Synthesis of C-1 alkyl and aryl glycals from pyranosyl or furanosyl chlorides by treatment with organolithium reagents

Article abstract of DOI:10.1002/ejoc.200900417

Glycosyl chlorides, with ether or isopropylidene acetal protecting groups, readily available from furanoses or pyranoses, can be conveniently transformed into C-1 alkyl or aryl glycals by reaction with alkyl or aryl organolithium reagents.

Full text of DOI:10.1002/ejoc.200900417

FULL PAPER
DOI: 10.1002/ejoc.200900417
Synthesis of C-1 Alkyl and Aryl Glycals from Pyranosyl or Furanosyl
Chlorides by Treatment with Organolithium Reagents
Ana M. Gómez,*[a] Ana Pedregosa,[a] Marta Casillas,[a] Clara Uriel,[a] and
J. Cristóbal López*[a]
Keywords: Lithium / Carbohydrates / C-Glycosides / Protecting groups
Glycosyl chlorides, with ether or isopropylidene acetal pro-
tecting groups, readily available from furanoses or pyr-
anoses, can be conveniently transformed into C-1 alkyl or aryl
glycals by reaction with alkyl or aryl organolithium reagents.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2009)
groups.[20] They showed that C-1 lithiated glycals could be
generated by either direct proton abstraction[17] or by trans-
metalation of C-1 tributylstannyl glycals.[18,19,21] The reac-
tion of the resulting alkenyllithium species with electro-
philes (e.g., alkyl halides,[17] aldehydes,[6b,18,19] ketones,[19,22]
Introduction
C-1 Substituted glycals (e.g., 1, 2) have become key
carbohydrate precursors in a variety of synthetic transfor-
mations leading to carbohydrate mimetics.[1,2] Compared to
glycals,[3] they incorporate a substituent at C-1 while main-
taining their enol ether functionality. The former facilitates
an easy retrosynthetic correlation with biologically relevant
C-glycosides (e.g., 3; Figure 1),[4,5] whereas the latter per-
mits the incorporation of further functionalities to the
carbohydrate moiety. Accordingly, the unsaturation in these
compounds has been submitted to a variety of synthetic
transformations that include: epoxidation,[6] hydrobora-
tion,[7] hydrogenation,[8] dihydroxylation,[9] mercuration,[10]
and azidoselenation.[11] C-1 glycals have also been used
as substrates in Claisen rearrangements,[12] hetero
Diels–Alder reactions,[13] acid-catalyzed spiroacetal forma-
tion,[14] selenium-induced spirocyclization,[15] radical ad-
dition of electrophilic radicals,[16] or Ferrier rearrange-
ment,[17] all of them leading to functionalized C-glycosides.
oxiranes,[23] quinones,[24] or hexacarbonyl chromium[25]
)
generated the sought C-1 substituted glycals (Scheme 1a, X
= H). Despite the straightforward nature of this approach,
the preparation and handling of these lithio reagents is not
trivial[26] and the alkylation reactions are particularly chal-
lenging, as the intermediate C-1 lithioglycals might cause
undesired side reactions.[27] In this context, Schmidt and co-
workers described the direct 1-C-lithiation of 2-phenylsulf-
inyl--glucals, which was facilitated by both inductive ef-
fects and intramolecular complexation of the lithiated spe-
cies [Scheme 1a, X = S(O)Ph].[28,29] In contrast, C-1 stan-
nyl,[30,31] or C-1 iodo glycals, obtained therefrom, have been
successfully used in palladium-mediated coupling reac-
tions[15,32,33] with activated substrates (Scheme 1b). This ap-
proach was also applied to furanoid C-1 glycals.[34] These
methods generally lead to good yields of C-1 glycals; how-
ever, they necessitate an initial metalation step for the prep-
aration of the required C-1 stannyl glycal.
Approaches to C-1 alkyl glycals, based on open-chain
derivatives, have also been described (Scheme 1c, d).[1] In
this context, Postema and co-workers designed an approach
based on an enol ether–olefin ring closing metathesis proto-
col (Scheme 1c),[8,14,35,36–38] 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 1d).[39]
Base-induced elimination of 1-CN glycosides has been
used in the preparation of 1-cyanoglycals (Scheme 1e, X =
CN), which are useful precursors of heterocyclic C-1 gly-
cals.[10,40] 2,3-Dehydroneuraminic acid derivatives, which
can be regarded as C-1 substituted glycals, have been ob-
Figure 1. C-1 glycals 1 and 2 and C-glycoside 3.
Synthetic strategies to the title compounds based on C-1
deprotonation of substituted glycal derivatives were pion-
eered by Nicolaou’s,[17] Hanessian’s[18] and Beau’s[19]
[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
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.200900417.
Eur. J. Org. Chem. 2009, 3579–3588
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A. M. Gómez, A. Pedregosa, M. Casillas, C. Uriel, J. C. López
FULL PAPER
Our studies with chloride 5 started with its reaction with
methyllithium (5 equiv.) in THF at room temperature,
which afforded C-1 methyl glycal 6 in 66% yield (Table 1,
Entry i). Next, we explored the reaction of compound 5
with various (primary, secondary, and tertiary) alkyl
organolithium reagents for the preparation of C-1 glycals
6–9 (Table 1, Entries ii–iv). Modest yield of C-1 glycal 8 was
obtained when sec-butyllithium was used (Table 1, En-
try iii). The reaction with tert-butyllithium was best carried
out at 0 °C and permitted the preparation of tert-butyl gly-
cal 9 in 62% yield (Table 1, Entry iv). In contrast, treatment
of 5 with phenyllithium gave raise to aryl C-1 glycal 10 in
77% yield (Table 1, Entry v). Finally, treatment of 5 with a
combination of tert-butyllithium and phenyllithium yielded
tert-butyl glycal 9 exclusively (vide infra; Table 1, Entry vi).
Scheme 1. Strategies for the synthesis of C-1 glycals.
tained mainly by elimination procedures on peracetylated
neuraminic ester derivatives (Scheme 1e, X = COOR).[41]
These biologically relevant compounds, related to neur-
aminidase inhibitors,[42,43] can be used in the preparation of
sialic acid derivatives functionalized at C-3.[44] Other meth-
ods have also been used in the preparation of C-1 substi-
tuted glycals.[45]
Table 1. Preparation of C-1 alkyl and C-1 phenyl glycals 6–10 by
reaction of mannopyranosyl chloride 5 with organolithium rea-
gents (5 equiv.).
Our group has been interested in the synthesis of C-1
glycals. We recently reported a method for the preparation
of furanosyl C-1 glycals based on the reaction of π-allyl
palladium complexes generated from epoxy-exo-glycals
(Scheme 1f).[46] In contrast, some time ago, as part of our
interest in the reaction of sugar derivatives with organo-
lithium reagents,[47] we described the synthesis of pyranosyl
C-1 glycals by reaction of glycosyl chlorides with organo-
lithium reagents.[48,49] In this paper we would like to report
on the continuation of our studies on the scope of the trans-
formation, including its extension to the preparation of fu-
ranoid C-1 glycals.
Entry T [°C]
RLi
Glycal
Yield [%]
i
ii
iii
iv
v
r.t.
r.t.
r.t.
0
r.t.
0
MeLi
nBuLi
sBuLi
tBuLi
PhLi
6, R = Me
7, R = nBu
8, R = sBu
9, R = tBu
10, R = Ph
66
50
36
62
77
20
vi
tBuLi (1equiv.) + PhLi (5equiv.) 9, R = tBu
We subsequently turned our attention to the influence, in
the reaction yield, of the configuration of the substituent at
C-2 in the glycosyl chloride and to more synthetically useful
benzyl protecting groups. Accordingly, we prepared gluco-
and mannopyranosyl chlorides 12 and 14 (Scheme 3) from
tetra-O-benzyl--glucopyranose 11 and tetra-O-benzyl--
mannopyranose 13, respectively, by treatment of the former
with the Vilsmeier reagent.
Results and Discussion
Our initial studies were carried out with permethylated
glycosyl chloride 5. Its synthesis was effected from -man-
nose and involved Fischer glycosylation,[50] methylation,
and acidic hydrolysis to provide hexose 4 (Scheme 2). Gly-
cosyl chloride 5 was obtained by treatment of the latter with
oxalyl chloride in the presence of a catalytic amount of
N,N-dimethylformamide (DMF).
Scheme 3. Synthesis of gluco- and mannopyranosyl chlorides 12
and 14.
The results from the reaction of pyranosyl chlorides 12
and 14 with organolithium reagents are outlined in Table 2.
Then, no reaction was observed when chloride 12 was
Scheme 2. Preparation of glycosyl chloride 5.
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C-1 Alkyl and Aryl Glycals from Pyranosyl or Furanosyl Chlorides
treated with MeLi at –78 °C (Table 2, Entry i). However, at into furanosyl chloride 22 upon treatment with PPh3 and
0 °C a smooth reaction took place that permitted the isola- CCl4 in THF at 60 °C.[54] However, unlike previously re-
tion of C-1 methyl glycal 15 in 74% yield (Table 2, Entry ii). ported by us, application of these reaction conditions to
pyranose 21 caused isomerization previous to chlorination
Table 2. Preparation of C-1 alkyl and C-1 phenyl glycals by reac-
and resulted in the formation of 20. The formation of
tion of glycopyranosyl chlorides with organolithium reagents.
pyranosyl chloride 22 was carried out without isomeriza-
tion under the conditions recommended by Hung and
Wong[55] by treatment of 21 with nBuLi followed by
ClPO(OPh)2 in THF at –78 °C.
Entry
Chloride
RLi
T [°C]
Glycal
Yield [%]
i
ii
iii
iv
v
vi
vii
viii
ix
x
12
12
12
12
12
12
12
14
14
14
14
MeLi
MeLi
nBuLi
nBuLi
PhLi
–78
0
0 or r.t.
–78
–78
0
15, R = Me
15, R = Me
16, R = nBu decomposition
16, R = nBu
17, R = Ph
17, R = Ph
18, R = tBu
no reaction
74
50
no reaction
65
PhLi
tBuLi
nBuLi
nBuLi
PhLi
0
35
0 or r.t.
–78
–78
0
16, R = nBu decomposition
16, R = nBu
17, R = Ph
17, R = Ph
55
no reaction
72
xi
PhLi
Reaction of chlorides 12 and 14 with 3 equiv. of nBuLi
at 0 °C or at room temperature caused extensive decompo-
sition of the starting material (Table 2, Entries iii and viii).
It was found, however, that lowering the temperature to
–78 °C had a beneficial effect on the reaction, thus allowing
the isolation of C-1 butyl glycal 16 in 50 and 55% yield
from the reaction of 12 and 14, respectively (Table 2, En-
tries iv and ix). No reaction of either 12 or 14 and phen-
yllithium was observed at –78 °C (Table 2, Entries v and x);
however, upon warming to 0 °C phenyl C-1 glycal 17 could
be obtained in 65 and 72% yield, respectively (Table 2, En-
tries vi and xi). Finally, reaction of glucopyranosyl chloride
12 with tert-butyllithium at 0 °C yielded C-1 glycal 18 in
35% yield. Albeit, the observed yields in the reactions with
benzyl-protected glycosyl chlorides were only moderate, we
were not able to observe any byproducts.
Scheme 4. Preparation of mannofuranosyl and mannopyranosyl
chlorides 20 and 22, respectively, from -mannose.
The results obtained in the reaction of mannosyl chlo-
rides 20 and 22 with organolithium reagents are outlined in
Tables 3 and 4, respectively. They displayed a similar behav-
ior giving raise to C-1-glycals in moderate to good yields.
We found that slightly better yields of C-1 glycals were ob-
tained when the reaction was carried out at 0 °C than at
room temperature (Table 3, compare Entries i, ii and v, vi).
Best yields of C-1 glycals were obtained when sec-butyllith-
ium was used as the organolithium partner (Table 3, En-
try iv; Table 4, Entry iii), a result that contrasts the one ob-
tained with pyranosyl chloride 5 (Table 1, Entry iii). tert-
From the results in Tables 1 and 2 it could be inferred
that the relative orientation of the oxygen substituent at C-
2 has little or no effect on the formation of the C-1 glycals.
The C-1 glycal formation reaction proceeded smoothly at
room temperature with chloride 5, but required lower tem-
peratures in the case of chlorides 12 and 14, very likely as a
result of the relatively acidic nature of the benzylic protons.
Regarding the organolithium reagents, PhLi led consist-
ently to higher yields of C-1 glycals than the corresponding
alkyllithiums.
Table 3. Preparation of C-1 alkyl and C-1 phenyl glycals 23–27 by
reaction of mannofuranosyl chloride 20 with organolithium rea-
gents (3 equiv.) in THF.
Our interest in the preparation of furanosyl and pyran-
osyl glycal derivatives in which the allylic (3)-OH group is
unprotected[43,51] led us to consider 2,3-O-isopropylidene
derivatives as interesting substrates for this reaction.
Along this line, we prepared mannose-derived furanosyl
and pyranosyl chlorides 20 and 22, respectively, from -
mannose as outlined in Scheme 4. Acetonation of -man-
nose under thermodynamic control[52] granted access to fur-
anose 19, whereas kinetic acetonation of -mannose[53] led
to pyranose 21. The former was conveniently transformed
Entry
T [°C]
RLi
Glycal
Yield [%]
i
ii
iii
iv
v
vi
vii
r.t.
0
0
0
r.t.
0
MeLi
MeLi
nBuLi
sBuLi
tBuLi
tBuLi
PhLi
23, R = Me
23, R = Me
24, R = nBu
25, R = sBu
26, R = tBu
26, R = tBu
27, R = Ph
50
60
54
71
37
46
58
0
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A. M. Gómez, A. Pedregosa, M. Casillas, C. Uriel, J. C. López
FULL PAPER
Butyllithium gave modest yields of C-1 glycals 26 and 31 cal 10. We then reasoned that aryllithium derivatives gener-
(Table 3, Entries v and vi; Table 4, Entry iv), in agreement ated by directed ortho-metalation,[57] devoid of this equilib-
with the results observed with chlorides 5, 12, and 14.
rium, could be used in the preparation of C-1 glycals. Ac-
cordingly, 2-lithio-1-methoxynaphthalene generated by re-
action of 1-methoxynaphthalene (33) with tBuLi reacted
with furanosyl chloride 20 to furnish C-1 glycal 36 in 46%
yield (Scheme 5c).
Table 4. Preparation of C-1 alkyl and C-1 phenyl glycals 28–32 by
reaction of mannopyranosyl chloride 22 with organolithium rea-
gents (3 equiv.) in THF.
Finally, we attempted the reaction of lithium phenylace-
tylide and 2-lithiomethylpyridine[58] [generated by treatment
of phenyl acetylene (37) and 2-methylpyridine (39) with
nBuLi, respectively] with furanosyl chloride 20 (Scheme 5d,
e). Under a variety of reaction conditions, we were not able
to detect any of the desired C-1 glycals, 38 or 40, and most
of glycosyl chloride 20 could be recovered unreacted.
Entry
T [°C]
RLi
Glycal
Yield [%]
i
ii
iii
iv
v
0
0
0
0
0
MeLi
nBuLi
sBuLi
tBuLi
PhLi
28, R = Me
29, R = nBu
30, R = sBu
31, R = tBu
32, R = Ph
65
62
82
49
60
Conclusions
Next, we decided to evaluate if this method could be ex-
tended to aryl organolithiums other than PhLi. Thus, bro-
momethoxy naphthalene 34, prepared by NBS-mediated
bromination[56] of 1-methoxynaphthalene (33) in acetoni-
trile, was treated with tBuLi in THF at –78 °C to generate
the corresponding lithiated species 35. Upon exposure of
pyranosyl chloride 5 to lithiated 35, we observed a complex
reaction mixture from which only tert-butyl glycal 10 could
be isolated (Scheme 5a). This result was explained on the
basis of the equilibrium shown in Scheme 5b, where the re-
generated tBuLi could react with chloride 5 to give C-1 gly-
The reaction of pyranosyl and furanosyl chlorides with
organolithium reagents provides an efficient method for the
preparation of C-1 substituted glycals. Regarding the
organolithium reagents, commercially available alkyllith-
iums provide from modest to good yields of C-1 glycals and
PhLi gives good yields of C-1 phenyl glycals. Organolithium
reagents obtained by directed ortho-metalation also gave
moderate yields of aryl C-1 glycals. In contrast, less basic
organolithium derivatives such as lithium phenylacetylide
or 2-lithiomethylpyridine did not give any of the sought C-
1 glycals. In this context, the basicity of the organolithium
reagent appears to be an important issue, as we have al-
ready observed in the exclusive formation of glycal 10 when
chloride 5 was treated with a mixture of tert-butyllithium
and phenyllithium (Table 1 Entry vi) or tert-butyllithium
and 4-lithium-1-methoxynaphthalene (Scheme 5a, b). These
results will be in agreement with the suggested mechanism
for this transformation advanced by Kurihara and co-
workers,[49] in which abstraction of the anomeric proton
was proposed to take place in the first step (e.g., I Ǟ II,
Scheme 6).
Scheme 6. Possible reaction pathway for the formation of C-1 gly-
cals from glycosyl chlorides, as proposed by Kurihara and co-
workers.[49]
Concerning the chloride counterparts, furanosyl and
pyranosyl chlorides displayed a similar behavior, and they
both can be successfully used in this reaction. Nevertheless,
the presence of ether protecting groups seems to be of prime
importance for the reaction to proceed towards C-1 glycals.
Scheme 5. Reaction of different organolithiums with chlorides 5
and 20.
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C-1 Alkyl and Aryl Glycals from Pyranosyl or Furanosyl Chlorides
it was warmed to room temperature and stirred for 1 h. The reac-
tion crude was then concentrated, the residue was taken up in
EtOAc/hexane (1:1), and the suspension was filtered through silica
gel to give after evaporation of the solvents pyranosyl chloride 5
(583 mg, 92%). 1H NMR (300 MHz, CDCl3): δ = 3.39 (s, 3 H,
OMe), 3.50 (s, 3 H, OMe), 3.53 (s, 3 H, OMe), 3.54 (s, 3 H, OMe),
3.51–3.85 (m, 6 H), 6.18 (d, J = 1.4 Hz, 1 H, 1-H) ppm.
Indeed, previous investigations on the reaction of organo-
lithiums with acyl-substituted glycosyl chlorides reported
the mere replacement of the anomeric chlorine to afford
anomeric mixtures of C-glycosides.[59] In this context, ether
or isopropylidene acetal substituents can be used as protect-
ing groups, although benzyl groups do require lower reac-
tion temperatures than methyl, probably due to the higher
acidity of the benzylic protons. Further studies are under
consideration in our laboratory.
General Procedure for C-1 Glycal Formation: A solution of the gly-
cosyl chloride (1 mmol) in dry THF was cooled to the appropriate
temperature and then treated with the corresponding organo-
lithium reagent (3 equiv.). After stirring for 0.5–2 h, and once TLC
analyses showed total disappearance of the starting material, the
reaction mixture was quenched with a saturated aqueous solution
of NH4Cl. After partitioning between water and diethyl ether, the
organic layer was dried with MgSO4 and concentrated. The ensuing
residue was then purified by flash chromatography.
Experimental Section
General: All reactions were performed in dry flasks fitted with glass
stoppers or rubber septa under a positive pressure of argon, unless
otherwise noted. Air- and moisture-sensitive liquids and solutions
were transferred by syringe or stainless steel cannula. Optical rota-
tions were determined with a Perkin–Elmer 241 MC polarimeter.
Flash column chromatography was performed by using 230–
400 mesh silica gel. Thin-layer chromatography was conducted on
Kieselgel 60 F254 (Merck). Spots were observed first under UV
irradiation (254 nm) then by charring with a solution of 20% aque-
ous H2SO4 (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 by using
a rotary evaporator. Solvents were dried and purified by using stan-
dard methods. 1H and 13C NMR spectra were recorded with an
Inova-300 (300 and 50 MHz, respectively) as CDCl3 or C6D6 solu-
tions. Chemical shifts are expressed in parts per million (δ scale)
downfield from tetramethylsilane and are referenced to residual
protium in the NMR solvent (CHCl3: δ = 7.25 ppm). Compounds
20 and 36 (Supporting Information) were prepared according to
ref.[60]
1,5-Anhydro-3,4,6-tri-O-methyl-2-deoxy-1-C-methyl-D-arabino-hex-
1-enitol (6): Using the general procedure, chloride 5 (103 mg,
0.41 mmol) was treated with MeLi (1.6  in diethyl ether, 0.82 mL,
1.23 mmol) at room temperature. Extractive workup was followed
by flash chromatography (5% EtOAc/hexane) to give C-1 glycal 7
(54 mg, 66%). [α]2D5 = +13.1 (c = 0.92, CHCl3).1H NMR (300 MHz,
C6D6): δ = 1.64 (d, J = 1.2 Hz, 3 H, Me), 3.16 (s, 3 H, OMe), 3.18
(s, 3 H, OMe), 3.39 (s, 3 H, OMe), 3.62 (m, 3 H, 2ϫ6-H, 4-H),
3.90 (m, 1 H, 3-H), 4.00 (ddd, J = 2.7, 4.7, 7.9 Hz, 1 H, 5-H), 4.56
(m, 1 H, 2-H) ppm. 13C NMR (50 MHz, CDCl3): δ = 19.6, 56.5,
58.9, 59.2, 70.9, 75.7, 76.3, 77.1, 95.2, 152.7 ppm. MS (EI): m/z =
171.0 [M – 31]+, 149.0, 127.0, 125.0, 102.0, 101.0, 85.0, 71.0, 55.0.
C10H18O4 (202.12): calcd. C 59.37, H 8.98; found C 59.09, H 8.97.
1,5-Anhydro-3,4,6-tri-O-methyl-2-deoxy-1-C-n-butyl-D-arabino-hex-
1-enitol (7): According to the general procedure, this compound
was prepared at room temperature from chloride 5 (151 mg,
0.59 mmol) and nBuLi (1.6  in n-hexane, 1.1 mL, 1.77 mmol). Pu-
rification by flash chromatography (10% EtOAc/hexane) afforded
pure C-1 glycal 7 (72 mg, 50%). [α]2D5 = –1.9 (c = 1.07, CHCl3).
2,3,4,6-Tetra-O-methyl-D-mannose (4): Required hemiacetal 4 was
prepared from -mannose following the procedure of Nicolaou and
co-workers.[61] Concentrated H2SO4 (2 mL) was added to a solution
of -mannose (3.6 g, 20.0 mmol) in MeOH (60 mL) at room tem-
perature. After 9 h of stirring, the reaction mixture was neutralized
by the addition of 3  aqueous NaOH and concentrated. The re-
sulting solid was then taken up in EtOAc (100 mL), filtered through
a short pad of silica gel, and concentrated. The residue was then
dried under high vacuum and dissolved in DMF (20 mL), cooled to
0 °C, and treated portionwise with 60% NaH (6.40 g, 160.0 mmol,
8 equiv.). After 30 min, methyl iodide (9.8 mL, 160.0 mmol,
6 equiv.) was added by syringe over 5 min. The reaction was
warmed to room temperature and stirred overnight. The solution
was carefully quenched with water, diluted with Et2O, washed with
H2O, dried, and concentrated. The resulting residue was then dis-
solved in 6  aqueous HCl (15 mL) and warmed to 60 °C. After
24 h, the reaction mixture was concentrated in vacuo directly. The
resulting residue was purified by flash chromatography (60%
EtOAc/hexane) to give desired hemiacetal 5 (3.21 g, 68%). 1H
NMR (300 MHz, CDCl3): δ = 5.25 (s, 1 H, 1-H), 4.62 (br. s, 1 H),
3.86 (td, J = 7.3, 1.8 Hz, 1 H), 3.59–3.51 (m, 4 H), 3.45 (s, 3 H,
OMe), 3.44 (s, 3 H, OMe), 3.43 (s, 3 H, OMe), 3.32 (s, 3 H, OMe),
3.26 (t, J = 9.2 Hz, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ =
91.5, 80.8, 74.5, 77.1, 72.7, 70.3, 60.6, 59.1, 58.8, 57.6 ppm.
25
25
[α]
= –5.3 (c = 1.07, CHCl3). [α]
= –2.1 (c = 1.07,
Hg(365)
Hg(435)
25
25
CHCl3). [α]
= –1.6 (c = 1.07, CHCl3). [α]
= –1.1 (c =
Hg(546)
Hg(578)
1.07, CHCl3). C13H24O4 (244.33): calcd. C 63.89, H 9.91; found C
64.17, H 9.61. 1H NMR (300 MHz, CDCl3): δ = 0.90 (t, J = 7.3 Hz,
3 H, Me), 1.35 (m, 2 H, CH2), 1.46 (m, 2 H, CH2), 2.06 (t, J =
7.5 Hz, 2 H, CH2), 3.39 (s, 3 H, OMe), 3.41 (s, 3 H, OMe), 3.43
(dd, J = 5.5, 7.8 Hz, 1 H, 4 H) 3.53 (s, 3 H, OMe), 3.64 (m, 2 H,
6-H), 3.83 (m, 1 H, 3-H), 3.98 (ddd, J = 2.7, 4.7, 7.8 Hz, 1 H, 5-H),
4.62 (d, J = 3.1 Hz, 1 H, 2-H) ppm. 13C NMR (50 MHz, CDCl3): δ
= 13.7, 22.1, 28.8, 33.1, 55.4, 58.8, 59.1, 70.9, 75.7, 76.2, 76.9, 94.2,
156.3 ppm. MS (EI): m/z = 171.0 [M – 31]+, 167.3, 144.3, 143.2,
125.2, 112.2, 102.3, 101.1, 85.1. C13H24O4 (244.32): calcd. C 63.91,
H 9.90; found C 63.84, H 9.75.
1,5-Anhydro-3,4,6-tri-O-methyl-2-deoxy-1-C-sec-butyl-D-arabino-
hex-1-enitol (8): Using the general procedure, chloride 5 (72 mg,
0.28 mmol) was treated with sBuLi (1.4  in cyclohexane, 0.6 mL,
0.84 mmol) at room temperature. Extractive workup was followed
by flash chromatography (10% EtOAc/hexane) to give C-1 glycal 8
as a 1:1 mixture of diastereomers (22 mg, 36 %). 1H NMR
(300 MHz, CDCl3) selected data: δ = 3.84 (m, 1 H, 3-H), 3.97 (m,
1 H, 5-H), 4.58 (d, J = 3.4 Hz, 0.5 H, 2-H one isomer), 4.61 (d, J
= 3.4 Hz, 0.5 H, 2-H other isomer) ppm. MS (EI): m/z = 244.4
[M]+, 212.2, 167.1, 144.3, 143.2, 125.2, 102.3, 101.2, 85.1, 71.1.
2,3,4,6-Tetra-O-methyl-α-D-mannopyranosyl Chloride (5): To a solu-
tion of 4 (590 mg, 1.7 mmol) and DMF (170 µL) dissolved in dry 1,5-Anhydro-3,4,6-tri-O-methyl-2-deoxy-1-C-tert-butyl-
D
-arabino-
CH2Cl2 (6 mL) was added a solution of oxalyl chloride (445 µL,
5.1 mmol, 3 equiv.) in dry CH2Cl2 (2 mL) dropwise at 0 °C. The
mixture was stirred at that temperature for 30 min, after which time
hex-1-enitol (9): According to the general procedure, this com-
pound was prepared at 0 °C from chloride 5 (99 mg, 0.39 mmol)
and tBuLi (1.7  in n-pentane, 0.7 mL, 1.17 mmol). Purification by
Eur. J. Org. Chem. 2009, 3579–3588
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3583

A. M. Gómez, A. Pedregosa, M. Casillas, C. Uriel, J. C. López
FULL PAPER
flash chromatography (5% EtOAc/hexane) afforded pure C-1 glycal
9 (59 mg, 62%). [α]2D5 = –3.1 (c = 0.97, CHCl3). 1H NMR
4.52–4.60 (m, 4 H, 2 ϫ OCH2Ph), 4.65 (d, J = 11.2 Hz, 1 H,
OCH2Ph), 4.69 (d, J = 2.8 Hz, 1 H, 2-H), 4.82 (d, J = 11.4 Hz, 1 H,
(300 MHz, C6D6): δ = 1.07 (s, 9 H, tBu), 3.40 (s, 3 H, OMe), 3.40 OCH2Ph), 7.32 (m, 15 H, Ph) ppm. 13C NMR (50 MHz, CDCl3): δ
(m, 1 H, 4-H), 3.41 (s, 3 H, OMe), 3.51 (s, 3 H, OMe), 3.63 (m, 2 = 20.3, 69.2, 70.8, 73.9, 74.0, 74.7, 77.6, 78.2, 96.1, 128.1, 128.3,
H, 6-H), 3.82 (dd, J = 3.2, 5.6 Hz, 1 H, 3-H), 3.94 (ddd, J = 3.5,
128.5, 128.9, 138.8, 139.1, 153.4 ppm. MS (EI): m/z = 430.1 [M]+,
408.8, 376.2, 134.2, 339.1, 323.2, 309.1, 253.0, 181.0, 163.0, 107.9,
5.1, 7.7 Hz, 1 H, 5-H), 4.66 (d, J = 3.2 Hz, 1 H, 2-H) ppm. 13C
NMR (50 MHz, CDCl3): δ = 24.6, 26.3, 57.5, 59.6, 60.3, 72.3, 76.3, 91.0, 90.2, 79.0 ppm. C28H30O4 (430.54): calcd. C 78.11, H 7.02;
79.9, 80.6, 101.0, 156.4 ppm. MS (EI): m/z = 244.4 [M]+, 244.1675, found C 77.97, H 7.45.
212.3, 197.2, 167.1, 144.3, 143.2, 142.5, 125.2, 102.3, 101.2, 85.1,
1,5-Anhydro-3,4,6-tri-O-benzyl-2-deoxy-1-C-butyl-D-arabino-hex-1-
71.1, 57.1. C13H24O4 (244.33): calcd. C 63.91, H 9.90; found C
63.80, H 9.83.
enitol (16): According to the general procedure, this compound was
prepared at –78 °C from chloride 12 (102 mg, 0.18 mmol) and
nBuLi (1.6  in n-hexane, 0.33 mL, 0.54 mmol). Purification by
flash chromatography (5% EtOAc/hexane) afforded pure C-1 glycal
16 (42 mg, 50%). In a different experiment, this compound was
prepared from chloride 14 (131 mg, 0.24 mmol) and nBuLi (1.6 
in n-hexane, 0.45 mL, 0.72 mmol). Purification by flash chromatog-
raphy (5% EtOAc/hexane) afforded C-1 glycal 16 (61 mg, 55%).
1,5-Anhydro-3,4,6-tri-O-methyl-2-deoxy-1-C-phenyl-D-arabino-hex-
1-enitol (10): Using the general procedure, chloride 5 (140 mg,
0.55 mmol) was treated with PhLi (1.8  in di-n-butyl ether,
0.92 mL, 1.65 mmol) at 0 °C. Extractive workup was followed by
flash chromatography (15% EtOAc/hexane) to give C-1 glycal 10
(112 mg, 77%). [α]2D5 = –8.9 (c = 0.90, CHCl3). 1H NMR (300 MHz,
C6D6): δ = 3.19 (s, 3 H, OMe), 3.21 (s, 3 H, OMe), 3.40 (s, 3 H,
OMe), 3.68 (m, 3 H, 2ϫ6-H and 4-H), 4.04 (dd, J = 3.1, 6.1 Hz,
1 H, 3-H), 4.11 (ddd, J = 2.7, 5.1, 8.3 Hz, 1 H, 5-H5), 5.38 (d, J
3.1 Hz, 1 H, 2-H), 7.10 (m, 3 H, Ph), 7.39 (m, 1 H, Ph), 7.68 (m,
1 H, Ph) ppm. 13C NMR (50 MHz, C6D6): δ = 55.4, 58.8, 59.0,
71.3, 76.3, 77.6, 78.6, 96.2, 125.6, 127.2, 129.0, 135.3, 152.9 ppm.
MS (EI): m/z = 264.2 [M]+, 239.2, 233.2, 187.0, 164.2, 163.2, 162.5,
161.5, 128.3, 115.1, 105.1, 102.1, 85.1, 71.1, 70.4, 45.3. C15H20O4
(264.13): calcd. C 68.15, H 7.63; found C 68.32, H 7.18.
1
[α]2D5 = –4.7 (c = 0.56, CHCl3). H NMR (300 MHz, CDCl3): δ =
0.91 (t, J = 7.3 Hz, 3 H, Me), 1.32 (m, 2 H, CH2), 1.49 (m, 2 H,
CH2), 2.09 (t, J = 7.3 Hz, 2 H, CH2), 3.81 (m, 3 H, 6-H, 4-H), 4.09
(ddd, J = 3.4, 4.9, 8.0 Hz, 1 H 5-H), 4.17 (m, 1 H, 3-H), 4.54 (d, J
= 11.7 Hz, 1 H, OCH2Ph), 4.56 (d, J = 12.2, 1 H, OCH2Ph), 4.61
(d, J = 12.2 Hz, 1 H, OCH2Ph), 4.62 (d, J = 11.7 Hz, 1 H,
OCH2Ph), 4.66 (d, J = 11.5 Hz, 1 H, OCH2Ph), 4.68 (d, J = 3.4 Hz,
1 H, 2-H), 4.81 (d, J = 11.5, 1 H, OCH2Ph), 7.32 (m, 15 H, Ph)
ppm. 13C NMR (50 MHz, CDCl3): δ = 13.9, 22.3, 29.0, 33.3, 68.7,
70.2, 73.3, 73.4, 76.0, 76.7, 94.7, 127.6, 127.7, 127.8, 128.3, 138.3,
138.6, 156.5 ppm. MS (EI): m/z = 473.3 [M + 1]+, 391.2, 366.2,
365.2, 285.2, 257.0, 219.2, 197.1, 181.0, 90.9. C31H36O4 (472.62):
calcd. C 78.77, H 7.68; found C 78.38, H 7.43.
2,3,4,6-Tetra-O-benzyl-α-D-glucopyranosyl Chloride (12): To a solu-
tion of 11 (704 mg, 1.1 mmol) and DMF (110 µL) dissolved in dry
CH2Cl2 (6 mL) was added a solution of oxalyl chloride (288 µL,
3.3 mmol, 3 equiv.) in dry CH2Cl2 (3 mL) dropwise at 0 °C. The
mixture was stirred at that temperature for 30 min, after which time
it was warmed to room temperature and stirred for 1 h. The reac-
tion crude was then concentrated, the residue was taken up in
EtOAc/hexane (1:2), and the suspension was filtered through silica
gel to give after evaporation of the solvents chloride 12[62] (546 mg,
75%). 1H NMR (200 MHz, CDCl3): δ = 3.63 (dd, J = 2.0, 11.2 Hz,
1 H, 6-H), 3.82 (m, 2 H), 3.86 (dd, J = 2.7, 11.0 Hz, 1 H, 6-H),
4.11–4.20 (m, 2 H), 4.44–4.99 (m, 8 H), 6.06 (d, J = 3.7 Hz, 1 H,
1-H), 7.14–7.34 (m, 20 H) ppm.
1,5-Anhydro-3,4,6-tri-O-benzyl-2-deoxy-1-C-phenyl-D-arabino-hex-
1-enitol (17): Using the general procedure, chloride 12 (120 mg,
0.21 mmol) was treated with PhLi (0.35 mL, 1.8  in di-n-butyl
ether, 0.63 mmol) at 0 °C. Extractive workup was followed by flash
chromatography (15% EtOAc/hexane) to give C-1 glycal 17 (65 mg,
65%). In a different experiment, this compound was prepared from
chloride 14 (120 mg, 0.21 mmol) and PhLi (1.8  in di-n-butyl
ether, 0.35 mL, 0.63 mmol). Purification by flash chromatography
(5% EtOAc/hexane) afforded C-1 glycal 17 (75 mg, 72%). M.p. 63–
65 °C (Et2O/Hexane) (ref.[32d] 65–66 °C). [α]D = –6.2 (c = 0.71,
CHCl3) {ref.[32d] [α]D = –7.0 (c = 1.0, CHCl3)}. 1H NMR
(300 MHz, CDCl3): δ = 3.93 (m, 2 H, 6-H), 4.00 (dd, J = 6.1,
7.7 Hz, 4-H), 4.29 (ddd, J = 3.1, 4.8, 7.7 Hz, 1 H,5-H), 4.41 (dd, J
= 2.6, 6.1 Hz, 1 H, 3-H), 4.66 (m, 4 H, 2ϫOCH2Ph), 4.74 (d, J =
11.5 Hz, 1 H, OCH2Ph), 4.89 (d, 1 H, J = 11.5 Hz, OCH2Ph), 5.46
(d, J = 2.6 Hz, 1 H, 2-H), 7.20–7.60 (m, 20 H, Ph) ppm. 13C NMR
(50 MHz, CDCl3): δ = 68.6, 70.5, 73.4 (ϫ2), 74.4, 76.6, 77.4, 96.0,
127.3, 127.5, 127.6, 127.7, 127.9, 128.1, 128.4, 128.6, 134.5, 138.3,
138.5, 152.7 ppm. MS (EI): m/z = 493.3 [M + 1]+, 461.2, 425.2,
415.2, 385.2, 295.0, 253.0, 217.0, 181.0, 157.0, 91.0. C33H32O4
(492.23): calcd. C 80.45, H 6.55; found C 80.15, H 6.63.
2,3,4,6-Tetra-O-benzyl-α-D-mannopyranosyl Chloride (14): To a
solution of 13 (1.4 g, 2.1 mmol) and DMF (210 µL) dissolved in
dry CH2Cl2 (8 mL) was added a solution of oxalyl chloride
(550 µL, 6.3 mmol, 3 equiv.) in dry CH2Cl2 (4 mL) dropwise at
0 °C. The mixture was stirred at that temperature for 30 min, after
which time it was warmed to room temperature and stirred for 1 h.
The reaction crude was then concentrated, the residue was taken
up in EtOAc/hexane (1:2), and the suspension was filtered through
silica gel to give after evaporation of the solvents chloride 14[55,63]
1
(1.2 g, 81%). H NMR (400 MHz, CDCl3): δ = 3.69 (dd, J = 11.2,
1.2 Hz, 1 H, 6-H), 3.81 (dd, J = 11.2, 4.4 Hz, 1 H, 6-H), 3.87 (dd,
J = 3.1, 1.4 Hz, 1 H, 2-H), 4.01 (m, 1 H, 5-H), 4.09 (t, J = 9.4 Hz,
1 H, 4-H), 4.18 (dd, J = 9.4, 3.1 Hz, 1 H, 3-H), 4.49–4.79 (m, 7
H), 4.89 (d, J = 10.7 Hz, 1 H, CH2Ph), 6.10 (d, J = 1.4 Hz, 1 H,
1-H), 7.16–7.34 (m, 20 H) ppm.
1,5-Anhydro-3,4,6-tri-O-benzyl-2-deoxy-1-C-tert-butyl-D-arabino-
hex-1-enitol (18): According to the general procedure, this com-
pound was prepared at 0 °C from glycosyl chloride 12 (137 mg,
0.25 mmol) and tBuLi (1.7  in n-pentane, 0.44 mL, 0.75 mmol).
Purification by flash chromatography (5% EtOAc/hexane) afforded
C-1 glycal 18 (41 mg, 35%). [α]2D5 = –3.5 (c = 0.60, CHCl3).
1,5-Anhydro-3,4,6-tri-O-benzyl-2-deoxy-1-C-methyl-D-arabino-hex-
1-enitol (15): Using the general procedure, chloride 12 (120 mg,
0.21 mmol) was treated with MeLi (1.6  in diethyl ether, 0.40 mL,
0.63 mmol) at 0 °C. Extractive workup was followed by flash
chromatography (5 % EtOAc/hexane) to give C-1 glycal 15[19]
25
25
[α]
[α]
= –8.6 (c = 0.60, CHCl3). [α]
= –5.5 (c = 0.60, CHCl3). [α]
= –6.7 (c = 0.60, CHCl3).
= –4.4 (c = 0.60, CHCl3).
Hg365
Hg435
25
25
Hg546
Hg578
1
(67 mg, 74%). M.p. 29–30 °C. [α]2D5 = +9.1 (c = 0.79, CHCl3). H
1H NMR (300 MHz, CDCl3): δ = 1.10 (s, 9 H, tBu), 3.81 (m, 3 H,
NMR (300 MHz, CDCl3): δ = 1.82 (br. s, 3 H, Me), 3.78 (m, 2 H,
6-H, 4-H), 4.03 (m, 1 H, 5-H), 4.19 (dd, J = 2.9, 5.8 Hz, 1 H, 3-
6-H), 3.85 (dd, J = 5.8, 8.2 Hz, 1 H, 4-H), 4.11 (m, 1 H, 3-H), H), 4.59 (m, 4 H, OCH2Ph), 4.69 (d, J = 11.3 Hz, 1 H, OCH2Ph),
3584 Eur. J. Org. Chem. 2009, 3579–3588
www.eurjoc.org
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

C-1 Alkyl and Aryl Glycals from Pyranosyl or Furanosyl Chlorides
4.70 (d, J = 2.9 Hz, 1 H, 2-H), 4.81 (d, J = 11.3 Hz, 1 H, OCH2Ph),
7.32 (m, 15 H, Ph) ppm. 13C NMR (50 MHz, CDCl3): δ = 25.9,
1,4-Anhydro-5,6-O-isopropyliden-2-deoxy-1-C-tert-butyl-
hex-1-enitol (26): Using the general procedure, chloride 20 (95 mg,
D-arabino-
27.0, 68.8, 70.3, 73.2, 73.4, 74.6, 76.6, 76.9, 91.8, 127.4, 127.5, 0.34 mmol) was treated with tBuLi (1.7  in pentane, 0.60 mL,
127.6, 127.8, 128.0, 128.3, 138.7, 138.8, 163.3 ppm. MS (EI): m/z
1.02 mmol) at 0 °C. Extractive workup was followed by quick flash
chromatography (20% EtOAc/hexane) to give C-1 glycal 26 (38 mg,
= 473.3 [M + 1], 393.2, 366.2, 365.2, 275.0, 257.0, 219.2, 197.0,
181.0, 90.9. C31H36O4 (472.62): calcd. C 78.77, H 7.68; found C 46%). M.p. 83–85 °C (hexane/EtOAc). [α]2D5 = –27.8 (c = 0.64,
1
78.39, H 7.72.
CHCl3). H NMR (300 MHz, C6D6): δ = 1.13 (s, 9 H, tBu), 1.35
(s, 3 H, Me), 1.48 (s, 3 H, Me), 4.10 (m, 2 H, 6-H), 4.25 (t, J =
6.4 Hz, 1 H, 4-H), 4.58 (m, 1 H, 5-H), 4.71 (m, 1 H, 3-H), 4.75 (d,
J = 2.0 Hz, 1 H, 2-H) ppm. 13C NMR (50 MHz, CDCl3): δ = 25.4,
26.2, 27.7, 32.2, 66.7, 73.3, 77.7, 84.8, 95.4, 109.1, 172.3 ppm. MS
(EI): m/z = 243.1 [M + 1], 225.1, 203.1, 185.0, 183.0, 167.0, 101.0.
2,3:4,6-Di-O-isopropylidene-α-D
-mannopyranosyl Chloride (22):[55]
A solution of 2,3:4,6-di-O-isopropylidene--mannopyranose (3.4 g,
13.1 mmol) in dry THF (60 mL) was cooled to 0 °C and treated
with nBuLi (1.6  in n-hexane, 8.2 mL, 13.1 mmol) followed by
chlorodiphenylphosphate (2.6 mL, 13.0 mmol). After stirring for
15 min, the reaction mixture was warmed up to room temperature
and then stirred for an additional 15 h. Solids were filtered, and
the filtrate was evaporated in vacuo. Purification by flash
chromatography (15% EtOAc/hexane) afforded chloride 22 (2.8 g,
78%). 1H NMR (300 MHz, CDCl3): δ = 1.36 (s, 3 H, Me), 1.45 (s,
3 H, Me), 1.52 (s, 3 H, Me), 1.55 (s, 3 H, Me), 3.86 (m, 4 H), 4.31
(m, 1 H), 4.44 (dd, J = 0.7, 5.3 Hz, 1 H, 2-H), 6.20 (d, J = 0.7 Hz,
1 H, 1-H) ppm. 13C NMR (50 MHz, CDCl3): δ = 18.8, 26.6, 28.4,
29.0, 61.4, 64.4, 72.3, 74.0, 79.0, 90.7, 100.0, 110.5 ppm. MS (API-
ES+): m/z = 279.1 [M + 1]+.
1,4-Anhydro-5,6-O-isopropyliden-2-deoxy-1-C-phenyl-D-arabino-
hex-1-enitol (27): Using the general procedure, chloride 20 (87 mg,
0.32 mmol) was treated with PhLi (1.8  in di-n-butyl ether,
0.53 mL 0.96 mmol) at 0 °C. Extractive workup was followed by
quick flash chromatography (20% EtOAc/hexane) to give C-1 gly-
cal 27 (58 mg, 71%). [α]2D5 = +7.8 (c = 0.33, CHCl3). 1H NMR
(300 MHz, C6D6): δ = 1.31 (s, 3 H, Me), 1.45 (s, 3 H, Me), 4.10
(m, 2 H, 6-H), 4.25 (t, J = 6.7 Hz, 1 H, 4-H), 4.55 (m, 1 H, 5-H),
4.70 (dd, J = 2.9, 6.7 Hz, 1 H, 3-H), 5.39 (d, J = 2.9 Hz, 1 H, 2-
H), 7.10 (m, 3 H, Ph), 7.56 (m, 2 H, Ph) ppm. 13C NMR (50 MHz,
C6D6): δ = 25.5, 27.0, 67.0, 73.6, 74.0, 85.6, 99.2, 109.2, 124.1,
125.9, 128.3, 129.4, 159.8 ppm. MS (EI): m/z = 263.1 [M + 1]+.
1,4-Anhydro-5,6-O-isopropyliden-2-deoxy-1-C-methyl-D-arabino-
hex-1-enitol (23): Using the general procedure, chloride 20 (250 mg,
0.89 mmol) was treated with MeLi (1.6  in diethyl ether, 1.7 mL,
2.67 mmol) at 0 °C. Extractive workup was followed by quick flash
chromatography (10% EtOAc/hexane) to give C-1 glycal 23 (65 mg,
1,5-Anhydro-4,6-O-isopropyliden-2-deoxy-1-C-methyl-D-arabino-
hex-1-enitol (28): Using the general procedure, chloride 22 (150 mg,
0.75 mmol) was treated with MeLi (1.6  in diethyl ether, 1.4 mL,
2.25 mmol) at 0 °C. Extractive workup was followed by quick flash
chromatography (10 % EtOAc/hexane) to give C-1 glycal 28
60%). [α]2D5 = –4.5 (c = 0.42, CHCl3). H NMR (300 MHz, C6D6):
1
δ = 1.28 (s, 3 H, Me), 1.41 (s, 3 H, Me), 1.56 (s, 3 H, Me), 4.05 (m,
2 H, 6-H), 4.14 (dd, J = 6.1, 7.4 Hz, 1 H, 4-H), 4.53 (dt, J = 7.4, (97.5 mg, 65%). [α]2D5 = +23.8 (c = 1.0, CHCl3). 1H NMR
6.0 Hz, 1 H, 5-H), 4.68 (m, 1 H, 3-H), 4.69 (m, 1 H, 2-H) ppm.
13C NMR (50 MHz, C6D6): δ = 25.3, 25.8, 27.4, 67.5, 74.0, 74.6,
86.3, 100.6, 105.9, 169.0 ppm. MS (EI): m/z = 201.0 [M + 1]+, 200.0
[M]+, 199.0, 185.0, 167.0, 141.0, 127.0, 125.0, 101.0, 73.0, 59.0,
43.0.
(300 MHz, CDCl3): δ = 1.42 (s, 3 H, Me), 1.51 (s, 3 H, Me), 1.72
(m, 3 H, Me), 3.71 (m, 2 H, 4-H, 5-H), 3.81 (t, J = 10.2 Hz, 1 H,
6-H), 3.93 (dd, J = 5.1, 10.2 Hz, 1 H, 6-H), 4.28 (br. s, 1 H, 3-H),
4.49 (m, 1 H, 2-H) ppm. 13C NMR (50 MHz, CDCl3): δ = 19.3,
19.5, 29.2, 62.0, 68.0, 69.2, 73.9, 99.5, 99.9, 152.6 ppm. MS (API-
ES+): m/z = 201.0 [M + 1]+, 223.1 [M + Na]+. C10H16O4 (200.23):
calcd. C 59.98, H 8.05; found C 59.77, H 8.09.
1,4-Anhydro-5,6-O-isopropyliden-2-deoxy-1-C-n-butyl-D-arabino-
hex-1-enitol (24): Using the general procedure, chloride 20 (108 mg,
0.39 mmol) was treated with nBuLi (1.6  in hexane, 0.73 mL,
1.17 mmol) at 0 °C. Extractive workup was followed by quick flash
chromatography (20% EtOAc/hexane) to give C-1 glycal 24 (50 mg,
54%). [α]2D5 = –30.8 (c = 0.78, CHCl3). 1H NMR (300 MHz, C6D6):
δ = 0.79 (t, J = 7.3 Hz, 3 H, Me), 1.11 (m, 2 H, CH2), 1.20 (m, 2
H, CH2), 1.28 (s, 3 H, Me), 1.42 (s, 3 H, Me), 2.02 (t, J = 7.3 Hz,
2 H, CH2), 4.07 (m, 2 H, 6-H), 4.18 (t, J = 7.0 Hz, 1 H, 4-H), 4.55
(dt, J = 6.0, 7.0 Hz, 1 H, 5-H), 4.70 (m, 1 H, 3-H), 4.75 (m, 1 H,
2-H) ppm. 13C NMR (50 MHz, C6D6): δ = 13.9, 22.5, 25.5, 27.0,
28.1, 28.8, 67.1, 73.7, 74.0, 85.6, 99.2, 109.1, 164.0 ppm. MS (EI):
m/z = 243.1 [M + 1]+, 227.0, 225.1, 207.1, 199.0, 185.1, 183.0,
167.0, 165.0, 125.0, 100.9.
1,5-Anhydro-4,6-O-isopropyliden-2-deoxy-1-C-n-butyl-D-arabino-
hex-1-enitol (29): Using the general procedure, chloride 22 (150 mg,
0.61 mmol) was treated with nBuLi (1.6  in hexane, 1.14 mL,
1.83 mmol) at 0 °C. Extractive workup was followed by quick flash
chromatography (20% EtOAc/hexane) to give C-1 glycal 29 (91 mg,
62%). [α]2D5 = +7.6 (c = 0.43, CHCl3). 1H NMR (300 MHz, CDCl3):
δ = 0.87 (t, J = 7.1 Hz, 3 H, Me), 1.29 (m, 4 H, CH2), 1.42 (s, 3
H, Me), 1.51 (s, 3 H, Me), 1.98 (t, J = 7.1 Hz, 2 H, CH2), 3.67 (m,
2 H, 4-H, 5-H), 3.80 (t, J = 10.0 Hz, 1 H, 6-H), 3.94 (dd, J = 5.4,
10.0 Hz, 1 H, 6-H), 4.28 (br. s, 1 H, 3-H), 4.48 (m, 1 H, 2-H) ppm.
13C NMR (50 MHz, CDCl3): δ = 13.9, 19.1, 23.3, 26.6, 29.1, 32.9,
61.9, 67.7, 69.1, 73.9, 98.7, 99.8, 155.9 ppm. MS (API-ES+): m/z =
243.3 [M + 1]+. C13H22O4 (242.31): calcd. C 64.44, H 9.15; found
C 63.96, H 9.01.
1,4-Anhydro-5,6-O-isopropyliden-2-deoxy-1-C-sec-butyl-D-arabino-
hex-1-enitol (25): Using the general procedure, chloride 20 (90 mg,
0.32 mmol) was treated with sBuLi (1.4  in cyclohexane, 0.69 mL,
0.97 mmol) at 0 °C. Extractive workup was followed by quick flash
chromatography (20% EtOAc/hexane) to give C-1 glycal 25 (50 mg,
54 %) as a 2:1 mixture of diastereomers. Selected peaks for the
major isomer.1H NMR (200 MHz, CDCl3): δ = 0.87 (t, J = 7.4 Hz,
1,5-Anhydro-4,6-O-isopropyliden-2-deoxy-1-C-sec-butyl-D-arabino-
hex-1-enitol (30): Using the general procedure, chloride 22 (150 mg,
0.61 mmol) was treated with sBuLi (1.4  in cyclohexane, 1.31 mL,
1.83 mmol) at 0 °C. Extractive workup was followed by quick flash
chromatography (20 % EtOAc/hexane) to give C-1 glycal 30
3 H, Me), 1.07 (d, J = 6.9 Hz, 3 H, Me), 1.37 (s, 3 H, Me), 1.39 (121 mg, 82%) as a 3:1 mixture of diastereomers. Selected peaks
1
(m, 2 H, CH2), 1.45 (s, 3 H, Me), 2.2 (m, 1 H, CH), 4.01 (m, 2 H), for the major isomer: H NMR (200 MHz, CDCl3): δ = 0.86 (t, J
4.16 (dd, J = 6.2, 8.0 Hz, 1 H, 6-H), 4.47 (dt, J = 8.0, 6.2 Hz, 1 H,
6-H), 4.86 (m, 2 H) ppm. 13C NMR (50 MHz, CDCl3): δ = 11.3,
17.2, 25.3, 26.8, 26.9, 34.5, 66.9, 73.2, 73.8, 84.6, 97.4, 109.1,
168.6 ppm. MS (API-ES+): m/z = 243.3 [M + 1]+.
= 7.3 Hz, 3 H, Me), 1.02 (d, J = 7.1 Hz, 3 H, Me), 1.30 (m, 2 H,
CH2), 1.44 (s, 3 H, Me), 1.54 (s, 3 H, Me), 2.01 (m, 1 H, CH), 3.67
(m, 2 H, 4-H, 5-H), 3.82 (t, J = 10.0 Hz, 1 H, 6-H), 3.96 (dd, J =
5.4, 10.0 Hz, 1 H, 6-H), 4.32 (br. s, 1 H, H-3), 4.50 (m, 1 H, 2-H)
Eur. J. Org. Chem. 2009, 3579–3588
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3585

A. M. Gómez, A. Pedregosa, M. Casillas, C. Uriel, J. C. López
FULL PAPER
ppm.13C NMR (50 MHz, CDCl3): δ = 11.7, 17.9, 19.2, 27.0, 29.1,
39.0, 61.9, 68.1, 69.1, 74.0, 99.8, 159.5 ppm. MS (API-ES+): m/z =
243.1 [M + 1]+, 265.0 [M + Na]+. C13H22O4 (242.31): calcd. C
64.44, H 9.15; found C 64.19, H 8.97.
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hex-1-enitol (31): Using the general procedure, chloride 22 (100 mg,
0.41 mmol) was treated with tBuLi (1.7  in pentane, 0.72 mL,
1.23 mmol) at 0 °C. Extractive workup was followed by quick flash
chromatography (20% EtOAc/hexane) to give C-1 glycal 31 (49 mg,
49%). [α]2D5 = +4.6 (c = 0.75, CHCl3). 1H NMR (300 MHz, CDCl3):
δ = 1.06 (s, 9 H, tBu), 1.44 (s, 3 H, Me), 1.54 (s, 3 H, Me), 3.66
(m, 2 H, 4-H, 5-H), 3.83 (t, J = 10.2 Hz, 1 H, 6-H), 3.97 (dd, J =
5.4, 10.2 Hz, 1 H, 6-H), 4.33 (m, 1 H, 3-H), 4.56 (d, J = 2.1 Hz, 1
H, 2-H) ppm. 13C NMR (50 MHz, CDCl3): δ = 19.4, 28.1, 29.3,
35.1, 62.1, 68.3, 69.2, 74.0, 95.5, 99.9, 163.4 ppm. MS (EI): m/z =
243.1 [M + 1]+. C13H22O4 (242.31): calcd. C 64.44, H 9.15; found
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[M + 1]+. C15H18O4 (262.30): calcd. C 68.68, H 6.92; found C
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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. thanks the
Ministerio de Ciencia y Tecnología for a scholarships. A. P. is
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