Chiral salan aluminium ethyl complexes and their application in lactide polymerization

Article abstract of DOI:10.1002/chem.200900799

Synthetic routes to aluminium ethyl complexes supported by chiral tetradentate phenoxyamine (salan-type) ligands [Al(OC₆H ₂(R-O-R4)CH₂)₂{CH₃N(C ₆H₁₀)NCH₃}-C₂H₅] (4, 7: R = H; 5, 8: R = Cl; 6, 9: R = CH3) are reported. Enantiomerically pure salan ligands 1-3 with (R,R) configurations at their cyclohexane rings afforded the complexes 4, 5, and 6 as mixtures of two diastereoisomers (a and b). Each diastereoisomer a was, as determined by X-ray analysis, monomeric with a five-coordinated aluminium central core in the solid state, adopting a cis-(O,O) and cis-(Me,Me) ligand geometry. From the results of variabletemperature (VT) ¹H NMR in the tern-perature range of 220-335 K, ¹H- ¹H NOESY at 220K, and diffusion-ordered spectroscopy (DOSY), it is concluded that each diastereoisomer b is also monomeric with a five-coordinated aluminium central core. The geometry is intermediate between square pyramidal with a cis-(O,O), trans-(Me,Me) ligand disposition and trigonal bipyramidal with a rrans-(O,O) and trans(Me,Me) disposition. A slow exchange between these two geometries at 220 K was indicated by ¹H-¹H NOESY NMR. In the presence of propan-2-ol as an initiator, enantiomerically pure (R,R) complexes 4-6 and their racemic mixtures 7-9 were efficient catalysts in the ring-opening polymerization of lactide (LA). Polylactide materials ranging from isotactically biased (P_m up to 0.66) to medium heterotactic (P _r up to 0.73) were obtained from rac-lactide, and syndiotactically biased polylactide (P_r up to 0.70) from wicso-lactide. Kinetic studies revealed that the polymerization of (S,S)-LA in the presence of 4/propan-2-ol had a much higher polymerization rate than (R,R)-LA polymerization (k_ss/k_RR = 10.1).

Full text of DOI:10.1002/chem.200900799

DOI: 10.1002/chem.200900799
Chiral Salan Aluminium Ethyl Complexes and
Their Application in Lactide Polymerization
Hongzhi Du,[a, b, c] Aldrik H. Velders,[d] Pieter J. Dijkstra,[b, e] Jingru Sun,[a]
Zhiyuan Zhong,[e] Xuesi Chen,*[a] and Jan Feijen*[b]
Abstract: Synthetic routes to alumini-
um ethyl complexes supported by
perature range of 220–335 K, 1H–1H
NOESY at 220 K, and diffusion-or-
dered spectroscopy (DOSY), it is con-
cluded that each diastereoisomer b is
also monomeric with a five-coordinat-
ed aluminium central core. The geome-
try is intermediate between square pyr-
amidal with a cis-(O,O), trans-(Me,Me)
ligand disposition and trigonal bipyra-
midal with a trans-(O,O) and trans-
(Me,Me) disposition. A slow exchange
between these two geometries at 220 K
was indicated by 1H–1H NOESY
NMR. In the presence of propan-2-ol
as an initiator, enantiomerically pure
(R,R) complexes 4–6 and their racemic
mixtures 7–9 were efficient catalysts in
the ring-opening polymerization of lac-
tide (LA). Polylactide materials rang-
ing from isotactically biased (Pm up to
0.66) to medium heterotactic (Pr up to
0.73) were obtained from rac-lactide,
and syndiotactically biased polylactide
(Pr up to 0.70) from meso-lactide. Ki-
netic studies revealed that the polymer-
ization of (S,S)-LA in the presence of
4/propan-2-ol had a much higher poly-
merization rate than (R,R)-LA poly-
merization (kSS/kRR =10.1).
chiral
(salan-type) ligands [Al
4)CH2)2A{CH3N(C6H10)NCH3}-C2H5] (4,
tetradentate
phenoxyamine
A
CHTUNGTRENNUNG
C
ACHTUNGTRENNUNG
7: R=H; 5, 8: R=Cl; 6, 9: R=CH3)
are reported. Enantiomerically pure
salan ligands 1–3 with (R,R) configura-
tions at their cyclohexane rings afford-
ed the complexes 4, 5, and 6 as mix-
tures of two diastereoisomers (a and
b). Each diastereoisomer a was, as de-
termined by X-ray analysis, monomeric
with a five-coordinated aluminium cen-
tral core in the solid state, adopting a
cis-(O,O) and cis-(Me,Me) ligand ge-
ometry. From the results of variable-
Keywords: aluminum · chirality ·
lactide · polymerization · salan
1
temperature (VT) H NMR in the tem-
Introduction
different methods for the synthesis of PLAs have been ex-
ploited, the most convenient is the ring-opening polymeri-
zation (ROP) of lactide (LA), the cyclic dimer of lactic acid.
Current research in this area is particularly focused on the
design and synthesis of single-site catalyst/initiators of gener-
Poly(lactic acid)s (PLAs) prepared from renewable resour-
ces are important biodegradable materials for biomedical,
pharmaceutical, and agricultural applications.[1] Although
[a] Dr. H. Du, Dr. J. Sun, Prof. Dr. X. Chen
Changchun Institute of Applied Chemistry
Chinese Academy of Sciences, Changchun 130022 (China)
Fax : (+86)431-85262112
[d] Dr. A. H. Velders
Laboratory of Supermolecular Chemistry and Technology
University of Twente, 7500 AE, Enschede (The Netherlands)
[e] Dr. P. J. Dijkstra, Prof. Dr. Z. Zhong
E-mail: xschen@ciac.jl.cn
Biomedical Polymers Laboratory and
[b] Dr. H. Du, Dr. P. J. Dijkstra, Prof. Dr. J. Feijen
Department of Polymer Chemistry and BioMaterials
Faculty of Science and Technology
Jiangsu Key Laboratory of Organic Chemistry
College of Chemistry, Chemical Engineering and Materials Science
Soochow University, Suzhou 215123 (China)
Institute for Biomedical Technology, University of Twente
7500 AE, Enschede (The Netherlands)
Fax : (+31)53-4892155
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200900799.
E-mail: J.Feijen@tnw.utwente.nl
[c] Dr. H. Du
Graduate School of Chinese Academy of Sciences
Beijing 100039 (China)
9836
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 9836 – 9845

FULL PAPER
al formula LnMR,[2] in which M is a central metal atom, li-
gated with Ln, which represents an ancillary ligand. R is the
initiating group covalently linked through a remaining
vacant orbital. The steric and electronic properties of the
ligand affect the activity and the stereoselectivity of the cat-
alyst. Appropriate combinations of Ln with M and R have
generated numerous catalyst/initiators containing Ca,[3] Al,[4]
Zn or Mg,[5] Ti,[6] or Fe,[7] as well as the rare earth elements[8]
as central metal atoms. Most of these catalysts are highly ef-
ficient and lactide polymerization proceeds in a well-con-
trolled manner. Moreover, in certain cases stereoregular
PLAs have been obtained from rac-LA [an equimolar mix-
ture of (S,S)-LA and (R,R)-LA)] or meso-LA by use of
these metal complexes.[9–11] Some recent breakthroughs in
the stereoselective polymerization of lactide in the presence
of rare earth metals complexed by achiral phenoxyamine li-
gands have been achieved by the groups of Carpentier[12]
and Cui,[13] who have prepared highly heterotactic PLAs
from rac-LA.
LA polymerization, affording highly isotactic PLAs with Pi
values of up to 0.93.[9c,d] In this paper we describe the syn-
thesis and structures of chiral salan aluminium ethyl com-
plexes with regard to their ligand wrapping modes, as well
as to their catalytic behavior in lactide polymerization in the
presence of propan-2-ol as an initiator.
Results and Discussion
Synthesis of chiral salan aluminium ethyl complexes: Enan-
tiomeric (R,R)-1,2-diaminocyclohexane was obtained from
trans-1,2-diaminocyclohexane by a procedure described by
Larrow et al.[26] The synthesis of the ligand precursors
(R,R)-1 and rac-1 (Scheme 1) was accomplished by a three-
step procedure. Firstly, a condensation between racemic or
(R,R)-1,2-diaminocyclohexane and salicylaldehyde (2 equiv)
yielded the salen intermediate. Subsequent reduction of the
imine bonds in the presence of an excess of NaBH4 afforded
the salan intermediate. The ligand precursors were obtained
by condensation of the secondary amine groups with an
excess of formaldehyde and reduction with an excess of
NaBH4 (Scheme S1 in the Supporting Information). The
syntheses of the ligand precursors rac-2, (R,R)-2, rac-3, and
(R,R)-3 (Scheme 1) were carried out similarly, except that
the salan intermediates were synthesized through Mannich
condensations of 2,4-substituted phenols, formaldehyde, and
racemic or (R,R)-1,2-diaminocyclohexane (Scheme S2 in the
Supporting Information). All ligands were isolated as white
crystalline solids in high yields after recrystallization from
acetone.
Tetradentate phenoxyamine ligands are usually referred
to as salan-type ligands, which can be considered fully re-
duced Schiff base (salen) ligands (Scheme 1).[14] The salan-
Treatment of the enantiomeric pure salan ligand precur-
sors (R,R)-1, (R,R)-2, or (R,R)-3 with equimolar amounts of
AlEt3 in toluene at 708C resulted in the formation of salan
aluminium ethyl complexes 4, 5, and 6, respectively
(Scheme 1). Interestingly, the 1H NMR spectroscopic data
for 4, 5, and 6 in [D8]toluene at 295 K clearly revealed the
presence of two species in each case. One species (a) gives a
dissymmetric resonance pattern, whereas the other (b) gives
a symmetric resonance pattern. The molar ratios of a/b in 4,
5, and 6 were 10:4, 10:2.5, and 10:3, respectively. As an ex-
Scheme 1. Structures of salan ligands and their aluminium ethyl com-
plexes. The configurations at the cyclohexane rings are either (R,R) or
racemic mixtures of (R,R) and (S,S).
type ligands have more flexible structures than salen ligands,
due to the sp3 hybridization of their amine nitrogen atoms.
A salan ligand containing a trans-1,2-diaminocyclohexane
bridge may lead to various kinds of interesting chiral metal
1
ample, in the H NMR spectrum of 4 (Figure 1), the appear-
ꢀ
complexes. Recently, chiral Fe
(salan)[18] complexes have been studied and applied in the
asymmetric oxidation of sulfides. Chiral Ti
(salan)[19–21] com-
plexes have been exploited in the asymmetric addition of
metal alkyls to aldehydes, whereas Mo
(salan)[22] complexes
A
N
ance of four doublets for the benzylic ArCH2 NCH3 pro-
2
V
A
tons at 3.70, 3.60, 3.19, and 2.71 ppm with a J
N
U
pling constant of 13.0 Hz, together with the two singlets at
ꢀ
1.84 and 1.72 ppm for the N CH3 protons (Figure 1, top),
N
both indicated dissymmetric surroundings of these groups in
the salan complex, which was denoted 4a. On the other
hand, the symmetric resonance pattern includes two dou-
have been used in the enantioselective pinacol coupling of
aryl aldehydes. Moreover, Kol and co-workers have demon-
ꢀ
strated that chiral Zr
(salan) complexes have the ability to
blets for the benzylic ArCH2 NCH3 protons appearing at
2
initiate isospecific polymerization of hex-1-ene, 4-methyl-
pent-1-ene,[23] or vinylcyclohexane,[24] as well as the cyclopo-
lymerization of hexa-1,5-diene.[23]
3.44 and 3.28 ppm with the same J
N
ꢀ
and a singlet at 1.80 ppm for the N CH3 protons (Figure 1,
top), and this complex was denoted 4b. Moreover, the meth-
ylene protons in the aluminium ethyl groups in 4a or 4b dis-
played a significant difference in chemical shift (Figure 1,
bottom), showing that these protons in 4a or 4b are all dia-
stereotopic. Because of the gem-hydrogen effect, each quar-
The structures and catalytic applications of chiral Al-
ACHTUNGTRENNUNG
(salan) complexes, however, have never been reported.[25]
Previously, we described a chiral Jacobsen salen aluminium
isopropoxide, which exerts significant stereocontrol in rac-
Chem. Eur. J. 2009, 15, 9836 – 9845
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
9837

X. Chen et al.
Figure 2. Molecular structure of 4a; all hydrogen atoms are omitted for
clarity.
The complex 4a was monomeric with a five-coordinated
central aluminium atom (Figure 2). The geometry around
such a five-coordinated aluminium atom would ideally be
square pyramidal or trigonal bipyramidal and can be ex-
pressed by a t value, which is 0 in the case of an ideal
square pyramidal (sqp) and 1 in that of an ideal trigonal bi-
pyramidal (tbp) geometry.[27] The t value of 4a is 0.53, re-
vealing a geometry intermediate between A, an ideal sqp,
and B, an ideal tbp in this complex (Scheme 2, below). The
t value of 4a is higher than that of the corresponding chiral
salen aluminium methyl complex (t=0.35),[28] indicating a
more flexible ligand geometry, as a result of the sp3 hybridi-
zation of the tertiary amine nitrogen atoms in the salan
complex. The two phenolic oxygen atoms exist in a cis ar-
Figure 1. Expanded region of the 1H NMR spectrum of 4, indicating the
presence of two diastereoisomers a and b. Top) 600MHz, [D8]toluene,
ꢀ
295 K, ArCH2 NCH3. Bottom) AlCH2CH3.
tet is spilt into an unresolved double quartet. The 1H–1H
NOESY spectrum of 4 in [D8]toluene at 295 K revealed no
slow exchange between the species 4a and 4b on the NMR
timescale (Figure S1 in the Supporting Information). Single
crystals of 4a were isolated from a saturated toluene solu-
tion at room temperature and characterized by X-ray analy-
sis (Figure 2; for crystallographic data see Table 1). Despite
several attempts, only single crystals of species 4a were ob-
tained.
ꢀ
rangement relative to the central aluminium. The Al1 N1
ꢀ
[2.115(3) ꢁ] and Al1 N2 [2.222(4) ꢁ] bond lengths
(Table S1 in the Supporting Information) are both in the
ꢀ
2.01–2.26 ꢁ range, values generally observed for Al N bond
lengths in tetradentate salen aluminium ethyl complexes.[29]
The two methyl groups on the nitrogen atoms are in a cis
configuration relative to the five-membered ring formed by
Al1, N1, N2, C1, and C6. The nitrogen atoms have become
chiral, due to the coordination with Al. The configurations
of the two nitrogen atoms are R for N2 and S for N1.
Table 1. Crystallographic data for 4a and 9a.
4a
9a
formula
crystal size [mm]
formula weight
cryst. syst.
space group
a [ꢁ]
b [ꢁ]
c [ꢁ]
a [8]
C24H33AlN2O2
0.20ꢂ0.19ꢂ0.09
408.50
monoclinic
P21
7.7422(10)
17.058(2)
8.7022(10)
90
C28H41AlN2O2
0.27ꢂ0.13ꢂ0.08
464.61
monoclinic
P21/c
14.5190(12)
14.5891(11)
12.3277(10)
90
100.100(2)
90
2570.8(4)
4
1.200
MoKa (0.71073)
26.08
0.106
To clarify the structure of 4b further, additional NMR
characterization was performed. In 27Al NMR, four-coordi-
nated aluminium complexes give resonance signals at
~70 ppm, whereas five- or six-coordinated aluminium com-
plexes give resonance signals at ~40 and ~0 ppm, respective-
ly.[30] The 27Al NMR spectrum of 4 did not exhibit any peaks
in the ꢀ70 to 280 ppm range, perhaps due to the asymmetric
coordination of the salan ligand around the aluminium
center.[31] However, DOSY NMR measurements revealed
that 4a and 4b have comparable diffusion coefficients, indi-
cating similar effective molecular radii, and further demon-
strating that 4b is also monomeric. This also indicates that
b [8]
100.678(2)
90
1129.4(2)
2
g [8]
V [ꢁ3]
Z
1calcd [gcmꢀ3
]
1.201
radiation (l), [ꢁ]
2q max [8]
MoKa (0.71073)
26.05
0.112
m [mmꢀ1
]
F
G
440
1008
14235
305
no. of obsd reflns
6374
1
4b may be a diastereoisomer of 4a. The VT H NMR spec-
no. of params refnd
265
GOF
R1
wR2
1.050
0.0625
0.0731
1.017
0.0583
0.1269
tra of 4 ([D8]toluene) in the 295–335 K temperature range
did not reveal any tendency for the resonances of the ben-
ꢀ
zylic ArCH2 NCH3 protons of 4b to coalesce (Figure S2 in
9838
www.chemeurj.org
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 9836 – 9845

Lactide Polymerization
FULL PAPER
the Supporting Information). This indicates that the two
ꢀ
Al N bonds in 4b are stable at room temperature or even
higher temperatures. The symmetric resonance pattern for
ꢀ
the four benzylic ArCH2 NCH3 protons of 4b at 295 K indi-
cates that these protons are symmetrically arranged in the
complex. From this information, either the highly symmetric
sqp geometry C or the tbp geometry D, or even a geometric
intermediate between C and D, was considered the most
probable for 4b (Scheme 2, below). Because of the presence
of only one singlet for the N-methyl groups of 4b at 295 K,
it is assumed that the two N-methyl groups exist in a trans
arrangement. To reveal the structure of 4b fully, 1D and
2D NMR experiments were carried out.
1
Firstly, VT H NMR analysis of 4 in [D8]toluene was per-
formed. With decreasing temperature the two doublets for
ꢀ
the four benzylic ArCH2 NCH3 protons of 4b seen at 295 K
Figure 4. 1H–1H NOESY NMR spectrum of 4 at in [D8]toluene 220 K
split into two doublets (partly overlapping) and a broad
peak at 220 K (Figure 3). It is speculated that with a further
decrease in the temperature this broad peak should also
split into two doublets. Moreover, the singlet representing
ꢀ
(ArCH2 NCH3 region). Evidence for the exchange between the two geo-
metries of 4b is provided by the presence of additional exchange-NOE
cross-peaks labeled X.
ꢀ
the N CH3 protons at 295 K split into two broad peaks at
220 K (Figure S3 in the Supporting Information).
Figure 3. VT 1H NMR spectra of 4 in [D8]toluene between 220–295 K
Scheme 2. Schematic representation of the geometries adopted by diaste-
reoisomers a and b.
ꢀ
(ArCH2 NCH3 region).
The 1H–1H NOESY NMR spectrum of 4 at 220 K dis-
played positive off-diagonal cross-peaks (with the diagonal
cross-peaks phased in positive sign, and the NOE cross-
rations (with respect to the nitrogen centers) or even mix-
tures of the two are present in 4b (Scheme 2).
On the basis of the NMR and X-ray analysis, it is reasona-
ble to assume two different pathways by which these chiral
salan aluminium ethyls were formed. Because the conforma-
tion of the cyclohexane ring is fixed upon formation of the
five-coordinated aluminium complex, the positions of the
methyl groups on the nitrogen atoms will also be fixed.
Once the free ligand in the solution coordinates the alumini-
um atom with the N-methyl groups in a cis position, a wrap-
ping mode with a cis-(O,O) geometry in-between A (sqp)
and B (tbp) should be favored. The chiral salan ligand gen-
erates diastereoisomer 4a with (R,S) chiral nitrogen centers.
On the other hand, if the free ligand in the solution adopts
a conformation with the N-methyl groups in a trans position,
a geometry intermediate between C (sqp) and D (tbp) as in
ꢀ
peaks observed at opposite sign) between the ArCH2 NCH3
ꢀ
protons (Figure 4) as well as the N CH3 protons of 4b (Fig-
ure S4 in the Supporting Information). All of these observa-
tions indicate that at 220 K a slow exchange takes place be-
tween two geometries of 4b. From these data, it is assumed
that diastereoisomer 4b adopts a geometry intermediate be-
tween C and D with the N-methyl groups existing in a trans
orientation (Scheme 2). At 295 K, diastereoisomer 4b shows
a fast exchange between the sqp geometry C and the tbp ge-
ometry D on the NMR timescale. At low temperatures, the
exchange between these two geometries was slow enough to
be observable by NMR. So far, however, we have not been
able to conclude whether either the (R,R) or (S,S) configu-
Chem. Eur. J. 2009, 15, 9836 – 9845
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
9839

X. Chen et al.
diastereoisomer 4b should be favored, with either (R,R) or
(S,S)—or even both—configurations for the chiral nitrogen
centers.
The configurations of the two nitrogen atoms are R for N2
and S for N1.
The salan aluminium complexes 7–9 were obtained from
racemic mixtures of the ligands 1–3 (Scheme 1). Only single
crystals of 9a could be isolated from a saturated toluene so-
lution at room temperature. X-ray analysis of 9a (Figure 5;
Ring-opening polymerization of rac- and meso-LA in solu-
tion: Because it had so far not been possible to separate dia-
stereoisomers a and b, complexes 4–6 and 7–9 were each
treated with propan-2-ol (1 equiv) to generate the active iso-
propoxide initiators for the ROP of rac- or meso-LA in situ.
All polymerizations were carried out in toluene at 708C,
and the levels of conversion were monitored by 1H NMR
determination of samples withdrawn from the reaction mix-
tures. In the presence of propan-2-ol as an initiator, 4–6 and
7–9 furnished PLAs with similar number average molecular
weights as calculated, as well as narrow molecular weight
distributions, indicating well-controlled polymerization.
Representative polymerization results are summarized in
Table 2.
The tacticities of the resulting polymers were determined
by inspection of the methine region in their homonuclear
decoupled 1H NMR spectra. Compound 4/propan-2-ol and
compound 7/propan-2-ol polymerized rac-LA to form iso-
tactically biased polymers with Pm values of 0.66 (Figure 6a)
and 0.62, respectively. In contrast, 6/propan-2-ol and 9/
propan-2-ol, with methyl substituents at the ortho and para
positions of their phenolic groups, furnished atactic materi-
Figure 5. Molecular structure of 9a; all hydrogen atoms are omitted for
clarity.
for crystallographic data see
Table 2. Polymerization of rac- and meso-LA in the presence of salan aluminium ethyl compounds 4–9 and
propan-2-ol.[a]
Table 1) revealed that the com-
plex was also dissymmetric
with a five-coordinated central
aluminium atom as in 4a. The
packing modes in the unit cell
of 9a show that a racemate
crystallization had occurred. A
t value of 0.90 is calculated, in-
dicating a trigonal bipyramidal
geometry with N1 and O2 oc-
cupying the axial positions, and
N2, C17, and O1 located in the
equatorial plane. The central
aluminium atom deviates from
the equatorial plane by ca.
0.201 ꢁ in the direction of O2.
[c]
[d]
[b]
LA
Catalyst
t [h]
Conv. [%][b]
Mn,calcd ꢂ103
Mn,GPC ꢂ103
Mn,NMR ꢂ103
PDI
Pm,Pr[e]
rac
rac
rac
meso
meso
meso
rac
rac
rac
4
5
6
4
5
6
7
8
9
10
57
69
23
27
27
9
70.7
87.6
87.0
97.3
83.1
93.5
89.0
84.8
85.5
5.09
6.31
6.27
7.01
5.99
6.74
6.41
6.11
6.16
5.45
5.59
6.26
5.79
4.38
5.86
8.00
5.59
5.71
5.81
6.97
6.03
6.56
5.14
6.91
8.19
6.00
6.05
1.09
1.10
1.10
1.12
1.09
1.10
1.12
1.10
1.09
P
P
P
P
P
P
P
P
P
G
CHTUNGTRENNUNG
CHTUNGTRENNUNG
CHTUNGTRENNUNG
CHTUNGTRENNUNG
CHTUNGTRENNUNG
34
53
CHTUNGTRENNUNG
CHTUNGTRENNUNG
[a] All polymerizations were carried out in toluene at 708C, [LA]0 =0.534m, [Al]0 =10.7 mm. [b] Determined
from 1H NMR. [c] Mn of PLA calculated from Mn =144.13ꢂ50 ꢂconv%. [d] Determined by GPC (THF), rela-
[33]
tive to PS standards. The value of Mn was calculated according to Mn =0.58Mn,GPC
.
[e] The parameters Pm
and Pr are the probabilities of meso and racemic enchainments of monomer units, respectively. Pm was calcu-
lated from: [mmm]=P2m + (1ꢀPm)Pm/2, [mmr]=[rmm]=(1ꢀPm)Pm, [rmr]=(1ꢀPm)2, and [mrm]=[(1ꢀPm)2
+
P
N
ꢀ
The axial bond length for Al1
O2 [1.7931(18) ꢁ] is slightly
ꢀ
longer than that for its equatorial counterpart Al1 O1
[1.7631(17) ꢁ]. Moreover, in relation to N2, placed in the
equatorial plane with a bond length of 2.039(2) ꢁ from Al1,
the N1 atom located at the axial site is weakly coordinated
als from rac-LA with Pr values of 0.55 and 0.57, respectively.
Interestingly, 5/propan-2-ol afforded heterotactically biased
PLAs with a Pr value of 0.64. Heterotactic PLAs cannot be
obtained from rac-LA through a site control mechanism
(SCM) with use of an enantiomeric pure complex, so this re-
veals the existence of a chain-end control mechanism
(CEM) with use of 5/propan-2-ol in the rac-LA polymeri-
zation. The heterotacticity of the PLA resulting from rac-
LA increased to 0.73 when 8/propan-2-ol was used (Fig-
ure 6b), which probably indicates the operation of a propa-
gating chain exchange mechanism as proposed by Coates
and co-workers.[9b] In this case, the heteroselectivity of 8/
ꢀ
to Al1 with a longer Al1 N1 distance [2.448(2) ꢁ]. Similar
weak interactions were also observed in an aluminium com-
plex ligated by an achiral salan ligand reported by Gibson
and co-workers[25] and in an aluminium complex stabilized
by a 1,w-dithiaalkanediyl-bridged bis(phenolate) ligand re-
ported by Okuda et al.[4c] As in 4a, the methyl groups on the
nitrogen atoms exist in a cis arrangement relative to the
five-membered ring formed by C6, C1, N2, N1, and Al1.
9840
www.chemeurj.org
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 9836 – 9845

Lactide Polymerization
FULL PAPER
propan-2-ol should be enhanced relative to that of 5/
propan-2-ol because of a more frequent positive cooperation
effect between a CEM and a SCM, resulting from the occur-
rence of rapid exchange between propagating chains bound
to each different enantiomeric ligand before insertion of a
subsequent monomer unit (Scheme 3). The 4/propan-2-ol, 5/
propan-2-ol, and 6/propan-2-ol systems afforded syndiotacti-
cally biased PLAs from meso-LA with Pr values of 0.64, 0.70
(Figure 6c), and 0.69, respectively. This clearly confirms the
operation of a SCM in meso-LA polymerization with use of
these chiral complexes.
To gain a better insight into the polymerization mecha-
nism, detailed kinetic studies of rac-LA in the presence of
4–6 and 7–9 together with propan-2-ol as initiator were per-
formed. Conversion of rac-LA over time at various concen-
trations of 7/propan-2-ol in toluene at 708C were monitored
by 1H NMR spectroscopy ([LA]0 =0.534m, [Al]0 =10.7 to
21.4 mm, and [LA]0 =0.267m, [Al]0 =8.9 mm). In each case,
first-order kinetics in monomer were observed and the ap-
propriate semilogarithmic plots are shown in Figure 7a. The
polymerization of rac-LA in the presence of 7/propan-2-ol
as catalyst/initiator thus proceeds according to:
ꢀd½LAꢁ=dt ¼ kapp½LAꢁ
ð1Þ
where kapp =kp[Al]x, and kp is the propagation rate constant.
To determine the order in aluminium (x), kapp was plotted
against [Al]0 (Figure 7b). In this plot, kapp increased linearly
with the aluminium concentration, indicating a first order in
aluminium (x). Therefore, the polymerization of rac-LA in
the presence of 7/propan-2-ol followed the overall kinetic
equation:
Figure 6. Methine regions of homonuclear decoupled 1H NMR spectra of
PLAs produced: from rac-LA by use of a) 4/propan-2-ol, b) 8/propan-2-
ol, and c) from meso-LA with 5/propan-2-ol as catalyst/initiator system.
Scheme 3. Proposed polymer exchange mechanism for the explanation of the enhancement of heteroselectivity and activity of 8 compared to 5 (* indi-
cates the aluminium isopropoxides formed by 8 upon addition of propan-2-ol).
Chem. Eur. J. 2009, 15, 9836 – 9845
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
9841

X. Chen et al.
[(S,S)-LA:
k
app =517ꢂ10ꢀ3 hꢀ1
;
(R,R)-LA:
kapp =51.0ꢂ
10ꢀ3 hꢀ1, Figure S6 in the Supporting Information], indicat-
ing that 4 has a marked preference for the polymerization
of (S,S)-LA over that of (R,R)-LA, which is evidence for
the operation of a SCM. However, the kinetic resolution
ability of 4 for rac-LA (kSS/kRR =10.1, Table 4, entry 1) is
Table 4. Apparent rate constants for (S,S)- and (R,R)-LA polymeri-
zations in the presence of 4, 5, and 6 as catalysts and propan-2-ol as an
initiator.[a]
Entry Complex kapp,(S,S)-LA [ꢂ10ꢀ3 hꢀ1
]
kapp,(R,R)-LA [ꢂ10ꢀ3 hꢀ1
]
kSS/kRR
1
2
3
4
5
6
517
27.5
29.0
51.0
44.5
35.4
10.1
0.62
0.82
[a] All polymerizations were carried out in toluene at 708C, [LA]0 =
0.534m, [Al]0 =10.7 mm.
much lower than that of other reported chiral Schiff base
aluminium systems [kRR/kSS ꢂ20 reported by Spassky for
[9a]
(R)-(SalBinap)AlOCH3
and kSS/kRR ꢂ14 reported by us
for (R,R)-cyclohexylsalen-AlOiPr[9d]). Moreover, the intro-
duction of chlorine atoms or methyl groups both lead to de-
creased kinetic resolution for 5 and 6 with (R,R)- and (S,S)-
LA. Unlike 4, which shows a preference towards (S,S)-LA,
5 has a preference toward (R,R)-LA with a kSS/kRR value of
0.62 (Table 4, entry 2, Figure S7), as does 6, with a kSS/kRR
value of 0.82 (Table 4, entry 3, Figure S8).
Figure 7. a) First-order kinetic plots for the ROP of rac-LA by 7/propan-
2-ol as catalyst/initiator system in toluene at 708C with [LA]0 =0.534 m:
I) [LA]0/[Al]0 =25; II) [LA]0/[Al]0 =35; III) [LA]0/[Al]0 =50, [LA]0 =
0.267m; IV) [LA]0/[Al]0 =30. b) Linear plot of kapp vs [Al]0 for the poly-
merization of rac-LA with 7/propan-2-ol as catalyst/initiator system.
ꢀd½LAꢁ=dt ¼ kp½Alꢁ½LAꢁ
ð2Þ
Finally, conversion versus time data were collected for the
polymerization of rac-LA in the presence of 5/propan-2-ol
or 8/propan-2-ol and of 6/propan-2-ol or 9/propan-2-ol (tolu-
ene, 708C, [LA]0 =0.534m, [Al]0 =10.7 mm). In each case,
first-order kinetics in monomer were observed, and the sem-
ilogarithmic plots for these polymerizations are shown in
Figure 8a and b, respectively. The kapp and kp values deter-
mined are collected in Table 3. The kapp and kp values for 8/
propan-2-ol (kp =5.26mꢀ1 hꢀ1) and 9/propan-2-ol (kp =
3.32mꢀ1 hꢀ1) are both slightly higher than those for 5 (kp =
3.49mꢀ1 hꢀ1) and 6 (kp =2.88mꢀ1 hꢀ1), respectively, which fur-
ther confirms a positive cooperation effect between a CEM
and a SCM resulting from the occurrence of polymer ex-
change. The substituents on the salan ligand phenolate rings
also affect the polymerization rate significantly. Introducing
methyl groups results in a remarkable decrease in kp from
23.8mꢀ1 hꢀ1 for 7 to 3.32mꢀ1 hꢀ1 for 9. The kp values for 5
and 8 are much lower than the kp value for 7 (23.8mꢀ1 hꢀ1).
This indicates that the introduction of chlorine substituents
does not enhance the polymerization rate. Several studies
have indicated that electron-withdrawing chlorine substitu-
ents on ligands increase Lewis acidities of metal centers,
thereby enhancing rates of lactone polymerization.[32] These
results indicate that the polymerization rate constant in-
cludes several steps, including monomer approach and bind-
ing, nucleophilic addition through the metal–alkoxide bond,
and rearrangement causing the cleavage of the acyl–oxygen
bond. Although the enhancement of the Lewis acidity of the
metal center most probably leads to a more facile approach
A kp value of 23.8mꢀ1 hꢀ1 was calculated (Table 3, entry 3)
for rac-LA polymerization in the presence of 7/propan-2-ol
in toluene at 708C.
Table 3. Kinetic results for rac-LA polymerization in the presence of
complexes 5–9.[a]
[c]
Entry
Complex
kapp[b] [ꢂ10ꢀ3 hꢀ1
]
kP [mꢀ1 hꢀ1
]
1
2
3
4
5
5
6
7
8
9
37.3
30.8
269
56.2
35.5
3.49
2.88
23.8[d]
5.26
3.32
[a] All polymerizations were carried out in toluene at 708C, [LA]0 =
0.534m, [Al]0 =10.7 mm. [b] Measured by 1H NMR. [c] Calculated from:
kp =kapp/[Al]0. [d] Deduced from the linear plot of kapp against [Al]0.
Conversion versus time data were also collected for the
polymerization of rac-LA in the presence of 4/propan-2-ol
(toluene, 708C, [LA]0 =0.534m, [Al]0 =10.7 and 17.8 mm,
and [LA]0 =0.267m, [Al]0 =6.68 mm). In each case, a signifi-
cant deviation from a first-order plot for ln[LA]0/[LA]t
versus time was observed at high levels of conversion (Fig-
ure S5 in the Supporting Information), suggesting a kinetic
preference of 4 for a certain lactide enantiomer. The poly-
merization of (S,S)- or (R,R)-LA with application of 4/
propan-2-ol revealed a difference between kapp values of one
order of magnitude at the same aluminium concentration
9842
www.chemeurj.org
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 9836 – 9845

Lactide Polymerization
FULL PAPER
Experimental Section
General conditions: All manipulations requiring a dry atmosphere were
performed under dry argon by use of standard Schlenk techniques or in a
glovebox (M. Braun, Germany). Solvents were dried by heating at reflux
over sodium/benzophenone (toluene and hexane) or calcium hydride
(propan-2-ol) for at least 24 h. Anhydrous deuterated solvents
([D8]toluene and [D6]benzene, Aldrich) were kept under nitrogen over
molecular sieves (4 ꢁ). Starting materials for the synthesis of ligand pre-
cusors 1–3 were purchased from Aldrich and were used without further
purification. The ligands 1–3 were synthesized by literature procedures.[21]
Triethylaluminium from Aldrich was used as received. (S,S)-, rac-, and
meso-LA (Purac Biochem b.v., the Netherlands) were purified by recrys-
tallization three times from anhydrous toluene, followed by drying under
vacuum at 308C for 24 h before use.
Instruments and measurements: Nuclear magnetic resonance (NMR)
spectra were recorded on a Bruker AV 400 MHz instrument at 298 K or
a
Varian Inova 600 MHz spectrometer at 295 K. [D1]Chloroform,
[D6]benzene, and [D8]toluene were used as solvents. Homonuclear de-
coupled 1H NMR, 1H–1H COSY, 1H–1H NOESY, and diffusion-ordered
(DOSY) spectra were recorded on a Bruker Avance II 600 MHz spec-
trometer operating at 600.13 MHz. The spectrometer was fitted with a
Great 3/10 gradient amplifier and a triple-nucleus TXI probe with z-gra-
dient. All experiments were performed at 295 K with use of standard
pulse sequences from the Bruker library. Pulsed field gradient stimulated
echo (PFGSE) diffusion experiments were performed by use of the bipo-
lar stimulated echo sequence with 32 increments in the gradient strength
(2–95%), typically 16 averages per increment step, and 100 ms diffusion
time. Levels of monomer conversion were determined from the integrals
of signals at 1.65 ppm, representing lactide monomer, and 1.59 ppm, rep-
resenting PLA. Pm (the probability of meso linkages) and Pr values (the
probability of racemic linkages) were calculated from different tetrad in-
tensities measured by homonuclear decoupled 1H NMR. Gel permeation
chromatography (GPC) measurements were conducted with a Waters
Figure 8. a) First-order kinetic plots for the ROP of rac-LA in the pres-
ence of 8 or 5 and propan-2-ol in toluene at 708C with [LA]0 =0.534m,
[Al]0 =10.7 mm. b) First-order kinetic plots for the ROP of rac-LA in the
presence of 9 or 6 and propan-2-ol in toluene at 708C with [LA]0 =0.534
m, [Al]0 =10.7 mm.
and binding of the monomer, other changes resulting from
the introduction of chlorine atoms may reduce the rates of
other steps.
410GPC instrument with THF as the eluent (flow rate: 1 mLminꢀ1
,
358C). The molecular weights were determined relative to polystyrene
standards.
Compound (R,R)-1: 1H NMR (400MHz, CDCl3, 298 K): d=10.33 (br,
4
3
2H; ArOH), 7.18 (td, J
(d, 3J(H,H)=7.2 Hz, 2H; ArH), 6.80 (m, 4H; ArH), 3.84 (d, 2J
13.2 Hz, 2H; ArCH2NCH3), 3.64 (d, 2J
(H,H)=12.9 Hz, 2H;
ArCH2NCH3), 2.71 (d, 3J
(H,H)=8.4 Hz, 2H; CH), 2.23 (s, 6H; NCH3),
2.02 (d, 2J
(H,H)=10.2 Hz, 2H; cyclohexane hydrogens), 1.81 (d,
3J
(H,H)=6.9 Hz, 2H; cyclohexane hydrogens), 1.15 ppm (m, 4H; cyclo-
ACHUTGTNREN(NUG H,H)=1.2 Hz, JACHTNUGTRENNUNG
Conclusions
G
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
In conclusion, a series of aluminium ethyl complexes ligated
by chiral salan ligands has been reported. The structures of
two different diastereoisomers—a and b—of these alumini-
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
hexane hydrogens); 13C NMR (100MHz, CDCl3, 298 K): d=157.84
(ArCOH), 129.03 (ArCH), 128.61 (ArCH), 122.31 (ArCH), 119.03
(ArCCH2), 116.49 (ArCH), 61.91 (cyclohexane carbons), 56.97
(ArCH2NCH3), 35.53 (NCH3), 25.27 (cyclohexane carbons), 22.32 ppm
(cyclohexane carbons); elemental analysis calcd (%) for C22H30N2O2: C
74.54, H 8.53, N 7.90; found: C 74.99, H 8.32, N 7.94.
1
um ethyl complexes were revealed by H NMR and X-ray
analysis. Further NMR measurements demonstrated slow
exchange between sqp and tbp geometries for diastereoiso-
mers b at low temperatures. In the presence of propan-2-ol,
the aluminium ethyl complexes acted as efficient initiators
for the ROP of rac-LA and of meso-LA. Microstructural
analysis of the resulting polymers and detailed kinetics stud-
ies indicate the coexistence of a CEM and a SCM in lactide
polymerization. A propagating chain exchange mechanism
was proposed in order to explain the enhanced heteroselec-
tivity and activity of 8 towards rac-LA polymerization, rela-
tive to those of 5. Furthermore, kinetic analysis revealed
first-order kinetics for 7 in both rac-LA monomer and cata-
lyst, as well as a kinetic resolution by 4 in favor of (S,S)-LA.
Future work will focus on the separation of diastereoisomers
a and b to explore their different catalytic behavior in lac-
tide polymerization in detail.
Compound (R,R)-2: 1H NMR (400MHz, [D6]Me2SO, 298 K): d=7.32 (d,
4J(H,H)=2.7 Hz, 2H; ArH), 7.18 (d, 4J
ACTHNUGRTNENUG HCATUNGTERNN(UGN H,H)=2.7 Hz, 2H; ArH), 3.80
2
2
(d, J
G
ACHTUNGTREN(NUGN H,H)=13.2 Hz, 2H;
ArCH2NCH3), 2.87 (d, 3J
AHCTUNGTRENNUNG
1.98 (d, 2H; cyclohexane hydrogens), 1.76 (d, 2H; cyclohexane hydro-
gens), 1.19 ppm (m, 4H; cyclohexane hydrogens); 13C NMR (100 MHz,
[D6]Me2SO, 298 K): d=153.46 (ArCOH), 128.65 (ArCH), 127.92
(ArCH), 126.97 (ArC), 122.17 (ArC), 120.86 (ArC), 61.96 (cyclohexane
carbons), 52.97 (ArCH2NCH3), 35.37 (NCH3), 24.53 (cyclohexane car-
bons), 22.40 ppm (cyclohexane carbons); elemental analysis calcd (%)
for C22H26Cl4N2O2: C 53.68, H 5.32, N 5.69; found: C 54.09, H 5.02, N
5.76.
Compound (R,R)-3: 1H NMR (400MHz, CDCl3, 298 K): d=10.00 (br,
2H; ArOH), 6.78 (s, 2H; ArH), 6.56 (s, 2H; ArH), 3.67 (d, 2J
ACHTUNGTRENNUNG
13.2 Hz, 2H; ArCH2NCH3), 3.50 (d, 2J
ArCH2NCH3), 2.59 (d, 3J
2.09 (s, 6H; ArCH3), 2.06 (s, 6H; ArCH3), 1.92 (d, J
cyclohexane hydrogens), 1.73 (d, 2H; cyclohexane hydrogens), 1.06 ppm
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
3
AHCTUNGTREG(NNUN H,H)=8.1 Hz, 2H;
Chem. Eur. J. 2009, 15, 9836 – 9845
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
9843

X. Chen et al.
(m, 4H; cyclohexane hydrogens); 13C NMR (100 MHz, CDCl3, 298 K):
d=153.59 (ArCOH), 130.60 (ArCH), 127.32 (ArCCH3), 127.12 (ArCH),
125.07 (ArCCH3), 121.81 (ArCCH2), 61.46 (cyclohexane carbons), 57.00
(ArCH2NCH3), 35.31 (NCH3), 25.32 (cyclohexane carbons), 22.27 (cyclo-
hexane carbons), 20.47 (ArCH3), 15.68 ppm (ArCH3); elemental analysis
calcd (%) for C26H38N2O2: C 76.06, H 9.33, N 6.82; found: C 76.09, H
9.02, N 6.76.
12.0 Hz, 1H; ArCH2NCH3), 3.27 (d, 2J
ArCH2NCH3), 2.70 (d, 2J
(H,H)=12.0 Hz, 1H; ArCH2NCH3), 2.60 (s,
ACHTUNGTREN(NUGN H,H)=12.0 Hz, 1H;
AHCTUNGTRENNUNG
3H; ArCH3), 2.46 (s, 3H; ArCH3), 2.36 (s, 6H; ArCH3), 2.01 (td, 1H; cy-
clohexane hydrogens), 1.89 (s, 3H; NCH3), 1.73 (s, 3H; NCH3), 1.57 (t,
3H; AlCH2CH3), 1.39 (m, 4H; cyclohexane hydrogens), 0.62 (m, 4H; cy-
clohexane hydrogens), 0.06 (dq, 1H; AlCH2CH3), ꢀ0.05 ppm (dq, 1H;
AlCH2CH3); 1H NMR (complex 6b, 600MHz, [D8]toluene, 295 K): d=
7.03 (s, 2H; ArH), 6.64 (s, 2H; ArH), 3.46 (br, 2H; ArCH2NCH3), 3.32
Compound 4: A solution of triethylaluminium in toluene (2.0m, 2 mL)
was added dropwise by syringe at room temperature to a solution of
(R,R)-1 (1.42 g, 4 mmol) in toluene (2 mL). Instantaneous evolution of
ethane was observed. The colorless reaction mixture was stirred at 708C
overnight and allowed to cool slowly to room temperature. The solvent
was removed under reduced pressure, and the residue was repeatedly
washed with anhydrous n-hexane to afford the product as colorless crys-
tals (1.09 g, 2.68 mmol, 67%). The 1H NMR spectra clearly indicated the
(d, 2J
ACHTNUGTRNEG(UN H,H)=12.0 Hz, 2H; ArCH2NCH3), 2.59 (s, 6H; ArCH3), 2.34 (s,
6H; ArCH3), 2.09 (m, 2H; CH), 1.79 (s, 6H; NCH3), 1.44 (t, 3H;
AlCH2CH3), 1.37 (m, 4H; cyclohexane hydrogens), 0.65 (m, 4H; cyclo-
hexane hydrogens), 0.21 (dq, 1H; AlCH2CH3), 0.20 ppm (dq, 1H;
AlCH2CH3); 13C NMR (100 MHz, [D6]benzene, 298 K): d=157.08,
156.45, 131.79, 131.59, 131.41, 126.85, 126.48, 124.25, 122.84, 62.84, 61.17,
59.42, 53.16, 42.09, 35.19, 24.30, 22.69, 22.20, 21.76, 16.29, 11.50,
11.12 ppm; elemental analysis calcd (%) for C28H41AlN2O2: C 72.38, H
8.89, N 6.03; found: C 72.09, H 9.02, N 6.26.
1
presence of two complexes. H NMR (complex 4a, 600MHz, [D8]toluene,
295 K): d=7.17 (dd, 4J
G
E
3
3
General procedure for lactide polymerization: In a typical polymeri-
zation experiment, rac-LA (1.00 g, 6.94 mmol), 4 (0.057 g, 0.14 mmol),
propan-2-ol (8.41 mg, 0.14 mmol in toluene, 4 mL), and additional tolu-
ene (9 mL) were introduced successively into a flame-dried vessel con-
taining a magnetic bar. The vessel was placed in an oil bath thermostated
at 708C. After certain time intervals, aliquots were taken out for determi-
nation of the level of monomer conversion by 1H NMR. The polymer
was isolated by precipitation into cold methanol. The precipitate was col-
lected and dried under vacuum at 408C for 24 h.
(t, J
A
(m, 2H; ArH), 3.70 (d, 2J
2J
A
ArCH2NCH3), 2.71 (d, 2J
4J
4J
N
N
(t, 3H; AlCH2CH3), 1.51 (d, 2H; cyclohexane hydrogens), 1.34 (m, 2H;
cyclohexane hydrogens), 0.58 (m, 4H; cyclohexane hydrogens), 0.10 (dq,
1H; AlCH2CH3), ꢀ0.07 ppm (dq, 1H; AlCH2CH3); 1H NMR (complex
4b, 600MHz, [D8]toluene, 295 K): d=7.22 (m, 4H; ArH), 6.90 (dd,
X-ray crystallographic studies: Suitable single crystals of 4a and 9a were
grown from saturated toluene solutions at room temperature. The inten-
sity data were collected from the w scan mode (187 K) on a Bruker
Smart APEX diffractometer with a CCD detector with use of MoKa radi-
ation (l=0.71073 ꢁ). The crystal structures were solved by use of the
SHELXTL program by means of direct methods; the remaining atoms
were located from the difference Fourier synthesis, followed by full-
matrix, least-squares refinements. The positions of the hydrogen atoms
were calculated theoretically and included in the final cycles of refine-
ments in a riding model along with attached carbons. The molecular
structures of 4a and 9a are shown in Figures 2 and 5, respectively, and
their main crystallographic data are summarized in Table 1.
4J
1.2 Hz, 3J
ArCH2NCH3), 3.28 (d, 2J
AHCTUNGTRENNUNG
G
E
ACHTUNGTRNE(NUNG H,H)=
N
ACHTUNGTRENNUNG
2H; CH), 1.80 (s, 6H; NCH3), 1.45 (t, 3H; AlCH2CH3), 1.41 (d, 2H; cy-
clohexane hydrogens), 0.78 (m, 2H; cyclohexane hydrogens), 0.67 (m,
4H; cyclohexane hydrogens), 0.23 (dq, 1H; AlCH2CH3), 0.04 ppm (dq,
1H; AlCH2CH3); 13C NMR (100 MHz, [D6]benzene, 298 K): d=162.39,
161.75, 131.40, 131.07, 129.56, 129.21, 122.75, 121.06, 120.83, 120.18,
117.32, 116.73, 63.44, 61.55, 60.47, 53.47, 42.74, 36.34, 24.85, 23.48, 22.84,
22.21, 11.99 ppm; elemental analysis calcd (%) for C24H33AlN2O2: C
70.56, H 8.14, N 6.86; found: C 71.09, H 8.02, N 6.76.
CCDC 632143 and 628811 contain the supplementary crystallographic
data for this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_
request/cif
Compound 5: The procedure was similar to that described for 4, starting
with (R,R)-2 (1.97 g, 4 mmol). A white powder was isolated (1.75 g,
1
3.20 mmol, 80%). The H NMR spectra clearly indicated the presence of
1
two complexes. H NMR (complex 5a, 600MHz, [D8]toluene, 295 K): d=
7.36 (dd, 4J(H,H)=2.4 Hz, 3J
ACHTUNGTRENNUNG ACHTUNGTRENNUNG
ArH), 6.66 (dd, 4J
2J
A
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
Acknowledgements
AHCTUNGTRENNUNG
ACHTUNGTRENNUNG
The authors thank the Chinese Academy of Sciences and the Royal
Netherlands Academy of Arts and Sciences for funding of the CAS-
KNAW joint training PhD program (06PhD09). A.H.V acknowledges the
Dutch nanotechnology program NanoNed and J. Sun acknowledges the
National Natural Science Foundation of China (NSFC) project
(20604030) for financial support.
CH), 1.59 (s, 3H; NCH3), 1.51 (t, 3H; AlCH2CH3), 1.45 (s, 3H; NCH3),
1.42 (m, 2H; cyclohexane hydrogens), 1.24 (m, 2H; cyclohexane hydro-
gens), 0.68–0.48 (m, 4H; cyclohexane hydrogens), ꢀ0.10 (dq, 1H;
AlCH2CH3), ꢀ0.22 ppm (dq, 1H; AlCH2CH3); 1H NMR (complex 5b,
600MHz, [D8]toluene, 295 K): d=7.38 (d, 2H; ArH), 6.62 (d, 2H; ArH),
2
2
2.96 (d, JACHTUNGTRENNUNG(H,H)=13.2 Hz, 2H; ArCH2NCH3), 2.57 (d, JACHTUTGNREN(NUGN H,H)=13.2 Hz,
2H; ArCH2NCH3), 2.16 (m, 2H; CH), 1.87 (m, 2H; cyclohexane hydro-
gens), 1.62 (s, 6H; NCH3), 1.32 (t, 3H; AlCH2CH3), 1.17 (m, 2H; cyclo-
hexane hydrogens), 0.76 (m, 4H; cyclohexane hydrogens), 0.05 (dq, 1H;
AlCH2CH3), ꢀ0.16 ppm (dq, 1H; AlCH2CH3); 13C NMR (100 MHz,
[D6]benzene, 298 K): d=156.02, 155.55, 130.64, 130.52, 127.84, 127.56,
126.26, 126.13, 124.43, 123.30, 121.53, 120.08, 63.74, 62.06, 59.51, 58.63,
42.96, 35.83, 24.53, 23.40, 22.81, 22.57, 11.43, 0.86 ppm; elemental analysis
calcd (%) for C24H29AlCl4N2O2: C 52.77, H 5.35, N 5.13; found: C 52.56,
H 5.58, N 5.76.
[1] a) B. Jeong, Y. H. Bae, D. S. Lee, S. W. Kim, Nature 1997, 388, 860;
b) K. E. Uhrich, S. M. Cannizzaro, R. S. Langer, K. M. Shakesheff,
Chem. Rev. 1999, 99, 3181; c) Y. Kikkawa, H. Abe, T. Iwata, Y.
Inoue, Y. Doi, Biomacromolecules 2002, 3, 350; d) A. Finne, A.-C.
Albertsson, Biomacromolecules 2003, 4, 684.
[2] a) B. J. O’Keefe, M. A. Hillmyer, W. B. Tolman, J. Chem. Soc.
Dalton Trans. 2001, 2215; b) O. Dechy-Cabaret, B. Martin-Vaca, D.
Bourissou, Chem. Rev. 2004, 104, 6147; c) M. H. Chisholm, Z. P.
Zhou, J. Mater. Chem. 2004, 14, 3081; d) Z. Zhong, P. J. Dijkstra, J.
Feijen, J. Biomater. Sci. Polym. Ed. 2004, 15, 929; e) J. Wu, T.-L. Yu,
C.-T. Chen, C.-C. Lin, Coord. Chem. Rev. 2006, 250, 602.
Compound 6: The procedure was similar to that described for 4, starting
from (R,R)-3 (4.10 g, 10 mmol). A white powder was isolated (3.35 g,
1
7.20 mmol, 72%). The H NMR spectra clearly indicated the presence of
1
two complexes. H NMR (complex 6a, 600MHz, [D8]toluene, 295 K): d=
[3] a) M. H. Chisholm, J. C. Gallucci, K. Phomphrai, Inorg. Chem. 2004,
43, 6717; b) Z. Zhong, S. Schneiderbauer, P. J. Dijkstra, M. Wester-
hausen, J. Feijen, Polym. Bull. 2003, 51, 175; c) M. H. Chisholm, J.
7.02 (d, 2J(H,H)=12.0 Hz, 2H; ArH), 6.56 (d, 3J
ACHTUNGTRENNUNG ACHTUNGTRENNUNG
ArH), 3.71 (d, 2J
N
ACHTUNGTRENNUNG
9844
www.chemeurj.org
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 9836 – 9845

Lactide Polymerization
FULL PAPER
Gallucci, K. Phomphrai, Chem. Commun. 2003, 48; d) H.-Y. Chen,
H.-Y. Tang, C.-C. Lin, Polymer 2007, 48, 2257.
d) M. H. Chisholm, J. C. Gallucci, K. Phomphrai, Inorg. Chem. 2004,
43, 6717; e) T. R. Jensen, L. E. Breyfogle, M. A. Hillmyer, W. B.
Tolman, Chem. Commun. 2004, 2504; f) H.-Y. Chen, H.-Y. Tang, C.-
C. Lin, Macromolecules 2006, 39, 3745; g) H. Ma, T. P. Spaniol, J.
Okuda, Angew. Chem. 2006, 118, 7982; Angew. Chem. Int. Ed. 2006,
45, 7818; h) A. J. Chmura, C. J. Chuck, M. G. Davidson, M. D. Jones,
M. D. Lunn, S. D. Bull, Angew. Chem. 2007, 119, 2330; Angew.
Chem. Int. Ed. 2007, 46, 2280; and references [9b,j,12,13].
[11] For the formation of syndiotactic PLAs, see references [9b,10a,12b].
[12] a) C.-X. Cai, A. Amgoune, G. W. Lehmann, J.-F. Carpentier, Chem.
Commun. 2004, 330; b) A. Amgoune, C. M. Thomas, T. Roisnel, J.-
F. Carpentier, Chem. Eur. J. 2006, 12, 169; c) A. Amgoune, C. M.
Thomas, J.-F. Carpentier, Macromol. Rapid Commun. 2007, 28, 693.
[13] X. Liu, X. Shang, T. Tang, N. Hu, F. Pei, D. Cui, X. Chen, X. Jing,
Organometallics 2007, 26, 2747.
[14] D. A. Atwood, J. Benson, J. A. Jegier, N. F. Lindholm, K. J. Martin,
R. A. Pitura, D. Rutherford, Main Group Chem. 1995, 1, 99.
[15] H. Egami, T. Katsuki, J. Am. Chem. Soc. 2007, 129, 8940.
[16] H. Egami, T. Katsuki, Synlett 2008, 1543.
[17] K. P. Bryliakov, E. P. Talsi, Eur. J. Org. Chem. 2008, 3369.
[18] J. Sun, C. Zhu, Z. Dai, M. Yang, Y. Pan, H. Hu, J. Org. Chem. 2004,
69, 8500.
[19] Z. Dai, C. Zhu, M. Yang, Y. Zheng, Y. Pan, Tetrahedron: Asymme-
try 2005, 16, 605.
[20] Z. Dai, M. Shao, X. Hou, C. Zhu, Y. Zhu, Y. Pan, Appl. Catal. A
2005, 19, 898.
[21] A. Yeori, S. Groysman, I. Goldberg, M. Kol, Inorg. Chem. 2005, 44,
4466.
[22] H. Yang, H. Wang, C. Zhu, J. Org. Chem. 2007, 72, 10029.
[23] A. Yeori, I. Goldberg, M. Shuster, M. Kol, J. Am. Chem. Soc. 2006,
128, 13062.
[4] a) H. Li, C. Wang, F. Bai, J. Yue, H.-G. Woo, Organometallics 2004,
23, 1411; b) S. Doherty, R. J. Errington, N. Housley, W. Clegg, Orga-
nometallics 2004, 23, 2382; c) H. Ma, G. Melillo, L. Oliva, T. P. Span-
iol, U. Englert, J. Okuda, J. Chem. Soc. Dalton Trans. 2005, 721;
d) B. Lian, C. M. Thomas, O. L. Casagrande, C. W. Lehmann, T.
Roisnel, J.-F. Carpentier, Inorg. Chem. 2007, 46, 328.
[5] a) M. H. Chisholm, N. W. Eilerts, J. C. Huffman, S. S. Iyer, M.
Pacold, K. Phomphrai, J. Am. Chem. Soc. 2000, 122, 11845; b) M. S.
Hill, P. B. Hitchcock, J. Chem. Soc. Dalton Trans. 2002, 4694; c) D.
Chakraborty, E. Y.-X. Chen, Organometallics 2003, 22, 769; d) C. K.
Williams, L. E. Breyfogle, S. K. Choi, W. Nam, V. G. Young, M. A.
Hillmyer, W. B. Tolman, J. Am. Chem. Soc. 2003, 125, 11350;
e) A. P. Dove, V. C. Gibson, E. L. Marshall, A. J. P. White, D. J. Wil-
liams, J. Chem. Soc. Dalton Trans. 2004, 570; f) T. Chivers, C. Fe-
dorchuk, M. Parvez, Organometallics 2005, 24, 580; g) J. Ejfler, M.
Kobylka, L. B. Jerzykiewicz, P. Sobota, J. Chem. Soc. Dalton Trans.
2005, 2047; h) B.-H. Huang, C.-N. Lin, M.-L. Hsueh, T. Athar, C.-C.
Lin, Polymer 2006, 47, 6622.
[6] a) Y. Kim, J. G. Verkade, Organometallics 2002, 21, 2395; b) Y. Ta-
kashima, Y. Nakayama, K. Watanabe, T. Itono, N. Ueyama, A. Na-
kamura, H. Yasuda, A. Harada, Macromolecules 2002, 35, 7538;
c) C. K. A. Gregson, I. J. Blackmore, V. C. Gibson, N. J. Long, E. L.
Marshall, A. J. P. White, J. Chem. Soc. Dalton Trans. 2006, 3134;
d) J. Ejfler, M. Kobylka, L. B. Jerzykiewicz, P. Sobota, J. Mol. Catal.
A 2006, 257, 105.
[7] a) V. C. Gibson, E. L. Marshall, D. Navarro-Llobet, A. J. P. White,
D. J. Williams, J. Chem. Soc. Dalton Trans. 2002, 4321; b) B. J.
OꢃKeefe, L. E. Breyfogle, M. A. Hillmyer, W. B. Tolman, J. Am.
Chem. Soc. 2002, 124, 4384.
[8] a) H. Ma, T. P. Spaniol, J. Okuda, J. Chem. Soc. Dalton Trans. 2003,
4770; b) H. Ma, J. Okuda, Macromolecules 2005, 38, 2665; c) I.
Westmoreland, J. Arnold, J. Chem. Soc. Dalton Trans. 2006, 4155;
d) Y. Yang, S. Li, D. Cui, X. Chen, X. Jing, Organometallics 2007,
26, 671.
[24] S. Segal, A. Yeori, M. Shuster, Y. Rosenberg, M. Kol, Macromole-
cules 2008, 41, 1612.
[25] Achiral salan aluminium methyl complexes and their application in
rac-LA polymerization has been reported: P. Hormnirum, E. L.
Marshall, V. C. Gibson, A. J. P. White, D. J. Williams, J. Am. Chem.
Soc. 2004, 126, 2688.
[9] For the formation of isotactic or stereoblock PLAs, see: a) N. Spas-
sky, M. Wisniewski, C. Pluta, A. Le Borgne, Macromol. Chem. Phys.
1996, 197, 2627; b) T. M. Ovitt, G. W. Coates, J. Am. Chem. Soc.
2002, 124, 1316; c) Z. Zhong, P. J. Dijkstra, J. Feijen, Angew. Chem.
2002, 114, 4692; Angew. Chem. Int. Ed. 2002, 41, 4510; d) Z. Zhong,
P. J. Dijkstra, J. Feijen, J. Am. Chem. Soc. 2003, 125, 11291; e) N.
Nomura, R. Ishii, M. Akakura, K. Aoi, J. Am. Chem. Soc. 2002, 124,
5938; f) Z. Tang, X. Chen, X. Pang, Y. Yang, X. Zhang, X. Jing, Bio-
macromolecules 2004, 5, 965; g) Z. Tang, X. Chen, Y. Yang, X. Pang,
J. Sun, X. Zhang, X. Jing, J. Polym. Sci., Part A: Polym. Chem.
2004, 42, 5974; h) R. Ishii, N. Nomura, T. Kondo, Polym. J. 2004, 36,
261; i) P. Hormnirum, E. L. Marshall, V. C. Gibson, R. I. Pugh,
A. J. P. White, Proc. Natl. Acad. Sci. USA 2006, 103, 15343; j) A. P.
Dove, H. Li, R. C. Pratt, B. G. G. Lohmeijer, D. A. Culkin, R. M.
Waymouth, J. L. Hedrick, Chem. Commun. 2006, 2881; k) L. Zhang,
F. Nederberg, J. M. Messman, R. C. Pratt, J. L. Hedrick, C. G. Wade,
J. Am. Chem. Soc. 2007, 129, 12610; l) N. Nomura, R. Ishii, Y. Ya-
mamoto, T. Konda, Chem. Eur. J. 2007, 13, 4433; m) M. Bouyahyi,
E. Grunova, N. Marquet, E. Kirillov, C. M. Thomas, T. Roisnel, J.-F.
Carpentier, Chem. Eur. J. 2008, 14, 5815.
[26] J. F. Larrow, E. N. Jacobsen, Y. Gao, Y. Hong, X. Nie, C. M. Zepp, J.
Org. Chem. 1994, 59, 1939.
[27] a) A. W. Addison, T. N. Rao, J. Reedijk, J. Van Rijn, G. C. Ver-
schoor, J. Chem. Soc. Dalton Trans. 1984, 1349; b) D. A. Atwood,
M. S. Hill, J. A. Jegier, D. Rutherford, Organometallics 1997, 16,
2659.
[28] J. P. Duxbury, J. N. D. Warne, R. Mushtaq, C. Ward, M. Thornton-
Pett, M. Jiang, R. Greatrex, T. P. Kee, Organometallics 2000, 19,
4445.
[29] D. A. Atwood, Coord. Chem. Rev. 1997, 165, 267.
[30] a) J. W. Akitt, R. H. Duncan, J. Magn. Reson. 1974, 15, 162; b) O.
Kriz, B. Casensky, A. Lycka, J. Fusek, S. Hermanek, J. Magn. Reson.
1984, 60, 375.
[31] N. Nomura, T. Aoyama, R. Ishii, T. Kondo, Macromolecules 2005,
38, 5363.
[32] a) P. A. Cameron, D. Jhurry, V. C. Gibson, A. J. P. White, D. J. Wil-
liams, S. Williams, Macromol. Rapid Commun. 1999, 20, 616; b) D.
Jhurry, A. Bhaw-Luximon, N. Spassky, Macromol. Symp. 2001, 175,
67; c) H. Du, X. Pang, H. Yu, X. Zhuang, X. Chen, D. Cui, X.
Wang, X. Jing, Macromolecules 2007, 40, 1904.
[10] For the formation of heterotactic PLAs, see: a) B. M. Chamberlain,
M. Cheng, D. R. Moore, T. M. Ovitt, E. B. Lobkovsky, G. W. Coates,
J. Am. Chem. Soc. 2001, 123, 3229; b) M. H. Chisholm, J. C. Huff-
man, K. Phomphrai, J. Chem. Soc. Dalton Trans. 2001, 222; c) M. H.
Chisholm, J. Gallucci, K. Phomphrai, Inorg. Chem. 2002, 41, 2785;
[33] J. Baran, A. Duda, A. Kowalski, R. Szymanski, S. Penczek, Macro-
mol. Rapid Commun. 1997, 18, 325.
Received: March 27, 2009
Published online: August 18, 2009
Chem. Eur. J. 2009, 15, 9836 – 9845
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
9845