Inverse stereoselectivity in the nucleophilic attack on five-membered ring oxocarbenium ions. Application to the total synthesis of 7-epi-(+)-goniofufurone

Article abstract of DOI:10.1016/j.tet.2008.10.087

A highly stereoselective nucleophilic substitution at the anomeric position of 1,2-O-isopropylidene furanose derivatives was employed for the synthesis of 7-epi-(+)-goniofufurone and two of its stereoisomers. According to Woerpel's model, the stereoselect

Full text of DOI:10.1016/j.tet.2008.10.087

Tetrahedron 65 (2009) 139–144
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Tetrahedron
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Inverse stereoselectivity in the nucleophilic attack on five-membered ring
oxocarbenium ions. Application to the total synthesis of 7-epi-(þ)-goniofufurone
a
a
b
a
a,
*
´
´
´
¨
Luıs Hernandez-Garcıa , Leticia Quintero , Herbert Hopfl , Martha Sosa , Fernando Sartillo-Piscil
a Centro de Investigacio´n de la Facultad de Ciencias Qu´ımicas, BUAP, 14 Sur Esq. San Claudio, San Manuel, 72570 Puebla, Mexico
b Centro de Investigaciones Qu´ımicas, Universidad Auto´noma del Estado de Morelos, Av. Universidad 1001, 62209 Cuernavaca, Mexico
a r t i c l e i n f o
a b s t r a c t
Article history:
A highly stereoselective nucleophilic substitution at the anomeric position of 1,2-O-isopropylidene fu-
ranose derivatives was employed for the synthesis of 7-epi-(þ)-goniofufurone and two of its stereoiso-
mers. According to Woerpel’s model, the stereoselectivity depends essentially on stereoelectronic factors
that lead to a preferred nucleophilic attack on the inside face of the five-membered ring oxocarbenium
ion in a folded conformation, whereby the stereochemical outcome generally is controlled by the sub-
stituent at the C3 position (OR group). Herein, we developed a strategy for a reverse stereoselective
nucleophilic substitution, by placing an acetyl group at the C5 position of the xylofuranose ring, leading
now to the nucleophilic approach on the outside face of the respective oxocarbenium ion. With this
Received 10 September 2008
Received in revised form 17 October 2008
Accepted 28 October 2008
Available online 5 November 2008
This work is dedicated to the memory of Pily
methodology, starting from diacetone-D-glucose derivative, we were able to achieve in seven steps the
total synthesis of the powerful anti-tumor compound 7-epi-(þ)-goniofufurone in a remarkable overall
yield of 33%.
Ó 2008 Elsevier Ltd. All rights reserved.
R
O
1. Introduction
X = Leavig group
R = Alkyl or aryl
X
A
The C-glycosylation reaction of carbohydrate-furanose deriva-
tives has emerged as a useful technology for the construction of
a number of biologically important compounds.1 With exception of
a limited number of examples where the SN2-type mechanism is
proposed,2 this reaction follows a SN1-type mechanism.3 Further-
more, the reaction is frequently highly stereoselective.4 Initially,
steric interactions were invoked to explain the stereoselectivity for
this reaction,5 however, those considerations were insufficient to
explain several highly stereoselective reactions.4 Then, an elegant
stereoelectronic model formulated by Woerpel appeared and the
mechanistic situation became clearer.6 This model that is also
known as the inside attack model postulates that: the nucleophilic
substitution at the anomeric position occurs via a SN1-type mech-
anism, where the nucleophilic attack takes place preferentially on
the inside face of a five-membered ring oxocarbenium ion having
a folded conformation (B or C, Scheme 1). This reaction gives the
1,3-cis-product as major diastereoisomer. Additionally, according to
this model, the preferential pseudo-axial orientation of the alkoxyl
group at the C-3 position plays a key role for the preferential nu-
cleophilic approach on the inside face of the oxocarbenium ion
(B or C).7
R1O
Lewis acid
inside face
R
O
R1
O
O
R
R
O
1
Nu
1
Nu
Nu
R
O
3
3
or
R1
R1O
R1O
C
O
1,3-cis product
1,3-cis product
Nu
B
major diastereoisomer
inside face
major diastereoisomer
Scheme 1. Woerpel’s model for the C-glycosylation in furanose derivatives.
Having this model in mind, we recently applied the nucleophilic
substitution reaction at the anomeric position of 1,2-O-iso-
propylidene-
goniofufurone diastereoisomers 2 and 3 (Scheme 2).8,9 The nucleo-
philic substitution reaction afforded as the major di-
D-xylofuranose derivative 1 for the synthesis of
4
astereoisomer, with the stereochemistry in accordance with the
expected preferential nucleophilic attack on the inside face of the
oxocarbenium ion D (Scheme 2).
2. Results and discussions
Continuing with our efforts on the synthesis of goniofufurone
diastereoisomers, we decided to apply the above strategy to the
stereoselective transformation of the ribofuranose derivative 7 to 8
(presumably expected as the major diastereoisomer), which could
* Corresponding author. Tel./fax: þ52 2222295500x7391.
E-mail address: fsarpis@siu.buap.mx (F. Sartillo-Piscil).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.10.087

´
´
140
L. Hernandez-Garcıa et al. / Tetrahedron 65 (2009) 139–144
Ph
O
H
HO
O
O
Ph
HO
Ph
H
2
O
Ph
O
O
4 steps
Nu
BF3·OEt2
BnO
BnO
O
BnO
H
OH
1
BnO
O
86%
4
HO
major diastereoisomer
O
O
BF3·OEt2
HO
H
3
attack on the
Inside face
OBn
Nu
O
Bn
Ph
H
R
O
Ph
H
O
O
HO
O
HO
O
O
O
H
O
HO
H
HO
H
6
OBF3
5
(+)-Goniofufurone
7-epi-(+)-Goniofufurone
D
Scheme 2. Nucleophilic substitution of the xylofuranose derivative 1 for the synthesis of the goniofufurone diastereoisomers 2 and 3.
OH
HO
H
thought that it might be possible to prepare the naturally occurring
goniofufurones 5 and 6 from 9 and 10 by inversion of the stereo-
chemistry at the C5-OH group. Thus, we tried to selectively oxidize
the C5-OH group with a number of oxidizing agents in order to
stereoselectively reduce the formed carbonyl group. However, in all
the cases the C7-OH group was always oxidized.14 Changing the
strategy, we reasoned that incorporating a temporal internal nu-
cleophile in the xylofuranose derivative 14 could block the nucle-
ophile approach on the favored inside face of the oxocarbenium ion
F, inducing now a reverse nucleophilic attack to give 15 as the major
diastereoisomer. Therefore, we concluded that an O-acetyl group at
the C5 position (14) could provide the required internal nucleophile
(Scheme 5).
O
Ph
O
Nu = Allyltrimethylsilane
O
H
H
9
Ph
O
Ph
O
O
Nu
BF3·OEt2
BnO
BnO
OH
O
BnO
O
OH
7
BnO
8
Ph
O
O
HO
H
10
BF3·OEt2
Ph
BnO
It is important to mention that we chose to place the acetyl
group at the C5 position rather than the C3 position, since
a destabilizing effect of the acetyl or phosphate group at C3 on the
cation center has been observed that inhibits the incorporation of
an external nucleophile.8,15Additionally, another recent report has
shown that an O-acetyl group participates effectively in the ster-
eoselective nucleophilic addition to five-membered ring N-acyli-
minium ions to afford 5-substituted-2-pyrrolidinones.16 With this
new strategy in mind, we decided to apply it to the total synthesis
of 7-epi-(þ)-goniofufurone 6,17 which was recently found to be
a more efficient cytotoxic agent against several neoplastic cell
lines18 than (þ)-goniofufurone.
O
O
Bn
O
OBF3
E
Scheme 3. Synthetic strategy for the synthesis of goniofufurone diastereoisomers 9
and 10.
then be converted into the goniofufurone diastereoisomers 9 and
10 (Scheme 3).
The ribofuranose derivatives 7a and 7b were obtained in two
steps from diacetone-
D
-allofuranose 11.10 First, a sequential hy-
Compound 14 was stereoselectively obtained19 in two steps
drolysis–oxidation–Grignard reagent addition (SHOGRA) pro-
cedure11 was carried out whereupon the hydroxyl group
was protected by treatment with benzylbromide and NaH
(Scheme 4).
from diacetone-D-glucose derivative 16 and then submitted to
classical nucleophilic substitution conditions (vide supra). As
planned, the nucleophilic substitution of 14 with allyl-
trimethylsilane and BF3$OEt2 was highly stereoselective,
affording the 1,3-trans-product 15 in high yield and as a single
diastereoisomer (Scheme 6).
As expected, and in accordance with Woerpel’s model, the
treatment of 7a0 and 7b0 with allyltrimethylsilane in the presence of
BF3$OEt2 afforded 8a and 8b as the major diastereoisomers. The
lactonization of 8a and 8b to 13a and 13b was achieved by a se-
quential dihydroxylation–dehomologation–oxidation procedure.9
Finally a debenzylation of 13a and 13b with H2 and Pd(OH)2
afforded the goniofufurone diastereoisomers 9 and 10 (Scheme 4).
The absolute stereochemistry of 10 was determined by comparison
of its spectroscopic data.12 Additionally, the stereochemistry of 9
was verified by single-crystal X-ray diffraction (Fig. 1).13
The completion of the synthesis of the 7-epi-(þ)-goniofufurone
is outlined in Scheme 6. The lactone 17 was prepared using the
above sequential procedure (dihydroxylation–dehomologation–
oxidation). The selective removal of the acetyl group was difficult to
achieve, therefore, a basic hydrolysis protocol was applied, which
led to lactone ring opening. However, the relactonization was
achieved with DCC to give 18. Finally, debenzylation with H2 and
Pd(OH)2 afforded the 7-epi-(þ)-goniofufurone in seven steps
Having developed an accessible stereoselective route for the
synthesis of the goniofufurone diastereoisomers 9 and 10, we
starting from diacetone-
overall yield of 33%.
D-glucose derivative 16 in a remarkable

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L. Hernandez-Garcıa et al. / Tetrahedron 65 (2009) 139–144
141
RO
Ph
RO
Ph
O
O
O
O
O
O
H5IO6, AcOEt,
O
+
O
PhMgBr
82%
O
RO
O
RO
O
HO
11
BnBr,
NaH
90%
BnBr,
NaH
90%
7b: R = H
7b': R = Bn
7a: R = H
ratio 7a/7b (3:1)
7a': R = Bn
BnO
Ph
O
BnO
+
O
Ph
BnO
OH
7a'
BnO
OH
OH
83%
SiMe3
BF3 OEt2
8a
8a'
ratio 8a/8a' = 96:4
BnO
BnO
O
O
7b'
82%
Ph
BnO
Ph
OH
BnO
8b'
8b
ratio 8b/8b' = 96:4
OH
H
OBn
H
2
1
O
5
6
O
H2, Pd(OH)2
EtOH
90%
3
7
Ph
Ph
O
4
O
O
O
8a
HO
H
9
BnO
OBn
H
13a
70%
72%
cat OsO4, NMO
NaIO4, PCC
OH
H
H
O
O
H2, Pd(OH)2
Ph
Ph
8b
O
O
EtOH
90%
O
O
HO
H
BnO
H
13b
10
Scheme 4. Synthesis of the goniofufurone diastereoisomers 9 and 10.
3. Conclusions
In conclusion, the success of the short and simple synthesis of
the 7-epi-(þ)-goniofufurone 6 and two of its diastereoisomers 9
and 10 depended on the development of a highly stereoselective
nucleophilic substitution at the anomeric position of the xylo- and
ribofuranose derivatives, and also on the adequate application of
two sequential procedures. The above methodology is currently
being used by our group in further syntheses of related biologically
important compounds and will be reported soon.
4. Experimental
4.1. General
Figure 1. Perspective view of the molecular goniofufurone diastereoisomer 9.
The reagents were obtained from commercial sources and used
without purification. The solvents were used as technical grade and
freshly distilled prior use. NMR studies were carried out with 400
and 300 MHz spectrometers. TMS was used as internal reference
for 1H and 13C NMR. Chemical shifts (
d) are stated in parts per
Inside face
blocked
OAc
O
O
AcO 5
Ph
Ph
BnO
O
1
O
Ph
O
5 or 6
3
BF3·OEt2
O
OH
15
O
BnO
1,3-trans product
BnO
14
O
Nu
OBF3
F
attack on the
outside face
Scheme 5. Synthetic strategy for the synthesis of naturally occurring goniofufurones 5 or 6.

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L. Hernandez-Garcıa et al. / Tetrahedron 65 (2009) 139–144
O
AcO
O
O
O
AcO
O
1. refs. 11, 19
2. anhydride
acetic
O
SiMe3
O
BnO
Ph
BnO
O
Ph
BnO
BF3 OEt2
90%
O
16
OH
14
15
(72% from 16)
as single diastereoisomer
OAc
BnO
H
OH
H
O
O
cat OsO4, NMO
NaIO4, PCC
1. NaOH
2. DCC
H2
Pd(OH)2
88%
Ph
Ph
15
6
O
O
O
O
H
17
BnO
H
18
(70%)
(82%)
Scheme 6. Synthesis of the 7-epi-(þ)-goniofufurone 6.
million (ppm). COSY, HSQC, and NOESY experiments have been
carried out in order to assign the 1H and 13C spectra completely.
4.6. (5S)-3,5-Di-O-benzyl-1,2-O-isopropylidene-5-phenyl-
a-D
-ribofuranose (7a0)
Yield 90%, mp¼84–86 ꢁC. [
a
]
þ97.2 (c 1.0, CHCl3). 1H NMR
D
4.2. General protocol for the sequential hydrolysis–
oxidation–Grignard reagent addition (SHOGRA) procedure11
(300 MHz, CDCl3)
d
: 1.30 (s, 3H), 1.48 (s, 3H), 3.91 (dd, 1H, J¼4.4,
8.8 Hz), 4.15 (d, 1H, J¼12.4 Hz), 4.21 (dd, 1H, J¼2.8, 8.8 Hz), 4.33 (d,
1H, J¼11.7 Hz), 4.48 (d, 1H, J¼3.2 Hz), 4.53 (m, 3H), 5.78 (d, 1H,
A solution of diacetone-D-allofuranose 11 (0.8 mmol) and peri-
J¼3.6 Hz), 7.31 (m, 15H). 13C NMR (75 MHz, CDCl3)
d: 26.5, 26.7,
odic acid (0.9 mmol) in 50 mL of dry ethyl acetate was stirred for
2 h, whereby a solid formed was separated by filtration. Evapora-
tion under reduced pressured afforded a colorless syrup, which was
dissolved in 10 mL of dry THF (Et2O for the case of 1619), and cooled
to ꢀ30 ꢁC. Then, phenyl magnesium bromide (21 mmol) was added
and the reaction mixture was allowed to react for 6 h at the same
temperature before adding a saturated solution of NH4Cl (20 mL).
The product was extracted with ethyl acetate (3ꢂ50 mL) and the
solution dried over Na2SO4. The solution was evaporated under
reduced pressure and the residue was purified by column
chromatography.
70.6, 72.0, 77.3, 77.8, 78.6, 81.8,104.2,112.7,127.6,127.8,127.8,128.0,
128.1, 128.2, 137.6, 137.8, 138.3. FABMS m/z (rel intensity) 447
([MþH]þ, 14); FAB-HRMS m/z 447.2170 [MþH]þ (calcd for
C28H31O5: 447.2172).
4.7. (5R)-3,5-Di-O-benzyl-1,2-O-isopropylidene-5-phenyl-
a-D
-ribofuranose (7b0)
Yield 90%, colorless oil. [
a
]
D
þ28.0 (c 1.0, CHCl3). 1H NMR
(400 MHz, CDCl3)
d
: 1.32 (s, 3H), 1.57 (s, 3H), 3.65 (dd, 1H, J¼4.8,
8.4 Hz), 4.31 (d, 1H, J¼12.0 Hz), 4.35 (d, 1H, J¼12.0 Hz), 4.43 (m, 2H),
4.54 (m, 2H), 4.61 (d, 1H, J¼12.0 Hz), 5.62 (d, 1H, J¼3.6 Hz), 7.24 (m,
4.3. (5S)-1,2-O-Isopropylidene-5-phenyl-a-D-ribofuranose (7a)
15H). 13C NMR (100 MHz, CDCl3)
d: 26.8, 27.1, 71.0, 71.8, 77.3, 77.6,
Yield 57%, mp¼116–118 ꢁC. [
a
]
þ25.5 (c 1.0, CHCl3). 1H NMR
D
80.2, 82.1, 104.3, 113.0, 127.2, 127.6, 127.6, 127.9, 127.9, 128.0, 128.1,
128.1, 136.9, 137.3, 138.0. FABMS m/z (rel intensity) 447 ([MþH]þ,
22);FAB-HRMSm/z447.2171 [MþH]þ (calcdforC28H31O5:447.2172).
(400 MHz, CDCl3)
d
: 1.36 (s, 3H), 1.55 (s, 3H), 2.26 (d, 1H, J¼10.0 Hz),
2.60 (br, 1H), 3.99 (dd, 1H, J¼3.6, 8.8 Hz), 4.08 (m, 1H), 4.58 (t,
1H, J¼4.0 Hz), 4.81 (br, 1H), 5.82 (d, 1H, J¼3.6 Hz), 7.36 (m, 5H). 13C
NMR (100 MHz, CDCl3) d: 26.6, 26.7, 71.8, 72.8, 78.7, 83.4, 103.9,
4.8. Typical acetylation reaction
112.8, 126.5, 127.8, 128.3, 140.2. FABMS m/z (rel intensity) 267
([MþH]þ,18); FAB-HRMS m/z 267.1144 [MþH]þ (calcd for C14H19O5:
267.1145).
To a solution of (5S)-1,2-O-isopropylidene-3-O-benzyl-5-phe-
nyl-xylofuranose19 in pyridine (2.5 mL) at 0 ꢁC was added acetic
anhydride (2.5 mL). The reaction mixture was allowed to react for
2 h at room temperature before adding dropwise an aqueous so-
lution of HCl (1 N). After neutralization with HCl, it was extracted
with EtOAc (3ꢂ50 mL), washed with brine, dried over Na2SO4, and
evaporated under reduced pressure. The residue was purified by
column chromatography.
4.4. (5R)-1,2-O-Isopropylidene-5-phenyl-a-D-ribofuranose (7b)
Yield 25%, mp¼130–132 ꢁC. [
a
]
þ6.05 (c 1.0, CHCl3). 1H NMR
D
(400 MHz, CDCl3)
d
: 1.35 (s, 3H), 1.55 (s, 3H), 4.03 (dd, 1H, J¼4.0,
8.4 Hz), 4.06 (br, 1H), 4.56 (dd, 1H, J¼4.0, 4.8 Hz), 4.98 (d, 1H,
J¼4.0 Hz), 5.78 (d, 1H, J¼3.6 Hz), 7.37 (m, 5H). 13C NMR (100 MHz,
CDCl3) d: 26.9, 27.0, 71.6, 73.4, 79.4, 83.4, 103.9, 126.5, 128.2, 128.5,
128.3, 139.2. FABMS m/z (rel intensity) 267 ([MþH]þ, 22); FAB-
4.9. (5S)-1,2-O-Isopropylidene-3-O-benzyl-5-phenyl-5-acetyl-
a-D-xylofuranose (14)
HRMS m/z 267.1145 [MþH]þ (calcd for C14H19O5: 267.1145).
4.5. Typical hydroxyl group protection
Yield 92%, white solid, mp¼121–123 ꢁC. [
D þ4.3 (c 1.0, CHCl3).
a
]
1H NMR (400 MHz, CDCl3)
d: 1.29 (s, 3H), 1.53 (s, 3H), 2.03 (s, 3H),
To a suspension of corresponding 1,3-diol (1.5 mmol) and NaH
(4.5 mmol) in dry THF (30 mL) was added dropwise benzylbromide
(4.5 mmol) dissolved in THF (5 mL). The reaction mixture was
allowed to react for 4 h at room temperature before adding 30 mL
of water. The aqueous layer was extracted three times with CH2Cl2
(30 mL), the organic phase dried over Na2SO4, and concentrated in
vacuo.
3.44 (d, 1H, J¼4.4 Hz), 4.06 (d, 1H, J¼15.6 Hz), 4.45 (m, 1H), 4.39 (d,
1H, J¼15.6 Hz), 4.53 (d, 1H, J¼4.0 Hz), 4.60 (d, 1H, J¼4.4 Hz), 6.01 (d,
1H, J¼5.2 Hz), 6.10 (d, 1H, J¼12.0 Hz), 7.37 (m, 10H). 13C NMR
(75 MHz, CDCl3) d: 21.0, 26.2, 26.7, 72.2, 80.8, 81.2, 81.7, 105.1, 111.7,
127.5, 127.6, 127.9, 128.3, 128.4, 137.0, 138.2, 168.9. FABMS m/z (rel
intensity) 399 ([MþH]þ, 20); FAB-HRMS m/z 399.1805 [MþH]þ
(calcd for C23H27O6: 399.1808).

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L. Hernandez-Garcıa et al. / Tetrahedron 65 (2009) 139–144
143
4.10. General procedure for the stereoselective substitution
reaction of 1,2-O-isopropylidene-furanose derivatives
mother solution was evaporated under reduced pressure. The res-
idue was purified by column chromatography.
A solution of the corresponding 1,2-O-isopropylidene-furanose
derivatives (2.0 mmol) in 50 mL of dry CH2Cl2 at 0 ꢁC was treated
with allyltrimethylsilane (4.0 mmol) and BF3$OEt2 (4.0 mmol). The
reaction mixture was warmed to room temperature and allowed to
react for 4 h (20 h is necessary for compound 14). The reaction
mixture was treated with a saturated aqueous solution of NaHCO3
(50 mL) and extracted with EtOAc (3ꢂ50 mL). The organic phase
was dried with Na2SO4, concentrated in vacuo, and purified by
column chromatography on silica gel.
4.15. (7S)-3,6-Anhydro-7,5-di-O-benzyl-2-deoxy-7-phenyl-
D-altro-1,4-heptanolactone (13a)
Yield 70%. [
a
]
D þ5.4 (c 0.8, CHCl3). 1H NMR (300 MHz, CDCl3)
d:
2.64 (m, 2H), 4.15 (m, 2H), 4.18 (d, 1H, J¼11.8 Hz), 4.35 (d, 1H,
J¼11.4 Hz), 4.41 (d,1H, J¼2.4 Hz), 4.55 (d,1H, J¼11.7 Hz), 4.57 (d, 1H,
J¼11.4 Hz), 4.8 (m, 2H), 7.35 (m, 15H). 13C NMR (75 MHz, CDCl3)
d:
36.5, 70.7, 72.6, 77.4, 78.9, 79.5, 81.0, 84.5, 127.5, 127.8, 127.9, 128.0,
128.1, 128.4, 137.1, 137.7, 137.8, 175.4. FABMS m/z (rel intensity) 431
([MþH]þ, 11); FAB-HRMS m/z 431.1853 [MþH]þ (calcd for
C27H27O5: 431.1858).
4.11. (10S,2R,3R,4S,5R)-2-Allyl-4-benzyloxy-5[(benzyloxy)-10-
phenyl-methyl]-tetrahydro-furan-3-ol (8a)
4.16. (7R)-3,6-Anhydro-7,5-di-O-benzyl-2-deoxy-7-phenyl-
D-altro-1,4-heptanolactone (13b)
Yield 80%, white solid, mp¼93–95 ꢁC. [
a]
þ23.0 (c 1.0, CHCl3).
D
1H NMR (400 MHz, CDCl3)
d: 2.41–2.49 (m, 2H), 3.75 (ddd, 1H,
J¼3.2, 7.2, 10.0 Hz), 3.87 (dd, 1H, J¼3.6, 8.0 Hz), 4.00 (dd, 1H, J¼4.8,
6.4 Hz), 4.22 (m, 3H), 4.33 (d, 1H J¼11.2 Hz), 4.37 (d, 1H, J¼4.8 Hz),
4.57 (d, 1H, J¼11.2 Hz), 5.06 (m, 1H), 5.14 (m, 1H), 5.84 (m, 1H), 7.37
Yield 72%, mp¼95–97 ꢁC. [
a
]
þ12.8 (c 0.8, CHCl3). 1H NMR
D
(400 MHz, CDCl3)
d
: 2.68 (m, 2H), 3.99 (t, 1H, J¼4.8 Hz), 4.31 (m,
3H), 4.51 (m, 3H), 4.75 (dd, 1H, J¼5.2, 8.8 Hz), 4.86 (t, 1H, J¼5.2 Hz),
(m, 15H). 13C NMR (100 MHz, CDCl3)
d: 31.5, 70.2, 70.4, 72.4, 80.4,
7.23 (m, 15H). 13C NMR (100 MHz, CDCl3)
d: 36.7, 71.3, 72.2, 77.6,
80.7, 81.0, 83.1, 116.8, 127.0, 127.5, 127.6, 127.7, 127.8, 127.9, 128.0,
128.2, 128.3, 128.4, 128.5, 128.6, 134.7, 137.1, 138.1, 138.2. FABMS m/z
(rel intensity) 431 ([MþH]þ, 13); FAB-HRMS m/z 431.2223 [MþH]þ
(calcd for C28H31O4: 431.2222).
77.6, 81.2, 81.4, 86.0, 127.1, 127.5, 127.6, 127.7, 127.9, 128.1, 128.2,
128.3, 136.5, 136.8, 137.5, 175.1. FABMS m/z (rel intensity) 431
([MþH]þ, 15); FAB-HRMS m/z 431.1859 [MþH]þ (calcd for
C27H27O5: 431.1858).
4.12. (10R,2R,3R,4S,5R)-2-Allyl-4-benzyloxy-5[(benzyloxy)-10-
4.17. (7S)-3,6-Anhydro-7-O-acetyl-5-O-benzyl-2-deoxy-7-
phenyl-methyl]-tetrahydro-furan-3-ol (8b)
phenyl-
D-ido-heptono-1,4-lactone (17)
Yield 80%. [
a
]
D þ90.4 (c 1.2, CHCl3). 1H NMR (400 MHz, CDCl3)
d
:
Yield 70%. [
a
]
D þ18.8 (c 1.0, CHCl3). 1H NMR (400 MHz, CDCl3)
d:
2.43 (m, 2H), 3.94 (ddd, 1H, J¼4.4, 10.0, 13.6 Hz), 4.07 (m, 1H), 4.21
2.05 (s, 3H), 2.74 (m, 2H), 3.72 (d, 1H, J¼4.0 Hz), 4.25 (d, 1H,
J¼11.6 Hz), 4.33 (d, 1H, J¼11.6 Hz), 4.48 (dd, 1H, J¼4.0, 8.4 Hz), 4.79
(d, 1H, J¼4.4 Hz), 5.07 (dt, 1H, J¼4.4, 1.6 Hz), 6.04 (d, 1H, J¼8.8 Hz),
(m, 4H), 4.41 (d, 1H, J¼16.4 Hz), 4.62 (m, 2H), 5.07 (m, 1H), 5.15 (m,
1H), 5.86 (m, 1H), 7.31 (m, 15H). 13C NMR (100 MHz, CDCl3)
d: 33.7,
70.6, 71.5, 72.1, 79.5, 81.6, 81.7, 84.5, 116.7, 127.0, 127.5, 127.6, 127.7,
127.9, 127.9, 128.3, 128.3, 128.4, 134.9, 137.0, 138.0, 138.3. FABMS m/z
(rel intensity) 431 ([MþH]þ, 15); FAB-HRMS m/z 431.2225 [MþH]þ
(calcd for C28H31O4: 431.2222).
7.32 (m, 10H). 13C NMR (100 MHz, CDCl3)
d: 21.2, 36.1, 72.8, 74.8,
77.6, 81.5, 82.7, 84.6, 127.7, 128.2, 128.5, 128.6, 128.7, 136.6, 136.7,
169.8, 175.2. FABMS m/z (rel intensity) 383 ([MþH]þ, 4), 323
([MþHꢀOAc]þ, 34); FAB-HRMS m/z 323.1369 [MþHꢀOAc]þ (calcd
for C20H19O4: 323.1383 [MþHꢀOAc]þ).
4.13. (10S,2R,3R,4S,5R)-2-Allyl-4-benzyloxy-5[(O-acetyl)-10-
phenyl-methyl]-tetrahydro-furan-3-ol (15)
4.18. Procedure for removal of acetyl group
Yield 90%. [
a
]
D þ2.8 (c 1.0, CHCl3). 1H NMR (400 MHz, CDCl3)
d
:
To a solution of 17 (0.2 g, 0.52 mmol) in methanol (2 mL) was
added dropwise sodium hydroxide (1 mL, 1 M in water) at 0 ꢁC. The
reaction mixture was allowed to react for 5 min and rapidly was
extracted with CH2Cl2 (3ꢂ15 mL), the organic phase was dried with
Na2SO4, and the solvent was removed in vacuo. The residue was
dissolved in 15 mL of CH2Cl2 and treated with DCC (0.109 g,
0.54 mmol) for 4 h at room temperature. The solids formed were
filtered off and the liquid mother solution was evaporated under
reduced pressure. The residue was purified by column chroma-
tography with hexane/EtOAc (v/v¼4:1).
2.05 (s, 3H), 2.44 (m, 1H), 2.56 (m, 1H), 3.42 (dd, 1H, J¼2.6, 4.4 Hz),
3.86 (m, 1H), 4.04 (dd,1H, J¼1.6, 2.8 Hz), 4.14 (d, 1H, J¼11.2 Hz), 4.33
(d, 1H, J¼11.2 Hz), 4.43 (dd, 1H, J¼4.4, 8.4 Hz), 5.09 (br, 2H), 5.85 (m,
1H), 6.01 (d, 1H, J¼8.0 Hz), 7.35 (m, 10H). 13C NMR (100 MHz, CDCl3)
d
: 21.3, 38.0, 71.8, 75.3, 77.3, 82.1, 85.0, 85.6, 117.4, 127.5, 127.7, 127.8,
128.1, 128.2, 128.3, 134.2, 137.3, 137.5, 170.1. FABMS m/z (rel in-
tensity) 383 ([MþH]þ, 12); FAB-HRMS m/z 383.1854 [MþH]þ (calcd
for C23H27O5: 383.1858).
4.14. General procedure for the sequential dihydroxylation–
dehomologation–PCC oxidation procedure
4.19. (7S)-3,6-Anhydro-5-O-benzyl-2-deoxy-7-phenyl-D-ido-
heptono-1,4-lactone (18)
To a stirred solution of corresponding olefin (1.0 mmol) in 30 mL
of a mixture of acetone/water (10:1) were added 4-methyl-
morpholine N-oxide (NMO, 2.0 mmol) and OsO4 (0.08 mmol20).
The reaction mixture was stirred for 2 h at room temperature be-
fore adding NaIO4 (1.2 mmol) dissolved in 5 mL water. The re-
actions mixture was further stirred for 1 h at the same temperature.
The solids formed were filtered off and the liquid mother solution
was extracted with EtOAc (3ꢂ50 mL). The extract was washed with
brine and dried over Na2SO4. Evaporation of the solvent gave
a residue, which was submitted to PCC (2 mmol) oxidation in
CH2Cl2 for 4 h. The solids formed were filtered off and the liquid
Yield 82%, mp¼146–148 ꢁC; [
a
]
D
þ25.5 (c 0.5, CHCl3); [lit.18
mp¼146–147 ꢁC; [
a
]
D
þ39.9 (c 0.67, CHCl3)]. 1H NMR (400 MHz,
CDCl3)
d
: 2.70 (apparent d, 1H, J¼4.0 Hz), 2.80 (apparent d, 1H,
J¼0.7 Hz), 3.90 (d,1H, J¼4.0 Hz), 4.23 (dd,1H, J¼6.4, 3.6 Hz), 4.42 (d,
1H, J¼11.6 Hz), 4.53 (d, 1H, J¼11.6 Hz), 4.88 (d, 1H, J¼4.4 Hz), 5.02
(d, 1H, J¼6.8 Hz), 5.08 (q, 1H, J¼7.6 Hz), 7.33 (m, 10H). 13C NMR
(100 MHz, CDCl3) d: 35.9, 72.7, 72.8, 77.3, 81.9, 84.6, 85.1, 126.8,
127.7, 128.2, 128.3, 128.4, 128.6, 136.5, 139.6, 175.1. FABMS m/z (rel
intensity) 323 ([MꢀH2O]þ, 35); FAB-HRMS m/z 323.1286
[MþHꢀH2O]þ (calcd for C20H19O4: 323.1283ꢀH2O).

´
´
L. Hernandez-Garcıa et al. / Tetrahedron 65 (2009) 139–144
144
4.20. General procedure for debenzylation reaction
References and notes
1. (a) Postema, M. H. D. C-Glycoside Synthesis; CRS: Boca Raton, FL, 1995; (b) Levy,
D. E.; Tang, C. The Chemistry of C-Glycosides; Pergamon: Oxford, 1995; (c) Du, Y.;
Linhardt, R. J. Tetrahedron 1998, 54, 9913; (d) Harmange, J.-L.; Figadere´, B. Tet-
rahedron: Asymmetry 1993, 4, 1711.
2. (a) Denmark, S. E.; Willson, T. M. J. Am. Chem. Soc. 1989, 111, 3475; (b) Denmark,
S. E.; Willson, T. M. In Selectivities in Lewis Acid Promoted Reactions; Schinzer, D.,
Ed.; Kluwer Academic: Boston, MA, 1989; p 247.
Hydrogenolysis of the corresponding protected lactones
(0.5 mmol) was carried out in methanol with 10% of Pd(OH)2
(100 mg). It is important to mention that 100 psi is needed to ac-
complish the reactions with high yield.
3. (a) Sammakia, T. S.; Smith, R. S. J. Am. Chem. Soc. 1992, 114, 10998; (b) Sam-
makia, T. S.; Smith, R. S. J. Am. Chem. Soc. 1994, 116, 7915.
4.21. (7S)-3,6-Anhydro-2-deoxy-7-phenyl-D-altro-1,4-
4. (a) Araki, Y.; Kobayashi, N.; Ishido, Y. Carbohydr. Res. 1987, 171, 125; (b) Mu-
kaiyama, T.; Shimpuku, T.; Takashima, T.; Kobayashi, S. Chem. Lett. 1989, 145; (c)
heptanolactone (9)
´
´
´
Jaouen, V.; Jegou, A.; Lemee, L.; Veyrleres, A. Tetrahedron 1999, 55, 9245.
5. (a) Schmitt, A.; Reissig, H.-U. Synlett 1990, 40; (b) Schmitt, A.; Reissig, H.-U.
Chem. Ber. 1995, 128, 871; (c) Schmitt, A.; Reissig, H.-U. Eur. J. Org. Chem. 2000,
3893; (d) Schmitt, A.; Reissig, H.-U. Eur. J. Org. Chem. 2001, 1169.
6. (a) Larsen, C. H.; Ridgway, B. H.; Shaw, T. J.; Woerpel, K. A. J. Am. Chem. Soc. 1999,
121, 12208; (b) Smith, D. M.; Tran, M. B.; Woerpel, K. A. J. Am. Chem. Soc. 2003,
125, 14149; (c) Larsen, C. H.; Ridgway, B. H.; Shaw, J. T.; Smith, D. M.; Woerpel,
K. A. J. Am. Chem. Soc. 2005, 127, 10879; (d) Smith, D. M.; Woerpel, K. A. Org. Lett.
2004, 6, 2063.
Yield 90%, white solid, mp¼121–123 ꢁC. [
D þ9.2 (c 1.0, EtOH).
a
]
1H NMR (400 MHz, CDCl3,)
d
: 2.69 (dd, 1H, J¼1.6, 19.2 Hz), 2.79 (dd,
1H, J¼6.0, 18.8 Hz), 3.97 (dd, 1H, J¼3.2, 7.6 Hz), 4.37 (br, 1H), 4.80 (d,
1H, J¼2.8 Hz), 4.87 (ddd, 1H, J¼1.2, 4.8, 6.0 Hz), 4.95 (t, 1H,
J¼4.8 Hz), 7.35 (m, 5H). 13C NMR (100 MHz, CDCl3)
d: 37.0, 72.9, 73.1,
76.4, 82.8, 84.5, 126.3, 128.1, 128.4, 140.0, 174.5. FABMS m/z 251
([MþH]þ, 5), 232 ([MþHꢀH2O]þ, 14). Anal. Calcd for C13H14O5: C,
62.39; H, 5.64. Found: C, 62.45; H, 5.82.
7. Chamberland, S.; Ziller, J. W.; Woerpel, K. A. J. Am. Chem. Soc. 2005, 127,
5322.
8. Romero, M.; Herna´ndez, L.; Quintero, L.; Sartillo-Piscil, F. Carbohydr. Res. 2006,
´
341, 2883; See also previous study: Garcıa-Tellado, F.; De Armas, P.; Marrero-
Tellado, J. J. Angew. Chem., Int. Ed. 2000, 39, 2727.
4.22. (7R)-3,6-Anhydro-2-deoxy-7-phenyl-D-altro-1,4-
´
9. Sartillo-Melendez, C.; Cruz-Gregorio, S.; Quintero, L.; Sartillo-Piscil, F. Lett. Org.
heptanolactone (10)12
Chem. 2006, 3, 504.
10. Although diacetone-
D
-allofuranose is commercially available, it can be easily
-glucose: Cruz-Gregorio, S.;
Yield 90%. [
a
]
D þ3.8 (c 0.6, CHCl3) [lit.18
[
a
]
D ꢀ32.4 (c 1.0, CHCl3)].
prepared in one pot reaction from diacetone-
Herna´ndez, L.; Vargas, M.; Quintero, L.; Sartillo-Piscil, F. J. Mex. Chem. Soc. 2005,
49, 20.
D
1H NMR (400 MHz, CDCl3, CD3OD)
d
: 2.75 (dd, 1H, J¼1.2, 18.4 Hz),
2.76 (dd, 1H, J¼6.0, 18.8 Hz), 4.03 (dd, 1H, J¼4.4, 7.6 Hz), 4.21 (dd,
11. Sartillo-Piscil, F.; Cruz-Gregorio, S.; Sa´nchez, M.; Ho¨pfl, H.; Anaya de Parrodi, C.;
Quintero, L. Tetrahedron 2003, 59, 4077.
1H, J¼4.4, 7.2 Hz), 4.78 (m, 2H), 4.91 (t, 1H, J¼4.8 Hz), 7.33 (m, 5H).
12. NMR data is identical to the data obtained by Mereyala et al. However, optical
13C NMR (100 MHz, CDCl3, CD3OD)
d: 37.0, 73.0, 74.1, 76.1, 83.6, 84.2,
rotation was different: lit.18
[
a
]
D ꢀ32.4 (c 1.0, CHCl3); this work: [ D þ3.8 (c 0.6,
a
]
126.4, 127.7, 128.0, 139.4, 175.7. FABMS m/z 251 ([MþH]þ, 9), 232
([MþHꢀH2O]þ, 14). Anal. Calcd for C13H14O5: C, 62.39; H, 5.64.
Found: C, 62.26; H, 5.70.
CHCl3). See Mereyala, H. B.; Gadikota, R. R.; Krishnan, R. J. Chem. Soc., Perkin
Trans. 1 1997, 3567.
13. Crystallographic data were deposited in Cambridge Crystallographic Data Base
(CCDC 695099).
14. In some cases we obtained in poor yield the corresponding diketone, however,
reduction of both carbonyl groups afforded a number of byproducts.
15. Ewing, G. J.; Robins, M. J. Org. Lett. 1999, 1, 635.
16. Vieira, A. S.; Perreira, F. P.; Fiorante, P. F.; Guadagnin, R. C.; Stefani, H. A. Tet-
rahedron 2008, 64, 3306.
4.23. 7-epi-(D)-Goniofufurone (6)
Yield 88%, mp¼200–203 ꢁC. [
a
]
þ102 (c 0.5, EtOH) [lit.18
D
17. (a) Shing, T. K. M.; Tsui, H. C.; Zhou, Z. H. Tetrahedron 1992, 48, 8659; (b) Pra-
kash, K. R. C.; Rao, S. P. Tetrahedron 1993, 49, 1505; (c) Ye, J.; Bhatt, R. K.; Falck, J.
R. Tetrahedron Lett. 1993, 34, 8007; (d) Gracza, T.; Jaeger, V. Synthesis 1994, 1359;
(e) Yang, Z.-C.; Zhou, W.-S. Tetrahedron 1995, 51, 1429; (f) Mukai, C.; Hirai, S.;
Kim, I. J.; Masaru, K.; Hanaoka, M. Tetrahedron 1996, 52, 6547; (g) Yi, X.-H.;
Meng, Y.; Hua, X.-G.; Li, C.-J. J. Org. Chem. 1998, 63, 7472; (h) Bruns, R.; Wernicke,
A.; Koll, P. Tetrahedron 1999, 55, 9793; (i) Mereyala, H. B.; Gadikota, R. R. Indian J.
Chem., Sect. B 2000, 39B, 166; (j) Su, Y.-L.; Yang, C.-S.; Teng, S.-J.; Zhao, G.; Ding,
Y. Tetrahedron 2001, 57, 2147; (k) Ruiz, P.; Murga, J.; Carda, M.; Marco, J. A. J. Org.
Chem. 2005, 70, 713; (l) Fernandez de la Pradilla, R.; Fernandez, J.; Alma, V.;
Fernandez,J.;Gomez,A.Heterocycles2006,68,1579;(m)Prasad,K.R.;Dhaware,M.G.
Synthesis 2007, 3697; (n) Yadav, V. K.; Agrawal, D. Chem. Commun. 2007, 5232.
18. Popsavin, V.; Benedekovic, G.; Sreco, B.; Popsavin, M.; Francruz, J.; Kojic, V.;
Bogdanovic, G. Org. Lett. 2007, 9, 4235.
mp¼197–200 ꢁC; [
a
]
þ108 (c 0.75, EtOH)]. 1H NMR (400 MHz,
D
CDCl3)
d
: 2.72 (m, 2H), 4.20 (t, 1H, J¼3.6 Hz), 4.36 (d, 1H, J¼3.6 Hz),
4.87 (d, 1H, J¼4.0 Hz), 5.07 (d, 1H, J¼4.0 Hz), 5.11 (td, 1H, J¼1.2,
5.6 Hz). 13C NMR (100 MHz, CDCl3)
87.9, 126.5, 128.3, 128.6, 140.0, 175.0.
d: 29.6, 36.0, 72.6, 75.2, 83.1,
Acknowledgements
We gratefully acknowledge financial support from CONACyT
(grant number: 62203). We also thank Vladimir Carranza-Tellez for
technical assistance.
19. Gracza, T.; Szolcsa´nyi, P. Molecules 2000, 5, 1386.
20. We used a solution of OsO4 0.1 M in t-BuOH.