Polyaldol synthesis by direct organocatalyzed crossed polymerization of bis(ketones) and bis(aldehydes)

Article abstract of DOI:10.1021/ma402108y

Synthesis of polyaldols consisting of β-keto alcohol monomer units is described. These polymers were obtained by direct step-growth polymerization of purposely designed bifunctional enolizable bis(ketone) monomers playing the role of nucleophilic donors,

Full text of DOI:10.1021/ma402108y

Article
pubs.acs.org/Macromolecules
Polyaldol Synthesis by Direct Organocatalyzed Crossed
Polymerization of Bis(ketones) and Bis(aldehydes)
Na Liu,†,‡ Anthony Martin,§,∥ Frederic Robert,§,∥ Jean-Marc Vincent,§,∥,* Yannick Landais,§,∥,*
́
́
Joan Vignolle,†,‡ Henri Cramail,†,‡,* and Daniel Taton†,‡,*
†University of Bordeaux, LCPO, UMR 5629, F-33600 Pessac, France
‡CNRS, LCPO, UMR 5629, F-33600 Pessac, France
§University of Bordeaux, ISM, UMR 5255, 33400 Talence, France
∥CNRS, ISM, UMR 5255, 33400 Talence, France
S
* Supporting Information
ABSTRACT: Synthesis of polyaldols consisting of β-keto alcohol
monomer units is described. These polymers were obtained by direct
step-growth polymerization of purposely designed bifunctional enolizable
bis(ketone) monomers playing the role of nucleophilic donors, and
activated nonenolizable bis(aldehyde)s serving as electrophilic acceptors.
Monofunctional ketone and aldehyde homologues were first synthesized
as models to establish the aldol reaction conditions using reaction
partners at stoichiometry. A bifunctional organocatalytic system
consisting of pyrrolidine in conjunction with acetic acid allowed
performing polyaldolizations of stoichiometric amounts of the bis(aldehyde) and the bis(ketone) in solution in THF,
DMSO, or DMF, at room temperature. However, polar solvents and/or prolonged reaction time induced further aldol reactions
between aldol units of polymer chains, as indicated by the relatively broad molecular weight distribution of related polyaldols
observed by size exclusion chromatography. Analysis by NMR spectroscopy confirmed the formation of β-keto alcohol units, but
also evidenced that the latter were also partly dehydrated into conjugated ketones via a crotonization reaction (from 20 to 33%
depending on the structure of the initial monomers).
the industrial scale, via an enantioselective aldol process
employing L-proline as an organocatalyst.14−17 This reaction
is known as the Hajos−Parrish−Eder−Sauer−Wiechert reac-
tion18 and is considered as the origin of asymmetric
organocatalysis.4,19−21
INTRODUCTION
■
The aldol reaction is an extremely popular C−C bond forming
addition reaction that is generally catalyzed by a Brønsted or
Lewis acid or base, yielding a β-ketohydroxy adduct.1−4 The
term aldolization has been generalized to the addition reaction
of any enolizable carbonyl-containing nucleophilic reagent (in
general a ketone) onto an electrophilic nonenolizable substrate
(mostly aldehydes).5 Formation of a nucleophilic enolate, prior
to its reaction with the aldehyde, is also common and refers to
as the indirect aldolization. To this end, silylenol ethers have
been extensively employed in the so-called Mukaiyama−aldol
reaction.6−8 The aldol adduct can yet undergo a dehydration
(called crotonization) and be converted into the corresponding
α,β-unsaturated carbonyl derivative, the driving force being the
formation of a conjugated system.1−4
An asymmetric carbon atom is also created during
aldolization, and control of the stereochemistry of the aldol
reaction has been the focus of extensive studies.9−11 Naturally
occurring enzymes, such as aldolases of type I or II, can trigger
the aldol formation, via a cooperative stereospecific mecha-
nism.12 Chiral organometallic catalysts13 and, more recently,
small chiral organocatalysts4 have been developed for
asymmetric aldolization of prochiral substrates. A representative
example is the synthesis of the Wieland−Miescher ketone
(WMK), a bicyclic diketone (enedione) developed in 1970 at
In polymer chemistry, only a few examples of polyaldol
synthesis, by repetition of aldol condensation reactions (=
polyaldolization), have been reported.22−28 However, these
examples deal with the self-polymerization of aldehydes or
ketones. For instance, self-polyaldolization of acetaldehyde
catalyzed by Na/Hg amalgam or amines or transition metals led
to poly(vinyl alcohol),22−24 though the polymer also contained
vinylidene units due to partial dehydration of vinyl alcohol
units. The latter feature was exploited to derive π-conjugated
polymers. Thus, a polyol precursor obtained by self-
polyaldolization of 5-methylfuran-2-carbaldehyde readily dehy-
drated into poly(2,5-furandiylvinylene).25 Kreja et al. further
applied this approach to synthesize poly(2,5-thienyleneviny-
lene) and related copolymers.26 On the other hand, Cataldo
reported that a solid resin was obtained by polyaldolic
condensation of acetone in the presence of H2SO4,
Received: October 15, 2013
Revised: January 2, 2014
Published: January 14, 2014
© 2014 American Chemical Society
525
dx.doi.org/10.1021/ma402108y | Macromolecules 2014, 47, 525−533

Macromolecules
Article
CF3SO3H, or AlCl3.27 The structure of the polymers resembled
that of poly(methylacetylene) incorporating carbonyls and
hydroxyls in the main chain. With bases as catalysts (e.g.,
NaOH or NaOEt) to trigger acetone polymerization, it was
shown that isophorone was the first acetone condensation
product, the obtained resin eventually resulting from both the
condensation of acetone with isophorone and the self-
condensation of isophorone.28
Alternatively, Itsuno’s group developed an indirect synthetic
pathway to polyaldols by repeated crossed Mukaiyama−aldol
reactions between bis(silylenolether) and bis(aldehyde) mono-
mers.29−31 Specific chiral Lewis acids allowed synthesizing
optically active polyaldols by asymmetric step-growth polymer-
ization. More generally, only a few examples of step-growth
polymerization of bis(aldehyde)s have been reported.32 Itsuno
et al. investigated the asymmetric Hosomi-Sakurai polyaddition
of bis-allylsilanes and bis(aldehyde)s, forming chiral polymers
consisting of allylic alcohol monomer units.31−37 Aromatic
polyesters could be synthesized by direct polyaddition of
bis(aldehyde)s,38−41 involving repeated disproportionation
Tishchenko42,43 reactions between aldehyde functions. More
recently, the group of Klok applied the Baylis−Hilman reaction
in step-growth polymerization of bis(aldehyde)s and bis-
(acrylate)s, leading to polyesters featuring allylic units.44,45
Not only linear polymers but also hyperbranched polyesters
were derived.46 Finally, the direct polyaddition of bis-
(aldehyde)s catalyzed by a cyanide anion or by N-heterocyclic
carbenes, as a means to access so-called polybenzoins, was also
described.47−49
ards. Size exclusion chromatography (SEC) analyses were also
performed in DMF at 80 °C with 1g/L LiBr and a flow rate of 0.8
mL/min. The setup consisted of a PL-GPC 50 Plus integrated GPC
(Polymer Laboratories, Varian) with a series of three PLgel 5 μm
MIXED-D columns. The elution of the filtered samples was monitored
using simultaneous UV and refractive index detectors. The elution
times were converted to molar mass using a calibration curve based on
low dispersity (Mw/Mn) polystyrene standards. Toluene was used as a
flow-marker. Differential scanning calorimetry (DSC) measurements
were performed on a DSC Q100 apparatus from TA Instruments.
Data were recorded during the second run for temperatures ranging
from 20 to 200 °C at a heating rate of 10 °C min−1. The cooling rate
between the first and second runs was also equal to 10 °C min−1. The
glass transition temperature (Tg) was determined by taking the
inflection point of the transition. Thermogravimetric analysis (TGA)
analyses were performed on a TA Instruments TGA-Q500, under N2
atmosphere at a heating rate of 5 °C/min.
Synthesis of Benzyl 4-Formylbenzoate (2b). To a dispersion of 4-
formylbenzoic acid (2 g, 13.3 mmol) in a 10/1 MeOH/water mixture
(67 mL) was added a 20% aq. Cs2CO3 solution up to pH = 8. The
resulting solution was stirred at 25 °C for 20 min and concentrated to
dryness under vacuum. The residue was dried under vacuum at 60 °C
and treated with benzyl bromide (2.4 mL, 20 mmol) in DMF (30
mL). The slurry was stirred under argon at 25 °C for 18 h. The
reaction mixture was diluted with a saturated aqueous NaHCO3
solution (30 mL) and extracted with EtOAc (50 mL). The organic
layer was then separated and washed again with a saturated aqueous
NaHCO3 solution (30 mL), then treated with brine (30 mL), dried
with Na2SO4, filtered and the organic solvent evaporated. The residue
was chromatographed on silica gel (petroleum ether/EtOAc, 9/1 to 7/
3) to afford 2b a white solid (2.5 g, 78%). Rf = 0.38 (petroleum ether/
EtOAc, 9/1); mp =147−148 °C. IR (KBr), νmax: 3377, 2964, 2845,
2744, 1719, 1704, 1577, 1501, 1453, 1370 cm−1. 1H NMR (200 MHz,
CDCl3), δ (ppm): 10.10 (s, 1H), 8.28−8.19 (m, 2H), 7.99−7.90 (m,
2H), 7.50−7.33 (m, 5H), 5.40 (s, 2H). 13C NMR (50 MHz, CDCl3), δ
(ppm): 191.71, 165.50, 139.34, 135.66, 135.21, 130.42, 129.62, 128.81,
128.62, 128.46, 67.44. HRMS (ESI) [M + Na]+ C15H12O3Na:
calculated, 263.06841; found, 263.0681.
Synthesis of 1,1′-(1,3-Phenylenebis(methylene))bis(piperidin-4-
one) (5). To a suspension of 4-piperidone hydrochloride (4.03 g,
26.04 mmol) in a 30/1 CH2Cl2/MeOH mixture (124 mL) in a round-
bottom flask equipped with a magnetic stirrer, were successively added
K2CO3 (7,2 g, 52.08 mmol) and 1,3-bis(bromomethyl)benzene (3.44
g, 13.02 mmol). The reaction mixture was stirred at room temperature
for 48h, and water (150 mL) was added. After separation, the organic
layer was washed with water and brine, dried over Na2SO4, filtered,
and the organic solvent evaporated. The residue was purified by
column chromatography on silica gel (CH2Cl2/MeOH, 100/0 to 95/
5) to afford 5 as a white solid. (3.91 g, quantitative yield). IR (KBr),
νmax: 2959, 2912, 2812, 2769, 1714 cm−1. 1H NMR (300 MHz,
CDCl3), δ (ppm): 7.36−7.24 (m, 4H), 3.63 (s, 4H), 2.75 (t, J = 6.0
Hz, 8H), 2.46 (t, J = 6.0 Hz, 8H). 13C NMR (75 MHz, CDCl3), δ
(ppm): 209.3, 138.4, 129.4, 128.5, 128.0, 62.0, 53.0, 41.4. IR (KBr),
νmax: 2959, 2912, 2812, 2769, 1714 cm−1.
Synthesis of 1,1′-(1,4-Phenylenebis(methylene))bis(piperidin-4-
one) (6). The same protocol was used for the synthesis of 1,1′-(1,3-
phenylenebis(methylene))bis(piperidin-4-one) (6). The residue was
purified by column chromatography on silica gel (CH2Cl2/MeOH,
97/3), affording a white solid (3.63 g, 71%). Analytical data matched
those reported in the literature.50 Rf = 0.34 (CH2Cl2/MeOH, 95/5),
1H NMR (200 MHz, CDCl3): δ (ppm) = 7.32 (s, 4H), 3.61 (s, 4H),
Here we report a novel synthetic strategy to polyaldols, by
repetition of direct intermolecular aldolization reactions
between properly selected bis(aldehyde) and bis(ketone)
monomers. These polyaldolization reactions were triggered
via an organocatalyzed pathway utilizing pyrrolidine in
conjunction with acetic acid. To the best of our knowledge,
although the amine-catalyzed direct intermolecular aldol
reaction between a ketone and an aldehyde is extremely well
documented in molecular chemistry, the application of this
elementary reaction to polyaldol synthesis has never been
reported.
EXPERIMENTAL SECTION
■
Materials. All reagents and solvents were of commercial grade and
used as received. Deuterated solvents for NMR spectroscopy were
acquired from Armar Chemicals (Dottigen, Switzerland). 1-Benzyl-4-
piperidone (1, 99%, Sigma-Aldrich), p-nitrobenzaldehyde (2a, 99.5%,
Sigma-Aldrich), 4,4′-pentamethylenebis(acetophenone) (8, 99%,
Sigma-Aldrich), 4-formylbenzoic acid (≥95.0%, Sigma-Aldrich),
benzyl bromide (98%, Sigma-Aldrich), 4-piperidone hydrochloride
(98%, Sigma-Aldrich), 1,3-bis(bromomethyl)benzene (97%, Sigma-
Aldrich), 1,4-bis(bromomethyl)benzene (≥98%, Sigma-Aldrich), 1,4-
diiodobenzene (99%, Sigma-Aldrich), acetylacetone (98%, Sigma-
Aldrich), 3-hydroxy-4-nitrobenzaldehyde (97%, Sigma-Aldrich), 1,5-
diiodopentane (97%, Sigma-Aldrich), and diethylene glycol di(p-
toluenesulfonate) (98%, Sigma-Aldrich) were used as received.
Pyrrolidine (99.5%, Alfa) was purified by fractional distillation from
KOH.
2.75 (t, J = 6.1 Hz, 8H), 2.46 (t, J = 6.1 Hz, 8H).
Instrumentation. NMR spectra were recorded on a Bruker AC-
400 spectrometer in appropriate deuterated solvents. Molar masses
were determined by size exclusion chromatography (SEC) at 25 °C, in
THF as the eluent (1 mL/min) and with trichlorobenzene as a flow
marker, using both refractometric (RI) and UV detectors (Varian).
Analyses were performed using a three-column set of TSK gel
TOSOH (G4000, G3000, G2000 with pore sizes of 20, 75, and 200 Å
respectively, connected in series) calibrated with polystyrene stand-
Synthesis of 1,1′-(1,4-Phenylene)bis(propan-2-one) (7). A proce-
dure reported in the literature was followed,51,52 and analytical data
matched those reported.
Synthesis of 1,4-Phenylenebis(methylene) Bis(4-formylbenzoate)
(9). To a suspension of NaH (160.0 mg, 6.6 mmol) in anhydrous
DMF (15 mL) was slowly added a solution of 4-formylbenzoic acid
(1g, 6.66 mmol) in anhydrous DMF (5 mL), at 0 °C under argon, and
the reaction mixture was stirred for 15 min at 0 °C. A solution of 1,4-
526
dx.doi.org/10.1021/ma402108y | Macromolecules 2014, 47, 525−533

Macromolecules
Article
Table 1. Screening of Catalysts and Reaction Conditions for the Polyaldolization at 25 °C between Bis(ketone)s and
Bis(aldehyde)s
catalyst
(0.3
equiv)
[M]
AcOH
(equiv)
time
(h)
M
(g/mol)
M
(g/mol)
M
(g/mol)
M
̅
w(DMF)
̅
̅
̅
n(THF)
w(THF)
n(DMF)
a
b
b
b
d
d
d
entry bis(ketone) bis(aldehyde) (mol/L)
solvent
D
(g/mol)
D
c
1
5
5
5
5
5
5
5
5
5
5
5
6
7
8
5
9
0.5
0.5
0.5
1
A−E
F
none
none
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
120
72
72
72
240
48
48
48
48
18
72
18
18
72
72
THF
THF
THF
oligomers
−
−
−
6700
7800
11 100
−
15 000
15 400
11 900
8800
14 300
17 000
14 700
7600
−
−
12 900
20 400
54 700
−
117 000
118 600
54 700
24 900
103 000
145 000
105 400
23 500
−
−
e
2
9
2360
3570 (3600 )
1.51
1.68
1.90
1.9
2.6
4.9
e
3
9
F
2570
4330 (5400 )
i
e
4
9
F
THF
2860
5460 (8050 )
c
5
−
9
1
F
THF
oligomers
−
−
−
−
−
−
−
−
−
−
−
−
−
7.7
i
6
1
F
DMSO
−
−
−
−
−
−
−
−
−
−
−
−
−
−
−
−
−
−
i
7
9
1
F
DMF
7.7
i
8
9
1
F
CH2Cl2
4.6
f
9
9
1
F
Toluene
2.9
g
g
g
i
10
11
12
13
14
15
9
1
F
THF
7.2
i
11
9
1
F
THF
8.5
i
1
F
THF
7.19
3.11
gh
,
9
1
F
THF
THF
THF
g
g
c
c
9
1
F
oligomers
−
−
10
1
F
oligomers
−
−
a
b
Concentration of monomers. Molecular weights and dispersity of precipitated polymers as determined by SEC in THF (calibration using
polystyrenes as standards). Only oligomers were formed. Molecular weight and dispersity of precipitated polymer were determined by SEC in
DMF (calibration using polystyrenes as standards). Molecular weights correspond to first peaks observed by SEC. Polymer was precipitated after 5
min of reaction; the yield was 50%. Pyrrolidine was distilled over KOH. Gelation occurred at the end of the polymerization. A 55−60% yield was
c
d
e
f
g
h
i
obtained.
bis(bromomethyl)benzene (586 mg, 2.22 mmol) in anhydrous DMF
(5 mL) was slowly added. The reaction mixture was stirred at 0 °C for
10 min, and then at 60 °C for 12h. A 1 M HCl solution (30 mL) was
then added. The aqueous layer was extracted with EtOAc (3 × 90 mL)
and the organic layers were washed with a saturated aqueous solution
of KCl (2 × 30 mL), and then with a 1 M NaOH solution (2 × 30
mL), dried over Na2SO4, filtered, and the solvents evaporated in
vacuum. The crude product was purified by flash chromatography
(CH2Cl2/MeOH, 100/0 to 90/10), yielding 9 as a white solid (681
mg, 76%). Rf = 0.72 (petroleum ether/EtOAc, 1/1); mp =169−170
(2.50 g, 15.00 mmol) in DMF (60 mL) were added oxybis(ethane-2,1-
diyl) bis(4-methylbenzenesulfonate) (3.10 g, 7.48 mmol) and K2CO3
(6.21 g, 44.88 mmol). The reaction mixture was heated to 80 °C under
N2 for 15h, and quenched with a 1 M HCl solution (60 mL). The
aqueous layer was extracted with EtOAc (3 × 60 mL) and the organic
layers were washed with a saturated aqueous NaHCO3 solution (3 ×
60 mL), then with water (2 × 60 mL) and brine (2 × 60 mL) dried
over Na2SO4, filtered, and the solvents evaporated in vacuum. The
crude product was purified by flash chromatography (CHCl3/EtOAc,
9/1), producing 11 as a light yellow solid (2.20 g, 73%). Rf = 0.16
(petroleum ether/EtOAc, 7/3); mp =97−98 °C, IR (neat), νmax: 1705,
1607, 1523, 1291, 1277 cm−1. 1H NMR (300 MHz, CDCl3), δ (ppm):
10.04 (s, 2H), 7.90 (d, J = 8.1 Hz, 2H), 7.59 (d, J = 1.4 Hz, 2H), 7.52
(dd, J = 8.1 Hz, 1.5 Hz, 2H, H5), 4.23 (t, J = 6.1 Hz, 4H), 2.02−1.88
(m, 4H), 1.80−1.66 (m, 2H). 13C NMR (75 MHz, CDCl3), δ (ppm):
190.5, 152.6, 143.6, 139.7, 126.0, 122.4, 113.7, 69.8, 28.4, 22.5, HRMS
(ESI) [M + Na]+ C19H18N2O8Na: calcd, 425.0955; found, 425.0937.
Synthesis of 1-Benzyl-3-(hydroxy(4-nitrophenyl)methyl)piperidin-
4-one 3a by Aldol Reaction from 1 and 2a. A typical aldol reaction
utilizing stoichiometric amounts of substrates 1 and 2a and pyrrolidine
as catalyst is as follows. To a solution of 4-nitrobenzaldehyde (2a)
(400 mg, 2.64 mmol) in THF were added 1-benzylpiperidin-4-one (1)
(490 μL, 2.642 mmol) and pyrrolidine (52 μL, 0.528 mmol). The
resulting solution was heated to 40 °C for six days, then quenched
with a saturated NH4Cl solution (40 mL) and DCM (50 mL) was
added. The aqueous layer was extracted with DCM (2 × 50 mL) and
the organic layers were washed with brine (60 mL) dried over Na2SO4,
filtrated, and the solvents evaporated under vacuum. The crude
material was purified by flash chromatography (DCM/EtOAc, 9/1) to
afford the desired product 3a as a yellow oil (270 mg, 30%). Rf = 0.32
(DCM/EtOAc, 9/1). IR (neat), νmax: 3369, 2960, 2868, 1712, 1518,
1
°C. IR (neat), νmax: 2947, 2847, 2746, 1708 cm−1. H NMR (400
MHz, CDCl3), δ (ppm): 10.10 (s, 2H), 8.23 (d, J = 8.2 Hz, 4H),
7.97−7.92 (m, 4H), 7.50 (s, 4H), 5.41 (s, 4H). 13C NMR (75 MHz,
CDCl3), δ (ppm): 191.7, 165.4, 139.4, 136.0, 135.1, 130.4, 129.6,
128.8, 67.0. HRMS (ESI) [M + Na]+ C24H18O6Na: calcd, 425.1001;
found, 425.1002.
Synthesis of 3,3′-Pentane-1,5-diylbis(oxy))bis(4-nitrobenzalde-
hyde) (10). To a solution of 3-hydroxy-4-nitrobenzaldehyde (500
mg, 2.99 mmol) in DMF (12 mL) were added 1,5-diiodopentane (223
μL, 1.5 mmol) and K2CO3 (1.24 g, 8.98 mmol). The reaction mixture
was heated to 80 °C under N2 for 15 h, and the mixture was quenched
with a 1 M HCl solution (15 mL). The aqueous layer was extracted
with EtOAc (3 × 15 mL) and the organic layers were washed with a
saturated aqueous NaHCO3 solution (3 × 15 mL), then with water (2
× 15 mL) and brine (2 × 15 mL), dried over Na2SO4, filtrated, and the
solvents evaporated in vacuum. The crude product was purified by
flash chromatography (petroleum ether/EtOAc, 8/2 to 1/1), affording
10 as a white solid (189 mg, 31%). Rf = 0.29 (petroleum ether/EtOAc,
7/3); mp =128−129 °C. IR (neat), νmax: 2958, 1703, 1609, 1527,
1
1288, 1171, 1018, 842, 790 cm−1. H NMR (300 MHz, CDCl3), δ
(ppm): 10.04 (s, 2H), 7.90 (d, J = 8.1 Hz, 2H), 7.59 (d, J = 1.4 Hz,
2H), 7.52 (dd, J = 8.1, 1.5 Hz, 2H), 4.23 (t, J = 6.1 Hz, 4H), 2.02−1.88
(m, 4H), 1.80−1.66 (m, 2H). 13C NMR (75 MHz, CDCl3), δ (ppm):
190.45, 152.55, 143.60, 139.75, 125.97, 122.44, 113.73, 69.85, 28.44,
22.53, HRMS (ESI) [M + Na]+ C19H18N2O8Na: calcd, 425.0955;
found, 425.0937.
1
1344 cm−1. H NMR (300 MHz, THF-d8), δ (ppm): 8.24−8.01 (m,
2H), 7.60−7.44 (m, 2H), 7.36−7.14 (m, 5H), 5.32 (d, J = 3.8 Hz,
0.5H), 5.25 (d, J = 7.0 Hz, 1H), 3.66 (dd, J = 14.5, 7.0 Hz, 1H), 3.42
(dd, J = 13.0, 2.8 Hz, 1H), 2.93−2.29 (m, 7H). 13C NMR (75 MHz,
THF-d8), δ (ppm): 207.52, 152.58, 151.33, 148.00, 147.77, 139.15,
139.03, 129.73, 129.51, 128.91, 128.82, 128.20, 127.89, 127.75, 127.70,
Synthesis of 3,3′-((Oxybis(ethane-2,1-diyl))bis(oxy))bis(4-nitro-
benzaldehyde) (11). To a solution of 3-hydroxy-4-nitrobenzaldehyde
527
dx.doi.org/10.1021/ma402108y | Macromolecules 2014, 47, 525−533

Macromolecules
Article
Figure 1. Monofunctional ketone and aldehyde models used for aldol reaction, and structure of the BIP catalyst.
Figure 2. Bis(ketone)s and bis(aldehyde)s investigated in this work.
123.57, 72.66, 70.62, 62.44, 62.42, 58.32, 56.97, 56.20, 54.23, 53.87,
53.33, 41.61, 41.28. HRMS (ESI) [M + H]+ C19H21N2O4: calcd,
341.1501; found, 341.1491. The crotonization reaction product 4,
namely, 1-benzyl-3-(4-nitrobenzylidene)piperidin-4-one, formed
under these conditions. Rf = 0.76 (DCM/EtOAc:9/1); mp =167−
168 °C. IR (neat), νmax: 2956, 2913, 2849, 1687, 1600, 1515, 1343
resulting polymer was obtained as a white solid (100 mg, 55%). Mw =
145 000 g/mol, D = 8.5 analyzed in SEC DMF (UV detector). Results
of the other polymerization experiments are provided in Table 1.
RESULTS AND DISCUSSION
■
While a large excess of ketone and quite a high loading in
catalyst (30 mol %) are generally employed for the aldol
reaction in molecular chemistry,4,19,21 polyaldol synthesis by
step-growth polymerization requires antagonist bifunctional
monomers employed at stoichiometry. In addition, the
aldehyde should not self-dimerize (or self-polymerize) under
the reaction conditions, hence it should preferably be
nonenolizable. Aldehydes carrying electron withdrawing groups
such as −NO2 or an ester group are expected to exhibit an
enhanced reactivity as electrophilic partners. In contrast, the
nucleophilic ketone should be enolizable, but its reaction by
self-condensation should also be avoided. Finally, further
dehydration of the aldol product under the reaction conditions,
forming CC double bonds, has also to be taken into account.
On the basis of our previous investigations,53 preliminary
studies on catalyzed aldol reactions were carried out using
benzimidazole-pyrrolidine (BIP) (I, Figure 1), using stoichio-
metric amounts of ketones and aldehydes. Ketone 1 and
aldehydes 2a,b, in line with the above requirements, were
selected as suitable candidates for model reactions. The aldol
process between equimolar amounts of 1 and 2a and 2b, in the
presence of 10 mol % of BIP and 20 mol % of trifluoroacetic
acid, effectively afforded corresponding aldol products 3a,b in
satisfying yields, albeit with modest diastereoselectivity (see
Supporting Information), along with the crotonization product
4. Although leading to partial dehydration in one case, these
model reactions constituted encouraging results for an
extension of the aldol reaction to polymer synthesis. In order
to avoid any complication with further determination of
enantiomeric purity of the resulting polymers, it was envisioned
to test the aldolization reaction using pyrrolidine, a simpler
analogue of BIP. On the basis of the above results, the reaction
involving stoichiometric amounts of monofunctional model
reagents 1 and 2a in the presence of a catalytic amount of
pyrrolidine was tested (see Experimental Section). The targeted
aldol product 3a was obtained, though formation of the
1
cm−1. H NMR (300 MHz, CDCl3), δ (ppm): 8.29−8.20 (m, 2H),
7.57 (s, 1H), 7.54−7.41 (m, 3H), 7.40−7.24 (m,7H), 3.79−3.68 (m,
4H), 2.98−2.85 (m, 2H), 2.77−2.66 (m, 2H). 13C NMR (75 MHz,
THF-d8), δ (ppm): 196.64, 148.45, 142.52, 139.19, 137.80, 132.25,
131.78, 129.57, 129.04, 127.98, 124.24, 62.85, 56.39, 50.62, 39.89.
HRMS (ESI) [M + H]+ C19H19N2O3: calcd, 323.1396; found,
323.1396.
General Polymerization Procedure (See Table 1). To a
solution of bis(ketone) at 0.25 mol/L in the selected solvent was
added 30 mol % of catalyst in the presence or the absence of 150 mol
% of acetic acid. After 10 min of stirring, a stoichiometric amount of
the bis(aldehyde) (0.25 mol/L) was added. After a given time, the
polymer was purified by two consecutive precipitations in 10-fold
excess of diethyl ether to eliminate catalyst, unreacted monomers and
oligomers. After filtration, the polymers were dried under vacuum and
obtained as white solids. In a typical experiment, polymerization of bis-
piperidinone 5 and bis(aldehyde) 9 was carried out as follows (entry
10 in Table 1). 1,1′-(1,3-Phenylenebis(methylene))bis(piperidin-4-
one) (5) (80 mg, 0.25 mmol) was dissolved in 0.5 mL of THF.
Pyrrolidine (6 μL, 30 mol %) and acetic acid (21 μL, 150 mol %) were
then added. After the solution was stirred for 10 min at room
temperature, 1,4-phenylenebis(methylene) bis(4-formylbenzoate) (9)
(100 mg, 0.25 mmol) was added. The initial suspension turns to a
clear and yellow solution after the reaction started. After 3 days of
reaction at 25 °C, the crude solution was analyzed by 1H NMR (THF-
d8) to determine the conversion (85%), and the solution was
precipitated twice in diethyl ether. The polymer was obtained as a
white solid (100 mg, 60%). Mw = 103 000 g/mol, D = 7.2 analyzed in
SEC DMF (UV detector).
Another typical polymerization experiment of bis(piperidinone) 5
and bis(aldehyde) 11 was as follows (entry 11, Table 1). 1,1′-(1,3-
Phenylenebis(methylene))bis(piperidin-4-one) (5) (80 mg, 0.25
mmol) was dissolved in THF (0.5 mL). Pyrrolidine (6 μL, 30 mol
%) and acetic acid (21 μL, 150 mol %) were added. After stirring the
solution for 10 min at room temperature, 3,3′-((oxybis(ethane-2,1-
diyl))bis(oxy))bis(4-nitrobenzaldehyde) (11) (101 mg, 0.25 mmol)
was added. After 3 days of reaction at 25 °C, the crude solution was
1
analyzed by H NMR (THF-d8) to determine the conversion (82%),
and the solution was precipitated twice in diethyl ether and the
528
dx.doi.org/10.1021/ma402108y | Macromolecules 2014, 47, 525−533

Macromolecules
Article
crotonized product 4 (by water elimination) was also noted
under these conditions.
present in other cyclic amines including cyclohexylamine or
morpholine.54 Under such conditions, polymers with an
apparent weight-average molecular weights Mw = 12 900 g/
mol and a dispersity (D = Mw/Mn) of 1.9 (SEC in DMF,
relative to PS standards, entry 2, Table 1) could be obtained
after 3 days at room temperature. SEC traces of polymers
synthesized in this way showed multimodal distributions
(Figure 4) typical of a step-growth polyaddition process.
On the basis of these premises, extension of the model
reactions to the polyaldolization was then carried out using a
selection of bis(ketone)s and bis(aldehyde)s, as shown in
Figure 2. Thus, N-substituted bis-piperidinones, such as 5 or 6,
were selected over bis-cyclohexanones as potential monomers,
the latter substrates featuring two asymmetric carbon atoms,
which would result in a complex NMR analysis of related
polyaldols.
Both the bis(piperidinone) 5 and the bis(aldehyde) 9 were
first selected as reaction partners for a screening of
polyaldolization reaction conditions at room temperature.
Considering preliminary results obtained with BIP and
pyrrolidine, various cyclic and acyclic secondary and tertiary
amines were tested as organic catalysts for repeated aldol
reactions (Figure 3; see also Table 1). The aldolization
mechanism catalyzed by a secondary amine, forming iminium
and enamine intermediates is depicted in Scheme 1.
Figure 4. SEC traces in THF of polymers obtained from the
polymerization of bis-piperidone 5 and bis(aldehyde) 9 at 25 °C in
THF, in the presence of 30 mol % pyrrolidine (blue curve, entry 2)
and [Monomers] = 0.5M; 30 mol % pyrrolidine and 150 mol % acetic
acid and [monomers] = 0.5 M (black curve, entry 3); 30 mol %
pyrrolidine and 150 mol % acetic acid and [monomers] = 1 M (red
curve, entry 4).
Figure 3. Secondary and tertiary amine catalysts investigated in this
work.
Scheme 1. Secondary Amine−Catalytic Cycle of Direct
Aldolization (from the Iminium to the Enamine, a Proton Is
Generated)
Note that apparent molecular weights determined by SEC in
THF (also relative to PS standards) were 3−4 times lower
compared to values obtained in DMF. It is however highly
likely that apparent polymer molecular weights as determined
by SEC in DMF are overestimated.
Interestingly, use of acetic acid (AcOH, 150 mol % relative to
monomers) allowed increasing the molecular weight at room
temperature (entry 3), as also illustrated in Figure 4 (black
curve). Such a bifunctional bicomponent catalytic system using
pyrrolidine and AcOH in a 1 to 3 molar ratio was previously
reported by Barbas et al. for aldol reactions of α,α-
dialkylaldehyde donors and arylaldehyde acceptors.53 The role
of acetic acid would be to increase the electrophilicity of
carbonyl groups of the bis(ketone), through protonation or H-
bonding, thus facilitating the nucleophilic addition of the
pyrrolidine and, consequently, the formation of iminium and
enamine intermediates (see Scheme 1).4,55 A significant
increase in Mw of the resulting polymers, from 20 400 g/mol
(entry 3) to 54 700 g/mol (entry 4), was noted in SEC traces in
DMF by simply increasing monomer concentration from 0.5 to
1M. A control experiment showed that bis(ketone) 5 could not
undergo self-polyaldolization: only oligomers did form under
the crossed polymerization reaction conditions (entry 5, Table
1).
Acyclic secondary amines, such as diisopropylamine, and
tertiary amines such as triethylamine and diisopropylethylamine
proved inefficient to promote crossed polyalolization, even after
5 days at room temperature. Similarly, six-membered ring cyclic
secondary amines such morpholine and piperidine did not
show any noticeable catalytic activity, in spite of the well-known
ability of cyclic secondary amines to catalyze the aldol reaction
via enamine or iminium type activation (Scheme 1).4 In
contrast, the closely related five-membered ring cyclic
secondary amine, namely, pyrrolidine was found to be
catalytically active, though a rather high loading of 30 mol %
relative to monomers was needed. The nucleophilicity of
pyrrolidine originates from the ability of the nitrogen center to
donate electrons, decreasing ring strain, a feature which is less
Representative 13C and 1H NMR spectra of a polymer
derived from polyaddition of bis-piperidinone 5 and bis-
(aldehyde) 9 are shown in Figure 5. Formation of aldol
monomer units can be evidenced through the presence of
characteristic signals f and d at 208.2 and 73.4−71.4 ppm,
corresponding to the ketone group and CHOH groups of the
529
dx.doi.org/10.1021/ma402108y | Macromolecules 2014, 47, 525−533

Macromolecules
Article
Figure 5. 1H NMR (a) and 13C NMR (b) spectra (THF-d8) of compound resulting from the polymerization of bis(piperidinone) 5 and
bis(aldehyde) 9 (entry 4, Table 1).
aldol moiety, respectively. The signal g at 166.1 ppm can be
assigned to the main-chain ester functions, while the sharp peak
at 192.0 ppm is due to the resonance of aldehyde end-groups.
Noteworthy is the presence of a further ketone signal (k) at
196.9 ppm, that is, 11 ppm downshifted compared to signal f,
which can be assigned to the carbon atom of an α,β-unsaturated
ketone. These conjugated double bonds thus arise from partial
dehydration (crotonization) of aldol monomer units, the enone
moiety being the thermodynamic product, as depicted in
Scheme 2.
Scheme 2. Polyaldol Synthesis from Bis(ketone) 5 and
Bis(aldehyde) 9 and Subsequent Formation of Vinylene
Units Forming the Corresponding Polyaldol by Dehydration
under Acidic Conditions
The splitting of some signals appearing both in the 13C and
the 1H NMR spectra are due to the formation of
diastereoisomers (e.g., carbon d in Figure 5b) during repeated
aldol reactions. Analysis by two-dimensional NMR confirms the
presence of these two configurations (Figure S1, Supporting
Information). Quantitative analysis by 13C NMR allowed us to
roughly determine the extent of crotonization and the presence
of α,β-unsaturated ketone double bonds (Figure S2). The
percentage was calculated from the intensity of peaks k and f,
using the following equation: % of dehydration = Ik/(Ik + If),
where I is the intensity of corresponding signals. For instance,
the polyaldol obtained from monomers 5 and 9 (entry 4, Table
1) was constituted of ∼20% of conjugated double bonds, as a
result of the dehydration of parent aldol units.
530
dx.doi.org/10.1021/ma402108y | Macromolecules 2014, 47, 525−533

Macromolecules
Article
Scheme 3. Branching Formation by Intermolecular Aldol Reactions Involving Aldol Units (Case of the Polyaldol Obtained from
Monomers 5 and 9)
Further analysis of the same polyaldol by differential
scanning calorimetry (DSC) indicated that this polymer was
amorphous, with a glass transition temperature (Tg) of 32.9 °C
after the second heating cycle (Figure S3). Thermogravimetric
analysis (TGA) showed an initial weight loss of the polymer at
100 °C presumably due to dehydration of aldol monomer units,
and further degradation continuing up to 900 °C (Figure S4).
We next noticed that purifying pyrrolidine by distillation
prior to use led to higher apparent mass-average molecular
weights: Mw from 54 700 g/mol to 103 000 g/mol by SEC in
DMF, relatively to PS standards (entry 10, see also Figure S5).
This can be attributed to the presence of residual water and/or
carbonation of crude pyrrolidine, hampering optimal reactivity
of the secondary amino function. Analysis by quantitative 13C
NMR of the corresponding polyaldol revealed the formation of
up to 33% of vinylene units generated by dehydration (Figure
S6). Hence, a catalytic system consisting of purified pyrrolidine
in conjunction with acetic acid provided a higher polyaldoliza-
tion rate, but also favored subsequent dehydration of aldol
units.
Solvent effect on the polymerization of bis(piperidinone) 5
and bis(aldehyde) 9 was also studied. DMSO, DMF and DCM
were all found suitable polyaldolization solvents, similar Mw
values being observed by SEC (entries 6−8, Table 1) under
otherwise identical experimental conditions. In contrast,
toluene led to a lower Mw value (24 900 g/mol, entry 9),
likely due to the poor solubility of the resulting polyaldol.
However, polar solvents such as DMF and DMSO also led to
polyaldols with a significantly higher molecular weigh
distribution. We hypothesized that this could be ascribed to
subsequent intermolecular aldolization reactions leading to
branched polymers, thus increasing the polyaldol dispersity
(Scheme 3). Ultimately, cross-linking could be observed under
forcing conditions and/or with specific monomers (see
further).
To extend the scope of the pyrrolidine/acetic acid-induced
polyaldolization reaction, different combinations of bis-
(aldehyde)s and bis(ketone)s were tested, using the following
optimized conditions: 30 mol % purified pyrrolidine in the
presence of 150 mol % acetic acid, 1 M monomer
concentration, in THF at 25 °C. Not surprisingly, the 1,3-
bis(piperidinone) 5 could be polymerized smoothly with the
more reactive bis(nitroaldehyde) 11, leading, within 12 h, to a
polyaldol with an apparent Mw value of 145 000 g/mol (entry
11). A quite high dispersity was also observed in this case (D =
8.5), presumably due to the incidence of intermolecular
reactions between aldol monomer units discussed above.
Similarly, the isomeric 1,4-bis(piperidinone) monomer 6
could be polymerized with bis(aldehyde) 9 (entry 12),
affording the corresponding polyaldol with an average
molecular weight of 105 400 g/mol and a dispersity of D =
7.19 within 18 h. The quantitative 13C NMR analysis of the
latter polymer indicated formation of up to 25% of dehydrated
aldol units (Figure S7). The p-substituted bis(ketone) 7 was
also found suitable to engage in polyaldolization with
bis(aldehyde) 9, although lower average molecular weight
was obtained (Mw = 23 500 g/mol, D = 3.11; entry 13). In the
latter case, prolonged reaction time led to gel formation
(formation of an insoluble polymer) which may be the result of
competitive intermolecular couplings of polymer chains. The
presence of even more acidic protons in the aldol units arising
from 7, in comparison to 5, may favor these aldol reactions
leading, ultimately, to a 3D cross-linked polymer (see Scheme
S1). Further studies are needed to confirm this hypothesis.
In contrast, reaction between the commercial bis-acetophe-
none 8 and the bis(aldehyde) 9 yielded only oligomers (entry
14), even after a reaction time of 3 days. This was consistent
with the fact that acetophenone (not shown), which can viewed
as the monofunctional analogue of 8, did not form any aldol
when reacted with p-nitrobenzaldehyde 2. Finally, polymer-
531
dx.doi.org/10.1021/ma402108y | Macromolecules 2014, 47, 525−533

Macromolecules
Article
ization of the bis-piperidinone 5 with the bis(aldehyde) 10
(entry 15) also resulted in the production of oligomers, even
after prolonged reaction time (up to 3 days). In this case, the
lower reactivity of the bis(aldehyde) 10 might be ascribed to
the presence of a deactivating mesomeric donor oxygen atom in
para position of the aldehyde function.
*E-mail: (D.T.) taton@enscbp.fr.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Financial support from ANRProgramme Blanc (Chirpol,
Grant No. 09-BLAN-0178-02) is acknowledged. Anne-Laure
Wirotius (LCPO, UMR 5629, Bordeaux) is acknowledged for
her help in the characterization by NMR.
CONCLUSIONS
■
Bis(ketone) and bis(aldehyde) monomers can be directly
polymerized under stoichiometric conditions by a crossed step-
growth polyaldolization process, affording unprecedented
organosoluble poly(β-ketoalcohol)s referred to as polyaldols.
N-substituted bis(piperidinone)s are nucleophilic and enoliz-
able monomers of choice that can efficiently react with
nonenolizable bis(aldehyde)s, the reactivity of which can be
enhanced by incorporating electron withdrawing groups, such
as nitro or ester groups. Such a monomer design allows
selectively driving the polymerization toward direct aldol-type
polymers, without the occurrence of the self-polymerization of
the bis(aldehyde) or the bis(ketone) under the experimental
conditions examined in this work. Triggering these polymer-
izations by an organocatalyic pathway utilizing pyrrolidine in
conjunction with acetic acid produces polyaldols exhibiting a
multimodal molecular weight distribution that is characteristic
of a step-growth polymerization. A subtle change of the catalyst
structure has a dramatic impact on the molecular features of the
obtained polyaldols. Moreover, polar solvents such as DMF or
DMSO or prolonged reaction time in THF can significantly
broaden the molecular weight distribution of polyaldols, owing
to branchings occurring by competitive intermolecular aldol
reactions involving monomer units. Monomer concentration is
also momentous, formation of insoluble cross-linked polyaldols
being triggered by a too high monomer concentration.
REFERENCES
■
(1) Heathcock, C. H. 1.5 - The Aldol Reaction: Acid and General
Base Catalysis. In Comprehensive Organic Synthesis; Barry, M. T., Ian,
F., Eds. Pergamon: Oxford, U.K., 1991; p 133.
(2) Mahrwald, R. Vol. 1: Enolates, Organocatalysis, Biocatalysis and
Natural Product Synthesis. In Modern Aldol Reactions; Wiley-VCH:
Weinhem, Germany, 2004.
(3) Schetter, B.; Mahrwald, R. Aldol Reactions. In Quaternary
Stereocenters; Wiley-VCH: Weinhem, Germany, 2006; p 51.
(4) For a review, see: List, B. Amine-catalyzed Aldol Reactions. In
Modern Aldol Reactions; Wiley-VCH: Weinhem, Germany, 2008; p
161.
(5) Richard, J. P.; Nagorski, R. W. J. Am. Chem. Soc. 1999, 121, 4763.
(6) Li, J. Mukaiyama aldol reaction. In Name Reactions; Springer:
Berlin Heidelberg: 2009; p 375.
(7) Mukaiyama, T.; Banno, K.; Narasaka, K. J. Am. Chem. Soc. 1974,
96, 7503.
(8) Carreira, E. Mukaiyama Aldol Reaction. In Comprehensive
Asymmetric Catalysis; Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.
Springer Verlag: Berlin, 1999; Vol. III; p 998.
(9) Heathcock, C. H. I. The Aldol Addition Reaction. In Asymmetric
Synthesis. Stereodifferentiating Reactions, Part B, Morrison, J. D., Ed.;
Academic: New York, 1984.
(10) Mahrwald, R. Chem. Rev. 1999, 99, 1095.
Polyaldols can also undergo partial dehydration forming
conjugated ketone units whose extent depends on the
experimental conditions and the structure of the parent
polymer. This feature could be further exploited to achieve π-
conjugated polymers arising from complete dehydration of
polyaldols grown by the metal-free synthetic approach
developed in the present work. This study, along with
preliminary results on aldol reactions with the homochiral
BIP catalyst, also open avenues to design chiral polyaldols
through the use of chiral catalysts via asymmetric polymer-
ization. It is foreseen that the transfer of chirality from the
catalyst to the prochiral centers would occur at each aldol
reaction step. It might be expected that physicochemical
properties of related chiral polyaldols be different than those of
racemic counterparts.
(11) Palomo, C.; Oiarbide, M.; Garcia, J. M. Chem. Soc. Rev. 2004, 33,
65.
(12) Machajewski, T. D.; Wong, C.-H. Angew. Chem., Int. Ed. 2000,
39, 1352.
(13) Palyi, G.; Caglioti, L. 2. Metal-catalysed Asymmetric Aldol
Reaction. In Organometallic chirality, Zucchi, C., Ed.; Stem Mucchi
Editore: Modena, 2008; p 128.
(14) Hajos, Z. G.; Parrish, D. R. Asymmetric synthesis of optically
active polycyclic organic compounds, German Patent, 1971.
(15) Hajos, Z. G.; Parrish, D. R. J. Org. Chem. 1974, 39, 1615.
(16) Bui, T.; Barbas, C. F. Tetrahedron Lett. 2000, 41, 6951.
(17) Mukherjee, S.; Yang, J. W.; Hoffmann, S.; List, B. Chem. Rev.
2007, 107, 5471.
(18) Wang, Z. Hajos-Parrish-Eder-Sauer-Wiechert Reaction. In
Comprehensive Organic Name Reactions and Reagents: John Wiley &
Sons, Inc.: New York, 2010.
(19) List, B.; Lerner, R. A.; Barbas, C. F. J. Am. Chem. Soc. 2000, 122,
2395.
ASSOCIATED CONTENT
* Supporting Information
■
(20) Berkessel, A.; Groger, H.Asymmetric Organocatalysis − From
Biomimetic Concepts to Applications in Asymmetric Synthesis; Wiley:
New York, 2005.
(21) Barbas, C. F. Angew. Chem., Int. Ed. 2008, 47, 42.
(22) Imoto, T.; Matsubara, T. J. Polym. Sci. Part A: Gen. Pap. 1964, 2,
4573.
(23) Yamamoto, T.; Konagaya, S.; Yamamoto, A. J. Polym. Sci., Polym.
Lett. Ed. 1977, 15, 729.
̈
S
Experimental procedures for the reaction of 1 and 2a,b,
catalyzed by BIP, 2D and quantitative 13C NMR spectra, SEC,
DSC, TGA analyses of some polyaldols, and a scheme showing
further aldol reactions from polyaldols leading to gel formation.
This material is available free of charge via the Internet at
http://pubs.acs.org
(24) Yamamoto, T.; Konagaya, S.; Yamamoto, A. J. Polym. Sci., Polym.
Lett. Ed. 1978, 16, 7.
AUTHOR INFORMATION
Corresponding Authors
*E-mail: (J.-M.V.) jm.vincent@ism.u-bordeaux1.fr.
*E-mail: (Y.L.) y.landais@ism.u-bordeaux1.fr.
*E-mail: (H.C.) cramail@enscbp.fr.
■
(25) Koßmehl, G.; Bischoff, R.; Betz, G. Polym. J. 1994, 26, 179.
(26) Kreja, L.; Kurzawa, M.; Kurzawa. J. Macromol. Chem. Phys. 1997,
198, 643.
(27) Cataldo, F. Angew. Makromol. Chem. 1996, 236, 1.
(28) Cataldo, F. Angew. Makromol. Chem. 1996, 236, 21.
532
dx.doi.org/10.1021/ma402108y | Macromolecules 2014, 47, 525−533

Macromolecules
Article
(29) Itsuno, S.; Komura, K. Tetrahedron 2002, 58, 8237.
(30) Komura, K.; Itsuno, S. Macromol. Chem. Phys. 2002, 203, 931.
(31) Itsuno, S. Prog. Polym. Sci. 2005, 30, 540.
(32) Aromatic dialdehydes such as o-phthalaldehyde can readily
undergo well defined chain-growth cyclopolymerization, using ionic or
coordinative initiators, yielding polyphthalaldehyde (PPA) featuring
five-membered rings in the polymer backbone. For a review, see:
Kostler, S. Polym. Int. 2012, 61, 1221. For a recent contribution in this
̈
area, see: Kaitz, J. A.; Moore, J. S. Macromolecules 2013, 46, 608.
(33) Itsuno, S.; Kumagai, T. Helv. Chem. Acta 2002, 85, 3185.
(34) Kumagai, T.; Itsuno, S. Macromolecules 2000, 33, 4995.
(35) Kumagai, T.; Itsuno, S. Tetrahedron Asym. 2001, 12, 2509.
(36) Kumagai, T.; Itsuno, S. Macromolecules 2001, 34, 7624.
(37) Kumagai, T.; Itsuno, S. Macromolecules 2002, 35, 5323.
(38) Yamaguchi, I.; Kimishima, T.; Osakada, K.; Yamamoto, T. J.
Polym. Sci., Polym. Chem. 1997, 35, 2821.
(39) Yamaguchi, I.; Kimishima, T.; Osakada, K.; Yamamoto, T. J.
Polym. Sci., Part A: Polym. Chem. 1997, 35, 1265.
(40) Choi, S. H.; Yashima, E.; Okamoto, Y. Polym. J. 1997, 29, 261.
(41) Onozawa, S. Y.; Sakakura, T.; Tanaka, M.; Shiro, M. Tetrahedron
1996, 52, 4291.
(42) Dzik, W. I.; Gooßen, L. J. Angew. Chem., Int. Ed. 2011, 50,
11047.
(43) Seki, T.; Nakajo, T.; Onaka, M. Chem. Lett. 2006, 35, 824.
(44) Ji, S.; Bruchmann, B.; Klok, H.-A. Macromolecules 2011, 44,
5218.
(45) Ji, S.; Bruchmann, B.; Klok, H.-A. Macromol. Chem. Phys. 2011,
212, 2612.
(46) Ji, S.; Bruchmann, B.; Wurm, F.; Klok, H.-A. J. Polym. Sci., Part
A: Polym. Chem. 2012, 50, 25.
(47) Kaul, S. N.; Fernandez, J. E. Macromolecules 1990, 23, 2875.
(48) Peeters, L. D.; Verreyt, G. A.; Jacobs, S. G.; Geise, H. J.
Macromolecules 1996, 29, 4216.
(49) Pinaud, J.; Vijayakrishna, K.; Taton, D.; Gnanou, Y. Macro-
molecules 2009, 42, 4932.
(50) Vijayakumar, V.; Rajesh, K.; Suresh, J.; Narasimhamurthy, T.;
Lakshman, P. L. N. Acta Crystallographica Section E 2010, 66, 170.
(51) Bartoli, S.; De Nicola, G.; Roelens, S. J. Org. Chem. 2003, 68,
8149.
(52) He, C.; Guo, S.; Huang, L.; Lei, A. J. Am. Chem. Soc. 2010, 132,
8273.
(53) For organoatalyzed aldol reactions using BIP I, see: (a) Lacoste,
E.; Landais, Y.; Schenk, K.; Verlhac, J.-B.; Vincent, J.-M. Tetrahedron
Lett. 2004, 45, 8035. (b) Lacoste, E.; Vaique, E.; Berlande, M.; Pianet,
I.; Vincent, J.-M.; Landais, Y. Eur. J. Org. Chem., 2007, 167. (c) Vincent,
J.-M.; Margottin, C.; Berlande, M.; Cavagnat, D.; Buffeteau, T.;
Landais, Y. Chem. Commun. 2007, 4782. (d) Liautard, V.; Jardel, D.;
Davies, C.; Berlande, M.; Buffeteau, T.; Cavagnat, D.; Robert, F.;
Vincent, J. M.; Landais, Y. Chem.Eur. J. 2013, 19, 14532.
(54) Petronijevic, F. R.; Nappi, M.; MacMillan, D. W. C. J. Am. Chem.
Soc. 2014, dx.doi.org/10.1021/ja410478a.
(55) Mase, N.; Tanaka, F.; Barbas, C. F. Org. Lett. 2003, 5, 4369.
533
dx.doi.org/10.1021/ma402108y | Macromolecules 2014, 47, 525−533