Sequential directed epoxydation-acidolysis from glycals with MCPBA. A flexible approach to protected glycosyl donors

Article abstract of DOI:10.1021/jo201165v

4,6-Di-O-protected glucal and allal derivatives react with MCPBA to afford manno- and allo-1-O-m-chlorobenzoate derivatives, respectively, as a result of a syn epoxidation directed by the allylic hydroxyl group, and consecutive ring-opening by m-ClBzOH. When glucal and allal derivatives are fully protected, initial epoxidation proceeds mainly anti to the allylic group to give, after ring-opening, the corresponding pyranosyl chlorobenzoates. Stereoselectivity in the reaction of fully protected galactal derivatives was complete, although only a moderate increase in the syn epoxidation product was observed in 4,6- and 3,4-di-O-protected derivatives. 1-O-m-Chlorobenzoate 18 was selectively protected and activated as donor in the synthesis of disaccharide 21.

Full text of DOI:10.1021/jo201165v

ARTICLE
pubs.acs.org/joc
Sequential Directed Epoxydation-Acidolysis from Glycals with MCPBA.
A Flexible Approach to Protected Glycosyl Donors
Irene Marín, Javier Castilla, M. Isabel Matheu, Yolanda Díaz,* and Sergio Castillꢀon*
Departament de Química Analítica i Química Orgꢁanica, Universitat Rovira i Virgili, C/Marcel lí Domingo s/n, 43007 Tarragona, Spain
3
S Supporting Information
b
ABSTRACT: 4,6-Di-O-protected glucal and allal derivatives
react with MCPBA to afford manno- and allo-1-O-m-chloro-
benzoate derivatives, respectively, as a result of a syn epoxida-
tion directed by the allylic hydroxyl group, and consecutive ring-
opening by m-ClBzOH. When glucal and allal derivatives are
fully protected, initial epoxidation proceeds mainly anti to the
allylic group to give, after ring-opening, the corresponding
pyranosyl chlorobenzoates. Stereoselectivity in the reaction of fully protected galactal derivatives was complete, although only a
moderate increase in the syn epoxidation product was observed in 4,6- and 3,4-di-O-protected derivatives. 1-O-m-Chlorobenzoate
18 was selectively protected and activated as donor in the synthesis of disaccharide 21.
’ INTRODUCTION
Scheme 1. (a) Stoichiommetric Epoxidation Methods of
Glycals. (b) Tandem EpoxidationÀAlcoholysis or Epoxida-
tionÀGlycosylation of Glycals
The synthesis of carbohydrate-based structures has become an
important field of research and one of the biggest challenges of
organic synthesis and medicinal chemistry.1 In this context,
efficient functionalization and selective protection procedures
are key points in the synthesis of complex oligosaccharides.1
Glycals have recently found a wide application as synthetic
building blocks in the construction of various glycoconjugates.2
One of the most direct strategies for activation of the double
bond in glycals is epoxidation3 to furnish 1,2-anhydrosugars,
which are used as glycosyl donors, or as precursors of more stable
glycosyl donors (Scheme 1a).4 This transformation, however,
suffers from several limitations due to the sensitive nature of the
1,2-anhydrosugar. On one hand, many epoxidation reactions lead
to glycoside derivatives as a consequence of acid-catalyzed ring-
opening of the labile anhydrosugar initially formed. Furthermore,
an efficient epoxidation reaction of glycals must render the
anhydrosugar free of any coproducts, as purification of the crude
epoxide from a complex mixture is precluded. Practically the only
reagent used for that purpose is dimethyldioxirane (DMDO).3
1,2-Anhydrosugars synthesized this way have been directly used
in glycosylation events or transformed in a series of glycosyl
donors, such as thioglycosides,5 pentenyl glycosides,6 amino
glycosides,7 glycosyl fluorides,7 or glycosyl phosphates.8 How-
ever, DMDO is unstable, has to be freshly prepared and poses
serious safety problems, although the methods that generate it
in situ9 partially circumvent these problems. Other stoichiom-
metric oxidants, namely MCPBA/KF10 or perfluoro-cis-2,3-dialkyl-
oxaziridines,11 have been described to furnish highly pure sugar
epoxides free of coproducts in a operationally easy way but have
not found wide application in glycoconjugate synthesis, probably
because of limited reaction scope or the use of nonconventional
perfluorinated solvents/reagents.12
The elusive nature of 1,2-anhydro carbohydrates has moti-
vated the development of one-pot epoxidationÀglycosylation or
epoxidationÀhydrolysis of glycals in order to obtain stable
glycosides or 1,2-sugar diols, that in turn are useful intermediates
in several organic transformations. The stoichiometric system
Tf2O/diphenyl sulfoxide13 promotes glycal oxidation via epox-
idationÀglycosylation processes. Interestingly, the use of Tf2OÀ
dibenzothiophene 5-oxide allows α-mannopyranosides to be
obtained from glucal derivatives.
Received: June 6, 2011
Published: September 13, 2011
r
2011 American Chemical Society
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The need for atomic economy and environmental awareness
spurred the development of new catalytic epoxidation methods,
but so far none have been able to provide sugar epoxides.
Transition metal-based catalysts such as Ru-porphyrin,14 CH3ReO3
(MTO),15,16 Ti(O-i-Pr)4,17 Venturello’s peroxotungstate (PW4O243),17
Table 1. MCPBA-Induced Stereoselective Tandem Epoxi-
dationÀGlycosylation of Glucals 1aÀf
18
and [Mo]/TBHP or H2O2 typically provide compounds
resulting from sequential epoxidationÀalcoholysis or hydrolysis19
reactions (Scheme 1b). Most of these reactions have been
explored with fully protected glucals and render the glucopyrano-
side derivatives as major products, as a consequence of initial
sterically controlled epoxidation, mainly exerted by the substi-
tuent at C-3.
On the other hand, the synthesis of mannosylated structures20
and related neoglycoconjugates mimicking natural systems is a
hot spot in glycobiology. One of the goals is to obtain multivalent
carbohydrate systems in order to enhance the weak affinity of
individual carbohydrateÀprotein interactions. Another objective
is the synthesis of oligosaccharides for biochemical studies. Both
synthetic approaches rely on protection and deprotection stra-
tegies leading to multistep syntheses and too often represent the
bottleneck of these synthetic strategies. Some examples of synth-
esis of orthogonally protected galactose,21 N-acetyl glucosamine,22
and mannose23 derivatives have been described.
In this context, the aim of this work was to provide an easy
access to orthogonally protected mannopyranoside derivatives.
Here we present a systematic study of the epoxidationÀ
glycosylation of glycals with MCPBA in order to obtain glyco-
pyranosides. The idea is to use partially protected glycals with
free hydroxyl groups in the allylic position in order to deliver the
electrophilic oxygen to the sterically more congested glycal
stereoface syn to the allylic alcohol, by promoting hydrogen
bonding between the hydroxyl group and MCPBA. This trans-
formation is anticipated to invert the typical stereoselectivity
outcome of the oxidation reactions from fully protected glycals.
The directed syn-oxidation of allylic alcohols with MCPBA has
been widely documented, but it has not been systematically
applied to unprotected glycals.24
a Conditions: 0.36 mmol of glycal, 0.72 mmol of MCPBA, 11.5 mL of
anhydrous CH2Cl2, rt. b Determined by NMR by integration of the
anomeric protons of the crude reaction mixture. c Both compounds were
obtained as α/β mixtures. d Only the α anomer was detected.
Scheme 2. MCPBA-Mediated Tandem Epoxidation-Ring-
Opening of Glycals
’ RESULTS AND DISCUSSION
Oxidation of tri-O-acetyl-D-glucal (1a) with MCPBA in di-
chloromethane as the solvent afforded a mixture of m-chloro-
benzoyl-gluco- (2a) and manno-pyranoside (3a) in a ratio 80:20
(Table 1, entry 1), as a result of glycal epoxidation to give the
gluco- and manno-epoxides followed by ring-opening by the m-
chlorobenzoate anion generated in situ (Scheme 2). Tri-O-
benzyl-glucal (1b) provided a similar behavior, and the corre-
sponding glycosides were obtained in quantitative yield and
comparatively improved stereoselectivity, ratio gluco:manno =
84:16 (Table 1, entry 2). The use of bulkier protecting groups,
such as pivaloate groups in glycal 1c,25 did not afford better
stereoselectivities (Table 1, entry 3). Although α/β mixtures
were obtained in all cases, the product derived from the α-
epoxide (gluco), trans to the C-3 substituent, was the major one.
Oxidation of the conformationally more rigid glucal derivative
1d furnished glycosides 2d and 3d with similar stereoselectivity
to those of the previous examples (Table 1, entry 4). In order to
reverse the stereoselectivity of the process, the directing effect of
a hydroxyl group at the allylic position was explored. Gratifyingly,
when partially protected glucal 1e26 reacted with MCPBA,
glycoside 3e derived from the manno-epoxide was exclusively
obtained in 83% yield (Table 1, entry 5). In rigid systems such as
this one, the directing effect can be conditional on conforma-
tional effects. The high level of stereoselectivity obtained in 1e,
however, is indicative of a directing effect, and actually the 4H5
conformation of glycal 1e seems to fit well with the postulated
transition state model for MCPBA epoxidation of allylic alcohols,
where the dihedral angle ranges 120À140° (Figure 1a).27 Oxida-
tion of 4,6-di-O-acetyl-D-glucal (1f)28 was carried out in order to
confirm the hydroxyl group directing effect in conformationally
more flexible compounds (Table 1, entry 6). The product
derived from the manno-epoxide 3f was again preferentially
obtained in 76% yield with a selectivity gluco:manno 10:90.
MCPBA oxidation of allal derivatives 4a and 4b,29 with an
allylic substituent in a pseudoaxial position, was also analyzed
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Table 2. MCPBA-Induced Stereoselective Tandem Epoxi-
dationÀGlycosylation of Galactal Derivatives 7aÀf
Figure 1. Proposed transition states for the 3-OH directed epoxidation
with MCPBA of glucal 1e (a), allal 4b (b), and galactal 7d (c).
Scheme 3. MCPBA-Mediated EpoxidationÀAcidolysis of
(a) Protected Allal 4a and (b) Partially Protected Allal 4b
(Scheme 3). As expected, oxidation of fully protected allal 4a
rendered altro-glycoside 5a as the major product, as a conse-
quence of epoxidation on the more accessible glycal face.
Reaction from partially protected allal 4b, in contrast, furnished
exclusively allo-glycoside 6b in 90% yield, confirming the direct-
ing effect of the allylic hydroxyl group in the MCPBA-mediated
oxidation of glycals (Figure 1b).
a Conditions: 0.36 mmol of glycal, 0.72 mmol of MCPBA, 11.5 mL of
anhydrous CH2Cl2, rt. b Determined by NMR by integration of the
anomeric protons of the crude reaction mixture. c Both compounds were
obtained as α/β mixtures.
The effect of glycal configuration in the stereoselectivity of
MCPBA-mediated epoxidationÀglycosylation was extended to
galactal derivatives (Table 2). Oxidation of tri-O-acetyl-D-galactal
(7a) afforded galactoside 8a as the major product (8a/9a ratio =
82:18) (Table 2, entry 1), similar to the selectivity obtained for
the glucal analogue. Similarly, oxidation of tri-O-benzyl derivative
7b furnished 8b as the major product with a galacto:talo ratio =
85:15 (Table 2, entry 2), again similar to the selectivity obtained
in the glucal analogue. Oxidation of tri-O-pivaloyl-D-galactal
(7c)25 afforded exclusively 8c in 88% yield (Table 2, entry 3),
improving the selectivity obtained with the gluco analogue 1c.
The axial substituent at C-4 plays a major role in the stereofacial
bias of the glycal toward epoxidation, directing oxygen transfer
preferentially from the opposite face.
Partially protected galactal derivatives having free hydroxyl
groups at positions 3, 4, or 6 (7dÀf) were also tested. When
compound7d,28 witha free allylichydroxyl group, was treatedwith
MCPBA, the galacto derivative 8d was still the major product
although the percentage of the talo derivative 9d increased
significantly (galacto:talo ratio = 67:33) (Table 2, entry 4). The
presence of an axial substituent at C-4 may destabilize the
transition state that involves the complexation of MCPBA to the
3-OH(Figure1c). Virtually thesameselectivitywas obtained from
oxidation of glycal 7e,30 with a a free hydroxyl group at position 6
(Table 2, entry 5), although implication of a directing effect of the
distal hydroxyl group is rather unlikely, especially if the 4H5 half-
chair conformation of the glycal is considered. Oxidation of
Scheme 4. MCPBA-Mediated Epoxidation of Partially Pro-
tected Glucal 1e
galactal 7f31 led to the galacto derivative 8f in 85% yield with an
excellent stereoselectivity (8f/9f ratio = 90:10). Homoallylic
hydroxyl groups can direct epoxidation in cyclic systems, especially
if they occupy axial positions. Probably the presence of bulky
groups at positions 3 and 6 limits the coordination of MCPBA to
the hydroxyl group. Thus, the directing effect of a hydroxyl group
in the oxidation of galactals is rather weak and is very sensitive to
steric interferences.
Tandem epoxidationÀalcoholysis has been reported using
mainly metal catalysts.15À17 We explored this tandem reaction
using MCPBA in methanol as a solvent. Under these condi-
tions, methyl glycosides 10 and 1132 were obtained (Scheme 4)
in a 17:83 ratio, with a manno stereoselectivity partially eroded
with respect to its analogous reaction in CH2Cl2 (compare with
Table 1, entry 5, where only the manno derivative was
detected). The use of polar alcoholic solvents may partially
cancel this syn-directing effect by disturbing the hydrogen
bonding. EpoxidationÀmethanolysis of tri-O-acetyl-D-glucal
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Scheme 5. Synthesis of Orthogonally Protected α-Mannopyranoside Building Blocks
Scheme 6. Synthesis of Disaccharide 21
with methyltrioxorhenium (MTO) or supported MTO deriva-
tives and urea hydrogen peroxide adduct in ionic liquids have
been described to give, at best, 36:64 mixtures of the gluco:
manno methyl glycosides,15,16 whereas the analogous reaction
with Ti(O-i-Pr)4 provided highly stereoselectivity (gluco/manno
ratio = 6:94) although it required long reaction times (170 h) and
did not lead to full conversion.17
thichloroacetamidite, which was treated in situ with the acceptor 20
and TMSOTf as activator. The reaction was conducted for 2 h to
afford disaccharide 21 in 49% yield (Scheme 6).
’ CONCLUSION
Partially unprotected glycals with free hydroxyl groups in the
allylic position direct the stereoselectivity of the epoxidation with
MCPBA to give the syn-epoxide, which is opened in situ under
the reaction conditions to give glycosylated compounds. The
reaction was completely stereoselective when glucal 1e and allal
4b derivatives were the starting materials and very stereoselective
with glucal 1f. Oxidation of galactal derivatives proceeded with
much lower stereocontrol, probably due to destabilization of the
transition state by the presence of an axial substituent at C-4. When
the allyl hydroxyl group was protected, products derived from the
anti-epoxide were obtained. Orthogonally protected manno-glyco-
syl donors 16 and 18 have been synthesized using this procedure in
only five and four steps in 20% and 37% overall yields, respectively.
Compound 18 was hydrolyzed, activated as the trichloroacetimidate,
and used as a donor to afford disaccharide 21, which demonstrates
that this compound can be used as glycosyl donor.
The usefulness of the directed tandem epoxidationÀglycosylation
procedure developed in this paper was demonstrated by the
straightforward synthesis of the manno-glycosyl donors 16 and
18 (Scheme 5). Compound 13 was prepared from D-glucal (12)
following reported procedures.33 The reaction of 13 with
MCPBA under the previously reported conditions afforded com-
pound 14 in 50% yield. Monoprotection of the equatorial hydroxyl
function in 14 by forming first the stannyl acetal and consecutive
addition of p-methoxybenzyl chloride afforded compound 15.34
Subsequent acylation of the free hydroxyl group at position 2 with
levulinic acid/DCC gave orthogonally protected mannopyranoside
16 in 43% yield (two steps).35 Compound 18 was prepared from
diol 14 via sequential silylation and pivaloylation following the
Seeberger procedure.36 Orthogonally protected chlorobenzyl α-
mannopyranosides 16 and 18 were synthesized in five and four steps
from D-glucal in overall yields of 20% and 37%, respectively.
Compound 18 was then selected to test its potential use as
donor in glycosylation reactions. Thus, the treatment of 18 with
2-aminoethanol afforded mannose derivative 19 in 88% yield. Then,
19 was reacted with trichloroacetonitrile to form the corresponding
’ EXPERIMENTAL SECTION
General Experimental Methods. All chemicals used were
reagent grade and used as supplied. Glucals 1a,b and galactals 7a,b were
commercially available. Glycals 1d and 4a were obtained through a
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1
conventional procedure for acetylation. All other glycals were synthe-
sized according to literature procedures: 1c,25 1e,26 1f,28 4b,29 7c,25 7d,28
7e,30 7f,31 13.33 HPLC grade dichloromethane (CH2Cl2), tetrahydro-
furan (THF), dimethylformamide (DMF), and diethyl ether were dried
using a solvent purification system. The other solvents were purified
using standard procedures.37 1H and 13C NMR spectra were recorded in
CDCl3 as solvent at 400 and 100 MHz, respectively, with chemical shifts
(δ) referenced to internal standards CDCl3 (7.27 ppm 1H, 77.23
ppm 13C) or Me4Si as an internal reference (0.00 ppm), unless otherwise
specified. The 2D correlation spectra (TOCSY, gCOSY, NOESY,
gHSQC, gHMBC) were visualized using VNMR program. Optical
rotations were measured at 598 nm at room temperature with 10 cm
cells. Analytical thin layer chromatography (TLC) was performed on
silica gel 60 F254 glass or aluminum plates. Compounds were visualized
by UV (254 nm) irradiation or dipping the plate in a suitable developing
solution. Flash column chromatography was carried out using forced
flow or by gravity of the indicated solvent on silica gel 60 (230À400 mesh).
Radial chromatography was performed on 1, 2, or 4 mm plates of
60 PF254 silica gel, depending on the amount of product.
Data for 6bβ: [α]25 À15.65 (c 0.3, CHCl3). H NMR (CDCl3,
D
400 MHz) δ in ppm: 8.08 (dd, 1H, J = 1.6, 1.6 Hz), 7.99 (d, 1H, J =
8.0 Hz), 7.56 (ddd, 1H, J = 8.0, 1.2, 1.2 Hz), 7.40 (dd, 1H, J = 8.0, 8.0
Hz), 6.07 (d, 1H, J = 8.4 Hz), 4.32 (dd, 1H, J = 2.8, 2.4 Hz), 4.03À3.96
(m, 2H), 3.81 (dd, 1H, J = 8.4, 3.6 Hz), 3.77À3.69 (m, 2H), 1.53 (s, 3H),
1.46 (s, 3H). 13C NMR (CDCl3, 100.6 MHz) δ in ppm: 164.3, 134.8,
133.9, 131.1, 130.3, 130.0, 128.5, 100. 0, 94.3, 71.3, 70.6, 69.6, 64.9, 62.3,
29.1, 19.4. FT-IR (neat) ν in cmÀ1: 3390, 2941, 1734, 1250, 1066, 1024,
747. HRMS (ESI+) m/z calcd for C16H19ClNaO7 [M À Na]: 381.0717,
found: 381.0679.
Spectroscopic data of 6bα from the α/β mixture: 1H NMR (CDCl3,
400 MHz) δ in ppm: 8.05 (d, 1H, J = 1.6 Hz), 7.97 (dd, 1H, J = 7.6, 1.6
Hz), 7.61 (d, 1H, J = 8.0 Hz), 7.45 (dd, 1H, J = 8.0, 7.6 Hz), 6.56 (d, 1H,
J = 4.0 Hz), 5.57 (dd, 1H, J = 3.2, 1.2 Hz), 5.41 (dd, 1H, J = 10.4, 3.2 Hz),
4.38 (dd, 1H, J = 7.2, 6.8 Hz), 4.27 (dd, 1H, J = 10.4, 4.0 Hz), 4.11 (dd,
1H, J = 10.8, 6.8 Hz), 4.05 (dd, 1H, J = 10.8, 7.2 Hz), 1.28 (s, 9H), 1.22
(s, 9H), 1.13 (s, 9H). 13C NMR (CDCl3, 100.6 MHz) δ in ppm: 178.9,
178.0, 177.0, 164.0, 135.1, 134.1, 130.9, 130.3, 130.1, 128.2, 93.2, 70.7,
69.7, 67.3, 67.2, 61.1, 39.3, 39.2, 38.9, 27.4, 27.3, 27.2.
General Procedure for MCPBA Epoxidation. To a solution of
glycal (0.36 mmol) in dry CH2Cl2 (11.5 mL) was added MCPBA (180 mg,
0.72 mmol). The mixture was stirred at room temperature. The reaction
was monitored by TLC until the starting material was consumed. The
solution was extracted with CH2Cl2 and washed successively with
saturated aqueous NaHCO3 and water. The solution was dried over
MgSO4, and then the solvent was removed under reduced pressure. The
resulting residue was analyzed by 1H NMR.
1-O-(3-Chlorobenzoyl)-3,4,6-tri-O-pivaloyl-α-D-galacto-
pyranoside (8cα) and 1-O-(3-Chlorobenzoyl)-3,4,6-tri-O-pi-
valoyl-β-D-galactopyranoside (8cβ). Following the general pro-
cedure for MCPBA epoxidation, 8cα and 8cβ were synthesized from 7c
(0.08 g, 0.2 mmol) and MCPBA (0.10 g, 0.4 mmol). The final products
8cα and 8cβ were obtained in a ratio 21:79, respectively. Purification by
radial chromatography (hexane/EtOAc 9:1) afforded compounds 8cα
(0.03 g, 0.06 mmol, 27%) and 8cβ (0.07 g, 0.12 mmol, 61%) as colorless
syrups (overall yield 88%).
1-O-(3-Chlorobenzoyl)-4,6-O-isopropylidene-α-D-manno-
pyranoside (3e). Following the general procedure, 1e (0.05 g,
0.27 mmol) was reacted with MCPBA (0.07 g, 0.54 mmol) to furnish
compound 3e as a white solid (0.08 g, 0.22 mmol, 83%), after purification
by flash chromatography (hexane/EtOAc 1:2). Mp 175À177 °C.
Data for 3e: [α]25D +17.8 (c 1.18, CHCl3). 1H NMR (CDCl3, 400
MHz) δ in ppm: 7.99 (bs, 1H), 7.94 (dd, 1H, J = 8.0, 1.2 Hz), 7.59 (ddd,
1H, J = 8.0, 1.2, 1.2 Hz), 7.43 (dd, 1H, J = 8.0, 8.0 Hz), 6.37 (d, 1H, J =
1.2 Hz), 4.18 (bs, 1H), 4.09 (d, 1H, J = 5.2 Hz), 3.91À3.76 (m, 4H), 1.54
(s, 3H), 1.45 (s, 3H). 13C NMR (CDCl3, 100.6 MHz) δ in ppm: 163.4,
135.0, 134.0, 131.0, 130.2, 130.0, 128.3, 100.5, 94.5, 70.9, 70.2, 69.3, 66.8,
62.1, 29.3, 19.5. FT-IR (neat) ν in cmÀ1: 3418, 3291, 2994, 2925, 1730,
1252, 1083, 961, 856, 744. HRMS (ESI+) m/z calcd for C16H19ClNaO7
[M À Na]: 381.0717, found: 381.0703.
Data for 8cα: [α]25D +30.5 (c 0.74, CHCl3). 1H NMR (CDCl3, 400
MHz) δ in ppm: 8.05 (d, 1H, J = 1.6 Hz), 7.97 (dd, 1H, J = 7.6, 1.6 Hz),
7.61 (d, 1H, J = 8.0 Hz), 7.45 (dd, 1H, J = 8.0, 7.6 Hz), 6.56 (d, 1H, J =
4.0 Hz), 5.57 (dd, 1H, J = 3.2, 1.2 Hz), 5.41 (dd, 1H, J = 10.4, 3.2 Hz),
4.38 (dd, 1H, J = 7.2, 6.8 Hz), 4.27 (dd, 1H, J = 10.4, 4.0 Hz), 4.11 (dd,
1H, J = 10.8, 6.8 Hz), 4.05 (dd, 1H, J = 10.8, 7.2 Hz), 1.28 (s, 9H), 1.22
(s, 9H), 1.13 (s, 9H). 13C NMR (CDCl3, 100.6 MHz) δ in ppm: 178.9,
178.0, 177.0, 164.0, 135.1, 134.1, 130.9, 130.3, 130.1, 128.2, 93.2, 70.7,
69.7, 67.3, 67.2, 61.1, 39.3, 39.2, 38.9, 27.4, 27.3, 27.2. FT-IR (neat) ν
in cmÀ1: 3462, 2970, 1738, 1365, 1217. FT-IR (neat) ν in cmÀ1: 3462,
2970, 1738, 1365, 1229, 1217, 1023, 748. HRMS (ESI+) m/z calcd for
C28H39ClNaO10 [M À Na]: 593.2129, found: 593.2101.
1
Data for 8cβ: [α]25 +9.39 (c 1.94, CHCl3). H NMR (CDCl3,
D
4,6-Di-O-acetyl-1-O-(3-chlorobenzoyl)-α-D-mannopyrano-
side (3f). Following the general procedure, 1f (0.03 g, 0.13 mmol) was
reacted with MCPBA (0.05 g, 0.26 mmol) to afford a 1:9 mixture of
compounds 2f and 3f. Purification by radial chromatography (hexane/
EtOAc 1:2) afforded compound 3f as a white solid (0.04 g, 0.10 mmol,
400 MHz) δ in ppm: 8.09 (dd, 1H, J = 2.0, 2.0 Hz), 8.01 (dd, 1H, J =
7.6, 2.0 Hz), 7.57 (dd, 1H, J = 8.0, 2.0 Hz), 7.41 (dd, 1H, J = 8.0, 7.6 Hz),
5.87 (d, 1H, J = 8.0 Hz), 5.48 (d, 1H, J = 3.2 Hz), 5.16 (dd, 1H, J = 10.4,
3.2 Hz), 4.24À4.03 (m, 4H), 1.29 (s, 9H), 1.20 (s, 9H), 1.18 (s, 9H). 13C
NMR (CDCl3, 100.6 MHz) δ in ppm: 178.4, 178.1, 177.0, 163.9, 134.8,
134.0, 130.9, 130.3, 130.2, 128.5, 95.2, 73.2, 72.3, 69.3, 66.9, 61.0, 39.3,
39.1, 38.9, 27.4, 27.3, 27.2. FT-IR (neat) ν in cmÀ1: 3447, 2970, 1739,
1365, 1217, 1066, 746. HRMS (ESI+) m/z calcd for C28H39ClNaO10
[M À Na]: 593.2129, found: 593.2096.
76%). Mp 140À142 °C.
1
Data for 3f: [α]25 +4.79 (c 0.7, CHCl3). H NMR (CDCl3, 400
D
MHz) δ in ppm: 7.98 (s, 1H), 7.92 (d, 1H, J = 8.0 Hz), 7.60 (ddd, 1H, J =
8.0, 1.2, 1.2 Hz), 7.44 (dd, 1H, J = 8.0, 8.0 Hz), 6.43 (d, 1H, J = 2.0 Hz),
5.19 (dd, 1H, J = 9.6, 9.6 Hz), 4.38 (dd, 1H, J = 12.4, 4.4 Hz), 4.14 (dd,
1H, J = 9.6, 2.0 Hz), 4.16À4.05 (m, 3H), 2.17 (s, 3H), 2.09 (s, 3H). 13C
NMR (CDCl3, 100.6 MHz) δ in ppm: 172.1, 171.1, 163.2, 134.2, 134.2,
130.9, 130.3, 130.0, 128.3, 94.0, 70.8, 70.5, 70.0, 69.5, 62.4, 21.2, 21.0.
FT-IR (neat) ν in cmÀ1: 3424, 3303, 2931, 1733, 1250, 1084, 964, 858,
744. HRMS (ESI+) m/z calcd for C17H19ClNaO9 [M À Na]: 425.0615,
found: 425.0606.
3,6-Di-O-tert-butyldimethylsilyl-1-O-(3-chlorobenzoyl)-α-D-galac-
topyranoside (8fα) and 3,6-Di-O-tert-butyldimethylsilyl-1-
O-(3-chlorobenzoyl)-β-D-galactopyranoside (8fβ). Following
the general procedure, 7f (0.08 g, 0.16 mmol) was reacted with MCPBA
(0.10 g, 0.32 mmol) to afford 8f (0.07 g, 0.14 mmol, 85%) as a mixture
α:β = 57:43, from a mixture of diastereoisomers galacto/talo = 90:10.
Products 8fα and 8fβ were obtained in a pure form by purification by
1-O-(3-Chlorobenzoyl)-4,6-O-isopropylidene-α-D-allopyr-
anoside (6bα) and 1-O-(3-Chlorobenzoyl)-4,6-O-isopropyli-
dene-β-D-allopyranoside (6bβ). Following the general procedure,
4b (0.04 g, 0.21 mmol) was reacted with MCPBA (0.11 g, 0.42 mmol) to
afford 6b (0.07 g, 0.19 mmol, 90%) as a mixture α:β = 48:52. Compound
6bβ was obtained in a pure form by purification by radial chromatog-
raphy (hexane/EtOAc 2:1) as a white solid. Mp 88À90 °C.
radial chromatography (hexane/EtOAc 3:1) as colorless syrups.
1
Data for 8fα: [α]25 +40.57 (c 0.3, CHCl3). H NMR (CDCl3,
D
400 MHz) δ in ppm: 7.93 (dd, 1H, J = 2.0, 2.0 Hz), 7.86 (d, 1H, J =
7.6 Hz), 7.53 (ddd, 1H, J = 7.6, 2.0, 0.8 Hz), 7.36 (dd, 1H, J = 7.6, 7.6
Hz), 6.43 (d, 1H, J = 4.0 Hz), 4.12À4.09 (m, 1H), 3.99À3.95 (m, 2H),
3.92À3.83 (m, 2H), 3.73 (dd, 1H, J = 10.0, 5.2 Hz), 2.65 (bs, 1H), 0.90
(s, 9H), 0.81 (s, 9H), 0.20 (s, 6H), 0.06 (s, 6H). 13C NMR (CDCl3,
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ARTICLE
1
100.6 MHz) δ in ppm: 164.3, 134.9, 133.7, 131.8, 130.1, 130.0, 128.1,
93.7, 72.9, 72.5, 69.5, 68.7, 62.1, 26.0, 25.9, 18.5, 18.4, À4.2, À4.4, À5.2,
À5.3. FT-IR (neat) ν in cmÀ1: 3447, 2927, 1735, 1253, 1099, 835, 778.
HRMS (ESI+) m/z calcd for C25H43ClNaO7Si2 [M À Na]: 569.2134,
found: 569.2123.
Data for 15: [α]25 +65.6 (c 2.76, CHCl3). H NMR (400 MHz,
D
CDCl3) δ in ppm: 7.93 (s, 1H); 7.86 (d, 1H, J = 7.6 Hz); 7.60 (dt, 1H, J =
7.6, 1.0, 1.0 Hz); 7.43 (t, 1H, J = 7.6 Hz); 7.35 (d, 2H, J = 8.4 Hz); 6.90
(d, 2H, J = 8.4 Hz); 6.32 (d, 1H, J = 1.6 Hz); 4.96 (d, 1H, J = 11.2 Hz);
4.78 (d, 1H, J = 11.2 Hz); 4.39 (t, 1H, J = 10.0 Hz); 4.12 (dd, 1H, J =
10.0, 4.6 Hz); 4.02 (dd, 1H, J = 3.6, 1.6 Hz); 3.98 (t, 1H, J = 10.0 Hz);
3.88 (td, 1H, J = 10.0, 4.6 Hz), 3.82À3.76 (m, 4H); 2.93 (bs, 1H), 1.11
(s, 9H), 1.04 (s, 9H). 13C NMR (CDCl3) δ in ppm: 162.9, 159.5, 134.6,
133.8, 131.1, 130.0, 130.0, 129.8, 129.7, 127.9, 114.5, 93.8, 76.8, 74.6,
Spectroscopic data of 8fβ from the reaction crude product: 1H NMR
(CDCl3, 400 MHz) δ in ppm: 7.96À7.87 (m, 2H), 7.64À7.55 (m, 2H),
5.77 (d, 1H, J = 8.0 Hz), 4.20À3.73 (m, 6H), 0.95 (s, 9H), 0.88 (s, 9H),
0.17 (s, 6H), 0.08 (s, 6H). 13C NMR (CDCl3, 100.6 MHz) δ in ppm:
164.3, 134.7, 133.6, 131.4, 129.9, 128.1, 128.0, 95.2, 75.4, 75.3, 71.1, 70.8,
68.8, 61.5, 26.0, 25.8, 18.4, 18.3, À4.4, À4.6, À5.1, À5.2.
73.5, 69.8, 69.3, 66.4, 55.3, 27.5, 27.1, 22.7, 20.0. FT-IR (neat) ν in cmÀ1
3416, 2960, 2923, 2890, 2858, 1735, 1251, 1094, 1026, 853, 823, 763.
HRMS (ESI+) m/z calcd for C29H39ClNaO8Si [M À Na]: 601.1995,
found: 601.1937.
4,6-Di-O-(tert-butyl)silanediyl-1-O-(3-chlorobenzoyl)-2-
O-levulinoyl-3-O-(4-methoxybenzyl)-α-D-mannopyranoside
(16):35 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide (50.6 mg, 0.25
mmol) and DMAP (21.3 mg, 0.17 mmol) were added under argon to a
solution of 15 (50.0 mg, 0.09 mmol) and levulinic acid (15.3 mg,
0.13 mmol) in dichloromethane (1.2 mL). The reaction mixture was
stirred at room temperature overnight. Then the solvent was removed
under reduced pressure, and the residue was purified by flash chroma-
tography (hexane/EtOAc 3:1) to give the desired product as a colorless
:
Methyl 4,6-O-Isopropylidene-β-D-glucopyranoside (10)
and Methyl 4,6-O-Isopropylidene-α-D-mannopyranoside (11).32
To a solution of 1e (0.06 g, 0.32 mmol) in dry MeOH (10 mL) was
added MCPBA (144 mg, 0.64 mmol). The mixture was stirred at room
temperature. The reaction was monitored by TLC until the starting material
was consumed. After 5 h, the solution was extracted with EtOAc and washed
successively with saturated aqueous NaHCO3 and water. The solution
was dried over MgSO4, and then the solvent was removed under reduced
pressure to afford a 17:83 mixture of compounds 10 and 11. Purification by
radial chromatography (hexane/EtOAc 1:2), afforded compounds 10
(0.06 g, 0.26 mmol, 80%) and 11 (0.01 g, 0.04 mmol, 13%) as white solids
(overall yield 93%).
oil (37.3 mg, 0.09 mmol, 85%).
Data for 10: Mp 74À76 °C. 1H NMR (CDCl3, 400 MHz) δ in ppm:
4.29 (d, 1H, J = 8.0 Hz), 3.95 (dd, 1H, J = 10.8, 5.6 Hz), 3.81 (dd, 1H, J =
10.8, 10.4 Hz), 3.69 (dd, 1H, J = 9.2, 8.8 Hz), 3.58 (dd, 1H, J = 10.0, 9.2
Hz), 3.57 (s, 3H), 3.46 (dd, 1H, J = 8.8, 8.0 Hz), 3.29 (ddd, 1H, J = 10.0,
10.0, 5.6 Hz), 1.52 (s, 3H), 1.45 (s, 3H). 13C NMR (CDCl3, 100.6 MHz)
δ in ppm: 104.3, 100.0, 74.9, 73.7, 73.3, 67.5, 62.2, 57.7, 29.9, 29.2.
1
Data for 16: [α]25 +33.8 (c 1.87, CHCl3). H NMR (400 MHz,
D
CDCl3) δ in ppm: 7.88 (t, 1H, J = 1.6 Hz); 7.77 (dt, 1H, J = 8.0, 1.6 Hz);
7.59 (dt, 1H, J = 8.0, 1.6 Hz); 7.41 (t, 1H, J = 8.0 Hz); 7.33 (d, 2H, J =
8.4 Hz); 6.89 (d, 2H, J = 8.4 Hz); 6.20 (d, 1H, J = 1.6 Hz); 5.31 (dd, 1H,
J = 3.6, 1.6 Hz); 4.73 (s, 2H); 4.26 (t, 1H, J = 9.6 Hz); 4.09 (dd, 1H, J =
10.0, 4.6 Hz); 3.96 (t, 1H, J = 10.0 Hz); 3.86À3.77 (m, 5H); 2.81À2.69
(m, 4H); 2.18 (s, 3H); 1.09 (s, 9H), 1.01 (s, 9H). 13C NMR (CDCl3) δ
in ppm: 206.3, 172.1, 162.7, 159.5, 134.0, 134.0, 130.9, 130.2, 130.2,
130.0, 129.7, 128.1, 114.0, 92.2, 74.8, 74.4, 72.5, 70.3, 69.3, 66.5, 55.3,
55.4, 38.2, 28.2, 27.6, 27.2, 22.9, 20.1. FT-IR (neat) ν in cmÀ1: 2933,
2893, 2859, 1742, 1721, 1471, 1104, 1081, 1065, 1033, 859, 824, 1033.
HRMS (ESI+) m/z calcd for C34H45ClNaO10Si [M À Na]: 699.2363,
found: 699.2322.
3-O-tert-Butyldimethylsilyl-4,6-di-O-(tert-butyl)silanediyl-1-
O-(3-chlorobenzoyl)-α-D-mannopyranoside (17):36 Compound
14 (259.8 mg, 0.57 mmol) was azeotropically dried with toluene
(3 Â 5 mL) and taken up in DMF (7 mL). Imidazole (93.5 mg, 1.43 mmol)
and tert-butyldimethylsilyl chloride (99.1 mg, 0.69 mmol) were added, and
the reaction mixture was stirred overnight. Diethyl ether (15 mL) was
added and washed with 5 mL of each of the following: NaHCO3 (aq, s),
H2O, and brine. The organic layer was dried over MgSO4, filtered, and
concentrated. The residue was purified by flash chromatography (from
hexane/EtOAc 10:1 to 3:1) to give the desired product as a colorless oil
1
Data for 11: Mp 107À109 °C. H NMR (CDCl3, 400 MHz) δ in
ppm: 4.74 (d, 1H, J = 1.2 Hz), 4.02 (dd, 1H, J = 3.2, 1.2 Hz), 3.97À3.91
(m, 2H), 3.90À3.80 (m, 2H), 3.66À3.60 (m, 1H), 3.37 (s, 3H), 1.53 (s,
3H), 1.43 (s, 3H). 13C NMR (CDCl3, 100.6 MHz) δ in ppm: 101.4,
100.3, 71.5, 71.1, 69.3, 63.9, 62.4, 55.2, 29.4, 19.5.
4,6-Di-O-(tert-butyl)silanediyl-1-O-(3-chlorobenzoyl)-α-D-
mannopyranoside (14). Following the general procedure, 13 (0.68 g,
2.36 mmol) was reacted with MCPBA (1.16 g, 4.72 mmol) to afford a
14:86 mixture of compounds β-gluco and α-manno 14. Purification by
radial chromatography (hexane/EtOAc 1:2) afforded compound 14 as a
white solid (0.2 g, 0.44 mmol, 50%). Mp 125À127 °C.
1
Data for 14: [α]25 +31.44 (c 0.63, CHCl3). H NMR (CDCl3,
D
400 MHz) δ in ppm: 7.97 (d, 1H, J = 2.0 Hz), 7.91 (ddd, 1H, J = 8.0, 0.8,
0.8 Hz), 7.59 (ddd, 1H, J = 8.0, 2.0, 0.8 Hz), 7.43 (dd, 1H, J = 8.0,
8.0 Hz), 6.36 (d, 1H, J = 1.6 Hz), 4.21À4.16 (m, 2H), 4.14 (dd, 1H, J =
10.0, 4.8 Hz), 4.02 (dd, 1H, J = 9.6, 3.6 Hz), 3.97 (dd, 1H, J = 10.0, 10.0
Hz), 3.89 (ddd, 1H, J = 10.0, 9.6, 4.8 Hz), 2.90 (bs, 1H), 2.77 (bs, 1H),
1.08 (s, 9H), 1.02 (s, 9H). 13C NMR (CDCl3, 100.6 MHz) δ in ppm:
163.2, 135.1, 134.0, 131.2, 130.2, 130.1, 128.1, 93.9, 74.3, 71.9, 69.7, 69.5,
66.3, 27.6, 27.1, 22.9, 20.2. FT-IR (neat) ν in cmÀ1: 3504, 3270, 2933,
2858, 1737, 1253, 1104, 959, 855, 825, 763. HRMS (ESI+) m/z calcd for
C21H31ClNaO7Si [M À Na]: 481.1425, found: 481.1417.
(283.6 mg, 0.53 mmol, 93%).
1
Data for 17: [α]25 +0.30 (c 4.57, CHCl3). H NMR (400 MHz,
D
CDCl3) δ in ppm: 7.98 (t, 1H, J = 1.8 Hz); 7.77 (dt, 1H, J = 8.0, 1.6 Hz);
7.60 (dt, 1H, J = 8.0, 1.6 Hz); 7.45 (t, 1H, J = 8.0 Hz); 6.39 (d, 1H, J =
1.6 Hz); 4.13 (t, 1H, J = 9.4 Hz); 4.12 (dd, 1H, J = 10.0, 4.6 Hz); 3.98
(dd, 1H, J = 9.4, 3.4 Hz); 3.92 (t, 1H, J = 9.4 Hz); 3.92 (m, 1H); 3.87 (td,
1H, J = 9.4, 4.6 Hz); 1.06 (s, 9H); 1.02 (s, 9H); 0.95 (s, 9H); 0.22
(s, 3H); 0.19 (s, 3H). 13C NMR (CDCl3) δ in ppm: 163.2, 135.1, 133.9,
131.3, 130.2, 130.1, 128.0, 93.7, 74.5, 72.8, 71.1, 69.7, 66.5, 27.7, 27.2,
26.0, 22.9, 20.1, 18.3, À4.0, À4.7. FT-IR (neat) ν in cmÀ1: 3563, 2933,
2891, 2858, 1740, 1471, 1094, 861, 837, 825, 765. (ESI+) m/z calcd for
C27H49ClNO7Si2 [M À NH4]: 590.2736, found: 590.2741.
4,6-Di-O-(tert-butyl)silanediyl-1-O-(3-chlorobenzoyl)-3-
O-(4-methoxybenzyl)-α-D-mannopyranoside (15).34 A mix-
ture of 14 (137.4 mg, 0.32 mmol) and dibutyltin oxide (89.2 mg,
0.35 mmol) in toluene (8.6 mL) was refluxed under DeanÀStark condi-
tions for 3 h. The reaction mixture was allowed to cool to room
temperature, and DMF (0.3 mL) was added to the mixture. 4-Methox-
ybenzyl chloride (46 μL, 0.35 mmol) and TBAI (122.2 mg, 0.35 mmol)
were added, and the mixture was heated at reflux for 3 h. Then, the
mixture was diluted with EtOAc (5 mL), washed with H2O (2 Â 5 mL),
and dried over MgSO4. The solvent was removed under reduced
pressure, followed by flash chromatography on silica gel (hexane/
EtOAc 3:1), affording the title compound as a colorless oil (88.9 mg,
0.16 mmol, 51%).
3-O-tert-Butyldimethylsilyl-4,6-di-O-(tert-butyl)silanediyl-1-
O-(3-chlorobenzoyl)-2-O-pivaloyl-α-D-mannopyranoside (18):36
Compound 17 (286.3 mg, 0.50 mmol) was azeotropically dried with
toluene (3 Â 5 mL) and taken up in CH2Cl2 (3.8 mL). DMAP (159 mg,
1.30 mmol) and pivaloyl chloride (0.73 mL, 0.62 mmol) were added,
and the reaction was stirred for 2 h. CH2Cl2 was added and washed
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The Journal of Organic Chemistry
ARTICLE
with saturated NaHCO3, H2O, and brine. The organic layer was dried
over Na2SO4, filtered, and concentrated. The crude product was purified
by column chromatography (from hexane to hexane/EtOAc 15:1) to
afford 18 as a colorless oil (283.1 mg, 0.44 mmol, 87%).
1473, 1454, 1362, 1251, 1084, 1026, 864, 839. HRMS (ESI+) m/z calcd
for C58H86NO11SSi2 [M + NH4]: 1060.5460, found: 1060.5476.
’ ASSOCIATED CONTENT
Data for 18: [α]25D +21.43 (c 4.60, CHCl3). 1H NMR (400 MHz,
CDCl3) δ in ppm: 7.99 (t, 1H, J = 1.9 Hz), 7.90 (dt, 1H, J = 8.0, 1.2 Hz),
7.62 (ddd, 1H, J = 8.0, 2.2, 1.0 Hz), 7.46 (t, 1H, J = 8.0 Hz), 6.16 (d, 1H,
J = 1.9 Hz), 5.21 (dd, 1H, J = 3.0, 2.0 Hz), 4.22À4.09 (m, 3H), 3.92
(t, 1H, J = 10.0 Hz), 3.85 (td, 1H, J = 8.4, 4.8 Hz), 1.26 (s, 9H), 1.08 (s,
9H), 1.01 (s, 9H), 0.92 (s, 9H), 0.18 (s, 3H), 0.14 (s, 3H). 13C NMR
(CDCl3) δ in ppm: 177.2, 163.0, 135.1, 134.0, 131.1, 130.3, 130.1, 127.9,
92.4, 74.7, 70.9, 70.9, 70.3, 66.9, 39.1, 27.7, 27.3, 27.2, 25.9, 23.0, 20.1,
18.4, À4.4, À4.8. FT-IR (neat) ν in cmÀ1: 2932, 2894, 2859, 1741,
1473, 1113, 854, 838, 825, 746. (ESI+) m/z calcd for C32H53ClNaO8Si2
[M À Na]: 679.2865; found: 679.2813.
S
Supporting Information. Copies of NMR spectra of com-
b
pounds 3e, 3f, 6bβ, 8cα, 8cβ, 8fα, 10, 11, 14À19, 21. This material
is available free of charge via the Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: (Y.D.) yolanda.diaz@urv.cat; (S.C.) sergio.castillon@
urv.cat.
3-O-tert-Butyldimethylsilyl-4,6-di-O-(tert-butyl)silanediyl-2-
O-pivaloyl-α-D-mannopyranose (19):38 Compound 18 (253.0 mg,
0.42 mmol) was dissolved in EtOAc (1.7 mL). 2-Aminoethanol (84 μL,
1.43 mmol) was added, and the mixture was stirred at room temperature for
2 h. The solvent was evaporated in vacuo, and the crude product was
purified by column chromatography (from hexane to hexane/EtOAc 9:1)
to afford 19 as a colorless oil (176 mg, 0.37 mmol, 88%).
’ ACKNOWLEDGMENT
Financial support of D.G.I. (CTQ2008-01569-BQU), Con-
solider Ingenio 2010 (CSD2006-0003) (Ministerio de Ciencia y
Tecnología, Spain), and technical assistance from the Servei de
Recursos Científics (URV) are gratefully acknowledged. I.M. and
J.C. thank Ministry of Education (Spain) for a fellowship.
Data for 19: 1H NMR (CDCl3, 400 MHz) δ in ppm: 5.00À4.93 (m,
2H), 4.01 (dd, 1H, J = 9.7, 4.7 Hz), 3.97À3.90 (m, 2H), 3.86 (ddd, 1H,
J = 8.6, 8.0, 4.8 Hz), 3.82À3.75 (m, 1H), 2.78 (s, 1H), 1.12 (s, 9H), 0.96
(s, 9H), 0.91 (s, 9H), 0.78 (s, 9H), 0.03 (s, 3H), 0.00 (s, 3H). 13C NMR
(CDCl3, 100.6 MHz) δ in ppm: 177.8, 93.2, 75.3, 72.6, 70.2, 68.0, 67.3,
39.1, 27.8, 27.4, 27.2, 25.9, 23.1, 20.1, 18.3, À4.3, À4.7. FT-IR (neat) ν
in cmÀ1: 3422, 2931, 2858, 1738, 1714, 1473, 1159, 1123, 1107, 1082,
1022, 865, 838, 825. HRMS (ESI+) m/z calcd for C25H51O7Si2
[M À NH4]: 519.3173, found: 519.3150.
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ecular sieves (51 mg) and trichloroacetonitrile (102 μL, 0.97 mmol) were
added to a solution of compound 19 (102 mg, 0.20 mmol) in CH2Cl2
(2.2 mL) at room temperature. The reaction mixture was stirred for
10 minfollowedbytheadditionofcesium carbonate (71mg, 0.20 mmol),
and stirring was continued for another 45 min. The reaction mixture was
then filtered over Celite, and the solvent was removed under reduced
pressure. The crude product was used in the glycosylation reaction
without further purification.
A solution of trichloroacetimidate donor, thiophenyl acceptor 20
(326 mg, 0.61 mmol), and 4 Å molecular sieves (1.2 g) in dry CH2Cl2
(51 mL) was stirred at room temperature for 30 min. After cooling to
À20 °C, TMSOTf (10 μL, 0.05 mmol) was added. The resulting
mixture was stirred for 2 h and then diluted with CH2Cl2. Saturated
aqueous NaHCO3 was added to quench the reaction. The molecular
sieves were filtered off through a Celite pad. The filtrate was washed with
brine, dried over Mg2SO4, and concentrated. The residue was purified by
column chromatography (from hexane to hexane/CH2Cl2 3:2) to afford
21 (102 mg, 0.10 mmol, 49%) as a white syrup.
Data for 21: [α]25D +0.66 (c 3.58, CHCl3). 1H NMR (CDCl3, 400
MHz) δ in ppm: 7.50À7.14 (m, 20H), 5.47 (d, 1H, J = 1.7 Hz), 5.20
(t, 1H, J = 2.1 Hz), 4.93 (d, 1H, J = 1.6 Hz), 4.84 (d, 1H, J = 10.7 Hz),
4.74À4.65 (m, 2H), 4.59 (d, 1H, J = 12.1 Hz), 4.53 (d, 1H, J = 9.5 Hz),
4.50 (d, 1H, J = 11.9 Hz), 4.33À4.26 (m, 1H), 4.20 (t, 1H, J = 2.3 Hz),
4.07À3.96 (m, 2H), 3.89 (dd, 1H, J = 9.0, 2.6 Hz), 3.87À3.64 (m, 6H),
1.20 (s, 9H), 1.04 (s, 9H), 0.95 (s, 9H), 0.88 (s, 9H), 0.10 (s, 3H), 0.09
(s, 3H). 13C NMR (CDCl3, 100.6 MHz) δ in ppm: 177.2, 138.4, 138.3,
138.2, 134.2, 133.7, 132.1, 129.3, 128.7, 128.6, 128.5, 128.3, 128.0, 128.0,
127.8, 127.7, 126.8, 99.5, 87.8, 80.3, 75.5, 75.3, 75.1, 75.1, 73.4, 73.0,
72.6, 72.1, 70.5, 69.4, 68.6, 67.1, 39.0, 27.7, 27.4, 27.2, 25.9, 23.0, 20.1,
18.3, À4.4, À4.7. FT-IR (neat) ν in cmÀ1: 3063, 3031, 2928, 2857, 1737,
9628
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The Journal of Organic Chemistry
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