Fluorinated β-lactones and poly(β-hydroxyalkanoate)s: synthesis via epoxide carbonylation and ring-opening polymerization

Article abstract of DOI:10.1016/j.tet.2008.03.108

Efficient and mild reaction conditions were developed for the catalytic carbonylation of fluorinated epoxides to their corresponding β-lactones. Six new lactones with fluorinated side chains were prepared in high isolated yields. These lactones were polymerized to form a series of new poly(β-hydroxyalkanoate)s with fluorinated side chains, and their properties were examined with respect to their hydrocarbon analogs. Finally, copolymerizations were performed with fluorinated lactones and β-butyrolactone, which resulted in tapered copolymers rather than the expected random copolymers.

Full text of DOI:10.1016/j.tet.2008.03.108

Tetrahedron 64 (2008) 6973–6978
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Fluorinated b-lactones and poly(b-hydroxyalkanoate)s: synthesis
via epoxide carbonylation and ring-opening polymerization
*
John W. Kramer, Geoffrey W. Coates
Department of Chemistry and Chemical Biology, Baker Laboratory, Cornell University, Ithaca, NY 14853-1301, United States
a r t i c l e i n f o
a b s t r a c t
Article history:
Efficient and mild reaction conditions were developed for the catalytic carbonylation of fluorinated
Received 5 February 2008
Received in revised form 25 March 2008
Accepted 31 March 2008
Available online 8 April 2008
epoxides to their corresponding
in high isolated yields. These lactones were polymerized to form a series of new poly(
alkanoate)s with fluorinated side chains, and their properties were examined with respect to their
hydrocarbon analogs. Finally, copolymerizations were performed with fluorinated lactones and
b
-lactones. Six new lactones with fluorinated side chains were prepared
-hydroxy-
b
b
-butyrolactone, which resulted in tapered copolymers rather than the expected random copolymers.
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
Recent work in our laboratory has focused on the synthesis of
b
-lactones through the catalytic carbonylation of epoxides9 and the
Since the serendipitous discovery of poly(tetrafluoroethylene)
by DuPont in 1938, fluorinated polymers have become widespread
in specialty and commodity materials.1 The incorporation of fluo-
rinated monomers into polymers can produce materials with
distinctive properties relative to their non-fluorinated analogs. In
particular, fluorinated polymers often display low coefficients of
friction, good chemical resistance, and low surface energies.2 These
properties have made fluorinated polymers useful in applications
ranging from membranes and coatings1 to medical devices.3
ring-opening polymerization of these lactones to produce PHAs.10
The availability of epoxides in both racemic and enantiomerically
pure11 forms has enabled the synthesis of a wide range of
b-lac-
tones.9e The ring-opening polymerization of these lactones to
produce PHAs creates the opportunity for the synthesis of a num-
ber of different polymer microstructures. Herein, we report on the
highly efficient carbonylation of epoxides with fluorinated side
chains to their respective b-lactones, and the subsequent homo-
and co-polymerization of these
PHAs.
b-lactones to form fluorinated
Poly(b-hydroxyalkanoate)s (PHAs) are a class of aliphatic poly-
esters that are naturally produced by bacteria as a form of energy
storage during nutrient-rich periods.4 Due to their biodegradability,
and therefore their potential use in biomedical applications, they
have received increasing attention in recent years.4,5 The me-
chanical properties of PHAs are dependent on the monomer com-
position,6 so polymers with diverse material properties and
degradation rates can be produced by incorporating different
monomers.7 PHAs containing a wide variety of functional side
groups have been prepared by bacterial fermentation, including the
incorporation of fluorinated side chains.8 A high content of halo-
genated side groups has been shown to increase the melting tem-
perature (Tm) and glass transition temperature (Tg) of the PHAs.
Unfortunately, the synthesis of PHAs with high degrees of fluori-
nation has been difficult to achieve using fermentation methods,8a,c
and attempts to produce highly fluorinated homopolymers by
these methods have not been successful.
2. Results and discussion
2.1. Optimization of epoxide carbonylation
Previous work in our group has identified a number of catalysts
that are active for the carbonylation of a functionally diverse array
of epoxides.9 However, the carbonylation of fluorinated epoxides
has never been reported. We recently discovered the catalyst
[(salph)Cr(THF)2]þ[Co(CO)4]ꢀ (1, Fig. 1, salph¼N,N0-bis(3,5-di-tert-
butylsalicylidene)1,2-phenylene-diamine, THF¼tetrahydrofuran)
that is active for epoxide carbonylation under mild reaction
-
L
Co(CO)4
N
O
N
O
+
Cr
L
t
t
Bu
Bu
t
t
Bu
Bu
L = THF
[(salph)Cr(THF)2]+[Co(CO)4]-; 1
Figure 1. Structure of epoxide carbonylation catalyst 1.
* Corresponding author.
E-mail address: gc39@cornell.edu (G.W. Coates).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.03.108

6974
J.W. Kramer, G.W. Coates / Tetrahedron 64 (2008) 6973–6978
Table 2
O
O
O
2 mol % 1
O
Effect of CO pressure on epoxide carbonylation
+
+
CO
25 °C, 8 h
O
F3C
100 psi
F3C
26% conversion
O
2 mol % 1
O
+
CO
F9C4
F9C4
25 °C, 6 h
1.0 M DME
O
O
2 mol % 1
CO
100 psi
Conversiona (%)
F3C
F3C
Entry
CO pressure
25 °C, 6 h
1
2
3
4
800 psi
400 psi
100 psi
1 atm (14.7 psi)
>99
>99
>99
44
>99% conversion
Figure 2. Efficient carbonylation of epoxides with a methylene group linking the
epoxide and fluorinated side chain.
a
Determined by 1H NMR spectroscopy.
conditions (room temperature and 1 atm CO).9f Additionally with
this catalyst, epichlorohydrin, a traditionally difficult substrate, was
carbonylated to 4-chloromethylpropiolactone with nearly the same
rate and yield as the analogous non-chlorinated 1,2-epoxybutane.9f
This led us to explore other halogenated epoxides as carbonylation
substrates.
chosen to facilitate efficient carbonylation without the requirement
of stainless steel, high pressure reactors.
2.2. Carbonylation of fluorinated epoxides
Subsequent exploration into the substrate scope revealed that
epoxides with fluorinated side chains were carbonylated effectively
A variety of epoxides with fluorinated side chains are either
commercially available or accessible through the straightforward
epoxidation of the corresponding alkenes. Using the optimized
carbonylation conditions, a range of epoxides with different fluor-
to their respective
b-lactones. Though 3,3,3-trifluoro-1,2-epoxy-
propane suffered from incomplete conversion, epoxides with
a methylene spacer between the epoxide and fluorinated side chain
inated groups were carbonylated to their respective
b-lactones.
were efficiently converted to
b-lactones (Fig. 2). We were thus
Both branched and straight-chain perfluoroalkyl epoxides (Table 3,
intrigued by the possible materials that could be prepared from
these fluorinated lactones.
Table 3
Upon identification of this new substrate class, the reaction
conditions were optimized for efficient carbonylation. Our previous
work has demonstrated that the choice of reaction solvent is
extremely important for epoxide carbonylation efficiency,12 so
initial studies focused on identifying the optimal solvent. Table 1
shows the results of the solvent screening. In general, non-
coordinating solvents (entries 1 and 2) generally decreased the rate
of reaction compared to ether solvents (entries 3–6). However, con-
trary to other carbonylation catalysts in which the rate of carbonyl-
ation was accelerated by THF,12 the strongly donating solvent THF
(entry 4) severely inhibited conversion. We believe that solvents
such as THF bind too strongly to the Lewis acid and inhibit epoxide
coordination. Thus, moderately donating ether solvents such as
1,2-dimethoxyethane (DME, entry 3), 2,5-dimethyltetrahydrofuran
(entry 5), and 1,4-dioxane (entry 6) were favorable for the carb-
onylation of fluorinated epoxides. Because of its high volatility and
low cost, DME was selected as the optimal reaction solvent.
The effect of CO pressure on the carbonylation reaction was also
examined. Catalyst 1 has been shown to be active and selective for
Carbonylation of fluorinated epoxides using 1 at 100 psi CO
O
O
2 mol % 1
O
+
CO
100 psi
25 °C, 6 h
1.0 M DME
RF
RF
2
3
Entry
1
Epoxide
b
-Lactone
Conversiona
(% yield)
O
F3C
F
O
O
F3C
F3C
F
2a
2b
3a 99 (86)
F3C
O
F
F
O
O
F
F
O
2
3
4
3b 99 (79)
3c 99 (85)
3d 99 (88)
3e 99 (91)
O
H
H
F
F
F
F
O
F
F F
F
F
F
O
O
F
F F F
2c
F3C
F3C
b
-lactone formation at CO pressures as low as 1 atm.9f Table 2
F
F
F
F
shows the effect of lowering the CO pressure on the reaction rate.
Although no attenuation of rate was observed at CO pressures as
low as 100 psi, dropping the pressure to 1 atm (entry 4) resulted in
O
F
F F
O
O
F
F F
F
F
2d
F3C
(S)
F3C
(R)
incomplete conversion to
b-lactone. A pressure of 100 psi was
F
F
F
F
O
O
F3C F F
F3C
O
Table 1
O
O
F3C F F
F3C
Effect of reaction solvent on epoxide carbonylation
5
6
2e
2f
O
F
F
F
F
O
2 mol % 1
O
+
CO
100 psi
F9C4
F
F F
F
O
F9C4
25 °C, 3 h
1.0 M Solvent
F
F F
F
3f
99 (71)
F3C
5
F3C
5
F
F
F
F
Entry
Solvent
Toluene
1,2-Difluorobenzene
1,2-Dimethoxyethane
Tetrahydrofuran
2,5-DMTHFb
Conversiona (%)
F
F
1
2
3
4
5
6
36
18
46
9
47
43
O
F
F
F
F
F
F
O
O
7
2g
3g 99 (82)
F
F
1,4-Dioxane
a
a
Determined by 1H NMR spectroscopy.
2,5-DMTHF¼2,5-dimethyltetrahydrofuran (cis/trans mixture).
b
-Lactone was the sole product as determined by 1H NMR spectroscopy; % yield
b
of isolated, analytically pure material.

J.W. Kramer, G.W. Coates / Tetrahedron 64 (2008) 6973–6978
6975
2.3. Polymerization of fluorinated lactones
iPr
iPr
F9C4
O
O
iPr
ZnOiPr
iPr
A number of catalyst systems have been developed for the
O
N
N
polymerization of b b-diiminate
-lactones to PHAs.10,13 However, the
O
F9C4
n
(BDI) Zn alkoxide catalysts developed in our laboratory are among
the most active and selective catalysts for the synthesis of high
molecular weight PHAs.10 To our satisfaction, our most active
3c
Mn = 18,000 g/mol
PDI = 1.16
4
catalyst for
b
-butyrolactone (BBL) polymerization, [(BDI)ZnOiPr]
(4), was also active for the polymerization of fluorinated lactones
(Fig. 3). During the polymerization at 50 ꢁC, the homogeneous
reaction mixture became cloudy with precipitated polymer, and in
less than 6 h, all monomer had been consumed.
Figure 3. Polymerization of 3c to produce PHA using a
b-diiminate zinc catalyst.
entries 1, 3–6) were completely converted to b-lactone within 6 h at
room temperature. Other functionalities, such as ether (entry 2)
and perfluoroaryl (entry 7) groups were also tolerated under the
optimized reaction conditions. Analytically pure b-lactone products
were readily isolated in high yields (see Section 4).
After optimization, most of the polymerizations achieved high
conversions within 6 h at 50 ꢁC, though the polymerization of 3c
and 3d (entries 3 and 4) only required 2 h for complete conver-
sion of monomer. During the polymerization of every monomer
except 3g, polymer precipitated from solution near the end of the
reaction. The polymerization of 3f was not practical due to the
extremely low solubility of the lactone and polymer in nearly
every solvent.14
The atactic polymers (Table 4, entries 1–3, 5, 6) were amorphous
as determined by DSC analysis, though they were stable to
temperatures >250 ꢁC by TGA. The Tg values of the perfluoroalkyl-
substituted PHAs appear to increase with fluorine content and
Importantly, optically pure epoxides can be carbonylated to
their respective
b-lactones with retention of absolute stereo-
chemistry.12a Optically pure epoxide 2d was prepared using the
well-established kinetic resolution methodology developed by
Jacobsen and co-workers.11c This epoxide was then subjected to the
optimized carbonylation conditions to produce 3d in quantitative
conversion.
Table 4
Homopolymerization of fluorinated lactones using 4a
iPr
O
iPr
ZnOiPr
iPr
RF
O
N
N
O
O
n
RF
3a-g
iPr
5a-g
4
c
d
d
Entry
1
Lactone
RF
Time (h)
6
Conversionb (%)
Mnc (g/mol)
Mn/Mw
Tg (ꢁC)
Tm (ꢁC)
F3C
F3C
F
3a
5a
>95
17,000
1.13
14
nde
nde
F
F
O
2
3
4
5
3b
3c
3d
3e
5b
5c
5d
5e
6
2
2
6
>95
>95
>95
>95
20,000
18,000
16,000
8000
1.14
1.16
1.11
1.21
ꢀ12
H
F
F
F
F F
F
F
F
4
nde
24
nde
82
F3C
F
F
F
F F
F3C
F
F
F3C F F
F3C
nde
F
F
F
F
F
F
6
3g
5g
6
>95
23,000f
1.16
53
nde
F
a
Polymerization conditions: [lactone]/[4]¼100, [lactone]¼1.0 M in toluene, Trxn¼50 ꢁC.
Determined by 1H NMR spectroscopy of crude reaction mixture.
Determined using gel-permeation chromatography in THF; calibrated with polystyrene standards.
Determined by differential scanning calorimetry.
b
c
d
e
f
nd¼Not detected.
Mn¼34,000 determined by end group analysis.

6976
J.W. Kramer, G.W. Coates / Tetrahedron 64 (2008) 6973–6978
side chain branching. Overall, the fluorinated PHAs display higher
Tg values than their hydrocarbon analogs. For example, naturally
F
F5C6
O
O
F
F
F
Me
O
O
O
O
1 mol % 4
-hydroxyoctanoate) displays a Tg of ꢀ35 ꢁC,6 while
+
produced poly(
b
50 °C, 24 h
1.0 M toluene
O
n O
5c, the fluorocarbon analog, has a significantly higher Tg of 4 ꢁC. The
only polymer that displayed a melting point was 5d (entry 4).
Analysis by 13C NMR spectroscopy showed that 5d is isotactic, an
observation consistent with the polymerization of other optically
pure lactones by 4.10 The 13C NMR spectra of the atactic polymers
contain two peaks in the carbonyl region, assigned to the m and r
diads; 5d shows just one sharp peak, which corresponds to the m
diad. This observation is further supported by the detection of a Tm,
as crystallinity has been shown to be a function of tacticity for
PHAs.13a
m
3g
BBL
F
M
n = 14,000 g/mol
PDI = 1.28
Figure 5. Copolymerization of 3g and BBL using 4 to produce tapered copolymers.
3. Conclusions
In this work, we efficiently prepared a new class of b-lactones
with fluorinated side chains. These lactones were polymerized to
form fluorinated PHAs, which are inaccessible through biological
fermentation routes. Copolymerization of the highly fluorinated b-
2.4. Copolymerization of fluorinated lactones with BBL
lactones with BBL formed tapered rather than random copolymers.
Further study of the synthesis and properties of these fluorinated
copolymers will be the subject of future reports.
PHA copolymers have been shown to display drastically differ-
ent properties than their respective homopolymers;6 thus, we were
interested in examining the copolymerization of fluorinated lac-
tones with BBL. Our initial attempt on an NMR-scale provided
a surprising result. Unlike the copolymerization of hydrocarbon-
4. Experimental
substituted
b-lactones where both monomers are consumed at
similar rates, the rate of fluorinated lactone polymerization was
noticeably faster than BBL incorporation (Fig. 4). This difference in
polymerization rates produces tapered copolymers rather than
random copolymers. Furthermore, the high reactivity of the
fluorinated monomers enables production of PHAs with short,
fluorinated end blocks, which may have similar surface properties
to the fluorinated homopolymers without requiring high ratios of
fluorinated monomer.
On a larger scale, the copolymerization of 3g with BBL also
produced tapered copolymers (Fig. 5).15 The copolymer was de-
termined to be monomodal by GPC analysis, consistent with the
incorporation of both monomers into one polymer chain rather
than the formation of two homopolymers.
4.1. General comments
All manipulations of air- and/or water-sensitive compounds
were carried out using standard Schlenk line techniques or in an
MBraun Unilab drybox under an atmosphere of dry nitrogen, and
all solvents were dried according to standard procedures. NMR
spectra were recorded using Varian Mercury 300 MHz or Inova
500 MHz spectrometers (1H NMR, 300 MHz; 13C NMR, 125 MHz;
19F NMR, 470 MHz) and referenced against residual solvent shifts
for 1H and 13C NMR and hexafluorobenzene for 19F NMR spectra.
Mass spectra were acquired using a JEOL GCMate II mass spec-
trometer operating at 3000 resolving power for high-resolution
measurements in positive ion mode and an electron ionization
potential of 70 eV. Samples were introduced via a GC inlet using an
Agilent HP 6890N GC equipped with a 30 m (0.25 mm i.d.) HP-5ms
CF3
F3C
capillary GC column. The carrier gas was helium with a flow rate of
1 mL/min. The lactones were generally not stable to GC or MS, and
all except 3g underwent decarboxylation to the alkene. Therefore,
exact masses of the alkenes were reported, and NMR spectra
showing the product lactones can be found in Supplementary data.
O
O
F
Me
O
O
O
O
1 mol % 4
F3C
F3C
F
+
50 °C
1.0 M CDCl3
O
n O
m
3a
BBL
Optical rotations were measured on a Perkin–Elmer 241 digital
[3a]n
[BBL]n
T
polarimeter and are reported in the following format: [
a
]
D
r
(c, solvent), where T¼temperature in ꢁC, D refers to the sodium D
line (589 nm), r is the measured rotation, and c is the concentration
in g/dL. IR spectra of lactones (neat, NaCl plate) were measured on
a Mattson RS-10500 Research Series FTIR. Gel-permeation chro-
matography (GPC) analyses were carried out using a Waters
instrument, (M515 pump, 717þ Autosampler) equipped with
a Waters UV486 and Waters 2410 differential refractive index
3a BBL
d)
c)
b)
a)
t = 48 h
t = 4 h
t = 2 h
t = 0
detectors, and three 5 mm PSS SDV columns (Polymer Standards
Service; 50 Å, 500 Å, and Linear M porosities) in series. The GPC
columns were eluted with THF at 40 ꢁC at 1 mL/min and were cali-
brated using 20 monodisperse polystyrene standards. Differential
scanning calorimetry was performed on a TA Instruments Q1000
instrument equipped with a LNCS and automated sampler. Typical
DSC experiments were made in crimped aluminum pans under ni-
trogen with a heating rate of 10 ꢁC/min from ꢀ100 ꢁC to 230 ꢁC. All
epoxides were purchased from Oakwood or Aldrich chemicals, ex-
cept 2g, which was prepared according to an established procedure.
Catalysts 19f and 410 were prepared according to literature pro-
cedures, though 1 is commercially available from Aldrich (cas
#909553-60-2). All epoxides and liquid lactones were dried for 1
5.5
5.0
4.5
Figure 4. Copolymerization of 3a and BBL. Prior to polymerization (a), the two lactone
methine peaks were observed in a 1:1 ratio. Within 2 h at 50 ꢁC (b), nearly all of 3a had
been polymerized, and after 4 h (c) the polymerization of BBL was proceeding. After
24 h (d), both lactones had been consumed and the polymer methine peaks were
observed in a 1:1 ratio.

J.W. Kramer, G.W. Coates / Tetrahedron 64 (2008) 6973–6978
6977
week over CaH2 and degassed by three freeze–pump–thaw cycles;
solid lactones were dried under vacuum following sublimation.
recovered as a white solid (1.6 g, 88%). 1H NMR (
d
, CDCl3, 300 MHz)
2.44–2.67 (m,1H), 2.70–2.93 (m,1H), 3.34 (dd, 3J¼4.3 Hz, 2J¼16.7 Hz,
1H), 3.77 (dd, 3J¼5.8 Hz, 2J¼16.7 Hz, 1H), 4.88 (dddd, 3J¼3.9 Hz,
4.2. General procedure for the carbonylation
of fluorinated epoxides
3J¼4.1 Hz, 3J¼5.6 Hz, 3J¼6.1 Hz, 1H); 13C NMR (
d, CDCl3, 125 MHz)
36.1 (t, JCF¼21.6 Hz), 44.6, 63.8, 166.2 (The fluorine-substituted
2
carbons could not be definitively identified.); 19F NMR (
d, CDCl3,
This procedure is analogous to the previously published low
pressure carbonylation of epoxides.9f In a drybox, 1 (110 mg,
0.20 mmol) was dissolved in DME (3.0 mL). The solution was
transferred to an oven-dried Fisher–Porter bottle with a magnetic
stir bar and the reactor was sealed. Epoxide (6.0 mmol) and DME
(3.0 mL) were drawn into a GastightÒ syringe, the needle of which
was inserted into a septum to avoid air contamination upon
removal from the glove box. The reactor and syringe were removed
from the glove box and the reactor was immediately pressured
with CO (20 psi) and cooled to 0 ꢁC. After 3 min, the epoxide
solution was added to the stirring catalyst solution under a light
flow of CO. The reactor was then pressured with CO (100 psi) and
warmed to room temperature. After 6 h, the reactor was carefully
vented in a fume hood and the lactone was isolated as described
below.
470 MHz) ꢀ128.9, ꢀ127.3, ꢀ116.3, ꢀ83.9. IR: nCO¼1831 cmꢀ1
.
25
Mp¼33–34 ꢁC. [
a]
D
ꢀ10.8 (c 1.0, CH2Cl2). HRMS (EI) calculated
(C8H5F9O2ꢀCO2) 260.0247; measured 260.0237, fit ꢀ3.9 ppm.
4.2.5. 4-(2,2,3,3,4,5,5,5-Octafluoro-4-(trifluoromethyl)pentyl)-2-
propiolactone (3e)
The general procedure was followed with epoxide 2e (2.0 g,
6.0 mmol). The product was purified by distillation at 60 ꢁC under
vacuum and 3e was recovered as a slightly pink oil (1.9 g, 91%). 1H
NMR (d, CDCl3, 300 MHz) 2.45–2.67 (m, 1H), 2.71–2.94 (m, 1H), 3.34
(dd, 3J¼4.3 Hz, 2J¼16.7 Hz, 1H), 3.78 (dd, 3J¼5.9 Hz, 2J¼16.7 Hz, 1H),
4.88 (dddd, 3J¼4.0 Hz, 3J¼4.2 Hz, 3J¼5.6 Hz, 3J¼6.1 Hz, 1H); 13C NMR
2
(d
, CDCl3, 125 MHz) 36.1 (t, JCF¼21.9 Hz), 44.5, 64.0, 90.1 (dsept,
2JCF¼34.4 Hz, 1JCF¼223.5 Hz), 112.3 (tdt, JCF¼26.6 Hz, JCF¼36.0 Hz,
2
2
1JCF¼266.4 Hz), 117.3 (tt, JCF¼34.5 Hz, JCF¼258.1 Hz), 119.0 (qd,
2
1
2JCF¼27.1 Hz, JCF¼289.9 Hz), 166.5; 19F NMR (
d, CDCl3, 470 MHz)
1
4.2.1. 4-(2,3,3,3-Tetrafluoro-2-(trifluoromethyl)-
propyl)-2-propiolactone (3a)
The general procedure was followed with epoxide 2a (1.4 g,
6.0 mmol). The product was purified by distillation at 60 ꢁC under
vacuum and 3a was recovered as a colorless oil (1.3 g, 86%). 1H NMR
ꢀ189.2, ꢀ119.5, ꢀ116.3, ꢀ75.3. IR: nCO¼1842 cmꢀ1. HRMS (EI) calcu-
lated (C9H5F11O2ꢀCO2) 310.0215; measured 310.0203, fit ꢀ4.0 ppm.
4.2.6. 4-(2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9,9-Heptadecafluorononyl)-2-
propiolactone (3f)
(
d
, CDCl3, 300 MHz) 2.45–2.63 (m, 1H), 2.72–2.90 (m, 1H), 3.29 (dd,
The general procedure was followed with epoxide 2f (0.95 g,
2.0 mmol). The product was purified by column chromatography
(silica gel eluted with CH2Cl2) and 3f was recovered as a white solid
3J¼4.2 Hz, 2J¼16.7 Hz, 1H), 3.73 (dd, 3J¼5.8 Hz, 2J¼16.7 Hz,1H), 4.83
(m, 1H); 13C NMR (
d
, CDCl3, 125 MHz) 33.8 (d, JCF¼19.7 Hz), 44.7,
2
2
1
64.3, 90.4 (dsept, JCF¼32.4 Hz, JCF¼204.4 Hz), 120.5 (qd,
(0.72 g, 71%). 1H NMR (
d, CDCl3, 300 MHz) 2.45–2.67 (m, 1H),
2JCF¼26.8 Hz, JCF¼284.7 Hz), 166.2; 19F NMR (
d, CDCl3, 470 MHz)
2.72–2.94 (m, 1H), 3.35 (dd, 3J¼4.3 Hz, 2J¼16.7 Hz, 1H), 3.78 (dd,
1
ꢀ188.3, ꢀ79.9, ꢀ79.5. IR: nCO¼1842 cmꢀ1. HRMS (EI) calculated
(C7H5F7O2ꢀCO2) 210.0279; measured 210.0271, fit ꢀ3.9 ppm.
3J¼5.9 Hz, 2J¼16.7 Hz, 1H), 4.88 (dddd, 3J¼4.0 Hz, 3J¼4.2 Hz,
3J¼5.6 Hz, 3J¼6.0 Hz, 1H); 13C NMR (
d, CDCl3, 125 MHz) 36.3 (t,
2JCF¼21.5 Hz), 44.7, 63.8, 166.1 (The fluorine-substituted carbons
4.2.2. 4-(1,1,2,2-Tetrafluoroethoxymethyl)-2-propiolactone (3b)
The general procedure was followed with epoxide 2b (1.0 g,
6.0 mmol). The product was purified by distillation at 70 ꢁC under
vacuum and 3b was recovered as a colorless oil (0.96 g, 79%). 1H
could not be definitively identified.); 19F NMR (
d, CDCl3, 470 MHz)
ꢀ129.0, ꢀ126.2, ꢀ125.6, ꢀ124.8, ꢀ124.8, ꢀ124.5, ꢀ116.0, ꢀ83.6.
IR: nCO¼1815 cmꢀ1
.
Mp¼84–85 ꢁC. HRMS (EI) calculated
(C12H5F17O2ꢀCO2) 460.0120; measured 460.0119, fit ꢀ0.3 ppm.
NMR (
d
, CDCl3, 300 MHz) 3.42 (dd, 3J¼4.2 Hz, 2J¼16.5 Hz, 1H), 3.61
(dd, 3J¼6.3 Hz, 2J¼16.5 Hz, 1H), 4.23 (dd, 3J¼4.5 Hz, 2J¼11.7 Hz, 1H),
4.2.7. 4-(Pentafluorophenylmethyl)-2-propiolactone (3g)
4.37 (dd, 3J¼3.3 Hz, 2J¼11.7 Hz, 1H), 4.76 (dddd, 3J¼4.2 Hz,
The general procedure was followed with epoxide 2g (1.3 g,
6.0 mmol). The product was purified by concentration of the crude
reaction mixture followed by sublimation (60 ꢁC; cold finger cooled
3J¼4.5 Hz, 3J¼6.0 Hz, 3J¼7.5 Hz, 1H), 5.78 (tt, JHF¼2.6 Hz,
3
2JHF¼54.0 Hz, 1H); 13C NMR (
d, CDCl3, 125 MHz) 39.8, 63.5, 67.3,
2
1
2
107.6 (tt, JCF¼41.1 Hz, JCF¼249.8 Hz), 117.3 (tt, JCF¼28.4 Hz,
to ꢀ78 ꢁC) and 3g was recovered as a white solid (1.2 g, 82%). (
d,
1JCF¼268.4 Hz), 166.7; 19F NMR (
d
, CDCl3, 470 MHz) ꢀ139.9, ꢀ139.7,
CDCl3, 300 MHz) 3.16–3.32 (m, 3H), 3.60 (dd, 3J¼5.8 Hz, 2J¼16.6 Hz,
ꢀ94.7. IR: nCO¼1839 cmꢀ1. HRMS (EI) calculated (C6H6F4O3ꢀCO2)
1H), 4.71 (dddd, 3J¼4.1 Hz, 3J¼4.3 Hz, 3J¼5.8 Hz, 3J¼6.0 Hz, 1H); 13
C
2
158.0355; measured 158.0350, fit ꢀ3.0 ppm.
NMR (
d
, CDCl3, 125 MHz) 27.7, 43.2, 68.4, 108.7 (t, JCF¼18.6 Hz),
137.7, 140.7, 145.5, 166.6; 19F NMR (
d
, CDCl3, 470 MHz) ꢀ164.3,
4.2.3. 4-(2,2,3,3,4,4,5,5,5-Nonafluoropentyl)-2-propiolactone (3c)
The general procedure was followed with epoxide 2c (1.7 g,
6.0 mmol). The product was purified by concentration of the crude
reaction mixture followed by sublimation (35 ꢁC; cold finger cooled
to 0 ꢁC) and 3c was recovered as a white solid (1.6 g, 85%). 1H NMR
ꢀ157.4, ꢀ145.3. IR: nCO¼1819 cmꢀ1. Mp¼72–74 ꢁC. HRMS (EI)
calculated (C10H5F5O2) 252.0210; measured 252.0219, fit 3.7 ppm.
4.3. General procedure for the polymerization
of fluorinated lactones
(d, CDCl3, 300 MHz) 2.44–2.67 (m, 1H), 2.71–2.94 (m, 1H), 3.34 (dd,
3J¼4.3 Hz, 2J¼16.7 Hz,1H), 3.78 (dd, 3J¼5.8 Hz, 2J¼16.7 Hz, 1H), 4.88
(dddd, 3J¼3.9 Hz, 3J¼4.1 Hz, 3J¼5.6 Hz, 3J¼6.1 Hz, 1H); 13C NMR (
d
,
In a drybox, catalyst 4 (4.9 mg, 0.01 mmol) and lactone
2
CDCl3, 125 MHz) 36.1 (t, JCF¼21.6 Hz), 44.6, 63.8, 166.3 (The
(1.0 mmol) were weighed into separate dry, 4 mL vials. A stir bar
was added to the vial with 4. Dry toluene (0.5 mL) was added to
each of the vials, and the catalyst solution was transferred to the
vial with lactone. The vial was then capped with a Teflon-lined cap,
removed from the drybox, and immediately submerged into an oil
bath preheated to 50 ꢁC. After the reaction mixture was stirred for
6 h, the vial was cooled to room temperature and the polymeriza-
tion was quenched with the addition of five drops MeOH. The
polymers were isolated as described below.
fluorine-substituted carbons could not be definitively identified.); 19
F
NMR
(
d
,
CDCl3, 470 MHz) ꢀ129.1, ꢀ127.5, ꢀ116.5, ꢀ84.1. IR:
nCO¼1844 cmꢀ1. Mp¼41–42 ꢁC. HRMS (EI) calculated (C8H5F9O2ꢀCO2)
260.0247; measured 260.0250, fit 1.1 ppm.
4.2.4. (R)-4-(2,2,3,3,4,4,5,5,5-Nonafluoropentyl)-2-propiolactone (3d)
The general procedure was followed with epoxide 2d (1.7 g,
6.0 mmol). The product was purified as in 3c and lactone 3d was

6978
J.W. Kramer, G.W. Coates / Tetrahedron 64 (2008) 6973–6978
4.3.1. Poly(
b
-hydroxy-5,6,6,6-tetrafluoro-5-
and added to a solution of 4. The copolymerization proceeded for
(trifluoromethyl)hexanoate) (5a)
24 h before being quenched with MeOH.
The general procedure was followed with lactone 3a (250 mg,
1.0 mmol). The polymer precipitated from the reaction mixture and
was filtered, washed twicewithtoluene, and dried under vacuum.1H
Acknowledgements
NMR (
d
, (CD3)2CO, 300 MHz) 2.61–2.95 (m, 4H), 5.51–5.67 (m, 1H);
This work was supported by the National Science Foundation
(CHE-0243605) and the Department of Energy (DE-FG02-
05ER15687), and by the National Institutes of Health through
a Chemical/Biology Interface (CBI) Training Grant (to J.W.K.).
2
13C NMR (
d
, (CD3)2CO, 125 MHz) 32.6 (d, JCF¼19.0 Hz), 39.3, 65.7,
2 1 2
92.1 (dsept, JCF¼32.9 Hz, JCF¼205.0 Hz), 121.8 (qd, JCF¼28.0 Hz,
1JCF¼286.2 Hz), 169.1, 169.2.
4.3.2. Poly(b-hydroxy-4-(1,1,2,2-tetrafluoroethoxy)butyrate) (5b)
Supplementary data
The general procedure was followed with lactone 3b (200 mg,
1.0 mmol). The polymer precipitated from the reaction mixture and
was filtered, washed twice with toluene, and dried under vacuum.
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2008.03.108.
1H NMR (
d, (CD3)2CO, 300 MHz) 2.77–2.86 (m, 2H), 4.19–4.32 (m,
2H), 5.42–5.54 (m, 1H), 6.22 (tt, 3JHF¼2.6 Hz, 2JHF¼52.5 Hz, 1H); 13
C
References and notes
NMR (
d
, (CD3)2CO, 125 MHz) 35.4, 65.4, 69.0, 108.9 (tt, 2JCF¼41.8 Hz,
2
1JCF¼249.1 Hz), 118.3 (tt, JCF¼29.3 Hz, 1JCF¼267.7 Hz), 169.5, 169.6.
1. Grainger, D. W.; Stewart, C. W. Fluorinated Surfaces, Coatings, and Films; Castner,
D. G., Grainger, D. W., Eds.; ACS Symposium Series 787; American Chemical
Society: Washington, DC, 2001; pp 1–14.
4.3.3. Poly(
b
-hydroxy-5,5,6,6,7,7,8,8,8-nonafluorooctanoate) (5c)
2. Imae, T. Curr. Opin. Colloid Interface Sci. 2003, 8, 307–314.
3. Reddy, V. S.; Bruma, M.; Fitch, J.; Cassidy, P. Fluoropolymers 1: Synthesis;
Houghton, G., Cassidy, P. E., Johns, K., Davidson, T., Eds.; Topics in Applied
Chemistry; Kluwer Academic/Plenum: New York, NY, 1999; pp 3–10.
4. Mu¨ller, H.-M.; Seebach, D. Angew. Chem., Int. Ed. Engl. 1993, 32, 477–502.
5. Lenz, R. W.; Marchessault, R. H. Biomacromolecules 2005, 6, 1–8.
6. Williams, S. F.; Martin, D. P. Biopolymers; Steinbuchel, A., Ed.; Wiley VCH: 2004;
Vol. 4, pp 91–120.
7. For the properties of PHA copolymers, see: (a) Kunioka, M.; Tamaki, A.; Doi, Y.
Macromolecules 1989, 22, 694–697; (b) Noda, I.; Green, P. R.; Satkowski, M. M.;
Schectman, L. A. Biomacromolecules 2005, 6, 580–586; For the degradation of
copolymers, see: (c) Doi, Y.; Kanesawa, Y.; Kunioka, M.; Saito, T. Macromolecules
1990, 23, 26–31.
The general procedure was followed with lactone 3c (300 mg,
1.0 mmol). The polymer precipitated from the reaction mixture and
was filtered, washed twice with toluene, and dried under vacuum.
1H NMR (
1H); 13C NMR (
64.7, 169.1, 169.1.
d, (CD3)2CO, 300 MHz) 2.61–2.97 (m, 4H), 5.66–5.79 (m,
2
d
, (CD3)2CO, 125 MHz) 34.5 (t, JCF¼29.84 Hz), 39.2,
4.3.4. Poly((R)-b-hydroxy-5,5,6,6,7,7,8,8,8-nonafluorooctanoate) (5d)
The general procedure was followed with lactone 3d (300 mg,
1.0 mmol). The polymer precipitated from the reaction mixture and
was filtered, washed twice with toluene, and dried under vacuum.
8. (a) Kim, O.; Gross, R. A.; Hammar, W. J.; Newmark, R. A. Macromolecules 1996,
29, 4572–4581; (b) Mesiano, A. J.; Beckman, E. J.; Russell, A. J. Biotechnol. Prog.
2000, 16, 64–68; (c) Takagi, Y.; Yasuda, R.; Maehara, A.; Yamane, T. Eur. Polym. J.
1H NMR (
d, (CD3)2CO, 300 MHz) 2.64–2.94 (m, 4H), 5.66–5.78 (m,
2004, 40, 1551–1557; For examples of other fluorinated
b-lactones, see: (d)
1H); 13C NMR (
64.7, 169.1.
d
, (CD3)2CO, 125 MHz) 34.4 (t, JCF¼20.9 Hz), 39.1,
2
McBee, E. T.; Kim, Y. S.; Braendlin, H. P. J. Am. Chem. Soc. 1962, 84, 3154–3157; (e)
Anello, L. G.; Price, A. K.; Sweeney, R. F. J. Org. Chem. 1968, 33, 2692–2696; (f)
Lavalle´e, C.; Leborgne, A.; Spassky, N.; Prud’homme, R. E. J. Polym. Sci., Part A
1986, 25, 1315–1328.
4.3.5. Poly(
(trifluoromethyl)octanoate) (5e)
b
-hydroxy-5,5,6,6,7,8,8,8-octafluoro-7-
9. For a review of epoxide carbonylation, see: (a) Church, T. L.; Getzler, Y. D. Y. L.;
Byrne, C. M.; Coates, G. W. Chem. Commun. 2007, 657–674; For recent examples,
see: (b) Getzler, Y. D. Y. L.; Mahadevan, V.; Lobkovsky, E. B.; Coates, G. W. J. Am.
Chem. Soc. 2002, 124, 1174–1175; (c) Mahadevan, V.; Getzler, Y. D. Y. L.; Coates,
G. W. Angew. Chem., Int. Ed. 2002, 41, 2781–2784; (d) Schmidt, J. A. R.;
Mahadevan, V.; Getzler, Y. D. Y. L.; Coates, G. W. Org. Lett. 2004, 6, 373–376; (e)
Schmidt, J. A. R.; Lobkovsky, E. B.; Coates, G. W. J. Am. Chem. Soc. 2005, 127,
11426–11435; (f) Kramer, J. W.; Lobkovsky, E. B.; Coates, G. W. Org. Lett. 2006, 8,
3709–3712.
The general procedure was followed with lactone 3e (350 mg,
1.0 mmol). The polymer precipitated from the reaction mixture and
was filtered, washed twice with toluene, and dried under vacuum.
1H NMR (
d, (CD3)2CO, 300 MHz) 2.63–2.93 (m, 4H), 5.64–5.80 (m,
1H); 13C NMR (
169.0.
d, (CD3)2CO, 125 MHz) 34.6, 39.1, 64.8, 91.0, 119.8,
10. Rieth, L. R.; Moore, D. R.; Lobkovsky, E. B.; Coates, G. W. J. Am. Chem. Soc. 2002,
124, 15239–15248.
11. For a recent, comprehensive review of asymmetric epoxidation, see: (a) Xia,
Q.-H.; Ge, H.-Q.; Ye, C.-P.; Liu, Z.-M.; Su, K.-X. Chem. Rev. 2005, 105, 1603–1662;
For kinetic resolution of epoxides, see: (b) Tokunaga, M.; Larrow, J. F.; Kakiuchi,
F.; Jacobsen, E. N. Science 1997, 227, 936–938; (c) Schaus, S. E.; Brandes, B. D.;
Larrow, J. F.; Tokunaga, M.; Hansen, K. B.; Gould, A. E.; Furrow, M. E.; Jacobsen,
E. N. J. Am. Chem. Soc. 2002, 124, 1307–1315.
4.3.6. Poly(b-hydroxy-4-pentafluorophenyl-butyrate) (5g)
The general procedure was followed with lactone 3g (250 mg,
1.0 mmol). The polymer, which did not precipitate from toluene
solution, was precipitated by addition of the solution to hexanes
(4 mL). The precipitated polymer was filtered and washed twice
12. For solvent effects in epoxide carbonylation to
b-lactones, see: (a) Church,
with hexanes and dried under vacuum. 1H NMR (
d
, (CD3)2CO,
300 MHz) 2.57–2.76 (m, 2H), 3.01–3.22 (m, 2H), 5.31–5.48 (m, 1H);
13C NMR (
, (CD3)2CO, 125 MHz) 27.1, 38.3, 69.7, 111.6, 138.3, 141.0,
T. L.; Getzler, Y. D. Y. L.; Coates, G. W. J. Am. Chem. Soc. 2006, 128, 10125–
10133; For solvent effects in epoxide carbonylation to anhydrides, see: (b)
Rowley, J. M.; Lobkovsky, E. B.; Coates, G. W. J. Am. Chem. Soc. 2007, 129,
4948–4960.
d
13. (a) Tanahashi, N.; Doi, Y. Macromolecules 1991, 24, 5732–5733; (b) Hori, Y.;
Suzuki, M.; Yamaguchi, A.; Nishishita, T. Macromolecules 1993, 26, 5533–5534;
(c) Schechtman, L. A.; Kemper, J. J. Polym. Prepr. (Am. Chem. Soc., Div. Polym.
Chem.) 1999, 40, 508–509.
14. The polymerization of 3f in CHCl3 produced some polymer, which was slightly
soluble in hexafluoroisopropanol. However, characterization was difficult due
to the polymer’s insolubility.
146.5, 169.6, 169.6, 169.7.
4.4. General procedure for the polymerization
of fluorinated lactones
The general procedure was analogous to that of the homo-
polymerization. A solution of both lactones was prepared in toluene
15. The copolymerization of 3g and BBL was analogous to 3a and BBL as monitored
by 1H NMR spectroscopy.