β-Fragmentation of primary alkoxyl radicals versus hydrogen abstraction: Synthesis of polyols and α,ω-differently substituted cyclic ethers from carbohydrates

Article abstract of DOI:10.1021/jo034442f

The β-fragmentation of primary alkoxyl radicals, described in many cases as low-yielding and plagued by side reactions, can proceed in satisfactory yields using carbohydrate substrates. The only reaction that can compete significantly with the β-scission

Full text of DOI:10.1021/jo034442f

â-F r a gm en ta tion of P r im a r y Alk oxyl Ra d ica ls ver su s Hyd r ogen
Abstr a ction : Syn th esis of P olyols a n d r,ω-Differ en tly Su bstitu ted
Cyclic Eth er s fr om Ca r boh yd r a tes
Alicia Boto, Da´cil Herna´ndez, Rosendo Herna´ndez,* and Ernesto Sua´rez*
Instituto de Productos Naturales y Agrobiologı´a del C.S.I.C., Carretera de La Esperanza 3,
38206 La Laguna, Tenerife, Spain
rhernandez@ipna.csic.es
Received April 7, 2003
The â-fragmentation of primary alkoxyl radicals, described in many cases as low-yielding and
plagued by side reactions, can proceed in satisfactory yields using carbohydrate substrates. The
only reaction that can compete significantly with the â-scission is the intramolecular hydrogen
abstraction. The ratio of â-fragmentation to hydrogen abstraction can be varied according to the
reaction conditions, the stereochemistry of the substituents (e.g., R- or â-anomeric substituents),
and the protecting groups chosen. The carbohydrate substrates are easily prepared, and the mild
reaction conditions are compatible with most functional groups. The â-scission reaction provides
an expedient way toward shorter and less common sugar series and also toward R,ω-differently
substituted cyclic ethers. These units are useful building blocks and are present in many natural
products with interesting biological activity.
SCHEME 1. â-F r a gm en ta tion of P r im a r y Alk oxyl
Ra d ica ls (R1 ) R2 ) H) ver su s Hyd r ogen
Abstr a ction
In tr od u ction
The â-fragmentation of alkoxyl radicals (ARF) (Scheme
1) is a useful synthetic methodology for the synthesis of
a wide range of compounds, including medium- and large-
sized rings, heterocycles, halogenated compounds, etc.1
For instance, the syntheses of natural products2,3 such
as deoxyvernolepin,2b,3f cyclophellitol,2i,o rapamycin,3k and
muscone3q used a â-scission as the key step. This frag-
mentation takes place easily when a tertiary alkoxyl
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radical is generated from the corresponding alcohol.
However, with secondary or primary alkoxyl radicals the
fragmentation usually competes with other reactions,
such as intramolecular hydrogen abstraction (IHA),4,5
addition to double bonds,6 or oxidation.1j In the case of
primary alkoxyl radicals (I, R1 ) R2 ) H) the scission is
usually a very minor process, unless the resultant radical
(II) is stabilized in some way, and hence has been seldom
used in synthesis.
To provide stabilization to the C-radical (II), some
functional groups R3 such as aromatic rings, carbonyl
groups, and heteroatoms could be used. When the C-
radical is stabilized by heteroatoms,7 it can evolve under
oxidative conditions to a carbenium ion (III),8 thus
10.1021/jo034442f CCC: $25.00 © 2003 American Chemical Society
Published on Web 05/28/2003
5310
J . Org. Chem. 2003, 68, 5310-5319

â-Fragmentation of Primary Alkoxyl Radicals
making the fragmentation process irreversible. We rea-
soned that by carrying out the scission of primary alkoxyl
radicals in carbohydrate chains (Figure 1, eq 1), the
resultant radical would be stabilized by the adjacent
oxygen functions and under oxidative conditions would
evolve to an oxycarbenium ion, which could be trapped
by nucleophiles. If this strategy worked, it would be a
direct way to reduce by one carbon the chain length of
polyols (eq 1) and to transform carbohydrates into
shorter, less common series.8,9 Other compounds that
would be easily achieved are R,ω-differently substituted
tetrahydrofuran or tetrahydropyran rings (Figure 1, eq
2). These heterocycles are present in a variety of natural
products10 such as marine polyethers,10a,k,l,q,r alkaloids,10i,j
F IGURE 1. Synthetic use of the â-scission of primary alkoxyl
radicals in polyols and carbohydrates.
terpenoids,10c-h acetogenins,10u and pheromones,10x many
of which have potent biological activities.
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In our research group we have developed the system
diacetoxyiodobenzene (DIB) and iodine, or iodosylbenzene
(PhIO) and iodine, to generate alkoxyl radicals from
alcohols.1d,8 The reaction conditions are mild, compatible
with many functional groups, and hence very suitable to
generate alkoxyl radicals from carbohydrate substrates.
If the â-fragmentation takes place, the initial C-radical
can be easily oxidized by excess reagent into an oxycar-
benium ion. The feasibility of this approach and the
synthesis of polyol derivatives and cyclic ethers with
different substituents at the R,ω-positions is reported
herein.
Resu lts a n d Discu ssion
Syn th esis of P r ecu r sor s for th e F r a gm en ta tion -
Oxid a tion Rea ction . To study the ARF reaction of
primary alkoxyl radicals, substrates 1-7 were synthe-
sized (Figure 2). In compound 1 the alkoxyl radical would
be formed in a chain with more rotational freedom than
in the rest of the substrates. Compounds 2 and 3 allow
us to compare the fragmentation of anomeric alkoxyl
radicals versus primary alkoxyl radicals. Substrates 4-7
are relatively rigid bicyclic systems, with different pro-
tecting groups in the anomeric position. Compounds 6
and 7 have a different C1 stereochemistry, to study the
competition between C1-H abstraction and â-fragmenta-
tion.
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J . Org. Chem, Vol. 68, No. 13, 2003 5311

Boto et al.
SCHEME 3. ARF ver su s IHA for Com p ou n d 1
F IGURE 2. Precursors of the fragmentation-oxidation reac-
tion.
SCHEME 2. Syn th esis of Su bstr a tes 2 a n d 3a
To obtain substrate 3, the benzyl-R-D-glucofuranoside
12 was treated with benzoyl chloride, affording compound
14, which underwent hydrogenolysis, giving the diol 3.
Compound 4 was formed from D-ribose according to
reported procedures.13 Compounds 5-7 were obtained
from 5-O-tert-(butyldimethylsilyl)-2,3-O-isopropylidene-
D-ribose following existing methodology.14,15
Stu d y of th e ARF -Oxid a tion Rea ction of P r i-
m a r y Alk oxyl Ra d ica ls ver su s IHA. To study the
possible competition between ARF and IHA, the polyol
1 was chosen as a substrate (Scheme 3), because the
corresponding alkoxyl radical 1a would be generated in
an acyclic chain with considerable rotational freedom.
When the product 1 was treated with DIB and iodine,
â-fragmentation took place, generating C-radical 1b. This
radical was oxidized to an oxycarbenium ion 1c, which
reacted with acetate ions coming from DIB, yielding
compounds 15 and 16 (37%, 3:1).16 However, the hydro-
gen abstraction was also an important pathway, generat-
ing C-radical 1d that was oxidized to intermediate 1e.
a
Conditions: (i) NaH, PhCH2Br, THF, 0 °C, 85%; (ii) TFA-
H2O 1:1, 98%; (iii) BnOH, camphorsulfonic acid, rt, yielded 11
(33%) and 12 (45%); (iv) NaH, MeI, THF, 0 °C, 94%; (v) H2, 10%
Pd(OH)2/C, EtOAc, rt, yielded 2, 88% or 3, 94%; (vi) BzCl, Py, 93%.
Substrates 1-7 were prepared from commercial sug-
ars. Compound 1 was synthesized from ribonolactone by
treatment with 2,2-dimethoxypropane and p-TsOH.11a
The resultant methyl 2,3:4,5-diisopropylidene-D-ribonic
ester was reduced with lithium aluminum hydride11b to
the polyol 1, in excellent yield.
Compounds 2 and 3 were obtained from D-glucofura-
nose derivative 812 (Scheme 2). After protection of the
primary hydroxy group as its benzyl ether 9, the isoprop-
ylidene acetal was cleaved, and the resultant diol 10 was
selectively benzylated at the anomeric position, yielding
the benzyl-â-D-glucofuranoside 11 and its R anomer 12
in good yield. Compound 11 was methylated to compound
13, and then the benzyl groups were removed by hydro-
genolysis to afford product 2.
(13) Duvold, T.; Francis, G. W.; Papaioannou, D. Tetrahedron Lett.
1995, 36, 3153-3156.
(11) (a) Barton, D. H. R.; Liu, W. Tetrahedron 1997, 53, 12067-
12088. (b) Aslani-Shotorbani, G.; Buchanan, J . G.; Edgar, A. R.;
Shahidi, P. K. Carbohydr. Res. 1985, 136, 37-52.
(12) Marin˜o-Albernas, J . R.; Verez-Bencomo, V.; Gonzalez, L.; Perez,
C. S. Carbohydr. Res. 1987, 165, 197-206.
(14) (a) Kaskar, B.; Heise, G. L.; Michalak, R. S.; Vishnuvajjala, B.
R. Synthesis 1990, 1031-1032. (b) Francisco, C. G.; Gonza´lez, C. C.;
Sua´rez, E. J . Org. Chem. 1998, 63, 2099-2109.
(15) Francisco, C. G.; Freire, R.; Gonza´lez, C. G.; Leo´n E. I.; Riesco-
Fagundo, C.; Sua´rez, E. J . Org. Chem. 2001, 66, 1861-1866.
5312 J . Org. Chem., Vol. 68, No. 13, 2003

â-Fragmentation of Primary Alkoxyl Radicals
SCHEME 4. F r a gm en ta tion of An om er ic Alk oxyl
Ra d ica ls ver su s P r im a r y Alk oxyl Ra d ica lsa
As expected, when the photolysis of substrate 2 was
carried out, the fragmentation of the anomeric alkoxyl
radical 2a was the major pathway. The C1-C2 scission
generated C-radical 2b, which was oxidized in situ to an
oxycarbenium ion. Intramolecular trapping of the latter
by the primary hydroxy group18 afforded pyranoside 19.
The reaction proceeded in 45% yield when the photolysis
was carried out with iodosylbenzene and iodine.
The photolysis of substrate 3 gave an unexpected
result. In this case, no products from the anomeric
alkoxyl radical fragmentation were isolated. The main
product was the bicyclic acetal 20,20 resulting from
fragmentation of the primary alkoxyl radical 3a . To our
knowledge, this is the first reported case in which the
â-fragmentation of primary alkoxyl radicals predomi-
nates over the scission of anomeric radicals and high-
lights the importance of the substituents in determining
the preferred reaction pathway. In effect, the â-fragmen-
tation can be a reversible process, and hence the stabilitiy
of the resulting radicals influences the reaction outcome.
The oxidation step is also determinant because it renders
the entire process irreversible. When the 2-alkoxy group
was replaced by an acyloxy group, the C-radical resulting
from the C1-C2 fragmentation was less stabilized; the
oxidation of this radical to an oxycarbenium ion was also
hindered, because the acyloxy group is less electron-
donating than the alkoxy group. This gave time for the
fragmentation of the primary alkoxyl radical 3a to take
place. The resultant C-radical 3b was adjacent to an
alkoxyl group, which was easily oxidized to an oxycar-
benium ion 3c, shifting the whole process to the forma-
tion of the unusual diacetal 20.
The competition between ARF and IHA was then
studied with substrates 4 and 5, which are relatively rigid
bicyclic systems (Scheme 5). In these substrates, the
anomeric R-hydrogen (C1-H) would be out of reach from
the primary alkoxyl radical; however, the distance be-
tween the alkoxyl radical and the C2-H (about 2.7-2.9
Å)21 is appropriate for abstraction.
When the benzyl â-D-ribofuranoside derivative 4 was
reacted, an unexpected result was obtained. The major
product was the seven-membered benzylic acetal 2122
(Table 1, entry 1). Although the IHA required an eight-
membered transition state, the intermediate benzylic
radical was stabilized by the adjacent oxygen and the
phenyl group. However, no C2-H abstraction was ob-
served, probably because the resulting planar C-radical
would generate a strained bicyclic system.23
a
Conditions: (i) PhIO (2 equiv), I2 (2 equiv), CH2Cl2, rt, yielded
19 (45%) or 20 (33%); (ii) DIB (2 equiv), I2 (2 equiv), CH2Cl2, 23%.
Subsequent intramolecular nucleophilic addition afforded
the cyclic acetals 17 and 1817 in 40% yield (3:1). These
cyclic acetals are interesting examples of the transforma-
tion of common aldoses from the D-series to unusual
ketoses from the L-series.
In the substrates 2 and 3 (Scheme 4) the primary
alkoxyl radical would be generated in a chain with less
rotational freedom than in the previous case. In addition,
in these substrates anomeric alkoxyl radicals could also
be generated. The fragmentation of anomeric alkoxyl
radicals is reported to be faster than the fragmentation
of primary alkoxyl radicals,18 but the influence of the
substituents on their relative rates has still been scarcely
studied.19
The â-fragmentation also took place as the minor
pathway, yielding the acetate 22 as a single isomer.24
Compound 22 was formed when the intermediate oxy-
carbenium ion was trapped by acetate ions released from
DIB.
(16) The stereochemistry of acetates 15 and 16 was determined in
base to their coupling constants J 2,3. Thus, for acetate 15 (1S) J 2,3
)
3.5 Hz (cis), while for compound 16 (1R) J 2,3 ) 1.8 Hz (trans). For
similar examples, see ref 8a. Besides, a NOESY experiment for
compound 16 showed a net spatial interaction between C1-H (δH 6.26)
and C3-H (δH 4.03).
(17) The enantiomers of products 17 and 18 have been previously
described: Collins, P. M.; Gupta, P.; Travis, A. S. J . Chem. Soc., Perkin
Trans. 1 1980, 277-281.
(18) de Armas, P.; Francisco, C. G.; Sua´rez, E. J . Am. Chem. Soc.
1993, 115, 8865-8866.
(20) In the minimum energy conformation for compound 5R, (cal-
culated with ChemBats3D ultra 6.0, CambridgeSoft.com) the dihedral
angle H5-C5-C4-H4 was 86°, which would give a coupling constant
of J ) 0 Hz. This result agrees with the observed signal for C5-H (δ )
5.19), which appears as a singlet. In the case of the 5S isomer, the
dihedral angle H5-C5-C4-H4 was calculated to be -35°; the resulting
J (about 5 Hz) would not match the experimental one.
(21) Calculations using a MM2 force field model implanted in
ChemBats3D ultra 6.0, CambridgeSoft.com.
(19) (a) An example of the influence of the substituents on the
relative rate of hydrogen abstraction versus â-fragmentation has been
reported: Allen, P. R.; Brimble, M. A.; Fare`s, F. A. J . Chem. Soc.,
Perkin Trans. 1 1998, 2403-2411. (b) See also: Francisco, C. G.;
Gonza´lez, C.; Sua´rez, E. J . Org. Chem. 1998, 63, 8092-8093.
(22) The stereochemistry of compound 21 was determined in base
to the 1H and NOESY experiments. Thus, the benzylic proton had a
strong spatial interaction with one of the C5-H (C5-Ha). C5-Ha was
coupled with C4-H (J ) 2.2 Hz); on the other hand, C5-Hb showed no
coupling with C4-H.
J . Org. Chem, Vol. 68, No. 13, 2003 5313

Boto et al.
TABLE 1. F r a gm en ta tion ver su s Hyd r ogen Abstr a ction for Su bstr a tes 4-7a
â-scission
H-abstraction
yield (%)
overall
yield (%)
entry
substrate
reagents
solvent
products (%)b
21 (42), 22 (28)
23 (33), 24 (15)
25 (10), 26 (32)
25 (2), 26 (6), 27 (10), 28 (50)
27 (15), 28 (66)
29 (26), 30 (35)
29 (53), 30 (7), 31 (17)
29 (54), 31 (30)
yield (%)
1
2
3
4
5
6
7
8
4
5
6
6
6
7
7
7
DIB, I2
DIB, I2
DIB, I2
DIB, I2
PhIO, I2
DIB, I2
DIB, I2
PhIO, I2
CH2Cl2
CH2Cl2
CH2Cl2
MeCN
MeCN
CH2Cl2
MeCN
MeCN
28
48
42
68
81
35
24
30
42
70
48
42
68
81
61
77
84
26
53
54
a
All reactions were performed with DIB or PhIO (2 equiv) and iodine (1 equiv) in dry solvents (10 mL per mmol of substrate) under
b
nitrogen at room temperature, using irradiation with two 80-W tungsten-filament lamps for 1 h. Yields are given for products purified
by chromatography on silica gel.
SCHEME 5. In flu en ce of Su bstitu en ts on ARF :IHA
Ra tio
SCHEME 6. In flu en ce of Ster eoch em istr y of
Su bstitu en ts on ARF :IHA Ra tio
It was clear that if the â-fragmentation was to pre-
dominate, the anomeric protecting group should be
changed. With this objective in mind, the 1â-benzoyloxy
derivative 5 was used as a substrate (Scheme 5). The
reaction was carried out with DIB and iodine in dichlo-
romethane (Table 1, entry 2), yielding the fragmentation
products 23 and 24 (48% total yield; 23:24, 2:1). To our
satisfaction, no products from IHA were formed.
The next step was to determine the importance of C1-H
abstraction in the reaction outcome. The 1-pivaloyloxy
epimers 6 and 7 were synthesized and reacted as shown
in Scheme 6. The alkoxyl radical 6a , derived from the
1â-pivaloyloxyribose 6, reacted exclusively by â-fragmen-
tation. On treatment with DIB-iodine in dichloromethane
(Table 1, entry 3) the diacyloxy derivatives 25 and 26
were obtained as a separable mixture (42%; 25: 26, 1:3).
When the reaction was run with DIB-iodine in acetoni-
trile (entry 4), two new fragmentation products, the
4-amido-1-pivaloyloxy derivatives 27 and 28, were the
major ones (60%; 27:28 1:5). Rewardingly, when the
fragmentation was carried out with PhIO-iodine in
acetonitrile (entry 5), the yield of the amidoderivatives
was increased (81%; 27:28, 1:4). Compounds 27 and 28
were generated by a Ritter reaction between the oxycar-
benium ion 6b and acetonitrile, followed by addition of
water to the intermediate during the workup.25
(23) No products arising from the geometrically possible abstraction
of the C2-H have been isolated, since this abstraction was disfavored
by steric and stereoelectronic factors. See also: (a) Francisco, C. G.;
Herrera, A. J .; Sua´rez, E. J . Org. Chem. 2002, 67, 7439-7445. (b)
Francisco, C. G.; Freire, R.; Herrera, A. J .; Pe´rez-Mart´ın, I.; Sua´rez,
E. Org. Lett. 2002, 4, 1959-1961. (c) Francisco, C. G.; Herrera, A. J .;
Sua´rez, E. Tetrahedron Lett. 2000, 41, 7869-7873. (d) For studies on
stereoelectronic effects in IHA reactions, see: Malatesta, V.; Ingold,
K. U. J . Am. Chem. Soc. 1981, 103, 609-614. (e) Beckwith, A. L. J .;
Easton, C. J . J . Am. Chem. Soc. 1981, 103, 615-619.
(24) (a) For a preliminary communication of this work, see: Boto,
A.; Herna´ndez, R.; Sua´rez, E. Tetrahedron Lett. 2002, 43, 1821-1824.
(b) For a related work from our group where acyloxyaldoses were
formed from uronic acids, see: Francisco, C. G.; Gonza´lez, C. C.;
Sua´rez, E. Tetrahedron Lett. 1997, 38, 4141-4144.
(25) (a) Bishop, R. In Comprehensive Organic Synthesis; Trost, B.
M., Fleming, I., Eds.; Pergamon Press: Oxford, 1991; Vol. 6, pp 261-
300. (b) Kita, Y.; Shibata, N.; Kawano, N.; Yoshida, N.; Matsumoto,
K.; Takebe, Y. J . Chem. Soc., Perkin Trans. 1 1996, 2321-2329.
5314 J . Org. Chem., Vol. 68, No. 13, 2003

â-Fragmentation of Primary Alkoxyl Radicals
TABLE 2. Syn th esis of 1-Ben zoyloxy-4-ch lor ofu r a n ose
32a
SCHEME 7. Syn th esis of r,ω-Differ en tly
Su bstitu ted Cyclic Eth er sa
scission
yield (%)
entry
reagents (equiv)
products (%)b
1
2
DIB (2.0), I2 (1.0)
DIB (2.0), I2 (1.0),
n-Bu4NCl (5.0)
23 (15), 24 (33)
23 (16), 24 (20), 32 (7)
48
43
3
4
5
6
PhICl2 (2.0), I2 (1.0)
DIB (2.0), ICl (1.0)
PhIO (2.0), ICl (1.0)
complex mixture
23 (10), 24 (11), 32 (53)
74
complex mixturec
PhICl2 (2.0), ICl (1.0) complex mixture
a
All reactions were run in dichloromethane, under irradiation
of two 80-W tungsten-filament lamps for 1 h, at room temperature.
b Yields are given for products purified by chromatography on silica
gel. c The reaction with PhIO was very slow because of the low
solubility of the reagent in CH2Cl2, and gave a complex mixture.
be an expedient way to obtain this kind of compound, as
shown in Scheme 7. The easily obtained 1â-benzoyloxy
derivative 5 was used to test this strategy and was
treated under the conditions listed in Table 2. In all cases,
the reaction was carried out in dichloromethane to avoid
the Ritter reaction. The best conditions were obtained
when substrate 5 was treated with DIB and iodine
monochloride (ICl) at room temperature (entry 4). A
small amount of the two isomeric acetates 23 and 24 was
isolated (21%), but the major product was the desired
chloroderivative 32 (53%). The regioselective introduction
of a lateral chain at the C4 position by a radical reaction
was tried next. To our pleasure, when compound 32 was
treated with allyltributyltin and catalytic AIBN in ben-
zene, the allyl derivative 33 was obtained in 82% yield,
supporting the feasibility of this synthetic strategy.
In summary, the â-fragmentation of primary alkoxyl
radicals in carbohydrates proceeds in satisfactory yields
when the hydrogen abstraction is disfavored. The ratio
of â-fragmentation to hydrogen abstraction can be varied
according to the reaction conditions, the stereochemistry
of the substituents (e.g., R- or â-anomeric substituents),
and the protecting groups chosen. The â-scission reaction
provides an expedient way toward shorter and less
common sugar series and also toward R,ω-differently
substituted cyclic ethers. These units are useful building
blocks and are present in many natural products with
interesting biological activity.
a
Conditions: (i) DIB (2.0 equiv), ICl (1.0 equiv), CH2Cl2, hν,
rt, 23 (10%), 24 (11%), 32 (53%); (ii) Bu3SnCH2CHdCH2, AIBN,
PhH, reflux, 82%.
In the case of the alkoxyl radical 7a , derived from the
1R-pivaloyloxy derivative 7, the distance C5-O‚‚‚H-C1
(about 2.6-2.8 Å) was appropriate for abstraction.21 If
this abstraction took place, the resulting C-radical would
be stabilized by two oxygen functions and its oxidation
to an oxycarbenium ion 7c would probably be very fast.
According to these considerations, the photolysis of
substrate 7 (entries 6-8) gave lactone 2926 as the major
product. The best yields of 29 (53-54%) were obtained
when the photolysis was run in acetonitrile (entries 7 and
8). Two minor products, resulting from â-fragmentation,
were the diacyloxy derivative 30 and the 4-amido-1-
pivaloyloxyfuranose 31.
These results show that the fragmentation of primary
alkoxyl radicals in carbohydrates proceeds in good yields
when the hydrogen abstraction reaction is hindered. This
encouraged us to study the synthesis of cyclic ethers (V)
with different substituents at the R,ω-positions (Scheme
7). As commented before, this unit is present in many
products10 with biological activity; accordingly, different
strategies have been developed to synthesize these
systems.27 A direct way to achieve this objective could
start from the cyclic aldoses (VI). For instance, using
Y ) halogen and Z ) alkoxy or acyloxy group, it would
be possible to introduce a W substituent by a radical
reaction28 and an X substituent by an ionic one.29
Syntheses of the asymmetrical R-acyloxy (or alkoxy)-
ω-haloaldoses (VI) are scarce.30 Our methodology could
Exp er im en ta l Section
Gen er a l Meth od s. Melting points were determined with
a hot-stage apparatus and are uncorrected. Optical rotations
were measured at the sodium line at ambient temperature in
CHCl3 solutions. IR spectra were recorded in CHCl3 solutions.
NMR spectra were determined at 500 MHz for 1H and 125.7
MHz for 13C in CDCl3 unless otherwise stated in the presence
of TMS as internal standard. Mass spectra were determined
at 70 eV unless otherwise specified. Merck silica gel 60 PF254
and 60 (0.063-0.2 mm) were used for preparative thin-layer
chromatography and column chromatography, respectively.
Commercial reagents and solvents were of analytical grade
or were purified by standard procedures prior to use.31 All
reactions involving air- or moisture-sensitive materials were
carried out under a nitrogen atmosphere. The spray reagents
for TLC analysis were 0.5% vanillin in H2SO4-EtOH (4:1) or
0.25% ninhydrin in EtOH, and the TLC was heated until
development of color.
(26) Csuk, R.; Ku¨hn, M.; Scho¨hl, D. Tetrahedron 1997, 53, 1311-
1322.
(27) (a) Krause, N.; Hoffmann-Ro¨der, A.; Canisius, J . Synthesis 2002,
1759-1774. (b) Nicolaou, K. C.; Mitchell, H. J . Angew. Chem., Int. Ed.
2001, 40, 1576-1624. (c) Lee, E. In Radicals in Organic Synthesis;
Renaud, P., Sibi, M. P., Eds.; Wiley-VCH: Weinheim, 2001; Vol. 2, pp
303-333. (d) Brimble, M. A.; Fare`s, F. A. Tetrahedron 1999, 55, 7661-
7706. (e) Hoberg, J . O. Tetrahedron 1998, 54, 12631-12670. (f) Hoppe,
R.; Scharf, H. D. Synthesis 1995, 1447-1464. (g) Harmange, J . C.;
Figade`re, B. Tetrahedron: Asymmetry 1993, 4, 1711-1754.
(28) Keck, G. E.; Yates, J . B. J . Am. Chem. Soc. 1982, 104, 5831-
5833.
(29) (a) For a review, see: Schmidt, R. R. In Comprehensive Organic
Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon Press: Oxford,
1991; Vol. 6, pp 33-64. (b) For a recent work, see: Pilli, R. A.; Riatto,
V. B. Tetrahedron: Asymmetry 2000, 11, 3675-3686 and references
therein.
(30) (a) Giese, B.; Linker, T. Synthesis 1992, 46-48. (b) Ferrier, R.
J .; Tyler, P. C. J . Chem. Soc., Perkin Trans. 1 1980, 2767-2773.
(31) Perrin, D. D.; Armarego, W. L. F. Purification of Laboratory
Chemicals, 3rd ed.; Pergamon Press: New York, 1988.
J . Org. Chem, Vol. 68, No. 13, 2003 5315

Boto et al.
2,3:4,5-Di-O-isop r op ylid en er ibitol (1). Compound 1 was
prepared by LiAlH4 reduction11b of the methyl 2,3:4,5-di-O-
isopropylidene-D-ribonate obtained by a one-pot procedure from
D-ribo-1,4-lactone11a as a syrup; [R]D +26 (c ) 0.2) {lit. [R]D
+24, (c ) 1.8)}.11b Compound 1 was poorly described in the
2.01 mmol) in benzyl alcohol (3.8 mL) was added camphor-
sulfonic acid (60 mg, 0.26 mmol), and the reaction mixture was
stirred for 6 h at room temperature. The reaction was
concentrated under high vacuum, and the residue was purified
by column chromatography on silica gel (hexanes-EtOAc, 7:3)
to yield compounds 11 (260 mg, 33%) and 12 (352 mg, 45%).
1
literature:11b IR 3505 cm-1; H NMR δ 1.34 (3H, s), 1.36 (3H,
s), 1.40 (3H, s), 1.41 (3H, s), 3.80 (1H, dd, J ) 11.9, 5.4 Hz),
3.86 (1H, dd, J ) 11.9, 5.4 Hz), 3.94 (1H, dd, J ) 7.3, 3.1 Hz),
4.05 (1H, dd, J ) 9.4, 5.8 Hz), 4.13-4.18 (2H, m), 4.35 (1H,
ddd, J ) 7.3, 5.7, 5.7 Hz); 13C NMR δ 25.2 (CH3), 25.4 (CH3),
26.7 (CH3), 27.8 (CH3), 60.6 (CH2), 68.1 (CH2), 73.3 (CH), 77.4
(CH), 78.1 (CH), 108.8 (C), 110.1 (C); MS m/z (rel intensity)
217 (M+ - Me, 26), 143 (27), 131 (19), 101 (63), 85 (13), 72
(12), 59 (100); HRMS calcd for C10H17O5 217.1076, found
217.1041. Anal. Calcd for C11H20O5: C, 56.88; H, 8.68. Found:
C, 56.97; H, 8.50.
-78 (c ) 0.2); IR 3607, 3089, 3066
Compound 11: syrup; [R]D
cm-1; H NMR δ 3.46 (3H, s), 3.47 (3H, s), 3.62 (1H, dd, J )
10.7, 4.9 Hz), 3.73 (1H, ddd, J ) 9.0, 4.9, 2.1 Hz), 3.75 (1H,
dd, J ) 5.2, 1.6 Hz), 3.85 (1H, dd, J ) 10.7, 2.1 Hz), 4.24 (1H,
d, J ) 1.6 Hz), 4.33 (1H, dd, J ) 9.0, 5.1 Hz), 4.68 (1H, d, J )
12.3 Hz), 4.61 (2H, s), 4.71 (1H, d, J ) 12.3 Hz), 4.93 (1H, s),
7.27-7.39 (10H, m); 13C NMR (50.3 MHz) δ 57.9 (CH3), 58.4
(CH3), 69.6 (CH2), 69.7 (CH2), 73.3 (CH2), 78.0 (CH), 78.5 (CH),
79.8 (CH), 85.3 (CH), 107.4 (CH), 127.4 (CH), 127.6 (2 × CH),
127.7 (CH), 128.0 (2 × CH), 128.2 (2 × CH), 128.3 (2 × CH),
137.6 (C), 138.5 (C); MS m/z (rel intensity) 282 (M+ + H -
C7H7O, 2), 280 (M+ - C7H7OH, 2), 91 (100); HRMS calcd for
1
6-O-Ben zyl-1,2-isop r op ylid en e-3,5-d i-O-m eth yl-r-D-glu -
cofu r a n ose (9). To a solution of 1,2-isopropylidene-3,5-di-O-
methyl-R-D-glucofuranose (8)12 (630 mg, 2.42 mmol) in THF
(20 mL) was added 60% NaH (150 mg, 3.75 mmol) portionwise,
at 0 °C and under N2. When hydrogen evolution ceased, benzyl
bromide (0.4 mL, 3.36 mmol) was added at 0 °C. The temper-
ature was allowed to reach room temperature, and the reaction
mixture was stirred for 5 h. Then MeOH (1 mL) was added,
and the resulting mixture was poured into water and extracted
with CH2Cl2. The combined extracts were dried (Na2SO4) and
concentrated at reduced pressure. The residue was then
purified by column chromatography on silica gel (hexanes-
EtOAc, 4:1) to yield product 9 (695 mg, 85%) as a crystalline
solid: mp 78-80 °C (from n-hexane); [R]D -40 (c ) 0.4); {lit.
mp 80.8-81.3 °C (from ligroin), [R]D -41.65 (c ) 10)}.12
Compound 9 was poorly described in the literature:12 IR 3080,
C
15H22O5 282.1467, found 282.1463. Anal. Calcd for C22H28O6:
C, 68.02; H, 7.26. Found: C, 68.00; H, 7.36. Compound 12:
syrup; [R]D +50 (c ) 0.3); IR 3544, 3089, 3066 cm-1; 1H NMR
δ 3.46 (3H, s), 3.49 (3H, s), 3.61 (1H, dd, J ) 10.5, 5.3 Hz),
3.66 (1H, ddd, J ) 7.5, 5.3, 2.1 Hz), 3.79 (1H, dd, J ) 4.4, 2.0
Hz), 3.82 (1H, dd, J ) 10.6, 2.1 Hz), 4.18 (1H, dd, J ) 4.8, 2.0
Hz), 4.28 (1H, dd, J ) 8.3, 4.4 Hz), 4.58 (1H, d, J ) 12.3 Hz),
4.60 (1H, d, J ) 12.1 Hz), 4.62 (1H, d, J ) 12.3 Hz), 4.82 (1H,
d, J ) 11.7 Hz), 5.19 (1H, d, J ) 4.6 Hz), 7.27-7.39 (10H, m);
13C NMR (50.3 MHz) δ 57.6 (CH3), 58.3 (CH3), 70.1 (2 × CH2),
73.4 (CH2), 75.9 (CH), 77.4 (CH), 77.6 (CH), 85.9 (CH), 100.1
(CH), 127.4 (CH), 127.5 (2 × CH), 128.0 (CH), 128.1 (2 × CH),
128.3 (2 × CH), 128.5 (2 × CH), 132.0 (C), 138.6 (C); MS m/z
(rel intensity) 388 (M+, <1), 91 (100); HRMS calcd for C22H28O6
388.1886, found 388.1884. Anal. Calcd for C22H28O6: C, 68.02;
H, 7.26. Found: C, 68.03; H, 7.23.
1
3065 cm-1; H NMR δ 1.33 (3H, s), 1.49 (3H, s), 3.44 (3H, s),
3.48 (3H, s), 3.60 (1H, dd, J ) 10.6, 5.3 Hz), 3.67 (1H, ddd, J
) 9.3, 5.4, 2.0 Hz), 3.80 (1H, d, J ) 3.6 Hz), 3.87 (1H, dd, J )
10.6, 2.0 Hz), 4.20 (1H, dd, J ) 9.3, 3.1 Hz), 4.56 (1H, d, J )
3.8 Hz), 4.60 (2H, s), 5.87 (1H, d, J ) 3.8 Hz), 7.24-7.37 (5H,
m); 13C NMR δ 26.3 (CH3), 26.7 (CH3), 57.6 (CH3), 58.2 (CH3),
70.1 (CH2), 73.3 (CH2), 76.8 (CH), 78.6 (CH), 81.4 (CH), 83.6
(CH), 105.0 (CH), 111.6 (C), 127.2 (CH), 127.4 (2 × CH), 128.2
(2 × CH), 138.5 (C); MS m/z (rel intensity) 338 (M+, 21), 323
(M+ - Me, 4), 101 (62), 91 (100); HRMS calcd for C18H26O6
338.1729, found 338.1725. Anal. Calcd for C18H26O6: C, 63.89;
H, 7.74. Found: C, 63.74; H, 7.62.
Ben zyl 6-O-Ben zyl-2,3,5-tr i-O-m eth yl-â-D-glu cofu r a n o-
sid e (13). A solution of alcohol 11 (152 mg, 0.392 mmol) in
THF (5 mL) was treated with 60% NaH (26 mg, 0.65 mmol),
under N2 at 0 °C. When the hydrogen evolution ceased, methyl
iodide (0.05 mL, 0.8 mmol) was added at 0 °C, and the reaction
was stirred at room temperature for 5 h. Then MeOH (0.1 mL)
was added, and the reaction mixture was poured into water
and extracted with CH2Cl2. The combined extracts were dried
(Na2SO4) and concentrated at reduced pressure. The residue
was purified by column chromatography on silica gel (hex-
anes-EtOAc, 4:1) to yield the tri-O-methyl derivative 13 (148
6-O-Ben zyl-3,5-d i-O-m eth yl-D-glu cofu r a n ose (10). Com-
pound 9 (695 mg, 2.06 mmol) was dissolved in 50% aqueous
trifluoroacetic acid (10 mL) and stirred at room temperature
for 8 h, and then the reaction mixture was poured into water
and extracted with EtOAc. Column chromatography on silica
gel (hexanes-EtOAc, 1:4) gave 10 (601 mg, 98%) as an
inseparable anomeric mixture (R:â, 1.6:1): syrup; [R]D -7 (c
mg, 94%) as a syrup: [R]D -80 (c ) 0.2); IR 3089, 3066, cm-1
;
1H NMR δ 3.37 (3H, s), 3.46 (3H, s), 3.48 (3H, s), 3.61 (1H, dd,
J ) 10.6, 5.0 Hz), 3.74 (1H, ddd, J ) 9.1, 5.0, 2.1 Hz), 3.78
(1H, s), 3.79 (1H, d, J ) 4.6 Hz), 3.85 (1H, dd, J ) 10.6, 2.1
Hz), 4.21 (1H, dd, J ) 9.1, 4.5 Hz), 4.49 (1H, d, J ) 12.3 Hz),
4.61 (2H, s), 4.71 (1H, d, J ) 12.3 Hz), 4.99 (1H, s), 7.27-7.39
(10H, m); 13C NMR δ 57.5 (CH3), 58.0 (CH3), 58.1 (CH3), 69.8
(CH2), 69.9 (CH2), 73.3 (CH2), 78.0 (CH), 79.7 (CH), 82.8 (CH),
87.7 (CH), 105.8 (CH), 127.4 (CH), 127.5 (2 × CH), 127.6 (CH),
127.9 (2 × CH), 128.2 (2 × CH), 128.3 (2 × CH), 137.6 (C),
138.6 (C); MS m/z (rel intensity) 296 (M+ - C7H7 - CH3, 1),
91 (100); HRMS calcd for C15H20O6 296.1260, found 296.1294.
Anal. Calcd for C23H30O6: C, 68.63; H, 7.51. Found: C, 68.74;
H, 7.57.
1
) 0.3); IR 3603, 3416, 3089 cm-1; H NMR δ anomer R 3.42
(3H, s), 3.46 (3H, s), 3.60 (1H, dd, J ) 12.5, 3.8 Hz), 3.68 (1H,
m), 3.77 (1H, d, J ) 4.1 Hz), 3.82 (1H, dd, J ) 12.5, 3.7 Hz),
4.07 (1H, d, J ) 4.0 Hz), 4.26 (1H, dd, J ) 8.5, 4.1 Hz), 4.59
(2H, s), 5.40 (1H, d, J ) 4.0 Hz), 7.25-7.35 (5H, m); δ anomer
â 3.45 (3H, s), 3.46 (3H, s), 3.60 (1H, dd, J ) 12.5, 3.8 Hz),
3.68 (1H, m), 3.77 (1H, d, J ) 4.0 Hz), 3.91 (1H, dd, J ) 12.5,
4.0 Hz), 4.18 (1H, s), 4.29 (1H, dd, J ) 9.5, 4.0 Hz), 4.58 (1H,
d, J ) 11.3 Hz), 4.60 (1H, d, J ) 11.1 Hz), 5.40 (1H, s), 7.25-
7.35 (5H, m); 13C NMR (50.3 MHz) δ anomer R 58.1 (CH3),
58.5 (CH3), 70.2 (CH2), 73.7 (CH2), 74.1 (CH), 77.7 (CH), 77.8
(CH), 85.7 (CH), 97.1 (CH), 127.2 (CH), 127.3 (2 × CH), 128.0
(2 × CH), 138.3 (C); δ anomer â 58.2 (CH3), 58.7 (CH3), 66.8
(CH2), 73.8 (CH2), 74.1 (CH), 77.0 (CH), 78.0 (CH), 84.7 (CH),
103.7 (CH), 127.2 (CH), 127.3 (2 × CH), 128.0 (2 × CH), 138.0
(C); MS m/z (rel intensity) 280 (M+ - H2O, 1), 91 (100); HRMS
calcd for C15H20O5 280.1311, found 280.1314. Anal. Calcd for
2,3,5-Tr i-O-m eth yl-D-glu cofu r a n ose (2). To a solution of
compound 13 (177 mg, 0.44 mmol) in EtOAc (15 mL) was
added 10% Pd(OH)2/C (75 mg), and the mixture was hydro-
genated at room temperature for 16 h. The suspension was
filtered through silica gel-Celite, 1:1, and the organic layers
were concentrated. Column chromatography on silica gel
(hexanes-EtOAc, 1:1) gave 2 (86 mg, 88%) as an inseparable
anomeric mixture (â: R, 1.2:1): syrup; [R]D -39 (c ) 0.2); IR
3538 cm-1; 1H NMR δ anomer â 3.44 (3H, s), 3.45 (3H, s), 3.49
(3H, s), 3.60 (1H, m), 3.78 (1H, dd, J ) 11.8, 3.4 Hz), 3.78 (1H,
s), 3.83 (1H, d, J ) 3.9 Hz), 3.91 (1H, dd, J ) 11.8, 4.4 Hz),
4.15 (1H, dd, J ) 9.1, 3.9 Hz), 4.77 (1H, s, OH), 5.21 (1H, s);
δ anomer R 3.44 (3H, s), 3.46 (3H, s), 3.50 (3H, s), 3.53 (1H,
C
15H22O6: C, 60.39; H, 7.43. Found: C, 60.72; H, 7.42.
Ben zyl 6-O-Ben zyl-3,5-d i-O-m et h yl-â-D-glu cofu r a n o-
sid e (11) a n d Ben zyl 6-O-Ben zyl-3,5-d i-O-m eth yl-r-D-
glu cofu r a n osid e (12). To a solution of product 10 (600 mg,
5316 J . Org. Chem., Vol. 68, No. 13, 2003

â-Fragmentation of Primary Alkoxyl Radicals
m), 3.70 (1H, dd, J ) 4.0, 1.1 Hz), 3.72 (1H, dd, J ) 12.0, 3.5
Hz), 3.82 (1H, dd, J ) 3.7, 1.1 H), 3.87 (1H, dd, J ) 12.0, 4.3
Hz), 4.13 (1H, dd, J ) 8.7, 3.7 Hz), 4.75 (1H, s, OH), 5.45 (1H,
d, J ) 4.0 Hz); 13C NMR δ anomer â 57.6 (2 × CH3), 58.2 (CH3),
61.33 (CH2), 78.19 (CH), 81.2 (CH), 82.1 (CH), 85.3 (CH), 100.6
(CH); δ anomer R 57.5 (CH3), 57.7 (CH3), 58.7 (CH3), 61.27
(CH2), 78.26 (CH), 82.1 (CH), 82.4 (CH), 85.3 (CH), 96.7 (CH);
MS m/z (rel intensity) 223 (M+ + H, 1), 205 (49), 173 (80), 141
(49), 115 (33), 101 (100), 87 (80) 75 (80); HRMS calcd for
C9H19O6 223.1182, found 223.1100. Anal. Calcd for C9H18O6:
C, 48.64; H, 8.17. Found: C, 48.43; H, 8.46.
Compounds 5-7 were prepared from 5-O-tert-(butyldi-
methylsilyl)-2,3-O-isopropylidene-D-ribose14a as previously
described.14b,15 1-O-Ben zoyl 2,3-O-isop r op ylid en e-â-D-r i-
bofu r a n ose (5): mp 102-104 °C (from EtOAc-n-pentane);
[R]D -42 (c ) 0.2) {lit.14b mp 101-103 °C (from n-hexane-
EtOAc); [R]D -39.5 (c ) 0.2)}. 2,3-O-Isop r op ylid en e-1-O-
p iva loyl-â-D-r ibofu r a n ose (6): mp 95-96 °C (from EtOAc-
n-hexane); [R]D -62 (c ) 0.2) {lit.15 mp 93-94 °C (from
n-hexane); [R]D -61.6 (c ) 0.268)}. 2,3-O-Isop r op ylid en e-1-
O-p iva loyl-r-D-r ibofu r a n ose (7): {[R]D +28 (c ) 0.2) {lit.15
[R]D +27 (c ) 0.24)}.
Gen er a tion of P r im a r y Alk oxyl Ra d ica ls a n d Su bse-
qu en t ARF or IHA. Gen er a l P r oced u r es. Meth od A. A
solution of the substrate (0.2 mmol) in dry dichloromethane
(2 mL) was treated with (diacetoxyiodo)benzene (DIB) (129 mg,
4 mmol) and iodine (51 mg, 0.2 mmol) under nitrogen. The
reaction mixture was irradiated with two tungsten-filament
lamps for 1 h at 22-25 °C, poured into aqueous 10% sodium
thiosulfate, and extracted with CH2Cl2. The organic layer was
dried (Na2SO4) and evaporated under vacuum, and the result-
ing residue was purified by column chromatography on silica
gel.
Meth od B. Similar to Method A, but replacing DIB by
iodosylbenzene (PhIO) (2 equiv). Longer reaction times were
generally required (2-6 h).
Meth od C. Similar to Method A, but using MeCN as
solvent.
Ben zyl 6-O-Ben zyl-2-ben zoyl-3,5-d i-O-m eth yl-r-D-glu -
cofu r a n osid e (14). To a solution of product 12 (150 mg, 0.386
mmol) in dry pyridine (2.5 mL), at 0 °C and under N2, was
slowly added benzoyl chloride (0.2 mL, 1.72 mmol), and the
mixture was stirred at room temperature for 16 h. The reaction
mixture was poured into iced water and extracted with CH2-
Cl2. The combined extracts were washed with 10% aqueous
HCl, aqueous NaHCO3 and water, dried (Na2SO4), and con-
centrated under vacuum. Chromatography on silica gel of the
residue (hexanes-EtOAc, 85:15) gave the product 14 (176 mg,
93%) as a syrup: [R]D +68 (c ) 0.2); IR 3090, 3066, 1720, 1602
1
cm-1; H NMR δ 3.49 (3H, s), 3.51 (3H, s), 3.64 (1H, dd, J )
10.5, 5.3 Hz), 3.73 (1H, ddd, J ) 7.2, 5.3, 2.1 Hz), 3.84 (1H,
dd, J ) 10.5, 2.2 Hz), 4.20 (1H, dd, J ) 5.1, 3.0 Hz), 4.38 (1H,
dd, J ) 8.0, 5.2 Hz), 4.50 (1H, d, J ) 12.1 Hz), 4.62 (2H, s),
4.73 (1H, d, J ) 12.1 Hz), 5.26 (1H, dd, J ) 4.4, 3.0 Hz), 5.45
(1H, d, J ) 4.5 Hz) 7.14-7.19 (5H, m), 7.27 (1H, dd, J ) 7.2,
7.1 Hz), 7.33 (2H, dd, J ) 7.6, 7.1 Hz), 7.38 (2H, d, J ) 7.1
Hz), 7.46 (2H, dd, J ) 7.8, 7.7 Hz), 7.59 (1H, dd, J ) 7.5, 7.5
Hz), 8.07 (2H, d, J ) 7.2 Hz); 13C NMR δ 58.0 (CH3), 58.3 (CH3),
69.9 (CH2), 70.0 (CH2), 73.4 (CH2), 76.7 (CH), 77.7 (CH), 77.9
(CH), 83.3 (CH), 99.8 (CH), 127.3 (2 × CH), 127.36 (CH), 127.40
(CH), 127.5 (2 × CH), 128.1 (2 × CH), 128.3 (2 × CH), 128.4
(2 × CH), 129.7 (C), 129.8 (2 × CH), 133.2 (CH), 137.6 (C),
138.5 (C), 165.9 (C); MS m/z (rel intensity) 401 (M+ - C7H7,
1), 105 (51), 91 (100); HRMS calcd for C22H25O7 401.1600, found
401.1556. Anal. Calcd for C29H32O7: C, 70.71; H, 6.55. Found:
C, 70.81; H, 6.65.
Ra d ica l Rea ction of 2,3:4,5-Di-O-isop r op ylid en er ibitol
(1). Meth od A. The products were 1-acetoxy-1,2:3,4-di-O-
isopropylidene-R-D-erythritol (15) (27%), 1-acetoxy-1,2:3,4-di-
O-isopropylidene-â-D-erythritol (16) (10%), 1,2:3,4-di-O-iso-
propylidene-â-L-ribulofuranose (17) (30%), and 1,2:3,4-di-O-
isopropylidene-R-L-ribulofuranose (18) (10%). Compound 15:
1
syrup; [R]D -90 (c ) 0.1); IR 1747 cm-1; H NMR δ 1.33 (3H,
s), 1.38 (3H, s), 1.41 (3H, s), 1.48 (3H, s), 2.09 (3H, s), 4.02
(1H, dd, J ) 8.8, 4.8 Hz), 4.08-4.12 (2H, m), 4.29 (1H, ddd, J
) 7.7, 5.8, 5.0 Hz), 6.30 (1H, d, J ) 3.5 Hz); 13C NMR δ 21.2
(CH3), 25.2 (CH3), 26.0 (CH3), 26.8 (CH3), 28.1 (CH3), 67.0
(CH2), 73.1 (CH), 79.5 (CH), 93.7 (CH), 109.4 (C), 112.2 (C)
170.0 (C); MS m/z (rel intensity) 259 (M+ - H, <1), 245 (M+
-
2-O-Ben zoyl-3,5-d i-O-m eth yl-D-glu cofu r a n ose (3). To a
solution of compound 14 (176 mg, 0.358 mmol) in EtOAc (16
mL) was added 10% Pd(OH)2/C (77 mg), and the mixture was
hydrogenated at room temperature for 4 h. The suspension
was filtered through silica gel-Celite (1:1), and the organic
layers were concentrated under vacuum. Column chromatog-
raphy on silica gel (hexanes-EtOAc, 3:7) gave the benzoyl
derivative 3 (105 mg, 94%) as an inseparable anomeric mixture
(R:â, 4:1): syrup; [R]D +21 (c ) 0.4); IR 3532, 3090, 3065, 1728,
1602 cm-1; 1H NMR δ anomer â 3.46 (3H, s), 3.63 (3H, s), 3.68
(1H, ddd, J ) 9.3, 3.6, 3.5 Hz), 3.81 (1H, dd, J ) 11.8, 3.1 Hz),
3.97 (1H, dd, J ) 11.9, 4.0 Hz), 4.00 (1H, d, J ) 3.8 Hz), 4.26
(1H, dd, J ) 9.2, 3.9 Hz), 5.36 (1H, s), 5.37 (1H, s), 7.46 (2H,
dd, J ) 7.8, 7.7 Hz), 7.60 (1H, dd, J ) 7.5, 7.4 Hz), 8.01 (2H,
d, J ) 7.3 Hz); δ anomer R 3.45 (3H, s), 3.52 (3H, s), 3.53 (1H,
ddd, J ) 9.1, 3.5, 3.4 Hz), 3.74 (1H, dd, J ) 12.2, 3.3 Hz), 3.90
(1H, dd, J ) 12.1, 3.4 Hz), 4.05 (1H, dd, J ) 3.8, 1.3 Hz), 4.38
(1H, dd, J ) 8.6, 4.3 Hz), 5.29 (1H, d, J ) 4.3, 2.0 Hz), 5.69
(1H, d, J ) 4.1 Hz), 7.49 (2H, dd, J ) 7.6, 7.5 Hz), 7.61(1H,
dd, J ) 7.5, 7.4 Hz), 8.06 (2H, d, J ) 7.3 Hz); 13C NMR δ
anomer R 57.7 (CH3), 58.3 (CH3), 61.1 (CH2), 78.1 (CH), 78.3
(CH), 80.8 (CH), 82.1 (CH), 101.1 (CH), 128.4 (2 × CH), 128.9
(C), 129.7 (2 × CH), 133.6 (CH), 163.3 (C); δ anomer â 57.6
(CH3), 57.9 (CH3), 60.8 (CH2), 76.2 (CH), 77.3 (CH), 77.5 (CH),
83.2 (CH), 96.1 (CH), 128.4 (2 × CH), 129.0 (C), 129.7 (2 ×
Me, 25), 101 (100), 85 (80), 59 (60); HRMS calcd for C12H19O6
259.1182, found 259.1209. Anal. Calcd for C12H20O6: C, 55.37;
H, 7.74. Found: C, 55.54; H, 7.55. Compound 16: mp 38-40
°C (from n-pentane); [R]D +56 (c ) 0.2); IR 1748 cm-1; 1H NMR
δ 1.34 (3H, s), 1.41 (3H, s), 1.45 (3H, s), 1.48 (3H, s), 2.09 (3H,
s), 3.92 (1H, dd, J ) 8.5, 4.7 Hz), 4.03 (1H, ddd, J ) 8.2, 5.8,
4.9 Hz), 4.10 (1H, dd, J ) 8.4, 6.1 Hz), 4.12 (1H, dd, J ) 8.3,
1.9 Hz), 6.26 (1H, d, J ) 1.8 Hz); 13C NMR δ 21.2 (CH3), 25.2
(CH3), 26.7 (CH3), 27.0 (CH3), 27.6 (CH3), 66.8 (CH2), 75.2 (CH),
82.4 (CH), 96.9 (CH), 110.0 (C), 112.9 (C) 170.1 (C); MS m/z
(rel intensity) 245 (M+ - Me, 34), 101 (100); HRMS calcd for
C
11H17O6 245.1025, found 245.1030. Anal. Calcd for C12H20O6:
C, 55.37; H, 7.75. Found: C, 55.18; H, 7.69. Compound 17:
syrup; [R]D +130 (c ) 0.3); IR 1202, 1067, 856 cm-1; 1H NMR
δ 1.31 (3H, s), 1.39 (3H, s), 1.42 (3H, s), 1.45 (3H, s), 3.87 (1H,
dd, J ) 10.4, 3.7 Hz), 3.94 (1H, d, J ) 10.4 Hz), 4.05 (1H, d, J
) 9.7 Hz), 4.27 (1H, d, J ) 9.7 Hz), 4.55 (1H, d, J ) 5.8 Hz),
4.84 (1H, dd, J ) 5.8, 3.7 Hz); 13C NMR δ 24.9 (CH3), 26.2
(CH3), 26.3 (CH3), 26.5 (CH3), 69.2 (CH2), 71.2 (CH2), 80.1 (CH),
84.7 (CH), 111.5 (C), 112.5 (C) 112.7 (C); MS m/z (rel intensity)
215 (M+ - Me, 60), 155 (7), 117 (44), 114 (29), 97 (85), 85 (59),
59 (100); HRMS calcd for C10H15O5 215.0919, found 215.0949.
Anal. Calcd for C11H18O5: C, 57.38; H, 7.88. Found: C, 57.28;
H, 8.04. Compound 18: mp 89-91 °C (from n-pentane); [R]D
CH), 133.6 (CH), 165.5 (C); MS m/z (rel intensity) 281 (M+
-
1
+9 (c ) 0.2); IR 1232 cm-1; H NMR δ 1.36 (3H, s), 1.44 (3H,
OMe, 1), 105 (100), 77 (17); HRMS calcd for C14H17O6 281.1600,
found 281.1556. Anal. Calcd for C15H20O7: C, 57.68; H, 6.45.
Found: C, 57.41; H, 6.51.
s), 1.52 (3H, s), 1.60 (3H, s), 3.95 (1H, dd, J ) 10.4, 5.4 Hz),
3.97 (1H, d, J ) 9.1 Hz), 3.99 (1H, dd, J ) 10.4, 2.7 Hz), 4.02
(1H, d, J ) 9.0 Hz), 4.45 (1H, d, J ) 6.6 Hz), 4.78 (1H, ddd, J
) 6.6, 5.5, 2.7 Hz); 13C NMR δ 25.8 (CH3), 26.0 (2 × CH3),
26.7 (CH3), 69.8 (CH2), 71.4 (CH2), 78.7 (CH), 81.0 (CH), 108.8
(C), 111.9 (C) 115.3 (C); MS m/z (rel intensity) 231 (M+ + 1,
<1), 215 (M+ - Me, 43), 201 (33), 157 (16), 143 (94), 117 (24),
Ben zyl 2,3-O-Isop r op ylid en e-â-D-r ibofu r a n osid e (4).
Mp 109-110 °C (from acetone-n-hexane); [R]D -114 (c ) 0.2)
{lit.13 mp 108-110 °C (from EtOAc-n-hexane); [R]D -113
(c ) 1)}.
J . Org. Chem, Vol. 68, No. 13, 2003 5317

Boto et al.
114 (17), 101 (100), 97 (27), 85 (36), 59 (69); HRMS calcd for
11H19O5 231.1232, found 231.1280. Anal. Calcd for C11H18O5:
C, 57.38; H, 7.88. Found: C, 57.16; H, 8.12.
CH), 133.7 (CH), 164.7 (C), 169.0 (C); MS m/z (rel intensity)
307 (M+ - Me, 5), 217 (3), 105 (100), 77 (13); HRMS calcd for
C15H15O7 307.0818, found 307.0810. Anal. Calcd for C16H18O7:
C
C, 59.62; H, 5.63. Found: C, 59.54; H, 5.42.
Meth yl 3-O-F or m yl-2,4-d i-O-m eth yl-r-D-a r a bin op yr a -
n osid e (19). Compound 2 was treated according to Method B
yielding product 19 in 45% yield: syrup; [R]D -155 (c ) 0.1);
Radical Reaction of 2,3-O-Isopr opyliden e-1-O-pivaloyl-
â-D-r ibofu r a n ose (6). Meth od C. The reaction afforded (4S)-
4-O-acetyl-2,3-isopropylidene-1-O-pivaloyl-â-D-erythro-tetra-
dialdo-1,4-furanose (25) (2%), (4R)-4-O-acetyl-2,3-isopropylidene-
1-O-pivaloyl-â-D-erythro-tetradialdo-1,4-furanose (26) (6%),
(4R)-4-O-acetylamino-2,3-isopropylidene-1-O-pivaloyl-â-D-eryth-
ro-tetradialdo-1,4-furanose (27) (10%), and (4S)-4-O-acety-
lamino-2,3-isopropylidene-1-O-pivaloyl-â-D-erythro-tetradialdo-
1,4-furanose (28) (50%). Compound 25: syrup; [R]D -54 (c )
1
IR 1725 cm-1; H NMR δ 3.45 (3H, s), 3.46 (3H, s), 3.49 (3H,
s), 3.71 (1H, dd, J ) 12.8, 1.3 Hz), 3.72 (1H, m), 3.76 (1H, dd,
J ) 10.2, 3.5 Hz), 3.79 (1H, dd, J ) 12.9, 3.2 Hz), 4.92 (1H, d,
J ) 3.5 Hz), 5.26 (1H, dd, J ) 10.2, 3.2 Hz), 8.18 (1H, s); 13C
NMR δ 55.6 (CH3), 57.6 (CH3), 58.3 (CH2), 59.0 (CH3), 71.3
(CH), 75.7 (CH), 76.7 (CH), 98.6 (CH), 160.5 (CH); MS m/z (rel
intensity) 219 (M+ - H, <1), 205 (M+ - Me, <1), 115 (64),
101 (100); HRMS calcd for C9H15O6 219.0869, found 219.0835.
Anal. Calcd for C9H16O6: C, 49.09; H, 7.32. Found: C, 48.87;
H, 7.20.
1
0.3); IR 1732 cm-1; H NMR δ 1.20 (9H, s), 1.38 (3H, s), 1.54
(3H, s), 2.16 (3H, s), 4.67 (1H, d, J ) 5.9 Hz), 4.95 (1H, dd, J
) 5.9, 4.1 Hz), 6.14 (1H, d, J ) 4.1 Hz), 6.24 (1H, s); 13C NMR
δ 20.8 (CH3), 25.6 (CH3), 25.9 (CH3), 26.9 (3 × CH3), 38.8 (C),
77.9 (CH), 82.9 (CH), 98.0 (2 × CH), 114.6 (C), 169.0 (C), 176.6
(C); MS m/z (rel intensity) 287 (M+ - Me, 35), 217 (17), 201
(93), 143 (60), 57 (100); HRMS calcd for C13H19O7 287.1131,
found 287.1177. Anal. Calcd for C14H22O7: C, 55.62; H, 7.33.
Found: C, 55.89; H, 7.12. Compound 26: mp 57-59 °C (from
(5S)-1,5-An h yd r o-2-b en zoyl-3,5-d i-O-m et h yl-â-D-xylo-
p en ta d ia ld o-1,4-fu r a n ose (20). Compound 3 was treated
under Method A or B conditions, giving product 20 in 23% and
33% yield, respectively. Compound 20: syrup; [R]D -42 (c )
1
0.1); IR 3094, 3065, 1721, 1602 cm-1; H NMR δ 3.45 (3H, s),
3.48 (3H, s), 3.87 (1H, d, J ) 5.1 Hz), 4.76 (1H, d, J ) 5.1 Hz),
4.89 (1H, s), 5.19 (1H, s), 5.71 (1H, s), 7.46 (2H, dd, J ) 7.8,
7.7 Hz), 7.59 (1H, dd, J ) 7.4, 7.4 Hz), 8.06 (2H, d, J ) 7.2
Hz); 13C NMR δ 55.4 (CH3), 59.0 (CH3), 78.0 (CH), 78.9 (CH),
83.2 (CH), 98.2 (CH), 102.7 (CH), 128.5 (2 × CH), 129.3 (C),
129.8 (2 × CH), 133.5 (CH), 165.5 (C); MS m/z (rel intensity)
280 (M+, <1), 249 (M+ - OMe, 2), 105 (100); HRMS calcd for
n-pentane); [R]D -9 (c ) 0.2); IR 1748 cm-1; H NMR δ 1.21
1
(9H, s), 1.34 (3H, s), 1.50 (3H, s), 2.06 (3H, s), 4.75 (1H, d, J )
5.7 Hz), 4.78 (1H, d, J ) 5.8 Hz), 6.30 (1H, s), 6.31 (1H, s); 13
C
NMR δ 20.9 (CH3), 25.0 (CH3), 26.3 (CH3), 26.8 (3 × CH3), 38.6
(C), 83.8 (CH), 83.9 (CH), 102.6 (CH), 102.8 (CH), 113.6 (C),
168.9 (C), 176.3 (C); MS m/z (rel intensity) 287 (M+ - Me, 11),
243 (8), 201 (44), 159 (11), 143 (61), 129 (24), 101 (8), 85 (38),
57 (100); HRMS calcd for C13H19O7 287.1131, found 287.1121.
Anal. Calcd for C14H22O7: C, 55.62; H, 7.33. Found: C, 55.57;
H, 7.28. Compound 27: mp 140-142 °C (from acetone-n-
C
14H16O6 280.0947, found 280.0939. Anal. Calcd for C14H16O6:
C, 60.00; H, 5.75. Found: C, 59.92; H, 6.04.
Ra d ica l Rea ction of Ben zyl 2,3-O-Isop r op ylid en e-â-D-
r ibofu r a n osid e (4). Meth od A. The reaction afforded 1,5-
benzylidene-2,3-isopropylidene-â-D-ribofuranose (21) and 1-O-
benzyl (4R)-4-O-acetyl-2,3-isopropylidene-â-D-erythro-tetradialdo-
1,4-furanose (22) in 70% overall yield (21:22, 4:3). Compound
21: mp 94-95 °C (from n-pentane); [R]D + 34 (c ) 0.2); IR
pentane); [R]D -47 (c ) 0.2); IR 3436, 1740, 1694 cm-1 1H
;
NMR δ 1.21 (9H, s), 1.37 (3H, s), 1.54 (3H, s), 2.07 (3H, s),
4.69 (1H, d, J ) 5.8 Hz), 4.70 (1H, dd, J ) 5.9, 3.4 Hz), 5.93
(1H, dd, J ) 10.0, 3.3 Hz), 6.10 (1H, s), 6.39 (1H, d, J ) 9.8
1
3094, 3068 cm-1 1H NMR δ 1.34 (3H, s), 1.52 (3H, s), 3.79
;
Hz); H NMR (C6D6) δ 1.15 (3H, s), 1.18 (9H, s), 1.46 (3H, s),
1.47 (3H, s), 4.13 (1H, dd, J ) 5.8, 3.4 Hz), 4.47 (1H, d, J )
5.8 Hz), 6.18 (1H, d, J ) 9.9 Hz), 6.25 (1H, dd, J ) 10.1, 3.4
Hz), 6.56 (1H, s); 13C NMR δ 23.4 (CH3), 24.8 (CH3), 26.1 (CH3),
27.9 (3 × CH3), 38.9 (C), 77.8 (CH), 81.1 (CH), 87.9 (CH), 98.0
(CH), 113.5 (C), 169.7 (C), 176.8 (C); MS m/z (rel intensity)
302 (M+ + H, <1), 286 (2), 200 (83), 57 (100); HRMS calcd for
(1H, dd, J ) 12.6, 2.2 Hz), 4.05 (1H, d, J ) 12.6 Hz), 4.65 (1H,
d, J ) 2.1 Hz), 4.75 (1H, d, J ) 6.2 Hz), 4.76 (1H, d, J ) 6.0
Hz), 5.63 (1H, s), 5.77 (1H, s), 7.36 (3H, m), 7.47 (2H, m); 13C
NMR δ 24.7 (CH3), 26.3 (CH3), 72.0 (CH2), 81.9 (CH), 87.8 (CH),
88.3 (CH), 100.7 (CH), 105.7 (CH), 112.3 (C), 125.9 (2 × CH),
128.3 (2 × CH), 128.8 (CH), 138.5 (C); MS m/z (rel intensity)
278 (M+, 27), 263 (4), 105 (100), 77 (85); HRMS calcd for
C
14H24NO6 302.1604, found 302.1591. Anal. Calcd for C14H23-
NO6: C, 55.80; H, 7.69; N, 4.69. Found: C, 55.57; H, 7.99; N,
4.64. Compound 28: mp 128-131 °C (from acetone-n-pen-
tane); [R]D -4 (c ) 0.2); IR 3445, 1744, 1693 cm-1; 1H NMR δ
1.22 (9H, s), 1.32 (3H, s), 1.49 (3H, s), 1.97 (3H, s), 4.76 (1H,
d, J ) 5.9 Hz), 4.77 (1H, d, J ) 5.9 Hz), 5.90 (1H, d, J ) 8.4
Hz), 6.09 (1H, d, J ) 7.8 Hz), 6.19 (1H, s); 13C NMR δ 23.3
(CH3), 25.0 (CH3), 26.3 (CH3), 26.9 (3 × CH3), 38.6 (C), 84.3
(CH), 84.4 (CH), 89.1 (CH), 103.2 (CH), 113.4 (C), 169.0 (C),
176.3 (C); MS m/z (rel intensity) 302 (M+ + H, <1), 200 (100);
HRMS calcd for C14H24NO6 302.16036, found 302.16039. Anal.
Calcd for C14H23NO6: C, 55.80; H, 7.69; N, 4.65. Found: C,
55.57; H, 7.99; N, 4.64.
C
H
15H18O5 278.11542, found 278.11494. Anal. Calcd for C15
18O5: C, 64.73; H, 6.52. Found: C, 64.61; H, 6.74. Compound
-
22: mp 94-96 °C (from acetone-n-pentane); [R]D -36 (c )
0.2) {lit.24b 93-94.5 °C (from n-hexane-EtOAc); [R]D -34.4}.
Radical Reaction of 1-O-Ben zoyl-2,3-O-isopr opyliden e-
â-D-r ibofu r a n ose (5). Meth od A. Compounds (4R)-4-O-
acetyl-1-O-benzoyl-2,3-O-isopropylidene-â-D-erythro-tetradialdo-
1,4-furanose (23) and (4S)-4-O-acetyl-1-O-benzoyl-2,3-isoprop-
ylidene-R-D-erythro-tetradialdo-1,4-furanose (24) were obtained
in 48% overall yield (23:24, 2:1). Compound 23: syrup; [R]D
+53 (c ) 0.6); IR 1735, 1602 cm-1 1H NMR δ 1.36 (3H, s),
;
1.53 (3H, s), 1.98 (3H, s), 4.87 (1H, d, J ) 5.7 Hz), 4.94 (1H, d,
J ) 5.7 Hz), 6.37 (1H, s), 6.56 (1H, s), 7.46 (2H, dd, J ) 7.9,
7.8 Hz), 7.60 (1H, dd, J ) 7.5, 7.4 Hz), 8.04 (2H, d, J ) 8.4
Hz); 13C NMR δ 20.9 (CH3), 25.0 (CH3), 26.3 (CH3), 83.8 (CH),
83.9 (CH), 102.6 (CH), 103.0 (CH), 113.7 (C), 128.4 (2 × CH),
129.4 (C), 129.7 (2 × CH), 133.6 (CH), 164.5 (C), 168.9 (C);
MS m/z (rel intensity) 307 (M+ - Me, 42), 263 (16), 217 (22),
163 (46), 143 (32), 129 (55), 105 (100), 77 (72); HRMS calcd
Radical Reaction of 2,3-O-Isopr opyliden e-1-O-pivaloyl-
r-D-r ibofu r a n ose (7). Meth od C. The reaction afforded 2,3-
O-isopropylidene-D-ribono-1,4-lactone (29) (53%), (4R)-4-O-
acetyl-2,3-isopropylidene-1-O-pivaloyl-R-D-erythro-tetradialdo-
1,4-furanose (30) (7%), and (4S)-4-O-acetylamino-2,3-isoprop-
ylidene-1-O-pivaloyl-R-D-erythro-tetradialdo-1,4-furanose (31)
(17%). Lactone 29: mp 135-137 °C (from acetone-n-pentane);
[R]D -78 (c ) 0.2) {lit.25 138-139 °C; [R]D -84.17 (c ) 0.9)}.
Acetate 30: mp 53-56 °C (dryness from n-pentane); [R]D -25
for
C15H15O7 307.0818, found 307.0762. Anal. Calcd for
C
16H18O7: C, 59.62; H, 5.63. Found: C, 59.76; H, 5.44.
(c ) 0.2); IR 1748, 1737 cm-1 1H NMR δ 1.26 (9H, s), 1.36
;
Compound 24: syrup; [R]D -7 (c ) 0.2); IR 1733, 1602 cm-1
;
1H NMR δ 1.40 (3H, s), 1.57 (3H, s), 2.17 (3H, s), 4.86 (1H, d,
J ) 5.8 Hz), 5.04 (1H, dd, J ) 5.4, 4.5 Hz), 6.26 (1H, d, J )
4.0 Hz), 6.49 (1H, s), 7.45 (2H, dd, J ) 7.9, 7.6 Hz), 7.60 (1H,
dd, J ) 7.6, 7.3 Hz), 8.01 (2H, d, J ) 8.0 Hz); 13C NMR δ 20.8
(CH3), 25.6 (CH3), 25.9 (CH3), 70.9 (CH), 83.1 (CH), 98.2 (CH),
98.8 (CH), 114.7 (C), 128.5 (2 × CH), 129.1 (C), 129.9 (2 ×
(3H, s), 1.50 (3H, s), 2.09 (3H, s), 4.69 (1H, d, J ) 6.0 Hz),
4.95 (1H, dd, J ) 5.7, 4.2 Hz), 6.06 (1H, d, J ) 4.0 Hz), 6.25
(1H, s); 13C NMR δ 20.9 (CH3), 25.7 (CH3), 26.2 (CH3), 27.0 (3
× CH3), 38.8 (C), 77.8 (CH), 83.1 (CH), 97.8 (CH), 98.7 (CH),
114.5 (C), 169.2 (C), 176.6 (C); MS m/z (rel intensity) 287 (M+
- Me, 12), 243 (9), 129 (75), 101 (25), 85 (79), 57 (100); HRMS
5318 J . Org. Chem., Vol. 68, No. 13, 2003

â-Fragmentation of Primary Alkoxyl Radicals
calcd for C13H19O7 287.1131, found 287.1130. Anal. Calcd for
tive 32 (30 mg, 0.1 mmol) in dry C6H6 (3 mL) was added
allyltributyl tin (90 µL, 0.4 mmol) and AIBN (6 mg) under N2,
and the mixture was heated to reflux for 4 h. After being cooled
to room temperature, the solution was treated with KF (10
mg) in CH3CN-H2O (4 mL, 3:1) for 1 h, poured into water,
and extracted with CH2Cl2. The organic layers were dried (Na2-
SO4) and evaporated. The residue was purified by column
chromatography on silica gel (hexanes-EtOAc, 95:5), giving
the allyl derivative 33 (26 mg, 85%) as a crystalline solid: mp
55-56 °C (from n-pentane); [R]D -49 (c ) 0.3); IR 3066, 1725,
C
14H22O7: C, 55.62; H, 7.33. Found: C, 55.64; H, 7.30.
Acetylamide 31: mp 56-58 °C (from n-pentane); [R]D -23 (c
1
) 0.2); IR 3446, 3368, 1728, 1691 cm-1; H NMR δ 1.26 (9H,
s), 1.36 (3H, s), 1.55 (3H, s), 2.01 (3H, s), 4.87 (1H, dd, J )
6.7, 2.0 Hz), 5.10 (1H, dd, J ) 6.7, 4.5 Hz), 5.33 (1H, dd, J )
6.9, 1.9 Hz), 6.20 (1H, d, J ) 4.5 Hz), 6.30 (1H, d, J ) 6.5 Hz);
13C NMR δ 23.3 (CH3), 25.4 (CH3), 26.3 (CH3), 27.1 (3 × CH3),
38.8 (C), 79.9 (CH), 84.0 (CH), 85.9 (CH), 98.0 (CH), 114.9 (C),
170.6 (C), 177.2 (C); MS m/z (rel intensity) 286 (M+ - Me, 5),
200 (43), 100 (15), 85 (27), 71 (26), 57 (100); HRMS calcd for
1643, 1602 cm-1 1H NMR δ 1.35 (3H, s), 1.53 (3H, s), 2.34
;
C
13H20NO6 286.1291, found 286.1278. Anal. Calcd for C14H23-
(1H, ddd, J ) 15.4, 8.0, 7.7 Hz), 2.48 (1H, ddd, J ) 14.1, 7.2,
6.4 Hz), 4.41 (1H, dd, J ) 7.8, 7.8 Hz), 4.70 (1H, d, J ) 5.8
Hz), 4.90 (1H, d, J ) 5.9 Hz), 5.07 (1H, dd, J ) 17.0, 1.5 Hz),
5.09 (1H, dd, J ) 9.1, 1.4 Hz), 5.79 (1H, dddd, J ) 17.1, 10.4,
7.0, 6.6 Hz), 6.45 (1H, s), 7.45 (2H, dd, J ) 7.9, 7.7 Hz), 7.58
(1H, dd, J ) 7.4, 7.4 Hz), 8.01 (2H, d, J ) 7.1 Hz); 13C NMR δ
25.1 (CH3), 26.5 (CH3), 39.1 (CH2), 83.3 (CH), 85.5 (CH), 87.5
(CH), 103.3 (CH), 112.9 (C), 118.1 (CH2), 128.5 (2 × CH), 129.6
(2 × CH + C), 133.4 (2 × CH), 165.0 (C); MS m/z (rel intensity)
289 (M+ - Me, 5), 105 (100), 77 (17); HRMS calcd for C16H17O5
289.1076, found 289.1098. Anal. Calcd for C17H20O5: C, 67.09;
H, 6.62. Found: C, 66.89; H, 6.80.
NO6: C, 55.80; H, 7.69; N 4.65. Found: C, 55.56; H, 7.73; N,
4.37.
(4R)-4-Ch lor o-4-d eoxy-2,3-isop r op ylid en e-1-O-ben zoyl-
â-D-er yth r o-tetr a d ia ld o-1,4-fu r a n ose (32). The photolysis
of compound 5 (59 mg, 0.2 mmol) was performed with DIB
(129 mg, 0.4 mmol) and ICl (36 mg, 0.22 mmol) in dichloro-
methane at room temperature for 1 h. Usual workup and
chromatography afforded the acetates 23 (6 mg, 10%) and 24
(7 mg 11%), as well as (4R)-4-chloro-4-deoxy-2,3-isopropy-
lidene-1-O-benzoyl-â-D-erythro-tetradialdo-1,4-furanose (32)
(30 mg, 53%): mp 82-84 °C (dryness from CH2Cl2); [R]D -7
(c ) 0.2); IR 1732, 1602 cm-1 1H NMR δ 1.37 (3H, s), 1.51
;
(3H, s), 5.04 (1H, d, J ) 5.6 Hz), 5.14 (1H, d, J ) 5.6 Hz), 6.15
(1H, s), 6.60 (1H, s), 7.46 (2H, dd, J ) 7.9, 7.7 Hz), 7.60 (1H,
dd, J ) 7.5, 7.3 Hz), 8.08 (2H, d, J ) 7.3 Hz); 13C NMR δ 25.2
(CH3), 25.3 (CH3), 83.8 (CH), 88.2 (CH), 96.8 (CH), 104.1 (CH),
104.1 (C), 128.5 (2 × CH), 130.1 (C), 130.1 (2 × CH), 133.6
(CH), 164.6 (C); MS m/z (rel intensity) 285/283 (M+ - Me,
Ack n ow led gm en t. This work was supported by the
Investigation Programmes PB96-1461 and PPQ2000-
0728 of the Plan Nacional de Investigacio´n Cient´ıfica,
Desarrollo e Innovacio´n Tecnolo´gica, Direccio´n General
de Investigacio´n, Ministerio de Ciencia y Tecnolog´ıa,
Spain. We also thank the financial support from FEDER
funds. D.H. thanks C.S.I.C.-Comunidad de Canarias for
a fellowship.
3/10), 195/193 (3/9), 105 (100), 77 (18); HRMS calcd for C13H12
-
37ClO5/C13H1235ClO5 285.0345/283.0373, found 285.0311/
283.0342. Anal. Calcd for C14H15ClO5: C, 56.29; H, 5.06.
Found: C, 56.35; H, 5.12.
1-O-Ben zoyl-5,6,7-tr id eoxy-2,3-isop r op ylid en e-â-D-r ibo-
h ep t-6-en ofu r a n ose (33). To a solution of the chloro deriva-
J O034442F
J . Org. Chem, Vol. 68, No. 13, 2003 5319