Solid-phase [2+2] cycloadditions between chlorosulfonyl isocyanate and chiral vinyl ethers

Article abstract of DOI:10.1002/1099-0690(200207)2002:14<2377::AID-EJOC2377>3.0.CO;2-I

Vinyl ethers 10, 23, and 33 were attached to Wang resin through the p-oxyphenylsulfonyl linker. The [2+2] cycloadditions between chlorosulfonyl isocyanate and the polymer-bound vinyl ethers 12, 24, and 34, followed by intramolecular alkylation of the β-la

Full text of DOI:10.1002/1099-0690(200207)2002:14<2377::AID-EJOC2377>3.0.CO;2-I

FULL PAPER
Solid-Phase [2؉2] Cycloadditions between Chlorosulfonyl Isocyanate and
Chiral Vinyl Ethers
Robert Łysek,[a] Bartłomiej Furman,[a] Maciej Cierpucha,[a] Barbara Grzeszczyk,[a]
Łukasz Matyjasek,[a] and Marek Chmielewski*[a]
Keywords: Chiral vinyl ethers / Cycloaddition / Lactams / Solid-phase synthesis
Vinyl ethers 10, 23, and 33 were attached to Wang resin
oxetane 30, respectively. This cyclization/cleavage step was
through the p-oxyphenylsulfonyl linker. The [2+2] cycloaddi- performed in the presence of the strong organic bases BEMP
tions between chlorosulfonyl isocyanate and the polymer-
bound vinyl ethers 12, 24, and 34, followed by intramolecular
alkylation of the β-lactam nitrogen atom, gave mixtures of
the corresponding diastereomeric clavams 8/9 and 21/22 or
the oxacephams 31/32, accompanied by the oxirane 7 or the
and DBU. The corresponding reaction sequences performed
in solution provided the oxabicyclic β-lactams without the ac-
companying anhydrosugars.
( Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany,
2002)
Introduction
For this study we selected 5-O-vinyl[5] and (Z)-5-O-pro-
penyl ethers of 1,2-O-isopropylidene-α--glucofuranose and
(Z)-3-O-propenyl ethers of 1,2-O-isopropylidene-α--xylo-
Solid-phase organic synthesis (SPOS) enables a large furanose.[6] In reactions performed in solution, these af-
number of structurally akin molecules to be prepared in a forded high stereoselectivity, providing the (S) and the (R)
short time, and provides a valuable tool for lead discovery configuration, respectively, at C-4 of the azetidin-2-one.
in the search for new therapeutics.[1] Thanks to the import- Binding of the vinyl ether to the polymer support through
ance of β-lactam antibiotics, a number of SPOS approaches a sulfonyl linker seemed to be the most attractive approach,
to this class of compounds have recently been reported.[2,3] since the intramolecular alkylation of the nitrogen atom
In particular, [2ϩ2] cycloadditions between ketenes and after the cycloaddition step, to form the bicyclic structure,
resin-bound imines have attracted the attention of many would remove the product from the resin by a cyclization/
laboratories.[3] Alternative to the [2ϩ2] cycloaddition of cleavage methodology (Scheme 1).[7]
ketenes to imines [2ϩ2] cycloadditions between isocyanates
and olefins by SPOS methodology, however, have not so far
been reported.
We have shown that [2ϩ2] cycloadditions between chlo-
rosulfonyl isocyanate (CSI) and chiral vinyl ethers proceed
in many cases with excellent stereoselectivity and allow con-
Scheme 1. a) i. CSI, Na2CO3; ii. Red-Al
trol of the configuration at C-4 of the 4-alkoxyazetidin-2-
one.[4] The cycloadducts offer a route to 5-oxacephams and
clavams through suitable transformation of a chiral auxili-
ary.[4] The experience we have gained in [2ϩ2] cycloaddition Results and Discussion
reactions between CSI and vinyl ethers has prompted us
to investigate these reactions under solid-phase conditions.
We have recently reported a procedure for the polymer-
When undertaking this task, we were aware that simple bound sulfonylation of alcohols based on p-pivaloyloxy-
transfer of reaction conditions from solution to solid-phase phenylsulfonate esters.[8] After deprotection, the phenolic
may not always provide the expected results.
group of the sulfonate ester is suitable for attachment to the
hydroxymethyl terminals of the Wang resin by the Mitsu-
nobu procedure.[9] This procedure does not leave any free
sulfonyl acid group on the resin. This could be critical, since
[2ϩ2] cycloaddition reactions carried out on sugar vinyl
ethers bound to a polymer using chlorosulfonylated resins
followed by the cyclization/cleavage methodology did not
produce any β-lactam.[10]
[a]
Institute of Organic Chemistry of the Polish Academy of
Sciences,
Kasprzaka 44, 01-224 Warsaw, Poland
Fax: (internat.) ϩ 48-22/632-6681
E-mail: chmiel@icho.edu.pl
Supporting information for this article is available on the
WWW under http://www.eurjoc.com or from the author.
Eur. J. Org. Chem. 2002, 2377Ϫ2384  WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002 1434Ϫ193X/02/0714Ϫ2377 $ 20.00ϩ.50/0
2377

M. Chmielewski et al.
FULL PAPER
Sulfonylation of 1 with p-pivaloyloxybenzenesulfonyl
It has been shown that cycloadditions between CSI and
chloride (2)[11] gave compound 3, which was transformed (E)- and (Z)-alkenyl ethers are stereospecific, affording
into the vinyl ether 4 by transetherification.[12] Subsequent trans-3,4-disubstituted azetidin-2-ones from the former and
treatment of 4 with CSI in toluene under standard condi- the cis counterparts from the latter.[15] In the cases of the
tions[13] afforded a mixture of the β-lactams 5 and 6 in rela- two chiral propenyl ethers, the direction of asymmetric in-
tively low yield (26%) and with 60% de. The intramolecular duction at C-4 of each cis diastereomeric azetidin-2-one was
alkylation of the nitrogen atom in the 5/6 mixture provided the same as that found for the corresponding unsubstituted
the known clavams 8 and 9 in a ratio of ca. 4.7:1, respect- vinyl ether. Since (Z)-propenyl ethers can be obtained in
ively.
high yield by potassium tert-butoxide rearrangement of the
On the other hand, the pivaloyl residue in 4 was removed corresponding allyl ethers,[16] we decided to use propenyl
with sodium in methanol and the resulting phenol 10 was ethers rather than vinyl ethers for model studies.
then attached to the Wang resin 11 by the Mitsunobu reac-
As was expected, [2ϩ2] cycloadditions performed on 4
tion procedure.[9] The [2ϩ2] cycloaddition between CSI and and on (Z)-5-O-propenyl ether 18 in solution gave similar
the solid-phase-bound vinyl ether 12 gave a mixture of ad- proportions of diastereomers 5/6 and 19/20, amounting to
ducts 13, which was subjected to the cyclization/cleavage ca. 4:1 and 5:1, respectively (Scheme 2).
methodology in the presence of 2-tert-butylimino-2-di-
ethylamino-1,3-dimethylperhydro-1,3,2-diazaphosphorine
Vinyl ether 17 was bound to the Wang resin 11 through
the phenol 23, by the procedure used for 4. Subsequent
(BEMP) or DBU to furnish a mixture of the known com- cycloaddition with CSI, followed by reduction of the adduct
pounds 7,[14] 8, and 9[5] in a ratio of about 0.1:3:1.
25 and the cyclization/cleavage step in the presence of
Scheme 2. a) PivOC6H4SO2Cl (2), Py, DMAP; b) Hg(OAc)2, ∆T; c) i. CSI, Na2CO3, CH2Cl2/toluene, Ϫ78 to Ϫ30 °C, 2Ϫ0 h, ii. Red-Al;
d) BEMP or DBU, CH3CN, ∆T; e) Na/MeOH; f) Wang resin (11), DEAD, TPP, CH2Cl2, 48 h; g) 60% NaH in mineral oil, DMF, AllBr;
h) 1% p-TsOH, MeOH; i) tBuOK, DMSO, 50 °C
2378
Eur. J. Org. Chem. 2002, 2377Ϫ2384

Solid-Phase [2ϩ2] Cycloadditions between Chlorosulfonyl Isocyanate and Chiral Vinyl Ethers
FULL PAPER
Scheme 3. a) PivOC6H4SO2Cl (2), Py, DMAP; b) i. CSI, Na2CO3, CH2Cl2/toluene, Ϫ78 to Ϫ30 °C, 2Ϫ10 h, ii. Red-Al; c) BEMP or
DBU, ∆T, CH3CN; d) Na/MeOH; e) Wang resin (11), DEAD, TPP, CH2Cl2, 48 h
BEMP or DBU, provided the clavams 21 and 22 and the mixtures 38/39 and 40/41 allowed them to be attached to
oxirane 7 in a ratio of about 5:1:9. Prolongation of heating the resin by a Mitsunobu procedure.
(24 h) of 25 in the presence of BEMP resulted in partial
epimerization of the resulting clavams 21/22 at the C-6Ј provided a mixture of 7 and 21/22 in a ratio of about 2:9:1,
atom. whereas in the case of 47, the same reaction sequence gave
In the case of 46, the cycloaddition/cleavage sequence
A similar reaction pattern was observed for 3-O-propenyl a mixture of 30, 31, and 32 in a ratio of about 3:2:6. In
ether 27, obtained from the known compound 26. Cycload- each case, the proportion of products was significantly dif-
dition between CSI and the ether 27 afforded a mixture of ferent from that obtained from the [2ϩ2] cycloaddition step
cycloadducts 28 and 29 (26% de), which were subjected to performed under solid-phase conditions. The experiments
the intramolecular alkylation to provide the known ce-
phams 31 and 32 in a ratio of about 1.5:1.0 (Scheme 3).
Cycloaddition with the resin-bound vinyl ether 34 and sub-
sequent cyclization/cleavage gave a mixture of 31 and 32,
accompanied by the oxetane 30,[17] in a ratio of about
1.2:1.1:1.0.
The formation of the oxirane 7 in the case of the cycload-
dition/cyclization sequence involving 24, and that of the ox-
etane 30 in that of the same process involving 34, require
explanation. The corresponding reactions performed in so-
lution did not show any evidence either of 7 or of 30. The
formation of both compounds might have been caused by
the presence of moisture, which might have hydrolyzed
either the vinyl ether or the cycloadduct with simultaneous
liberation of the corresponding hydroxy group. The basic
conditions of the cycloaddition/cleavage step would sub-
sequently result in formation of the epoxide or oxetane.
Careful drying of 24 and 34, however, did not change the
proportion of the corresponding anhydrosugar. In order to
clarify the reaction pathway, CSI cycloadditions to both
ethers 36 and 37 were performed in solution to afford the
cycloadducts 38/39 and 40/41 with de values of 63 and 13%,
room temp., 15 min; c) Wang resin (11), DEAD, TPP, CH2Cl2,
respectively (Scheme 4). Desilylation of both diastereomeric 48 h; d) BEMP or DBU, CH3CN, ∆T, 1.5 h
Scheme 4. a) PivOC6H4SO2Cl (2), Py, DMAP; b) TBAB, THF,
Eur. J. Org. Chem. 2002, 2377Ϫ2384
2379

M. Chmielewski et al.
FULL PAPER
shown in Scheme 5 testify to the formation of anhydrosu- Experimental Section
gars 7 and 30 as an innate feature of the cyclization/cleavage
General: Melting points were determined with a Boetius micromelt-
ing point apparatus and are uncorrected. Optical rotations were
measured at ambient temperature with a JASCO P 3010 polari-
meter. IR spectra were recorded with a PerkinϪElmer FT-IR Spec-
step performed on the resin. This suggests that, on the resin,
the adoption of geometries giving rise to the epoxide 7 or
oxetane 30 competes with those affording the clavams 21
and 22 or cephams 31 and 32, respectively. This correlates
well with the change in the proportions of the diastereom-
eric β-lactams during the cyclization/cleavage step. No such
difference in the rates of reaction of both diastereomers was
observed in solution; in all cases investigated the propor-
tions of diastereomeric β-lactams and the corresponding
clavams[5] or cephams[4c] were similar. This clearly points to
different energies of the transition states of the cyclization
reactions in solution and on solid support.
1
trum 2000 spectrophotometer. H and 13C NMR spectra were ob-
tained with Varian Gemini AC 200 and Bruker Avance 500 spectro-
meters at ambient temperature with solutions in CDCl3. Mass spec-
tra were determined with an AMD 604 Inectra GmbH
spectrometer. All reactions were performed under argon in anhyd-
rous solvents, distilled from the following desiccants: CH2Cl2 and
pyridine from CaH2, and THF from Na/benzophenone. The pro-
gress of the reactions performed in solution was monitored by thin
layer chromatography (TLC) on Merck 60-F254 silica gel plates.
Column flash chromatography was performed with Merck 60 silica
gel (230Ϫ400 mesh).
Sources of Compounds: Wang resin 11 (Rapp Polymere; capacity:
1.13 mmol/g, 200Ϫ400 mesh) was reagent grade and used as pur-
chased without further purification. p-Pivaloyloxybenzenesulfonyl
chloride (2) was obtained from the commercially available sodium
salt of p-hydroxybenzenesulfonic acid by the known procedure.[11]
Compounds 1,[18] 14,[19] and 26[6] were obtained by literature pro-
cedure. The syntheses and spectral and analytical data of com-
pounds 3, 15, 16, and 17 are provided in the Supporting Informa-
tion.[20]
Synthesis of Compounds 3, 18 and 27. General Procedure: Com-
pounds 3, 18, and 27 were obtained from the respective alcohols 1,
17,[20] and 26 (10 mmol) by treatment with p-pivaloyloxybenzene-
sulfonyl chloride (2) (14 mmol) in pyridine solution (20 mL) at 0
°C overnight. The standard workup, followed by chromatographic
purification, afforded compounds 3, 18, and 27 in good yield.
Scheme 5
1,2-O-Isopropylidene-3-O-methyl-6-O-(p-pivaloyloxyphenyl-
sulfonyl)-5-O-vinyl-α-D-glucofuranose (4): Compound 4 was ob-
tained from 3 by the known mercury acetate catalyzed trans-
etherification method[12] (82%). Oil. [α]2D2 ϭ Ϫ28.8 (c ϭ 0.72,
1
CH2Cl2). H NMR (500 MHz, CDCl3): δ ϭ 1.32, 1.48 (2 s, 6 H, 2
Conclusion
ϫ Me), 1.38 [s, 9 H, (CH3)3CC(O)Ϫ], 3.37 (s, 3 H, CH3OϪ), 3.73
(d, J ϭ 3.1 Hz, 1 H, H-3), 4.03 (dd, J ϭ 1.8 Hz, 1 H and J ϭ
6.4 Hz, H-2Јa), 4.10Ϫ4.18 (m, 2 H, H-4, H-6a), 4.25Ϫ4.29 (m, 1
H, H-5), 4.33 (dd, J ϭ 1.8 Hz, 1 H and J ϭ 13.9 Hz, H-2Јb), 4.46
(dd, J ϭ 2.0 Hz, 1 H and J ϭ 10.7 Hz, H-6b), 4.55 (d, J ϭ 3.7 Hz,
1 H, H-2), 5.83 (d, J ϭ 3.7 Hz, 1 H, H-1), 6.23 (dd, J ϭ 6.4 Hz, 1
H and J ϭ 13.9 Hz, H-1Ј), 7.20Ϫ7.26, 7.93Ϫ7.97 (2 m, 4 H, phenyl)
ppm. 13C NMR (125 MHz, CDCl3): δ ϭ 26.18, 26.69, 26.91, 39.16,
57.43, 70.40, 74.47, 77.83, 81.10, 82.86, 89.72, 105.12, 111.93,
122.28, 129.65, 132.74, 151.02, 155.17, 176.01 ppm. IR (film): ν˜ ϭ
1759, 1638, 1594, 1370, 1104, 1028 cmϪ1. HRMS (LSIMS): calcd.
It should be stressed that numerous attempts to perform
the cycloaddition/cyclization sequence under solid-phase
conditions with better overall yield failed. Neither careful
drying of the vinyl ether bound to the polymer, nor protec-
tion of remaining free hydroxy groups on the resin by
acetylation or silylation prior to cycloaddition raised the
yields of diastereomeric clavams 8/9 and 21/22 or cephams
31/32, nor did they eliminate formation of the correspond-
ing anhydrosugars 7 and 30. The low yield of the cycloaddi-
tion/cyclization sequence and the noticeable difference in
the rates of reaction of the two diastereomers during the
cyclization step did not allow us to assign asymmetric in-
duction in the reactions investigated. It should, however,
be reasonable to assume that stereoselectivity in the [2ϩ2]
cycloaddition step was in the same range as observed for us
for reactions performed in solution.[4c,5] Finally, it is worth
noting that in all investigated cases the cyclization/cleavage
step could be performed with either BEMP or DBU. The
standard basic conditions used by us previously[4Ϫ6,13]
failed, providing only the anhydrosugars 7 and 30.
for [M
ϩ
H]ϩ (C23H33O10S) 501.17944, found 501.17777.
C23H32O10S (500.58): calcd. C 55.19, H 6.44; found C 55.46, H
6.88. [2ϩ2] Cycloadditions between chlorosulfonyl isocyanate and
the vinyl ethers 4, 18, and 27 were performed according to the
known procedure.[5,6,13]
(4ЈS)- and (4ЈR)-1,2-O-Isopropylidene-3-O-methyl-5-O-(2Ј-oxoazeti-
din-4Ј-yl)-6-O-(p-pivaloyloxyphenylsulfonyl)-α-
D-glucofuranose
(5
and 6): A mixture of compounds 5/6 in a ratio of ca. 4:1 was ob-
tained from 4 by the known procedure.[5,6,13] Purification by flash
chromatography on silica gel (65% EtOAc in hexane) furnished a
mixture of 5/6 as a solid foam (26%). 5: 1H NMR (500 MHz,
CDCl3, selected signals taken from the spectrum of the mixture):
δ ϭ 2.85 (dd, J ϭ 0.7 Hz, 1 H and J ϭ 15.2 Hz, H-3Јa), 3.77 (d,
2380
Eur. J. Org. Chem. 2002, 2377Ϫ2384

Solid-Phase [2ϩ2] Cycloadditions between Chlorosulfonyl Isocyanate and Chiral Vinyl Ethers
FULL PAPER
J ϭ 2.7 Hz, 1 H, H-3), 4.57 (d, J ϭ 3.7 Hz, 1 H, H-2), 5.28 (dd, Preparation of Polymer-Bound Sulfonate Esters 12, 24, and 34 by
J ϭ 1.4 Hz, 1 H and J ϭ 4.0 Hz, H-4Ј), 5.80 (d, J ϭ 3.7 Hz, 1 H, the Mitsunobu Reaction. General Procedure: Phenol 10 (0.63 g,
H-1), 6.29 (br. s, 1 H, NH) ppm. 6: 1H NMR (CDCl3, selected 1.5 mmol) and PPh3 (0.39 g, 1.5 mmol) were added to a suspension
signals taken from the spectrum of the mixture): δ ϭ 2.79 (dd, J ϭ
0.7 Hz, 1 H and J ϭ 15.0 Hz, H-3Јa), 3.75 (d, J ϭ 2.8 Hz, 1 H, H-
of Wang resin 11 (0.38 g, 0.43 mmol) in CH2Cl2 (5 mL). The mix-
ture was cooled to 0 °C, DEAD (diethyl azodicarboxylate, 0.24 mL,
3), 4.55 (d, J ϭ 3.7 Hz, 1 H, H-2), 5.14 (dd, J ϭ 1.4 Hz, 1 H and 1.5 mmol) was added dropwise over 10 min, and the reaction mix-
J ϭ 4.0 Hz, H-4Ј), 5.82 (d, J ϭ 3.7 Hz, 1 H, H-1), 6.52 (br. s, 1 H, ture was allowed to warm to room temperature. The suspension
NH) ppm. IR (CH2Cl2): ν˜ ϭ 3418, 1759, 1736, 1365, 1178, 1082, was stirred for 48 h, it was then filtered and washed [2 ϫ 10 mL
1026 cmϪ1. HRMS (LSIMS): calcd. for [M ϩ H]ϩ (C24H34O11NS) each CH2Cl2, MeOH, THF, THF/water (2:1), THF, MeOH,
544.18526, found 544.18485. C24H33NO11S (543.60): calcd. C
53.02, H 6.10, N 2.57; found C 52.69, H 6.43, N 2.47.
CH2Cl2, and Et2O], and then dried for 6 h under vacuum to give
resin 12. IR (KBr disk): ν˜ ϭ 1636, 1599, 1373, 1167, 1079, 756
cmϪ1. 12: calcd. S 2.49; found S 2.27. Elemental analysis indicating
2.27% S corresponds to a 91% yield. Capacity of 12: 0.71 mmol/g.
(4S,3ЈR,5ЈS)- and (4S,3ЈR,5ЈR)-4-C-(4Ј-Dethia-4Ј-oxapenam-3Ј-yl)-
1,2-O-isopropylidene-3-O-methoxy-β-L-threofuranose (8 and 9): The
[2؉2] Cycloadditions between CSI and Resin-Bound Vinyl Ethers 12,
24, and 34. General Procedure: CSI (0.24 mL, 2.8 mmol) was added
at Ϫ78 °C to a suspension of anhydrous Na2CO3 (0.2 g) and resin
12 (0.4 g, 0.28 mmol) in a CH2Cl2/toluene mixture (1:1, v/v;
12 mL). The reaction mixture was stirred at Ϫ78 °C for 30 min,
and then at Ϫ30 °C for another 10 h. Subsequently, the suspension
was cooled to Ϫ78 °C, diluted with the CH2Cl2/toluene mixture
(14 mL), treated with Red-Al (1  solution in toluene, 2.8 mL), and
left for 30 min, whilst the temperature of the reaction mixture was
maintained. The temperature was then allowed to rise to 0 °C, and
water (2.8 mL) was added. The mixture was stirred for 30 min, and
then filtered and washed (3 ϫ 10 mL) with 10% aqueous potassium
sodium tartrate, H2O, DMF, H2O, MeOH, THF, MeOH, CH2Cl2,
and Et2O, and then dried for 16 h under vacuum to give β-lactam
bound to the resin. 13: IR (KBr disk): ν˜ ϭ 3370, 1778, 1599, 1492,
1364, 1164, 1075, 747 cmϪ1. calcd. N 0.96; found N 0.87. Elemental
analysis indicating 0.87% N corresponds to a 91% yield. Capacity
of 13: 0.62 mmol/g.
mixture of 5 and 6 (0.24 g, 0.44 mmol) was dissolved in anhydrous
CH3CN (12 mL) and treated with Bu4NBr (0.18 g, 0.57 mmol) and
pulverized K2CO3 (0.6 g). The mixture was stirred and kept under
reflux for ca. 1 h (TLC). Subsequently, toluene (10 mL) was added,
the residue was filtered, washed with water, and dried (Na2SO4),
and the solvents were evaporated. The crude product was separated
by flash chromatography on silica gel with an ethyl acetate/hexane
mixture (1:5, v/v) as eluent to give 8 (0.076 g, 61%) and 9 (0.010 g,
8%). The spectral and analytical data of compound 8 are identical
to those reported in the literature.[5] 9: Oil. [α]2D2 ϭ ϩ30.3 (c ϭ 0.1,
1
CH2Cl2). H NMR (500 MHz, CDCl3): δ ϭ 1.32, 1.49 (2 s, 6 H, 2
ϫ Me), 2.87 (d, J ϭ 15.9 Hz, 1 H, H-6Јa), 3.13 (dd, J ϭ 7.1 Hz, 1
H and J ϭ 11.5 Hz, H-2Јa), 3.23 (dd, J ϭ 2.5 Hz, 1 H and J ϭ
15.9 Hz, H-6Јb), 3.43 (s, 3 H, CH3OϪ), 3.75 (d, J ϭ 3.3 Hz, 1 H,
H-3), 3.90 (dd, J ϭ 5.4 Hz, 1 H and J ϭ 11.5 Hz, H-2Јb), 4.13 (dd,
J ϭ 3.3 Hz, 1 H and J ϭ 6.8 Hz, H-4), 4.51 (q, J ϭ 6.8 Hz, 1 H,
H-3Ј), 4.56 (d, J ϭ 3.7 Hz, 1 H, H-2), 5.19 (d, J ϭ 2.5 Hz, 1 H, H-
5Ј), 5.87 (d, J ϭ 3.7 Hz, 1 H, H-1) ppm. 13C NMR (125 MHz,
CDCl3): δ ϭ 26.30, 26.87, 44.69, 48.68, 57.99, 80.31, 81.38, 81.64,
Synthesis of Clavams 8, 9, 21, and 22 and 5-Oxacephams 31 and 32
by the Cyclization/Cleavage Step. General Procedure: The resin 13
(0.1 g, 0.062 mmol) was suspended in anhydrous CH3CN (3 mL)
and treated with BEMP (0.036 mL, 0.124 mmol) or DBU
(0.018 mL, 0.124 mmol). The mixture was stirred and kept under
reflux for ca. 3 h. The resin was filtered and washed (3 ϫ 5 mL
each) with THF and Et2O. The organic layer was separated and
the solvents were evaporated. The residue was diluted with CH2Cl2
(15 mL), washed with 10% citric acid and water, dried (MgSO4),
and concentrated. The crude mixture was separated on a silica gel
column with an ethyl acetate/hexane mixture (1:5, v/v) as eluent to
give 8, 9, and the anhydrosugar 7.
83.82, 84.63, 105.17, 112.01, 177.01 ppm. IR (film): ν˜ ϭ 1784 cmϪ1
.
HRMS (LSIMS): calcd. for [M ϩ H]ϩ (C13H20O6N) 286.12906,
found 286.12765.
Synthesis of Compounds 10, 23, and 33. General Procedure: Com-
pounds 10, 23, and 33 were obtained from the corresponding p-
pivaloyloxyphenylsulfonates 4, 18, and 27 (6 mmol) by treatment
with sodium (10 mmol) in MeOH solution (10 mL) at room tem-
perature. After 1Ϫ2 h, the reaction mixtures were treated with solid
carbon dioxide and extracted with CH2Cl2. The extracts were
washed with water and dried (MgSO4), and the solvents were evap-
orated to give crude products. Chromatographic purification af-
forded compounds 10, 23, and 33, respectively.
5,6-Anhydro-1,2-O-isopropylidene-3-O-methyl-α-D-glucofuranose
(7): Compound 7, obtained from 13, 25, and 46, displayed spectral
6-O-(p-Hydroxyphenylsulfonyl)-1,2-O-isopropylidene-3-O-methyl-5-
and analytical data identical to those reported in the literature.[14]
O-vinyl-α-D-glucofuranose (10): Compound 10 was obtained from
1,2-O-Isopropylidene-3-O-methyl-6-O-(p-pivaloyloxyphenyl-
sulfonyl)-5-O-(prop-1Ј-enyl)-α-D-glucofuranose (18): Compound 18
4 by the procedure described above (87%). Oil. [α]2D2 ϭ Ϫ27.9 (c ϭ
1
0.7, CH2Cl2). H NMR (500 MHz, CDCl3): δ ϭ 1.31, 1.46 (2 s, 6
was obtained from 17 by the general procedure described earlier[6]
(74%). Oil. [α]2D2 ϭ Ϫ25.1 (c ϭ 0.42, CH2Cl2). 1H NMR (500 MHz,
CDCl3): δ ϭ 1.31, 1.47 (2 s, 6 H, 2 ϫ Me), 1.37 [s, 9 H,
(CH3)3CC(O)Ϫ], 1.52 (dd, 3 H, J ϭ 1.6 Hz and J ϭ 6.8 Hz, CH3-
3Ј), 3.35 (s, 3 H, CH3OϪ), 3.71 (d, J ϭ 2.7 Hz, 1 H, H-3),
4.07Ϫ4.14, 4.35Ϫ4.43 (2 m, 5 H, H-2, H-4, H-5, H-6a, H-6b), 4.53
(d, J ϭ 3.7 Hz, 1 H, H-2), 5.81 (d, J ϭ 3.7 Hz, 1 H, H-1), 5.95 (dq,
J ϭ 6.1 Hz, 1 H and J ϭ 1.7 Hz, H-1Ј), 7.23Ϫ7.26, 7.92Ϫ7.95 (2
H, 2 ϫ Me), 3.36 (s, 3 H, CH3OϪ), 3.73 (d, J ϭ 3.1 Hz, 1 H, H-
3), 4.02 (dd, J ϭ 1.7 Hz, 1 H and J ϭ 6.3 Hz, H-2Јa), 4.08 (dd,
J ϭ 6.8 Hz, 1 H and J ϭ 10.7 Hz, H-6a), 4.09Ϫ4.16 (m, 1 H, H-
4), 4.22Ϫ4.27 (m, 1 H, H-5), 4.32 (dd, J ϭ 1.7 Hz, 1 H and J ϭ
13.9 Hz, H-2Јb), 4.38 (dd, J ϭ 2.0 Hz, 1 H and J ϭ 10.7 Hz, H-
6b), 4.55 (d, J ϭ 3.7 Hz, 1 H, H-2), 5.82 (d, J ϭ 3.7 Hz, 1 H, H-
1), 6.24 (dd, J ϭ 6.3 Hz, 1 H and J ϭ 13.9 Hz, H-1Ј), 6.89Ϫ6.93,
7.75Ϫ7.79 (2 m, 4 H, phenyl) ppm. 13C NMR (125 MHz, CDCl3):
δ ϭ 26.18, 26.72, 57.57, 70.14, 74.67, 78.02, 81.20, 82.94, 89.86,
105.18, 112.14, 115.95, 126.87, 130.51, 151.17, 160.69 ppm. IR
m, 4 H, phenyl) ppm. IR (film): ν˜ ϭ 1759, 1669, 1370, 1106 cmϪ1
.
HRMS (EI): calcd. for [M]ϩ (C24H34O10S) 514.18727, found
514.18716. C24H34O10S (514.61): calcd. C, 56.02, H 6.66; found C
55.95, H 6.67.
(film): ν˜ ϭ 3403, 1638, 1603, 1589, 1355, 1165, 1080, 841 cmϪ1
.
HRMS (LSIMS): calcd. for [M ϩ H]ϩ (C18H25O9S) 417.12193,
found 417.12239. C18H24O9S (416.45): calcd. C 51.90, H 5.81;
found C 52.25, H 6.72.
(3ЈR,4ЈS)- and (3ЈS,4ЈR)-1,2-O-Isopropylidene-3-O-methyl-5-O-(3Ј-
methyl-2Ј-oxoazetidin-4Ј-yl)-6-O-(p-pivaloyloxyphenylsulfonyl)-α-
D-
Eur. J. Org. Chem. 2002, 2377Ϫ2384
2381

M. Chmielewski et al.
FULL PAPER
glucofuranose (19 and 20): Compounds 19/20 were obtained in a
ratio of ca. 5:1 from 18 by the known procedure.[5,6,13] Chromato-
Resin 24: Resin 24 was obtained according to the Mitsunobu pro-
cedure described above. IR (KBr disk): ν˜ ϭ 3487, 1669, 1599, 1373,
graphic separation on silica gel with a hexane/ethyl acetate mixture 1166, 1079, 692 cmϪ1. calcd. S 2.47; found S 2.08. Elemental ana-
(4:6, v/v) as eluent gave 19/20 (69%). Solid foam. 19: 1H NMR
(500 MHz, CDCl3, selected signals taken from the spectrum of the
mixture): δ ϭ 1.20 (d, J ϭ 7.5 Hz, 3 H, CH3-3Ј), 3.29Ϫ3.35 (m, 1
H, H-3Ј), 3.40 (s, 3 H, CH3OϪ), 3.77 (d, J ϭ 2.6 Hz, 1 H, H-3),
4.57 (d, J ϭ 3.7 Hz, 1 H, H-2), 5.27 (d, J ϭ 4.3 Hz, 1 H, H-4Ј),
lysis indicating 2.08% S corresponds to an 84% yield. Capacity of
24: 0.65 mmol/g.
Resin 25: Resin 25 was obtained according to the general procedure
described above. IR (KBr disk): ν˜ ϭ 3468, 1748, 1600, 1374, 1241,
1025, 827 cmϪ1. calcd. N 0.87; found N 0.99. Elemental analysis
indicating 0.99% N corresponds to a 99% yield. Capacity of 25:
0.65 mmol/g. Compounds 7, 21, and 22 were obtained from the
resin 25 according to the general procedure described above to pro-
vide a mixture in a ratio of about 5:1:9, respectively
1
5.81 (d, J ϭ 3.7 Hz, 1 H, H-1), 6.24 (br. s, 1 H, NH) ppm. 20: H
NMR (500 MHz, CDCl3, selected signals taken from the spectrum
of the mixture): δ ϭ 1.19 (d, J ϭ 7.5 Hz, 3 H, CH3-3Ј), 3.25Ϫ3.28
(m, 1 H, H-3Ј), 3.39 (s, 3 H, CH3OϪ), 3.75 (d, J ϭ 3.0 Hz, 1 H,
H-3), 4.56 (d, J ϭ 3.7 Hz, 1 H, H-2), 5.09 (d, J ϭ 4.4 Hz, 1 H, H-
4Ј), 5.82 (d, J ϭ 3.7 Hz, 1 H, H-1), 6.53 (br. s, 1 H, NH) ppm. IR
(film): ν˜ ϭ 3355, 1761, 1367, 1107 cmϪ1. HRMS (LSIMS): calcd.
for [M ϩ H]ϩ (C25H36O11NS) 558.20091, found 558.20224.
1,2-O-Isopropylidene-5-O-(p-pivaloyloxyphenylsulfonyl)-3-O-(prop-
1Ј-enyl)-α-D-xylofuranose (27): Compound 27 was obtained from
26 according to the procedure described above (93%). Oil. [α]2D2
ϭ
1
Ϫ7.1 (c ϭ 0.61, CH2Cl2). H NMR (200 MHz, CDCl3): δ ϭ 1.30,
1.48 (2 s, 6 H, 2 ϫ Me), 1.44 [s, 9 H, (CH3)3CC(O)Ϫ], 1.47 (dd, 3
H, J ϭ 1.7 Hz and J ϭ 6.9 Hz, CH3-3Ј), 4.15 (d, J ϭ 3.0 Hz, 1 H,
H-3), 4.24 (dd, J ϭ 6.2 Hz, 1 H and J ϭ 10.1 Hz, H-5a), 4.31 (dd,
J ϭ 5.3 Hz, 1 H and J ϭ 10.1 Hz, H-5b), 4.41Ϫ4.59 (m, 3 H, H-
2Ј, H-2, H-4), 5.88 (d, J ϭ 3.7 Hz, 1 H, H-1), 5.89 (dq, J ϭ 6.1 Hz,
1 H and J ϭ 1.7 Hz, H-1Ј), 7.23Ϫ7.30, 7.90Ϫ7.98 (2 m, 4 H,
(4S,3ЈR,5ЈS,6ЈR)- and (4S,3ЈR,5ЈR,6ЈS)-4-C-(4Ј-Dethia-6Ј-methyl-
4Ј-oxapenam-3Ј-yl)-1,2-O-isopropylidene-3-O-methoxy-β-L-threo-
furanose (21 and 22): Compounds 21/22 were obtained from the 19/
20 mixture by the procedure described for 8/9. After chromato-
graphic separation with a hexane/ethyl acetate mixture (8.5:1.5, v/
v) as eluent, the pure components were obtained. 21: Oil. [α]2D2
ϭ
Ϫ124.2 (c ϭ 0.49, CH2Cl2). 1H NMR (500 MHz, CDCl3): δ ϭ 1.15
(d, J ϭ 7.6 Hz, 3 H, CH3-6Ј), 1.32, 1.49 (2 s, 6 H, 2 ϫ Me), 2.98
(ddd, 1 H, J ϭ 0.6 Hz, J ϭ 7.2 Hz and J ϭ 12.0 Hz, H-2Јa), 3.39
(ddd, 1 H, J ϭ 0.5 Hz, J ϭ 3.2 Hz and J ϭ 15.0 Hz, H-6Ј), 3.42
(s, 3 H, CH3OϪ), 3.77 (d, J ϭ 3.3 Hz, 1 H, H-3), 3.91 (dd, J ϭ
6.4 Hz, 1 H and J ϭ 12.0 Hz, H-2Јb), 4.30 (dd, J ϭ 3.3 Hz, 1 H
and J ϭ 5.7 Hz, H-4), 4.32Ϫ4.34 (m, 1 H, H-3Ј), 4.55 (d, J ϭ
3.7 Hz, 1 H, H-2), 5.30 (d, J ϭ 3.2 Hz, 1 H, H-5Ј), 5.87 (d, J ϭ
3.7 Hz, 1 H, H-1) ppm. 13C NMR (125 MHz, CDCl3): δ ϭ 7.71,
26.23, 26.86, 47.29, 48.97, 58.09, 78.90, 80.96, 81.71, 84.10, 87.10,
105.28, 111.92, 182.56 ppm. IR (film): ν˜ ϭ 1783 cmϪ1. HRMS (EI):
calcd. for [M]ϩ (C14H21NO6) 299.13689, found 299.13655.
C14H21NO6 (299.33): calcd. C 56.18, H 7.07, N 4.68; found C
phenyl) ppm. IR (CHCl3): ν˜ ϭ 1757, 1670, 1376, 1108, 979 cmϪ1
.
HRMS (LSIMS): calcd. for [M ϩ Na]ϩ (C22H30NaO9S) 493.15082,
found 493.15203. C22H30O9S (470.55): calcd. C 56.16, H 6.43;
found C 56.41, H 6.78
(3ЈS,4ЈR)- and (3ЈR,4ЈS)-1,2-O-Isopropylidene-3-O-(3Ј-methyl-2Ј-
oxoazetidin-4Ј-yl)-5-O-(p-pivaloyloxyphenylsulfonyl)-α-D-xylo-
furanose (28 and 29): A 28/29 mixture in a ratio of ca. 1.7:1 was
obtained from 27 according to the general procedure described
1
earlier above (52%). Oil. 28: H NMR (500 MHz, CDCl3, selected
signals taken from the spectrum of the mixture): δ ϭ 1.16 (d, J ϭ
6.7 Hz, 3 H, CH3-3Ј), 1.31, 1.47 (s, 3 H, 2 ϫ Me), 4.16 (dd, J ϭ
5.5 Hz, 1 H and J ϭ 9.8 Hz, H-5a), 4.28 (dd, J ϭ 7.3 Hz, 1 H and
J ϭ 9.8 Hz, H-5b), 4.57 (d, J ϭ 3.7 Hz, 1 H, H-2), 5.10 (d, J ϭ
4.4 Hz, 1 H, H-4Ј), 5.88 (d, J ϭ 3.7 Hz, 1 H, H-1), 6.43 (br. s, 1
H, NH) ppm. 29: 1H NMR (500 MHz, CDCl3, selected signals
taken from the spectrum of the mixture): δ ϭ 1.14 (d, J ϭ 6.7 Hz,
3 H, CH3Ϫ3Ј), 1.32, 1.48 (s, 3 H, 2 ϫ Me), 4.15 (dd, J ϭ 5.2 Hz,
1 H and J ϭ 9.7 Hz, H-5a), 4.29 (dd, J ϭ 7.7 Hz, 1 H and J ϭ
9.7 Hz, H-5b), 4.51 (d, J ϭ 3.6 Hz, 1 H, H-2), 5.13 (d, J ϭ 4.2 Hz,
1 H, H-4Ј), 5.87 (d, J ϭ 3.6 Hz, 1 H, H-1), 6.57 (br. s, 1 H, NH)
ppm. IR (film): ν˜ ϭ 3341, 1761 cmϪ1. HRMS (LSIMS): calcd. for
55.92, H 6.97, N 4.62. 22: White solid. M.p. 68Ϫ71 °C. [α]2D2
ϭ
ϩ42.9 (c ϭ 0.43, CH2Cl2). 1H NMR (500 MHz, CDCl3): δ ϭ 1.19
(d, J ϭ 7.6 Hz, 3 H, CH3-6Ј), 1.32, 1.48 (2 s, 6 H, 2 ϫ Me), 3.11
(ddd, 1 H, J ϭ 0.7 Hz, J ϭ 7.2 Hz and J ϭ 11.6 Hz, H-2Јa),
3.37Ϫ3.42 (m, 1 H, H-6Ј), 3.43 (s, 3 H, CH3OϪ), 3.75 (d, J ϭ
3.2 Hz, 1 H, H-3), 3.83 (dd, J ϭ 5.4 Hz, 1 H and J ϭ 11.6 Hz, H-
2Јb), 4.09 (dd, J ϭ 3.3 Hz, 1 H and J ϭ 7.1 Hz, H-4), 4.52Ϫ4.56
(m, 1 H, H-3Ј), 4.54 (d, J ϭ 3.7 Hz, 1 H, H-2), 5.17 (d, J ϭ 3.0 Hz,
1 H, H-5Ј), 5.87 (d, J ϭ 3.7 Hz, 1 H, H-1) ppm. 13C NMR
(125 MHz, CDCl3): δ ϭ 7.74, 26.34, 26.86, 47.90, 48.27, 58.02,
79.84, 81.19, 81.66, 83.97, 87.42, 105.15, 111.99, 181.69 ppm. IR
[M
ϩ
H]ϩ (C23H32NO10S) 514.17469, found 514.17593.
C23H31NO10S (513.58): calcd. C 53.79, H 6.08, N 2.73; found C
53.40, H 6.57, N 2.58.
(CH2Cl2): ν˜
ϭ .
1780 cmϪ1 HRMS (EI): calcd. for [M]ϩ
(C14H21NO6) 299.13689, found 299.13661. C14H21NO6 (299.33):
calcd. C 56.18, H 7.07, N 4.68; found C 56.24, H 7.21, N 4.52.
(3aR,4aR,7S,7aR,8aS,8bR)- and (3aR,4aR,7R,7aS,8aS,8bR)-2,2-
Dimethyl-hexahydro-1,3,4,8-tetraoxa-5a-aza-cyclobuta[f]indeno-
[b]cyclopentan-6-one[21] (31 and 32): A mixture of 31 and 32 was
obtained from the 28/29 mixture according to the procedure
described above. Chromatographic separation on silica gel with a
hexane/ethyl acetate mixture (3:7, v/v) as eluent gave compounds
31 and 32, with spectral and analytical data identical to those re-
ported in the literature.[6]
6-O-(p-Hydroxyphenylsulfonyl)-1,2-O-isopropylidene-3-O-methyl-5-
O-(prop-1Ј-enyl)-α-D-glucofuranose (23): Compound 23 was ob-
tained from 18 by the procedure described above (86%). Oil. [α]2D2
ϭ
1
Ϫ25.5 (c ϭ 0.4, CH2Cl2). H NMR (500 MHz, CDCl3): δ ϭ 1.31,
1.48 (2 s, 6 H, 2 ϫ Me), 1.52 (dd, 3 H, J ϭ 1.6 Hz and J ϭ 6.8 Hz,
CH3Ϫ3Ј), 1.64 (br. s, 1 H, ϪOH), 3.36 (s, 3 H, CH3OϪ), 3.72 (d,
J ϭ 2.4 Hz, 1 H, H-3), 4.03Ϫ4.15, 4.33Ϫ4.42 (2 m, 5 H, H-2Ј, H-
4, H-5, H-6a, H-6b), 4.54 (d, J ϭ 3.7 Hz, 1 H, H-2), 5.81 (d, J ϭ
5-O-(p-Hydroxyphenylsulfonyl)-1,2-O-isopropylidene-3-O-(prop-1Ј-
enyl)-α-D-xylofuranose (33): Compound 33 was obtained from 27
3.7 Hz, 1 H, H-1), 5.97 (dq, J ϭ 6.1 Hz, 1 H and J ϭ 1.6 Hz, H- by the procedure described above (72%). Oil. [α]2D2 ϭ Ϫ8.6 (c ϭ
1Ј), 6.89Ϫ6.93, 7.76Ϫ7.79 (2 m, 4 H, phenyl) ppm. IR (film): ν˜ ϭ 1.17, CH2Cl2). 1H NMR (200 MHz, CDCl3): δ ϭ 1.30, 1.48 (2 s, 6
3411, 1669, 1589, 1357, 1081 cmϪ1. HRMS (EI): calcd. for [M]ϩ
H, 2 ϫ Me), 1.47 (dd, 3 H, J ϭ 1.7 Hz and J ϭ 6.8 Hz, CH3-3Ј),
(C19H26O9S) 430.12975, found 430.12740. C19H26O9S (430.48): 4.16 (d, J ϭ 3.3 Hz, 1 H, H-3), 4.20 (dd, J ϭ 6.6 Hz, 1 H and J ϭ
calcd. C 53.01, H 6.09.found C 52.57, H 6.22.
10.2 Hz, H-5a), 4.31 (dd, J ϭ 5.5 Hz, 1 H and J ϭ 10.2 Hz, H-5b),
2382
Eur. J. Org. Chem. 2002, 2377Ϫ2384

Solid-Phase [2ϩ2] Cycloadditions between Chlorosulfonyl Isocyanate and Chiral Vinyl Ethers
FULL PAPER
4.42Ϫ4.60 (m, 2 H, H-2Ј, H-4), 4.54 (d, J ϭ 3.6 Hz, 1 H, H-2), Na]ϩ (C23H36NaO8SSi) 523.17979, found 523.18033. C23H36O8SSi
5.87Ϫ5.93 (m, 2 H, H-1, H-1Ј), 6.87Ϫ6.93, 7.73Ϫ7.80 (2 m, 4 H, (500.69): calcd. C 55.17, H 7.45; found C 54.83, H 7.42.
phenyl) ppm. IR (CHCl3): ν˜ ϭ 3582, 1670, 1376, 1168, 1082 cmϪ1
.
(3ЈR,4ЈS)- and (3ЈS,4ЈR)-6-O-(p-tert-Butyldimethylsilyloxyphenyl-
sulfonyl)-1,2-O-isopropylidene-3-O-methyl-5-O-(3Ј-methyl-2Ј-
oxoazetidin-4Ј-yl)-α-D-glucofuranose (38 and 39): Compounds 38/
HRMS (LSIMS): calcd. for [M ϩ H]ϩ (C17H23O8S) 387.11136,
found 387.11053. C17H22O8S (386.43): calcd. C 52.84, H 5.74;
found C 53.09, H 6.14.
39 were obtained from 36, in a ratio of ca. 5.1:1, by the known
procedure.[5,6,13] Purification by flash chromatography on silica gel
(40% EtOAc in hexane) furnished 38/39 as an oil (77%). 38: 1H
NMR (500 MHz, CDCl3, selected signals taken from the spectrum
of the mixture): δ ϭ 1.19 (d, J ϭ 7.5 Hz, 3 H, Me), 3.77 (d, J ϭ
2.3 Hz, 1 H, H-3), 4.57 (d, J ϭ 3.7 Hz, 1 H, H-2), 5.31 (d, J ϭ
4.3 Hz, 1 H, H-4Ј), 5.80 (d, J ϭ 3.7 Hz, 1 H, H-1), 6.25 (br. s, 1
H, NH) ppm. 39: 1H NMR (CDCl3, selected signals taken from
the spectrum of the mixture): δ ϭ 1.18 (d, J ϭ 7.5 Hz, 3 H, Me),
3.75 (d, J ϭ 3.0 Hz, 1 H, H-3), 4.56 (d, J ϭ 3.7 Hz, 1 H, H-2), 5.09
(d, J ϭ 4.4 Hz, 1 H, H-4Ј), 5.82 (d, J ϭ 3.7 Hz, 1 H, H-1), 6.55
(br. s, 1 H, NH) ppm. IR (film): ν˜ ϭ 3297, 1773, 1363, 1281, 1022,
905 cmϪ1. HRMS (LSIMS): calcd. for [M ϩ H]ϩ (C26H42NO10SSi)
588.22987, found 588.23078. C26H41NO10SSi (583.78): calcd. C
53.13, H 7.03, N 2.38; found C 52.92, H 7.35, N 2.39.
Resin 34: Resin 34 was obtained by the Mitsunobu procedure as
described above. IR (KBr disk): ν˜ ϭ 3341, 1669, 1597, 1512, 1493,
1374, 1166, 1078, 976, 692 cmϪ1. calcd. S 2.55; found S 2.05. Ele-
mental analysis indicating 2.05% S corresponds to an 80% yield.
Capacity of 34: 0.65 mmol/g.
Resin 35: Resin 35 was obtained according to the general procedure
described above. IR (KBr disk): ν˜ ϭ 1778, 1595, 1512, 1493, 1373,
1163, 1067 cmϪ1. calcd. N 1.03; found N 1.00. Elemental analysis
indicating 1.00% N corresponds to a 97% yield. Capacity of 35:
0.64 mmol/g. Compounds 30, 31, and 32 were obtained from the
resin 35 by the procedure described above.
3,5-Anhydro-1,2-O-isopropylidene-α-D-xylofuranose (30): Com-
pound 30, obtained from 35 and 47, displayed spectral and analyt-
ical data identical to those reported in the literature.[17]
(3ЈS,4ЈR)- and (3ЈR,4ЈS)-5-O-(p-tert-Butyldimethylsilyloxyphenyl-
s u l fo ny l ) - 1 , 2 - O - i s o p ro py l i d e n e - 3 - O - ( 3 Ј - m e t h y l - 2 Ј -
oxoazetidin-4Ј-yl)-α-D-xylofuranose (40 and 41): Compounds 40/41,
6-O-(p-tert-Butyldimethylsilyloxyphenylsulfonyl)-1,2-O-isopropyl-
idene-3-O-methyl-5-O-(prop-1Ј-enyl)-α-D-glucofuranose (36): A so-
in a ratio of ca. 1.3:1, were obtained from 37 by the procedure
described above. Purification by flash chromatography on silica gel
(25% EtOAc in hexane) furnished 40/41 as an oil (67%). 40: 1H
NMR (500 MHz, CDCl3, selected signals taken from the spectrum
of the mixture): δ ϭ 1.15 (d, J ϭ 7.5 Hz, 3 H, Me), 1.30, 1.46 (2 s,
6 H, 2 ϫ Me), 4.57 (d, J ϭ 3.7 Hz, 1 H, H-2), 5.12 (d, J ϭ 4.4 Hz,
1 H, H-4Ј), 5.88 (d, J ϭ 3.7 Hz, 1 H, H-1), 6.39 (br. s, 1 H, NH)
lution of tert-butyldimethylsilyl chloride (0.88 g, 5.86 mmol) in
CH3CN (5 mL) was added dropwise at 0 °C to a stirred solution
of 23 (2.1 g, 4.88 mmol) and imidazole (0.8 g, 11.7 mmol) in dry
CH3CN (20 mL). The temperature of the reaction mixture was al-
lowed to rise to room temperature. After 2 h, the solvent was re-
moved, the mixture was poured into water, extracted with Et2O,
and dried (MgSO4), and the solvents were evaporated. The crude
product was purified on silica gel with an ethyl acetate/hexane mix-
1
ppm. 41: H NMR (CDCl3, selected signals taken from the spec-
trum of the mixture): δ ϭ 1.16 (d, J ϭ 7.5 Hz, 3 H, Me), 1.31, 1.47
(2 s, 6 H, 2 ϫ Me), 4.51 (d, J ϭ 3.6 Hz, 1 H, H-2), 5.15 (d, J ϭ
4.2 Hz, 1 H, H-4Ј), 5.86 (d, J ϭ 3.6 Hz, 1 H, H-1), 6.59 (br. s, 1
H, NH) ppm. IR (film):ν˜ ϭ 3340, 1770, 1591, 1363, 1176, 908
cmϪ1. HRMS (LSIMS): calcd. for [M ϩ H]ϩ (C24H38NO9SSi)
544.20366, found 544.20194. C24H37NO9SSi (543.72): calcd. C
53.02, H 6.86, N 2.57; found C 52.81, H 7.02, N 2.84.
ture (1:1, v/v) as eluent to yield 36 (2.3 g, 86%) as an oil. [α]2D2
ϭ
1
Ϫ22.8 (c ϭ 1.17, CH2Cl2). H NMR (500 MHz, CDCl3): δ ϭ 0.25
(s, 6 H, tBuMe2SiϪ), 0.99 (s, 9 H, tBuMe2SiϪ), 1.31, 1.47 (2 s, 6
H, 2 ϫ Me), 1.53 (dd, 3 H, J ϭ 1.7 Hz and J ϭ 6.8 Hz, CH3-3Ј),
3.35 (s, 3 H, CH3OϪ), 3.71 (d, J ϭ 2.3 Hz, 1 H, H-3), 4.05Ϫ4.13,
4.34Ϫ4.41 (2 m, 5 H, H-2Ј, H-4, H-5, H-6a, H-6b), 4.53 (d, J ϭ
3.7 Hz, 1 H, H-2), 5.80 (d, J ϭ 3.7 Hz, 1 H, H-1), 5.96 (dq, J ϭ
6.0 Hz, 1 H and J ϭ 1.6 Hz, H-1Ј), 6.89Ϫ6.93, 7.76Ϫ7.79 (2 m, 4
H, phenyl) ppm. 13C NMR (125 MHz, CDCl3): δ ϭ Ϫ4.42, 9.14,
18.20, 25.52, 26.21, 26.79, 57.53, 70.77, 75.74, 78.22, 81.23, 83.07,
101.82, 105.25, 111.98, 120.40, 127.94, 130.21, 145.10, 160.51 ppm.
IR (film): ν˜ ϭ 1670, 1496, 1365, 1082, 907 cmϪ1. HRMS (LSIMS):
(3ЈR,4ЈS)- and (3ЈS,4ЈR)-6-O-(p-Hydroxyphenylsulfonyl)-1,2-O-iso-
propylidene-3-O-methyl-5-O-(3Ј-methyl-2Ј-oxoazetidin-4Ј-yl)-α-D-
glucofuranose (42 and 43): The mixture of 38 and 39 (1.75 g,
2.98 mmol) was dissolved in THF (40 mL), and TBAF·3H2O
(0.47 g, 1.49 mmol) was added. The mixture was stirred for ca.
10 min (TLC), the solvent was then evaporated, and the crude
product was separated on a silica gel column with a hexane/EtOAc
mixture (1:4, v/v) as eluent to give a mixture of stereoisomers 42/
43 in a ratio of ca. 5.2:1 (1.15 g, 94%). 42: 1H NMR (500 MHz,
CDCl3, selected signals taken from the spectrum of the mixture):
δ ϭ 3.77 (d, J ϭ 2.0 Hz, 1 H, H-3), 4.58 (d, J ϭ 3.7 Hz, 1 H, H-
2), 5.30 (d, J ϭ 4.3 Hz, 1 H, H-4Ј), 5.82 (d, J ϭ 3.7 Hz, 1 H, H-
calcd. for [M
ϩ
Na]ϩ (C25H40NaO9SSi) 567.20600, found
567.20757. C25H40O9SSi (544.74): calcd. C 55.12, H 7.4; found C
55.08, H 7.66.
5-O-(p-tert-Butyldimethylsilyloxyphenylsulfonyl)-1,2-O-isopropyl-
idene-3-O-(prop-1Ј-enyl)-α-D-xylofuranose (37): Compound 37 was
obtained from 33 by the procedure described above (89%). Oil.
[α]2D2 ϭ Ϫ11.9 (c ϭ 0.46, CH2Cl2). H NMR (500 MHz, CDCl3):
1
1
1), 6.41 (br. s, 1 H, NH) ppm. 43: H NMR (CDCl3, selected sig-
δ ϭ 0.24 (s, 6 H, tBuMe2SiϪ), 0.99 (s, 9 H, tBuMe2SiϪ), 1.29, 1.47
(2 s, 6 H, 2 ϫ Me), 1.46 (dd, 3 H, J ϭ 1.7 Hz and J ϭ 6.9 Hz,
CH3-3Ј), 4.15 (d, J ϭ 3.1 Hz, 1 H, H-3), 4.20 (dd, J ϭ 6.2 Hz, 1 H
and J ϭ 10.2 Hz, H-5a), 4.27 (dd, J ϭ 6.1 Hz, 1 H and J ϭ 10.2 Hz,
H-5b), 4.42Ϫ4.54 (m, 2 H, H-2Ј, H-4), 4.51 (d, J ϭ 3.6 Hz, 1 H,
H-2), 5.87 (d, J ϭ 3.6 Hz, 1 H, H-2), 5.90 (dq, J ϭ 6.0 Hz, 1 H
and J ϭ 1.7 Hz, H-1Ј), 6.87Ϫ6.93, 7.73Ϫ7.80 (2 m, 4 H, phenyl)
ppm. 13C NMR (125 MHz, CDCl3): δ ϭ Ϫ4.42, 9.13, 18.19, 25.50,
26.25, 26.79, 66.35, 77.40, 82.67, 82.87, 104.36, 105.08, 112.31,
120.47, 127.64, 130.22, 143.21, 160.75 ppm. IR (CHCl3): ν˜ ϭ 1670,
nals taken from the spectrum of the mixture): δ ϭ 3.74 (d, J ϭ
2.7 Hz, 1 H, H-3), 4.57 (d, J ϭ 3.7 Hz, 1 H, H-2), 5.11 (d, J ϭ
4.4 Hz, 1 H, H-4Ј), 5.84 (d, J ϭ 3.7 Hz, 1 H, H-1), 6.66 (br. s, 1
H, NH) ppm. IR (film): ν˜ ϭ 3342, 1749, 1588, 1360, 1022, 842
cmϪ1. HRMS (LSIMS): calcd. for [M ϩ H]ϩ (C20H28NO10S)
474.14339, found 474.14369. C20H27NO10S (473.51): calcd. C,
50.73, H 5.74, N 2.95; found C 50.62, H 6.11, N 2.79.
(3ЈS,4ЈR)- and (3ЈR,4ЈS)-5-O-(p-Hydroxyphenylsulfonyl)-1,2-O-iso-
propylidene-3-O-(3Ј-methyl-2Ј-oxoazetidin-4Ј-yl)-α-D-xylofuranose
1496, 1371, 1083, 908 cmϪ1. HRMS (LSIMS): calcd. for [M ϩ (44 and 45): Compounds 44/45 were obtained, in a ratio of ca.
Eur. J. Org. Chem. 2002, 2377Ϫ2384 2383

M. Chmielewski et al.
FULL PAPER
[2h]
5909Ϫ5912.
3, 337Ϫ340.
M. Massimiliano, M. Taddei, Org. Lett. 2001,
1.1:1, from 40/41 according to the procedure described for 42/43
(94%). 44: 1H NMR (500 MHz, CDCl3, selected signals taken from
the spectrum of the mixture): δ ϭ 1.10 (d, J ϭ 7.5 Hz, 3 H, Me),
1.29, 1.46 (2 s, 6 H, 2 ϫ Me), 4.05 (d, J ϭ 3.3 Hz, 1 H, H-3), 4.57
(d, J ϭ 3.7 Hz, 1 H, H-2), 5.15 (d, J ϭ 4.4 Hz, 1 H, H-4Ј), 6.81
(br. s, 1 H, NH) ppm. 45: 1H NMR (CDCl3, selected signals taken
from the spectrum of the mixture): δ ϭ 1.09 (d, J ϭ 7.5 Hz, 3 H,
Me), 1.31, 1.48 (2 s, 6 H, 2 ϫ Me), 4.07 (d, J ϭ 3.1 Hz, 1 H, H-
3), 4.51 (d, J ϭ 3.6 Hz, 1 H, H-2), 5.16 (d, J ϭ 4.2 Hz, 1 H, H-4Ј),
6.93 (br. s, 1 H, NH) ppm. IR (film): ν˜ ϭ 3334, 1749, 1351, 1076,
978 cmϪ1. HRMS (LSIMS): calcd. for [M ϩ H]ϩ (C18H24NO9S)
430.11718, found 430.11740. C18H23NO9S (429.46): calcd. C 50.34,
H 5.39, N 3.26; found C 49.96, H 5.76, N 3.08.
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2.39. Elemental analysis indicating 0.99% N corresponds to a 92%
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This research was supported by the Polish State Committee for
Scientific Research (KBN), grant no. T09/PBZ.6.04. R. Ł. thanks
the Foundation for Polish Science for the FNP 2001 scholarship.
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Received January 16, 2002
[O02021]
2384
Eur. J. Org. Chem. 2002, 2377Ϫ2384