Stereoselective Construction of 2,8-Dioxabicyclo[3.3.1]nonane/nonene Systems from 3-C-Branched Glycals

Article abstract of DOI:10.1002/ejoc.201301665

A stereoselective approach for the formation of 2,8-dioxabicyclo[3.3.1]nonane/nonene frameworks through the formation of 3-C-branched glycals encompassing the Claisen rearrangement of the carbohydrate-derived allyl-vinyl ethers and TMSOTf-catalyzed acetalization reactions as key steps is revealed. A novel acetalization of 3-C-branched glycals with a tentative mechanism is proposed. The expedient protocol is evaluated by synthesizing a number of 2,8-dioxabicyclo[3.3.1]nonane/nonene architectures.

Full text of DOI:10.1002/ejoc.201301665

FULL PAPER
DOI: 10.1002/ejoc.201301665
Stereoselective Construction of 2,8-Dioxabicyclo[3.3.1]nonane/nonene Systems
from 3-C-Branched Glycals
Gadi Madhusudhan Reddy[a] and Perali Ramu Sridhar*[a]
Dedicated to Professor M. Periasamy on the occasion of his 60th birthday
Keywords: Carbohydrates / Chiral pool / Acetals / Fused-ring systems / Diastereoselectivity / Rearrangement
A stereoselective approach for the formation of 2,8-dioxa-
bicyclo[3.3.1]nonane/nonene frameworks through the forma-
tion of 3-C-branched glycals encompassing the Claisen re-
arrangement of the carbohydrate-derived allyl-vinyl ethers
and TMSOTf-catalyzed acetalization reactions as key steps
is revealed. A novel acetalization of 3-C-branched glycals
with a tentative mechanism is proposed. The expedient pro-
tocol is evaluated by synthesizing a number of 2,8-dioxabicy-
clo[3.3.1]nonane/nonene architectures.
Introduction
Bicyclic acetals/ketals possessing the [3.3.1] skeleton exist
ubiquitously in nature as a rigid conformation in a number
of bioactive natural products.[1] As part of this group of
bicycles, the 2,8-dioxabicyclo[3.3.1]nonane architecture is
one of most important skeletons, and is present in biolo-
gically active compounds such as diinsininol (1), diinsinin
(2), and procyanidin A1 (3) and A2 (4).[2] Natural products
1 and 2 have been shown to be potent inhibitors of prosta-
glandin synthesis as well as platelet activating-factor (PAF)
induced exocytosis. Bridged bicyclic ketal 3 has been found
to suppress human peripheral blood mononuclear cell
(PBMC) proliferation activated with phytohemagglutinin
(PHA), possibly by blocking interleukin-2 (IL-2) and inter-
feron-γ (IFN-γ) production.[3] The diastereomer of 3, com-
pound 4, has been discovered to be highly active in vitro as
an antiviral agent, relative to the ribavirin, against the ca-
nine distemper virus (CDV).[4] Interestingly, in all the above
compounds the [3.3.1]-bicyclic system is linearly fused with
diaromatic rings (Figure 1).
Figure 1. Some bioactive natural products containing a 2,8-dioxa-
bicyclo[3.3.1]nonane framework fused with aromatic rings.
On the other hand, semburin (5), isosemburin (6), and
neosemburin (7), possessing the 2,8-dioxabicyclo[3.3.1]-
nonane framework, are volatile monoterpenoids that are
isolated from the herb Swertia Japonica (Gentianaceae;
Japanese name, semburi).[5] The extract of this herb is com-
monly used in Japan as a folk medicine for stomach disor-
ders. (+)-Lineatin (8), a pheromone used for mass trapping
of Trypodendron lineatum Olivier, which is a deleterious pest
responsible for the infestation of coniferous forests in
Europe and North America,[6] also possesses the 2,8-dioxa-
bicyclo[3.3.1]nonane framework. Monoterpenoids 5–8 are
fully aliphatic bridged bicyclic/tricyclic acetals possessing
intriguing biological properties (Figure 2).
Despite their wide occurrence, synthetic methods for the
straightforward construction of the 2,8-dioxabicyclo[3.3.1]-
nonane/nonene motifs are scarce.[7] Recently, synthesis of
aryl-ring-fused 2,8-dioxabicyclo[3.3.1]nonane systems has
been reported by using the PdII-catalyzed cascade reaction
[a] School of Chemistry, University of Hyderabad,
Hyderabad 500046, India
E-mail: prssc@uohyd.ernet.in
http://chemistry.uohyd.ernet.in/~prs/
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201301665.
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Synthesis of 2,8-Dioxabicyclo[3.3.1]nonane Frameworks
Results and Discussion
We planned to synthesize the precursor 3-C-branched
glycals by the Claisen rearrangement[15] of the sugar derived
allyl-vinyl ethers of type 12, which could be obtained from
glycals by following the procedure reported previously from
our laboratory.[14a] Thus, hydrolysis of glycoside 10,[14a] ob-
tained by the Ferrier rearrangement[16] of 3,4,6-tri-O-acetyl-
d-glucal 9, followed by benzylation, provided glycoside 11.
Oxidation of 11 with NaIO4 followed by treatment with
N,N-diisopropylamine gave allyl-vinyl ether 12. The Claisen
rearrangement of 12, upon heating in nitrobenzene and
N,N-dimethylaniline at 160 °C, provided the 3-C-branched
aldehyde derivative 13 in 80% yield. Serendipitously, expo-
sure of aldehyde 13 to TMSOTf in CH2Cl2 at –40 °C pro-
vided a single diastereomer in 83% yield. A careful spectro-
scopic analysis revealed that the product was a 2,8-dioxa-
bicyclo[3.3.1]non-6-ene derivative 14 (Scheme 1). To the
best of our knowledge, this is the first observation of the
formation of an acetal by the reaction between aldehyde
and vinyl ether.
Figure 2. Some aliphatic bioactive natural products possessing a
2,8-dioxabicyclo[3.3.1]nonane framework.
through (2-hydroxyphenyl)boronic acid[8] or AgOTf-cata-
lyzed domino reaction of phenols/naphthols,[9] with a series
of 2-hydroxychalcone derivatives. A catalyst-free[10] or io-
dine-catalyzed[11] Michael condensation of 2-hydroxychalc-
ones with the activated methylene groups followed by bicy-
clization reaction to provide 2,8-dioxabicyclo[3.3.1]nonane
derivatives has also recently been reported. However, all the
above methods have been directed to the synthesis of mono-
or bi-aryl fused 2,8-dioxabicyclo[3.3.1]nonane systems in-
volving 2-hydroxy chalcone derivatives as one of the com-
mon precursors. Very recently, Franzén et al. reported an
organocatalytic approach towards the synthesis of N,O-
and O,O-acetals in an asymmetric fashion by condensing 5-
amino/5-hydroxy α,β-unsaturated aldehydes, replacing the
2-hydroxy chalcone, and 1,3-diketones.[12] Except for this
report, to the best of our knowledge, there has been no
straightforward methodology for the construction of fully
aliphatic 2,8-dioxabicyclo[3.3.1]nonane/nonene skeleton.
Carbohydrates have long been the source of unique chiral
raw materials for the synthesis of biologically relevant small
molecular libraries.[13] In a continuation of our efforts to
develop the use of carbohydrate building blocks for the con-
struction of chiral architectures relevant to bioactive natu-
ral products, we previously reported the synthesis of cis-
fused perhydrofuro[2,3-b]furans and perhydro-5-oxofuro-
[2,3-b]furans from 3-C-branched sugar derivatives.[14] In our
further investigations in this direction, herein, we report an
efficient methodology for the stereoselective formation of
the completely aliphatic 2,8-dioxabicyclo[3.3.1]nonane/
nonene systems from the 3-C-branched glycal derivatives
(Figure 3).
Scheme 1. Synthesis of d-allose-based 2,8-dioxabicyclo[3.3.1]non-
6-ene derivative 14. Reagents and conditions: (a) PhSeCH2CH2OH,
BF3·OEt2, benzene, 0–25 °C, 5 min, 88%; (b) i. K2CO3, MeOH;
ii. NaH, BnBr, THF, 95% (two steps); (c) i. NaIO4, NaHCO3,
MeOH/H2O (6:1), 1 h; ii. DIPA, benzene, reflux, 30 min, 75% (two
steps); (d) N,N-dimethylaniline, nitrobenzene, 160 °C, 3 h, 80%;
(e) TMSOTf (15 mol-%), CH2Cl2, 4 Å MS, –40 °C, 83%. DIPA =
N,N-diisopropylamine. TMSOTf = trimethylsilyl trifluoromethane-
sulfonate.
Encouraged with the above results, a series of 2-phenyl-
selenenylethyl glycosides, 15, 19, 23, 27, 31, and 35, were
prepared[17] from the corresponding protected glycals and
subjected to oxidative elimination to give sugar-derived allyl
vinyl ethers 16, 20, 24, 28, 32 and 36, respectively, in good
yield. Claisen rearrangement of these vinyl glycosides by
heating in nitrobenzene and N,N-dimethylaniline at 160 °C
resulted the formation of 3-C-branched glycal derivatives
17, 21, 25, 29, 33,[14a] and 37.[14a] Subjecting these 3-C-
branched glycals to TMSOTf-mediated cyclization reaction
provided 2,8-dioxabicyclo[3.3.1]non-6-ene frameworks 18,
22, 26, 30, 34 and 38. In all the above cases, the reactions
proceeded efficiently and provided the products as single
diastereomers (Table 1).
A plausible mechanism for TMSOTf-catalyzed forma-
tion of bridged bicyclic acetal 14 from 3-C-branched glycal
13 is proposed, based on the observed products. As shown
in Scheme 2, activation of aldehyde by TMSOTf would give
the silyl-vinyl ether 39 and triflic acid. Addition of triflic
Figure 3. Stereoselective synthesis of bicyclic acetals from 3-C-
branched glycal derivatives.
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Table 1. Stereoselective synthesis of carbohydrate-derived 2,8-dioxabicyclo[3.3.1]non-6-ene systems.
[a] Isolated yield after column chromatography.
acid on glucal would lead to the formation of intermediate clo[3.3.1]nonane framework. Thus, aldehyde 13 was re-
oxonium ion 40. Trapping of this intermediate in an intra- duced to alcohol 41 and subjected to catalytic TMSOTf-
molecular fashion by the silyl-vinyl ether would result the mediated acetalization reaction. As expected, the reaction
formation of 2,8-dioxabicyclo[3.3.1]non-6-ene derivative 14 proceeded very smoothly and provided the fully saturated
along with the regeneration of catalyst, TMSOTf 2,8-dioxabicyclo[3.3.1]nonane derivative 42 as a single dia-
(Scheme 2).
stereomer in excellent yield (Scheme 3).
After successful evaluation of the generality of the meth-
The generality of this reaction was also investigated by
odology, we envisaged that an intramolecular hydroetherifi- applying it to a series of 3-C branched alcohols 43, 45, 47
cation reaction would be enable access to the 2,8-dioxabicy- and 50,[14a] which were obtained by reduction of aldehydes
Scheme 2. Proposed mechanism for formation of 2,8-dioxabicyclo[3.3.1]non-6-ene derivative 14.
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Eur. J. Org. Chem. 2014, 1496–1504

Synthesis of 2,8-Dioxabicyclo[3.3.1]nonane Frameworks
panies and were of the highest purity. The reactions were carried
out under an inert atmosphere and monitored by thin-layer
chromatography (TLC) using silica gel GF254 plates with detection
by charring with 5% (v/v) H2SO4 in methanol or by phosphomol-
ybdic acid (PMA) stain or by ultra violet (UV) detection unless
otherwise mentioned. Benzene, N,N-diisopropylamine, CH2Cl2,
THF, methanol and TMSOTf used in the reactions were distilled
from dehydrating agents prior to use. Silica gel (100–200 mesh) was
used for column chromatography. 1H, 13C, DEPT, COSY, NOESY
spectra were recorded with Bruker 400 MHz or 500 MHz spec-
trometers in CDCl3. 1H NMR chemical shifts are reported in ppm
(δ) with TMS as internal standard (δ = 0.00 ppm); 13C NMR data
are reported in chemical shifts with solvent reference (CDCl3, δ =
77.00 ppm). IR spectra were recorded with a JASCO FT/IR-5300
spectrometer. High-resolution mass spectra were recorded with a
Bruker maXis ESI-TOF spectrometer.
Scheme 3. Synthesis of d-allose-based 2,8-dioxabicyclo[3.3.1]-
nonane derivative 42. Reagents and conditions: (a) NaBH4, EtOH,
0 °C, 30 min, 96%; (b) TMSOTf (15 mol-%), CH2Cl2, 4 Å MS,
0 °C, 92%.
17, 33, 37 and 49, respectively. Reaction of these alcohols
with catalytic TMSOTf in CH2Cl2 provided bridged bicyclic
acetals 44, 46, 48 and 51 in good yield (Table 2).
Table 2. Stereoselective synthesis of carbohydrate derived 2,8-di-
oxabicyclo[3.3.1]nonane systems.
2-Phenylselenenylethyl
4,6-Di-O-acetyl-2,3-dideoxy-α-D-erythro-
hex-2-enopyranoside (10):[14a] To a solution of 3,4,6-tri-O-acetyl-d-
glucal (0.75 g, 2.76 mmol) in anhydrous benzene (10 mL) was
added 2-(phenylselenenyl)ethanol (0.55 g, 2.76 mol) and the mix-
ture was cooled to 0–5 °C. BF3·Et2O (0.1 mL, 0.8 mmol) was added
dropwise and the solution was stirred until complete disappearance
of the starting material (30 min). Et3N (0.4 mL) was added at 0–
5 °C to quench the reaction. The solvent was completely evapo-
rated under reduced pressure to obtain the crude compound 10.
Purification by column chromatography over silica gel (hexanes/
ethyl acetate) provided 10 (1.05 g, 88%). 1H NMR (400 MHz,
CDCl3): δ = 7.51–7.23 (m, 5 H), 5.88–5.77 (m, 2 H), 5.30 (dd, J =
1.6, 8.0 Hz, 1 H), 5.03 (br. s, 1 H), 4.24 (dd, J = 5.6, 12.0 Hz, 1 H),
4.15–4.09 (m, 2 H), 4.01–3.05 (m, 4 H), 2.07 (s, 3 H), 2.04 (s, 3
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 170.6, 170.2, 132.4,
129.5, 129.1, 129.0, 127.4, 126.9, 94.5, 68.3, 66.9, 65.0, 62.8, 26.7,
20.9, 20.7 ppm.
2-Phenylselenenylethyl
4,6-Di-O-benzyl-2,3-dideoxy-α-D-erythro-
hex-2-enopyranoside (11): To a solution of 10 (2.50 g, 6.02 mmol)
in methanol (20 mL) under an inert atmosphere was added K2CO3
(8.3 mg, 0.06 mmol) and the solution was stirred until completion
of reaction (ca. 3 h). Methanol was completely evaporated under
reduced pressure to obtain the crude deacetylated derivative. The
crude material thus obtained was dissolved in anhydrous THF un-
der an inert atmosphere and the mixture was cooled to 0 °C. NaH
(60%, 0.26 g, 18.06 mmol) was added portionwise with stirring
over a period of 20 min. After continuous stirring for a further 1 h
at 0 °C, benzyl bromide (3.08 g, 18.06 mmol) and TBAI (cat) were
added and the mixture was stirred overnight at 25 °C. The reaction
was quenched with slow addition of cold water and extracted with
CH2Cl2. The combined organic layers were dried with anhydrous
Na2SO4 and concentrated under reduced pressure to obtain crude
benzylated derivative. Purification of the crude product by column
chromatography over silica gel (hexanes/ethyl acetate) provided
pure 11 (2.91 g, 95%). Rf = 0.65 (EtOAc/hexanes, 20%). IR (neat):
[a] Isolated yield after column chromatography.
Conclusions
A stereoselective methodology for the formation of the
2,8-dioxabicyclo[3.3.1]nonane/nonene architecture starting
from 3-C-branched carbohydrates has been revealed. The
developed methodology has been successfully applied for
the synthesis of a number of bicyclic systems possessing the
above skeleton. The methodology was shown to be effective
with benzyl and acetyl protective groups, which are the two
most important protecting groups in carbohydrate chemis-
try. Application of the developed methodology for the
stereoselective synthesis of bioactive natural products pos-
sessing this skeleton is in progress.
ν
= 3663, 3024, 2865, 1742, 1572, 1457 cm–1. 1H NMR
˜
max
(400 MHz, CDCl3): δ = 7.53–7.50 (m, 2 H), 7.35–7.24 (m, 13 H),
6.10 (d, J = 10.4 Hz, 1 H), 5.77 (td, J = 2.4, 10.4 Hz, 1 H), 5.05
(d, J = 0.8 Hz, 1 H), 4.66–4.60 (m, 2 H), 4.52 (dd, J = 12.4, 18.0 Hz,
2 H), 4.20 (dd, J = 1.2, 9.2 Hz, 1 H), 4.03–3.97 (m, 2 H), 3.83–3.66
(m, 3 H), 3.15–3.11 (m, 2 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 138.1, 138.0, 132.5, 130.8, 129.8, 129.0, 128.3, 128.3, 127.7,
127.6, 126.9, 126.2, 94.8, 73.4, 71.0, 70.2, 69.3, 68.8, 68.0,
27.0 ppm. HRMS (ESI): calcd. for C28H30O4SeNa [M + Na]+
533.1207; found 533.1211.
Experimental Section
General Methods: All the chemicals were purchased from Car-
Vinyl 4,6-Di-O-benzyl-2,3-dideoxy-α-
D-erythro-hex-2-enopyranoside
bosynth, Spectrochem, Merck and Sigma–Aldrich Chemical Com-
(12): To a solution of 11 (10.55 g, 20.70 mmol) in methanol/water
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G. M. Reddy, P. R. Sridhar
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(6:1, 280 mL), sodium periodate (6.64 g, 31.05 mmol) and sodium
hydrogen carbonate (1.91 g, 22.77 mmol) were added sequentially,
and the mixture was stirred at 25 °C. After complete disappearance
of the starting material (1 h), the suspension was filtered through
a Celite 545 plug and concentrated under reduced pressure. The
crude material thus obtained was taken into ethyl acetate and
washed with water and the organic layers were dried with anhy-
drous Na2SO4 and concentrated under reduced pressure. The ob-
tained crude selenoxide was dissolved in anhydrous benzene
(100 mL), N,N-diisopropylamine (14.76 mL, 96.95 mmol) was
added and the mixture was heated to reflux for 30 min. After com-
pletion of the reaction, the solvent was evaporated and purified
over silica gel (hexanes/ethyl acetate) to obtain pure 12 (5.47 g, 75%
(ESI): calcd. for C22H24O4Na [M + Na]+ 375.1573; found 375.1571.
2-Phenylselenenylethyl 4,6-Di-O-benzyl-2,3-dideoxy-α-D-threo-hex-
2-enopyranoside (15): Synthesized from 2-phenylselenenylethyl 4,6-
di-O-acetyl-2,3-dideoxy-α-d-threo-hex-2-enopyranoside[14a] by fol-
lowing the procedure described for 11, yield 90%. IR (neat): ν
˜
max
= 3063, 2915, 2865, 1572, 1479, 1457 cm–1. 1H NMR (400 MHz,
CDCl3): δ = 7.52–7.49 (m, 2 H), 7.35–7.23 (m, 13 H), 6.15 (dd, J
= 5.2, 10.0 Hz, 1 H), 5.98 (dd, J = 3.2, 10.0 Hz, 1 H), 5.10 (d, J =
2.8 Hz, 1 H), 4.65 (dd, J = 8.0, 12.0 Hz, 2 H), 4.57 (dd, J = 1.6,
11.6 Hz, 2 H), 4.31 (dt, J = 2.8, 6.4 Hz, 1 H), 4.05–3.99 (m, 1 H),
3.83–3.78 (m, 2 H), 3.76–3.71 (m, 2 H), 3.19–3.09 (m, 2 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 138.3, 138.2, 132.5, 129.8, 129.3,
129.1, 128.4, 128.3, 127.8, 127.7, 127.6, 127.2, 126.9, 94.0, 73.4,
71.1, 69.6, 69.4, 67.8, 67.2, 27.0 ppm. HRMS (ESI): calcd. for
C28H30O4SeNa [M + Na]+ 533.1207; found 533.1209.
after two steps). R = 0.65 (EtOAc/hexanes, 10%). IR (neat): ν
˜
f
max
= 3035, 2915, 2860, 1638, 1452 cm–1. 1H NMR (400 MHz, CDCl3):
δ = 7.36–7.28 (m, 10 H), 6.55 (dd, J = 6.4, 14.0 Hz, 1 H), 6.19 (d,
J = 10.4 Hz, 1 H), 5.84 (td, J = 2.0, 10.6 Hz, 1 H), 5.36 (br. s, 1
H), 4.69–4.47 (m, 5 H), 4.28 (dd, J = 1.2, 9.2 Hz, 1 H), 4.21 (dd, J
= 1.2, 6.4 Hz, 1 H), 3.80–3.69 (m, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 149.3, 138.1, 137.9, 131.9, 128.4, 128.3, 127.9, 127.8,
127.8, 127.6, 125.1, 93.9, 91.7, 73.3, 71.2, 69.8, 68.4 ppm. HRMS
(ESI): calcd. for C22H24O4Na [M + Na]+ 375.1573; found 375.1567.
Vinyl 4,6-Di-O-benzyl-2,3-dideoxy-α-
(16): Synthesized from 15 by following the procedure described for
12, yield 78%. R = 0.40 (EtOAc/hexanes, 10%). IR (neat): ν
D-threo-hex-2-enopyranoside
=
max
˜
f
3029, 2914, 2859, 1643, 1456 cm–1. 1H NMR (400 MHz, CDCl3):
δ = 7.35–7.28 (m, 10 H), 6.56 (dd, J = 6.8, 14.0 Hz, 1 H), 6.23 (dd,
J = 5.2, 10.0 Hz, 1 H), 6.04 (dd, J = 2.8, 10.0 Hz, 1 H), 5.40 (d, J
= 2.4 Hz, 1 H), 4.66–4.55 (m, 5 H), 4.31 (dt, J = 2.4, 6.4 Hz, 1 H),
4.22 (dd, J = 1.2, 6.4 Hz, 1 H), 3.88 (dd, J = 6.8, 10.0 Hz, 1 H),
3.79–3.74 (m, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 149.1,
138.2, 138.1, 128.3, 128.3, 128.0, 127.9, 127.8, 127.7, 127.6, 127.5,
93.3, 91.7, 73.3, 71.3, 69.9, 68.9, 66.8 ppm. HRMS (ESI): calcd. for
C22H28NO4 [M + NH4]+ 370.2018; found 370.2027.
2-[(2R,3S,4S)-3-(Benzyloxy)-2-(benzyloxymethyl)-3,4-dihydro-2H-
pyran-4-yl]acetaldehyde (13): To vinyl glycoside 12 (5.0 g,
14.18 mmol) in nitrobenzene (40 mL) was added N,N-dimethylanil-
ine (0.4 mL) and the mixture was heated at 150–170 °C until the
disappearance of the starting material was observed (5–6 h). After
cooling the reaction mixture to 25 °C, the mixture was directly
loaded onto a silica-gel column and the product was purified by
column chromatography over silica gel (hexanes/ethyl acetate) to
obtain 3-C-branched glucal derivative 13 (4.0 g, 80%). Rf = 0.45
2-[(2R,3R,4S)-3-(Benzyloxy)-2-(benzyloxymethyl)-3,4-dihydro-
2H-pyran-4-yl]acetaldehyde (17): Synthesized from 16 by following
the procedure described for 13, yield 80%. Rf = 0.50 (EtOAc/hex-
anes, 20%). IR (neat): ν
= 3441, 3063, 2915, 2865, 1715, 1643,
˜
max
(EtOAc/hexanes, 10%). IR (neat): ν
= 3063, 2865, 1715, 1643,
˜
max
1452 cm–1. H NMR (400 MHz, CDCl3): δ = 9.71 (t, J = 1.6 Hz,
1 H), 7.37–7.28 (m, 10 H), 6.42 (dd, J = 1.6, 6.0 Hz, 1 H), 4.69–
4.61 (m, 2 H), 4.57 (dd, J = 9.2, 12.0 Hz, 2 H), 4.45 (d, J = 12.0 Hz,
1 H), 4.06–4.02 (m, 1 H), 3.75 (dd, J = 7.2, 10.0 Hz, 1 H), 3.56
(dd, J = 4.4, 10.0 Hz, 1 H), 3.46–3.44 (m, 1 H), 2.83–2.78 (m, 1
H), 2.47 (dt, J = 0.8, 6.0 Hz, 2 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 200.5, 143.1, 137.8, 137.7, 128.4, 128.3, 127.9, 127.7,
101.4, 74.0, 73.5, 72.8, 71.3, 68.5, 48.8, 28.8 ppm. HRMS (ESI):
calcd. for C22H28NO4 [M + NH4]+ 370.2018; found 370.2039.
1
1651, 1457 cm–1. 1H NMR (400 MHz, CDCl3): δ = 9.74 (t, J =
1.2 Hz, 1 H), 7.35–7.22 (m, 10 H), 6.35 (dd, J = 1.2, 6.0 Hz, 1 H),
4.69 (dd, J = 4.8, 6.0 Hz, 1 H), 4.60 (d, J = 4.4 Hz, 2 H), 4.51 (d,
J = 10.8 Hz, 2 H), 3.99–3.95 (m, 1 H), 3.88–3.85 (m, 1 H), 3.75–
3.74 (m, 2 H), 3.11–3.08 (m, 1 H), 2.79 (ddd, J = 1.6, 7.2, 17.6 Hz,
1 H), 2.40 (ddd, J = 1.2, 6.8, 17.2 Hz, 1 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 201.2, 143.1, 137.9, 137.5, 128.4, 128.4,
128.1, 127.8, 101.39, 73.67, 73.01, 72.5, 72.1, 69.0, 45.8, 28.9 ppm.
HRMS (ESI): calcd. for C22H24O4Na [M + Na]+ 375.1573; found
375.1574.
(1S,3R,4R,5R)-4-(Benzyloxy)-3-(benzyloxymethyl)-2,8-dioxabi-
cyclo[3.3.1]non-6-ene (18): Synthesized from 17 by following the
procedure described for 14, yield 85%. Rf = 0.80 (EtOAc/hexanes,
(1S,3R,4S,5R)-4-(Benzyloxy)-3-(benzyloxymethyl)-2,8-dioxabi-
cyclo[3.3.1]non-6-ene (14): To a solution of 3-C-branched glycal 13
(0.10 g, 0.28 mmol) in anhydrous CH2Cl2 (10 mL) under an inert
atmosphere was added powdered 4 Å molecular sieves and the mix-
ture was cooled to –40 °C. Freshly distilled TMSOTf (15 mol-%)
was added and the mixture was stirred until completion of the reac-
tion (1 h). Upon complete disappearance of the starting material,
the reaction was quenched with Et3N at –40 °C and brought to
25 °C, filtered, and concentrated under reduced pressure. The crude
material thus obtained was purified by column chromatography
over silica gel (hexanes/ethyl acetate) to obtain compound 14
30%). IR (neat): ν
= 3040, 2920, 2849, 1632, 1452 cm–1. 1H
˜
max
NMR (400 MHz, CDCl3): δ = 7.34–7.29 (m, 10 H), 6.68 (d, J =
6.0 Hz, 1 H), 5.45 (s, 1 H), 4.96–4.92 (m, 1 H), 4.67 (d, J = 12.0 Hz,
1 H), 4.62 (d, J = 12.0 Hz, 1 H), 4.51 (t, J = 11.6 Hz, 2 H), 4.25
(dt, J = 2.0, 6.0 Hz, 1 H), 3.64 (d, J = 6.4 Hz, 2 H), 3.42 (br. s, 1
H), 2.67–2.66 (m, 1 H), 2.44 (dd, J = 2.0, 12.8 Hz, 1 H), 1.54 (d, J
= 12.8 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 147.0,
138.1, 138.0, 128.2, 127.7, 127.5, 101.9, 93.1, 74.1, 73.4, 71.4, 70.2,
70.0, 25.4, 23.6 ppm. HRMS (ESI): calcd. for C22H28NO4 [M +
NH4]+ 370.2018; found 370.2037.
(83 mg, 83%). R = 0.55 (EtOAc/hexanes, 10%). IR (neat): ν
=
˜
f
max
3063, 2926, 2854, 1649, 1463 cm–1. 1H NMR (400 MHz, CDCl3):
δ = 7.37–7.25 (m, 10 H), 6.66 (d, J = 6.0 Hz, 1 H), 5.39 (d, J =
1.6 Hz, 1 H), 4.99 (dt, J = 1.2, 7.6 Hz, 1 H), 4.67 (d, J = 12.4 Hz,
1 H), 4.62 (d, J = 11.6 Hz, 1 H), 4.54 (d, J = 12.4 Hz, 1 H), 4.44
(d, J = 11.6 Hz, 1 H), 3.91 (td, J = 2.8, 9.6 Hz, 1 H), 3.74–3.70 (m,
3 H), 2.76–2.74 (m, 1 H), 1.96 (ddd, J = 2.0, 4.0. 12.8 Hz, 1 H),
1.89 (ddd, J = 2.0, 4.0, 12.8 Hz, 1 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 145.2, 138.2, 138.1, 128.4, 128.3, 127.8, 127.7, 127.5,
2-Phenylselenenylethyl 4-O-Benzyl-2,3-dideoxy-β-L-rhamno-2-eno-
pyranoside (19): Synthesized from 2-phenylselenenylethyl 4-O-
acetyl-2,3-dideoxy-β-l-rhamno-2-enopyranoside[14a] by following
the procedure described for 11, yield 94%. Rf = 0.50 (EtOAc/hex-
anes, 10%). IR (neat): ν
= 3068, 2975, 2926, 2871, 1578, 1484,
˜
max
1457 cm–1. H NMR (400 MHz, CDCl3): δ = 7.38–7.33 (m, 2 H),
7.32–7.24 (m, 8 H), 6.09 (d, J = 10.4 Hz, 1 H), 5.76 (td, J = 2.4,
10.4 Hz, 1 H), 4.95 (br. s, 1 H), 4.68 (d, J = 11.6 Hz, 1 H), 4.55 (d,
1
101.1, 91.9, 75.4, 73.4, 72.4, 70.9, 69.0, 28.2, 25.8 ppm. HRMS J = 11.6 Hz, 1 H), 4.00–3.90 (m, 2 H), 3.79–3.71 (m, 2 H), 3.12 (t,
1500 Eur. J. Org. Chem. 2014, 1496–1504
www.eurjoc.org
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Synthesis of 2,8-Dioxabicyclo[3.3.1]nonane Frameworks
J = 7.2 Hz, 2 H), 1.28 (d, J = 6.4 Hz, 3 H) ppm. 13C NMR
2-[(3R,4S)-3-(Benzyloxy)-3,4-dihydro-2H-pyran-4-yl]acetaldehyde
(100 MHz, CDCl3): δ = 138.0, 132.5, 130.8, 129.7, 129.0, 128.3, (25): Synthesized from 24 by following the procedure described for
127.7, 126.9, 126.4, 94.5, 76.2, 70.7, 67.7, 65.7, 26.9, 18.1 ppm. 13, yield 90%. R = 0.50 (EtOAc/hexanes, 20%). IR (neat): ν
=
max
˜
f
3435, 2926, 2876, 1720, 1649, 1452 cm–1 1H NMR (400 MHz,
.
Vinyl 4-O-Benzyl-2,3-dideoxy-β- -rhamno-2-enopyranoside (20):
Synthesized from 19 by following the procedure described for 12,
yield 84 %. R = 0.60 (EtOAc/hexanes, 10 %). IR (neat): ν
L
CDCl3): δ = 9.74 (t, J = 1.6 Hz, 1 H), 7.36–7.31 (m, 5 H), 6.36 (dd,
J = 2.0 Hz, 1 H), 4.65–4.53 (m, 3 H), 4.10 (dd, J = 3.2 Hz, 1 H),
3.75 (dd, J = 8.4, 10.8 Hz, 1 H), 3.44–3.40 (m, 1 H), 2.87–2.80 (m,
1 H), 2.55 (ddd, J = 2.8, 7.2, 16.4 Hz, 1 H), 2.43 (ddd, J = 1.6, 6.8,
16.4 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 201.1, 143.8,
137.6, 128.4, 127.9, 101.4, 74.5, 71.6, 65.5, 47.9, 32.6 ppm. HRMS
(ESI): calcd. for C14H16O3Na [M + Na]+ 255.0997; found 255.1497.
=
max
˜
f
3033, 2975, 2898, 2860, 1638, 1457 cm–1 1H NMR (400 MHz,
.
CDCl3): δ = 7.36–7.30 (m, 5 H), 6.51 (dd, J = 6.4, 14.0 Hz, 1 H),
6.16 (d, J = 10.4 Hz, 1 H), 5.82–5.79 (m, 1 H), 5.24 (s, 1 H), 4.70–
4.52 (m, 3 H), 4.18 (dd, J = 1.2, 6.4 Hz, 1 H), 3.96–3.89 (m, 1 H),
3.74 (dd, J = 1.6, 9.2 Hz, 1 H), 1.31 (d, J = 6.4 Hz, 3 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 149.3, 137.9, 131.8, 128.4, 127.8,
125.3, 93.7, 91.5, 75.9, 70.9, 66.4, 18.1 ppm. HRMS (ESI): calcd.
for C15H18O3Na [M + Na]+ 269.1154; found 269.1155.
(1R,4R,5R)-4-(Benzyloxy)-2,8-dioxabicyclo[3.3.1]non-6-ene (26):
Synthesized from 25 by following the procedure described for 14,
yield 81 %. R = 0.60 (EtOAc/hexanes, 20%). IR (neat): ν
=
˜
f
max
3068, 2964, 2931, 2876, 1643, 1452 cm–1 1H NMR (400 MHz,
.
2-[(2S,3R,4R)-3-(Benzyloxy)-2-methyl-3,4-dihydro-2H-pyran-4-yl]-
acetaldehyde (21): Synthesized from 20 by following the procedure
described for 13, yield 89%. Rf = 0.40 (EtOAc/hexanes, 10%). IR
CDCl3): δ = 7.49–7.27 (m, 5 H), 6.67 (d, J = 6.0 Hz, 1 H), 5.40 (s,
1 H), 4.98 (dt, J = 1.6, 6.8 Hz, 1 H), 4.65 (dd, J = 12.4, 16.4 Hz, 2
H), 3.95 (dd, J = 2.0, 12.4 Hz, 1 H), 3.86 (d, J = 12.8 Hz, 1 H),
3.34 (d, J = 0.8 Hz, 1 H), 2.63–2.62 (m, 1 H), 2.51–2.46 (m, 1 H),
1.54–1.50 (m, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 146.8,
138.3, 128.4, 127.6, 127.5, 102.4, 93.0, 74.1, 70.7, 62.1, 26.1,
24.0 ppm. HRMS (ESI): calcd. for C14H16O3Na [M + Na]+
255.0997; found 255.0999.
(neat): ν
= 3413, 2975, 2871, 1720, 1457 cm–1 1H NMR
.
˜
max
(400 MHz, CDCl3): δ = 9.76 (t, J = 1.2 Hz, 1 H), 7.37–7.30 (m, 5
H), 6.29 (dd, J = 1.2, 6.0 Hz, 1 H), 4.66 (dd, J = 4.4, 5.6 Hz, 1 H),
4.56 (q, J = 11.6, 20.0 Hz, 2 H), 3.99–3.92 (m, 1 H), 3.49 (dd, J =
5.6, 8.0 Hz, 1 H), 3.13–3.06 (m, 1 H), 2.80 (ddd, J = 1.2, 6.8,
17.2 Hz, 1 H), 2.41 (ddd, J = 1.2, 6.8, 17.6 Hz, 1 H), 1.32 (d, J =
6.4 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 201.4, 143.0,
137.6, 128.4, 128.1, 127.9, 101.3, 72.0, 69.8, 45.7, 28.6, 17.6 ppm.
HRMS (ESI): calcd. for C15H18O3Na [M + Na]+ 269.1154; found
269.1157.
2-Phenylselenenylethyl 4-O-Benzyl-2,3-dideoxy-α-D-arabino-2-eno-
pyranoside (27): Synthesized from 2-phenylselenenylethyl 4-O-
acetyl-2,3-dideoxy-α-d-arabino-2-enopyranoside[14a] by following
the procedure described for 11, yield 95%. Rf = 0.40 (EtOAc/hex-
anes, 10%). 1H NMR (400 MHz, CDCl3): δ = 7.54–7.24 (m, 10 H),
6.13 (dd, J = 4.8, 10.0 Hz, 1 H), 5.97–5.93 (m, 1 H), 5.03 (t, J =
2.8 Hz, 1 H), 4.65 (dd, J = 4.0, 12.0 Hz, 1 H), 4.60 (dd, J = 4.0,
11.6 Hz, 1 H), 4.09–4.05 (m, 1 H), 4.03–3.92 (m, 2 H), 3.81–3.74
(m, 1 H), 3.77–3.69 (m, 1 H), 3.13–3.08 (m, 2 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 138.2, 132.6, 129.3, 129.1, 128.4, 127.7,
127.1, 127.0, 93.5, 70.4, 67.4, 67.2, 61.5, 27.1 ppm.
(1R,3S,4R,5S)-4-(Benzyloxy)-3-methyl-2,8-dioxabicyclo[3.3.1]non-
6-ene (22): Synthesized from 21 by following the procedure de-
scribed for 14, yield 83%. Rf = 0.50 (EtOAc/hexanes, 10%). IR
1
(neat): ν
= 3073, 2964, 2931, 2859, 1643, 1462 cm–1. H NMR
˜
max
(400 MHz, CDCl3): δ = 7.38–7.30 (m, 5 H), 6.64 (d, J = 6.0 Hz, 1
H), 5.29 (d, J = 1.6 Hz, 1 H), 4.98 (t, J = 6.4 Hz, 1 H), 4.69 (d, J
= 11.6 Hz, 1 H), 4.53 (d, J = 11.6 Hz, 1 H), 3.89–3.82 (m, 1 H),
3.24 (dd, J = 3.6, 9.2 Hz, 1 H), 2.73–2.71 (m, 1 H), 1.87 (t, J =
0.8 Hz, 2 H), 1.28 (d, J = 6.4 Hz, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 145.2, 138.1, 128.4, 127.7, 101.2, 91.8, 81.6, 70.8, 68.6,
Vinyl 4-O-Benzyl-2,3-dideoxy-α-
Synthesized from 27 by following the procedure described for 12,
yield 80 %. R = 0.55 (EtOAc/hexanes, 10%). IR (neat): ν
D-arabino-2-enopyranoside (28):
=
max
˜
f
28.6, 25.8, 18.2 ppm. HRMS (ESI): calcd. for C15H18O3Na [M + 3030, 2915, 1860, 1693, 1457 cm–1. 1H NMR (400 MHz, CDCl3):
Na]+ 269.1154; found 269.1154.
δ = 7.36–7.34 (m, 5 H), 6.52 (dd, J = 6.4, 14.0 Hz, 1 H), 6.21–6.16
(m, 1 H), 6.03 (ddd, J = 0.8, 3.2, 10.0 Hz, 1 H), 5.34 (dd, J = 0.4,
2.8 Hz, 1 H), 4.63 (s, 1 H), 4.60 (s, 1 H), 4.58 (dd, J = 1.6, 14.0 Hz,
1 H), 4.21 (dd, J = 0.4, 6.4 Hz, 1 H), 4.03 (d, J = 2.8 Hz, 1 H), 4.02
(t, J = 1.6 Hz, 1 H), 3.73–3.71 (m, 1 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 149.2, 138.0, 128.5, 128.1, 127.8, 92.6, 91.6, 70.5, 66.9,
61.9 ppm. HRMS (ESI): calcd. for C14H16O3Na [M + Na]+
255.0997; found 255.1473.
2-Phenylselenenylethyl 4-O-Benzyl-2,3-dideoxy-α-L-arabino-2-eno-
pyranoside (23): Synthesized from 2-phenylselenenylethyl 4-O-
acetyl-2,3-dideoxy-α-l-arabino-2-enopyranoside[14a] by following
the procedure described for 11, yield 90%. Rf = 0.45 (EtOAc/hex-
anes, 10%). 1H NMR (400 MHz, CDCl3): δ = 7.54–7.24 (m, 10 H),
6.13 (dd, J = 4.8, 10.0 Hz, 1 H), 5.97–5.93 (m, 1 H), 5.03 (t, J =
2.8 Hz, 1 H), 4.65 (dd, J = 4.0, 12.0 Hz, 1 H), 4.60 (dd, J = 4.0,
11.6 Hz, 1 H), 4.09–4.05 (m, 1 H), 4.03–3.92 (m, 2 H), 3.81–3.74
(m, 1 H), 3.77–3.69 (m, 1 H), 3.13–3.08 (m, 2 H) ppm. 13C NMR
2-[(3S,4R)-3-(Benzyloxy)-3,4-dihydro-2H-pyran-4-yl]acetaldehyde
(29): Synthesized from 28 by following the procedure described for
(100 MHz, CDCl3): δ = 138.2, 132.6, 129.3, 129.1, 128.4, 127.7, 13, yield 88%. R = 0.50 (EtOAc/hexanes, 20%). IR (neat): ν
=
˜
f
max
127.1, 127.0, 93.5, 70.4, 67.4, 67.2, 61.5, 27.1 ppm.
Vinyl 4-O-Benzyl-2,3-dideoxy-α- -arabino-2-enopyranoside (24):
Synthesized from 23 by following the procedure described for 12,
yield 79 %. R = 0.55 (EtOAc/hexanes, 10%). IR (neat): ν
3435, 2926, 2876, 1720, 1649, 1452 cm–1 1H NMR (400 MHz,
.
CDCl3): δ = 9.74 (t, J = 1.6 Hz, 1 H), 7.36–7.31 (m, 5 H), 6.36 (dd,
J = 2.0 Hz, 1 H), 4.65–4.53 (m, 3 H), 4.10 (dd, J = 3.2 Hz, 1 H),
3.75 (dd, J = 8.4, 10.8 Hz, 1 H), 3.44–3.40 (m, 1 H), 2.87–2.80 (m,
1 H), 2.55 (ddd, J = 2.8, 7.2, 16.4 Hz, 1 H), 2.43 (ddd, J = 1.6, 6.8,
16.4 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 201.1, 143.8,
137.6, 128.4, 127.9, 101.4, 74.5, 71.6, 65.5, 47.9, 32.6 ppm. HRMS
(ESI): calcd. for C14H16O3Li [M + Li]+ 239.1259; found 239.1541.
L
=
max
˜
f
3030, 2915, 1860, 1693, 1457 cm–1. 1H NMR (400 MHz, CDCl3):
δ = 7.36–7.34 (m, 5 H), 6.52 (dd, J = 6.4, 14.0 Hz, 1 H), 6.21–6.16
(m, 1 H), 6.03 (ddd, J = 0.8, 3.2, 10.0 Hz, 1 H), 5.34 (dd, J = 0.4,
2.8 Hz, 1 H), 4.63 (s, 1 H), 4.60 (s, 1 H), 4.58 (dd, J = 1.6, 14.0 Hz,
1 H), 4.21 (dd, J = 0.4, 6.4 Hz, 1 H), 4.03 (d, J = 2.8 Hz, 1 H), 4.02 (1S,4S,5S)-4-(Benzyloxy)-2,8-dioxabicyclo[3.3.1]non-6-ene (30):
(t, J = 1.6 Hz, 1 H), 3.73–3.71 (m, 1 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 149.2, 138.0, 128.5, 128.1, 127.8, 92.6, 91.6, 70.5, 66.9,
61.9 ppm. HRMS (ESI): calcd. for C14H16O3Na [M + Na]+
255.0997; found 255.1473.
Synthesized from 29 by following the procedure described for 14,
yield 80 %. R = 0.60 (EtOAc/hexanes, 20%). IR (neat): ν
=
max
˜
f
3068, 2964, 2931, 2876, 1643, 1452 cm–1
.
1H NMR (400 MHz,
CDCl3): δ = 7.49–7.27 (m, 5 H), 6.67 (d, J = 6.0 Hz, 1 H), 5.40 (s,
Eur. J. Org. Chem. 2014, 1496–1504
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1501

G. M. Reddy, P. R. Sridhar
FULL PAPER
1 H), 4.98 (dt, J = 1.6, 6.8 Hz, 1 H), 4.65 (dd, J = 12.4, 16.4 Hz, 2 2-Phenylselenenylethyl 4-O-Acetyl-2,3-dideoxy-β-D-arabino-2-eno-
H), 3.95 (dd, J = 2.0, 12.4 Hz, 1 H), 3.86 (d, J = 12.8 Hz, 1 H),
3.34 (d, J = 0.8 Hz, 1 H), 2.63–2.62 (m, 1 H), 2.51–2.46 (m, 1 H),
pyranoside (35):[14a] To a solution of 3,4-di-O-acetyl-d-arabinal
(2.0 g, 9.99 mmol) in anhydrous benzene (50 mL) was added 2-
1.54–1.50 (m, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 146.8, (phenylselenenyl)ethanol (2.0 g, 9.99 mmol) and the mixture was
138.3, 128.4, 127.6, 127.5, 102.4, 93.0, 74.1, 70.7, 62.1, 26.1,
24.0 ppm. HRMS (ESI): calcd. for C14H16O3Na [M + Na]+
255.0997; found 255.0999.
cooled to 0–5 °C. BF3·Et2O (0.246 mL, 1.99 mmol) was added
dropwise and the solution was stirred until complete disappearance
of the starting material was observed (30 min). Et3N (1 mL) was
added to quench the reaction at 0–5 °C. The solvent was completely
evaporated under reduced pressure to obtain crude product, which
was purified by column chromatography over silica gel (hexanes/
2-Phenylselenenylethyl 4-O-Acetyl-2,3-dideoxy-α-L-rhamno-2-eno-
pyranoside (31):[14a] To a solution of 3,4-di-O-acetyl-l-rhamnal
(2.0 g, 9.33 mmol) in anhydrous benzene (50 mL) was added 2-
(phenylselenenyl)ethanol (1.87 g, 9.33 mmol) and the mixture was
cooled to 0–5 °C. BF3·Et2O (0.23 mL, 1.86 mmol) was added drop-
wise and the solution was stirred until complete disappearance of
the starting material was observed (30 min). Et3N (1 mL) was
added at 0–5 °C to quench the reaction. The solvent was completely
evaporated under reduced pressure and purification of the obtained
crude product by column chromatography over silica gel (hexanes/
ethyl acetate) provided pure 31 (2.90 g, 87%). Rf = 0.70 (EtOAc/
ethyl acetate) to give pure 35 (3.0 g, 88%). Rf = 0.50 (EtOAc/hex-
1
anes, 20 %). IR (neat): ν
= 3059, 2932, 1732, 1371 cm–1. H
˜
max
NMR (400MHz, CDCl3): δ = 7.51–7.49 (m, 2 H), 7.24–7.23 (m, 3
H), 6.07 (dd, J = 5.2, 10 Hz, 1 H), 5.99 (dd, J = 2.8, 10 Hz, 1 H),
5.00 (d, J = 2.4 Hz, 1 H), 4.93 (d, J = 2.8 Hz, 1 H), 4.17 (dd, J =
2.8, 13.2 Hz, 1 H), 4.00–3.94 (m, 1 H), 3.82 (d, J = 12.8 Hz, 1 H),
3.77–3.74 (m, 1 H), 3.10 (t, J = 6.8 Hz, 2 H), 2.06 (s, 3 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 170.3, 132.5, 130.4, 129.5, 128.9,
126.8, 124.9, 92.9, 67.7, 63.0, 61.1, 26.8, 20.9 ppm. HRMS (ESI):
calcd. for C15H18O4SeNa [M + Na]+ 365.0268; found 365.0268.
hexanes, 20%). IR (neat): ν
= 3466, 2978, 2934, 1743, 1579,
˜
max
1477 cm–1. 1H NMR (400MHz, CDCl3): δ = 7.51–7.49 (m, 2 H),
7.24–7.23 (m, 3 H), 5.84 (d, J = 10.4 Hz, 1 H), 5.76 (dd, J = 0.8,
10.4 Hz, 1 H), 5.04 (d, J = 9.2 Hz, 1 H), 4.95 (s, 1 H), 4.00–3.93
(m, 2 H), 3.79–3.73 (m, 1 H), 3.10 (t, J = 6.8 Hz, 2 H), 2.06 (s, 3
H), 1.19 (d, J = 6 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ
= 170.3, 132.5, 129.6, 128.9, 127.4, 126.8, 94.3, 70.6, 67.8, 64.8,
26.9, 20.9, 17.8 ppm. HRMS (ESI): calcd. for C16H20O4SeNa [M
+ Na]+ 379.0425; found 379.0425.
Vinyl 4-O-Acetyl-2,3-dideoxy-α-
Synthesized from 35 by following the procedure described for 12,
yield 73 %. R = 0.70 (EtOAc/hexanes, 20%). IR (neat): ν
D
-arabino-2-enopyranoside (36):[14a]
=
max
˜
f
3445, 2920, 1726, 1364 cm–1. 1H NMR (400 MHz, CDCl3): δ =
6.47 (dd, J = 6.4, 14.0 Hz, 1 H), 6.15 (dd, J = 5.2, 10.0 Hz, 1 H),
6.06 (dd, J = 3.2, 10.4 Hz, 1 H), 5.30 (d, J = 3.2 Hz, 1 H), 4.96
(dd, J = 2.8, 5.2 Hz, 1 H), 4.55 (dd, J = 1.6, 14.0 Hz, 1 H), 4.19
(dd, J = 2.6, 6.8 Hz, 1 H), 4.13 (dd, J = 2.8, 13.2 Hz, 1 H), 3.87
(dd, J = 1.2, 13.2 Hz, 1 H), 2.06 (s, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 170.3, 149.0, 129.3, 125.7, 92.0, 91.7, 62.7, 61.6,
20.9 ppm. HRMS (ESI): calcd. for C9H12O4Na [M + Na]+
207.0364; found 207.0364.
Vinyl 4-O-Acetyl-2,3-dideoxy-α-
Synthesized from 31 by following the procedure described for 12,
yield 74 %. R = 0.30 (EtOAc/hexanes, 10%). IR (neat): ν
L
-rhamno-2-enopyranoside (32):[14a]
=
max
˜
f
2982, 2934, 1743, 1641 cm–1. 1H NMR (400 MHz, CDCl3): δ =
6.47 (dd, J = 6.4, 14.0 Hz, 1 H), 5.92 (d, J = 10.0 Hz, 1 H), 5.83
(td, J = 2.4, 10.4 Hz, 1 H), 5.24 (s, 1 H), 5.06 (dd, J = 1.6, 9.2 Hz,
1 H), 4.54 (dd, J = 1.6, 14.0 Hz, 1 H), 4.17 (dd, J = 1.2, 6.4 Hz, 1
H), 3.97–3.90 (m, 1 H), 2.06 (s, 3 H), 1.20 (d, J = 6.4 Hz, 3 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 170.3, 149.1, 130.6, 126.3, 93.4,
91.6, 70.4, 65.4, 20.9, 17.7 ppm. HRMS (ESI): calcd. for
C10H14O4Na [M + Na]+ 221.0790; found 221.0790.
(3S,4R)-4-(2-Oxoethyl)-3,4-dihydro-2H-pyran-3-yl Acetate (37):[14a]
Synthesized from 36 by following the procedure described for 13,
yield 80 %. R = 0.50 (EtOAc/hexanes, 20%). IR (neat): ν
=
˜
f
max
3430, 2876, 2728, 1736, 1643, 1364, 1250, 1090, 1046, 964,
926 cm–1. 1H NMR (400 MHz, CDCl3): δ = 9.76 (s, 1 H), 6.39 (dd,
J = 1.6, 6.0 Hz, 1 H), 4.80 (dd, J = 5.6, 8.0 Hz, 1 H), 4.65 (dd, J
= 3.6, 6.0 Hz, 1 H), 3.96 (dd, J = 2.8, 11.2 Hz, 1 H), 3.88 (dd, J =
6.64, 11.2 Hz, 1 H), 2.80 (d, J = 2.8 Hz, 1 H), 2.60 (dd, J = 1.2,
6.0 Hz, 1 H), 2.56 (dd, J = 1.2, 6.0 Hz, 1 H), 2.07 (s, 3 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 199.9, 170.1, 143.7, 100.8, 69.2,
64.0, 48.2, 30.4, 20.8 ppm. HRMS (ESI): calcd. for C9H12O4Na [M
+ Na]+ 207.0634; found 207.0634.
(2S,3R,4R)-2-Methyl-4-(2-oxoethyl)-3,4-dihydro-2H-pyran-3-yl
Acetate (33):[14a] Synthesized from 32 by following the procedure
described for 13, yield 72%. Rf = 0.40 (EtOAc/hexanes, 20%). IR
(neat): ν
= 3468, 2982, 2939, 1732, 1649 cm–1 1H NMR
.
˜
max
(400 MHz, CDCl3): δ = 9.74 (t, J = 1.2 Hz, 1 H), 6.29 (dd, J = 2.0,
6.4 Hz, 1 H), 4.93 (t, J = 5.6 Hz, 1 H), 4.57 (dd, J = 3.6, 6.4 Hz, 1
H), 4.06 (t, J = 6.4 Hz, 1 H), 3.10–3.04 (m, 1 H), 2.62 (ddd, J =
1.6, 7.2, 17.6 Hz, 1 H), 2.44 (ddd, J = 1.6, 6.4, 17.6 Hz, 1 H), 2.03
(s, 3 H), 1.25 (d, J = 6.4 Hz, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 200.2, 169.9, 142.5, 100.1, 70.9, 69.8, 45.2, 26.9, 20.7,
16.8 ppm. HRMS (ESI): calcd. for C10H14O4Na [M + Na]+
221.0790; found 221.0790.
(1S,4S,5S)-2,8-Dioxabicyclo[3.3.1]non-6-en-4-yl Acetate (38): Syn-
thesized from 37 by following the procedure described for 14, yield
84%. R = 0.60 (EtOAc/hexanes, 20%). IR (neat): ν
= 2980,
˜
f
max
2942, 1731, 1643, 1369 cm–1. 1H NMR (400 MHz, CDCl3): δ =
6.65 (d, J = 6.0 Hz, 1 H), 5.37 (br. s, 1 H), 5.00–4.97 (m, 1 H), 4.63
(br. s, 1 H), 4.02 (dd, J = 2.4, 13.2 Hz, 1 H), 3.71 (d, J = 13.2 Hz,
1 H), 2.52 (br. s, 1 H), 2.32 (dd, J = 2.0, 13.2 Hz, 1 H), 2.09 (s, 3
H), 1.54 (d, J = 12.8 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 170.4, 147.1, 101.5, 92.5, 69.4, 62.2, 25.8, 24.0, 21.1 ppm.
HRMS (ESI): HRMS (ESI): calcd. for C9H12O4Na [M + Na]+
207.0634; found 207.0634.
(1R,3S,4R,5S)-3-Methyl-2,8-dioxabicyclo[3.3.1]non-6-en-4-yl Acet-
ate (34): Synthesized from 33 by following the procedure described
for 14, yield 72 %. Rf = 0.65 (EtOAc/hexanes, 20 %). 1H NMR
(400 MHz, CDCl3): δ = 6.63 (d, J = 6.0 Hz, 1 H), 5.28 (d, J =
1.2 Hz, 1 H), 4.88 (dt, J = 1.6, 6.4 Hz, 1 H), 4.62 (dd, J = 4.0, 2-[(2R,3S,4S)-3-(Benzyloxy)-2-(benzyloxymethyl)-3,4-dihydro-
9.6 Hz, 1 H), 3.92–3.85 (m, 1 H), 2.67–2.64 (m, 1 H), 2.04 (s, 3 H), 2H-pyran-4-yl]ethanol (41): To a solution of aldehyde 13 (0.93 g,
2.00 (dd, J = 2.0, 12.8 Hz, 1 H), 1.84 (ddd, J = 2.0, 4.4, 12.8 Hz, 2.63 mmol) in absolute ethanol (10 mL) at 0–5 °C was added
1 H), 1.16 (d, J = 6.0 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): NaBH4 (0.129 g, 3.4 mmol) and the mixture was stirred for 15 min
δ = 170.2, 145.6, 100.5, 91.7, 76.0, 67.2, 28.6, 26.6, 21.0, 17.7 ppm.
HRMS (ESI): calcd. for C10H14O4Na [M + Na]+ 221.0790; found
221.0790.
at the same temperature. After complete disappearance of the start-
ing material, the reaction was quenched by slow addition of aq.
NH4Cl solution (2 mL) and filtered through Celite 545. The filtrate
1502
www.eurjoc.org
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 1496–1504

Synthesis of 2,8-Dioxabicyclo[3.3.1]nonane Frameworks
obtained was concentrated under reduced pressure and purified by
column chromatography over silica gel (hexanes/ethyl acetate) to
(neat): νmax = 3397, 3063, 3030, 2926, 2871, 1649, 1501, 1452 cm–1.
˜
1H NMR (400 MHz, CDCl3): δ = 7.36–7.30 (m, 5 H), 6.28 (dd, J
obtain alcohol 41 (0.89 g, 96%). Rf = 0.35 (EtOAc/hexanes, 40%). = 1.6, 6.0 Hz, 1 H), 4.67 (dd, J = 4.8, 6.0 Hz, 1 H), 4.64 (dd, J =
1
IR (neat): ν
= 3424, 3024, 2871, 1649, 1501, 1452 cm–1. H
11.6, 26.0 Hz, 2 H), 4.08–4.02 (m, 1 H), 3.76–3.70 (m, 1 H), 3.69–
3.63 (m, 1 H), 3.47 (dd, J = 5.6, 7.6 Hz, 1 H), 2.61–2.55 (m, 1 H),
2.30 (s, 1 H), 1.97–1.88 (m, 1 H), 1.57–1.49 (m, 1 H), 1.32 (d, J =
6.4 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 142.0, 137.7,
˜
max
NMR (400 MHz, CDCl3): δ = 7.36–7.26 (m, 10 H), 6.35 (d, J =
6.0 Hz, 1 H), 4.71–4.55 (m, 5 H), 4.12–4.08 (m, 1 H), 3.87 (dd, J
= 5.6, 13.6 Hz, 1 H), 3.77 (d, J = 4.0 Hz, 2 H), 3.73–3.62 (m, 2 H),
2.59–2.53 (m, 1 H), 2.03 (br. s, 1 H), 1.99–1.90 (m, 1 H), 1.57–1.48 128.3, 127.8, 127.7, 101.5, 77.6, 71.3, 69.6, 60.5, 34.0, 29.8,
(m, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 142.2, 137.9, 17.7 ppm. HRMS (ESI): calcd. for C15H21O3 [M + H]+ 249.1491;
137.7, 128.3, 128.2, 127.8, 127.6, 127.5, 101.6, 73.4, 73.0, 72.8, 71.3,
69.2, 60.4, 34.6, 30.1 ppm. HRMS (ESI): calcd. for C22H26O4Na
[M + Na]+ 377.1729; found 377.1733.
found 249.1492.
(1R,3S,4R,5R)-4-(Benzyloxy)-3-methyl-2,8-dioxabicyclo[3.3.1]-
nonane (46): Synthesized from 45 by following the procedure de-
(1S,3R,4S,5S)-4-(Benzyloxy)-3-(benzyloxymethyl)-2,8-dioxabi- scribed for 42, yield 88%. Rf = 0.60 (EtOAc/hexanes, 30%). IR
cyclo[3.3.1]nonane (42): To a solution of 3-C-branched alcohol 41
(0.66 g, 1.86 mmol) in anhydrous CH2Cl2 (60 mL) under an inert
atmosphere, was added powdered 4 Å molecular sieves and the
mixture was cooled to 0 °C. Freshly distilled TMSOTf (15 mol-%)
was added and the mixture was stirred until completion of the reac-
tion (1 h). After complete disappearance of starting material, the
reaction was quenched with slow addition of Et3N at 0 °C and
brought to 25 °C. The reaction mixture was filtered and concen-
trated under reduced pressure, and the crude material thus ob-
tained was purified over silica gel (hexanes/ethyl acetate) to obtain
(neat): ν
= 3030, 2926, 2865, 1457 cm–1. 1H NMR (400 MHz,
˜
max
CDCl3): δ = 7.38–7.30 (m, 5 H), 5.17 (br. s, 1 H), 4.63 (d, J =
11.6 Hz, 1 H), 4.46 (d, J = 11.6 Hz, 1 H), 4.17–4.10 (m, 1 H), 3.99–
3.93 (m, 1 H), 3.79–3.72 (m, 1 H), 3.24 (dd, J = 4.0, 9.2 Hz, 1 H),
2.51 (br. d, J = 4.0 Hz, 1 H), 2.24 (dd, J = 8.4, 15.6 Hz, 1 H), 2.17–
2.12 (m, 1 H), 1.79–1.71 (m, 1 H), 1.63 (d, J = 13.6 Hz, 1 H), 1.30
(d, J = 6.0 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 138.2,
128.3, 127.6, 127.5, 92.1, 81.5, 70.26, 67.01, 60.49, 28.4, 23.8, 22.1,
19.3 ppm. HRMS (ESI): calcd. for C15H20O3Na [M + Na]+
271.1310; found 271.1311.
42 (0.60 g, 92%). R = 0.60 (EtOAc/hexanes, 30%). IR (neat): ν
˜
f
max
(3S,4R)-4-(2-Hydroxyethyl)-3,4-dihydro-2H-pyran-3-yl Acetate
(47):[14a] Synthesized from 37 by following the procedure described
= 2926, 2860, 1501, 1457, 1367 cm–1. 1H NMR (500 MHz, CDCl3):
δ = 7.38–7.24 (m, 10 H), 5.28 (s, 1 H), 4.70–4.36 (m, 4 H), 4.19–
4.16 (m, 1 H), 4.01–3.96 (m, 1 H), 3.80–3.68 (m, 4 H), 2.55 (br. s,
1 H), 2.25–2.19 (m, 1 H), 2.16 (qd, J = 2.0, 13.5 Hz, 1 H), 1.82–
1.70 (m, 1 H), 1.70 (d, J = 13.5 Hz, 1 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 138.3, 138.1, 128.3, 128.2, 127.7, 127.5,
127.4, 92.3, 74.9, 73.3, 71.2, 70.3, 69.8, 60.4, 28.2, 23.9, 22.2 ppm.
HRMS (ESI): calcd. for C22H30NO4 [M + NH4]+ 372.2175; found
372.2185.
for 41, yield 92%. R = 0.5 (EtOAc/hexanes, 40%). IR (neat): ν
˜
f
max
1
= 3398, 2924, 1736, 1649 cm–1. H NMR (400 MHz, CDCl3): δ =
6.34 (d, J = 6.4 Hz, 1 H), 4.79 (s, 1 H), 4.65 (t, J = 4.8 Hz, 1 H),
3.90 (dd, J = 4.0, 11.6 Hz, 1 H), 3.84 (d, J = 11.2 Hz, 1 H), 3.73–
3.61 (m, 2 H), 2.76 (s, 1 H), 2.23 (s, 1 H), 2.02 (s, 3 H), 1.61–1.46
(m, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 170.9, 142.9,
102.0, 69.9, 63.5, 59.3, 37.5, 32.0, 20.9 ppm. HRMS (ESI): calcd.
for C9H14O4Na [M + Na]+ 209.0790; found 209.0790.
2-[(2R,3R,4S)-3-(Benzyloxy)-2-(benzyloxymethyl)-3,4-dihydro-
2H-pyran-4-yl]ethanol (43): Synthesized from 17 by following the
procedure described for 41, yield 98%. Rf = 0.25 (EtOAc/hexanes,
(1R,4S,5R)-2,8-Dioxabicyclo[3.3.1]nonan-4-yl Acetate (48): Synthe-
sized from 47 by following the procedure described for 42, yield
78%. R = 0.60 (EtOAc/hexanes, 50%). IR (neat): ν
= 2931,
˜
f
max
30 %). IR (neat): ν
= 3441, 3063, 3024, 2931, 2871, 1643,
˜
max
1736, 1441, 1364, 1249 cm–1. 1H NMR (500 MHz, CDCl3): δ =
4.79 (d, J = 2.0 Hz, 1 H), 4.10–4.04 (m, 2 H), 3.99 (dd, J = 5.5,
10.5 Hz, 1 H), 3.58 (t, J = 10.5 Hz, 1 H), 3.24–3.19 (m, 1 H), 2.0
(s, 3 H), 2.01–1.99 (m, 1 H), 1.96 (dd, J = 7.0, 13.0 Hz, 1 H), 1.90
(dd, J = 3.5, 13.0 Hz, 1 H), 1.41–1.35 (m, 2 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 171.0, 98.2, 79.8, 62.5, 62.2, 35.2, 32.3,
31.9, 21.0 ppm. HRMS (ESI): calcd. for C09H14O4Na [M + Na]+
209.0790; found 209.0790.
1452 cm–1. H NMR (400 MHz, CDCl3): δ = 7.36–7.27 (m, 10 H),
6.41 (d, J = 6.4 Hz, 1 H), 4.69 (t, J = 4.8 Hz, 1 H), 4.63–4.62 (m,
5 H), 4.10–4.07 (m, 1 H), 3.77 (dd, J = 7.8, 10.0 Hz, 1 H), 3.67 (dt,
J = 2.0, 6.0 Hz, 2 H), 3.61 (dd, J = 4.4, 10.0 Hz, 1 H), 3.52 (br. s,
1 H), 2.34–2.33 (m, 1 H), 1.59–1.49 (m, 2 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 142.3, 137.9, 137.8, 128.5, 128.4, 128.3,
127.9, 127.9, 127.7, 102.6, 74.6, 73.5, 72.8, 71.4, 68.7, 60.1, 38.1,
31.0 ppm. HRMS (ESI): calcd. for C22H30NO4 [M + NH4]+
372.2175; found 372.2181.
1
[(2R,3S,4S)-3-Acetoxy-4-(2-oxoethyl)-3,4-dihydro-2H-pyran-2-yl]-
methyl Acetate (49):[14a] To a solution of 10 (3.1 g, 7.5 mmol) in
MeOH/H2O (6:1, 28 mL) was added NaIO4 (2.40 g, 11.25 mmol)
and NaHCO3 (0.693 g, 8.25 mol) and the mixture was stirred until
the disappearance of starting material was observed (1 h). The reac-
tion mass was filtered through a Celite 545 plug and the filtrate
was concentrated under reduced pressure. The crude product ob-
tained was dissolved in ethyl acetate (100 mL) and washed with
water. The aqueous layer was extracted with ethyl acetate (2 ϫ
25 mL) and the combined organic layers were dried with anhydrous
Na2SO4 and concentrated under reduced pressure to obtain the
crude selenoxide derivative. To a solution of crude selenoxide deriv-
ative in anhydrous benzene (25 mL) was added N,N-diisopropyl-
amine (5.14 mL, 36.1 mmol) and the mixture was heated to reflux
until the disappearance of starting material was observed (20 min).
(1S,3R,4R,5S)-4-(Benzyloxy)-3-(benzyloxymethyl)-2,8-dioxabi-
cyclo[3.3.1]nonane (44): Synthesized from 43 by following the pro-
cedure described for 42, yield 85 %. Rf = 0.60 (EtOAc/hexanes,
30%). IR (neat): ν
= 3030, 2926, 2871, 1720, 1463 cm–1. 1H
˜
max
NMR (400 MHz, CDCl3): δ = 7.35–7.27 (m, 10 H), 5.33 (s, 1 H),
4.66 (d, J = 11.6 Hz, 1 H), 4.62 (d, J = 12.0 Hz, 1 H), 4.52–4.44
(m, 3 H), 3.96–3.90 (m, 1 H), 3.81–3.71 (m, 2 H), 3.67 (dd, J = 6.0,
9.2 Hz, 1 H), 3.33 (br. s, 1 H), 2.45 (br. d, J = 10.0 Hz, 1 H), 2.18
(d, J = 13.6 Hz, 1 H), 2.02–1.94 (m, 1 H), 1.83 (d, J = 13.6 Hz, 1
H), 1.74–1.66 (m, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
138.3, 138.1, 128.2, 127.7, 127.5, 127.4, 93.5, 73.3, 71.3, 69.8, 66.9,
59.5, 25.4, 23.3, 22.5 ppm. HRMS (ESI): calcd. for C22H30NO4 [M
+ NH4]+ 372.2175; found 372.2180.
2-[(2S,3R,4R)-3-(Benzyloxy)-2-methyl-3,4-dihydro-2H-pyran-4-yl]- The solvent was evaporated under reduced pressure to obtain the
ethanol (45): Synthesized from 33 by following the procedure de-
scribed for 41, yield 95%. Rf = 0.20 (EtOAc/hexanes, 20%). IR
crude vinyl glycoside. Purification of the crude product by column
chromatography over silica gel (hexanes/ethyl acetate) provided
Eur. J. Org. Chem. 2014, 1496–1504
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1503

G. M. Reddy, P. R. Sridhar
FULL PAPER
pure vinyl glycoside, yield 55% (two steps). 1H NMR (400 MHz,
CDCl3): δ = 6.43 (dd, J = 2.0, 14.0 Hz, 1 H), 5.92–5.81 (m, 2 H),
5.27 (s, 2 H), 4.53 (dd, J = 1.2, 14.0 Hz, 1 H), 4.23–4.05 (m, 4 H),
2.03 (s, 3 H), 2.02 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ
= 170.5, 170.0, 148.8, 130.0, 126.3, 93.2, 92.1, 67.3, 64.6, 62.3, 20.7,
20.6 ppm.
EMR-II]. G. M. R. thanks CSIR for a senior research fellowship
(SRF).
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Compound 49 was synthesized form the above vinyl glycoside by
following the procedure described for 13, yield 85%. 1H NMR
(400 MHz, CDCl3): δ = 9.74 (t, J = 1.2 Hz, 1 H), 6.35 (dd, J = 2.0,
6.4 Hz, 1 H), 5.19 (dd, J = 5.6, 7.6 Hz, 1 H), 4.69 (d, J = 4.4,
6.0 Hz, 1 H), 4.33 (dd, J = 6.0, 12.0 Hz, 1 H), 4.21 (dd, J = 3.2,
12.0 Hz, 1 H), 4.12–4.09 (m, 1 H), 3.15–3.10 (m, 1 H), 2.66 (dd, J
= 1.2, 7.2 Hz, 1 H), 2.47 (dd, J = 1.2, 6.4 Hz, 1 H), 2.03 (s, 3 H),
2.02 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 199.8, 170.5,
169.5, 142.6, 101.0, 71.1, 66.7, 62.0, 45.3, 27.5, 20.6 ppm.
[2]
[3]
[4]
[5]
[6]
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2-yl]methyl Acetate (50):[14a] Synthesized from 49 by following the
procedure described for 41, yield 95%. Rf = 0.25 (EtOAc/hexanes,
40%). IR (neat): ν
= 3449, 2947, 1743, 1649, 1437 cm–1. 1H
˜
max
J. Chem. Ecol. 1977, 3, 549–561.
NMR (400 MHz, CDCl3): δ = 6.28 (dd, J = 2.0, 6.0 Hz, 1 H), 5.07
(t, J = 6.0 Hz, 1 H), 4.66 (dd, J = 4.0, 6.0 Hz, 1 H), 4.26–4.22 (m,
1 H), 4.17–4.11 (m, 2 H), 3.69–3.62 (m, 2 H), 2.61–2.58 (m, 1 H),
2.05 (s, 3 H), 2.04 (s, 3 H), 1.75–1.66 (m, 1 H), 1.51–1.42 (m, 1
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 170.7, 170.1, 141.5,
101.5, 71.7, 67.5, 62.4, 59.8, 33.3, 28.8, 20.7, 20.6 ppm. HRMS
(ESI): calcd. for C12H18O6Na [M + Na]+ 281.1001; found 281.1001.
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[(1S,3R,4S,5S)-4-Acetoxy-2,8-dioxabicyclo[3.3.1]nonan-3-yl]methyl
Acetate (51): Synthesized from 50 by following the procedure de-
scribed for 42, yield 90%. Rf = 0.40 (EtOAc/hexanes, 50%). IR
[10] G. Yin, T. Ren, Y. Rao, Y. Zhou, Z. Li, W. Shu, A. Wu, J. Org.
Chem. 2013, 78, 3132–3141.
(neat): ν
= 2953, 2926, 1742, 1369 cm–1. 1H NMR (400 MHz,
˜
max
[11] N. C. Ganguly, P. Mondal, S. Roy, Tetrahedron Lett. 2013, 54,
CDCl3): δ = 5.25 (s, 1 H), 4.85 (dd, J = 4.4, 10.4 Hz, 1 H), 4.31–
4.27 (m, 1 H), 4.21 (dd, J = 4.8, 12.0 Hz, 1 H), 4.14 (dd, J = 2.0,
12.0 Hz, 1 H), 3.96–3.90 (m, 1 H), 3.75–3.68 (m, 1 H), 2.54 (br. d,
J = 3.6 Hz, 1 H), 2.14–2.09 (m, 2 H), 2.07 (s, 3 H), 2.05 (s, 3 H),
1.82–1.72 (m, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 171.0,
169.9, 92.5, 69.9, 67.6, 63.7, 60.0, 27.8, 24.9, 22.3, 21.0, 20.9 ppm.
HRMS (ESI): calcd. for C12H18O6Na [M + Na]+ 281.1001; found
281.1002.
2386–2390.
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Received: November 6, 2013
Supporting Information (see footnote on the first page of this arti-
cle): Copies of the 1H, 13C, DEPT NMR and HRMS spectra of all
new compounds and 2D spectra of 1H-1H COSY and 1H-1H
NOESY of bridged bicycles 14 and 42.
Acknowledgments
Published Online: December 20, 2013
This work was supported by the Council of Scientific and Indus-
trial Research (CSIR), New Delhi [grant number 01(2408)/10/
1504
www.eurjoc.org
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Eur. J. Org. Chem. 2014, 1496–1504