Hydrogen-bonding catalysts based on fluorinated alcohol derivatives for living polymerization

Article abstract of DOI:10.1002/anie.200901006

Recognize this! A hydrogen-bonding motif based on hexafluorinated alcohol derivatives (see picture; O red, F yellow) activates electrophilic substrates. The catalytic activity of the hydrogen-bonded systems was demonstrated for the ring-opening polymeriza

Full text of DOI:10.1002/anie.200901006

Communications
DOI: 10.1002/anie.200901006
Organocatalysis
Hydrogen-Bonding Catalysts Based on Fluorinated Alcohol
Derivatives for Living Polymerization**
Olivier Coulembier, Daniel P. Sanders, Alshakim Nelson, Andrew N. Hollenbeck, Hans W. Horn,
Julia E. Rice, Masaki Fujiwara, Philippe Dubois, and James L. Hedrick*
Hydrogen bonding plays a vital role in biological systems,
which include the mediation of recognition between DNA
base pairs, binding of ligands to receptor sites, folding of
proteins into secondary structures, and enzymatic catalysis.[1]
Metal-free organic catalyst systems that utilize multiple
reversible noncovalent interactions to activate the substrate
in a manner analogous to natural systems are of particular
interest. For example, the use of urea, thiourea, guanidine,
and amidine functionalities (Scheme 1) in a number of
organic transformations have been investigated.[2]
organic bicyclic guanidine catalysts.[4] The ROP of LAs with
thiourea-amine catalyst 1 proceeds by activation of the
carbonyl group of the monomer by the thiourea to become
more electrophilic, and activation of the initiating or prop-
agating alcohol by the tertiary amine to become more
nucleophilic. Mechanistic studies show that both the hydro-
gen-bond-donating thiourea and hydrogen-bond-accepting
amine groups are necessary for high activity in LA ROP. In
the case where the thiourea and amine moieties are not part
of the same molecule, (À)-sparteine was found to be the most
effective base for activation when used in combination with a
thiourea derivative.[3b] Predictable molecular weights with
narrow polydispersities were achieved with shorter reaction
times and retention of stereochemistry in the resulting
polylactide (PLA).
Alcohol-containing catalysts such as biphenols and chiral
diols are another class of hydrogen-bond donors that have
been shown to form hydrogen-bonded complexes with
carbonyl-containing compounds and have been shown to
accelerate a number of reactions, including Diels–Alder
cycloaddition reactions (4–5; Scheme 2).[5] A number of
Scheme 1. Representative structures of urea 1 (X=O), thiourea 1
(X=S), guanidinium 2, and amidinium ions 3 (charges omitted).
Recently, we reported the use of a cyclic guanidine as well
as a thiourea-containing bifunctional organocatalyst for the
ring-opening polymerization (ROP) of lactides (LAs),
wherein both catalysts are believed to proceed by hydrogen-
bonding mechanisms.[3] Computational methods were used to
demonstrate the importance of hydrogen-bonding activation
in the ring-opening reaction of l-LAs in the presence of the
Scheme 2. Representative structures of diol hydrogen-bonding donor
catalysts.
[*] Dr. D. P. Sanders, Dr. A. Nelson, Dr. H. W. Horn, Dr. J. E. Rice,
Dr. J. L. Hedrick
oxidation reactions that use hydrogen peroxide have been
reported to show significantly enhanced reaction rates when
carried out in fluorinated tertiary-alcohol-based solvents,
furthermore, computational methods suggested that hydro-
gen bonding promoted the catalyst activity.[6] The utility of
alcohol-based catalysts for ring-opening polymerization of
LA is limited by their inability to sufficiently activate the
monomer as well as their tendency to act as initiator or chain
transfer agents. Herein, we introduce a new hydrogen-
bonding catalyst based on fluorinated tertiary alcohols, so-
called hexafluoroalcohols (HFAs), for the ROP of strained
heterocycles (catalyst 6, Scheme 2). In this context, the bulky
electron-withdrawing fluorinated groups serve to increase the
acidity of the alcohol (increasing hydrogen bonding), while
steric factors reduce the nucleophilicity of the alcohols and
prevent their participation in initiation or chain-transfer
IBM Almaden Research Center
650 Harry Road, San Jose, CA 95120 (USA)
E-mail: hedrick@almaden.ibm.com
Dr. O. Coulembier, Prof. P. Dubois
Laboratory of Polymeric and Composite Materials
University of Mons-Hainaut, Mons (Belgium)
Dr. M. Fujiwara
Central Glass International, San Jose, CA (USA)
A. N. Hollenbeck
Department of Chemistry, Indiana University, Bloomington (USA)
[**] O.C. and P.D. thank the Materia Nova research center and the
Belgian Federal Science Policy Office (SSTC-PAI 6/27). O.C. is an
FNRS Research Associate of Belgium. The authors also thank
Central Glass for providing several of the HFA compounds.
Supporting information (experimental procedures and character-
ization data) for this article is available on the WWW under http://
dx.doi.org/10.1002/anie.200901006.
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Chemie
reactions. A number of HFA compounds that were surveyed
as catalysts are shown in Scheme 3.
6a with VL was also confirmed by cryometric analysis (see
Figure S2 in the Supporting Information).[8]
The hydrogen-bonding capability of this new catalyst
platform was first investigated by using NMR spectroscopy to
The strength of the hydrogen-bonding interaction was
subsequently investigated by using 1H NMR spectroscopy.
When VL was titrated into a solution of 6a in C6D6 , the
hydroxy protons were most affected, as indicated by the large
~
change in chemical shift of the OH resonance ( d = 4.82).
This shift suggests that a strong hydrogen-bonding interaction
takes place between VL and the catalyst and results in the
proximity of the lactone and the aromatic methine group, and
causes a downfield shift of the methine resonance, which is
ortho to both HFA functionalities (Figure 1 and Figure S1 in
the Supporting Information). Similar results were observed
for the single-hydrogen-bonding catalysts. The combined
multinuclear NMR spectroscopy results suggest that both
type of catalysts interact with the monomer through a strong
intermolecular hydrogen-bonding interaction between the
hydroxyl group and the carbonyl group of VL.
To gain an initial understanding of the catalytic activity of
this new compound, we studied the interaction of l-lactide
10a with the catalyst 6c, using B3LYP/cc-pVTZ//B3LYP/6-
31 + G* density functional calculations[10,11] in the presence of
a continuum dielectric e = 2.38 (toluene) using IEF-PCM[12] as
implemented in GAMESS-US.[13] This result was compared to
the corresponding interaction with a model thiourea, which
has been reported to be a hydrogen-bonding catalyst
(Figure 2).[2] It can be inferred that 6c is a more potent
Scheme 3. Double- (6a–d) and single- (7a,b and 8a–c) hydrogen-
bonding catalysts and cyclic esters (9, 10a,b, 11), and carbonate (12).
compare the properties of single- versus double- hydrogen-
bonding catalysts. 13C NMR spectroscopy was used for the
identification of complexes formed by hydrogen-bonding
interactions with the carbonyl groups of the catalysts 6a and
8b.[7] When a solution of valerolactone (VL, 9) in C6D6 was
titrated with either the single-hydrogen-bonding catalyst 8b
or the double-hydrogen-bonding catalyst 6a, the carbonyl
resonance in the 13C NMR spectrum was observed to shift
downfield (see Figure S1 in the Supporting Information).
Maximum displacements of the carbonyl signal were
observed for catalyst/VL mole ratios of 2 and 0.85 for
catalysts 8b and 6a, respectively (Figure 1). These results
strongly suggest that 8b interacts with VL in a 2:1 ratio, and
that 6a interacts with VL in a 1:1 ratio. The 1:1 interaction of
Figure 2. Comparison of l-lactide 10a adduct with 6c and model
thiourea catalysts: hydrogen-bond lengths, carbonyl bond lengths, and
partial charges on the hydrogen atoms that participate in hydrogen
bonding to the oxygen atom of the carbonyl group.
hydrogen-bonding catalyst since the hydrogen-bonding dis-
tances are shorter than for the thiourea catalyst, and the
Lꢀwdin charges[14] assigned to the hydrogen atoms of the
catalyst are correspondingly larger (0.46 versus 0.41/0.39).
Initial studies on the mechanism of the rate-determining step
also confirm the importance of this adduct interaction, since
this mechanism occurs entirely through hydrogen bonding
with the catalyst (and the base), in a manner similar to that
demonstrated for the potent guanidinium catalyst.[4]
Figure 1. a) Chemical shifts in the 1H NMR spectrum observed by
titration of VL (9) with 6a (solvent C6D6); b) 13C NMR chemical shifts
observed by titration of VL with 8b (top) and 6a (bottom; solvent
C6D6)
The HFA compounds were surveyed as organocatalysts
for the ROP of LA (Scheme 4). Polymerizations were
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Figure S3 in the Supporting Information and confirms the
structure and end-group fidelity. 13C NMR analysis (Figure S4
in the Supporting Information shows no evidence of race-
mization, with only one peak in the carbonyl region).
Catalysts 6b, 6c, and 8b proved to be more active than 6a
and 6d as well as 7a and 7b. The broader PDI (polydispersity
index) of the poly(lactide) produced using catalyst 8a
(Table 1, entry 12) indicates that 8a can participate in the
reaction (presumably because of lower steric hindrance).
Catalyst 8c did not show any activity towards polymerization,
irrespective of the catalyst concentration; this inactivity is
likely a result of its steric bulk. Combinations of catalysts 6c,
6b, or 8b/BnOH/S show activities toward the ROP of lactide
comparable to that of the previously studied thiourea/BnOH/
S system (see the Supporting Information).
Scheme 4. ROP of a lactide by HFA catalysts.
conducted at ambient temperature using an alcohol initiator,
such as benzyl alcohol (BnOH), with (À)-sparteine (S) as a
cocatalyst base. It is important to note that without the
cocatalysts, no polymerization was observed for any of the
HFA catalysts at the concentrations surveyed. The ROP of l-
lactide 10a was evaluated in CH2Cl2 for a [10a]/[BnOH]/
[S]/[catalyst] ratio of 200:1:1:5 ([10a]0 = 1m), and the relative
conversions were determined by using 1H NMR spectroscopy
(Table 1 and Figure 3; a typical 1H NMR spectrum is shown in
The molecular weight (Mn) values obtained with each
catalyst (determined by gel permeation chromatography
(GPC) analysis) vary linearly with the conversion
(Figure 4). The linearity of this plot demonstrates the
Table 1: Properties of poly(l-lactide)s obtained using HFA catalysts.[a]
Conv.[c]
[%]
Mn
PDI
[d]
Entry
Cat.
t [h]
[gmolÀ1
]
1
2
3
4
5
6
7
8
6a
6a
6b
6b
6c
6d
6d
7a
7a
7b
7b
8a
8b
8b
8b
8c
52
91
52
91
47
47
72
49
121
52
91
23
23
26
50
143
47
68
73
95
72
26
30
12
15
27
54
91
23
13[b]
75
0
15300
21300
25900
27500
19000
5900
5900
3700
4400
11800
20300
12900
9500
3300
22400
–
1.09
1.09
1.07
1.08
1.06
1.08
1.07
1.08
1.08
1.07
1.09
1.28
1.06
1.08
1.09
–
9
10
11
12
13
14
15
16
Figure 4. Plot of Mn (estimated by GPC) versus LA conversion
(estimated by 1H NMR; CH2Cl2, RT, [10a]0 =1m, [10a]/[catalyst]/
[BnOH]/[S]=200/5/1/1).
controlled character of each polymerization and indicates
that little chain transfer occurs (Figure 4).[9] End-group
fidelity was investigated by the formation of an oligomer
that contained pyrene butanol as an initiator. This procedure,
which could be followed with the refractive index (RI) and
UV detectors in the GPC setup, demonstrated that the pyrene
group was attached to the chain end (Figure S4 in the
Supporting Information). 1H NMR spectroscopy was also
used to confirm the presence of the initiating (pyrene) and
terminal (hydroxy) chain ends (Figure S5 in the Supporting
Information). To provide further support for the living nature
and end-group control of this polymerization, two chain-
extension experiments were also successfully performed from
an initial polymerization using d,l-lactide 10b ([10b]0 =
2.95m; [10b]/[BnOH]/[S]/[6c] = 500:1:5:50) carried out at
room temperature for 19 hours to give a polylactide with
Mn = 43000 gmolÀ1 (PDI = 1.13), as determined by size-
exclusion chromatography (relative to polystyrene stand-
ards). Additional 10b (3.5 ꢁ 10À3 mol, 0.4 equivalents) was
added to this solution and the solution was allowed to react
for an additional 23 hours. The molecular weight of the
sample increased to 99000 gmolÀ1 (PDI = 1.15). This solution
was charged again with 4.2 ꢁ 10À3 mol (0.45 equivalents) of
[a] Reaction was performed in CH2Cl2 with BnOH as an initiator. l,l-
lactide [10a]0 =1m, [10a]/[catalyst]/[BnOH]/[S]=200:5:1:1. [b] [10a]/
[catalyst]/[BnOH/[S]=200:250:1:1. [c] Determined by 1H NMR spec-
troscopy. [d] Determined by size-exclusion chromatography.
Figure 3. Time-conversion curves obtained from ROPs of LA in CH2Cl2
at RT ([10a]/[catalyst]/[BnOH]/[S]=200:5:1:1; [10a]0 =1m).
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Chemie
1928, 14, 359 – 362; e) J. D. Bernal, H. D. Megaw, Proc. R. Soc.
10b and diluted slightly by addition of CH2Cl2 (1 mL). After
71 hours, the final molecular weight of the polymer increased
to 114000 gmolÀ1, with no real change in the polydispersity
(1.09). These characteristics are typical of a living system.
Finally, in order to demonstrate the versatility of these
catalyst systems, we surveyed the use of b-butyrolactone (BL,
11) and the cyclic carbonate MTC-Et (12; Scheme 3). In each
case, BnOH and S were used as the initiator and cocatalysts,
respectively (Table 2). Narrowly dispersed polymers were
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Table 2: Molecular characterizations of poly(BL) and poly(MTC-Et) as
obtained from HFA catalysts in different solvents.
[d]
Monomer
Cat.[a]
Solvent
t [h]
Conv.
[%]
Mn
PDI
[gmolÀ1
]
11
11
12
12
6a
6a
6c
6c
C6D6
C6D6
CH2Cl2
CH2Cl2
138[b]
357[b]
7.5
71
52
51
88
6500[c]
10600[d]
2100[c]
3200[c]
1.05
1.10
1.13
1.13
22.5
[a] 0.2 equiv of sparteine ([catalyst]/[S]=5). [b] Reaction performed at
508C. [c] BnOH initiator, DP (degree of polymerization) target: 100.
[d] Determined by size-exclusion chromatography. [e] BnOH initiator, DP
target: 425.
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A new hydrogen-bonding motif based on fluorinated
tertiary alcohols has been described, and its ability to activate
electrophilic substrates was demonstrated by NMR spectros-
copy, cryometric analysis, and computational methods. The
catalytic activity of the hydrogen-bonded catalysts towards
ROP produced narrowly dispersed polymers of predictable
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Received: February 20, 2009
Revised: April 28, 2009
Published online: June 12, 2009
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Keywords: alcohols · hydrogen bonds · organocatalysis ·
polylactides · polymerization
.
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