Synthesis of pyranoid and furanoid glycals from glycosyl sulfoxides by treatment with organolithium reagents

Article abstract of DOI:10.1002/ejoc.200800318

Glycosyl sulfoxides can be conveniently transformed into pyranoid or furanoid glycals by treatment with organolithium reagents. The more likely reaction pathway involves a sulfoxide/metal exchange reaction to generate a glycosyllithium derivative that und

Full text of DOI:10.1002/ejoc.200800318

FULL PAPER
DOI: 10.1002/ejoc.200800318
Synthesis of Pyranoid and Furanoid Glycals from Glycosyl Sulfoxides by
Treatment with Organolithium Reagents
Ana M. Gómez,*[a] Marta Casillas,[a] Aitor Barrio,[a] Anna Gawel,[a] and
J. Cristóbal López*[a]
Dedicated to Prof. Serafín Valverde on the occasion of his 70th birthday
Keywords: Glycosyl sulfoxides / Organolithium reagents / Pyranoid glycals / Furanoid glycals / Sulfoxide ligand exchange
Glycosyl sulfoxides can be conveniently transformed into py-
ranoid or furanoid glycals by treatment with organolithium
reagents. The more likely reaction pathway involves a sulf-
oxide/metal exchange reaction to generate a glycosyllithium
derivative that undergoes β-elimination of its C-2 substitu-
ent.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2008)
Introduction
Over the past three decades a considerable amount of
work has been devoted to the study of the synthesis and
chemistry of pyranoid glycals (1,5-anhydro-2-deoxy-1-en-
itols) such as 1 (Scheme 1).[1] These carbohydrate deriva-
tives are frequently employed as useful starting materials in
the synthesis of oligosaccharide motifs,[2] C-glycosides,[3] C-
nucleosides,[4] and other biologically important molecules.[5]
More recently, glycals have also been shown to be excellent
starting substrates for library development, thanks to their
rigid structures and inherent stereochemical diversity. These
attributes have been exploited in the synthesis of carbo-
hydrate-based scaffolds,[6] and also in the preparation of
molecules with distinct skeletal frameworks in diversity-ori-
ented synthesis (DOS).[7]
Many synthetic approaches for the preparation of glycals Scheme 1. Strategies for the synthesis of pyranoid glycals; P = pro-
have been devised.[8] The original Fischer–Zach method,[9]
tecting group.
which uses zinc dust in acetic acid in the reductive elimi-
nation of acylated glycosyl bromides, has been one of the
aluminum amalgam,[13] SmI2,[14] potassium graphite,[15]
most popular methods for synthesizing glycals (Scheme 1a).
lithium/ammonia,[16] chromium(II),[17,18] zinc/base,[19] co-
It has been suggested that heterolytic cleavage of the car-
balt(II),[20] and titanium(III).[21] A glucal derivative has also
bon–halogen bond occurs under these acidic conditions,
been prepared by introduction of a halogen atom at C-2,
initially to give an anomeric carbocation that, after taking
followed by a reductive elimination reaction in the opposite
two electrons from the zinc atom, generates a transient
sense.[22] In spite of the ready availability of glycosyl halides,
carbanion that evolves through the splitting off of an ace-
tate anion.[10] Other reducing agents used in this transfor-
mation with glycosyl halides include sodium and potassium
metal,[11] sodium naphthalide,[11] zinc/silver graphite,[12]
their rather sensitive natures have led to the consideration
of the more stable 1-thio- and 1-sulfonylglycosyl derivatives
(e.g., 3, Scheme 1b) as glycal precursors. Compounds 3 are
thus conveniently transformed into glycals when treated
with lithium naphthalide,[23] chromium(II) complexes in
aqueous medium,[24] or SmI2.[14,25] In the last case, electron
transfer to the glycosyl phenylsulfone to generate a 1-glyco-
syl radical has been proposed; a (glycosyl)samarium deriva-
[a] Instituto de Química Orgánica General, CSIC,
Juan de la Cierva 3, 28006 Madrid, Spain
Fax: +34-915-644853
E-mail: anago@iqog.csic.es
clopez@iqog.csic.es
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A. M. Gómez, M. Casillas, A. Barrio, A. Gawel, J. C. López
FULL PAPER
tive would then be formed,[14,25] with subsequent β-acetate as diastereomeric mixtures, the corresponding α-glycopyr-
elimination resulting in the formation of the expected gly- anosyl sulfoxides 12 and 13 were obtained with excellent
cal. Potassium graphite laminate (C8K) has also been used stereoselectivity upon oxidation of the parent thioglyco-
to transform phenyl thioglycosides into glycals.[26] More re- sides. These results are in agreement with studies carried
cent strategies have focused on the use of acyclic derivatives out by Crich and co-workers, who inferred that the stereo-
as glycal precursors (Scheme 1c). In this context, strategies selectivity in the oxidation step is dictated predominantly
based on the hetero-Diels–Alder reaction,[27] ring-closing by steric effects and the conformation imposed on the thi-
metathesis,[28] metal-promoted alkynol endo cycloisomeriza- oglycosides by the exo-anomeric effect.[39] In general, in α-
tion,[29] and iodonium-mediated 6-endo cyclization followed thioglycosides the pro-S lone pair would be substantially
by elimination,[30] have been described.
hindered by the pyranose ring and by the axial hydrogen
Earlier work in our group showed that glycosyl sulfox- atoms, whereas the pro-R lone pair of the thioglycoside
ides (e.g., 4, Scheme 1d) can also be useful precursors in the would be exposed to attack. In the case of β-thioglycosides
preparation of glycals. In fact, some years ago we reported the two lone pairs are sterically less differentiated, and mix-
reactions between anomeric glycosyl sulfoxides and organo- tures of sulfoxides result.
lithium reagents as an efficient approach for the synthesis
of pyranoid glycals.[31] The method was thought to occur
by generation of a carbanion at the anomeric position, fol-
lowed by β-elimination of the C-2 substituent.[32] In this
paper we report our studies on the scope of this transforma-
tion in full, as well as its extension to the preparation of
furanoid glycals. We also disclose our studies directed
towards shedding light on the reaction pathway for this
conversion.
Results and Discussion
Our initial studies were carried out with galactose-de-
rived sulfoxide 7[33] (Scheme 2; 1.5:1 diastereomeric mixture
with respect to the sulfur atom). Its synthesis was effected
from the known tetraacetate 5,[34] and involved three steps:
Zemplèn deacetylation,[35] exhaustive methylation, and oxi-
dation of the sulfide 6 with m-chloroperoxybenzoic acid (m-
Scheme 3. Preparation of glycosyl sulfoxides.
CPBA) at low temperature. Accordingly, treatment of gal-
actosyl sulfoxide 7 with 3 equiv. of nBuLi[36] in THF at
–78 °C for 20 min resulted in a clean reaction mixture[37]
from which the protected galactal 8 could be isolated in
59% yield.
Treatment of sulfoxides 12–14 with nBuLi (3 equiv.) in
THF at low temperature resulted in the exclusive formation
of the expected glycal derivatives (Scheme 4). From the re-
sults in Schemes 2 and 4, it seems that α-sulfoxides, regard-
less of the relative orientation of the oxygen substituent at
C-2, gave better yields than equatorial sulfoxides.
Scheme 2. Preparation of galactal derivative 8.
Scheme 4. Formation of glycals by treatment of pyranosyl sulfox-
ides with nBuLi (3 equiv.) in THF at –78 °C.
We subsequently extended this reaction to a variety of
glycosyl sulfoxides – 12, 13, 14 – with different stereochemi-
cal patterns (Scheme 3).[38] These sulfoxides were unevent-
fully prepared from -galactose-, -mannose-, and -glu-
Since the methyl ether protecting groups in sulfoxides 8
cose-derived sulfides 9, 10, and 11, respectively, in five steps. and 12–14 are not synthetically very useful, we decided to
α-Galactopyranosyl sulfoxide 12 was chosen for purposes test our procedure with glycosyl sulfoxides with more ap-
of comparison with β-galactopyranosyl sulfoxide 7. Unlike pealing protecting groups. Thus, by oxidation of the parent
β-glycopyranosyl sulfoxides 7 and 14, which were obtained thioglycosides, we prepared the benzyl-protected β--gluco-
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Pyranooid and Furanooid Glycals from Glycosyl Sulfoxides
pyranosyl sulfoxide 16 and the isopropylidene-protected α- 22 with nBuLi furnished, after column chromatography in
and β--mannopyranosyl sulfoxides 17 and 18 (Scheme 5). the presence of 1% NEt3,[42] the desired furanoid glycal 23
Treatment of sulfoxides 16–18 with nBuLi at –78 °C re- in 79% yield.
sulted in their conversion into glycal derivatives 19 and 20.
We also examined the effect of the organolithium reagent
From the results shown in Schemes 2, 4, and 5, some con- on the formation of the corresponding glycals. Our results,
clusions could be drawn. The transformations of β-gluco displayed in Table 1, seem to indicate that changes in the
sulfoxides 14 and 16, and those of α-manno derivatives 13 organolithium reagent have little or no effect in the forma-
and 17 (differing in the protecting groups) into the corre- tion of the target glycals (Table 1, compare Entries i–iii, iv–
sponding glycals seem to indicate that the leaving-group vii, viii–xi, xii–xv).
abilities of the substituents at C-2 play a significant role in
the yields of the glycals obtained. Again, the results ob-
tained in the preparation of glycal 20 from both α-manno
and β-manno sulfoxides 17 and 18 (Scheme 5) appear to
indicate that α-sulfoxides are more convenient starting ma-
terials for this transformation.
Table 1. Treatment of anomeric sulfoxides with organolithium rea-
gents in THF at –78 °C.
Entry
Sulfoxide
RLi
Glycal
Yield
i
ii
iii
iv
v
7
nBuLi
tBuLi
PhLi
nBuLi
tBuLi
PhLi
MeLi
nBuLi
tBuLi
PhLi
MeLi
nBuLi
tBuLi
PhLi
8
51%
50%
50%
72%
70%
74%
67%
86%
88%
85%
83%
79%
81%
79%
85%
7
8
7
8
13
13
13
13
17
17
17
17
22
22
22
22
15
15
15
15
20
20
20
20
23
23
23
23
vi
vii
viii
ix
x
xi
xii
xiii
xiv
xv
MeLi
Mechanistic Considerations
During the course of these studies some mechanistic as-
pects drew our attention. It is known that a sulfoxide pos-
sessing a hydrogen atom on its α-carbon atom can give an
α-sulfinyl carbanion upon treatment with organolithium
reagents (e.g., 25, Scheme 7a), and many examples of this
reaction pathway have been reported.[43] On the other hand,
Oae and co-workers have shown that alkyllithium reagents
can also react with some sulfoxides to give anions (e.g., 30,
Scheme 7b) through a sulfoxide/metal exchange reaction (or
sulfoxide/ligand exchange reaction).[44,45] In this case, the
reaction involves the attack of the organolithium reagent
on the sulfur atom of the sulfoxide to generate a pentacoor-
dinate σ-sulfurane 27, with the sulfur atom in the center of
a trigonal bypyramid.[46] By way of a pseudorotation pro-
cess different complexes can be formed, with the ligands
occupying equatorial and apical positions (e.g., 28, 29). The
complex that has the most electronegative group (G) occu-
pying the apical position is the most stable and the one that
undergoes bond rupture to generate the anion.[47]
Scheme 5. Formation of glycals 19 and 20 by treatment of pyran-
osyl sulfoxides 16–18 with nBuLi in THF at –78 °C.
To extend the scope of this methodology further, we
have evaluated its potential for the preparation of syntheti-
cally useful furanoid glycals (1,4-anhydro-2-deoxy-1-en-
itols).[40,41] Accordingly, furanosyl sulfoxide 22, easily syn-
thesized from hemiacetal 21 by thioglycosidation[26] fol-
lowed by controlled oxidation, was chosen as our starting
material (Scheme 6). To our delight, treatment of sulfoxide
According to these precedents, reactions of glycosyl sulf-
oxides to give glycals (e.g., 17 Ǟ 20, Scheme 8) could take
place by (at least) two reaction pathways (Scheme 8a, b).
The first pathway would involve a direct sulfoxide/metal ex-
change reaction to give pentacoordinate species 32, which
could evolve by releasing a phenyl sulfoxide derivative and
producing glycosyllithium compound 33 (Scheme 8,
path a). This might then induce β-elimination of its C-2
substituent, leading to 20. The second option (Scheme 8,
Scheme 6. Formation of furanoid glycal 23 by treatment of fu-
ranosyl sulfoxides 22 with nBuLi (3 equiv.) in THF at –78 °C.
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A. M. Gómez, M. Casillas, A. Barrio, A. Gawel, J. C. López
FULL PAPER
Scheme 7. Possible reaction pathways of reactions between sulfoxides and organolithium reagents.
Scheme 8. Possible pathways for the transformation of sulfoxide 17 into glycal 20 mediated by organolithium reagents.
path b) would entail a combination of both of the processes
In order to gain some mechanistic insight into this trans-
outlined in Scheme 7: initially, the alkyllithium reagent formation, we prepared the deuterated compounds 39 and
could abstract the acidic hydrogen atom on the anomeric 41[50] (Scheme 10), as analogues of sulfoxides 17 and 18,
carbon atom to give the α-sulfinyl carbanion 34, which respectively, with deuterium at their anomeric positions.[51]
could then evolve to the vinyl sulfoxide 35 by β-elimination Treatment of 39 with nBuLi (3 equiv., THF, –78 °C) gave
of the substituent at C-2. This could then undergo a sulfox- C-1-deuterated glycal 43 exclusively. Likewise, treatment of
ide/metal exchange reaction (as in Scheme 7b) to give glycal β-sulfoxide 41 with nBuLi also resulted in the formation
20 via the pentacoordinate α-sulfurane 36 and release of of 43. From these results, the second mechanistic option
vinyllithium species 37, which would subsequently be pro- (Scheme 8, path b) could be ruled out, since it would have
tonated to glycal 20. Indeed, we have observed that com- implied the disappearance of the deuterium atom on the
pound 38 (obtained from either 17 or 18, on treatment with glycal. By corollary, we believe that a direct ligand-exchange
LHMDS or LDA,[48] respectively) reacted with nBuLi, in mechanism, involving the presence of glycosyllithium inter-
THF at –78 °C to yield glycal 20 (Scheme 9). On the other mediates (e.g., 40, 42, Scheme 10), which also explains the
hand, Milne and Kocienski have reported sulfoxide/metal presence of deuterium in the glycal (Scheme 8, path a), is
exchange reactions of α-benzenesulfinyl enol ethers (related responsible for the transformation.
to 38) with tBuLi, in Et2O/THF at –78 °C, to give α-lithi-
Along similar lines, the generation of glycosyllithium de-
ated glycals.[49]
rivatives[52] in reactions between glycosyl sulfoxides and
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Pyranooid and Furanooid Glycals from Glycosyl Sulfoxides
Scheme 9. Reaction of C-1-deuterated glycosyl sulfoxides with nBuLi to give deuterated glycal 20.
Scheme 10. Reactions of deuterated sulfoxides 39 and 41 with nBuLi.
Ar, unless otherwise noted. Air- and moisture-sensitive liquids and
organolithium reagents has been applied in carbohydrate
chemistry. Fernández-Mayoralas and co-workers elegantly
exploited it in their approach to C-glycosides from glycosyl
sulfoxides.[53]
solutions were transferred by syringe or stainless steel cannula. Op-
tical rotations were determined for solutions in chloroform. Flash
column chromatography was performed on 230–400 mesh silica gel.
Thin-layer chromatography was conducted on Kieselgel 60 F254
(Merck). Spots were first observed 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 evapora-
tor. Optical rotations were measured at 20 °C. Solvents were dried
and purified by standard methods. Unless otherwise noted, 1H and
13C NMR spectra were recorded in CDCl3 at 300 MHz and
50 MHz, respectively. Chemical shifts are expressed in ppm (δ scale)
downfield from tetramethylsilane and are referenced to residual
protium in the NMR solvent (CHCl3: δ = 7.25 ppm).
Conclusions
We have described a general method for the transforma-
tion of glycosyl sulfoxides into glycols, involving treatment
of the former compounds with organolithium reagents. The
process is believed to take place through a direct ligand-
exchange mechanism that generates anomeric glycosyl-
lithium species, which trigger β-elimination of the substituent
at C-2. A variety of organolithium reagents can be used
to effect this transformation without major changes in the
observed yields. The procedure can be applied to the prepa-
ration either of pyranoid or furanoid glycals. This method-
ology, when applied to 2,3-O-isopropylidene derivatives
(e.g., 17, 18, 22, 39, 41), represents a valuable route to syn-
thetically useful fully protected furanoid and pyranoid gly-
cal derivatives in which the allylic 3-OH group is unprotec-
ted.[54]
Phenyl 2,3,4,6-Tetra-O-methyl-1-thio-β-D-galactopyranoside (6): A
solution of phenyl 2,3,4,6-tetra-O-acetyl-1-thio-β--galactopyrano-
side[34] (5 g, 11.3 mmol) in MeOH (55 mL) was treated with freshly
prepared NaOMe (619 mg, 11.3 mmol) and stirred for 10 h. The
reaction mixture was then neutralized with Amberlite H+ resin, fil-
tered, and concentrated. The residue was then dried under high
vacuum and dissolved in DMF (75 mL), cooled to 0 °C, and
treated portionwise with NaH (60%, 3.61 g, 90.4 mmol, 8 equiv.).
After 30 min, methyl iodide (4.2 mL, 67.8 mmol, 6 equiv.) was
added by syringe over 5 min. The reaction mixture was allowed to
warm to room temperature and stirred overnight. The solution was
carefully quenched with water, diluted with Et2O, washed with
H2O, dried, and concentrated. The product was then purified by
flash chromatography (20% EtOAc/hexane) to afford 6[55] as a col-
Experimental Section
General Remarks: All reactions were performed in dry flasks fitted
with glass stoppers or rubber septa under a positive pressure of
Eur. J. Org. Chem. 2008, 3933–3942
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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3937

A. M. Gómez, M. Casillas, A. Barrio, A. Gawel, J. C. López
3.43–3.56 (m, 1 H), 3.48 (s, 3 H), 3.46 (s, 3 H), 3.38 (s, 3 H), 3.26
FULL PAPER
1
orless oil (3.22 g, 87%), [α]D = –23.9 (c = 1.05, CHCl3). H NMR
(CDCl3, 300 MHz): δ = 7.50–7.55 (m, 2 H), 7.20–7.30 (m, 3 H), (s, 3 H) ppm. 13C NMR (CDCl3, 50 MHz): δ = 141.8, 131.1, 128.8,
4.50 (d, J = 9.6 Hz), 3.70 (d, J = 3.0 Hz, 1 H), 3.58 (s, 3 H), 3.56
(s, 3 H), 3.45–3.65 (m, 3 H), 3.52 (s, 3 H), 3.41 (m, 1 H), 3.36 (s, 3
124.6, 101.1, 85.8, 85.5, 84.4, 78.5, 71.6, 59.1, 58.0, 57.4 ppm. MS
(EI): m/z = 345.1 [M]+. C16H24O6S (344.13): calcd. C 55.80, H 7.02,
H), 3.20 (dd, J = 3.1, 9.2 Hz, 1 H) ppm. 13C NMR (CDCl3, S 9.31; found C 56.03, H 7.03, S 9.02.
50 MHz): δ = 134.7, 131.5, 128.9, 127.2, 87.8, 86.0, 79.4, 77.0, 75.3,
2,3,4,6-Tetra-O-methyl-1-[(R)-phenylsulfinyl]-α-
D
-mannopyranoside
70.9, 61.2, 61.0, 59.1, 58.2 ppm. MS (EI): m/z (%) = 328.1 [M]+.
(13): A solution of phenyl 2,3,4,6-tetra-O-acetyl-1-thio-α--manno-
pyranoside[34] (2 g, 4.5 mmol) in MeOH (22 mL) was treated with
freshly prepared NaOMe (248 mg, 4.5 mmol) and stirred for 10 h.
C16H24O5S (328.12): calcd. C 58.51, H 7.37, S 9.76; found C 58.65,
H 7.49, S 9.60.
2,3,4,6-Tetra-O-methyl-1-(phenylsulfinyl)-β-D
-galactopyranoside (7): The reaction mixture was then neutralized with Amberlite H+ resin,
A solution of compound 6 (205 mg, 0.62 mmol) in dichlorometh-
ane (10 mL) was cooled to –78 °C, and then m-CPBA (173 mg,
0.65 mmol) was added. After 5 h of stirring, the reaction mixture
was diluted with CH2Cl2, and sequentially washed with Na2S2O3
(20%) and saturated NaHCO3 solutions. The organic layer was
then dried with Na2SO4, concentrated in vacuo, and subjected to
purification by flash chromatography (20% EtOAc/hexane) to af-
ford a mixture (1.5:1) of sulfoxides 7 (183 mg, 86%). 1H NMR
(CDCl3, 300 MHz): δ = 7.40–7.70 (m, 5 H), 4.20 (d, J = 8.9 Hz, 1
filtered, and concentrated. The residue was then dried under high
vacuum and dissolved in DMF (30 mL), cooled to 0 °C, and
treated portionwise with NaH (60%, 1.4 g, 36.1 mmol, 8 equiv.).
After 30 min, methyl iodide (1.8 mL, 27.1 mmol, 6 equiv.) was
added by syringe over 5 min. The reaction mixture was allowed to
warm to room temperature and stirred overnight. The solution was
carefully quenched with water, diluted with Et2O, washed with
H2O, dried, and concentrated. The product was then purified by
flash chromatography (20% EtOAc/hexane) to afford phenyl
2,3,4,6-tetra-O-methyl-1-thio-α--mannopyranoside[56] as a color-
less, viscous oil (1.25 g, 85%), [α]D +128.6 (c = 4.6, CHCl3). 1H
NMR (CDCl3, 300 MHz): δ = 7.54–7.51 (m, 2 H), 7.35–7.20 (m, 3
Hmajor), 3.97 (t, J = 8.9 Hz, 1 Hminor), 3.83 (t, J = 9.7 Hz, 1 Hmin),
3.70 (d, J = 9.7 Hz, 1 Hminor) 3.20–3.65 (m, 5 H), 3.73 (s, 3 Hminor),
3.55 (s, 3 Hminor), 3.53 (s, 3 Hminor), 3.50 (s, 3 Hmajor), 3.48 (s, 3
Hmajor), 3.46 (s, 3 Hmajor), 3.37 (s, 3 Hmajor), 3.14 (s, 3 Hmajor) ppm. H), 5.68 (d, J = 1.5 Hz, 1 H), 4.15–4.09 (m, 1 H), 3.86 (dd, J =
13C NMR (CDCl3, 50 MHz): δ = 141.7, 140.5, 131.2, 129.1, 129.0, 3.1, 1.7 Hz, 1 H), 3.71–3.49 (m, 4 H), 3.57 (s, 3 H), 3.55 (s, 3 H),
125.6, 125.2, 96.6, 94.2, 88.6, 86.1, 78.7, 78.0, 75.2, 75.1, 74.8, 74.7, 3.48 (s, 3 H), 3.41 (s, 3 H) ppm. 13C NMR (CDCl3, 50 MHz): δ =
71.0, 70.6, 61.6, 61.4, 60.5, 59.5, 59.4, 59.3, 58.4, 58.2 ppm. MS
(EI): m/z = 345.3 [M]+. C16H24O6S (344.13): calcd. C 55.80, H 7.02,
S 9.31; found C 55.60, H 6.90, S 9.15.
134.6, 131.0, 129.0, 127.2, 84.6, 81.5, 78.7, 76.2, 72.1, 71.2, 60.7,
59.1, 58.1, 57.7 ppm. C16H24O5S (328.42): calcd. C 58.51, H 7.37,
S 9.76; found C 58.52, H 7.39, S 9.71. A solution of the above
sulfide (710 mg, 2.16 mmol) in dichloromethane (30 mL) was co-
oled to –78 °C. m-CPBA (683 mg, 2.37 mmol) was then added. Af-
ter 5 h of stirring, the reaction mixture was diluted with CH2Cl2,
and sequentially washed with Na2S2O3 (20%) and saturated
NaHCO3 solutions. The organic layer was then dried with Na2SO4,
concentrated in vacuo, and subjected to purification by flash
chromatography (35% EtOAc/hexane) to afford the dia-
stereomerically pure sulfoxide 13[56] (580 mg, 78%), [α]D = –54.2 (c
2,3,4,6-Tetra-O-methyl-1-[(R)-phenylsulfinyl]-α-D-galactopyranoside
(12): A solution of phenyl 2,3,4,6-tetra-O-acetyl-1-thio-α--galac-
topyranoside[34] (1 g, 2.26 mmol) in MeOH (11 mL) was treated
with freshly prepared NaOMe (124 mg, 2.23 mmol) and stirred for
8 h. The reaction mixture was then neutralized with Amberlite H+
resin, filtered, and concentrated. The residue was then dried under
high vacuum and dissolved in DMF (15 mL), cooled to 0 °C, and
treated portionwise with NaH (60%, 722 mg, 18.1 mmol, 8 equiv.).
After 30 min, methyl iodide (840 µL, 13.6 mmol, 6 equiv.) was
added by syringe over 5 min. The reaction mixture was allowed to
warm to room temperature and stirred overnight. The solution was
carefully quenched with water, diluted with Et2O, washed with
H2O, dried, and concentrated. The product was then purified by
flash chromatography (20% EtOAc/hexane) to afford phenyl
2,3,4,6-tetra-O-methyl-1-thio-α--galactopyranoside[55] as a color-
1
= 0.44, CHCl3). H NMR (CDCl3, 300 MHz): δ = 7.62–7.59 (m, 2
H), 7.49–7.45 (m, 3 H), 4.48 (d, J = 1.7 Hz, 1 H), 4.12 (dd, J =
3.4, 1.9 Hz, 1 H), 3.86 (ddd, J = 10.0, 5.1, 2.0 Hz, 1 H), 3.76 (dd,
J = 9.3, 3.4 Hz, 1 H), 3.56–3.44 (m, 3 H), 3.50 (s, 3 H), 3.48 (s, 3
H), 3.28 (s, 6 H) ppm. 13C NMR (CDCl3, 50 MHz): δ = 141.6,
131.2, 129.0, 124.2, 94.8, 80.8, 77.2, 75.2, 73.4, 71.3, 60.5, 59.1,
58.1, 57.7 ppm. C16H24O6S (344.42): calcd. C 55.80, H 7.02, S 9.31;
found C 55.73, H 6.98, S 9.19.
1
less oil (615 mg, 83%), [α]D = –235.0 (c = 1.33, CHCl3). H NMR
(CDCl3, 300 MHz): δ = 7.50–7.55 (m, 2 H), 7.20–7.30 (m, 3 H), Phenyl 2,3,4,6-Tetra-O-methyl-1-(phenylsulfinyl)-β-
D
-glucopyranos-
ide (14): A solution of phenyl 2,3,4,6-tetra-O-acetyl-1-thio-β--
glucopyranoside[34] (5 g, 11.3 mmol) in MeOH (55 mL) was treated
5.78 (d, J = 5.5 Hz), 4.40 (t, J = 6.8 Hz, 1 H), 3.97 (dd, J = 5.5,
10.2 Hz, 1 H), 3.77 (d, J = 2.9 Hz, 1 H), 3.64–3.38 (m, 3 H), 3.59
(s, 3 H), 3.55 (s, 3 H), 3.52 (s, 3 H), 3.36 (s, 3 H) ppm. 13C NMR with freshly prepared NaOMe (619 mg, 11.3 mmol) and stirred for
(CDCl3, 50 MHz): δ = 134.6, 131.3, 128.7, 127.1, 90.4, 89.5, 84.9,
80.5, 78.6, 72.2, 59.2, 59.0, 58.0, 57.6 ppm. MS (EI): m/z = 328.0
[M]+. C16H24O5S (328.12): calcd. C 58.51, H 7.37, S 9.76; found C
58.80, H 7.60, S 9.48. A solution of the above sulfide (610 mg,
1.86 mmol) in dichloromethane (20 mL) was cooled to –78 °C. m-
CPBA (561 mg, 1.95 mmol) was then added. After 5 h of stirring,
the reaction mixture was diluted with CH2Cl2 and sequentially
washed with Na2S2O3 (20%) and saturated NaHCO3 solutions.
The organic layer was then dried with Na2SO4, concentrated in
vacuo, and subjected to purification by flash chromatography (35%
EtOAc/hexane) to afford the diastereomerically pure sulfoxide 12
(496 mg, 78%), [α]D = +13.4 (c = 0.57, CHCl3). 1H NMR (CDCl3,
10 h. The reaction mixture was then neutralized with Amberlite H+
resin, filtered, and concentrated. The residue was then dried under
high vacuum and dissolved in DMF (75 mL), cooled to 0 °C, and
treated portionwise with NaH (60%, 3.61 g, 90.4 mmol, 8 equiv.).
After 30 min, methyl iodide (4.2 mL, 67.8 mmol, 6 equiv.) was
added by syringe over 5 min. The reaction mixture was allowed to
warm to room temperature and stirred overnight. The solution was
carefully quenched with water, diluted with Et2O, washed with
H2O, dried, and concentrated. The product was then purified by
flash chromatography (20% EtOAc/hexane) to afford phenyl
2,3,4,6-tetra-O-methyl-1-thio-β--glucopyranoside (3.18 g, 86%),
1
m.p. 69–70 °C, [α]D = –24.9 (c = 1.25, CHCl3). H NMR (CDCl3,
300 MHz): δ = 7.65–7.70 (m, 2 H), 7.45–7.55 (m, 3 H), 4.50 (d, J 300 MHz): δ = 7.50–7.55 (m, 2 H), 7.20–7.35 (m, 3 H), 4.48 (d, J
= 2.1 Hz, 1 H), 4.41 (dd, J = 2.1, 3.0 Hz, 1 H), 4.21 (dd, J = 4.1, = 9.8 Hz, 1 H), 3.50–3.66 (m, 3 H), 3.65 (s, 3 H), 3.60 (s, 3 H), 3.53
6.8 Hz, 1 H), 3.95 (dd, J = 3.0, 6.8 Hz, 1 H), 3.49–3.51 (m, 2 H), (s, 3 H), 3.38 (s, 3 H), 3.24–3.28 (m, 1 H), 3.19 (t, J = 8.6 Hz, 1 H),
3938
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 3933–3942

Pyranooid and Furanooid Glycals from Glycosyl Sulfoxides
3.04 (dd, J = 8.6, 9.8 Hz, 1 H) ppm. 13C NMR (CDCl3, 50 MHz): δ
ganic layer was then dried with Na2SO4, concentrated in vacuo,
= 134.5, 132.2, 129.2, 127.7, 89.1, 87.8, 83.1, 79.8, 71.8, 61.3, 61.2, and subjected to purification by flash chromatography (20 %
60.8, 59.8 ppm. MS (EI): m/z = 328.1 [M]+. C16H24O5S (328.12):
calcd. C 58.51, H 7.37, S 9.76; found C 58.81, H 7.62, S 9.96. A
solution of the above sulfide (3.0 g, 9.14 mmol) in dichloromethane
(60 mL) was cooled to –78 °C. m-CPBA (2.76 g, 9.6 mmol) was
then added. After 5 h of stirring, the reaction mixture was diluted
with CH2Cl2, and sequentially washed with Na2S2O3 (20%) and
saturated NaHCO3 solutions. The organic layer was then dried
with Na2SO4, concentrated in vacuo, and subjected to purification
by flash chromatography (35% EtOAc/hexane) to afford a 1:1 dia-
stereomeric mixture of sulfoxides 13 (2.45 g, 78%). 1H NMR
(CDCl3, 300 MHz): δ = 7.45–7.70 (m, 10 H), 4.22 (d, J = 10.0 Hz,
2 H), 3.00–3.80 (m, 12 H), 3.75 (s, 3 H), 3.67 (s, 3 H), 3.59 (s, 3
H), 3.50 (s, 3 H), 3.49 (s, 3 H), 3.43 (s, 3 H), 3.36 (s, 3 H), 3.08 (s,
3 H) ppm. 13C NMR (CDCl3, 50 MHz): δ = 141.2, 140.0, 131.3,
129.1, 129.0, 125.6, 125.1, 96.2, 93.6, 88.9, 88.7, 80.7, 79.7, 79.5,
79.3, 72.3, 71.5, 71.4, 71.2, 61.9, 61.2, 60.9, 60.8, 60.6, 60.0, 59.8,
59.7 ppm. MS (EI): m/z = 345.1 [M]+. C16H24O6S (344.13): calcd.
C 55.80, H 7.02, S 9.31; found C 55.52, H 6.82, S 9.08.
EtOAc/hexane) to afford diastereomerically pure sulfoxide 17
(879 mg, 85%), [α]D = –84.2 (c = 0.68, CHCl3). H NMR (CDCl3,
1
300 MHz): δ = 7.20–7.60 (m, 5 H), 4.78 (s, 1 H), 4.77 (d, J = 5.3 Hz,
1 H), 4.33 (m, 1 H), 3.88–3.93 (m, 1 H), 3.73–3.81 (m, 2 H), 3.63–
3.70 (m, 1 H), 1.49 (s, 6 H), 1.43 (s, 3 H), 1.32 (s, 3 H) ppm. 13C
NMR (CDCl3, 50 MHz): δ = 141.1, 131.5, 129.2, 124.3, 109.2, 99.7,
95.6, 74.6, 71.8, 70.4, 67.2, 61.4, 28.7, 27.9, 25.8, 18.6 ppm. MS
(EI): m/z = 368 [M]+. C18H24O6S (368.44): C 58.68, H 6.57, S 8.70;
found C 58.81, H 6.77, S 8.52.
2,3:4,6-Bis-O-isopropylidene-1-(phenylsulfinyl)-β-D-mannopyran-
oside (18): Phenyl 1-thio-β--glucopyranoside[34] (300 mg,
1.17 mmol) and pTsOH monohydrate (30 mg) were dissolved in
acetone (5 mL), and the solution was then treated with 2,2-dimeth-
oxypropane (1.6 mL, 13 mmol). After the mixture had been stirred
for 7 h, solid Na2CO3 was added, and the reaction mixture was
filtered through a Celite® pad and concentrated. The residue was
then purified by flash chromatography (10% EtOAc/hexane) to af-
ford phenyl 2,3:4,6-bis-O-isopropylidene-1-thio-β--mannopyrano-
side (334 mg, 81 %), m.p. 139–141 °C, [α]D = –1.0 (c = 0.63,
CHCl3). 1H NMR (CDCl3, 300 MHz): δ = 7.50–7.60 (m, 2 H),
7.25–7.35 (m, 3 H), 5.10 (d, J = 2.4 Hz, 1 H), 4.47 (dd, J = 2.4,
5.3 Hz, 1 H), 4.09 (dd, J = 5.3, 8.0 Hz, 1 H), 3.81–3.96 (m, 3 H),
3.18 (dt, J = 5.9, 9.9 Hz, 1 H), 1.62 (s, 3 H), 1.52 (s, 3 H), 1.42 (s,
6 H) ppm. 13C NMR (CDCl3, 50 MHz): δ = 134.6, 131.2, 129.0,
127.7, 110.6, 99.7, 84.7, 76.7, 76.2, 72.5, 69.8, 61.8, 29.0, 28.3, 26.3,
18.9 ppm. MS (EI): m/z = 352.1 [M]+. C18H24O5S (352.45): calcd.
C 61.34, H 8.86, S 9.10; found C 61.09, H 7.01, S 9.40. A solution
of the above sulfide (210 mg, 0.59 mmol) in CH2Cl2 (20 mL) was
treated at –78 °C with m-CPBA (60%,186 mg, 0.65 mmol). After
2 h, the reaction mixture was diluted with CH2Cl2 and sequentially
washed with Na2S2O3 (20 %) and saturated NaHCO3 solutions.
The organic layer was then dried with Na2SO4, concentrated in
vacuo, and subjected to purification by flash chromatography (20%
EtOAc/hexane) to afford a diastereomeric mixture of sulfoxides 18
(184 mg, 85 %), from which the major isomer could be charac-
terized (unassigned stereochemistry), [α]D = +30.6 (c = 0.60,
CHCl3). 1H NMR (CDCl3, 300 MHz): δ = 7.70–7.75 (m, 5 H),
7.45–7.55 (m, 3 H), 4.70 (dd, J = 2.5, 5.1 Hz, 1 H), 4.25 (d, J =
2.5 Hz, 1 H), 4.10 (dd, J = 5.1, 8.0 Hz, 1 H), 3.85 (dd, J = 8.0,
10.1 Hz, 1 H), 3.70–3.67 (m, 2 H), 3.00 (ddd, J = 7.3, 8.1, 10.1 Hz,
1 H), 1.65 (s, 3 H), 1.49 (s, 3 H), 1.46 (s, 3 H), 1.37 (s, 3 H) ppm.
13C NMR (CDCl3, 50 MHz): δ = 142.0, 131.6, 128.8, 125.2, 110.9,
99.8, 92.4, 76.1, 72.4, 71.7, 70.7, 61.3, 28.7, 28.3, 26.3, 18.7 ppm.
MS (EI): m/z = 368 [M]+. C18H24O6S (368.44): C 58.68, H 6.57, S
8.70; found C 58.30, H 6.68, S 8.63.
2,3,4-Tri-O-benzyl-1-(phenylsulfinyl)-β-D-glucopyranoside (16): A
solution of phenyl 2,3,4-tri-O-benzyl-1-thio-β--glucopyrano-
side[57] (450 mg, 0.83 mmol) in CH2Cl2 (20 mL) was treated at
–78 °C with m-CPBA (60%, 250 mg, 0.87 mmol). After 2 h, the
reaction mixture was diluted with CH2Cl2 and sequentially washed
with Na2S2O3 (20%) and saturated NaHCO3 solutions. The or-
ganic layer was then dried with Na2SO4, concentrated in vacuo,
and subjected to purification by flash chromatography (40%
EtOAc/hexane) to afford a mixture of sulfoxides (3:1, 361 mg,
78%), from which the major isomer could be characterized, [α]D
=
1
–82.8 (c = 0.99, CHCl3). H NMR (CDCl3, 300 MHz): δ = 7.20–
7.70 (m, 20 H), 4.95 (d, J = 1.7 Hz, 2 H), 4.61–4.85 (m, 2 H), 4.08
(dd, J = 9.8, 9.3 Hz, 1 H), 3.94 (d, J = 9.8 Hz, 1 H), 3.81 (t, J =
9.3 Hz, 1 H), 3.62 (t, J = 9.3 Hz, 1 H), 3.48–3.55 (m, 2 H), 3.18–
3.23 (m, 1 H), 2.25 (br. s, 1 H) ppm. 13C NMR (CDCl3, 50 MHz):
δ = 139.8, 138.4, 137.7, 131.5 129.2, 128.7, 128.6, 128.5, 128.4,
128.3, 128.0, 127.9, 127.8, 125.2, 96.5, 86.5, 80.6, 77.9, 77.6, 76.1,
75.9, 75.4, 62.1 ppm. MS (EI): m/z = 433.2 [M – SOPh]+.
C33H34O6S (558.21): C 70.95, H 6.13, S 5.74; found C 71.23, H
6.28, S 5.58.
2,3:4,6-Bis-O-isopropylidene-1-[(R)-phenylsulfinyl]-α-D-manno-
pyranoside (17): Phenyl 1-thio-α--mannopyranoside[34] (3.1 g,
12.1 mmol) and p-toluenesulfonic acid (pTsOH) monohydrate
(200 mg, 10%) were dissolved in acetone (20 mL), and the solution
was then treated with 2,2-dimethoxypropane (11 mL, 87 mmol).
After the mixture had been stirred for 7 h, solid Na2CO3 was
added, and the reaction mixture was filtered through a Celite®
pad and concentrated. The residue was then purified by flash
chromatography (10% EtOAc/hexane) to afford phenyl 2,3:4,6-bis-
O-isopropylidene-1-thio-α--mannopyranoside (3.83 g, 90%), m.p.
128–129 °C, [α]D = +171.0 (c = 1.0, CHCl3). 1H NMR (CDCl3,
300 MHz): δ = 7.48–7.58 (m, 2 H), 7.25–7.35 (m, 3 H), 5.77 (s, 1
H), 4.38 (d, J = 5.7 Hz, 1 H), 4.21 (dd, J = 5.7, 8.0 Hz, 1 H), 4.01
(dt, J = 10.1, 5.9 Hz, 1 H), 3.83 (dd, J = 8.0, 10.1 Hz, 1 H), 3.69–
3.79 (m, 2 H), 1.56 (s, 3 H), 1.51 (s, 3 H), 1.37 (s, 3 H) ppm. 13C
NMR (CDCl3, 50 MHz): δ = 132.8, 132.2, 129.1, 127.9, 109.7, 99.7,
84.5, 76.4, 74.8, 72.9, 62.6, 61.7, 29.0, 28.2, 26.2, 18.7 ppm. MS
(EI): m/z = 352.1 [M]+. C18H24O5S (352.45): calcd. C 61.34, H 8.86,
S 9.10; found C 61.62, H 7.13, S 8.99. A solution of the above
sulfide (991 mg, 2.81 mmol) in CH2Cl2 (60 mL) was treated at
–78 °C with m-CPBA (60%, 888 mg, 3.1 mmol). After 2 h, the reac-
tion mixture was diluted with CH2Cl2, and sequentially washed
with Na2S2O3 (20%) and saturated NaHCO3 solutions. The or-
General Procedure for the Glycal Formation: A solution of the gly-
cosyl sulfoxide (1 mmol) in dry THF was cooled to –78 °C
and then treated with the corresponding organolithium reagent
(3 equiv.). After stirring for 30 min, the reaction mixture was
quenched with a saturated aqueous solution of NH4Cl. After par-
titioning between water and diethyl ether, the organic layer was
dried with MgSO4 and concentrated. The residue was purified by
flash chromatography.
1,5-Anhydro-3,4,6-tri-O-methyl-2-deoxy-D-lyxo-hex-1-enitol (8):
Sulfoxide 7 (160 mg, 0.49 mmol) was treated with nBuLi (918 µL,
1.6  solution in hexane, 1.47 mmol) as base as described in the
General Procedure to give 8[58] (55 mg, 59%), [α]D = +15.0 (c =
0.81, CHCl3). 1H NMR (CDCl3, 300 MHz): δ = 6.25 (d, J =
6.1 Hz, 1 H), 4.83 (dd, J = 6.1, 2.1 Hz, 1 H), 3.40–4.17 (m, 5 H),
3.53 (s, 3 H), 3.42 (s, 3 H), 3.39 (s, 3 H) ppm.
Eur. J. Org. Chem. 2008, 3933–3942
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3939

A. M. Gómez, M. Casillas, A. Barrio, A. Gawel, J. C. López
FULL PAPER
1,5-Anhydro-3,4,6-tri-O-methyl-2-deoxy-
D
-arabino-hex-1-enitol 1,5-Anhydro-4,6-O-isopropylidene-1-(phenylsulfinyl)-2-deoxy-
D-ara-
(15): Sulfoxide 13 (100 mg, 0.3 mmol) was treated with nBuLi
(562 µL, 1.6  solution in hexane, 0.9 mmol) as base as described
in the General Procedure to give 15[59] (40 mg, 72%). In a different
experiment and by the same procedure, sulfoxide 14 (121 mg,
bino-hex-1-enitol (38): A solution of 17 (900 mg, 2.45 mmol) in dry
THF (11 mL) was cooled to –78 °C and then treated with lithium
diisopropylamide (12 mL, 0.8  solution in THF, 9.78 mmol).
After stirring for 30 min, the reaction mixture was quenched with
a saturated aqueous solution of NH4Cl. After partitioning between
0.35 mmol) was also converted into glycal 15 (51 mg, 51%), [α]D
=
+17.0 (c = 0.5, CHCl3). 1H NMR (CDCl3, 300 MHz): δ = 6.31 (d, water and diethyl ether, the organic layer was dried with MgSO4
J = 6.1 Hz, 1 H), 4.83 (dd, J = 6.1, 2.1 Hz, 1 H), 3.36–3.95 (m, 5
H), 3.54 (s, 3 H), 3.42 (s, 3 H), 3.40 (s, 3 H) ppm. C9H16O4 (188.10):
calcd. C 57.43, H 8.57; found C 57.37, H 8.23.
and concentrated. The residue was then purified by flash
chromatography (50% EtOAc/hexane) to give sulfoxide 38 (580 mg,
76 %), [α]D = –128.0 (c = 0.35, CHCl3). 1H NMR (CDCl3,
300 MHz): δ = 7.65–7.80 (m, 2 H), 7.45–7.60 (m, 3 H), 5.74 (d, J
= 2.2 Hz, 1 H), 4.47 (m, 1 H), 3.65–3.90 (m, 4 H), 3.10 (s, 1 H),
1.44 (s, 3 H), 1.40 (s, 3 H) ppm. 13C NMR (CDCl3, 50 MHz): δ =
156.2, 131.7, 129.7, 125.9, 124.4, 106.9, 100.5, 73.0, 71.2, 69.1, 61.6,
29.3, 19.5 ppm. MS (EI): m/z = 311.1 [M + 1]+. C15H18O5S
(310.09): calcd. C 58.05, H 5.85, S 10.33; found C 57.89, H 5.13, S
9.97.
1,5-Anhydro-3,4-di-O-benzyl-2-deoxy-D-arabino-hex-1-enitol (19):
Sulfoxide 16 (94 mg, 0.49 mmol) was treated with nBuLi (1.2 mL
1.6  solution in hexane, 1.96 mmol, 4 equiv.) as base as described
in the General Procedure to give 19[60] (35 mg, 63%), [α]D = –102.0
1
(c = 1.0, CHCl3). H NMR (CDCl3, 300 MHz): δ = 7.20–7.50 (m,
10 H), 6.41 (dd, J = 6.1, 1.2 Hz, 1 H), 4.61–5.07 (m, 5 H), 4.26 (m,
1 H), 3.62 (t, J = 9.3 Hz, 1 H), 3.80–4.00 (m, 4 H), 2.04 (m, 1 H)
ppm. C20H22O4 (326.15): calcd. C 73.60, H 6.79; found C 73.46, H
6.53.
1-Deuterio-2,3:4,6-bis-O-isopropylidene-1-(phenylsulfinyl)-α-
mannopyranoside (39) and 1-Deuterio-2,3:4,6-bis-O-isopropylidene-
1-(phenylsulfinyl)-β- -mannopyranoside (41): A solution of 2,3:4,6-
D-
D
1,5-Anhydro-4,6-O-isopropylidene-2-deoxy-D-arabino-hex-1-enitol
bis-O-isopropylidene--mannono-1,5-lactone[60] (254 mg,
0.98 mmol) in THF (20 mL) was cooled to 0 °C, and a cold solu-
tion of NaBD4 (82 mg, 1.96 mmol) in D2O (800 µL) was added
dropwise.[61] The mixture was stirred for 20 min and then poured
into cold, saturated NaHCO3 solution (20 mL), stirred for 1 h, and
extracted with CH2Cl2 (2ϫ15 mL), and the extract was washed
with water (2ϫ15 mL), dried with MgSO4, and concentrated. The
residue was then purified by flash chromatography (30% EtOAc/
hexane) to give the corresponding 1-deuteriomannopyranose
(20): Sulfoxide 17 (101 mg, 0.27 mmol) was treated with nBuLi
(506 µL, 1.6  solution in hexane, 0.81 mmol) as base as described
in the General Procedure to give 20[60] (44 mg, 86%). In a different
experiment and by the same procedure, sulfoxide 18 (177 mg,
0.48 mmol) was also converted into glycal 20 (56 mg, 62%), [α]D
=
–19.0 (c = 1.2, CHCl3). 1H NMR (CDCl3, 300 MHz): δ = 6.31 (dd,
J = 6.1, 1.2 Hz, 1 H), 4.75 (dd, J = 6.2, 2.0 Hz, 1 H), 4.36 (m, 1
H), 3.70–4.00 (m, 4 H), 2.10 (d, J = 4.4 Hz, 1 H), 1.55 (s, 3 H),
1
1.45 (s, 3 H) ppm. H NMR (C6D6, 300 MHz): δ = 6.18 (dd, J =
1
(220 mg, 86%). H NMR (CDCl3, 300 MHz): δ = 4.19–4.22 (m, 2
6.1, 1.2 Hz, 1 H), 4.68 (dd, J = 6.2, 1.8 Hz, 1 H), 4.36 (m, 1 H),
3.70–4.00 (m, 4 H), 2.10 (d, J = 4.4 Hz, 1 H), 1.55 (s, 3 H), 1.45
(s, 3 H) ppm.
H), 3.74–3.90 (m, 4 H), 2.76 (m, 1 H), 1.56 (s, 3 H), 1.52 (s, 3 H),
1.44 (s, 3 H), 1.37 (s, 3 H) ppm. 13C NMR (CDCl3, 50 MHz): δ =
109.4, 99.7, 92.2, 76.2, 74.6, 72.7, 62.0, 61.4, 28.9, 28.0, 26.0,
18.7 ppm. MS (EI): m/z = 246.1 [M – 15]+. A solution of the above
deuteriomannopyranose (220 mg, 0.84 mmol) in dry dichlorometh-
ane (15 mL) was treated with PhSSPh (200 mg, 0.92 mmol) and
Bu3P (211 µL, 1.68 mmol). After 24 h, the reaction mixture was
diluted with CH2Cl2 and washed with water and brine. The organic
layer was then dried with MgSO4, filtered, and concentrated under
vacuum. The residue was filtered through a short pad of silica gel
to provide a mixture of anomers (β/α = 4:1) of phenyl 1-deuterio-
2,3:5,6-di-O-isopropylidene-1-thio--mannofuranose (236 mg,
80%), which were separated by careful flash chromatography (15%
EtOAc/hexane). α-Anomer: [α]D = +91.9 (c = 0.56, CHCl3). 1H
NMR (CDCl3, 300 MHz): δ = 7.48–7.65 (m, 2 H), 7.25–7.35 (m, 3
H), 4.38 (d, J = 5.4 Hz, 1 H), 4.19 (dd, J = 5.4 Hz, 1 H), 4.02 (dt,
J = 5.7, 9.9 Hz, 1 H), 3.83 (dd, J = 7.9, 9.9 Hz, 1 H), 3.69–3.79
(m, 2 H), 1.56 (s, 3 H), 1.51 (s, 3 H), 1.45 (s, 3 H), 1.37 (s, 3 H)
ppm. 13C NMR (CDCl3, 50 MHz): δ = 132.8, 132.2, 129.1, 127.9,
109.7, 99.7, 84.5, 76.4, 74.8, 72.9, 62.6, 61.7, 29.0, 28.2, 26.2,
18.7 ppm. MS (EI): m/z = 353.1 [M]+. β-Anomer: [α]D = –119.6 (c
2,3:5,6-Di-O-isopropylidene-1-(phenylsulfinyl)-β-D-mannofuranose
(22): A solution of phenyl 2,3:5,6-di-O-isopropylidene-1-thio-β--
mannofuranose[26] (500 mg, 1.42 mmol) in CH2Cl2 (20 mL) was
treated at –55 °C with m-CPBA (60%, 463 mg, 1.56 mmol). After
2 h, the reaction mixture was diluted with CH2Cl2 and sequentially
washed with Na2S2O3 (20%) and saturated NaHCO3 solutions.
The organic layer was then dried with Na2SO4, concentrated in
vacuo, and subjected to purification by flash chromatography (40%
EtOAc/hexane) to afford a 5:1 mixture of sulfoxides (470 mg, 90%),
from which the major isomer (unassigned) could be characterized,
1
[α]D = +102.4 (c = 1.0, CHCl3). H NMR (CDCl3, 300 MHz): δ =
7.72 (m, 2 H), 7.48 (m, 3 H), 5.12 (dd, J = 6.0, 4.2 Hz, 1 H), 4.85
(dd, J = 6.0, 4.2 Hz, 1 H), 4.38 (m, 1 H), 4.23 (d, J = 4.2 Hz, 1 H),
4.00 (dd, J = 8.7, 6.3 Hz, 1 H), 3.88 (dd, J = 8.7, 4.2 Hz, 1 H), 3.65
(dd, J = 6.3, 4.2 Hz, 1 H), 1.62 (s, 3 H), 1.39 (s, 3 H), 1.32 (s, 6 H)
ppm. 13C NMR (CDCl3, 50 MHz): δ = 141.7, 131.4, 128.7, 125.3,
114.5, 109.1, 97.5, 82.8, 80.5, 80.2, 72.8, 66.0, 26.6, 25.5, 25.1,
24.3 ppm. MS (EI): m/z = 369.2 [M + Na]+. C18H24O6S (368.13):
calcd. C 58.68, H 6.57, S 8.70; found C 58.51, H 6.31, S 8.59.
1
= 0.69, CHCl3). H NMR (CDCl3, 300 MHz): δ = 7.48–7.60 (m, 2
H), 7.25–7.35 (m, 3 H), 4.44 (d, J = 5.3 Hz, 1 H), 4.07 (dd, J =
5.3, 8.0 Hz, 1 H), 3.79–3.93 (m, 3 H), 3.16 (dt, J = 6.2, 9.7 Hz, 1
H), 1.60 (s, 3 H), 1.50 (s, 3 H), 1.40 (s, 6 H) ppm. 13C NMR
(CDCl3, 50 MHz): δ = 134.5, 131.0, 128.9, 127.6, 110.4, 99.6, 84.7,
76.6, 76.0, 72.4, 69.6, 61.7, 28.9, 28.2, 26.2, 16.7 ppm. MS (EI):
m/z = 353.1 [M]+. A solution of phenyl 1-deuterio-2,3:5,6-di-O-
isopropylidene-1-thio-α--mannopyranose (50 mg, 0.14 mmol) in
CH2Cl2 (2 mL) was treated at –55 °C with m-CPBA (60%,46.3 mg,
0.156 mmol). After 2 h, the reaction mixture was diluted with
CH2Cl2 and sequentially washed with Na2S2O3 (20%) and satu-
rated NaHCO3 solutions. The organic layer was then dried with
1,4-Anhydro-2-deoxy-5,6-O-isopropylidene-D-arabino-hex-1-enitol
(23): Sulfoxide 22 (300 mg, 0.81 mmol) was treated with nBuLi as
base as described in the General Procedure to give 23[26] (119 mg,
1
79%), [α]D = –78.9 (c = 1.0, CHCl3). H NMR (C6D6, 300 MHz):
δ = 6.57 (d, J = 2.7 Hz, 1 H), 5.23 (t, J = 2.7 Hz, 1 H), 4.91 (dd,
J = 6.6, 2.7 Hz, 1 H), 4.49 (ddd, J = 7.8, 6.3, 5.1 Hz, 1 H), 4.17–
4.12 (m, 1 H), 4.15 (dd, J = 8.7, 6.3 Hz, 1 H), 4.00 (dd, J = 8.7,
5.1 Hz, 1 H), 2.19 (br. s, 1 H), 1.45 (s, 3 H), 1.37 (s, 3 H) ppm. 13
C
NMR (CDCl3, 50 MHz): δ = 150.3, 109.3, 103.9, 84.7, 72.8 (ϫ2),
66.8, 26.8, 25.1 ppm.
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Pyranooid and Furanooid Glycals from Glycosyl Sulfoxides
[5] A. G. Tolstikov, G. A. Tolstikov, Russ. Chem. Rev. 1993, 62,
579–601.
Na2SO4, concentrated in vacuo, and subjected to purification by
flash chromatography (20 % EtOAc/hexane) to afford a dia-
stereomerically pure sulfoxide 39 (44 mg, 85%), [α]D = –32.7 (c =
0.3, CHCl3). 1H NMR (CDCl3, 300 MHz): δ = 7.20–7.60 (m, 5 H),
4.77 (d, J = 5.3 Hz, 1 H), 4.33 (m, 1 H), 3.88–3.93 (m, 1 H), 3.73–
3.81 (m, 2 H), 3.63–3.70 (m, 1 H), 1.49 (s, 6 H), 1.43 (s, 3 H), 1.32
(s, 3 H) ppm. 13C NMR (CDCl3, 50 MHz): δ = 141.1, 131.5, 129.2,
124.3, 109.2, 99.7, 95.6, 74.6, 71.8, 70.4, 67.2, 61.4, 28.7, 27.9, 25.8,
18.6 ppm. MS (EI): m/z = 369 [M]+. A solution of phenyl 1-de-
uterio-2,3:5,6-di-O-isopropylidene-1-thio-β--mannopyranose
(50 mg, 0.14 mmol) in CH2Cl2 (2 mL) was treated at –55 °C with
m-CPBA (60%, 46.3 mg, 0.156 mmol). After 2 h, the reaction mix-
ture was diluted with CH2Cl2 and sequentially washed with
Na2S2O3 (20 %) and saturated NaHCO3 solutions. The organic
layer was then dried with Na2SO4, concentrated in vacuo, and sub-
jected to purification by flash chromatography (20% EtOAc/hex-
ane) to afford a diastereomeric mixture of sulfoxides 41 (46 mg,
86%), from which the major isomer could be characterized (unas-
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1
signed stereochemistry), [α]D = +20.3 (c = 0.83, CHCl3). H NMR
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(CDCl3, 300 MHz): δ = 7.70–7.75 (m, 5 H), 7.45–7.55 (m, 3 H),
4.70 (d, J = 5.1 Hz, 1 H), 4.10 (m, 1 H), 3.85 (dd, J = 8.0, 10.1 Hz,
1 H), 3.70–3.67 (m, 2 H), 3.00 (ddd, J = 7.3, 8.0, 10.1 Hz, 1 H),
1.65 (s, 3 H), 1.51 (s, 3 H), 1.46 (s, 3 H), 1.37 (s, 3 H) ppm. 13C
NMR (CDCl3, 50 MHz): δ = 131.7, 128.8, 125.2, 110.9, 99.8, 92.4,
76.1, 72.4, 71.7, 70.7, 61.3, 28.7, 28.3, 26.3, 18.7 ppm.
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Acknowledgments
This research has been supported with funds from the Ministerio
de Ciencia y Tecnología (Grant CTQ-2006-C03). M. C. and A. B.
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A. M. Gómez, M. Casillas, A. Barrio, A. Gawel, J. C. López
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Received: March 26, 2008
Published Online: June 6, 2008
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© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 3933–3942