Revisiting thiol-yne chemistry: Selective and efficient monoaddition for block and graft copolymer formation

Article abstract of DOI:10.1002/pola.27345

The untapped potential of radical thiol-yne mono-addition chemistry is exploited to overcome the known limitations of thiol-ene chemistry in polymer coupling and block copolymer formation. By careful choice of alkyne, the reaction can selectively lead to

Full text of DOI:10.1002/pola.27345

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Revisiting Thiol-yne Chemistry: Selective and Efficient Monoaddition
for Block and Graft Copolymer Formation
This manuscript is for the special edition celebrating Prof. Frechet’s 70th birthday and is dedicated to his extraordinary
contributions to field of polymer science.
Johannes K. Sprafke,1 Jason M. Spruell,1 Kaila M. Mattson,1,2 Damien Montarnal,1
1
1,3
Alaina J. McGrath, Robert Potzsch, Daigo Miyajima,1,4 Jerry Hu,1 Allegra A. Latimer,1,2
€
Brigitte I. Voit,3 Takuzo Aida,4 Craig J. Hawker1,2,5
1Materials Research Laboratory, University of California, Santa Barbara, California 93106
2Department of Chemistry and Biochemistry, University of California, Santa Barbara, California 93106
3Leibniz Institute of Polymer Research Dresden, Hohe Strasse 6, 01069 Dresden, Germany
4Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku,
Tokyo 113-8656, Japan
5Department of Materials, University of California, Santa Barbara, California 93106
Correspondence to: C. J. Hawker (E-mail: hawker@mrl.ucsb.edu)
Received 6 June 2014; accepted 29 July 2014; published online 00 Month 2014
DOI: 10.1002/pola.27345
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synthesis of a variety of diblock and graft copolymers. 2014
ABSTRACT: The untapped potential of radical thiol-yne mono-
addition chemistry is exploited to overcome the known limita-
tions of thiol-ene chemistry in polymer coupling and block
copolymer formation. By careful choice of alkyne, the reaction
can selectively lead to the mono-addition product with efficien-
cies surpassing those achieved by traditional thiol-ene chemis-
try. This improvement is illustrated by the nearly quantitative
Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem.
2014, 00, 000–000
KEYWORDS: block copolymers; click chemistry; functionalization
of polymers; synthesis; thiol-yne
illustrated by “click” strategies, a set of highly efficient and
orthogonal chemistries that have been widely used in the syn-
thesis of small molecules and the functionalization of poly-
mers.3 The additional challenges inherent in the coupling of
two polymer chain ends have been highlighted by Barner-
Kowollik et al.4 who proposed further requirements, including
equimolar stoichiometries, simplified purification, high yields
and fast timescales. One of the most widely used reactions in
the context of click chemistry is the radical hydrothiolation of
alkenes, referred to as thiol-ene chemistry, which has been
used in the synthesis of polymer networks,5 functional surfa-
ces,6 and dendrimers.7,8 Advantages of this reaction over other
methodologies include facile synthetic access to both alkenes
and thiols as well as spatiotemporal control that can be
achieved by using a radical photoinitiator. Efficient polymer–
polymer coupling, which can be regarded as a litmus test for
any “click” reaction, has, despite significant efforts, thus far
been elusive by means of thiol-ene chemistry with reported
coupling efficiencies reaching only 25%.9
INTRODUCTION Block copolymers and related advanced
macromolecular architectures have played a pivotal role in
the development of nanostructured materials, enabling trans-
formative technologies ranging from thermoplastic elasto-
mers to drug delivery vehicles.1 Polymer–polymer coupling
provides an efficient synthetic route to a wide variety of
block copolymers, particularly when it is challenging to find
sequential polymerization conditions compatible with vari-
ous monomer families. An additional benefit from a polymer-
coupling strategy is the ability to start from stable, well-
defined starting polymers leading to the reproducible syn-
thesis of block copolymers with predetermined molecular
weights (Scheme 1).2 Synthetically, polymer coupling reac-
tions are among the most challenging chemical transforma-
tions and are limited by low end group concentration, steric
effects and decreased reactivity.
In recent years, the potential of polymer–polymer coupling
reactions for the preparation of block copolymers have been
Johannes K. Sprafke and Jason M. Spruell contributed equally to this work.
Additional Supporting Information may be found in the online version of this article.
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carbon centered radical. Indeed, thiol-ene reactions of sty-
rene or methacrylates involving highly stabilized radicals
have much lower hydrogen abstraction rates, resulting in a
variety of side reactions, particularly homopolymerization,
that lower the efficiency of the coupling reaction.8(b)
In order to improve the efficiency of reactions involving
readily available thiol chain ends for block copolymer syn-
thesis, we turned our attention to radical intermediates that
are less stable than the sp3-centered radicals formed from
the commonly used alkenes in thiol-ene chemistry. Vinyl rad-
icals are intermediates in the thiol-yne reaction and are
known to be significantly less stable than alkyl radicals. This
suggests that thiol-yne monoaddition may be a more efficient
alternative to the classic thiol-ene reaction.
SCHEME 1 Graphical representation of thiol-yne monoaddition
as a “Click” reaction for block copolymer formation.
The factors that determine the efficiency of the radical thiol-
ene reaction are well understood, as is the reaction mecha-
nism [Scheme 2(a)].8(b),10 In short, a radical initiator acti-
vated by either heat or light converts a thiol into a thiyl
radical that then adds to the alkene, generating a sp3
carbon-centered radical (propagation step). This radical then
abstracts a hydrogen atom from another thiol to form the
thioether product and regenerates a thiyl radical that propa-
gates a further cycle (chain transfer step). Electron-rich
alkenes have the highest radical addition rates, while the
rate of hydrogen abstraction is limited by the stability of the
While the thiol-yne reaction has recently gained popularity
for its ability to cleanly form bis-adducts without significant
monoadduct accumulation,11 initial studies nearly a century
ago demonstrated that for select substrates, such as phenyla-
cetylene derivatives, quantitative monoaddition could be
achieved.12 This selectivity can be explained by the generally
accepted mechanism for the thiol-yne reaction that follows
the identical propagation and chain transfer steps as the
thiol-ene reaction [Scheme 2(b)].11(a) The first addition of
the thiol to the alkyne forms a vinyl sulfide intermediate
that can then react with another thiol to form the bis-
adduct. In both reactions, the addition of the thiyl radical is
reversible, whereas the hydrogen abstraction is irreversible.
Therefore, the selectivity for mono- or bis-addition is solely
determined by the ratio of the two hydrogen abstraction
steps, kCT1 and kCT2, which in turn depends on the relative
stability of the carbon-centered radical intermediates. In the
case of the thiol-yne reaction with phenylacetylene, the stabi-
lized benzyl radical formed in the second addition step
results in a significantly lower kCT2 when compared to kCT1
,
and the initial vinyl radical. A direct consequence of this is
the high selectivity for monoaddition when 1 equiv of thiol
is used in conjugation with phenylacetylene derivatives,
which as noted above is in direct contrast to the bis-
additions typically observed for thiol-yne reactions.
EXPERIMENTAL
Additional examples can be found in the Supporting
Information.
General Information
Unless otherwise noted, all commercially obtained solvents
and reagents were used without further purification. Poly(di-
methylsiloxane-co-[(mercaptopropyl)methylsiloxane]) (PDMS-
co-PMMS8k) 9 was purchased from Gelest. Methyl 4-
ethynylbenzoate was purchased from Sigma-Aldrich. Polyeth-
ylene oxide (PEO) samples PEO1k 3, PEO2k 4, and PEO5k
5
were synthesized according to a published procedure.13
NMR spectra were collected on a Varian VNMRS 600 MHz
SB, Bruker Avance DMX 500 MHz SB, or a Varian Unity Inova
400-MHz spectrometer. All diffusion measurements were
SCHEME 2 Mechanism of (a) the thiol-ene reaction and (b) the
thiol-yne reaction.
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carried out on a Bruker 300-MHz super-wide bore NMR
spectrometer. Chemical shifts are reported in parts per mil-
lion (ppm) and referenced to the residual solvent signal.
Matrix-assisted laser desorption/ionization time-of-flight
mass spectrometry (MALDI-TOF MS) data were collected on
to obtain the pure PS6k 1 (2.5 g, 0.42 mmol, 93%) as a col-
orless solid.
1H NMR (600 MHz, CDCl3): d 7.74–7.72 (br, 2H, CHAr), 7.52–
7.49 (br, 2H, CHAr), 7.33–6.31 (br, 282H, CHAr), 4.15–3.87
(br, 2H, CH2O2C), 3.23 (s, 1H, CCH), 2.57–0.84 (br, 182H,
CH2, CHAr), 0.80–0.57 (br, 6H, CH3); Mn (1H NMR) 5 6070
gꢁmol21; GPC (CHCl3, PS standard): Mn 5 6000 gꢁmol21, PDI
a
Bruker Microflex LRT, with a 60-Hz nitrogen laser
(337 nm). Micromass QTOF2 Quadrupole/time-of-flight tan-
dem mass spectrometer was used for high-resolution mass
analysis using electrospray ionization (ESI). Photolumines-
cence spectra were recorded on a Cary Eclipse fluorescence
spectrophotometer and UV–vis absorption spectra on a Shi-
madzu UV3600 UV-NIR spectrometer. Gel permeation chro-
matography (GPC) analysis was performed on a Waters
Alliance HPLC system equipped with two 300 3 7.5 mm
Agilent PLGEL 5 mm MIXED-D columns, a Waters 2410 dif-
ferential refractometer (refractive index, RI), and a Waters
2998 photodiode array detector. Thiol-yne reactions were
irradiated using a UVP Black Ray UV bench lamp XX-15L,
which emits 365-nm light at 15 W. Reactions under micro-
wave irradiation were carried out in a Biotage microwave
reactor.
(Mw/Mn) 5 1.08; MALDI-TOF MS: Mn 5 6060 gꢁmol21
.
Preparation of Hydroxyl-Terminated Polycaprolactone
(PCL): PCL-OH11k
In a flame-dried sealed tube, dry e-caprolactone (4.0 g, 35
mmol, 3.7 mL) (distilled from CaH2) and benzyl alcohol
(14 mg, 0.13 mmol, 13 mL) were dissolved in dry toluene
(9 mL) under argon and the mixture was heated to 110 ꢀC.
Freshly distilled Sn(Oct)2 (100 mg, 0.25 mmol, 63 mL) was
added and the reaction mixture stirred for 2 h at 110 ꢀC.
The product PCL-OH11k (2.7 g) was obtained as a colorless
solid from precipitation into hexanes.
1H NMR (600 MHz, CDCl3): d 7.36–7.31 (br, 5H, CHAr), 5.11
(s, 2H, ArCH2OR), 4.05 (t, J 5 6.7 Hz, 182 H, CH2OCO), 3.64
(t, J 5 6.5 Hz, 2H, CH2OH), 2.30 (t, J 5 7.5 Hz, 185H, O2CCH2),
1.67–1.61 (m, 397H, CH2), 1.41–1.35 (m, 185H, CH2); Mn
(1H NMR) 5 10,700 gꢁmol21; GPC (CHCl3, PS standard):
Mn 5 20,200 gꢁmol21, PDI (Mw/Mn) 5 1.15.
Representative Synthesis of Hydroxyl-Terminated
Polystyrene: Preparation of PS-OH6k
Styrene polymerization with s-BuLi as initiator was per-
formed in dry cyclohexane under a purified argon atmos-
phere. About 1.4 M s-BuLi (6.4 mL, 9.0 mol) was added to
500 mL cyclohexane at room temperature followed by the
addition of purified styrene (50 mL, 0.43 mol). After stirring
for 10 min, the reaction mixture was heated to 45 ꢀC and
stirred overnight (ca. 12 h). Before the termination of the
reaction, an excess amount of ethylene oxide (3.0 g) was
added to the resulting reaction solution in order to end-cap
the polystyrene (PS). After stirring for 10 min, the polymer-
ization was quenched by the addition of an excess amount of
MeOH (10 mL). The resultant PS was purified by precipita-
tion into MeOH from CH2Cl2.
Synthesis of Phenylacetylene End-Functionalized PCL
from Hydroxyl-Terminated Precursor: Preparation of
PCL11k (2)
PCL-OH11k (0.75 g, 70 mmol), 4-ethylbenzoic acid (52 mg,
0.35 mmol), and 4-(dimethylamino)pyridinium p-toluenesul-
fonate (21 mg, 70 mmol) were placed in a dry flask under
argon atmosphere and dissolved in dry CH2Cl2 (8 mL). Dicy-
clohexylcarbodiimide (73 mg, 0.35 mmol) was added and
the reaction stirred under argon at room temperature for 24
h. Then, the reaction mixture was filtered and the solvent
removed. The crude product was passed through a short
plug of silica (CH2Cl2) and then purified using a short gravi-
metric SEC column (toluene). The product PCL11k 2 was
obtained by precipitation from CH2Cl2 into hexanes as a col-
orless powder (690 mg, 64 mmol, 92%).
1H NMR (500 MHz, CDCl3): d 7.31–6.32 (br, 277H, CHAr),
3.31 (s, 2H, CH2OH), 2.53–0.87 (br, 210H, CH2, CHAr), 0.78–
0.60 (br, 6H, CH3); Mn (1H NMR) 5 5770 gꢁmol21; GPC
(CHCl3, PS standard): Mn 5 5900 gꢁmol21, polydispersity
index (PDI) (Mw/Mn) 5 1.05; MALDI-TOF MS: Mn 5 5930
1H NMR (600 MHz, CDCl3): d 7.98 (d, J 5 8.2 Hz, 2H, CHAr),
7.54 (d, J 5 7.9 Hz, 2H, CHAr), 7.38–7.31 (br, 5H, CHAr), 5.11
(s, 2H, ArCH2OR), 4.32 (t, J 5 6.5 Hz, 2H, CH2OCOAr), 4.06 (t,
J 5 6.7 Hz, 187 H, CH2OCO), 3.23 (s, 1H, CCH), 2.30 (t, J 5 7.5
Hz, 189H, O2CCH2), 1.68–1.62 (m, 410H, CH2), 1.41–1.36 (m,
190H, CH2); Mn (1H NMR) 5 11,400 gꢁmol21; GPC (CHCl3, PS
standard): Mn 5 21,800 gꢁmol21, PDI (Mw/Mn) 5 1.12.
gꢁmol21
.
Representative Synthesis of Phenylacetylene End-
Functionalized PS from Hydroxyl-Terminated Precursor:
Preparation of PS6k (1)
PS-OH6k (2.7 g, 0.45 mmol), 4-ethylbenzoic acid (0.55 g, 3.8
mmol), 4-dimethylaminopyridine (99 mg, 0.81 mmol), and 4-
(dimethylamino)pyridinium p-toluenesulfonate (0.24 g, 0.81
mmol) were placed in a dry flask under argon atmosphere
and dissolved in dry CH2Cl2 (30 mL). Dicyclohexylcarbodii-
mide (0.78 g, 3.8 mmol) was added and the reaction stirred
under argon at room temperature for 24 h. The reaction mix-
ture was then filtered and the solvent removed. The crude
product was passed through a short plug of silica (CH2Cl2)
Representative Synthesis of Chlorine-Terminated
Polysiloxane: Preparation of PDMS-Cl1k
About 20 g of hexamethylcyclotrisiloxane (D3) was dried with
500 mg of NaH in a Schlenk tube over night at 80 ꢀC. The pure
D3 monomer was distilled bulb to bulb to a three-neck round
bottom flask cooled in liquid nitrogen bath. The net weight of
pure D3 monomer was 13.8 g. About 200 mL of
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TABLE 1 Product Distribution of the Thiol-yne Reaction
Between Phenylacetylene and 1-Hexanethiol
Alkyne
Alkyne:Thiol Mono-
Cis/trans Bis-Adduct
Conc. (mM) (Feed)
Adduct (%) Ratio
(%)
5
1:1
100
100
100
97
72/28
40/60
19/81
16/84
15/85
16/84
14/86
20/80
0
50
1:1
0
500
500
500
500
500
500
1:1
0
1:1.25
1:1.5
1:2
3
94
6
86
14
64
95
1:5
36
1:10
5
Si(O)(CH3)(CH3)); Mn (1H NMR) 5 1240 gꢁmol21; GPC (CHCl3,
PS standard): Mn 5 1300 gꢁmol21, PDI (Mw/Mn) 5 1.30.
SCHEME 3 Product distribution of the thiol-yne reaction
between phenylacetylene and 1-hexanethiol.
Synthesis of Poly[styrene-co-(4-ethynyl styrene)]
(PS-co-PES20k 8)
tetrahydrofuran (THF) was added into the flask. 10 mL of
1.4 M s-BuLi was added into the solution at room temperature.
After 2 h, 4.5 mL of chloro(3-chloropropyl)dimethylsilane was
added to quench the reaction. About 10 h later, the mixture
was precipitated in 500 mL of MeOH/H2O twice. 1H NMR (400
MHz, CDCl3): d 3.51 (t, J 5 7.0 Hz, 2H, CH2CH2Cl), 1.84–1.76
(m, 2H, CH2CH2Cl), 1.61–1.51 (m, 1H, CH2CH3), 1.19–1.09 (m,
1H, CH2CH3), 0.96–0.90 (2 x t, 6H, CH3), 0.68–0.61 (m, 2H,
SiCH2), 0.58–0.49 (m, 1H, CH3CH), 0.16–0.03 (m, 78H,
Si(O)(CH3)(CH3)); Mn (1H NMR) 5 1160 gꢁmol21; GPC (CHCl3,
PS standard): Mn 5 1100 gꢁmol21, PDI (Mw/Mn) 5 1.27.
Styrene (1.10 mL, 8.91 mmol), 4-(30-trimethylsilylpropargy-
loxy)styrene14 (0.309 g, 1.54 mmol), and azobisisobutyroni-
trile (0.012 g, 0.071 mmol) were diluted in benzene (8 mL)
in a Schlenk tube. The solution was deoxygenated by freez-
ing in liquid nitrogen, evacuating the flask, and then thawing
at room temperature. This process was repeated four times,
upoꢀn which the vessel was placed in an oil bath heated to
70 C for 14 h. The reaction was terminated by exposing to
air, concentrating the solution in vacuo, then precipitating
twice into MeOH (100 mL) affording a white powder
(0.325 g, conversion 5 25%). This solid was dissolved in
THF (3 mL) at room temperature, after which a solution of
tetra-n-butylammonium fluoride (TBAF, 3.0 mL of 1.0 M in
THF) was added dropwise. The reaction mixture was stirred
for 12 h, concentrated in vacuo, and precipitated twice into
MeOH (100 mL) affording 8 as a white powder (0.301 g):
Mn 5 20,400 gꢁmol21, PDI (Mw/Mn) 5 1.65.
Synthesis of Thiol-Terminated Polysiloxane from
Chlorine-Terminated Precursor: Preparation of PDMS1k
(6)
Polydimethylsiloxane (PDMS)-Cl1k (1.00 g, 862 mmol) and
potassium thioacetate (520 mg, 4.55 mmol) were dissolved in
a mixture of N,N-dimethylformamide (2.5 mL) and dimethoxy-
1H NMR (600 MHz, CDCl3): d 7.33–6.18 (br, 21H, CHAr), 3.04
(s, 1H, CHacet), 2.27–0.86 (br, 15H, CH2, CHAr). Styrene:al-
kyne ratio 5 77:23.
ꢀ
ethane (2.5 mL) and heated at 110 C for 2 h in a microwave
reactor. To the reaction, mixture were added CH2Cl2 and water.
The phases were separated and the organic phase washed
twice with water and once with brine. The crude product was
dried under high vacuum and directly used for the following
deprotection. The crude product (700 mg) was dissolved in
Synthesis of Silyl-Protected Catechol Derivative CatSH
(19)
ꢀ
THF (3 mL) under argon atmosphere and cooled to 0 C. To
To a round bottom flask were added ((4-allyl-1,2-phenylene)-
bis(oxy))bis(triethylsilane)15 (10.9 g, 28.9 mmol), ethane
dithiol (19.4 mL, 231 mmol) and 2,2-dimethoxy-2-phenylace-
tophenone (148 mg, 0.58 mmol) and sparged with argon for
30 min. The reaction was irradiated with UV light for 1 h
and checked by gas chromatograph (GC) to ensure complete
consumption of alkene. The excess ethane dithiol was
removed by vacuum distillation and the resulting mixture
was passed through a column using 25% CH2Cl2/hexanes as
the eluent to remove residual impurities to afford (CatSH
19) (11.6 g, 85%) as a colorless oil.
the solution was added hydrazine (35% in H2O, 0.29 mL, 8.18
mmol) and then stirredꢀat room temperature for 30 min, fol-
lowed by stirring at 35 C for 2 h. After the addition of glacial
acetic acid (1 mL) and water (10 mL), the organic phase was
washed twice with water and then dried over sodium sulfate.
After removal of the solvent, the pure product (600 mg) was
obtained as a colorless oil.
1H NMR (600 MHz, CDCl3): d 2.53 (dt, J 5 7.5 Hz, 2H,
CH2CH2SH), 1.67–1.62 (m, 2H, CH2CH2SH), 1.60–1.53 (m, 1H,
CH2CH3), 1.32 (t, J 5 7.9 Hz, 1H, CH2SH), 1.18–1.11 (m, 1H,
CH2CH3), 0.95–0.91 (2 x t, 6H, CH3), 0.66–0.62 (m, 2H,
SiCH2), 0.57–0.51 (m, 1H, CH3CH), 0.13–0.01 (m, 85H,
1H NMR (500 MHz, CDCl3): d 6.72 (d, J 5 8.0 Hz, 1H), 6.63
(d, J 5 2.0 Hz, 1H), 6.59 (dd, J 5 8.0, 2.0 Hz, 1H), 2.79–2.64
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FIGURE 1 Thiol-yne monoaddition of PS6k 1 and PEO2k 4. (a) Reaction scheme, (b) 1H NMR spectrum of diblock PS6k-b-PEO2k 11
(C6D6, 298 K, 600 MHz) (c) GPC traces of PEO2k 4 (blue dotted line), PS6k 1 (red dashed-dotted line), and PS6k-b-PEO2k 11 (black
line) (d) Overlay of the MALDI-TOF mass spectra of PS6k-b-PEO2k 11 (black), PS6k 1 (red), and PEO2k 4 (blue) allowing determina-
tion of the exact molecular weights Mn (PEO2k 4) 5 1750 gꢁmol21, Mn (PS6k 1) 5 6060 gꢁmol21 and Mn (PS6k-b-PEO2k 11) 5 7810
gꢁmol21. The mass of the diblock corresponds to the sum of the two homopolymers.
(m, 4H), 2.59 (t, J 5 7.4 Hz, 2H), 2.50 (t, J 5 7.4 Hz, 2H), 1.85
(p, J 5 7.4 Hz, 2H), 1.71 (t, J 5 7.8 Hz, 1H), 0.98 (td, J 5 7.9,
2.6 Hz, 18 H), 0.79 (qd, J 5 7.9, 2.7 Hz, 12H); 13C NMR (500
MHz, CDCl3): d 146.7, 145.1, 134.5, 121.4, 120.9, 120.4, 36.3,
34.1, 31.4, 24.9, 6.8, 5.3; high-resolution mass spectrometry
(ESI-/TOF) calculated (M 1 Na)1 495.2219, observed
(M 1 Na)1 495.2204.
hexanethiol with 5 mol % DMPA as the photoinitiator were
investigated.12(f) The reactions were carried out in d6-ben-
zene and followed by 1H NMR spectroscopy, which allowed
complete identification and quantification of the products
(Scheme 3 and Table 1). After 1 h of irradiation, complete
and selective conversion to the vinyl sulfide monoadduct
(mixture of cis and trans products) was observed under vari-
ous starting concentrations (5–500 mM). It should be noted
that no evidence of the 1,1-disubstituted vinyl sulfide mono-
adduct was observed under any conditions.16
General Procedure for Thiol-yne Coupling Reactions
The phenylacetylene-functionalized polymer (25 mM), thiol
(27.5 mM), and photoinitiator 2,2-dimethoxy-2-phenylacetophe-
none (DMPA) (0.2 equiv per thiol) were dissolved in benzene.
The reaction mixture was purged with argon and irradiated with
UV light (365 nm, 15 W) until the reaction was complete, as indi-
cated by 1H NMR, and the product could be isolated.
This high efficiency, particularly at low concentrations, dem-
onstrates the potential of this reaction for polymer coupling
given the molecular weight dilution of the chain ends even
for low molecular weight polymers. The strong preference
for monoaddition is further emphasized by the formation of
only 14% bis-adduct when 2 equiv of thiol are used under
the highest concentration conditions. Surprisingly, to push
the bis-addition reaction to near completion, 10 equiv of
thiol were required. Encouraged by the selectivity and effi-
ciency of the model reactions, we then applied the reaction
to polymer–polymer coupling.
RESULTS AND DISCUSSION
Small Molecule Model Studies
To demonstrate the potential of this modified thiol-yne reac-
tion for polymer–polymer coupling and functionalization, a
series of model reactions between phenylacetylene and 1-
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TABLE 2 GPC Data of Starting Homopolymers and Coupling
model compound with the help of correlation spectroscopy
and nuclear Overhauser effect spectroscopy two-dimensional
NMR techniques (see Supporting Information). Further evi-
dence for formation of diblock PS6k-b-PEO2k 11 comes from
both matrix-assisted laser desorption/ionization [Fig. 1(d)]
and diffusion-ordered spectroscopy (DOSY) which showed an
array of peaks corresponding to a single diffusing species
(Supporting Information Fig. S3).
Products
No.
Homopolymer
Mn (kDa)a
PDIa
1
PS6k (alkyne)
6.0
1.08
1.12
1.10
1.10
1.06
1.30
1.16
1.65
1.81
PDIa
1.10
1.11
1.14
1.10
1.08
1.22
2.12
2.20
1.57
2
PCL11k (alkyne)
PEO1k (thiol)
21.8
1.9
3
4
PEO2k (thiol)
4.0
5
PEO5k (thiol)
11.0
1.3
Confirmation of High Coupling Efficiency
6
PDMS1k (thiol)
PDMS3k (thiol)
PS-co-PES20k (alkyne)
PDMS-co-PMMS8k (thiol)
Coupling Product
PS6k-b-PEO1k
While the above studies provide structural evidence for
diblock formation, it is critical to quantify the coupling effi-
ciency. Initial evidence for the high efficiency of the reaction
comes from integration of the 1H NMR signals of the vinyl
sulfide protons in the crude reaction mixture. Based on the
PS chain end as calibration, the sum of the integrals of the
cis and trans signals of vinyl proton “d” is close to the
expected value of 1.0 (Supporting Information Fig. S2). Fur-
ther support for the efficiency of the coupling process comes
from comparison of the analytical data of the crude material
with that of the purified product. Precipitation of the crude
material into methanol would be expected to remove any
unreacted PEO2k 4 and possible disulfide byproduct. Signifi-
cantly, the GPC trace remained essentially unchanged after
purification with integration of the PS versus the PEO back-
bone signals in the 1H NMR spectrum matching the ratio
expected for PS6k-b-PEO2k 11 (Supporting Information Fig.
S5). This absence of change in the NMR and GPC data
strongly suggests the minimal presence of unreacted PEO
homopolymer/byproducts and confirms the high efficiency
of the coupling reaction under a variety of conditions.
7
3.3
8
20.4
8.1b
Mn (kDa)a
9.1
9
No.
10
11
12
13
14
15
16
17
18
PS6k-b-PEO2k
10.1
16.4
8.7
PS6k-b-PEO5k
PS6k-b-PDMS1k
PS6k-b-PDMS3k
PCL11k-b-PEO5k
PS20k-g-Catechol
PS20k-g-Octyl
10.4
30.4
83.9
28.1
82.0c
PDMS8k-g-PS6k
All values determined by GPC (CHCl3) using:
a
PS standards.
b
PDMS standards.
MALS detector.
c
The unique absorption feature of the vinyl sulfide linkage
(strong absorption at 320 nm, extending to 370 nm, Sup-
porting Information Fig. S6) also provides a useful means of
selectively detecting vinyl sulfide containing species in the
presence of potential impurities, such as the starting PEO
and PS homopolymers, which do not absorb in this region.
When overlaid, the GPC trace obtained at 330 nm is in good
agreement with the chromatogram obtained from the RI
detector. However, a small shoulder at shorter retention
times is present in the RI trace that is absent in the 330 nm
absorption. This shoulder indicates the presence of a small
amount of higher molecular weight polymers that may arise
from bis-adduct formation or be products from radical
recombination processes. These impurities can be removed
by column chromatography and are minor (ꢂ5%) (Support-
ing Information Fig. S5).
Structural Evidence for Diblock Formation
To demonstrate the applicability of this modified thiol-yne
reaction for block copolymer formation, coupling of phenylace-
tylene end-functionalized PS PS6k 1 and thiol-terminated
PEO2k 4 to form the PS6k-b-PEO2k diblock copolymer 11 was
investigated (Fig. 1). The starting polymers were synthesized
by postpolymerization modification of hydroxyl-terminated
precursors that were either commercially available (PEO2k 4)
or synthesized by anionic polymerization (PS6k 1). After opti-
mizing the reaction conditions for polymer coupling (25 mM
reactant concentration, 2 h irradiation, 20 mol % DMPA), a
range of analytical techniques were used to confirm the high
efficiency of diblock copolymer formation. For example, GPC
analysis revealed a reduction in retention time for the product
obtained from the coupling reaction when compared to both
starting polymers with a low PDI being maintained [Fig. 1(c)].
In a similar fashion, the 1H NMR spectrum of 11 shows the
expected disappearance of the resonance for the terminal
alkyne group of the starting PS6k 1 with peaks corresponding
to the linker group derived from the end functionalities of 1
and 4 (peaks a, b, j, k) being shifted compared to the starting
polymers (Supporting Information Fig. S2). Direct evidence for
formation of the vinyl sulfide group comes from the appear-
ance of doublets “e” and “d,” for both the cis and the trans
vinylic protons, between 6.0 and 6.5 ppm [Fig. 1(b)]. These
and all other peaks were assigned unambiguously using a
Utilizing Thiol-yne Monoaddition to Prepare Complex
Polymer Architectures
Diverse Diblock Copolymers
The generality and utility of thiol-yne monoaddition for poly-
mer coupling was demonstrated by the successful synthesis
of a variety of diblock copolymers from both higher molecu-
lar weight starting materials and alternate backbones (Table
2). In addition to thiol-terminated PEO1k 3 and PEO5k 5, two
PDMS derivatives PDMS1k 6 and PDMS3k 7 were synthesized
6
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lar architectures, a variety of graft copolymers were pre-
pared. Copolymerization of styrene with silyl-protected 4-
ethynyl styrene followed by TBAF deprotection, afforded the
random copolymer poly[styrene-co-(4-ethynyl styrene)] PS-
co-PES20k 8 with 23% backbone incorporation of phenylace-
tylene groups. This polymer was successfully functionalized
with both 1-octanethiol 20 and the more complex catechol
derivative CatSH 19 (Fig. 2) that has been shown to provide
polymers with strong adhesion under
environments.18
a
variety of
Formation of Grafted Copolymers
The grafting process maintains its high degree of fidelity if
the backbone functionalities are thiols rather than phenyla-
cetylene groups and even tolerates the grafting of polymer
chains. This is exemplified by the grafting of PS6k 1 onto the
commercially available, PDMS-based copolymer, PDMS-co-
PMMS8k 9, where 13% of the repeat units bear a mercapto-
propyl side chain (Fig. 3). GPC of the crude product shows a
dramatic increase in molecular weight after 2 h of irradiation
[Fig. 3(b) and Supporting Information Fig. S32]. The Mn of
the graft polymer was found to be 82 kgꢁmol21, which corre-
lates with efficient grafting and the near-quantitative nature
of this process is supported by the complete conversion of
end-functional group resonances as determined by 1H NMR
spectroscopy (Supporting Information Fig. S31).
FIGURE 2 Grafting of CatSH 19 onto PS-co-PES20k 8. (a) Reac-
tion scheme, m 5 0.23, n 5 0.77, (b) overlaid DOSY plots from
independent diffusion measurements of CatSH 19 (blue), PS-
co-PES20k 8 (red), and PS20k-g-Cat 16 (black) in CDCl3 at 298 K.
by anionic polymerization followed by end group conversion
into the desired thiol. Significantly, all of these polymers
gave excellent coupling efficiencies with PS6k 1 (see Support-
ing Information). The successful coupling of phenylacetylene-
terminated polycaprolactone PCL11k 2 with PEO5k 5 further
extends the range of the coupling methodology to alternate
diblock copolymers and increased molecular weights with
high coupling efficiency.
Functionalization of Polyfunctional Backbones
The utility of selective radical thiol-yne monoaddition for the
preparation of complex macromolecular architectures was
further examined by grafting small molecules or polymer
chains to a polyfunctional backbone. It should be noted that
grafting reactions can be even more challenging than diblock
formation due to steric crowding along the backbone and
the likelihood of radical-radical coupling between the multi-
functional backbones.17
FIGURE 3 Grafting of PS6k 1 onto PDMS-co-PMMS8k 19. (a)
Reaction scheme, (b) GPC (CHCl3) traces of PDMS-co-PMMS8k
As a further demonstration of the efficiency of thiol-yne
monoaddition for the preparation of complex macromolecu-
9
(blue dotted line), PS6k 1 (red dashed-dotted line), and
PDMS8k-g-PS6k 18 after purification by precipitation (black line).
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Joralemon, C. J. Hawker, K. L. Wooley, Chem. Eur. J. 2006, 12,
6776–6786; (f) J. N. Hunt, K. E. Feldman, N. A. Lynd, J. Deek, L. M.
Campos, J. M. Spruell, B. M. Hernandez, E. J. Kramer, C. J.
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Bowman, J. Polym. Sci. Part A: Polym. Chem. 2013, 51, 1749–1757.
CONCLUSIONS
In summary, we have identified selective thiol-yne monoad-
dition to phenylacetylene derivatives as a powerful synthetic
tool for the construction of macromolecular architectures, as
demonstrated by the efficient synthesis of both diblock and
graft copolymers. Advantages of this new approach include
facile synthesis of starting materials, equimolar stoichiome-
tries of building blocks, high overall yields and efficient cou-
pling. The high functional group tolerance of thiol-yne
chemistry makes this methodology applicable to the synthe-
sis of a wide range of functionalized polymers. In a wider
context, the use of phenylacetylene derivatives also repre-
sents a critical improvement over vinyl substrates tradition-
ally used in the radical thiol-ene reaction and offers wide
application in many areas of materials chemistry.
4 C. Barner-Kowollik, Du F. E. Prez, P. Espeel, C. J. Hawker, T.
Junkers, H. Schlaad, Van W. Camp, Angew. Chem. Int. Ed. 2011,
50, 60–62.
5 (a) N. B. Cramer, J. P. Scott, C. N. Bowman, Macromolecules
2002, 35, 5361–5366; (b) H. W. Ooi, K. S. Jack, A. K. Whittaker, H.
Peng, J. Polym. Sci. Part A: Polym. Chem. 2013, 51, 4626–4636.
6 (a) N. Gupta, B. F. Lin, L. M. Campos, M. D. Dimitriou, S. T.
Hikita, N. D. Treat, M. V. Tirrell, D. O. Clegg, E. J. Kramer, C. J.
Hawker, Nat. Chem. 2010, 2, 138–145; (b) L. M. Campos, I.
Meinel, R. G. Guino, M. Schierhorn, N. Gupta, G. D. Stucky, C.
J. Hawker, Adv. Mater. 2008, 20, 3728–3734.
7 K. L. Killops, L. M. Campos, C. J. Hawker, J. Am. Chem. Soc.
2008, 130, 5062–5064.
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ACKNOWLEDGMENTS
We thank Eric D. Pressly for helpful discussions. This work was
supported by the NSF MRSEC and RISE Programs under award
no. DMR-1121053 (J. K. Sprafke, D. Montarnal, R. Potzsch, D.
Miyajima, J. Hu, A. J. McGrath, K. M. Mattson, A. A. Latimer, and
C. J. Hawker). Partial support by the National Institutes of
€
9 (a) S. P. S. Koo, M. M. Stamenovic, R. A. Prasath, A. J. Inglis, Du
F. E. Prez, C. Barner-Kowollik, Van W. Camp, T. Junkers, J. Polym.
Sci. Part A: Polym. Chem. 2010, 48, 1699–1707; (b) P. Derboven, D.
R. D’hooge, M. M. Stamenovic, P. Espeel, G. B. Marin, Du F. E.
Prez, M. F. Reyniers, Macromolecules 2013, 46, 1732–1737.
Health as
a Program of Excellence in Nanotechnology
(HHSN268201000046C) (A. J. McGrath, A. A. Latimer, and C. J.
Hawker) is also gratefully acknowledged. J. M. Spruell thanks
the California NanoSystems Institute for an Elings Prize Fellow-
10 B. H. Northrop, R. N. Coffey, J. Am. Chem. Soc. 2012, 134,
13804–13811.
11 (a) A. B. Lowe, C. E. Hoyle, C. N. Bowman, J. Mater. Chem.
2010, 20, 4745–4751; (b) D. Konkolewicz, A. Gray-Weale, S.
Perrier, J. Am. Chem. Soc. 2009, 121, 18075–18080; (c) O.
€
ship. R. Potzsch thanks the Studienstiftung des deutschen
€
Volkes for a PhD scholarship and Forderverein des Leibniz-
€
Instituts fur Polymerforschung for a travel support. K. M. Matt-
€ €
Turunc¸, M. A. R. Meier, J. Polym. Sci. Part A: Polym. Chem.
son thanks the NSF Graduate Research Fellowship and ConvEne
IGERT Program (NSF-DGE 0801627) for funding. The MRL
Shared Experimental Facilities are supported by the MRSEC
Program of the National Science Foundation under award NSF
2012, 50, 1689–1695; (d) Y. Shen, Y. Ma, Z. Li, J. Polym. Sci.
Part A: Polym. Chem. 2013, 51, 708–715; (e) N. Ren, X. Huang,
X. Huang, Y. Qian, C. Wang, Z. Xu, J. Polym. Sci. Part A:
Polym. Chem. 2012, 50, 3149–3157.
12 (a) S. Ruhemann, H. E. Stapelton, J. Chem. Soc. Trans. 1900, 77,
1179–1185; (b) S. Ruhemann, J. Chem. Soc. Trans. 1905, 87, 461–468;
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DMR-1121053;
a member of the NSF-funded Materials
Research Facilities Network.
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8
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Polymer coupling reactions are some of the most challenging chemical transforma-
tions due to low end-group concentration, steric hindrance, and decreased reactivity.
Thiol-yne chemistry is shown to be a near-quantitative and selective strategy for the
coupling of pre-formed polymers to give block and graft copolymers. With aromatic
alkynes under a wide range of conditions, specific mono-addition is achieved with
efficiencies surpassing those of traditional thiol-ene chemistry.