Highly diastereoselective synthesis of chiral aminophenolate zinc complexes and isoselective polymerization of rac-lactide

Article abstract of DOI:10.1039/c3cc44980g

An enantiopure zinc complex supported by an aminophenolate ligand with multiple stereogenic centers has been diastereoselectively synthesized via the variation of the ortho-substituent of a phenoxy moiety and the N-alkyl group of a chiral pyrrolidinyl ring in the ligand framework, which displays high isoselectivity in the polymerization of rac-lactide.

Full text of DOI:10.1039/c3cc44980g

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Highly diastereoselective synthesis of chiral
aminophenolate zinc complexes and isoselective
polymerization of rac-lactide†
Cite this: Chem. Commun., 2013,
49, 8686
Received 3rd July 2013,
Accepted 30th July 2013
Haobing Wang and Haiyan Ma*
DOI: 10.1039/c3cc44980g
www.rsc.org/chemcomm
An enantiopure zinc complex supported by an aminophenolate metals such as Mg, Ca and Zn have proved to be excellent single
ligand with multiple stereogenic centers has been diastereoselectively site initiators, capable of initiating the ROP of rac-LA with high
synthesized via the variation of the ortho-substituent of a phenoxy activity and in selected cases high heteroselectivity.6a–e,7a It is
moiety and the N-alkyl group of a chiral pyrrolidinyl ring in the ligand suggested that highly heterotactic PLA produced by these com-
framework, which displays high isoselectivity in the polymerization of plexes is a widely accepted result of chain end control.6 For
rac-lactide.
achieving isoselectivity in the ROP of rac-LA via enantiomorphic
site control, some zinc complexes supported by ligands containing
Biodegradable polymers such as poly(lactic acid) (PLA) inherently stereogenic centers have been investigated.7 Unfortunately, only
provide an environmental advantage over petroleum-based polymers one example reported very recently by Otero’s group afforded
because of their biodegradability and biocompatibility desirable for isotactic-enriched PLAs (Pi = 0.77), most of those chiral initiators
applications ranging from packaging and agricultural materials to did not achieve the desired effect.7e In this work, in an effort to
drug delivery and medical facilities.1a,b Stereocontrolled ring-opening isolate enantiomerically pure zinc complexes, we introduced
polymerization (ROP) of rac-lactide (rac-LA) catalyzed by various multiple stereogenic centers into the tridentate aminophenolate
catalytic systems (metal complexes,1 organic compounds,2 and ligand framework. As shown in Scheme 1, the inherent carbon
enzymes) have been of intense interest for the past two decades, chirality of the N-alkylpyrrolidinyl fragment deviated from that of
since the physical, mechanical as well as degradation properties L-proline in combination with the variation of the N-alkyl group of
of PLAs are intimately dependent on the chain stereochemistry. pyrrolidinyl and the ortho-substituent of the phenoxy ring success-
For instance, the melting temperature of stereocomplexed fully induced the formation of an enantiopure zinc complex,
polylactides yielded by optimally isoselective ROP of rac-LA which displayed high isoselectivity for the ROP of rac-LA.
can be 30–60 1C higher than that of homochiral PLAs.3–5
The NNO-type aminophenols L1H to L5H were synthesized
In particular, there have been many studies on metal-based from enantiopure (S)-prolinamide, according to modifications of
complexes as initiators for the ROP of rac-LA including complexes the published procedures, via alkylation, reduction, condensation–
of Al,4,5 Zn,6,7 rare earth metals,8,9 alkali and alkaline earth reduction, and Mannich reaction (Scheme S1, ESI†). Initially, the
metals,10 and other main group11 or transition metals.1c Among aminophenol proligand L1H reacted smoothly with Zn[N(SiMe3)2]2
them, discrete aluminum complexes show outstanding isoselectivity, to afford the desired zinc silylamido complex 1, nevertheless, as a
which have been extensively investigated and reported.4,5 However, mixture of two diastereomers (Scheme 1). The ratio of two iso-
their potential industrial applications are restricted by inherently mers hardly changed after repeated recrystallization procedures.
low catalytic activities and poisonousness of the possible metal
residues.1 Besides, only a few examples of isoselective initiators
based on In11 and Y9 complexes were reported recently, affording
PLA with Pm = 0.77–0.84. Complexes of environmentally friendly
Shanghai Key Laboratory of Functional Materials Chemistry and Laboratory of
Organometallic Chemistry, East China University of Science and Technology,
130 Meilong Road, Shanghai, 200237, P. R. China.
E-mail: haiyanma@ecust.edu.cn; Fax: +86 21 64253519; Tel: +86 21 64253519
† Electronic supplementary information (ESI) available: Full experimental details,
representative NMR spectra and DSC traces of polymers. CCDC 936900 (3a),
936901 (5) and 936902 (1). For ESI and crystallographic data in CIF or other
electronic format see DOI: 10.1039/c3cc44980g
Scheme 1 Synthesis of chiral zinc complexes.
c
8686 Chem. Commun., 2013, 49, 8686--8688
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Table 1 ROPs of rac-LA initiated by zinc complexes 1–5a
Conv.b Mn,calcd
Mn
(104)
Mwd/
c
d
Feed
Cat. ratio
Time
(min) (%)
e
(104)
Mn
Pm
1
1
1
2
2
3
3
4
4
5
5
5
5
200 : 1 : 0
25
2
20
10
5
60
15
360
90
180
90
98
99
95
97
93
91
99
86
93
84
99
82
71
2.82
2.85
20.5
2.78
2.68
2.62
2.85
2.47
2.68
2.42
2.85
11.8
2.04
3.10 1.79 0.39
1.78 1.53 0.40
200 : 1 : 1
1500 : 1 : 1
200 : 1 : 0
200 : 1 : 1
200 : 1 : 0
200 : 1 : 1
200 : 1 : 0
200 : 1 : 1
200 : 1 : 0
200 : 1 : 1
1000 : 1 : 1
200 : 1 : 1
10.8
1.13 0.41
2.33 1.78 0.59
2.01 1.61 0.59
5.72 1.59 0.74
2.63 1.33 0.73
Fig. 1 Molecular structures of 1a (left) and 1b (right). Hydrogen atoms are
13.2
1.47 0.77
3.72 1.08 0.77
2.95 1.66 0.80
3.00 1.12 0.80
7.44 1.14 0.81
1.95 1.24 0.84
omitted for clarity.
As shown in Fig. 1, the X-ray diffraction study of twin crystals of 1
revealed the molecular structures of these two isomers. It must be
noted that, in addition to the unsymmetrically tetra-coordinated zinc
center and the inherent carbon chirality in the N-ethylpyrrolidinyl
fragment in 1, there are two prochiral N atoms in proligand L1H that
become new stereogenic centers upon complexation, and thus in
total four pairs of diastereomers may be conceived. From Fig. 1, it is
found that, due to a more stable conformation of two substituents
located in trans in the N-ethylpyrrolidinyl moiety, the inherent
carbon chirality of S induces exclusively the S-configuration of the
N stereogenic center (N2 and N4 in Fig. 1). Consequently, only a
pair of diastereomers could be observed in 1H and 13C NMR
spectra of 1, which are shown to have a reversed configuration
at both the skeleton N atom (N1 and N3 in Fig. 1) and the zinc
center, and can be denoted as (SCSNRNRZn)-1a and (SCSNSNSZn)-1b.
The reaction of L2–4H with Zn[N(SiMe3)2]2 also led to the
corresponding zinc silylamido complexes 2–4 as a mixture of
two diastereomers but with different molar ratio.12 Although
being in a 1 : 1 ratio, single crystals of isomer 3a could be isolated
and characterized (Fig. S7, ESI†). By comparing the relative amount
360
56 hf
a
b
[LA]0 = 1.0 mol LÀ1, feed ratio = [LA]0/[Zn]0/[iPrOH]0, toluene, 25 1C.
Determined by 1H NMR spectroscopy. Mn,calcd
=
[LA]0/[Zn]0
Â
c
Conv.% Â 144.13 g molÀ1
.
Determined by GPC. Determined by
d
e
analysis of all of the tetrad signals in the methine region of the
homonuclear-decoupled 1H NMR spectrum.13 f At À38 1C.
the ROP of rac-LA. In the presence of isopropanol, complex 1
could convert 1500 equiv. of rac-LA to 95% monomer within
20 min (Table 1). This result is comparable to the most active
zinc initiators reported by Hillmyer and Tolman.6c Besides,
the entiomerically pure 5 could also polymerize 1000 equiv. of
rac-LA in a controlled manner (Fig. S9, ESI†).
We were more interested to observe a stereoselectivity switch
from heterotactic bias to isotactic dominant during the ROP of
rac-LA by using these zinc complexes as initiators. Complex 1
with ortho-chloro substitution provided heterotactic-bias PLAs
(Pm = 0.39).13 When the ortho-substituent of the phenolate ring
was changed to a Me, tBu or a trityl group, an obvious increase in
isotacticity of the resultant polymer was observed (Pm = 0.59, 0.74
and 0.77). With further replacement of N-ethyl by N-nbutyl, the
enantiopure complex 5, shown to be the most isoselective among
them, produced isotactic PLA with Pm of 0.81 at ambient
temperature. To achieve higher stereoselectivity, the reaction
temperature was decreased to À38 1C, a strategy normally
adopted in the literature,6e,7a,9b and an even higher isotacticity
(Pm = 0.84, Fig. 3) was obtained.13 It was found that the
coordinative solvent had an ignorable influence on the stereo-
selectivity, so did iPrOH acting as a chain-transfer agent
(Table 1 and Table S2, ESI†).
1
of two diastereomers in 1–4 via H NMR spectroscopy, the more
steric bulkiness of the ortho-substituent of the phenoxy moiety
yielded more isomer a of SCSNRNRZn configuration, which suggested
that one of the diastereomers might be suppressed by increasing
the steric bulkiness of the ligand. Accordingly, the N-ethyl group of
the pyrrolidinyl was changed to the N-nbutyl group in L5H and as
expected the corresponding reaction afforded complex 5 as a single
isomer, which was further determined by X-ray diffraction studies to
possess an absolute configuration similar to that of 1a (Fig. 2).
The above mixtures of diastereomers 1–4 and enantiopure 5
were used as such to evaluate their catalytic performance for
Fig. 3 Methine region of the homonuclear decoupled 1H NMR spectrum of isotactic
PLA produced by initiator 5 ([LA]0 : [Zn]0 : [iPrOH]0 = 200 : 1 : 1, [LA]0 = 1.0 mol LÀ1
in toluene at À38 1C).
,
Fig. 2 Molecular structure of complex 5. Hydrogen atoms are omitted for clarity.
c
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As reported in the literature, while most of the isoselective showed interesting stereoselectivity variation from heterotactic
ROPs of rac-LA are contributed by chiral metal initiators via an bias to high isoselectivity, likely a benefit of enhanced content
enantiomorphic site control mechanism,4,11 there are also some of one specific diastereomer that resulted from the increased
achiral Al5 and Y9b complexes that are isoselective as a result of steric bulkiness of the aminophenolate ligands. Further studies
being operated probably by a chain end control. To probe which aimed at a comprehensive understanding of the mechanism
mechanism is responsible for the highly isoselective ROP of rac-LA operating in this isoselective initiating system are underway.
in this work and quantitatively compare the selectivity of initiator 5
Financial support from the National Natural Science Founda-
for both monomers, preliminary kinetic studies were conducted tion of China (NNSFC, 21074032) and the Fundamental Research
for the ROP of D- and L-LA in C6D6 at 20 1C, respectively. The Funds for the Central Universities (WK1214048, WD1113011) is
polymerization reactions were found to be of first-order in gratefully acknowledged.
monomer concentration with the apparent rate constants being
3.93 Â 10À2 minÀ1 for D-LA and 1.12 Â 10À2 minÀ1 for L-LA (Fig. S10,
Notes and references
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(Fig. S18, ESI†). The high isotacticity was also confirmed by the 11 D. C. Aluthge, B. O. Patrick and P. Mehrkhodavandi, Chem. Commun.,
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proportion of tetrads observed for the methine carbon atom and
12 Similar to that of 1, the ratio of two isomers in 2 to 4 was unchanged
hexads observed for the carbonyl carbon atom in the 13C NMR
after repeated recrystallization procedures.
spectrum of the polymer sample (Fig. S20, ESI†).14
In conclusion, we have developed a highly isoselective (Pm = 0.84)
zinc initiator for the ROP of rac-LA which was obtained by elegantly
13 The Pm values were determined for all tetrads based on Bernoulli
statistics, and their average value was used. The resolution of the
integrals for the peaks corresponding to the iis, iii, and isi tetrads
was improved using peak deconvolution methods9b
.
adjusting the steric hindrance of the ligand. Complexes 1 to 5 14 J. E. Kasperczyk, Macromolecules, 1996, 28, 3937.
c
8688 Chem. Commun., 2013, 49, 8686--8688
This journal is The Royal Society of Chemistry 2013