[2+2] Cycloaddition of chlorosulfonyl isocyanate to allenyl-sugar ethers

Article abstract of DOI:10.1016/S0957-4166(00)00260-3

The direction and magnitude of asymmetric induction in the [2+2] cycloaddition of chlorosulfonyl isocyanate to 3-O-allenyl-α-D-xylofuranoses was investigated. It is shown that gem terminal dimethylallenes react more readily than methyl free congeners. The configuration of adducts was established by X-ray and CD-spectroscopy of alkylidene cephams. A stereochemical model of the transition state for the [2+2] cycloaddition of chlorosulfonyl isocyanate and allenyl ethers is proposed, based on the lowest energy conformation of the cumulene. Copyright (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0957-4166(00)00260-3

Tetrahedron: Asymmetry 11 (2000) 3131±3150
[2+2] Cycloaddition of chlorosulfonyl isocyanate to allenyl-
sugar ethers
.
Robert —ysek,a Bart•omiej Furman,a Zbigniew Ka•uza,a Jadwiga Frelek,a
Kinga Suwinska,b Zo®a Urbanczyk-Lipkowskaa and Marek Chmielewskia,*
aInstitute of Organic Chemistry of the Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland
bInstitute of Physical Chemistry of the Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland
Received 21 June 2000; accepted 30 June 2000
Abstract
The direction and magnitude of asymmetric induction in the [2+2] cycloaddition of chlorosulfonyl isocyanate
to 3-O-allenyl-a-d-xylofuranoses was investigated. It is shown that gem terminal dimethylallenes react
more readily than methyl free congeners. The con®guration of adducts was established by X-ray and CD-
spectroscopy of alkylidene cephams. A stereochemical model of the transition state for the [2+2] cycloaddition
of chlorosulfonyl isocyanate and allenyl ethers is proposed, based on the lowest energy conformation of
the cumulene. # 2000 Elsevier Science Ltd. All rights reserved.
1. Introduction
b-Lactam antibiotics with an exo-methylene double bond, such as asparenomycins A, B, C 1±3,
6643-X 4,1 Ro 15-1903 5,2 6-(Z)-methoxymethylene-penicillanic acid 6,3 and 7-alkylidene-
cephalosporins 74 display high activities as b-lactamase inhibitors (Fig. 1).
In 1985 Buynak et al.5 reported on the synthesis of (þ)-asparenomycin C via 3-isopropylidene-
4-acetoxy-azetidin-2-one 9 which in turn has been obtained by [2+2] cycloaddition of chloro-
sulfonyl isocyanate (CSI) to acetoxyallene 8 (Scheme 1).6 Other allenes have also been shown to
react with CSI to form b-lactams with an exo double bond next to the carbonyl group.7,8
Recently, we have initiated a synthetic project aimed at transforming sugar-derived chiral vinyl
ethers into 5-dethia-5-oxacephams and clavams.9,10 The crucial step of the synthesis involved the
[2+2] cycloaddition of vinyl ethers and CSI, which has been shown to display an excellent
diastereoselectivity in many cases.9,10 It was of interest to examine alkoxyallenes in these
reactions and to demonstrate that the [2+2] cycloaddition strategy o€ers an entry to 5-oxacephams
and clavams featuring an exo double bond.
* Corresponding author. Tel: +48 22 6323789; fax: +48 22 6326681; e-mail: chmiel@icho.edu.pl
0957-4166/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(00)00260-3

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R. —ysek et al. / Tetrahedron: Asymmetry 11 (2000) 3131±3150
Figure 1.
Scheme 1.
The search for new b-lactam antibiotics has shown that the carbon atom next to the carbonyl
group can be substituted by a variety of groups while keeping the desired biological activity.11
Introduction of the exo-alkylidene fragment to the b-lactam ring provides an easy access to other
antibiotics via synthetic transformations of the double bond.
2. Results and discussion
For the present studies we selected ®ve allenes 10±14. Compound 10 was obtained from 16 by
the standard method,12,13 whereas 12 was obtained from 17 via a but-2-yne ether stage 19. The
synthesis of gem dimethyl-substituted allenes 11, 13 and 14 has been reported recently.13 An
attempt to isomerize the propargyl ether 15 led to the formation of a bicyclic compound 18
(Fig. 2).
ꢀ
14
[2+2] Cycloaddition of CSI/Na2CO3 to 10 in toluene at ^60 C, followed by the reduction of
the N-chlorosulfonyl group with Red-Al,15 gave b-lactam 20 as a 1:1 mixture of two dia-
stereomers in ca. 6% yield only. The post-reaction mixture contained substantial amounts of
unreacted allene 10. All attempts to increase the yield of the reaction by raising the temperature,
changing the solvent, etc. were unsuccessful; we only observed a decomposition of the substrate 10.
[2+2] Cycloaddition of CSI to 11 under standard conditions a€orded a mixture of b-lactams 21
and 22 in a ratio 2.3:1 (de=39%), respectively, in 65% yield. An acid catalyzed detritylation of

R. —ysek et al. / Tetrahedron: Asymmetry 11 (2000) 3131±3150
3133
Figure 2.
21/22 gave a mixture 23/24, which was subjected to tosylation of terminal hydroxymethyl groups
followed by intramolecular N-alkylation to a€ord a mixture of cephams 27 and 28y which were
separated into the pure components.
The absolute con®guration of the stereogenic center at C-40 in 27 and 28 was proved by NOE
experiments. In the case of diastereomer 28 an irradiation of the signal H-40 (ꢀ 5.17) showed the
enhancement of H-3 (ꢀ 4.14) by 6.6%. Conversely, the signal due to H-40 was enhanced by 3.7%
when H-3 was irradiated. Cepham 27 did not demonstrate any spin±spin interaction between H-3
(ꢀ 4.16) and H-40 (ꢀ 5.41). X-Ray structure analyses of compound 28 (Table 3, Fig. 9) and
diacetate 31 (Table 3, Fig. 10) obtained from a mixture of compounds 23/24, unequivocally
proved the con®guration at C-40 to be (S) in the former and (R) in the latter. Thus, the
con®guration of related compounds 21±27 was also established.
[2+2] Cycloaddition of CSI to 12 o€ers higher stereoselectivity (de=55%) in the formation of
(40R) stereoisomer 29 than the corresponding cycloaddition to 11 (Fig. 3).
Diminution of the size of the terminal sugar substituent by transforming a trityloxymethyl into
a methyl group 13 leads to the decrease in the face-di€erentiation of the double bond in the
cycloaddition. Under the standard reaction conditions the mixture of two diastereomers 32 and
33 was obtained in a ratio of about 1.3:1 (de=13%), respectively.
The absolute con®gurations of compounds 32 and 33 were assigned by comparison of their CD
spectrum with corresponding data of mixtures 21/22, 23/24, 25/26 and 29/30. All CD and UV
data for mixtures of 21/22, 23/24, 25/26, 29/30 and 32/33 are provided in Table 1. CD spectra of
mixtures 21/22, 23/24, 25/26 and 29/30 showed the same positive sign of the long wavelength CD
band at ca. 250 nm and of the short wavelength CD band around 210 nm (Fig. 5). In all cases, an
additional CD band around 230 nm of opposite sign to the ®rst two was present. The positive
sign of the 250 nm CD band can be assigned to the same con®guration at C-40 of the azetidin-2-
one ring. The absolute stereochemistry assignment could be done empirically based on the
combined analysis of the NMR, CD, X-ray data as well as chemical correlation of synthetic steps.
According to the NOE experiments for compounds 27 and 28, we were able to describe the
y
For the sake of simplicity, numbering of cephams refer to sugar nomenclature.

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R. —ysek et al. / Tetrahedron: Asymmetry 11 (2000) 3131±3150
Figure 3.
absolute con®guration of minor diastereomers in the mixtures of 21/22 and 23/24 to be (40S). The
reliability of this assignment was con®rmed by X-ray analysis of 28. Thus, the absolute
con®guration at C-40 in the major diastereomers in the mixtures 21/22, 23/24, 25/26 and 29/30
should be (R) owing to the same shape of the CD curves. In the case of mixture 32/33 (Fig. 5)
there was only one positive CD band visible at 207 nm in its spectrum. This can be explained on
the basis of the low diastereocontrol in this reaction leading to the mixture of 32:33 in a ratio of
1.3:1 only. However, the positive sign of the 207 nm CD band allows us to describe the (40R)
absolute con®guration to the major diastereomer in this case too.
Table 1
UV and CD data of b-lactams 21±26, 29, 30, 32±35 measured in acetonitrile
It should be mentioned at this stage that a comparison of the bond lengths in the azetidin-2-one
ring of diacetate 31 with the respective bond lengths of the (4R)-methylazetidin-2-one model
compound shows a di€erence in the C-20±C-30 bond length equal to 0.17 A16 (cf. Experimental).

R. —ysek et al. / Tetrahedron: Asymmetry 11 (2000) 3131±3150
3135
The shortening of the C-20±C-30 bond in compound 31 unequivocally indicates a participation of
the exo double bond with the b-lactam chromophoric system. Therefore, the b-lactam octant rule
is not applicable to the investigated compounds and cannot be used for determination of their
absolute con®guration.
The lower asymmetric induction found for 13 versus that found for 11 and 12 was not fully
understood, therefore we decided to investigate the stereoselectivity in the addition of CSI to 14
which, compared to 11, did not contain a dioxolane ring. Due to the instability of 14 under the
reaction conditions, a mixture of compounds 34 and 35 was obtained in a low yield and a ratio of
about 2.6:1 (de=44%), respectively. Compounds 34 and 35 were separated and puri®ed. The
absolute con®gurations of 34 and 35 were proved, as for the mixture 32/33, by CD spectroscopy
(Fig. 4). As shown in Table 1 and Fig. 5, the CD spectra of both epimers fell under two di€erent
patterns of sign sequence. In the case of compound 34, the negative long wavelength CD band
was followed by the positive and by the negative short wavelength ones. For compound 35 the
opposite relation of sign pattern was observed, i.e. the positive long wavelength CD band was
followed by the negative and positive ones. Hence, according to the aforementioned discussion,
the prevailing diastereomer 34 had an (S) con®guration at the C0-4 carbon atom whereas its
epimer 35 had an (R) con®guration at the same carbon of the azetidin-2-one ring.
Figure 4.
. .
Figure 5. CD spectra of 29/30 (Ð), 32/33 (- - -), 34 (- -), 35 ( ) in acetonitrile
..
....

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R. —ysek et al. / Tetrahedron: Asymmetry 11 (2000) 3131±3150
According to the Hammond postulate, the transition states of exothermic reactions resemble
the starting materials, in energy and geometry. It would therefore be reasonable to use the
ground-state conformation of ole®ns to re¯ect the geometry in the transition state of [2+2]
cycloadditions with CSI. Recently, using NOE coecients, we have assigned the most favorable
ground state conformation of sugar derived alkoxyallenes.13 The NOE studies on compounds 11,
13 and 14 have shown with high con®dence that the s-cis conformation should dominate in a
solution and the presence of s-trans conformer in solution is negligible in modelling ground-state
conformations of the investigated molecules. Consequently, conformation of the alkoxyallene
fragment and con®guration of the main diastereomer testify to the preferred si-entry of CSI to
allenes 11±13 and the re-entry to 14 (Fig. 6).
Figure 6. Stereochemical model of the CSI addition to allenes: (a) 11±13 and (b) 14
The comparison of the face-discrimination found for addition of CSI to 11±13 and to the vinyl
ether 369 is particularly interesting. The lower face-discrimination found for 11±13 is a
consequence of the s-cis conformation of the alkoxyallene, which makes both sides of the double
bond similarly accessible. The role of both methyl groups perpendicular to the vinyloxy double
bond in the stereoselectivity of [2+2] cycloaddition deserves, however, further elucidation.
In order to explain the contribution of gem methyl groups of allene, we synthesized two
cumulenes 37 and 38. Introduction of trimethylsilyl groups to 10 and 11 was accomplished by the
standard procedure involving lithiation followed by silylation with TMSCl.17
We expected that an introduction of the trimethylsilyl group to the diastereo-zeroplane should
not in¯uence the face-discrimination, whereas allenes 37 and 38 should react more readily and be
more resistant to the cycloaddition conditions.
[2+2] Cycloaddition of CSI to 37 proceeded with high face-discrimination to a€ord the
corresponding b-lactams 39 and 41 in a ratio of about 18:1 (de=89%), respectively (Scheme 2).
Compound 38 a€orded a lower asymmetric induction but a better yield of cycloaddition. A
mixture of compounds 40 and 42 was obtained in a ratio of 3.2:1 (de=52%), respectively
(Scheme 2). In both reactions the total yields were increased by 30% as compared to the additions

R. —ysek et al. / Tetrahedron: Asymmetry 11 (2000) 3131±3150
3137
Scheme 2.
involving the silyl-free allenes 10 and 11, respectively. The mixtures 39/41 and 40/42 were
separated into the pure components.
Absolute con®gurations of compounds 39±42 were assigned by a combination of X-ray crystal-
lography and CD spectroscopy. We were able to obtain a crystalline b-lactam 43 by N-acetylation
of compound 40 (Table 3, Fig. 10). The known con®guration of 40 and a comparison of CD
spectra of b-lactams 39±42 (Fig. 7, Table 2) provided the proof of their con®guration. As can be
seen in Table 2 and Fig. 7, compounds 39 and 40 display the same shape of their CD curves,
whereas compounds 41 and 42 display the opposite pattern of sign sequence. Taking into account
the known absolute con®guration of compound 40 (40R) and the same negative sign of the long
wavelength CD band, the con®guration of compound 39 also has to be (40R). Consequently,
con®guration at C-40 of compounds 41 and 42 has to be (S).
.. ....
Figure 7. CD spectra of 39 (- -), 40 (Ð), 41 ( ), 42 (- - -) in acetonitrile
Unexpectedly, the preferred direction of asymmetric induction in 37 and 38 di€ered from that
predicted by the analogy to the cycloaddition involving 11. We were not able to assign the
preferred ground-state conformation of 37 and 38 either by X-ray or by NOE coecients.13,18 It
could be assumed, however, that the two bulky lipophilic substituents, trityl and trimethylsilyl
interact with the repulsive force causing the C(3)±C(4) bond of the furanoid ring to become

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R. —ysek et al. / Tetrahedron: Asymmetry 11 (2000) 3131±3150
perpendicular to the diastereo-zero plane which consists of the vinyloxy double bond, O(3) oxygen
atom and C(3) carbon atom (Fig. 8). Such a geometry of allenes allows, as postulated by us earlier,13,18
stereoelectronic interaction between the p-electrons of the vinyloxy fragment and the ꢁ* orbital of
the C(3)±C(4) bond. If the proposed ground-state conformation of the allenes 37 and 38 (Fig. 8)
re¯ects the transition-state conformation, then the si side of the double bond is blocked by a
trityloxymethyl substituent and consequently the attack of the isocyanate occurs from the re side,
a€ording preferentially (R) con®gurations of the products 39 and 40.
Table 2
UV and CD data of b-lactams 39±42 measured in acetonitrile
Figure 8. Stereochemical model of the CSI addition to allenes 33 and 34
The experiments performed on 37 and 38 demonstrate the decisive role of the gem-methyl
groups in the allene fragment, which certainly activate a vinyloxy double bond of the allenes for
cycloaddition. This was proved by the experiment performed on the mixture of 37 and 38 and 0.5
equiv. of CSI. It resulted in exclusive formation of cephams 40 and 42.
The lower stereoselectivity found for 38 versus 37 can be explained by the increased reaction
rate in the case of dimethylallene 38.
An attempt to perform an intramolecular cyclization of 45, readily available by the standard
detritylation±tosylation sequence was unsuccessful. Both reaction conditions,9,19 usually applied
by us, gave compound 46 as the only isolated product in the yield not exceeding 18% (Scheme 3).
The structure and con®guration of 46 was proved by X-ray crystallography (Table 3, Fig. 11).
In summary, we have demonstrated that the [2+2] cycloaddition of CSI to alkoxyallene
provides b-lactams with a moderate stereoselectivity. Assuming that the transition state of the
cycloaddition resembles the ground-state conformation of alkoxyallene, we were able to explain
the direction and magnitude of the asymmetric induction.

R. —ysek et al. / Tetrahedron: Asymmetry 11 (2000) 3131±3150
3139
Scheme 3.
Table 3
Crystal data and structure re®nement for compounds 28, 31, 43, and 46

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R. —ysek et al. / Tetrahedron: Asymmetry 11 (2000) 3131±3150
3. Experimental
Melting points were determined on a Ko¯er hot-stage apparatus with microscope and are
uncorrected. 1H NMR spectra were obtained on Bruker Avance 500 and Varian Gemini AC-200
spectrometers for solutions in CDCl3 or benzene-d6 with tetramethylsilane as an internal standard
and are expressed as ꢀ values. Signals for aromatic protons (phenyls) were not characteristic and
therefore they were not included in spectral data. IR spectra were recorded on a Perkin±Elmer
FT-IR Spectrum 2000 spectrophotometer. Mass spectra were determined with an AMD 604
Inectra GmbH spectrometer. Optical rotations were measured using a JASCO P 3010 polarimeter
at ambient temperature. CD spectra were recorded on a J-715 spectropolarimeter in acetonitrile.
Column chromatography was performed on Merck silica gel (230±400 mesh).
3.1. 1,2-O-Isopropylidene-3-O-propargyl-ꢂ-d-xylofuranose 15
Compound 15 was obtained from 1,2:5,6-di-O-isopropylidene-3-O-propargyl-a-d-glucofuranose12
by the standard reaction sequence13 involving deprotection of the isopropylidene grouping,
glycolic cleavage of a terminal diol and a reduction of the aldehyde to the alcohol. The crude
product was puri®ed by column chromatography on silica gel using hexane:ethyl acetate, 7:3 v/v,
as an eluent to give 15 (83%): oil; ‰ꢂŠD22=^66.1 (0.9, CH2Cl2); IR (®lm) 2117, 3275, 3486 cm^1; 1H
NMR (200 MHz, CDCl3) ꢀ: 1.33, 1.51 (2s, 6H, 2ÂMe), 2.51 (t, 1H, J=2.4 Hz, ꢁCH), 3.84 (dd,
1H, J=5.5 and 12.0 Hz, H-5a), 3.93 (dd, 1H, J=5.3 and 12.0 Hz, H-5b), 4.01^4.20 (m, 2H,
^OCH2^), 4.19 (d, 1H, J=3.4 Hz, H-3), 4.14^4.34 (m, 3H, H-4, ^OCH2^), 4.62 (d, 1H, J=3.8 Hz,
H-2), 5.95 (d, 1H, J=3.8 Hz, H-1); anal. calcd for C11H16O5 (228.25): C, 57.88; H, 7.06. Found:
C, 57.64; H, 7.26.
3.2. 5-O-t-Butyldimethylsilyl-3-O-propargyl-1,2-O-isopropylidene-ꢂ-d-xylofuranose 17
To a stirred solution of 16 (6 g, 26.3 mmol) and imidazole (3.76 g, 55.2 mmol) in dry CH3CN
(40 mL) at 0ꢀC, a solution of t-butyldimethylsilyl chloride (4.36 g, 28.9 mmol) in CH3CN (15 mL)
was added dropwise. The temperature of the reaction was allowed to rise to room temperature.
After 2 h, the solvent was removed and the mixture was poured into water, extracted with Et2O,
dried (MgSO4) and evaporated. The crude product was puri®ed by column chromatography on
silica gel using hexane:ethyl acetate, 94:6 v/v, as an eluent to give 17 (8.1 g, 90%): syrup;
[ꢂ]D=^39.0 (c 1.9, CHCl3); IR (®lm) 2119, 3271, 3312 cm^1 (lit.,12 oil, ‰ꢂŠD22=^37.6 (c 1.9, CHCl3);
IR (KBr) 1100, 1200, 1380, 2100, 3300 cm^1).
3.3. 1,2-O-Isopropylidene-3-O-(prop-10,20-dienyl)-5-O-trityl-ꢂ-d-xylofuranose 10
To a solution of 15 (4.70 g, 10 mmol) in a 1:1 v/v mixture of t-BuOH:DMSO (30 mL) freshly
sublimated t-BuOK (1.12 g, 10 mmol) was added. The solution was heated at 55ꢀC for 1.5 h
(TLC monitoring), cooled to room temperature, and water (50 mL) and t-butyl methyl ether (50
mL) were added. The aqueous phase was extracted with t-butyl methyl ether (3Â60 mL). The
combined ether extracts were dried (Na2SO4) and evaporated. The residue was puri®ed by
column chromatography to give 10 (85%): oil; ‰ꢂŠ2D2=^6.6 (c 1.1, CH2Cl2); IR (®lm) 1954 cm^1;
1H NMR (200 MHz, CDCl3) ꢀ: 1.32, 1.54 (2s, 6H, 2ÂMe), 3.32 (dd, 1H, J=6.8 and 9.3 Hz, H-
5a), 3.42 (dd, 1H, J=5.8 and 9.3 Hz, H-5b), 4.28 (d, 1H, J=3.0 Hz, H-3), 4.38 (ddd, 1H, J=3.0,

R. —ysek et al. / Tetrahedron: Asymmetry 11 (2000) 3131±3150
3141
5.8 and 6.8 Hz, H-4), 4.55 (d, 1H, J=3.8 Hz, H-2), 5.44 (dd, 1H, J=6.0 and 8.5 Hz, HAHBCˆ),
5.55 (dd, 1H, J=6.0 and 8.5 Hz, HAHBCˆ), 5.86 (d, 1H, J=3.8 Hz, H-1), 6.58 (t, 1H, J=6.0 Hz,
=CHO^); MS (EI, HR) m/z: M+ calcd for C30H30O5: 470.20932. Found: 470.20818; anal. calcd
for C30H30O5 (470.58): C, 76.57; H, 6.42. Found C, 76.50; H, 6.54.
3.4. 1,2-O-Isopropylidene-3-O:5-O-(prop-10-en-10,20-diyl)-ꢂ-d-xylofuranose 18
Compound 15 under the isomerization conditions (see procedure described for 10) a€orded 18
22
1
(74%): oil; ‰ꢂŠD =+67.0 (c 1.5, CH2Cl2); IR (®lm) 1677 cm^1; H NMR (200 MHz, CDCl3) ꢀ:
1.32, 1.54 (2s, 6H, 2ÂMe), 1.60 (d, 3H, J=1.2 Hz, Me), 4.18 (dd, 1H, J=9.5, 11.5 Hz, H-5a),
4.29 (dd, 1H, J=6.2, 11.5 Hz, H-5b), 4.51 (d, 1H, J=3.2 Hz, H-3), 4.56 (d, 1H, J=3.7, H-2),
4.60^4.64 (m, 1H, H-4), 5.62 (d, 1H, J=1.2 Hz, ^OCH=), 5.85 (d, 1H, J=3.7, H-1); MS (EI,
HR) m/z: M+ calcd for C11H16O5: 228.0998. Found: 228.1008; anal. calcd for C11H16O5 (228.25):
C, 57.88; H, 7.06. Found: C, 57.75; H, 7.22.
3.5. 3-O-(But-20-ynyl)-5-O-t-butyldimethylsilyl-1,2-O-isopropylidene-ꢂ-d-xylofuranose 19
To a solution of n-BuLi (2.5 M in hexane, 9.56 mL, 23.9 mmol) and a mixture of dry
THF:HMPA (9:1 v/v, 40 mL) under argon was added 17 (6.3 g, 18.4 mmol) in THF (10 mL) at
^60ꢀC with stirring. The mixture was allowed to slowly warm up to ^20ꢀC and then treated with
MeI (1.48 mL, 23.9 mmol). Stirring was continued for 1 h while warming up to room temperature.
The mixture was diluted with t-butyl methyl ether:hexane, 1:1 v/v, washed with brine, dried
(MgSO4), and concentrated. The residue was puri®ed on a silica gel column using hexane:ethyl
acetate, 94:6 v/v, as an eluent to give 19 (3.8 g, 58%): oil; ‰ꢂŠ2D2=^40.0 (c 0.48, CH2Cl2); IR
(CH2Cl2) 2226 cm^1; 1H NMR (200 MHz, benzene-d6) ꢀ: 0.07 (s, 6H, t-BuMe2Si±), 0.95 (s, 9H, t-
BuMe2Si±), 1.11, 1.41 (2s, 6H, 2ÂMe), 1.46 (t, 3H, J=2.3 Hz, Me^Cꢁ), 3.91±4.15 (m, 4H, H-5a,
H-5b, H-10a, H-10b), 4.22 (d, 1H, J=3.4 Hz, H-3), 4.41 (d, 1H, J=3.8 Hz, H-2), 4.51±4.60 (m,
1H, H-4), 5.88 (d, 1H, J=3.8 Hz, H-1); MS (EI, HR) m/z: (M^CH3)+ calcd for C17H29O5Si:
341.1784. Found: 341.1788.
3.6. 5-O-t-Butyldimethylsilyl-1,2-O-isopropylidene-3-O-(30-methyl-buta-10,20-dienyl)-ꢂ-d-xylo-
furanose 12
To a solution of 19 (2.7 g, 7.57 mmol) in dry THF (20 mL) at ^45ꢀC was added n-BuLi (2.2 M
in hexane, 4.13 mL, 9.1 mmol). After 25 min at ^45ꢀC, MeI (0.56 mL, 9.1 mmol) was added, then
the solution was warmed to 25ꢀC over 20 min. Subsequently, t-butyl methyl ether (100 mL) and
saturated aqueous NaCl solution (50 mL) were added. The organic layer was separated, washed
with water, dried (MgSO4), and concentrated. The residue was puri®ed on a silica gel column,
using hexane:ethyl acetate, 95:5 v/v, as an eluent to give 12 (1.4 g, 50%): oil; ‰ꢂŠ2D2=^30.2 (c 0.5,
1
CH2Cl2); IR (®lm) 1959 cm^1; H NMR (200 MHz, CDCl3) ꢀ: 0.07 (s, 6H, t-BuMe2Si^), 0.89 (s,
9H, t-BuMe2Si^), 1.30, 1.51 (2s, 6H, 2ÂMe), 1.82 (d, 3H, J=2.1 Hz, Me), 1.85 (d, 3H, J=2.1 Hz,
Me), 3.82 (dd, 1H, J=6.0 and 10.0 Hz, H-5a), 3.88 (dd, 1H, J=6.9 and 10.0 Hz, H-5b), 4.16 (d,
1H, J=3.0 Hz, H-3), 4.30 (ddd, 1H, J=3.0, 6.0 and 6.9 Hz, H-4), 4.54 (d, 1H, J=3.7 Hz, H-2),
5.86 (d, 1H, J=3.7 Hz, H-1), 6.40 (sept., 1H, J=2.1 Hz, H-10); MS (HR, LSIMS) m/z: (M+H)+
calcd for C19H35O5Si: 371.2254. Found: 371.2227; anal. calcd for C19H34O5Si (370.57): C, 61.58;
H, 9.23. Found: C, 61.02; H, 9.37.

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3.7. [2+2]Cycloaddition of chlorosulfonyl isocyanate to alkoxyallenes 10±14. General procedure
To a suspension of anhydrous Na2CO3 (0.15 g) in dry toluene (2 mL) chlorosulfonyl isocyanate
(0.114 mL, 1.3 mmol) was added. The mixture was stirred and upon cooling to ^70ꢀC a solution
of alkoxyallenes 10±14 (1 mmol) in dry toluene (2 mL) was added dropwise. The temperature of
the mixture was allowed to rise to ^30ꢀC and it was maintained for 1.5 h. The mixture was then
cooled to ^70ꢀC, diluted with toluene (6 mL), treated with Red-Al (1 M solution in toluene, 1.3
mL), and left for 30 min while maintaining the temperature. The cooling bath was removed and
water (0.2 mL) was added at 0ꢀC. After 15 min of an intensive stirring the suspension was ®ltered
through Celite, the solvent was evaporated and the residue was puri®ed by chromatography on
silica gel to give the respective products.
3.8. (40R) and (40S) 1,2-O-Isopropylidene-3-O-(30-methyleneazetidin-20-on-40-yl)-5-O-trityl-ꢂ-d-
xylofuranoses 20
In a ratio of ca. ꢂ1:1 (6%): oil; IR (®lm) 1772, 3296 cm^1; 1H NMR (500 MHz, CDCl3) selective
signals taken for the mixture: major isomer ꢂ52%: ꢀ 4.23 (d, 1H, J=3.0 Hz, H-3), 4.46 (d, 1H,
J=3.8 Hz, H-2), 5.15 (d, 1H, J=1.9 Hz, HAHBCˆ), 5.42 (s, 1H, H-40), 5.73 (m, 1H, HAHBCˆ),
6.52 (br s, 1H, NH). Minor isomer ꢂ48%: 4.19 (d, 1H, J=3.0 Hz, H-3), 4.51 (d, 1H, J=3.8 Hz,
H-2), 5.20 (d, 1H, J=1.9 Hz, HAHBCˆ), 5.40 (s, 1H, H-40), 5.68 (m, 1H, HAHBCˆ), 6.34 (br s,
1H, NH); MS (HR, LSIMS) m/z: (M+Na)+ calcd for C31H31O6NNa: 536.2049. Found: 536.2037.
3.9. (40R) and (40S) 1,2-O-Isopropylidene-3-O-[30-(1-methylethylidene)azetidin-20-on-40-yl]-5-O-
trityl-ꢂ-d-xylofuranose 21 and 22
In a ratio of ca. 2.3:1 (60%): oil; IR (®lm) 1729, 1763, 3408 cm^1. Compound 21: 1H NMR (500
MHz, benzene-d6) selective signals taken for the mixture: ꢀ 1.44 (s, 3H, Me), 1.81 (s, 3H, Me),
3.35 (dd, 1H, J=5.0 and 9.9 Hz, H-5a), 3.81 (d, 1H, J=3.0 Hz, H-3), 4.33 (d, 1H, J=3.7 Hz, H-
2), 4.58^4.61 (m, 1H, H-4), 4.76 (s, 1H, H-40), 5.85 (br s, 1H, NH), 5.90 (d, 1H, J=3.8 Hz, H-1).
Compound 22: 1H NMR (500 MHz, benzene-d6) selective signals taken for the mixture: ꢀ 1.46 (s,
3H, Me), 1.80 (s, 3H, Me), 3.34 (dd, 1H, J=5.0 and 9.9 Hz, H-5a), 3.94 (d, 1H, J=3.0 Hz, H-3),
4.34 (d, 1H, J=3.7 Hz, H-2), 4.63^4.66 (m, 1H, H-4), 4.85 (s, 1H, H-40), 5.75 (br s, 1H, NH), 5.94
(d, 1H, J=3.8 Hz, H-1); MS (HR, LSIMS) m/z: (M+Na)+ calcd for C33H35O6NNa: 564.2362.
Found: 564.2390; anal. taken for the mixture calcd for C33H35O6N (541.66): C, 73.18; H, 6.98; N,
2.58. Found: C, 72.98; H, 6.77; N, 2.41.
3.10. (40R) and (40S) 1,2-O-Isopropylidene-3-O-[30-(1-methylethylidene)azetidin-20-on-40-yl]-ꢂ-
d-xylofuranose 23 and 24
The mixture 21/22 was detritylated with 0.2% of p-TsOH in MeOH at room temperature (ꢂ2
h, TLC monitoring). The crude product was puri®ed by column chromatography using hex-
ane:ethyl acetate, 2.5:7.5 v/v, as an eluent to give a mixture of compounds 23 and 24, in a ratio ca.
1
2:1 (75%): oil; IR (®lm) 1746, 3307, 3459 cm^1. Compound 23: H NMR (500 MHz, CDCl3)
selective signals taken for the mixture: ꢀ 1.31, 1.49 (2s, 6H, 2ÂMe), 1.87 (s, 3H, Me), 2.08 (s, 3H,
Me), 4.22 (d, 1H, J=3.4 Hz, H-3), 4.51 (d, 1H, J=3.8 Hz, H-2), 5.94 (d, 1H, J=3.8 Hz, H-1),
1
6.66 (br s, 1H, NH). Compound 24: H NMR (500 MHz, CDCl3) selective signals taken for the

R. —ysek et al. / Tetrahedron: Asymmetry 11 (2000) 3131±3150
3143
mixture: ꢀ 1.32, 1.50 (2s, 6H, 2ÂMe), 1.84 (s, 3H, Me), 2.07 (s, 3H, Me), 4.17 (d, 1H, J=3.3 Hz,
H-3), 4.59 (d, 1H, J=3.7 Hz, H-2), 5.93 (d, 1H, J=3.7 Hz, H-1), 6.82 (br s, 1H, NH); MS (HR,
LSIMS) m/z: (M+H)+ calcd for C14H22O6N: 300.1447. Found: 300.1427; anal. taken for the mixture
calcd for C14H21O6N (299.33): C, 56.18; H, 7.07; N, 4.68. Found: C, 56.09; H, 7.33; N, 4.41.
3.11. (40R) and (40S) 1,2-O-Isopropylidene-3-O-[30-(1-methylethylidene)azetidin-20-on-40-yl]-5-
O-tosyl-ꢂ-d-xylofuranose 25 and 26
The mixture of 25/26 was obtained from 23/24 by a standard tosylation procedure (82%): oil;
1
IR (®lm) 1730, 1759, 3323 cm^1. Compound 25: H NMR (200 MHz, CDCl3) selective signals
taken for the mixture: ꢀ 2.46 (s, 3H, tosyl), 4.43 (d, 1H, J=3.8 Hz, H-2), 5.59 (s, 1H, H-40), 5.85
1
(d, 1H, J=3.8 Hz, H-1), 6.61 (br s, 1H, NH). Compound 26: H NMR (200 MHz, CDCl3)
selective signals taken for the mixture: ꢀ 2.46 (s, 3H, tosyl), 4.57 (d, 1H, J=3.7 Hz, H-2), 5.57 (s,
1H, H-40), 5.86 (d, 1H, J=3.7 Hz, H-1), 6.52 (br s, 1H, NH); MS (HR, LSIMS) m/z: (M+H)+
calcd for C21H28O8NS: 454.1536. Found: 454.1531; anal. calcd for C21H27O8NS (453.52): C,
55.62; H, 6.00; N, 3.08. Found: C, 55.79; H, 6.15; N, 3.05.
3.12. (40R) and (40S) 5-Deoxy-1,2-O-isopropylidene-3-O:5-C-[30-(1-methylethylidene)azetidin-
20-on-10,40-diyl)-ꢂ-d-xylofuranose 27 and 28
A mixture of compounds 25/26 (1.1 g, 2.42 mmol) was dissolved in anhydrous CH3CN (45 mL)
and treated with Bu4NBr (0.92 g, 2.90 mmol) and pulverized K2CO3 (3.0 g). The mixture was
stirred under re¯ux for 45 min (TLC). Subsequently, toluene (50 mL) was added, the mixture was
®ltered, washed with water, dried (Na2SO4) and evaporated. The crude product was separated by
¯ash chromatography on a silica gel (25^40% ethyl acetate±hexane) to give 27 (0.35 g, 51%) and
28 (0.20 g, 30%). Compound 27: colorless crystals; mp 64.5^67ꢀC; ‰ꢂŠD22=+136.1 (0.28, CHCl3);
IR (®lm) 1759 cm^1; 1H NMR (500 MHz, CDCl3) ꢀ: 1.33, 1.48 (2s, 6H, 2ÂMe), 1.84 (s, 3H, Me),
2.06 (s, 3H, Me), 3.36 (dd, 1H, J=3.3 and 14.4 Hz, H-5a), 4.06 (dd, 1H, J=6.9 and 14.4 Hz, H-
5b), 4.16 (d, 1H, J=3.0 Hz, H-3), 4.50 (m, 1H, H-4), 4.61 (d, 1H, J=3.8 Hz, H-2), 5.41 (s, 1H, H-
40), 5.99 (d, 1H, J=3.8 Hz, H-1); MS (EI, HR) m/z: M+ calcd for C14H19O5N: 281.1263. Found:
281.1266; anal. calcd for C14H19O5N (281.31): C, 59.78; H, 6.81; N, 4.98. Found: C, 60.20; H,
7.06; N, 4.92. Compound 28: colorless crystals; mp 186^191ꢀC; ‰ꢂŠD22=^44.2 (0.53, CH2Cl2); IR
1
(®lm) 1748 cm^1; H NMR (500 MHz, CDCl3) ꢀ: 1.31, 1.49 (2s, 6H, 2ÂMe), 1.82 (s, 3H, Me),
2.03 (s, 3H, Me), 3.36 (dd, 1H, J=4.0 and 15.2 Hz, H-5a), 4.05 (dd, 1H, J=1.7 and 4.0 Hz, H-4),
4.13 (d, 1H, J=15.2 Hz, H-5b), 4.14 (d, 1H, J=1.7 Hz, H-3), 4.51 (d, 1H, J=3.7 Hz, H-2), 5.17
(s, 1H, H-40), 5.89 (d, 1H, J=3.7 Hz, H-1); MS (EI, HR) m/z: (M^CH3)+ calcd for C13H16O5N:
266.1028. Found: 266.1030; anal. calcd for C14H19O5N (281.32): C, 59.78; H, 6.81; N, 4.98.
Found: C, 59.53; H, 7.03; N, 4.83.
3.13. X-Ray structure analysis of compounds 28, 31, 43 and 46
X-ray data for crystals of compounds 28 (Fig. 9) and 31 (Fig. 10) were collected on a Nonius
MACH3 four-circle di€ractometer using EXPRESS procedure.20 !±2ꢃ Scanning mode was
applied. Unit cell parameters were obtained by re®nement of 15 re¯ections in the ꢃ-range 14.2±
19.4 and 16.8±21.4ꢀ, for compounds 28 and 31, respectively. Data reduction was performed with
the use of an OpenMoleN system of programs.21

3144
R. —ysek et al. / Tetrahedron: Asymmetry 11 (2000) 3131±3150
Figure 9. Molecular structure of the compound 28 with the crystallographic numbering scheme
Figure 10. Molecular structure of the compound 31 with the crystallographic numbering scheme
X-Ray data for crystals of compounds 43 (Fig. 11) and 46 (Fig. 12) were collected on a Nonius
KappaCCD di€ractometer.22 Detector: 1242 (horizontal)Â1152 (vertical) pixels, CCD pixel size
is 22.5Â22.5 mm which gives at the input a pixel of 110Â110 mm (with 2Â2 binning). Compound
43: 99 frames with p® scan and 27 frames with ! scan were collected, scan angle 2ꢀ, scan time 40
s/frame. Compound 46: 132 frames with ꢄ scan were collected, scan angle 1.5ꢀ, scan time 450
s/frame. Unit cell parameters and data reduction with Denzo and Scalepak,23 structures were

R. —ysek et al. / Tetrahedron: Asymmetry 11 (2000) 3131±3150
3145
Figure 11. Molecular structure of the compound 43 with the crystallographic numbering scheme
Figure 12. Molecular structure of the compound 46 with the crystallographic numbering scheme
solved with direct methods SHELXS-8624 and re®ned with SHELXL-97,25 molecular diagrams
with ATOMS.26 Crystal data and details of structure solution and re®nement are shown in
Table 3.27

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R. —ysek et al. / Tetrahedron: Asymmetry 11 (2000) 3131±3150
3.14. (40R) and (40S) 5-O-t-Butyldimethylsilyl-3-O-[30-(1-methylethylidene)azetidin-20-on-40-yl]-
1,2-O-isopropylidene-ꢂ-d-xylofuranose 29 and 30
In a ratio of ca. 3:1, compounds 29 and 30 were obtained from 12 according to the general
procedure described earlier. Chromatographic separation on silica gel, using hexane:ethyl acetate,
1
7.5:2.5 v/v, as an eluent, gave 29/30 (48%): oil; IR (®lm) 1755, 3296 cm^1. Compound 29: H
NMR (200 MHz, CDCl3) selective signals taken for the mixture: ꢀ 1.31, 1.51 (2s, 6H, 2ÂMe), 1.86
(s, 3H, Me), 2.06 (s, 3H, Me), 4.12 (d, 1H, J=3.2 Hz, H-3), 4.52 (d, 1H, J=3.7 Hz, H-2), 5.56 (s,
0
1
1H, H-4 ), 5.90 (d, 1H, J=3.7 Hz, H-1), 6.65 (br s, 1H, NH). Compound 30: H NMR (CDCl3)
selective signals taken for the mixture: 1.33, 1.52 (2s, 6H, 2ÂMe), 1.83 (s, 3H, Me), 2.05 (s, 3H,
Me), 4.57 (d, 1H, J=3.8 Hz, H-2), 5.46 (s, 1H, H-40), 5.89 (d, 1H, J=3.8 Hz, H-1), 6.87 (br s, 1H,
NH); MS (EI, HR) m/z: (M^CH3)+ calcd for C19H32O6NSi: 398.1999. Found: 398.2018; anal.
taken for the mixture calcd for C20H35O6NSi (413.60): C, 58.08; H, 8.53; N, 3.39. Found: C,
58.19; H, 8.77; N, 3.44.
3.15. (40R) 5-O-Acetyl-3-O-[N-acetyl-30-(1-methylethylidene)azetidin-20-on-40-yl]-1,2-O-isopropyl-
idene-ꢂ-d-xylofuranose 31
A solution of 23/24 (0.05 g, 0.167 mmol) and DMAP (0.01g) in acetic anhydride and pyridine
1:2 v/v (2 mL) was stirred at room temperature until the reaction was complete (TLC). After 1 h,
the mixture was poured into water, extracted with CH2Cl2, dried (Na2SO4), and evaporated. The
residue was puri®ed by ¯ash chromatography using ethyl acetate:hexane, 3:7 v/v, as an eluent to
give a mixture of 40-stereoisomers in a ratio of ca. 2:1 (0.057 g, 89%).
The major compound 31 was isolated in pure form by crystallization from a Et2O^hexane
mixture: colorless crystals; mp 125^127ꢀC; ‰ꢂŠD22=^48.2 (0.8, CH2Cl2); IR (CH2Cl2) 1701, 1744,
1
1784 cm^1; H NMR (500 MHz, CDCl3) ꢀ: 1.31, 1.51 (2s, 6H, 2ÂMe), 1.93 (s, 3H, Me), 2.15 (s,
3H, Me), 2.09 (s, 3H,CH3C(O)±), 2.45 (s, 3H, CH3C(O)±), 4.29 (dd, 1H, J=6.0 and 11.3 Hz, H-
5a), 4.33 (dd, 1H, J=6.5 and 11.3 Hz, H-5b), 4.43 (ddd, 1H, J=2.9, 6.0 and 6.5 Hz, H-3), 4.53 (d,
1H, J=3.7 Hz, H-2), 4.59 (d, 1H, J=2.9 Hz, H-3), 5.73 (s, 1H, H-40), 5.90 (d, 1H, J=3.8 Hz, H-1);
MS (LSIMS, HR) m/z: (M+Na)+ calcd for C18H25O8NNa: 406.14779. Found: 406.14847; anal.
calcd. for C18H25O8N (383.41): C, 56.39; H, 6.57; N, 3.65. Found: C, 56.67; H, 6.87; N, 3.35.
3.16. (40R) and (40S) 1,2-O-Isopropylidene-3-O-[30-(1-methylethylidene)azetidin-20-on-40-yl]-ꢂ-
d-xylofuranose 23/24
A mixture of compounds 29/30 (1.3 g, 3.14 mmol) was dissolved in THF (40 mL) and
.
TBAF 3H2O (0.99 g, 3.14 mmol) was added. The mixture was stirred for 15 min (TLC), then the
solvent was evaporated and a crude product was separated on silica gel column, using hex-
ane:ethyl acetate, 2.5:7.5 v/v, as an eluent, to give a mixture of stereoisomers 23/24 in a ratio of
ca. 3:1 (0.87 g, 92%).
3.17. (40R) and (40S) 5-O-Deoxy-1,2-O-isopropylidene-3-O-(30-(1-methylethylidene)-azetidin-20-
on-40-yl)-d-xylofuranose 32 and 33
A mixture of compounds 32/33 in a ratio of ꢂ1.3:1, was obtained from 13 according to the
procedure described earlier (40%): oil; IR (CH2Cl2) 1728, 1762, 3411 cm^1; compound 32: 1H NMR

R. —ysek et al. / Tetrahedron: Asymmetry 11 (2000) 3131±3150
3147
(200 MHz, CDCl3) taken for the mixture: ꢀ 3.96 (d, 1H, J=3.0 Hz, H-3), 4.51 (d, 1H, J=3.8 Hz,
H-2), 5.56 (s, 1H, H-40), 6.68 (br s, 1H, NH). Compound 33: 1H NMR (200 MHz, CDCl3) taken
for the mixture: ꢀ 3.96 (d, 1H, J=3.0 Hz, H-3), 4.58 (d, 1H, J=3.8 Hz, H-2), 5.68 (s, 1H, H-40),
6.65 (br s, 1H, NH); MS (HR, LSIMS) m/z: (M+H)+ calcd for C14H22O5N: 284.1498. Found:
284.1471; anal. taken for the mixture calcd for C14H21O5N (283.33): C, 59.35; H, 7.47; N, 4.94.
Found: C, 58.97; H, 7.56; N, 4.76.
3.18. (40S) and (40R) 1,4-Anhydro-2-deoxy-3-O-[30-(1-methylethylidene)azetidin-20-on-40-yl]-5-
O-trityl-d-treo-pentitol 34/35
A mixture of compounds 34/35, in a ratio of ꢂ2.6:1, was obtained from 14 according to the
procedure described earlier (17%). Products were separated into the pure components by
chromatography. Compound 34: oil; ‰ꢂŠD22=+23.5 (c 0.15, CH2Cl2); IR (CH2Cl2) 1727, 1759, 3412
cm^1; 1H NMR (500 MHz, CDCl3) ꢀ: 1.61 (s, 3H, Me), 1.87^1.93 (m, 1H, H-2a), 2.00 (s, 3H, Me),
2.03^2.10 (m, 1H, H-2b), 3.14 (dd, 1H, J=5.8 and 9.6 Hz, H-5a), 3.45 (dd, 1H, J=6.1 and 9.6
Hz, H-5b), 3.78^3.83 (m, 1H, H-1a), 3.88^3.92 (m, 1H, H-1b), 4.00 (ddd, 1H, J=4.3, 4.8 and 6.8
Hz, H-4), 4.34^4.37 (m, 1H, H-3), 5.36 (s, 1H, H-40), 6.11 (br s, 1H, NH); MS (HR, LSIMS) m/z:
(M+Na)+ calcd for C30H31O4NNa: 492.2151. Found: 492.2162. Compound 35: oil; ‰ꢂŠ2D2=^9.2 (c
1
0.35, CH2Cl2); IR (CH2Cl2) 1728, 1759, 3413 cm^1; H NMR (500 MHz, CDCl3): ꢀ 1.55 (s, 3H,
Me), 1.98 (s, 3H, Me), 1.99^2.04 (m, 1H, H-2a), 2.12^2.20 (m, 1H, H-2b), 3.15 (dd, 1H, J=5.4
and 9.8 Hz, H-5a), 3.46 (dd, 1H, J=6.4 and 9.8 Hz, H-5b), 3.82^3.87 (m, 1H, H-4), 3.95^4.01 (m,
2H, H-1a, H-1b), 4.28 (m, 1H, H-3), 5.41 (s, 1H, H-40), 6.12 (br s, 1H, NH); MS (HR, LSIMS)
m/z: (M+Na)+ calcd for C30H31O4NNa: 492.2151. Found: 492.2140; anal. calcd for C30H31O4N
(469.60): C, 76.73; H, 6.65; N, 2.98. Found: C, 76.50; H, 6.48; N, 2.83.
3.19. 1,2-O-Isopropylidene-3-O-(10-trimethylsilylpropa-10,20-dienyl)-5-O-trityl-ꢂ-d-xylo-furanose 37
To a solution of 10 (2.65 g, 5.63 mmol) in dry THF (25 mL) at ^50ꢀC, n-BuLi (2.5 M in hexane,
2.7 mL, 6.75 mmol) was added. After 30 min at ^30ꢀC, trimethylsilyl chloride (0.86 mL, 6.75
mmol) was added. Stirring was continued for 45 min while warming up to room temperature. The
mixture was diluted with 1:1 t-butyl methyl ether:hexane, washed with brine, dried (MgSO4), and
the solvent evaporated. The residue was puri®ed on a silica gel column using hexane:ethyl acetate,
94:6 v/v, as an eluent to give 37 (2.35 g, 77%): oil; ‰ꢂŠ2D2=^9.4 (c 0.65, CH2Cl2); IR (®lm) 1925
cm^1; 1H NMR (200 MHz, CDCl3) ꢀ: ^0.04 (s, 9H, ^SiMe3), 1.32, 1.54 (2s, 6H, 2ÂMe), 3.29 (dd,
3H, J=5.3 and 9.8 Hz, H-5a), 3.39 (dd, 3H, J=6.4 and 9.8 Hz, H-5b), 4.30 (d, 1H, J=3.2 Hz, H-
3), 4.37^4.45 (m, 1H, H-4), 4.47 (d, 1H, J=3.8 Hz, H-2), 5.11 (d, 1H, J=8.8 Hz, HAHBCˆ), 5.24
(d, 1H, J=8.8 Hz, HAHBCˆ), 5.86 (d, 1H, J=3.8 Hz, H-1); MS (EI, HR) m/z: M+ calcd for
C33H38O5Si: 542.2488. Found: 542.2496.
3.20. 1,2-O-Isopropylidene-3-O-(30-methyl-10-trimethylsilylbuta-10,20-dienyl)-5-O-trityl-ꢂ-d-xylo-
furanose 38
Compound 38 was obtained from 11 according to the procedure described above (87%): oil;
1
[ꢂ]D=+8.6 (c 0.51, CH2Cl2); IR (®lm) 1934 cm^1; H NMR (200 MHz, CDCl3) ꢀ: ^0.06 (s, 9H,
^SiMe3), 1.31, 1.53 (2s, 6H, 2ÂMe), 1.70 (s, 3H, Me), 1.78 (s, 3H, Me), 3.35 (d, 2H, J=16.9 Hz,
H-5a, H-5b), 4.26 (d, 1H, J=3.2 Hz, H-3), 4.35^4.47 (m, 1H, H-4), 4.45 (d, 1H, J=3.8 Hz, H-2),

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R. —ysek et al. / Tetrahedron: Asymmetry 11 (2000) 3131±3150
5.83 (d, 1H, J=3.7 Hz, H-1); MS (EI, HR) m/z: M+ calcd for C35H42O5Si: 570.28015. Found:
570.27947; anal. calcd for C35H42O5Si (570.82): C, 73.65; H, 7.42. Found: C, 73.64; H, 7.60.
3.21. (40R) and (40S) 1,2-O-Isopropylidene-3-O-[30-methylene-40-trimethylsilylazetidin-20-on-40-
yl]-5-O-trityl-ꢂ-d-xylofuranose 39 and 41
In a ratio of ꢂ18:1, compounds 39 and 41 were obtained from 37 according to the general
procedure described earlier. Chromatographic separation on silica gel, using hexane:ethyl acetate,
7:3 v/v, as an eluent, gave 39 (28%) and 41 (2%). Compound 39: oil; ‰ꢂŠ2D2=^38.9 (c 0.65,
1
CH2Cl2); IR (®lm) 1757, 3237 cm^1; H NMR (200 MHz, CDCl3) ꢀ: ^0.08 (s, 9H, ^SiMe3), 1.31,
1.53 (2s, 6H, 2ÂMe), 2.99 (dd, 1H, J=3.6 and 10.2 Hz, H-5a), 3.47 (dd, 1H, J=6.9 and 10.2 Hz,
H-5b), 4.16 (d, 1H, J=3.4 Hz, H-3), 4.29 (d, 1H, J=3.8 Hz, H-2), 4.42^4.49 (m, 1H, H-4), 4.60
(d, 1H, J=1.8 Hz, HAHBCˆ), 5.58 (d, 1H, J=1.8 Hz, HAHBCˆ), 5.88 (d, 1H, J=3.8 Hz, H-1),
6.60 (br s, 1H, NH); MS (HR, LSIMS) m/z: (M+Na)+ calcd for C34H39O6NSiNa: 608.2444.
22
1
Found: 608.2454. Compound 41: oil; ‰ꢂŠD =^2.4 (c 0.4, CH2Cl2); IR (®lm) 1759, 3201 cm^1; H
NMR (200 MHz, CDCl3) ꢀ: ^0.11 (s, 9H, ^SiMe3), 1.31, 1.53 (2s, 6H, 2ÂMe), 3.02 (dd, 1H,
J=6.8 and 9.4 Hz, H-5a), 3.50 (dd, 1H, J=5.3 and 9.4 Hz, H-5b); 4.25 (d, 1H, J=3.7 Hz, H-2),
4.31 (d, 1H, J=3.0 Hz, H-3), 4.33^4.43 (m, 1H, H-4), 5.28 (d, 1H, J=1.7 Hz, HAHBCˆ), 5.84 (d,
1H, J=3.7 Hz, H-1), 5.87 (br s, 1H, NH), 5.91 (d, 1H, J=1.7 Hz, HAHBCˆ); MS (HR, LSIMS)
m/z: (M+Na)+ calcd for C34H39O6NSiNa: 608.2444. Found: 608.2453; anal. calcd for
C34H39O6NSi (585.79): C, 69.72; H, 6.70; N, 2.39. Found: C, 69.43; H, 6.91; N, 2.27.
3.22. (40R) and (40S) 1,2-O-Isopropylidene-3-O-[30-(1-methylethylidene)-40-trimethylsilylazetidin-
20-on-40-yl]-5-O-trityl-ꢂ-d-xylofuranose 40 and 42
In a ratio of ꢂ3:1, compounds 40 and 42 were obtained from 38 according to the general proce-
dure described earlier. Chromatographic separation on silica gel, using hexane:ethyl acetate, 8:2
v/v, as an eluent, gave 40 (62%) and 42 (21%). Compound 40: oil; ‰ꢂŠ2D2=^15.0 (c 0.63, CH2Cl2);
1
IR (®lm) 1737, 3216 cm^1; H NMR (500 MHz, CDCl3) ꢀ: ^0.06 (s, 9H, ^SiMe3), 1.18 (s, 3H,
Me), 1.30, 1.53 (2s, 6H, 2ÂMe), 1.98 (s, 3H, Me), 3.10 (dd, 1H, J=2.2 and 10.6 Hz, H-5a), 3.43
(dd, 1H, J=7.8 and 10.6 Hz, H-5b), 4.07 (d, 1H, J=3.6 Hz, H-3), 4.44 (d, 1H, J=3.8 Hz, H-2),
4.48 (ddd, 1H, J=2.2, 3.6 and 7.8 Hz, H-4), 5.89 (d, 1H, J=3.8 Hz, H-1), 6.13 (br s, 1H, NH);
MS (HR, LSIMS) m/z: (M+Na)+ calcd for C36H43O6NSiNa: 636.27576. Found: 636.27641; anal.
calcd for C36H43O6Si (613.84): C, 70.44; H, 7.06; N, 2.28. Found: C, 70.29; H, 7.10; N, 2.17.
Compound 42: oil; [ꢂ]D=+30.3 (c 0.65, CH2Cl2); IR (®lm) 1738, 3168 cm^1; 1H NMR (200 MHz,
CDCl3) ꢀ: ^0.11 (s, 9H, ^SiMe3), 1.29, 1.52 (2s, 6H, 2ÂMe), 1.80 (s, 3H, Me), 2.10 (s, 3H, Me),
3.04 (dd, 1H, J=5.2 and 9.9 Hz, H-5a), 3.42 (dd, 1H, J=6.2 and 9.9 Hz, H-5b), 4.24 (d, 1H,
J=3.3 Hz, H-3), 4.27 (d, 1H, J=3.7 Hz, H-2), 4.35 (ddd, 1H, J=3.2, 5.2 and 6.2 Hz, H-4), 5.55
(br s, 1H, NH), 5.86 (d, 1H, J=3.7 Hz, H-1); MS (HR, LSIMS) m/z: (M+Na)+ calcd for
C36H43O6NSiNa: 636.27576. Found: 636.27452; anal. calcd for C36H43O6Si (613.84): C, 70.44; H,
7.06; N, 2.28. Found: C, 69.91; H, 7.17; N, 2.30.
3.23. (40R) 3-O-[N-Acetyl-30-(1-methylethylidene)-40-trimethylsilylazetidin-20-on-40-yl]-1,2-O-iso-
propylidene-5-O-trityl-ꢂ-d-xylofuranose 43
Compound 43 was obtained from 40 according to the procedure described for 31 (76%):
colorless crystals; mp 190^192ꢀC; ‰ꢂŠ2D2=+25.9 (c 0.42, CH2Cl2); IR (CH2Cl2) 1692, 1766 cm^1; 1H

R. —ysek et al. / Tetrahedron: Asymmetry 11 (2000) 3131±3150
3149
NMR (500 MHz, CDCl3) ꢀ: ^0.01 (s, 9H, ^SiMe3), 1.28, 1.50 (2s, 6H, 2ÂMe), 1.34 (s, 3H, Me),
2.12 (s, 3H, Me), 2.38 (s, 3H, acetyl), 3.11 (dd, 1H, J=2.4 and 10.4 Hz, H-5a), 3.42 (dd, 1H,
J=7.4 and 10.4 Hz, H-5b), 4.07 (d, 1H, J=4.7 Hz, H-3), 4.40 (d, 1H, J=4.0 Hz, H-2), 4.48 (ddd,
1H, J=2.4, 4.6 and 7.4 Hz, H-4), 5.91 (d, 1H, J=4.0 Hz, H-1); MS (HR, EI) m/z: M+ calcd for
C38H45O7NSi: 655.2965. Found: 655.2969; anal. calcd for C38H45O7NSi (655.89): C, 69.59; H,
6.91; N, 2.13. Found: C, 69.57; H, 6.86; N, 2.21.
3.24. (40R) 1,2-O-Isopropylidene-3-O-[30-methylene-40-trimethylsilylazetidin-20-on-40-yl]-ꢂ-d-xylo-
furanose 44
Compound 44 was obtained from 39 according to the procedure described for 23/24 (78%); oil,
22
1
‰ꢂŠD =^62.0 (c 0.47, CH2Cl2); IR (®lm) 1734, 1769, 3396, 3601 cm^1; H NMR (500 MHz,
CDCl3) ꢀ: 0.14 (s, 9H, ^SiMe3), 1.30, 1.47 (2s, 6H, 2ÂMe), 1.87 (br s, 1H, ^OH), 3.69^3.75 (m,
1H, H-5a), 3.84^3.89 (m, 1H, H-5b), 4.29^4.33 (m, 2H, H-3, H-4), 4.39 (d, 1H, J=3.7 Hz, H-2),
5.35 (d, 1H, J=1.6 Hz, HAHBCˆ), 5.89 (d, 1H, J=3.7 Hz, H-1), 5.91 (d, 1H, J=1.6 Hz,
HAHBCˆ), 6.76 (br s, 1H, NH); MS (EI, HR) m/z: M+ calcd for C14H22O6NSi: 328.1216. Found:
328.1227.
3.25. (40R) 1,2-O-Isopropylidene-3-O-[30-methylene-40-trimethylsilylazetidin-20-on-40-yl]-5-O-tosyl-
ꢂ-d-xylofuranose 45
Compound 45 was obtained from 44 by the standard tosylation procedure (82%): oil,
22
1
‰ꢂŠD =^40.7 (c 0.21, CH2Cl2); IR (®lm) 1761, 3267 cm^1; H NMR (500 MHz, CDCl3) ꢀ: 0.12 (s,
9H, ^SiMe3), 1.27, 1.39 (2s, 6H, 2ÂMe), 2.45 (s, 3H, tosyl), 4.08 (dd, 1H, J=5.6 and 9.8 Hz, H-
5a), 4.18 (dd, 1H, J=6.9 and 9.8 Hz, H-5b), 4.26 (m, 1H, H-4), 4.30 (d, 1H, J=3.3 Hz, H-3), 4.39
(d, 1H, J=3.6 Hz, H-2), 5.47 (d, 1H, J=1.9 Hz, HAHBCˆ), 5.78 (d, 1H, J=3.6 Hz, H-1), 5.94 (d,
1H, J=1.9 Hz, HAHBCˆ), 6.76 (br s, 1H, NH), 7.35, 7.78 (2m, 4H, tosyl); MS (EI, HR) m/z: M+
calcd for C21H28O8NSi: 482.1305. Found: 482.1318.
3.26. (40S) 5-Deoxy-1,2-O-isopropylidene-3-O:5-C-[E-30-(trimethylsilylmethylene)azetidin-20-on-
10,40-diyl)-ꢂ-d-xylofuranose 46 (Fig. 12)
Compound 46 was obtained from 45 according to the procedure described for 27/28 (18%):
colorless crystals; mp 157^158ꢀC (from AcOEt±hexane); ‰ꢂŠ2D2=^75.2 (c 0.3, CH2Cl2); IR
1
(CH2Cl2) 1765 cm^1; H NMR (500 MHz, CDCl3) ꢀ: 0.17 (s, 9H, ^SiMe3), 1.31, 1.49 (2s, 6H,
2ÂMe), 3.43 (dd, 1H, J=4.0 and 15.2 Hz, H-5a); 4.06 (m, 1H, H-4), 4.17 (m, 1H, H-3), 4.18 (d,
1H, J=15.2 Hz, H-5b), 4.50 (d, 1H, J=3.7 Hz, H-2), 5.19 (d, 1H, J=1.0 Hz, H-40), 5.88 (d, 1H,
J=3.7 Hz, H-1), 6.32 (d, 1H, J=1.0 Hz, TMSHCˆ); MS (EI, HR) m/z: M+ calcd for
C15H23O5NSi: 325.1345. Found: 325.1354.
Acknowledgements
The authors wish to thank the State Committee for Scienti®c Research Grant No T 09/PBZ.6.04
for support of this work.

3150
R. —ysek et al. / Tetrahedron: Asymmetry 11 (2000) 3131±3150
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