Bifunctional Squaramides as Organocatalysts for Lactide Polymerization: Catalytic Performance and Comparison with Monofunctional Analogues

Article abstract of DOI:10.1002/cctc.201700272

Amine-functionalized squaramides 1 and 2 were prepared and shown to be suitable polymerization organocatalysts for the controlled ring-opening polymerization (ROP) of l-lactide (l-LA) in the presence of an alcohol source such as BnOH (which acts as an initiator) to afford chain-length-controlled and narrow-dispersion poly(l-lactide) (PLLA) under mild reaction conditions. The ROP experimental and polymer analysis data are consistent with the action of 1 and 2 as bifunctional hydrogen-bonding (HB) catalysts that are able to activate both the lactide monomer and initiator BnOH thanks to their dual HB acceptor and donor properties. As a comparison, aminosquaramide 3, a direct analogue of 1 but a weaker HB donor because of the absence of electron-withdrawing NH substituents, displays little lactide ROP activity, which highlights the key role of monomer activation through HB in the present systems. Unlike aminosquaramides 1 and 2, related monofunctional squaramides 4 and 5 are inactive in l-LA ROP in the presence of BnOH, but the addition of NEt₃, as an external HB acceptor, allows the ROP to proceed with the production of well-defined PLLA. A cooperative dual activation with an activated monomer/activated chain-end mechanism is most likely operative in the lactide ROP mediated by 1 and 2 in the presence of BnOH.

Full text of DOI:10.1002/cctc.201700272

Accepted Article
Title: Bi-functional Squaramides as Organocatalysts for lactide
polymerization: Catalytic Performance and Comparison with
Mono-functional Analogues
Authors: Samuel Dagorne
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Bi-functional Squaramides as Organocatalysts for Lactide
Polymerization: Catalytic Performance and Comparison with
Mono-functional Analogues
David Specklin,[a] Frédéric Hild,[a] Li Chen,[a][b] Lucas Thévenin,[a] Maxime Munch,[a] Françoise Dumas,[b]
Franck Le Bideau,*[b] and Samuel Dagorne*[a]
Dedication ((optional))
Abstract: Amino-functionalized squaramides 1 and 2 were prepared
and shown to be suitable polymerization organocatalysts for the
controlled ROP of L-lactide (L-LA) in the presence of an alcohol
source such as BnOH (acting as initiator) to afford chain-length-
controlled and narrowly disperse poly(L-lactide) (PLLA) under mild
reaction conditions. All ROP experimental and polymer analysis data
are consistent with 1 and 2 acting as bifunctional H-bonding
catalysts able to activate both the lactide monomer and initiator
BnOH thanks to their dual HB acceptor and donor properties. As a
comparison, amino-squaramide 3, a direct analogue of 1 but less HB
donor due to the absence of electron-withdrawing NH-substituents,
displays little lactide ROP activity, highlighting the key role of
monomer activation through HB in the present systems. Unlike
amino-squaramides 1 and 2, related mono-functional squaramides 4
and 5 are inactive in lactide ROP in the presence of BnOH, but the
addition of NEt3, as an external HB acceptor, allows the ROP to
proceed with the production of well-defined PLLA. A cooperative
dual activation with an activated-monomer/activated chain-end
mechanism is most likely operative in the lactide ROP mediated by
catalysts 1 and 2 in the presence of BnOH.
performed using either metal-based initiators (organometallic
catalysis) and small organic molecules (organocatalysis).[2,3]
Industrially, PLA is currently produced via the ROP of lactide
using a Sn-based catalyst.[4] However, the typical lower toxicity
of organic vs. metal-based species prompted the development
of organocatalyzed ROP of lactide over the past 15 years for the
production of metal-free and well-defined PLA material. In this
area, non-covalent hydrogen-bonding (HB) ROP of lactide is
presently of particular interest as a versatile and mild approach
for the efficient production of PLA.[5] An interesting category of
HB catalysis lies on the combination of a strong HB donor (for
C=O activation of an electrophilic monomer such as lactide) with
a Brønsted base acting as a hydrogen-bond acceptor to
enhance the nucleophilicity of the initiating moiety (typically an
alcohol substrate). Such a dual activation was shown to
efficiently promote the ROP of lactide using, most notably, a
variety of thiourea-, amidine-, amide-, sulfonamide-based HB
donors in association with an amine moiety acting as a HB
acceptor for alcohol (initiator) activation.[5,6] These catalytic
systems may either be single-component, with a discrete
bifunctional organo-catalyst containing both HB donor and
Brønsted base functions, or, more frequently, bi-component,
with the involvement of two monofunctional molecular entities
(i.e. a HB donor and a Brønsted base).[7,8] Ongoing studies in the
area also involve the development of new types of HB
donor/acceptor catalysts for enhanced HB activation, including
acid/base pair binary systems, ionic HB catalysts and bis-/tris-
thioureas HB donors.[9,10,11]
Introduction
Poly(lactic acid) (PLA), a biodegradadable polyester composed
of lactic acid (i.e. a renewable resource) units, is currently
attracting attention as a thermoplastic polymer of potential
usefulness for a variety of applications ranging from food
packaging to electronic devices.[1] Such a material may also
constitute a viable alternative to classical petrochemically-based
thermoplastics such as polyethylene (PE), polypropylene (PP)
and polystyrene (PS). The ring-opening polymerization (ROP) of
lactide, a dimer of lactic acid, constitutes the method of choice to
access PLA with controllable properties, and may be best
Since the first report by Rawal et al.[12] and thanks to their
specific properties as strong HB donors[13], squaramides with
various skeletons have recently being successfully used as
bifunctional catalysts for the mediation of various asymmetric
organic
transformations
such
as
cycloadditions[14]
,
domino/cascade reactions[15], 1,4-conjugate additions and aldol
reactions[16]. Therefore, squaramides may stand as a suitable
HB ROP catalysts for lactide polymerization and their potential in
this area clearly remains unexplored. To date, squaramide-
mediated ROP of lactide was reported on one occasion using a
squaramide/(–)-sparteine bi-component catalytic mixture.[17a]
While the present study was in progress, a Pt-functionalized
amino-squaramide was also reported to oligomerize
lactide.[Erreur ! Signet non défini.b]
[a]
[b]
Dr. D. Specklin, Dr. F. Hild, Dr. L. Chen, L. Thévenin, M. Munch, Dr.
S. Dagorne
Institut de Chimie de Strasbourg
CNRS and Université de Strasbourg
1 rue Blaise Pascal, 67000 Strasbourg, France
E-mail: dagorne@unistra.fr
Dr. F. Dumas, Dr; F. Le Bideau
Here we report
a
complete study on various amine-
BioCIS, Univ. Paris-Sud
CNRS and Université Paris-Saclay
92290 Châtenay-Malabry, France
functionalized squaramides (1, 2 and 3, scheme 1), thus
containing a HB donor and a Brønsted base function, able to act
as single-component organocatalysts for the effective and
controlled ROP of lactide in the presence of an alcohol source
Supporting information for this article is given via a link at the end of
the document.((Please delete this text if not appropriate))
1
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10.1002/cctc.201700272
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Results and Discussion
acting as initiator. The catalytic performance of such systems
are also compared with that of related bi-component
squaramide/amine catalysts (using squaramides
scheme 1).
4 and 5,
Synthesis of Squaramides 1-5. Catalyst
1 was initially
prepared through three steps protocol starting from
a
dimethylsquarate 6 (Scheme 2) in 20% overall yield following a
literature procedure.[18] The rather low yield in 1 is due to the
Eschweiler-Clarke reaction (last step, 24% yield) allowing the
incorporation of the dimethyl amino group. A low yield one pot
synthesis of catalyst 3 (36% yield) was also recently reported.
Due to these low yields and the relatively high cost of (R,R)-
diaminocyclohexane 9, we chose another route to compounds 1
and 3 involving the pre-formation of diamine 11 (obtained in
three steps and 69% yield as previously reported[19]). Catalyst 1
(respectively 3) was thus synthesized via a sequential addition
of aryl amine 7 (respectively benzylamine 8) and then compound
11 onto diethylsquarate 10, in 70% yield (respectively 60% yield).
Catalyst 2 was prepared according to a reported procedure.[20]
The new squaramide 4 (respectively 5) was prepared in 25%
yield (respectively 58% yield) following a similar procedure with
two equivalents of arylamine 7 (respectively sequential addition
of 1 equivalent of (S)-(–)-methylbenzylamine 12 and arylamine
7).
Ring-opening polymerization of lactide catalyzed by
squaramides 1-5. The amine-functionalized squaramides 1-3
and the mono-functional derivatives 4 and 5 were tested as ROP
initiators of L-lactide under various conditions; i.e. in the
absence/presence of PhCH2OH (acting as an initiator) and NEt3
for initiator activation through HB. The polymerization runs were
all performed at room temperature in CH2Cl2 and the results are
summarized in Table 1. Remarkably, when combined with
initiator BnOH (5 equiv vs. 1), the cyclohexylamino-squaramide
1 was found to polymerize 100 equiv L-LA at room temperature
in a controlled manner in the absence of NEt3 to afford well-
defined and narrow disperse PLLA in high conversion, as
deduced from GPC and NMR data (entry 1, Table 1). Increasing
the monomer feed from 100 to 600 equiv. (with [L-LA]0/[BnOH]0
= 20) led to the controlled ROP of 450 equiv of L-LA within 23 h
to afford well-defined PLLA, indicating the effectiveness of
catalyst 1 in lactide ROP catalysis (entry 2, Table 1). With
[LA]0/[BnOH]0 = 60 and 120 and starting from 600 equiv of L-LA
(entries 3 and 4, Table 1), the production of narrow disperse
PLLA with higher chain length (Mn = 6800 g.mol-1, Đ = 1.13 and
Mn = 14600 g.mol-1, Đ = 1.06, respectively) was achieved within
48-72 h at room temperature in CH2Cl2. The ROP activity of
organocatalyst 1 is thus comparable to that of the thiourea–
amine single-component systems developed by Waymouth and
Hedrick.[Erreur ! Signet non défini.a] For all runs (entries 1-4, Table 1),
the polydispersities (Đ) of the produced PLA are below 1.15,
with GPC data featuring in all cases monomodal traces (see, for
instance, Figures S7 and S7', SI) and the PLA Mn values match
reasonably well the expected theoretical values. Besides, kinetic
data also support a well-controlled polymerization process
including: i) an observed first order reaction rate relative to L-LA
(Figure 1) and ii) a linear correlation between the Mn of the
produced PLA and the monomer-to-polymer conversion (Figure
2; for additional kinetic data, see Figure S6, SI). Regarding the
nature of the produced PLA, the NMR along with MALDI-TOF
Scheme 1. Squaramide derivatives used as lactide ROP catalysts in the
present study.
Scheme 2. Preparation of the squaramide organocatalysts.
2
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10.1002/cctc.201700272
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data agree with the production of linear and OBn-ester-ended
PLA. For instance, for the ROP of L-LA mediated by catalyst 1 in
the presence of 600 equiv of L-LA and 10 equiv of BnOH (entry
3, Table 1), the MALDI-TOF mass spectrum only contains
equally spaced peaks (by 144 u.a.), thus consistent with the
absence of any substantial (and detrimental) transesterification
reactions as the ROP proceeds (Figure 3). The mass values
also unambiguously agree with the presence of a BnO moiety at
the ester end of the formed PLA (Figures S8 and S9, SI).
the ROP reaction rate on [1] was determined by performing
several ROP runs at constant [L-LA]0 and [BnOH]0
concentrations ([L-LA]0/[BnOH]0
=
20) but at different
concentrations in 1, leading to a set of different kobs values. As
depicted in figure 4, there is a linear correlation between kobs and
[1]: this indicates a first order dependence of the reaction rate
relative to [1], which is in line with compound 1 being the actual
catalyst of the ROP process and thus with a dual activation at a
single molecular catalyst.[Erreur ! Signet non défini.,Erreur ! Signet non défini.]
For further insight on the ROP catalysis mediated by
organocatalyst 1 in the presence of BnOH, the dependence of
Table 1. ROP of L-lactide catalyzed by squaramides 1-5 in the presence of BnOH [a]
1-5 (cat.)
BnOH
O
O
with/without
NEt3
O
O
BnO
n H
O
CH2Cl2, RT
PLLA
O
[d]
[e]
Entry
1
Catalyst
L-LA/BnOH/NEt3
100/5/0
Time (h) [b]
Conv. (%) [c]
Mn
Mn
Đ [f]
(theo)
(exp)
1
1
1
1
2
2
3
4
4
4
5
5
5
18
23
48
72
18
23
23
48
25
32
48
40
40
95
75
94
90
90
50
10
57
93
91
27
83
48
2750
2150
8100
15600
2600
1400
-
2300
1800
6800
14600
2800
1200
-
1.08
1.16
1.11
1.06
1.13
1.13
-
2
600/30/0
600/10/0
600/5/0
3
4
5
100/5/0
6
600/30/0
600/30/0
600/30/1
600/30/10
600/10/10
600/30/1
600/30/10
600/10/10
7
8
1600
2700
7800
800
1600
2600
6300
800
1.15
1.06
1.10
1.02
1.05
1.08
9
10
11
12
13
2400
4150
2100
3700
[a] [L-LA]0 = 2 M, CH2Cl2, room temperature. [b] Reaction time. [c] Monomer conversion to PLLA as determined by 1H NMR. [d] Calculated using Mn
=
(theo)
[L-LA]0/[BnOH]0 × ML-LA × conv. [e] Calculated using Mn (theo) = [L-LA]0/[BnOH]0 × ML-LA × conv. e Measured by GPC in THF (30 °C) using polystyrene standards and
corrected by applying the appropriate correcting factor (0.58).[21] [f] Measured by GPC in THF (30 °C).
3
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Figure 2. Plot of the Mn (g.mol-1) of the produced PLA versus monomer
conversion in the ROP of L-LA mediated by amino-squaramide 1 in the
presence of BnOH. Conditions: L-LA/BnOH/1 = 600/30/1, room temperature,
CH2Cl2.
Figure 1. Plot ln([M]0/[M]) (M = monomer = L-LA) versus time in the ROP of L-
LA mediated by amino-squaramide 1 in the presence of BnOH. Conditions: L-
LA/BnOH/1 = 600/30/1, room temperature, CH2Cl2.
Figure 3. MALDI-TOF analysis of the isolated from the ROP of L-LA mediated by amino-squaramide 1 in the presence of BnOH. Conditions: L-LA/BnOH/1 =
600/10/1, room temperature, CH2Cl2 (48 h, 94% conv. to PLLA).
LA and BnOH. Conditions: [L-LA]0
= 2 M, [L-LA]0/[BnOH]0 = 20, room
temperature, CH2Cl2.
Amino-squaramide 2, which contains a more flexible CH2-CH2-
NMe2 amino side-arm vs. that in catalyst 1, also mediates the
ROP of L-LA in a controlled manner but is less active than its
analogue 1 (entries 5 and 6, Table 1). Thus, in the presence of
600 equiv of L-LA and 30 equiv of BnOH, species 2 may
polymerize up to 300 equiv of L-LA within 23 h (CH2Cl2, room
temperature) while 450 equiv of monomer are polymerized by
catalyst 1 under identical reaction conditions (entry 5 vs. 2;
Table 1). Kinetic data with catalyst 2 are also consistent with a
well-controlled ROP catalysis (Figures S12 and S13, SI) and
with catalyst 2 being roughly twice slower than its analogue 1
(Figure S1 vs. Figure S12). Polymer analysis data for the ROP
Figure 4. Plot of kobs versus [1] in the ROP of L-LA mediated by amino-
squaramide 1 in the presence of BnOH at constant initial concentrations of L-
4
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mediated by 2 agree with the formation of BnO-ester-ended
PLLA (Figures S11 and S14, SI). When compared to catalyst 2,
the rigidity and the steric bulk of the cyclohexyl backbone in 1
certainly further favors a conformational arrangement in which
the NMe2 moiety lies in the vicinity of the NH amido functions (as
depicted in scheme 1 for squaramide 1), a key feature for an
effective bifunctional ROP catalysis (monomer and initiator
activation in close proximity). Note that catalysts 1 and 2 also
mediate the ROP of rac-LA (with a similar reaction rate and
polymerization control to that observed with L-LA) to afford
atactic PLA, while they are both essentially inactive in the ROP
of other lactones such as ε-caprolactone.
The nature of the squaramide NH-substituents also
appears of importance for an efficient ROP process. Thus, the
cyclohexylamino-squaramide 3 (Scheme 1), which bears a
PhCH2-NH moiety vs. a 3,5-(CF3)2-PhCH2-NH group in 1, only
displays a moderate ROP activity in the presence of 600 equiv
LA, with only a 10% consumption of monomer after 23 h at room
temperature (CH2Cl2, 30 equiv of BnOH; entry 7, Table 1). The
presence of electron withdrawing NH-substituents is thus clearly
required to enhance the HB donor character of these
bifunctional catalysts and hence ensure an effective monomer
activation, as previously observed.[5,7,8]
10 equiv of NEt3 increases the ROP reaction rate by a factor of
6.5. To probe this issue further, the ROP reaction rate
dependence on [NEt3] was studied at constant [L-LA]0, [BnOH]0
and [4]0 ([L-LA]0/[BnOH]/[4]0 = 600/30/1) but at different NEt3
concentrations. The observed linear correlation of kobs vs. [NEt3]
agree with a first order dependence of the reaction rate on [NEt3]
(Figure 5), thus confirming the beneficial effect (on reaction rate)
of an excess of NEt3. As a comparison and in contrast,
Kiesewetter and co-workers showed that cocatalyst binding
effects in such bi-component systems, i.e. amine/HB donor
interactions, may be detrimental to catalytic activity at higher
amine/HB donor ratios in the case of DBU/thiourea (DBU = 1,8-
Signet non
dizabicyclo[5.4.0]undec-7-ene) catalytic systems.[Erreur !
défini.j] In our case, the lower Lewis basicity of NEt3 (vs. DBU), yet
allowing an effective initiator activation, along with the
systematic use of an excess initiator (vs. squaramide) certainly
disfavor substantial NEt3/4 HB interactions.
The bifunctional nature of amino-squaramide catalysts 1
and
2 was further evidenced by comparing their ROP
performances with those of their mono-functional counterparts 4
and 5 (Figure 1). Thus, unlike species 1-3, both 4 and 5 are
inactive in L-LA ROP in the presence of BnOH under various
reactions (CH2Cl2, room temperature, 100 or 600 equiv of L-LA,
10 or 30 equiv of BnOH), highlighting the fact that initiator (i.e.
BnOH) activation is crucial for the ROP to proceed with the
present catalytic systems. Accordingly, the addition of an
external Lewis base such as NEt3 for initiator activation
promoted the ROP reaction. Thus, in the presence of 600 equiv
of L-LA and 30 equiv of BnOH, the 1/1 4/NEt3 catalytic mixture
afforded PLA in a controlled manner with a 57% conv. after 48 h
at room temperature as deduced from NMR and GPC data
(entry 8, Table 1; Figures S15-S17, SI). As a comparison, with
an identical monomer/initiator feed, bifunctional catalyst 1 is
clearly more effective with a 75% conv. to PLA within 23 h (entry
2 vs. entry 8, Table 1), showing that the intramolecular proximity
of the HB donor/acceptor sites for monomer and initiator
activation is clearly beneficial to ROP catalysis. Comparing the
observed ROP rate constant (kobs) of a 1/1 4/NEt3 catalyst vs.
amino–squaramide 1 (kobs = 0.0173 and 0.0433 h-1, respectively;
Figures S15 vs. S1), the ROP reaction is 2.5 times faster with
the bifunctional catalyst 1 than with the 1/1 4/NEt3 bi-component
system. The ROP performance of the 4/NEt3 catalytic mixture
may be significantly improved upon increasing feed in NEt3.
Thus a 1/10 4/NEt3 catalyst mixture readily polymerizes L-LA to
afford chain-length controlled PLLA in high conversion in the
presence of BnOH as initiator (600 equiv L-LA, > 90% conv. to
PLLA within 25 or 32 h, 10 or 30 equiv of BnOH; entries 9 and
10, Table 1). All kinetic and polymer characterization data agree
with a well-controlled process (Figures S18-S21, SI). The kinetic
data for the 1/1 vs. 1/10 4/NEt3 catalytic system (kobs = 0.0173 vs.
0.111 h-1; Figures S15 and S18, SI) indicate that going from 1 to
Figure 5. Plot of kobs versus [NEt3] in the ROP of L-LA mediated by 4/NEt3 at
constant initial concentrations of 4, L-LA and BnOH. Conditions: [L-LA]0 = 1 M,
[L-LA]0/[BnOH]0/4 = 600/30/1, room temperature, CH2Cl2.
The mono-functional squaramide 5 (Scheme 2), which only
bears one electron withdrawing NH-substituent, also mediates
the controlled ROP of L-LA in the presence of BnOH and NEt3
(entries 11-13, Table 1; Figures S22-S25, SI) though with a
lower activity than analogue 4, presumably reflecting the lower
HB donor ability (for monomer activation) of 5 vs. 4.
Overall, the kinetic and characterization data on L-LA ROP
catalysis by bifunctional amino-squaramides 1-3 (including their
comparison with their mono-functional analogues 4 and 5)
clearly hints at a ROP process occurring through a cooperative
dual activation of the monomer and initiator/polymer chain-end
thanks to the HB donor ability of the squaramide moiety (for
lactide activation) and the HB accepting character of the NMe2
moiety (for initiator/polymer chain-end activation). The proposed
bifunctional
activation
mechanism,
i.e.
activated
is
monomer/activated chain-end mechanism (AM/ACEM)[3h]
,
depicted in Scheme 3. Such a dual activation at a single
molecular catalyst is documented in the literature with other
lactide ROP organocatalysts, most notably amino-functionalized
thioureas and amidine-type organics.[Erreur ! Signet non défini.]
5
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10.1002/cctc.201700272
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O
O
Scan accumulation and data processing were performed with
FlexAnalysis 3.4 software. α-cyano-4-hydroxy-cinnamic acid (CHCA),
dithranol (DIT) or super-DHB (a 9/1 mixture of dihydroxybenzoid acid/2-
hydroxy-5-methoxybenzoic acid) was used as matrix for analysis of the
PLA samples. SEC analyses were performed on a SEC system equipped
with a Shimadzu RID10A refractometer detector using HPLC-grade THF
as an eluent. Molecular weights and dispersities (Đ) were calculated
using polystyrene standards. In the case of molecular weight number
(Mn), these were corrected with the appropriate correcting factor (0.58)
for the Mn values. The synthesis and characterization of squaramides 1-5
are described in the Supporting Information.
O
O
O
N
H
N
H
F3
C
N
H
N
H
F3
C
1/BnOH
O
NMe2
H
NMe2
O
O
O
H
CF3
CF3
O
O
O
O
Ph
O
O
O
O
O
Ph
O
O
O
n
O
O
O
H
Ph
O
O n+1
O
General procedure for ROP of L-lactide mediated by squaramides 1-
5 in the presence of BnOH. In a glovebox, the squaramide catalyst 1-5
(2 mg, 3.54 × 10-6 mol) was charged in a vial equipped with a TeflonTM-
tight screw-cap and dissolved in dichloromethane (0.2 mL). In a separate
vial, the appropriate amount of L-lactide (from 100 to 600 equiv, 2.12 ×
10-3 mol) and of BnOH (from 5 to 30 equiv, 1.06 × 10-4 mol) were
dissolved in dichloromethane (0.8 mL) and added all at once to the
Scheme 3. Bifunctional activation mechanism for the ROP of L-LA catalyzed
by amino-squaramides 1 and 2 in the presence of BnOH, taking the example
of squaramide 1.
catalyst solution ([L-LA]0
= 2 M). In the case of mono-functional
Conclusions
squaramides 4 and 5, NEt3 (10 equiv, 3.54 × 10-5, 4.9 µL) was also
added to the reaction mixture. The mixture was vigorously stirred at room
temperature during the appropriate time and the reaction was monitored
by 1H NMR spectroscopy. After the appropriate time, the vial was then
removed from the glovebox and the reaction mixture was quenched with
an excess of methanol, provoking the precipitation of the polymer which
was washed several times with methanol, dried in vacuo until constant
weight and subsequently subjected to 1H NMR, GPC and MALDI-TOF
analysis.
Amino-functionalized squaramides
1
and
2
are suitable
polymerization organocatalysts for the controlled ROP of L-LA in
the presence of an alcohol source such as BnOH acting as
initiator to afford chain-length-controlled and narrowly disperse
PLLA. When compared to related mono-functional squaramides
4 and 5 (which require the presence of an external HB acceptor
for the ROP to occur), the ROP results with catalysts 1 and 2
agree with a cooperative dual activation ROP mechanism of the
type AM/ACEM being operative due to their bifunctional nature
(i.e. HB donor and acceptor). Given the steric and electronic
tunability of squaramide derivatives (through variation of NH
substituents) along with their straightforward access via well-
Acknowledgements ((optional))
The authors thank the CNRS, the University of Strasbourg and
the University of Paris-Sud for financial support.
established
synthetic
procedures,
such
HB-based
organocatalysts may also be of potential interest for the
polymerization of various polar cyclic monomers.
Keywords: lactide • polymerization • squaramide •
organocatalysis • hydrogen-bonding
Experimental Section
[1]
a) E. Castro-Aguirre, F. Iñiguez-Franco, H. Samsudin, X. Fang, R.
Auras, Adv. Drug Deliv. Rev. 2016, 107, 333; b) S. Slomkowski, S.
Penczek, A. Duda, Polym. Adv. Technol. 2014, 25, 436; b) L. S. Nair, C.
T. Laurencin, Prog. Polym. Sci. 2007, 32, 762; c) M. Vert,
Biomacromolecules 2005, 6, 538.
All experiments were carried out under N2 using standard Schlenk
techniques or in a MBraun Unilab glovebox. Toluene, dichloromethane,
and pentane were first dried through a solvent purification system
(MBraun SPS) and stored for at least a couple of days over activated
molecular sieves (4 Å) in a glovebox prior to use. CD2Cl2 was purchased
from Eurisotope (CEA, Saclay, France), degassed under a N2 flow, and
stored over activated molecular sieves (4 Å) in a glovebox prior to use.
Benzyl alcohol (BnOH) was also dried for 24 h over activated molecular
sieves (4 Å) prior to use. All other chemicals were used as received. L-
lactide was sublimed once prior to use. NMR spectra were recorded on
BrukerAC 300 or 400 MHz NMR spectrometers in Teflon-valved J-Young
NMR tubes at ambient temperature, unless otherwise indicated. 1H and
13C chemical shifts are reported versus SiMe4 and were determined by
reference to the residual 1H and 13C solvent peaks. Chemical shifts (δ)
are given in ppm. Mass spectra were performed at the Mass
Spectrometry Department of the University of Strasbourg. Mass spectra
were acquired on a time-of-flight mass spectrometer (MALDI-TOF-TOF
Autoflex II TOF-TOF, Bruker Daltonics, Bremen, Germany) equipped with
a nitrogen laser (λ = 337 nm). An external multi-point calibration was
carried out before each measurement with a standard peptide mixture
and a standard protein mixture (depending on the mass range analysed).
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7
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Title
Single-component amino-squaramides reported herein act as effective bifunctional
hydrogen-bonding catalysts for the controlled ROP of lactide under mild conditions
in the presence of BnOH. Such organocatalysts perform better in lactide ROP than
related squaramide/NEt3 bi-component catalysts.
8
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