Substituent effects on the SmI2/Pd(0)-promoted carbohydrate ring-contraction of 5-alkynylpyranosides

Article abstract of DOI:10.1016/S0040-4020(03)01103-7

The effect of substituents on the reactivity and stereoselectivity of the SmI₂/Pd(0)-promoted ring-contraction of 5-alkynylpyranosides has been examined using substrates substituted only at selected positions. While formation of 2-ethynylcyclopentanols takes place efficiently, an internal alkyne did not afford the expected product. The presence of peripheral alkoxy substituents leads to variable stereoselectivities that depend on the number and orientation of such groups. Thus, an isolated OBn substituent at C(3) (carbohydrate numbering) exerts a significant stereochemical control while additional substitution with the same group at C(4) either enhances or drastically reduces stereoselectivity depending on its orientation (α or β, respectively).

Full text of DOI:10.1016/S0040-4020(03)01103-7

Tetrahedron 59 (2003) 7111–7121
Substituent effects on the SmI2/Pd(0)-promoted carbohydrate
ring-contraction of 5-alkynylpyranosides
*
Jose M. Aurrecoechea, Jesus H. Gil and Beatriz Lopez
´
´
´
´ ´ ´
Departamento de Quımica Organica II, Facultad de Ciencias, Universidad del Paıs Vasco, Apartado 644, 48080 Bilbao, Spain
Received 17 April 2003; revised 16 June 2003; accepted 11 July 2003
Abstract—The effectof substituents on the reactivityand stereoselectivity of the SmI2/Pd(0)-promoted ring-contraction of 5-alkynylpyranosides
has been examined using substrates substituted only at selected positions. While formation of 2-ethynylcyclopentanols takes place efficiently,
an internal alkyne did not afford the expected product. The presence of peripheral alkoxy substituents leads to variable stereoselectivities that
depend on the number and orientation of such groups. Thus, an isolated OBn substituent at C(3) (carbohydrate numbering) exerts a
significant stereochemical control while additional substitution with the same group at C(4) either enhances or drastically reduces
stereoselectivity depending on its orientation (a or b, respectively).
q 2003 Elsevier Ltd. All rights reserved.
1. Introduction
reactive sites, and to extend the scope of the method, we
have now examined the corresponding reactions on selected
substrates where some or all of the oxygenated ring-
substituents (R¼OP in structure I) have been removed.
Additional impetus for this work came from literature reports
showing that the sense and extent of diastereoselectivity in
We have reported a Pd-catalyzed SmI2-mediated carbo-
hydrate ring-contraction1 that starting from substrates of
type I leads to cyclopentanes of types VI, VII (Scheme 1).2a
This transformation features the intramolecular propargyla-
tion of a carbonyl-tethered allenylsamarium III originated
in the SmI2 reduction of an allenylpalladium complex II
derived from I. Useful levels of diastereoselectivity have
already been realized using fully oxygenated glucose-,
mannose- and galactose derivatives, where a general
preference for a relative trans-relationship between the
ethynyl- and hydroxyl-substituted stereogenic centers was
generally observed. This preference is probably the result of
a cyclization step proceeding through open- (IV, R2¼H)
rather than cyclic (V, R2¼H)3 TS’s as a consequence of the
dominant effect of the relatively strong Lewis-acidic
character of the Sm(III)4 salts present in the medium, that
coordinate to the carbonyl group. The stereochemical
picture is actually more complex as the absolute configur-
ation of the above-mentioned stereogenic centers was found
to be substrate- and catalyst-dependent. While it is apparent
that substantial stereochemical scrambling takes place at the
level of intermediates II and/or III,5 other factors such as
the steric and/or electronic effects of peripheral substituents
(R¼OP) are likely to also play a role. To have a better
understanding of the intrinsic stereochemical preferences of
these reactions without the incidence of the steric and/or
electronic effects associated to stereocenters adjacent to the
Keywords: carbohydrate ring-contraction; allenylpalladium; intramolecular
propargylation; samarium.
*
Corresponding author. Tel.: 34-94-601-2578; fax: 34-94-464-8500;
e-mail: qopaufem@lg.ehu.es
Scheme 1.
0040–4020/$ - see front matter q 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0040-4020(03)01103-7

7112
J. M. Aurrecoechea et al. / Tetrahedron 59 (2003) 7111–7121
the related allylzirconium intramolecular carbonyl addition
heavily depend on the presence and orientation of the
substituent immediately adjacent to the nucleophilic
center.1b,g
the former substrate that disfavors development of oxocarbe-
nium-like character at C(1) (carbohydrate numbering)
during the ring opening leading to intermediate II.
Alternatively, the substituent at C(4) in I could hinder the
anti approach of the Pd(0) catalyst to the propargylic ether
moiety to effect the required SN20-like displacement8 of the
leaving group in the oxidative addition leading to II.
2. Results and discussion
2.1. Non-carbohydrate substrates
Alkynylpyranosides 4 lacking all of the peripheral oxygen
substituents were tested first. The presence of an alkyl
substituent in the alkynyl portion of 4b would also allow an
assessment of the possibility of applying this chemistry to
carbohydrate-derived substrates containing an internal
alkyne. Substrates 4 were prepared according to Scheme 2.
Thus, alkynylmetal addition to the known monoprotected
dialdehyde 16a (prepared from cyclopentene according to
the oxidative cleavage method of Schreiber6) afforded
propargylic alcohols 2. Hydrolysis of the acetal function in 2
and acetylation of the resulting lactols 3 led to the desired
substrates 4, that were obtained as nearly 1:1 diastereomeric
mixtures.
ð1Þ
On the other hand, the internal alkyne 4b displayed a
completely different reactivity as no cyclopentane product
analogous to 5 was found, and enol ether 6b was obtained as
major product together with smaller amounts of tetra-
hydropyran 7 (Eq. (2)).
ð2Þ
Therefore, it appears that the steric effect of the alkyl
substituent at the alkynyl terminus retards the oxidative
addition of the propargylic ether moiety to Pd(0) so that
other competing reactions take over. While the formation of
alkenes related to 6b has been observed before,2b com-
pounds of type 7 are unprecedented in these Pd(0)/SmI2-
promoted reactions. The formation of 7 appears to imply the
intervention of anomeric radical VIII and/or organosamar-
ium IX as intermediates (Scheme 3). Radical VIII could
arise by direct reduction of the acetoxy ether function of 4b
by SmI2 (path a), a process that has ample precedent in
the corresponding reactions of glycosyl bromides, -chlor-
ides, -phosphates and -pyridylsulfones.9 Radical dispropor-
tionation10 would then account for the formation of both 6b
and 7. Alternatively, further reduction of VIII to organo-
samarium IX9 followed by protonation or samarium hydride
elimination9a,11 could also lead to 7 and 6b, respectively.
Scheme 2.
Treatment of 4a with SmI2 (3 equiv.) and catalytic
(5 mol%) Pd(PPh3)4 at room temperature afforded cylopen-
tane 5 (Eq. (1)) as a 92:8 trans/cis mixture, according to
GC–MS analysis on the crude product. After chromato-
graphic purification 57 was isolated in undetermined overall
1
yield due to the volatility of this material. The H NMR
spectrum of the crude product also contained signals
compatible with the presence of enol ether 6a (,15%
with respect to 5). However, this product was not isolated
and instead, small amounts of lactol 3a, probably the result
of hydrolysis of 6a, were found during chromatographic
purification of 5. In any case, these results obtained with 4a,
a substrate devoid of structural constraints, evidence a high
intrinsic preference for a ring closure that proceeds through
a TS of type IV. This is in contrast to observations made on
the related reaction starting from ketone substrates of type I0
(R¼H; R2¼Me), that led to a very poor diastereoselectivity
under the same reaction conditions.2c It is also interesting to
note that the reaction 4a!5 took only 1.5 h to go to
completion at room temperature. In comparison, fully
oxygenated carbohydrate-derived substrates I need much
longer reaction times (24 h) or higher temperatures (408C)
to produce VI, VII.2a The lower reactivity of I (R¼OP,
R2¼H) with respect to 4a could be due to the inductive
electron-withdrawing character of the alkoxy substituents in
Scheme 3.
To test for the formation of VIII and IX from 4b, this
substrate was treated with cyclohexanone and SmI2 under
samarium Barbier conditions12 at room temperature
(Eq. (3)). Alkene 6b was again obtained as major product,
this time accompanied by the expected coupling product,

J. M. Aurrecoechea et al. / Tetrahedron 59 (2003) 7111–7121
7113
the alcohol 8. While the formation of 8 supports the notion
that radicals VIII are formed from 4b, several consider-
ations argue against VIII and IX being in the major path to
6b. Thus, the ratio 6b:7 is too high for these compounds to
originate exclusively in a disproportionation process.
Furthermore, anomeric organosamariums analogous to IX
are known to lead efficiently to coupling products with
ketones rather than undergoing b-hydride elimination.9
Therefore, the comparatively low yield of 8 with respect to
6b indicates that the incidence of radicals VIII and/or
organosamariums IX in these reactions is small, and points
to the Lewis-acidic character of SmI2, and Sm(III) formed
thereof,4 as responsible for formation of 6 via elimination of
AcOH from 4 (path b, Scheme 3). Small amounts of VIII
could then be formed by SmI2 reduction of an oxonium ion
generated from either 4b or 6b.
triol 9 afforded diol 10. This was subjected to the Barton–
McCombie dehydroxylation protocol14 to yield after
desilylation the doubly dehydroxylated derivative 12.15
Swern oxidation using diisopropylethylamine16 and direct
ethynylation with dimethyl 1-diazo-2-oxopropylphos-
phonate17 then afforded the required alkyne 13.
The synthesis of 2-deoxy substrates 18 and 19 is depicted in
Scheme 5. Starting from either commercial tri-O-acetyl-D-
glucal (series a) or tri-O-acetyl-D-galactal (series b),
protecting group manipulation led to suitably protected
triols 15 in 87 and 61% overall yields, respectively.
Glycoside formation with triphenylphosphine hydrobromide/
methanol18 and desilylation afforded primary alcohols 16
(90 and 75% yields) as mixtures of anomers. Alcohol 16a
was obtained with a 71:29 a/b anomer ratio and was carried
forward as a mixture, whereas for 16b the initial 94:6 a/b
anomer mixture could be separated and the synthesis was
continued with the a-anomer alone. Alcohols 16 were then
converted into alkynes 18a and 18b. Thus, Swern
oxidation16 was followed by either a modified Corey–
Fuchs19 procedure, using triethylamine in the dibromo-
methylenation step20 and LDA21 for the dehydrobromina-
tion, or by direct ethynylation17 to afford alkynes 18a and
18b in 38% and 62% yields for these three- and two-step
protocols, respectively. Enyne 19 was also obtained in 7%
yield along with alkyne 18b.
ð3Þ
2.2. Carbohydrate-derived substrates
The tendency of the acetate leaving group to form alkenes
by elimination of AcOH, together with the expected lower
reactivity of substrates with alkoxy substituents (vide supra)
advised the choice of the more robust methyl pyranosides,
with a methoxy leaving group, for the reactions discussed
next and involving partially oxygenated carbohydrate-
derived substrates.
Substrate 13, featuring a single protected hydroxyl group at
a remote position from the carbons involved in cyclization,
was prepared from commercial methyl a-D-galactopyrano-
side as shown in Scheme 4. Thus, selective monobenzyla-
tion at the C(3)-hydroxyl following David’s method13 and
silylation of the primary alcohol function in the so formed
Scheme 5. (a) NaOMe, MeOH, room temperature. (b) TBSCl, Im, DMF,
room temperature. (c) (i) NaH, THF, 08C; (ii) BnBr, n-Bu4NI, room
temperature. (d) TPPHB, MeOH, CH2Cl2, room temperature. (e) n-Bu4NF,
THF, room temperature. (f) (i) (COCl)2, DMSO, 2458C; (ii) i-Pr2EtN,
2458C!room temperature. (g) PPh3, CBr4, Et3N, CH2Cl2, 08C. (h) LDA,
THF, 2788C. (i) Dimethyl 1-diazo-2-oxopropylphosphonate, K2CO3,
MeOH, room temperature.
Scheme 4. (a) (i) Bu2SnO, benzene, Dean–Stark; (ii) n-Bu4NI, BnBr, reflux
(49%). (b) TBSCl, Im, DMF, room temperature (87%). (c) (i) NaH, CS2,
THF, room temperature; (ii) MeI, room temperature (90%). (d) n-Bu3SnH,
AIBN, toluene, reflux. (e) n-Bu4NF, THF, room temperature (34% for three
steps from 10). (f) (i) (COCl)2, DMSO, 2708C; (ii) i-Pr2EtN,
2708C!room temperature. (g) Dimethyl 1-diazo-2-oxopropylphospho-
nate, K2CO3, MeOH, room temperature (65% for two steps from 12).
Results for the reactions of 13, 18a and 18b with SmI2/Pd(0)
are collected in Eqs. (4)–(6). As expected based on previous
experience, these acetals were inert to SmI2/Pd(0) at room
temperature. However, they reacted rapidly upon heating to

7114
J. M. Aurrecoechea et al. / Tetrahedron 59 (2003) 7111–7121
yield the expected cyclopentanes 20–22. A combination
of Pd(OAc)2 and P(n-Bu)3 in a 1:4 ratio was used as
catalyst precursor since it had been found to give the best
results with other carbohydrate-derived substrates.2a Not
unexpectedly, the substrate with a single OBn substituent
(13) displayed the highest reactivity, the reaction being
complete in less than 5 min, whereas the presence of a
second OBn in substrates 18 led to somewhat longer
reaction times (,1–3 h) for high conversions. The reaction
of 18a, while proceeding rapidly in the initial stages, did not
go to completion and some starting material was recovered.
Interestingly, the anomeric ratio in the recovered material
(a/b¼22:78) was significantly different from the initial
64:36 a/b value. This observation suggests a higher
reactivity of the a-anomer relative to the alternative
b-configuration, and this could be due to stereoelectronic
assistance provided by the endocyclic oxygen to departure
of an axially oriented leaving group during ring-opening in
the a-anomer.
Chart 1. Summary of relevant n.O.e. data for compounds 20–22.
ð4Þ
products (relative to ethynyl and free hydroxyl groups) in
cyclopentane 22 (Eq. (6)).
A model that fits the stereochemical tendencies
observed in the formation of 20–22 (and more highly
substituted products obtained under similar conditions)2a
is suggested in Scheme 6. Thus, under high temperature
conditions that favor rapid interconversion between the
two allene configurations,5 allenylsamariums III could
form the observed products through anticlinal confor-
mations X and XI.3 Formation of 20 and 21 then would
take place predominantly from the more stable confor-
mation X. On the other hand, starting from 18b
(Y¼OBn), the pseudoaxial Y substituent could destabi-
lize1b,g X relative to XI and reduce the energy gap
between them, thus resulting in nearly equal amounts of
22a and 22b being produced.
ð5Þ
ð6Þ
Cyclopentanes 20–22 were obtained in all cases as mixtures
of diastereoisomers that were either separated or enriched in
the major isomer. The stereochemistry of the individual
diastereoisomers was unambiguously determined with the
aid of n.O.e. experiments. A summary of relevant n.O.e.
data is given in Chart 1. In line with the stereochemical
result obtained for 4a, products 20–22 were formed with a
very predominant trans relationship between the alkynyl
and free hydroxyl substituents. Cyclopentane 20 was
obtained in a 85:15 ratio with another isomer of unknown
stereochemistry (Eq. (4)). Therefore, it is seen that a single
remote substituent at C(3) (carbohydrate numbering) in the
cyclizing chain is enough to provide a good stereochemical
control during cyclization. The particular trans-isomer
obtained as major product displayed a syn relationship
between the ethynyl and 4-OBn groups. The same trend was
observed when, additionally, an a-OBn substituent was
incorporated at C(4) of 18a, and this in fact resulted in an
enhanced stereochemical control as the major diastereomer
21 amounted to 95% of the isomer mixture (Eq. (5)).
However, the corresponding b-OBn substituted 18b
afforded a nearly 1:1 mixture of the two possible trans-
Scheme 6.

J. M. Aurrecoechea et al. / Tetrahedron 59 (2003) 7111–7121
7115
3. Conclusions
between CH2Cl2 (90 mL) and water (60 mL). The aqueous
layer was extracted with CH2Cl2 (2£80 mL), and the
combined organic layers were dried (Na2SO4). The residue
after evaporation was purified by Kugelrohr distillation
(60–708C, 0.5 mm Hg) to yield 13 g of a 3.2:1 mixture of
5,5-dimethoxypentanal (1)6a and 2,6-dimethoxytetrahydro-
pyran26 that without further purification was dissolved
under in THF (320 mL). To this solution at 08C under Ar
was added ethynylmagnesium bromide (0.5 M in THF,
320 mL, 160 mmol). The reaction mixture was allowed to
reach room temperature, stirred for 14 h and quenched with
saturated NH4Cl (150 mL) at 08C. The layers were
separated, and the aqueous layer was extracted with
EtOAc (2£170 mL). The combined organic extracts were
washed with brine (30 mL) and dried (Na2SO4). The residue
after evaporation was purified by flash chromatography
(30% EtOAc/hexanes) to yield the propargylic alcohol 2a
(6.26 g, 30% for two steps) as an oil: 1H NMR d 1.46–1.76
(m, 6H), 2.44 (d, J¼2.0 Hz, H-7, overlapped with OH
signal, total 2H), 3.30 (s, 6H, OCH3), 4.36 (apparent t, H-1;
overlapped with m at 4.34–4.38, H-5; 2H); 13C NMR d
20.2, 31.9, 37.2, 52.6, 61.9, 72.8, 84.8, 104.3. These data
coincide with those given in the literature for the same
compound.25
The SmI2/Pd(0)-promoted carbohydrate ring-contraction of
5-ethynylpyranosides has been extended to substrates with
limited peripheral functionality. This has unraveled import-
ant reactivity and stereochemical details of the reaction.
Thus, the a-configuration at the anomeric center is found to
be desirable for high reactivity whereas substitution at the
alkynyl terminus has a very detrimental effect on the
outcome of the reaction. A single OBn substituent at C(3)
(carbohydrate numbering) is found to exert a significant
control over the absolute configuration at the alkynyl- and
free hydroxyl-bearing carbons in the resulting trans-2-
ethynylcyclopentanol products. Additional substitution with
another a-OBn group at C(4) enhances this stereocontrol,
but the presence of an analogous b-OBn group leads to
nearly equal proportions of both trans-isomers, probably as
a result of conformational and configurational interconver-
sion between intermediate allenylsamariums.
4. Experimental
4.1. General
4.1.2. 1,1-Dimethoxytridec-6-yn-5-ol (2b). n-Butyllithium
(1.6 M in hexanes, 22 mL, 36.16 mmol) was added to a
solution of 1-octyne (6.40 mL, 43.4 mmol) in THF
(105 mL) at 2788C under Ar, and the resulting solution
was stirred at the same temperature for 30 min. A solution of
1 (prepared as described above, 6.37 g of mixture,
33.0 mmol of 1) in THF (97 mL) was then added, and the
reaction mixture was allowed to reach room temperature
and worked-up as described above for 2a. The crude product
was purified by flash chromatography (25% EtOAc/
hexanes) to yield the propargylic alcohol 2b (6.22 g, 34%
for two steps from cyclopentene) as an oil: 1H NMR d 0.80
(t, J¼6.7 Hz, 3H, H-12), 1.18–1.63 (m, 16H), 2.11 (td,
J¼6.9, 1.8 Hz, 2H, H-8), 2.67 (br s, W1/2¼7.1 Hz, 1H, OH),
3.23 (s, 6H, OCH3), 4.23–4.32 (m, 2H, H-1 and H-5); 13C
NMR d 13.8, 18.5, 20.2, 22.3, 28.3, 28.5, 31.1, 31.9, 37.7,
52.3, 62.1, 81.2, 85.1, 104.3; IR (neat) n 3650–3100 (m, br,
All reactions involving air- and moisture-sensitive materials
were performed using standard bench-top techniques.22
Tetrahydrofuran and toluene were freshly distilled from
sodium/benzophenone and, for reactions with SmI2 and
n-Bu3SnH, they were deoxygenated prior to use. Acetic
anhydride, dichloromethane, dimethylsulfoxide, dimethyl-
formamide, pyridine, triethylamine and diisopropylamine
were distilled from CaH2. Methanol was dried by treatment
with Mg–I2 and distillation. Carbon tetrabromide was
purified by sublimation. SmI2 (ca 0.1 M in THF) was
prepared as reported23 from Sm metal and diiodomethane.
n-Tributylphosphine (Fluka, 95%) was used from a Sure-
Seal bottle. Flash column chromatography24 was performed
on silica gel (230–400 mesh). HPLC purifications were
carried out with a LiChrosorb Si60 column (7 mm,
1
25£2.5 cm) using a refraction index detector. Routine H
and 13C NMR spectra were obtained at 250 and 62.9 MHz,
respectively, using CDCl3 as solvent and internal reference
O–H), 2205 (w, CuC) cm21
.
1
(d 7.26 for H and d 77.0 for 13C). IR data include only
4.1.3. 6-Ethynyltetrahydropyran-2-yl acetate (4a). A
solution of 2a (2.08 g, 12.1 mmol) in acetic acid/water
(1:1, 27 mL) was stirred and refluxed for 1 h. After cooling,
the solution was made neutral with saturated K2CO3
(30 mL), water (70 mL) was added and the aqueous layer
was extracted with EtOAc (4£200 mL). The combined
organic extracts were washed with brine (16 mL) and dried
(Na2SO4). Purification by flash chromatography (25%
EtOAc/hexanes) afforded the lactol 3a (1.02 g, 67%) as
a 2.1:1 diastereomeric mixture: 1H NMR d 1.50–1.93
(m, 6H), 2.44 and 2.46 (2d, J¼2.8 Hz, 1H, H-20), 3.23–3.27
(m, OH, major isomer), 3.58–3.60 (m, OH, minor isomer),
4.24 (dt, J¼10.3, 2.8 Hz, H-6, minor isomer), 4.72–4.82
(m), 5.30 (br d, H-2, major isomer). A solution of the crude
lactol 3a [prepared from 2a (2.05 g, 11.9 mmol)] in Et3N
(2.50 mL, 17.5 mmol) was treated with Ac2O (2.24 mL,
23.8 mmol) and DMAP (459 mg, 3.68 mmol) at room
temperature for 17 h. The solution was diluted with diethyl
ether (100 mL) and poured over ice/water (,10 mL). The
characteristic absorptions. Mass spectra were obtained at
70 eV. GC–MS analysis were performed at 70–2108C
(208C/min) with a stationary phase of methylphenylsilicone
(0.25 mm, 30 m£0.25 mm). In Kugelrohr distillations the
boiling point refers to the external oven air temperature.
4.1.1. 7,7-Dimethoxyhept-1-yn-3-ol (2a).25 Cyclopentene
(13.0 mL, 142 mmol) was dissolved in CH2Cl2/CH3OH
(5:1, 564 mL) at 2788C and a mixture of ozone/oxygen
(0.6 A, 70–100 L/h) was bubbled through the solution until
this had turned into a light blue (,3 h). Ar was then bubbled
through the solution at 2788C until colorless, p-TsOH
(2.30 g, 12.1 mmol) was added, and the solution was
allowed to reach room temperature. After 90 min solid
NaHCO3 (2.43 g, 29 mmol) was added, and the mixture was
stirred for 15 min. Dimethyl sulfide (23 mL, 313 mmol) was
added, and the mixture was further stirred at room
temperature for 12 h. The solution was evaporated to a
volume of ca. 20–25 mL and the residue was partitioned

7116
J. M. Aurrecoechea et al. / Tetrahedron 59 (2003) 7111–7121
aqueous layer was extracted with ether (3£50 mL). The
combined organic layers were washed successively with
1 M HCl (10 mL), 1 M NaOH (10 mL) and H2O (5 mL),
and dried (Na2SO4). The crude product was purified by
flash chromatography (10% EtOAc/hexanes) to yield
the acetate 4a (1.34 g, 89% for two steps from 2a) as a
1.3:1 cis/trans mixture: 1H NMR d 1.52–2.02 (m, 6H), 2.03
and 2.04 (2s, 3H, OCOCH3), 2.41 and 2.43 (2d, J¼2.2 Hz,
1H, H-20), 4.33–4.39 (m, H-6, cis-4a), 4.58 (br d, J¼7.9 Hz,
W1/2¼13.6 Hz, H-6, trans-4a), 5.68–5.72 (dd, J¼7.1,
2.9 Hz, H-2, cis-4a), 6.12 (br s, W1/2¼5.9 Hz, H-2, trans-
4a); 13C NMR d 19.0, 20.8, 22.5, 29.4, 30.2, 32.0, 32.2,
62.7, 65.6, 72.2, 73.3, 81.8, 82.0, 91.1, 92.5, 166.4, 166.6;
IR (neat) n 3290 (m, uC–H), 2120 (w, CuC), 1755
(s, CvO) cm21; LRMS (EI) m/z (%) 167 (M21, 3), 125
(20), 111 (12), 109 (91), 107 (28), 97 (14), 86 (14), 80 (41),
79 (base), 77 (16), 68 (16), 65 (11); HRMS calcd for
C9H11O3 (M2H) 167.0708, found 167.0710.
(s, C–O–C) cm21; [a]D20¼þ141.438 (c¼3.21, CHCl3);
LRMS (EI) m/z (%) 284 (M), 92 (9), 91 (base); HRMS calcd
for C14H20O6 284.1260, found 284.1252.
4.1.6. Methyl 3-O-benzyl-6-O-(tert-butyldimethylsilyl)-
a-D-galactopyranoside (10). A solution of 9 (8.67 g,
30.5 mmol), imidazole (4.34 g, 64.1 mmol) and tert-butyl-
dimethylsilyl chloride (5.06 g, 33.6 mmol) in DMF
(140 mL) was stirred at room temperature for 12 h. The
mixture was diluted with diethyl ether (400 mL), and the
resulting solution was washed with H2O (2£150 mL).
The aqueous layers were back-extracted with diethyl ether
(2£130 mL), and the combined organic layers were dried
(Na2SO4). The crude after evaporation was purified by flash
chromatography (50% EtOAc/hexanes) to yield 10 (10.60 g,
87%): 1H NMR d 0.07 (s, 6H, Si–CH3), 0.89 (s, 9H, t-Bu),
2.22 (d, J¼7.8 Hz, 1H, OH), 2.63 (s, 1H, OH), 3.40 (s, 3H,
OCH3), 3.60 (dd, J¼9.7, 3.2 Hz, 1H, H-3), 3.70 (apparent t,
J¼5.8 Hz, 1H, H-5), 3.78 (dd, J¼10.3, 5.6 Hz, 1H, H-6),
3.86 (dd, J¼10.2, 6.2 Hz, 1H, H-6), 4.01 (ddd, J¼9.6, 7.9,
3.9 Hz, 1H, H-2), 4.05 (br s, W1/2¼7.1 Hz, 1H, H-4), 4.72
(s, 2H, OCH2Ph), 4.80 (d, J¼3.9 Hz, 1H, H-1), 7.29–7.40
(m, 5H, Ar); 13C NMR d 25.5, 18.2, 25.8, 55.1, 62.6, 66.8,
68.5, 69.9, 71.9, 78.5, 99.3, 127.8, 127.9, 128.5, 137.9; IR
4.1.4. 6-(Oct-1-ynyl)tetrahydropyran-2-yl acetate (4b).
Lactol 3b was first prepared from 2b following the
procedure described above for 3a. The crude product
could be purified by flash chromatography (20% EtOAc/
hexanes) to yield 3b (59%) as a 1.9:1 mixture of
0
1
diastereoisomers: H NMR d 0.86 (t, J¼6.5 Hz, 3H, H-8 ),
1.20-1.84 (m, 14H), 2.10–5.57 (m, 2H, H-30), 3.10–3.60
(m, 1H, OH), 4.17–4.20 (m, H-6, minor isomer), 4.35–4.77
(m), 5.25–5.29 (m, H-2, major isomer). Alternatively, the
crude lactol 3b was treated with Et3N, Ac2O and DMAP as
described above for 4a to yield after flash chromatography
(6% EtOAc/hexanes) acetate 4b (53% yield for two steps
(neat) n 3450 (m, OH), 1080 (s, C–O–C) cm21
;
[a]2D0¼90.258 (c¼3.61, CHCl3); LRMS (EI) m/z (%) 398
(M), 117 (17), 91 (73), 91 (base), 91 (58), 75 (12), 75 (13);
HRMS calcd for C20H34O6Si 398.2124, found 398.2114.
4.1.7. Methyl 3-O-benzyl-6-O-(tert-butyldimethylsilyl)-
2,4-bis-O-(methylsulfanylthiocarbonyl)-a-D-galacto-
pyranoside (11). A mixture of 10 (150.0 mg, 0.38 mmol),
NaH (60% dispersion in mineral oil, 80.0 mg, 2.0 mmol)
and imidazole (10 mg) in THF (12 mL) was stirred at room
temperature for 0.5 h. Carbon disulfide (4 mL) was added
and the resulting yellow suspension was stirred for 7 h, after
which CH3I (0.11 mL, 1.8 mmol) was added. The mixture
was further stirred for 12 h, diluted with diethyl ether
(70 mL), and the solution was washed with H2O (30 mL)
and saturated NH4Cl (30 mL). The aqueous layers were
back-extracted with diethyl ether (60 mL), and the com-
bined organic layers were dried (Na2SO4). The crude after
evaporation was purified by flash chromatography (10%
1
from 2b) as a 1.2:1 trans/cis diastereomeric mixture: H
NMR d 0.86 (t, J¼6.7 Hz, 3H, H-80), 1.24–1.95 (m, 14H),
2.07 (s, 3H, OCOCH3), 2.18 (tt, J¼7.0, 2.4 Hz, 2H, H-30),
4.30–4.35 (m, H-6, cis-4b), 4.62 (dm, J¼8.5 Hz, H-6,
trans-4b), 5.69 (dd, J¼7.9, 2.7 Hz, H-2, cis-4b) 6.17 (br s,
W1/2¼5.5 Hz, H-2, trans-4b); 13C NMR d 13.7, 17.4, 18.4,
18.4, 20.0, 20.8, 22.2, 28.0, 28.2, 28.9, 31.0, 31.3, 31.4,
62.6, 66.4, 78.2, 85.1, 85.7, 91.6, 93.3, 168.9; IR (neat) n
3600–3200 (m, O–H), 2240 (w, CuC), 1760 (s, CvO)
cm21; LRMS (EI) m/z (%) 251 (M21, 7), 209 (16), 207
(18), 191 (10), 138 (11), 137 (base), 113 (14), 105 (16), 99
(18), 95 (14), 93 (11), 91 (13), 85 (10), 81 (18), 79 (19), 77
(12), 71 (40), 69 (17), 67 (31); HRMS calcd for C15H24O3
252.1725, found 252.1718.
1
EtOAc/hexanes) to yield 11 (0.197 g, 90%) as an oil: H
NMR d 0.07 (s, 6H, SiCH3), 0.89 (s, 9H, t-Bu), 2.56 (s, 3H,
SCH3), 2.59 (s, 3H, SCH3), 3.40 (s, 3H, OCH3), 3.61–3.74
(m, 2H, H-6), 4.04 (t, J¼6.3 Hz, 1H, H-5), 4.20 (dd, J¼10.3,
3.1 Hz, 1H, H-3), 4.53 (d, J¼12.0 Hz, 1H, OCHPh), 4.75 (d,
J¼12.0 Hz, 1H, OCHPh), 5.21 (d, J¼3.4 Hz, 1H, H-1), 5.94
(dd, J¼10.3, 3.5 Hz, 1H, H-2), 6.55 (br s, W1/2¼2.8 Hz, 1H,
H-4), 7.26–7.32 (m, 5H, Ar); 13C NMR d 25.5, 18.2, 19.0,
19.3, 25.6, 55.4, 61.6, 70.2, 72.3, 73.6, 76.7, 78.4, 96.4,
127.6, 127.8, 128.3, 137.6, 216.0, 216.1; IR (neat) n 1200
(m, CvS), 1050 (m, C–O–C) cm21; [a]D20¼þ83.338
(c¼1.14, CHCl3).
4.1.5. Methyl 3-O-benzyl-a-D-galactopyranoside (9).
Methyl a-D-galactopyranoside monohydrate (13.50 g,
64 mmol) and dibutyltin oxide (15.84 g, 64 mmol) were
heated in benzene (250 mL) with azeotropic separation of
water (Dean–Stark) for 16 h. Tetrabutylammonium iodide
(23.32 g, 64 mmol) and benzyl bromide (16.0 mL,
128 mmol) were added to the cooled solution and the
mixture was refluxed for 4 h. Solvent evaporation afforded a
crude product that was purified by flash chromatography
(EtOAc) to yield 9 (8.82 g, 49%): 1H NMR d 2.31
(d, J¼7.8 Hz, 1H, OH), 2.61 (d, J¼4.6 Hz, 1H, OH), 2.85
(s, 1H, OH), 3.40 (s, 3H, OCH3), 3.61 (dd, J¼9.6, 3.2 Hz,
1H, H-3), 3.69–4.03 (m, 4H, H-2, H-5 and H-6), 4.06 (br s,
W1/2¼7.9 Hz, 1H, H-4), 4.71 (s, 2H, OCH2Ph), 4.83
(d, J¼3.8 Hz, 1H, H-1), 7.25–7.37 (m, 5H, Ar); 13C NMR
d 55.3, 62.6, 67.9, 68.2, 69.3, 72.0, 78.0, 99.5, 127.8,
128.0, 128.5, 137.6; IR (neat) n 3200–3500 (m, OH), 1050
4.1.8. Methyl 3-O-benzyl-2,4-dideoxy-a-D-threo-hexa-
pyranoside (12).15 Starting from 10 (9.49 g, 23.86 mmol)
the above procedure was followed to obtain a partially
purified 11 (13.95 g) after flash chromatography. To a
refluxing solution of this material and AIBN (80 mg) in
toluene (250 mL) was added n-Bu3SnH (48 mL,
18.12 mmol) and the mixture was stirred while heated

J. M. Aurrecoechea et al. / Tetrahedron 59 (2003) 7111–7121
7117
under reflux. After 16 and 24 h of total reaction time further
portions of AIBN (0.5 and 0.4 g) and n-Bu3SnH (8 and
4 mL) were added. Refluxing was continued until a total
reaction time of 36 h. After solvent evaporation the residue
was subjected to flash chromatography eluting first with
hexanes to remove non-polar material and then with EtOAc
to collect the polar fraction. The latter was evaporated and
the residue (8.07 g) was redissolved in THF (200 mL). To
this solution at 08C was added tetrabutylammonium fluoride
(1 M in THF, 44 mL, 44 mmol), and the mixture was stirred
at room temperature for 12 h and then quenched with
saturated NH4Cl (70 mL). The layers were separated, the
aqueous layer was extracted with EtOAc (3£100 mL) and
the combined organic layers were dried (Na2SO4). The
crude after evaporation was purified by flash chromato-
graphy (20% and then 40% EtOAc/hexanes) to yield 12
4.1.10. 1,5-Anhydro-3,4-di-O-benzyl-6-O-(tert-butyldi-
methylsilyl)-2-deoxy-D-arabino-hex-1-enitol (15a).
A
solution of 14a15 (18.2 g, 69.9 mmol) in THF (55 mL) was
added to a slurry of NaH (60% dispersion in mineral oil, 10.5 g,
262 mmol) in THF (150 mL) at 08C. The mixture was allowed
to reach room temperature and stirred for 1.5 h. Benzyl
bromide (18.1 mL, 152.0 mmol) and tetrabutylammonium
iodide (900 mg, 2.43 mmol) were added, and the mixture was
stirred at room temperature for 7 h and then quenched at 08C
with saturated NH4Cl (150 mL). The aqueous layer was
extracted with diethyl ether (2£150 mL), and the combined
organic phases were washed with brine (20 mL) and dried
(Na2SO4). The residue after evaporation was purified by flash
chromatography (hexanes, then5% EtOAc/hexanesand finally
7% EtOAc/hexanes) to yield 15a (27.9 g, 93%) as a colorless
oil: 1H NMR d 0.07 and 0.08 (2s, 6H, SiCH3), 0.91 (s, 9H, SiC
(CH3)3), 3.88–4.00 (m, 4H, H-6, H-4 and H-5), 4.19–4.22 (m,
1H, H-3), 4.58 (d, J¼11.7 Hz, 1H, OCHPh), 4.66 (d,
J¼11.7 Hz, 1H, OCHPh), 4.75 (d, J¼11.1 Hz, 1H, OCHPh),
4.84(dd, J¼6.0, 2.6 Hz, H-2)and4.87(d, J¼11.1 Hz, OCHPh)
(total 2H), 6.39 (dd, J¼6.0, 1.3 Hz, 1H, H-1), 7.27–7.37 (m,
10H, Ar); 13C NMR d 25.4, 25.2, 18.3, 25.9, 61.6, 70.6, 73.9,
74.1, 75.8, 78.0, 99.7, 127.6, 127.7, 127.9, 128.4, 138.3, 144.7;
1
(2.05 g, 34% for three steps from 10) as an oil: H NMR d
1.38 (q, J¼11.9 Hz, 1H, H-4a), 1.57 (ddd, J¼12.5, 11.3,
3.4 Hz, 1H, H-2b), 1.99 (dt, J¼12.3, 2.4 Hz, 1H, H-4b),
2.21 (ddd, J¼12.7, 2.0, 2.4 Hz, 2H, H-2a, OH), 3.32 (s, 3H,
OCH3), 3.58–3.63 (m, 2H, H-6), 3.70–4.01 (m, 2H, H-3
and H-5), 4.54 (s, 2H, OCH2Ph), 4.90 (d, J¼3.2 Hz, 1H,
H-1), 7.24–7.35 (m, 5H, Ar); 13C NMR d 33.5, 36.4, 54.6,
65.7, 68.4, 69.9, 70.5, 99.1, 127.5, 128.3, 138.4; IR (neat) n
3447 (m, OH), 1050 (s, C–O–C) cm21. These spectro-
scopic data coincide with those reported in the literature for
the same compound.15
IR (neat) n 1647 (m, CvC), 1102 (s, Si–O) cm21
.
4.1.11. Methyl 3,4-di-O-benzyl-2-deoxy-D-arabino-hexo-
pyranoside (16a). To a solution of 15a (6.27 g, 14.2 mmol)
in CH2Cl2 (80 mL) were added methanol (1.80 mL,
44.4 mmol) and triphenylphosphine hydrobromide (250 mg,
0.70 mmol). The mixture was stirred at room temperature
for 20 min and diluted with CH2Cl2 (100 mL). The solution
was washed with saturated NaHCO3 (2£100 mL) and brine
(50 mL), and dried (Na2SO4). The residue after evaporation
was dissolved in THF (54 mL) and treated with tetrabutyl-
ammonium fluoride (1.0 M in THF, 18.0 mL, 18.0 mmol)
for 2 h. Saturated NH4Cl (50 mL) was then added. The
aqueous layer was extracted with EtOAc (3£75 mL), and
the combined organic layers were washed with brine
(50 mL) and dried (Na2SO4). The residue after evaporation
was purified by flash chromatography (40% EtOAc/
hexanes) to yield 16a (4.58 g, 90%) as a 71:29 a/b anomer
4.1.9. Methyl 3-O-benzyl-2,4,6-trideoxy-a-D-threo-hept-
6-ynopyranoside (13). To a solution of oxalyl chloride
(0.64 mL, 7.32 mmol) in CH2Cl2 (33 mL) at 2708C under
Ar, was added a solution of DMSO (1.1 mL, 14.9 mmol) in
CH2Cl2 (30 mL). After 15 min a solution of 12 (1.50 g,
5.95 mmol) in CH2Cl2 (30 mL) was added, and the resulting
mixture was stirred for 2 h at 2708C. Diisopropylethylamine
(5.18 mL, 29.7 mmol) was then added, and the mixture was
allowed to reach room temperature over a period of 2 h. The
solution was diluted with CH2Cl2 (120 mL), successively
extracted with saturated NaHCO3 (3£50 mL) and water
(2£50 mL), 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 alde-
hyde.15 Without further manipulation, this was dissolved in
dry methanol (65 mL), and to this solution was added
anhydrous K2CO3 (1.64 g, 11.9 mmol) followed by a solution
of dimethyl 1-diazo-2-oxopropylphosphonate17a (1.40 g,
7.32 mmol) in methanol (20 mL). The mixture was stirred
for 3 h, it was diluted with diethyl ether (200 mL), and the
solution was washed with saturated NaHCO3 (60 mL) and
dried (Na2SO4). The crude after evaporation was purified by
flash chromatography (10% EtOAc/hexanes) to yield alkyne
13 (0.95 g, 65%, for two steps from 12) as an oil: 1H NMR d
1.63 (ddd, J¼12.3, 11.5, 3.6 Hz, 1H, H-2b), 1.73 (q,
J¼11.9 Hz, 1H, H-4b), 2.17 (ddd, J¼12.7, 2.4, 2.0 Hz, 1H,
H-2a),2.31(dt,J¼12.5,2.0 Hz,1H,H-4a),2.46(d,J¼2.0 Hz,
1H, H-7), 3.38 (s, 3H, OCH3), 3.85 (m, 1H, H-3), 4.40–4.61
(m, 3H, OCH2Ph, H-5), 4.90 (d, J¼3.2 Hz, 1H, H-1,), 7.25–
7.39(m, 5H, Ar);13C NMR d 36.0, 38.1, 55.1, 58.4, 69.8, 69.9,
72.6, 82.3, 99.4, 127.4, 127.5, 127.6, 138.3; IR (neat) n 3288
1
mixture: H NMR d 1.58 (m, H-2b, a-16a), 1.67 (ddd,
J¼13.1, 11.3, 3.6 Hz, H-2b, b-16a), 2.01(br s, W1/2¼13.5 Hz,
1H, OH), 2.31 (ddd, J¼13.1, 5.1, 1.1 Hz, H-2a, a-16a,
overlapped with signals of the same proton of b-16a, total
1H), 3.31 (s, OCH3 a-16a, overlapped with signals of
b-16a), 3.44–3.75 (m), 3.80 (dd, J¼5.4, 3.5 Hz, 1H of
a-16a), 3.87 (dd, J¼4.7, 3.0 Hz, 1H of b-16a, overlapped
with signals of other protons of b-16a), 4.01 (ddd,
J¼11.3, 8.6, 5.1 Hz, H-3, a-16a), 4.41 (dd, J¼9.7, 1.9 Hz,
H-1, b-16a), 4.82 (dm, H-1, a-16a), 4.61–4.74 (m, 3H,
OCH2Ph), 4.97 (d, J¼11.1 Hz, 1H, OCHPh), 7.27–7.39 (m,
10H, Ar); 13C NMR d 35.3, 36.5, 54.5, 56.7, 62.1, 71.0,
71.4, 71.6, 74.8, 75.0, 75.1, 77.3, 77.9, 78.0, 79.0, 98.4,
100.8, 127.5, 127.7, 127.8, 128.0, 128.0, 128.3, 128.4,
138.1, 138.3, 138.5; IR (neat) n 3464 (m, OH) cm21; LRMS
(EI) m/z (%) 267 (M291, 44), 235 (30), 161 (21), 143 (12)
(129 (45), 113 (17), 111 (21), 107 (16), 105 (37), 99 (12), 92
(27), 91 (base), 77 (12), 69 (11); HRMS calcd for C21H26O5
358.1780, found 358.1794.
(m, uC–H), 2123 (w, CuC), 1048 (s, C–O–C) cm21
;
[a]2D0¼þ122.58 (c¼0.7, CHCl3);LRMS (EI) m/z (%) 246 (M),
91 (base); HRMS calcd for C15H18O3 246.1256, found
246.1256.
4.1.12. Methyl 3,4-di-O-benzyl-7,7-dibromo-2,6,7-tri-
deoxy-D-arabino-hept-6-enopyranoside (17). To a solution

7118
J. M. Aurrecoechea et al. / Tetrahedron 59 (2003) 7111–7121
of oxalyl chloride (350 mL, 4.04 mmol) in CH2Cl2 (25 mL)
at 2458C under argon, was added DMSO (580 mL,
8.18 mmol). After 10 min a solution of 16a (1.18 g,
3.30 mmol, 71:29 a/b anomer mixture) in CH2Cl2 (9 mL)
was added, and the resulting mixture was stirred for 1 h
20 min. Diisopropylethylamine (2.88 mL, 16.50 mmol) was
then added, and the mixture was allowed to reach room
temperature over a period of 30 min. The mixture was
extracted with saturated NaHCO3 (3£5 mL) and water
(2£5 mL). The organic layer was diluted with CH2Cl2
(25 mL), washed with saturated CuSO4 (5 mL) 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 (1.14 g) [1H
NMR d 1.63–1.74 (m, 1H, H-2), 2.16–2.30 (m, 1H, H-2),
3.34 (s, OCH3 a-anomer), 3.51 (s, OCH3 b-anomer), 3.46–
3.92 (m), 4.02–4.12 (m), 4.18 (d, J¼9.5 Hz), 4.52–4.69
(m), 4.80–4.94 (m), 7.32–7.33 (m, 10H, Ar), 9.72 and 9.75
(2s, 1H, CHO)]. Without further manipulation, this
aldehyde was used in the next step as follows. To a solution
of Ph3P (3.52 g, 13.44 mmol) in CH2Cl2 (13 mL) at room
temperature was added dropwise a solution of CBr4 (2.19 g,
6.61 mmol) in CH2Cl2 (9.5 mL). The resulting orange slurry
was stirred 40 min at the same temperature and then Et3N
(2.20 mL, 15.78 mmol) was added. After cooling the
resulting purple slurry to 08C, the crude aldehyde (1.14 g)
in CH2Cl2 (16 mL) was added dropwise. The mixture was
allowed to reach room temperature and was stirred at that
temperature for 2 h. The solvents were partially evaporated
until 3–5 mL remained, and the resulting residue was
filtered through silica gel (1 cm, B¼6.8 cm) that had been
previously saturated with Et3N. The solid residue was
washed with the minimum volume of CH2Cl2 and then with
25% EtOAc/hexanes (100 mL). The combined filtrate and
washings were filtered and the solvents were evaporated.
The crude product was purified by flash chromatography
(10% EtOAc/hexanes) to yield dibromoolefin 17 (0.802 g,
48% for two steps from 16a) as a 65:35 a/b anomer
yield 18a (0.422 g, 80%) as a 64:36 a/b anomer mixture: 1H
NMR d 1.63–1.76 (m, 1H, H-2), 2.20–2.31 (m, 1H, H-2),
2.49 (d, J¼2.3 Hz, H-7, a-18a), 2.52 (d, J¼2.3 Hz, H-7,
b-18a), 3.35 (s, OCH3 a-18a), 3.49–3.57 (m), 3.86 (ddd,
J¼11.5, 8.8, 5.0 Hz, H-3, a-18a), 4.00 (dd, J¼9.2, 2.0 Hz,
1H of b-18a), 4.35 (dd, J¼9.6, 1.9 Hz, 1H), 4.63 and 4.68
(AB system, J¼11.2 Hz, 2H, OCH2Ph), 4.82 (d, J¼2.8 Hz,
H-1, a-18a), 4.87 (d, J¼10.5 Hz, 1H, OCHPh), 4.95 (d,
J¼10.5 Hz, 1H, OCHPh), 7.29–7.41 (m, 10H, Ar); 13C
NMR d 35.3, 36.5, 55.0, 56.8, 62.0, 65.9, 71.9, 72.2, 73.1,
73.6, 75.4, 75.5, 76.0, 77.7, 80.8, 81.6, 81.9, 82.1, 98.6,
100.8, 127.5, 127.6, 127.7, 127.8, 128.1, 128.2, 128.3,
128.3, 128.3, 128.4, 138.0, 138.1, 138.1, 138.4; IR (neat) n
3282 (m, uC–H) cm21; LRMS (EI) m/z (%) 261 (M291,
12), 229 (6), 175 (10), 123 (7), 105 (9), 101 (5), 99 (12), 92
(10), 91 (base), 77 (4), 65 (6); HRMS calcd for C22H24O4
352.1675, found 352.1687.
4.1.14. Methyl 3,4-O-dibenzyl-2,6,7-trideoxy-a-D-lyxo-
hept-6-ynopyranoside (18b). Prepared from 16b27 as
described above for 13. The crude product was purified by
flash chromatography (10% EtOAc/hexanes) to yield enyne
19 (7%) followed by alkyne 18b (62%, for two steps from
16b) as transparent oils. Data for 18b: 1H NMR d 1.93 (dd,
J¼12.7, 4.6 Hz, 1H, H-2a), 2.25 (td, J¼12.6, 3.6 Hz,
1H, H-2b), 2.46 (d, J¼2.3 Hz, 1H, H-7), 3.37 (s, 3H,
OCH3), 3.84 (ddd, J¼11.9, 4.6, 2.6 Hz, 1H, H-3), 3.91 (br s,
W1/2¼7.5 Hz, 1H, H-4), 4.47–4.53 (m, 3H, H-5, OCH2Ph),
4.91–4.96 (m, 3H, H-1, OCH2Ph), 7.29–7.50 (m, 10H, Ar);
13C NMR d 30.6, 55.3, 62.2, 70.3, 73.3, 73.6, 74.5, 75.0,
80.6, 99.2, 127.3, 127.5, 127.6, 128.1, 128.3, 128.4, 138.2,
138.5; IR (neat) n 3280 (m, uC–H), 2120 (w, CuC), 1120
(s, C–O–C), 1050 (s, C–O) cm21; [a]D20¼þ121.08
(c¼1.38, CHCl3); LRMS (EI) m/z (%) 352 (M), 105 (13),
104 (35), 91 (base), 77 (12); HRMS calcd for C22H24O4
352.1675, found 352.1679. Data for methyl 1,5-anhydro-3-
O-benzyl-2,4,6,7-tetradeoxy-a-L-glycero-hept-4-en-6-yno-
1
pyranoside (19): H NMR d 1.93–2.11 (m, 2H, H-2), 2.93
1
mixture: H NMR d 1.54–1.71 (m, 1H, H-2a), 2.24–2.36
(s, 1H, H-7), 3.54 (s, 3H, OCH3), 4.14 (dd, J¼9.3, 5.6 Hz,
1H, H-3), 4.53 and 4.58 (AB system, J¼11.7 Hz, 2H,
OCH2Ph), 5.00 (dd, J¼6.1, 3.0 Hz, 1H, H-1), 5.52 (d,
J¼3.8 Hz, 1H, H-4), 7.34–7.36 (m, 5H, Ar); 13C NMR d
32.8, 56.5, 67.2, 70.0, 76.1, 78.3, 99.3, 109.5, 127.6, 127.7,
128.4, 135.4, 138.0; IR (neat) n 3265 (m, uC–H), 2095 (w,
CuC), 1630 (CvC), 1130 (s, C–O–C), 1040 (s, C–O)
cm21; [a]D20¼þ255.248 (c¼1.01, CHCl3); LRMS (EI) m/z
(%) 244 (M), 105 (15), 91 (base), 77 (13); HRMS calcd for
C15H16O3 244.1099, found 244.1098.
(m, 1H, H-2b), 3.28–3.37 (m, 1H), 3.37 and 3.49 (2s, 3H,
OCH3), 3.68 (ddd, J¼11.5, 8.5, 5.0 Hz, 1H, b-17), 3.94–
4.04 (m, 1H), 4.36 (t, J¼9.1 Hz, H-5, a-17), 4.40 (dd,
J¼9.7, 2.0 Hz, H-1, b-17), 4.61–4.71 (m, 3H, OCH2Ph),
4.76 (dm, J¼2.6 Hz, H-1 a-17), 4.84 (d, J¼11.0 Hz, 1H,
OCHPh), 6.32 (d, J¼8.8 Hz, H-6, a-17), 6.39 (d, J¼8.2 Hz,
H-6, b-17), 7.27–7.40 (m, 10H, Ar); 13C NMR d 35.5, 36.5,
55.0, 56.8, 71.3, 71.8, 72.1, 75.0, 75.0, 75.1, 76.8, 78.4,
80.5, 80.9, 95.0, 95.4, 98.5, 100.7, 127.6, 127.7, 127.8,
127.9, 128.4, 128.5, 135.7, 136.2, 137.8, 138.0, 138.1,
138.4; IR (neat) n 1723 (m), 1636 cm21
.
4.2. General procedure for reactions with SmI2/Pd(0)
4.1.13. Methyl 3,4-di-O-benzyl-2,6,7-trideoxy-D-arabino-
hept-6-ynopyranoside (18a). A solution of LDA (,0.43 M
in THF, 7.7 mL, 3.31 mmol) was added dropwise to a
solution of 17 (0.760 g, 1.50 mmol) in THF (3.3 mL) at
2788C. Additional portions of LDA solution were added
until disappearance of the dibromoolefin as judged by TLC.
After addition of H2O (10 mL), the mixture was allowed to
reach room temperature. The layers were separated, the
aqueous layer was extracted with EtOAc (3£20 mL), and
the combined organic extracts were dried (Na2SO4). The
residue obtained after evaporation of the solvents was
purified by flash chromatography (15% EtOAc/hexanes) to
Preparation of Pd(0) catalyst solutions: Pd(Ph3P)4 was
prepared using the literature procedure28 and directly
dissolved in admixture with the substrate. A THF solution
of Pd(OAc)2/4(n-Bu3)P was prepared by adding (n-Bu3)P
(80 mL, 0.30 mmol) to a solution of Pd(OAc)2 (15 mg,
0.07 mmol) in THF (4 mL). An immediate color change
from orange to yellow was observed. A portion of this
solution was immediately added to a solution of the
substrate (4, 13, 18) in THF to obtain a final molar ratio
of substrate to catalyst of about 19:1. In a typical
23
experiment, to a solution of SmI2 (1.88 mmol) in THF
(19 mL) under Ar was added a solution of substrate 4, 13, 18

J. M. Aurrecoechea et al. / Tetrahedron 59 (2003) 7111–7121
7119
(0.63 mmol) and the Pd(0) catalyst (0.03 mmol) in THF
(4 mL). The resulting solution was stirred at room
temperature (4) or in an oil bath at 75–808C (13, 18) until
TLC indicated the total disappearance of the starting
material or no further evolution was observed. After
cooling, saturated K2CO3 (15 mL) was added. The layers
were separated, the aqueous layer was extracted with Et2O
(4£20 mL), and the combined organic extracts were washed
with brine (10 mL) and dried (Na2SO4). The residue after
evaporation was purified as specified for the individual
cases to afford cyclopentanes 5, 20–22.
nol (22). Obtained from 18b in 75% yield after a reaction
time of 1 h. The crude product was purified by flash
chromatography (32% EtOAc/hexanes) to yield 22 as a
54:46 diastereomeric mixture. The isomers were separated
by HPLC (32% EtOAc/hexanes, 8 mL/min). Data for the
1
(1S,2R)-isomer (22b): tR¼31 min; H NMR d 1.92–1.99
(m, 1H, H-5b), 2.14–2.20 (m, 1H, H-5a), 2.23 (d,
J¼2.6 Hz, 1H, CuCH), 2.90 (d, J¼9.7 Hz, 1H, OH), 3.03
(t, J¼3.2 Hz, 1H, H-2), 3.89 (dd, J¼6.3, 4.0 Hz, 1H, H-3),
4.02–4.08 (m, 1H, H-4), 4.12–4.21 (m, 1H, H-1), 4.58–
4.77 (m, 4H, OCH2Ph), 7.32–7.37 (m, 10H, Ar); 13C NMR
d 37.8, 43.9, 71.5, 71.9, 72.1, 77.0, 78.5, 84.1, 84.9, 127.7,
128.3, 137.8, 138.0; IR (neat) n 3420 (m, OH), 3290
(m, uC–H), 2100 (w, CuC), 1120 (s, C–O–C), 1060
(s, C–O) cm21; [a]D20¼233.338 (c¼0.75, CHCl3); LRMS
(EI) m/z (%) 322 (M), 232 (14), 231 (93), 107 (43), 105 (17),
92 (16), 91 (base); HRMS calcd for C21H22O3 322.1569,
found 322.1575. Data for the (1R,2S)-isomer (22a):
tR¼43 min; 1H NMR d 1.89 (ddd, J¼12.9, 7.9, 4.3 Hz,
1H, H-5a), 2.19 (s, J¼9.5 Hz, 1H, OH), 2.26 (d, J¼2.6 Hz,
1H, CuCH), 2.27–2.40 (m, 1H, H-5b), 2.65 (ddd, J¼6.9,
4.3, 2.5 Hz, 1H, H-2), 4.01–4.12 (m, 2H, H-3, H-4), 4.49
and 4.54 (AB system, J¼12.1 Hz, 2H, OCH2Ph), 4.57–4.62
(m, 1H, H-1), 4.84 and 4.89 (AB system, J¼12.1 Hz, 2H,
OCH2Ph), 7.26–7.47 (m, 10H, Ar); 13C NMR d 37.2, 43.1,
71.5, 71.9, 73.1, 75.8, 78.8, 79.8, 82.4, 127.5, 127.5, 127.9,
128.2, 128.3, 138.2, 138.5; IR (neat) n 3400 (m, OH), 3290
(m, uC–H), 2100 (w, CuC), 1130 (s, C–O–C), 1060
(s, C–O) cm21; [a]D20¼þ9.828 (c¼0.55, CHCl3); LRMS
(EI) m/z (%) 322 (M), 231 (22), 107 (17), 105 (23), 91
(base); HRMS calcd for C21H22O3 322.1569, found
322.1583.
4.2.1. trans-2-Ethynylcyclopentanol7 (5). Obtained from
4a using Pd(PPh3)4 as catalyst in 1.5 h. The crude product (a
92:8 trans/cis mixture as determined by GC–MS) was
purified by flash chromatography (25% EtOAc/hexanes) to
1
yield 5 as a volatile oil: GC–MS tR¼6.8 and 7.1 min; H
NMR d 1.51–1.78 (m, 4H), 1.93–2.10 (m, 3H), 2.48–2.59
(m, 2H), 4.15–4.21 (m, 1H, H-1); 13C NMR d 21.6, 30.7,
33.3, 39.1, 69.5, 79.0, 86.3. These spectroscopic data
coincide with those described in the literature for the same
compound.7
4.2.2. (1R,2S,4S)-4-Benzyloxy-2-ethynylcyclopentanol
(20). Obtained from 13 in 81% yield after a reaction time
of 6 min. The crude product was purified by flash
chromatography (30% EtOAc/hexanes) to yield the title
compound in a 85:15 mixture with another isomer.
Repeated flash chromatography enriched this mixture to a
1
97:3 ratio. Data for the major (1R,2S,4S)-isomer (20): H
NMR d 1.76–1.91 (m, 2H, H-5a, H-3a), 2.08 (br s, W1/
¼10.3 Hz, 1H, OH), 2.13–2.25 (m, 2H, uC–H, H-5b),
2
2.42–2.59 (m, 2H, H-3b, H-2), 4.06–4.10 (m, 1H, H-4),
4.39 (dd, J¼14.3, 7.1 Hz, 1H, H-1), 4.47 (s, 2H, OCH2Ph),
7.30–7.35 (m, 5H, Ar); 13C NMR d 37.3, 39.8, 69.7, 70.7,
76.2, 76.3, 85.1, 127.3, 127.4, 128.1, 138.0; IR (neat) n 3380
4.2.5. Reaction of 4b with SmI2/Pd(PPh3)4. The general
procedure was followed with Pd(PPh3)4 as catalyst at room
temperature for 4 h. The crude product was subjected to
flash chromatography (1% EtOAc/hexanes) to yield in order
of elution 6b (50%) and 7 (11%). Data for 2-(oct-1-ynyl)-
3,4-dihydro-2H-pyran (6b): The characterized sample was
obtained after additional purification by HPLC (1% EtOAc/
hexanes, 8 mL/min; tR¼17 min); 1H NMR d 0.88 (t,
J¼6.7 Hz, 3H, H-80), 1.26–1.57 (m,0 9H), 1.82–2.17 (m,
5H), 2.21 (td, J¼7.0, 1.9 Hz, 2H, H-3 ), 4.59–4.65 (m, 1H,
H-2), 4.67–4.73 (m, 1H, H-5), 6.31 (dt, J¼6.1, 1.4 Hz, 1H,
H-6); 13C NMR d 14.0, 18.5, 18.7, 22.5, 28.5, 28.7, 31.3,
65.2, 78.4, 85.7, 100.7, 142.7; IR (neat) n 3060 (w, vC–H),
2240 (w, CuC), 1650 (m, CvC) cm21; LRMS (EI) m/z (%)
192 (M, 6), 191 (36), 179 (15), 165 (5), 162 (7), 137 (91),
137 (11), 133 (8), 123 (12), 121 (12), 121 (13), 119 (17), 117
(10), 110 (15), 109 (13), 108 (14), 107 (33), 105 (23), 97
(14), 96 (10), 95 (41), 94 (14), 93 (56), 30 (92), 91 (60), 83
(26), 81 (56), 80 (28), 79 (96), 79 (13), 77 (46), 70 (34), 69
(45), 68 (15), 67 (base), 66 (19), 65 (28); HRMS calcd for
C13H18O (M2H) 191.1436, found 191.1438. Data for
2-(oct-1-ynyl)tetrahydropyran (7): The characterized
sample was obtained after additional purification by
HPLC (4% EtOAc/hexanes, 8 mL/min; tR¼25 min); 1H
NMR d 0.88 (t, J¼6.7 Hz, 3H, H-80), 1.26–1.86 (m, 14H),
2.21 (td, J¼6.7, 1.9 Hz, 2H, H-30), 3.45–3.55 (m, 1H, H-6),
3.94–4.00 (m, 1H, H-6), 4.20–4.24 (m, 1H, H-2); 13C NMR
d 14.0, 18.7, 21.9, 22.5, 25.7, 28.5, 28.6, 29.6, 31.3, 32.5,
66.6, 67.3, 79.1, 85.8; LRMS (EI) m/z (%) 194 (M, 15), 193
(base), 165 (6), 151 (7), 137 (71), 124 (27), 111 (20), 109
(m, OH), 3285 (s, uC–H), 2100 (w, CuC) cm21
;
[a]2D0¼242.68 (c¼0.61, CHCl3); LRMS (EI) m/z (%) 215
(M21, 23), 123 (25), 108 (20), 107 (45), 106 (27), 105
(base), 91 (60), 79 (18), 77 (29); HRMS calcd for C14H16O2
216.1150, found 216.1141.
4.2.3. (1R,2S,3R,4R)-3,4-Bis(benzyloxy)-2-ethynylcyclo-
pentanol (21). Prepared from 18a in 61% yield (72%
yield based on recovered starting material) after a reaction
time of 3 h. The crude product was purified by flash
chromatography (20% EtOAc/hexanes) and HPLC (35%
EtOAc/hexanes, 10 mL/min, tR¼25 min). The product was
characterized from an inseparable 95:5 diastereomeric
1
mixture: H NMR d 1.94–2.05 (m, 1H, H-5), 2.11–2.25
(m, 1H, 0H-5), 2.26–2.40 (m, 1H, OH), 2.27 (d, J¼2.38 Hz,
1H, H-2 ), 2.67–2.74 (m, 1H, H-2), 4.01–4.07 (m, 2H, H-3
and H-4), 4.32 (dd, J¼14.0, 6.9 Hz, 1H, H-1), 4.50 (s, 2H,
OCH2Ph), 4.64 (d, J¼11.7 Hz, 1H, OCHPh), 4.76 (d,
J¼11.7 Hz, 1H, OCHPh), 7.27–7.38 (m, 10H, Ar); 13C
NMR d 38.2, 44.6, 71.3, 71.4, 72.0, 75.4, 82.0, 83.8, 88.1,
127.6, 127.7, 127.8, 128.3, 137.7, 137.9; IR (neat) n 3420,
3292, 2116 cm21; [a]D20¼210.58 (c¼0.95, CHCl3); LRMS
(EI) m/z (%) 231 (M291, 23), 143 (4), 107 (10), 105 (13),
92 (11), 91 (base), 77 (4), 65 (5); HRMS (FAB) calcd for
C21H21O3 (M2H) 321.1569, found 321.1487.
4.2.4. (3S,4R)-3,4-Bis(benzyloxy)-2-ethynylcyclopenta-

7120
J. M. Aurrecoechea et al. / Tetrahedron 59 (2003) 7111–7121
5. Enantioenriched allenylsamarium species are readily race-
mized: (a) Mikami, K.; Yoshida, A. Angew. Chem., Int. Ed.
Engl. 1997, 36, 858–860. (b) Mikami, K.; Yoshida, A.
Tetrahedron 2001, 57, 889–898. On the other hand, chiral
allenylpalladiums are known to undergo racemization in
Pd(0)-catalyzed processes: (c) Marshall, J. A.; Schaaf, G. M.
J. Org. Chem. 2001, 66, 7825–7831. (d) Marshall, J. A.;
Chobanian, H. R.; Yanik, M. M. Org. Lett. 2001, 3,
3369–3372, and references cited therein.
(16), 107 (10), 98 (27), 95 (17), 93 (16), 91 (16), 81 (27), 80
(16), 79 (28), 77 (13), 71 (15), 69 (18), 67 (47), 65 (10);
HRMS calcd for C13H20O (M2H) 193.1592, found
193.1597.
4.2.6. Reaction of 4b with SmI2 and cyclohexanone. To a
stirred solution of SmI2 (,0.1 M in THF, 12.4 mL,
1.24 mmol) at room temperature under Ar was added a
solution of 4b (140 mg, 0.55 mmol) and cyclohexanone
(60 mL, 0.58 mmol) in THF (5 mL). The mixture was stirred
for 2.5 h and worked-up as indicated in the general
procedure. The crude product was subjected to flash
chromatography (1% and then 6% EtOAc/hexanes) to
yield in order of elution 6b (43 mg, 43%) and 8 (14 mg,
9%, 92:8 diastereomeric mixture as measured by GC–MS).
Data for 1-[6-(oct-1-ynyl)tetrahydropyran-2-yl]cyclohexa-
nol (8): 1H NMR d 0.89 (t, J¼6.6 Hz, 3H, H-80), 1.2–1.9 (m,
24H), 2.00 (s, 1H, OH), 2.22 (td, J¼6.8, 1.9 Hz, 2H, H-30),
3.70 (dd, J¼11.4, 2.2 Hz, 1H, H-2), 4.76 (br s, W1/2¼8.7 Hz,
1H, H-6); 13C NMR d 14.0, 18.7, 19.2, 21.7, 22.6, 24.4,
26.0, 28.5, 28.7, 30.8, 31.3, 32.4, 34.6, 65.7, 72.3, 76.3,
78.4, 87.3; IR (neat) n 3600–3300 (O–H), 2230 (w, CuC)
cm21. GC–MS tR¼18.6 and 19.5 min; LRMS (EI) m/z (%)
291 (M21, 1), 275 (3), 235 (1), 209 (2), 194 (4), 192 (4),
176 (3), 165 (2), 147 (2), 125 (3), 124 (28), 123 (4), 121 (2),
106 (7), 99 (base), 98 (7), 97 (5), 95 (8), 95 (8), 93 (7), 91
(7), 81 (30), 80 (16), 79 (13), 77 (5), 69 (5), 67 (11); HRMS
calcd for C19H32O2 292.2402, found 292.2392.
6. (a) Schreiber, S. L.; Claus, R. E.; Reagan, J. Tetrahedron Lett.
1982, 23, 3867–3870. (b) Claus, R. E.; Schreiber, S. L. Org.
Synth. 1985, 64, 150–156.
7. (a) Carlson, R. G.; Cox, W. W. J. Org. Chem. 1977, 42,
2382–2386. (b) Hanack, M.; Kunzmann, E.; Schumacher, W.
Synthesis 1978, 26–27.
8. Elsevier, C. J.; Kleijn, H.; Boersma, J.; Vermeer, P.
Organometallics 1986, 5, 716–720.
9. (a) Depouilly, P.; Chenede, A.; Mallet, J. M.; Sinay, P. Bull.
Soc. Chim. Fr. 1993, 130, 256–265. (b) Mazeas, D.;
Skrydstrup, T.; Doumeix, O.; Beau, J. M. Angew. Chem.,
Int. Ed. Engl. 1994, 33, 1383–1386. (c) Hung, S. C.; Wong,
C. H. Angew. Chem., Int. Ed. Engl. 1996, 35, 2671–2674. (d)
Vlahov, I. R.; Vlahova, P. I.; Linhardt, R. J. J. Am. Chem. Soc.
1997, 119, 1480–1481. (e) Skrydstrup, T.; Jarreton, O.;
Mazeas, D.; Urban, D.; Beau, J. M. Chem. Eur. J. 1998, 4,
655–671. (f) Urban, D.; Skrydstrup, T.; Beau, J. M. J. Org.
Chem. 1998, 63, 2507–2516. (g) Andersen, L.; Mikkelsen,
L. M.; Beau, J. M.; Skrydstrup, T. Synlett 1998, 1393–1395.
(h) Jarreton, O.; Skrydstrup, T.; Espinosa, J. F.; Jimenez-
Barbero, J.; Beau, J. M. Chem. Eur. J. 1999, 5, 430–441. (i)
Mikkelsen, L. M.; Krintel, S. L.; Jimenez-Barbero, J.;
Skrydstrup, T. J. Org. Chem. 2002, 67, 6297–6308. (j)
Mikkelsen, L. M.; Skrydstrup, T. J. Org. Chem. 2003, 68,
2123–2128, and references cited herein.
Acknowledgements
´
Financial support by the Universidad del Paıs Vasco
(170.310-EB001/99 and 9/UPV00041.310-144471/2002)
10. Carey, F. A.; Sundberg, R. J. Advanced Organic Chemistry
Part A; 3rd ed. Plenum: New York, 1990; p 652.
´
and Ministerio de Educacion y Cultura (Spain) (DGI
BQU2000-01354) 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.
11. (a) Murakami, M.; Hayashi, M.; Ito, Y. Synlett 1994,
179–180. (b) Hanamoto, T.; Sugimoto, Y.; Sugino, A.;
Inanaga, J. Synlett 1994, 377–378.
12. (a) Molander, G. A. Chem. Rev. 1992, 92, 29–68. (b) Krief,
A.; Laval, A. M. Chem. Rev. 1999, 99, 745–777.
`
13. David, S.; Thieffry, A.; Veyrieres, A. J. Chem. Soc., Perkin
Trans. 1 1981, 1796–1801.
References
14. Barton, D. H. R.; McCombie, S. W. J. Chem. Soc., Perkin
Trans. 1 1975, 1574–1585.
1. Leading references into carbohydrate ring-contraction pro-
cedures: (a) Dalko, P. I.; Sinay¨, P. Angew. Chem. Int. Ed. 1999,
38, 773–777. (b) Ito, H.; Motoki, Y.; Taguchi, T.; Hanzawa,
Y. J. Am. Chem. Soc. 1993, 115, 8835–8836. (c) Hanzawa, Y.;
Ito, H.; Taguchi, T. Synlett 1995, 299–305. (d) Jenkins, D. J.;
Riley, A. M.; Potter, B. V. L. J. Org. Chem. 1996, 61,
7719–7726. (e) Yoshida, Y.; Nakagawa, T.; Sato, F. Synlett
1996, 437–438. (f) Paquette, L. A.; Arbit, R. M.; Funel, J. A.;
Bolshakov, S. Synthesis 2002, 2105–2109. (g) Paquette, L. A.;
15. Paquette, L. A.; Oplinger, J. A. J. Org. Chem. 1988, 53,
2953–2959.
16. Omura, K.; Swern, D. Tetrahedron 1978, 34, 1651–1660.
17. (a) Callant, P.; D’Haenens, L.; Vandewalle, M. Synth.
Commun. 1984, 14, 155–161. (b) Muller, S.; Liepold, B.;
Roth, G. J.; Bestmann, H. J. Synlett 1996, 521–522.
18. Bolitt, V.; Mioskowski, C.; Lee, S.-G.; Falck, J. R. J. Org.
Chem. 1990, 55, 5812–5813.
`
Cuniere, N. Org. Lett. 2002, 4, 1927–1929.
2. (a) Aurrecoechea, J. M.; Lopez, B.; Arrate, M. J. Org. Chem.
19. Corey, E. J.; Fuchs, P. L. Tetrahedron Lett. 1972, 3769–3772.
20. Marshall, J. A.; Bartley, G. S.; Wallace, E. M. J. Org. Chem.
1996, 61, 5729–5735.
´
2000, 65, 6493–6501. (b) Aurrecoechea, J. M.; Fan˜anas, R.;
´
Lopez, B. Arkivoc 2000, 1, 124–139. (c) Aurrecoechea, J. M.;
´
21. Mourin˜o, A.; Torneiro, M.; Vitale, C.; Fernandez, S.;
´
Perez-Sestelo, J.; Anne, S.; Gregorio, C. Tetrahedron Lett.
1997, 38, 4713–4716.
´
Fan˜anas, R.; Arrate, M.; Gorgojo, J. M.; Aurrekoetxea, N.
J. Org. Chem. 1999, 64, 1893–1901.
3. Kadota, I.; Hatakeyama, D.; Seki, K.; Yamamoto, Y.
Tetrahedron Lett. 1996, 37, 3059–3062.
22. Brown, H. C.; Kramer, G. W.; Levy, A. B.; Midland, M. M.
Organic Synthesis Via Boranes; Wiley: New York, 1975.
23. Molander, G. A. Organic Reactions, Paquette, L. A., Ed.;
Wiley: New York, 1994; Vol. 46, pp 211–367.
4. Imamoto, T. Lanthanides in Organic Synthesis; Academic:
London, 1994; p 67.

J. M. Aurrecoechea et al. / Tetrahedron 59 (2003) 7111–7121
7121
´
27. Aurrecoechea, J. M.; Arrate, M. H.; Gil, J. H.; Lopez, B.
24. Still, W. C.; Kahn, M.; Mitra, A. J. Org. Chem. 1978, 43,
2923–2925.
Tetrahedron 2003, 59, 5515–5522.
28. Coulson, D. R. Inorg. Synth. 1972, 13, 121–124.
25. Weinreb, S. M.; Smith, D. T. Synthesis 1998, 509–521.
26. Griesbaum, K.; Neumeister, J. Chem. Ber. 1982, 115,
2697–2706.