Asymmetric alternating copolymerization of cyclohexene oxide and CO2 with dimeric zinc complexes

Article abstract of DOI:10.1021/ja028666b

Dimeric zinc complex 2a [= Et₂Zn₂(1a)₂] has been synthesized by the reaction of Et₂Zn and (S)-diphenyl(pyrrolidin-2-yl)methanol (1a-H). X-ray crystallography revealed that the alkoxide ligand replaced one of the two ethyl groups of Et₂Zn and formed a five-membered chelate ring through a Zn - N dative bond. Two zinc centers were bridged by oxygen atoms to form a Zn₂O₂ four-membered ring with a syn relationship between the two ethyl groups on the zinc centers. Dimeric zinc complex 2a was an active catalyst for asymmetric alternating copolymerization of cyclohexene oxide and CO₂. An MALDI-TOF mass spectrum of the obtained copolymer showed that the copolymerization was initiated by the insertion of CO₂ into Zn - alkoxide to give [(S)-diphenyl(pyrroridin-2-ly)methoxy] - [C(=O)O - (1,2-cyclohexylene) - O]n -H (copolymer I), including chiral ligand 1a as an initiating group. Complex 3a-OEt (= EtZn(1a)₂ZnOEt), in which an ethoxy group replaced one of the two ethyl groups in 2a, also polymerized cyclohexene oxide and CO₂ with higher catalytic activity and enantioselectivity than 2a and afforded EtO - [C(=O)O - (1,2- cyclohexylene) - O]_n - H (= copolymer III), including an ethoxy group as an initiating group. Throughout the studies, dimeric zinc species are indicated to be the active species for the copolymerization. It is also depicted that the substituent on the aryl moiety in diaryl(pyrrolidin-2-yl)methanol 2b - e influenced the polymerization activity.

Full text of DOI:10.1021/ja028666b

Published on Web 04/08/2003
Asymmetric Alternating Copolymerization of Cyclohexene
Oxide and CO2 with Dimeric Zinc Complexes
Koji Nakano,† Kyoko Nozaki,*,†,‡ and Tamejiro Hiyama§
Department of Chemistry and Biotechnology, Graduate School of Engineering, The UniVersity of
Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan, ConVersion and Control by AdVanced
Chemistry, PRESTO, Japan Science and Technology Corporation, and Department of Material
Chemistry, Graduate School of Engineering, Kyoto UniVersity, Sakyo-ku, Kyoto 606-8501, Japan
Received September 24, 2002; E-mail: nozaki@chembio.t.u-tokyo.ac.jp
Abstract: Dimeric zinc complex 2a [ ) Et2Zn2(1a)2] has been synthesized by the reaction of Et2Zn and
(S)-diphenyl(pyrrolidin-2-yl)methanol (1a-H). X-ray crystallography revealed that the alkoxide ligand replaced
one of the two ethyl groups of Et2Zn and formed a five-membered chelate ring through a ZnsN dative
bond. Two zinc centers were bridged by oxygen atoms to form a Zn2O2 four-membered ring with a syn
relationship between the two ethyl groups on the zinc centers. Dimeric zinc complex 2a was an active
catalyst for asymmetric alternating copolymerization of cyclohexene oxide and CO2. An MALDI-TOF mass
spectrum of the obtained copolymer showed that the copolymerization was initiated by the insertion of
CO2 into Znsalkoxide to give [(S)-diphenyl(pyrroridin-2-ly)methoxy]s[C(dO)Os(1,2-cyclohexylene)sO]ns
H (copolymer I), including chiral ligand 1a as an initiating group. Complex 3a-OEt ( ) EtZn(1a)2ZnOEt), in
which an ethoxy group replaced one of the two ethyl groups in 2a, also polymerized cyclohexene oxide
and CO2 with higher catalytic activity and enantioselectivity than 2a and afforded EtOs[C(dO)Os(1,2-
cyclohexylene)sO]nsH ( ) copolymer III), including an ethoxy group as an initiating group. Throughout
the studies, dimeric zinc species are indicated to be the active species for the copolymerization. It is also
depicted that the substituent on the aryl moiety in diaryl(pyrrolidin-2-yl)methanol 2b-e influenced the
polymerization activity.
are polymerization of conjugated 1,3-dienes3 or cyclic olefins,4
Introduction
cyclopolymerization of dienes,5 copolymerization of R-olefins
In the past decades, synthetic chemists have discovered a
variety of asymmetric catalysts which can convert prochiral
small molecules into chiral compounds with enantioenriched
forms, indispensable for the synthesis of pharmaceuticals,
agrochemicals, and other fine chemicals.1 A small amount of
chiral catalyst repeatedly activates prochiral molecules and
controls the stereochemistry to give a large amount of optically
active molecules. When such a powerful synthetic strategy is
applied to polymerization, optically active polymers with main-
chain chirality can be produced from optically inactive, prochiral
monomers. This type of polymerization reaction is classified
into asymmetric synthesis polymerization and is attracting much
attention as one of the more efficient and economical methods
for accessing optically active polymers which are considered
as candidates for new and valuable materials.2 Some ac-
complished examples in asymmetric synthesis polymerization
with carbon monoxide,6 and Diels-Alder polymerization of a
bisdienophile monomer with a bisdiene monomer.7 These
achievements are the fruits of fine organic synthesis.
In the course of our studies on asymmetric synthesis
polymerization, we considered a possibility of asymmetric
alternating copolymerization of meso-epoxide with CO2. Since
the first report by Inoue and Tsuruta on the alternating
copolymerization of epoxides and CO2,8 intensive studies have
been directed to the copolymerization, and a significant advance
(3) (a) Pino, P. AdV. Polym. Sci. 1965, 4, 393. (b) Natta, G.; Farina, M.; Donari,
M. Makromol. Chem. 1961, 43, 251. (c) Natta, G.; Porri, L.; Valenti, S.
Macromol. Chem. 1963, 67, 225. (d) Tsunetsugu, T.; Fueno, T.; Furukawa,
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Tsutsumi, H.; Oishi, T. Polym. J. 2002, 34, 18.
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T.; Matsubara, T.; Koga, N. J. Am. Chem. Soc. 1997, 119, 12779. (b) Jiang,
Z.; Sen, A. J. Am. Chem. Soc. 1995, 117, 4455. (c) Bronco, S.; Consiglio,
G.; Hutter, R.; Batistini, A.; Suter, U. W. Macromolecules 1994, 27, 4436.
(d) Brookhart, M.; Wagner, M. I.; Balavoine, G. G. A.; Haddou, H. A. J.
Am. Chem. Soc. 1994, 116, 3641.
† The University of Tokyo.
‡ Japan Science and Technology Corporation.
§ Kyoto University.
(1) For recent reviews, see: (a) ComprehensiVe Asymmetric Catalysis; Jacobsen,
E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer: New York, 1999. (b)
Catalytic Asymmetric Synthesis, 2nd ed.; Ojima, I., Ed.; Wiley: New York,
2000.
(2) For recent reviews, see: (a) Okamoto, Y.; Nakano, T. Chem. ReV. 1994,
94, 349. (b) Coates, G. W. In ComprehensiVe Asymmetric Catalysis;
Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer: New York,
1999; Vol. III, Chapter 36.
(7) (a) Kumagai, T.; Itsuno, S. Macromolecules 2002, 35, 5323. (b) Kumagai,
T.; Itsuno, S. Macromolecules 2001, 34, 7624 and references cited therein.
(8) Inoue, S.; Koinuma, H.; Tsuruta, T. J. Polym. Sci., Part B 1969, 7, 287.
9
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J. AM. CHEM. SOC. 2003, 125, 5501-5510
5501

A R T I C L E S
Scheme 1
Nakano et al.
Scheme 2
Scheme 3. Synthesis of Complex 2a
in catalytic activity has been achieved in the (last decade by
use of well-defined metal complexes as catalysts or supercritical
CO2 as a solvent.9-14 Accepted reaction mechanisms are (i) the
CO2 insertion into Zn-alkoxide bond and (ii) the ring-opening
of epoxide by backside attack of the resulting carbonate (Scheme
1).11,13,15,16 Because the ring-opening of a meso-epoxide proceeds
with inversion at one of the two chiral centers, a successful
asymmetric ring-opening by a chiral catalyst can give optically
active aliphatic polycarbonate with an (R,R)- or (S,S)-trans-1,2-
diol unit. From the viewpoint that a chiral catalyst does not
create new chiral centers but selects one of the chiral centers
of meso-compounds, this meso-desymmetrizing polymerization
differs from the asymmetric synthesis polymerization with
olefinic compounds as monomers. Although such a concept of
enantioselective desymmetrization of meso-materials is an
attractive and extremely powerful method in asymmetric
synthesis,17 there have been few cases of the application to
asymmetric polymerization.18 In 1999, we reported the first
example of the asymmetric alternating copolymerization of
meso-epoxide and CO2 (Scheme 2).19 Optically active poly-
[cyclohexene oxide-alt-CO2] (70% ee) was obtained by using
an equimolar mixture of Et2Zn and (S)-diphenyl(pyrrolidin-2-
yl)methanol (1a-H) as a chiral catalyst. The determination of
the degree of asymmetric induction on the resulting copolymer
was performed by a unique method. Polycarbonate can be easily
hydrolyzed into trans-1,2-diol and CO2 by alkali-treatment,
which enables us to evaluate the degree of asymmetric induction
unambiguously.20 This is in contrast with the conventional
studies on asymmetric synthesis polymerization which relied
on the measurement of optical rotation which has, in most cases,
no information on stereochemical purity. In 2000, Coates et al.
reported asymmetric alternating copolymerization with the well-
defined Zn-imine oxazoline ligand (IOx) complex, which
showed higher activity under mild conditions and controlled
molecular weight.21
In our previous report, we used a zinc complex generated in
situ, not isolated, and had little information about the real active
species. Here, we describe the isolation and the solid-state
characterization of Et2Zn-amino alcohol complex 2a. This
complex has a dimeric structure and can catalyze the asymmetric
copolymerization of cyclohexene oxide and CO2. Determination
of a polymer end group (initiating group) was achieved by
MALDI-TOF mass spectroscopy, which gave us an insight into
developing the Zn-amino alcohol complex with higher catalytic
activity and enantioselectivity. Addition of an alcohol to dimeric
zinc complex 2a improved the catalytic activity and enantiose-
lectivity. The zinc catalyst is indicated to maintain a dimeric
structure in the polymerization.
(9) For review articles on the copolymerization of epoxides and CO2, see: (a)
Rokicki, A.; Kuran, W. J. Macromol. Sci., ReV. Macromol. Chem. 1981,
C21, 135. (b) Inoue, S. Carbon Dioxide as a Source of Carbon; Aresta,
M., Forti, G., Eds.; Reidel Publishing Co.: Dordrecht, Germany, 1987; p
331. (c) Darensbourg, D. J.; Holtcamp, M. W. Coord. Chem. ReV. 1996,
153, 155. (d) Super, M.; Beckmann, E. J. Trends Polym. Sci. 1997, 5, 236.
(10) Aida, T.; Ishikawa, M.; Inoue, S. Macromolecules 1986, 19, 8.
(11) (a) Darensbourg, D. J.; Holtcamp, M. W. Macromolecules 1995, 28, 7577.
(b) Darenbourg, D. J.; Holtcamp, M. W.; Struck, G. E.; Zimmer, M. S.;
Niezgoda, S. A.; Rainey, P.; Robertson, J. B.; Draper, J. D.; Reibenspies,
J. H. J. Am. Chem. Soc. 1999, 121, 107. (c) Darensbourg, D. J.; Wildeson,
J. R.; Yarbrough, J. C.; Reibenspies, J. H. J. Am. Chem. Soc. 2000, 122,
12487. (d) Darensbourg, D. J.; Rainey, P.; Yarbrough, J. Inorg. Chem. 2001,
40, 986. (e) Darensbourg, D. J.; Yarbrough, J. J. Am. Chem. Soc. 2002,
124, 6335.
(12) (a) Super, M.; Berluche, E.; Costello, C.; Beckman, E. Macromolecules
1997, 30, 368. (b) Super, M.; Beckman, E. J. Macromol. Symp. 1998, 127,
89. (c) Sarbu, T.; Styranec, T.; Beckman, E. J. Nature 2000, 405, 165.
(13) (a) Cheng, M.; Lobkovsky, E. B.; Coates, G. W. J. Am. Chem. Soc. 1998,
120, 11018. (b) Cheng, M.; Moore, D. R.; Reczek, J. J.; Chamberlain, B.
M.; Lobkovsky, E. B.; Coates, G. W. J. Am. Chem. Soc. 2001, 123, 8738.
(c) Moore, D. R.; Cheng, M.; Lobkovsky, E. B.; Coates, G. W. Angew.
Chem., Int. Ed. 2002, 41, 2599.
(14) (a) Mang, S.; Cooper, A. I.; Colclough, M. E.; Chauhan, N.; Holmes, A.
B. Macromolecules 2000, 33, 303. (b) Stamp, L. M.; Mang, S. A.; Holmes,
A. B.; Knights, K. A.; de Miguel, Y. R.; McConvey, I. F. Chem. Commun.
2001, 2502.
(15) The theoretical study of the copolymerization catalyzed by (â-diiminato)-
ZnOR complexes was also investigated; see: Liu, Z.; Torrent, M.;
Morokuma, K. Organometallics 2002, 21, 1056.
(16) Using achiral Zn catalysts, the ring-opening has been reported to proceed
in a completely SN2 fashion; see: Inoue, S.; Koinuma, H.; Yokoo, Y.;
Tsuruta, T. Makromol. Chem. 1971, 143, 97.
Results and Discussion
Synthesis and Characterization of Dimeric Zinc Complex
2a. (S)-Diphenyl(pyrroridin-2-yl)methanol (1a-H) was synthe-
sized using the procedure reported by Corey et al.22 The zinc
complex 2a was obtained as a single crystal by treatment of
Et2Zn with 1 equiv of 1a-H in THF at 60 °C for 2 h, followed
by recrystallization from THF/hexane at -20 °C (Scheme 3).
X-ray single-crystal diffraction revealed that the obtained zinc
complex 2a formed a dimeric structure in which two zinc centers
were coordinated in a distorted tetrahedral geometry, as il-
(20) For an example of the optical purity determination of the polymer with
main-chain chirality by degrading into chiral repeating units, see ref 7a.
(21) Cheng, M.; Darling, N. A.; Lobkovsky, E. B.; Coates, G. W. Chem.
Commun. 2000, 2007.
(17) For review, see: Willis, M. C. J. Chem. Soc., Perkin Trans. 1 1999, 1765.
(18) Spassky, N.; Momtaz, A.; Kassamaly, A.; Sepulchre, M. Chirality 1992,
4, 295 and references cited therein.
(19) Nozaki, K.; Nakano, K.; Hiyama, T. J. Am. Chem. Soc. 1999, 121, 11008.
(22) Corey, E. J.; Link, J. O. Tetrahedoron Lett. 1989, 30, 6275.
9
5502 J. AM. CHEM. SOC. VOL. 125, NO. 18, 2003

Copolymerization with Dimeric Zinc Complexes
A R T I C L E S
Scheme 4
Scheme 5
Å) and O(2)-Zn(1) bond (2.024 Å) were very close to the
internal O(1)-Zn(1) bond (2.038 Å) and O(2)-Zn(2) bond
(2.030 Å), respectively. Such a relationship between the bridging
O-Zn and the internal O-Zn bond lengths of complex 2a is
in contrast to that in the case of the Me2Zn-(-)-DAIB
complexes.24 In the Me2Zn-(-)-DAIB complexes, the bridging
O-Zn bonds were 4% longer than the internal O-Zn bonds.
Based on such a context, the very small difference between the
bridging O-Zn bonds and the internal O-Zn bonds in complex
2a indicates the high degree of electron delocalization in the
Zn2O2 four-membered ring, contributing to stabilization of the
dimer form.
Copolymerization of Cyclohexene Oxide and CO2 with
Dimeric Zinc Complex 2a. We investigated the ability of the
isolated complex 2a to initiate and catalyze the copolymerization
of cyclohexene oxide and CO2. In an autoclave containing a
toluene solution of dimeric zinc complex 2a and cyclohexene
oxide (cyclohexene oxide/2a ) 40), the copolymerization was
initiated by introducing 30 atm of CO2 at 40 °C to give the
completely alternating copolymer in 57% yield with an Mn value
of 11 800 and a large Mw/Mn ratio of 15.7 (Scheme 5). The
completely alternating structure was verified by no observable
signal assignable to the repeating oxy(1,2-cyclohexene) unit (δ
3.4 ppm, ether linkage) in the 1H NMR spectrum of the resulting
copolymer.26 Hydrolysis of the copolymer gave a trans-1,2-
cyclohexane diol of 49% ee [(R,R)/(S,S) ) 74.5/25.5] in an
almost quantitative yield. Thus, dimeric zinc complex 2a was
found to be active for the asymmetric alternating copolymeri-
zation of cyclohexene oxide and CO2, while catalytic activity
and enantioselectivity were lower than those (>99% yield, 70%
ee) with a mixture of Et2Zn and 1a-H reported in our
communication (vide infra).19
Figure 1. ORTEP drawing of complex 2a with thermal ellipsoids shown
at the 50% probability level. All hydrogen atoms are ommitted for clarity.
Table 1. Selected Bond Distances (Å) and Bond Angles (deg) for
Complex 2a
Bond Distances
Zn(1)-O(1)
Zn(1)-O(2)
Zn(1)-N(1)
Zn(l)-C(18)
2.0382(15)
2.0242(15)
2.1357(18)
1.987(2)
Zn(2)-O(2)
Zn(2)-O(1)
Zn(2)-N(2)
Zn(2)-C(37)
2.0301(15)
2.0355(15)
2.1560(19)
1.987(2)
Bond Angles
O(l)-Zn(l)-O(2)
O(l)-Zn(l)-N(1)
O(I)-Zn(I)-C(18)
O(2)-Zn(1)-N(1)
O(2)-Zn(1)-C(18)
N(I)-Zn(1)-C(18)
84.22(6)
81.30(6)
131.64(8)
116.11(7)
114.81(9)
120.97(9)
O(2)-Zn(2)-O(1)
O(2)-Zn(2)-N(2)
O(2)-Zn(2)-C(37)
O(l)-Zn(2)-N(2)
O(1)-Zn(2)-C(37)
N(2)-Zn(2)-C(37)
84.14(6)
80.43(7)
133.68(9)
117.90(6)
118.07(8)
115.72(9)
lustrated in Figure 1 and Table 1. Diethyl zinc reacted with
1a-H to form a tricoordinate monomeric zinc complex in which
one of the two ethyl groups of Et2Zn was replaced with 1a and
another one remained on the zinc center without reacting with
an NH group (Scheme 4).23 The nitrogen atom coordinated to
a zinc atom to form a prolinol-Zn five-membered chelate ring
(the O-Zn bond in this chelate ring is named as an internal
bond). Then, this coordinatively unsaturated monomeric zinc
complex dimerized into dimeric zinc complex 2a through the
two bridging O-Zn bond to form a Zn2O2 four-membered ring.
The two ethyl groups on the zinc centers of 2a are oriented in
a syn fashion, which is common to the dimer of R2Zn-(-)-
DAIB.24,25 In complex 2a, the bridging O(1)-Zn(2) bond (2.036
The completely alternating structure of the copolymer enabled
the determination of an end group by MALDI-TOF mass
(24) Dimeric zinc complexes from Me2Zn and a â-amino alcohol: (a) Kitamura,
M.; Okada, S.; Suga, S.; Noyori, R. J. Am. Chem. Soc. 1989, 111, 4028.
(b) Kitamura, M.; Suga, S.; Niwa, M.; Noyori, R. J. Am. Chem. Soc. 1995,
117, 4832. (c) Kitamura, M.; Yamakawa, M.; Oka, H.; Suga, S.; Noyori,
R. Chem.sEur. J. 1996, 2, 1173.
(25) The solid-state structures of other dimeric zinc complexes [RZn-L]2 (L )
chiral monoanionic chelate ligand) were also characterized by X-ray
analysis. See the following references. Aminothiolato ligand: (a) Rijnberg,
E.; Jastrzebski, J. T. B. H.; Jassen, M. D.; Boersma, J.; van Koten, G.
Tetrahedron Lett. 1994, 35, 6521. (b) Rijnberg, E.; Hovestad, N. J.; Kleij,
A. W.; Jastrzebski, J. T. B. H.; Boersma, J.; Jassen, M. D.; Spek, A. L.;
van Koten, G. Organometallics 1997, 16, 2847. Aminoalkolato ligand:
Mimoun, H.; Laumer, J. Y. S.; Giannini, L.; Scopelliti, R.; Floriani, C. J.
Am. Chem. Soc. 1999, 121, 6158. Pyridylalkolato ligand: Bolm, C.;
Schlingloff, G.; Harms, K. Chem. Ber. 1992, 125, 1191.
(23) In our previous communication, both of the ethyl groups of Et2Zn were
reported to be protonated with -OH and -NH groups, based on the
disappearance of the 1H NMR signals assigned to ethyl group when 1.0
equiv of 1a-H was added to Et2Zn in hexane-toluene-d8 at 20 °C. The
disappearance of the signals may result from the overlapping with other
signals or the signal broadening.
(26) Koinuma, H.; Hirai, H. Makromol. Chem. 1977, 178, 1283.
9
J. AM. CHEM. SOC. VOL. 125, NO. 18, 2003 5503

A R T I C L E S
Nakano et al.
Scheme 6. A Possible Reaction Mechanism Initiated by Complex
2a
Figure 2. MALDI-TOF mass specrtum of the copolymer obtained with
complex 2a.
Table 2. Copolymerization of Cyclohexene Oxide and CO2 with a
Mixture of Complex 2a and Ethanola
EtOH
yield (%)
of polymerb
% eed
(R,R)
run
(equiv to 2a)
Mn (Mw/Mn)c
1e
2
3
4
5
6
7
0.0
0.2
0.4
0.6
0.8
1.0
2.0
57
94
95
>99
91
71
trace
11800 (15.7)
12300 (7.18)
12000 (1.30)
9900 (1.39)
6300 (1.43)
4500 (1.82)
49
64
74
72
75
76
Figure 3. Structures of copolymer I and II.
spectroscopy, which gave us valuable information about the
polymerization mechanism.27 Figure 2 shows the mass spectrum
of the copolymer produced with 2a. This spectrum was obtained
with 1,8-dihydroxy-9(10H)-anthracenone (dithranol) as a matrix
and sodium trifluoroacetate as a cationizing agent. In the mass
spectrum, only one series of signals with regular intervals of
142.2 (repeating unit) could be observed, and the mass number
of each signal matches [142.2n (repeating unit) + 252.3 (1a)
+ 1.0 (H) + 23.0 (Na+ ion)]. This result shows that copoly-
merization was initiated by 1a on a zinc center and terminated
by protolysis to give either copolymer I or II (Figure 3). The
difference between copolymer I and II is attributed to the two
possible initiation mechanisms: (i) the insertion of CO2 into a
Zn-alkoxide bond of 2a to initiate the copolymerization
affording copolymer I or (ii) the ring-opening of epoxide by
the nucleophilic attack of alkoxide in 2a to start the copoly-
merization giving copolymer II. Judging from the instability
of carbonic acid monoester which is a terminal group of
copolymer II, we conclude that copolymer I is the reasonable
structure and the initiation reaction should be the CO2 insertion
into the Zn-alkoxide bond of 2a. The dissociation of chelating
ligand 1a required such a high energy that the initiation reaction
did not occur at the same time, which may have caused the
large polymer weight distribution of the copolymer.11d
a Cyclohexene oxide (10 mmol) was treated with CO2 (30 atm) in the
presence of a mixture of the zinc complex 2a (0.25 mmol) and a desirable
amount of EtOH in toluene (17 mL) at 40 °C for 19 h. b Calculated based
on cyclohexene oxide. c Estimated by size-exclusion chromatography
analysis using a polystyrene standard. d Determined based on the enantio-
meric excess of a trans-1,2-cyclohexane diol given after hydrolysis of
copolymer. e The same as Scheme 5.
illustrated in Scheme 6. During the polymerization, a monomeric
zinc species possibly interacts with the active zinc center through
coordination of the oxygen atom; that is, the monomeric zinc
species works as a chiral ligand. Consequently, the remaining
chiral ligand 1a is able to control the enantioselectivity of the
ring-opening of epoxide.
Improvement of the Catalytic Activity and Enantioselec-
tivity: Effect of Addition of an Alcohol to Complex 2a.
While, as mentioned previously, asymmetric alternating copo-
lymerization was achieved by use of dimeric zinc complex 2a,
ligand dissociation from the catalytic center would have
diminished the degree of asymmetric induction. To realize the
inhibition of the ligand dissociation, we added an alcohol to
complex 2a: additional alcohol should replace (an) ethyl group-
(s) on the zinc centers to give (a) new Zn-OR bond(s), so that
copolymerization would be initiated not by the chiral ligand 1a
but by the resulting alkoxide ligand.
The determination of a polymer end group poses a question
of how asymmetric induction was achieved to give the optically
active copolymer of 49% ee despite the dissociation of a chiral
ligand from the catalytically active zinc center after the initiation
reaction. This may explain the participation of a dimeric zinc
species in the copolymerization process, as was also mentioned
in precedent reports.28 A possible reaction mechanism is
Copolymerization of cyclohexene oxide and CO2 was carried
out with a mixture of complex 2a and varying amounts of
ethanol, as summarized in Table 2. Addition of 0.2-0.8 equiv
of ethanol to 2a improved the chemical yield quantitatively and
enantioselectivity to almost up to 75% and achieved the control
of molecular weight (runs 2-5). Addition of 1.0 equiv of ethanol
resulted in a slight decrease in catalytic activity (71% yield),
(27) For reviews on mass spectrometry of synthetic polymers, see: (a) Nielen,
M. W. Mass Spectrom. ReV. 1999, 18, 309. (b) Hanton, S. D. Chem. ReV.
2001, 101, 527.
(28) Kuran, W.; Listos, T. Macromol. Chem. Phys. 1994, 195, 401. (b) Kuran,
W.; Listos, T. Macromol. Chem. Phys. 1994, 195, 977. (c) Listos, T.; Kuran,
W.; Siwiec, R. J. Macromol. Sci., Pure Appl. Chem. 1995, A32, 393.
9
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Copolymerization with Dimeric Zinc Complexes
A R T I C L E S
Figure 6. 1H NMR spectrum of the copolymer of cyclohexene oxide and
CO2 with use of a 2a-ethanol (0.8 equiv) system at 40 °C (500 MHz,
CDCl3).
Scheme 7. A Plausible Reaction Mechanism with Complex 3a
Figure 4. MALDI-TOF mass spectra of the copolymers obtained with a
mixture of complex 2a and 0.2-1.0 equiv of ethanol (a-e). The signals
assigned to copolymer I and III were represented by In and IIIn, respectively.
Figure 5. Structure of copolymer III with an ethoxy group as an initiating
group.
in Scheme 7. Copolymerization is initiated by CO2 insertion
into the Zn-OEt bond of dimeric zinc complex 3a-OEt, which
has an ethoxy group on one zinc center and an ethyl group on
the other zinc center. The active zinc center in the resulting
complex 3a-OCO2Et is coordinated in a tetrahedral geometry
and has no epoxide binding site, although it was reported in
the literature that one epoxide binding site was necessary for
the epoxide ring-opening.11c Accordingly, one of the two oxygen
atoms or the nitrogen atom attached to the active zinc center
may have worked as a hemi-labile ligand. Subsequent ring-
opening of epoxide and the insertion of CO2 afford complex
3a-OP (P, polymer chain) which is converted to copolymer III
after hydrolysis. Because of lack of chelate stabilization, CO2
insertion into the Zn-OEt bond in 3a-OEt is faster than that
into Zn-amino alkoxide 1a to give copolymer III selectively,
and complex 3a-OEt can catalyze the copolymerization mini-
mizing the dissociation of the chiral ligands. The lowered
molecular weight distribution also indicates the smooth initiation
reaction by a Zn-OEt complex. Thus, higher catalytic activity,
lower Mw/Mn and higher stereocontrol have been realized with
3a-OEt.30
although enantioselectivity was maintained (76% ee) (run 6).
However, addition of 2.0 equiv of ethanol caused the drastic
decrease of catalytic activity (run 7).
The introduction of an ethoxy end group was confirmed by
MALDI-TOF mass spectra of the obtained copolymers (Figure
4). Besides the series of signals assigned to the amino alcohol-
attached copolymer I, we observed another series of signals with
regular intervals of 142.2 when 0.2 equiv of ethanol was added
(Figure 4a). With the increase of the amount of additional
ethanol, this new series of signals grew in intensity, whereas
the signals of copolymer I diminished (Figure 4b-e). The mass
number of the new signals matched [142.2n (repeating unit) +
45.1 (EtO) + 1.0 (H) + 23.0 (Na+ ion)] and can be assigned to
copolymer III bearing an ethoxy group as the initiating group
(Figure 5). The structure of copolymer III initiated by the Zn-
OEt complex was also confirmed by the 1H NMR spectrum of
the produced copolymer (Figure 6). The signal assigned to
methylene protons (a) of the ethoxy group was observed at 4.18
1
ppm (quartet), which did not appear in the H NMR spectrum
of copolymer I. Two small signals at 4.40 and 3.58 ppm were
assignable to methine protons (c, d) in the terminal hydroxy-
(1,2-cyclohexylene) group.29
Here, it is anticipated whether, prior to the copolymerization,
dimeric zinc complex 3a-OEt dissociated into monomeric zinc
complexes EtZn(1a) and EtOZn(1a) which would have been
One possible explanation for the effect of ethanol is a reaction
mechanism involving dimeric zinc complex 3a-OEt, as shown
(29) Nakano, K.; Nozaki, K.; Hiyama, T. Macromolecules 2001, 34, 6325.
9
J. AM. CHEM. SOC. VOL. 125, NO. 18, 2003 5505

A R T I C L E S
Scheme 8
Nakano et al.
given by the dissociation of Et2Zn2(1a)2 ( ) 2a) and (EtO)2Zn2-
(1a)2, respectively. However, the involvements of these two
monomeric complexes EtZn(1a) and EtOZn(1a) in the copo-
lymerization are less plausible based on the experimental results
that (i) copolymer I which was produced by 2a was hardly
formed when 0.8-1.0 equiv of ethanol was added to 2a and
that (ii) the addition of 2.0 equiv of ethanol to 2a, which would
have converted 2a to (EtO)2Zn2(1a)2, was inert for the copo-
lymerization.
Ideally, addition of 1.0 equiv of ethanol would transform 2a
to 3a-OEt quantitatively, although the optimum conditions of
in situ generation of 3a-OEt are accomplished by the addition
of 0.8 equiv of ethanol to 2a. To isolate the pure complex 3a-
OEt, reprecipitation of the product given by the reaction of
complex 2a with 0.5 equiv of ethanol was performed from THF/
hexane to yield a colorless solid, unsuitable for X-ray analysis.
This obtained zinc complex was shown to be a good catalyst to
afford the completely alternating copolymer of 80% ee, the
highest enantiomeric excess ever reported (Scheme 8). Dif-
ferential scanning calorimetry of the copolymer showed glass
the transition temperature (Tg) at 117 °C, the value being very
close to the ones previously reported for the copolymers with
a lower stereoregularity.21,31
As we previously reported, the mixture of Et2Zn and 1a-H
produced a copolymer of 70% ee,19 while the isolated complex
2a gave the copolymer of only 49% ee (Table 2, run 1). The
difference may have resulted from the impurity of Et2Zn,
probably EtZn-OEt; in other words, the reaction mixture of
Et2Zn and 1a-H might have contained both 2a and 3a-OEt. In
fact, the MALDI-TOF mass spectrum of the copolymer obtained
with the Et2Zn/1a-H mixture exhibited two series of signals
assignable to copolymer I and III.32
Relationship between the Monomer Conversion and the
Number Average Molecular Weight. A plot of molecular
weight and polydispersity of the copolymer versus conversion
of cyclohexene oxide is shown in Figure 7 for the copolymer-
ization with in situ generated 3a-OEt (Table 3). As the
copolymerization reaction proceeded, a linear increase of
molecular weight was observed. Furthermore, the copolymers
at each conversion showed unimodal elution curves in the GPC
chromatogram and a relatively narrow polydispersity. These
results indicated the living nature of the copolymerization of
cyclohexene oxide and CO2 with 3a-OEt.
Figure 7. Plot of molecular weight (Mn) and polydispersity (Mw/Mn) of
the copolymer as a function of the conversion of cyclohexene oxide using
a mixture of 2a and 0.8 equiv of EtOH (cyclohexene oxide/2a ) 120).
Table 3. Relationship between Monomer Conversion and the
Resulting Copolymera
conversion (%) of
cyclohexene oxideb
isolated yield (%)
of polymerc
M
n (Mw/Mn)d
% ee (R,R)e
37
67
92
36
68
88
6100 (1.70)
12300 (1.26)
16100 (1.19)
74
73
70
a Cyclohexene oxide (30 mmol) was treated with CO2 (30 atm) in the
presence of a mixture of the zinc complex 2a (0.25 mmol) and EtOH (0.20
mmol) in toluene (17 mL) at 40 °C. b Determined by GC analysis.
c Calculated based on cyclohexene oxide. d Estimated by size-exclusion
chromatography analysis using a polystyrene standard. e Determined based
on the enantiomeric excess of a trans-1,2-cyclohexane diol given after
hydrolysis of copolymer.
Table 4. Effects of Alcohols: Copolymerization with a Mixture of
2a and Various Alcohols, ROHa
yield (%)
of polymerb
% ee
(R,R)d
run
ROH
M
n (Mw/Mn)c
1e
2
3
4
5
EtOH
MeOH
91
99
91
97
99
86
6300 (1.43)
8400 (1.50)
4100 (2.23)
5000 (1.85)
6500 (1.49)
6800 (1.58)
75
75
74
78
78
60
BnOH
iPrOH
tBuOH
6
CF3CH2OH
a Cyclohexene oxide (10 mmol) was treated with CO2 (30 atm) in the
presence of a mixture of the zinc complex 2a (0.25 mmol) and ROH (0.20
mmol) in toluene (17 mL) at 40 °C for 19 h. b Calculated based on
cyclohexene oxide. c Estimated by size-exclusion chromatography analysis
using a polystyrene standard. d Determined based on the enantiomeric excess
of a trans-1,2-cyclohexane diol given after hydrolysis of copolymer. e The
same as run 5 of Table 2.
the copolymer bearing the added alcohol as the initiating group.
For each case, the introduction of added alcohol into the
polymer-chain end was ascertained by MALDI-TOF mass
spectra.33 These results suggest that the copolymerization was
initiated by CO2 insertion into 3a-OR to form complex 3a-
OCO2R, as was the case for ethanol. After the initiation
reaction, the same species (zinc-carbonate complex) should be
generated to catalyze the following polymerization.
A slight decrease of activity and enantioselectivity was
observed by the addition of trifluoroethanol. In addition, three
series of copolymers were detected by mass spectrum; these
are copolymer I with an amino alkoxide 1a as an initiating
Alcohol Effect. To test the effect of the initiating alkoxide,
several alcohols were examined in combination with complex
2a, and the results are listed in Table 4. Copolymerization
proceeded in good yields and with high stereoselectivity to give
(30) Recently, Coates and co-workers have reported that the copolymerization
of cyclohexene oxide with CO2 initiated by [{Zn(OR)(BDI)}2] complexes
are second order in [Zn(OR)(BDI)], which suggests the participation of
di-zinc species in the enchainment of monomer. See ref 13c. At present,
the possibility for the further aggregation of 3a-OR cannot be omitted.
(31) Koning, C.; Wildeson, J.; Parton, R.; Plum, B.; Steeman, P.; Darensbourg,
D. J. Polymer 2001, 42, 3995.
(32) We checked that copolymerization with an equimolar mixture of carefully
stored Et2Zn and 1a-H afforded the copolymer of 55% ee in 67% yield.
This result was almost the same when isolated complex 2a was used.
(33) See Supporting Information.
9
5506 J. AM. CHEM. SOC. VOL. 125, NO. 18, 2003

Copolymerization with Dimeric Zinc Complexes
A R T I C L E S
Scheme 9
Table 5. Effects of Ligands: Copolymerization with a Mixture of
Et2Zn, (S)-Diaryl-pyrrolidin-2-yl-methanols 1(a-e)-H, and EtOHa
amino
yield (%)
of polymerb
% ee
(R,R)d
alcohol
M
n (Mw/Mn)c
1a-H
1b-H
1c-H
1d-H
1e-H
99
99
99
74
34e
6400 (1.43)
7200 (1.37)
4400 (1.98)
3700 (1.56)
12700 (32)
77
64
45
racemic
3
Figure 8. ORTEP drawing of complex 2e with thermal ellipsoids shown
at the 50% probability level. All hydrogen atoms and toluene molecules
are ommitted for clarity.
a Cyclohexene oxide (10 mmol) was treated with CO2 (30 atm) in the
presence of a mixture of Et2Zn (0.50 mmol), 1 (0.50 mmol), and EtOH
(0.20 mmol) in toluene (17 mL) at 40 °C for 19 h. b Calculated based on
cyclohexene oxide. c Estimated by size-exclusion chromatography analysis
using a polystyrene standard. d Determined based on the enantiomeric excess
of a trans-I,2-cyclohexane diol given after hydrolysis of copolymer.
e [carbonate linkage]/[ether linkage] ) 4.6/1.
Table 6. Selected Bond Distances (Å) and Bond Angles (deg) for
Complex 2e
Bond Distances
Zn(l)-O(l)
Zn(l)-O(2)
Zn(l)-N(I)
Zn(1)-C(20)
2.048(3)
2.035(3)
2.126(4)
1.990(5)
Zn(2)-O(2)
Zn(2)-O(1)
Zn(2)-N(2)
Zn(2)-C(41)
2.041(3)
2.030(3)
2.139(4)
1.994(5)
group, a copolymer initiated by CO2 insertion into the Zn-
OCH2CF3 bond, and a copolymer initiated by the ring-opening
of epoxide. Possibly, lower nucleophilicity of CF3CH2O- led
amino alkoxide ligand 1a into initiating the reaction to give
copolymer I, and the electron-withdrawing nature of a trifluo-
romethyl group made the zinc center of the complex 3a-
OCH2CF3 more electron deficient so that the efficient epoxide
coordination was accomplished to favor the ring-opening of
epoxide as the initiation step.
Bond Angles
O(1)-Zn(1)-O(2)
O(I)-Zn(1)-N(I)
O(I)-Zn(1)-C(20)
O(2)-Zn(I)-N(1)
84.26(12) O(2)-Zn(2)-O(1)
84.58(12)
82.40(14)
80.14(14) O(2)-Zn(2)-N(2)
133.6(2)
102.97(15) O(1)-Zn(2)-N(2)
O(2)-Zn(2)-C(41) 130.00(19)
103.99(15)
O(1)-Zn(2)-C(41) 128.85(17)
N(2)-Zn(2)-C(41) 115.5(2)
O(2)-Zn(1)-C(20) 126.6(2)
N(I)-Zn(1)-C(20) 117.4(2)
Ligand Effect. Catalytic activities depended greatly on the
substituents on the phenyl group of 1a. All (S)-diaryl(pyrroridin-
2-yl)methanols (1b-e)-H were synthesized using the same
procedure as described for 1a-H with the corresponding aryl-
magnesium bromide.34 All copolymerization reactions were
carried out using the zinc complexes generated in situ by the
reaction of Et2Zn, 1-H, and EtOH (1/1/0.4) (Scheme 9),35 and
the results are summarized in Table 5. While monosubstitution
at the meta-position (1b, 1c) resulted in a slight loss of
enantiomeric excess of copolymers, other ligands (substitution
at both of the meta-positions (1d) or at the para-position (1e))
resulted in a significant decrease of catalytic activity and
enantioselectivity. Particularly, when p-trifluoromethyl substi-
tuted ligand 1e-H was used, the continuous ring-opening of
epoxide was facilitated to give the nonalternating copolymer
with ether linkages in addition to carbonates. This may have
been caused by the electron-withdrawing nature of the trifluo-
romethyl group, making the zinc centers more acidic to activate
an epoxide more strongly. The trifluoromethyl group also
affected the crystal structure of the Et2Zn2(1e)2 complex (2e).
As depicted in Figure 8, 2e had a dimeric structure where the
two ethyl groups on the zinc centers were oriented in an anti
fashion, which was contrastive to the structure of complex 2a.
The two bridging O-Zn bonds (O(1)-Zn(2), 2.030 Å; O(2)-
Zn(1), 2.035 Å) were very close to the internal O-Zn bonds
(O(1)-Zn(1), 2.048 Å; O(2)-Zn(2), 2.041 Å) in the same
tendency as 2a (Table 6). Each side of the two planes of a central
Zn2O2 four-membered ring was covered with one pyrrolidine
ring that concealed the active zinc centers, which would result
in the decrease of catalytic activity.
Conclusions
We have reported the asymmetric alternating copolymeriza-
tion of cyclohexene oxide and CO2 with chiral dimeric zinc
complexes. The isolated zinc complex 2a, prepared by the
reaction of Et2Zn with (S)-diphenyl(pyrroridin-2-yl)methanol
(1a-H), was characterized by X-ray single-crystal diffraction.
The zinc centers, each of which is coordinated by two bridging
oxygens, one nitrogen in a pyrrolidine ring, and one ethyl group,
possess distorted tetrahedral geometries and two ethyl groups
oriented in syn fashion. The dimeric zinc complex 2a was found
to be effective for the asymmetric alternating copolymerization
of cyclohexene oxide and CO2 to give optically active poly-
(34) Mathre, D. J.; Jones, T. K.; Xavier, L. C.; Blacklock, T. J.; Reamer, R. A.;
Mohan, J. J.; Jones, E. T. T.; Hoogsteen, K.; Baum, M. W.; Grabowski, E.
J. J. J. Org. Chem. 1991, 56, 751.
(35) Except for 1f, recrystallization from the reaction mixture of Et2Zn and 1
did not give the suitable single crystals for X-ray analysis.
9
J. AM. CHEM. SOC. VOL. 125, NO. 18, 2003 5507

A R T I C L E S
Nakano et al.
mL) was added to the resulting mixture. Vigorous stirring of the
biphasic solution gave a pale yellow precipitation of N-benzyl-(S)-
dipheny(pyrrolidine-2-yl)methanol hydrochloride, which was collected
by filtration. To liberate the free base, the salt was suspended in ether
(300 mL) and 1 M aqueous NaOH (100 mL), and then the resulting
mixture was stirred vigorously until the salt was completely dissolved.
After the organic layer was separated, the aqueous layer was extracted
with ether (100 mL × 2). The combined organic layers were washed
with brine (50 mL), dried over anhydrous Na2SO4, filtered, and
concentrated under reduced pressure to give almost pure 4a, which
was used for the next reaction without further purufication.
carbonate at 49% ee. The MALDI-TOF mass spectrum of the
copolymer proved that the chiral ligand 1a worked as an initiator
and that the copolymerization was initiated by the insertion of
CO2 into a Zn-O bond of 2a. Addition of ethanol to 2a gave
dimeric zinc complex 3a-OEt with which the catalytic activities
and enantioselectivities were improved up to 95% yield and
80% ee, respectively. From these results, we indicated a
possibility of the reaction mechanism in which dimeric zinc
species took part in the copolymerization, and a high degree of
chiral recognition was achieved by the aggregated zinc complex
bearing two chiral ligands. Various prolinol derivatives with a
substituent on the phenyl group of 1a-H was also investigated
and shown to have a great effect on catalytic activity and
stereoselectivity, suggesting that further optimization of the
ligand would lead to an achievement of the improved catalyst.
Synthesis of (S)-Diphenyl(pyrrolidin-2-yl)methanol (1a-H). In a
250-mL Schlenk tube were placed 4a (7.3 g, 21 mmol), palladium
hydroxide on carbon (20 wt %, 900 mg), acetic acid (1.3 mL, 23 mmol),
dichloromethane (20 mL), and methanol (40 mL). The mixture was
stirred under a hydrogen atmosphere (1 atm) at room temperature for
47 h, filtered, and concentrated in vacuo. To liberate the free base, the
salt was suspended in ether (300 mL) and 1 M aqueous NaOH (100
mL), and then the resulting mixture was stirred vigorously until the
salt was completely dissolved. The organic layer was separated, and
the aqueous layer was extracted with ether (100 mL × 2). The combined
organic extracts were washed with brine (100 mL), dried over anhydrous
Na2SO4, filtered, and concentrated under reduced pressure. Purification
of the residue by silica gel column chromatography with ethyl acetate
Experimental Section
General Methods. All manipulations involving air- and/or moisture-
sensitive compounds were carried out using the standard Schlenk
technique under argon purified by passing it through a hot column
packed with BASF catalyst R3-11. NMR spectra were recorded in
deuteriochloroform on a Varian Mercury 200 (1H 200 MHz; 13C 50
MHz) or JEOL JNM-ECP500 (1H 500 MHz; 13C 125 MHz) spectrom-
eter. Chemical shifts are reported in ppm from an internal standard:
as an eluent gave 1a-H (4.9 g, 92% yield) as a colorless solid. [R]22
D
-60.0° (c 0.95, MeOH) [lit.34 [R]21 -54.3° (c 0.261, MeOH)]; H
1
D
1
and 13C NMR data were identical with literature.34
tetramethylsilane (0 ppm) for H and deuteriochloroform (77.0 ppm)
for 13C. Melting points were determined on a Yanaco MP-500D melting
point apparatus. Optical rotation was measured on a JASCO DIP-360
spectrometer using a 1-dm cell. IR spectra were recorded on a JASCO
IR-810 spectrometer or a SHIMADZU FTIR-8100A spectrometer. Gel
permeation chromatography (GPC) analyses were carried out using a
GL Sciences instrument (HPLC pump PU610, LC column oven
MODEL556) equipped with a Shodex SE-61 RI detector, SIC GPC
board, and two columns (Shodex KF-804L). The GPC columns were
eluted with tetrahydrofuran at 40 °C at 1 mL/min. Gas chromatography
was performed on a SHIMADZU GC-14B with a J&W Scientific DB-1
column and helium as the carrier gas. Differential scanning calorimetry
(DSC) measurements were performed on a Mettler DSC 30. Heating
rates were 10 °C/min. The reported Tg value was determined from the
second heating scan. Elemental analyses were performed at the
Microanalysis Center, Kyoto University.
Synthesis of N-Benzyl-(S)-bis(3-methyphenyl)(pyrrolidin-2-yl)-
methanol (4b). A crude sample was prepared from 3-bromo-1-
methylbenzene (3.0 mL, 25 mmol) and N-benzyl-(S)-proline methyl
ester (2.2 g, 10 mmol) according to the procedure described previously.
Purification by silica gel column chromatography with hexanes-ethyl
acetate (10:1, Rf 0.26) as an eluent gave 4b (3.5 g, 94% yield) as a
1
white solid, mp 86-88 °C. [R]22 95.5° (c 0.43, CHCl3); H NMR
D
(CDCl3) δ 7.54 (s, 1H), 7.46 (d, 1H, J ) 7.8 Hz), 7.40 (s, 1H), 7.35
(d, 1H, J ) 7.8 Hz), 7.25-7.12 (m, 5H), 7.04 (d, 2H, J ) 6.9 Hz),
6.97 (d, 1H, J ) 7.8 Hz), 6.89 (d, 1H, J ) 7.8 Hz), 4.86 (brs, 1H),
3.92 (dd, 1H, J ) 9.6, 4.6 Hz), 3.17 (d, 1H, J ) 12.8 Hz), 3.01 (d, 1H,
J ) 12.8 Hz), 2.91 (m, 1H), 2.37-2.26 (m, 7H), 2.01-1.92 (m, 1H),
1.80-1.72 (m, 1H), 1.69-1.55 (m, 2H); 13C NMR (CDCl3) δ 147.90,
146.48, 139.80, 137.61, 137.58, 128.57, 128.05, 127.96, 127.78, 127.05,
126.96, 126.76, 126.38, 126.22, 122.83, 122.56, 77.96, 70.72, 60.57,
55.60, 29.82, 24.22, 21.71, 21.66. Anal. Calcd for C26H29NO: C, 84.06;
H, 7.87. Found: C, 84.02; H, 7.92.
All the solvents and cyclohexene oxide used for reactions were
distilled under argon after drying over an appropriate drying reagent.
Most of the reagents were purchased from Aldrich Chemical Co. or
Wako Pure Chemical Industries Ltd and were used without further
purification unless otherwise specified. Carbon dioxide (Teisan Co.,
99.8%) was used as received. For silica gel column chromatography,
Wako-gel C-200 was used.
Synthesis of (S)-Bis(3-methyphenyl)(pyrrolidin-2-yl)methanol
(1b-H). This compound was prepared from 4b (3.3 g, 8.9 mmol)
according to the procedure described for 1a-H. Purification by silica
gel column chromatography with ethyl acetate (Rf 0.18) as an eluent
gave 1b-H (2.5 g, 99% yield) as a colorless viscous oil. [R]22D -63.0°
(c 0.28, CHCl3);1H NMR (CDCl3) δ 7.38 (s, 1H), 7.36-7.32 (m, 2H),
7.26 (d, 1H, J ) 7.8 Hz), 7.19-7.13 (m, 2H), 6.96 (d, 2H, J ) 7.3
Hz) 4.22 (t, 1H, J ) 7.6 Hz), 3.03-2.98 (m, 1H), 2.95-2.88 (m, 1H),
2.31 (s, 3H), 2.30 (s, 3H), 1.77-1.52 (m, 4H); 13C NMR (CDCl3) δ
148.13, 145.31, 137.72, 137.44, 127.14, 127.03, 126.62, 126.13, 122.49,
64.47, 46.70, 26.22, 25.48, 21.66, 21.65. Anal. Calcd for C19H23NO:
C, 81.10; H, 8.24. Found: C, 81.07; H, 8.36.
Ligand Synthesis
Synthesis of N-Benzyl-(S)-diphenyl(pyrrolidin-2-yl)methanol (4a).
A flame-dried 200-mL two-necked flask fitted with an argon inlet and
a 50-mL addition funnel containing bromobenzene (6.2 mL, 59 mmol)
in THF (35 mL) was charged with magnesium turnings (1.5 g, 62 mmol)
and THF (15 mL). A small portion (2 mL) of a solution of
bromobenzene in THF was added with stirring at room temperature.
After the exothermic reaction started, the reaction flask was cooled at
10 °C with a water bath. The remaining bromobenzene was added with
stirring over 30 min, and then the reaction mixture was stirred at room
temperature for 3 h. A solution of N-benzyl-(S)-proline methyl ester
(5.2 g, 24 mmol) in THF (10 mL) was placed in the addition funnel
and added slowly with stirring at 10 °C. After the addition, the reaction
mixture was stirred at room temperature for 20 h, and then acidified
with 3 M aqueous HCl (50 mL). The whole mixture was concentrated
by evaporation to remove most of the amount of THF, and ether (100
Synthesis of N-Benzyl-(S)-bis(3-methoxyphenyl)(pyrrolidin-2-yl)-
methanol (4c). The reaction was carried out with 3-bromo-1-meth-
oxybenzene (2.2 mL, 18 mmol) and N-benzyl-(S)-proline methyl ester
(1.5 g, 7.0 mmol) according to the procedure described previously.
Acidification with 3 M aqueous HCl and removal of most of the amount
of THF gave a pale yellow oil. After the acidic aqueous layer was
removed by decantation, the remaining oil was completely dissolved
in ether (200 mL) and 1 M aqueous NaOH (100 mL) to give free base.
After the organic layer was separated, the aqueous layer was extracted
with ether (100 mL × 2). The combined organic layers were washed
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5508 J. AM. CHEM. SOC. VOL. 125, NO. 18, 2003

Copolymerization with Dimeric Zinc Complexes
A R T I C L E S
with brine (100 mL), dried over anhydrous Na2SO4, filtered and
concentrated under reduced pressure. Purification of the residue by silica
gel column chromatography with hexanes-ethyl acetate (3:1, Rf 0.45)
acetate as an eluent to give 1e-H (2.9 g, 91% yield) as a colorless solid.
[R]22 -38.7° (c 1.7, MeOH) [lit.34 [R]20 -34.2° (c 0.789, MeOH)];
D
D
1H and 13C NMR data were identical with literature.34
gave 4c (2.30 g, 81% yield) as a colorless viscous oil. [R]22 68.4° (c
Synthesis of Complex 2a from Et2Zn and 1a-H. In a flame-dried
80-mL Schlenk tube was placed (S)-diphenyl(pyrrolidin-2-yl)methanol
1a-H, (0.53 g, 2.1 mmol) and THF (20 mL). To the solution was added
Et2Zn (1.05 M in hexane, 2.0 mL, 2.1 mmol) with stirring at room
temperature. After ethane gas evolution ceased, the resulting mixture
was stirred at 60 °C for 2 h and then concentrated and dried in vacuo.
The resulting white solid was recrystallized from THF/hexane at -20
°C to give colorless crystals (350 mg, 51% yield).
Synthesis of Complex 2e from Et2Zn and 1e-H. In a flame-dried
80-mL Schlenk tube was placed 1e-H (0.78 g, 2.0 mmol) and toluene
(10 mL). To the solution was added Et2Zn (1.05 M in hexane, 1.9 mL,
2.0 mmol) with stirring at room temperature. After ethane gas evolution
ceased, the resulting mixture was stirred at 60 °C for 2 h and then
concentrated in vacuo. The resulting white solid was recrystallized from
toluene/hexane at -20 °C to give colorless crystals (521 mg, 49%
yield).
X-ray Crystallography. Suitable single crystals were selected under
ambient conditions, attached to the tip of a glass fiber and then mounted
in a Bruker SMART system at 130 K. The X-ray data were collected
on a Bruker SMART CCD diffractometer and were covered more than
a hemisphere of reciprocal space by three sets of frames. Each of the
frame sets had a different æ, and each of the frames were collected
with 0.30° steps in ω.
Space groups were determined on the basis of systematic absences
and intensity statistics. The crystal structures were solved by direct
method and refined by full-matrix least-squares. All non-hydrogen
atoms were refined anisotropically, and all hydrogen atoms were placed
in ideal positions with isotropic thermal parameters. Crystallographic
data for 2a and 2e are summarized in Table 7.
D
0.60, CHCl3);1H NMR (CDCl3) δ 7.34-7.13 (m, 9H), 7.06 (d, 2H, J
) 6.9 Hz), 6.70, (dd, 1H, J ) 7.8, 2.3 Hz), 6.63 (dd, 1H, J ) 8.3, 2.3
Hz), 4.97 (brs, 1H), 3.92 (dd, 1H, J ) 9.2, 4.6 Hz), 3.79 (s, 3H), 3.75
(s, 3H), 3.28 (d, 1H, J ) 12.8 Hz), 3.05 (d, 1H, J ) 12.8 Hz), 2.94-
2.89 (m, 1H), 2.39-2.31 (m, 1H), 2.01-1.91 (m, 1H), 1.79-1.71 (m,
1H), 1.68-1.55 (m, 2H); 13C NMR (CDCl3) δ 159.47, 159.31, 149.75,
148.14, 139.73, 128.94, 128.55, 128.09, 118.18, 111.75, 111.72, 111.43,
111.38, 77.76, 70.54, 60.44, 55.52, 55.12, 29.78, 24.08. Anal. Calcd
for C26H29NO3: C, 77.39; H, 7.24. Found: C, 77.28; H, 7.24.
Synthesis of (S)-Bis(3-methoxyphenyl)(pyrrolidin-2-yl)methanol
(1c-H). A crude material was prepared from 4c (2.1 g, 5.3 mmol)
according to the procedure described for 1a-H. Purification of the crude
product by silica gel column chromatography with ethyl acetate (Rf
0.12) as an eluent gave 1c-H (1.6 g, 97% yield) as a colorless viscous
oil. [R]22D -62.4° (c 0.83, CHCl3);1H NMR (CDCl3) δ 7.25-7.11 (m,
6H), 6.72-6.68 (m, 2H), 4.19 (t, 1H, J ) 7.6 Hz), 3.77, (s, 3H), 3.76
(s, 3H), 3.03-2.98 (m, 1H), 2.94-2.88 (m, 1H), 1.77-1.52 (m, 4H);
13C NMR (CDCl3) δ 159.50, 159.27, 149.81, 146.85, 129.09, 128.83,
118.02, 117.88, 112.07, 111.48, 111.45, 76.93, 64.42, 55.08, 46.66,
26.17, 25.40. Anal. Calcd for C19H23NO3: C, 72.82; H, 7.40. Found:
C, 72.86; H, 7.52.
Synthesis of N-Benzyl-(S)-bis(3,5-dimethylphenyl)(pyrrolidin-2-
yl)methanol (4d). This was prepared from 1-bromo-3,5-dimethylben-
zene (3.1 mL, 23 mmol) and N-benzyl-(S)-proline ethyl ester (2.1 g,
9.0 mmol) according to the procedure described previously and purified
by silica gel column chromatography with hexanes-ethyl acetate (10:
1, Rf 0.44) as an eluent to give 4d (3.3 g, 92% yield) as a colorless
1
viscous oil. [R]22 106° (c 1.20, CHCl3); H NMR (CDCl3) δ 7.28 (s,
D
2H), 7.26-7.16 (m, 5H), 7.06-7.03 (m, 2H), 6.80 (s, 1H), 6.70 (s,
1H), 4.77 (brs, 1H), 3.88 (dd, 1H, J ) 9.6, 4.1 Hz), 3.14 (d, 1H, J )
12.8 Hz), 3.00 (d, 1H, J ) 12.8 Hz), 2.93-2.88 (m, 1H), 2.37-2.30
(m, 1H), 2.30 (s, 3H), 2.24 (s, 3H), 2.01-1.91 (m, 1H), 1.80-1.72
(m, 1H), 1.68-1.52 (m, 2H); 13C NMR (CDCl3) 147.85, 146.40, 139.95,
137.32, 137.27, 128.63, 128.03, 127.98, 127.88, 126.73, 123.48, 123.45,
77.99, 70.78, 60.59, 55.67, 29.87, 24.29, 21.63, 21.55. Anal. Calcd for
C28H33NO: C, 84.17; H, 8.32. Found: C, 84.27; H, 8.39.
Synthesis of (S)-Bis(3,5-dimethylphenyl)(pyrrolidin-2-yl)methanol
(1d-H). This material was prepared from 4d (3.1 g, 7.7 mmol) according
to the procedure described for 1a-H and purified by silica gel column
chromatography with hexanes-ethyl acetate(1:2, Rf 0.11) as an eluent
to give 1d-H (2.2 g, 92% yield) as a colorless solid. 1H and 13C NMR
data were identical with literature.34
Copolymerization of Cyclohexene Oxide and CO2 with Dimeric
Zinc Complex 2a. A flame-dried 80-mL Schlenk tube was charged
with zinc complex 2a (170 mg, 0.25 mmol) and toluene (17 mL). After
complex 2a was allowed to dissolve completely by stirring at 60 °C,
the resulting homogeneous solution was cooled to room temperature
and transferred into a 50-mL autoclave followed by introduction of
cyclohexene oxide (1.0 mL, 10 mmol) and carbon dioxide (30 atm).
After stirring at 40 °C for 19 h, the reaction mixture was cooled to
ambient temperature and the CO2 pressure was slowly released. The
mixture was diluted with toluene (30 mL) and washed with aq HCl
(1M, 10 mL × 2) and brine (10 mL × 2). The organic layer was dried
over Na2SO4 and concentrated to 5 mL by evaporation. The copolymer
was precipitated by adding MeOH (100 mL), filtered through a pad of
Celite, washed with MeOH, and eluted by CH2Cl2. The eluent was
concentrated by evaporation and dried in vacuo to give the copolymer.
MALDI-TOF Mass Spectroscopy. MALDI-TOF mass spectro-
metric measurements were performed on a PerSeptive Biosystems
Voyager DE-STR equipped with a 337-nm nitrogen laser (pulse width,
3 ns), along with a delayed extraction capability. An accelerating voltage
of 20 kV was used, and all mass spectra were recorded in the linear
mode. In general, mass spectra from 256 laser shots were accumulated
to produce a final spectrum. Angiotensin I (human; MW ) 1296.5)
(BACHEM) and insulin (bovine pancreas 28.3; MW ) 5733.50)
(Nacalai) were used as internal standards to calibrate the mass scale.
Samples for analysis were prepared by mixing the copolymer (1.0
wt % in THF), a matrix (1,8-dihydroxy-9(10H)-anthracenone; dithranol,
5.0 wt % in THF), and a cationizing agent (sodium trifluoroacetate,
1.0 wt %) in the weight ratio 1/40/1. Then, 1.0-µL portions of the
mixture were placed onto the hollows on the gold-coated plate and
dried under ambient conditions.
Synthesis of N-Benzyl-(S)-bis[4-(trifluoromethyl)phenyl](pyrro-
lidin-2-yl)methanol (4e). This material was prepared from 1-bromo-
4-trifluoromethylbenzene (2.5 mL, 17.5 mmol) and N-benzyl-(S)-proline
ethyl ester (1.63 g, 7.0 mmol) according to the procedure described
previously and purified by silica gel column chromatography with
hexanes-ethyl acetate (10:1, Rf 0.48) as an eluent to give 4e (3.0 g,
1
91% yield) as a colorless viscous oil. [R]22 49.8° (c 2.0, CHCl3); H
D
NMR (CDCl3) δ 7.86 (d, 2H, J ) 8.3 Hz), 7.70 (d, 2H, J ) 8.3 Hz),
7.58-7.52 (m, 4H), 7.27-7.18 (m, 3H), 7.03-6.99 (m, 2H), 5.23 (brs,
1H), 4.04 (dd, 1H, J ) 9.2, 4.1 Hz), 3.26 (d, 1H, J ) 12.8 Hz), 3.11
(d, 1H, J ) 12.8 Hz), 2.98-2.93 (m, 1H), 2.41-2.39 (m, 1H), 2.01-
1.90 (m, 1H), 1.69-1.61 (m, 2H); 13C NMR (CDCl3) δ 151.46, 149.84,
138.96, 129.05 (q, 32 Hz), 128.83 (q, 32 Hz), 128.36, 128.30, 127.12,
125.97, 125.80, 125.38 (q, 3.8 Hz), 125.25 (q, 3.8 Hz), 124.07 (q, 272
Hz), 123.99 (q, 272 Hz), 77.55, 70.35, 60.40, 55.45, 29.82, 23.92. Anal.
Calcd for C26H23NOF6: C, 65.13; H, 4.84. Found: C, 65.08; H, 4.85.
Synthesis of (S)-Bis[4-(trifluoromethyl)phenyl](pyrrolidin-2-yl)-
methanol (1e-H). This amino alcohol was prepared from 4e (3.9 g,
8.2 mmol) according to the procedure described previously and purified
of the crude product by silica gel column chromatography with ethyl
Representative Procedure for Copolymerization of Cyclohexene
Oxide and CO2 with In Situ Generated 3a-OR. To the homogeneous
toluene (17 mL) solution of zinc complex 2a (170 mg, 0.25 mmol),
prepared in the same manner as mentioned previously, in a 50-mL
9
J. AM. CHEM. SOC. VOL. 125, NO. 18, 2003 5509

A R T I C L E S
Nakano et al.
Table 7. Crystallographic Data for Complexes 2a and 2e
compound
empirical formula
FW
2a
2e
C38H46N2O2Zn2
693.51
C49H50FI2N2O2Zn2
1057.65
crystal system
space group
color of crystal
unit cell dimensions
a, Å
monoclinic
P2(1)
colorless
orthorhombic
P2(1)2(1)2(1)
colorless
9.3266(5)
14.5089(16)
b, Å
15.8144(8)
14.6962(16)
c, Å
11.1575(6)
22.214(3)
R, deg
90
90
90
90
4736.6(9)
â, deg
90.1950(10)
90
1645.66(15)
γ, deg
V, Å3
Z
2
4
T, K
130(2)
1.400
1.494
13569
130(2)
1.483
1.101
37630
d
calcd, g/cm3
absorption coefficient, nm-1
reflections collected
independent reflections
max. and min. transmission
goodness-of-fit on F2
8977 [R(int) ) 0.0176]
0.7544 and 0.6628
0.977
13358 [R(int) ) 0.0988]
0.7336 and 0.6672
0.632
final R indices [I > 2σ(I)]
R indices (all data)
R1 ) 0.0310, wR2 ) 0.0703
R1 ) 0.0341, wR2 ) 0.0711
R1 ) 0.0480, wR2 ) 0.0898
R1 ) 0.1398, wR2 ) 0.1196
autoclave were added a specified amount of alcohol (0.20 M in toluene),
cyclohexene oxide (1.0 mL, 10 mmol), and CO2 (30 atm). After stirring
at 40 °C for 19 h, the reaction mixture was cooled to ambient
temperature and the CO2 pressure was slowly released. The workup
procedure as described in the copolymerization with 2a gave the
copolymer.
Copolymerization of Cyclohexene Oxide and CO2 as a Function
of Conversion. All copolymerization reactions were carried out with
3a-OEt which was generated in situ by the reaction of 2a and 0.8 equiv
of ethanol. After an appropriate reaction time, decane was added as
internal standard for GC analysis. An aliquot (∼0.2 mL) of the resulting
mixture was withdrawn, quenched with methanol, and analyzed by GC.
The rest of the reaction mixture was worked up in the same manner as
previously mentioned to give the copolymer.
and then concentrated in vacuo. The resulting white solid was
recrystallized from THF/hexane at -20 °C to give colorless crystals.
Acknowledgment. We are grateful to Professor Mitsuo
Sawamoto and Professor Masami Kamigaito (Kyoto University)
for the MALDI-TOF mass spectrometic analysis and helpful
discussions. Professor Takashi Kato and Mr. Masafumi Yoshio
(The University of Tokyo) are kindly acknowledged for their
assistance in measuring DSC. This work was partially supported
by the Grant-in-Aids for COE Research on Elements Science,
No. 12CE2005 from the Ministry of Education, Culture, Sports,
Science and Technology, Japan.
Supporting Information Available: Crystallographic infor-
mation files (CIF) for 2a and 2e. MALDI-TOF mass spectra of
the copolymers with a mixture of 2a and various alcohols, ROH
(R ) Me, Bn, Pr, Bu, CF3CH2) (PDF). This material is
available free of charge via the Internet at http://pubs.acs.org.
Preparation of 3a-OEt. In a flame-dried 80-mL Schlenk tube was
placed 1a-H (0.51 g, 2.0 mmol) and THF (18 mL). To the solution
was added Et2Zn (1.10 M in hexane, 1.8 mL, 2.0 mmol) with stirring
at room temperature. After ethane gas evolution was ceased, the
resulting mixture was stirred at 60 °C for 2 h and then cooled to room
temperature. Following the addition of ethanol (51 µL, 0.90 mmol) in
toluene (1.0 mL), the mixture was stirred at room temperature for 1 h
i
t
JA028666B
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5510 J. AM. CHEM. SOC. VOL. 125, NO. 18, 2003