This journal is c The Royal Society of Chemistry 2012 Chem. Commun., 2012, 48, 10481–10483 10481

Cite this: Chem. Commun., 2012, 48, 10481–10483

Ping-pong polymerization by allylation and hydroformylation for

alternating vinyl alcohol–vinyl monomer copolymersw

Shingo Ito,* Masaki Noguchi and Kyoko Nozaki*

Received 12th July 2012, Accepted 23rd August 2012

DOI: 10.1039/c2cc34980a

Inspired by the enzymatic ping-pong mechanism, we designed a novel

‘‘ping-pong polymerization’’, which employs allylation and hydro-

formylation in an iterative and alternating manner. Thus, alternating

and regioregular vinyl alcohol–vinyl monomer copolymers possessing

multiple hydroxy groups in a periodical manner were successfully

synthesized.

The ping-pong mechanism is well known in enzymatic reactions.

This mechanism is characterized by two independent reactions

that are promoted by one catalyst in an iterative and alternating

manner, where the catalyst is moving back and forth like a ping-

pong ball (Fig. 1(A)).1,2 Inspired by the enzymatic ping-pong

mechanism, we designed a reaction where a substrate, not a

catalyst, shuttles between two courts like a ping-pong ball

(Fig. 1(B)). In reaction (1), a red monomer adds to a polymer

chain end and subsequently reaction (2) activates the chain

end for the next addition of a blue monomer. In this manner,

the red and blue monomers are iteratively incorporated to

produce a polymer chain, so-called an alternating copolymer.

Herein, we demonstrate a novel ‘‘ping-pong polymerization’’, which

employs nucleophilic allylation3 and rhodium-catalyzed hydro-

formylation4 in a ping-pong manner to synthesize alternating and

regioregular vinyl alcohol–vinyl monomer copolymers. The present

study provides opportunities to make novel functional polymeric

materials by a new polymerization methodology in which the main

chain is propagated by alternating repetition of two mechanistically

distinct transformations.5–8

Synthesis of sequence-regulated functionalized vinyl polymers

is one of the most challenging goals in polymer science.9 We

focused on the synthesis of vinyl alcohol–vinyl monomer

copolymers with a highly regulated structure. Polymers having

hydroxy groups directly attached on their main chain, such as

poly(vinyl alcohol-co-ethylene), show a wide range of applica-

tions owing to their hydrophilicity.10 Current industrial processes

for such copolymers include radical copolymerization of vinyl

acetate and ethylene followed by saponification, producing

polymers with a degree of branch structures and with random

incorporation of the hydroxy groups.11 Recently, synthesis of

highly linear ethylene–vinyl(allyl) alcohol copolymers was

accomplished by the palladium-catalyzed coordination copoly-

merization of vinyl12,13 or allyl13,14 acetate with ethylene

followed by saponification.15 Still, these copolymers have

randomly-distributed hydroxy group sequences in their main

chain. Intensive efforts have been devoted to synthesize linear

polyethylenes having periodically attached hydroxy groups.

Examples include ring-opening metathesis polymerization

(ROMP) of functionalized cyclic alkenes,16,17 acyclic diene

metathesis (ADMET) polymerization of functionalized dienes,18

and group transfer polymerization (GTP) of 1-[(trimethylsilyl)-

oxy]buta-1,3-diene,19 followed by hydrogenation in all the cases.

However, these methods are currently limited to the synthesis of

vinyl alcohol–ethylene copolymers, and have not accomplished

perfect control of regioregularity.20

Fig. 2 illustrates our synthetic strategy for sequentially-

regulated alternating vinyl alcohol–vinyl monomer copolymers

by the ping-pong polymerization. First, aldehyde initiator A

undergoes allylation with allylic metal compounds to afford

homoallylic alkoxide B. The terminal olefinic double bond of B

is then amenable to linear-selective hydroformylation under

Fig. 1 Illustrations of (A) the enzymatic ping-pong mechanism and

(B) the present ping-pong polymerization. S1, S2 = substrates; P1,

P2 = products; E, E0 = enzyme catalysts; red and blue circles =

monomer.

Department of Chemistry and Biotechnology, Graduate School ofEngineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku,Tokyo 113-8656, Japan. E-mail: ito_shingo@chembio.t.u-tokyo.ac.jp,nozaki@chembio.t.u-tokyo.ac.jp; Fax: +81 3-5841-7263;Tel: +81 3-5841-7261w Electronic supplementary information (ESI) available: Experimentalprocedures, supplementary experiments, and spectra for new polymersand compounds. See DOI: 10.1039/c2cc34980a

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10482 Chem. Commun., 2012, 48, 10481–10483 This journal is c The Royal Society of Chemistry 2012

rhodium catalysis to give aldehyde C, which undergoes further

allylation.21 Thus, the repetition of these processes followed by

hydrolysis affords polymer E, which has sequential hydroxy

groups in its 1 + 4n positions.19a The polymer corresponds to

the completely alternating and regioregular copolymers of vinyl

alcohol and vinyl monomer, which have rarely been obtained

by other synthetic methods.22

The synthesis of regioregular poly(vinyl alcohol-alt-vinyl

monomer)s by the ping-pong polymerization was achieved by

using allylic boronates as a monomer (Table 1). The polymeriza-

tion was carried out by exposing allylic boronates to a rhodium

catalyst under H2–CO pressure in toluene. The crude polymers

were obtained as a borate, and were hydrolyzed by treatment

with sodium hydroxide in THF, then washed with water to

afford the corresponding polyols. A polymer of Mn = 1.7 �103 was obtained when pinacol (E)-crotyl boronate 1 was used,

but the conversion of 1 did not reach 100% due to the low

reactivity of pinacol ester (entry 1). Thus, more nucleophilic

allylic boronates 2 and 3 were next examined.23 Ethylene

glycol ester 2 produced a polymeric material, but its insolubi-

lity inhibited the polymerization and led to a lower yield of

29% (entry 2). In contrast, tartrate ester 324 exhibited excellent

reactivity to afford an almost quantitative yield of the polymer

with Mn = 2.4 � 103 (entry 3). Notably, polymerization with

an additional initiator, 2-naphthaldehyde, gave polymers with

the same molecular weight (entry 4).25 Under this condition,

the conversion of 3 against time monitored by 1H NMR

spectroscopy did not exhibit linear correlation but a curved

line with slower rate in the early stage of the polymerization

(Fig. S1, ESIw). Combined with the fact that lower molecular

weights (up to Mn = 2.4 � 103) were observed than the

theoretical value determined by the monomer/initiator ratio

(Mn(calc) = 8.7 � 103), it is suggested that the allylic boronate

also served as an initiator (vide infra).13C NMR and distortionless enhancement by polarization

transfer (DEPT) analyses of the polymer obtained using 3

revealed that signals of a (CH), b (CH), c (CH2), d (CH2), and

e (CH3) were observed as major peaks, indicating the presence

of repeated units of I (Fig. 3(A)). The signal of a (CH)

observed at 76–78 ppm is consistent with predominantly

linear-selective hydroformylation during polymerization. If

branch-selective hydroformylation occurred, the resulting

polymer would have a partial structure of II, which would

give a signal around 82 ppm (Fig. S11, ESIw); however, it wasestimated to be less than 3%.26 Four peaks were observed for

the signal of a (CH), which indicated low stereoregularity of

the polymers. In the 1H NMR spectrum (Fig. 3(B)), the signals

of the main chain units, Ha and Hb–Hd, were observed at

3.2 ppm and 0.8–1.7 ppm, respectively. The OH protons were

observed at 4.2 ppm, as it disappeared upon addition of D2O,

leaving the other signals assigned as Ha–He unchanged.

Matrix-assisted laser desorption–ionization time-of-flight

mass (MALDI-TOF-MS) spectra exhibited ion signals repeating

at an interval of 86 Da, which correspond to the repeating

units of the vinyl alcohol–propylene copolymer. Several lines

of signals were observed depending on chain ends, all of which

were successfully assigned (Fig. S12 and S13, ESIw). Based on

the mass analysis, we propose a plausible mechanism of the ping-

pong polymerization (Scheme S2, ESIw). The polymerization is

initiated by hydroformylation of a small amount of allyl

boronate 30, presumably formed from 3 via 1,3-boron shift.27

Thus, the initiation chain end would initially be a borylated

butyl group, but converted to the 1-butyl group by proto-

deboronation during the work up. In the presence of

2-naphthaldehyde, the polymerization is also initiated by

allylation of 2-naphthaldehyde. As to termination, three

pathways dominate as shown in Scheme S3 (ESIw): (i) dehydra-tion after hydroformylation and acetal formation, (ii) dehydro-

genation after hydroformylation and acetal formation, and

(iii) hydrogenation after allylation.

Fig. 2 Mechanism of the ping-pong polymerization.

Table 1 Ping-pong polymerization by allylation and hydroformylationa

EntryAllylicboronate Conversionb

Yieldc

(g)Yieldc

(%)Mn

d

(103)Mw/Mn

d

1 1 84 (0.83)e –– 1.7 1.22 2 ––f 0.25 29 2.0 1.53 3 100 0.91 100 2.4 1.34g 3 100 0.82 95 2.3 1.45g,h 4 100 0.53 36 1.6 1.56g,h 5 93 0.70 70 0.8 ––

a Allylic boronate (10 mmol), Rh(acac)(CO)2 (0.02 mmol), and Xantphos

(0.04 mmol) in toluene were stirred under H2–CO (1.5/1.5 MPa) pressure

for 24 h at 100 1C in a 50 mL autoclave unless otherwise noted;

Xantphos = 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene. b Conver-

sion of allylic boronate determined by 1HNMRanalysis. c Yield of polymer

after hydrolysis. d Determined by SEC analysis using polystyrene as

an internal standard. e The product was contaminated by pinacol.f Conversion could not be determined due to the insolubility of the

crude polymer. g The reaction was performed in the presence of

2-naphthaldehyde (0.10 mmol). h Allylic boronate was generated

in situ and used without isolation.

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This journal is c The Royal Society of Chemistry 2012 Chem. Commun., 2012, 48, 10481–10483 10483

The optimal conditions were applied to other comonomers

such as cinnamyl (4 in Table 1, entry 5) and prenyl boronates

(5 in Table 1, entry 6). The polymerization with 4 produced

solid products with molecular weight up to Mn of 1.6 � 103.

On the other hand, the polymerization with prenyl boronate 5

gave a highly viscous oil consistent with a product of lower

molecular weight. The lower molecular weights in both cases

could be attributed to relatively fast hydroformylation compared

with allylboration; cinnamyl boronate 4 may be more active for

hydroformylation than boronate 3, and prenyl boronate 5 has a

much lower allylation activity than 3.

In summary, we demonstrated a conceptually-new approach

for the synthesis of completely alternating and regioregular

vinyl alcohol–vinyl monomer copolymers using allylboration

and hydroformylation in a ping-pong manner. We hope

that the present ping-pong methodology will be a novel break-

through in designing and synthesizing functional polymeric

materials.

This work was supported by Funding Program for Next

Generation World-Leading Researchers, Green Innovation

and the Global COE Program ‘‘Chemistry Innovation

through Cooperation of Science and Engineering’’ from

MEXT/JSPS, Japan, and Mitsubishi Foundation. We

are grateful to Prof. R. W. Hoffmann (Philipps-Universitat

Marburg), Prof. K. B. Wagener (U Florida), and Prof. D. G.

Hall (U Alberta) for helpful discussion. We also acknowledge

Mr H. Tanaka and Prof. T. Aida (U Tokyo) for X-ray diffrac-

tion analysis and JEOL Ltd. for MALDI-TOF-MS analysis.

Notes and references

1 Biochemistry, ed. D. Voet and J. G. Voet, 4th edn, Wiley, 2011.2 W. W. Cleland, Biochim. Biophys. Acta, 1963, 67, 104.

3 H. Lachance and D. G. Hall, Org. React. (Hoboken, NJ, U. S.),2008, 73, 1.

4 I. Ojima, C.-Y. Tsai, M. Tzamarioudaki and D. Bonafoux, Org.React. (Hoboken, NJ, U. S.), 2000, 56, 1.

5 J.-C. Waslike, S. J. Obrey, R. T. Baker and G. C. Bazan, Chem.Rev., 2005, 105, 1001, and references cited therein.

6 For iterative tandem catalysis polymerization to control the stereo-regularity of polymers, see: J. van Buijtenen, B. A. C. van As,J. Meuldijk, A. R. A. Palmans, J. A. J. M. Vekemans,L. A. Hulshof and E. W. Meijer, Chem. Commun., 2006, 3169.

7 In chain shuttling polymerization, polymer chains move betweentwo catalytic cycles albeit in a non-alternating manner. See:D. J. Arriola, E. M. Carnahan, P. D. Hustad, R. L. Kuhlmanand T. T. Wenzel, Science, 2006, 312, 714.

8 Representative examples of completely alternating copolymeriza-tion are as follows: (a) For alternating radical copolymerization oftwo comonomers, see: H. Hirai and Y. Gotoh, in PolymericMaterials Encyclopedia, ed. J. C. Salamone, CRC Press, BocaRaton, FL, 1996, vol. 1, p. 192; (b) For alternating alkene–carbonmonoxide copolymerization, see: E. Drent and P. H. M. Budzelaar,Chem. Rev., 1996, 96, 663; (c) For alternating epoxide–carbondioxide copolymerization, see: D. J. Darensbourg, Chem. Rev.,2007, 107, 2388; (d) For alternating epoxide–acid anhydride copo-lymerization, see: C. Robert, F. de Montigny and C. M. Thomas,Nat. Commun., 2011, 2, 586.

9 K. Satoh, S. Ozawa, M. Mizutani, K. Nagai and M. Kamigaito,Nat. Commun., 2010, 1, 6.

10 F. L. Marten, in Encyclopedia of Polymer Science and Engineering,ed. H. F. Mark, N. M. Bikales, C. G. Overberger and G. Menges,Wiley, New York, 2nd edn, 1989, vol. 17, p. 167.

11 D. C. Bugada and A. Rubin, Eur. Polym. J., 1992, 28, 219.12 S. Ito, K. Munakata, A. Nakamura and K. Nozaki, J. Am. Chem.

Soc., 2009, 131, 14606.13 B. P. Carrow and K. Nozaki, J. Am. Chem. Soc., 2012, 134, 8802.14 S. Ito, M. Kanazawa, K. Munakata, J. Kuroda, Y. Okumura and

K. Nozaki, J. Am. Chem. Soc., 2011, 133, 1232.15 A. Nakamura, S. Ito and K. Nozaki, Chem. Rev., 2009, 109, 5215.16 I. Cho, Prog. Polym. Sci., 2000, 25, 1043.17 (a) S. Ramakrishnan and T. C. Chung, Macromolecules, 1990,

23, 4519; (b) M. A. Hillmyer, W. R. Laredo and R. H. Grubbs,Macromolecules, 1995, 28, 6311; (c) O. A. Scherman, H. M. Kimand R. H. Grubbs, Macromolecules, 2002, 35, 5366; (d) O. A.Scherman, R. Walker and R. H. Grubbs, Macromolecules, 2005,38, 9009; (e) S. E. Lehman, K. B. Wagener, L. S. Baugh,S. P. Rucker, D. N. Schulz, M. Varma-Nair and E. Berluche,Macromolecules, 2007, 40, 2643.

18 D. J. Valenti and K. B. Wagener, Macromolecules, 1998, 31, 2764.19 (a) Y. Mori, H. Sumi, T. Hirabayashi, Y. Inai and K. Yokota,

Macromolecules, 1994, 27, 1051; (b) K. Yokota, Prog. Polym. Sci.,1999, 24, 517.

20 Specifically, metathesis polymerizations (ADMET or ROMP) givepoly(vinyl alcohol-alt-ethylene)s, in most cases, as a mixture ofregioisomers (ref. 16 and 17). Polymers obtained by aldol GTPconsist of a mixture of two chemically isomeric substructures:1,4-addition structures and 3,4-addition structures (ref. 18).

21 For tandem hydroformylation–allylation reactions, see:(a) K. R. Hornberger, C. L. Hamblett and J. L. Leighton,J. Am. Chem. Soc., 2000, 122, 12894; (b) R. W. Hoffmann,D. Bruckner and V. J. Gerusz, Heterocycles, 2000, 52, 121;(c) R. W. Hoffmann and D. Bruckner,New J. Chem., 2001, 25, 369.

22 For alternating copolymerization of vinyl alcohol and maleicanhydride, see: A. K. Cederstav and B. M. Novak, J. Am. Chem.Soc., 1994, 116, 4073.

23 H. C. Brown, U. S. Racherla and P. J. Pellechia, J. Org. Chem.,1990, 55, 1868.

24 W. R. Roush, A. E. Walts and L. K. Hoong, J. Am. Chem. Soc.,1985, 107, 8186.

25 Molecular weights were determined regardless of monomer/initiatorratios. See Table S1 (ESIw) for details.

26 We synthesized oligo(vinyl alcohol-alt-propylene)s as modelcompounds using step-wise hydroformylation and allylborationreactions. See the ESIw.

27 (a) K. G. Hancock and J. D. Kramer, J. Am. Chem. Soc., 1973,95, 6463; (b) R. W. Hoffmann and H.-J. Zeiss, J. Org. Chem., 1981,46, 1309.

Fig. 3 (A) 13C NMR (CD3OD) and (B) 1H NMR (DMSO-d6)

spectra of the vinyl alcohol–propylene copolymer.

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