Conformational effects in β-diiminate ligated magnesium and zinc amides. Solution dynamics and lactide polymerization

Article abstract of DOI:10.1016/S0020-1693(02)01510-4

The preparation of the compounds LMg(NⁱPr₂)(THF) (1) ; and LZnNⁱPr₂ (2), are reported for L=the bulky β-diiminate ligand, CH(CMeN-2-^tBuC₆H ₄)₂. In solution compound 2 is shown to exist as a mixture of syn- and anti-rotamers that do not interconvert significantly. Compound 1 readily and reversibly dissociates THF in benzene-d₆ or toluene-d₈ from a site where THF is syn to the ^tBu group of L. Both 1 and 2 are catalyst precursors for the ring-opening polymerization of lactides and it is shown that the syn-conformer of 2 reacts much faster than the anti. Polymerization of rac-lactide employing 2 in benzene or CH ₂Cl₂ or 1 in THF yield approximately 90% heterotactic PLA (isi+sis). These results are compared with related work by Coates [J. Am. Chem. Soc. 123 (2001) 3229]; and us [J. Chem. Soc., Dalton Trans. (2001) 222] and us employing the symmetric β-diiminate ligand CH(CMeN-2,6-ⁱPr ₂C₆H₃)₂.

Full text of DOI:10.1016/S0020-1693(02)01510-4

Inorganica Chimica Acta 350 (2003) 121Á125
/
www.elsevier.com/locate/ica
Conformational effects in b-diiminate ligated magnesium and zinc
amides. Solution dynamics and lactide polymerization
Malcolm H. Chisholm *, Khamphee Phomphrai
Newman and Wolfrom Laboratories, Department of Chemistry, The Ohio State University, 100W. 18th Avenue, Columbus, OH 43210-1185, USA
Received 20 May 2002; accepted 4 September 2002
Dedicated to Professor Pierre Braunstein
Abstract
The preparation of the compounds LMg(NiPr2)(THF) (1); and LZnNiPr2 (2), are reported for Lꢀ
the bulky b-diiminate ligand,
/
CH(CMeN-2-tBuC6H4)2. In solution compound 2 is shown to exist as a mixture of syn- and anti-rotamers that do not interconvert
significantly. Compound 1 readily and reversibly dissociates THF in benzene-d6 or toluene-d8 from a site where THF is syn to the
tBu group of L. Both 1 and 2 are catalyst precursors for the ring-opening polymerization of lactides and it is shown that the syn-
conformer of 2 reacts much faster than the anti. Polymerization of rac-lactide employing 2 in benzene or CH2Cl2 or 1 in THF yield
approximately 90% heterotactic PLA (isiꢁsis). These results are compared with related work by Coates [J. Am. Chem. Soc. 123
/
(2001) 3229]; and us [J. Chem. Soc., Dalton Trans. (2001) 222] and us employing the symmetric b-diiminate ligand CH(CMeN-
2,6-iPr2C6H3)2.
# 2002 Elsevier Science B.V. All rights reserved.
Keywords: Conformational effects; b-Diiminate ligated magnesium; Zinc amides
1. Introduction
zinc complex [13,14]. Another challenge in PLA micro-
structure is to make a 1:1 mixture of -PLA and -PLA,
called a stereocomplex, that has a high melting tem-
perature (Tm) Â230 8C compared with Tm 180 8C of
pure -PLA [15Á17]. This higher melting temperature
L
D
Polylactide (PLA) has been gaining attention in both
academic and industrial circles due to its biocompat-
/
ibility and biodegradability [1Á3]. It can be used in
/
L
/
applications such as biodegradable packaging materials,
artificial tissue matrices, surgical sutures, and drug
delivery systems [4]. In order to obtain desired mechan-
ical properties, PLA is often copolymerized with other
gives rise to a broader range of applications. However,
the normal synthesis of the stereocomplex requires a
chiral separation of the enantiomers L- and D-lactide
which adds significantly to the cost of production. Baker
et al. tried to circumvent this problem by using a racemic
aluminum isopropoxide catalyst to polymerize rac-
lactide [11]. The idea was that one catalyst enantiomer
monomers such as glycolide and caprolactone [5Á9].
/
Recently, single-site catalysts have been employed in
lactide polymerization providing an entry point to new
PLA microstructures [10,11]. For example, syndiotactic
PLA was synthesized from meso-lactide using a chiral
aluminum isopropoxide catalyst by Coates et al. [12]
and, in their subsequent work, they were able to make
heterotactic PLA from rac-lactide using a b-diiminato
would polymerize
enantiomer would polymerize
thereby giving a mixture of pure
D
-lactide and the other catalyst
-lactide in parallel
-PLA and -PLA
L
D
L
chains. However, this result was later challenged by
Coates et al. who, upon detailed examination of the
polymer microstructure, showed that the resulting
polymer was not the stereocomplex but rather a stereo
* Corresponding author. Tel.: ꢁ
0368.
E-mail
Chisholm).
/
1-614-292 7216; fax: ꢁ
/
1-614-292
block [(
fore, the synthesis of the stereocomplex from commer-
D-PLA)m(
L
-PLA)m]n where m Â11 [18]. There-
/
address:
chisholm@chemistry.ohio-state.edu (M.H.
cially available rac-lactide remains to be achieved [19].
0020-1693/02/$ - see front matter # 2002 Elsevier Science B.V. All rights reserved.
doi:10.1016/S0020-1693(02)01510-4

122
M.H. Chisholm, K. Phomphrai / Inorganica Chimica Acta 350 (2003) 121Á125
/
Prompted by these considerations and the success of
single-site catalyst systems employing zinc and magne-
sium with b-diiminato ligands [13,14,20,21], we under-
took the following study employing the 2-((2-tert-
butylphenyl)amino)-4-((2-tert-butylphenyl)imino)-2-
pentene ligand (LH). The premise was a simple one,
namely that the bulky tBu groups would prefer to adopt
the anti conformation, in preference to the syn as
represented by the drawings shown in A and B,
respectively. The anti-confirmation has virtual C2 sym-
metry and thus the metal center is chiral and exists as a
50:50 enantiomeric mixture.
LZnNSi2Me6 was characterized by Coates et al. where
CH(CMeN-2,6-iPr2C6H3)2 [22]. What is particularly
pertinent is the disposition of the two Bu groups in 1
and 2.
1
The H NMR spectrum of the zinc compound 2 in
toluene-d8 reveals the presence of two species in the
Lꢀ
/
t
temperature range of ꢂ70 to 80 8C. The relative
/
concentration of each species is little influenced by
variations in temperature and the NMR spectra can be
assigned as arising from a mixture of anti:syn confor-
mers in an approximately 60:40 ratio. These do not
interconvert rapidly on the NMR time-scale nor as we
show later even on the chemical reaction time-scale. For
the anti-conformer the NiPr groups are equivalent but
contain diastereotopic methyl groups. For the syn-
conformer there is a virtual mirror plane of symmetry
1
i
and the H NMR spectrum shows only one Pr methyl
doublet within the ꢂ70 to 80 8C temperature range
indicating that rotation about the Znꢀ
NiPr2 bond is
/
/
rapid on the NMR time-scale. These key features are
shown in Fig. 1.
The solution behavior of the magnesium compound 1
is slightly more complicated because of the reversible
equilibrium shown in Eq. (1) which is temperature
dependent in toluene-d8. As shown in Fig. 2, the spectra
are temperature dependent, although only one set of
signals for the various groups present is ever seen at any
given temperature. For example, we observe only one
NiPr2 methyl doublet which is sharp at high temperature
and again at low temperature. The line broadening that
occurs in between is clearly due to the relative rates of
exchange involving THF-ligated and THF-free metal
complex.
2. Results and discussion
2.1. Syntheses and characterization
2.1.1. LMg(NiPr2)(THF) (1)
The reaction of Mg(NiPr2)2 with 1 equiv. of the free b-
diiminato ligand LH in refluxing THF gives compound
LMg(NiPr2)(THF)XLMg(NiPr2)ꢁTHF
(1)
t
(LꢀCH(CMeNꢂ2ꢂ BuC6H4)2)
1 as a greenÁyellow solid.
/
In the presence of added THF, the low temperature
spectra indicate that the equilibrium 1 lies to the extreme
2.1.2. LZn(NiPr2) (2)
Our best preparation of compound 2 is from the
reaction between LiNiPr2 (2 equiv.), LH (1 equiv.) and a
solution of ZnCl2 (1 equiv.) in THF. Subsequent
extraction of the dried reaction residue with hexanes
gave compound 2 as a yellow solid. Elemental analyses
and full details of the preparation are given in the
Section 3 together with spectroscopic data.
2.2. Solution characterization of compounds 1 and 2
With our recent characterization of related b-diimi-
nato complexes of magnesium and zinc [20], there can be
no doubt that compound 1 has a four-coordinate Mg2ꢁ
ion in a distorted tetrahedral environment and that
compound 2 contains a trigonal-planar three coordinate
Zn2ꢁ ion. A similar trigonal-planar zinc complex
Fig. 1. 1H NMR spectra (400 MHz, C6D6) of the methyl groups of the
diisopropyl amide in (a) LMg(NiPr2)(THF) and (b) LZn(NiPr2).

M.H. Chisholm, K. Phomphrai / Inorganica Chimica Acta 350 (2003) 121Á
/125
123
under comparable conditions for the zinc compound 2,
both syn- and anti-conformers are present and are not
interconverting rapidly on the NMR time-scale. We
shall return to the significance of this later.
2.3. Polymerization of lactide employing 1 and 2
Both the magnesium and zinc compounds are active
in the polymerization of lactide. The magnesium com-
pound is notably more reactive polymerizing 100 equiv.
of lactide in THF within 2 min at room temperature.
With rac-lactide, the polymer formed is significantly
enhanced in heterotactic tetrads, sis and isi, when the
polymerization is carried out in THF, but in benzene,
the polymer is atactic. In contrast, the zinc compound
polymerizes rac-lactide (100 equiv.) to give approxi-
mately 90% heterotactic PLA in THF, CH2Cl2 and
benzene. The latter result parallels that of Coates et al.
employing the related b-diiminate complex [HC(CMeN-
2,6-iPr2C6H3)2Zn(m-OiPr)]2 [13]. However, an examina-
tion of the molecular weight profile for the polymeriza-
tion of 100 equiv. of lactide by 1 and 2 (and with that of
Coates catalyst noted above), revealed some interesting
Fig. 2. VT 1H NMR spectra (400 MHz, toluene-d8) of
LMg(NiPr2)(THF) when 0.5 equiv. of THF was added.
left, and furthermore, that exchange between free and
coordinated THF is frozen out on the NMR time-scale.
This parallels our earlier observation of the related
magnesium complex [CH(CMeN-2,6-iPr2C6H3)2]Mg(Ot-
differences. For 1 in THF, Mnꢀ
1.6 but for 2, Mnꢀ29.3 kDa and PDIꢀ
polymerization catalyst wherein kinitiation
we would expect MnÂ14.4 kDa and a PDI of 1.0. The
/
14.7 kDa and PDIꢀ
1.5. For a living
kpropagation
/
1
Bu)(THF) [20,21]. The H NMR spectra indicate that
/
/
irrespective of temperature, only the syn-conformer of
the b-diiminate ligand is present at the metal center. This
caused us to question whether or not the THF was
Â
/
/
latter is close to what is found for the zinc catalyst of
Coates. The observed Mn value of approximately 30
kDa found employing the zinc compound 2 thus
requires comment. We propose that this high molecular
weight arises from the fact that the syn-conformer is
much more active in the polymerization of lactide
t
adjacent or removed from the Bu group of the b-
diiminate. These possibilities are pictorially represented
by C and D below.
relative to the anti, and that rotation about the Nꢀ
C(aryl) bond does not occur in solution to a significant
extent. The syn Áanti ratio observed reflects the forma-
tion of the compound. This is supported by two
observations. (1) The syn Áanti ratio of 2 is found to
/
/
/
be independent of solvent (THF, toluene-d8, C6D6) and
added donor ligands such as pyridine. (2) When
compound 2 was allowed to react with approximately
0.5 equiv. of rac-lactide, we observed the preferential
depletion of the syn-conformer. Upon lactide ring-
opening, all of the syn-conformer signals associated
with LZnNiPr2 disappeared and only those of anti-
LZniPr2 remained and did not react to regenerate syn-
LZnNiPr2. A slower kinitiation relative to kpropagation
could be responsible for a broad PDI as well as
transesterification that occurs at high conversion.
In an attempt to address this matter, we employed
NOE difference spectroscopy at low temperature
(ꢂ
70 8C). Irradiation of the tBu protio-resonance
/
caused an enhancement of the a-proton of the coordi-
nated THF ligand. From this, we can reasonably
conclude that the THF molecule is bound in close
proximity to the syn-tBu groups. The bulky NiPr2 group
is thus further removed from these groups.
2.4. Concluding remarks
Steric factors evidently suppress the interconversion
of syn- and anti-conformers of these sterically demand-
ing b-diiminate complexes and the syn-conformer is
significantly more active in lactide polymerization.
1
From the H NMR spectra of 1 at high temperature,
we can infer that only the syn-conformer is present, yet

124
M.H. Chisholm, K. Phomphrai / Inorganica Chimica Acta 350 (2003) 121Á125
/
Polymerization of rac-lactide yields heterotactic PLA
via the syn-conformer which is achiral prior to the
formation of the optically-active growing polymer chain
LMOC*HMeR.
(s, 6H, a-Me), 1.51 (s, 18H, tBu), 1.31 (br, 4H,
O(CH2CH2)2), 1.11 (d, 12H, Jꢀ6.3 Hz, CHMe2).
13C{1H} NMR (C6D6): 168.28 (CÄ
N), 150.58, 143.07,
129.02, 127.57, 126.44, 124.71 (ArꢀC), 94.18 (b-C),
/
/
/
69.52 (O(CH2CH2)2), 48.22 (CHMe2), 36.30 (CMe3),
32.60 (CMe3), 28.13 (CHMe2), 25.18 (O(CH2CH2)2),
24.96 (a-Me).
3. Experimental
3.4. LZn(NiPr2) (2)
3.1. General considerations
The manipulation of air-sensitive compounds in-
volved the use of anhydrous solvents and dry and
oxygen-free nitrogen employing standard Schlenk line
and drybox techniques. rac-Lactide was purchased from
Aldrich and was sublimed three times prior to use.
Tetrahydrofuran, dichloromethane, and hexanes were
distilled under nitrogen from sodium/benzophenone,
calcium hydride, and potassium metal, respectively.
The b-diiminato ligand CH(CMeN-2-tBuC6H4)2 [23]
and Mg(NiPr2)2 [24] were prepared according to litera-
ture procedures. Hydrous ZnCl2 was dried using chlor-
otrimethylsilane [25]. LiNiPr2 was prepared from the
reaction of BuLi and HNiPr2.
THF (20 ml) was added to a mixture of LH (1.00 g,
2.76 mmol) and LiNiPr2 (0.592 g, 5.53 mmol) at r.t. The
resulting solution was then stirred for 30 min and then
added a solution of ZnCl2 (0.380 g, 2.79 mmol) in 10 ml
THF slowly. The mixture was then stirred for 1 h and
any volatile components were removed under dynamic
vacuum. The product was extracted with 20 ml hexanes
giving a light yellow sticky solid (0.98 g, 68%). MS (EI):
m/zꢀ
/
525.3 (Mꢁ). Anal. Calc. for C31H47N3Zn: C,
70.69; H, 8.92; N, 7.97. Found: C, 70.01; H, 8.94; N,
1
7.47%. H NMR (C6D6) anti: 6.70Á
/
7.40 (m, 8H, ArH),
6.3 Hz, CHMe2),
1.67 (s, 6H, a-Me), 1.49 (s, 18H, Bu), 0.95 (d, 6H, Jꢀ
6.4 Hz, CHMe2), 0.65 (d, 6H, Jꢀ6.3 Hz, CHMe2). syn:
6.70Á7.40 (m, 8H, ArH), 4.78 (s, 1H, b-CH), 2.87 (sept,
2H, Jꢀ6.4 Hz, CHMe2), 1.64 (s, 6H, a-Me), 1.45 (s,
18H, Bu), 0.84 (d, 6H, Jꢀ
6.4 Hz, CHMe2). 13C{1H}
NMR (C6D6) anti: 168.04 (CÄN), 148.47, 142.58,
129.22, 128.43, 126.48, 125.56 (ArꢀC), 95.42 (b-C),
4.86 (s, 1H, b-CH), 3.03 (sept, 2H, Jꢀ
/
t
/
/
3.2. Measurements
/
/
1H and 13C{1H} spectra were recorded in C6D6 and
toluene-d8 on Bruker DPX-400 NMR spectrometers
and were referenced to the residual protio impurity peak
t
/
/
/
1
(C6D6, d 7.15; toluene-d8, d 2.09 for H and, C6D6, d
49.99 (CHMe2), 36.40 (CMe3), 33.13 (CMe3), 28.16
128.0; toluene-d8, d 20.4 for 13C{1H}). Elemental
analyses were done by Atlantic Microlab, Inc. Gel
permeation chromatography measurements were carried
out using a Waters 1525 binary HPLC pump and
Waters 410 differential refractometer equipped with
(CHMe2), 25.57 (CHMe2), 25.12 (a-Me). syn: 168.67
(CÄ
/
N), 149.06, 142.60, 129.29, 129.03, 126.93, 125.65
C), 95.60 (b-C), 48.89 (CHMe2), 36.13 (CMe3),
(Arꢀ
/
32.44 (CMe3), 27.55 (CHMe2), 25.03 (a-Me).
˚
styragel HR 2&4 columns (100 and 10 000 A). The
3.5. General polymerization procedure
GPC was eluted with THF at 35 8C running at 1 ml
minꢂ1 and was calibrated using polystyrene standard.
Mass spectrometry was done by electron impact ioniza-
tion at 60 eV using a Kratos MS890 double-focusing
magnetic-sector instrument at 6000 V ion-acceleration
energy in the extended mass-range mode of the magnet.
rac-Lactide (0.500 g, 3.47 mmol) was dissolved in 6.0
ml CH2Cl2 or THF. A solution of the corresponding
catalyst (0.0347 mmol) in 1.5 ml CH2Cl2 or THF was
then added to the lactide solution (100:1 [lactide]:[cata-
lyst]). The reaction was stirred at r.t., and at the desired
time, small aliquots were taken to monitor the conver-
sion. When the conversion was greater than 90%, the
polymerization was quenched with excess methanol. The
polymer precipitate was then filtered and dried under
vacuum to constant weight.
3.3. LMg(NiPr2)(THF) (1)
THF (15 ml) was added to a mixture of LH (0.500 g,
1.38 mmol) and Mg(NiPr2)2 (0.310 g, 1.38 mmol). The
clear solution was then refluxed for 2.5 h. After cooled
down to room temperature (r.t.), the volatile compo-
nents were removed under dynamic vacuum giving a
greenÁ/yellow solid (0.71 g, 92%). By NMR analysis, the
Acknowledgements
product is 100% in a syn conformation. Anal. Calc. for
C35H55N3OMg: C, 75.38; H, 9.86; N, 7.53. Found: C,
We thank the Department of Energy, Office of Basic
Energy Sciences, Chemistry Division for financial sup-
port of this work. K.P. acknowledges the Institute for
the Promotion of Teaching Science and Technology
1
75.01; H, 9.76; N, 7.44%. H NMR (C6D6): 7.42, 6.88Á
/
7.13 (m, 8H, Arꢀ
/
H), 4.71 (s, 1H, b-CH), 3.64 (br, 4H,
O(CH2CH2)2), 3.13 (sept, 2H, Jꢀ
/6.3 Hz, CHMe2), 1.68

M.H. Chisholm, K. Phomphrai / Inorganica Chimica Acta 350 (2003) 121Á
/125
125
[10] N. Spassky, M. Wisniewski, C. Pluta, A. Le Borgne, Macromol.
Chem. Phys. 197 (1996) 2627.
(IPST), Thailand, for an opportunity to work on this
project.
[11] C.P. Radano, G.L. Baker, M.R. Smith, III, J. Am. Chem. Soc.
122 (2000) 1552.
[12] T.M. Ovitt, G.W. Coates, J. Am. Chem. Soc. 121 (1999) 4072.
[13] M. Cheng, A.B. Attygalle, E.B. Lobkovsky, G.W. Coates, J. Am.
Chem. Soc. 121 (1999) 11583.
References
[14] B.M. Chamberlain, M. Cheng, D.R. Moore, T.M. Ovitt, E.B.
Lobkovsky, G.W. Coates, J. Am. Chem. Soc. 123 (2001) 3229.
[15] N. Yui, P.J. Dijkstra, J. Feijen, Makromol. Chem. 191 (1990) 481.
[16] H. Tsuji, Y. Ikada, Polymer 40 (1999) 6699.
[17] Y. Ikada, K. Jamshidi, H. Tsuji, S.H. Hyon, Macromolecules 20
(1987) 904.
[1] B.J. O’Keefe, M.A. Hillmyer, W.B. Tolman, J. Chem. Soc.,
Dalton Trans. (2001) 2215.
[2] G.W. Coates, J. Chem. Soc., Dalton Trans. (2002) 467.
[3] M.H. Chisholm, N.W. Eilerts, J.C. Huffman, S.S. Iyer, M.
Pacold, K. Phomphrai, J. Am. Chem. Soc. 122 (2000) 11845.
[4] Examples of polyesters in pharmaceutical products are Dexon†
,
Vicryl†, Leupron Depot† and Zoldex† from Davis & Geek Inc.,
Ethicon Inc., Takeda Chemical Industries Ltd., and ICI pharma-
ceuticals, respectively.
[18] T.M. Ovitt, G.W. Coates, J. Polym. Sci., Part A: Polym. Chem. 38
(2000) 4686.
[19] N. Nomura, R. Ishii, M. Akakura, K. Aoi, J. Am. Chem. Soc. 124
(2002) 5938.
[5] N. Spassky, V. Simic, in: C. Scholz, R.A. Gross (Eds.) Polymers
from renewable resources; Biopolyesters and Biocatalysis, ACS
Symp. Ser. 764 ACS, Washington D.C., 2000, p. 146.
[6] P.J.A. In’t Veld, E.M. Velner, P. Van De Witte, J. Hamhuis, P.J.
Dijkstra, J. Feijen, J. Polym. Sci., Part A: Polym. Chem. 35 (1997)
219.
[20] M.H. Chisholm, J. Gallucci, K. Phomphrai, Inorg. Chem. 41
(2002) 2785.
[21] M.H. Chisholm, J.C. Huffman, K. Phomphrai, J. Chem. Soc.,
Dalton Trans. (2001) 222.
[22] M. Cheng, D.R. Moore, J.J. Reczek, B.M. Chamberlain, E.B.
Lobkovsky, G.W. Coates, J. Am. Chem. Soc. 123 (2001) 8738.
[23] R.F. Jordan, M.P. Coles, US Patent 6,228,794, 1998.
[24] E.C. Ashby, J.J. Lin, A.B. Goel, J. Org. Chem. 43 (1978) 1564.
[25] P. Boudjouk, J.H. So, M.N. Ackermann, S.E. Hawley, B.E. Turk,
Inorg. Synth. 29 (1992) 108.
[7] D.D. Hile, M.V. Pishko, J. Polym. Sci., A: Polym. Chem. 39
(2001) 562.
[8] P. Dobrzynski, J. Kasperczyk, H. Janeczek, M. Bero, Macro-
molecules 34 (2001) 5090.
[9] P. Dobrzynski, J. Kasperczyk, M. Bero, Macromolecules 32
(1999) 4735.