Direct carbohydrate to carbocycle conversions via intramolecular allylation with Et2Zn/Pd(0)

Article abstract of DOI:10.1016/S0040-4020(03)00825-1

Treatment of 5-vinylpyranosides with Et₂Zn and catalytic Pd(0), in the presence of ZnCl₂, results in the formation of 5-membered carbocyclic products. This carbohydrate ring-contraction features an intramolecular allylation of a ring-opened carbohydrate aldehyde by an in situ-generated nucleophilic allylzinc species. The stereoselectivity about vinyl and free hydroxyl groups at the newly created stereogenic centers varies from low to moderate while both its extent and sense are found to depend on particular structural features (e.g. the configuration of the starting carbohydrate).

Full text of DOI:10.1016/S0040-4020(03)00825-1

Tetrahedron 59 (2003) 5515–5522
Direct carbohydrate to carbocycle conversions via intramolecular
allylation with Et2Zn/Pd(0)
*
Jose M. Aurrecoechea, Monica Arrate, Jesus H. Gil and Beatriz Lopez
´
´
´
´
´ ´ ´
Departamento de Quımica Organica II, Facultad de Ciencias, Universidad del Paıs Vasco, Apartado 644, 48080 Bilbao, Spain
Received 19 February 2003; revised 7 May 2003; accepted 27 May 2003
Abstract—Treatment of 5-vinylpyranosides with Et2Zn and catalytic Pd(0), in the presence of ZnCl2, results in the formation of 5-membered
carbocyclic products. This carbohydrate ring-contraction features an intramolecular allylation of a ring-opened carbohydrate aldehyde by an
in situ-generated nucleophilic allylzinc species. The stereoselectivity about vinyl and free hydroxyl groups at the newly created stereogenic
centers varies from low to moderate while both its extent and sense are found to depend on particular structural features (e.g. the
configuration of the starting carbohydrate). q 2003 Elsevier Science Ltd. All rights reserved.
1. Introduction
particular metal employed. Thus, allylzirconium inter-
mediates lead to a syn relationship between vinyl and
hydroxyl groups in the cyclized products,3 whereas
allylsamariums yield preferentially the corresponding anti
products, particularly at high temperatures.2e Since up to
four possible diastereoisomeric possibilities exist for
products 2 when generated from 1, changes in the nature
of the metal moiety of the allylic intermediates could
reasonably lead to different stereochemical results and
therefore add flexibility to this strategy.
The use of carbohydrates as readily available, inexpensive
starting materials in the preparation of complex non-
racemic substances has aroused considerable interest in
recent years, and this strategy has found particular
application in the stereoselective synthesis of densely
functionalized carbocycles.1 A commonly used approach
has involved the initial manipulation of the carbohydrate to
yield acyclic precursors capable of ring-closure using
conventional procedures.1c,d,f The alternative direct one-
pot conversion of carbohydrate-like structures into
functionalized carbocycles offers the advantage of requiring
only simple functional group manipulations of the starting
carbohydrate, but this approach has been much less
utilized.2,3 For example, modified carbohydrates 1, where
the terminal carbon has been elaborated into a vinyl unit, are
useful precursors of cyclopentanes 2 via the intramolecular
reaction between aldehyde and allylmetal species generated
in situ from 1 (Scheme 1).2e,3a–d
The Pd(0)-promoted ring-opening of 1, leading to inter-
mediate allylpalladium complexes 3, has already given
access to allylsamarium intermediates 5 (M¼SmI2), and
could provide an entry into other carbonyl-tethered
nucleophilic allylmetal species 5 if transmetalations with
appropriate metal reagents 4, other than SmI2,2e were
possible (Scheme 2). Support for this hypothesis is found in
the already reported Pd(0)-catalyzed intermolecular allyl-
ations of aldehydes and ketones with allylic organometallics
derived from the umpolung of allylpalladiums with SnCl2,
Et3B, InI or Et2Zn.4 With these precedents in hand, the aim
of this work was to explore the possibility of using the
Pd(0)/Et2Zn5 system with representative substrates of type 1
to effect the conversions 1!2 by intramolecular allylation
of the aldehyde moiety masked in 1 with allylzinc species 5
It is found that different stereochemical outcomes are
possible in the final cyclopentanes 2 depending on the
Scheme 1.
Keywords: allylations; carbohydrates; cyclizations; palladium; zinc.
*
Corresponding author. Tel.: þ34946012578; fax: þ34944648500;
e-mail: qopaufem@lg.ehu.es
Scheme 2.
0040–4020/03/$ - see front matter q 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4020(03)00825-1

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J. M. Aurrecoechea et al. / Tetrahedron 59 (2003) 5515–5522
acetylation of the resulting lactol afforded acetate 10b. The
acid-sensitive nature of the functionality present in 8 and 9
precluded a similar treatment of these particular substrates
to obtain the corresponding acetates.
Interestingly, these substrates were inert to Pd(0)/Et2Zn in
THF even under refluxing conditions. This is in sharp
contrast with the similar reactions run with Pd(0)/SmI2 that
had led to formation of cylopentanes of type 2.2e These
results evidence the need for a Lewis acid to assist the
departure of an OX leaving group in the initial oxidative
addition/ring opening step 1!3. Thus, SmI2 (or the
corresponding trivalent species originated in the reductive
transmetalation) is Lewis-acidic enough to activate the
substrate, whereas the weakly acidic Et2Zn is not.8 There-
fore, an external Lewis acid had to be introduced, and ZnCl2
was found to be a suitable one. Following our previous
experience in Pd(0)/SmI2-promoted 1!2 conversions2e and
that of other authors in Pd(0)/Et2Zn-mediated allylations,5,6
Pd(PPh3)4 was chosen as catalyst for these new allylations.
The alternative use of Tsuji’s catalyst, Pd(OAc)2/P(n-Bu)3
(1:1),9 was found to give occasionally better yields but its
use could not be generalized. Upon treatment of substrates
6–10 with Et2Zn/Pd(PPh3)4/ZnCl2 the expected cyclo-
pentane products 19–23 were generally obtained in good
yields as diastereomeric mixtures (Scheme 4, Table 1).
After chromatographic separation, the stereochemistry of
the individual diastereoisomers was unambiguously
elucidated using selective homodecoupling and n.O.e.
experiments (22, 23) or by direct comparison with literature
data (19–21). Yields, reaction conditions and diastereo-
meric ratios are collected in Table 1. Chart 2 includes a
summary of relevant n.O.e. data for compounds 22 and 23.
Chart 1.
(M¼ZnX) generated in situ from 1. An isolated example is
found in the literature of a related intramolecular allylation
that, starting from an allylic acetate substrate, performs a
macrocyclization through the same kind of intermediates.6
2. Results and discussion
Substrates 6–10 with different configuration and substi-
tution patterns were used in this study (Chart 1). The
preparation of 6–8 had already been described elsewhere2e
while the new substrates 9 and 10 were prepared from
commercially available methyl b-D-galactopyranoside (11)
and tri-O-acetyl-D-galactal (15), respectively, as shown in
Scheme 3. Thus, standard protection–deprotection proto-
cols led to primary alcohol 14 that was subjected to Swern
oxidation and Wittig olefination to afford the required acetal
9. The same oxidation/olefination sequence provided acetal
10a from 18. This alcohol was obtained by glycosidation of
the protected galactal 17 with triphenylphosphine hydro-
bromide7 and methanol, followed by silyl ether cleavage
with TBAF. Acid hydrolysis of acetal 10a followed by
As shown in Table 1, successful reactions are realized with
both configurations (a or b) at the anomeric center. A
methoxide leaving group was sufficiently reactive in most
cases to afford the cyclopentane products. However, in some
cases the corresponding acetates were used more con-
veniently due to their higher reactivity. Thus, 6b and 7b
already reacted at room temperature (entries 2 and 4) and
this translated into higher diastereoselectivies in the
Scheme 3. (a) Acetone, H2SO4, rt (b) TrCl, pyridine, DMAP, rt (c) TBSCl, imidazole, DMF, rt (d) HCO2H, Et2O, rt (e) MOMCl, i-Pr2NEt, CH2Cl2, rt
(f) n-Bu4NF, THF, rt (g) (i) (COCl)2, DMSO, CH2Cl2, 2708C; (ii) i-Pr2NEt, 2708C to rt (h) Ph3PvCH2, 2788C to rt (i) NaOMe, MeOH, rt (j) NaH, BnBr,
TBAI, rt (k) Ph3P·HBr, MeOH, CH2Cl2, rt (l) H2O:AcOH (1:1), reflux. (m) Ac2O, Et3N, DMAP.

J. M. Aurrecoechea et al. / Tetrahedron 59 (2003) 5515–5522
5517
formation of 19 and 20, respectively, when compared with
the high-temperature reactions of their corresponding
acetals. In contrast, acetal 10a reacted very sluggishly and
even the corresponding acetate 10b (entry 8) required
refluxing conditions to enter the reaction. Despite these
more forcing conditions substrate 10b maintained the same
levels of diastereoselectivity as the configurationally related
7b (entry 4).
In common with alternative methodologies that effect the
same transformations, a high degree of functionalization is
incorporated into the products. A limited number of
hydroxyl protecting groups have been tested, and of these
benzyl, methoxymethyl and the acetonide bridge were
shown to be compatible with this chemistry. However,
substantial loss of the TBS group took place in the major
product 22b from 9 (entry 7), and this resulted in the
additional formation of diol 22b0. In this case, the
stereochemistry of diol 22b0 was determined with the aid
of n.O.e. experiments while that of TBS-protected 22b was
secured after conversion into 22b0 upon treatment with
TBAF.
Scheme 4.
Table 1. Reactions of vinylpyranosides 6–10 with Et2Zn/ZnCl2/Pd(0)
Substrate
t (h)
Diastereomeric
ratioc
T (8 C)a
Product (yieldb)
a
b
c
d
1
2
3
4
5
6f
7
8
6a
6b
7a
7bd
8
75
25
50
25
75
75
75
75
14
21
20
24
22
2
19(32)
19(73)
20(57)
20(64)
21(73e)
21(94)
22(80)
23(52)
–
6
–
–
9
8
3
4
9
6
63 28
75 13
58 16 26
70 11 19
24 47 20
29 48 15
8
9
32
1
70g
70 17
9
18
9
10bh
Unless otherwise indicated, all reactions were run with 3 equiv. of Et2Zn,
1.2 equiv. of ZnCl2 and 5 mol% of Pd(PPh3)4.
a
Bath temperature.
Within brackets isolated total yield of 19–23 (%).
Diastereomeric ratios determined by weight of isolated diastereoisomers
after chromatographic separation.
While the results shown in Table 1 demonstrate the
feasibility of using Et2Zn/Pd(0) to effect the conversion of
pyranoside derivatives 6–10 into cyclopentanes 19–23,
rationalization of the stereochemical data appears difficult
as both the extent and sense of diastereoselectivity of these
new carbohydrate ring-contraction reactions are substrate-
dependent and do not appear to follow the same stereo-
chemical trends as either SmI22 2e or ‘Cp2Zr’3-promoted
b
c
d
a/b¼3.8:1.
e
Yield based on recovered starting material.
Pd(OAc)2/P(n-Bu)3 (1:1) (5 mol% with respect to 8) was used as catalyst
f
precursor.
Combined amounts of 22b and 22b0(see text).
a/b¼19:1.
g
h
Chart 2. Summary of relevant n.O.e. data for compounds 22, 23.

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J. M. Aurrecoechea et al. / Tetrahedron 59 (2003) 5515–5522
analogous cyclizations. One clearly discernible feature in
the Et2Zn-mediated reactions is an overall preference for an
anti relationship between vinyl and adjacent OR groups at
C(4)10 in the cyclization products, that is much more
pronounced than that found in the corresponding SmI2-
promoted reactions.2e,11 The C(4)/C(5)10 anti/syn ratio is
particularly high where, additionally, the newly created
stereogenic centers present a predominant syn relationship
between the vinyl and hydroxyl groups (entries 4, 7, 8). This
effect has been previously observed in the chemistry of
related allylzirconiums and it is believed to be steric in
origin,3 while a syn relationship between substituents at the
newly created stereogenic centers in these cases is taken as
an indication of the involvement of chelated cyclic
transition state structures in the cyclization step.2e,3,12
However, in contrast with allylzirconium chemistry where
a general preference for anti C(4)/C(5) and syn C(1)/C(5)10
relationships is observed, in these new Et2Zn-promoted
cyclizations it becomes apparent that small structural
changes are enough to break those tendencies, as shown,
for example, by bicyclic substrate 8 where the change in
protecting groups brings about a reversal in the configur-
ation at C(5) in the major product (entries 5, 6). An even
more pronounced turn in the same direction is observed with
a change in the starting carbohydrate configuration as in the
mannose-derived 6 (entries 1, 2). This gave an overall 55%
isolated yield of 19c as major product, where an anti
relationship exists between the vinyl and free hydroxyl
groups.13 It should be noted that in this last case SmI2/Pd(0)
and ‘Cp2Zr’ yield preferentially isomers 19b and 19a,
respectively, in useful yields.2e,3a
using CDCl3 as solvent and internal reference (d 7.26 for 1H
and d 77.0 for 13C). IR data include only characteristic
absorptions. Mass spectra were obtained at 70 eV.
4.1.1. Methyl 2-O-(tert-butyldimethylsilyl)-b-D-galacto-
pyranoside (12). Commercial methyl b-D-galactopyrano-
side (8.00 g, 41.2 mmol) was converted into methyl 3,4-O-
isopropylidene-b-D-galactopyranoside.17 The crude product
(9.05 g) was dissolved in pyridine (73 mL) and treated with
trityl chloride (13.7 g, 49.0 mmol) and DMAP (0.698 g,
5.70 mmol) at rt for 14 h. After addition of hexanes
(100 mL), the solvents were removed in vacuo and the
residue was dissolved in CH2Cl2 (150 mL). The solution
was washed with sat. CuSO4 (3£20 mL), the combined
aqueous layers back-extracted with CH2Cl2 (2£20 mL), and
the combined organic layers were washed with brine
(20 mL) and dried (Na2SO4). The residue after evaporation
was purified by flash chromatography (35% EtOAc/hexanes
and then 50% EtOAc/hexanes) to afford methyl 3,4-O-
isopropylidene-6-O-trityl-b-D-galactopyranoside (10.3 g,
56%) that was dissolved in DMF (23 mL) and treated with
imidazole (3.29 g, 48.4 mmol) and tert-butyldimethylsilyl
chloride (5.13 g, 33.0 mmol) at rt for 18 h. The mixture was
diluted with EtOAc (250 mL), extracted with water
(2£100 mL) and then with sat. CuSO4 (2£50 mL). The
combined aqueous layers were back-extracted with EtOAc
(2£75 mL), and the combined organic layers were dried
(Na2SO4). The residue after evaporation was purified by
flash chromatography (5% EtOAc/hexanes) to afford methyl
2-O-(tert-butyldimethylsilyl)-3,4-O-isopropylidene-6-O-
trityl-b-D-galactopyranoside (10.6 g, 86%). A portion of
this (8.40 g, 14.0 mmol) was dissolved in Et2O (42 mL), and
to the solution was added HCO2H (96%, 42 mL). The
resulting solution was stirred for 12 min and diluted with
Et2O (100 mL). The mixture was washed with NaCl
(2£10 mL) and sat. NaHCO3 until neutral. After drying
(Na2SO4) and evaporation, the residue was purified by flash
chromatography (EtOAc) to yield the title compound
(2.87 g, 67%): 1H NMR d 0.10 and 0.12 (2s, 6H, Si–
CH3), 0.90 (s, 9H, t-Bu), 2.3 (br s, W1/2¼21.0 Hz, 1H, OH),
2.4 (br s, W1/2¼10.3 Hz, 1H, OH), 2.8 (br s, W1/2¼13.1 Hz,
1H, OH), 3.51–3.64 (m, 6H), 3.52 (s, OCH3 included in m
at 3.51–3.63), 3.90–3.97 (m, 2H), 4.0 (br s, W1/2¼7.1 Hz,
1H), 4.12 (d, J¼7.1 Hz, 1H, H-1); 13C NMR d 24.9, 24.3,
18.3, 25.9, 57.2, 62.4, 69.4, 73.2, 73.9, 74.6, 104.7; IR (neat)
n 3480, 3300, 1250, 1070 cm21. [a]D20¼215.38 (c¼0.3,
CHCl3); HRMS calcd for C12H25O5Si (M2CH3O)
277.1471, found 277.1465.
3. Conclusion
In conclusion, the use of Et2Zn and catalytic Pd(0), in the
presence of a Lewis acid, provides a new possibility for
cyclopentane formation by carbohydrate ring-contraction.
While diastereoselectivities are only moderate and sub-
strate-dependent, the method can give access to prepara-
tively useful yields of isomers that are not available using
alternative methodologies.
4. Experimental
4.1. General
All reactions involving air- and moisture-sensitive materials
were performed using standard bench-top techniques.14
Tetrahydrofuran (THF) and diethyl ether were freshly
distilled from sodium/benzophenone. For reactions with
Et2Zn, THF was deoxygenated prior to use. Acetic
anhydride, CH2Cl2, DMSO, DMF, diisopropylethylamine,
pyridine and triethylamine were distilled from CaH2. MeOH
was dried by treatment with Mg–I2 and distillation.
Pd(PPh3)4 was prepared according to a literature pro-
cedure.15 P(n-Bu)3 (Fluka, 95%) was used from a Sure-Seal
bottle. Flash column chromatography16 was performed on
silica gel (230–400 mesh). HPLC purifications were carried
out with a LiChrosorb Si60 column (7 mm, 25£2.5 cm)
using a refraction index detector. Routine 1H and 13C NMR
spectra were obtained at 250 and 62.9 MHz, respectively,
4.1.2. Methyl 2,6-di-O-(tert-butyldimethylsilyl)-3,4-O-
di(methoxymethyl)-b-D-galactopyranoside (13). To a
solution of 12 (2.81 g, 9.12 mmol) in DMF (14 mL) was
added imidazole (1.37 g, 20.0 mmol) followed by tert-
butyldimethylsilyl chloride (1.51 g, 10.0 mmol), and the
solution was stirred at rt for 14 h. After addition of ether
(70 mL) the solution was washed with water (2£25 mL), the
aqueous layer was back-extracted with ether (3£50 mL),
and the combined organic layers were washed with sat.
CuSO4 (2£20 mL). After drying (Na2SO4) and evaporation,
the crude product was purified by flash chromatography
(20% EtOAc/hexanes) to yield methyl 2,6-O-di(tert-butyl-
dimethylsilyl)-b-D-galactopyranoside (3.58 g, 93%). To a
stirred solution of this (3.18 g, 7.53 mmol) and i-Pr2NEt

J. M. Aurrecoechea et al. / Tetrahedron 59 (2003) 5515–5522
5519
(12 mL) in CH2Cl2 (150 mL) at 08C was added MOMCl
(3.4 mL, 45.4 mmol), and the mixture was allowed to reach
rt. New portions of MOMCl (7 mL, 92.1 mmol) and
i-Pr2NEt (22 mL) were added after the mixture had been
stirred for16 and 36 h, and again after 60 h (3.4 and 12 mL
of MOMCl and i-Pr2NEt, respectively). Stirring was
continued until complete conversion into the product
(total time 156 h). After adding Et2O (300 mL) the solution
was washed with water (100 mL) and then with brine
(100 mL). After drying (Na2SO4) and evaporation the crude
product was purified by flash chromatography (3% and then
10% EtOAc/hexanes) to yield 13 (3.01 g, 78%) as an oil: 1H
NMR d 0.06 and 0.08 (2s, 12H, SiCH3), 0.87 and 0.88 (2s,
18H, t-Bu), 3.39 (s, 3H, OCH3), 3.41 (s, 3H, OCH3), 3.46 (s,
OCH3 overlapped with a signal of another proton, total 4H),
3.71–3.78 (m, 3H), 4.01 (d, J¼2.2 Hz, 1H), 4.09 (d,
J¼7.3 Hz, 1H, H-1), 4.69 (d, J¼6.5 Hz, 1H, OCHOCH3),
4.71 (d, J¼6.5 Hz, 1H, OCHOCH3), 4.76 (d, J¼6.5 Hz, 1H,
OCHOCH3), 4.92 (d, J¼6.7 Hz, 1H, OCHOCH3); 13C NMR
d 25.5, 25.3, 24.5, 18.1, 18.2, 25.8, 55.7, 56.8, 61.6, 72.4,
72.7, 74.9, 79.2, 96.8, 97.0, 105.0; IR (neat) n 1250, 1000–
1050 cm21; [a]D20¼236.08 (c¼1.38, CHCl3); LRMS (EI)
m/z (%) 510 (M), 403 (27), 315 (base), 231 (36), 89 (43), 73
(36); HMRS calcd for C23H50O8Si2 510.3044, found
510.3022.
1.76 mL, 2.34 mmol) was added to a suspension of
methyltriphenylphosphonium bromide (1.01 g, 2.81 mmol)
in THF (15 mL) at 08C. After 30 min the mixture was
cooled at 2788C, and a solution of the crude aldehyde in
THF (10 mL) was added. After 15 min, the reaction mixture
was allowed to warm to rt, and saturated NH4Cl (15 mL)
was added. The aqueous phase was extracted with Et2O
(2£25 mL), and the combined organic extracts were dried
(Na2SO4). The crude product after evaporation was purified
by flash chromatography (15% EtOAc/hexanes) to yield 9
(0.38 g, 62% for two steps) as an oil: 1H NMR d 0.06 (s, 3H,
CH3–Si), 0.08 (s, 3H, CH3–Si), 0.87 (s, 9H, t-Bu), 3.37 (s,
3H, OCH3), 3.41 (s, 3H, OCH3), 3.49 (s, 3H, OCH3), 3.55
(dd, J¼9.7, 2.8 Hz, 1H, H-3), 3.78 (dd, J¼9.6, 7.4 Hz, 1H,
H-2), 3.92 (d, J¼2.6 Hz, 1H, H-4), 3.95–3.97 (m, 1H, H-5),
4.11 (d, J¼7.5 Hz, 1H, H-1), 4.60 (d, J¼6.9 Hz, 1H,
OCH2O), 4.68 (d, J¼6.7 Hz, 1H, OCH2O), 4.78 (d,
J¼6.7 Hz, 1H, OCH2O), 4.34 (d, J¼6.9 Hz, 1H, OCH2O),
5.21–5.26 (dt, J¼10.5, 1.5 Hz, 1H, H-7), 5.36–5.44 (dt,
J¼17.4, 1.5 Hz, 1H, H-7), 5.86–5.99 (ddd, J¼17.4, 10.6,
5.1 Hz, 1H, H-6); 13C NMR d 24.5, 18.2, 25.8, 55.9, 56.8,
72.1, 74.9, 75.6, 79.7, 97.0, 97.3, 104.8, 116.7, 134.6; IR
(neat) n 3000–2800, 1250 cm21; [a]D20¼265.48 (c¼2.6,
CHCl3). LRMS (EI) m/z (%) 299 (M293), 259 (35), 218
(96), 131 (67), 89 (34), 73 (base); HRMS calcd for
C15H27O4Si (M2MeOH–OMOM) 299.1686, found
299.1679.
4.1.3. Methyl 3,4-di-O-(methoxymethyl)-2-O-(tert-butyl-
dimethylsilyl)-b-D-galactopyranoside (14). To a solution
of 13 (2.96 g, 5.80 mmol) in THF (200 mL) at 08C was
added n-Bu4NF (1 M in THF, 7.3 mL, 7.3 mmol). After 1 h
the reaction was quenched with sat. NH4Cl (70 mL). The
aqueous layer was extracted with EtOAc (3£70 mL), and all
the organic extracts combined and dried (Na2SO4). The
residue after evaporation was purified by flash chromato-
graphy (20% and then 40% EtOAc/hexanes) to yield 14
(2.05 g, 93%) as an oil: 1H NMR d 0.061 (2 s, 6H, Si–CH3),
0.86 (s, 9H, t-Bu), 2.8 (br s, W1/2¼17.1 Hz, 1H, OH), 3.39
(s, 3H, OCH3), 3.42 (s, 3H, OCH3), 3.46 (s, 3H, OCH3),
3.53–3.59 (m, 2H, H-6, H-4), 3.68–3.75 (m, 3H, H-2, H-3,
H-6), 4.0 (br s, W1/2¼6.37 Hz, 1H, H-5), 4.07 (d, J¼7.5 Hz,
1H, H-1), 4.65–4.69 (m, 2H, OCH2O), 4.79 (d, J¼6.5 Hz,
1H, OCHO), 4.97 (d, J¼6.7 Hz, 1H, OCHO); 13C NMR d
24.5, 18.14, 25.8, 55.8, 56.2, 56.9, 60.8, 72.4, 73.8, 74.4,
4.1.5. 1,2-Dideoxy-6-O-(tert-butyldimethylsilyl)-D-liso-
hex-1-enopyranose (16). To a solution of tri-O-acetyl-D-
galactal (16.16 g, 59.30 mmol) in methanol (80 mL) was
added MeONa in MeOH (3.0 M, 0.6 mL, 1.8 mmol), and
the mixture was stirred at rt for 3 h. After solvent
evaporation the solid residue was purified by flash
chromatography (acetone) and dissolved in DMF (80 mL).
Imidazole (9.00 g, 0.130 mol) and tert-butyldimethylsilyl
chloride (10.00 g, 66.36 mmol) were added, and the mixture
was stirred for 12 h. Et2O (400 mL) was added, and the
solution was washed with water (2£100 mL) and sat.
CuSO4 (2£80 mL). The residue after evaporation was
purified by flash chromatography (30% EtOAc/hexanes) to
1
yield 16 (10.78 g, 70% for two steps) as an oil: H NMR d
0.09 (s, 6H, Si–CH3), 0.89 (s, 9H, t-Bu), 3.0 (br s,
W1/2¼28.5 Hz, 1H, OH), 3.3 (br s, W1/2¼17.0 Hz, 1H, OH),
3.90–3.96 (m, 3H, H-5, H-6), 4.1 (br s, W1/2¼11.5 Hz, 1H,
H-4), 4.3 (br s, W1/2¼12.7 Hz, 1H, H-3), 4.68 (dt, J¼6.1,
2.0 Hz, 1H, H-2), 6.35 (d, J¼6.1 Hz, 1H, H-1); 13C NMR d
25.5, 18.2, 25.7, 63.2, 64.2, 65.9, 75.7, 102.9, 144.4; IR
(neat) n 3404, 2953, 1647 cm21; [a]D20¼þ17.708 (c¼1.26,
CHCl3); LRMS (EI) m/z (%) 260 (M), 225 (62), 185 (73),
175 (base), 117 (72), 75 (77), 73 (62); HRMS calcd for
C12H24O4Si 260.1444, found 260.1440.
80.1, 97.9, 98.3, 104.9; IR (neat) n 3475, 1251, 1045 cm21
;
[a]2D0¼2101.58 (c¼1.06, CHCl3); HMRS calcd for
C17H36O8Si 396.2179, found 396.2165.
4.1.4. Methyl 6,7-dideoxy-3,4-di-O-(methoxymethyl)-2-
O-(tert-butyldimethylsilyl)-b-D-galacto-hept-6-enopyra-
noside (9). To a solution of oxalyl chloride (170 mL,
1.92 mmol) in CH2Cl2 (7 mL) at 2708C under argon, was
added a solution of DMSO (280 mL, 3.92 mmol) in CH2Cl2
(5 mL). After 10 min a solution of 14 (0.62 g, 1.56 mmol) in
CH2Cl2 (7 mL) was added, and the resulting mixture was
stirred for 2 h at 2708C. i-Pr2NEt (1.36 mL, 7.8 mmol) was
then added, and the mixture was allowed to reach rt over a
period of 2 h. The solution was diluted with CH2Cl2
(20 mL), successively extracted with saturated NaHCO3
and water, and dried (Na2SO4). Removal of the solvent in
vacuo afforded a residue that was dissolved in benzene and
evaporated (three times) to yield the corresponding
aldehyde which, without further manipulation, was used in
the next step as follows. n-BuLi (1.33 M in hexanes,
4.1.6. 1,2-Dideoxy-3,4-di-O-benzyl-6-O-(tert-butyl-
dimethylsilyl)-D-liso-hex-1-enopyranose (17). To a sus-
pension of NaH (60% dispersion in mineral oil, 6.17 g,
0.150 mmol) in THF (150 mL) was added 16 (10.57 g,
40.60 mmol) in THF (100 mL), and the mixture was stirred
for 20 min before adding benzyl bromide (15.4 mL,
0.130 mol) and tetrabutylammonium iodide (1.17 g,
3.17 mmol). After stirring for 12 h sat. NH4Cl (8 mL) was
added, and the mixture was extracted with ether (150 and
2£70 mL). The combined organic layers were dried

5520
J. M. Aurrecoechea et al. / Tetrahedron 59 (2003) 5515–5522
(Na2SO4), and the crude product after evaporation was
purified by flash chromatography (6% EtOAc/hexanes) to
yield 17 (15.21 g, 87%) as an oil: H NMR d 0.06 (s, 6H,
138.5, 138.7; IR (neat) n 3020, 1495, 1350, 1050 cm21
;
[a]2D0¼þ85.08 (c¼0.8, CHCl3); LRMS (EI) m/z (%) 354
(M), 240 (14), 91 (base); HRMS calcd for C22H26O4
354.1831, found 354.1843.
1
Si–CH3), 0.90 (s, 9H, t-Bu), 3.81–3.93 (m, 2H, H-6), 4.00–
4.05 (m, 2H, H-4, H-5), 4.22 (br s, W1/2¼8.7 Hz, 1H, H-3),
4.62 and 4.68 (AB system, J¼10.9 Hz, 2H, OCH2Ph), 4.66
(s, 1H, OCHPh), 4.70 (d, J¼11.9 Hz, 1H, OCHPh), 4.86
(dd, J¼6.1, 1.2 Hz, 1H, H-2), 4.93 (d, J¼11.9 Hz, 1H,
OCHPh), 6.35 (d, J¼6.1 Hz, 1H, H-1), 7.29–7.35 (m, 10H,
Ar-H); 13C NMR d 25.3, 18.3, 25.9, 61.3, 70.7, 70.9, 71.1,
73.5, 77.5, 99.9, 127.4, 127.5, 127.6, 128.0, 128.2, 128.3,
4.1.9. O-Acetyl-3,4-di-O-benzyl-2-deoxy-a-D-liso-hept-6-
enopyranose (10b). A solution of 10a (1.75 g, 0.49 mmol)
in H2O:AcOH (1:1, 5 mL) was heated at reflux for 24 h.
After cooling the mixture, sat. K2CO3 (40 mL) was added.
The aqueous layer was extracted with EtOAc (4£50 mL),
and the combined organic layers were dried (Na2SO4). The
crude product after evaporation was purified by flash
chromatography (20–30% EtOAc/hexanes gradient) to
yield the corresponding lactol (0.83 g, 50%). This was
dissolved in Et3N (1.0 mL, 7.2 mmol), and to this solution
were added DMAP (0.88 g, 0.72 mmol) and Ac2O
(0.51 mL, 5.4 mmol). The resulting solution was stirred
for 24 h at rt. EtOAc (25 mL) was added and the mixture
was poured over H2O-crushed ice (10 mL). The phases were
separated and the organic layer was washed successively
with water (25 mL), 1 M HCl (25 mL) and 1 M NaOH
(50 mL). The combined aqueous phases were back-
extracted with EtOAc (2£50 mL), and the combined
organic extracts were washed with brine (3£10 mL) and
dried (Na2SO4). The crude product was purified by flash
chromatography (20% EtOAc/hexanes) to afford 10b
(0.75 g, a/b¼84:26, 78%). Data from a 19:1 a/b anomer
mixture: 1H NMR d 2.07 (s, CH3, overlapped with the
signal of H-2b, total 4H), 2.35–2.47 (apparent ddd, 1H,
H-2a), 3.9 (br s, W1/2¼5.7 Hz, 1H, H-4), 3.95 (ddd, J¼12.0,
4.4, 2.4 Hz, 1H, H-3), 4.31 (d, J¼5.9 Hz, 1H), 4.63 (s,
2H, PhCH2O), 4.72 (d, J¼11.8 Hz, 1H, PhCHO), 4.93
(d, J¼11.8 Hz, 1H, PhCHO), 5.23 (dt, J¼10.5, 1.4 Hz,
1H, H-7), 5.36 (dt, J¼17.4, 1.4 Hz, 1H, H-7), 5.93 (ddd,
J¼17.1, 10.5, 6.2 Hz, 1H, H-6), 6.39 (d, J¼2.6 Hz, H-1),
7.25–7.39 (m, 10H, Ar-H); 13C NMR d 21.1, 29.5, 70.2,
73.8, 74.3, 74.6, 75.3, 92.6, 116.9, 127.2, 127.5, 127.6,
128.1, 128.2, 128.3, 134.9, 137.9, 138.3, 169.3; IR (neat)
3030–2800, 1743 cm21; [a]D20¼59.18 (c¼0.05, CHCl3);
LRMS (EI) m/z (%) 382 (M), 291 (17), 266 (23), 231 (27),
91 (base); HMRS calcd for C23H26O5 382.1780, found
382.1776.
138.5, 144.1; IR (neat) n 3050, 1638, 1094 cm21
;
[a]2D0¼243.048 (c¼2.50, CHCl3); HRMS calcd for
C26H36O4Si 440.2383, found 440.2366.
4.1.7. Methyl 3,4-di-O-benzyl-2-deoxy-a-D-liso-hexa-
pyranoside (18). To a solution of 17 (0.385 g, 0.87 mmol)
in CH2Cl2 (5 mL) were added MeOH (0.1 mL) and
triphenylphosphine hydrobromide (15 mg, 0.04 mmol).
The mixture was stirred at rt for 1 h and diluted with
CH2Cl2 (15 mL). The solution was washed with sat.
NaHCO3 (2£15 mL) and brine (15 mL), and dried
(Na2SO4). The residue after evaporation was dissolved in
THF (7 mL) and tetrabutylammonium fluoride (1.0 M in
THF, 1.1 mL, 1.1 mmol) was added. After 2 h of stirring,
sat. NH4Cl (7 mL) was added. The aqueous layer was
extracted with EtOAc (3£7 mL), and the combined organic
layers were washed with brine (15 mL) and dried (Na2SO4).
The residue after evaporation was purified by flash
chromatography (45% EtOAc/hexanes) to yield 18
(a-anomer, 190 mg, 63%) followed by the anomeric
mixture (a/b¼64:36, 38 mg, 13%). The total yield for two
1
steps was 76% (a/b¼94:6). Data for 18 (a-anomer): H
NMR d 1.89 (br s, W1/2¼9.9 Hz, 1H, OH), 2.03 (dd, J¼12.7,
4.6 Hz, 1H, H-2a), 2.24 (td, J¼12.3, 3.6 Hz, 1H, H-2b),
3.32 (s, 3H, OCH3), 3.53 (dd, J¼10.7, 4.6 Hz, 1H, CH–
OH), 3.69–3.86 (m, 3H, H-4, H-5, CH–OH), 3.92 (ddd,
J¼11.9, 4.6, 2.4 Hz, 1H, H-3), 4.63 (s, 2H, OCH2Ph), 4.67
(d, J¼11.8 Hz, 1H, OCHPh), 4.92 (d, J¼2.8 Hz, 1H, H-1),
4.97 (d, J¼11.7 Hz, 1H, OCHPh), 7.36 (m, 10H, Ar-H); 13C
NMR d 30.9, 54.8, 63.0, 70.5, 70.6, 72.9, 73.9, 74.8, 98.9,
127.2, 127.5, 127.9, 128.4, 128.5, 138.3; IR (neat) n 3448,
1051 cm21; [a]D20¼þ55.298 (c¼1.89, CHCl3); LRMS (EI)
m/z (%) 358 (M), 235 (36), 91 (base); HRMS calcd for
C21H26O5 358.1780, found 358.1774.
4.1.10. General procedure for preparation of cyclo-
pentanes 19–23 from 6–10. To a solution of 6–10
(0.41 mmol) and Pd(PPh3)4 (24 mg, 0.02 mmol) in THF
(5 mL) was added ZnCl2 (1.0 M in Et2O, 0.50 mL,
0.50 mmol) and Et2Zn (1.0 M in hexanes, 1.23 mL,
1.23 mmol). The reaction was maintained at the appropriate
temperature (Table 1) until complete disappearance of the
starting material (as judged by TLC; Table 1). The solution
was allowed to reach rt, diluted with EtOAc (5 mL), and
washed successively with 1 M HCl (5 mL), sat. NaHCO3
(5 mL) and brine (5 mL). The diastereomeric mixture of
cyclopentanes 19–23 was purified and separated as
indicated below for the individual cases. Yields and
diastereomeric ratios are collected in Table 1. Cyclo-
pentanes 19–21 have been previously described.2e,3a
4.1.8. Methyl 3,4-di-O-benzyl-2-deoxy-a-D-liso-hept-6-
enopyranoside (10a). The oxidation and methylenation
procedures used in the preparation of 9 were followed
starting from 18 (1.31 g, 3.65 mmol). Purification of the
crude product by flash chromatography (10% and then 18%
EtOAc/hexanes) afforded 10a (0.87 g, 68% for two steps) as
1
an oil: H NMR d 2.01 (ddd, J¼12.7, 4.7, 1.1 Hz, 1H,
H-2a), 2.27 (td, J¼12.4, 3.6 Hz, 1H, H-2b), 3.32 (s, 3H,
OCH3), 3.77 (s, 1H, H-4), 3.92 (ddd, J¼12.0, 4.6, 2.4 Hz,
1H, H-3), 4.13 (d, J¼6.1 Hz, 1H, H-5), 4.59 (br s,
W1/2¼4.0 Hz, 2H, OCH2Ph), 4.70 (d, J¼11.8 Hz, 1H,
OCHPh), 4.90 (d, J¼11.6 Hz, 1H, OCHPh) and 4.94 (br s,
W1/2¼6.3 Hz, H-1) (total 2 H), 5.18 (dd, J¼10.4, 2.7 Hz,
1H, H-7), 5.33 (dd, J¼17.4, 2.7 Hz, 1H, H-7), 5.94 (ddd,
J¼17.4, 10.5, 6.1 Hz, 1H, H-6), 7.25–7.39 (m, 10H, Ar-H);
13C NMR d 30.7, 54.9, 70.3, 71.9, 74.2, 74.6, 75.7, 98.9,
116.5, 127.2, 127.4, 127.5, 128.1, 128.2, 128.4, 135.8,
4.1.11. (2S,3S,4S)-2-O-(tert-Butyldimethylsilyl)-5-
ethenyl-3,4-di-O-(methoxymethyl)cyclopentanetetraol
(22). Prepared from 9. The product was purified by flash
chromatography (10% and then 50% EtOAc/hexanes) and

J. M. Aurrecoechea et al. / Tetrahedron 59 (2003) 5515–5522
5521
the individual isomers were separated by HPLC (40%
4.2. Preparation of 22b0 from 22b
EtOAc/hexanes, 8 mL/min). Data for 22c from a 76:24
mixture with 22a (not isolated): tR¼14 min; 1H NMR d 0.14
(s, 3H, CH3–Si), 0.15 (s, 3H, CH3–Si), 0.92 (s, 9H, t-Bu),
2.52 (m, 1H, H-5), 2.72 (d, J¼5.7 Hz, 1H, OH), 3.36 (s, 3H,
CH3O), 3.40 (s, 3H, CH3O), 3.93 (dd, J¼6.1, 4.4 Hz, 1H,
H-3), 3.97 (dd, J¼7.1, 6.2 Hz, 1H, H-1), 4.15 (dd, J¼5.4,
4.2 Hz, 1H, H-4), 4.23 (apparent t, 1H, H-2), 4.601–4.75 (m,
4H, OCH2O), 5.15 (dd, J¼10.3, 0.9 Hz, 1H, H-2 ), 5.21 (dd,
J¼17.2,00.9 Hz, 1H, H-20), 5.93 (ddd, J¼17.3, 10.3, 8.5 Hz,
1H, H-1 ); 13C NMR d 25.1, 24.7, 18.0, 25.7, 53.2, 55.7,
72.9, 74.9, 76.1, 82.9, 96.1, 96.5, 117.1, 136.1; IR (neat) n
3600–3200, 3100–2800, 1650, 1254 cm21; [a]D20¼27.58
(c¼0.5, CHCl3); LRMS (EI) m/z (%) 363 (Mþ1), 271 (29),
199 (base), 117 (93), 75 (82); HRMS calcd for C17H35O6Si
(Mþ1) 363.2203, found 363.2218; HRMS calcd for
C15H29O4Si (M2OMOM) 300.1712, found 300.1705.
To a solution of 22b (19 mg, 0.052 mmol) in THF (1 mL) at
0 8C was added TBAF (1.0 M in THF, 0.15 mL,
0.15 mmol). The solution was allowed to reach rt and was
stirred for 2 h. The mixture was partitioned between sat.
NH4Cl (2 mL) and EtOAc (10 mL). The aqueous layer was
extracted with EtOAc (3£10 mL), and the combined
organic extracts were washed with brine (2 mL) and dried
(Na2SO4). The residue after evaporation was purified by
flash chromatography (50% EtOAc/hexanes) to yield 22b0
(13 mg, 100%) as a colorless oil.
4.2.1. (3S,4R)-3,4-Di-O-benzyl-2-ethenylcyclopentane-
triol (23). Prepared from 10b (a/b¼19:1). The product
was purified by flash chromatography (20% EtOAc/
hexanes) and the individual isomers were separated by
HPLC (40% EtOAc/hexanes, 8 mL/min). Data for 23a:
tR¼19 min; 1H NMR d 1.95 (ddd, J¼14.7, 7.2, 2.2 Hz, 1H,
H-5b), 2.39 (ddd, J¼8.7, 4.9, 3.8 Hz, 1H, H-2), 2.56 (ddd,
J¼14.8, 8.3, 7.0 Hz, 1H, H-5a), 2.94 (d, J¼11.3 Hz, 1H,
OH), 3.91 (ddd, J¼8.4, 7.4, 3.6 Hz, 1H, H-4), 3.99 (t,
J¼3.6 Hz, 1H, H-3), 4.05 (m, 1H, H-1), 4.58 (s, 2H,
OCH2Ph), 4.64 (d, J¼11.6 Hz, 1H, OCHPh), 4.92 (d,
J¼11.6 Hz, 1H, OCHPh), 5.19 (dt, J¼17.2, 2.1 Hz, 1H,
H-20), 5.25 (dd, J¼10.6, 2.1 Hz, 1H, H-20), 6.23 (ddd,
J¼17.2, 10.3, 8.7 Hz, 1H, H-10), 7.26–7.36 (m, 10H, Ar-H);
13C NMR d 40.2, 50.9, 71.8, 73.7, 74.2, 81.1, 82.4, 117.8,
127.4, 127.6, 127.7, 128.3, 128.4, 134.2, 138.2, 138.4; IR
(neat) n 3540, 3040, 1645, 1130 cm21; [a]D20¼230.08
(c¼0.01, CHCl3); LRMS (EI) m/z (%) 323 (M), 92 (10),
91 (base); HRMS calcd for C21H24O3 324.1725, found
1
Data for 22b: tR¼16 min; H NMR d 0.12 (s, 3H, CH3–
Si), 0.14 (s, 3H, CH3–Si), 0.90 (s, 9H, t-Bu), 2.52 (d,
J¼4.7 Hz, 1H, OH), 2.75 (m, 1H, H-5), 3.35 (s, 3H, CH3O),
3.39 (s, 3H, CH3O), 3.98 (dd, J¼5.6, 3.8 Hz, 1H, H-2 or
H-3), 4.10–4.19 (m, 3H, H-1, H-3 or H-2, H-4), 4.65 and
4.69 (AB system, J¼6.7 Hz, 2H, OCH2O), 4.71 and 4.75
(AB system, J¼6.7 Hz, 2H, OCH2O), 5.17 (dd, J¼10.3,
1.8 Hz, 1H, H-20), 5.21 (dd, J¼17.2, 1.8 Hz, 1H, H-20), 5.91
(ddd, J¼17.2, 10.3, 8.9 Hz, 1H, H-10); 13C NMR d 25.0,
24.8, 17.9, 25.6, 51.1, 55.6, 55.7, 71.4, 77.2, 78.6, 80.6,
95.9, 96.6, 117.6, 135.9; IR (neat) n 3600–3200, 3100–
2800, 1640, 1255 cm21; [a]D20¼216.48 (c¼0.01, CHCl3);
LRMS (EI) m/z (%) 362 (M), 199 (base), 171 (49), 129 (65),
75 (96); HRMS calcd for C17H34O6Si 362.2125, found
362.2127. Data for 22d: tR¼20 min; 1H NMR d 0.10 (s, 3H,
CH3–Si), 0.11 (s, 3H, CH3–Si), 0.88 (s, 9H, t-Bu), 2.13 (d,
J¼7.7 Hz, 1H, OH), 2.64 (dd, J¼14.4, 8.2 Hz, 1H, H-5),
3.34 (s, 3H, CH3O), 3.40 (s, 3H, CH3O), 3.63 (m, 1H, H-1),
3.87 (apparent t, 1H, H-3), 3.97–4.01 (m, 2H, H-2, H-4),
4.67 (s, 2H, OCH2O), 4.73 and 4.77 (AB system, J¼6.6 Hz,
2H, OCH2O), 5.12 (d, J¼10.1 Hz, 1H, H-20), 5.21 (d,
J¼17.2 Hz, H-20), 5.83 (ddd, J¼17.0, 10.1, 8.5 Hz, 1H,
H-10); 13C NMR d 24.9, 24.7, 17.9, 25.7, 55.3, 55.5, 55.6,
79.4, 80.9, 81.6, 95.8, 96.3, 116.8, 138.1; IR (neat) n 3600–
1
324.1697. Data for 23b: tR¼23 min; H NMR d 1.7 (br s,
W1/2¼10.7 Hz, 1H, OH), 1.88 (ddd, J¼14.8, 5.9, 2.9 Hz,
1H, H-5a), 2.28 (ddd, J¼14.8, 6.7, 2.9 Hz, 1H, H-5b), 2.99
(m, 1H, H-2), 3.92 (dd, J¼9.8, 4.8 Hz, 1H, H-3), 4.08 (m,
1H, H-4), 4.30 (dd, J¼6.1, 2.8 Hz, 1H, H-1), 4.50–4.67 (m,
4H, OCH2Ph), 5.27 (dt, J¼17.2, 0.8 Hz, 1H, H-20), 5.46 (dt,
J¼10.0, 00.8 Hz, 1H, H-20), 5.59 (ddd, J¼17.2, 10.0, 8.8 Hz,
1H, H-1 ), 7.26–7.39 (m, 10H, Ar-H); 13C NMR d 38.7,
51.8, 70.7, 71.2, 71.9, 75.8, 81.8, 119.1, 127.5, 127.8, 127.9,
128.2, 128.3, 135.3, 138.3, 138.5; IR (neat) n 3500–3200,
3100–3000, 1640 cm21; [a]D20¼262.08 (c¼0.04, CHCl3);
LRMS (EI) m/z (%) 324 (M), 233 (62), 169 (61), 107 (base);
HRMS calcd for C21H24O3 324.1725, found 324.1717. Data
for 23c: tR¼25 min; 1H NMR d 1.8 (br s, W1/2¼10.5 Hz, 1H,
OH), 1.91 (ddd, J¼13.2, 8.1, 4.5 Hz, 1H, H-5a), 2.28–2.44
(m, 2H, H-2, H-5b), 4.02 (apparent t, 1H, H-3), 4.13 (td,
J¼7.7, 3.6 Hz, 1H, H-4), 4.28–4.41 (m, 1H, H-1), 4.57 (s,
2H, OCH2Ph), 4.63 (d, J¼12.0 Hz, 1H, OCHPh), 4.79 (d,
J¼12.0 Hz, 1H, OCHPh), 5.16 (dd, J¼10.1, 1.7 Hz, 1H,
H-20), 5.18 (d, J¼17.5 Hz, 1H, H-20), 6.08 (dt, J¼17.2,
10.3 Hz, 1H, H-10), 7.26–7.36 (m, 10H, Ar-H); 13C NMR d
37.5, 55.8, 71.5, 73.1, 74.7, 79.9, 81.8, 117.2, 127.4, 127.5,
127.6, 128.2, 128.3, 136.5, 138.4, 138.8; IR (neat) n 3400,
3040, 1640, 1150 cm21; [a]D20¼255.658 (c¼1.31, CHCl3);
LRMS (EI) m/z (%) 323 (M), 92 (10), 91 (base); HMRS
calcd for C21H23O3 323.1647, found 323.1658.
3200, 3100–2800, 1640, 1253 cm21
;
[a]2D0¼210.58
(c¼0.03, CHCl3); LRMS (EI) m/z (%) 363 (Mþ1), 271
(29), 199 (base), 117 (93), 75 (82); HRMS calcd for
C16H31O5Si (M2OMe) 331.1941, found 331.1929; HRMS
calcd for C15H29O4Si (M2OMOM) 301.1835, found
301.1836. Also isolated by flash chromatography was
(1S,2S,3S,4S,5R)-5-ethenyl-3,4-di-O-(methoxymethyl)-
cyclopentanetetraol (22b0): 1H NMR d 2.6 (br s,
W1/2¼8.0 Hz, 1H, OH), 2.73 (m, 1H, H-5), 3.34 (s, 3H,
CH3O), 3.46 (s, 3H, CH3O), 3.8 (br s, W1/2¼8.0 Hz, 1H,
OH), 3.93 (apparent t, 1H, H-3), 4.05 (apparent t, 1H, H-2),
4.14 (apparent t, 1H, H-1), 4.25 (t, J¼7.1 Hz, 1H, H-4), 4.65
and 4.68 (AB system, J¼6.7 Hz, 2H, OCH2O), 4.72 (d,
J¼6.9 Hz, 1H, OCHO), 4.80 (d, J¼06.9 Hz, 1H, OCHO),
5.22 (dd, J¼10.2, 1.6 Hz, 1H, H-2 ), 5.24 (dd, J¼17.3,
1.6 Hz, 1H, H-20), 5.97 (ddd, J¼17.2, 10.3, 8.3 Hz, 1H,
H-10); 13C NMR d 51.7, 55.5, 56.0, 71.7, 73.5, 77.3,
83.8, 96.0, 97.6, 117.9, 135.2; IR (neat) n 3600–3200,
3100–2800, 1640 cm21; [a]D20¼234.68 (c¼0.02, CHCl3);
LRMS (EI) m/z (%) 248 (M), 127 (base), 104 (55), 83
(81); HRMS calcd for C11H20O6 248.1260, found
248.1266.
Acknowledgements
´
Financial support by the Universidad del Paıs Vasco

5522
J. M. Aurrecoechea et al. / Tetrahedron 59 (2003) 5515–5522
6. Marshall, J. A.; McNulty, L. M.; Zou, D. J. Org. Chem. 1999,
64, 5193–5200.
(9/UPV00041.310-144471/2002) and Ministerio de
´
Educacion y Cultura (Spain) (DGI BQU2000-01354 and
7. Bolitt, V.; Mioskowski, C.; Lee, S.-G.; Falck, J. R. J. Org.
Chem. 1990, 55, 5812–5813.
Fellowship to M. A.) is gratefully acknowledged. We also
thank Gobierno Vasco and European Commission (Alfa
Project ALR/B73011/94.04-6.0192.9) for Fellowships to
B. L. and J. H. G., respectively.
8. Fuji, K.; Kinoshita, N.; Tanaka, K. Chem. Commun. 1999,
1895–1896.
9. (a) Mandai, T.; Matsumoto, T.; Kawada, M.; Tsuji, J. J. Org.
Chem. 1992, 57, 1326–1327. (b) Mandai, T.; Matsumoto, T.;
Kawada, M.; Tsuji, J. J. Org. Chem. 1992, 57, 6090–6092.
(c) Mandai, T.; Matsumoto, T.; Tsuji, J. Tetrahedron Lett.
1993, 34, 2513–2516. For an application of Tsuji’s catalyst in
a Et2Zn-mediated intramolecular Pd-catalyzed Zn-Ene
reaction, see: (d) Oppolzer, W.; Flachsmann, F. Tetrahedron
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