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Reductive opening of carbohydrate phenylsulfonylethylidene (PSE) acetals
Carbohydrate Research 417 (2015) 117–124
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Carbohydrate Research j o u r n a l h o m e p a g e : w w w. e l s e v i e r. c o m / l o c a t e / c a r r e s
Reductive opening of carbohydrate phenylsulfonylethylidene (PSE) acetals Florence Chéry a, Elena Cabianca a,b, Arnaud Tatibouët a, Ottorino De Lucchi b, Thisbe K. Lindhorst c, Patrick Rollin a,* a
Université d’Orléans et CNRS, ICOA, UMR 7311, BP 6759, F-45067 Orléans, France Dipartimento di Chimica, Università Ca’Foscari di Venezia, Dorsoduro 2137, I-30123 Venezia, Italy c Otto Diels Institute of Organic Chemistry, Christiana Albertina University of Kiel, Otto-Hahn-Platz 3/4, D-24118 Kiel, Germany b
A R T I C L E
I N F O
Article history: Received 16 July 2015 Received in revised form 20 September 2015 Accepted 21 September 2015 Available online 26 September 2015 Keywords: Carbohydrate protecting groups Sulfones Phenylsulfonylethylidene (PSE) acetals Reductive desulfonylation SET Vinyl ethers
A B S T R A C T
The phenylsulfonylethylidene (PSE) acetal is a relatively new protecting group in carbohydrate chemistry. However, carbohydrate-derived phenylsulfonylethylidene (PSE) acetals show a different behavior in reductive desulfonylation than simple symmetrical acetals. Here we have investigated various SET-type reaction conditions in order to open PSE acetals regioselectively and to produce chiral ω-hydroxyethenyl ethers. Whereas sodium amalgam leads to a mixture of regioisomeric vinyl ethers besides the ethylidene acetal, samarium iodide is suited for regioselective ring opening. This is shown with seven different carbohydrate PSE acetals, both of the 1,3-dioxane and the 1,3-dioxolane type. © 2015 Elsevier Ltd. All rights reserved.
1. Introduction In previous times, we have introduced a new protecting group in carbohydrate chemistry, namely the phenylsulfonylethylidene (PSE) acetal. PSE acetals (Scheme 1, 3) are readily accessible by reacting a diol of choice (1) with 1,2-bis(phenylsulfonyl)ethylene (2),1 a conversion that proceeds according to a double Michael addition pathway with extrusion of a sulfinate. Whereas at first, this procedure was applied to a number of symmetrical non-carbohydrate substrates (1a–e),2 it has later on been extended to numerous glycosides, such as glucopyranoside 1f,3 and thus the PSE protecting group has found a variety of applications in the field of carbohydratebased synthetic methodology.4–8 In a subsequent step, PSE acetals can be converted into ω-hydroxyethenyl ethers (4). This is effected by elimination of a sulfonyl group through reductive cleavage of the C—S bond, a step well known in the chemistry of sulfones.9 In introductory work, we have disclosed an efficient procedure for the conversion of symmetrical cyclic PSE acetals such as 3a–e 2,10 into the corresponding ω-hydroxyethenyl ethers 4a–e2 (Fig. 1). Employment of sodium
* Corresponding author. Université d’Orléans et CNRS, ICOA, UMR 7311, BP 6759, F-45067 Orléans, France. Tel.: +33 238 417 370; fax: +33 238 417 281. E-mail address: [email protected] (P. Rollin). http://dx.doi.org/10.1016/j.carres.2015.09.011 0008-6215/© 2015 Elsevier Ltd. All rights reserved.
amalgam in anhydrous methanol gave the desulfonylated products in yields between 48% and 90%. Contrary to our expectation, ethylidene acetals were not formed and this reduction step. The PSE acetals 3a–3e, derived from catechol (1a), (R,R)-tartrate (1b), propane-1,3-diol (1c), butane-1,4-diol (1d) and (Z)-but-2-ene1,4-diol (1e) were obtained as reported earlier.2,10 Full analytical details of 3c–3e (Fig. 1) are reported in this account (cf. Section 4). Reductive ring opening led to ω-hydroxyethenyl ethers 4a–4e (Fig. 1) in 48%–90%.2 As shown in Scheme 1, the methyl glucoside 1f resembles a diol substructure similar to the symmetrical compound 1c. Thus, in our earlier work, the corresponding PSE acetal 3f3 was investigated toward its stability under various reaction conditions. It was found to be stable against triisobutylaluminum (TIBAL)4 and DDQ5 and to be inert under acidic conditions.3 On the contrary, it undergoes cleavage under strongly reductive conditions (LiAlH4).3 Under protic conditions, treatment with base (e.g. KOH) restores the respective starting material (1) and aprotic strongly basic conditions (n-BuLi in THF) lead to primary and secondary alkoxyvinyl sulfones depending on whether pyranosides or furanosides were employed.11 However, desulfonylation did not occur under the latter conditions. Here it has been our goal to test reductive ring opening conditions for desulfonylation with unsymmetrical carbohydrate PSE acetals having in mind a novel access to carbohydrate-based O-vinylated species.
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Scheme 1. Two-step procedure to access ω-hydroxyethenyl ethers (4): diols (1) react with 1,2-bis(phenylsulfonyl)ethylene to give PSE acetals (3), which undergo reductive ring opening.
2. Results and discussion Various reaction conditions were tried for reductive desulfonylation of the 4,6-acetal substructure in methyl 2,3-di-Obenzyl-4,6-O-(2-phenylsulfonyl)ethylidene-α-d-glucopyranoside 3f, resembling an unsymmetrical PSE acetal. Typically, metal amalgams can be employed in this case to effect PSE reduction according to a single electron transfer (SET) mechanism. Thus, according to our standard conditions,2,12,13 3f was first treated with sodium amalgam in anhydrous methanol in the presence of solid phosphate buffer NaH2PO4. Contrary to 3a–3e, ring opening of the PSEprotected glucoside 3f leads to two regioisomeric products. In addition, the corresponding ethylidene acetal was obtained in this case. Hence, after chromatographic purification, the regioisomeric 4-O- and 6-O-vinyl ethers 5 and 6 were isolated in 27% and 35% respective yields, together with the ethylidene acetal 714 in 32% (Scheme 2). Thus apparently, opening of phenylsulfonylethylidene acetals in carbohydrates is less straightforward than in the case of the symmetrical PSE acetals 3a–3e. In order to improve PSE ring opening, first the Na/Hg reduction protocol was varied. Some of these attempts are collected in Table 1 and show that optimization of the sodium amalgam-mediated reduction did not lead to satisfactory results. The overall yields were always excellent, but in all cases, the reaction led to the regioisomeric vinyl ethers together with the ethylidene acetal. These three isomeric
products were regularly obtained in a ratio around 1:1:1. This mixture could be separated by column chromatography but nevertheless we sought for an improved method for PSE cleavage. Magnesium in methanol has been described in the literature as substitute for sodium amalgam in desulfonylation reactions:15 it was therefore tested next, albeit without appreciable benefit. In contrast, the use of samarium(II) iodide16 was found suited to reduce the number of isomeric products to two. Thus, reductive desulfonylation of 3f with SmI2 according to conditions developed by Sinaÿ17 and Beau18 gave rise to the 4-O-vinyl ether 5 as the only ring opening product and to the ethylidene acetal 7 in equimolar amounts (Table 1). The regioselectivity observed in the ring opening reaction with samarium(II) iodide might be due to an intermediate organosamarium species that exclusively opens to the 4-Ovinyl ether (rather than the 6-O-vinyl ether). With sodium or magnesium, the situation must be different, as with these metals both regioisomeric ring opening products are obtained. Reductive desulfonylation with SmI2 is based on a single electron transfer (SET) process in which, according to the literature,17,18 one electron is transferred to the LUMO of the phenyl sulfone I (Scheme 3). Thus, after extrusion of a sulfinate, a transient radical II is formed which in turn can add SmI2 to form an intermediate organosamarium species III, that generates the ethylidene acetal IV (such as 7) after protonation. On the other hand, homolytic dissociation of the acetal C—O bond, α-positioned to the radical center,
Fig. 1. Structures of symmetrical PSE acetals 3a–3f and of the hydroxyvinyl ethers 4a–4f.
Scheme 2. Reductive ring opening of the PSE acetal 3f leads to the three isomeric products 5, 6, and 7.
F. Chéry et al./Carbohydrate Research 417 (2015) 117–124
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Scheme 3. Through a SET process SmI2 converts PSE acetals into ethylidene acetals and by regioselective ring opening into 4-O-vinyl ethers.
Table 1 Reductive opening of PSE acetal 3f (cf. Scheme 2) Reaction conditions
5
6
7
Total yield
Na/Hg, MeOH, NaH2PO4, rt Na/Hg, MeOH, NaH2PO4, 50 °C Na/Hg, MeOH/THF 1:1, NaH2PO4, rt Na/Hg, MeOH, rt, no buffer Mg, MeOH SmI2, THF/HMPA 20:1, rt
35% 39% 40% 35% 25% 35%
27% 29% 28% 32% 25% —
32% 29% 29% 27% 29% 35%
94% 97% 97% 94% 79% 70%
Table 2 Reductive opening of PSE acetals 8–14 (cf. Scheme 4) PSE acetal 8 9 10 11 12 13 14
Reaction conditions
Prim. O-vinyl
Sec. O-vinyl
Ethylidene
Total yield
Na/Hg SmI2 Na/Hg SmI2 Na/Hg Na/Hg SmI2 Na/Hg SmI2 Na/Hg SmI2 Na/Hg SmI2
12% — 29% — 22% 32% — 26% — 29% — 27% —
35% 41% 27% 40% 20% 33% 44% 32% 30% 28% 35% 28% 48%
34% 41% 30% 40% 35% 34% 40% 35% 30% 27% 35% 28% 48%
81% 82% 86% 80% 77% 99% 84% 93% 60% 84% 70% 83% 96%
can furnish V, finally leading to the corresponding γ-hydroxyethenyl ether VI (such as 5). However, a conclusive mechanistic rational about the fact that the 6-O-vinyl ring opening product is not observed in this reaction cannot be provided at this stage. It might be suggested that regioselective samarium complexation involving the endocyclic ring oxygen is the basis of the observed selectivity. In the next step it was important to test the optimized Na/Hg protocol as well as the SmI2 procedure with various saccharidic PSE acetals as it is typical that the chemistry of carbohydrates varies considerably depending on their configuration. Thus, the glucoside 3f was supplemented by the analogous mannoside 8,3 the galactoside 9,3 furthermore, more ring-strained sugars, the glucal 103 and the epoxide 11,3 were tested, followed by the 1,2-O-isopropylidene3,5-O-(2-phenylsulfonyl)ethylidene-α-d-xylofuranose 123 and the glucofuranose derivatives 133 and 143 (Scheme 2). This small library of acetals resembles a collection of PSE 1,3-dioxanes and 1,3dioxolanes. The results of the Na/Hg as well as the SmI2 reduction protocol are collected in Table 2. The tested PSE acetals (Scheme 4) behave all very similar in SETtype reductive desulfonylation providing good to excellent overall yields. Again, sodium amalgam leads to three isomeric products in almost similar amounts (Table 2). Only the mannoside 8 delivers more than double the amount of the secondary 4-O-vinyl ether than that of the primary 6-O-vinyl ether. This might arise from the axially positioned 2-hydroxyl group that could add to complexation of
Scheme 4. A collection of structurally varied carbohydrate-derived PSE acetals, 8–14, were tested in reductive desulfonylation employing two different SET-type reaction conditions. Three different isomeric products can be obtained, the primary or secondary O-vinyl ether, respectively, or the ethylidene acetal. For yields and ratios cf. Table 2.
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sodium amalgam at the β-face of the sugar ring, thus facilitating regioselective ring opening in favor of the 4-O-vinyl ether. With SmI2, in all tested cases the primary vinyl ether was not observed. The regioselectivity of this ring opening reaction seems not to be guided by the carbohydrate ring template of the PSE acetal that is used as starting material. This underlines again that the samarium-mediated regioselective ring opening of asymmetrical PSE acetals is a reaction of wide applicability in sugar chemistry. 3. Conclusion While the benzylidene acetal is a well established and versatile protecting group in carbohydrate chemistry, PSE acetals are relatively new and far less explored. Here we have investigated a total of eight PSE acetals derived from structurally varied carbohydrates. SET-type desulfonylation can lead to three isomeric products, the corresponding ethylidene acetal and two regioisomeric O-vinyl ethers which are interesting chiral intermediates with a high and diversified reactivity, namely in metathesis or cycloaddition processes.13,19 It was shown that the result of ring opening clearly depends on the reductive reagent used. While sodium amalgam furnishes all three possible products in all tested cases, SmI2 on the other hand reliably effects regioselective ring opening. 4. Experimental 4.1. Methods and materials Air- and/or moisture-sensitive reactions were carried out under argon atmosphere in predried flasks, using anhydrous solvents (which were distilled when necessary according to D. D. Perrin, W. L. F. Armarego and D. R. Perrin in Purification of Laboratory Chemicals, Pergamon: Oxford, 1986). TLC on precoated aluminum-back plates (Merck Kieselgel 60F254) were visualized by UV light (254 nm) and by charring after exposure to a 10% H2SO4 solution in methanol or to a 5% solution of phosphomolybdic acid in ethanol. Flash column chromatography was carried out using Kieselgel Si 60, 40–63 μm (E. Merck). Melting points (°C) were obtained using a Büchi 510 capillary apparatus and are uncorrected. Optical rotations were measured at 20 °C with a Perkin Elmer 341 polarimeter (Na-D-line 589 nm) with a path length of 1 dm. 1H and 13C NMR spectra were recorded on a 250 MHz Bruker Avance DPX250 or a 400 MHz Bruker Avance2 instrument. Chemical shifts are expressed in parts per million (ppm) downfield from TMS internal standard and coupling constants are given in Hz. IR absorption frequencies (Thermo-Nicolet AVATAR 320 spectrometer) are given in cm−1. Mass spectra were recorded on a Perkin Elmer Sciex API 300 spectrometer for negative (ISN) and positive (ISP) electrospray ionization. High resolution mass spectra (HRMS) were recorded with a MicrOTOF-QII spectrometer in the electrospray ionization (ESI) mode or in chemical ionization (CI) mode. All PSE acetals were prepared by applying the conditions reported in Reference 3. 2-Phenylsulfonylmethylbenzo-1,3-dioxolane 3a[18554331-1] and (4R,5R)-2-phenylsulfonylmethyl-4,5-bis-methoxycarbonyl1,3-dioxolane 3b[425633-62-1] were previously described.10 Reductive desulfonylation of PSE acetals 4c (3-ethenyloxypropan-1-ol, [611822-5]) and 4d (4-ethenyloxybutan-1-ol, [17832-28-9]) was previously described.20 4.2. General procedures 4.2.1. General procedure for the reduction of PSE acetals by sodium amalgam To a dry MeOH solution (10 mL) of the PSE acetal (# 0.5 mmol), 1.2% sodium amalgam (8 g, 4.16 mmol Na, # 8 equiv) and solid phosphate buffer NaH2PO4.H2O (4 g, 29 mmol) were added. The mixture was stirred at rt while monitoring the consumption of the acetal
by TLC (4–5 h). The suspension was filtered over a Celite® pad, which was then washed with dichloromethane. The organic phase was washed with 5% aqueous NaHCO3, then dried over K2CO3 and the residue obtained after concentration under reduced pressure was purified by silica gel column chromatography (petroleum ether/EtOAc).
4.2.2. General procedure for the reduction of PSE acetals by samarium(II) iodide A dry THF solution (5 mL) of the PSE acetal (# 0.2 mmol) maintained at 0 °C was degassed by 1 h argon bubbling, then 6 equiv SmI2 (0.1 M solution in THF, 12 mL) was added dropwise, giving rise to a blue color. HMPA (0.8 mL, 23 equiv) was then added dropwise by syringe, whereupon the color of the solution turned to purple. After 1 h stirring at rt, the yellow mixture was treated by saturated aqueous NH4Cl (5 mL) then decanted; after extraction of the aqueous phase with ethyl acetate (2×), the combined organic phases were dried over MgSO4, filtered and concentrated in vacuo and the residue was purified by column chromatography.
4.2.3. General procedure for silylation according to the literature11 A regioselective silylation of the primary hydroxyl was applied when the regioisomeric vinyl ethers could not be readily separated by column chromatography. The crude mixture of vinyl ethers (1 mmol) was dissolved in dry DMF (10 mL) under argon. After cooling to 0 °C, Et3N (1 equiv.), TBDMSCl (1 equiv.) and DMAP (0.5 equiv.) were added and the mixture was then stirred 12 h at rt. The mixture was treated with cold water and diluted with EtOAc (10 mL) then decanted. The organic phase was washed with water, then dried over MgSO4; after filtration and concentration of the solution in vacuo, the residue was purified by column chromatography.
4.3. Analytical data of phenylsulfonylethylidene (PSE) acetals 4.3.1. 2-Phenylsulfonylmethyl-1,3-dioxane [425429-10-3] (3c) White crystals (91% yield), mp 85–87 °C; 1H NMR δ 1.31 (m, 1H, H-5eq), 1.99 (m, 1H, H-5ax), 3.42 (d, 2H, CH2SO2), 3.74 (dt, 2H, J = 12.3, 2.5, H-4ax, H-6ax), 4.00 (dd, 2H, J = 10.6, 4.9, H-4eq, H-6eq), 5.03 (t, 1H, Jvic = 4.9, H-2), 7.51–7.68 (m, 3H, PhSO2), 7.91 (m, 2H, orthoH-PhSO2); 13C NMR δ 25.4 (C-5), 61.0 (CH2SO2), 67.2 (C-4, C-6), 97.0 (C-2), 128.5 (CH—ortho-PhSO2), 129.3 (CH—meta-PhSO2), 134.0 (CH—para-PhSO2), 140.3 (CIV—PhSO2); MS IS m/z = 243 [M + H]+, 260 [M + NH4]+.
4.3.2. 2-Phenylsulfonylmethyl-1,3-dioxepane [425429-11-4] (3d) Colorless gum (90%); 1H NMR δ 1.66 (m, 4H, H-5, H-6), 3.43 (d, 2H, CH2SO2), 3.48 (bd, 2H, H-4b, H-7b), 3.72 (bd, 2H, H-4a, H-7a), 5.16 (t, 1H, Jvic = 5.3, H-2), 7.51–7.67 (m, 3H, PhSO2), 7.91 (m, 2H, orthoH-PhSO2); 13C NMR δ 29.1 (C-5, C-6), 59.9 (CH2SO2), 66.7 (C-4, C-7), 97.2 (C-2), 128.5 (CH—ortho-PhSO2), 129.2 (CH—meta-PhSO2), 133.8 (CH—para-PhSO2), 140.4 (CIV—PhSO2); MS IS m/z = 257 [M + H]+, 274 [M + NH4]+.
4.3.3. 2-Phenylsulfonylmethyl-4,7-dihydro-1,3-dioxepine [425429-12-5] (3e) White crystals (94% yield), mp 56–58 °C; 1H NMR δ 3.52 (d, 2H, CH2SO2), 4.05 (bd, 2H, H-4b, H-7b), 4.22 (bd, 2H, H-4a, H-7a), 5.24 (t, 1H, Jvic = 5.3, H-2), 5.63 (bs, 2H, H-5, H-6), 7.52–7.65 (m, 3H, PhSO2), 7.92 (m, 2H, ortho-H-PhSO2); 13C NMR δ 59.5 (CH2SO2), 66.0 (C-4, C-7), 98.9 (C-2), 128.5 (CH—ortho-PhSO2), 129.3 (C-5, C-6, CH—metaPhSO2), 133.9 (CH—para-PhSO2), 140.2 (CIV—PhSO2); MS IS m/z = 255 [M + H]+, 272 [M + NH4]+, 277 [M + Na]+.
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4.4. Analytical data of symmetrical vinyl ethers 4.4.1. 2-Ethenyloxyphenol [58981-47-8] (4a) Colorless syrup (90% yield); 1H NMR δ 4.50 (dd, 1H, H-2′Z), 4.80 (dd, 1H, Jgem = 2.0, H-2′E), 6.61 (dd, 1H, J1′–2′E = 13.7, J1′–2′Z = 5.9, H-1′), 6.82–7.04 (m, 4H, H—Ar); 13C NMR δ 95.9 (C-2′), 116.2, 117.1, 120.8, 124.8 (CH—Ar), 143.8, 146.7 (CIV—Ar), 148.5 (C-1′); MS IS m/z = 137 [M + H]+. IR (film): 3478 (OH), 1642, 1627 (C=C). 4.4.2. Dimethyl 2-O-ethenyl-L-tartrate [425429-15-8] (4b) Colourless syrup (72% yield); [α]D +5 (c = 7.7, CHCl3); 1H NMR δ 3.23(d, 1H, Jvic = 7.6, OH), 3.83 (s, 6H, OMe), 4.17 (dd, 1H, H-2′Z), 4.27 (dd, 1H, Jgem = 2.8, H-2′E), 4.69 (m, 2H, H-2, H-3), 4.69 (m, 2Η, Η-2,Η3), 6.37 (dd, 1H, J1′–2′E = 14.0, J1′–2′Z = 6.6, H-1′);13C NMR δ 53.0, 53.4 (OMe), 71.8 (C−3), 77.7 (C−2, 90.2 (C-2′), 150.3 (C-1′), 168.5, 171.3 (CO); MS IS m/z = 205 [M + H]+, 227 [M + Na]+. 4.4.3. (Z)-4-Ethenyloxybut-2-en-1-ol [425429-14-7] (4e) Colorless syrup (63% yield); 1H NMR δ 4.06 (dd, 1H, Jgem = 2.1, H-2′Z), 4.19–4.33 (m, 5H, H-1, H-4, H-2′E), 5.68–5.88 (m, 2H, H-2, H-3), 6.46 (dd, 1H, J1′–2′E = 14.1, J1′–2′Z = 6.8, H-1′); 13C NMR δ 58.8 (C−1), 63.9 (C−4), 87.4 (C-2′), 127.0 (C-2), 132.4 (C-3), 151.3 (C-1′); MS IS m/z = 71 [M-OCH=CH2]+. 4.5. Reductive ring cleavage of methyl 2,3-di-O-benzyl-4,6-O(2-phenylsulfonyl)ethylidene-β-D-glucopyranoside (3f)3 From 270 mg (0.5 mmol) the following were successively obtained from chromatography. 4.5.1. Methyl 2,3-di-O-benzyl-4,6-O-ethylidene-α-Dglucopyranoside [178455-78-2] (7)14 Colorless gum (70 mg, 35% yield); [α]D +15 (c 1.0, CHCl3),14 [α]D +19 (c 1.16, CHCl3)]; 1H NMR δ 1.37 (d, 3H, Jvic = 5.1, CH3CH), 3.36 (t, 1H, J4–5 = 9.4, H-4), 3.38 (s, 3H, OMe), 3.48 (t, 1H, J5–6b = 10.2, H-6b), 3.50 (dd, 1H, J2–3 = 9.4, H-2), 3.68 (ddd, 1H, J5–6a = 4.7, H-5), 3.94 (t, 1H, J3–4 = 9.4, H-3), 4.08 (dd, 1H, Jgem = 10.2, H-6a), 4.56 (d, 1H, J1–2 = 3.8, H-1), 4.67 and 4.84 (2d, AB system, 2H, Jgem = 12.3, PhCH2O), 4.71 (q, 1H, H-7), 4.82 and 4.89 (2d, AB system, 2H, Jgem = 11.3, PhCH2O), 7.26–7.42 (m, 10H, H-Ar); 13C NMR δ 20.8 (CH3CH), 55.7 (OMe), 62.7 (C-5), 68.9 (C-6), 74.1, 75.6 (2PhCH2O), 79.0 (C-3), 79.6 (C-2), 82.1 (C-4), 99.5 (C-1), 99.9 (C-7), 127.9, 128.3, 128.5, 128.7, 128.8 (CH—Ar), 138.6, 139.2 (CIV—Ar); MS IS m/z = 423.5 [M + Na]+; HRMS: C23H28O6: calcd. 400.1886; found 400.1875. 4.5.2. Methyl 2,3-di-O-benzyl-6-O-vinyl-α-D-glucopyranoside (6) Colorless gum (64 mg, 32% yield); [α]D +13 (c = 1.0, CHCl3); 1H NMR δ 3.39 (s, 3H, OMe), 3.50–3.59 (m, 1H, H-6b), 3.55 (dd, 1H, J2-3 = 9.6, H-2), 3.74–3.84 (m, 2H, H-4, H-5), 3.88–3.95 (m, 1H, H-3), 3.92 (dd, 1H, J5-6a = 2.9, Jgem = 11.1, H-6a), 4.01 (dd, 1H, J1′–2′Z = 6.8, H-2′Z), 4.22 (dd, 1H, J2′E–2′Z = 2.3, H-2′E), 4.64 (d, 1H, J1–2 = 3.6, H-1), 4.66 and 4.78 (2d, AB system, 2H, Jgem = 11.9, PhCH2O), 4.71 and 5.04 (2d, AB system, 2H, Jgem = 11.5, PhCH2O), 6.48 (dd, 1H, J1′–2′E = 14.3, H-1′), 7.31–7.38 (m, 10H, H—Ar); 13C NMR δ 55.7 (OMe), 67.4 (C-6), 69.7 (C-5), 70.2 (C-3), 73.5, 75.8 (2PhCH2O), 80.1 (C-2), 81.8 (C-4), 87.4 (C-2′), 98.6 (C-1), 128.4, 128.5, 128.9, 129.1 (CH—Ar), 138.5, 139.3 (CIV—Ar), 152.3 (C-1′); IR (film) 3489 (OH), 2997, 2938 (=CH2), 1635, 1631 (C=C), 1076, 1022, 973 (=C—OR); MS IS m/z = 401.5 [M + H]+, 423.5 [M + Na]+; HRMS: C23H28O6: calcd. 400.1886; found 400.1892. 4.5.3. Methyl 2,3-di-O-benzyl-4-O-vinyl-α-D-glucopyranoside (5) Colorless gum (54 mg, 27% yield), [α]D +66 (c = 0.6, CHCl3); 1H NMR δ 3.40 (s, 3H, OMe), 3.47 (dd, 1H, J2–3 = 9.6, H-2), 3.49 (m, 2H, H-6a, H-6b), 3.71–3.81 (m, 2H, H-4, H-5), 3.94 (dd, 1H, J3–4 = 8.3, H-3), 4.05 (dd, 1H, J1′–2′Z = 6.4, H-2′Z), 4.46 (dd, 1H, J2′E–2′Z = 1.7, H-2′E), 4.58 (d, 1H, J1–2 = 3.6, H-1), 4.66 and 4.83 (2d, AB system, 2H, Jgem = 12.1,
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PhCH2O), 4.81 (s, 2H, PhCH2O), 6.42 (dd, 1H, J1′–2′E = 13.8, H-1′), 7.30–7.41 (m, 10H, H—Ar); 13C NMR δ 55.7 (OMe), 61.7 (C-6), 70.4 (C-5), 74.0, 76.0 (2PhCH2O), 79.4 (C-4), 79.6 (C-2), 80.9 (C-3), 89.6 (C-2′), 98.7 (C-1), 128.1, 128.3, 128.5, 128.7, 128.8, 128.9 (CH-Ar), 138.5, 138.8 (2CIV—Ar), 153.1 (C-1′); IR (film): 3499 (OH), 2987, 2936 (=CH 2 ), 1637, 1621 (C=C), 1079, 1025, 978 (=C—OR); MS IS m/z = 401.5 [M + H] + , 423.5 [M + Na] + ; HRMS: C 23 H 28 O 6 : calcd. 400.1886; found 400.1880. 4.6. Reductive ring cleavage of methyl 2,3-di-O-benzyl-4,6-O(2-phenylsulfonyl)ethylidene-β-D-mannopyranoside (8)3 From 275 mg (0.51 mmol) the following were successively obtained from chromatography. 4.6.1. Methyl 2,3-di-O-benzyl-4,6-O-ethylidene-α-D-mannopyranoside Colorless gum (70 mg, 34% yield); [α]D +46 (c = 1.0, CHCl3); 1H NMR δ 1.37 (d, 3H, Jvic = 5.1, CH3CH), 3.30 (s, 3H, OMe), 3.79 (dd, 1H, J2–3 = 3.2, H-2), 3.85 (dd, 1H, J3-4 = 9.8, H-3), 3.62–3.71 (m, 2H, H-5, H-6b), 3.98–4.03 (m, 2H, H-4, H-6a), 4.62 (s, 2H, PhCH2O), 4.65 (d, 1H, J1–2 = 1.7, H-1), 4.69 and 4.78 (2d, AB system, 2H, Jgem = 12.4, PhCH2O), 4.81 (q, 1H, H-7), 7.30–7.36 (m, 10H, H—Ar); 13C NMR δ 20.8 (CH3CH), 55.0 (OMe), 64.3 (C-5), 68.6 (C-6), 73.3, 73.9 (2PhCH2O), 76.4 (C-2), 76.8 (C-3), 78.7 (C-4), 100.0 (C-7), 100.7 (C-1), 127.8, 127.9, 128.0, 128.3, 128.7 (CH—Ar), 138.6, 139.1 (CIV—Ar); MS IS m/z = 418.5 [M + NH4]+, 423.5 [M + Na]+, 439.5 [M + K]+; HRMS: C23H28O6: calcd. 400.1886; found 400.1900. 4.6.2. Methyl 2,3-di-O-benzyl-6-O-vinyl-α-D-mannopyranoside Colorless gum (33 mg, 16% yield), [α]D +11 (c = 0.7, CHCl3); 1H NMR δ 3.36 (s, 3H, OMe), 3.69 (dd, 1H, J3-4 = 9.3, H-3), 3.74–3.78 (m, 1H, H-5), 3.80 (dd, 1H, J2–3 = 3.2, H-2), 3.92 (dd, 1H, J5–6b = 6.4, Jgem = 11.1, H-6b), 3.99 (t, 1H, J4–5 = 9.3, H-4), 4.01 (dd, 1H, J1′–2′Z = 6.8, H-2′Z), 4.05 (dd, 1H, J5–6a = 2.3, H-6a), 4.25 (dd, 1H, J2′E–2′Z = 2.1, H-2′E), 4.63 and 4.71 (2d, AB system, 2H, Jgem = 12.3, PhCH2O), 4.43 and 4.85 (2d, AB system, 2H, Jgem = 11.7, PhCH2O), 4.80 (d, 1H, J1–2 = 1.7, H-1), 6.57 (dd, 1H, J1′–2′E = 14.3, H-1′), 7.28–7.37 (m, 10H, H—Ar); 13C NMR δ 55.1 (OMe), 67.2 (C-5), 68.1 (C-6), 71.1 (C-4), 71.8, 72.8 (2PhCH2O), 73.7 (C-2), 80.0 (C-3), 87.1 (C-2′), 99.4 (C-1), 127.8, 128.0, 128.2, 128.6, 128.8 (CH—Ar), 138.3, 138.4 (2CIV—Ar), 152.3 (C-1′); IR (film) 2986, 2937 (=CH2), 1636, 1623 (C=C), 1082, 1022, 968 (=C—OR); MS IS m/z = 418.5 [M + NH4]+, 423.5 [M + Na]+, 439.5 [M + K]+; HRMS: C23H28O6: calcd. 400.1886; found 400.1896. 4.6.3. Methyl 2,3-di-O-benzyl-4-O-vinyl-α-D-mannopyranoside Colorless gum (71 mg, 35% yield), [α]D +39 (c = 0.7, CHCl3); 1H NMR δ 3.31 (s, 3H, OMe), 3.64 (ddd, 1H, J5–6a = 4.3, H-5), 3.75 (dd, 1H, J5–6b = 1.7, H-6b), 3.76 (dd, 1H, J2–3 = 3.2, H-2), 3.79 (dd, 1H, Jgem = 13.1, H-6a), 3.82 (dd, 1H, J3–4 = 9.4, H-3), 4.02 (dd, 1H, J1′–2′Z = 6.2, H-2′Z), 4.19 (t, 1H, J4–5 = 9.3, H-4), 4.42 (dd, 1H, J2′E–2′Z = 1.7, H-2′E), 4.55 and 4.66 (2d, AB system, 2H, Jgem = 11.7, PhCH2O), 4.67 and 4.78 (2d, AB system, 2H, Jgem = 12.3, PhCH2O), 4.69 (d, 1H, J1–2 = 1.5, H-1), 6.47 (dd, 1H, J1′–2′E = 13.8, H-1′), 7.29–7.36 (m, 10H, H—Ar); 13C NMR δ 55.0 (OMe), 61.9 (C-6), 71.6 (C-5), 72.8, 73.2 (2PhCH2O), 75.1 (C-3), 76.7 (C-4), 78.6 (C-2), 88.9 (C-2′), 99.6 (C-1), 127.7, 127.9, 128.0, 128.3, 128.5 (CH—Ar), 138.3, 138.5 (2CIV—Ar), 153.2 (C-1′); IR (film) 2985, 2932 (=CH2), 1634, 1611 (C=C), 1082, 1019, 977 (=C—OR); MS IS m/z = 418.5 [M + NH4]+, 423.5 [M + Na]+, 439.5 [M + K]+; HRMS: C23H28O6: calcd. 400.1886; found 400.1889. 4.7. Reductive ring cleavage of methyl 2,3-di-O-benzyl-4,6-O(2-phenylsulfonyl)ethylidene-α-D-galactopyranoside (9)3 From 260 mg (0.48 mmol) the following were successively obtained from chromatography.
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4.7.1. Methyl 2,3-di-O-benzyl-6-O-vinyl-β-D-galactopyranoside Amorphous solid (58 mg, 29% yield); [α]D +7 (c = 0.8, CHCl3); 1H NMR δ 3.49–3.52 (m, 1H, H-5), 3.53 (dd, 1H, J3–4 = 3.4, H-3), 3.57 (s, 3H, OMe), 3.63 (dd, 1H, J2–3 = 9.4, H-2), 3.94 (t, 1H, J5–6b = 5.9, H-6b), 4.00 (dd, 1H, J5–6a = 1.7, Jgem = 10.5, H-6a), 4.01 (m, 1H, H-4), 4.04 (dd, 1H, J1′–2′Z =6.6, H-2′Z), 4.26 (dd, 1H, J2′E–2′Z =2.1, H-2′E), 4.29 (d, 1H, J1-2 = 7.4, H-1), 4.72 and 4.90 (2d, AB system, 2H, Jgem = 11.1, PhCH2O), 4.73 (s, 2H, PhCH2O), 6.48 (dd, 1H, J1′–2′E = 14.3, H-1′), 7.28–7.41 (m, 10H, H—Ar); 13 C NMR δ 57.5 (OMe), 67.0 (C-4), 67.3 (C-6), 72.8 (C-5), 72.9, 75.5 (2PhCH2O), 79.3 (C-2), 80.8 (C-3), 87.7 (C-2′), 105.1 (C-1), 128.1, 128.3, 128.4, 128.7, 128.9 (CH—Ar), 138.1, 139.0 (2CIV—Ar), 152.0 (C-1′); IR (film) 3500 (OH), 2977, 2931 (=CH2), 1639, 1624 (C=C), 1075, 1021, 972 (=C—OR); MS IS m/z = 418.5 [M + NH4]+, 423.5 [M + Na]+, 439.5 [M + K]+; HRMS: C23H28O6: calcd. 400.1886; found 400.1872. 4.7.2. Methyl 2,3-di-O-benzyl-4,6-O-ethylidene-β-D-galactopyranoside Colorless gum (60 mg, 31% yield); [α]D −3 (c = 1.0, CHCl3); 1H NMR δ 1.46 (d, 3H, Jvic = 5.2, CH3CH), 3.21 (ddd, 1H, J5–6a = 1.5, H-5), 3.48 (dd, 1H, J3–4 = 3.8, H-3), 3.57 (s, 3H, OMe), 3.79 (dd, 1H, J2–3 = 9.8, H-2), 3.81 (t, 1H, J5–6b = 1.9, H-6b), 3.90 (dd, 1H, J3–4 = 3.8, H-4), 4.16 (dd, 1H, Jgem = 12.3, H-6a), 4.26 (d, 1H, J1–2 = 7.7, H-1), 4.71 (q, 1H, H-7), 4.73 and 4.79 (2d, AB system, 2H, Jgem = 12.3, PhCH2O), 4.78 and 4.91 (2d, AB system, 2H, Jgem = 10.8, PhCH2O), 7.25–7.42 (m, 10H, H—Ar); 13 C NMR δ 21.5 (CH3CH), 57.5 (OMe), 66.7 (C-5), 69.1 (C-6), 72.7, 75.7 (2PhCH2O), 74.0 (C-4), 79.0 (C-2), 79.3 (C-3), 99.8 (C-7), 105.1 (C1), 127.9, 128.1, 128.3, 128.5, 128.7 (CH—Ar), 138.7, 139.3 (2CIV—Ar); MS IS m/z = 418.5 [M + NH4]+, 423.5 [M + Na]+, 439.5 [M + K]+; HRMS: C23H28O6: calcd. 400.1886; found 400.1879. 4.7.3. Methyl 2,3-di-O-benzyl-4-O-vinyl-β-D-galactopyranoside Colorless gum (54 mg, 28% yield); [α]D +26 (c = 1.0, CHCl3); 1H NMR δ 3.52 (m, 1H, H-5), 3.54 (dd, 1H, J3–4 = 2.9, H-3), 3.58 (s, 3H, OMe), 3.69 (m, 1H, H-6b), 3.72 (dd, 1H, J2–3 = 9.8, H-2), 3.83 (t, 1H, J5–6a = 1.9, Jgem = 12.5, H-6a), 4.04 (dd, 1H, J1–2′Z = 6.4, H-2′Z), 4.09 (dd, 1H, J4–5 = 0.8, H-4), 4.31 (d, 1H, J1–2 = 7.7, H-1), 4.45 (dd, 1H, J2′E–2′Z = 1.9, H-2′E), 4.71 and 4.76 (2d, AB system, 2H, Jgem = 11.9, PhCH2O), 4.74 and 4.88 (2d, AB system, 2H, Jgem = 10.8, PhCH2O), 6.39 (dd, 1H, J1′–2′E = 13.8, H-1′), 7.28–7.37 (m, 10H, H—Ar); 13C NMR δ 57.7 (OMe), 61.9 (C-6), 73.3, 75.7 (2PhCH2O), 74.7 (C-5), 75.4 (C-4), 79.9 (C-2), 80.5 (C-3), 89.1 (C-2′), 105.3 (C-1), 128.0, 128.2, 128.4, 128.7, 128.8 (CH—Ar), 138.5, 139.1 (2CIV—Ar), 153.2 (C-1′); IR (film) 3491 (OH), 2984, 2931 (=CH2), 1633, 1625 (C=C),1078, 1027, 969 (=C—OR); MS IS m/z = 418.5 [M + NH4]+, 423.5 [M + Na]+, 439.5 [M + K]+; HRMS: C23H28O6: calcd. 400.1886; found 400.1870. 4.8. Reductive ring cleavage of 1,5-anhydro-4,6-O(2-phenylsulfonyl)ethylidene-D-arabino-hex-1-enitol (10)3 From 169 mg (0.54 mmol) the following were successively obtained from chromatography. 4.8.1. 1,5-Anhydro-2-deoxy-4,6-O-ethylidene-D-arabino-hex-1-enitol Colorless gum (32.5 mg, 35% yield), [α]D −6 (c = 3.3, CHCl3); 1H NMR δ 1.36 (d, 3H, J = 4.9, CH3CH), 2.61 (d, 1H, OH), 3.56 (dd, 1H, J3–4 = 7.4, H-4), 3.57 (t, 1H, J5–6b = 10.4, H-6b), 3.75 (dt, 1H, J4–5 = 10.4, H-5), 4.17 (dd, J5–6a = 4.9, Jgem = 10.4, H-6a), 4.40 (bdd, 1H, J1–3 = 1.5, H-3), 4.72 (dd, 1H, J2–3 = 2.1, H-2), 4.78 (q, 1H, H-7), 6.28 (dd, 1H, J1–2 = 5.9, H-1); 13C NMR δ 20.5 (CH3CH), 66.7 (C-3), 67.9 (C-6), 68.5 (C-5), 80.2 (C-4), 99.7 (C-7), 103.8 (C-2), 144.2 (C-1); MS IS m/z = 173.0 [M + H] + , 195.0 [M + Na] + ; HRMS: C 8 H 12 O 4 : calcd. 172.0736; found 172.0744. 4.8.2. 1,5-Anhydro-2-deoxy-6-O-vinyl-D-arabino-hex-1-enitol Colorless gum (21 mg, 23% yield), [α]D +30 (c = 0.4, CHCl3); 1H NMR δ 3.79 (dd, 1H, J4–5 = 9.4, H-4), 3.97–4.06 (m, 3H, H-5, H-6a,
H-6b), 4.07 (dd, 1H, J1′–2′Z = 6.8, H-2′Z), 4.27 (ddd, 1H, J1–3 = 1.3, H-3), 4.28 (dd, 1H, J2′E–2′Z = 2.3, H-2′E), 4.74 (dd, 1H, J2–3 = 1.7, H-2), 6.35 (dd, 1H, J1–2 = 5.9, H-1), 6.51 (dd, 1H, J1–2′E = 14.3, H-1′); 13C NMR δ 67.0 (C-6), 70.2 (C-3), 70.5 (C-4), 76.4 (C-5), 87.7 (C-2′), 102.9 (C-2), 144.6 (C-1), 151.7 (C-1′); MS IS m/z = 173.0 [M + H]+, 195.0 [M + Na]+; IR (film) 3500 (OH), 1625, 1613 (C=C), 1013, 995 (=C—OR); HRMS: C8H12O4: calcd. 172.0736; found 172.0751. 4.8.3. 1,5-Anhydro-2-deoxy-4-O-vinyl-D-arabino-hex-1-enitol Colorless gum (19 mg, 20% yield), [α]D +13 (c = 0.8, CHCl3); 1H NMR δ 1.95 (t, 1H, OH-6), 2.28 (d, 1H, OH-3), 3.79–4.04 (m, 4H, H-4, H-5, H-6a, H-6b), 4.12 (dd, 1H, J1′–2′Z = 6.4, H-2′Z), 4.40 (m, 1H, H-3), 4.49 (dd, 1H, J2′E–2′Z = 2.2, H-2′E), 4.79 (d, 1H, J2–3 = 2.6, H-2), 6.39 (dd, 1H, J1–2 = 5.9, J1–3 = 1.3, H-1), 6.48 (dd, 1H, J1′–2′E = 13.8, H-1′); 13C NMR δ 61.4 (C-6), 67.9, 76.8, 78.0 (C-3, C-4, C-5), 90.2 (C-2′), 102.7 (C2), 144.4 (C-1), 152.1 (C-1′); IR (film) 3489 (OH), 1615, 1610 (C=C), 1023, 985 (=C—OR); MS IS m/z = 173.0 [M + H]+, 195.0 [M + Na]+; HRMS: C8H12O4: calcd. 172.0736; found 172.0733. 4.9. Reductive ring cleavage of methyl 2,3-anhydro-4,6-O(2-phenylsulfonyl)ethylidene-α-D-allopyranoside (11)3 From 171 mg (0.50 mmol) the following were successively obtained from chromatography. 4.9.1. Methyl 2,3-anhydro-4,6-O-ethylidene-α-D-allopyranoside [6958-77-6]21 Crystalline solid (34 mg, 34% yield), mp 124 °C (126–128 °C21), [α]D +72 (c = 0.7, CHCl3); 1H NMR δ 1.37 (d, 3H, Jvic = 5.1, CH3CH), 3.42–3.50 (m, 3H, H-2, H-3, H-6b), 3.44 (s, 3H, OMe), 3.72 (dd, 1H, J3–4 = 1.2, H-4), 3.91 (dt, 1H, J4–5 = 9.1, J5–6b = 10.2, H-5), 4.06 (dd, 1H, J5–6a = 4.9, Jgem = 10.2, H-6a), 4.77 (q, 1H, H-7), 4.84 (d, 1H, J1–2 = 2.3, H-1); 13C NMR δ 20.6 (CH3CH), 50.8 (C-3), 53.2 (OMe), 56.0 (C-2), 60.1 (C-5), 68.5 (C-6), 76.7 (C-4), 95.4 (C-1), 100.6 (C-7); MS IS m/z = 203.0 [M + H]+, 220.0 [M + NH4]+, 225.0 [M + Na]+; HRMS: C9H14O5: calcd. 202.0841; found 202.0829. 4.9.2. Methyl 2,3-anhydro-6-O-vinyl-α-D-allopyranoside Colorless amorphous solid (32 mg, 32% yield), [α]D +75 (c = 1.0, CHCl3); 1H NMR δ 3.46 (s, 3H, OMe), 3.50 (dd, 1H, J3–4 = 1.9, H-3), 3.59 (dd, 1H, J2–3 = 4.2, H-2), 3.78–3.84 (m, 1H, H-5), 3.93 (m, 2H, H-6a, H-6b), 4.02–4.05 (m, 1H, H-4), 4.05 (dd, 1H, J1′–2′Z = 6.8, H-2′Z), 4.25 (dd, 1H, J2′E–2′Z = 2.1, H-2′E), 4.93 (d, 1H, J1–2 = 3.2, H-1), 6.50 (dd, 1H, J1–2′E = 14.3, H-1′); 13C NMR δ 54.1 (OMe), 55.9 (C-3), 56.0 (C-2), 65.9 (C-4), 67.2 (C-6), 67.7 (C-5), 87.4 (C-2′), 94.7 (C-1), 151.8 (C1′); IR (film) 3495 (OH), 2987, 2936 (=CH2), 1637, 1621 (C=C), 1079, 1025, 978 (=C—OR); MS IS m/z = 171.0 [M-OMe]+, 203.0 [M + H]+, 220.0 [M + NH4]+, 225.0 [M + Na]+; HRMS: C9H14O5: calcd. 202.0841; found 202.0832. 4.9.3. Methyl 2,3-anhydro-6-O-tert-butyldimethylsilyl-4-Ovinyl-α-D-allopyranoside Isolated via selective 6-O-silylation from the mixture of regioisomeric alcohols (52 mg, 33% over two steps), colorless gum; [α]D +111 (c = 0.8, CHCl3); 1H NMR δ 0.09 (s, 6H, Me2Si), 1.25 (s, 9H, t-BuSi), 3.41 (dd, 1H, J2–3 = 4.2, H-2), 3.45 (s, 3H, OMe), 3.55 (dd, 1H, J3–4 = 1.4, H-3), 3.71–3.84 (m, 3H, H-5, H-6a, H-6b), 4.12 (dd, 1H, J1′–2′Z = 6.6, H-2′Z), 4.26 (dd, 1H, J4–5 = 9.1, H-4), 4.44 (dd, 1H, J2′E–2′Z = 1.9, H-2′E), 4.90 (d, 1H, J1–2 = 2.9, H-1), 6.45 (dd, 1H, J1′–2′E = 14.3, H-1′); 13 C NMR δ −4.8 (Me2Si), 18.5 (CIV—tBuSi), 26.1 (Me3CSi), 51.5 (C-3), 54.8 (C-2), 55.7 (OMe), 62.0 (C-6), 67.8 (C-5), 71.7 (C-4), 89.7 (C2′), 94.7 (C-1), 150.6 (C-1′); IR (film) 2981, 2933 (=CH2), 1632, 1623 (C=C), 1078, 1022, 977 (=C—OR); MS IS m/z = 317.5 [M + H]+, 334.5 [M + NH4]+, 339.5 [M + Na]+; HRMS: C15H28O5Si: calcd. 316.1706; found 316.1730.
F. Chéry et al./Carbohydrate Research 417 (2015) 117–124
4.10. Reductive ring cleavage of 1,2-O-isopropylidene-3,5-O(2-phenylsulfonyl)ethylidene-α-D-xylofuranose (12)3 From 178 mg (0.50 mmol) the following were successively obtained from chromatography.
4.10.1. 3,5-O-Ethylidene-1,2-O-isopropylidene-α-D-xylofuranose Colorless gum (38 mg, 35% yield), [α]D −1 (c = 1.2, CHCl3); 1H NMR δ 1.32 (d, 3H, Jvic = 5.1, CH3CH), 1.32, 1.49 (2s, 6H, Me2C), 3.93 (dd, 1H, J4–5b = 2.1, H-5b), 4.03 (dd, 1H, J4–5a < 0.5, H-4), 4.20 (bd, 1H, J3–4 = 2.3, H-3), 4.28 (d, 1H, Jgem = 13.2, H-5a), 4.54 (d, 1H, J2–3 < 0.5, H-2), 4.64 (q, 1H, H-7), 6.03 (d, 1H, J1–2 = 3.8, H-1); 13C NMR δ 20.9 (CH3CH), 26.3, 26.8 (Me2C), 66.3 (C-5), 72.2 (C-4), 78.5 (C-3), 84.0 (C-2), 97.4 (C-6), 105.7 (C-1), 112.4 (Me2C); MS IS m/z = 217.0 [M + H]+, 234.0 [M + NH4]+, 239.0 [M + Na]+; HRMS: C10H16O5: calcd. 216.0998; found 216.1005.
4.10.2. 1,2-O-Isopropylidene-5-O-vinyl-α-D-xylofuranose Colorless gum (34 mg, 32% yield), [α]D −12 (c = 1.4, CHCl3); 1H NMR δ 1.32, 1.50 (2s, 6H, Me2C), 4.04 (d, 2H, H-5a, H-5b), 4.09 (dd, 1H, J1′–2′Z = 6.8, H-2′Z), 4.25 (dd, 1H, J2′E–2′Z = 2.6, H-2′E), 4.30 (d, 1H, J3–4 = 2.6, H-3), 4.38 (m, 1H, H-4), 4.53 (d, 1H, J2–3 < 0.5, H-2), 5.96 (d, 1H, J1–2 = 3.8, H-1), 6.48 (dd, 1H, J1′–2′E = 14.3, H-1′); 13C NMR δ 26.1, 26.7 (Me2C), 65.5 (C-5), 75.5 (C-3), 77.7 (C-4), 85.2 (C-2), 87.7 (C-2′), 104.8 (C-1), 111.8 (Me2C), 151.1 (C-1′); IR (film) 3495 (OH), 2989, 2946 (=CH2), 1628 (C=C), 1081, 1032, 972 (=C—OR); MS IS m/z = 217.0 [M + H]+, 234.0 [M + NH4]+, 239.0 [M + Na]+; HRMS: C10H16O5: calcd. 216.0998; found 216.0993.
4.10.3. 5-O-tert-Butyldimethylsilyl-1,2-O-isopropylidene-3-O-vinylα-D-xylofuranose Isolated via selective 5-O-silylation from the mixture of regioisomeric alcohols (43 mg, 26% over two steps; thick syrup, [α]D −35 (c = 1.1, CHCl3); 1H NMR δ 0.05, 0.06 (2s, 6H, Me2Si), 0.88 (s, 9H, t-BuSi), 1.32, 1.52 (2s, 6H, Me2C), 3.84 (d, 2H, H-5a, H-5b), 4.12 (dd, 1H, J1′2′Z = 6.8, H-2′Z), 4.29–4.35 (m, 2H, H-3, H-4), 4.37 (d, 1H, J2′E–2′Z = 2.3, H-2′E), 4.57 (d, 1H, J2–3 < 0.5, H-2), 5.89 (d, 1H, J1–2 = 4.0, H-1), 6.36 (dd, 1H, J1–2′E = 14.3, H-1′); 13C NMR δ −4.8 (Me2Si), 18.4 (CIV—tBuSi), 26.0 (Me3CSi), 26.4, 26.9 (Me2C), 59.8 (C-5), 80.1, 80.2 (C-3, C-4), 82.2 (C-2), 89.2 (C-2′), 105.1 (C-1), 112.0 (Me2C), 150.3 (C-1′); IR (film) 2946 (=CH2), 1638, 1625 (C=C),1082, 1021, 962 (=C—OR); MS IS m/z = 331.5 [M + H]+, 348.5 [M + NH4]+, 353.5 [M + Na]+; HRMS: C16H30O5Si: calcd. 330.1863; found 330.1880.
4.11. Reductive ring cleavage of 1,2-O-isopropylidene-5,6-O(2-phenylsulfonyl)ethylidene-α-D-glucofuranoses (13)3 From 193 mg (0.50 mmol) the following were successively obtained from chromatography.
4.11.1. (7R,S)-1,2-O-Isopropylidene-5,6-O-ethylidene-α-D -glucofuranoses Colorless gum (33 mg, 27% yield, 2:1 C-7 epimeric ratio), [α]D −12 (c = 1.4, CHCl3); 1H NMR δ 1.31, 1.49 (2s, 6H, Me2C), 1.36 (d, Jvic = 5.1, CH3CHmajor), 1.39 (d, Jvic = 5.1, CH3CHminor), 2.60 (m, 1H, OH3), 3.86 (dd, J5–6b = 6.2, Jgem = 8.1, H-6bmajor), 3.98 (dd, J5–6b = 6.8, Jgem = 8.7, H-6bminor), 4.02–4.08 (m, H-3, H-6aminor), 4.11 (dd, J5–6a = 2.8, H-6amajor), 4.22–4.36 (m, 2H, H-4, H-5), 4.53 (d, 1H, J2–3 < 0.5, H-2), 5.00 (q, H-7minor), 5.16 (q, H-7major), 5.93 (d, 1H, J1–2 = 3.6, H-1); 13C NMR δ 19.9, 20.1 (CH3CH), 26.3, 26.4, 26.9 (Me2C), 68.6, 69.0 (C-6), 72.9, 73.6, 75.1, 75.2 (C-4, C-5), 81.0, 81.5 (C-3), 85.2 (C-2), 102.1, 102.2 (C-7), 105.3,
123
105.4 (C-1), 112.0 (Me 2 C); MS IS m/z = 247.0 [M + H] + , 264.0 [M + NH4]+, 269.0 [M + Na]+; HRMS: C11H18O6: calcd. 246.1103; found 246.1111. 4.11.2. 1,2-O-Isopropylidene-6-O-vinyl-α-D-glucofuranose Colorless gum (37 mg, 30% yield), [α]D −10 (c = 1.4, CHCl3); 1H NMR δ 1.32, 1.49 (2s, 6H, Me2C), 2.85, 3.20 (2m, OH-3, OH-5), 3.84 (dd, 1H, J5–6b = 6.2, Jgem = 10.2, H-6b), 3.98 (dd, 1H, J5–6a = 3.2, H-6a), 3.99–4.06 (m, 2H, H-3, H-5), 4.09 (dd, 1H, J1′–2′Z = 6.8, H-2′Z), 4.12 (dd, 1H, J3–4 = 2.7, J4–5 = 6.6, H-4), 4.27 (dd, 1H, J2′E–2′Z = 2.3, H-2′E), 4.55 (d, 1H, J2–3 < 0.5, H-2), 5.97 (d, 1H, J1–2 = 3.6, H-1), 6.50 (dd, 1H, J1′–2′E = 14.3, H-1′); 13C NMR δ 26.3, 26.9 (Me2C), 68.6 (C-4), 69.2 (C-6), 75.8, 79.6 (C-3, C-5), 85.2 (C-2), 87.8 (C-2′), 105.3 (C-1), 112.0 (Me2C), 151.4 (C-1′); IR (film) 3499 (OH), 2977, 2938 (=CH2), 1635, 1619 (C=C), 1075, 1025, 971 (=C—OR); MS IS m/z = 247.0 [M + H] + , 264.0 [M + NH4]+, 269.0 [M + Na]+; HRMS: C11H18O6: calcd. 246.1103; found 246.1112. 4.11.3. 1,2-O-Isopropylidene-6-O-tert-butyldimethylsilyl-5-O-vinylα-D-glucofuranose Isolated via selective 6-O-silylation from the mixture of regioisomeric alcohols (51 mg, 28% over two steps; colorless gum, [α]D −4 (c = 2.0, CHCl3); 1H NMR δ 0.07 (s, 6H, Me2Si), 0.90 (s, 9H, t-BuSi), 1.31, 1.48 (2s, 6H, Me2C), 3.07 (d, 1H, J3-OH = 3.8, OH-3), 3.73–3.76 (m, 1H, H-5), 3.77 (dd, 1H, J5–6b = 4.7, H-6b), 3.94 (dd, 1H, J 5–6a = 4.2, J gem = 11.1, H-6a), 4.06 (dd, 1H, J 1′–2′Z = 6.6, H-2′ Z ), 4.19–4.32 (m, 2H, H-3, H-4), 4.37 (dd, 1H, J2′E–2′Z = 2.3, H-2′E), 4.51 (d, 1H, J2–3 < 0.5, H-2), 5.93 (d, 1H, J1–2 = 3.8, H-1), 6.37 (dd, 1H, J1′–2′E = 14.3, H-1′); 13C NMR δ −4.7 (Me2Si), 18.4 (CIV—tBuSi), 26.2 (Me3CSi), 26.6, 27.1 (Me2C), 62.7 (C-6), 75.4, 76.2 (C-4, C-5), 79.1 (C3), 85.3 (C-2), 89.8 (C-2′), 105.0 (C-1), 112.0 (Me2C), 151.6 (C-1′); IR (film) 2978, 2931 (=CH2), 1625 (C=C), 1078, 1025, 973 (=C—OR); MS IS m/z = 361.5 [M + H]+, 378.5 [M + NH4]+, 383.5 [M + Na]+; HRMS: C17H32O6Si: calcd. 360.1968; found 360.1987. 4.12. Reductive ring cleavage of 3-O-benzyl-1,2-O-isopropylidene5,6-O-(2-phenylsulfonyl)ethylidene-α-D-glucofuranoses (14)3 From 238 mg (0.50 mmol) the following were successively obtained from chromatography. 4.12.1. (7R,S)-3-O-Benzyl-1,2-O-isopropylidene-5,6-O-ethylideneα-D-glucofuranoses Colorless gum (47 mg, 28% yield, 1:1 C-7 epimeric ratio), [α]D −25 (c = 1.1, CHCl3); 1H NMR δ 1.31, 1.49 (2s, 6H, Me2C), 1.36, 1.39 (2d, Jvic = 5.2, CH3CH), 3.89–4.40 (m, 5H, H-3, H-4, H-5, H-6a, H-6b), 4.57–4.67 (m, 3H, PhCH2O, H-2), 5.02, 5.14 (2q, H-7), 5.91 (d, J1–2 = 3.8, H-1); 13C NMR δ 20.0, 20.1 (CH3CH), 26.4, 27.0 (Me2C), 68.2 (C-6), 72.4, 72.5 (C-5), 72.6, 73.0 (PhCH2O), 81.3, 81.4, 81.7, 81.9, 82.6, 82.8 (C-2, C-3, C-4), 101.6, 101.9 (C-7), 105.4 (C-1), 112.0 (Me2C ), 127.7, 127.8, 128.0, 128.1, 128.6, (CH—Ar), 137.6, 137.8 (CIV—Ar); MS IS m/z = 337.5 [M + H] + , 359.5 [M + Na] + ; HRMS: C 18 H 24 O 6 : calcd. 336.1573; found 336.1583. 4.12.2. 3-O-Benzyl-1,2-O-isopropylidene-6-O-vinyl-α-Dglucofuranose Colorless gum (45 mg, 27% yield), [α]D −31 (c = 1.2, CHCl3); 1H NMR δ 1.33, 1.49 (2s, 6H, Me2C), 3.78 (d, 1H, J5–6b = 5.9, H-6b), 3.94 (dd, 1H, J5–6a =2.9, Jgem = 10.2, H-6a), 4.03 (dd, 1H, J1′–2′Z =6.8, H-2′Z), 4.13–4.17 (m, 3H, H-3, H-4, H-5), 4.23 (dd, 1H, J2′E–2′Z = 2.1, H-2′E), 4.59 and 4.73 (2d, AB system, 2H, Jgem = 11.7, PhCH2O), 4.63 (d, 1H, J2–3 < 0.5, H-2), 5.94 (d, 1H, J1–2 = 3.8, H-1), 6.48 (dd, 1H, J1′–2′E = 14.5, H-1′), 7.31–7.38 (m, 5H, H—Ar); 13C NMR δ 26.9, 27.4 (Me2C), 68.4 (C-5), 70.5 (C-6), 72.9
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(PhCH2O), 80.2, 82.6 (C-3, C-4), 82.8 (C-2), 87.9 (C-2′), 105.8 (C-1), 112.5 (Me2C), 128.6, 128.8, 129.3 (CH—Ar), 137.8 (CIV—Ar), 152.2 (C1′); MS IS m/z = 337.5 [M + H]+, 359.5 [M + Na]+; IR (film) 3500 (OH), 3068, 3025, 2992 (CH—Ar, = CH), 1614, 1611 (C=C), 1026, 987 (=C—OR); HRMS: C18H24O6: calcd. 336.1573; found 336.1579.
4.12.3. 3-O-Benzyl-1,2-O-isopropylidene-5-O-vinyl-α-Dglucofuranose Colorless gum (47 mg, 28% yield), [α]D −27 (c = 1.1, CHCl3); 1H NMR δ 1.28, 1.45 (2s, 6H, Me2C), 3.74 (d, 1H, J5–6b = 5.3, H-6b), 3.95 (dd, 1H, Jgem = 12.6, H-6a), 3.96 (d, 1H, J3–4 = 2.8, H-3), 4.09 (dd, 1H, J1′–2′Z = 6.8, H-2′Z), 4.26 (dd, 1H, J4–5 = 8.9, H-4), 4.28 (dd, 1H, J2′E–2′Z = 2.6, H-2′E), 4.38 (ddd, 1H, J5–6a = 2.6, H-5), 4.51 and 4.55 (2d, AB system, 2H, Jgem = 11.8, PhCH2O), 4.61 (d, 1H, J2–3 < 0.5, H-2), 5.87 (d, 1H, J1–2 = 3.6, H-1), 6.48 (dd, 1H, J1′–2′E = 14.3, H-1′), 7.30–7.41 (m, 5H, H—Ar); 13C NMR δ 26.4, 27.0 (Me2C), 62.9 (C-6), 72.5 (PhCH2O), 78.3 (C-4), 81.3 (C-3), 81.7, 81.8 (C-2, C-5), 89.8 (C-2′), 105.4 (C-1), 112.1 (Me2C), 127.7, 128.0, 128.1, 128.4 (CH—Ar), 137.8 (CIV—Ar), 151.3 (C1′); IR (film) 3493 (OH), 3068, 3020, 2990 (CH—Ar, =CH), 1625, 1610 (C=C), 1024, 983 (=C—OR); MS IS m/z = 337.5 [M + H]+, 359.5 [M + Na]+; HRMS: C18H24O6: calcd. 336.1573; found 336.1588. Acknowledgements Thisbe K. Lindhorst thanks the ICOA for support of her sabbatical stay at the Université d’Orléans.
References 1. De Lucchi O, Pasquato L, Rollin P, Tatibouët A. 1,2-bis(phenylsulfonyl)ethylene. In: e-EROS encyclopedia of reagents for organic synthesis. New York: John Wiley & Sons, Inc.; 2005 doi:10.1002/047084289X.rb183. 2. Cabianca E, Chéry F, Rollin P, Tatibouët A, De Lucchi O. Tetrahedron Lett 2002;43:585–7. And references cited therein. 3. Chéry F, Rollin P, De Lucchi O, Cossu S. Synthesis 2001;286–92. 4. Chevalier-du Roizel B, Cabianca E, Rollin P, Sinaÿ P. Tetrahedron 2002;58:9579–83. 5. Cabianca E, Tatibouët A, Rollin P. Polish J Chem 2005;79:317–22. 6. Uttaro JP, Uttaro L, Tatibouët A, Rollin P, Mathé C, Périgaud C. Tetrahedron Lett 2007;48:3851–4. 7. Fernandes A, Dell’Olmo M, Tatibouët A, Imberty A, Philouze C, Rollin P. Tetrahedron Lett 2008;49:3484–8. 8. Gabrielli G, Melani F, Bernasconi S, Lunghi C, Richichi B, Rollin P, et al. J Carbohydr Chem 2009;28:124–41. 9. Grossert JS. Patai S, Rappoport Z, Stirling CJM, editors. The chemistry of sulphones and sulphoxides. Chichester: John Wiley & Sons; 1988 [chapter 20]. 10. Cossu S, De Lucchi O, Fabris F, Ballini R, Bosica G. Synthesis 1996;1481–4. 11. Chéry F, Cabianca E, Tatibouët A, De Lucchi O, Rollin P. Tetrahedron 2012;68:544– 51. 12. Cabianca E, Chéry F, Rollin P, Cossu S, De Lucchi O. Synlett 2001;1962–3. 13. Chéry F, Desroses M, Tatibouët A, De Lucchi O, Rollin P. Tetrahedron 2003;59:4563–72. 14. Hajko J, Szabovik G, Kerekgyarto J, Kajtar M, Liptak A. Aust J Chem 1996;49:357– 63. 15. Brown AC, Carpino LA. J Org Chem 1985;50:1749–50. 16. Künzer H, Stahnke M, Sauer G, Wiechert R. Tetrahedron Lett 1991;32:1949–52. 17. de Pouilly P, Chénedé A, Malet JM, Sinaÿ P. Bull Soc Chim Fr 1993;130:256–65. 18. Skrydstrup T, Mazéas D, Elmouchir M, Doisneau G, Riche C, Chiaroni A, et al. Chem Eur J 1997;3:1342–56. 19. Desroses M, Chéry F, Tatibouët A, De Lucchi O, Rollin P. Tetrahedron Asymmetry 2002;13:2535–9. 20. Bailey WF, Punzalan ER, Zarcone LMJ. Heteroat Chem 1992;3:55–61. 21. Goodman L, Christensen JB. J Org Chem 1963;28:158–64.
Contents lists available at ScienceDirect
Carbohydrate Research j o u r n a l h o m e p a g e : w w w. e l s e v i e r. c o m / l o c a t e / c a r r e s
Reductive opening of carbohydrate phenylsulfonylethylidene (PSE) acetals Florence Chéry a, Elena Cabianca a,b, Arnaud Tatibouët a, Ottorino De Lucchi b, Thisbe K. Lindhorst c, Patrick Rollin a,* a
Université d’Orléans et CNRS, ICOA, UMR 7311, BP 6759, F-45067 Orléans, France Dipartimento di Chimica, Università Ca’Foscari di Venezia, Dorsoduro 2137, I-30123 Venezia, Italy c Otto Diels Institute of Organic Chemistry, Christiana Albertina University of Kiel, Otto-Hahn-Platz 3/4, D-24118 Kiel, Germany b
A R T I C L E
I N F O
Article history: Received 16 July 2015 Received in revised form 20 September 2015 Accepted 21 September 2015 Available online 26 September 2015 Keywords: Carbohydrate protecting groups Sulfones Phenylsulfonylethylidene (PSE) acetals Reductive desulfonylation SET Vinyl ethers
A B S T R A C T
The phenylsulfonylethylidene (PSE) acetal is a relatively new protecting group in carbohydrate chemistry. However, carbohydrate-derived phenylsulfonylethylidene (PSE) acetals show a different behavior in reductive desulfonylation than simple symmetrical acetals. Here we have investigated various SET-type reaction conditions in order to open PSE acetals regioselectively and to produce chiral ω-hydroxyethenyl ethers. Whereas sodium amalgam leads to a mixture of regioisomeric vinyl ethers besides the ethylidene acetal, samarium iodide is suited for regioselective ring opening. This is shown with seven different carbohydrate PSE acetals, both of the 1,3-dioxane and the 1,3-dioxolane type. © 2015 Elsevier Ltd. All rights reserved.
1. Introduction In previous times, we have introduced a new protecting group in carbohydrate chemistry, namely the phenylsulfonylethylidene (PSE) acetal. PSE acetals (Scheme 1, 3) are readily accessible by reacting a diol of choice (1) with 1,2-bis(phenylsulfonyl)ethylene (2),1 a conversion that proceeds according to a double Michael addition pathway with extrusion of a sulfinate. Whereas at first, this procedure was applied to a number of symmetrical non-carbohydrate substrates (1a–e),2 it has later on been extended to numerous glycosides, such as glucopyranoside 1f,3 and thus the PSE protecting group has found a variety of applications in the field of carbohydratebased synthetic methodology.4–8 In a subsequent step, PSE acetals can be converted into ω-hydroxyethenyl ethers (4). This is effected by elimination of a sulfonyl group through reductive cleavage of the C—S bond, a step well known in the chemistry of sulfones.9 In introductory work, we have disclosed an efficient procedure for the conversion of symmetrical cyclic PSE acetals such as 3a–e 2,10 into the corresponding ω-hydroxyethenyl ethers 4a–e2 (Fig. 1). Employment of sodium
* Corresponding author. Université d’Orléans et CNRS, ICOA, UMR 7311, BP 6759, F-45067 Orléans, France. Tel.: +33 238 417 370; fax: +33 238 417 281. E-mail address: [email protected] (P. Rollin). http://dx.doi.org/10.1016/j.carres.2015.09.011 0008-6215/© 2015 Elsevier Ltd. All rights reserved.
amalgam in anhydrous methanol gave the desulfonylated products in yields between 48% and 90%. Contrary to our expectation, ethylidene acetals were not formed and this reduction step. The PSE acetals 3a–3e, derived from catechol (1a), (R,R)-tartrate (1b), propane-1,3-diol (1c), butane-1,4-diol (1d) and (Z)-but-2-ene1,4-diol (1e) were obtained as reported earlier.2,10 Full analytical details of 3c–3e (Fig. 1) are reported in this account (cf. Section 4). Reductive ring opening led to ω-hydroxyethenyl ethers 4a–4e (Fig. 1) in 48%–90%.2 As shown in Scheme 1, the methyl glucoside 1f resembles a diol substructure similar to the symmetrical compound 1c. Thus, in our earlier work, the corresponding PSE acetal 3f3 was investigated toward its stability under various reaction conditions. It was found to be stable against triisobutylaluminum (TIBAL)4 and DDQ5 and to be inert under acidic conditions.3 On the contrary, it undergoes cleavage under strongly reductive conditions (LiAlH4).3 Under protic conditions, treatment with base (e.g. KOH) restores the respective starting material (1) and aprotic strongly basic conditions (n-BuLi in THF) lead to primary and secondary alkoxyvinyl sulfones depending on whether pyranosides or furanosides were employed.11 However, desulfonylation did not occur under the latter conditions. Here it has been our goal to test reductive ring opening conditions for desulfonylation with unsymmetrical carbohydrate PSE acetals having in mind a novel access to carbohydrate-based O-vinylated species.
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Scheme 1. Two-step procedure to access ω-hydroxyethenyl ethers (4): diols (1) react with 1,2-bis(phenylsulfonyl)ethylene to give PSE acetals (3), which undergo reductive ring opening.
2. Results and discussion Various reaction conditions were tried for reductive desulfonylation of the 4,6-acetal substructure in methyl 2,3-di-Obenzyl-4,6-O-(2-phenylsulfonyl)ethylidene-α-d-glucopyranoside 3f, resembling an unsymmetrical PSE acetal. Typically, metal amalgams can be employed in this case to effect PSE reduction according to a single electron transfer (SET) mechanism. Thus, according to our standard conditions,2,12,13 3f was first treated with sodium amalgam in anhydrous methanol in the presence of solid phosphate buffer NaH2PO4. Contrary to 3a–3e, ring opening of the PSEprotected glucoside 3f leads to two regioisomeric products. In addition, the corresponding ethylidene acetal was obtained in this case. Hence, after chromatographic purification, the regioisomeric 4-O- and 6-O-vinyl ethers 5 and 6 were isolated in 27% and 35% respective yields, together with the ethylidene acetal 714 in 32% (Scheme 2). Thus apparently, opening of phenylsulfonylethylidene acetals in carbohydrates is less straightforward than in the case of the symmetrical PSE acetals 3a–3e. In order to improve PSE ring opening, first the Na/Hg reduction protocol was varied. Some of these attempts are collected in Table 1 and show that optimization of the sodium amalgam-mediated reduction did not lead to satisfactory results. The overall yields were always excellent, but in all cases, the reaction led to the regioisomeric vinyl ethers together with the ethylidene acetal. These three isomeric
products were regularly obtained in a ratio around 1:1:1. This mixture could be separated by column chromatography but nevertheless we sought for an improved method for PSE cleavage. Magnesium in methanol has been described in the literature as substitute for sodium amalgam in desulfonylation reactions:15 it was therefore tested next, albeit without appreciable benefit. In contrast, the use of samarium(II) iodide16 was found suited to reduce the number of isomeric products to two. Thus, reductive desulfonylation of 3f with SmI2 according to conditions developed by Sinaÿ17 and Beau18 gave rise to the 4-O-vinyl ether 5 as the only ring opening product and to the ethylidene acetal 7 in equimolar amounts (Table 1). The regioselectivity observed in the ring opening reaction with samarium(II) iodide might be due to an intermediate organosamarium species that exclusively opens to the 4-Ovinyl ether (rather than the 6-O-vinyl ether). With sodium or magnesium, the situation must be different, as with these metals both regioisomeric ring opening products are obtained. Reductive desulfonylation with SmI2 is based on a single electron transfer (SET) process in which, according to the literature,17,18 one electron is transferred to the LUMO of the phenyl sulfone I (Scheme 3). Thus, after extrusion of a sulfinate, a transient radical II is formed which in turn can add SmI2 to form an intermediate organosamarium species III, that generates the ethylidene acetal IV (such as 7) after protonation. On the other hand, homolytic dissociation of the acetal C—O bond, α-positioned to the radical center,
Fig. 1. Structures of symmetrical PSE acetals 3a–3f and of the hydroxyvinyl ethers 4a–4f.
Scheme 2. Reductive ring opening of the PSE acetal 3f leads to the three isomeric products 5, 6, and 7.
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Scheme 3. Through a SET process SmI2 converts PSE acetals into ethylidene acetals and by regioselective ring opening into 4-O-vinyl ethers.
Table 1 Reductive opening of PSE acetal 3f (cf. Scheme 2) Reaction conditions
5
6
7
Total yield
Na/Hg, MeOH, NaH2PO4, rt Na/Hg, MeOH, NaH2PO4, 50 °C Na/Hg, MeOH/THF 1:1, NaH2PO4, rt Na/Hg, MeOH, rt, no buffer Mg, MeOH SmI2, THF/HMPA 20:1, rt
35% 39% 40% 35% 25% 35%
27% 29% 28% 32% 25% —
32% 29% 29% 27% 29% 35%
94% 97% 97% 94% 79% 70%
Table 2 Reductive opening of PSE acetals 8–14 (cf. Scheme 4) PSE acetal 8 9 10 11 12 13 14
Reaction conditions
Prim. O-vinyl
Sec. O-vinyl
Ethylidene
Total yield
Na/Hg SmI2 Na/Hg SmI2 Na/Hg Na/Hg SmI2 Na/Hg SmI2 Na/Hg SmI2 Na/Hg SmI2
12% — 29% — 22% 32% — 26% — 29% — 27% —
35% 41% 27% 40% 20% 33% 44% 32% 30% 28% 35% 28% 48%
34% 41% 30% 40% 35% 34% 40% 35% 30% 27% 35% 28% 48%
81% 82% 86% 80% 77% 99% 84% 93% 60% 84% 70% 83% 96%
can furnish V, finally leading to the corresponding γ-hydroxyethenyl ether VI (such as 5). However, a conclusive mechanistic rational about the fact that the 6-O-vinyl ring opening product is not observed in this reaction cannot be provided at this stage. It might be suggested that regioselective samarium complexation involving the endocyclic ring oxygen is the basis of the observed selectivity. In the next step it was important to test the optimized Na/Hg protocol as well as the SmI2 procedure with various saccharidic PSE acetals as it is typical that the chemistry of carbohydrates varies considerably depending on their configuration. Thus, the glucoside 3f was supplemented by the analogous mannoside 8,3 the galactoside 9,3 furthermore, more ring-strained sugars, the glucal 103 and the epoxide 11,3 were tested, followed by the 1,2-O-isopropylidene3,5-O-(2-phenylsulfonyl)ethylidene-α-d-xylofuranose 123 and the glucofuranose derivatives 133 and 143 (Scheme 2). This small library of acetals resembles a collection of PSE 1,3-dioxanes and 1,3dioxolanes. The results of the Na/Hg as well as the SmI2 reduction protocol are collected in Table 2. The tested PSE acetals (Scheme 4) behave all very similar in SETtype reductive desulfonylation providing good to excellent overall yields. Again, sodium amalgam leads to three isomeric products in almost similar amounts (Table 2). Only the mannoside 8 delivers more than double the amount of the secondary 4-O-vinyl ether than that of the primary 6-O-vinyl ether. This might arise from the axially positioned 2-hydroxyl group that could add to complexation of
Scheme 4. A collection of structurally varied carbohydrate-derived PSE acetals, 8–14, were tested in reductive desulfonylation employing two different SET-type reaction conditions. Three different isomeric products can be obtained, the primary or secondary O-vinyl ether, respectively, or the ethylidene acetal. For yields and ratios cf. Table 2.
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sodium amalgam at the β-face of the sugar ring, thus facilitating regioselective ring opening in favor of the 4-O-vinyl ether. With SmI2, in all tested cases the primary vinyl ether was not observed. The regioselectivity of this ring opening reaction seems not to be guided by the carbohydrate ring template of the PSE acetal that is used as starting material. This underlines again that the samarium-mediated regioselective ring opening of asymmetrical PSE acetals is a reaction of wide applicability in sugar chemistry. 3. Conclusion While the benzylidene acetal is a well established and versatile protecting group in carbohydrate chemistry, PSE acetals are relatively new and far less explored. Here we have investigated a total of eight PSE acetals derived from structurally varied carbohydrates. SET-type desulfonylation can lead to three isomeric products, the corresponding ethylidene acetal and two regioisomeric O-vinyl ethers which are interesting chiral intermediates with a high and diversified reactivity, namely in metathesis or cycloaddition processes.13,19 It was shown that the result of ring opening clearly depends on the reductive reagent used. While sodium amalgam furnishes all three possible products in all tested cases, SmI2 on the other hand reliably effects regioselective ring opening. 4. Experimental 4.1. Methods and materials Air- and/or moisture-sensitive reactions were carried out under argon atmosphere in predried flasks, using anhydrous solvents (which were distilled when necessary according to D. D. Perrin, W. L. F. Armarego and D. R. Perrin in Purification of Laboratory Chemicals, Pergamon: Oxford, 1986). TLC on precoated aluminum-back plates (Merck Kieselgel 60F254) were visualized by UV light (254 nm) and by charring after exposure to a 10% H2SO4 solution in methanol or to a 5% solution of phosphomolybdic acid in ethanol. Flash column chromatography was carried out using Kieselgel Si 60, 40–63 μm (E. Merck). Melting points (°C) were obtained using a Büchi 510 capillary apparatus and are uncorrected. Optical rotations were measured at 20 °C with a Perkin Elmer 341 polarimeter (Na-D-line 589 nm) with a path length of 1 dm. 1H and 13C NMR spectra were recorded on a 250 MHz Bruker Avance DPX250 or a 400 MHz Bruker Avance2 instrument. Chemical shifts are expressed in parts per million (ppm) downfield from TMS internal standard and coupling constants are given in Hz. IR absorption frequencies (Thermo-Nicolet AVATAR 320 spectrometer) are given in cm−1. Mass spectra were recorded on a Perkin Elmer Sciex API 300 spectrometer for negative (ISN) and positive (ISP) electrospray ionization. High resolution mass spectra (HRMS) were recorded with a MicrOTOF-QII spectrometer in the electrospray ionization (ESI) mode or in chemical ionization (CI) mode. All PSE acetals were prepared by applying the conditions reported in Reference 3. 2-Phenylsulfonylmethylbenzo-1,3-dioxolane 3a[18554331-1] and (4R,5R)-2-phenylsulfonylmethyl-4,5-bis-methoxycarbonyl1,3-dioxolane 3b[425633-62-1] were previously described.10 Reductive desulfonylation of PSE acetals 4c (3-ethenyloxypropan-1-ol, [611822-5]) and 4d (4-ethenyloxybutan-1-ol, [17832-28-9]) was previously described.20 4.2. General procedures 4.2.1. General procedure for the reduction of PSE acetals by sodium amalgam To a dry MeOH solution (10 mL) of the PSE acetal (# 0.5 mmol), 1.2% sodium amalgam (8 g, 4.16 mmol Na, # 8 equiv) and solid phosphate buffer NaH2PO4.H2O (4 g, 29 mmol) were added. The mixture was stirred at rt while monitoring the consumption of the acetal
by TLC (4–5 h). The suspension was filtered over a Celite® pad, which was then washed with dichloromethane. The organic phase was washed with 5% aqueous NaHCO3, then dried over K2CO3 and the residue obtained after concentration under reduced pressure was purified by silica gel column chromatography (petroleum ether/EtOAc).
4.2.2. General procedure for the reduction of PSE acetals by samarium(II) iodide A dry THF solution (5 mL) of the PSE acetal (# 0.2 mmol) maintained at 0 °C was degassed by 1 h argon bubbling, then 6 equiv SmI2 (0.1 M solution in THF, 12 mL) was added dropwise, giving rise to a blue color. HMPA (0.8 mL, 23 equiv) was then added dropwise by syringe, whereupon the color of the solution turned to purple. After 1 h stirring at rt, the yellow mixture was treated by saturated aqueous NH4Cl (5 mL) then decanted; after extraction of the aqueous phase with ethyl acetate (2×), the combined organic phases were dried over MgSO4, filtered and concentrated in vacuo and the residue was purified by column chromatography.
4.2.3. General procedure for silylation according to the literature11 A regioselective silylation of the primary hydroxyl was applied when the regioisomeric vinyl ethers could not be readily separated by column chromatography. The crude mixture of vinyl ethers (1 mmol) was dissolved in dry DMF (10 mL) under argon. After cooling to 0 °C, Et3N (1 equiv.), TBDMSCl (1 equiv.) and DMAP (0.5 equiv.) were added and the mixture was then stirred 12 h at rt. The mixture was treated with cold water and diluted with EtOAc (10 mL) then decanted. The organic phase was washed with water, then dried over MgSO4; after filtration and concentration of the solution in vacuo, the residue was purified by column chromatography.
4.3. Analytical data of phenylsulfonylethylidene (PSE) acetals 4.3.1. 2-Phenylsulfonylmethyl-1,3-dioxane [425429-10-3] (3c) White crystals (91% yield), mp 85–87 °C; 1H NMR δ 1.31 (m, 1H, H-5eq), 1.99 (m, 1H, H-5ax), 3.42 (d, 2H, CH2SO2), 3.74 (dt, 2H, J = 12.3, 2.5, H-4ax, H-6ax), 4.00 (dd, 2H, J = 10.6, 4.9, H-4eq, H-6eq), 5.03 (t, 1H, Jvic = 4.9, H-2), 7.51–7.68 (m, 3H, PhSO2), 7.91 (m, 2H, orthoH-PhSO2); 13C NMR δ 25.4 (C-5), 61.0 (CH2SO2), 67.2 (C-4, C-6), 97.0 (C-2), 128.5 (CH—ortho-PhSO2), 129.3 (CH—meta-PhSO2), 134.0 (CH—para-PhSO2), 140.3 (CIV—PhSO2); MS IS m/z = 243 [M + H]+, 260 [M + NH4]+.
4.3.2. 2-Phenylsulfonylmethyl-1,3-dioxepane [425429-11-4] (3d) Colorless gum (90%); 1H NMR δ 1.66 (m, 4H, H-5, H-6), 3.43 (d, 2H, CH2SO2), 3.48 (bd, 2H, H-4b, H-7b), 3.72 (bd, 2H, H-4a, H-7a), 5.16 (t, 1H, Jvic = 5.3, H-2), 7.51–7.67 (m, 3H, PhSO2), 7.91 (m, 2H, orthoH-PhSO2); 13C NMR δ 29.1 (C-5, C-6), 59.9 (CH2SO2), 66.7 (C-4, C-7), 97.2 (C-2), 128.5 (CH—ortho-PhSO2), 129.2 (CH—meta-PhSO2), 133.8 (CH—para-PhSO2), 140.4 (CIV—PhSO2); MS IS m/z = 257 [M + H]+, 274 [M + NH4]+.
4.3.3. 2-Phenylsulfonylmethyl-4,7-dihydro-1,3-dioxepine [425429-12-5] (3e) White crystals (94% yield), mp 56–58 °C; 1H NMR δ 3.52 (d, 2H, CH2SO2), 4.05 (bd, 2H, H-4b, H-7b), 4.22 (bd, 2H, H-4a, H-7a), 5.24 (t, 1H, Jvic = 5.3, H-2), 5.63 (bs, 2H, H-5, H-6), 7.52–7.65 (m, 3H, PhSO2), 7.92 (m, 2H, ortho-H-PhSO2); 13C NMR δ 59.5 (CH2SO2), 66.0 (C-4, C-7), 98.9 (C-2), 128.5 (CH—ortho-PhSO2), 129.3 (C-5, C-6, CH—metaPhSO2), 133.9 (CH—para-PhSO2), 140.2 (CIV—PhSO2); MS IS m/z = 255 [M + H]+, 272 [M + NH4]+, 277 [M + Na]+.
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4.4. Analytical data of symmetrical vinyl ethers 4.4.1. 2-Ethenyloxyphenol [58981-47-8] (4a) Colorless syrup (90% yield); 1H NMR δ 4.50 (dd, 1H, H-2′Z), 4.80 (dd, 1H, Jgem = 2.0, H-2′E), 6.61 (dd, 1H, J1′–2′E = 13.7, J1′–2′Z = 5.9, H-1′), 6.82–7.04 (m, 4H, H—Ar); 13C NMR δ 95.9 (C-2′), 116.2, 117.1, 120.8, 124.8 (CH—Ar), 143.8, 146.7 (CIV—Ar), 148.5 (C-1′); MS IS m/z = 137 [M + H]+. IR (film): 3478 (OH), 1642, 1627 (C=C). 4.4.2. Dimethyl 2-O-ethenyl-L-tartrate [425429-15-8] (4b) Colourless syrup (72% yield); [α]D +5 (c = 7.7, CHCl3); 1H NMR δ 3.23(d, 1H, Jvic = 7.6, OH), 3.83 (s, 6H, OMe), 4.17 (dd, 1H, H-2′Z), 4.27 (dd, 1H, Jgem = 2.8, H-2′E), 4.69 (m, 2H, H-2, H-3), 4.69 (m, 2Η, Η-2,Η3), 6.37 (dd, 1H, J1′–2′E = 14.0, J1′–2′Z = 6.6, H-1′);13C NMR δ 53.0, 53.4 (OMe), 71.8 (C−3), 77.7 (C−2, 90.2 (C-2′), 150.3 (C-1′), 168.5, 171.3 (CO); MS IS m/z = 205 [M + H]+, 227 [M + Na]+. 4.4.3. (Z)-4-Ethenyloxybut-2-en-1-ol [425429-14-7] (4e) Colorless syrup (63% yield); 1H NMR δ 4.06 (dd, 1H, Jgem = 2.1, H-2′Z), 4.19–4.33 (m, 5H, H-1, H-4, H-2′E), 5.68–5.88 (m, 2H, H-2, H-3), 6.46 (dd, 1H, J1′–2′E = 14.1, J1′–2′Z = 6.8, H-1′); 13C NMR δ 58.8 (C−1), 63.9 (C−4), 87.4 (C-2′), 127.0 (C-2), 132.4 (C-3), 151.3 (C-1′); MS IS m/z = 71 [M-OCH=CH2]+. 4.5. Reductive ring cleavage of methyl 2,3-di-O-benzyl-4,6-O(2-phenylsulfonyl)ethylidene-β-D-glucopyranoside (3f)3 From 270 mg (0.5 mmol) the following were successively obtained from chromatography. 4.5.1. Methyl 2,3-di-O-benzyl-4,6-O-ethylidene-α-Dglucopyranoside [178455-78-2] (7)14 Colorless gum (70 mg, 35% yield); [α]D +15 (c 1.0, CHCl3),14 [α]D +19 (c 1.16, CHCl3)]; 1H NMR δ 1.37 (d, 3H, Jvic = 5.1, CH3CH), 3.36 (t, 1H, J4–5 = 9.4, H-4), 3.38 (s, 3H, OMe), 3.48 (t, 1H, J5–6b = 10.2, H-6b), 3.50 (dd, 1H, J2–3 = 9.4, H-2), 3.68 (ddd, 1H, J5–6a = 4.7, H-5), 3.94 (t, 1H, J3–4 = 9.4, H-3), 4.08 (dd, 1H, Jgem = 10.2, H-6a), 4.56 (d, 1H, J1–2 = 3.8, H-1), 4.67 and 4.84 (2d, AB system, 2H, Jgem = 12.3, PhCH2O), 4.71 (q, 1H, H-7), 4.82 and 4.89 (2d, AB system, 2H, Jgem = 11.3, PhCH2O), 7.26–7.42 (m, 10H, H-Ar); 13C NMR δ 20.8 (CH3CH), 55.7 (OMe), 62.7 (C-5), 68.9 (C-6), 74.1, 75.6 (2PhCH2O), 79.0 (C-3), 79.6 (C-2), 82.1 (C-4), 99.5 (C-1), 99.9 (C-7), 127.9, 128.3, 128.5, 128.7, 128.8 (CH—Ar), 138.6, 139.2 (CIV—Ar); MS IS m/z = 423.5 [M + Na]+; HRMS: C23H28O6: calcd. 400.1886; found 400.1875. 4.5.2. Methyl 2,3-di-O-benzyl-6-O-vinyl-α-D-glucopyranoside (6) Colorless gum (64 mg, 32% yield); [α]D +13 (c = 1.0, CHCl3); 1H NMR δ 3.39 (s, 3H, OMe), 3.50–3.59 (m, 1H, H-6b), 3.55 (dd, 1H, J2-3 = 9.6, H-2), 3.74–3.84 (m, 2H, H-4, H-5), 3.88–3.95 (m, 1H, H-3), 3.92 (dd, 1H, J5-6a = 2.9, Jgem = 11.1, H-6a), 4.01 (dd, 1H, J1′–2′Z = 6.8, H-2′Z), 4.22 (dd, 1H, J2′E–2′Z = 2.3, H-2′E), 4.64 (d, 1H, J1–2 = 3.6, H-1), 4.66 and 4.78 (2d, AB system, 2H, Jgem = 11.9, PhCH2O), 4.71 and 5.04 (2d, AB system, 2H, Jgem = 11.5, PhCH2O), 6.48 (dd, 1H, J1′–2′E = 14.3, H-1′), 7.31–7.38 (m, 10H, H—Ar); 13C NMR δ 55.7 (OMe), 67.4 (C-6), 69.7 (C-5), 70.2 (C-3), 73.5, 75.8 (2PhCH2O), 80.1 (C-2), 81.8 (C-4), 87.4 (C-2′), 98.6 (C-1), 128.4, 128.5, 128.9, 129.1 (CH—Ar), 138.5, 139.3 (CIV—Ar), 152.3 (C-1′); IR (film) 3489 (OH), 2997, 2938 (=CH2), 1635, 1631 (C=C), 1076, 1022, 973 (=C—OR); MS IS m/z = 401.5 [M + H]+, 423.5 [M + Na]+; HRMS: C23H28O6: calcd. 400.1886; found 400.1892. 4.5.3. Methyl 2,3-di-O-benzyl-4-O-vinyl-α-D-glucopyranoside (5) Colorless gum (54 mg, 27% yield), [α]D +66 (c = 0.6, CHCl3); 1H NMR δ 3.40 (s, 3H, OMe), 3.47 (dd, 1H, J2–3 = 9.6, H-2), 3.49 (m, 2H, H-6a, H-6b), 3.71–3.81 (m, 2H, H-4, H-5), 3.94 (dd, 1H, J3–4 = 8.3, H-3), 4.05 (dd, 1H, J1′–2′Z = 6.4, H-2′Z), 4.46 (dd, 1H, J2′E–2′Z = 1.7, H-2′E), 4.58 (d, 1H, J1–2 = 3.6, H-1), 4.66 and 4.83 (2d, AB system, 2H, Jgem = 12.1,
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PhCH2O), 4.81 (s, 2H, PhCH2O), 6.42 (dd, 1H, J1′–2′E = 13.8, H-1′), 7.30–7.41 (m, 10H, H—Ar); 13C NMR δ 55.7 (OMe), 61.7 (C-6), 70.4 (C-5), 74.0, 76.0 (2PhCH2O), 79.4 (C-4), 79.6 (C-2), 80.9 (C-3), 89.6 (C-2′), 98.7 (C-1), 128.1, 128.3, 128.5, 128.7, 128.8, 128.9 (CH-Ar), 138.5, 138.8 (2CIV—Ar), 153.1 (C-1′); IR (film): 3499 (OH), 2987, 2936 (=CH 2 ), 1637, 1621 (C=C), 1079, 1025, 978 (=C—OR); MS IS m/z = 401.5 [M + H] + , 423.5 [M + Na] + ; HRMS: C 23 H 28 O 6 : calcd. 400.1886; found 400.1880. 4.6. Reductive ring cleavage of methyl 2,3-di-O-benzyl-4,6-O(2-phenylsulfonyl)ethylidene-β-D-mannopyranoside (8)3 From 275 mg (0.51 mmol) the following were successively obtained from chromatography. 4.6.1. Methyl 2,3-di-O-benzyl-4,6-O-ethylidene-α-D-mannopyranoside Colorless gum (70 mg, 34% yield); [α]D +46 (c = 1.0, CHCl3); 1H NMR δ 1.37 (d, 3H, Jvic = 5.1, CH3CH), 3.30 (s, 3H, OMe), 3.79 (dd, 1H, J2–3 = 3.2, H-2), 3.85 (dd, 1H, J3-4 = 9.8, H-3), 3.62–3.71 (m, 2H, H-5, H-6b), 3.98–4.03 (m, 2H, H-4, H-6a), 4.62 (s, 2H, PhCH2O), 4.65 (d, 1H, J1–2 = 1.7, H-1), 4.69 and 4.78 (2d, AB system, 2H, Jgem = 12.4, PhCH2O), 4.81 (q, 1H, H-7), 7.30–7.36 (m, 10H, H—Ar); 13C NMR δ 20.8 (CH3CH), 55.0 (OMe), 64.3 (C-5), 68.6 (C-6), 73.3, 73.9 (2PhCH2O), 76.4 (C-2), 76.8 (C-3), 78.7 (C-4), 100.0 (C-7), 100.7 (C-1), 127.8, 127.9, 128.0, 128.3, 128.7 (CH—Ar), 138.6, 139.1 (CIV—Ar); MS IS m/z = 418.5 [M + NH4]+, 423.5 [M + Na]+, 439.5 [M + K]+; HRMS: C23H28O6: calcd. 400.1886; found 400.1900. 4.6.2. Methyl 2,3-di-O-benzyl-6-O-vinyl-α-D-mannopyranoside Colorless gum (33 mg, 16% yield), [α]D +11 (c = 0.7, CHCl3); 1H NMR δ 3.36 (s, 3H, OMe), 3.69 (dd, 1H, J3-4 = 9.3, H-3), 3.74–3.78 (m, 1H, H-5), 3.80 (dd, 1H, J2–3 = 3.2, H-2), 3.92 (dd, 1H, J5–6b = 6.4, Jgem = 11.1, H-6b), 3.99 (t, 1H, J4–5 = 9.3, H-4), 4.01 (dd, 1H, J1′–2′Z = 6.8, H-2′Z), 4.05 (dd, 1H, J5–6a = 2.3, H-6a), 4.25 (dd, 1H, J2′E–2′Z = 2.1, H-2′E), 4.63 and 4.71 (2d, AB system, 2H, Jgem = 12.3, PhCH2O), 4.43 and 4.85 (2d, AB system, 2H, Jgem = 11.7, PhCH2O), 4.80 (d, 1H, J1–2 = 1.7, H-1), 6.57 (dd, 1H, J1′–2′E = 14.3, H-1′), 7.28–7.37 (m, 10H, H—Ar); 13C NMR δ 55.1 (OMe), 67.2 (C-5), 68.1 (C-6), 71.1 (C-4), 71.8, 72.8 (2PhCH2O), 73.7 (C-2), 80.0 (C-3), 87.1 (C-2′), 99.4 (C-1), 127.8, 128.0, 128.2, 128.6, 128.8 (CH—Ar), 138.3, 138.4 (2CIV—Ar), 152.3 (C-1′); IR (film) 2986, 2937 (=CH2), 1636, 1623 (C=C), 1082, 1022, 968 (=C—OR); MS IS m/z = 418.5 [M + NH4]+, 423.5 [M + Na]+, 439.5 [M + K]+; HRMS: C23H28O6: calcd. 400.1886; found 400.1896. 4.6.3. Methyl 2,3-di-O-benzyl-4-O-vinyl-α-D-mannopyranoside Colorless gum (71 mg, 35% yield), [α]D +39 (c = 0.7, CHCl3); 1H NMR δ 3.31 (s, 3H, OMe), 3.64 (ddd, 1H, J5–6a = 4.3, H-5), 3.75 (dd, 1H, J5–6b = 1.7, H-6b), 3.76 (dd, 1H, J2–3 = 3.2, H-2), 3.79 (dd, 1H, Jgem = 13.1, H-6a), 3.82 (dd, 1H, J3–4 = 9.4, H-3), 4.02 (dd, 1H, J1′–2′Z = 6.2, H-2′Z), 4.19 (t, 1H, J4–5 = 9.3, H-4), 4.42 (dd, 1H, J2′E–2′Z = 1.7, H-2′E), 4.55 and 4.66 (2d, AB system, 2H, Jgem = 11.7, PhCH2O), 4.67 and 4.78 (2d, AB system, 2H, Jgem = 12.3, PhCH2O), 4.69 (d, 1H, J1–2 = 1.5, H-1), 6.47 (dd, 1H, J1′–2′E = 13.8, H-1′), 7.29–7.36 (m, 10H, H—Ar); 13C NMR δ 55.0 (OMe), 61.9 (C-6), 71.6 (C-5), 72.8, 73.2 (2PhCH2O), 75.1 (C-3), 76.7 (C-4), 78.6 (C-2), 88.9 (C-2′), 99.6 (C-1), 127.7, 127.9, 128.0, 128.3, 128.5 (CH—Ar), 138.3, 138.5 (2CIV—Ar), 153.2 (C-1′); IR (film) 2985, 2932 (=CH2), 1634, 1611 (C=C), 1082, 1019, 977 (=C—OR); MS IS m/z = 418.5 [M + NH4]+, 423.5 [M + Na]+, 439.5 [M + K]+; HRMS: C23H28O6: calcd. 400.1886; found 400.1889. 4.7. Reductive ring cleavage of methyl 2,3-di-O-benzyl-4,6-O(2-phenylsulfonyl)ethylidene-α-D-galactopyranoside (9)3 From 260 mg (0.48 mmol) the following were successively obtained from chromatography.
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4.7.1. Methyl 2,3-di-O-benzyl-6-O-vinyl-β-D-galactopyranoside Amorphous solid (58 mg, 29% yield); [α]D +7 (c = 0.8, CHCl3); 1H NMR δ 3.49–3.52 (m, 1H, H-5), 3.53 (dd, 1H, J3–4 = 3.4, H-3), 3.57 (s, 3H, OMe), 3.63 (dd, 1H, J2–3 = 9.4, H-2), 3.94 (t, 1H, J5–6b = 5.9, H-6b), 4.00 (dd, 1H, J5–6a = 1.7, Jgem = 10.5, H-6a), 4.01 (m, 1H, H-4), 4.04 (dd, 1H, J1′–2′Z =6.6, H-2′Z), 4.26 (dd, 1H, J2′E–2′Z =2.1, H-2′E), 4.29 (d, 1H, J1-2 = 7.4, H-1), 4.72 and 4.90 (2d, AB system, 2H, Jgem = 11.1, PhCH2O), 4.73 (s, 2H, PhCH2O), 6.48 (dd, 1H, J1′–2′E = 14.3, H-1′), 7.28–7.41 (m, 10H, H—Ar); 13 C NMR δ 57.5 (OMe), 67.0 (C-4), 67.3 (C-6), 72.8 (C-5), 72.9, 75.5 (2PhCH2O), 79.3 (C-2), 80.8 (C-3), 87.7 (C-2′), 105.1 (C-1), 128.1, 128.3, 128.4, 128.7, 128.9 (CH—Ar), 138.1, 139.0 (2CIV—Ar), 152.0 (C-1′); IR (film) 3500 (OH), 2977, 2931 (=CH2), 1639, 1624 (C=C), 1075, 1021, 972 (=C—OR); MS IS m/z = 418.5 [M + NH4]+, 423.5 [M + Na]+, 439.5 [M + K]+; HRMS: C23H28O6: calcd. 400.1886; found 400.1872. 4.7.2. Methyl 2,3-di-O-benzyl-4,6-O-ethylidene-β-D-galactopyranoside Colorless gum (60 mg, 31% yield); [α]D −3 (c = 1.0, CHCl3); 1H NMR δ 1.46 (d, 3H, Jvic = 5.2, CH3CH), 3.21 (ddd, 1H, J5–6a = 1.5, H-5), 3.48 (dd, 1H, J3–4 = 3.8, H-3), 3.57 (s, 3H, OMe), 3.79 (dd, 1H, J2–3 = 9.8, H-2), 3.81 (t, 1H, J5–6b = 1.9, H-6b), 3.90 (dd, 1H, J3–4 = 3.8, H-4), 4.16 (dd, 1H, Jgem = 12.3, H-6a), 4.26 (d, 1H, J1–2 = 7.7, H-1), 4.71 (q, 1H, H-7), 4.73 and 4.79 (2d, AB system, 2H, Jgem = 12.3, PhCH2O), 4.78 and 4.91 (2d, AB system, 2H, Jgem = 10.8, PhCH2O), 7.25–7.42 (m, 10H, H—Ar); 13 C NMR δ 21.5 (CH3CH), 57.5 (OMe), 66.7 (C-5), 69.1 (C-6), 72.7, 75.7 (2PhCH2O), 74.0 (C-4), 79.0 (C-2), 79.3 (C-3), 99.8 (C-7), 105.1 (C1), 127.9, 128.1, 128.3, 128.5, 128.7 (CH—Ar), 138.7, 139.3 (2CIV—Ar); MS IS m/z = 418.5 [M + NH4]+, 423.5 [M + Na]+, 439.5 [M + K]+; HRMS: C23H28O6: calcd. 400.1886; found 400.1879. 4.7.3. Methyl 2,3-di-O-benzyl-4-O-vinyl-β-D-galactopyranoside Colorless gum (54 mg, 28% yield); [α]D +26 (c = 1.0, CHCl3); 1H NMR δ 3.52 (m, 1H, H-5), 3.54 (dd, 1H, J3–4 = 2.9, H-3), 3.58 (s, 3H, OMe), 3.69 (m, 1H, H-6b), 3.72 (dd, 1H, J2–3 = 9.8, H-2), 3.83 (t, 1H, J5–6a = 1.9, Jgem = 12.5, H-6a), 4.04 (dd, 1H, J1–2′Z = 6.4, H-2′Z), 4.09 (dd, 1H, J4–5 = 0.8, H-4), 4.31 (d, 1H, J1–2 = 7.7, H-1), 4.45 (dd, 1H, J2′E–2′Z = 1.9, H-2′E), 4.71 and 4.76 (2d, AB system, 2H, Jgem = 11.9, PhCH2O), 4.74 and 4.88 (2d, AB system, 2H, Jgem = 10.8, PhCH2O), 6.39 (dd, 1H, J1′–2′E = 13.8, H-1′), 7.28–7.37 (m, 10H, H—Ar); 13C NMR δ 57.7 (OMe), 61.9 (C-6), 73.3, 75.7 (2PhCH2O), 74.7 (C-5), 75.4 (C-4), 79.9 (C-2), 80.5 (C-3), 89.1 (C-2′), 105.3 (C-1), 128.0, 128.2, 128.4, 128.7, 128.8 (CH—Ar), 138.5, 139.1 (2CIV—Ar), 153.2 (C-1′); IR (film) 3491 (OH), 2984, 2931 (=CH2), 1633, 1625 (C=C),1078, 1027, 969 (=C—OR); MS IS m/z = 418.5 [M + NH4]+, 423.5 [M + Na]+, 439.5 [M + K]+; HRMS: C23H28O6: calcd. 400.1886; found 400.1870. 4.8. Reductive ring cleavage of 1,5-anhydro-4,6-O(2-phenylsulfonyl)ethylidene-D-arabino-hex-1-enitol (10)3 From 169 mg (0.54 mmol) the following were successively obtained from chromatography. 4.8.1. 1,5-Anhydro-2-deoxy-4,6-O-ethylidene-D-arabino-hex-1-enitol Colorless gum (32.5 mg, 35% yield), [α]D −6 (c = 3.3, CHCl3); 1H NMR δ 1.36 (d, 3H, J = 4.9, CH3CH), 2.61 (d, 1H, OH), 3.56 (dd, 1H, J3–4 = 7.4, H-4), 3.57 (t, 1H, J5–6b = 10.4, H-6b), 3.75 (dt, 1H, J4–5 = 10.4, H-5), 4.17 (dd, J5–6a = 4.9, Jgem = 10.4, H-6a), 4.40 (bdd, 1H, J1–3 = 1.5, H-3), 4.72 (dd, 1H, J2–3 = 2.1, H-2), 4.78 (q, 1H, H-7), 6.28 (dd, 1H, J1–2 = 5.9, H-1); 13C NMR δ 20.5 (CH3CH), 66.7 (C-3), 67.9 (C-6), 68.5 (C-5), 80.2 (C-4), 99.7 (C-7), 103.8 (C-2), 144.2 (C-1); MS IS m/z = 173.0 [M + H] + , 195.0 [M + Na] + ; HRMS: C 8 H 12 O 4 : calcd. 172.0736; found 172.0744. 4.8.2. 1,5-Anhydro-2-deoxy-6-O-vinyl-D-arabino-hex-1-enitol Colorless gum (21 mg, 23% yield), [α]D +30 (c = 0.4, CHCl3); 1H NMR δ 3.79 (dd, 1H, J4–5 = 9.4, H-4), 3.97–4.06 (m, 3H, H-5, H-6a,
H-6b), 4.07 (dd, 1H, J1′–2′Z = 6.8, H-2′Z), 4.27 (ddd, 1H, J1–3 = 1.3, H-3), 4.28 (dd, 1H, J2′E–2′Z = 2.3, H-2′E), 4.74 (dd, 1H, J2–3 = 1.7, H-2), 6.35 (dd, 1H, J1–2 = 5.9, H-1), 6.51 (dd, 1H, J1–2′E = 14.3, H-1′); 13C NMR δ 67.0 (C-6), 70.2 (C-3), 70.5 (C-4), 76.4 (C-5), 87.7 (C-2′), 102.9 (C-2), 144.6 (C-1), 151.7 (C-1′); MS IS m/z = 173.0 [M + H]+, 195.0 [M + Na]+; IR (film) 3500 (OH), 1625, 1613 (C=C), 1013, 995 (=C—OR); HRMS: C8H12O4: calcd. 172.0736; found 172.0751. 4.8.3. 1,5-Anhydro-2-deoxy-4-O-vinyl-D-arabino-hex-1-enitol Colorless gum (19 mg, 20% yield), [α]D +13 (c = 0.8, CHCl3); 1H NMR δ 1.95 (t, 1H, OH-6), 2.28 (d, 1H, OH-3), 3.79–4.04 (m, 4H, H-4, H-5, H-6a, H-6b), 4.12 (dd, 1H, J1′–2′Z = 6.4, H-2′Z), 4.40 (m, 1H, H-3), 4.49 (dd, 1H, J2′E–2′Z = 2.2, H-2′E), 4.79 (d, 1H, J2–3 = 2.6, H-2), 6.39 (dd, 1H, J1–2 = 5.9, J1–3 = 1.3, H-1), 6.48 (dd, 1H, J1′–2′E = 13.8, H-1′); 13C NMR δ 61.4 (C-6), 67.9, 76.8, 78.0 (C-3, C-4, C-5), 90.2 (C-2′), 102.7 (C2), 144.4 (C-1), 152.1 (C-1′); IR (film) 3489 (OH), 1615, 1610 (C=C), 1023, 985 (=C—OR); MS IS m/z = 173.0 [M + H]+, 195.0 [M + Na]+; HRMS: C8H12O4: calcd. 172.0736; found 172.0733. 4.9. Reductive ring cleavage of methyl 2,3-anhydro-4,6-O(2-phenylsulfonyl)ethylidene-α-D-allopyranoside (11)3 From 171 mg (0.50 mmol) the following were successively obtained from chromatography. 4.9.1. Methyl 2,3-anhydro-4,6-O-ethylidene-α-D-allopyranoside [6958-77-6]21 Crystalline solid (34 mg, 34% yield), mp 124 °C (126–128 °C21), [α]D +72 (c = 0.7, CHCl3); 1H NMR δ 1.37 (d, 3H, Jvic = 5.1, CH3CH), 3.42–3.50 (m, 3H, H-2, H-3, H-6b), 3.44 (s, 3H, OMe), 3.72 (dd, 1H, J3–4 = 1.2, H-4), 3.91 (dt, 1H, J4–5 = 9.1, J5–6b = 10.2, H-5), 4.06 (dd, 1H, J5–6a = 4.9, Jgem = 10.2, H-6a), 4.77 (q, 1H, H-7), 4.84 (d, 1H, J1–2 = 2.3, H-1); 13C NMR δ 20.6 (CH3CH), 50.8 (C-3), 53.2 (OMe), 56.0 (C-2), 60.1 (C-5), 68.5 (C-6), 76.7 (C-4), 95.4 (C-1), 100.6 (C-7); MS IS m/z = 203.0 [M + H]+, 220.0 [M + NH4]+, 225.0 [M + Na]+; HRMS: C9H14O5: calcd. 202.0841; found 202.0829. 4.9.2. Methyl 2,3-anhydro-6-O-vinyl-α-D-allopyranoside Colorless amorphous solid (32 mg, 32% yield), [α]D +75 (c = 1.0, CHCl3); 1H NMR δ 3.46 (s, 3H, OMe), 3.50 (dd, 1H, J3–4 = 1.9, H-3), 3.59 (dd, 1H, J2–3 = 4.2, H-2), 3.78–3.84 (m, 1H, H-5), 3.93 (m, 2H, H-6a, H-6b), 4.02–4.05 (m, 1H, H-4), 4.05 (dd, 1H, J1′–2′Z = 6.8, H-2′Z), 4.25 (dd, 1H, J2′E–2′Z = 2.1, H-2′E), 4.93 (d, 1H, J1–2 = 3.2, H-1), 6.50 (dd, 1H, J1–2′E = 14.3, H-1′); 13C NMR δ 54.1 (OMe), 55.9 (C-3), 56.0 (C-2), 65.9 (C-4), 67.2 (C-6), 67.7 (C-5), 87.4 (C-2′), 94.7 (C-1), 151.8 (C1′); IR (film) 3495 (OH), 2987, 2936 (=CH2), 1637, 1621 (C=C), 1079, 1025, 978 (=C—OR); MS IS m/z = 171.0 [M-OMe]+, 203.0 [M + H]+, 220.0 [M + NH4]+, 225.0 [M + Na]+; HRMS: C9H14O5: calcd. 202.0841; found 202.0832. 4.9.3. Methyl 2,3-anhydro-6-O-tert-butyldimethylsilyl-4-Ovinyl-α-D-allopyranoside Isolated via selective 6-O-silylation from the mixture of regioisomeric alcohols (52 mg, 33% over two steps), colorless gum; [α]D +111 (c = 0.8, CHCl3); 1H NMR δ 0.09 (s, 6H, Me2Si), 1.25 (s, 9H, t-BuSi), 3.41 (dd, 1H, J2–3 = 4.2, H-2), 3.45 (s, 3H, OMe), 3.55 (dd, 1H, J3–4 = 1.4, H-3), 3.71–3.84 (m, 3H, H-5, H-6a, H-6b), 4.12 (dd, 1H, J1′–2′Z = 6.6, H-2′Z), 4.26 (dd, 1H, J4–5 = 9.1, H-4), 4.44 (dd, 1H, J2′E–2′Z = 1.9, H-2′E), 4.90 (d, 1H, J1–2 = 2.9, H-1), 6.45 (dd, 1H, J1′–2′E = 14.3, H-1′); 13 C NMR δ −4.8 (Me2Si), 18.5 (CIV—tBuSi), 26.1 (Me3CSi), 51.5 (C-3), 54.8 (C-2), 55.7 (OMe), 62.0 (C-6), 67.8 (C-5), 71.7 (C-4), 89.7 (C2′), 94.7 (C-1), 150.6 (C-1′); IR (film) 2981, 2933 (=CH2), 1632, 1623 (C=C), 1078, 1022, 977 (=C—OR); MS IS m/z = 317.5 [M + H]+, 334.5 [M + NH4]+, 339.5 [M + Na]+; HRMS: C15H28O5Si: calcd. 316.1706; found 316.1730.
F. Chéry et al./Carbohydrate Research 417 (2015) 117–124
4.10. Reductive ring cleavage of 1,2-O-isopropylidene-3,5-O(2-phenylsulfonyl)ethylidene-α-D-xylofuranose (12)3 From 178 mg (0.50 mmol) the following were successively obtained from chromatography.
4.10.1. 3,5-O-Ethylidene-1,2-O-isopropylidene-α-D-xylofuranose Colorless gum (38 mg, 35% yield), [α]D −1 (c = 1.2, CHCl3); 1H NMR δ 1.32 (d, 3H, Jvic = 5.1, CH3CH), 1.32, 1.49 (2s, 6H, Me2C), 3.93 (dd, 1H, J4–5b = 2.1, H-5b), 4.03 (dd, 1H, J4–5a < 0.5, H-4), 4.20 (bd, 1H, J3–4 = 2.3, H-3), 4.28 (d, 1H, Jgem = 13.2, H-5a), 4.54 (d, 1H, J2–3 < 0.5, H-2), 4.64 (q, 1H, H-7), 6.03 (d, 1H, J1–2 = 3.8, H-1); 13C NMR δ 20.9 (CH3CH), 26.3, 26.8 (Me2C), 66.3 (C-5), 72.2 (C-4), 78.5 (C-3), 84.0 (C-2), 97.4 (C-6), 105.7 (C-1), 112.4 (Me2C); MS IS m/z = 217.0 [M + H]+, 234.0 [M + NH4]+, 239.0 [M + Na]+; HRMS: C10H16O5: calcd. 216.0998; found 216.1005.
4.10.2. 1,2-O-Isopropylidene-5-O-vinyl-α-D-xylofuranose Colorless gum (34 mg, 32% yield), [α]D −12 (c = 1.4, CHCl3); 1H NMR δ 1.32, 1.50 (2s, 6H, Me2C), 4.04 (d, 2H, H-5a, H-5b), 4.09 (dd, 1H, J1′–2′Z = 6.8, H-2′Z), 4.25 (dd, 1H, J2′E–2′Z = 2.6, H-2′E), 4.30 (d, 1H, J3–4 = 2.6, H-3), 4.38 (m, 1H, H-4), 4.53 (d, 1H, J2–3 < 0.5, H-2), 5.96 (d, 1H, J1–2 = 3.8, H-1), 6.48 (dd, 1H, J1′–2′E = 14.3, H-1′); 13C NMR δ 26.1, 26.7 (Me2C), 65.5 (C-5), 75.5 (C-3), 77.7 (C-4), 85.2 (C-2), 87.7 (C-2′), 104.8 (C-1), 111.8 (Me2C), 151.1 (C-1′); IR (film) 3495 (OH), 2989, 2946 (=CH2), 1628 (C=C), 1081, 1032, 972 (=C—OR); MS IS m/z = 217.0 [M + H]+, 234.0 [M + NH4]+, 239.0 [M + Na]+; HRMS: C10H16O5: calcd. 216.0998; found 216.0993.
4.10.3. 5-O-tert-Butyldimethylsilyl-1,2-O-isopropylidene-3-O-vinylα-D-xylofuranose Isolated via selective 5-O-silylation from the mixture of regioisomeric alcohols (43 mg, 26% over two steps; thick syrup, [α]D −35 (c = 1.1, CHCl3); 1H NMR δ 0.05, 0.06 (2s, 6H, Me2Si), 0.88 (s, 9H, t-BuSi), 1.32, 1.52 (2s, 6H, Me2C), 3.84 (d, 2H, H-5a, H-5b), 4.12 (dd, 1H, J1′2′Z = 6.8, H-2′Z), 4.29–4.35 (m, 2H, H-3, H-4), 4.37 (d, 1H, J2′E–2′Z = 2.3, H-2′E), 4.57 (d, 1H, J2–3 < 0.5, H-2), 5.89 (d, 1H, J1–2 = 4.0, H-1), 6.36 (dd, 1H, J1–2′E = 14.3, H-1′); 13C NMR δ −4.8 (Me2Si), 18.4 (CIV—tBuSi), 26.0 (Me3CSi), 26.4, 26.9 (Me2C), 59.8 (C-5), 80.1, 80.2 (C-3, C-4), 82.2 (C-2), 89.2 (C-2′), 105.1 (C-1), 112.0 (Me2C), 150.3 (C-1′); IR (film) 2946 (=CH2), 1638, 1625 (C=C),1082, 1021, 962 (=C—OR); MS IS m/z = 331.5 [M + H]+, 348.5 [M + NH4]+, 353.5 [M + Na]+; HRMS: C16H30O5Si: calcd. 330.1863; found 330.1880.
4.11. Reductive ring cleavage of 1,2-O-isopropylidene-5,6-O(2-phenylsulfonyl)ethylidene-α-D-glucofuranoses (13)3 From 193 mg (0.50 mmol) the following were successively obtained from chromatography.
4.11.1. (7R,S)-1,2-O-Isopropylidene-5,6-O-ethylidene-α-D -glucofuranoses Colorless gum (33 mg, 27% yield, 2:1 C-7 epimeric ratio), [α]D −12 (c = 1.4, CHCl3); 1H NMR δ 1.31, 1.49 (2s, 6H, Me2C), 1.36 (d, Jvic = 5.1, CH3CHmajor), 1.39 (d, Jvic = 5.1, CH3CHminor), 2.60 (m, 1H, OH3), 3.86 (dd, J5–6b = 6.2, Jgem = 8.1, H-6bmajor), 3.98 (dd, J5–6b = 6.8, Jgem = 8.7, H-6bminor), 4.02–4.08 (m, H-3, H-6aminor), 4.11 (dd, J5–6a = 2.8, H-6amajor), 4.22–4.36 (m, 2H, H-4, H-5), 4.53 (d, 1H, J2–3 < 0.5, H-2), 5.00 (q, H-7minor), 5.16 (q, H-7major), 5.93 (d, 1H, J1–2 = 3.6, H-1); 13C NMR δ 19.9, 20.1 (CH3CH), 26.3, 26.4, 26.9 (Me2C), 68.6, 69.0 (C-6), 72.9, 73.6, 75.1, 75.2 (C-4, C-5), 81.0, 81.5 (C-3), 85.2 (C-2), 102.1, 102.2 (C-7), 105.3,
123
105.4 (C-1), 112.0 (Me 2 C); MS IS m/z = 247.0 [M + H] + , 264.0 [M + NH4]+, 269.0 [M + Na]+; HRMS: C11H18O6: calcd. 246.1103; found 246.1111. 4.11.2. 1,2-O-Isopropylidene-6-O-vinyl-α-D-glucofuranose Colorless gum (37 mg, 30% yield), [α]D −10 (c = 1.4, CHCl3); 1H NMR δ 1.32, 1.49 (2s, 6H, Me2C), 2.85, 3.20 (2m, OH-3, OH-5), 3.84 (dd, 1H, J5–6b = 6.2, Jgem = 10.2, H-6b), 3.98 (dd, 1H, J5–6a = 3.2, H-6a), 3.99–4.06 (m, 2H, H-3, H-5), 4.09 (dd, 1H, J1′–2′Z = 6.8, H-2′Z), 4.12 (dd, 1H, J3–4 = 2.7, J4–5 = 6.6, H-4), 4.27 (dd, 1H, J2′E–2′Z = 2.3, H-2′E), 4.55 (d, 1H, J2–3 < 0.5, H-2), 5.97 (d, 1H, J1–2 = 3.6, H-1), 6.50 (dd, 1H, J1′–2′E = 14.3, H-1′); 13C NMR δ 26.3, 26.9 (Me2C), 68.6 (C-4), 69.2 (C-6), 75.8, 79.6 (C-3, C-5), 85.2 (C-2), 87.8 (C-2′), 105.3 (C-1), 112.0 (Me2C), 151.4 (C-1′); IR (film) 3499 (OH), 2977, 2938 (=CH2), 1635, 1619 (C=C), 1075, 1025, 971 (=C—OR); MS IS m/z = 247.0 [M + H] + , 264.0 [M + NH4]+, 269.0 [M + Na]+; HRMS: C11H18O6: calcd. 246.1103; found 246.1112. 4.11.3. 1,2-O-Isopropylidene-6-O-tert-butyldimethylsilyl-5-O-vinylα-D-glucofuranose Isolated via selective 6-O-silylation from the mixture of regioisomeric alcohols (51 mg, 28% over two steps; colorless gum, [α]D −4 (c = 2.0, CHCl3); 1H NMR δ 0.07 (s, 6H, Me2Si), 0.90 (s, 9H, t-BuSi), 1.31, 1.48 (2s, 6H, Me2C), 3.07 (d, 1H, J3-OH = 3.8, OH-3), 3.73–3.76 (m, 1H, H-5), 3.77 (dd, 1H, J5–6b = 4.7, H-6b), 3.94 (dd, 1H, J 5–6a = 4.2, J gem = 11.1, H-6a), 4.06 (dd, 1H, J 1′–2′Z = 6.6, H-2′ Z ), 4.19–4.32 (m, 2H, H-3, H-4), 4.37 (dd, 1H, J2′E–2′Z = 2.3, H-2′E), 4.51 (d, 1H, J2–3 < 0.5, H-2), 5.93 (d, 1H, J1–2 = 3.8, H-1), 6.37 (dd, 1H, J1′–2′E = 14.3, H-1′); 13C NMR δ −4.7 (Me2Si), 18.4 (CIV—tBuSi), 26.2 (Me3CSi), 26.6, 27.1 (Me2C), 62.7 (C-6), 75.4, 76.2 (C-4, C-5), 79.1 (C3), 85.3 (C-2), 89.8 (C-2′), 105.0 (C-1), 112.0 (Me2C), 151.6 (C-1′); IR (film) 2978, 2931 (=CH2), 1625 (C=C), 1078, 1025, 973 (=C—OR); MS IS m/z = 361.5 [M + H]+, 378.5 [M + NH4]+, 383.5 [M + Na]+; HRMS: C17H32O6Si: calcd. 360.1968; found 360.1987. 4.12. Reductive ring cleavage of 3-O-benzyl-1,2-O-isopropylidene5,6-O-(2-phenylsulfonyl)ethylidene-α-D-glucofuranoses (14)3 From 238 mg (0.50 mmol) the following were successively obtained from chromatography. 4.12.1. (7R,S)-3-O-Benzyl-1,2-O-isopropylidene-5,6-O-ethylideneα-D-glucofuranoses Colorless gum (47 mg, 28% yield, 1:1 C-7 epimeric ratio), [α]D −25 (c = 1.1, CHCl3); 1H NMR δ 1.31, 1.49 (2s, 6H, Me2C), 1.36, 1.39 (2d, Jvic = 5.2, CH3CH), 3.89–4.40 (m, 5H, H-3, H-4, H-5, H-6a, H-6b), 4.57–4.67 (m, 3H, PhCH2O, H-2), 5.02, 5.14 (2q, H-7), 5.91 (d, J1–2 = 3.8, H-1); 13C NMR δ 20.0, 20.1 (CH3CH), 26.4, 27.0 (Me2C), 68.2 (C-6), 72.4, 72.5 (C-5), 72.6, 73.0 (PhCH2O), 81.3, 81.4, 81.7, 81.9, 82.6, 82.8 (C-2, C-3, C-4), 101.6, 101.9 (C-7), 105.4 (C-1), 112.0 (Me2C ), 127.7, 127.8, 128.0, 128.1, 128.6, (CH—Ar), 137.6, 137.8 (CIV—Ar); MS IS m/z = 337.5 [M + H] + , 359.5 [M + Na] + ; HRMS: C 18 H 24 O 6 : calcd. 336.1573; found 336.1583. 4.12.2. 3-O-Benzyl-1,2-O-isopropylidene-6-O-vinyl-α-Dglucofuranose Colorless gum (45 mg, 27% yield), [α]D −31 (c = 1.2, CHCl3); 1H NMR δ 1.33, 1.49 (2s, 6H, Me2C), 3.78 (d, 1H, J5–6b = 5.9, H-6b), 3.94 (dd, 1H, J5–6a =2.9, Jgem = 10.2, H-6a), 4.03 (dd, 1H, J1′–2′Z =6.8, H-2′Z), 4.13–4.17 (m, 3H, H-3, H-4, H-5), 4.23 (dd, 1H, J2′E–2′Z = 2.1, H-2′E), 4.59 and 4.73 (2d, AB system, 2H, Jgem = 11.7, PhCH2O), 4.63 (d, 1H, J2–3 < 0.5, H-2), 5.94 (d, 1H, J1–2 = 3.8, H-1), 6.48 (dd, 1H, J1′–2′E = 14.5, H-1′), 7.31–7.38 (m, 5H, H—Ar); 13C NMR δ 26.9, 27.4 (Me2C), 68.4 (C-5), 70.5 (C-6), 72.9
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(PhCH2O), 80.2, 82.6 (C-3, C-4), 82.8 (C-2), 87.9 (C-2′), 105.8 (C-1), 112.5 (Me2C), 128.6, 128.8, 129.3 (CH—Ar), 137.8 (CIV—Ar), 152.2 (C1′); MS IS m/z = 337.5 [M + H]+, 359.5 [M + Na]+; IR (film) 3500 (OH), 3068, 3025, 2992 (CH—Ar, = CH), 1614, 1611 (C=C), 1026, 987 (=C—OR); HRMS: C18H24O6: calcd. 336.1573; found 336.1579.
4.12.3. 3-O-Benzyl-1,2-O-isopropylidene-5-O-vinyl-α-Dglucofuranose Colorless gum (47 mg, 28% yield), [α]D −27 (c = 1.1, CHCl3); 1H NMR δ 1.28, 1.45 (2s, 6H, Me2C), 3.74 (d, 1H, J5–6b = 5.3, H-6b), 3.95 (dd, 1H, Jgem = 12.6, H-6a), 3.96 (d, 1H, J3–4 = 2.8, H-3), 4.09 (dd, 1H, J1′–2′Z = 6.8, H-2′Z), 4.26 (dd, 1H, J4–5 = 8.9, H-4), 4.28 (dd, 1H, J2′E–2′Z = 2.6, H-2′E), 4.38 (ddd, 1H, J5–6a = 2.6, H-5), 4.51 and 4.55 (2d, AB system, 2H, Jgem = 11.8, PhCH2O), 4.61 (d, 1H, J2–3 < 0.5, H-2), 5.87 (d, 1H, J1–2 = 3.6, H-1), 6.48 (dd, 1H, J1′–2′E = 14.3, H-1′), 7.30–7.41 (m, 5H, H—Ar); 13C NMR δ 26.4, 27.0 (Me2C), 62.9 (C-6), 72.5 (PhCH2O), 78.3 (C-4), 81.3 (C-3), 81.7, 81.8 (C-2, C-5), 89.8 (C-2′), 105.4 (C-1), 112.1 (Me2C), 127.7, 128.0, 128.1, 128.4 (CH—Ar), 137.8 (CIV—Ar), 151.3 (C1′); IR (film) 3493 (OH), 3068, 3020, 2990 (CH—Ar, =CH), 1625, 1610 (C=C), 1024, 983 (=C—OR); MS IS m/z = 337.5 [M + H]+, 359.5 [M + Na]+; HRMS: C18H24O6: calcd. 336.1573; found 336.1588. Acknowledgements Thisbe K. Lindhorst thanks the ICOA for support of her sabbatical stay at the Université d’Orléans.
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