropoxide group initiates polymerization, while the â-di-
iminate ligand remains chelated to the zinc center. Current work
is directed at determining the factors which favor racemic over
meso enchainment, as well as employing 2 for the synthesis of
new polyester architectures.
Acknowledgment. We thank the NSF (Career Award CHE-9875261)
for support of this research. This work made use of the Cornell Center
for Materials Research facilities (supported by the NSF; DMR-9632275)
and the Cornell Department of Chemistry and Chemical Biology X-ray
Facility (supported by the NSF; CHE-9700441). G.W.C. gratefully
acknowledges a Camille and Henry Dreyfus New Faculty Award, an
Alfred P. Sloan Research Fellowship, a Research Corporation Research
Innovation Award, a 3M Untenured Faculty Grant, and an IBM
Partnership Award.
To determine that the isopropoxide group of 2 initiates
polymerization of lactide while the â-diiminate ligand remains
bound to the zinc center, we performed the following experiment.
(13) Pr is the probability of a racemic placement between monomer units
(i.e. (R,R)-1 followed by (S,S)-1, or vice versa). Pr can also be expressed in
terms of the enchainment rate constants: Pr ) kR/SS/(kR/SS + kR/RR) ) kS/RR
/
(kS/RR + kS/SS). The expressions for the tetrad concentrations in terms of Pr,
assuming Bernoullian statistics and the absence of transesterification, are as
follows:10,11d [mmm] ) (2(1 - Pr)2 + Pr(1 - Pr))/2; [mrm] ) (Pr2 + Pr(1 -
Pr))/2; [mmr] ) [rmm] ) (Pr(1 - Pr))/2; [rmr] ) Pr2/2.
Supporting Information Available: Synthesis of 2, polymerization
procedure, mass spectrometry data, and crystal structure data for 2 (PDF).
This material is free of charge via the Internet at http://pubs.acs.org.
(14) Thakur, K. A. M.; Kean, R. T.; Zell, M. T.; Padden, B. E.; Munson,
E. J. Chem. Commun. 1998, 1913-1914.
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