Baeyer-Villiger oxidation of an optically active 1,4-polyketone

Article abstract of DOI:10.1021/ma0359638

Baeyer-Villiger oxidation of poly[(S)-2-methyl-1-oxopropane-1,3-diyl] (1) with m-chloroperbenzoic acid provided poly(ketone/ester) (2) in a ratio of ketone/ester = 82/18 in 73% isolated yield. Methanolysis of 2 (M_n = 8600) gave only a trace amount of methyl 3-hydroxybutyrate (5) which resulted from neighboring two ester units, -[OCH(CH₃)CH₂C(=O)] ₂-. The major product was oligoketone CM_n = 650). A low yield of 5 indicates that an ester unit likely exists to distribute randomly in 2 rather than to form a block copolymer of a polyketone and a polyester.

Full text of DOI:10.1021/ma0359638

4484
Macromolecules 2004, 37, 4484-4487
Baeyer-Villiger Oxidation of an Optically Active 1,4-Polyketone
Na oyu k i Kosa k a ,† Ta m ejir o Hiya m a ,† a n d Kyok o Noza k i*,‡
Department of Material Chemistry, Graduate School of Engineering, Kyoto University,
Katsura, Nishikyo-ku, Kyoto 615-8510, J apan, and Department of Chemistry and Biotechnology,
Graduate School of Engineering, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-8656, J apan
Received December 20, 2003; Revised Manuscript Received March 31, 2004
ABSTRACT: Baeyer-Villiger oxidation of poly[(S)-2-methyl-1-oxopropane-1,3-diyl] (1) with m-chloro-
perbenzoic acid provided poly(ketone/ester) (2) in a ratio of ketone/ester ) 82/18 in 73% isolated yield.
Methanolysis of 2 (Mn ) 8600) gave only a trace amount of methyl 3-hydroxybutyrate (5) which resulted
from neighboring two ester units, -[OCH(CH3)CH2C(dO)]2-. The major product was oligoketone (Mn
)
650). A low yield of 5 indicates that an ester unit likely exists to distribute randomly in 2 rather than to
form a block copolymer of a polyketone and a polyester.
In tr od u ction
Poly((R)-3-hydroxybutyrate) (PHB) is a naturally oc-
curring polyester produced by a wide variety of bacte-
ria.1 Conventional synthetic routes to optically active
PHB are ring-opening polymerization of optically pure
(R)-3-butanolide without racemization of the stereogenic
center2 and kinetic resolution in the ring-opening po-
lymerization of racemic 3-butanolide using a chiral
catalyst.3 On the other hand, the repeating unit of PHB
might be produced, as we attempted here, by the
Baeyer-Villiger oxidation of optically active R-methyl-
γ-polyketone (1) transforming the ketone groups to the
ester groups.
Resu lts a n d Discu ssion
Ba eyer -Villiger Oxid a tion of P olyk eton e 1 w ith
m CP BA. We first employed mCPBA as an oxidant for
the Baeyer-Villiger oxidation of polyketone 1. Treat-
The polyketone 1 was synthesized in an optically
active form by asymmetric alternating copolymerization
of propene and CO.4,5 The structure of 1 is almost
completely controlled in a head-to-tail, isotactic, and
enantiomerially pure manner. Chemical modification of
the carbonyl group, a versatile functional group convert-
ible to others, provides new classes of chiral polymers.5e,6
Here we report the Baeyer-Villiger oxidation of opti-
cally active γ-polyketone 1 using m-chloroperbenzoic
acid (mCPBA). Although the Baeyer-Villiger oxidation
of polyketone was previously reported for the random
copolymer of ethene and carbon monoxide or ethene-
rich incompletely alternating copolymers, all of the
precedent examples contain no stereogenic centers in
the main chain.8 The Baeyer-Villiger oxidation of
dialkyl ketones is known to proceed with retention of
configuration of the migrating group with migratory
ability of tertiary > secondary > primary > methyl,
namely, a more substituted alkyl group migrates favor-
ably.7 Thus, the oxidation of polyketone 1 was expected
to provide with repeating unit of PHB (eq 1). Even a
relatively low conversion of the oxidation might be
enough to bestow biodegradable property on the original
polyketone.
ment of 1 (Mn ) 21 400, Mw/Mn ) 1.33, [R]25 -58.1 (c
D
1.01, CHCl3), ∆ꢀ ) -1.52 (CHCl3, 23 °C))4b with 8 mol
equiv of mCPBA in dichloromethane at room temper-
ature for 4 days (eq 2),9 followed by workup with
aqueous Na2SO3 and then with aqueous K2CO3, afforded
a crude polymer containing both ketone and ester
moieties (ketone/ester ) 82/18, determined by 1H NMR).
The crude polymer was purified by filtration through a
column of Sephadex LH-20 SEC resin and then by
preparative GPC to obtain poly(ketone/ester) 2 (ketone/
ester ) 82/18) in a 73% isolated yield.10
1
Figure 1 shows the H NMR spectrum of 2 in CDCl3.
Signals of a methine proton in an ester unit were
observed around 5.3 ppm. None of the peaks were
attributable to methylene next to the ester oxygen.
Thus, the oxidation proceeded exclusively at the site of
the methyl-substituted R-carbon rather than the un-
substituted R-carbon. When the sample was left in a
† Kyoto University.
‡ The University of Tokyo.
* Corresponding author: e-mail nozaki@chembio.t.u-tokyo.ac.jp.
10.1021/ma0359638 CCC: $27.50 © 2004 American Chemical Society
Published on Web 05/12/2004

Macromolecules, Vol. 37, No. 12, 2004
Baeyer-Villiger Oxidation of γ-Polyketone 4485
Ta ble 1. Meth a n olysis of Mod el Com p ou n d 6
run
6 (mmol)
NaOMe (equiv)
GC yield of 5 (%)
1
2
0.23
0.040
3
9
>95
80
mmol, 0.3% yield from ester unit in 2) was obtained,
indicating that consecutive ester units do exist but in
an almost negligible amount.
Next, we measured the molecular weight of poly-
(ketone/ester) 2 and the degraded oligoketone 4 to
compare the data with that of the parent polyketone 1.
The size exclusion chromatography (SEC) charts of the
samples are shown in Figure 2. The molecular weight
of poly(ketone/ester) 2 (Mn ) 8600) is found to be smaller
than that of polyketone 1 (Mn ) 21 400). The SEC chart
of 2 (Figure 2b) corresponds to an increase in low
molecular weight components, which might be derived
either from hydrolysis of the ester units in 2 under the
oxidation conditions or from the overestimated molec-
ular weight of polyketone 1 by SEC.11 Methanolysis of
F igu r e 1. 1H NMR spectrum of 2 in CDCl3. Signals around
5.3 ppm correspond to a methine proton in an ester unit.
CDCl3 or CD2Cl2 solution for several hours, the colorless
solution changed into a black one: furan units likely
formed from ketone units possibly due to acidic impuri-
ties (eq 3), as confirmed by observation of singlet signals
1
in 1.8 and 5.7 ppm in H NMR in CDCl3.
2 resulted in lowering the molecular weight to Mn
)
650 (Figure 2c), no trace of high molecular weight
components being observed. At this stage, no trace of
signals of methine proton at 5.3 ppm was observed for
1
the degraded oligomers by H NMR, indicating that all
the ester linkages in polymer 2 were cleaved by the
methanolysis to give oligoketone 4. Hence, the SEC
studies also suggest that ester units are randomly
distributed in the polymer chain rather than consecu-
tively.
Ba eyer -Villiger Oxid a t ion of 1 w it h Ot h er
Oxid a n ts. We further examined the Baeyer-Villiger
oxidation of 1 using other oxidizing agents (eq 5).
Distr ibu tion of Ester Un it in P olym er Ch a in . To
investigate the distribution of an ester unit in 2, we
subjected the polymer to methanolysis and assayed the
products (Scheme 1). When methanolysis was performed
in a small scale, not only methanolysis but also hydroly-
sis occurred due to a slight amount of water in the
reaction mixture. To test the feasibility of the assay
method, we first examined the small-scale experiment
of methanolysis using a low molecular weight model
compound, ethyl 3-hydroxybutyrate 6 (eq 4). The results
are shown in Table 1. Methanolysis of 6 (0.23 mmol) at
room temperature and quenching with acetic acid gave
5 in a quantitative yield as revealed by GC (run 1). A
smaller scale (0.040 mmol of 6) experiment was carried
out without any significant problem (run 2). Then,
polymer 2 was subjected to methanolysis: Polymer 2
was treated with 10 mol equiv (per ester unit) of sodium
methoxide for 44 h at room temperature. After quench-
ing with AcOH, only a trace amount of 5 (2.1 × 10-4
Results are summarized in Table 2. Magnesium mono-
peroxyphthalate (MMPP)12 was inert, and the substrate
polyketone was recovered quantitatively (run 1). The
use of trifluoroperacetic acid13 along with Na2HPO4 or
CaCO3 as a buffer converted ca. 8% of the ketone units
Sch em e 1. Meth a n olysis of P oly(k eton e/ester ) 2

4486 Kosaka et al.
Macromolecules, Vol. 37, No. 12, 2004
was performed with a J AI LC-908 chromatograph equipped
with J AIGEL-1H and -2H columns (chloroform as an eluent).
GC analysis was performed on a Shimadzu GC-14B gas
chromatograph equipped with a flame ionization detector.
Most of the reagents were purchased from Wako Pure Chemi-
cal Industries Ltd., Tokyo Kasei Kogyo Co., Ltd., Nacalai
Tesque, Ltd., Kanto Chemical Co., Ltd., or Aldrich Chemical
Co., Inc. All of the solvents used for the reactions were distilled
under argon after drying over a suitable drying agent. Silica
gel column chromatography was performed with Wako-gel
C-200. Sephadex LH-20 resin was purchased from Amersham
Biosciences.
Ba eyer -Villiger Oxid a tion of Op tica lly Active P oly-
k eton e 1 w ith m CP BA. Polyketone 1 (42 mg, 0.60 mmol of
a repeating unit) was added to a solution of m-chloroperbenzoic
acid (70%, 1.10 g, 4.8 mmol) in CH2Cl2 (8 mL) at room
temperature, and the resulting mixture was stirred at the
same temperature for 4 days before quenching with aqueous
Na2SO3 (40 mL) and chloroform (40 mL). The separated
organic layer was washed with aqueous K2CO3 (40 mL), dried
over anhydrous magnesium sulfate, filtered, and concentrated
to afford a crude polymer (ketone/ester ) 82/18 as determined
by 1H NMR). The crude polymer was filtered through a column
of Sephadex LH-20 gel (gel bed, 2.4 × 32 cm; eluent, chloform;
flow rate, 0.3 mL/min) and then purified with preparative GPC
to give poly(ketone/ester) 2 in a pure form (32 mg, 0.44 mmol
of a repeating unit, ketone/ester ) 82/18, 73% yield). 1H NMR
(CDCl3) δ: 0.80-1.36 (m, 3H, CH3), 2.13-2.77 (m, 1.1H), 2.77-
3.15 (m, 1.5H), 5.10-5.42 (br m, 0.18H, CHOCO). 13C NMR
(C6D6) δ: 16.1, 16.5, 19.7, 19.9, 30.1, 37.2, 37.4, 40.2, 41.1, 41.6,
44.9, 45.1, 47.0, 47.2, 67.6, 67.7, 169.0, 171.3, 209.3, 210.9,
F igu r e 2. SEC charts (polystyrene standard) and molecular
weights of (a) polyketone 1, (b) poly(ketone/ester) 2, and (c)
methanolysates of poly(ketone/ester) 4.
Ta ble 2. Ba eyer -Villiger Oxid a tion of 1 w ith Oth er
Oxid a n ts
recovery
run
1
oxidant
solvent
(%)
x/y/z
MMPP
(5 equiv to carbonyl)
CH2Cl2/DMF
(1/1)
97
100/0/0
2
3
(CF3CO)2O (14 equiv), CH2Cl2
H2O2 (4 equiv),
Na2HPO4 (4 equiv)
(CF3CO)2O (14 equiv), CH2Cl2
H2O2 (4 equiv),
73
82
<8/8/84
<8/8/84
211.6. IR (CH2Cl2): 1730, 1709 cm-1. [R]25 -40.4 (c 1.20,
D
CHCl3). Anal. Calcd for (C4H6O)0.82n(C4H6O2)0.18n: C, 65.84%;
H, 8.29%. Found: C, 62.92%; H, 7.86%.
CaCO3 (4 equiv)
Mod el Rea ction of Meth a n olysis. A mixture of ethyl
3-hydroxybutyrate 6 (30 mg, 0.23 mmol) and sodium methox-
ide in methanol (0.143 M, 4.5 mL, 0.64 mmol) was stirred at
room temperature for 17 h. 1,2-Diethoxyethane (42 mg) was
added into the reaction mixture as an internal standard for
GC analysis. A small amount of the solution (0.15 mL) was
extracted from the reaction mixture and was mixed with acetic
acid (0.01 mL). The resulting solution was analyzed with GC
(DB-1, 0.53 mm × 30 m). The yield of methyl 3-hydroxy-
butyrate was estimated to be >95%.
1
to ester units as estimated by H NMR (runs 2 and 3).
The resulting polymer (7) exhibited peaks around 110
ppm in 13C NMR, assignable to quarternary carbons as
evidenced by DEPT. These peaks was assigned as a
region of spiroketal units because quarternary spiro
carbons in poly(ketone/spiroketal)s with methyl side
chains exhibit 13C NMR peaks around 113 ppm in
solution5e,14 or solid state.5b,14b Thus, most of the re-
maining ketone units were transformed to spiroketal
units possibly due to the strong acidity of the reaction
conditions. The spiroketal form is protected from oxida-
tion, and thus no further reaction took place.
A smaller scale experiment was also examined. A mixture
of 6 (5.3 mg, 0.040 mmol) and sodium methoxide in methanol
(0.143 M, 2.5 mL, 0.36 mmol) was stirred at room temperature
for 17 h to give 5 (80% GC yield).
Meth a n olysis of P olym er 2. The mixture of polymer 2 (29
mg, ketone/ester ) 82/18, corresponding to 0.070 mmol of ester
unit) and sodium methoxide in methanol (0.143 M, 4.9 mL,
0.70 mmol) was stirred at room temperature for 44 h. 1,2-
Diethoxyethane (21 mg) was added to the reaction mixture as
an internal standard for GC analysis. A small amount of the
solution (0.15 mL) was extracted from the reaction mixture
and was added to acetic acid (0.01 mL). The resultant was
assayed by GC (DB-1) to estimate 0.3% yield (2.1 × 10-4 mmol)
of methyl 3-hydroxybutyrate 5.
Con clu sion
The Baeyer-Villiger oxidation of optically active
γ-polyketone 1 with mCBPA gave poly(ketone/ester) 2
in a ketone/ester ratio of 82/18 in 73% isolated yield.
The oxidation proceeded regioselectively, as was con-
firmed by 1H NMR, although the stereochemistry of the
resulting ester unit was unclear. Methanolysis of 2
afforded only a trace amount of methyl 3-hydroxy-
butyrate 5, an expected product derived from a continu-
ously oxidized moiety. The major product was oligomeric
ketone 4, which likely indicates that an ester unit
distributes randomly in the polymer chain.
Ba eyer -Villiger Oxid a tion of
1 w ith CF 3CO3H-
Na 2HP O4. To a suspension of Na2HPO4 (0.37 g, 2.6 mmol) in
dichloromethane (12 mL) was added trifluoroacetic anhydride
(1.93 g, 9.2 mmol) and 30% aqueous H2O2 (0.30 mL, 2.7 mmol)
at 0 °C. To the suspension was added polyketone 1 (45 mg,
0.64 mmol of a repeating unit) at 0 °C, and the resulting
mixture was stirred at room temperature for 45 h and then
treated with aqueous NaHCO3 (40 mL) and CHCl3 (40 mL) at
0 °C. Separated organic layer was washed with aqueous
Na2SO3 (15 mL) and H2O (25 mL), dried over anhydrous
magnesium sulfate, filtered, and concentrated. The residue
was purified by preparatve GPC to afford polymer 7 in a pure
form (33 mg, ketone/ester/spiroketal ) <8/8/84 as determined
by 1H NMR and IR, 0.46 mmol of a repeating unit, 72% yield).
1H NMR (CDCl3) δ: 0.75-1.33 (m, 3H, CH3), 1.33-3.08 (br
m, 2.3H), 5.10-5.40 (br m, 0.08H, CHOCO). 13C NMR (CDCl3)
δ: 11.4-15.3 (m), 29.6-43.5 (m), 67.6, 109.5-114.0 (m). IR
Exp er im en ta l Section
Gen er a l. Nuclear magnetic resonance spectra were taken
with a J EOL J NM-ECP500 (1H, 500 MHz; 13C, 126 MHz), a
J EOL EX-270 (1H, 270 MHz; 13C, 68 MHz), or a Varian
Mercury 200 (1H, 200 MHz; 13C, 50 MHz) spectrometer using
tetramethylsilane as an internal standard, and coupling
constants are given in hertz. Infrared spectra were recorded
on a Shimadzu FTIR-8400 spectrometer. Molecular weights
were estimated by SEC (Shodex, KF-804L, THF as an eluent)
using polystyrene as a standard. Preparative recycling GPC

Macromolecules, Vol. 37, No. 12, 2004
Baeyer-Villiger Oxidation of γ-Polyketone 4487
(CH2Cl2): 1790, 1736 cm-1. [R]23 -143 (c 0.81, CHCl3).
(5) (a) Wong, P. K. Eur. Pat. Appl. 384,517, 1990. (b) Batistini,
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Macromolecules 1994, 27, 4436. (d) Bronco, S.; Consiglio, G.
Macromol. Chem. Phys. 1996, 197, 355. (e) J iang, Z.; Sen, A.
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(6) (a) Nozaki, K.; Kosaka, N.; Muguruma, S.; Hiyama, T.
Macromolecules 2000, 33, 5340. (b) Nozaki, K.; Kosaka, N.;
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Polym. J . 2002, 34, 376.
D
(C4H6O)0.92n(C4H6O2)0.08n
58.46%; H, 7.33%.
:
C, 67.32%; H, 8.47%. Found: C,
Ba eyer -Villiger Oxid a t ion of
1
w it h CF 3CO3H -
Ca CO3. To a suspension of CaCO3 (0.26 g, 2.6 mmol) in
dichloromethane (12 mL) was added trifluoroacetic anhydride
(1.93 g, 9.2 mmol) and 30% aqueous H2O2 (0.30 mL, 2.7 mmol)
at 0 °C. To the suspension was added polyketone 1 (45 mg,
0.64 mmol of a repeating unit) at 0 °C, and the resulting
mixture was stirred at room temperature for 45 h. Workup
described above afforded polymer 7 (37 mg, ketone/ester/
(7) (a) Krow, G. R. Org. React. 1993, 43, 251. (b) Renz, M.;
1
Meunier, B. Eur. J . Org. Chem. 1999, 737, 7.
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tion of methine proton in ester units (around 5.3 ppm, 0.18
H) with methyl protons in the whole polymer chain (0.80-
1.36 ppm, 3 H). The integration values of all of the peaks
supported the ratio. Elemental analysis, however, did not
match exactly.
mmol of a repeating unit, 81% yield).
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MA0359638