Synthetic, structural, mechanistic, and computational studies on single-site β-diketiminate tin(II) initiators for the polymerization of rac-lactide

Article abstract of DOI:10.1021/ja061400a

A family of tin(II) complexes supported by β-diketiminate ligands has been investigated as initiators for the polymerization of rac-lactide. Kinetic studies reveal a first-order dependence on [lactide], but with a significant induction period. Linear plot

Full text of DOI:10.1021/ja061400a

Published on Web 07/07/2006
Synthetic, Structural, Mechanistic, and Computational Studies
on Single-Site â-Diketiminate Tin(II) Initiators for the
Polymerization of rac-Lactide
Andrew P. Dove, Vernon C. Gibson,* Edward L. Marshall, Henry S. Rzepa,
Andrew J. P. White, and David J. Williams
Contribution from the Department of Chemistry, Imperial College London, Exhibition Road,
London SW7 2AZ, U.K.
Received March 8, 2006; E-mail: V.Gibson@imperial.ac.uk
W This paper contains enhanced objects available on the Internet at
http://pubs.acs.org/journals/jacsat.
Abstract: A family of tin(II) complexes supported by â-diketiminate ligands has been investigated as initiators
for the polymerization of rac-lactide. Kinetic studies reveal a first-order dependence on [lactide], but with
a significant induction period. Linear plots of Mn versus conversion and [M]o/[I]o versus conversion, along
with narrow molecular weight distributions (typically 1.07-1.10), are indicative of well-controlled, “living”
polymerizations. Less sterically hindered derivatives promote faster propagation than their bulky analogues,
in accord with a more accessible active site. Enhanced rates of polymerization are observed for ligands
bearing halogenated N-aryl substituents, a consequence of the more Lewis acidic nature of the Sn(II) centers.
All of the initiators exhibit a similar bias toward heterotactic polylactide, which is attributed to a chain-end
control mechanism influenced predominantly by the presence of the Sn 5s2 lone pair of electrons rather
than the steric or electronic properties of the â-diketiminate ligand. The tin(II) isopropyl-(S)-lactate complex,
(
MeBDIDIPP)SnOCH(Me)COOiPr (14), has been synthesized as a model compound for the propagating
species by treatment of (MeBDIDIPP)Sn(NMe2) with isopropyl-(S)-lactate. An X-ray structure determination
showed that the lactate ligand forms a five-membered chelate ring with a weak donor bond from the carbonyl
oxygen atom to the tin center. A B3LYP density functional computational study indicates that insertion of
the first lactide monomer into the tin(II) alkoxide bond is facile, with the induction period arising from a
slower insertion of the second (and possibly third and fourth) monomer units.
Introduction
widely accepted that the active initiator in this catalyst system
is a tin(II) alkoxide species generated in situ upon reaction of
In recent years, there has been increasing interest in materials
derived from biorenewable resources as environmentally sus-
tainable alternatives to petrochemical-derived products. Among
the most prominent examples is polylactide (PLA),1 which is
presently being developed as a commodity polymer for packag-
ing, film, and fiber applications. Polylactide and its copolymers,
most typically derived from lactide and glycolide, have been
employed for many years in speciality biomedical applications,2
including their use as bioresorbable sutures and orthopedic
implants, drug delivery agents, and scaffolds for tissue engineer-
ing.
SnOct2 with alcoholic additives or feedstock impurities.5,6,8,9
Consistently, bis(alkoxide) complexes such as Sn(OBun)2 are
active initiators for lactide polymerization.10,11
Due to the importance of divalent tin catalysts in the
commercial production of polylactide and its copolymers, we
decided to investigate the possibility of stabilizing a single-site
tin(II) initiator that might polymerize lactide under relatively
mild conditions and in a well-controlled fashion in order to
facilitate the synthesis of tailored polylactide products. In an
earlier communication we showed that a mono-alkoxide tin(II)
complex can be synthesized using the sterically demanding N,N′-
bis(2,6-diisopropylphenyl) (DIPP) â-diketiminate ligand (Scheme
1), and we found that this complex polymerized rac-LA in a
well-controlled manner to give polylactide with a slight het-
At present, PLA is prepared industrially via the ring-opening
polymerization of L-lactide (LA) using tin(II) carboxylate
catalysts such as bis(2-ethylhexanoate)tin (SnOct2).3-7 It is now
(1) Drumright, R. E.; Gruber, P. R.; Henton, D. E. AdV. Mater. 2000, 12, 1841.
(2) Middleton, J. C.; Tipton, A. J. Biomaterials 2000, 21, 2335.
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25, 6419.
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P.; Feijen J. J. Polym. Sci. Part A: Polym. Chem. 1997, 35, 219.
(9) Du, Y. J.; Lemstra, P. J.; Nijenhuis, A. J.; van Aert, H. A. M.; Bastiaansen,
C. Macromolecules 1995, 28, 2124.
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Polym. Chem. 1997, 35, 3431.
(10) Kowalski, A.; Libiszowski, J.; Duda, A.; Penczek, S. Macromolecules 2000,
33, 1964.
(5) Kricheldorf, H. R.; Kreiser-Saunders, I.; Boettcher, C. Polymer 1995, 36,
1253.
(6) Kowalski, A.; Duda, A.; Penczek, S. Macromolecules 2000, 33, 689.
(11) Duda, A.; Penczek, S.; Kowalski, A.; Libiszowski, J. Macromol. Symp.
2000, 153, 41.
9
9834
J. AM. CHEM. SOC. 2006, 128, 9834-9843
10.1021/ja061400a CCC: $33.50 © 2006 American Chemical Society

Tin(II) Initiators for Polymerization of rac-Lactide
A R T I C L E S
Scheme 1
Scheme 2 a
a Reagents: (i) nBuLi, SnCl2; (ii) LiOiPr; (iii) LiNMe2; (iv) Sn(NMe2)2;
i
(v) PrOH.
Figure 1. (a) Plot of Mn vs monomer conversion for the polymerization
of rac-LA initiated by complex 2 (25 °C, CH2Cl2, [LA]0/[2] ) 100) (b)
Plot of Mn vs [LA]0/[2] (60 °C, toluene); polydispersities are given in
parentheses. Mn was determined by GPC in CHCl3 vs polystyrene calibrants
(see Supporting Information).
erotactic bias.12 This tin system forms part of a wider family of
single-site divalent metal initiators supported by â-diketiminate
ligands, including, for example, derivatives based on Zn,13,14
Mg,14-17 Fe,18 and Ca.19,20 Tolman and co-workers have
additionally reported a single-site tin(II) initiator supported by
sterically demanding benzamidinate ligands.21
Here, we report extensions of our work on divalent tin
initiators to a variety of other â-diketiminate ligands of general
formula [HC{C(R)dNAr}2] (abbreviated as RBDIAr). We were
especially interested in exploring the effect of changes to the
steric and electronic properties of the ligand substituents on
polymerization rates and molecular weight control, as well as
their potential for controlling the tacticity of the polylactide
products.
The second proceeds via the reaction of [MeBDIDIPP]H with Sn-
23
(NMe2)2 to afford [MeBDIDIPP]Sn(NMe2) (3), followed by its
i
alcoholysis with 1 equiv of PrOH.
Complex 2 polymerizes rac-LA slowly at room temperature,
requiring 50 h to attain >95% conversion of 100 monomer
equivalents. The polymerization is well-controlled, producing
PLA with an Mn value close to that predicted from the monomer-
to-initiator ratio [Mn(obs) ) 17 100 Da, Mn(calc) ) 14 400 Da]
and a very narrow molecular weight distribution (Mw/Mn )
1.05). In accord with a well-behaved chain propagation process,
Mn increases linearly with monomer conversion, and low Mw/
Mn values are maintained throughout the polymerization (Figure
1a). NMR spectroscopic analysis reveals a small bias toward a
heterotactic assembly,12 with notably increased concentrations
of the rmr and mrm tetrads24 compared to those predicted by
Bernoullian statistics for a random, atactic assembly.25 At 60
°C in toluene, the polymerization proceeds to >90% monomer
conversion within 4 h. Mn and Mw/Mn values are comparable
to those obtained at ambient temperature (Mn ) 17 100 Da, Mw/
Mn ) 1.08), with Mn again exhibiting a linear correlation with
monomer conversion and monomer-to-initiator stoichiometry
(Figure 1b).
Results
Polymerization of rac-Lactide by (MeBDIDIPP)SnOiPr.
[
MeBDIDIPP]Sn(OiPr) (2, DIPP ) 2,6-di-isopropylphenyl) can
be prepared by either of the two routes shown in Scheme 2.
One involves treatment of [MeBDIDIPP]Li with SnCl2 to give
[
MeBDIDIPP]SnCl (1),12,22 followed by its reaction with LiOiPr.
(12) Dove, A. P.; Gibson, V. C.; Marshall, E. L.; White, A. J. P.; Williams, D.
J. Chem. Commun. 2001, 283.
(13) Cheng, M.; Attygalle, A. B.; Lobkovsky, E. B.; Coates, G. W. J. Am. Chem.
Soc. 1999, 121, 11583.
(14) Chamberlain, B. M.; Cheng, M.; Moore, D. R.; Ovitt, T. M.; Lobkovsky,
E. B.; Coates, G. W. J. Am. Chem. Soc. 2001, 123, 3229.
(15) Chisholm, M. H.; Huffman, J. C.; Phomphrai, K. Dalton Trans. 2001, 222.
(16) Chisholm, M. H.; Gallucci, J.; Phomphrai, K. Inorg. Chem. 2002, 41, 2785.
(17) Gibson, V. C.; Marshall, E. L.; Dove, A. P. Patent WO 0238574.
(18) Gibson, V. C.; Marshall, E. L.; Navarro-Llobet, D.; White, A. J. P.;
Williams, D. J. Dalton Trans. 2002, 4321.
(19) Chisholm, M. H.; Gallucci, J.; Phomphrai, K. Chem. Commun. 2003, 48.
(20) Chisholm, M. H.; Gallucci, J.; Phomphrai, K. Inorg. Chem. 2004, 43, 6717-
6725.
The propagation process can be conveniently followed by
1H NMR spectroscopy at room temperature; selected spectra
of a 1:10 mixture of [2]:[LA] in CDCl3, recorded over a period
(22) Stender, M.; Wright, R. J.; Eichler, B. E.; Prust, J.; Olmstead, M. M.;
Roesky, H. W.; Power, P. P. Dalton Trans. 2001, 3465.
(23) Foley, P.; Zeldin, M. Inorg. Chem. 1975, 14, 2264.
(21) Aubrecht, K. B.; Hillmyer, M. A.; Tolman, W. B. Macromolecules 2002,
35, 644-650.
9
J. AM. CHEM. SOC. VOL. 128, NO. 30, 2006 9835

A R T I C L E S
Dove et al.
1
Figure 2. 250 MHz H NMR spectra (δ 2.9-5.5) for the reaction of complex 2 with rac-LA (25 °C, CDCl3, [LA]0/[1] ) 10); see text for assignments of
He-g
.
of 20 h, are shown in Figure 2. Initially, resonances are observed
for 2 (aryl CHaMe2 methine septets at δ 3.10 and δ 3.65, the
OCHbMe2 septet at δ 4.00, and a singlet at δ 4.95, due to the
methine group in the â-diketiminate backbone, Hc) and for
unconsumed monomer (the methine Hd resonance visible as a
quartet at δ 5.05). As the polymerization commences, these
resonances diminish in intensity and are replaced by signals
attributable to propagating species. These include a broad signal
at δ 5.2, He, due to the methine resonance of propagating PLA
oligomers and a multiplet at δ 4.55, Hf, corresponding to a
other notable feature of the spectra is the gradual broadening
of the â-diketiminate aryl CHMe2 resonances as Ha is replaced
by Hg; such broadening is consistent with the formation of
propagating chains differing only in chain length and/or tacticity.
A linear correlation between ln{[LA]t/[LA]0} and reaction
time indicates that propagation is first order in monomer concen-
tration. Similar analyses over a range of initiator concentrations
(Figure 3a) afforded a plot of ln kapp against ln [2] from which
the order in initiator was found to be 1.10 ( 0.04 (Figure 3b).
It is clear from Figure 3a that the plots would not extrapolate
through the origin and that there is an apparent induction period
of ∼42 min at 60 °C. Thereafter, propagation proceeds with an
apparent rate constant, kapp, of 0.736 ( 0.049 h-1. We shall re-
turn to examine the nature of this induction period in more detail.
i
CO2 Pr ester end-group; the corresponding doublet resonances
are observed at δ 0.95 and δ 0.87, respectively. The observation
of ester chain termini implies that ring-opening of the cyclic
ester monomer occurs via cleavage of an acyl-oxygen bond,
as found for other metal alkoxide initiating systems.26-33 The
Synthesis and Characterization of Related â-Diketiminate
Tin(II) Initiators. The synthetic pathways outlined in Scheme
2 have been used to synthesize derivatives containing a range
of â-diketiminate ligands of general formula [HC{C(R)d
NAr}2]; these are summarized in Figure 4.
(24) The m/r (m ) meso; r ) racemic) notation is an alternative to the i/s (i )
iso; s ) syndio) system also encountered in the literature.
(25) Kricheldorf, H. R.; Boettcher, C.; To¨nnes, K. U. Polymer 1992, 33, 2817.
(26) Trofimoff, L.; Aida, T.; Inoue, S. Chem. Lett. 1987, 991.
(27) Shimasaki, K.; Aida, T.; Inoue, S. Macromolecules 1987, 20, 3076.
(28) Kricheldorf, H. R.; Berl, M.; Scharnagl, N. Macromolecules 1988, 21, 286.
(29) Dubois, Ph.; Jacobs, C.; Je´roˆme, R.; Teyssie´, Ph. Macromolecules 1991,
24, 2266.
In addition to complexes 1-3, which contain methyl sub-
stituents on the ligand backbone, the chloride and isopropoxide
(30) Stevels, W. M.; Ankone´, M. J. K.; Dijkstra, P. J.; Feijen, J. Macromol.
Chem. Phys. 1995, 196, 1153.
(31) Chisholm, M. H.; Eilerts, N. W. Chem. Commun. 1996, 853.
(32) LeBorgne, A.; Pluta, C.; Spassky, N. Macromol. Rapid Commun. 1994,
15, 955.
(33) Ihara, E.; Tanabe, M.; Nakayama, Y.; Nakamura, A.; Yasuda, H. Macromol.
Chem. Phys. 1999, 200, 758.
9
9836 J. AM. CHEM. SOC. VOL. 128, NO. 30, 2006

Tin(II) Initiators for Polymerization of rac-Lactide
A R T I C L E S
Figure 3. (a) Semilogarithmic plots of rac-LA conversion with time
initiated by complex 2 (60 °C, toluene, [LA]0 ) 0.28 M; for I, [2] ) 0.0035
M; for II, [2] ) 0.0028 M; for III, [2] ) 0.0021 M; for IV, [2] ) 0.0014
M). (b) Plot of ln kapp vs ln [2] for the polymerization of rac-LA initiated
by 2 (60 °C, toluene).
Figure 4. (RBDIAr)SnX complexes synthesized in this study.
derivatives 4 and 5, bearing tert-butyl backbone substituents,
have been prepared. The effect of the tert-butyl substituents is
to force the N-aryl groups to project further forward, effectively
increasing steric hindrance around the active site.34,35 Lithiation
of [tBuBDIDIPP]H, followed by addition to SnCl2, afforded
[tBuBDIDIPP]SnCl (4) in good yield (ca. 80%). The reaction
required heating at 80 °C for 18 h, compared to 25 °C for the
analogous synthesis of 1, reflecting the increased steric hin-
drance of the tert-butyl-substituted diketimine. Addition of 1.0
equiv of LiOiPr to 4, followed by stirring at 80 °C for 18 h,
gave 5 in ca. 70% yield.
The less sterically crowded tin(II) alkoxides [MeBDIDMP]-
SnOiPr (7, DMP ) 2,6-dimethylphenyl) and [MeBDIPh]SnOiPr
(9) have been prepared in an analogous manner via the addition
of LiOiPr to the appropriate chloride complexes 6 and 8,
respectively. Although the synthesis of complex 7 proceeded
in high yield, 9 was initially isolated as an impure oily solid.
Purification was achieved by repeated washing with cold
heptane, but yields are consequently lowered (to ca. 20%). Due
to the problems associated with the synthesis of 9 via this route,
the corresponding amide, [MeBDIPh]SnNMe2 (10), was synthe-
sized by the addition of [MeBDIPh]H to Sn(NMe2)2 in toluene
(67%). However, attempts to convert 10 into 9 via treatment
Figure 5. Molecular structure of complex 3. The N(1)-Sn-N(16) angle
is 95.59(12)°; other relevant bond lengths and angles are given in Table
S1.
ward manner by addition of the â-diketimines [MeBDIDCP]H,
[MeBDITCP]H, and [MeBDITBP]H, respectively, to Sn(NMe2)2
(DCP ) 2,6-dichlorophenyl; TCP ) 2,4,6-trichlorophenyl; TBP
) 2,4,6-tribromophenyl).
X-ray Crystallography. X-ray-quality crystals of complexes
3, 9, and 12 were grown and analyzed as described in the
Supporting Information. Their molecular structures (Figures
5-7) all show the tin centers to adopt a trigonal pyramidal
geometry with angles of 90-100° between the nitrogen donors
of the â-diketiminate ligands and the oxygen or nitrogen donor
atoms of the ancillary alkoxide or amide ligands, respectively.
This geometrical constraint arises from the effect of a relativistic
contraction of the tin 5s orbital, resulting in only a small amount
of mixing with other tin-based orbitals. Thus, the bonding is
i
with PrOH resulted in unclean product mixtures.
The amide derivatives 11-13, containing electron-withdraw-
ing halo substituents, were similarly prepared in a straightfor-
(34) Budzelaar, P. H. M.; van Oort, A. B.; Orpen, A. G. Eur. J. Inorg. Chem.
1998, 1485.
(35) Bailey, P. J.; Coxall, R. A.; Dick, C. M.; Fabre, S.; Parsons, S.
Organometallics 2001, 20, 798.
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A R T I C L E S
Dove et al.
Table 1. Data for the Polymerization of rac-LA Using Tin(II)
Alkoxide and Amide Complexesa
time
(h)b
conv
(%)c
kapp
induction
period (min)d
Mn
(Da)e
Mw/
1
e
initiator
(h-
)
Mn
Prf
2
3
5
7
9
10
11
12
13
4
94 0.736 ( 0.049
92 0.703 ( 0.043
96 0.384 ( 0.020
92 0.996 ( 0.024
93 1.634 ( 0.024
42
150
67
24
8
11
10
8
17 100 1.06 0.64
17 000 1.18 0.64
16 000 1.16 0.63
16 800 1.12 0.65
17 100 1.13 0.67
17 600 1.18 0.67
19 500 1.23 0.64
21 000 1.19 0.62
20 300 1.24 0.64
7
8
3
2
2.25 93 1.403 ( 0.157
1.75 92 1.578 ( 0.024
1.5
91 1.884 ( 0.177
2.25 91 1.214 ( 0.095
12
a Polymerizations performed in toluene at 60 °C; [LA]/[initiator] ) 100;
[LA] ) 2.8 M. b Time required for monomer conversion >90%. c Conver-
sion, as determined by 1H NMR spectroscopy (CDCl3). d Determined by
extrapolation of kinetic data. e Determined by GPC (vs polystyrene standards
CHCl3). f Probability of racemic enchainment, as determined by homo-
1
nuclear decoupled H NMR.13
Figure 6. Molecular structure of complex 9. Selected bond angles (°):
N(1)-Sn-O(20) ) 98.2(4), N(3)-Sn-O(20) ) 93.8(3).
translated (along a) counterpart at C‚‚‚O ) 3.39 Å, H‚‚‚O )
2.51 Å, CsH‚‚‚O ) 153°. The two pendant aromatic rings in
complex 12 (Figure 7) are oriented virtually orthogonally (ca.
93°) to the {N1,C1,C3,N3} plane, and adjacent lattice-translated
(along b) molecules are linked by a weak CsH‚‚‚π interaction
between the C(8)sH proton and the C(12) phenyl ring, with
H‚‚‚π ) 2.89 Å and CsH‚‚‚π ) 132°. Further discussion of
other aspects of the structures of 3, 9, and 12, including a
comparison with related molecules, can be found in the
Supporting Information.
Polymerization Studies. The polymerization of rac-LA using
the alkoxides and amides described above is summarized in
Table 1. For the amide initiator 3, at first sight propagation
appears to be slower than for 2, with high conversions (>90%)
being achieved only after 7 h. However, on close examination,
a significant part of this (150 min) was found to be due to an
induction period and, once initiation had occurred, the apparent
rates of propagation for 2 and 3 are similar within experimental
error (kapp(2) ) 0.736 ( 0.049 h-1; kapp(3) ) 0.703 ( 0.043
h-1). The polymerization of rac-LA using 3 was still well-
controlled, with a linear dependence of Mn upon monomer
conversion, but the polydispersity was slightly higher than that
measured using its isopropoxide counterpart, which is attribut-
able to less efficient initiation by the more sterically hindered
NMe2 derivative (the presence of the CO2NMe2 chain end was
confirmed by 1H NMR spectroscopy; see Figure 12). The
polylactide produced using 3 displayed a microstructure identical
to that of the polylactide produced using 2.
Figure 7. Molecular structure of complex 12. Selected bond angles (°):
N(1)-Sn-N(18) ) 95.8(2), N(3)-Sn-N(18) ) 96.1(2).
dominated by interactions of the ligand donor atoms with the
tin p and d orbitals; the lone pair remains nonbonding and
occupies quite a large and diffuse region of space.
For complex 3 (Figure 5), the two 2,6-diisopropylphenyl rings
are oriented orthogonally (ca. 90°) to the {N(1),C(1),C(1A),
N(1A)} plane, a conformation that is possibly stabilized by pairs
of CsH‚‚‚N(pπ) interactions between the isopropyl methine
protons and the nitrogen center [H‚‚‚N ) 2.47 and 2.57 Å].36
There are no significant intermolecular interactions, the closest
approach to the phenyl ring being 3.19 Å from an isopropyl
methyl proton. In complex 9, the isopropoxide ligand is folded
back over the six-membered chelate ring (Figure 6), but any
potential interaction between the isopropyl methine proton and
the six-membered chelate ring is discounted on the basis of the
proton lying ca. 2.59 Å away from the {N1,C1,C3,N3} plane,
with a noticeably enlarged Sn-O(20)-C(21) angle of 129.8-
(8)°. The two phenyl rings, which are both less steeply inclined
to the {N1,C1,C3,N3} plane than in complex 3 (ca. 70°), are
involved in a series of weak intermolecular CsH‚‚‚π interac-
tions. The C(6) phenyl ring in one molecule is approached from
opposite sides by C(13)sH [H‚‚‚π ) 2.78 Å, CsH‚‚‚π ) 157°]
and C(22)sH [H‚‚‚π ) 2.82 Å, CsH‚‚‚π ) 154°] from two
symmetry-related molecules, the two interactions subtending an
angle of ca. 160° at the C(6)-ring centroid. The C(12) phenyl
ring is approached by the C(8)sH proton in another molecule
(H‚‚‚π ) 2.82 Å, CsH‚‚‚π ) 148°). The closest approach to
the O(20) oxygen atom is from the C(2)sH proton of a lattice-
The increased steric influence of the BDI ligand in 5 resulted
in a significant slowing of polymerization rate and an increase
in the induction period. The observed rate of propagation, kapp
) 0.384 ( 0.020 h-1, was approximately half that observed
for 2. Although the polymerization was slower, the polymer
microstructure remained unchanged.
A decrease in the size of the ortho substituents (cf. 7, 9, and
10) led to an increase in polymerization rate and a decrease in
induction period. Hence, 7 consumed >90% monomer within
3 h, with an induction period around half of that observed using
2. Even faster propagation and a shorter induction period were
observed for complexes 9 and 10. Interestingly, even with
sterically less hindered ligands, the tacticities of the polylactide
samples produced using 7, 9, and 10 are virtually identical to
those observed using complexes 2, 3, and 5.
(36) Dove, A. P.; Gibson, V. C.; Hormnirun, P.; Marshall, E. L.; Segal, J. A.;
White, A. J. P.; Williams, D. J. Dalton Trans. 2003, 3088.
9
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Tin(II) Initiators for Polymerization of rac-Lactide
A R T I C L E S
Figure 8. Plot of Mn vs monomer conversion for the polymerization of
rac-LA initiated by complex 12 (60 °C, toluene, [LA]0/[12] ) 100;
polydispersities in parentheses).
Scheme 3. Synthesis of the Sn(II) Lactate Complex, 14
The rate of propagation increases when electron-withdrawing
halo-substituted â-diketiminate ligands are used. A comparison
of the sterically similar N,N′-bis(2,6-dimethylphenyl) and N,N′-
bis(2,6-dichlorophenyl) derivatives, 7 and 11, shows a substan-
tial increase in the rate of propagation for the halogenated
derivative. Furthermore, the induction period using the amide
complex 11 was less than half of that observed using the
alkoxide 7, despite the presence in the former of the more bulky
amide nucleophile. The polymerization rate is further enhanced
for the 2,4,6-trichloro derivative, 12, whereas the lower elec-
tronegativity of the 2,4,6-tribromo-substituted analogue 13 (and
possibly its increased size) afforded a slightly slower polym-
erization. In all cases, the microstucture of the PLA showed no
discernible variation from the slight heterotactic bias observed
using 2.
Although Mn was found to increase linearly with conversion
for all three halo-substituted initiators (see, for example, Figure
8), the molecular weights of the isolated polymers derived from
11-13 were slightly higher than those prepared from their non-
halogenated counterparts. Broader molecular weight distributions
were also observed. This is most likely due, in part, to the use
of the NMe2 initiating group which, due to its larger size,
initiates less efficiently than OiPr (cf. 2 and 3, or 9 and 10,
Table 1). However, low levels of trans-esterification of the PLA
chains due to the increased reactivity of the more electron-
deficient metal center may also be responsible. An indication
that trans-esterification does occur is evident in the broadening
of Mw/Mn as the polymerization approached high levels of
monomer conversion (Figure 8).
Figure 9. (a) Molecular structure of complex 14. Selected bond lengths
(Å): N(1)-Sn ) 2.228(6); N(3)-Sn ) 2.223(5); O(30)-Sn ) 2.028(6);
O(33)-Sn ) 2.755(6). Selected bond angles (°): N(1)-Sn-N(3) ) 83.1-
(2); N(1)-Sn-O(30) ) 84.4(3); N(3)-Sn-O(30) ) 95.3(2); Sn-O(30)-
C(31) ) 122.0(5). (b) Space-filling representation showing the exposed tin
center.
equatorial and axial sites, while the Sn-O bond of the alkoxo
unit occupies an equatorial site. The carbonyl group of the lactate
ligand forms only a weak interaction (2.755(6) Å) to the tin by
binding in the remaining axial site, trans to N(1) of the BDI
ligand. The chelate ring has an asymmetric boat conformation,
with the metal atom and C(2) being displaced by 0.87 and 0.13
Å, respectively, out of the {N(1),C(1),C(3),N3} plane, whose
atoms are coplanar to within 0.01 Å. The two 2,6-diisopropyl-
phenyl rings are oriented approximately orthogonally to the
plane of the chelate ring, the torsional twists about the N(1)-
C(6) and N(3)-C(18) bonds being ca. 85 and 83°, respectively.
As was observed in the structure of 2, the O-donor ligand is
directed away from the chelate ring, in contrast to the observa-
tion in the structure of the related (trifluoromethanesulfonato-
O)tin(II) complex, where the sulfonato ligand is folded back to
lie over the plane of the chelate ring.36 The trigonal pyramidal
geometry at tin therefore places the metal atom in an exposed
position on the surface of the molecule (Figure 9b). There are,
however, no close intermolecular approaches to the metal center,
the nearest contacts being from the isopropyl group of the lactate
ligand in symmetry-related molecules.
Spectroscopic and Structural Characterization, and Po-
lymerization Behavior, of a Tin(II) Lactate Intermediate.
To obtain a better understanding of the propagating species,
i
the complex [MeBDIDIPP]SnOCH(Me)CO2 Pr (14) was synthe-
sized by treatment of 3 with isopropyl-(S)-lactate (Scheme 3).
Crystals of 14 suitable for X-ray diffraction were grown from
heptane at -10 °C. The coordination geometry may be viewed
(Figure 9a) as being derived from a trigonal bipyramid with a
vacant equatorial coordination site. The BDI ligand spans the
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A R T I C L E S
Dove et al.
Scheme 4. General Reaction Coordinate for the Ring-Opening
Scheme 5 a
Polymerization of Lactidea
a Pn ) propagating polyester chain.
The remarkably long metal-carbonyl oxygen interaction in
complex 14 contrasts the chelating role played by the lactate
ligand in the structure of the related zinc complex rac-
[
MeBDIDIPP]Zn(µ2-OCH(Me)CO2Me) (Zn-Ocarbonyl ) 2.189(2)
Å)14 but does still lie within the sum of tin and oxygen van der
Waals radii (2.17 + 1.52 ) 3.69 Å).37
To probe the coordination of the lactate ligand in solution,
1H NOESY and COSY NMR spectra were recorded.38 These
show that the methine proton of the [Sn-OCHMe] lactate
fragment closely approaches two of the aryl-iPr substituents.
However, the lactate methyl C(32) shows no interactions with
any of the â-diketiminate substituents, suggesting that rotation
about the Sn-O(30) and the O(30)-C(31) vectors does not
readily occur. The low symmetry of complex 14, arising from
the locked nature of the lactate ligand, results in a room-
temperature 1H NMR spectrum which includes four septets and
i
eight doublets, arising from the inequivalent Pr groups of the
â-diketiminate fragment, and two [HC(C(CH3)NAr)2] methyl
resonances. Although these data are consistent with coordination
of the C(33)-O(33) carbonyl to the tin center, the hindered
rotation may simply arise as a result of steric congestion around
the metal. Evidence for weak coordination of O(33) to the metal
in the solution state is provided by a 119Sn NMR chemical shift
of -265.3 ppm. Four-coordinate SnII chemical shifts generally
occur in the range δ -550 to δ -650,39 but the value for 14 is
nonetheless larger than the chemical shifts of a wide range of
three-coordinate (BDI)SnX complexes (e.g. δ -189.1 for 2),38
an observation consistent with weak coordination of the carbonyl
group.
A study into the polymerization of rac-LA initiated by 14
gave an apparent rate of propagation comparable to that
observed using 2 (kapp(14) ) 0.744 ( 0.072 h-1). The molecular
weight control is also almost identical (Mn ) 15 600, Mw/Mn
< 1.10), Mn values again increasing linearly with monomer
conversion and the PLA produced showing a comparable
heterotactic bias. However, somewhat surprisingly, 14 still
afforded an induction period s of approximately 20 min (cf.
42 min for 2) s before onset of polymerization. Thus, it is clear
a R, reactants; INT, monomer-bound intermediate, R‚LA; TI, tetrahedral
intermediate; TS, transition state; P, propagating species. The lone pair is
included in the illustrations of intermediates and transition states, not to
imply a specific coordination site for the lone pair but to remind the reader
that the geometry of the complex is strongly influenced by its presence.
that 14 is an imperfect model for the propagating species. To
understand why this should be so, and to gain more insight into
the origin of the induction period, we embarked upon a quantum
chemical study.
Computational Studies. Recently, we reported a theoretical
investigation into the ring-opening polymerization of rac-lactide
by â-diketiminate magnesium complexes.40 A schematic of the
computed reaction coordinate, which was found to contain two
energetically comparable transition states, is shown in Scheme
4. A similar B3-LYP density functional procedure has been
carried out on the N,N′-bis(2,6-diisopropylphenyl) â-diketimi-
nate tin(II) system with one key difference. To address the origin
of the induction period, the addition of an (S,S)-lactide monomer
to the tin(II) alkoxide initiator was first examined, followed by
insertion of a second (R,R)-monomer unit into the propagating
polyester chain.
(37) Bondi, A. J. Phys. Chem. 1964, 68, 441.
(38) See Supporting Information.
(39) Harris, R. K.; Mann, B. E. NMR and the Periodic Table; Academic Press:
London, 1978; pp 342-366.
(40) Marshall, E. L.; Gibson, V. C.; Rzepa, H. S. J. Am. Chem. Soc. 2005, 127,
6048.
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Tin(II) Initiators for Polymerization of rac-Lactide
A R T I C L E S
heterocycle then occurs on passing through TS2, comprising
an eight-membered ring with a Sn-Oalkoxide bond (2.31 Å) and
a longer Sn-Ocarbonyl donor interaction (2.44 Å). Extrusion of
the PLA chain from the tin coordination sphere occurs by
dissociation of the carbonyl donor interaction and migration of
the Sn-alkoxide bond to a resting coordination site similar to
the starting complex (R). The resting state of the first insertion
product, P1, contains a five-membered Sn lactate, with a long
Sn‚‚‚Ocarbonyl interaction of 2.88 Å, a value close to that found
in complex 14 (2.755(6) Å). The energy-minimized structure
of P1 is shown in Figure 10.
The second insertion follows a similar pattern, but the
incoming monomer molecule must now make its approach to
the five-membered Sn lactate of P1, rather than the simple
methoxide ligand of R. Monomer binds in an analogous site
trans to one of the nitrogen donors (INT′, Scheme 6), and a
turnstile-like rotation is again required in order to position the
monomer for attack by the alkoxide (TS1′). The gross features
of the subsequent steps are similar to those described above
for the insertion of the first monomer unit (full details are
provided in the Supporting Information).
Figure 10. Computed geometry of P1 (gray, carbon; blue, nitrogen; red,
oxygen; purple, tin).
Scheme 6
The free energies for the key steps of both first and second
monomer insertions are summarized in Figure 11 (values are
shown relative to R ) 0 kcal mol-1). A number of differences
are apparent for the two insertion steps: (i) TS1 is rate-
determining in the initiation step, whereas TS1′ and TS2′ have
nearly identical free energies for insertion of the second
monomer; (ii) intermediates TI1 and, to a lesser extent, TI2
are relatively low-lying (1.5 and 5.9 kcal mol-1, respectively)
for the first insertion, but relatively high-lying for the second
(TI1′ ) 12.1 kcal mol-1; TI2′ ) 7.7 kcal mol-1), a consequence
of the additional donor interaction with the Sn center; and (iii)
P1, the first insertion product, is a potential energy well (-5.9
kcal mol-1 relative to R) and has an activation free energy
barrier of 25.9 kcal mol-1 relative to INT, whereas the activation
energy for the second insertion is 30.7 kcal mol-1 (TS2′ -
INT′). P1 is therefore anticipated to form quite readily, but the
second monomer unit will insert more slowly. Additions of the
third and subsequent monomer units (which due to the size of
For the reaction between [MeBDIDIPP]SnOMe and (S,S)-
lactide, the monomer approach is found to be strongly affected
by the geometric constraints imposed by the tin lone pair. The
monomer initially binds weakly to a site trans to a nitrogen
donor of the BDI ligand (INT, Scheme 5). To proceed to TS1,
the first of the two major transition states, the monomer and
the alkoxide ligand first exchange sites via a turnstile rotation.
The tetrahedral intermediate thus generated (TI1) exhibits a
Sn‚‚‚OMe interaction of 3.23 Å, a distance comparable to the
long Sn-Ocarbonyl interaction observed in the molecular structure
of 14. Rotation around the Oalkoxide-C vector next affords TI2,
allowing the Oacyl atom to approach the tin in readiness for ring-
opening (Sn‚‚‚Oacyl ) 2.93 Å). Cleavage of the six-membered
Figure 11. Free-energy changes along the reaction coordinate for insertion of first and second monomer units.
W Computational details are available in HTML format, including molecular coordinates (in molfile format), normal mode animations (in XYZ format),
together with a Java applet for displaying these, and 3D orbital models (in 3DMF format).
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A R T I C L E S
Dove et al.
Figure 12. 1H NMR spectra of the reaction between 10 and 5.0 equiv of rac-LA (CD2Cl2, 250 MHz, 298 K).
the system we have not attempted to model) are expected to be
more favorable: as the extruding polymer chain is no longer
restricted by interactions with the active site, its entropy should
increase with respect to that of the shorter initial chains, thus
reducing the activation and reaction free energies for subsequent
steps.
For example, the quartets of the methine protons, Ha and Hc,
which are observed at δ 5.20 and δ 4.63 in P1, gradually
broaden, with the former (the methine nearest to the amide chain
end) shifting to ca. δ 5.4 as further insertions occur and broad
polymer methine resonances (Hg) appear between δ 5.1 and δ
5.2. In the same region of the spectrum, the â-diketiminate
methine proton (Hb) is initially observed as a sharp singlet at δ
4.98 but, once polymerization commences, gives rise to a
broader signal at ca. δ 5.00. For the terminal dimethylamino
groups, two sharp singlets are observed, at δ 2.95 and δ 2.87,
due to the diastereotopic methyl environments (Hd), a result of
the adjacent chiral center, C(Ha)(CHe3). These are replaced by
two slightly broader downfield resonances (Hd′) as the oligo-
merization reaction proceeds. The 13C NMR spectrum of P1
exhibits two carbonyl resonances, at δ 178.88 and δ 170.04,
consistent with the metal lactate resting state.
Experimental Verification of the Computational Results.
To obtain experimental verification of the computational find-
ings, we examined the reaction of the N,N′-bis(phenyl)-â-
diketiminate tin(II) amide complex 10 with 5 equiv of lactide
1
monomer by H NMR spectroscopy. 10 was chosen since its
1H NMR spectrum is largely free of resonances in the region
3-6 ppm (where key resonances of propagating species occur)
and it displays induction energetics amenable to room-temper-
ature monitoring by NMR spectroscopy. The spectra collected
in Figure 12 show that P1 is formed in essentially quantitative
yield within <5 min of mixing 10 with LA at room temperature.
The spectrum of P1 contains two â-diketiminate Me singlet
resonances, at δ 1.94 and δ 1.92, a feature shared by complex
14. P1 thus clearly lacks a plane of symmetry in solution, which
is attributed to the presence of a weak Sn-Ocarbonyl interaction.
Discussion
The kinetic studies, along with molecular weight data, clearly
show that 2 behaves as a nonaggregated, single-site initiator.
This contrasts with tin(II) initiators supported by amidinate
ligands,21,41 for which rate order dependences of 0.2-0.3 have
been ascribed to aggregation of metal centers by the propagating
ester functionalities. The â-diketiminate ligand presumably
Monitoring the reaction over time shows that P1 predominates
at room temperature for at least 45 min, after which additional
resonances become apparent as P1 is converted into P2, P3, etc.
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Tin(II) Initiators for Polymerization of rac-Lactide
A R T I C L E S
possesses sufficient steric influence to avert such aggregative
processes, allowing all of the metal centers to remain continu-
ously active throughout the polymerization. More generally, the
(BDI)Sn catalysts show the anticipated trends in polymerization
rates with changes to the size of initiating group and the size
and electronic properties of the ligand substituents. Thus, the
more bulky amide derivatives generally initiate more slowly
than their isopropoxide counterparts, and increases in the size
of the â-diketiminate aryl substituents or the backbone substit-
uents lead to slower rates of polymerization. Incorporating
electron-withdrawing aryl groups accelerates the polymerization,
a consequence of the enhanced electrophilicity of the tin centers
which will favor monomer binding.
Figure 13. View of INT′ showing the tin-centered lone pair.
Somewhat to our surprise, the effect of variations to the
â-diketiminate ligand on tacticity is minimal, unlike the
observations with the analogous zinc system, in which stereo-
selectivity is dramatically influenced by quite subtle changes
to the ancillary ligand substituents.14 The absence of a significant
ligand influence for the tin system suggests that the microstruc-
ture of the resultant polylactide is dominated by the tin-centered
lone pair, which is known to impose severe constraints on the
tin coordination geometry and may give rise to electrostatic
repulsions with the lone pairs of the oxygen functionalities of
the monomer and propagating chain. Tolman, Hillmyer, and
Aubrecht have noted comparable levels of heterotacticity when
LA is polymerized using amidinate tin(II) complexes.21 We have
also found that conventional lactide polymerization catalysts,
without additional co-ligands, give rise to PLA of similar
tacticity.42 This suggests more generally that divalent tin
catalysts are strongly influenced by their stereochemically active
metal-based lone pair and that the mechanism is more reasonably
described as a lone-pair-dominated, chain-end-controlled pro-
cess, rather than the ligand-assisted, chain-end-controlled
process found for other (BDI)M systems.
The computational study lends further support to the dominant
effect of the tin-based lone pair. A key difference between the
computed reaction pathway for the tin system and other (BDI)M
initiators is the requirement for a significant initial reorganization
of the metal coordination sphere whereby the alkoxide and
monomer units first have to interchange sites to allow attack
by the alkoxide ligand. This is a direct consequence of the
presence of the metal-based lone pair. Furthermore, the calcu-
lated geometries of stationary points indicate that minimization
of repulsive forces between carbonyl oxygen lone pairs (of either
monomer or ring-opened lactate-type structures) and the tin lone
pair is a key factor throughout the insertion process, particularly
noticeable in the conversion of INT into TS1, and in the
structure of P. The extent to which the lone pair dominates the
metal coordination sphere can be seen in the computed view of
INT′ shown in Figure 13.
The tin lone pair is also strongly implicated as the cause of
the induction period. The calculated free energies for the first
two insertion cycles show that, while the first insertion process
is exothermic, the subsequent conversion of P1 into P2 is far
less favorable, an observation verified by NMR spectroscopic
studies. It is expected that subsequent insertion steps will become
increasingly exothermic as the polymer chain grows, its
increased flexibility leading to a favorable entropy term.
Conclusions
In summary, sterically hindered â-diketiminate ligands have
been shown to support well-defined, single-site Sn(II) initiators
for the polymerization of rac-lactide, affording anticipated trends
in polymerization rates with variations to the size of the initiating
groups and the size and electronic properties of the ligand
substituents. Two key differences compared to the polymeri-
zation behavior of other metal â-diketiminate initiators are (i)
an invariance of the polylactide tacticity across ligands of widely
differing steric and electronic properties and (ii) a significant
induction period prior to the onset of polymerization. Both of
these effects are attributable to the tin-centered lone pair, which
not only presents constraints on the tin coordination geometry
but also can give rise to electronic repulsions with the lone pairs
of the oxygen functionalities in the monomer and in the
propagating polymer chain.
Acknowledgment. The Engineering and Physical Sciences
Research Council (U.K.) is thanked for financial support (a
studentship to A.P.D.).
Supporting Information Available: Full synthetic details and
characterization data for complexes 1-14; NOESY and COSY
spectra of 14; crystal data, refinement parameters, and crystal-
lographic information files for 3, 9, 12, and 14 (PDF, CIF).
This material is available free of charge via the Internet at
http://pub.acs.org.
(41) Nimitsiriwat, N.; Gibson, V. C.; Marshall, E. L.; Elsegood, M. R. J.; Dale,
S. H. Manuscript in preparation.
(42) Polylactide samples prepared using SnOct2 and Sn(NMe2)2/nBuOH in
toluene at 60 °C have both been found to possess heteroselectivities similar
to those observed for the â-diketiminate tin(II) initiators described here:
Gibson, V. C.; Marshall, E. L. Unpublished results.
JA061400A
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J. AM. CHEM. SOC. VOL. 128, NO. 30, 2006 9843