Synthesis of furanosyl C-1 glycals through palladium-catalyzed reactions of a furanosyl 2,3-anhydro-exe-glycal

Article abstract of DOI:10.1002/ejoc.200900585

A furanose-derived 2,3-anhydro-exo-glycal, readily available from D-mannose in four steps, has proven to be a useful substrate in the preparation of a variety of highly functionalized C-1 glycals. Upon treatment with Pd0 it affords a Tc-allyl palladium, c

Full text of DOI:10.1002/ejoc.200900585

FULL PAPER
DOI: 10.1002/ejoc.200900585
Synthesis of Furanosyl C-1 Glycals through Palladium-Catalyzed Reactions of
a Furanosyl 2,3-Anhydro-exo-glycal
Ana M. Gómez,*[a] Ana Pedregosa,[a] Aitor Barrio,[a] Serafín Valverde,[a] and
J. Cristóbal López*[a]
Keywords: Glycals / Carbohydrates / Electrophilic substitution / Nucleophilic substitution / Palladium / Umpolung
A furanose-derived 2,3-anhydro-exo-glycal, readily available
from -mannose in four steps, has proven to be a useful sub-
strate in the preparation of a variety of highly functionalized
C-1 glycals. Upon treatment with Pd0 it affords a π-allyl pal-
ladium complex that can react with nucleophiles such as
amines, ethyl malonate, or vinylstannanes. On the other
hand, umpolung of the π-allyl palladium complex with Et2Zn
facilitates its reaction with electrophilic aldehydes and
ketones.
D
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2009)
lithiation of 2-phenylsulfinyl--glycals [Scheme 1, a, X =
S(O)Ph].[17,18] On the other hand, C-1-stannyl[19,20] or C-1-
iodo glycals have been successfully used in palladium-medi-
ated coupling reactions[21–23] with activated substrates
(Scheme 1, b). This approach was also applied to furanoid
glycals.[24] These methods generally lead to good yields of
C-1 glycals, but they still need an initial metallation step for
the preparation of the required C-1 stannyl (or iodo) glycal.
Introduction
C-1-Substituted glycals (e.g., 1) are well-recognized inter-
mediates in a variety of synthetic protocols leading either
to carbohydrate mimetics or to complex molecules.[1,2] In
comparison with glycals (e.g., 2),[3] they present an ad-
ditional carbon substituent at the anomeric position (C-1)
while maintaining their enol ether functionality. The former
facilitates an easy retrosynthetic correlation with biolo-
gically relevant C-glycosides (e.g., 3),[4,5] whereas the enol
ether moiety permits the incorporation of additional func-
tionality in the carbohydrate entity (Figure 1).[6]
Figure 1. C-1 glycal (1), glycal (2), and C-glycoside (3).
The initial synthetic strategies directed towards C-1 gly-
cals were addressed by C-1 deprotonation of substituted
glycal derivatives.[7–9] It was thus shown that C-1-lithiated
glycals, generated either by direct proton abstraction or by
transmetallation of C-1 tributylstannyl glycals, could react
with diverse electrophiles (such as alkyl halides, aldehydes,
ketones, oxiranes, quinines, or hexacarbonyl chromium)[7–14]
to generate C-1-substituted glycals (Scheme 1, a, X = H).
Despite the straightforward nature of this approach, how-
ever, the preparation and handling of these lithio reagents
has been sometimes found to be troublesome.[15,16] In this
context, Schmidt and co-workers described the direct 1-C-
Scheme 1. Strategies for the synthesis of C-1 glycals.
Approaches to C-1 alkyl glycals, based on open-chain
derivatives, have been described recently (Scheme 1, c,d).[25]
In this context, Postema and co-workers designed an ap-
proach based on an enol ether–olefin ring-closing metathe-
sis protocol (Scheme 1, c),[25–29] whereas Mootoo and co-
workers employed an intramolecular oxocarbenium ion–al-
kene cyclization on an acetal-enol ether precursor as the
key step in the ring-forming reaction (Scheme 1, d).[30]
Base-induced elimination of 1-CN glycosides has been
used in the preparation of 1-cyanoglycals (Scheme 1, e),
which are useful precursors of heterocyclic C-1 glycals.[31,32]
[a] Instituto de Química Orgánica General, CSIC,
Juan de la Cierva 3, 28006 Madrid, Spain
Fax: +34-915644853
E-mail: anagomez@iqog.csic.es
clopez@iqog.csic.es
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2,3-Dehydroneuraminic acid derivatives, which can be re- cleophiles (NuH), electrophiles, and vinylstannanes (vide
garded as C-1-substituted glycals, have been obtained infra), to gain access to compounds of type 8, 9, and 10,
mainly by elimination procedures on peracetylated neur- respectively.
aminic ester derivatives (Scheme 1, e, X = COOR).[33] These
biologically relevant compounds, related to neuraminidase
inhibitors,[34,35] can be used in the preparation of sialic acid
derivatives functionalized at C-3.[36] Other methods have
also been used in the preparation of C-1-substituted gly-
cals.[37]
Reaction with Nucleophiles
π-Allylpalladium intermediates such as 7 are known to
react with soft carbon nucleophiles and amines to give sub-
stituted allylic alcohols such as 8. In order to test this trans-
formation, we first treated vinyloxirane 6 with Pd(OAc)2
and PPh3 in THF overnight at room temp. in the presence
of methyl malonate. We were able to isolate compound 11,
which displayed a signal at δ = 100.6 ppm (13C NMR), and
We have reported a method for the preparation of fu-
ranosyl and pyranosyl C-1 glycals based on treatment of
glycosyl chlorides with organolithium reagents (Scheme 1,
f).[38–40] More recently, we have become interested in the
preparation and chemistry of furanose-derived 2,3-anhydro
exo-glycals,[41] and found that they could be used in the
synthesis of C-1 glycals (Scheme 1, g).[42] Here we present a
detailed report on our studies on the versatility of 2,3-an-
hydro-exo-glycals in the synthesis of C-1 glycals.
1
a doublet at δ = 4.92 ppm (J = 2.9 Hz, H NMR), corre-
sponding to C-2 and H-2, respectively. From this, com-
pound 11 was the result of a 1,4-addition to the vinyloxir-
ane system. Similar results were obtained when the same
procedure was carried out with diverse primary and second-
ary amines to yield allylic derivatives 12–16 (Figure 2).
Results and Discussion
Synthesis
The key intermediate for these studies was the 2,3-an-
hydro exo-glycal 6 (Scheme 2). This compound can be ef-
ficiently prepared in four steps from commercially available
-mannose via the glycosyl chloride 4.[39]
Scheme 2. Preparation of the 2,3-anhydro exo-glycal 6.
Compound 6 is a valuable synthon for organic synthesis,
Figure 2. Allylic alcohols resulting from Pd0-catalyzed reactions be-
owing to its rich functionality. Of special interest to us was
the vinyloxirane moiety, because it was known that Pd0- tween vinyloxirane 6 and methyl malonate or primary or secondary
amines [Pd(OAc)2, PPh3, THF, room temp., overnight].
catalyzed reactions of vinyl epoxides could lead to π-allyl-
palladium intermediates such as 7 (Scheme 3).[43,44] Accord-
ingly, we set out to explore the behavior of 7 with pronu-
Reactions with Electrophiles
The reactions of electrophilic π-allylpalladium complexes
can only be applied to soft carbon nucleophiles.[45] Because
that limited reactivity implied a restraint to our methodol-
ogy, we turned our attention to π-allyl species that could
function as nucleophiles, rather than electrophiles, and
therefore react with carbon electrophiles. Several examples
of polarity inversion in π-allylpalladium species by transme-
tallation with low-valency metals had been described. These
included treatment with chromium,[46] tin,[47] samarium,[48]
and indium.[49] More recently, Et3B and Et2Zn have also
been used in the Pd-catalyzed generation of nucleophilic al-
lyl species from allyl esters and ethers.[50] In this context,
Scheme 3. Proposed Pd0-catalyzed reactions of vinyloxirane 6 with
nucleophiles, electrophiles, and vinylstannanes.
we decided to study the umpolung of the π-allylpalladium
species 7 with SmI2 and Et2Zn.
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Furanosyl C-1 Glycals from a Furanosyl 2,3-Anhydro-exo-glycal
We first examined the reaction between vinyloxirane 6 Table 1. Reactions between the vinyloxirane 6 and electrophiles (al-
dehydes, ketones, and lactones) mediated by Pd0/Et2Zn in THF.
and benzaldehyde (17) in the presence of Pd(PPh3)4 and
[51]
SmI2
(Scheme 4). However, no coupling products were
observed, and only the allylic iodide 18 could be isolated.
The same compound was also obtained when benzaldehyde
was omitted from the reaction media. The formation of 18
could be explained in terms of a 1,4 addition of SmI3 to
the vinyloxirane.[52]
Scheme 4. Reaction of vinyloxirane 6 with Pd0/SmI2.
We next turned our attention to the preparation of al-
lylzinc derivatives capable of reacting with electrophiles.[53]
To the best of our knowledge, at the onset of this work
there were no examples of the preparation of allylzinc deriv-
atives from vinyl epoxides.[54] The proposed reaction path-
way for this transformation[55] would involve ligand transfer
of the π-allylpalladium intermediate 7 to Et2Zn to generate
the reactive allylic zinc species (e.g., 19), which could react
with the electrophile (E) to generate the coupled derivative
9 (Scheme 5).
Scheme 5. Proposed reaction pathway for Pd0/Et2Zn-catalyzed re-
actions between vinyloxirane 6 and electrophiles.
Solutions containing the vinyl epoxide 6, Pd(PPh3)4, and
the corresponding electrophile in THF were thus treated at
room temperature with Et2Zn. As electrophiles we selected
aldehydes 17, 20–23, ketones 24, 25, and lactone 26, and
our results are displayed in Table 1.
The reactions took place smoothly, with disappearance
of the starting material normally occurring within 1–3 h.
The reactions between compound 6 and aldehydes gave
good yields of coupled products, with excellent 1,4-regio-
selectivities (Table 1, Entries i–vi). Benzaldehyde (17)
yielded a 1.5:1 diastereomeric mixture of allylic alcohols 27,
and o-methoxycinnamaldehyde similarly yielded the mix-
ture 20 (Table 1, Entries i and ii, respectively). Slightly
higher diastereomeric ratios (2.5:1) were observed in the re-
actions of 6 with citronellal (21) and isobutyraldehyde (22)
(Table 1, Entries iii and v, respectively). In view of some lit-
erature precedents on the effect of chiral ligands on the
enantioselective alkylation of aldehydes with Et2Zn,[56,57]
tose-derived aldehyde 23 yielded two single derivatives, 31
and 32, arising from regioisomeric attacks on the π-allylzinc
derivative, rather than from facial differentiation on the car-
bonyl group (Table 1, Entry vi). Ketones 24 and 25 gave
moderate yields of the tertiary hydroxy derivatives 33 and
34 (Table 1, Entries vii and viii, respectively). γ-Butyrolac-
tone (26), a poorer electrophile, yielded furan 35 in a re-
duced 23% yield.[58,59]
Reactions with Stannanes
In order to extend the usefulness of the π-allyl derivatives
we decided to evaluate the effect of the addition of (1S,2R)- generated from vinyloxirane 6 upon treatment with Pd0, we
ephedrine as a chiral additive in the reaction between citro- turned our attention to the significant work of Stille’s[60]
nellal (21) and the vinyloxirane 6. However, only a negligi- and Echavarren’s[61] groups on the use of stannanes as mild
ble increase in the diastereomeric ratio of 29 was observed nucleophiles in palladium-catalyzed couplings with vinyl
(Table 1, Entry iv). The reaction between 6 and the galac- epoxides.
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We first explored the reaction between 6 and the com- regioisomers was obtained (Table 2, Entries i–v). These re-
mercially available tetravinyltin under the conditions recom- sults are consistent with Stille’s previous findings. The C-1
mended by Stille and co-workers (Scheme 6).[60b] The reac- glycal derivatives (1,4-isomers) were always obtained as the
tion took place smoothly to give a mixture of the re- major isomers and proved to be very sensitive to acid, af-
gioisomeric derivatives 36 and 37, resulting from 1,4- and fording furan derivatives. Accordingly, Et3N (3%) was used
1,2-addition, respectively, to the allylic system. In keeping in all column chromatography purifications. The stereo-
with literature precedents, compound 37, generated by 1,2- chemistry at C-2 was unambiguously assigned, on the basis
addition, was obtained as the minor isomer. The structural of NOESY experiments (see Table 2), for compounds 47
assignments were based on study of the compounds’ 1H and 49, and was assumed in derivatives 43 and 45.
and 13C NMR spectra. Thus, with regard to regiochemistry,
Table 2. Reactions between vinyloxirane 6 and vinylstannanes 38–
in the case of 36 we were able to identify a signal at δ =
41.
32.7 ppm corresponding to C-1Ј (13C NMR), whereas a sig-
nal at δ = 83.5 ppm, corresponding to C-1Ј, was observed
in the 13C NMR spectrum of 37. Additionally, the observed
coupling patterns for the non-terminal vinylic proton in
compounds 36 and 37 were also indicative. The –CH= pro-
ton in compound 37 thus appeared, as expected, at δ =
5.78 ppm as a ddd (17.1, 10.0, and 6.8 Hz), whereas a po-
orly resolved multiplet was observed at δ = 5.84 ppm for
the –CH= proton in compound 36.
Scheme 6. Pd(CH3CN)2Cl2-catalyzed reaction between vinyloxir-
ane 6 and tetravinyltin.
The configuration at C-2 in compound 37, inferred on
mechanistic grounds, was confirmed by a NOESY experi-
ment that showed the correlation of H-3 with the non-ter-
minal vinylic proton.
We next decided to broaden this approach through the
use of more complex vinylstannanes. These are readily
available by Et3B-catalyzed radical addition of Bu3SnH to
terminal alkynes by a protocol described by Oshima and
co-workers.[62,63] Accordingly, we prepared the alkenyl-
stannanes 38–41 (Figure 3) from the corresponding alkynes.
The precursor for stannane 38 was commercially available
phenylacetylene, whereas the rest of the stannanes 39–41
were readily obtained by propargylation (propargyl bro-
mide, NaH) followed by Et3B-catalyzed stannylation.
Conclusions
The furanose-derived 2,3-anhydro-exo-glycal 6 has re-
vealed itself to be a valuable substrate in the preparation of
a variety of highly functionalized C-1 glycals. Upon treat-
ment with Pd0, compound 6 is smoothly transformed into
a π-allyl palladium species such as 7, which can react with
Figure 3. Vinylstannanes 38–41, prepared by Et3B-catalyzed radical
addition of Bu3SnH to terminal alkynes.
primary or secondary amines or with ethyl malonate to give
We applied Stille reaction conditions[60b] to the vinyloxir- C-1 glycals resulting from 1,4-addition to the allylic system.
ane 6 and the vinylstannanes 38–41, and our results are However, the π-allyl palladium species 7 also reacts with
outlined in Table 2. In each case a mixture of 1,4- and 1,2- stannanes to give mixtures of C-1 glycals (resulting from
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Furanosyl C-1 Glycals from a Furanosyl 2,3-Anhydro-exo-glycal
NMR: δ = 25.0, 26.6, 55.2, 57.1, 66.9, 72.9, 79.9, 87.3, 109.3,
157.2 ppm. MS (API-ES positive): m/z = 199.1 [M + 1]+. C10H14O4
(198.09): calcd. C 60.59, H 7.12; found C 60.37, H 7.03.
General Procedure for Pd0-Catalyzed Reactions between Epoxide 6
1,4-addition) and C-2 branched furanose exo-glycals (from
1,2-addition), with the former prevailing. Finally, umpo-
lung of 7 could be effected by treatment with Et2Zn, which
permits its coupling with electrophiles. Thus, aldehydes and
ketones gave moderate to good yields of allylic alcohols re-
sulting from 1,4-addition. The observed diastereomeric ex-
cesses varied from 2.5:1 to 3.5:1, and in the case of citronell-
al (21) the diastereomeric excess was not noticeably affected
by the addition of a chiral ligand. On the other hand, the
reaction between 6 and the galactose diacetonide aldehyde
23 was completely stereoselective, but still gave a mixture
of 1,2- and 1,4-regioisomers.
and Nucleophiles:
A solution of epoxide 6 in dry THF
(6 mLmmol–1) was treated under argon with Ph3P (1 equiv.),
Pd(OAc)2 (0.2 equiv.), and the corresponding nucleophile
(1.3 equiv.). The resulting suspension was stirred at room tempera-
ture under argon. After the starting materials had been consumed
(TLC), the mixture was diluted with EtOAc and washed with brine.
The organic layer was dried, concentrated, and subjected to silica
gel column chromatography.
Compound 11: Oxirane 6 (150 mg, 0.75 mmol), Ph3P (198 mg,
0.75 mmol), Pd(OAc)2 (16 mg, 0.07 mmol), and dimethyl malonate
(112 µL, 0.97 mmol) were treated according to the General Pro-
cedure. After purification (hexane/EtOAc, 40:60), compound 11
(213 mg, 86%) was obtained as a colorless oil: [α]2D5 = –20.0 (c =
Experimental Section
General Remarks: All reactions were performed in dry flasks fitted
with glass stoppers or rubber septa under positive pressure of Ar,
unless otherwise noted. Air- and moisture-sensitive liquids and
solutions were transferred by syringe or stainless steel cannula. Op-
tical rotations were determined for solutions in chloroform. Flash
column chromatography was performed with 230–400 mesh silica
gel. Thin-layer chromatography (TLC) was conducted on Kieselgel
60 F254 (Merck). Spots were observed first under UV irradiation
(254 nm) and then by charring with a solution of aqueous H2SO4
(20%, 200 mL) in AcOH (800 mL). Anhydrous MgSO4 or Na2SO4
were used to dry organic solutions during workup, and evaporation
of the solvents was performed under vacuum with a rotary evapo-
rator. Solvents were dried and purified by standard methods. Un-
less otherwise noted, 1H and 13C NMR spectra were recorded in
CDCl3 at 300 and 50 MHz, respectively. Chemical shifts are ex-
pressed in parts per million (δ scale) downfield from tetramethylsil-
ane and are referenced to residual protium in the NMR solvent
(CHCl3: δ = 7.25 ppm). API-ES stands for atmospheric pressure-
positive electrospray ionization.
1
3.0, CHCl3). H NMR (C6D6): δ = 1.32 (s, 3 H, Me), 1.39 (s, 3 H,
Me), 2.75 (d, J = 7.0 Hz, 2 H, CH2–CH), 3.62 (t, J = 7.5 Hz, 1 H,
CH–CH2), 3.69 (s, 6 H, OMe), 3.92 (dd, J = 5.4, 8.4 Hz, 1 H, 6-
H), 4.01 (dd, J = 6.3, 8.5 Hz, 6Ј-H), 4.13 (t, J = 6.8 Hz, 1 H, 4-H),
4.39–4.45 (m, 1 H, 5-H), 4.79–4.82 (br. m, 1 H, 3-H), 4.92 (d, J =
2.9 Hz,1 H, 2-H) ppm. 13C NMR: δ = 25.0, 26.6, 27.3, 49.0, 52.6,
66.4, 72.7, 73.3, 85.0, 100.6, 109.0, 159.4, 168.6, 168.7 ppm. MS
(API-ES positive): m/z = 330.2 [M]+, 331.1 [M + 1]+. C15H22O8
(330.13): calcd. C 54.54, H 6.71; found C 54.33, H 6.61.
Compound 12: Oxirane 6 (150 mg, 0.75 mmol), Ph3P (198 mg,
0.75 mmol), Pd(OAc)2 (16 mg, 0.07 mmol), and -alaninol (75 µL,
0.97 mmol) were treated according to the General Procedure. After
purification (MeOH/EtOAc, 10:90), compound 12 was obtained as
an oil (149 mg, 73%). [α]2D5 = –6.3 (c = 1.0, CHCl3). 1H NMR: δ =
1.04 (d, J = 6.4 Hz, 3 H, CH3–CH), 1.37 (s, 3 H, Me), 1.46 (s, 3
H, Me), 2.83 (m, 1 H, CH–CH3), 3.25–3.61 (m, 4 H, CH2–OH,
CH2–N), 4.0 (dd, J = 5.0, 8.7 Hz, 1 H, 6-H), 4.16 (dd, J = 6.3,
8.6 Hz, 1 H, 6Ј-H), 4.23 (dd, J = 6.4, 7.3 Hz, 1 H, 4-H), 4.47–4.53
(m, 1 H, 5-H), 4.89 (dd, J = 2.6, 6.3 Hz, 1 H, 3-H), 5.12 (d, J =
2.5 Hz, 1 H, 2-H) ppm. 13C NMR: δ = 16.8, 25.0, 26.7, 43.6, 53.7,
65.4, 66.7, 72.9, 73.4, 85.2, 100.5, 109.2, 161.3 ppm. MS (API-ES
positive): m/z = 274.0 [M + 1]+. C13H23NO5 (273.17): calcd. C
57.13, H 8.48, N 5.12; found C 56.99, H 8.54, N 5.19.
1,4-Anhydro-5,6-O-isopropylidene-2-deoxy-1-C-methyl-D-arabino-
hex-1-enitol (5): A solution of the glycosyl chloride 4[39] (2.5 g,
8.9 mmol) in dry THF (25 mL) was cooled to 0 °C and then treated
with MeLi (16.7 mL, 1.6  in Et2O, 26.7 mmol, 3 equiv.). After stir-
ring for 2 h, once TLC analyses showed total disappearance of the
starting material, the reaction mixture was quenched with a satu-
rated aqueous solution of NH4Cl. After partitioning between water
and diethyl ether, the organic layer was dried with MgSO4 and
concentrated. The residue was purified by flash chromatography
(hexane/EtOAc, 90:10) to give the C-1 glycal 5 (1.0 g, 60%): [α]2D5
= –4.5 (c = 0.42, in CHCl3). 1H NMR: δ = 6.1 (7.4 Hz, 1 H, 4-H),
4.53 (dt, J = 7.4, 6.0 Hz, 1 H, 5-H), 4.68 (m, 1 H, 3-H), 4.69 (br.
s, 1 H, 2-H) ppm. 13C NMR: δ = 25. 3, 25.8, 27.4, 67.5, 74.0, 74.6,
86.3, 100.6, 105.9, 169.0 ppm. MS: m/z = 201.0 [M + 1]+, 200.0
[M]+.
Compound 13: Oxirane 6 (150 mg, 0.75 mmol), Ph3P (198 mg,
0.75 mmol), Pd(OAc)2 (16 mg, 0.07 mmol), and (R)-(+)-α-methyl-
benzylamine (124 µL, 0.97 mmol) were treated according to the
General Procedure. After purification (hexane/EtOAc, 10:90), com-
pound 13 (149 mg, 73%) was obtained as an oil. [α]2D5 = +11.3 (c
= 1.5, CHCl3). 1H NMR: δ = 1.35 (d, J = 6.6 Hz, 3 H, CH3–), 1.38
(s, 3 H, Me), 1.45 (s, 3 H, Me), 3.19 (s, 2 H, CH2N), 3.80 (q, J =
6.6 Hz, 1 H, CH–NH), 3.99 (dd, J = 5.3, 8.5 Hz, 1 H, 6-H), 4.13
(m, 2 H, 4-H, 6Ј-H), 4.48 (m, 1 H, 5-H), 4.87 (dd, J = 2.6, 6.5 Hz,
1 H, 3-H), 5.05 (d, J = 2.6 Hz, 1 H, 2-H), 7–32 (m, 5 H,
Harom) ppm. MS (API-ES positive): m/z = 320.0 [M + 1]+.
C18H25NO4 (319.39): calcd. C 67.69, H 7.89, N 4.39; found C
67.51, H 7.67, N 4.23.
2,5:3,4-Dianhydro-1-deoxy-D-manno-hept-1-enitol (6): A solution of
Br2 (1.4 mL, 27.5 mmol) in CH2Cl2 (5 mL) was added dropwise to
a cooled (0 °C) solution of C-1 methyl glycal 5 (5.0 g, 25 mmol) in
CH2Cl2 (250 mL) containing Et3N (50 mL). The mixture was Compound 14: Oxirane 6 (150 mg, 0.75 mmol), Ph3P (198 mg,
stirred at room temperature overnight, after which the reaction
mixture was diluted with CH2Cl2 (300 mL) and washed with aque-
ous sodium thiosulfate (10%) and water. The organic layer was
then dried and concentrated and the residue was purified by flash
chromatography (hexane/EtOAc, 95:5) to give oxirane 6 (3.5 g,
0.75 mmol), Pd(OAc)2 (16 mg, 0.07 mmol), and morpholine
(85 µL, 0.97 mmol) were treated according to the General Pro-
cedure. After purification by flash chromatography (hexane/EtOAc,
30:70), compound 14 was obtained as a colorless oil (173 mg,
81%): [α]2D5 = –30.5 (c = 1.0, CHCl3). H NMR: δ = 1.37 (s, 3 H,
1
1
70%); m.p. 41–42 °C. [α]2D5 = + 56.2 (c =1.0, CHCl3). H NMR: δ
Me), 1.45 (s, 3 H, Me), 2.49 (t, J = 4.6 Hz, 4 H, 2ϫCH2N), 3.10
(m, 2 H, CH2N), 3.71 (t, J = 4.6 Hz, 4 H, 2ϫCH2O), 4.05 (dd, J
= 1.32 (s, 3 H, Me), 1.40 (s, 3 H, Me), 3.87–4.16 (m, 6 H), 4.32 (d,
J = 2.0 Hz, 1 H, 1-H), 4.44 (d, J = 2.0 Hz, 1 H, 1Ј-H) ppm. 13C = 4.8, 8.6 Hz, 1 H, 6-H), 4.14–4.22 (m, 2 H, 4-H, 6Ј-H), 4.45–4.52
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(m, 1 H, 5-H), 4.92 (dd, J = 2.6, 6.3 Hz, 1 H, 3-H), 5.14 (d, J =
Compound 27: Oxirane 6 (90 mg, 0.45 mmol), Pd(PPh3)4 (26 mg,
2.8 Hz, 1 H, 2-H) ppm. 13C NMR: δ = 25.1, 26.8, 53.5 (ϫ2), 55.4, 0.02 mmol), benzaldehyde (17) (68 µL, 0.67 mmol), and Et2Zn
66.7 (ϫ2), 67.1, 72.9, 73.4, 85.1, 102.4, 109.2, 159.3 ppm. MS (API-
ES positive): m/z = 286.4 [M + 1]+. C14H23NO5 (285,33): calcd. C
58.93, H 8.12, N 4.91; found C 58.79, H 7.97, N 4.81.
(1.0  solution in hexanes, 1.1 mL, 1.12 mmol) were treated accord-
ing to the General Procedure. Purification was carried out by flash
chromatography (hexane/EtOAc/Et3N, 35:60:5) to yield compound
27 as an inseparable 1.5:1 mixture of diastereomers (118 mg, 83%).
1H NMR (selected peaks for the major isomer): δ = 7.32 (m, 5 H),
5.00 (d, J = 2.9 Hz, 1 H, 2-H), 4.92 (m, 1 H), 4.81 (m, 1 H), 4.47
(m, 1 H), 4.20 (t, J = 7.0 Hz, 1 H), 4.12 (dd, J = 8.5, 6.4 Hz, 1 H),
3.99 (dd, J = 8.7, 5.1 Hz, 1 H), 2.56 (m, 2 H), 1.42 (s, 3 H), 1.34
(s, 3 H) ppm. 13C NMR (selected peaks for the major isomer): δ =
158.9, 131.0, 127.2, 126.3, 124.3, 107.8, 100.1, 83.8, 72.3, 71.7, 70.0,
65.3, 36.9, 25.4, 23.8 ppm. MS (API-ES positive): m/z = 307.3 [M
+ 1]+. C17H22O5 (306,35): calcd. C 66.65, H 7.24; found C 66.52,
H 7.17.
Compound 15: Oxirane 6 (150 mg, 0.75 mmol), Ph3P (198 mg,
0.75 mmol), Pd(OAc)2 (16 mg, 0.07 mmol), and 1-(4-meth-
oxyphenyl)piperazine (186 mg, 0.97 mmol) were treated according
to the General Procedure. After purification by flash chromatog-
raphy (hexane/EtOAc, 30:70), compound 15 was obtained as a col-
orless oil (251 mg, 86%): [α]2D5 = –30.7 (c = 2.7, CHCl3). 1H NMR:
δ = 1.38 (br. s, 3 H, Me), 1.46 (s, 3 H, Me), 2.71 (br. s, 4 H, CH2–
CH2), 3.10 (s, 4 H, CH2–CH2), 3.18 (d, J = 3.5 Hz, 2 H, CH2N),
3.85 (s, 3 H, OMe), 4.0 (dd, J = 4.7, 8.6 Hz, 1 H, 6-H), 4.21 (dd,
J = 6.1, 8.5 Hz, 1 H, 6Ј-H), 4.22 (dd, J = 6.4, 9.5 Hz, 1 H, 4-H),
4.47–4.54 (m, 1 H, 5-H), 4.93 (dd, J = 2.6, 6.4 Hz, 1 H, 3-H), 5.16
(d, J = 2.6 Hz, 1 H, 2-H), 6.8–7.02 (m, 4 H, Harom) ppm. 13C NMR:
δ = 25.6, 27.3, 50.7, 53.8, 55.6, 67.5, 73.4, 73.9, 85.5, 102.7, 109.6,
111.5, 118.6, 121.3, 123.3, 141.1, 125.6, 160.2 ppm. MS (API-ES
positive): m/z = 391.2 [M + 1]+. C21H30N2O5 (390.21): calcd. C
64.59, H 7.74, N 7.17; found C 64.49, H 7.80, N 6.98.
Compound 28: Oxirane 6 (90 mg, 0.45 mmol), Pd(PPh3)4 (26 mg,
0.02 mmol), 2-methoxycinnamaldehyde (20, 109 mg, 0.67 mmol),
and Et2Zn (1.0  solution in hexanes, 1.1 mL, 1.12 mmol) were
treated according to the General Procedure. Purification was car-
ried out by flash chromatography (hexane/EtOAc/Et3N, 25:70:5) to
yield compound 28 as an inseparable 1.5:1 mixture of dia-
1
stereomers (114 mg, 70%). H NMR (selected peaks for the major
Compound 16: Oxirane 6 (150 mg, 0.75 mmol), Ph3P (198 mg,
0.75 mmol), Pd(OAc)2 (16 mg, 0.07 mmol), and 4-benzylpiperidine
(170 µL, 0.97 mmol) were treated according to the General Pro-
cedure. After purification by flash chromatography (hexane/EtOAc,
30:70), compound 16 was obtained as a colorless oil (251 mg,
isomer): δ = 7.40 (m, 1 H), 7.12 (d, J = 7.5 Hz, 1 H), 6.88 (m, 3
H), 6.20 (dd, J = 6.8, 6.6 Hz, 1 H), 5.06 (s, 1 H), 4.86 (m, 1 H),
4.56 (m, 1 H), 4.25 (m, 1 H), 4.15 (m, 1 H), 4.04 (m, 1 H), 3.82 (s,
3 H), 2.50 (t, J = 6.0 Hz, 2 H), 1.45 (s, 3 H), 1.37 (s, 3 H) ppm.
13C NMR (selected peaks for the major isomer): δ = 160.6, 157.1,
132.1, 131.9, 129.2, 127.4, 125.9, 121.1, 111.2, 109.5, 101.9, 85.6,
74.1, 73.5, 71.0, 67.1, 55.8, 36.8, 27.2, 25.5 ppm. MS (API-ES posi-
tive): m/z = 363.4 [M + 1]+. C20H26O6 (362,41): calcd. C 66.28, H
7.23; found C 66.31, H 7.09.
81%): [α]2D5 = –29.9 (c = 0.6, CHCl3). H NMR: δ = 1.33 (m, 2 H,
1
CH2–), 1.38 (s, 3 H, Me), 1.45 (s, 3 H, Me), 1.55 (m, 3 H, CH–
and CH2–), 2.0 (m, 2 H, CH2–), 2.52 (d, J = 6.8 Hz, 2 H, CH2N),
2.88 (m, 2 H, CH2–N), 3.07 (m, 2 H, CH2N), 4.04 (dd, J = 4.9,
8.7 Hz, 1 H, 6-H), 4.16 (dd, J = 6.1, 8.5 Hz, 1 H, 6Ј-H), 4.20 (dd,
J = 6.3, 8.3 Hz, 1 H, 4-H), 4.48 (ddd, J = 5.0, 6.1, 8.3 Hz, 1 H, 5-
H), 4.90 (dd, J = 2.5, 6.3 Hz, 1 H, 3-H), 5.10 (d, J = 2.5 Hz, 1 H,
2-H), 7.26 (m, 5 H, Harom) ppm. 13C NMR: δ = 25.2, 26.8, 31.9
(ϫ2), 37.6, 43.1, 53.7, 54.0, 55.4, 67.1, 72.9, 73.5, 85.1, 101.9, 109.2,
125.7, 128.1, 129.1, 140.6, 160.2 ppm. MS (API-ES positive): m/z
= 374.0 [M + 1]+. C22H31NO4 (373,48): calcd. C 70.75, H 8.37, N
3.75; found C 70.69, H 8.28, N 3.91.
Compound 32: Oxirane 6 (90 mg, 0.45 mmol), Pd(PPh3)4 (26 mg,
0.02 mmol), (R)-citronellal (21, 102 µL, 0.67 mmol), and Et2Zn
(1.0  solution in hexanes, 1.1 mL, 1.12 mmol) were treated accord-
ing to the General Procedure. Purification was carried out by flash
chromatography (hexane/EtOAc/Et3N, 15:80:5) to yield compound
32 as separable mixture of diastereomers (3:1, 114 mg, 70%).
Major Isomer: M.p. 54–55 °C. [α]2D5 = –268.0 (c = 0.9, CHCl3). H
1
NMR: δ = 5.09 (m, 1 H), 5.02 (d, J = 2.6 Hz, 1 H), 4.50 (ddd, J =
7.0, 6.3, 5.1 Hz, 1 H), 4.23 (t, J = 7.0 Hz, 1 H), 4.16 (dd, J = 8.6,
6.3 Hz, 1 H), 4.02 (dd, J = 8.6, 5.1 Hz, 1 H), 3.90 (m, 1 H), 2.35
(dd, J = 14.8, 3.2 Hz, 1 H), 2.22 (dd, J = 14.8, 8.5 Hz, 1 H), 1.92
(m, 3 H), 1.68 (s, 3 H), 1.59 (s, 3 H), 1.45 (s, 3 H), 1.37 (s, 3 H),
1.36 (m, 2 H), 1.22 (m, 4 H), 0.91 (d, J = 6.4 Hz, 3 H) ppm. 13C
NMR: δ = 161.1, 131.4, 124.7, 109.2, 101.1, 85.2, 73.7, 73.1, 67.3,
66.8, 44.6, 36.7, 36.5, 29.3, 26.8, 25.7, 25.3, 25.2, 20.1, 17.7 ppm.
MS (API-ES positive): m/z = 353.2 [M + 1]+. C20H34O5 (352,24):
calcd. C 67.76, H 9.76; found C 67.58, H 9.83.
Compound 18: A solution of the oxirane 6 (150 mg, 0.75 mmol) in
dry THF (5 mL) was cooled to –78 °C and then treated with
Pd(PPh3)4 (30 mg, 0.02 mmol) and SmI2 (22.5 mL, 0.1  in THF,
2.25 mmol, 3 equiv.). After stirring for 2 h, as soon as TLC analyses
showed total disappearance of the starting material, the reaction
mixture was quenched with aqueous K2CO3. After partitioning be-
tween water and diethyl ether, the organic layer was dried with
MgSO4 and concentrated. The residue was purified by flash
chromatography (hexane/EtOAc/Et3N, 35:60:5) to give the highly
1
unstable compound 18 (97.8 mg, 40%). H NMR: δ = 5.20 (m, 1
Minor Isomer: [α]2D5 = –55.0 (c = 0.5, CHCl3). H NMR: δ = 5.10
1
H, 2-H), 4.85 (dd, J = 6.0, 2.9 Hz, 1 H, 3-H), 4.40 (m, 1 H, 4-H),
4.19 (dd, J = 8.3, 6.4 Hz, 1 H, 6Ј-H), 4.09 (m, 1 H, 5-H), 3.97 (dd,
J = 8.2, 4.9 Hz, 1 H, 6-H), 3.72 (s, 2 H, CH2I), 1.52 (s, 3 H, Me),
1.46 (s, 3 H, Me) ppm. 13C NMR: δ = 159.4, 109.4, 101.3, 85.6,
74.0, 72.8, 66.9, 26.8, 25.2, 6.0 ppm.
(m, 1 H), 5.02 (d, J = 2.7 Hz, 1 H), 4.92 (dd, J = 6.8, 2.7 Hz, 1 H),
4.49 (ddd, J = 4.9, J = 7.7, 6.3 Hz, 1 H), 4.23 (dd, J = 7.7, 6.5 Hz,
1 H), 4.16 (dd, J = 8.5, 6.3 Hz, 1 H), 4.02 (dd, J = 8.5, 4.9 Hz, 1
H), 3.90 (m, 1 H), 2.36 (dd, J = 15.0, 4.0 Hz, 1 H), 2.28 (dd, J =
15.0, 8.2 Hz, 1 H), 1.92 (m, 3 H), 1.67 (s, 3 H), 1.60 (s, 3 H), 1.46
(s, 3 H), 1.38 (s, 3 H), 1.22 (m, 4 H), 0.91 (d, J = 6.4 Hz, 3 H) ppm.
13C NMR: δ = 161.1, 131.4, 124.7, 109.3, 101.0, 85.2, 73.7, 73.1,
67.1, 66.9, 44.4, 37.8, 36.9, 28.9, 26.8, 25.7, 25.4, 25.2, 19.1,
17.6 ppm. MS (API-ES positive): m/z = 353.2 [M + 1]+. C20H34O5
(352,24): calcd. C 67.76, H 9.76; found C 67.59, H 9.51.
General Procedure for Pd0/Et2Zn-Catalyzed Reactions between Ep-
oxide 6 and Electrophiles: A solution of epoxide 6 in dry THF
(6 mLmmol–1) under argon was treated with Pd(PPh3)4 (0.2 equiv.),
the corresponding electrophile (1.3 equiv.), and Et2Zn. The re-
sulting mixture was stirred at room temperature under argon. After
the starting materials had been consumed (TLC), the mixture was
diluted with EtOAc and washed with aqueous NaHCO3 and brine.
The organic layer was dried, concentrated, and subjected to silica
gel column chromatography.
Compound 30: Oxirane 6 (90 mg, 0.45 mmol), Pd(PPh3)4 (26 mg,
0.02 mmol), isobutyraldehyde (22, 62 µL, 0.67 mmol), and Et2Zn
(1.1 mL, solution 1.0  in hexanes, 1.12 mmol) were treated accord-
4632
www.eurjoc.org
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 4627–4636

Furanosyl C-1 Glycals from a Furanosyl 2,3-Anhydro-exo-glycal
ing to the General Procedure. Purification was carried out by flash
chromatography (hexane/EtOAc/Et3N, 25:70:5) to yield compound
30 as an inseparable mixture of diastereomers (2.5:1, 77 mg, 63%).
1H NMR (selected peaks for the major isomer): δ = 5.01 (d, J =
2.4 Hz, 1 H), 4.85 (m, 1 H), 4.50 (dt, J = 11.6, 6.2 Hz, 1 H), 4.23
(dd, J = 13.6, 6.6 Hz, 1 H), 4.11 (dd, J = 8.7, 6.4 Hz, 1 H), 4.01
(ddd, J = 6.4, 5.1, 3.4 Hz, 1 H), 3.59 (m, 1 H), 2.29 (m, 2 H), 1.67
(m, 1 H), 1.45 (s, 3 H), 1.37 (s, 3 H), 0.92 (s, 6 H) ppm. 13C NMR
(selected peaks for the major isomer): δ = 161.8, 109.5, 101.3, 85.5,
74.2, 74.0, 73.4, 67.1, 33.8, 33.5, 27.1, 25.5, 18.9, 17.8 ppm. MS
(API-ES positive): m/z = 273.2 [M + 1]+. C14H24O5 (272.16): calcd.
C 61.74, H 8.88; found C 61.59, H 8.67.
H), 4.20 (t, J = 7.0 Hz, 1 H), 4.12 (dd, J = 8.5, 6.4 Hz, 1 H), 3.99
(dd, J = 8.7, 5.1 Hz, 1 H), 2.56 (m, 2 H), 1.42 (s, 3 H), 1.34 (s, 3
H) ppm. 13C NMR: δ = 158.9, 131.0, 127.2, 126.3, 124.3, 107.8,
100.1, 83.8, 72.3, 71.7, 70.0, 65.3, 36.9, 25.4, 23.8 ppm. MS (API-
ES positive): m/z = 383.2 [M + H]+. C23H26O5 (382.17): calcd. C
72.23, H 6.85; found C 71.98, H 6.69.
Compound 35: Oxirane 6 (90 mg, 0.45 mmol), Pd(PPh3)4 (26 mg,
0.02 mmol), γ-butyrolactone (26) (1.5 equiv., 110 µLmg,
0.67 mmol), and Et2Zn (1.0  solution in hexanes, 1.1 mL,
1.12 mmol) were treated according to the General Procedure. Puri-
fication was carried out by flash chromatography (hexane/EtOAc/
Et3N, 70:25:5) to yield compound 35 (28 mg, 23%). 1H NMR: δ =
Compounds 31 and 32: Oxirane 9 (90 mg, 0.45 mmol), Pd(PPh3)4 6.26 (d, J = 3.2 Hz, 1 H), 6.04 (d, J = 3.2 Hz, 1 H), 5.04 (t, J =
(26 mg, 0.02 mmol), aldehyde 26[64] (174 mg, 0.67 mmol), and
Et2Zn (1.0  solution in hexanes, 1.1 mL, 1.12 mmol) were treated
according to the General Procedure. Purification was carried out
by flash chromatography (hexane/EtOAc/Et3N, 25:70:5) to yield
compound 32 (29 mg, 14%), followed by compound 31 (88 mg,
43%).
7.6 Hz, 1 H), 4.20 (dd, J = 8.3, 6.4, Hz, 1 H), 4.08 (m, 3 H), 3.74
(ddd, J = 15.1, 8.3, 6.6 Hz, 1 H), 3.73 (ddd, J = 15.1, 8.3, 7.1 Hz,
1 H), 2.90 (dd, J = 14.9, 6.6 Hz, 1 H), 2.76 (dd, J = 14.9, 6.6 Hz,
1 H), 2.00 (m, 1 H), 2.05 (br. s, 1 H), 1.78 (m, 1 H), 1.45 (s, 3 H),
1.87 (s, 3 H), 1.49 (s, 3 H), 1.44 (m, 3 H) ppm. 13C NMR: δ = 153.8
(ϫ2), 109.7, 109.4, 107.2 (ϫ2), 71.4, 68.0, 67.8, 34.4, 31.1, 26.4,
26.0, 25.6 ppm. MS (API-ES positive): m/z = 282.3 [M + Na]+.
C14H20O5 (268.30): calcd. C 62.67, H 7.51; found C 62.47, H 7.69.
1
Compound 31: H NMR: δ = 5.53 (d, J = 4.9 Hz, 1 H), 5.08 (d, J
= 2.6 Hz, 1 H), 4.89 (dd, J = 6.2, 2.6 Hz, 1 H), 4.62 (dd, J = 8.1,
2.3 Hz, 1 H), 4.48 (m, 2 H), 4.31 (dd, J = 5.1, 2.3 Hz, 1 H), 4.23 General Procedure for the Preparation of Alkenylstannanes 39 and
(t, J = 6.5 Hz, 1 H), 4.14 (dd, J = 8.5, 6.2 Hz, 1 H), 3.99 (m, 2 H),
3.58 (dd, J = 8.2, 1.6 Hz, 1 H), 2.76 (dd, J = 15.2, 2.6 Hz, 1 H),
2.30 (dd, J = 15.2, 9.2 Hz, 1 H), 1.51 (s, 3 H), 1.46 (s, 3 H), 1.44
40: Triethylborane (0.1 mol equiv. of a hexane solution) was added
under argon at 0 °C to a stirred solution of the corresponding ter-
minal
alkyne
(1.0 mol equiv.)
and
tributyltin
hydride
(s, 3 H), 1.37 (s, 3 H), 1.36 (s, 3 H), 1.32 (s, 3 H) ppm. 13C NMR: (1.1 mol equiv.) in toluene (10 mLmmol–1). The reaction mixture
δ = 161.1, 109.3, 108.6, 101.1, 96.5, 85.3, 73.7, 73.1, 70.8, 70.7 (ϫ3),
69.7, 68.4, 66.9, 33.0, 26.9, 26.1, 26.0, 25.3, 25.0, 24.4 ppm. MS
(API-ES positive): m/z = 459.2 [M + 1]+. C22H34O10 (458.21): calcd.
C 57.63, H 7.47; found C 57.52, H 7.67.
was stirred for 24 h and was then concentrated under reduced pres-
sure. The residue was purified by flash chromatography.
Compound 39:[65] This compound was prepared from 1,2:5,6-di-O-
isopropylidene-3-O-propargyl-α--gluco-furanose[66] (700 mg, 2.34
1
Compound 32: H NMR: δ = 5.55 (d, J = 5.4 Hz, 1 H), 4.64 (dd, mmol). Workup entailed concentration of the mixture and subjec-
J = 8.0, 2.2 Hz, 1 H), 4.49 (m, 2 H), 4.41 (dd, J = 8.0, 2.2 Hz, 1 tion to chromatography (hexane/EtOAc, 98:2) to give 39 (mainly
1
H), 4.33 (m, 3 H), 4.26 (br. s, 1 H), 4.10 (m, 2 H), 3.99 (m, 2 H),
3.82 (dd, J = 9.0, 2.2 Hz, 1 H), 1.53 (s, 3 H), 1.45 (s, 3 H), 1.42 (s,
as the E isomer, 1.3 g, 95%). H NMR (200 MHz): δ = 6.26 (dt, J
= 1.2, J = 19.0 Hz, 1 H), 6.02 (dt, J = 5.0, J = 19.0 Hz, 1 H), 5.90
3 H), 1.36 (s, 6 H), 1.32 (s, 3 H) ppm. 13C NMR: δ = 160.2, 110.5, (d, J = 3.8 Hz, 1 H), 4.56 (d, J = 3.8 Hz, 1 H), 4.34 (m, 1 H), 4.05
109.2, 108.5, 96.4, 84.6 (ϫ2), 76.0, 73.4, 70.7 (ϫ3), 70.0, 68.3, 67.6, (m, 6 H), 1.51 (s, 3 H), 1.45 (s, 3 H), 1.44 (s, 3 H), 1.37 (s, 3 H),
52.5, 26.7, 25.9, 25.5, 25.1, 24.7, 24.5 ppm. MS (API-ES positive):
m/z = 459.2 [M + 1]+. C22H34O10 (458.21): calcd. C 57.63, H 7.47;
found C 57.45, H 7.31.
1.33 (s, 3 H), 1.29 (m, 6 H), 0.92 (m, 6 H), 0.90 (t, J = 7.2 Hz, 9
H) ppm. 13C NMR: δ = 144.0, 131.8, 111.8, 109.9, 105.3, 82.8, 81.3,
74.0, 72.6, 67.3, 29.15 (ϫ3), 27.3 (ϫ3), 26.9, 26.3, 25.5, 13.8 (ϫ3),
9.5 (ϫ3) ppm.
Compound 33: Oxirane 6 (90 mg, 0.45 mmol), Pd(PPh3)4 (26 mg,
0.02 mmol), isobutyl methyl ketone (24, 1.5 equiv., 110 µL,
0.67 mmol), and Et2Zn (1.0  solution in hexanes, 1.1 mL,
1.12 mmol) were treated according to the General Procedure. Puri-
fication was carried out by flash chromatography (hexane/EtOAc/
Et3N, 25:70:5) to yield compound 33 as an inseparable mixture of
diastereomers (2.5:1) (65 mg, 48%). 1H NMR (selected peaks for
the major isomer): δ = 5.00 (d, J = 2.7 Hz, 1 H), 4.88 (m, 1 H),
4.47 (ddd, J = 7.6, 6.4, 5.0 Hz, 1 H), 4.20 (m, 1 H), 4.14 (dd, J =
8.6, 6.4 Hz, 1 H), 3.99 (dd, J = 8.6, 5.0 Hz, 1 H), 2.34 (m, 2 H),
2.06 (br. s, 1 H), 2.05 (br. s, 1 H), 1.78 (m, 1 H), 1.45 (s, 3 H), 1.41–
1.37 (m, 2 H), 1.37 (s, 3 H), 1.21 (s, 3 H), 0.94 (m, 6 H) ppm. 13C
NMR (selected peaks for the major isomer): δ = 160.7, 109.3,
102.4, 85.3, 73.4, 73.0, 72.3, 66.8, 50.3, 41.1, 27.1, 26.8, 25.1, 24.8,
24.5, 24.2 ppm. MS (API-ES positive): m/z = 323.3 [M + Na]+.
C16H28O5 (300.19): calcd. C 63.97, H 9.40; found C 63.81, H 9.43.
Compound 40: This compound was prepared from N-propargylind-
ole[67] (600 mg, 3.86 mmol). Purification was carried out by flash
chromatography (hexane) to yield the alkenylstannane 39 (1.32 g,
1
76%, along with the Z isomer, 320 mg, 19%). H NMR: δ = 7.72
(d, J = 7.8 Hz, 1 H), 7.40 (d, J = 8.1 Hz, 1 H), 7.27 (dd, J = 8.1,
6.9 Hz, 1 H), 7.19 (dd, J = 7.8, 6.9 Hz, 1 H), 7.16 (d, J = 3.0 Hz,
1 H), 6.60 (d, J = 3.0 Hz, 1 H), 4.83 (d, J = 1.8 Hz, 2 H), 6.17 (m,
2 H), 1.54 (m, 6 H), 1.37 (m, 6 H), 0.96 (m, 15 H) ppm. 13C NMR:
δ = 142.5, 136.1, 131.6, 128.6, 127.9, 121.3, 120.8, 119.2, 109.8,
101.1, 52.0, 29.0 (ϫ3), 27.2 (ϫ3), 13.7 (ϫ3), 9.4 (ϫ3) ppm.
Compound 41:
A
solution of N-propargylindole (600 mg,
3.86 mmol) in dry toluene (60 mL) was cooled to 0 °C and treated
under argon with Pd2(dba)2 (80 mg, 0.015 mmol), PPh3 (102 mg,
0.36 mmol), and HSnBu3 (2 mL, 7.8 mmol). The resulting mixture
was stirred for 12 h. Workup involved concentration of the mixture
and subjection to chromatography (hexane/EtOAc, 98:2) to give 41
(863 mg, 50%), along with terminal stannane 40 (690 mg, 40%).
For 41: 1H NMR: δ = 7.66 (d, J = 7.8 Hz, 1 H), 7.32 (d, J = 7.8 Hz,
1 H), 7.21 (m, 1 H), 7.13 (m, 1 H), 7.08 (d, J = 3.3 Hz, 1 H), 6.55
(d, J = 3.3 Hz, 1 H), 5.67 (q, J = 1.8 Hz, 1 H), 5.35 (q, J = 1.8 Hz,
1 H), 4.89 (t, J = 1.8 Hz, 2 H), 1.42 (m, 6 H), 1.29 (m, 6 H), 0.90
(t, J = 7.5 Hz, 9 H), 0.81 (t, J = 8.1 Hz, 6 H) ppm.
Compound 34: Oxirane 6 (90 mg, 0.45 mmol), Pd(PPh3)4 (26 mg,
0.02 mmol), benzophenone (25, 1.5 equiv., 123 mg, 0.67 mmol),
and Et2Zn (1.0  solution in hexanes, 1.1 mL, 1.12 mmol) were
treated according to the General Procedure. Purification was car-
ried out by flash chromatography (hexane/EtOAc/Et3N, 30:65:5) to
1
yield compound 34 (117 mg, 68%). H NMR: δ = 7.32 (m, 10 H),
5.02 (d, J = 2.9 Hz, 1 H), 4.92 (m, 1 H), 4.81 (m, 1 H), 4.47 (m, 1
Eur. J. Org. Chem. 2009, 4627–4636
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4633

A. M. Gómez, J. C. López et al.
FULL PAPER
General Procedure for Reactions between the Vinyloxirane and
Alkenylstannanes: A solution of epoxide 6 in DMF (5 mLmmol–1)
was cooled to 0 °C and treated under argon with H2O (10 equiv.),
the corresponding vinylstannane (1.5 equiv.), and Pd(CH3CN)2Cl2
(0.05 equiv.). The resulting mixture was stirred at room temperature
under argon. After the starting materials had been consumed
(TLC), the mixture was diluted with EtOAc and washed with brine.
The organic layer was dried, concentrated, and subjected to silica
gel column chromatography.
Et3N, 70:25:5) to yield compounds 44 (68 mg, 55%) and 45 (15 mg,
12%).
1
Compound 44: H NMR: δ = 5.89 (d, J = 3.7 Hz, 1 H), 5.71 (m, 2
H), 4.95 (s, 1 H), 4.90 (br. s, 1 H), 4.54 (d, J = 3.7 Hz, 1 H), 4.48
(m, 1 H), 4.40–3.92 (m, 10 H), 2.93 (d, J = 3.0 Hz, 2 H), 1.86 (d,
J = 4.6 Hz, 1 H), 1.51 (s, 3 H), 1.44 (s, 6 H), 1.37 (s, 6 H), 1.33 (s,
3 H) ppm. 13C NMR (75 MHz): δ = 162.2, 129.0, 127.8, 111.7,
109.2, 108.9, 105.2, 99.2, 85.1, 82.8, 81.1, 73.7, 72.9, 72.4, 70.6,
67.2, 66.9, 31.2, 27.8, 26.8 (ϫ3), 26.2, 25.4, 25.2 ppm. MS (API-
ES positive): m/z = 498.1 [M]+. C25H38O10 (498.25): calcd. C 60.23,
H 7.62; found C 60.29, H 7.47.
Compounds 36 and 37: Oxirane 6 (50 mg, 0.25 mmol), Pd(CH3CN)2-
Cl2 (3 mg, 0.01 mmol), and tetravinyltin (68 µL, 0.37 mmol) were
treated according to the General Procedure. Purification was car-
ried out by flash chromatography (hexane/EtOAc/Et3N, 70:25:5) to
yield compounds 36 (29 mg, 51%) and 37 (9 mg, 15%).
1
Compound 45: H NMR: δ = 5.89 (d, J = 3.7 Hz, 1 H), 5.76 (d, J
= 8.3 Hz, 1 H), 5.72 (d, J = 8.3 Hz, 1 H), 4.55 (d, J = 3.7 Hz, 1
H), 4.40–3.93 (m, 14 H), 3.38 (br. s, 1 H), 2.52 (d, J = 4.0 Hz, 1
H), 1.51 (s, 3 H), 1.45 (s, 3 H), 1.44 (s, 3 H), 1.38 (s, 3 H), 1.37 (s,
3 H), 1.33 (s, 3 H) ppm. 13C NMR (75 MHz): δ = 161.9, 129.6,
129.2, 111.8, 109.7, 109.0, 105.2, 82.8, 82.5, 81.5, 81.1, 77.1, 75.9,
73.4, 72.3, 70.3, 67.5, 67.4, 52.9, 26.8 (ϫ3), 26.2, 25.4, 25.1 ppm.
MS (API-ES positive): m/z = 498.1 [M]+. C25H38O10 (498.25):
calcd. C 60.23, H 7.62; found C 60.17, H 7.51.
Compound 36: 1H NMR: δ = 5.84 (m, 1 H), 5.13 (m, 2 H), 4.95 (s,
1 H), 4.90 (br. s, 1 H), 4.49 (ddd, J = 8.1, 6.3, 5.1 Hz, 1 H), 4.17
(m, 2 H), 4.02 (dd, J = 8.4, 5.1 Hz, 1 H), 2.91 (m, 2 H), 1.82 (s, 1
H), 1.46 (s, 3 H), 1.39 (s, 3 H) ppm. 13C NMR: δ = 162.5, 132.4,
117.7, 109.2, 99.2, 85.1, 73.8, 73.0, 67.0, 32.7, 26.8, 25.2 ppm. MS
(API-ES positive): m/z = 227.0 [M + H]+. C12H18O4 (226.12): calcd.
C 63.70, H 8.02; found C 63.59, H 8.15.
Compounds 46 and 47: Oxirane 6 (50 mg, 0.25 mmol), Pd(CH3CN)2-
Cl2 (3 mg, 0.01 mmol), and the alkenylstannane 40 (167 mg,
0.37 mmol) were treated according to the General Procedure. Puri-
fication was carried out by flash chromatography (hexane/EtOAc/
Et3N, 70:25:5) to yield compounds 46 (54 mg, 61%) and 47 (17 mg,
20%).
1
Compound 37: H NMR: δ = 5.78 (ddd, J = 17.1, 10.0, 6.8 Hz, 1
H), 5.27 (dd, J = 17.1, 1.5 Hz, 1 H), 5.20 (dd, J = 10.0, 1.2 Hz, 1
H), 4.40 (s, 1 H), 4.34 (ddd, J = 8.8, 6.1, 4.9 Hz, 1 H), 4.26 (dd, J
= 6.8, 3.4 Hz, 1 H), 4.19 (dd, J = 8.8, 6.1 Hz, 1 H), 4.09 (dd, J =
8.6, 4.1 Hz, 1 H), 4.02 (dd, J = 8.8, 4.9 Hz, 1 H), 3.94 (s, 1 H), 3.36
(m, 1 H), 1.57 (s, 1 H), 1.44 (s, 3 H), 1.37 (s, 3 H) ppm. 13C NMR:
δ = 161.8, 134.7, 117.6, 109.7, 83.5, 82.6, 75.8, 73.4, 67.6, 54.1,
26.8, 25.2 ppm. MS (API-ES positive): m/z = 249.0 [M + H]+, 227.0
[M + H]+. C12H18O4 (226.12): calcd. C 63.70, H 8.02; found C
63.81, H 8.03.
1
Compound 46: H NMR: δ = 7.64 (d, J = 8.1 Hz, 1 H), 7.33 (d, J
= 7.9 Hz, 1 H), 7.21 (t, J = 8.1 Hz, 1 H), 7.13 (d, J = 8.1 Hz, 1 H),
7.10 (d, J = 2.7 Hz, 1 H), 6.52 (d, J = 2.7 Hz, 1 H), 5.79–5.54 (m,
2 H), 4.75–4.69 (s, 1 H), 4.88 (s, 1 H), 4.71 (d, J = 5.7 Hz, 2 H),
4.46 (ddd, J = 8.1, 6.3, 5.1 Hz, 1 H), 4.20–4.08 (m, 1 H), 4.15 (dd,
J = 8.7, 6.3 Hz, 1 H), 3.99 (dd, J = 8.7, 5.1 Hz, 1 H), 2.89 (d, J =
6.3 Hz, 2 H), 2.59 (d, J = 6.3 Hz, 1 H), 1.47 (s, 3 H), 1.39 (s, 3
H) ppm. 13C NMR: δ = 162.0, 133.0, 128.5, 127.6 (ϫ2), 127.3,
121.4, 120.9, 119.4, 109.5, 109.2, 101.3, 99.3, 85.1, 73.7, 72.9, 66.9,
47.9, 31.0, 26.8, 25.2 ppm. MS (API-ES positive): m/z = 356.0 [M
+ H]+. C21H25NO4 (355.42): calcd. C 70.96, H 7.09, N 3.94; found
C 71.03, H 7.15, N 3.89.
Compounds 42 and 43: Oxirane 6 (50 mg, 0.25 mmol), Pd(CH3CN)2-
Cl2 (3 mg, 0.01 mmol), and tributyl[(E)-styryl]tin 38 (145 mg,
0.37 mmol) were treated according to the General Procedure. Puri-
fication was carried out by flash chromatography (hexane/EtOAc/
Et3N, 70:25:5) to yield compounds 42 (33 mg, 44%) and 43 (14 mg,
19%).
Compound 42: 1H NMR: δ = 7.26–7.43 (m, 5 H), 6.15 (d, J =
15.8 Hz, 1 H), 6.14 (dd, J = 15.8, 7.0 Hz, 1 H), 5.00 (s, 1 H), 4.93
(br. s, 1 H), 4.43–4.32 (m, 1 H), 4.13–4.25 (m, 2 H), 4.04 (dd, J =
8.6, 5.1 Hz, 1 H), 3.08 (d, J = 7.0 Hz, 2 H), 2.58 (d, J = 3.8 Hz, 1
H), 1.48 (s, 3 H), 1.40 (s, 3 H) ppm. 13C NMR: δ = (CDCl3,
75 MHz) 162.5, 132.7, 128.5 (ϫ2), 128.2, 127.7, 127.3, 126.3, 109.7,
109.2, 99.3, 85.2, 73.8, 73.0, 67.5, 31.8, 26.8, 25.2 ppm. MS (API-
ES positive): m/z = 325.3 [M + Na]+. C18H22O4 (302.15): calcd. C
71.50, H 7.33; found C 71.37, H 7.23.
1
Compound 47: H NMR: δ = 7.65 (d, J = 8.0 Hz, 1 H), 7.31 (d, J
= 8.0 Hz, 1 H), 7.21 (dd, J = 6.9, 1.2 Hz, 1 H), 7.15 (dd, J = 10.3,
1.2 Hz, 1 H), 7.09 (d, J = 3.2 Hz, 1 H), 6.52 (d, J = 3.2 Hz, 1 H),
5.87 (ddt, J = 15.3, 5.7, 1.2 Hz, 1 H), 5.47 (ddt, J = 15.3, 6.9,
1.5 Hz, 1 H), 4.74 (d, J = 3.6 Hz, 1 H), 4.38 (s, 1 H), 4.31 (ddd, J
= 8.4, 6.0, 5.1 Hz, 1 H), 4.19–4.14 (m, 1 H), 4.03 (dd, J = 8.4,
4.2 Hz, 1 H), 3.99 (dd, J = 8.7, 4.8 Hz, 1 H), 3.89 (t, J = 1.5 Hz, 1
H), 3.32 (br. d, J = 5.4 Hz, 1 H), 2.55 (d, J = 3.9 Hz, 1 H), 1.43 (s,
3 H), 1.36 (s, 3 H) ppm. 13C NMR: δ = 161.6, 135.9, 129.4, 128.6,
128.5, 127.6, 121.5, 120.9, 119.4, 109.7, 109.5, 101.5, 83.7, 82.4,
75.7, 73.2, 67.4, 52.7, 47.8, 26.8, 25.1 ppm. MS (API-ES positive):
m/z = 356.0 [M + H]+. C21H25NO4 (355.42): calcd. C 70.96, H 7.09,
N 3.94; found C 70.87, H 7.01, N 3.79.
Compound 43: 1H NMR: δ = 7.25–7.42 (m, 5H), 5.78 (ddd, J =
17.1, 10.0, 6.8 Hz, 1 H), 5.27 (dd, J = 17.1, 1.5 Hz, 1 H), 5.20 (dd,
J = 10.0, 1.2 Hz, 1 H), 4.40 (s, 1 H), 4.34 (ddd, J = 8.8, 6.1, 4.1 Hz,
1 H), 4.26 (dd, J = 6.8, 3.4 Hz, 1 H), 4.19 (dd, J = 8.6, 6.1 Hz, 1
H), 4.09 (dd, J = 8.6, 4.1 Hz, 1 H), 4.02 (dd, J = 8.8, 4.9 Hz, 1 H),
3.94 (s, 1 H), 3.36 (m, 1 H), 1.57 (s, 1 H), 1.44 (s, 3 H), 1.37 (s, 3
H) ppm. 13C NMR: δ = 163.2, 136.3, 132.0, 128.7 (ϫ2), 128.6
(ϫ2), 128.4, 127.4, 109.9, 83.2, 82.2, 77.0, 73.6, 67.6, 48.8, 26.8,
25.2 ppm. MS (API-ES positive): m/z = 325.3 [M + Na]+.
C18H22O4 (302.15): calcd. C 71.50, H 7.33; found C 71.44, H 7.03.
Compounds 48 and 49: Oxirane 6 (50 mg, 0.25 mmol), Pd(CH3CN)2-
Cl2 (3 mg, 0.01 mmol), and the alkenylstannane 41 (167 mg,
0.37 mmol) were treated according to the General Procedure. Puri-
fication was carried out by flash chromatography (hexane/EtOAc/
Et3N, 70:25:5) to yield compounds 48 (44 mg, 50%) and 49 (16 mg,
20%).
1
Compounds 44 and 45: Oxirane 6 (50 mg, 0.25 mmol), Pd(CH3CN)2-
Cl2 (3 mg, 0.01 mmol), and the alkenylstannane 39 (221 mg,
0.37 mmol) were treated according to the General Procedure. Puri-
fication was carried out by flash chromatography (hexane/EtOAc/
Compound 48: H NMR: δ = 7.64 (d, J = 7.8 Hz, 1 H), 7.31 (d, J
= 8.3 Hz, 1 H), 7.21 (m, 1 H), 7.11 (m, 1 H), 7.09 (d, J = 3.0 Hz,
1 H), 6.52 (d, J = 3.2 Hz, 1 H), 5.07 (s, 1 H), 4.92 (s, 1 H), 4.85
(br. s, 1 H), 4.81 (m, 1 H), 4.72 (s, 2 H), 4.41 (ddd, J = 7.8, 6.4,
4634
www.eurjoc.org
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 4627–4636

Furanosyl C-1 Glycals from a Furanosyl 2,3-Anhydro-exo-glycal
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5.4 Hz, 1 H), 4.17–4.08 (m, 2 H), 3.96 (dd, J = 8.6, 5.4 Hz, 1 H),
2.86 (s, 2 H), 2.36 (s, 1 H), 1.46 (s, 3 H), 1.39 (s, 3 H) ppm. 13C
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119.4, 115.6, 109.7, 109.1, 101.3, 100.3, 85.2, 73.5, 72.9, 66.7, 60.3,
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[11]
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[13]
1
Compound 49: H NMR: δ = 7.64 (d, J = 7.8 Hz, 1 H), 7.30 (d, J
= 8.3 Hz, 1 H), 7.20 (m, 1 H), 7.11 (m, 1 H), 6.55 (d, J = 3.2 Hz,
1 H), 5.14 (s, 1 H), 4.93 (s, 1 H), 4.82 (d, J = 3.2 Hz, 2 H), 4.44 (s,
1 H), 4.29 (ddd, J = 8.3, 6.1, 4.9 Hz, 1 H), 4.14 (dd, J = 8.8, 6.1 Hz,
1 H), 4.08 (m, 1 H), 3.99–3.95 (m, 2 H), 3.90 (s, 1 H), 3. 24 (s, 1
H), 2.29 (d, J = 3.7 Hz, 1 H), 1.38 (s, 3 H), 1.34 (s, 3 H) ppm. 13C
NMR: δ = 161.8, 142.3, 136.0, 128.5, 128.1, 121.8, 121.1, 119.7,
115.4, 109.6, 109.5, 101.9, 83.9, 82.9, 74.9, 73.2, 67.4, 54.6, 50.5,
26.8, 25.1 ppm. MS (API-ES positive): m/z = 378.0 [M + Na]+,
356.0 [M + 1]+. C21H25NO4 (355.42): calcd. C 70.96, H 7.09, N
3.94; found C 70.79, H 7.03, N 3.81.
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Acknowledgments
This research was supported by funds from the Ministerio de Cien-
cia y Tecnología (MCYT) (grant CTQ-2006-C03). M. C. thanks
the MCYT for a scholarship. A. P. is thankful to Janssen-Cilag SA
for financial support.
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Received: May 28, 2009
Published Online: August 13, 2009
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