The Utility of a 3-O-Allyl Group as a Protective ... - ACS Publications

Biomacromolecules 2002, 3, 538-546

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The Utility of a 3-O-Allyl Group as a Protective Group for Ring-Opening Polymerization of r-D-Glucopyranose 1,2,4-Orthopivalate Derivatives Makoto Karakawa,* Hiroshi Kamitakahara, Toshiyuki Takano, and Fumiaki Nakatsubo Division of Forest and Biomaterials Science, Graduate School of Agriculture, Kyoto University, Sakyo-Ku, Kyoto 606-8502, Japan Received December 5, 2001; Revised Manuscript Received March 14, 2002

To clarify the utility as a protective group of 3-O-allyl group on ring-opening polymerization of R-D-glucopyranose 1,2,4-orthopivalate derivatives, four orthopivalate derivatives, 3-O-allyl-6-O-pivaloyl(1), 3-O-allyl-6-O-benzyl- (2), 3,6-di-O-allyl- (3), and 3-O-allyl-6-O-methyl-R-D-glucopyranose 1,2,4orthopivalates (4), were selected as starting monomers and were polymerized under -30 °C in CH2Cl2 using BF3‚Et2O as a catalyst. All the orthopivalate derivatives 1-4 were found to give stereoregular polysaccharides, (1f4)-β-D-glucopyranans. Thus, it was concluded that the allyl group as a protective group at 3-O position of glucose othropivalate is acceptable to yield stereoregular (1f4)-β-D-glucopyranans, cellulose derivatives. Introduction Cellulose is the most abundant biomacromolecule, existing as a main plant cell wall component, and is important as a biodegradable and renewable organic material.1 There are many functional cellulose derivatives, such as hydroxypropyl cellulose with liquid crystalline properties,2 cellulose phenylcarbamate derivative with chiral recognition ability,3 sulfated celluloses with anticoagulant and lung metastasis inhibition activities such as a heparin,4,5 branched cellulose derivatives with antitumor activity,6 and so on. However, much remains unknown about the relationship between their molecular structures and functions. For clarification of their correlation and for further development of cellulose-based advanced materials, it is indispensable to prepare cellulose derivatives with the defined structure having the desired functional groups at the expected position among 2,3,6-hydroxyl groups in the repeating anhydro glucose unit in cellulose molecules. Such high-regioselectively substituted cellulose derivatives may provide significant information to solve many problems in the research field of cellulose science and technology. On the other hand, biosynthesis and microfibril formation,7-9 molecular orientation of natural and regenerated cellulose crystal modifications,10,11 and biodegradation of cellulose derivatives12,13 are other important research fields of cellulose science. Several problems remaining in these fields may be also solved by the use of designed high-regioselectively substituted cellulose derivatives as cellulose model compounds. These cellulose derivatives can be obtained only by chemical synthesis, although regioselectively 6-O and 2,3di-O substituted cellulose derivatives14-16 have been prepared via tritylation at the 6-O position following its derivatization. * To whom correspondence may be addressed: kais.kyoto-u.ac.jp.

Karakawa@

Recently, Koshella et al.17 reported that the 3-O substituted celluloses were prepared using thexyldimethylsilyl groups, but the other regioselective 2-O or 3,6-di-O substituted celluloses could be scarcely prepared by conventional methods.14-17 Thus, chemical synthesis of cellulose is very important. We succeeded in the first chemical synthesis of cellulose both by a stepwise synthesis18 and by a cationic ring-opening polymerization of glucose orthopivalate derivative.19,20 The cationic ring-opening polymerization method of sugar orthopivalate derivative was then applied to other polysaccharide syntheses such as arabinofuranan,21 galactofuranan,22 and 6-deoxy cellulose.23 These synthesized polysaccharides can be converted to high-regioselectively substituted polysaccharides, because two secondary hydroxyl groups at C-2 and C-3 positions in the repeating anhydro glucose units in cellulose are already protected with ester and ether groups, pivaloyl and benzyl, respectively. Benzyl group as a protective group is very useful for our polymerization reaction, but the debenzylation needs more drastic reaction conditions: with palladium hydroxide under 4.5 kgf/cm2 hydrogen atmosphere over 1 day, repeated several times, especially in the case of polysaccharides.19,20 On the other hand, allyl groups are also used as protective groups of the hydroxyl groups in the field of carbohydrate chemistry. Allyl groups are expected to be removed under milder reaction conditions because the removal is conducted in the homogeneous reaction system. In this paper, the utility of allyl groups as a 3-O protective group of the starting glucose orthopivalate derivatives for the ring-opening polymerization is discussed. Results and Discussion Synthesis of 3-O-Allyl-r-D-Glucopyranose 1,2,4-Orthopivalate Derivatives. An allyl group has been removed

10.1021/bm015656e CCC: $22.00 © 2002 American Chemical Society Published on Web 04/25/2002

Utility of a 3-O-Allyl Group for Ring-Opening Polymerization

Biomacromolecules, Vol. 3, No. 3, 2002 539

Scheme 1. Synthetic Route for 3-O-Allyl-R-D-glucopyranose 1,2,4-Orthopivalate Derivatives (1-4)

a Pd-C/THF:EtOH (1/4, v/v)/H , 60 °C, overnight. b NaOMe/dioxane:MeOH (4/1, v/v), room temperature, 6 h. c Pd-C/THF:EtOH (1/4, v/v)/H , 60 °C, 2 2 overnight. d NaOMe/dioxane:MeOH (4/1, v/v), room temperature, 6 h. e AllBr/Ag2O/DMF, room temperature, 12 h. f AllBr/NaH/DMF, room temperature, 4 h. g NaOMe/dioxane:MeOH (4/1, v/v), room temperature, 6 h. h BnBr/NaH/DMF, room temperature, 4 h. i CH3I/NaH/DMF, room temperature, 4 h.

under mild conditions (i.e., t-BuOK/DMSO/0.1 N HCl/ acetone-water,24 SeO2/AcOH/dioxane,25 PdCl2/MeOH,26 and so on). The 3-O-allyl group of a glucose derivative has been found to effectively control stereoselectivity of the glycosylation reaction in cello-oligosaccharide synthesis.27 In addition, allyl groups may be used for the derivatization of polysaccharide: it is converted into other functional groups such as a propyl group by the reduction and the glycerol group by the oxidation. Thus, the allyl group may be very useful. Four R-D-glucopyranose 1,2,4-orthopivalate derivatives, that is, 3-O-allyl-6-O-pivaloyl- (1), 3-O-allyl-6-O-benzyl- (2), 3,6-di-O-allyl- (3), 3-O-allyl-6-O-methyl-R-D-glucopyranose 1,2,4-orthopivalates (4), were selected as starting monomers for the ring-opening polymerization for examining the availability of the 3-O-allyl group. All these orthopivalates, 1-4, were prepared from 3-O-benzyl-6-O-pivaloy-R-Dglucopyranose 1,2,4-orthopivalate (5)20 as shown in Scheme 1.

Debenzylation of compounds 5 and 8 was carried out with palladium charcoal28 under hydrogen atmosphere in THF/ ethanol (1/4, v/v) at 60 °C to yield compounds 6 and 9 in 83% and 93% yields, respectively. Compound 1 was obtained from compound 6 by neutral allylation with silver oxide and allyl bromide at room temperature in 93% yield. Compound 3 was obtained from compound 9 by allylation with sodium hydride and allyl bromide at room temperature in 95% yield. Compound 9 was prepared from compounds 6 and 8. Compound 2 was prepared in 81% yield from compound 7 by benzylation with sodium hydride and benzyl bromide after depivaloylation of

Table 1. Polymerizations of R-D-Glucopranose 1,2,4-Orthopivalate Derivatives (1)-(5) orthoyield, pivalate product 3-O 6-O % 1 2 3 4 5

poly(1) poly(2) poly(3) poly(4) poly(5)

All All All All Bn

Piv Bn All Me Piv

12a 90a 95a 68a 34c,d

[R]D, deg

10-3MGPCb

DPn

-8.45 -25.12 -11.71 -8.74 -1.3

5.58 7.26 9.47 6.70 3.7

15.1 19.3 29.1 22.3 8.8d

a Polymer was insoluble fraction in chloroform/n-hexane (ca. 1/15, v/v). Molecular weight was determined by gel permeation chromatography (GPC) using polystyrene standards. c As an oil. d Value after removing monomer. b

compound 1. Compound 4 was prepared in 95% yield from compound 7 by methylation with sodium hydride and methyl iodide. Thus, four orthopivalates 1-4 were prepared from compound 5 in high yields. Consequently, compound 5 was found to be a very useful compound for preparing various other orthopivalate derivatives. Polymerization of 3-O-Allyl-r-D-glucopyranose 1,2,4Orthopivalates 1-4. The results of polymerizations of orthopivalate derivatives 1-4 are summarized in Table 1. These polymerizations were carried out in a high vacuum system previously reported.18-23,29 All these reactions were carried out in the presence of 5 mol % concentration of BF3‚ Et2O as an acid catalyst with 50 g/100 mL monomer concentration at -30 °C for 20 h. Polymerization of orthopivalate 5 with a benzyl group at the 3-O position has been reported to give a cellulose derivative20 and was also done under the same reaction conditions for comparing the reactivity of 3-O-allyl derivatives with that of the 3-O-benzyl derivative. The yield of poly(1) after a precipitating procedure was low, because the products contained low molecular weight polymers, such as monomer and oligomers, but these were dissolved in chloroform/n-hexane (1/15, v/v), used for precipitating the polymer. Polymers 2-4 were obtained as precipitates in good yields, that is, the 6-O-pivaloyl group in 3-O-allyl-R-D-glucopyranose 1,2,4-orthopivatate reduces

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Biomacromolecules, Vol. 3, No. 3, 2002

Figure 1. 75 MHz

13C

Karakawa et al.

NMR spectra of poly(1) and poly(2).

the reactivity compared with those of 6-O-benzyl, allyl, and methyl groups. The product from orthopivate 5 did not give the precipitate from the above solvent system, suggesting low molecular weight products. Then, to calculate an actual yield of polymerization reaction, the product was applied onto a gel permeation column chromatography using Sephadex LH-60

eluted with methanol/chloroform (1/4, v/v) for the separation of monomer resulting in hydrolysis of starting orthopivalate (5) during workup, to give poly(5) as an oil in 34% yield. Number-averaged molecular weights were determined by gel permeation chromatography (GPC) using polystyrene standards. Number-averaged molecular weights of poly(1) to poly(4) were 5580, 7260, 9470 and 6700, respectively,

Utility of a 3-O-Allyl Group for Ring-Opening Polymerization Scheme 2. Conversion of Poly(1) and Poly(3) into Its Triacetates, Poly(1A) and Poly(3A)

a NaOMe/dioxane:MeOH (4/1, v/v), reflux, overnight. b Ac O/Pyr, 50 °C, 2 overnight. c PdCl2/MeOH:CHCl3 (1/1, v/v), 60 °C, 4 h. d Ac2O/Pyr, 50 °C, overnight.

while that of poly(5) from 3-O-benzyl orthopivalate (5) was only 3700 as expected from its behavior in the precipitating solvent system. There is a trend in the increase of yield and Mn values are decreased as the size of the protective groups at 3-O and 6-O positions. The mechanism of polymerization is probably considered the same mechanism in a previous report.20 First of all, an oxonium ion intermediate of orthopivalate is formed by the coordination of a trifluorobonate with oxygen at the C-4 position. Then, β-side attack of the next orthopivalate at the C-1 position of the oxonium ion intermediate accompanied by the scissions of the orthoester bonds results in the formation of dimeric trialkyloxonium ion. Subsequently, the continuous attacks of the orthopivalate on the trialkyloxonium ion afford a polymeric compound consisting of a β-(1f4) glucopyranan. Thus, the 3-O-allyl group giving a product with higher Mn in higher yield is concluded to be a better protective group than the 3-O-benzyl group. Structural Determination of Polymers. 13C NMR spectra of poly(1) and poly(2) are shown in Figure 1. The spectra of poly(1) and poly(2) show two anomeric peaks, i.e., at 100.1 and 100.5 ppm for poly(1) and at 99.2 and 99.4 ppm for poly(2). On the other hand, those of poly(3) and poly(4) give only single peaks at 99.6 and 100.1 ppm, respectively. That is, these data suggest that both poly(3) and poly(4) are stereo- and regioregular polysaccharides but suggest that both poly(1) and poly(2) may not be stereoregular. To further investigate whether poly(1) to poly(4) are actually stereoregular, poly(1) to poly(3) and poly(4) were converted into triacetyl and trimethyl derivatives, respectively, for comparing with these cellulose derivatives prepared from natural cellulose. The conversion of poly(1) to poly(3) into their triacetyl derivatives, poly(1A) to poly(3A), are shown in Schemes 2 and 3, and conversion of poly(4) into trimethyl derivative (4A) is shown in Scheme 4. Depivaloylations at 2-O and 6-O positions in poly(1), and at 2-O positions in poly(2) to poly(4) were carried out with sodium methoxide in dioxane/methanol (4/1, v/v) at refluxed temperature overnight. Debenzylation at 6-O position in compound 18 was carried out with palladium charcoal in THF/ethanol (1/4, v/v) under hydrogen atmosphere at 80 °C for 2 days. Deallylations at 3-O positions in compounds 12, 17, and 21, and that at 3-O and 6-O positions in compound

Biomacromolecules, Vol. 3, No. 3, 2002 541 Scheme 3. Conversion of Poly(2) into Its Triacetate, Poly(2A)

a PdCl /MeOH:CHCl (1/1, v/v), 60 °C, 4 h. b NaOMe/THF:MeOH (4:1, 2 3 v/v), reflux, overnight. c Ac2O/Pyr, 50 °C, overnight. d Pd-C/THF:EtOH (1/4, v/v)/H2, 80 °C, 2days. e Ac2O/Pyr, 50 °C, overnight.

Scheme 4. Conversion of Poly(4) into Its Trimethyl Polymer, Poly(4A)

a NaOMe/THF:MeOH (4/1, v/v), reflux, overnight. b CH I/NaH/DMF, 3 room temperature, overnight. c PdCl2/MeOH:CHCl3 (1/1, v/v), 60 °C, 4 h. d CH I/NaH/DMF, room temperature, overnight. 3

13 were carried out with palladium chloride in methanol/ chloroform (1/1, v/v) at 60 °C for 4 h in high yields. Acetylations of deprotected poly(1) to poly(3) were done with acetic anhydride and pyridine at 50 °C overnight in quantitative yields. Then, methylation of compounds 20 and 22 was carried out with methyl iodide and sodium hydride in dimethylformamide at room temperature overnight. In these reactions, allyl groups could be completely removed at 60 °C only after 4 h even in polymer, while debenzylation19,20 occurred at 80 °C for 2 days under high pressure conditions in polymer. Thus, the allyl group was found to be better than the benzyl group as a protective group in polymer because of it could be easily removed in polymer. The complete removal of the allyl group was supported by the disappearance of characteristic peaks assigned to allyl group on NMR spectrum. For example, the peaks at 5.8 ppm on 1H NMR and those at 115-138 ppm on 13C NMR spectra completely disappeared after deallylation. Thus, poly(1) to poly(3) and poly(4) were converted into triacetyl, poly(1A) to poly(3A), and trimethyl derivatives, poly(4A), respectively, without any depolymerization that was reconfirmed by GPC analysis after the deprotection and subsequent acetylation or methylation reactions. The 13C NMR spectra of poly(1A) to poly(3A) was compared with that of authentic cellulose triacetate (CTA) prepared from Avicel (Merck) as shown in Figure 2. All chemical shifts for the ring and carbonyl carbons of poly(3A) were completely identical with those of authentic CTA, indicating that poly(3A) is exactly CTA as suggested by the NMR analysis of poly(3). On the other hand, the main resonance peaks of poly(1A) and poly(2A) were completely identical with those of authentic CTA, but additional small side peaks marked as

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Figure 2. 75 MHz

13C

Karakawa et al.

NMR spectra of authentic CTA, poly(1A), poly(2A), and poly(3A).

C1′-C6′ as shown in Figure 2 were also observed. These side peaks may be assigned to ring carbons of the nonreducing terminal unit, just as reported by Buchanan et al.30 In fact, all chemical shifts for C1′-C6′ were identical with those of cellononaose triacetate reported by Buchanan et al.30

as shown in Table 2. Furthermore, those chemical shifts for C1′-C6′ were also identical with those of CTA with DPn 9.2 (Mn ) 2660) prepared from low molecular weights natural cellulose.31 Thus, poly(1A) and poly(2A) were also identified to be CTA. Consequently, poly(1) and poly(2) were

Utility of a 3-O-Allyl Group for Ring-Opening Polymerization Table 2.

13C


NMR Chemical Shifts (δ) for Cellulose Peracetates δ (ppm)a

sample

C-1

C-1′

C-2

C-2′

C-3

C-3′

C-4

C-4′

C-5

C-5′

C-6

C-6′

poly(1A) poly(2A) poly(3A)b CTA (DP ) 9)c CTA (DPn ) 9.2)d CTA (DPn ) 114)b,e

100.5 100.5 100.5 100.4 100.4 100.5

100.8 100.8

71.8 71.9 71.7 71.9 71.8 71.7

71.5 71.6

72.5 72.5 72.6 72.5 72.4 72.4

72.8 72.9

76.1 76.0 76.1 76.0 75.9 76.0

67.7 67.8

72.8 72.9 72.8 72.8 72.7 72.7

72.0 72.0

62.0 62.0 62.0 62.0 62.0 61.9

61.4 61.5

100.7 100.7

71.6 71.5

72.8 72.8

67.8 67.8

71.9 72.0

61.5 61.4

a C-1-6, ring carbons in the internal unit; C-1′-6′, ring carbons in the nonreducing unit. b Ring carbons in reducing and nonreducing end units were undetectable. c Data reported by Buchanan et al.30 d Prepared from low molecular weights cellulose.31 e Prepared from Avicel (authentic CTA in Figure 2).

Table 3. 13C NMR Chemical Shifts (δ) for 4A and 2,3,6-Tri-O-methyl Cellulose δ (ppm) sample

C-1

C-2

C-3

C-4

C-5

C-6 2-OMe 3-OMe 6-OMe

poly(4A) 103.2 83.5 85.0 77.4 74.8 70.2 TMCa 103.2 83.5 85.0 77.2 74.8 70.2

60.6 60.7

60.3 60.4

59.2 59.2

a 2,3,6-Tri-O-methyl cellulose prepared by methylation from commercial methyl cellulose (DS ) 1.8).

found to be a stereoregular β-(1f4) glucopyranan, cellulose derivatives: the complexity of the resonance signals of poly(1) and poly(2) shown in Figure 1 should be attributed to those of the reducing or nonreducing terminal units. Authentic trimethyl cellulose (TMC) was prepared from commercial methyl cellulose with degree of substitution 1.8 by methylation. 13C NMR chemical shifts for poly(4A) and authentic trimethyl cellulose are shown in Table 3. Both chemical shifts are almost completely identical, indicating that poly(4A) should be trimethyl cellulose. Thus, the structure of poly(4) was determined to be β-(1f4) glucopyranan, cellulose derivative. Conclusion All the ring-opening polymerizations of 3-O-allyl-R-Dglucopyranose 1,2,4-orthopivalates (1-4) afforded stereoregular polysaccharides, cellulose derivatives, analogously to those of polymerization of 3-O-benzyl-R-D-glucopyranose 1,2,4-orthopivalates.19,20 The perfect removal of allyl groups in the cellulose derivatives was achieved with palladium chloride in a mixed solvent of methanol/chloroform (1/1, v/v) at 60 °C only for 4 h: the removal of the allyl group is easier than that of the benzyl group, which needs to be removed at 80 °C for 2 days. Thus, the allyl group is better than the benzyl group as a protective group because its removal was easier than that of the benzyl group in the polymer and steric hindrance was reduced. We found that the allyl group is a useful protective group on the 3-O position in the starting monomer, glucose orthopivalate derivative, for the ring-opening polymerization giving cellulose derivatives. Experimental Section Materials. Gel for size-exclusion chromatography (Sephadex LH-60) was purchased from Pharmacia. The other reagents were purchased from Nakarai Tesque Inc. (Kyoto, Japan) or Wako Pure Chemical Industries, Ltd. (Osaka,

Japan). Anhydrous dichloromethane was obtained by distillation from CaH2. Products were purified on a silica gel column chromatography (Wakogel C-200, Wako Pure Chemical Industries, Ltd.). The standard workup procedure included diluting with ethyl acetate or chloroform, washing with aqueous NaHCO3, distilled water, and brine, drying over Na2SO4, and concentrating in vacuo. Measurements. 1H and 13C NMR spectra were recorded with a Varian INOVA300 FT-NMR (300 MHz) spectrometer in chloroform-d with tetramethylsilane (TMS) as an internal standard. Chemical shifts (δ) and coupling constants (J) are given in δ values (ppm) and Hz, respectively. Optical rotations were measured at 25 °C using a JASCO Dip-1000 digital polarimeter. Number averaged molecular weight of the polymer was analyzed by gel permeation chromatography (GPC) in THF or chloroform at 40 °C. Calibration curves were obtained by using polystyrene standards (Shodex). A Shimadzu liquid chromatography injector (LC-10ATvp), a Shimadzu column oven (CTO-10Avp), a Shimadzu UVvis detector (SPD-10Avp), a Shimadzu refractive index detector (RID-10A), a Shimadzu communication bus module (CBM-10A), a Shimadzu LC workstation (CLASS-LC10), and Shodex columns (KF802, KF802.5, KF803, and K805) were used. The flow rate was 1.0 mL/min. 6-O-Pivaloyl-r-D-glucopyranose 1,2,4-Orthopivalate (6). A solution of compound 520 (500 mg, 1.19 mmol) in THF/ ethanol (1/4, v/v) (12 mL) was treated with 10% palladium charcoal (600 mg) under hydrogen atmosphere at 60 °C overnight. The reaction mixture was filtered through Celite 535 and concentrated. The product was purified on a silica gel column eluted with dichloromethane and then ethyl acetate/n-hexane (1/1, v/v) to afford colorless oil (6) (324 mg, 83%). [R]D25 +46.08° (c ) 1, chloroform). 1H NMR (CDCl3): δ 1.05 (9H, piv-H), 1.22 (9H, piv-H), 4.15 (1H, collapsed dd, J2,3 ) 2.0, J3,4 ) 4.5, C3-H), 4.18 (1H, m, C4-H), 4.27 (2H, dd, Jgem ) 11.7, J5,6a ) 6.6, C6-Ha), 4.41 (1H, dt, J1,2 ) 4.8, J2,3 ) J2,4 ) 2.0, C2-H), 4.48 (1H, dd, Jgem ) 11.7, J5,6b ) 6.6, C6-Hb), 4.59 (1H, collapsed t, J5,6a ) J5,6b ) 6.6, C5-H), 5.76 (1H, d, J1,2 ) 4.8, C1-H). 13C NMR (CDCl3): δ 97.5 (C-1), 74.1, 64.7, 72.6, 75.1, 63.9 (C-2, C-3, C-4, C-5, C-6), 123.3 ((-O)3CC(CH3)3), 24.8 (orthopivalate-C(CH3)3), 35.7 (orthopivalate-C(CH3)3), 27.1 (piv-C(CH3)3), 38.8 (piv-C(CH3)3). 3-O-Allyl-6-O-pivaloyl-r-D-glucopyranose 1,2,4-Orthopivalate (1). To a solution of compound 6 (344 mg, 1.0 mmol) in DMF (4 mL), silver oxide (2.4 g, 10 mmol) and allyl bromide (0.9 mL, 10 mmol) were added. The solution

544


was stirred at room temperature for 12 h. The reaction mixture was filtered through Celite 535, and the residue was washed with ethyl acetate. The combined filtrates and washings were treated with a standard workup procedure to give yellow oil. The yellow oil was purified on a silica gel column eluted with dichloromethane/n-hexane (1/2, v/v) and then ethyl acetate/n-hexane (1/4, v/v) to give colorless oil (1) (363 mg, 93%): [R]D25 +36.25° (c ) 1, chloroform). 1H NMR (CDCl3): δ 1.05 (9H, piv-H), 1.23 (9H, piv-H), 3.90 (1H, collapsed dt, J2,4 ) 2.1, J3,4 ) 4.5, J4,5 ) 1.2, C4-H), 4.18 (1H, dd, J2,3 ) 2.1, J3,4 ) 4.5, C3-H), 4.29 (1H, dd, Jgem ) 11.1, J5,6a ) 6.9, C6-Ha), 4.39 (1H, dd, Jgem ) 11.1, J5,6b ) 6.9, C6-Hb), 4.46 (1H, dt, J1,2 ) 4.8, J2,3 ) J2,4 ) 2.1, C2-H), 4.50 (1H, collapsed t, J4,5 ) 1.2, J5,6a ) J5,6b ) 6.9, C5-H), 5.78 (1H, d, J1,2 ) 4.8, C1-H), 4.06, 4.13 (2H, two broad dd, J ) 12.9, 6.0, -CH2CHCH2), 5.24 (1H, dd, J ) 10.5, 1.8, -CH2CHCHcis), 5.32 (1H, dd, J ) 17.4, 1.8, -CH2CHCHtrans), 5.89 (1H, ddd, J ) 17.4, 10.5, 6.0, -CH2CHCH2). 13C NMR (CDCl3): δ 97.5 (C-1), 72.1, 71.4, 71.0, 75.2, 64.3 (C-2, C-3, C-4, C-5, C-6), 71.2, 133.7, 118.2 (-CH2CHCH2, -CH2CHCH2, -CH2CHCH2), 123.07 ((-O)3CC(CH3)3), 24.9 (orthopivalate-C(CH3)3), 35.7 (orthopivalate-C(CH3)3), 27.2 (piv-C(CH3)3), 38.7 (piv-C(CH3)3). 3-O-Allyl-r-D-glucopyranose 1,2,4-Orthopivalate (7). A solution of compound 1 (297 mg, 0.80 mmol) was dissolved in dioxane/methanol (4/1, v/v) (3.0 mL), and 28% sodium methoxide (0.162 mL, 0.80 mmol) was added. The solution was stirred at room temperature for 6 h. The reaction mixture was worked-up by the standard procedure to give colorless oil. The oil was purified on a silica gel column eluted with ethyl acetate/n-hexane (1/2, v/v) to give colorless oil (7) (207 mg, 90%). [R]D25 +25.49° (c ) 1, chloroform). 1H NMR (CDCl3): δ 1.05 (9H, piv-H), 3.80 (1H, dd, Jgem ) 11.7, J5,6a ) 5.4, C6-Ha), 3.92 (1H, collapsed dd, J2,4 ) 2.1, J3,4 ) 4.8, J4,5 ) 1.2, C4-H), 3.94 (1H, dd, Jgem ) 11.7, J5,6b ) 5.4, C6-Hb), 4.24 (1H, dd, J2,3 ) 2.1, J3,4 ) 4.8, C3-H), 4.45 (1H, dt, J1,2 ) 4.8, J2,3 ) J2,4 ) 2.1, C2-H), 4.50 (1H, collapsed t, J4,5 ) 1.2, J5,6a ) J5,6b ) 5.4, C5-H), 4.10, 4.16 (2H, broad dd, J ) 12.6, 5.7, -CH2CHCH2), 5.27 (1H, broad dd, J ) 10.2, 1.5, -CH2CHCHcis), 5.34 (1H, broad dd, J ) 17.4, 1.5, -CH2CHCHtrans), 5.90 (1H, ddd, J ) 17.4, 10.2, 5.7, -CH2CHCH2). 13C NMR (CDCl3): δ 97.6 (C-1), 71.9, 72.2, 71.06, 77.4, 62.8 (C-2, C-3, C-4, C-5, C-6), 71.4, 133.3, 118.7 (-CH2CHCH2, -CH2CHCH2, -CH2CHCH2), 123.2 ((-O)3CC(CH3)3), 24.8 (orthopivalate-C(CH3)3), 35.7 (orthopivalate-C(CH3)3). 3-O-Allyl-6-O-methyl-r-D-glucopyranose 1,2,4-Orthopivalate (4). To a solution of compound 7 (140 mg, 0.49 mmol) in DMF (2 mL), sodium hydride (59 mg, 1.47 mmol) and methyl iodide (0.06 mL, 0.98 mmol) were added. The solution was stirred at room temperature for 4 h. To the reaction mixture, MeOH was added to decompose the methyl iodide and sodium hydride, and then the mixture was worked-up to afford a yellow oil. The oil was purified on a silica gel column eluted with n-hexane and then ethyl acetate/ n-hexane (1/4, v/v) to give colorless oil (4) (140 mg, 95%). [R]D25 +27.08° (c ) 1, chloroform). 1H NMR (CDCl3): δ 1.03 (9H, piv-H), 3.56 (3H, s, OCH3), 3.60 (1H, dd, Jgem ) 9.6, J5,6a ) 6.9, C6-Ha), 3.71 (1H, dd, Jgem ) 9.6, J5,6b )

Karakawa et al.

6.9, C6-Hb), 3.89 (1H, collapsed dd, J2,4 ) 2.1, J3,4 ) 4.5, J4,5 ) 1.2, C4-H), 4.23 (1H, dd, J2,3 ) 2.1, J3,4 ) 4.5, C3H), 4.44 (1H, dt, J1,2 ) 4.5, J2,3 ) J2,4 ) 2.1, C2-H), 4.53 (1H, collapsed t, J4,5 ) 1.2, J5,6a ) J5,6b ) 6.9, C5-H), 5.77 (1H, d, J1,2 ) 4.5, C1-H), 4.05, 4.11 (2H, broad dd, J ) 12.9, 5.4, -CH2CHCH2), 5.23 (1H, broad dd, J ) 10.5, 1.8, -CH2CHCHcis), 5.31 (1H, broad dd, J ) 17.4, 1.8, -CH2CHCHtrans), 5.89 (1H, ddd, J ) 17.4, 10.5, 5.4, -CH2CHCH2). 13C NMR (CDCl3): δ 97.5 (C-1), 72.3, 71.2, 71.3, 75.5, 72.5 (C-2, C-3, C-4, C-5, C-6), 70.9, 133.9, 117.7 (-CH2CHCH2, -CH2CHCH2, -CH2CHCH2), 123.04 ((-O)3CC(CH3)3), 24.8 (orthopivalate-C(CH3)3), 35.7 (orthopivalate-C(CH3)3). r-D-Glucopyranose 1,2,4-Orthopivalate (9) (via compound 8). A solution of compound 5 (1.9 g, 4.5 mmol) was dissolved in dioxane/methanol (4:1, v/v) (20 mL), and 28% sodium methoxide (1.8 mL, 9.0 mmol) was added. The solution was stirred at room temperature for 6 h. The reaction mixture was worked-up by the standard procedure to give colorless oil. The oil was purified on a silica gel column eluted with ethyl acetate/n-hexane (1/2, v/v) to give colorless oil (8) (1.2 g, 85%). A solution of compound 8 (476 mg, 1.4 mmol) in THF/ethanol (1/4, v/v) (10 mL) was treated with 10% palladium charcoal (400 mg) under hydrogen atmosphere at 60 °C overnight. The reaction mixture was filtered through Celite 535 and concentrated to give a white solid (9) (228 mg, 93%) (via compound 6). A solution of compound 6 (125 mg, 0.38 mmol) was dissolved in dioxane/ methanol (4:1, v/v) (1.0 mL), and 28% sodium methoxide (0.154 mL, 0.76 mmol) was added. The solution was stirred at room temperature for 6 h. The reaction mixture was worked-up by the standard procedure to give colorless oil (9) (88 mg, 87%): [R]D25 +46.38° (c ) 1, chloroform). 1H NMR (CDCl3): δ 0.99 (9H, piv-H), 3.75 (1H, dd, Jgem ) 12.0, J5,6a ) 3.6, C6-Ha), 3.87 (1H, dd, Jgem ) 12.0, J5,6b ) 3.6, C6-Hb), 4.05 (1H, collapsed dd, J2,4 ) 1.8, J3,4 ) 4.5, J4,5 ) 2.1, C4-H), 4.23 (1H, dt, J2,3 ) 1.8, J3,4 ) 4.5, C3H), 4.35 (1H, ddd, J1,2 ) 4.8, J2,3 ) J2,4 ) 1.8, C2-H), 4.44 (1H, collapsed t, J4,5 ) 2.1, J5,6a ) J5,6b ) 3.6, C5-H), 5.76 (1H, d, J1,2 ) 4.8, C1-H). 13C NMR (CDCl3): δ 97.7 (C1), 74.0, 74.6, 63.6, 76.9, 61.6 (C-2, C-3, C-4, C-5, C-6), 123.1 ((-O)3CC(CH3)3), 24.7 (orthopivalate -C(CH3)3), 35.6 (orthopivalate-C(CH3)3). 3,6-Di-O-allyl-r-D-glucopyranose 1,2,4-Orthopivalate (3). To a solution of compound 9 (200 mg, 0.82 mmol) in DMF (2 mL), sodium hydride (146 mg, 3.67 mmol) and allyl bromide (0.21 mL, 2.45 mmol) were added at room temperature. After 4 h, the reaction mixture was worked-up to afford yellow oil. The oil was purified on a silica gel column eluted with n-hexane and then ethyl acetate/n-hexane (1/4, v/v) to give slightly yellow oil (3) (253 mg, 95%). [R]D25 +29.16° (c ) 0.5, chloroform). 1H NMR (CDCl3): δ 1.05 (9H, piv-H), 3.69 (1H, dd, Jgem ) 9.6, J5,6a ) 6.9, C6-Ha), 3.73 (1H, dd, Jgem ) 9.6, J5,6b ) 6.9, C6-Hb), 3.87 (1H, collapsed dd, J2,4 ) 2.1, J3,4 ) 4.5, J4,5 ) 1.2, C4-H), 4.25 (1H, dd, J2,3 ) 2.1, J3,4 ) 4.5, C3-H), 4.41 (1H, dt, J1,2 ) 4.5, J2,3 ) J2,4 ) 2.1, C2-H), 4.51 (1H, collapsed t, J4,5 ) 1.2, J5,6a ) J5,6b ) 6.9, C5-H), 5.74 (1H, d, J1,2 ) 4.5, C1H), 3.93-4.12 (4H, m, -CH2CHCH2), 5.15-5.32 (4H, m,

Utility of a 3-O-Allyl Group for Ring-Opening Polymerization


-CH2CHCH2), 5.80-5.96 (2H, m, -CH2CHCH2). 13C NMR (CDCl3): δ 97.5 (C-1), 72.3, 71.2, 71.4, 75.7, 70.0 (C-2, C-3, C-4, C-5, C-6), 70.9, 72.2, 133.9, 134.5, 117.3, 117.7 (-CH2CHCH2, -CH2CHCH2, -CH2CHCH2), 123.03 ((-O)3CC(CH3)3), 24.8 (orthopivalate-C(CH3)3), 35.7 (orthopivalate-C(CH3)3). 3-O-Allyl-6-O-benzyl-r-D-glucopyranose 1,2,4-Orthopivalate (2). To a solution of compound 7 (100 mg, 0.35 mmol) in DMF (2.0 mL), sodium hydride (17 mg, 0.7 mmol) and benzyl bromide (0.62 mL, 0.525 mmol) were added at room temperature. After 4 h, the reaction mixture was worked-up to afford yellow oil. The oil was purified on a silica gel column eluted with dichloromethane/n-hexane (1/1, v/v) and then ethyl acetate/n-hexane (1/4, v/v) to give slightly yellow oil (2) (113 mg, 81%). [R]D25 +20.25° (c ) 0.5, chloroform). 1H NMR (CDCl3): δ 1.04 (9H, piv-H), 3.69 (1H, dd, Jgem ) 9.6, J5,6a ) 6.9, C6-Ha), 3.77 (1H, dd, Jgem ) 9.6, J5,6b ) 6.9, C6-Hb), 3.87 (1H, collapsed dd, J2,4 ) 2.1, J3,4 ) 4.5, J4,5 ) 1.2, C4-H), 4.28 (1H, dd, J2,3 ) 2.1, J3,4 ) 4.5, C3-H), 4.41 (1H, dt, J1,2 ) 4.5, J2,3 ) J2,4 ) 2.1, C2-H), 4.56 (1H, collapsed t, J4,5 ) 1.2, J5,6a ) J5,6b ) 6.9, C5-H), 5.76 (1H, d, J1,2 ) 4.5, C1-H), 4.63, 4.49 (2H, two d, J ) 12.0, -CH2-Arom.), 3.95, 4.01 (2H, broad dd, J ) 12.9, 5.7, -CH2CHCH2), 5.18 (1H, broad dd, J ) 10.5, 1.5, -CH2CHCHcis), 5.24 (1H, broad dd, J ) 17.4, 1.5, -CH2CHCHtrans), 5.80 (1H, ddd, J ) 17.4, 10.5, 5.7, -CH2CHCH2), 7.23-7.45 (5H, aromatic). 13C NMR (CDCl3): δ 97.6 (C-1), 72.4, 71.1, 71.4, 75.7, 69.9 (C-2, C-3, C-4, C-5, C-6), 70.9, 133.9, 117.7 (-CH2CHCH2, -CH2CHCH2, -CH2CHCH2), 127.7, 127.9, 128.4, 138.0 (aromatic-C), 123.07 ((-O)3CC(CH3)3), 24.9 (orthopivalateC(CH3)3), 35.7 (orthopivalate-C(CH3)3). Polymerizations. All these polymerizations were carried out under a high vacuum system.18-23,29 Monomer was dried in a polymerization ampule by evacuating for approximately a day. Dichloromethane (50 g/100 mL) was distilled from CaH2. The solvent was transferred under high vacuum. The reaction apparatus was then separated by melting off and kept at -30 °C. To a solution of monomer, 5 mol % of BF3‚ Et2O was added and kept at -30 °C for 20 h. The reaction mixture was poured into chloroform/n-hexane (1/15, v/v), then precipitated polymer was collected by filtration, and finally dried in vacuo. Conversion of Poly(1-3) into Acetylated Polymers 1A3A. DepiValoylation and Acetylation Procedure. To a solution of polymer in THF/methanol (4/1, v/v) was added 28% sodium methoxide. The reaction mixture was kept at reflux temperature overnight. To the reaction mixture, 2 N HCl aqueous solution was added for neutralization and then filtered off. The product was treated with acetic anhydride and pyridine at 50 °C overnight to give a crude acetylated polymer. The polymer was dissolved in dichloromethane (1 mL) and then poured into a large amount of n-hexane (15 mL) to precipitate a polymer. The precipitated polymer was filtrated and collected. Deallylation and Acetylation Procedure. To a solution of the polymer in chloroform/methanol (1/1, v/v), palladium dichloride was added. The reaction mixture was kept at 60 °C for 4 h and then concentrated to dryness. The product

was treated with acetic anhydride and pyridine at 50 °C overnight to give a crude acetylated polymer. The polymer was dissolved in chloroform (1 mL) and then poured into a large amount of n-hexane (15 mL) to precipitate a polymer. The precipitated polymer was filtrated and collected. Debenzylation and Acetylation Procedure. A solution of polymer in THF/ethanol (1/4, v/v) was treated with 10% palladium charcoal under hydrogen atmosphere at 80 °C for 2 days and then concentrated to dryness. The product was treated with acetic anhydride and pyridine at 50 °C overnight to give a crude acetylated polymer. The polymer was dissolved in chloroform (1 mL) and then poured into a large amount of n-hexane (15 mL) to precipitate a polymer. At the final, the acetylated polymer was purified by gel permeation chromatography (LH-60) eluted with methanol/ chloroform (1/4, v/v) to afford yellow oil. Preparation of Authentic Cellulose Triacetate from Low Molecular Weight Natural Cellulose. To a solution of low molecular weight natural cellulose31 (30 mg) in pyridine (1 mL), acetic anhydride (1 mL) was added. The mixture was kept at 110 °C for 2 days. The solution was worked-up by standard procedure, and then concentrated to dryness to give cellulose triacetate (CTA). The CTA was precipitated in chloroform (1 mL) and n-hexane (15 mL) and filtered. The precipitate was dried to give cellulose triacetate (45 mg, DPn ) 9.2, Mn ) 2660). Preparation of Authentic Cellulose Triacetate from Natural Cellulose. To a solution of natural cellulose (Avicel, Merck) (250 mg) in DMAc (5 mL) and LiCl (375 mg), acetic anhydride (1.2 mL) and pyridine (1.2 mL) were added. The mixture was kept at 70 °C for 2 days. The solution was poured into ethanol to precipitate a polymer. The precipitate was filtered and then dried to give cellulose triacetate (430 mg, DPn ) 114, Mn ) 32880). Conversion of Poly(4) into Trimethyl Polymer (4A). To a solution of poly(4) (20 mg, 0.07 mmol) in THF/methanol (5 mL, 4:1, v/v) was added 28% sodium methoxide (0.27 mL, 1.3 mmol). The reaction mixture was kept at reflux temperature overnight. The reaction mixture was treated with 4 N HCl for neutralization and concentrated to dryness. To a solution of compound 20 (14 mg, 0.07 mmol) in DMF (2 mL), sodium hydride (53 mg, 1.3 mmol) was added and then methyl iodide (0.08 mL, 1.3 mmol) was added at 0 °C. The mixture was kept at room temperature overnight. The reaction mixture was neutralized with 4 N HCl and dried in vacuo. The polymer was purified by gel permeation chromatography (LH-60) eluted with methanol/chloroform (1/4, v/v) to afford compound 21. To a solution of the compound 21 (15 mg, 0.07 mmol) in chloroform/methanol (2 mL, 1/1, v/v), palladium dichloride (4.7 mg, 0.03 mmol) was added. The reaction mixture was kept at 60 °C for 4 h and then concentrated to give compound 22. Finally, methylation of compound 22 was carried out according to the above procedure. The crude polymer was purified by gel permeation chromatography (LH-60) eluted with methanol/chloroform (1/4, v/v) to give poly(4A) (5.3 mg, 37% overall yield).

546


Preparation of Authentic Tri-O-methyl Cellulose from Commercial Methyl Cellulose. To a solution of SM-400 (Shin-Etsu Chemical Co., Ltd. DS ) 1.8) (100 mg) in DMF (5 mL), powdered NaOH (500 mg) was added. Then methyl iodide (0.7 mL) was added. The mixture was kept at room temperature for 5 days. The solution was worked-up by standard procedure and then concentrated to dryness to give tri-O-methyl cellulose (85 mg). Acknowledgment. This investigation was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture of Japan (No. 11556031). References and Notes (1) See, for example: Nevell, T. P.; Zeronian, S. H. Cellulose chemistry fundamentals. In Cellulose Chemistry and its Applications; Nevell, T. P., Zeronian, S. H., Eds.; Ellis Horwood Limited, John Wiley & Sons: New York, 1985; p 15. (2) Gray, D. G. J. Appl. Polym. Sci., Appl. Polym. Symp. 1983, 37, 179. (3) Kubota, T.; Kusano, T.; Yamamoto, C.; Yashima, E.; Okamoto, Y. Chem. Lett. 2001, 7, 724. (4) Kamitakahara, H.; Nishigaki, F.; Mikawa, Y.; Hori, M.; Tsujihata, S.; Fujii, T.; Nakatsubo, F. J. Wood Sci., in press. (5) Yoshida, T. Prog. Polym. Sci. 2001, 26, 329. (6) Matsuzaki, K.; Yamamoto, I.; Sato, T.; Oshima, R. Makromol. Chem. 1985, 186, 449. (7) Einfeldt, L.; Klemm, D.; Schmauder, H. P. Nat. Prod. Lett. 1993, 2, 263. (8) Salmon, S.; Hudson, S. M. J. Macromol. Sci., ReV. Macromol. Chem. Phys. 1997, C37, 199.

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Okuda, K.; Mine, I. Cell. Commun. 1997, 4, 101. Atalla, R.; VanderHart, D. L. Science 1984, 223, 283. Sugiyama, J.; Vuong, R.; Chanzy, H. Macromolecules 1991, 24, 4168. Sakai K.; Yamauchi T.; Nakasu F.; Ohe T. Biosci., Biotechnol., Biochem. 1996, 60, 1617. Nojiri, M.; Kondo, T. Macromolecules 1996, 29, 2392. Liu, H.; Zhang, L.; Takaragi, A.; Miyamoto,T. Polym. Bull. 1998, 40, 741. Kondo, T. J. Polym. Sci., Part B: Polym. Phys. 1994, 32, 1229. Kondo, T. J. Polym. Sci., Part B: Polym. Phys. 1997, 35, 713. Koshella, A.; Heinze, T.; Klemm, D. Macromol. Biosci. 2001, 1, 49. Nishimura, T.; Nakatsubo, F. Cellulose 1997, 4, 109. Nakatsubo, F.; Kamitakahara, H.; Hori, M. J. Am. Chem. Soc. 1996, 118, 1677. Kamitakahara, H.; Hori, M.; Nakatsubo, F. Macromolecules 1996, 29, 6126. Hori, M.; Nakatsubo, F. Macromolecules 2000, 33, 1148. Tsujihata, S.; Nakatsubo, F. Abstracts of XVIIIth Japanese Carbohydrate Symposium 1996, 57. Hori, M.; Nakatsubo, F. Macromolecules 2001, 34, 2476. Kondo, T.; Gray, G. D. Carbohydr. Res. 1991, 220, 173. Kariyone, K.; Yazawa, H. Tetrahedron Lett. 1970, 2885. Ogawa, T.; Yamamoto, H. Agric. Biol. Chem. 1985, 49, 475. Takano, T.; Harada, Y.; Nakatsubo, F.; Murakami, K. Mokuzai Gakkaishi 1990, 36, 212. Heathcock, H. C.; Ratcliffe, R. J. Am. Chem. Soc. 1971, 93, 1746. Nishimura, T.; Nakatsubo, F. Carbohydrate Res. 1996, 294, 53. Buchanan, M. C.; Hyatt, A. J.; Kellyey, S. S.; Little, L. J. Macromolecules 1990, 23, 3747. Atalla, H. R.; Ellis, D. J.; Schroeder, R. L. J. Wood Chem. Technol. 1984, 4, 465.

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