Synthesims of 7-oxabicyclo[2.2.1]heptanes and 8-oxabicyclo[3.2.1]octanes from C-glycosides via an intramolecular cyclization

Article abstract of DOI:10.1021/jo3024973

A simple and effective method for the synthesis of 7-oxabicyclo[2.2.1] heptanes and 8-oxabicyclo[3.2.1]octanes from acetonyl C-glycoside substrates is described, which involves an intramolecular cyclization reaction through a nucleophilic substitution at C-5 or C-6 of C-glycosides by a 2′-enamine intermediate formed in the presence of pyrrolidine. Because anomeric epimerization occurs under these conditions, C-glycoside substrates with either anomeric configuration were converted to the same product(s) in same stereoselectivity and similar chemical yield.

Full text of DOI:10.1021/jo3024973

Note
pubs.acs.org/joc
Synthesis of 7‑Oxabicyclo[2.2.1]heptanes and
8‑Oxabicyclo[3.2.1]octanes from C‑Glycosides via an Intramolecular
Cyclization
Wei Zou* and Kannan Vembaiyan
Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario K1A 0R6, Canada
S
* Supporting Information
ABSTRACT: A simple and effective method for the synthesis of 7-
oxabicyclo[2.2.1]heptanes and 8-oxabicyclo[3.2.1]octanes from acetonyl C-
glycoside substrates is described, which involves an intramolecular cyclization
reaction through a nucleophilic substitution at C-5 or C-6 of C-glycosides by a
2′-enamine intermediate formed in the presence of pyrrolidine. Because
anomeric epimerization occurs under these conditions, C-glycoside substrates with either anomeric configuration were converted
to the same product(s) in same stereoselectivity and similar chemical yield.
xabicyclic [3.2.1] and [2.2.1] skeletons are commonly
found in a large number of natural products with diverse
cyclopropaned sugars,35,36 we reasoned if a leaving group is
installed at the 6-position of C-pyranosides or the 5-position of
C-furanosides a similar intramolecular SN2 reaction may occur
and provide a way to 8-oxabicyclo[3.2.1] and 7-oxabicy-
clo[2.2.1] compounds (see Scheme 1).
O
structural features and biological and medicinal importance.1−6
Significant advancements in the oxabicyclic ring construction
and thereafter ring expansion/opening have made them
attractive intermediates in organic and medicinal chemistry.7−12
Among the synthetic methods available, the Diels−Alder
reaction using furan and substituted furans has been most
common for the oxabicyclo[2.2.1]heptene framework,13−15
often in the presence of various catalysts,16−18 whereas
oxabicyclo[3.2.1]octene skeletons can also be produced by
cycloadditions of furan derivatives with various oxyallyl
cations.19−22 However, the Diels−Alder reaction produces an
enantiomeric mixture of exo and endo products and a chiral
control group is needed to achieve enantioselectivity.23−25 In
general, the synthetic methods for 7-oxabicyclic [2.2.1] skeleton
are not necessary applicable to the synthesis of oxabicyclic
[3.2.1] compounds. Thus, many reactions including 1,3-dipolar
cycloaddition,26,27 various other cycloadditions,28,29 and
oxidative cyclo-etherification,30 among others31,32 were devel-
oped.
Scheme 1
Two methods were employed in the preparation of 1-
acetonyl-C-glycosides. One involved 1-C-allylation followed by
olefin oxidation as previously reported;37 the other provided 1-
acetonyl-C-glycosides in one-step with acetylacetone in
aqueous sodium bicarbonate.38 The former was applied to
the synthesis of α-C-glycosides 8−15, 26, and 27; the latter was
used to produce β-C-glycosides 3, 6, and 16. In all substrates
except 16, the 6-iodides were derived by displacement of 6-
OMs with iodide ion in the presence of KI in DMF at 50 °C for
6 and 14 or at 80 °C for 8−13, and 15. Iodide 16 was prepared
by treatment of the 1-acetonyl-3-azido-1-C-allopyranoside with
Ph3P/I2/imidazole.39 The synthetic schemes are illustrated in
the Supporting Information.
Because we have previously observed 1,2-cyclopropanation
through an intramolecular replacement of 2-OTs (OMs) by 1′-
enolate under basic conditions (K2CO3/MeOH),35 similar
reaction conditions were attempted on C-ribofuranoside
substrates (2a and 2b) with a leaving group at C-5 (OTs and
OMs). The bases used included potassium carbonate, sodium
methoxide, DBU, piperidine, and pyrrolidine and the solvents
Through further manipulations such as dihydroxylation and
epoxidation the oxabicyclic intermediates from the Diels−Alder
approach can be converted to Tamiflu33 and sugar chirons.34
Retrospectively, oxabicyclo[3.2.1] and [2.2.1] compounds have
also been derived from sugars by an intramolecular nitrone
cycloaddition on substrates carrying an allyl group and an
enone−nitrone by an intramolecular RCM reaction,6 although
the method takes multiple steps and requires 1,4-cis
substitution on substrates. Because of the rich stereochemistry
and easy availability, carbohydrates could be a source to
oxabicyclo[2.2.1]heptane and oxabicyclo[3.2.1]octane skele-
tons provided a methylene (−CH2−) tether can be placed
between C1 and C5 of furanose or C1 and C6 of pyranose.
Since an intramolecular displacement of a leaving group (−OTs
and −OMs) at the C2-position of 1-acetonyl-1-C-mannopyr-
anosides by the 1′-enolate led to the formation of 1,2-
Received: November 27, 2012
Published: February 7, 2013
© 2013 American Chemical Society
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Note
were methanol, THF, acetonitrile, and DMF. The reaction only
proceeded efficiently when pyrrolidine was used as a base in
methanol and THF (see Table 1). The fast conversion of 2a to
Meanwhile, we also tested 6-O-Ms- and 6-iodo-C-glycopyr-
anoside derivatives (5 and 6) as substrates (see Scheme 3).
Scheme 3
Table 1. Formation of 4 under Various Base and Solvent
Combinations
a
entry
substrate
base
solvent
time (h)
20
yield (%)
1
2a
pyrrolidine
MeOH
THF
>90
2
∼15−20
0
3
piperidine
MeOH
THF
4
0
5
1% NaOMe
DBU
MeOH
<10
0
6
7
K2CO3
<10
>90
>90
40
8
3a
pyrrolidine
MeOH
THF
12
9
12
10
11
piperidine
DBU
THF
8 days
4 days
70
a
Reactions performed at room temperature; concentration of substrate
at 10 mg per mL; 4 equiv of base used; and the yields estimated by
Surprisingly, unlike the 5-OMs-C-glycofuranoside there was no
reaction observed when 5 was treated with pyrrolidine in
methanol and THF at room temperature, and the reaction
became complex at 50 °C. Consequently, 5 was converted to
iodide 6 by treatment with KI in DMF at 50 °C overnight, and
the subsequent cyclization to 7 from 6 was easily achieved with
pyrrolidine as base in THF. It is noteworthy that the reaction
was sluggish in methanol. Thus, the solvent played an
important role in facilitating a conformational change
particularly for C-pyranoside that requires higher free energy
than C-furanoside. An aprotic solvent such as THF is more
favorable to the conformation changes than MeOH due to the
less extent of solvation with substrates.41,42 Those results led us
to conclude that iodides are more suitable substrates, and
pyrrolidine and THF is the best combination of base and
solvent.
1HNMR on crude.
Scheme 2
The utility of this intramolecular cyclization was further
demonstrated by effective conversion of various substrates with
different functional groups into desired 7-oxabicyclic [2.2.1]
(17, 18) and 8-oxabicyclic [3.2.1] (19−25) products in good to
excellent yield upon treatment with pyrrolidine in THF (see
Table 2). As expected the benzyl and isopropylidene groups
were very stable under the conditions as well as the azido
group. Due to steric hindrance, the 4-OMs group in both C-
glycosides (6, 14) and 8-oxabicyclic products (7, 23) was
unreactive with nucleophiles such as iodide and azide ions, even
at elevated temperature (70 °C). Consequently, 4-azido-bicyclic
24 was obtained from 4-azido-6-iodo substrate 15 instead of 4-
OMs-oxabiclyclic 23. With O-acetylated substrates, 11 and 12,
partial de-O-acetylation did occur with prolonged reaction time,
leading to lower chemical yield. Since we had previously
synthesized nitroalkene C-glycosides (26, 27),43 we expected
that these molecules could undergo an intramolecular Michael
addition under the same conditions. Indeed, two 7-oxabicyclic
diasteromers in a ratio of ca. 1:1 were obtained from 26 and 27
in 64% and 54% overall yield, respectively.
4 occurred with pyrrolidine in methanol (see Scheme 2), which
resulted in a C−C bond between C-5 and C-1′ as evidenced by
1H and 13C NMR analysis [although the products are named in
the Experimental Section based on IUPAC nomenclature rules
(see red numbering), the numbering based on sugar (see black)
was used in the discussion and the NMR assignments]. High
yields were also obtained from 5-halo (Br-, I-) substituted
substrates (3a and 3b) under similar conditions. In addition, we
also found that the reaction of 3b under conditions of K2CO3/
MeOH went extremely slow at room temperature leading to
less than 50% conversion after 4 days. At elevated temperature,
e.g., 50 °C, the reaction produced more side products.
Apparently, this intramolecular cyclization was most effective
with pyrrolidine due to the superior nucleophilicity of its
enamine intermediate.40 The proper solvent for 5-OMs/OTs
furanosides is methanol (entry 1) and for 5-iodofuranosides
both methanol and THF are suitable solvents (entries 8 and 9).
The stereoselectivity of the reaction is controlled by the
stability of the transition state, which allowed the formation of a
single product (7, 17−25) with the 1′-C-acetyl group
equatorially substituted on the cyclohexane or cycloheptane
ring. A pair of diastereomers (28/29, 30/31) with 5,6-trans
configuration were obtained as a result of steric effect.
Additionally, because the β-elimination that leads to anomeric
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Table 2. Oxabicyles by an Intramolecular Cyclization
were obtained using a TOF/TOF MALDI mass spectrometer in
reflectron mode. The solvent and reagents were used without further
purification. The bicyclic products are named based on IUPAC
nomenclature rules, but the sugar numbering in the NMR assignments
is maintained.
General Procedures for the Preparation of Iodides. To a
solution of 5- or 6-OMs derivatives (0.2−4.0 g) in DMF (10−50 mL)
was added KI (2−5 equiv) and the solution was stirred at 50 °C for 6
and 14 or at 80 °C for 3a, 8−13 and 15 until the starting material
disappeared (16−40 h). The reaction mixture was diluted by the
addition of ethyl acetate and washed with brine three times. The
organic phase was dried and concentrated to a residue. The residue
was purified by flash column chromatography to give the desired
products except 16.
epimerization precedes the cyclization, the chemical yield and
stereoselectivity were not affected by the anomeric config-
uration of the substrates.
In summary, we have developed a simple and effective
method to access both the oxabicyclo[2.2.1] and oxabicy-
clo[3.2.1] compounds from 1-acetonyl-C-glycosides. The
intramolecular cyclization reaction, which forms a C−C bond
between C-1′ and C-6/C-5, was achieved through nucleophilic
substitution at C-5 or C-6 of C-glycosides by a 2′-enamine.
These bicycles can be useful intermediates for further chemical
modifications.
EXPERIMENTAL SECTION
General Methods. The NMR spectra were recorded with a 400
MHz instrument with CDCl3 as internal reference. The mass spectra
■
2-C-(5-Iodo-2,3-di-O-isopropylidene-5-deoxy-β-D-ribofuranosyl)-
acetone (3a). The 5-OMs substrate 2a (3.50 g, 11.4 mmol) was
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Note
converted to 3a (2.75 g, 71%) as a syrup: [α]D −9.0 (c 1, CHCl3); 1H
NMR (CDCl3) δ 1.30 (s, 3H, Me), 1.50 (s, 3H, Me), 2.18 (s, 3H,
Me), 2.75−2.80 (m, 2H, 1′-CH2), 3.27 (d, 2H, 5-CH2, J = 4.8 Hz),
3.84−3.89 (m, 1H, H-4), 4.28−4.35 (m, 1H, H-1), 4.42−4.47 (m, 2H,
H-2, 3); 13C NMR (CDCl3) δ7.5 (C-5), 25.7 (Me), 27.6 (Me), 31.1
(Me), 47.1 (C-1′), 80.8 (C-1), 82.9 (C-4), 84.7 (C-3), 85.4 (C-2),
115.2, 206.1 (C-2′); HRMS calcd for C11H18IO4 (M + H) + 341.0250,
found 341.0213.
(Ac), 169.6 (Ac), 170.1 (Ac), 204.4 (C-2′); HRMS calcd for
C15H21O8INa (M + Na)+ 479.0173; found: 479.0145.
2-C-(6-Iodo-2,3,4-tri-O-acetyl-6-deoxy-α-D-mannopyranosyl)-
acetone (12). The 6-OMs substrate (1.1 g, 2.59 mmol) was converted
to 12 (0.70 g, 60%) as a syrup, an anomeric mixture (α/β c.a. 1:1)
1
with about 5% residue solvent (EtOAc) as indicated by NMR: H
NMR (CDCl3) δ 1.96 (s, 3H, Ac), 1.98 (s, 3H, Ac), 1.99 (s, 3H, Ac),
2.14 (s, 3H, Me), 2.55 (dd, 1H, H-1′a, J = 4.4, 16.0 Hz), 2.76 (dd, 1H,
H-1′b, J = 9.2, 16.0 Hz), 3.19 (dd, 1H, H-6a, J = 8.4, 10.8 Hz), 3.33
(dd, 1H, H-6b, J = 6.0, 10.8 Hz), 3.65−3.70 (m, 1H, H-5), 4.39 (ddd,
1H, H-1, J = 1.0, 1.0, 5.2 Hz), 4.98 (dd, 1H, H-2, J = 3.2, 5.2 Hz), 5.03
(dd, 1H, H-4, J = 6.0, 7.2 Hz), 5.12 (dd, 1H, H-3, J = 3.2, 7.2 Hz); 13C
NMR (CDCl3) δ 2.8 (C-6), 20.66 (Ac), 20.76 (Ac), 20.79 (Ac), 30.8
(Me), 43.6 (C-1′), 68.0, 68.8, 69.3, 69.5, 73.9, 169.4, 169.6, 169.8,
204.7 (C-2′); HRMS calcd for C15H21O8INa (M + Na)+ 479.0173,
found 479.0122.
2-C-(6-Iodo-2,3-di-O-isopropylidene-4-O-mesyl-6-deoxy-β-D-
mannopyranosyl)acetone (6). The 6-OMs substrate (4.0 g, 8.9
mmol) was converted to 6 (3.8 g, 89%) as needles (EtOAc−hexanes):
1
mp 126−7 °C; H NMR (CDCl3) δ 1.38 (s, 3H, Me), 1.59 (s, 3H,
Me), 2.25 (s, 3H, Me), 2.75 (dd, 1H, H-1′a, J = 6.4, 17.2 Hz), 2.82
(dd, 1H, H-1′b, J = 6.4, 17.2 Hz), 3.21 (s, 3H, OMs), 3.27 (dd, 1H, H-
6a, J = 8.8, 11.2 Hz), 3.58 (dd, 1H, H-6b, J = 2.4, 11.2 Hz), 3.65 (ddd,
1H, H-1, J = 2.8, 10.8, 10.8 Hz), 4.17 (dd, 1H, J = 2.4, 11.2 Hz), 4.33
(dd, 1H, J = 2.4, 11.2 Hz), 4.45 (m, 1H, H-5), 4.64 (dd, 1H, H-4, J =
7.6, 10.0 Hz); 13C NMR (CDCl3) δ 4.0 (C-6), 25.7 (Me), 27.5 (Me),
30.9 (C-3′), 39.1, 45.6 (C-1′), 69.5, 72.6, 75.4, 76.2, 81.2, 110.7, 204.9
2-C-(6-Iodo-2,3,4-tri-O-benzyl-6-deoxy-α-D-glucopyranosyl)-
acetone (13). The 6-OMs substrate (0.3 g, 0.53 mmol) was converted
to 13 (0.215 g, 68%) as needles (EtOAc−hexanes): mp 100−1 °C;
1
+
[α]D +11 (c 2, CHCl3); H NMR (CDCl3) δ 2.19 (s, 3H, Me), 2.53
(C-2′); HRMS calcd for C13H21O7SINa (M + Na) 470.9945, found
(dd, 1H, H-1′a, J = 8.4, 15.2 Hz), 2.70 (dd, 1H, H-1′b, J = 3.6, 15.2
Hz), 3.03−3.10 (m, 1H, H-5), 3.25−3.47 (m, 4H, H-3, 4, 6a, 6b),
3.71−3.86 (m, 2H, H-1, 2), 4.55−4.79 (m, 2H, Bn), 4.86−4.95 (m,
4H, 2 × Bn), 7.24−7.37 (m, 15H, 3 × Bn); 13C NMR (CDCl3) δ 7.4
(C-6), 31.5 (Me), 45.8 (C-1′), 75.3 (Bn), 75.6 (C-1), 75.7 (Bn), 75.8
(Bn), 77.4 (C-5), 81.6 (C-3), 82.0 (C-4), 86.7 (C-2), 127.9, 128.0,
128.09, 128.13, 128.19, 128.22, 128.3, 128.71, 128.75, 128.8, 138.0,
138.1, 138.4, 206.8 (C-2′); HRMS calcd for C30H34IO5 (M + H)+
601.1451, found 601.1503.
470.9987.
2-C-(5-Iodo-2,3-di-O-benzyl-5-deoxy-β-D-ribofuranosyl)acetone
(8). The 5-OMs substrate (1.2 g, 2.68 mmol) was converted to 8 (1.04
1
g, 81%) as a syrup: [α]D +44 (c 2.6, CHCl3); H NMR (CDCl3) δ
2.04 (s, 3H, Me), 2.79 (dd, 1H, H-1′a, J = 6.4, 17.2 Hz), 2.91 (dd, 1H,
H-1′b, J = 8.0, 17.2 Hz), 3.22 (dd, 1H, H-5a, J = 4.0, 10.8 Hz), 3.36
(dd, 1H, H-5b, J = 4.0, 10.8 Hz), 3.76−3.90 (m, 2H, H-3, 4), 4.15 (dd,
1H, H-2, J = 4.0, 4.0 Hz), 4.40 (d, 1H, Bn, J = 11.2 Hz), 4.45−4.60 (m,
2H, H-1, Bn), 4.67 (d, 1H, Bn, J = 11.6 Hz), 4.74 (d, 1H, Bn, J = 11.2
Hz), 7.22−7.38 (m, 10H, 2 × Bn); 13C NMR (CDCl3) δ 9.7 (C-5),
30.6 (Me), 43.8 (C-1′), 72.9 (Bn), 73.8 (Bn), 76.6 (C-1), 77.6 (C-2),
77.8 (C-4), 83.7 (C-3), 127.8, 127.88, 127.95, 128.0, 128.06, 128.11,
128.2, 128.4, 128.46, 128.5, 128.6, 137.5, 138.1, 207.2 (C-2′); HRMS
calcd for C22H26IO4 (M + H)+ 481.0876, found 481.0887.
2-C-(5-Iodo-2,3-di-O-benzyl-5-deoxy-α/β-L-arabinofuranosyl)-
acetone (9). The 5-OMs substrate (1.1 g, 2.43 mmol) was converted
to 9 (0.93 g, 80%) as a syrup: 1H NMR (CDCl3) for a mixture of α/β
(c.a. 1:1) isomers: δ 2.16 and 2.17 (2s, 3H each, 2 × Me), 2.70−2.95
(m, 4H, 2 × 1′-CH2), 3.25−3.36 (m, 4H, 2 × 5-CH2), 3.89 (bt, 1H, H-
2), 4.03 (bd, 1H, H-3), 4.03 (bd, 1H, H-3), 4.11 (bt, 1H, H-2), 4.12
(m, 1H, H-4), 4.30 (m, 1H, H-4), 4.37 (d, 1H, Bn, J = 11.6 Hz), 4.49−
4.66 (m, 9H, 2 × H-1 and 3.5 × Bn), 7.22−7.38 (m, 20H, 4 × Bn);
13C NMR (CDCl3) for a mixture of α/β (c.a. 1:1) isomers: δ 6.7 (C-5,
α and β), 30.6 and 30.7 (Me), 43.4 and 47.1 (C-1′), 71.5, 71.8, 71.9,
72.1, 80.2, 82.7, 83.5, 83.8, 85.0, 86.1, 86.6, 127.79, 127.82, 127.9,
128.0, 128.52, 128.53, 137.48, 137.51, 137.6, 206.7, and 206.8 (C-2′);
HRMS calcd for C22H26IO4 (M + H)+ 481.0876, found 481.0877.
2-C-(6-Iodo-2,3-di-O-isopropylidene-6-deoxy-α-D -
mannopyranosyl)acetone (10). The 6-OMs substrate (0.3 g, 0.86
mmol) was converted to 10 (0.23 g, 71%) as needles (EtOAc−
hexanes): mp 115−7 °C; 1H NMR (CDCl3) δ 1.37 (s, 3H, Me), 1.52
(s, 3H, Me), 2.28 (s, 3H, Me), 2.69−2.72 (m, 2H, 1′-CH2), 3.40−3.45
(m, 2H, H-5, 6a), 3.50−3.54 (m, 1H, H-6b), 3.90 (dd, 1H, H-4, J =
7.6, 7.6 Hz), 4.11 (dd, 1H, H-2, J = 8.0, 8.0 Hz), 4.19−4.23 (m, 2H, H-
1, 3); 13C NMR (CDCl3) δ 7.6 (C-6), 25.2 (Me), 27.4 (Me), 30.9 (C-
3′), 46.7 (C-1′), 69.7 (C-3), 72.2 (C-2), 73.7 (C-4), 75.9 (C-5), 78.0
(C-1), 110.2, 205.9 (C-2′); HRMS calcd for C12H20O5I (M + H)+
371.0356; found: 371.0328.
2-C-(6-Iodo-2,3-di-O-benzyl-4-O-mesyl-6-deoxy-α-D -
glucopyranosyl)acetone (14). The 4,6-di-OMs substrate (0.278 g, 0.5
mmol) was converted to 14 (0.212 g, 72%) as needles (EtOAc−
hexanes): mp 133−4 °C, [α]D +42 (c 1, CHCl3); 1H NMR (CDCl3) δ
2.16 (s, 3H, Me), 2.74−2.80 (m, 2H, 1′-CH2), 3.20 (dd, 1H, H-6a, J =
7.6, 10.8 Hz), 3.60 (dd, 1H, H-6b, J = 4.0, 10.8 Hz), 3.66−3.75 (m,
2H, H-2, 5), 3.82 (dd, 1H, H-3, J = 7.2, 7.6 Hz) 4.45−4.51 (m, 2H, H-
4, Bn), 4.59 (d, 1H, Bn, J = 11.6 Hz), 4.64−4.72 (m, 3H, H-1, Bn),
4.90 (d, 1H, Bn, J = 11.6 Hz), 7.19−7.37 (m, 15H, 3 × Bn); 13C NMR
(CDCl3) δ 4.6 (C-6), 30.9 (Me), 38.7 (OMs), 41.6 (C-1′), 68.9 (C-1),
72.8 (Bn), 73.1 (C-5), 74.7 (Bn), 76.6 (C-3), 77.8 (C-2), 78.7 (C-4),
127.8, 128.1, 128.2, 128.4, 128.5, 128.6, 137.1, 137.2, 205.2 (C-2′);
HRMS calcd for C24H30IO7S (M + H)+ 589.0757, found 589.0785.
2-C-(6-Iodo-2,3-di-O-benzyl-4-azido-4,6-dideoxy-α-D-
galactopyranosyl)acetone (15). The 6-OMs substrate (0.4 g, 0.80
mmol) was converted to 15 (0.275 g, 64%) as oil: [α]D +19 (c 0.9,
CHCl3); 1H NMR (CDCl3) δ 2.08 (s, 3H, Me), 2.60 (dd, 1H, H-1′a, J
= 8.0, 16.0 Hz), 2.70 (dd, 1H, H-1′b, J = 6.0, 16.0 Hz), 3.23 (dd, 1H,
H-6a, J = 6.4, 10.4 Hz), 3.31 (dd, 1H, H-6b, J = 7.6, 10.4 Hz), 3.70−
3.77 (m, 2H, H-3, 5), 3.88 (dd, 1H, H-2, J = 4.8, 4.8 Hz), 4.12 (dd,
1H, H-4, J = 3.2, 3.2 Hz), 4.45−4.53 (m, 2H, H-1, Bn), 4.63 (d, 1H,
Bn, J = 15.6 Hz), 4.63 (s, 2H, Bn), 7.27−7.37 (m, 10H, 2 × Bn); 13C
NMR (CDCl3) δ 3.1 (C-6), 30.5 (Me), 41.9 (C-1′), 60.6 (C-4), 69.3
(C-1), 72.0 (C-5/3), 73.0 (Bn), 73.8 (Bn), 75.0 (C-2), 77.2 (C-3/5),
127.8, 128.07, 128.10, 128.14, 128.5, 128.6, 137.4, 137.7, 205.9 (C-2′);
HRMS calcd for C23H27N3IO4 (M + H)+ 536.1046, found 536.1029.
2-C-(6-Iodo-3-azido-3,6-dideoxy-β-D-allopyranosyl)acetone (16).
To a mixture of 2-C-(3-azido-3,6-dideoxy-β-D-allopyranosyl)acetone
(0.2 g), Ph3P (0.4 g), and imidazole (0.3 g) in toluene (20 mL) was
added iodine pellets (0.3 g). The mixture was refluxed for 1 h until all
starting material was consumed. After cooling, the solution was diluted
by the addition of ethyl acetate, washed with brine, 10% aqueous
sodium sulfite, and water, dried, and concentrated. Purification by
column chromatography (hexanes to EtOAc) gave 16 (0.15 g, 52%) as
needles (EtOAc/hexanes): mp 125−6 °C; [α] −7 (c 0.5, EtOAc); 1H
NMR (CDCl3) δ 2.24 (s, 3H, Me), 2.73 (dd, 1H, H-1′a, J = 6.4, 16.0
Hz), 2.81 (dd, 1H, H-1′b, J = 5.6, 16.0 Hz), 3.15 (m, 1H, H-5), 3.26
(dd, 1H, H-6a, J = 6.0, 11.2 Hz), 3.46 (dd, 1H, H-6b, J = 2.4, 11.2 Hz),
3.51 (dd, 1H, H-2, J = 3.2, 9.6 Hz), 3.54 (dd, 1H, H-4, J = 3.6, 9.2 Hz),
3.94 (m, 1H, H-1), 4.15 (dd, 1H, H-3, J = 3.2, 3.2 Hz); 13C NMR
2-C-(6-Iodo-2,3,4-tri-O-acetyl-6-deoxy-α-D-glucopyranosyl)-
acetone (11). The 6-OMs substrate (0.5 g, 1.18 mmol) was converted
1
to 11 (0.33 g, 61%) as an oil: [α]D +31 (c 1, CHCl3); H NMR
(CDCl3) δ 2.02 (s, 3H, Ac), 2.05 (s, 3H, Ac), 2.07 (s, 3H, Ac), 2.25 (s,
3H, Me), 2.75 (dd, 1H, H-1′a, J = 6.4, 16.4 Hz), 2.82 (dd, 1H, H-1′b, J
= 7.6, 16.4 Hz), 3.16 (dd, 1H, H-6a, J = 7.6, 10.8 Hz), 3.32 (dd, 1H,
H-6b, J = 4.0, 10.8 Hz), 3.65−3.72 (m, 1H, H-5), 4.77 (dd, 1H, H-1, J
= 6.0, 6.4 Hz), 4.88 (dd, 1H, H-4, J = 8.0, 8.0 Hz), 5.10 (dd, 1H, H-2, J
= 6.0, 5.6 Hz), 5.24 (dd, 1H, H-3, J = 5.6, 8.0 Hz); 13C NMR (CDCl3)
δ 7.6 (C-6), 20.7 (Ac), 20.8 (Ac), 20.9 (Ac), 30.8 (Me), 42.1 (C-1′),
68.3 (C-1), 69.5 (C-2), 69.7 (C-3), 71.6 (C-4), 72.3 (C-5), 169.5
2706
dx.doi.org/10.1021/jo3024973 | J. Org. Chem. 2013, 78, 2703−2709

The Journal of Organic Chemistry
Note
(CDCl3) δ 7.5, 31.6, 46.4, 66.4, 71.4, 72.0, 72.2, 74.5, 208.8; HRMS
calcd for C9H14N3O4INa (M + Na)+ 377.9927, found 377.9970.
General Procedure for Cyclization of Iodide. To a solution of
iodide (0.15−0.5 g) in THF was added pyrrolidine (4−10 equiv), and
the solution was stirred at room temperature for 6−12 h. After
completion of the reaction the mixture was diluted by the addition of
ethyl acetate and washed with 0.1 N HCl and brine. The organic phase
was dried and concentrated to a residue. The residue was purified by
flash column chromatography (hexanes/ethyl acetate 1:1) to give the
desired products.
(1S,2S,3R,4R,6S)-6-C-Acetyl-2,3-di-O-isopropylidene-7-
oxabicyclo[2.2.1]heptane (4). Iodide 3a (0.5 g, 1.47 mmol) was
converted to 4 (0.255 g, 82%) as a syrup: [α]D −12 (c 1.3, CHCl3);
1H NMR (CDCl3) δ 1.25 (s, 3H, Me), 1.47 (s, 3H, Me), 1.69−1.85
(m, 2H, H-5a, 5b), 2.24 (s, 3H, Me), 3.14 (m, 1H, H-1′), 4.11 (d, 1H,
H-3, J = 5.6 Hz), 4.22 (d, 1H, H-2, J = 5.6 Hz), 4.44 (d, 1H, H-4, J =
5.6 Hz), 4.62 (d, 1H, H-1, J = 5.6 Hz); 13C NMR (CDCl3,) δ 25.0
(Me), 25.6 (C-5), 25.9 (Me), 30.9 (C-3′), 52.4 (C-1′), 79.2 (C-1),
79.4 (C-3), 80.6 (C-4), 82.3 (C-2), 111.2 (CH), 205.7 (C-2′); HRMS
calcd for C11H17O4 (M + H)+ 213.1127, found 213.1117.
5.2, 5.2 Hz), 4.46 (d, 1H, H-5, J = 8.0 Hz), 4.50−4.58 (m, 3H, H-1, 3,
4), 4.84 (s, 1H, H-2); 13C NMR (CDCl3) δ 21.2 (Ac), 21.3 (2C, Ac),
28.0 (C-3′), 28.4 (C-6), 52.1 (C-1′), 69.7 (C-2), 71.0 (C-3), 71.1 (C-
1), 76.7 (C-5), 77.4 (C-4), 168.7 (Ac), 170.2 (Ac), 170.3 (Ac), 205.2
(C-2′); HRMS calcd for C15H20O8Na (M + Na)+ 351.1056, found
351.1017.
(1S,2R,3S,4R,5R,7S)-7-C-Acetyl-2,3,4-tri-O-acetyl-8-oxabicyclo-
[3.2.1]octane (21). Iodide 12 (0.20 g, 0.44 mmol) was converted to
21 (0.086 g, 60%) as a syrup: 1H NMR (CDCl3) δ 2.05 (s, 3H, OAc),
2.14 (s, 6H, 2 × OAc), 2.21 (s, 3H, Me), 2.25−2.32 (m, 1H, H-6a),
2.36−2.42 (m, 1H, H-6b), 3.46 (dd, 1H, H-1′, J = 5.2, 8.8 Hz), 4.45−
4.49 (m, 2H, H-1, 5), 4.72 (d, 1H, H-2, J = 1.2 Hz), 5.24−5.25 (m,
2H, H-3, 4, J = 3.2 Hz); 13C NMR (CDCl3) δ 20.7 (Ac), 20.9 (Ac),
21.0 (Ac), 27.7 (C-3′), 28.2 (C-6), 50.5 (C-1′), 65.8 (C-3/4), 67.8 (C-
4/3), 72.7 (C-2), 75.7 (C-5/1), 76.7 (C-1/5), 168.9 (Ac), 169.2 (Ac),
169.7 (Ac), 206.2 (C-2′); HRMS calcd for C15H20O8Na (M + Na)+
351.1056, found 351.1063.
(1S,2R,3S,4S,5R,7S)-7-C-Acetyl-2,3,4-tri-O-benzyl-8-oxabicyclo-
[3.2.1]octane (22). Iodide 13 (0.20 g, 0.33 mmol) was converted to
1
22 (0.138 g, 88%) as a syrup: [α]D +17 (c 2.1, CHCl3); H NMR
(CDCl3) δ 2.0−2.19 (m, 2H, H-6a, 6b), 2.10 (s, 3H, Me), 3.09 (dd,
1H, H-1′, J = 5.2, 8.8 Hz), 3.20 (s, 1H, H-4) 3.26 (s, 1H, H-3), 3.57 (s,
1H, H-2), 4.31 (s, 2H, Bn), 4.52 (m, 1H, H-5), 4.55 (s, 2H, Bn), 4.60
(s, 3H, H-1, Bn), 7.17−7.35 (m, 15H, 3 × Bn); 13C NMR (CDCl3) δ
27.8 (C-3′), 29.0 (C-6), 52.4 (C-1′), 71.1 (Bn), 71.2 (Bn), 72.1 (Bn),
75.5 (C-2), 76.0 (C-4), 76.3 (C-3), 76.8 (C-5), 77.5 (C-1), 127.7,
127.9, 127.96, 128.0, 128.1, 128.2, 128.6, 128.65, 128.7, 137.9, 138.3,
138.5, 207.2 (C-2′); HRMS calcd for C30H32O5Na (M + Na)+
495.2147, found 495.2144.
(1S,2R,3R,4S,5R,7S)-7-C-Acetyl-2,3-di-O-benzyl-4-O-mesyl-8-
oxabicyclo[3.2.1]octane (23). Iodide 14 (0.20 g, 0.34 mmol) was
converted to 23 (0.147 g, 94%) as a syrup: [α]D +19 (c 0.9, CHCl3);
1H NMR (CDCl3) δ 2.11 (s, 3H, Me), 2.21−2.27 (m, 2H, H6a, 6b),
3.01 (s, 3H, OMs), 3.16 (dd, 1H, H-1′, J = 7.6, 10.8 Hz), 3.23 (s, 1H,
H-2), 3.81 (s, 1H, H-3), 4.41 (d, 1H, Bn, J = 12.0 Hz), 4.48−4.65 (m,
6H, H-1, 4, 5, 1.5 × Bn), 7.21−7.37 (m, 10H, 2 × Bn); 13C NMR
(CDCl3) δ 27.9 (C-3′),28.9 (C-6), 39.2 (OMs), 51.7 (C-1′), 71.3
(Bn), 72.7 (Bn), 74.6 (C-3), 75.1 (C-4), 75.8 (C-2), 77.0 (C-5), 77.4
(C-1), 128.1, 128.17, 128.22, 128.5, 128.7, 128.8, 137.2, 137.7, 206.3
(C-2′); HRMS calcd for C24H28O7SNa (M + Na)+ 483.1453, found
483.1510.
(1S,2R,3S,4R,5R,7S)-7-C-Acetyl-4-azido-2,3-di-O-benzyl-8-
oxabicyclo[3.2.1]octane (24). Iodide 15 (0.20 g, 0.37 mmol) was
converted to 24 (0.135 g, 89%) as a syrup: [α]D +50 (c 1.3, CHCl3);
1H NMR (CDCl3) δ 1.97−2.05 (m, 1H, H-6a) 2.09 (s, 3H, Me), 2.59
(dd, 1H, H-6b, J = 10.0, 12.8 Hz), 3.26 (dd, 1H, H-1′, J = 5.2, 8.2 Hz),
3.37 (s, 1H, H-3), 3.76−3.80 (m, 2H, H-2, 4), 4.35−4.62 (m, 6H, H-1,
5, 2 × Bn), 7.26−7.38 (m, 10H, 2 × Bn); 13C NMR (CDCl3) δ 27.7
(C-3′), 28.2 (C-6), 51.8 (C-1′), 58.5 (C-4), 71.3 (Bn), 73.8 (Bn), 75.9
(C-3), 76.1 (C-5), 76.2 (C-2), 76.3 (C-1), 127.8, 127.9, 128.11,
128.13, 128.6, 137.3, 137.5, 206.8 (C-2′); HRMS calcd for
C23H25N3O4Na (M + Na)+ 430.1743, found 430.1744.
(1S,2R,3R,4S,5R,7S)-7-C-Acetyl-3-azido-8-oxabicyclo[3.2.1]octane
(25). Iodide 16 (0.15 g, 0.42 mmol) was converted to 25 (0.063 g,
65%) as needles (EtOAc−hexanes): mp 118−9 °C; [α]D −12 (c 0.37,
EtOAc); 1H NMR (CD3OD) δ 1.88 (dd, 1H, H-6a, J = 10.8, 12.4 Hz),
2.17 (s, 3H, Me), 2.21 (dd, 1H, H-6b, J = 5.6 Hz), 3.03 (dd, 1H, H-1′,
J = 5.6, 8.4 Hz), 3.22 (bs, 1H, H-3), 3.74 (bs, 1H, H-2), 3.82 (bs, 1H,
H-4), 4.34 (d, 1H, H-1, J = 8.0 Hz), 4.30 (bs, 1H, H-5); 13C NMR
(CD3OD) δ 28.3 (C-3′), 50.8 (C-1′), 54.5 (C-3), 71.2 (C-4), 71.6 (C-
2), 79.5 (C-1), 80.3 (C-5); HRMS calcd for C9H13O4N3Na (M + Na)+
250.0804, found 250.0820.
(1R,2R,3R,4R,5S,6S)-6-C-Acetyl-2,3-di-O-benzyl-5-nitromethyl-7-
oxabicyclo[2.2.1]heptane (28) and (1R,2R,3R,4R,5R,6R)-6-C-Acetyl-
2,3-di-O-benzyl-5-nitromethyl-7-oxabicyclo[2.2.1]heptane (29). A
solution of 26 (0.10 g, 0.24 mmol) in THF (1 mL) was added
pyrrolidine (50 μL). The mixture was kept at room temperature
overnight. The mixture was diluted by the addition of EtOAc (30 mL),
and the solution was washed with 0.1 N HCl and brine, dried, and
concentrated. The residue was subjected to column chromotagraphy
(1S,2S,3R,4R,5R,7S)-7-C-Acetyl-2,3-di-O-isopropylidene-4-O-
mesyl-l-8-oxabicyclo[3.2.1]octane (7). Iodide 6 (0.45 g, 1.0 mmol)
was converted to 7 (0.227 g, 71%) as needles (EtOAc−hexanes): mp
1
174−5 °C; [α]D +24 (c 0.65, EtOAc); H NMR (CDCl3) δ 1.37 (s,
3H, Me), 1.57 (s, 3H, Me), 1.94 (ddd, 1H, H-6a, J = 1.6, 9.6, 14.4 Hz),
2.21 (s, 3H, Me), 2.46 (ddd, 1H, H-6b, J = 4.8, 9.0, 14.4 Hz), 3.11 (s,
3H, Ms), 3.39 (dd, 1H, H-1′, J = 4.8, 9.6 Hz), 4.33 (d, 1H, H-1, J = 6.8
Hz), 4.47 (dd, 1H, H-2, J = 6.8, 6.8 Hz), 4.52 (d, 1H, H-3, J = 6.8 Hz),
4.60 (bd, 1H, H-5, J = 9.0 Hz), 4.76 (s, 1H, H-4); 13C NMR (CDCl3)
δ 24.6, 26.2, 27.0, 28.4, 39.1, 49.3, 70.0, 74.4, 76.8, 77.2, 78.2, 109.5,
206.4; HRMS calcd for C13H20O7SNa (M + Na)+ 343.0827, found
343.0844.
(1S,2R,3S,4R,6S)- 6-C-Acetyl-2,3-di-O-benzyl-7-oxabicyclo[2.2.1]-
heptane (17). Iodide 8 (0.48 g, 1.0 mmol) was converted to 17 (0.335
g, 95%) as a solid: [α]D +19 (c 0.4, CHCl3); 1H NMR (CDCl3) δ 1.42
(dd, 1H, H-6a, J = 9.2, 12.8 Hz), 1.94−2.02 (m, 1H, H-6b), 2.12 (s,
3H, Me), 2.37 (dd, 1H, H-1′, J = 4.8, 8.8 Hz), 3.68 (d, 1H, H-2, J = 6.0
Hz), 3.71 (d, 1H, H-3, J = 6.0 Hz), 4.55−4.72 (m, 6H, H-1, 4, 2 ×
Bn), 7.22−7.37 (m, 10H, 2 × Ph); 13C NMR (CDCl3) δ 28.0 (Me),
28.5 (C-5), 51.6 (C-1′), 72.8 (Bn), 73.0 (Bn), 79.4 (C-4), 80.9 (C-1),
82.1 (2C, C-2, 3), 77.8 (C-4), 83.7 (C-3), 127.8, 127.9, 128.0, 128.2,
128.3, 128.5, 128.6, 138.1, 138.2, 206.3 (C-2′); HRMS calcd for
C22H25O4 (M + H)+ 353.1753, found 353.1739.
(1R,2R,3R,4S,6S)-6-C-Acetyl-2,3-di-O-benzyl-7-oxabicyclo[2.2.1]-
heptane (18). Iodide 9 (0.225 g, 0.53 mmol) was converted to 18
(0.155 g, 83%) as a syrup: 1H NMR (CDCl3) δ 1.56 (dd, 1H, H-5a, J
= 9.2, 12.4 Hz), 2.11 (s, 3H, Me), 2.15 (ddd, 1H, H-5b, J = 5.6, 5.6,
12.4 Hz), 3.20 (dd, 1H, H-1′, J = 4.2, 9.2 Hz), 3.42 (d, 1H, H-3, J = 1.2
Hz), 3.93 (d, 1H, H-2, J = 4.8 Hz), 4.44−4.54 (m, 5H, H-4, 2 × Bn),
4.66 (d, 1H, H-1, J = 4.8 Hz), 7.27−7.36 (m, 10H, 2 × Ph); 13C NMR
(CDCl3) δ 28.4 (C-3′), 29.0 (C-5), 48.3 (C-1′), 71.3 (Bn), 73.1 (Bn),
78.6 (C-1), 81.0 (C-4), 86.1 (C-2), 86.2 (C-3), 128.0, 128.1, 128.2,
128.3, 128.7, 128.2, 137.6, 137.9, 207.4 (C-2′); HRMS calcd for
C22H25O4 (M + H)+ 353.1753, found 353.1749.
(1S,2R,3S,4R,5R,7S)-7-C-Acetyl-2,3-di-O-isopropyl-4-hydoxy-8-
oxabicyclo[3.2.1]octane (19). Iodide 10 (0.20 g, 0.54 mmol) was
converted to 19 (0.106 g, 81%) as needles (EtOAc−hexanes): mp
1
149−150 °C; [α]D +32 (c 0.2, EtOAc); H NMR (CDCl3) δ 1.36 (s,
3H, Me), 1.56 (s, 3H, Me), 1.97 (ddd, 1H, H-6a, J = 1.6, 9.6, 14.4 Hz),
2.21 (s, 3H, Me), 2.26 (d, 1H, 4-OH, J = 9.6 Hz), 2.37 (ddd, 1H, H-
6b, J = 4.8, 9.0, 14.4 Hz), 3.41 (dd, 1H, H-1′, J = 4.8, 9.6 Hz), 3.80 (d,
1H, H-4, J = 9.6 Hz), 4.24 (d, 1H, H-1, J = 6.8 Hz), 4.39−4.44 (m, 2H,
H-3, 5), 4.45 (dd, 1H, H-2, J = 6.4 Hz); 13C NMR (CDCl3) δ 24.5,
26.17, 26.22, 28.2, 49.6, 70.0, 70.8, 76.7, 77.3, 79.0, 109.0, 207.0;
HRMS calcd for C12H18O5Na (M + Na)+ 265.1052, found 265.1078.
(1S,2S,3S,4R,5R,7S)-7-C-Acetyl-2,3,4-tri-O-acetyl-8-oxabicyclo-
[3.2.1]octane (20). Iodide 11 (0.21 g, 0.46 mmol) was converted to
1
20 (0.10 g, 66%) as a syrup: [α]D +26 (c 1.7, CHCl3); H NMR
(CDCl3) δ 2.09 (s, 3H, OAc), 2.10−2.17 (m, 7H, H-6a, 2 × OAc),
2.20 (s, 3H, Me), 2.31−2.40 (m, 1H, H-6b), 3.16 (dd, 1H, H-1′, J =
2707
dx.doi.org/10.1021/jo3024973 | J. Org. Chem. 2013, 78, 2703−2709

The Journal of Organic Chemistry
Note
(hexanes to EtOAc−hexanes 1:3) to give 28 (30 mg, 30%) and 29 (34
mg, 34%).
ACKNOWLEDGMENTS
■
This is NRC−CNRC publication no. 50061. We thank Haitao
Yang for technical assistance, Ken Chan and Jacek Stupak for
MS analysis, and Nam Khieu and Milan Bhasin for the
assistance in NMR analysis.
Data for 28: needles (EtOAc−hexanes); mp 138−9 °C; [α]D +12 (c
1
1.7, CHCl3); H NMR (CDCl3) δ 2.08 (s, 3H, 3′-Me), 2.61 (dd, 1H,
H-1′, J = 5.2, 5.2 Hz), 3.14 (m, 1H, H-5), 3.57 (d, 1H, H-3, J = 1.6
Hz), 4.06 (bd, 1H, H-3, J = 4.8 Hz), 4.31−4.35 (m, 2H, H-6a, 6b),
4.37 and 4.57 (d and d, 1H each, Bn, J = 12.0 Hz), 4.44 (s, 1H, H-4),
4.43 and 4.57 (d and d, 1H each, Bn, J = 12.0 Hz), 4.89 (dd, 1H, H-1, J
= 5.2, 5.2 Hz), 7.22−7.41 (m, 10H, 2 × Bn); 13C NMR (CDCl3) δ
29.9 (C-3′), 38.3 (C-5), 58.5 (C-1′), 71.8 (Bn), 73.1 (Bn), 76.7 (C-6),
78.1 (C-1), 83.8 (C-4), 84.1 (C-3), 87.0 (C-2), 127.9, 128.2, 128.3,
128.7, 128.8, 137.0, 137.4, 201.2 (C-2′); HRMS calcd for
C23H25NO6Na (M + Na)+ 434.1580, found 434.1600.
REFERENCES
■
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Kobayashi, M. J. Am. Chem. Soc. 2006, 128, 3148−3149.
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Data for 29: syrup; [α]D +46 (c 3.0, CHCl3); 1H NMR (CDCl3) δ
2.12 (s, 3H, 3′-Me), 2.89 (d, 1H, H-1′, J = 5.6 Hz), 3.33 (m, 1H, H-5),
3.64 (s, 1H, H-3), 4.00 (d, 1H, H-2, J = 4.2 Hz), 4.30 (dd, 1H, H-6a, J
= 10.4, 13.6 Hz), 4.42 and 4.54 (d and d, 1H each, Bn, J = 12.0 Hz),
4.46−4.53 (m, 3H, H-6b, Bn), 4.61 (d, 2H, H-1, 4, J = 5.6 Hz), 7.22−
7.41 (m, 10H, 2 × Bn); 13C NMR (CDCl3) δ 28.4 (C-3′), 38.9 (C-5),
52.1 (C-1′), 71.5 (Bn), 73.4 (Bn), 74.3 (C-6), 79.8 (C-1/C-4), 81.0
(C-3), 82.5 (C-4/C-1), 85.7 (C-2), 128.2, 128.3, 128.6, 128.7, 128.8,
129.0, 137.2, 137.5, 205.1 (C-2′); HRMS calcd for C23H25NO6Na (M
+ Na)+ 434.1580, found 434.1572.
(1S,2R,3S,4R,5S,6S)-6-C-Acetyl-2,3-di-O-benzyl-5-nitromethyl-7-
oxabicyclo[2.2.1]heptane (30) and (1S,2R,3S,4R,5R,6R)-6-C-Acetyl-
2,3-di-O-benzyl-5-nitromethyl-7-oxabicyclo[2.2.1]heptane (31). A
solution of 27 (0.10 g, 0.24 mmol) in THF (1 mL) was added
pyrrolidine (50 μL). The mixture was kept at room temperature
overnight. The mixture was diluted by the addition of EtOAc (30 mL)
and the solution was washed with 0.1 N HCl and brine, dried, and
concentrated. The residue was subjected to column chromotagraphy
(hexanes to EtOAc−hexanes 1:3) to give 30 (27 mg, 27%) and 31 (27
mg, 27%).
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3241.
Data for 30: syrup; 1H NMR δ 2.02 (d, 1H, H-1′, J = 5.6 Hz), 2.15
(s, 3H, 3′-Me), 2.12 (m, 1H, H-5), 3.71 (d, 1H, H-2, J = 6.0 Hz), 3.88
(d, 1H, H-3, J = 6.0 Hz), 4.16 (dd, 1H, H-6a, J = 9.6, 13.2 Hz), 4.32
(dd, 1H, H-6b, J = 7.6, 13.2 Hz), 4.53 (s, 1H, H-1), 4.56 and 4.75 (d
and d, 1H each, Bn, J = 11.6 Hz), 4.64 (s, 2H, Bn), 4.65 (s, 1H, H-4),
7.22−7.41 (m, 10H, 2 × Bn); 13C NMR (CDCl3) δ 28.2 (C-3′), 38.8
(C-5), 56.1 (C-1′), 72.9 (Bn), 73.4 (Bn), 74.7 (C-6), 77.4 (C-3), 81.3
(C-4), 82.0 (C-2), 82.4 (C-1), 128.3, 128.4, 128.7, 128.8, 137.5, 137.7,
203.9 (C-2′); HRMS calcd for C23H25NO6Na (M + Na)+ 434.1580,
found 434.1608.
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Data for 31: syrup; [α]D −39 (c 1.5, CHCl3); 1H NMR (CDCl3) δ
2.00 (s, 3H, 3′-Me), 2.77 (dd, 1H, H-1′, J = 5.2, 5.2 Hz), 2.82 (m, 1H,
H-5), 3.58 (d, 1H, H-2, J = 6.0 Hz), 3.80 (d, 1H, H-3, J = 6.0 Hz), 4.16
(dd, 1H, H-6a, J = 7.6, 13.6 Hz), 4.29 (s, 1H, H-4), 4.38 (dd, 1H, H-
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Hz), 4.57 and 4.63 (d and d, 1H each, Bn, J = 12.0 Hz), 4.64 (s, 1H,
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434.1580, found 434.1558.
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ASSOCIATED CONTENT
■
S
* Supporting Information
Synthetic schemes for substrates 8−16; 1D and 2D NMR
spectra of compounds (4−31). This material is available free of
charge via the Internet at http://pubs.acs.org.
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AUTHOR INFORMATION
■
(30) Kawasumi, M.; Kanoh, N.; Iwabuchi, Y. Org. Lett. 2011, 13,
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Corresponding Author
*Tel: 1-(613)-991-0855. Fax: 1-(613)-952-9092. E-mail: wei.
zou@nrc-cnrc.gc.ca.
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Notes
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The authors declare no competing financial interest.
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