Model studies towards the synthesis of gilvocarcin M

Article abstract of DOI:10.1039/b512851j

In model studies towards the synthesis of gilvocarcin M, a convergent, xanthate-based free-radical strategy was tested in order to construct the key aromatic ring attached to the sugar unit. The Royal Society of Chemistry 2005.

Full text of DOI:10.1039/b512851j

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A R T I C L E
Model studies towards the synthesis of gilvocarcin M
Alejandro Cordero-Vargas,* Be´atrice Quiclet-Sire and Samir Z. Zard
Laboratoire de Synthe`se Organique associe´ au CNRS, Ecole Polytechnique, 91128, Palaiseau,
France. E-mail: cordero@dcso.polytechnique.fr
Received 12th September 2005, Accepted 24th October 2005
First published as an Advance Article on the web 16th November 2005
In model studies towards the synthesis of gilvocarcin M, a convergent, xanthate-based free-radical strategy was tested
in order to construct the key aromatic ring attached to the sugar unit.
Introduction
C-Aryl glycosides, or glycosylarenes, represent an important
class of natural products in which carbohydrates are directly
bound to an aromatic moiety through a C–C bond, and which
have been shown to be especially resistant to enzymatic and
acidic hydrolysis.1 These compounds constitute interesting syn-
thetic targets in the light of their biological activities and unique
structures. The anticancer gilvocarcins2 (1a–c) are metabolites
of certain Streptomyces species and belong to one of four classes
of naturally occurring C-aryl glycosides, in which the sugar is
located para to a phenolic hydroxyl group (Fig. 1).
Scheme 1 Xanthate-based approach to C-aryl glycosides.
Retrosynthetic analysis and strategy
The general features of our route are outlined in Scheme 2.
Gilvocarcin M (1a) would be prepared from protected tetralone
2 by simple aromatisation of the A ring. In the key step of the
synthesis, tetralone 2 would be obtained in a convergent manner
from an acetophenone xanthate (3) and the appropriate olefin
(4), the latter serving as an effective radical trap.
Fig. 1 Gilvocarcin class C-aryl glycosides.
Owing to their biological and synthetic utility, efficient
synthetic routes to C-aryl glycosides from sugar precursors have
been reported, based either on the regiocontrolled construction
of the C-naphthyl glycosidic linkage using various glycosyl
donors1,3 or on the elaboration of the naphthyl appendage via
transformation of a C-alkyl or a C-furanyl glycoside.1,4 Amongst
these methods, the O→C glycoside rearrangement reported by
Suzuki et al.5 is probably the most useful because it has several
advantages in terms of regio- and stereoselectivity. This method
was successfully applied to the total synthesis of the gilvocarcins
and their analogues.2 However, because this is a Lewis acid-
promoted process, the aromatic moieties that take part in the
reaction have to be electron-rich and the carbohydrate unit
solidly protected.
The required complex xanthate 3 would be obtained by
Friedel–Crafts type acylation of tricyclic lactone 5. On the basis
of the the synthesis of the gilvocarcin aglycon by Martin et al.,7
it was projected that the carbon–carbon bond joining rings B
and D would be constructed through a palladium-mediated
cyclisation and an esterification reaction between the known acid
chloride 68 and commercially available p-methoxyphenol (7).
In parallel, olefin 4 would be obtained by vinylation of the
known D-fucose derivative 8. Thus, in the synthetic direction,
reaction of lactol 8 with an organometallic compound (e.g.
vinylmagnesium bromide) would produce a diol intermediate
that could be cyclised stereoselectively to afford the desired
radical trap 4.
Recently, we reported a new acces to group I C-aryl glycosides
using a xanthate-mediated free-radical addition–cyclisation se-
quence followed by an efficient aromatisation protocol.6 This
process allows the synthesis of a wide variety of substituted
glycosylarenes under mild conditions (Scheme 1).
Furthermore, because this approach allows the use of a great
variety of substituents (including electron-withdrawing groups)
on the aromatic ring and on the sugar moiety, it should be useful
for the expedient preparation of a broad variety of analogues of
the natural products. Because of our continuing interest in the
synthetic applications of xanthate-based free-radical chemistry,
we decided to pursue the synthesis of gilvocarcin M using this
approach.
Results and discussion
Our synthesis starts with the preparation of the desired xanthate
3. The first step in this sequence was the esterification of
commercially available p-methoxyphenol with acid chloride
6 under standard conditions to afford ester 9 in 95% yield
(Scheme 3). With an appropiately placed iodine atom, interme-
diate 9 was used to test the Pd-mediated cyclisation reaction.
Thus, treatment of 9 with a catalytic amount (26 mol%) of
Pd(PPh3)2Cl2 and sodium acetate in N,N-dimethylacetamide
(DMA) at 130 ◦C simultaneously created the desired B–D bond
and completed the annulation of ring C in a single operation,
affording tricylic system 5 in 85% yield.
4 4 3 2
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 4 4 3 2 – 4 4 4 3
T h i s j o u r n a l i s
T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 5
©

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Scheme 3 Synthesis of the radical precursor (3).
Scheme 4 Proposed route to intermediate 3.
Scheme 2 Retrosynthetic analysis of gilvocarcin M (1a).
The next step required the introduction of the chloroacetyl
group at the C-2 position of tricycle 5. However, the Friedel–
Crafts-type acylation, an apparently simple transformation, was
the most challenging step in the preparation of the key xanthate.
After several unsuccesful attempts, we found that treatement of 5
with a large excess of chloroacetyl chloride (10 equiv.) and AlCl3
(10 equiv.) in CS2 at room temperature furnished the desired
compound (10), albeit in low yield (31%) together with several
side products. Finally, treatment of the latter with potassium
ethyl xanthate in acetone at room temperature afforded the
desired radical precursor 3 in 86% yield.
The unexpectedly low yield for the acylation step forced us
to explore an alternative synthetic route for the preparation
of compound 10. We envisaged that the use of a phenolic
acetophenone would provide a derivative 11 that would already
possess the required ketone moiety, and which could be used as
starting material for the synthesis of 10 via a chlorination (or
bromination) protocol (Scheme 4).
In order to test this route, we first prepared the required
acetophenone 11 in good overall yield by using the sequence
shown in Scheme 5. Esterification with acid chloride 6 under
standard conditions furnished compound 14 in 94% yield. How-
ever, when this compound was subjected to the typical reaction
conditions for the Pd-catalysed cyclisation, only acetophenone
11 (derived from the acyl exchange by attack of an acetate anion
at the ester carbonyl of 14), was recovered from the reaction
mixture.
Scheme 5 Alternative route to intermediate 3.
This problem had already been observed by Suzuki et al.2
during the total synthesis of the gilvocarcins. In fact, when
electron-poor aromatics are used for this coupling reaction
(as in the case of 14 due to the presence of the ketone), the
ester moiety becames highly electrophilic, thus favouring the
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 4 4 3 2 – 4 4 4 3
4 4 3 3

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attack of a nucleophile, and furnishing mostly the hydrolysis
product (e.g. 11). To circumvent this problem, Suzuki employed
a sterically hindered base (sodium pivalate), wich suppressed this
side reaction. When we applied this modification to intermediate
14, the expected coupling product was observed, unfortunately
as an inseparable 4 : 1 mixture of 15a and 15b in favour of the
undesired regioisomer 15a (Scheme 6).
refluxing THF resulted in the formation of diol 18 as an insep-
arable 12 : 1 mixture of distereoisomers in almost quantitative
yield (99%) (Scheme 9). Because at this stage it was not possible
to determine the stereochemistry of C-1, diol 18 was cyclised
by different methods. When the allylic alcohol (C-1) in 18 was
mesylated and the resulting sulfonyl derivative treated in basic
media, olefin 19 was obtained in 48% yield as an inseparable
mixture of diastereoisomers (ratio a/b = 1 : 5) by inversion of
configuration at the allylic position (path A). Alternatively, when
SOCl2 was added to a cold (−78 ◦C) solution of 18 in CH2Cl2,
the expected isomer (a) was formed in 84% yield by a double
inversion of configuration (global retention, path B).10
Scheme 6 Use of a hindered base for the Pd-catalysed cyclisation.
We next turned our attention to the directed Friedel–Crafts
acylation and to the Fries rearrangement. We expected that
a phenol like 16 could be prepared in order to perform the
acylation step under milder conditions and consequently with a
better yield (Scheme 7).
Scheme 9 Synthesis of olefin 20.
Before testing the radical sequence between olefin 20 and
xanthate 3, we decided to perform a model study in order to
evaluate the compatibility of the benzyl protections on sugar
20 with the radical process. Thus, xanthate 22, which possesses
a similar substitution pattern on the aromatic ring (a methoxy
group and an ester), and which can be easily prepared on a
multigram scale, was first synthesised from acetophenone 13 in
good overall yield (Scheme 10).
Scheme 7 Alternative route.
For this purpose, we envisaged that a benzyl protection in the
initial phenol moiety would not change the electronic nature
of the aromatic moiety and could be selectively removed after
the Pd-catalysed step, thus providing the desired alcohol 16.
The required ester (17) for the cyclisation step was prepared as
shown in Scheme 8. Unfortunately, when this compound was
treated with a catalytic amount of the palladium complex and
either sodium acetate or sodium pivalate, p-benzyloxyphenol
was observed as the only product.
Scheme 10 Preparation of model xanthate 22.
With model xanthate 22 in hand, we proceeded with the
radial sequence on olefin 20. When these two compounds were
allowed to react in a refluxing solution of 1,2-dichloroethane
(DCE) using dilauroyl peroxide (DLP) as initiator, the expected
adduct was not observed, but a complex mixture of degradation
products instead (Scheme 11).
Scheme 8 Use of benzyl protection.
Because of these unexpected difficulties, we decided that the
original approach (see Scheme 3) was the best way to access to
radical precursor 3, even if optimisation of the acylation step
must eventually be performed.
The elaboration of the carbohydrate moiety of gilvocarcin M
required a stereoselective coupling of D-fucose derivative 89 with
a suitable synthetic equivalent for the vinyl anion (see Scheme 2).
Treatement of 8 with an excess of vinylmagnesium bromide in
Scheme 11 Model study.
The reasons for the failure of this reaction are still unclear. It
is possible that intramolecular hydrogen abstraction, probably
from a benzylic position, followed by an uncontrolled sequence
competed successfully with the desired ring-closure to the
tetralone.
4 4 3 4
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 4 4 3 2 – 4 4 4 3

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Since the supposed reason for this failure was the presence
of the benzylic protections in the sugar moiety, we decided to
replace these protective groups. According to this, and in an
effort to simplify our route to the radical trap, we decided to
prepare lactone 23, which could be used as starting material for
a sequence involving nucleophilic addition and stereoselective
lactol reduction to furnish the desired olefin 25 (Scheme 12).3f ,11
Scheme 12 Lactone strategy.
Scheme 15 Trapping of the single addition product.
We started our route by the synthesis of the requisite lactone
in three steps from known bromo derivative 26,12 prepared in
one step from commercially available D-galactono-1,4-lactone
(Scheme 13). Protection of the hydroxyl groups in the form of
tert-butyldimethylsilyl ethers followed by radical reduction of
the bromine atom afforded lactone 28 in an excellent overall
yield (67%), in only three steps and on a multigram scale.
compound 30, or the unstable deprotected hemiketal 31, led only
to a complex mixture of degradation products (Scheme 16).
Scheme 16 Attempts to reduce hemiketal 30.
Scheme 13 Preparation of lactone 28.
The introduction of the vinyl substituent was finally achieved
using TMS-acetylene as a vinyl equivalent. When a cold
(−78 ◦C) solution of lactone 28 in dry THF was treated with a
slight excess of lithium TMS-acetylene and the resulting acetate
reduced under standard conditions (Et3SiH/BF3·OEt2), alkyne
32 was obtained in excellent overall yield (90% over 2 steps)
and as a single isomer (a) (Scheme 17). With precursor 32 in
hand, completion of the synthesis of the desired olefin 34 became
straightforward. Thus, deprotection of the TMS group in a basic
medium afforded terminal alkyne 33 in almost quantitative yield
(99%). Finally, hydrogenation over Lindlar catalyst completed
the sequence. In this way, olefin 34 was isolated in excellent yield
(98%).
The addition of vinylmagnesium bromide to lactone 28 was
then tested. Treatement of the latter with excess vinylmagnesium
bromide followed by reduction of the lactol intermediate with
Et3SiH and BF3·OEt2 unexpectedly gave compound 29 in 36%
yield as a single isomer13 (Scheme 14).
Scheme 14 Unexpected formation of compound 29.
In fact, formation of hemiketal 28c results from double ad-
dition of vinylmagnesium bromide to lactone 28. This problem
had already been observed by Xie et al.,14 but could not be
completely circumvented in order to provide the single addition
product. In order to solve this problem, we reasoned that a
highly oxophilic reagent such as trimethylsilyl chloride (TMSCl)
could trap the corresponding alcoholate after the addition of one
equivalent of vinylmagnesium bromide and formation of the
hemiketal (28c).15 Gratifyingly, when the Grignard reaction was
performed in the presence of 2 equivalents of TMSCl, silyl ether
30 was isolated in 52% yield as the only product (Scheme 15).
Although we were pleased to find that the Grignard addition
had been successful, attempts to reduce the lactol function in
Scheme 17 Synthesis of olefin 34.
With both building blocks required for the radical step now
in hand, we attempted the crucial reaction between xanthate 3
and olefin 34. Unfortunately, the insolubility of compound 3 in
the solvent typically used for this reaction (1,2-dichloroethane)
forced us to change the reaction conditions. When a diluted
(0.1 M) solution of xanthate 3 and olefin 34 were refluxed
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 4 4 3 2 – 4 4 4 3
4 4 3 5

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Table 1 Radical reactions between olefin 34 and xanthates 36–38
Adduct (% yield)a
in chlorobenzene (PhCl) using dilauroyl peroxide (DLP) as
initiator, only starting materials together with some degradation
products were isolated from the reaction mixture (Scheme 18).
Xanthate
Tetralone (% yield)
Degradation
Scheme 18 Attempt at the key radical reaction.
Because of this setback, we examined the radical reaction with
xanthate 22, since the coupling product could also be used in the
total synthesis of gilvocarcins. Thus, when compounds 22 and
34 were allowed to react under the standard reaction conditions
(refluxing 1,2-dichloroethane and DLP), adduct 35 was obtained
in 59% yield (83% yield based on recovered starting material).
However, when this compound was subjected to the conditions
for the radical cyclisation, a complex mixture of degradation
products was observed (Scheme 19).
Degradation
a Reaction conditions: refluxing 1,2-dichloroethane (1 M concentration)
using DLP as radical initiatior (0.15 to 0.2 equiv.). b Reaction conditions:
refluxing 1,2-dichloroethane (0.1 M concentration) using DLP as
initiator and oxidant (1 to 1.4 equiv.).
the aromatic ring. Although we have not been able to achieve the
total synthesis of gilvocarcin M so far, the successful synthesis of
building blocks 3 and 34 is particularly relevant in this context.
Furthermore, because this approach allows the use of a great
variety of substituents (including electron-withdrawing groups)
on the aromatic ring and on the sugar moiety, it should be useful
for the expedient preparation of a broad variety of analogues of
the natural product.
Scheme 19 Model study.
In order to understand the behaviour of olefin 34, we carried
out a series of experiments with diverse acetophenone xanthates
possessing electron-donating and electron-withdrawing groups.
The results for these reactions are summarised in Table 1.
As can be seen, the addition reaction succeeded for the three
starting xanthates, affording adducts 39–41 in good to moderate
yields. Neverthless, only compound 41 led to the formation of
the expected tetralone (42) after treatment with 1.2 equivalents
of DLP.
Experimental
Our hopes for constructing ring A have thus been tem-
porarily frustrated. The factors underlying the failure of the
cyclisation step are not clear, but are probably due to steric
constraints disfavouring the desired transition state. Earlier
model studies6 on other sugar olefins were quite encouraging.
In the present case, the closure to form the aromatic ring is
probably slower than possible competing side reactions such as
hydrogen abstraction (probably from C-5 and/or C-6 on the
sugar moiety). These side reactions could be at the beginning of
an uncontrolled sequence of steps that lead to the decomposition
of the starting material. When the aromatic ring bears only a para
substituent (41), cyclisation of the nucleophilic radical is faster
than the side reactions, and allows the formation of the expected
tetralone (42). Unfortunately, this compound does not bear the
substituents on the aromatic ring required for the total synthesis
of gilvocarcin M.
All reactions were carried under an inert atmosphere. Commer-
cial reagents were used as received without further purification.
All products were purified by using silica gel SDS 60 C. C. 40–
63 or by crystallisation. NMR spectra were recorded in CDCl3
with TMS as an internal standard at room temperature on a
Bruker AMX400 spectrometer operating at 400 MHz for 1H and
100 MHz for 13C. Infrared absorption spectra were recorded as
solutions in CCl4 with a Perkin–Elmer 1600 Fourier transform
spectrophotometer. Some mass spectra were determined at 70 eV
with an AutoSpec Micromass spectrometer, and the others were
recorded with an HP 5989B mass spectrometer using ammonia
as the reagent gas. Melting points were determined by a Reichert
microscope apparatus and are uncorrected.
2-Iodo-3-methoxy-5-methylbenzoic acid 4-methoxyphenyl ester
(9)
Neverthless, these preliminary results have shown that the use
of a free-radical strategy could be used for the construction of the
A ring of gilvocarcins if the appropiate substituents are present in
A
solution of 2-iodo-3-methoxy-5-methylbenzoyl chloride
(2.26 g, 7.73 mmol) in CH2Cl2 (15 mL) was added dropwise to
4 4 3 6
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 4 4 3 2 – 4 4 4 3

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an ice-cooled solution of p-methoxyphenol (0.8 g, 6.44 mmol)
and triethylamine (3.6 mL, 2.61 g, 25.77 mmol) in CH2Cl2
(64 mL). The mixture was stirred at room temperature for
1 h, basified with saturated aqueous NaHCO3, extracted with
dichloromethane, dried over Na2SO4 and concentrated under
reduced pressure. The residue was purified by flash column
chromatography (silica gel, petroleum ether–AcOEt, 95 : 5 to
8 : 2) and recrystallised with dichloromethane–petroleum ether
to give ester 9 (95% yield) as white needles (mp 101–103 ◦C):
1H NMR (CDCl3, 400 MHz) d 7.27 (s, 1H, CH arom.), 7.22
(d, 2H, CH arom., J = 8.0 Hz), 6.95 (d, 2H, CH arom., J =
8.0 Hz), 6.81 (s, 1H, CH arom.), 3.92 (s, 3H, OCH3), 3.83 (s,
3H, OCH3), 2.40 (s, 3H, CH3); 13C NMR (CDCl3, 100 MHz)
d 166.5 (O-CO), 158.6 (C-OMe), 157.5 (C-OMe), 144.3 (C-O-
CO), 140.0 (C–CO), 137.7 (C-Me), 123.5 (CH arom.), 122.4 (3C,
CH arom.), 114.5 (CH arom.), 82.9 (C-I), 56.8 (OCH3), 56.9
(OCH3), 21.4 (CH3); MS (CI + NH3) m/z: 419 (MH+ + NH3),
417 (MH+ + NH3), 399 (MH+), 397 (MH+); IR (cm−1, CCl4):
Dithiocarbonic acid S-[2-(2,10-dimethoxy-8-methyl-6-oxo-6H-
benzo[c]chromen-3-yl)-2-oxoethyl] ester O-ethyl ester (3)
To a solution of 10 (0.018 g, 0.05 mmol) in acetone (0.06 mL)
at 0 ◦C was added potassium O-ethyl xanthate (0.01 g, 0.06
mmol) and the reaction mixture was stirred for 2 h at 0 ◦C. After
consumption of all the starting material, acetone was evaporated
and the resulting mixture was diluted with water, extracted with
ethyl acetate, dried and concentrated. The residue was purified
by crystallisation with CH2Cl2–petroleum ether to afford 3 (86%)
as a yellow solid (mp 188–191 ◦C): 1H NMR (CDCl3, 400 MHz)
d 8.53 (s, 1H, CH arom.), 7.88 (s, 1H, CH arom.), 7.71 (s, 1H,
CH arom.), 7.17 (s, 1H, CH arom.), 4.62 (q, 2H, O-CH2, J =
7.1 Hz), 4.61 (s, 2H, CH2-S), 4.10 (s, 3H, OCH3), 4.00 (s, 3H,
OCH3), 2.51 (s, 3H, Ar-CH3), 1.41 (t, 3H, CH3, J = 7.1 Hz); 13
C
NMR (CDCl3, 100 MHz) d 213.6 (CS), 192.5 (CO), 161.0 (C-
OMe), 157.5 (C-OMe), 154.6 (C-O-CO), 126.0 (C-CO), 123.5
(C-Ar), 123.5 (C-COO), 123.2 (CH arom.), 122.8 (Ar-C), 120.0
(C-CH3), 118.7 (CH arom.), 118.1 (CH arom.), 110.6 (CH
arom.), 70.6 (O-CH2), 56.4 (OCH3), 56.0 (OCH3), 47.7 (CH2-S),
=
1751 (O–C O); HRMS calcd for C16H15O4I 398.00154; found
398.00139.
21.7 (Ar-CH3), 13.8 (CH3); MS (CI + NH3) m/z: 433 (MH+);
−1
=
=
=
IR (cm , CCl4): 1740 (O-C O), 1686 (C O), 1260 (O–C O);
HRMS calcd for C21H20O6S 432.07014; found 432.07097.
2,10-Dimethoxy-8-methylbenzo[c]chromen-6-one (5)
2,2-Dimethylpropionic acid 3-acetyl-4-hydroxyphenyl ester
(13). Trimetylacetyl chloride (0.89 mL, 0.87 g, 7.22
mmol) was added dropwise to a stirred solution of 2ꢀ,5ꢀ-
dihydroxyacetophenone (1 g, 6.57 mmol) in pyridine (2 mL)
at room temperature and the reaction mixture was stirred for
1 h at room temperature. The solution was then extracted
with CH2Cl2, the combined organic layers were dried, filtered
and concentrated in vacuo. The excess of pyridine was co-
evaporated with toluene under reduced pressure and the residue
was purified by flash chromatography (silica gel, petroleum
ether–ethyl acetate, 98 : 2 to 8 : 2) to yield 13 (79% yield) as a
colourless oil: 1H NMR (CDCl3, 400 MHz) d 12.16 (s, 1H, OH),
7.4 (d, 1H, CH arom., J = 2.8), 7.17 (dd, 1H, CH arom., J =
9.0, 2.6 Hz), 6.98 (d, 1H, CH arom., J = 9.6 Hz), 2.63 (s, 3H,
COCH3), 1.37 (s, 9H, (CH3)3); 13C NMR (CDCl3, 100 MHz)
d 204.0 (CO), 177.4 (O-CO), 160.0 (2C, C-OH and C-OPiv),
142.4 (C-CO), 130.2 (CH arom.), 122.6 (CH arom.), 119.3 (CH
arom.), 39.1 (C(CH3)3), 27.2 ((CH3)3), 26.8 (COCH3); MS (CI +
NH3) m/z: 254 (MH+ + NH3), 237 (MH+); IR (cm−1, CCl4):
A degassed, yellow suspension of ester 9 (1.9 g, 4.77 mmol),
Pd(PPh3)2Cl2 (0.87 g, 1.24 mmol, 26 mol%) and NaOAc (1.17 g,
14.31 mmol) in N,N-dimethylacetamide (430 mL) was heated
at 125 ◦C for 5 h. After the solution was cooled to room
temperature, the resulting dark brown suspension was diluted
with Et2O, and the mixture was washed with water, dried
(Na2SO4), and concentrated in vacuo. The residue was purified
by flash column chromatography (silica gel, petroleum ether–
AcOEt, 9 : 1 to 7:3) and recrystallised with dichloromethane–
petroleum ether to give lactone 5 (85% yield) as white needles
(mp 155–157 ◦C): 1H NMR (CDCl3, 400 MHz) d 8.36 (d, 1H, CH
arom., J = 2.8), 7.81 (s, 1H, CH arom.), 7.22 (d, 1H, CH arom.,
J = 8.8 Hz), 7.06 (s, 1H, CH arom.), 6.95 (dd, 1H, CH arom., J =
9.0, 3.0 Hz), 4.0 (s, 3H, OCH3), 3.85 (s, 3H, OCH3), 2.44 (s, 3H,
CH3); 13C NMR (CDCl3, 100 MHz) d 181.0 (O-CO), 157.1 (C-
OMe), 155.6 (C-OMe), 144.7 (C-O-CO), 139.8 (C-CO), 122.7
(C-Ar), 122.7 (CH arom.), 121.1 (Ar-C), 118.3 (C-Me), 117.8
(CH arom.), 117.7 (CH arom.), 117.4 (CH arom.), 115.1 (CH
arom.), 55.9 (OCH3), 55.7 (OCH3), 21.7 (CH3); MS (CI + NH3)
m/z: 288 (MH+ + NH3), 271 (MH+); IR (cm−1, CCl4): 1732 (O–
=
=
3486 (OH), 1752 (O–C O), 1650 (C O).
1-(5-Hydroxy-2-methoxyphenyl)ethanone (11). A solution of
phenol 13 (1.1 g, 4.65 mmol), Li2CO3 (1.03 g, 73.89 mmol)
and MeI (0.87 mL, 1.98 g, 13.96 mmol) in DMF (12 mL) was
heated at 100 ◦C for 26 h. After the solution was cooled to
room temperature, 5 mL of a 2 M NaOH aqueous solution
were added to the reaction mixture and the resulting solution
was heated at 100 ◦C for further 12 h. The resulting mixture
was then cooled at room temperature, neutralised with 2 N HCl
solution, extracted with Et2O, dried (Na2SO4), and concentrated
under reduced pressure. The residue was purified by flash column
chromatography (silica gel, petroleum ether–AcOEt, 4 : 1 to 2 :
=
C O); HRMS calcd for C16H14O4 270.08921; found 270.08953.
3-(2-Chloroacetyl)-2,10-dimethoxy-8-methylbenzo[c]chromen-6-
one (10)
To a well-stirred suspension of AlCl3 (0.25 g, 1.87 mmol) and
chloroacetyl chloride (0.15 mL, 0.21 g, 1.87 mmol) in CS2 (0.9
mL) at room temperature were added, portionwise, 0.05 g (0.18
mmol) of lactone 5. After standing at room temperature for
2 h, the residue was hydrolysed by careful addition of water
at 0 ◦C. Extraction with ether yielded compound 10 (31%
yield) after flash column chromatography (silica gel, petroleum
ether–AcOEt, 4 : 1) and recrystallisation with dichloromethane–
petroleum ether (white needles, mp 227–227 ◦C): 1H NMR
(CDCl3, 400 MHz) d 8.48 (s, 1H, CH arom.), 7.86 (s, 1H, CH
arom.), 7.76 (s, 1H, CH arom.), 7.16 (s, 1H, CH arom.), 4.77
(s, 2H, CH2-Cl), 4.10 (s, 3H, OCH3), 4.00 (s, 3H, OCH3), 2.50
(s, 3H, Ar-CH3); 13C NMR (CDCl3, 100 MHz) d 190.7 (CO),
183.9 (O-CO), 158.4 (C-OMe), 157.6 (C-OMe), 154.8 (C-O-
CO), 124.4 (C-CO), 123.7 (C-Ar), 123.5 (C-COO), 123.3 (CH
arom.), 119.9 (Ar-C), 119.0 (CH arom.), 118.2 (CH arom.),
115.6 (C-CH3), 110.6 (CH arom.), 56.4 (OCH3), 56.1 (OCH3),
51.3 (CH2-Cl), 21.7 (Ar-CH3); MS (CI + NH3) m/z: 349 (MH+),
1
1) to give compound 11 (83% yield) as a yellow oil: H NMR
(CDCl3, 400 MHz) d 7.43 (d, 1H, CH arom., J = 2.8 Hz), 7.30 (s,
1H, OH), 7.05 (dd, 1H, CH arom., J = 8.8, 2.8 Hz), 6.86 (d, 1H,
CH arom., J = 8.8 Hz), 3.85 (OCH3), 2.64 (s, 3H, COCH3); 13
C
NMR (CDCl3, 100 MHz) d 201.1 (CO), 153.8 (C-OMe), 149.9
(C-OH), 127.8 (C-CO), 121.6 (CH arom.), 116.6 (CH arom.),
113.3 (CH arom.), 56.0 (OCH3), 32.0 (COCH3).
2-Iodo-3-methoxy-5-methylbenzoic acid
3-acetyl-4-methoxyphenyl ester (14)
A
solution of 2-iodo-3-methoxy-5-methylbenzoyl chloride
(0.18 g, 0.60 mmol) in CH2Cl2 (1 mL) was added dropwise to
an ice-cooled solution of acetophenone 11 (0.05 g, 0.30 mmol)
and triethylamine (0.17 mL, 0.12 g, 1.20 mmol), in CH2Cl2
(3 mL). The mixture was stirred at room temperature for
+
−1
=
=
347 (MH ); IR (cm , CCl4): 1729 (O–C O), 1684 (C O), 1264
=
(O–C O).
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 4 4 3 2 – 4 4 4 3
4 4 3 7

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1 h, basified with saturated aqueous NaHCO3, extracted with
dichloromethane, dried over Na2SO4 and concentrated under
reduced pressure. The residue was purified by flash column
chromatography (silica gel, petroleum ether–AcOEt, 4 : 1) and
recrystallised with dichloromethane–petroleum ether to give
ester 14 (94% yield) as white needles (mp 114–115 ◦C): 1H NMR
(CDCl3, 400 MHz) d 7.65 (d, 1H, CH arom., J = 2.8 Hz), 7.41
(dd, 1H, CH arom., J = 8.8, 2.8 Hz), 7.26 (s, 1H, CH arom.),
7.02 (d, 1H, CH arom., J = 8.8 Hz), 6.8 (s, 1H, CH arom.), 3.93
(s, 3H, OCH3), 3.91 (s, 3H, OCH3), 2.64 (COCH3), 2.39 (s, 3H,
CH3); 13C NMR (CDCl3, 100 MHz) d 198.6 (CO), 166.3 (O-CO),
158.6 (C-OMe), 156.9 (C-OMe), 144.0 (C-O-CO), 140.1 (C-
CO), 137.1 (C-CO2Ar), 128.6 (C-Me), 126.8 (CH arom.), 123.6
(CH arom.), 123.2 (CH arom.), 114.8 (CH arom.), 112.6 (CH
arom.), 82.9 (C-I), 56.8 (OCH3), 56.0 (OCH3), 31.9 (COCH3),
dropwise Br2 (0.11 mL, 0.34 g, 2.12 mmol). The cooling bath was
then removed and the mixture was stirred at room temperature
for 2 h. When starting material was completely consumed, the
solvent was removed under reduced pressure, the resulting mass
decolourised with a 1 : 1 mixture of CH2Cl2–water, and extracted
with CH2Cl2. The combined organic extracts were dried and
evaporated, the residue dissolved in 4.2 mL of acetone, and 0.37 g
(2.33 mmol) of potassium O-ethylxanthate added. The reaction
mixture was stirred at room temperature for a further 1 h, the
solvent was evaporated and the resulting mixture partitioned
between water and CH2Cl2. The aqueous phase was extracted
with CH2Cl2, the combined organic extracts were dried over
Na2SO4 and concentrated under reduced pressure. The residue
was purified by recrystallisation with CH2Cl2–petroleum ether
to give xanthate 22 (77% overall yield from 21) as white crystals
(mp 63–65 ◦C): 1H NMR (CDCl3, 400 MHz) d 7.48 (d, 1H, CH
arom., J = 3.0 Hz), 7.23 (dd, 1H, CH arom., J = 8.9, 3.0 Hz),
7.0 (d, 1H, CH arom., J = 9.0 Hz), 4.61 (q, 2H, OCH2, J = 7.1
Hz), 4.61 (s, 2H, CH2-S), 3.96 (OCH3), 1.39 (t, 3H, CH3, J =
7.1 Hz), 1.34 (s, 9H, C(CH3)3); 13C NMR (CDCl3, 100 MHz) d
213.6 (CS), 192.8 (CO), 177.2 (O-CO), 156.4 (C-OMe), 144.7
(C-OPiv), 127.7 (CH arom.), 126.7 (C-CO), 123.7 (CH arom.),
112.5 (CH arom.), 70.5 (OCH2), 56.3 (OCH3), 47.6 (CH2-S),
39.1 (C(CH3)3), 27.2 (3C, C(CH3)3), 13.8 (CH3); MS (CI + NH3)
m/z: 388 (MH+ + NH3), 371 (MH+); IR (cm−1, CCl4): 1754 (O–
21.3 (CH3); MS (CI + NH3) m/z: 458 (MH+ + NH3), 441 (MH+);
−1
=
=
=
IR (cm , CCl4): 1754 (O–C O), 1682 (C O), 1270 (O–C O);
HRMS calcd for C18H17O5I 440.01210; found 440.01187.
2-Iodo-3-methoxy-5-methylbenzoic acid 4-benzyloxyphenyl ester
(17)
A
solution of 2-iodo-3-methoxy-5-methylbenzoyl chloride
(0.29 g, 0.99 mmol) in CH2Cl2 (2 mL) was added dropwise to an
ice-cooled solution of p-benzyloxyphenol (0.10 g, 0.50 mmol)
and triethylamine (0.28 mL, 0.20 g, 1.99 mmol), in CH2Cl2
(5 mL). The mixture was stirred at room temperature for
1 h, basified with saturated aqueous NaHCO3, extracted with
dichloromethane, dried over Na2SO4 and concentrated under
reduced pressure. The residue was purified by flash column
chromatography (silica gel, petroleum ether–AcOEt, 9 : 1 to
8 : 2) and recrystallised with dichloromethane–petroleum ether
to give ester 18 (84% yield) as white needles (mp 93–94 ◦C): 1H
NMR (CDCl3, 400 MHz) d 7.47–7.35 (m, 5H, CH arom.), 7.28
(s, 1H, CH arom.), 7.26 (d, 2H, CH arom., J = 8.0 Hz), 7.04 (d,
2H, CH arom., J = 8.0 Hz), 6.81 (s, 1H, CH arom.), 5.09 (s, 2H,
CH2-Ph), 3.93 (s, 3H, OCH3), 3.91 (s, 3H, OCH3), 2.41 (s, 3H,
CH3); 13C NMR (CDCl3, 100 MHz) d 166.5 (O-CO), 158.6 (C-
OMe), 156.7 (C-OBn), 144.5 (C-O-CO), 140.0 (C-CO), 137.6
(C-CH2), 136.8 (C-Me), 128.7 (CH arom.), 128.1 (CH arom.),
127.6 (CH arom.), 123.6 (CH arom.), 122.4 (3C, CH arom.),
115.6 (2C, CH arom.), 114.6 (CH arom.), 114.7 (CH arom.),
82.9 (C-I), 70.5 (CH2-Ph), 56.8 (OCH3), 21.4 (CH3); MS (CI +
NH3) m/z: 492 (MH+ + NH3), 475 (MH+); IR (cm−1, CCl4):
=
=
=
=
C
O), 1679 (C O), 1221 (S–C S), 1056 (O–C S).
Dithiocarbonic acid S-[2-(5-bromo-2-methoxyphenyl)-2-
oxoethyl] ester O-ethyl ester (37)
A
solution of 2ꢀ-hydroxy-5ꢀ-bromoacetophenone (2.0 g,
9.30 mmol), K2CO3 (2.6 g, 19.0 mmol) and MeI (0.72 mL,
0.91 g, 12.1 mmol) in acetone (20 mL) was refluxed for 3 h.
After the solution was cooled to room temperature, acetone
was evaporated and the resulting mixture was then extracted
with Et2O, washed with saturated aqueous NaCl solution, dried
(Na2SO4), and concentrated under reduced pressure. To a stirred
solution of the residue and AlCl3 (0.12 g, 0.93 mmol) in ether
(93 mL) at 0 ◦C was added dropwise Br2 (0.48 mL, 1.49 g,
9.3 mmol). The cooling bath was then removed and the mixture
was stirred at room temperature for 1 h. When starting material
was completely consumed, the solvent was removed under
reduced pressure and the resulting mass decolourised with a
1 : 1 mixture of CH2Cl2/water and extracted with CH2Cl2.
The combined organic extracts were dried and evaporated,
the residue dissolved in 19 mL of acetone, and 1.64 g (10.23
mmol) of potassium O-ethylxanthate added. The reaction
mixture was stirred at room temperature for a further 1 h,
the solvent was evaporated and the resulting mixture parti-
tioned between water and CH2Cl2. The aqueous phase was
extracted with CH2Cl2, the combined organic extracts were dried
over Na2SO4 and concentrated under reduced pressure. The
residue was purified by flash column chromatography (silica
gel, petroleum ether–AcOEt, 95 : 5 to 8 : 2) and recrystallised
with dichloromethane–petroleum ether to giv◦e xanthate 37
=
=
1753 (O–C O), 1185 (O–C O).
2,2-Dimethylpropionic acid 3-acetyl-4-methoxyphenyl ester (21)
A solution of phenol 13 (0.61 g, 2.58 mmol), Li2CO3 (0.57 g,
7.76 mmol) and MeI (0.48 mL, 1.10 g, 7.76 mmol) in DMF (6.5
mL) was heated at 120 ◦C for 4 h. The resulting mixture was
then cooled at room temperature, neutralised with saturated
citric acid solution, extracted with Et2O, dried (Na2SO4), and
concentrated under reduced pressure. The residue was purified
by flash column chromatography (silica gel, petroleum ether–
AcOEt, 9 : 1 to 8 : 2) to give compound 21 (82% yield) as a
colourless oil: 1H NMR (CDCl3, 400 MHz) d 7.42 (d, 1H, CH
arom., J = 2.8 Hz), 7.16 (dd, 1H, CH arom., J = 8.8, 2.8 Hz),
6.95 (d, 1H, CH arom., J = 8.8 Hz), 3.90 (OCH3), 2.61 (s, 3H,
COCH3), 1.34 (s, 9H, C(CH3)3); 13C NMR (CDCl3, 100 MHz)
d 198.7 (CO), 177.3 (O-CO), 156.6 (C-OMe), 144.3 (C-OPiv),
128.5 (C-CO), 126.8 (CH arom.), 123.2 (CH arom.), 112.4 (CH
arom.), 55.9 (OCH3), 39.1 (COCH3), 31.9 (C(CH3)3), 27.2 (3C,
1
(94% overall yield) as a white powder (mp 63 C): H NMR
(CDCl3, 400 MHz) d 7.86 (d, 1H, CH arom., J = 2.6 Hz),
7.60 (dd, 1H, CH arom., J = 8.8, 2.6 Hz), 6.90 (d, 1H,
CH arom., J = 8.9 Hz), 4.61 (q, 2H, O-CH2, J = 7.1 Hz),
4.56 (s, 2H, CH2-S), 3.95 (s, 3H, OCH3), 1.40 (t, 3H, CH3,
J = 7.1 Hz); 13C NMR (CDCl3, 100 MHz) d 213.4 (CS), 192.7
(CO), 157.7 (C-OMe), 136.8 (CH arom.), 133.5 (CH arom.),
127.9 (C-CO), 113.6 (CH arom.), 113.5 (C-Br), 70.6 (O-CH2),
561 (O-CH3), 47.4 (COCH2), 13.8 (CH3); MS (CI + NH3) m/z:
C(CH3)3); MS (CI + NH3) m/z: 268 (MH+ + NH3), 251 (MH+);
−1
+
+
−1
=
=
IR (cm , CCl4): 1753 (O–C O), 1682 (C O).
=
351 (MH ), 349 (MH ); IR (cm , CCl4): 1692 (C O), 1227
=
=
(S–C S), 1054 (O–C S).
2,2-Dimethylpropionic acid 3-(2-(ethoxythiocarbonylsulfanyl)-
acetyl)-4-methoxyphenyl ester (22)
1-Vinyl-2,3,5-tri-O-benzyl-D-fucocitol (18)
To a stirred solution of acetophenone 21 (0.53 g, 2.12 mmol) and
A solution of 2,3,5-tri-O-benzyl-D-fucose 8 (0.2 g, 0.46 mmol)
in dry THF (4.6 mL) was slowly added to a refluxing solution
AlCl3 (0.03 g, 0.21 mmol) in ether (3.5 mL) at 0 ◦C was added
4 4 3 8
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 4 4 3 2 – 4 4 4 3

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of vinylmagnesium bromide in THF (1.84 mL of a 1 M
solution, 1.84 mmol). The reaction mixture was refluxed for
further 30 min, cooled to room temperature and quenched with
saturated aqueous NH4Cl solution. Extraction with ethyl acetate
yielded compound 18 (yellow oil, 99% yield) after flash column
chromatography (silica gel, petroleum ether–AcOEt, 4 : 1) as an
inseparable 12 : 1 mixture of distereoisomers (only the major
H-4, J = 8.4, 2.4 Hz), 4.62–4.68 (m, 3H, CH2-Ph), 4.36 (d, 1H,
CH2-Ph, J = 12.0 Hz), 4.28 (d, 1H, CH2-Ph, J = 12.0 Hz),
4.13 (d, 1H, CH2-Ph, J = 11.6 Hz), 4.02 (dd, 1H, H-3, J = 8.4,
3.6 Hz), 3.94 (dd, 1H, H-5, J = 6.4, 2.4 Hz), 3.69 (d, 1H, H-2,
J = 2.4 Hz), 1.25 (d, 3H, H-6, J = 6.4 Hz); 13C NMR (CDCl3,
100 MHz) d 138.2 (C-CH2), 137.7 (C-CH2), 137.6 (C-CH2),
134.1 (C-1ꢀ), 128.6 (CH arom.), 128.5 (CH arom.), 128.3 (CH
arom.), 128.2 (CH arom.), 128.1 (CH arom.), 128.0 (CH arom.),
127.8 (CH arom.), 127.7 (CH arom.), 119.3 (C-2ꢀ), 81.8 (C-2),
77.6 (C-3), 73.5 (C-4), 73.0 (CH2-Ph), 72.9 (C-1), 72.8 (CH2-Ph),
72.0 (C-5), 70.6 (CH2-Ph), 15.6 (C-6); MS (CI + NH3) m/z: 462
(MH+ + NH3), 445 (MH+).
1
disatereoisomer is described): H NMR (CDCl3, 400 MHz) d
7.38–7.23 (m, 15H, CH arom.), 5.40 (ddd, 1H, H-1ꢀ, J = 17.2,
10.5, 5.6 Hz), 5.40 (dd, 1H, H-2ꢀ, J = 17.2, 1.5 Hz), 5.24 (dd,
1H, H-2ꢀ, J = 10.5, 1.4 Hz), 4.79 (d, 1H, CH2-Ph, J = 11.3 Hz),
4.69 (d, 2H, CH2-Ph, J = 11.4 Hz), 4.58 (d, 1H, CH2-Ph, J =
11.3 Hz), 4.49–4.44 (m, 1H, H-1), 4.36 (d, 1H, CH2-Ph, J =
11.6 Hz), 4.35 (d, 1H, CH2-Ph, J = 11.2 Hz), 3.94–3.86 (m,
1H, H-5), 3.79–3.74 (m, 2H, H-2 and H-3), 3.72–3.78 (m, 1H,
H-4), 3.19 (br, 1H, OH), 2.78 (br, 1H, OH), 1.36 (d, 3H, H-6,
J = 6.3 Hz); 13C NMR (CDCl3, 100 MHz) d 138.6 (C-1ꢀ), 138.4
(C-CH2), 138.1 (C-CH2), 138.0 (C-CH2), 128.5 (CH arom.),
128.2 (CH arom.), 128.1 (CH arom.), 127.9 (CH arom.), 127.8
(CH arom.), 116.1 (C-2ꢀ), 81.9 (C-2), 78.1 (C-3), 75.3 (C-4), 74.7
(CH2-Ph), 73.4 (CH2-Ph), 72.9 (C-5), 72.2 (C-1), 70.4 (CH2-Ph),
16.0 (C-6); MS (CI + NH3) m/z: 480 (MH+ + NH3), 463 (MH+);
[a]2D5 = −37.5 (c = 1, CHCl3).
2,3,5-Tri-O-tert-butyldimethylsilyl-6-bromo-6-deoxy-
D-galactono-1,4-lactone (27)
Tert-butyldimethylsilyl chloride (19.2 g, 127.4 mmol) was
added to a stirred solution of 6-bromo-6-deoxy-D-galactono-
1,4-lactone (26) (5.12 g, 21.24 mmol) and imidazole (11.57 g,
169.93 mmol) in DMF (85 mL) at room temperature, and the
reaction mixture was stirred for 48 h. The solution was then
extracted with ethyl ether, the combined organic layers were
dried (Na2SO4), filtered and concentrated in vacuo. The residue
was purified by flash chromatography (silica gel, petroleum
ether–AcOEt, 95 : 5 to 9 : 1) to yield 27 (68% yield) as a colourless
oil: 1H NMR (CDCl3, 400 MHz) d 4.51 (t, 1H, H-4, J = 1.8 Hz),
4.35 (m, 2H, H-2 and H-3), 4.02 (ddd, 1H, H-5, J = 9.3, 4.3,
1.7 Hz), 3.51 (t, 1H, H-6, J = 9.8 Hz), 3.37 (dd, 1H, H-6ꢀ, J =
10.2, 4.1 Hz), 0.92 (s, 9H, Si-C(CH3)3), 0.91 (s, 9H, Si-C(CH3)3),
0.89 (s, 9H, Si-C(CH3)3), 0.21 (s, 3H, Si-CH3), 0.16 (s, 3H, Si-
CH3), 0.15 (s, 3H, Si-CH3), 0.14 (s, 3H, Si-CH3), 0.13 (s, 6H,
Si-CH3); 13C NMR (CDCl3, 100 MHz) d 173.3 (C-1), 81.8 (C-4),
76.9 (C-2), 75.9 (C-3), 71.3 (C-5), 31.6 (C-6), 25.9 (Si-C(CH3)3),
25.8 (Si-C(CH3)3), 25.7 (Si-C(CH3)3), 18.3 (Si–C(CH3)3), 18.2
(Si–C(CH3)3), 17.9 (Si-C(CH3)3), −3.3 (Si-CH3), −3.9 (Si-CH3),
−4.0 (Si-CH3), −4.1 (Si-CH3), −4.3 (Si-CH3), −4.7 (Si-CH3);
MS (CI + NH3) m/z: 602 (MH+ + NH3), 600 (MH+ + NH3),
1-Vinyl-2,3,5-tri-O-benzyl-a-D-fucofuranose (19)
Methanesulfonyl chloride (0.016 mL, 0.025 g, 0.22 mmol) was
added dropwise to a stirred solution of diol 18 (0.05 g, 0.11
mmol) in CH2Cl2 (1 mL) at 0 ◦C, and the reaction mixture
was stirred for further 30 min at 0 ◦C. The solution was
then extracted with ethyl acetate, the combined organic layers
were dried, filtered and concentrated in vacuo. The residue was
then dissolved in 1 mL of DMF and 0.024 g (0.32 mmol) of
Li2CO3 were added to the reaction mixture. The solution was
stirred for 1 h at room temperature, neutralised with saturated
aqueous citric acid solution, extracted with diethyl ether and the
combined organic extracts were dried and concentrated in vacuo.
The residue was purified by flash column chromatography (silica
gel, petroleum ether–AcOEt, 98 : 2) to give compound 19 (48%
yield) as a colourless oil: 1H NMR (CDCl3, 400 MHz) d 7.38–
7.25 (m, 15H, CH arom.), 5.95 (ddd, 1H, H-1ꢀ, J = 17.2, 10.3,
7.0 Hz), 5.37 (dd, 1H, H-2ꢀ, J = 17.1, 1.4 Hz), 5.22 (dd, 1H, H-2ꢀ,
J = 10.3, 1.3 Hz), 4.66 (d, 1H, CH2-Ph, J = 12.0 Hz), 4.61 (d,
1H, CH2-Ph, J = 12.0 Hz), 4.53 (d, 1H, CH2-Ph, J = 10.8 Hz),
4.50 (d, 1H, CH2-Ph, J = 11.9 Hz), 4.47 (d, 1H, CH2-Ph, J =
11.1 Hz), 4.46 (dd, 1H, H-1, J = 1.22 Hz), 4.44 (d, 1H, CH2-Ph,
J = 11.6 Hz), 4.13 (s, 1H, H-3), 3.99–3.94 (m, 2H, H-2 and
H-4), 3.65 (dq, 1H, H-5, J = 6.4, 4.7 Hz), 1.23 (d, 3H, H-6, J =
6.4 Hz); 13C NMR (CDCl3, 100 MHz) d 138.7 (C-CH2), 138.0
(C-CH2), 137.9 (C-CH2), 136.9 (C-1ꢀ), 128.5 (CH arom.), 128.5
(CH arom.), 128.4 (CH arom.), 128.3 (CH arom.), 128.0 (CH
arom.), 127.9 (CH arom.), 127.9 (CH arom.), 127.8 (CH arom.),
127.6 (CH arom.), 127.6 (CH arom.), 127.5 (CH arom.), 117.5
(C-2ꢀ), 88.3 (C-2), 84.9 (C-4), 84.5 (C-3), 83.3 (C-1), 74.2 (C-5),
72.1 (2C, CH2-Ph), 71.2 (CH2-Ph), 15.9 (C-6); MS (CI + NH3)
m/z: 462 (MH+ + NH3), 445 (MH+).
+
+
−1
=
585 (MH ), 583 (MH ); IR (cm , CCl4): 1804 (O–C O), 1255
25
=
(O–C O); [a]D = − 3.2 (c = 1, CHCl3).
2,3,5-Tri-O-tert-butyldimethylsilyl-D-fucono-1,4-lactone (28)
A solution of 27 (7.5 g, 12.85 mmol), Bu3SnH (5.18 mL, 5.61 g,
19.27 mmol) and AIBN (0.02 g, 0.13 mmol) in a 1 : 1 toluene–
cyclohexane mixture (40 mL) was heated at 80–90 ◦C for 30 min.
When the starting material was totally consumed, the crude
mixture was cooled to room temperature, concentrated under
reduced pressure and purified by flash column chromatography
(silica gel, petroleum ether–AcOEt, 99◦: 1) to give lactone 28
(98% yield) as a white solid (mp 38–39 C): 1H NMR (CDCl3,
400 MHz) d 4.34 (t, 1H, H-3, J = 5.0 Hz), 4.29 (d, 1H, H-
2, J = 5.2 Hz), 4.07 (dd, 1H, H-5, J = 6.4, 3.6 Hz), 3.99 (t,
1H, H-4, J = 4.0 Hz), 1.33 (d, 3H, H-6, J = 6.4 Hz), 0.96
(s, 9H, Si-C(CH3)3), 0.94 (s, 9H, Si-C(CH3)3), 0.93 (s, 9H, Si-
C(CH3)3), 0.25 (s, 3H, Si-CH3), 0.20 (s, 3H, Si-CH3), 0.17 (s,
3H, Si-CH3), 0.16 (s, 3H, Si-CH3), 0.14 (s, 3H, Si-CH3), 0.13 (s,
3H, Si-CH3); 13C NMR (CDCl3, 100 MHz) d 173.8 (C-1), 87.6
(C-4), 76.7 (C-2), 75.8 (C-3), 67.2 (C-5), 25.9 (Si-C(CH3)3), 25.9
(Si-C(CH3)3), 25.8 (Si-C(CH3)3), 20.3 (C-6), 18.3 (Si-C(CH3)3),
18.2 (Si-C(CH3)3), 17.9 (Si-C(CH3)3), −3.5 (Si-CH3), −4.0 (Si-
CH3), −4.1 (Si-CH3), −4.3 (Si-CH3), −4.4 (Si-CH3), −4.7 (Si-
1-Vinyl-2,3,5-tri-O-benzyl-b-D-fucofuranose (20)
A solution of SOCl2 (0.03 mL, 0.05 mmol) in CH2Cl2 (4 mL)
was added dropwise to a stirred solution of diol 18 (0.18 g,
0.39 mmol) in CH2Cl2 (8 mL) at −78 ◦C. The reaction
mixture was warmed to room temperature over 2 h, neu-
tralised with saturated NaHCO3 solution, and extracted with
dichloromethane. The combined organic layers were dried,
filtered and concentrated. The residue was purified by flash
column chromatography (silica gel, petroleum ether–AcOEt,
98 : 2 to 95 : 5) to afford olefin 20 (84% yield) as a colourless oil:
1H NMR (CDCl3, 400 MHz) d 7.33–7.12 (m, 15H, CH arom.),
5.98 (ddd, 1H, H-1ꢀ, J = 17.2, 10.4, 6.8 Hz), 5.39 (d, 1H, H-2ꢀ,
J = 17.1 Hz), 5.3–5.27 (m, 2H, H-1 and H-2ꢀ), 4.87 (dd, 1H,
CH3); MS (CI + NH3) m/z: 522 (MH+ + NH3), 505 (MH+); IR
−1
=
=
(cm , CCl4): 1799 (O–C O) 1253 (O–C O); HRMS calcd for
C24H52O5Si3 504.31226; found 504.31258; [a]2D5 = − 2.8 (c = 1,
CHCl3).
1-(3ꢀ-Butenyl)-2,3-di-O-tert-butyldimethylsilyl-b-D-fucofuranose
(29)
A solution of lactone 28 (0.05 g, 0.10 mmol) in dry THF
(1 mL) was slowly added to a stirred solution of vinylmagnesium
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 4 4 3 2 – 4 4 4 3
4 4 3 9

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bromide in THF (0.40 mL of a 1 M solution, 0.40 mmol)
at r.t. The solution was then stirred at room temperature for
1 h, diluted with saturated NH4Cl solution, and extracted
with dichloromethane. The combined organic layers were dried,
filtered and concentrated. The residue was then dissolved in 2 mL
of CH2Cl2 and cooled to −78 ◦C. To this solution was added
Et3SiH (0.06 mL, 0.05 g, 0.40 mmol) followed by BF3·OEt2
(0.05 mL, 0.06 g, 0.40 mmol). When starting material was
completely consumed, the reaction was neutralised with triethy-
lamine and extracted with dichloromethane. The combined or-
ganic layers were dried (Na2SO4), filtered and concentrated. The
residue was purified by flash column chromatography (silica gel,
petroleum ether–AcOEt, 95 : 5) to afford olefin 29 (36% overall
yield from 28) as a colourless oil: 1H NMR (CDCl3, 400 MHz)
d 5.84 (tdd, 1H, H-3ꢀ, J = 16.9, 10.2, 6.5 Hz), 5.04 (dd, 1H,
H-4ꢀ, J = 17.1, 1.6 Hz), 4.98 (dd, 1H, H-4ꢀ, J = 10.2, 1.6 Hz),
3.98–3.88 (m, 4H, H-1, H-2, H-3 and H-5), 3.72 (dd, 1H, H-4,
J = 5.5 and 1.3 Hz), 2.93 (bs, 1H, OH), 2.25–2.16 (m, 1H, H-
2ꢀ), 2.14–2.05 (m, 1H, H-2ꢀ), 1.86–1.76 (m, 1H, H-1ꢀ), 1.71–1.62
(m, 1H, H-1ꢀ), 1.22 (d, 3H, H-6, J = 6.3 Hz), 0.89 (s, 18H, Si-
C(CH3)3), 0.10 (s, 3H, Si-CH3), 0.09 (s, 3H, Si-CH3), 0.08 (s, 3H,
Si-CH3), 0.08 (s, 3H, Si-CH3); 13C NMR (CDCl3, 100 MHz) d
138.3 (C-3ꢀ), 114.8 (C-4ꢀ), 91.4 (C-4), 87.1 (C-1), 82.8 (C-2), 81.5
(C-3), 67.4 (C-5), 32.1 (C-2ꢀ), 30.4 (C-1ꢀ), 25.8 (Si-C(CH3)3), 25.7
(Si-C(CH3)3), 19.7 (C-6), 18.0 (Si-C(CH3)3), 17.9 (Si-C(CH3)3),
−4.5 (Si-CH3), −4.5 (Si-CH3), −4.5 (Si-CH3), −4.6 (Si-CH3).
extracted with dichloromethane. The combined organic layers
were dried (Na2SO4), filtered and concentrated. The residue was
purified by flash column chromatography (silica gel, petroleum
ether–AcOEt, 99 : 1) and recrystallised with methanol to give
compound 32 (90% overall yield from 28) as white needles (mp
91–92 ◦C): 1H NMR (CDCl3, 400 MHz) d 4.71 (d, 1H, H-1, J =
2.7 Hz), 4.01 (dq, 1H, H-5, J = 8.0, 6.2 Hz), 3.87 (s, 1H, H-3),
3.84 (dd, 1H, H-2, J = 2.7, 0.9 Hz), 3.59 (d, 1H, H-4, J = 8.2 Hz),
1.14 (d, 3H, H-6, J = 6.3 Hz), 0.92 (s, 9H, Si-C(CH3)3),
0.90 (s, 9H, Si-C(CH3)3), 0.85 (s, 9H, Si-C(CH3)3), 0.16 (s,
12H, Si-(CH3)3 and Si-CH3), 0.12 (s, 6H, Si-CH3), 0.11 (s,
3H, Si-CH3), 0.07 (s, 3H, Si-CH3), 0.07 (s, 3H, Si-CH3); 13C
NMR (CDCl3, 100 MHz) d 101.7 (C-1ꢀ), 92.3 (C-1), 91.9 (C-
2ꢀ), 79.9 (C-4), 79.2 (C-5), 73.0 (C-2), 69.1 (C-3), 26.2 (Si-
C(CH3)3), 25.9 (Si-C(CH3)3), 25.7 (Si-C(CH3)3), 20.6 (C-6), 18.5
(Si-C(CH3)3), 18.3 (Si-C(CH3)3), 17.8 (Si-C(CH3)3), −0.1 (Si-
(CH3)3), −4.1 (Si-CH3), −4.4 (Si-CH3), −4.4 (Si-CH3), −4.5 (Si-
CH3), −4.7 (Si-CH3), −4.8 (Si-CH3); MS (CI + NH3) m/z: 604
(MH+ + NH3), 587 (MH+); IR (cm−1, CCl4): 2183 (TMS–C≡C);
[a]2D5 = − 7.2 (c = 1, CHCl3).
1-Ethynyl-2,3,5-tri-O-tert-butyldimethylsilyl-b-D-fucofuranose
(33)
Potassium carbonate (1.9 g, 13.79 mmol) was added to a
stirred solution of compound 32 (1.62 g, 2.76 mmol) in a 1 :
1 mixture of methanol–CH2Cl2 (30 mL) at room temperature,
and the reaction mixture was stirred for 4 h. The methanol was
then evaporated, the solution extracted with dichloromethane,
and the combined organic layers dried (Na2SO4), filtered and
concentrated in vacuo. The residue was purified by flash chro-
matography (silica gel, petroleum ether–AcOEt, 98 : 2 to 95 :
5) and recrystallised with◦methanol to yield 33 (99% yield) as
1-Trimethylsilyloxy-1-vinyl-2,3,5-tri-O-tert-butyldimethylsilyl-
a-D-fucofuranoside (30)
Vinylmagnesium bromide (1.18 mL of a 1 M solution in THF,
1.18 mmol) was slowly added to a stirred solution of lactone 28
(0.3 g, 0.59 mmol) and TMSCl (0.15 mL, 0.13 g, 1.18 mmol)
in dry THF (6 mL) at 0 ◦C. The solution was then stirred
at room temperature for 1 h, diluted with a saturated NH4Cl
solution, and extracted with dichloromethane. The combined
organic layers were dried, filtered and concentrated under
reduced pressure. The residue was purified by flash column
chromatography (silica gel, petroleum ether–AcOEt, 99 : 1) to
afford olefin 30 (52% yield) as a colourless oil: 1H NMR (CDCl3,
400 MHz) d 5.91 (dd, 1H, H-1ꢀ, J = 17.4, 10.6 Hz), 5.34 (dd, 1H,
H-2ꢀ, J = 17.4, 1.4 Hz), 5.17 (dd, 1H, H-2ꢀ, J = 10.8, 1.6 Hz),
3.88–3.79 (m, 4H, H-2, H-3, H-4 and H-5), 1.16 (d, 3H, H-6,
J = 5.2 Hz), 0.91 (s, 18H, Si-C(CH3)3), 0.86 (s, 9H, Si-C(CH3)3),
0.12 (s, 9H, O-Si(CH3)3), 0.11 (s, 3H, Si-CH3), 0.09 (s, 6H, Si-
CH3), 0.08 (s, 3H, Si-CH3), 0.06 (s, 3H, Si-CH3), 0.03 (s, 3H,
Si-CH3); 13C NMR (CDCl3, 100 MHz) d 139.6 (C-1ꢀ), 116.5 (C-
2ꢀ), 107.7 (C-1), 91.9 (C-4), 86.1 (C-2), 80.3 (C-3), 69.7 (C-5),
26.2 (Si-C(CH3)3), 25.9 (Si-C(CH3)3), 25.9 (Si-C(CH3)3), 20.4
(C-6), 18.5 (Si-C(CH3)3), 18.1 (Si-C(CH3)3), 18.0 (Si-C(CH3)3),
1.9 (O-Si(CH3)3), −4.1 (2C, Si-CH3), −4.1 (Si-CH3), −4.2 (Si-
CH3), −4.3 (Si-CH3), −4.4 (Si-CH3); MS (CI + NH3) m/z: 532
(MH+ − TMSOH + NH3), 515 (MH+ − TMSOH).
1
a white solid (mp 56–59 C): H NMR (CDCl3, 400 MHz) d
4.68 (t, 1H, H-1, J = 2.5 Hz), 4.01 (dq, 1H, H-5, J = 12.5, 6.3
Hz), 3.90 (s, 1H, H-3), 3.87 (dd, 1H, H-2, J = 2.8, 0.9 Hz), 3.61
(dd, 1H, H-4, J = 7.9, 0.7 Hz), 2.41 (d, 1H, H-2ꢀ, J = 2.2 Hz),
1.15 (d, 3H, H-6, J = 6.3 Hz), 0.92 (s, 9H, Si-C(CH3)3), 0.90
(s, 9H, Si-C(CH3)3), 0.87 (s, 9H, Si-C(CH3)3), 0.14 (s, 3H, Si-
CH3), 0.12 (s, 3H, Si-CH3), 0.11 (s, 3H, Si-CH3), 0.10 (s, 3H,
Si-CH3), 0.09 (s, 3H, Si-CH3), 0.08 (s, 3H, Si-CH3); 13C NMR
(CDCl3, 100 MHz) d 92.4 (C-1ꢀ), 80.0 (C-1), 79.0 (C-5), 79.0 (C-
3), 75.2 (C-2ꢀ), 72.3 (C-2), 69.1 (C-4), 26.2 (Si-C(CH3)3), 25.9
(Si-C(CH3)3), 25.7 (Si-C(CH3)3), 20.5 (C-6), 18.5 (Si-C(CH3)3),
18.3 (Si-C(CH3)3), 17.9 (Si-C(CH3)3), −4.1 (Si-CH3), −4.3 (Si-
CH3), −4.4 (Si-CH3), −4.5 (Si-CH3), −4.7 (Si-CH3), −4.8 (Si-
CH3); MS (CI + NH3) m/z: 532 (MH+ + NH3), 515 (MH+); IR
(cm−1, CCl4): 3312 (C≡C–H). [a]D25 = − 9.5 (c = 1, CHCl3).
1-Vinyl-2,3,5-tri-O-tert-butyldimethylsilyl-b-D-fucofuranose (34)
A mixture of compound 33 (0.84 g, 1.63 mmol), 20% Pd/CaCO3
(0.17 g) and 10% quinoline (0.08 g) in ethyl acetate (8 mL) was
hydrogenated at 1 atm at room temperature. The catalyst was
filtered off (over Celite) and the resulting solution evaporated
under reduced pressure. The residue was purified by flash
chromatography (silica gel, petroleum ether–AcOEt, 99 : 1) to
yield olefin 34 (98% yield) as a colourless oil: 1H NMR (CDCl3,
400 MHz) d 5.93 (ddd, 1H, H-1ꢀ, J = 17.5, 10,3, 7.7 Hz), 5.34
(ddd, 1H, H-2ꢀ, J = 17.4, 1,8, 0.9 Hz), 5.22 (ddd, 1H, H-2ꢀ, J =
10.4, 1,9, 0.6 Hz), 4.41 (dd, 1H, H-1, J = 7.8, 2.7 Hz), 3.97 (dq,
1H, H-5, J = 7.7, 6.3 Hz), 3.90 (s, 1H, H-3), 3.77 (dd, 1H, H-2,
J = 2.7, 0.8 Hz), 3.65 (dd, 1H, H-4, J = 7.8, 0.9 Hz), 1.15 (d,
3H, H-6, J = 6.4 Hz), 0.90 (s, 18H, Si-C(CH3)3), 0.88 (s, 9H,
Si-C(CH3)3), 0.10 (s, 3H, Si-CH3), 0.09 (s, 3H, Si-CH3), 0.08 (s,
3H, Si-CH3), 0.08 (s, 3H, Si-CH3), 0.07 (s, 3H, Si-CH3), 0.04 (s,
3H, Si-CH3); 13C NMR (CDCl3, 100 MHz) d 135.0 (C-1ꢀ), 118.2
(C-2ꢀ), 92.5 (C-4), 83.3 (C-1), 80.9 (C-2), 79.9 (C-3), 69.5 (C-5),
26.2 (Si-C(CH3)3), 25.9 (Si-C(CH3)3), 25.8 (Si-C(CH3)3), 20.6
(C-6), 18.5 (Si-C(CH3)3), 18.2 (Si-C(CH3)3), 17.9 (Si-C(CH3)3),
−4.0 (Si-CH3), −4.3 (Si-CH3), −4.4 (Si-CH3), −4.5 (Si-CH3),
1-Trimethylsilylethynyl-2,3,5-tri-O-tert-butyldimethylsilyl-
b-D-fucofuranose (32)
To a solution of TMS-acetylene (0.73 mL, 0.51 g, 5◦.15 mmol)
in THF (10 mL) was added under nitrogen at −10 C n-BuLi
(4.27 mL, 5.54 mmol, 1.3 mol L−1). The reaction mixture was
allowed to warm up to room temperature for 15 min and was
then cooled to −78 ◦C. A solution of lactone 28 (2 g, 3.96
mmol) in THF (10 mL) was added dropwise, the reaction
mixture was allowed to warm up to room temperature over
2 h and quenched with Ac2O (4 mL). The resulting mixture was
extracted with CH2Cl2. The combined extracts were dried and
concentrated in vacuo. To a cooled (−78 ◦C) solution of the
residue and triethylsilane (2.53 mL, 1.84 g, 15.84 mmol) in an-
hydrous CH2Cl2 (80 mL) was added dropwise BF3·OEt2 (2 mL,
2.25 g, 15.84 mmol). When the starting material was completely
consumed, the reaction was neutralised with triethylamine and
4 4 4 0
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 4 4 3 2 – 4 4 4 3

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−4.6 (Si-CH3), −4.7 (Si-CH3); MS (CI + NH3) m/z: 534 (MH+ +
NH3), 517 (MH+); [a]D25 = −19.9 (c = 1, CHCl3); HRMS calcd
for C26H56O4Si3 516.34865; found 516.34916.
8.8 Hz), 4.69–4.50 (m, 2H, H-12ꢀa and H-12ꢀb), 4.23 (td, 0.3H,
H-1ꢀb, J = 9.9 and 3.3 Hz), 4.02–3.99 (m, 1.7H, H-1a, H-1b
and H-1ꢀa), 3.91–3.86 (m, 3H, H-2a, H-2b, H-3a, H-3b, H-5a
and H-5b), 3.86 (s, 3H, OCH3a and OCH3b), 3.61 (t, 1H, H-4a
and H-4b, J = 9.1 Hz), 3.30–3.08 (m, 2H, H-3ꢀa and H-3ꢀb),
2.47–2.39 (m, 0.7H, H-2ꢀa), 2.32–2.24 (m, 0.7H, H-2ꢀa), 2.19–
2.13 (m, 0.3H, H-2ꢀb), 1.98–1.89 (m, 0.3H, H-2ꢀb), 1.41 (t, 2.1H,
H-13ꢀa, J = 7.1 Hz), 1.40 (t, 0.9H, H-13ꢀb, J = 7.1 Hz), 1.14 (d,
3H, H-6a and H-6b, J = 6.2 Hz), 0.94 (s, 2.7H, Si-C(CH3)3a),
0.90 (s, 6.3H, Si-C(CH3)3b), 0.87 (s, 11.7H, Si-C(CH3)3a, Si-
C(CH3)3b and Si-C(CH3)3b), 0.86 (s, 6.3H, Si-C(CH3)3a), 0.17
(s, 0.9H, Si-CH3b), 0.15 (s, 0.9H, Si-CH3b), 0.12 (s, 2.1H, Si-
CH3a), 0.11 (s, 0.9H, Si-CH3b), 0.10 (s, 5.1H, Si-CH3a, Si-CH3a
and Si-CH3b), 0.09 (s, 2.1H, Si-CH3a), 0.07 (s, 2.1H, Si-CH3a),
0.05 (s, 3H, Si-CH3a and Si-CH3b), 0.03 (s, 0.9H, Si-CH3b);
13C NMR (CDCl3, 100 MHz) d 213.9 (C-11ꢀb), 212.4 (C-11ꢀa),
200.6 (C-4ꢀa), 200.0 (C-4ꢀb), 157.8 (C-6ꢀb), 157.5 (C-6ꢀa), 136.0
(C-10ꢀb), 135.7 (C-10ꢀa), 132.9 (C-8ꢀa and C-8ꢀb), 129.9 (C-5ꢀa),
129.4 (C-5ꢀb), 113.6 (C-7ꢀb), 113.5 (C-7ꢀa), 113.2 (C-9ꢀb), 113.2
(C-9ꢀa), 92.9 (C-4a), 92.5 (C-4b), 81.1 (C-1b), 80.2 (C-1a), 79.1
(C-2a and C-2b), 78.3 (C-3a and C-3b), 69.9 (C-12ꢀa), 69.7 (C-
12ꢀb), 69.5 (C-5b), 69.4 (C-5a), 55.9 (OCH3b), 55.8 (OCH3a),
49.9 (C-1ꢀb), 47.5 (C-1ꢀa), 40.6 (C-3ꢀb), 40.2 (C-3ꢀa), 26.3 (C-
2ꢀa), 26.3 (C-2ꢀb), 26.1 (Si-C(CH3)3b), 25.9 (Si-C(CH3)3a), 25.9
(Si-C(CH3)3a), 25.8 (Si-C(CH3)3b), 25.7 (Si-C(CH3)3a and Si-
C(CH3)3b), 20.8 (C-6a), 20.6 (C-6b), 18.4 (Si-C(CH3)3a), 18.3
(Si-C(CH3)3b), 18.1 (Si-C(CH3)3b), 18.0 (Si-C(CH3)3a), 17.8 (Si-
C(CH3)3a and Si-C(CH3)3b), 13.9 (C-13ꢀb), 13.8 (C-13ꢀa), −3.4
(Si-CH3b), −3.9 (Si-CH3a), −4.1 (Si-CH3b), −4.2 (Si-CH3a),
−4.3 (Si-CH3a and Si-CH3a), −4.3 (Si-CH3b), −4.4 (Si-CH3b),
−4.7 (Si-CH3a), −4.8 (Si-CH3b), −5.2 (Si-CH3a), −5.3 (Si-
CH3b); MS (CI + NH3) m/z: 884 (MH+ + NH3), 882 (MH+ +
( )-S-[4-(2-Methoxy-5-trimethylacetylphenyl)-1-(2,3,5-tri-O-
tert-butyldimethylsilyl-b-D-fucofuranosyl)-4-oxobutyl]-O-
ethyldithiocarbonate (35)
A solution of xanthate 22 (0.05 g, 0.13 mmol) and olefin 34
(0.14 g, 0.27 mmol) in 0.14 mL of 1,2-dichloroethane (DCE)
was refluxed for 15 min under argon. Lauroyl peroxide (DLP)
was then added (5 mol%) to the refluxing solution, followed
by additional portions (5 mol% every 90 min). When the
starting material was completely consumed (after addition of
15 mol% of DLP), the mixture was cooled to room temperature,
concentrated under reduced pressure and the residue was
purified by flash column chromatography (silica gel, petroleum
ether–AcOEt, 95 : 5 to 9 : 1) to give adduct 35 (yellow oil,
59% yield, 83% based on recovered starting material) as an
inseparable 2 : 1 mixture of diastereoisomers (labelled a and
b): 1H NMR (CDCl3, 400 MHz) d 7.41 (d, 0.3H, H-10ꢀb, J = 2.9
Hz), 7.37 (d, 0.7H, H-10ꢀa, J = 2.9 Hz), 7.18–7.14 (m, 1H, H-8ꢀa
and H-8ꢀb), 6.95 (d, 0.3H, H-7ꢀb, J = 8.9 Hz), 6.93 (d, 0.7H, H-
7ꢀa, J = 8.9 Hz), 4.68–4.52 (m, 2H, H-12ꢀa and H-12ꢀb), 4.24 (td,
0.3H, H-1ꢀb, J = 9.9, 3.1 Hz), 4.06 (m, 1.7H, H-1a, H-1b and
H-1ꢀa), 3.93–3.87 (m, 3H, H-2a, H-2b, H-3a, H-3b, H-5a and
H-5b), 3.88 (s, 3H, OCH3a and OCH3b), 3.62 (t, 1H, H-4a and
H-4b, J = 8.0 Hz), 3.34–3.10 (m, 2H, H-3ꢀa and H-3ꢀb), 2.47–
2.40 (m, 0.7H, H-2ꢀa), 2.32–2.24 (m, 0.7H, H-2ꢀa), 2.21–2.15 (m,
0.3H, H-2ꢀb), 1.98–1.88 (m, 0.3H, H-2ꢀb), 1.41 (t, 2.1H, H-13ꢀa,
J = 7.1 Hz), 1.41 (t, 0.9H, H-13ꢀb, J = 7.0 Hz), 1.14 (d, 3H,
H-6a and H-6b, J = 6.2 Hz), 0.95 (s, 2,7H, Si-C(CH3)3a), 0.90 (s,
6,3H, Si-C(CH3)3b), 0.88 (s, 11,7H, Si-C(CH3)3a, Si-C(CH3)3b,
and Si-C(CH3)3b), 0.87 (s, 6.3H, Si-C(CH3)3a), 0.18 (s, 0.9H, Si-
CH3b), 0.15 (s, 0.9H, Si-CH3b), 0.12 (s, 2.1H, Si-CH3a), 0.10 (s,
5.1H, Si-CH3a, Si-CH3a and Si-CH3b), 0.09 (s, 3H, Si-CH3a and
Si-CH3b), 0.08 (s, 2,1H, Si-CH3a), 0.07 (s, 2,1H, Si-CH3a), 0.06
(s, 0,9H, Si-CH3b), 0.04 (s, 0,9H, Si-CH3b); 13C NMR (CDCl3,
100 MHz) d 213.9 (C-11ꢀb), 212.4 (C-11ꢀa), 200.7 (C-4ꢀa), 200.0
(C-4ꢀb), 177.3 (O-COa), 177.2 (O-COb), 156.5 (C-6ꢀb), 156.1
(C-6ꢀa), 144.3 (C-9ꢀa and C-9ꢀb), 128.7 (C-5ꢀa and C-5ꢀb), 126.6
(C-10ꢀb), 126.2 (C-10ꢀa), 123.1 (C-8ꢀb), 123.0 (C-8ꢀa), 112.4 (C-
7ꢀb), 112.2 (C-7ꢀa), 92.9 (C-4a), 92.5 (C-4b), 81.2 (C-1b), 80.2
(C-1a), 79.2 (C-2b), 79.1 (C-2a), 78.4 (C-3a), 78.3 (C-3b), 69.9
(C-12ꢀa), 69.7 (C-12ꢀb), 69.5 (C-5b), 69.4 (C-5a), 56.0 (OCH3b),
55.9 (OCH3a), 49.9 (C-1ꢀb), 47.6 (C-1ꢀa), 40.7 (C-3ꢀb), 40.2
(C-3ꢀa), 39.1 (C(CH3)3a and C(CH3)3b), 27.2 (C(CH3)3a and
C(CH3)3b), 26.4 (C-2ꢀb), 26.4 (C-2ꢀa), 26.1 (Si-C(CH3)3b), 26.0
(Si-C(CH3)3a), 25.9 (Si-C(CH3)3a), 25.9 (Si-C(CH3)3b), 25.7 (Si-
C(CH3)3a and Si-C(CH3)3b), 20.7 (C-6a), 20.6 (C-6a), 18.4 (Si-
C(CH3)3a), 18.3 (Si-C(CH3)3b), 18.1 (Si-C(CH3)3b), 18.0 (Si-
C(CH3)3a), 17.9 (Si-C(CH3)3a and Si-C(CH3)3b), 13.9 (C-13ꢀb),
13.7 (C-13ꢀa), −3.4 (Si-CH3b), −3.9 (Si-CH3a), −4.1 (Si-CH3b),
−4.2 (Si-CH3a), −4.3 (Si-CH3a), −4.3 (Si-CH3a), −4.4 (Si-
CH3b), −4.4 (Si-CH3b), −4.7 (Si-CH3a), −4.8 (Si-CH3b), −5.1
+
+
−1
=
NH3), 867 (MH ), 865 (MH ); IR (cm , CCl4): 1683 (C O),
=
=
1252 (S–C S), 1049 (O–C S).
( )-S-[4-(2-Methoxyphenyl)-1-(2,3,5-tri-O-tert-
butyldimethylsilyl-b-D-fucofuranosyl)-4-oxobutyl]-
O-ethyldithiocarbonate (40)
Using the same procedure as 35, xanthate 376 (0.05 g, 0.18 mmol)
and olefin 34 (0.19 g, 0.37 mmol) gave the adduct 40 (yellow
oil, 35% yield, 59% yield based on recovered starting material)
1
as an inseparable 2 : 1 mixture of diastereoisomers: H NMR
(CDCl3, 400 MHz) d 7.69 (dd, 0.3H, H-8ꢀb, J = 7.7, 1.7 Hz),
7.66 (dd, 0.7H, H-8ꢀa, J = 7.7, 1.7 Hz), 7.48–7.41 (m, 1H, H-
10ꢀa and H-10ꢀb), 7.00–6.93 (m, 2H, H-7ꢀa, H-7ꢀb, H-9ꢀa and
H-9ꢀb), 4.68–4.50 (m, 2H, H-12ꢀa and H-12ꢀb), 4.24 (td, 0.3H,
H-1ꢀb, J = 10.1, 3.2 Hz), 4.06–3.99 (m, 1.7H, H-1a, H-1b and
H-1ꢀa), 3.93–3.86 (m, 3H, H-2a, H-2b, H-3a, H-3b, H-5a and
H-5b), 3.87 (s, 3H, OCH3a and OCH3b), 3.62 (t, 1H, H-4a and
H-4b, J = 9.1 Hz), 3.32–3.10 (m, 2H, H-3ꢀa and H-3ꢀb), 2.49–
2.39 (m, 0.7H, H-2ꢀa), 2.33–2.25 (m, 0.7H, H-2ꢀa), 2.23–2.17
(m, 0.3H, H-2ꢀb), 2.00–1.90 (m, 0.3H, H-2ꢀb), 1.41 (t, 2.1H, H-
13ꢀa, J = 7.1 Hz), 1.40 (t, 0.9H, H-13ꢀb, J = 7.1 Hz), 1.14 (d,
3H, H-6a and H-6b, J = 6.2 Hz), 0.94 (s, 6.3H, Si-C(CH3)3a),
0.90 (s, 2.7H, Si-C(CH3)3b), 0.87 (s, 11.7H, Si-C(CH3)3a, Si-
C(CH3)3b and Si-C(CH3)3b), 0.86 (s, 6.3H, Si-C(CH3)3a), 0.18
(s, 0.9H, Si-CH3b), 0.15 (s, 0.9H, Si-CH3b), 0.12 (s, 2.1H, Si-
CH3a), 0.10 (s, 6H, Si-CH3a, Si-CH3a, Si-CH3b and Si-CH3b),
0.09 (s, 2.1H, Si-CH3a), 0.07 (s, 2.1H, Si-CH3a), 0.06 (s, 3H, Si-
CH3a and Si-CH3b), 0.04 (s, 0.9H, Si-CH3b); 13C NMR (CDCl3,
100 MHz) d 214.0 (C-11ꢀb), 212.5 (C-11ꢀa), 202.2 (C-4ꢀa), 201.5
(C-4ꢀb), 158.8 (C-6ꢀb), 158.5 (C-6ꢀa), 133.6 (C-10ꢀb), 133.3 (C-
10ꢀa), 130.4 (C-7ꢀa and C-7ꢀb), 128.6 (C-5ꢀa), 128.1 (C-5ꢀb), 120.7
(C-9ꢀa et C-9ꢀb), 111.6 (C-8ꢀb), 111.5 (C-8ꢀa), 92.9 (C-4a), 92.5
(C-4b), 81.2 (C-1b), 80.2 (C-1a), 79.2 (C-2a and C-2b), 78.3 (C-
3a and C-3b), 69.9 (C-12ꢀa), 69.6 (C-12ꢀb), 69.5 (C-5b), 69.4
(C-5a), 55.6 (OCH3b), 55.5 (OCH3a), 50.0 (C-1ꢀb), 47.6 (C-
1ꢀa), 40.7 (C-3ꢀb), 40.3 (C-3ꢀa), 26.5 (C-2ꢀa and C-2ꢀb), 26.1
(Si-C(CH3)3b), 25.9 (Si-C(CH3)3a), 25.9 (Si-C(CH3)3a), 25.7
(Si-CH3a), −5.3 (Si-CH3b); MS (CI + NH3) m/z: 887 (MH+);
−1
=
=
=
IR (cm , CCl4): 1741 (O–C O), 1680 (C O), 1255 (S–C S),
=
=
1109 (O–C O), 1048 (O–C S).
( )-S-[4-(2-Methoxy-5-bromophenyl)-1-(2,3,5-tri-O-tert-
butyldimethylsilyl-b-D-fucofuranosyl)-4-oxobutyl]-
O-ethyldithiocarbonate (39)
Using the same procedure as 35, xanthate 36 (0.05 g, 0.14 mmol)
and olefin 34 (0.15 g, 0.28 mmol) gave the adduct 39 (yellow oil,
45% yield, 64% yield based on recovered starting material) as
an inseparable 2 : 1 mixture of diastereoisomers (labelled a and
1
b): H NMR (CDCl3, 400 MHz) d 7.79 (d, 0.3H, H-10ꢀb, J =
2.6 Hz), 7.76 (d, 0.7H, H-10ꢀa, J = 2.6 Hz), 7.53 (dd, 0.3H,
H-8ꢀb, J = 9.2, 2.1 Hz), 7.51 (dd, 0.7H, H-8ꢀa, J = 8.8, 2.5 Hz),
6.85 (d, 0.3H, H-7ꢀb, J = 8.8 Hz), 6.83 (d, 0.7H, H-7ꢀa, J =
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 4 4 3 2 – 4 4 4 3
4 4 4 1

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(Si-C(CH3)3a, Si-C(CH3)3b and Si-C(CH3)3b), 20.8 (C-6a),
20.6 (C-6b), 18.4 (Si-C(CH3)3a), 18.3 (Si-C(CH3)3b), 18.1 (Si-
C(CH3)3b), 18.0 (Si-C(CH3)3a), 17.9 (Si-C(CH3)3a and Si-
C(CH3)3b), 13.9 (C-13ꢀb), 13.7 (C-13ꢀa), −3.4 (Si-CH3b), −3.9
(Si-CH3a), −4.1 (Si-CH3b), −4.2 (Si-CH3a), −4.3 (Si-CH3a and
Si-CH3a), −4.4 (Si-CH3b), −4.4 (Si-CH3b), −4.7 (Si-CH3a),
−4.8 (Si-CH3b), −5.1 (Si-CH3a), −5.3 (Si-CH3b); MS (CI +
NH3) m/z: 804 (MH+ + NH3), 787 (MH+); IR (cm−1, CCl4):
8.5, 0.8 Hz), 3.44 (td, 1H, H-1ꢀ, J = 10.1, 3.5 Hz), 2.95–2.84 (m,
2H, H-3ꢀ), 2.64–2.54 (m, 1H, H-2ꢀ), 2.20–2.11 (m, 1H, H-2ꢀ),
1.18 (d, 3H, H-6, J = 6.2 Hz), 0.92 (s, 9H, Si-C(CH3)3), 0.89 (s,
9H, Si-C(CH3)3), 0.87 (s, 9H, Si-C(CH3)3), 0.26 (s, 3H, Si-CH3),
0.20 (s, 3H, Si-CH3), 0.12 (s, 3H, Si-CH3), 0.11 (s, 3H, Si-CH3),
0.06(s, 3H, Si-CH3), 0.01 (s, 3H, Si-CH3); 13C NMR (CDCl3,
100 MHz) d 197.9 (C-4ꢀ), 146.9 (C-8ꢀ), 139.5 (C-5ꢀ), 131.1 (C-
10ꢀ), 129.5 (C-6ꢀ), 128.5 (C-7ꢀ), 127.8 (C-9ꢀ), 92.4 (C-4), 81.9
(C-1), 79.0 (C-2), 78.3 (C-3), 69.5 (C-5), 32.0 (C-1ꢀ), 34.5 (C-3ꢀ),
26.3 (Si-C(CH3)3), 26.0 (Si-C(CH3)3), 25.7 (Si-C(CH3)3), 25.2
(C-2ꢀ), 20.8 (C-6), 18.5 (Si-C(CH3)3), 18.4 (Si-C(CH3)3), 17.8
(Si-C(CH3)3), −2.1 (Si-CH3), −4.0 (Si-CH3), −4.2 (Si-CH3),
−4.3 (Si-CH3), −4.6 (Si-CH3), −5.2 (Si-CH3); MS (CI + NH3)
m/z: 688 (MH+ + NH3), 686 (MH+ + NH3), 671 (MH+), 669
=
=
=
1678 (C O), 1252 (S–C S), 1049 (S–C S).
( )-S-[4-(4-Chlorophenyl)-1-(2,3,5-tri-O-tert-
butyldimethylsilyl-b-D-fucofuranosyl)-4-oxobutyl]-
O-ethyldithiocarbonate (41)
Using the same procedure as 35, xanthate 38 (0.04 g, 0.15 mmol)
and olefin 34 (0.15 g, 0.29 mmol) gave the adduct 4115 (yellow oil,
72% yield) as an inseparable 2 : 1 mixture of diastereoisomers: 1H
NMR (CDCl3, 400 MHz) d 7.91 (d, 1.4H, H-6ꢀa, J = 8.6 Hz),
7.88 (d, 0.6H, H-6ꢀb, J = 8.6 Hz), 7.43 (d, 0.6H, H-7ꢀb, J =
8.6 Hz), 7.43 (d, 1.4H, H-7ꢀa, J = 8.6 Hz), 4.69–4.52 (m, 2H,
H-10ꢀa and H-10ꢀb), 4.25 (td, 0.3H, H-1ꢀb, J = 10.0, 3.2 Hz),
4.05–4.01 (m, 1.7H, H-1a, H-1b and H-1ꢀa), 3.92–3.60 (m, 3H,
H-2a, H-2b, H-3a, H-3b, H-5a and H-5b), 3.65–3.61 (m, 1H,
H-4a and H-4b), 3.35–3.12 (m, 2H, H-3ꢀa and H-3ꢀb), 2.48–
2.39 (m, 0.7H, H-2ꢀa), 2.33–2.25 (m, 0.7H, H-2ꢀa), 2.24–2.19
(m, 0.3H, H-2ꢀb), 2.05–1.88 (m, 0.3H, H-2ꢀb), 1.42 (t, 2.1H, H-
11ꢀa, J = 7.1 Hz), 1.41 (t, 0.9H, H-11ꢀb, J = 7.1 Hz), 1.14 (d,
2.1H, H-6a, J = 6.2 Hz), 1.14 (d, 0.9H, H-6b, J = 6.3 Hz),
0.94 (s, 2.7H, Si-C(CH3)3b), 0.90 (s, 6.3H, Si-C(CH3)3a), 0.89
(s, 6.3H, Si-C(CH3)3a), 0.88 (s, 2.7H, Si-C(CH3)3b), 0.86 (s, 9H,
Si-C(CH3)3a and Si-C(CH3)3b), 0.16 (s, 0.9H, Si-CH3b), 0.15 (s,
0.9H, Si-CH3b), 0.13 (s, 2.1H, Si-CH3a), 0.11 (s, 3H, Si-CH3a
and Si-CH3b), 0.10 (s, 2.1H, Si-CH3a), 0.09 (s, 2.1H, Si-CH3a),
0.09 (s, 0.9H, Si-CH3b), 0.07 (s, 2.1H, Si-CH3a), 0.06 (s, 0.9H,
+
−1
25
=
(MH ); IR (cm , CCl4): 1692 (C O); [a]D = − 13.0 (c = 1,
CHCl3). Diastereoisomer II (colourless oil): 1H NMR (CDCl3,
400 MHz) d 7.98 (d, 1H, H-6ꢀ, J = 8.4 Hz), 7.92 (d, 1H, H-9ꢀ,
J = 1.8 Hz), 7.31 (dd, 1H, H-7ꢀ, J = 8.4, 2.0 Hz), 4.08 (dd, 1H,
H-1, J = 10.0, 2.0 Hz), 3.93 (m, 3H, H-2, H-3 and H-5), 3.65
(d, 1H, H-4, J = 8.3 Hz), 3.28–3.23 (m, 1H, H-1ꢀ), 2.72–2.57
(m, 2H, H-3ꢀ), 2.21–2.13 (m, 1H, H-2ꢀ), 2.00–1.92 (m, 1H, H-2ꢀ),
1.20 (d, 3H, H-6, J = 6.4 Hz), 0.95 (s, 9H, Si-C(CH3)3), 0.91 (s,
9H, Si-C(CH3)3), 0.86 (s, 9H, Si-C(CH3)3), 0.19 (s, 3H, Si-CH3),
0.17 (s, 3H, Si-CH3), 0.12 (s, 3H, Si-CH3), 0.11 (s, 3H, Si-CH3),
0.10 (s, 3H, Si-CH3), 0.09 (s, 3H, Si-CH3); 13C NMR (CDCl3,
100 MHz) d 197.1 (C-4ꢀ), 148.0 (C-8ꢀ), 139.9 (C-5ꢀ), 130.7 (C-
10ꢀ), 130.3 (C-6ꢀ), 128.8 (C-7ꢀ), 127.6 (C-9ꢀ), 92.8 (C-4), 82.9
(C-1), 78.9 (C-2), 78.5 (C-3), 69.4 (C-5), 38.0 (C-1ꢀ), 36.2 (C-3ꢀ),
26.1 (Si-C(CH3)3), 25.9 (Si-C(CH3)3), 25.7 (2C, Si-C(CH3)3 and
C-2ꢀ), 20.7 (C-6), 18.3 (Si-C(CH3)3), 18.2 (Si-C(CH3)3), 17.9 (Si-
C(CH3)3), −3.0 (Si-CH3), −3.9 (Si-CH3), −4.1 (Si-CH3), −4.3
(Si-CH3), −4.5 (Si-CH3), −5.3 (Si-CH3); MS (CI + NH3) m/z:
688 (MH+ + NH3), 686 (MH+ + NH3), 671 (MH+), 669 (MH+);
−1
25
=
IR (cm , CCl4): 1691 (C O); [a]D = + 2.6 (c = 1, CHCl3).
Si-CH3b), 0.05 (s, 2.1H, Si-CH3a), 0.04 (s, 0.9H, Si-CH3b); 13
C
NMR (CDCl3, 100 MHz) d 214.1 (C-9ꢀb), 212.2 (C-9ꢀa), 198.6
(C-4ꢀa), 198.2 (C-4ꢀb), 139.7 (C-5ꢀb), 139.3 (C-5ꢀa), 135.4 (C-
8ꢀa), 135.1 (C-8ꢀb), 129.7 (C-6ꢀa), 129.6 (C-6ꢀb), 129.0 (C-7ꢀb),
128.9 (C-7ꢀa), 92.9 (C-4a), 92.5 (C-4b), 81.2 (C-1b), 80.1 (C-1a),
79.2 (C-2a), 79.1 (C-2b), 78.5 (C-3b), 78.4 (C-3a), 70.1 (C-10ꢀa),
69.9 (C-10ꢀb), 69.4 (C-5b), 69.3 (C-5a), 50.1 (C-1ꢀb), 47.5 (C-
1ꢀa), 35.4 (C-3ꢀb), 35.1 (C-3ꢀa), 26.3 (C-2ꢀa), 26.1 (C-2ꢀb), 26.1
(Si-C(CH3)3b), 25.9 (Si-C(CH3)3a), 25.9 (Si-C(CH3)3a), 25.8 (Si-
C(CH3)3b), 25.7 (Si-C(CH3)3a), 25.7 (Si-C(CH3)3b), 20.8 (C-6a),
20.6 (C-6b), 18.4 (Si-C(CH3)3a), 18.3 (Si-C(CH3)3b), 18.1 (Si-
C(CH3)3b), 18,0 (Si-C(CH3)3a), 17.9 (Si-C(CH3)3a), 17.8 (Si-
C(CH3)3b), 13.9 (C-11ꢀb), 13.8 (C-11ꢀa), −3.,4 (Si-CH3b), −3.8
(Si-CH3a), −4.1 (Si-CH3b), −4.2 (Si-CH3a), −4.3 (Si-CH3a),
−4.3 (Si-CH3a), −4.3 (Si-CH3a), −4.4 (Si-CH3b), −4.6 (Si-
CH3b), −4.7 (Si-CH3a), −5.1 (Si-CH3b), −5.2 (Si-CH3b); MS
(CI + NH3) m/z: 810 (MH+ + NH3), 808 (MH+ + NH3), 793
Acknowledgements
The authors wish to thank CONACyT (Mexico) and CNRS
(France) for their generous financial support to A.C.-V.
References and notes
1 For reviews see: (a) C. Jaramillo and S. Knapp, Synthesis, 1994,
1; (b) K. Suzuki and T. Matsumoto, in Preparative Carbohydrate
Chemistry, ed. S. Hanessian, Marcel-Dekker, New York, 1997,
pp. 527–542; (c) M. H. D. Posteme, Tetrahedron, 1992, 48, 8545A.
2 (a) T. Matsumoto, T. Hosya and K. Suzuki, J. Am. Chem. Soc., 1992,
114, 3568; (b) T. Hosoya, E. Takashiro, T. Matsumoto and K. Suzuki,
J. Am. Chem. Soc., 1994, 116, 1004.
3 (a) L. Kalvoda, J. Farkaa and F. Sorm, Tetrahedron Lett., 1970,
11, 2297; (b) A. O. Stewart and R. M. Williams, J. Am. Chem.
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and H. A. El-Shenawy, J. Am. Chem. Soc., 1988, 110, 8698; (d) T.
Matsumoto, M. Katsuki and K. Suzuki, Tetrahedron Lett., 1989, 30,
833; (e) M. Yokoyama, H. Toyoshima, M. Shimizu, J. Mito and H.
Togo, Synthesis, 1998, 409; (f) M. D. Lewis, K. Cha and Y. Kishi,
J. Am. Chem. Soc., 1982, 104, 4976; (g) S. A. Babirad, Y. Wang and
Y. K i s h i , J. Org. Chem., 1987, 52, 1370; (h) R. W. Friesen and C. F.
Sturino, J. Org. Chem., 1990, 55, 2572.
4 (a) D. E. Kaelin, O. D. Lopez and S. F. Martin, J. Am. Chem. Soc.,
2001, 123, 6937; (b) M. Yamaguchi, A. Horiguchi, C. Ikeura and T.
Minami, J. Chem. Soc., Chem. Commun., 1992, 434; (c) Y. Yamamoto,
T. Saigoku, T. Ohgai, H. Nishiyama and K. Itoh, Chem. Commun.,
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5275.
5 T. Matsumoto, T. Hosoya and K. Suzuki, Tetrahedron Lett., 1990,
31, 4629.
6 A. Cordero-Vargas, B. Quiclet-Sire and S. Z. Zard, Tetrahedron Lett.,
2004, 45, 7335.
+
+
−1
=
(MH ), 791 (MH ); IR (cm , CCl4): 1691 (C O), 1255 (S–
=
=
C
S), 1051 (O–C S).
( )-6-Chloro-4-(2,3,5-O-tert-butyldimethylsilyl-b-
D-fucofuranosyl)-3,4-dihydro-2H-naphthalen-1-one (42)
A solution of 41 (0.03 g, 0.04 mmol) in 1,2-dichloroethane
(0.4 mL) was refluxed for 15 min under argon. Lauroyl
peroxide (DLP) was then added portionwise (20 mol% h−1) to
the refluxing solution. When starting material was completely
consumed (after addition of 1.2 equiv. of DLP), the crude
mixture was cooled to room temperature, concentrated under
reduced pressure and purified by flash column chromatography
(silica gel, petroleum ether–AcOEt, 99 : 1) to give tetralone
42 (57% yield) as a separable mixture of diastereoisomers.
Diastereoisomer I (colourless oil): 1H NMR (CDCl3, 400 MHz)
d 8.01 (d, 1H, H-6ꢀ, J = 8.4 Hz), 7.39 (d, 1H, H-9ꢀ, J = 2.0 Hz),
7.33 (dd, 1H, H-7ꢀ, J = 8.4, 2.0 Hz), 3.98 (dd, 1H, H-1, J =
10.6, 2.5 Hz), 3.96 (s, 1H, H-3), 3.91 (td, 1H, H-5, J = 14.6,
6.2 Hz), 3.69 (d, 1H, H-2, J = 1.7 Hz), 3.59 (dd, 1H, H-4, J =
7 P. P. Deshpande and O. R. Martin, Tetrahedron Lett., 1990, 31,
6313.
8 D. J. Hart and G. H. Merriman, Tetrahedron Lett., 1989, 30,
5093.
9 T. Kinoshita and T. Miwa, Carbohydr. Res., 1985, 143, 249.
4 4 4 2
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 4 4 3 2 – 4 4 4 3

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10 Stereochemical assignements of compounds 19 and 20 were based on
NOE data. On this basis, and knowing the cyclisation mechanisms,
we established the absolute configuration of the open-chain glycoside
18 as R.
11 (a) S. Hanessian, J.-Y. Sance´au and P. Chemla, Tetrahedron, 1995, 51,
6669; (b) W. Pitsch, A. Russel, M. Zabel and B. Ko¨nig, Tetrahedron,
2001, 57, 2345; (c) A. Dondoni, G. Mariotti and A. Marra, J. Org.
Chem., 2002, 67, 4475.
12 K. Bock, I. Lundt and C. Petersen, Carbohydr. Res., 1979, 68,
313.
13 The stereochemistry at C-1 for compound 30 was not determined.
However, it should be aby correlation with olefin 20 and the reaction
mechanism.
14 J. Xie, F. Durrat and J.-M. Vale´ry, J. Org. Chem., 2003, 68, 7896.
15 (a) J. Barluenga, B. Pedregal and J. M. Concello´n, Tetrahedron Lett.,
1978, 307; (b) I. Shiina, Y. Imai, M. Suzuki, M. Yanagisawa and T.
Mukaiyama, Chem. Lett., 2000, 1062.
16 A. Cordero-Vargas, I. Pe´rez-Mart´ın, B. Quiclet-Sire and S. Z. Zard,
Org. Biomol. Chem., 2004, 2, 3018.
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 4 4 3 2 – 4 4 4 3
4 4 4 3