Chromium(II) chloride-promoted reductive β-elimination of 1,1-dihalo alditols. Synthesis of highly functionalized alk-1-enyl halides

Article abstract of DOI:10.1016/j.tet.2008.08.100

A new general synthetic route to obtain highly functionalized (Z)- and (E)-alk-1-enyl halides is described, where the halogen can be indistinctly F, Cl, Br, and I. The procedure involves CrCl₂-promoted reductive elimination of β-O-substituted gem-dihalo alditols easily accessible from carbohydrates. The simplicity and mildness of the reaction conditions and their compatibility with different functional groups increase the synthetic potential of this methodology.

Full text of DOI:10.1016/j.tet.2008.08.100

Tetrahedron 64 (2008) 10706–10713
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Chromium(II) chloride-promoted reductive
b-elimination of 1,1-dihalo alditols.
Synthesis of highly functionalized alk-1-enyl halides
*
*
´
´
´
Elisa I. Leon , Nieves R. Paz, Concepcion Riesco-Fagundo, Ernesto Suarez
Instituto de Productos Naturales y Agrobiolog´ıa del C.S.I.C., Carretera de La Esperanza 3, 38206-La Laguna, Tenerife, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 31 July 2008
Received in revised form 28 August 2008
Accepted 29 August 2008
Available online 10 September 2008
A new general synthetic route to obtain highly functionalized (Z)- and (E)-alk-1-enyl halides is described,
where the halogen can be indistinctly F, Cl, Br, and I. The procedure involves CrCl2-promoted reductive
elimination of b-O-substituted gem-dihalo alditols easily accessible from carbohydrates. The simplicity
and mildness of the reaction conditions and their compatibility with different functional groups increase
the synthetic potential of this methodology.
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
glycals 1 by an advantageous two-step methodology previously
developed in our laboratory,9 with the alkoxyl radical
b-frag-
Alk-1-enyl halides are useful synthetic intermediates1 and
probably the most widely used organic electrophiles in the Stille,
Suzuki, Nozaki–Hiyama–Kishi, and Heck cross-coupling reactions.2
Moreover, new strategic reactions are emerging for C–N and C–O
bond formation that employ this type of compounds as starting
materials and their importance as valuable synthons is increasing
accordingly.3 The synthetic utility of these reactions owes a great
deal to the ease with which the coupling partners can be
synthesized.
mentation (ARF) reaction of 2-deoxy-2-halo pyranoses 2 as the
key step.
O
O
OH
X
RO
RO
a
RO
RO
RO
RO
b
1
2
There are many methods for obtaining alk-1-enyl halides, but
very few of them are mild enough to be used with highly func-
tionalized or sensitive substrates.4 An overview reveals few general
procedures and these usually have to be optimized for each class of
vinyl halides. Elimination reactions are well known among the
earliest routes toward vinyl halides, especially base-promoted
dehydrohalogenation of vicinal or geminal dihalo compounds.5
RO
RO
I
c
RO
HOCO
X
RO
HOCO
X
OR
3
4
Scheme 1. General scheme for the synthesis of 1-halo-1-iodo-alditols. Reagents and
conditions: (a) Fluorohydrins: SelectfluorÔ, CH3NO2/H2O (4:1), rt, 14 h and then re-
fluxed 30 min. Chlorohydrins: N-chlorosuccinimide, THF/H2O, reflux, 8 h. Bromohy-
drins: N-bromoacetamide, THF/H2O, rt, 4 h. Iodohydrins: N-iodosuccinimide, THF/H2O,
Zinc-promoted reductive elimination of
b-heterosubstituted
polyhalogenated compounds have also been used but to a lesser
rt, 20 min; (b) PhI(OAc)2, I2, CH2Cl2, h
X¼F, Cl, Br, I.
n
; (c) CrCl2, THF/DMF, rt; R¼protective group;
extent.6 Some years ago the preparation of vinyl halides by a ster-
eoselective reductive
b-elimination of non-fluorinated O-acety-
lated gem-dihaloalkanols with samarium(II) iodide was reported.7
Recent advances, for instance, involve the use of transition-metal
reagents in the reductive dehalogenation of gem-trihalo com-
pounds promoted by CrCl2 or CuCl/2,20-bipyridine.8
2. Results and discussion
Treatment of
b-O-acetyl or b-O-benzyl-1,1-haloiodo alditols
with an excess of chromium(II) chloride as reducing agent has
allowed the formation of highly functionalized vinyl iodides, vinyl
bromides, vinyl chlorides, and vinyl fluorides as summarized in
Table 1. As far as we know, no examples of chromium-mediated
Herein we describe a facile and general synthetic route to
chiral polyhydroxylated alk-1-enyl halides 4 by chromium(II)-
mediated reductive b-elimination reaction of 1,1-dihalo alditols 3
(Scheme 1). These gem-dihalo derivatives are easily available from
b-elimination of dihalo compounds have been previously reported.
The reaction proceeds at room temperature in THF with an ex-
cess of a preformed complex of CrCl2 and DMF, since this donor
ligand enhances the reductive power of chromium(II),11a to give
* Corresponding authors. Tel.: þ34 922251004; fax: þ34 922260135.
´
´
E-mail addresses: eila@ipna.csic.es (E.I. Leon), esuarez@ipna.csic.es (E. Suarez).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.08.100

E.I. Leo´n et al. / Tetrahedron 64 (2008) 10706–10713
10707
Table 1
other vinyl halides from each series of O-acetyl-1,1-haloiodo aldi-
tols, vinyl fluoride 17 was obtained almost quantitatively from -O-
benzyl-1-fluoro-1-iodo alditol 13 (entry 9). This could suggest that
the reductive elimination of a -O-benzyl group is the best option
when a fluorine atom is present.
In comparison, preformed10 SmI2 was used at room temperature
as an alternative reducing agent for the elimination of the -O-
Reductive b
-elimination of 1-halo-1-iodo alditolsa
b
Entry
Substrate
Time (h)
Product
Yield (%, Z/E)
b
AcO
I
AcO
AcO
HOCO
X
AcO
HOCO
X
OAc
b
acetyl-1,1-haloiodo alditols 6–8 to obtain vinyl halides 10–12 (en-
tries 4, 6, and 8, Table 1), with higher diastereoselectivity but in
somewhat lower yields. Although vinyl fluoride 9 (entry 2) could
also be obtained from 1,1-fluoroiodo-alditol 5, heating to 50 ꢀC was
necessary and a notable decrease in yield was observed (entry 2,
1
2
3
4
5
6
7
8
5 X¼F
5 X¼F
6 X¼Cl
6 X¼Cl
7 X¼Br
7 X¼Br
8 X¼I
24
0.5
1
0.3
3
0.5
0.5
0.5
9 X¼F
9 X¼F
85, 1:1
52, 3:1b
92, 3:1
85, 5:1b
96, 3:2c
72, 5:1b
90, 3:2
77, 5:1b
10 X¼Cl
10 X¼Cl
11 X¼Br
11 X¼Br
12 X¼I
Table 1). SmI2 failed to lead to the reductive elimination of b-O-
8 X¼I
12 X¼I
benzylated-1,1-diiodo alditol 16, which afforded complex mixtures
of compounds, even when temperature and amounts of reagent
were reduced.
BnO
I
BnO
In order to test the scope and generality of our methodology the
reaction was examined with other types of gem-dihalo alditols as
substrates such as O-acetyl 1,1-dibromo- and 1,1-bromochloro
alditols 37 and 38 (Table 2).9b These were also suitable for the
BnO
X
BnO
HOCO
X
HOCO
OBn
9
13 X¼F
14 X¼Cl
15 X¼Br
16 X¼I
24
24
5
17 X¼F
18 X¼Cl
19 X¼Br
20 X¼I
99, 1:1
80, 2:1
81, 7:3c
81, 3:1d
10
11
12
cromium(II)-promoted
b-elimination and vinyl bromide 10 and
vinyl chloride 11 were formed under the usual conditions with
good yields (entries 1 and 2, Table 2).
1.5
Similar results were obtained when experiments using gem-
diiodo alditols 39, 41, and 44 were carried out. The reaction showed
tolerance to other O-protecting groups such as benzylidene acetal
of 39 and tert-butyldimethysilyl of 41 (entries 3 and 4, Table 2).
Elimination of this last alditol afforded mixtures of the expected
vinyl iodides 42 and their corresponding transesterification prod-
ucts 43. As can be observed in this case the presence of a cyclic
carbonate at the b-position had a decisive influence on the steric
course of the elimination, probably due to the conformational re-
striction introduced, and the diastereoselectivity improved
β-D-GalO
AcO
HOCO
I
β-D-GalO
AcO
HOCO
X
X
X
X
OAc
13e
14e
15e
16e
21 X¼F
24
2.5
6
25 X¼F
79, 3:1
81, 2:1f
92, 4:1c
93, 3:2
22 X¼Cl
23 X¼Br
24 X¼I
26 X¼Cl
27 X¼Br
28 X¼I
0.5
AcO
I
AcO
AcO
AcO
HOCO
OAc
HOCO
17
18
19
20
29 X¼F
30 X¼Cl
31 X¼Br
32 X¼I
24
1
3
33 X¼F
34 X¼Cl
35 X¼Br
36 X¼I
84, 1:1
96, 1:1
84, 3:2c
90, 1:1
Table 2
Reductive
b
-elimination of 1,1-dihalo alditolsa
Entry
Substrate
Time (h)
Product
Yield (%, Z/E)
1
a
b
c
d
e
f
AcO
Br
AcO
Reactions were performed with CrCl2–DMF in dry THF.
Reactions were performed with SmI2 in dry THF.
Vinyl iodide (3–11%) was also obtained.
20E contaminated with 20% of 20Z.
Gal in this case refers to the peracetylated moiety of galactose.
AcO
HOCO
X
AcO
HOCO
X
OAc
1
2
37 X¼Br
38 X¼Cl
1.5
1.5
11 X¼Br
10 X¼Cl
Ph
82, 1:1
83, 3:2
26E contaminated with 15% of starting material 22.
Ph
(Z)- and (E)-vinyl halides in good to excellent yields but with
moderate diastereoselectivity (Table 1).
O
O
I
O
O
3
4
1
91, 3:2
I
I
For the preparation of vinyl fluorides a higher excess of CrCl2–
DMF complex and in general longer reaction time (24 h) were
necessary (entries 1, 9, 13, and 17, Table 1). In preliminary experi-
ments we studied different temperature conditions and no effect
was observed in the diastereoisomeric ratio. However, yields be-
came lower as the temperature increased.
The reaction is compatible with O-acetyl or O-benzyl protecting
groups present in the structure of all gem-haloiodo alditols studied,
especially with the sensitive O-formyl protecting group. The gly-
cosidic linkage of O-acetylated derivatives 25–28 also remains
unaffected too. Iodides are considerably more reactive than fluo-
rides and chlorides in the reductive elimination reaction. Conse-
quently, vinyl fluorides (entries 1, 9, 13, and 17) and vinyl chlorides
(entries 3, 10, 14, and 18) were exclusively obtained. However, this
does not appear to be the case for 1-bromo-1-iodo alditols (7,15, 23,
and 31), since bromine was eliminated competitively and the vinyl
bromides (entries 5, 11, 15, and 19) were contaminated by small
amounts of the corresponding vinyl iodides. In contrast with the
fact that vinyl fluorides were obtained with lower yields than the
HOCO
OAc
HOCO
39
40
tBuMe2SiO
OR1
O
I
tBuMe2SiO
O
I
RO
I
O
HOCO
41
0.5
0.5
42 R¼OCOH; R1¼H
85, 3:7b
43 R¼H; R1¼OCOH
AcO
I
AcO
HOCO
5
86, 3:2c
I
HOCO
I
OAc
45
44
a
b
c
All reactions were performed with CrCl2–DMF in dry THF.
Inseparable mixtures of 42E with 43E and 42Z with 43Z.
Inseparable mixture of isomers.

10708
E.I. Leo´n et al. / Tetrahedron 64 (2008) 10706–10713
significantly toward the (E)-isomer (Z/E, 3:7). Reductive elimination
of a less substituted gem-dihalo alditol 44 afforded vinyl iodide 45,
which may be an alternative chiral synthon when the introduction
of only one stereogenic center is required.
4. Experimental section
4.1. General
Mechanistically, details of the formation of vinyl halides from
-O-substituted gem-dihalo alditols have yet to be elucidated.
Melting points were determined with a hot-stage apparatus.
Optical rotations were measured at the sodium line at ambient
temperature in CHCl3 solutions. IR spectra were recorded in CHCl3
solutions unless otherwise stated. NMR spectra were determined at
500 MHz for 1H, 100.6 MHz for 13C, and 376.4 MHz for 19F in CDCl3
b
The most important chromium-mediated reaction of gem-diha-
loalkanes, the E-olefination of carbonyl compounds developed by
Takai,11 is believed to proceed via a gem-dichromium carbenoid
(A), which nucleophilically attacks the carbonyl compounds, al-
though a gem-halo-chromium intermediate (B) may be involved
(Scheme 2). When we attempted the olefination of hydro-
unless otherwise stated. TMS was used as internal standard for 1
H
and 13C nuclei, while CCl3F was used as internal standard for 19F
nucleus. Mass spectra were determined at 70 eV. Merck silica gel 60
PF (0.063–0.2 mm) was used for column chromatography. Circular
layers of 1 mm of Merck silica gel 60 PF254 were used on a Chro-
matotron for centrifugally assisted chromatography. Anhydrous
CrCl2 was purchased from Aldrich. Samarium powder was pur-
chased from Strem. Solvents were analytical grade or were purified
by standard procedures prior to use. All reactions involving air- or
moisture-sensitive materials were carried out under a nitrogen
atmosphere, and the glassware was oven-dried. The spray reagents
for TLC analysis were conducted with 0.5% vanillin in H2SO4–EtOH
(4:1) and further heating until development of color.
cinnamaldehyde using different
b-substituted gem-diiodo alditols
b
-elimination products were exclusively obtained.9a It is proba-
ble that initially an oxidative addition of chromium into the C–X
bond (IꢁBr[Cl>F) takes place to generate the gem-halo-chro-
mium intermediate (C), followed by chromium-induced
b-elim-
ination of the oxygenated function at C-2, which must be faster
than the possible second reduction toward a geminal dichro-
mium species (Scheme 2).
CrIII
CrIII
I
R1CHI2
R1
R1
CrIII
4.2. General procedure for the synthesis of vinyl halides
with CrCl2
A
B
To a suspension of CrCl2 (4 mmol) in dry THF (8 mL) was added,
under nitrogen, dry DMF (4 mmol) and the mixture stirred for
30 min. A solution of the 1,1-dihalo alditol (1 mmol) in THF (10 mL)
was then added and the stirring continued at room temperature,
for the time specified in the tables. The reaction mixture was
poured into water and extracted with EtOAc, the organic layer was
washed with brine, dried over Na2SO4, and concentrated under
reduced pressure. The residue was purified by chromatography
(hexanes–EtOAc mixtures). For vinyl fluorides 9, 17, 25, and 33,
CrCl2 (6 mmol) in dry THF (18 mL) and dry DMF (6 mmol) were
used.
R2
X
H
I
CrII
R2
R2
X
X
H
CrIII
OR
RO
X= F, Cl, Br, I
C
Scheme 2. Tentative mechanism for CrCl2-promoted
b-elimination of gem-dihalo
alditols.
In general, reductive elimination of 1:1 diastereoisomeric
mixtures of gem-haloiodo alditols (3:2 for 30 and 31) afforded
(Z)- and (E)-vinyl halides with ratios different from those of the
starting material.
b-Elimination of the different gem-diiodo
4.3. General procedure for the synthesis of vinyl halides
with Sml2
alditols studied took place with variable diastereoselectivity. The
observed stereochemical course can be explained by a low de-
gree of control in the transition state. It is known that stereo-
selective reactions of gem-trihalogenated compounds promoted
A solution of freshly prepared SmI2 (3 mmol) in dry THF (30 mL)
was added dropwise over 30 min, under nitrogen, to a solution of
the 1,1-dihalo alditol (1 mmol) in THF (10 mL) at room temperature,
with the exception of the fluoride derivative, which was heated to
50 ꢀC. Stirring was continued for the time specified in Table 1, the
reaction mixture was treated with 10% aqueous HCl, and after usual
work up the residue was purified by chromatography (hexanes–
EtOAc mixtures).
by CrCl2 involve
termediate whose conformation is fixed by intramolecular co-
ordination of chromium(III) with an oxygen atom of a
-group.12
a gem-dihalogenated monochromium in-
b
Since gem-dihalo alditols show a high number of oxygenated
functions several chromium(III)–oxygen coordinations are feasi-
ble and different conformations of the gem-halo-chromium in-
termediate (C) are possible with the subsequent loss of
stereocontrol during the elimination.
4.4. Spectral and analytical data of alk-1-enyl halides
3. Conclusion
4.4.1. (Z)-3,5-Di-O-acetyl-1,2-dideoxy-1-fluoro-4-O-formyl-
erythro-pent-1-enitol (9Z) and (E)-3,5-di-O-acetyl-1,2-dideoxy-1-
fluoro-4-O-formyl- -erythro-pent-1-enitol (9E)
D-
In summary we have described an efficient and general new
methodology to obtain highly functionalized (Z)- and (E)-vinyl
D
halides by reductive elimination of
b
-O-acetyl- and
b
-O-benzyl-1,1-
Yield with CrCl2 85%, Z/E dr: 1:1. Yield with Sml2 52%, Z/E dr:
dihalo alditols. The easy accessibility of these starting products
from carbohydrates combined with the simplicity and mildness of
the elimination conditions and the exceptional tolerance of the
CrCl2 reagent toward different functional groups increase the po-
tential of this method to obtain those valuable synthons. The syn-
thesis of libraries of both (Z)- and (E)-vinyl halides is of interest for
comparative studies in biochemistry as well as in physical organic
chemistry, especially for vinyl fluorides since the presence of
a fluorine atom modifies their biological activity by altering their
physicochemical properties.13
3:1. Compound 9Z: oil, [
a]
þ15.5 (c 0.67); IR 1734 cmꢂ1
;
1H
D
NMR dH 2.06 (3H, s), 2.07 (3H, s), 4.16 (1H, dd, J¼12.1, 7.2 Hz),
3
4.24 (1H, dd, J¼12.1, 4.1 Hz), 4.93 (1H, ddd, JFH¼39.4 Hz, J¼9.2,
4.9 Hz), 5.46 (1H, ddd, J¼7.2, 4.3, 4.1 Hz), 5.93 (1H, dd, J¼9.2,
2
4.3 Hz), 6.61 (1H, dd, JFH¼82.1 Hz, J¼4.9 Hz), 8.10 (1H, s); 13C
3
NMR dC 20.6 (CH3), 20.8 (CH3), 61.6 (CH2), 64.9 (CH, JFC¼6.5 Hz),
4
2
70.7 (CH, JFC¼2.2 Hz), 105.3 (CH, JFC¼2.2 Hz), 151.2 (CH,
1JFC¼268.6 Hz), 159.8 (CH), 169.4 (C), 170.4 (C); 19F NMR dF
2
3
ꢂ119.8 (dd, JFH¼82.6 Hz, JFH¼41.3 Hz); MS m/z (rel intensity)
203 (MþꢂHOCO, 10), 189 (8), 160 (30), 131 (50), 117 (100); HRMS

E.I. Leo´n et al. / Tetrahedron 64 (2008) 10706–10713
10709
m/z calcd for C9H12FO4 203.0720, found 203.0728. Anal. Calcd for
C10H13FO6: C, 48.39; H, 5.28. Found: C, 48.37; H, 5.10. Compound
4.4.4. (Z)-3,5-Di-O-acetyl-1,2-dideoxy-4-O-formyl-1-iodo-
erythro-pent-1-enitol (12Z) and (E)-3,5-di-O-acetyl-1,2-dideoxy-4-
O-formyl-1-iodo- -erythro-pent-1-enitol (12E)
D-
9E: oil, [
a
]
þ21.7 (c 0.72); IR 1734 cmꢂ1
;
1H NMR dH 2.06 (3H, s),
D
D
2.07 (3H, s), 4.18 (1H, dd, J¼12.1, 6.5 Hz), 4.23 (1H, dd, J¼12.1, 3.9 Hz),
5.36 (3H, m), 6.82 (1H, dd, 2JFH¼81.3 Hz, J¼10.3 Hz), 8.09 (1H, s); 1H
NMR (C6D6) dH 1.54 (3H, s), 1.61 (3H, s), 3.94 (1H, dd, J¼11.9, 6.2 Hz),
Yield with CrCl2 90%, Z/E dr: 3:2. Yield with Sml2 77%, Z/E dr: 5:1.
Compound 12Z: oil, [
a
]
;
ꢂ2.8 (c 1.35); IR 1736 cmꢂ1 1H NMR dH
D
2.07 (6H, s), 4.18 (1H, dd, J¼12.1, 7.3 Hz), 4.26 (1H, dd, J¼12.1,
4.0 Hz), 5.49 (1H, ddd, J¼7.3, 4.2, 4.0 Hz), 5.72 (1H, dd, J¼8.5,
4.2 Hz), 6.32 (1H, dd, J¼8.5, 8.0 Hz), 6.74 (1H, d, J¼8.0 Hz), 8.10 (1H,
s); 13C NMR (125.7 MHz) dC 20.69 (CH3), 20.74 (CH3), 61.6 (CH2),
70.4 (CH), 74.3 (CH), 88.5 (CH), 134.4 (CH), 159.7 (CH), 169.3 (C),
170.4 (C); MS m/z (rel intensity) 356 (Mþ, 1), 229 (<1), 183 (100);
HRMS m/z calcd for C10H13IO6 355.9698, found 355.9695. Anal.
Calcd for C10H13IO6: C, 33.73; H, 3.68. Found: C, 33.58; H, 4.07.
3
3.98 (1H, dd, J¼11.9, 3.3 Hz), 5.21 (1H, ddd, JFH¼16.2 Hz, J¼11.0,
9.1 Hz), 5.31 (2H, m), 6.31 (1H, dd, 2JFH¼81.5 Hz, J¼11.0 Hz), 7.42 (1H,
s); 13C NMR dC 20.6 (CH3), 20.9 (CH3), 61.5 (CH2), 67.6 (CH,
3JFC¼11.4 Hz), 70.7 (CH, 4JFC¼3.2 Hz), 106.3 (CH, 2JFC¼11.2 Hz), 154.6
1
(CH, JFC¼266.6 Hz), 159.7 (CH), 169.5 (C), 170.4 (C); 19F NMR dF
ꢂ119.5 (dd, 2JFH¼82.6 Hz, 3JFH¼13.8 Hz); MS m/z (rel intensity) 203
(MþꢂHOCO, 18), 189 (7), 160 (32), 130 (40), 117 (100); HRMS m/z
calcd for C9H12FO4 203.0720, found 203.0705. Anal. Calcd for
C10H13FO6: C, 48.39; H, 5.28. Found: C, 48.24; H, 4.98.
Compound 12E: oil, [
a]
þ52.5 (c 1.14); IR 1734 cmꢂ1
;
1H NMR dH
D
2.07 (3H, s), 2.09 (3H, s), 4.19 (1H, dd, J¼12.4, 6.6 Hz), 4.26 (1H, dd,
J¼12.4, 3.8 Hz), 5.34 (1H, ddd, J¼6.6, 4.6, 3.8 Hz), 5.42 (1H, dd, J¼7.4,
4.6 Hz), 6.53 (1H, dd, J¼14.6, 7.4 Hz), 6.65 (1H, d, J¼14.6 Hz), 8.08
(1H, s); 13C NMR (125.7 MHz) dC 20.6 (CH3), 20.8 (CH3), 61.3 (CH2),
70.2 (CH), 73.3 (CH), 83.8 (CH), 138.3 (CH), 159.6 (CH), 169.3 (C),
170.4 (C); MS m/z (rel intensity) 356 (Mþ, <1), 313 (<1), 311 (<1),
229 (<1), 183 (100); HRMS m/z calcd for C10H13IO6 355.9757, found
355.9768. Anal. Calcd for C10H13IO6: C, 33.73; H, 3.68. Found: C,
33.61; H, 3.92.
4.4.2. (Z)-3,5-Di-O-acetyl-1-chloro-1,2-dideoxy-4-O-formyl-
erythro-pent-1-enitol (10Z) and (E)-3,5-di-O-acetyl-1-chloro-1,2-
dideoxy-4-O-formyl- -erythro-pent-1-enitol (10E)
D-
D
Yield with CrCl2 92%, Z/E dr: 3:1. Yield with Sml2 85%, Z/E dr:
5:1. Compound 10Z: oil, [
a
]
D
þ4.0 (c 0.38); IR 1738 cmꢂ1
;
1H
NMR dH 2.06 (3H, s), 2.08 (3H, s), 4.15 (1H, dd, J¼12.2, 7.3 Hz),
4.24 (1H, dd, J¼12.1, 4.0 Hz), 5.48 (1H, ddd, J¼8.0, 3.9, 3.9 Hz),
5.82 (1H, dd, J¼8.7, 7.4 Hz), 5.98 (1H, dd, J¼8.9, 4.1 Hz), 6.35 (1H,
dd, J¼7.4, 0.8 Hz), 8.09 (1H, s); 13C NMR (125.7 MHz) dC 20.6
(CH3), 20.7 (CH3), 61.6 (CH2), 67.8 (CH), 70.6 (CH), 124.4 (CH),
125.1 (CH), 159.7 (CH), 169.3 (C), 170.4 (C); MS m/z (rel intensity)
229 (MþꢂCl, 8), 133 (100); HRMS m/z calcd for C10H13O6
229.0712, found 229.0721. Anal. Calcd for C10H13ClO6: C, 45.38;
4.4.5. (Z)-3,5-Di-O-benzyl-1,2-dideoxy-1-fluoro-4-O-formyl-
erythro-pent-1-enitol (17Z) and (E)-3,5-di-O-benzyl-1,2-dideoxy-1-
fluoro-4-O-formyl- -erythro-pent-1-enitol (17E)
D-
D
Yield 99%, Z/E dr: 1:1. Compound 17Z: oil, [
a
]
D þ24.5 (c 0.31); IR
1727 cmꢂ1
;
1H NMR dH 3.64 (1H, dd, J¼10.7, 4.3 Hz), 3.68 (1H, dd,
H, 4.95. Found: C, 45.25; H, 5.02. Compound 10E: oil, [
a
]
þ44.1
J¼10.7, 6.0 Hz), 4.41 (1H, d, J¼11.7 Hz), 4.49 (1H, d, J¼12.0 Hz), 4.55
(1H, d, J¼12.0 Hz), 4.59 (1H, d, J¼11.7 Hz), 4.65 (1H, dd, J¼9.7,
D
(c 0.15); IR 1738 cmꢂ1 1H NMR dH 2.07 (3H, s), 2.08 (3H, s), 4.18
;
3
(1H, dd, J¼12.2, 6.5 Hz), 4.25 (1H, dd, J¼12.1, 3.9 Hz), 5.36 (1H,
ddd, J¼5.2, 5.2, 4.7 Hz), 5.48 (1H, dd, J¼8.3, 4.7 Hz), 5.93 (1H, dd,
J¼13.4, 8.3 Hz), 6.42 (1H, dd, J¼13.5, 0.8 Hz), 8.09 (1H, s); 13C
NMR (125.7 MHz) dC 20.6 (CH3), 20.8 (CH3), 61.4 (CH2), 70.3
(CH), 70.6 (CH), 125.8 (CH), 126.5 (CH), 159.6 (CH), 169.4 (C),
170.4 (C); MS m/z (rel intensity) 229 (MþꢂCl, 15), 81 (100);
HRMS m/z calcd for C10H13O6 229.0712, found 229.0713.
Anal. Calcd for C10H13ClO6: C, 45.38; H, 4.95. Found: C, 45.52; H,
5.02.
5.7 Hz), 4.90 (1H, ddd, JFH¼41.2 Hz, J¼9.7, 4.8 Hz), 5.30 (1H, ddd,
1
J 5.7, 5.7, 5.7 Hz), 6.70 (1H, dd, JFH¼84.0 Hz, J¼4.8 Hz), 7.26–7.35
¼
(10H, m), 8.11 (1H, s); 13C NMR dC 68.2 (CH2), 69.5 (CH, 3JFC¼5.4 Hz),
2
70.8 (CH2), 73.1 (CH), 73.3 (CH2), 108.0 (CH, JFC¼3.2 Hz), 127.67
(2ꢃCH), 127.74 (2ꢃCH), 127.8 (2ꢃCH), 128.36 (2ꢃCH), 128.39
(2ꢃCH), 137.68 (C), 137.74 (C), 151.3 (CH, 1JFC¼264.4 Hz), 160.4 (CH);
2
3
19F NMR dF ꢂ123.9 (dd, JFH¼82.6 Hz, JFH¼41.3 Hz); MS m/z (rel
intensity) 344 (Mþ, <1), 253 (<1),165 (3), 91 (100); HRMS m/z calcd
for C20H21FO4 344.1424, found 344.1413. Anal. Calcd for C20H21FO4:
C, 69.75; H, 6.15. Found: C, 69.82; H, 6.31. Compound 17E: oil, [a]
D
4.4.3. (Z)-3,5-Di-O-acetyl-1-bromo-1,2-dideoxy-4-O-formyl-
erythro-pent-1-enitol (11Z) and (E)-3,5-di-O-acetyl-1-bromo-1,2-
dideoxy-4-O-formyl- -erythro-pent-1-enitol (11E)
D
-
þ18.4 (c 0.51); IR 1727 cmꢂ1
;
1H NMR dH 3.63 (1H, dd, J¼10.6,
4.3 Hz), 3.70 (1H, dd, J¼10.6, 5.5 Hz), 4.02 (1H, dd, J¼9.5, 5.8 Hz),
4.37 (1H, d, J¼11.8 Hz), 4.50 (1H, d, J¼12.1 Hz), 4.52 (1H, d,
J¼12.0 Hz), 4.60 (1H, d, J¼11.8 Hz), 5.24 (1H, ddd, J¼5.8, 5.8, 5.8 Hz),
D
Yield with CrCl2 96%, Z/E dr: 3:2. Yield with Sml2 72%, Z/E dr:
3
5:1. Compound 11Z: oil, [
a
]
ꢂ1.7 (c 0.24); IR 1735 cmꢂ1
;
1H
5.35 (1H, ddd, JFH¼17.1 Hz, J¼11.3, 9.5 Hz), 6.63 (1H, dd,
D
NMR dH 2.06 (3H, s), 2.07 (3H, s), 4.17 (1H, dd, J¼12.2, 7.4 Hz),
4.26 (1H, dd, J¼12.2, 4.0 Hz), 5.50 (1H, ddd, J¼7.6, 4.0, 4.0 Hz),
5.91 (1H, dd, J¼8.6, 4.0 Hz), 6.18 (1H, dd, J¼8.6, 7.7 Hz), 6.54 (1H,
d, J¼7.7 Hz), 8.10 (1H, s); 13C NMR dC 20.6 (CH3), 20.7 (CH3), 61.6
(CH2), 70.2 (CH), 70.5 (CH), 114.0 (CH), 128.3 (CH), 159.7 (CH),
169.3 (C), 170.4 (C); MS m/z (rel intensity) 251/249 (MþꢂCH3CO2,
1JFH¼82.8 Hz, J¼11.3 Hz), 7.26–7.35 (10H, m), 8.09 (1H, s); 13C NMR
3
dC 67.8 (CH2), 70.3 (CH2), 72.8 (CH, JFC¼12.9 Hz), 73.1 (CH,
4JFC¼3.2 Hz), 73.4 (CH2),108.5 (CH, 2JFC¼8.6 Hz),127.7 (4ꢃCH),127.8
(2ꢃCH),128.5 (4ꢃCH),137.5 (C),137.6 (C),152.8 (CH, 1JFC¼264.4 Hz),
160.2 (CH); 19F NMR dF ꢂ121.8 (dd, 2JFH¼82.6 Hz, 3JFH¼18.4 Hz); MS
m/z (rel intensity) 344 (Mþ, <1), 253 (<1), 165 (3), 91 (100); HRMS
m/z calcd for C20H21FO4 344.1424, found 344.1427. Anal. Calcd for
C20H21FO4: C, 69.75; H, 6.15. Found: C, 70.04; H, 5.76.
29/25), 222/220 (15/16), 183 (29), 179/177 (39/39), 162/160 (11/
81
13), 141 (46), 81 (100); HRMS m/z calcd for C8H BrO4 250.9742,
10
found 250.9760. Anal. Calcd for C10H13BrO6: C, 38.86; H, 4.24.
Found: C, 38.90; H, 4.11. Compound 11E: oil, [
a
]
þ59.2 (c 1.14);
4.4.6. (Z)-3,5-Di-O-benzyl-1-choro-1,2-dideoxy-4-O-formyl-
erythro-pent-1-enitol (18Z) and (E)-3,5-di-O-benzyl-1-choro-1,2-
dideoxy-4-O-formyl- -erythro-pent-1-enitol (18E)
D-
D
IR 1734 cmꢂ1 1H NMR dH 2.07 (3H, s), 2.08 (3H, s), 4.19 (1H,
;
dd, J¼12.2, 6.6 Hz), 4.25 (1H, dd, J¼12.2, 3.9 Hz), 5.36 (1H, ddd,
J¼5.2, 5.2, 4.7 Hz), 5.45 (1H, dd, J¼8.0, 4.7 Hz), 6.21 (1H, dd,
J¼13.8, 8.0 Hz), 6.56 (1H, d, J¼13.8 Hz), 8.08 (1H, s); 13C NMR dC
20.6 (CH3), 20.8 (CH3), 61.4 (CH2), 70.4 (CH), 71.5 (CH), 113.3
(CH), 130.5 (CH), 159.6 (CH), 169.3 (C), 170.4 (C); MS m/z (rel
intensity) 251/249 (MþꢂCH3CO2, 5/5), 222 (15), 183 (26), 179/177
D
Yield 80%, Z/E dr: 2:1. Compound 18Z: oil, [
a
]
D þ0.9 (c 0.22); IR
1728 cmꢂ1
;
1H NMR dH 3.65 (1H, dd, J¼10.8, 4.1 Hz), 3.68 (1H, dd,
J¼10.8, 6.3 Hz), 4.44 (1H, d, J¼12.1 Hz), 4.49 (1H, d, J¼12.1 Hz), 4.56
(1H, d, J¼11.7 Hz), 4.58 (1H, d, J¼11.7 Hz), 4.72 (1H, dd, J¼9.0,
5.4 Hz), 5.34 (1H, ddd, J¼5.4, 5.4, 5.4 Hz), 5.83 (1H, dd, J¼9.0,
7.2 Hz), 6.38 (1H, d, J¼7.2 Hz), 7.27–7.35 (10H, m), 8.10 (1H, s); 13C
NMR (125.7 MHz) dC 68.2 (CH2), 71.0 (CH2), 72.6 (CH), 73.0 (CH),
73.3 (CH2), 123.8 (CH), 127.6–128.4 (10ꢃCH), 128.4 (CH), 137.66 (C),
(30/32), 163/161 (13/13), 141 (43), 81 (100), HRMS m/z calcd for
81
C8H BrO4 250.9742, found 250.9780. Anal. Calcd for C10H13BrO6:
10
C, 38.86; H, 4.24. Found: C, 38.89; H, 4.13.

10710
E.I. Leo´n et al. / Tetrahedron 64 (2008) 10706–10713
137.73 (C), 160.3 (CH); MS m/z (rel intensity) 271/269 (MþꢂBn, <1/
J¼7.8, 5.7 Hz), 4.40 (1H, d, J¼11.8 Hz), 4.50 (2H, s), 4.60 (1H, d,
J¼11.7 Hz), 5.21 (1H, ddd, J¼5.7, 5.6, 4.2 Hz), 6.43 (1H, d, J¼14.6 Hz),
6.52 (1H, dd, J¼14.6, 7.8 Hz), 7.27–7.35 (10H, m), 8.07 (1H, s); 13C
NMR (125.7 MHz) dC 67.6 (CH2), 71.0 (CH2), 72.5 (CH), 73.3 (CH2),
72.4 (CH), 81.5 (CH), 127.5–128.4 (10ꢃCH), 137.7 (2ꢃC), 142.1 (CH),
160.2 (CH); MS m/z (rel intensity) 361 (MþꢂBn, <1), 325 (<1), 273
(18), 91 (100). HRMS m/z calcd for C13H14IO4 360.9937, found
360.9953. Anal. Calcd for C20H21IO4: C, 53.11; H, 4.68. Found: C,
53.28; H, 4.88.
37
<1), 183/181 (1/2), 91 (100); HRMS m/z calcd for C13
H ClO4
14
271.0551, found 271.0557. Anal. Calcd for C20H21ClO4: C, 66.65; H,
5.88. Found: C, 66.55; H, 6.04. Compound 18E: oil, [
a
]
þ29.8 (c
D
0.28); IR 1727 cmꢂ1
;
1H NMR dH 3.63 (1H, dd, J¼10.6, 4.3 Hz), 3.70
(1H, dd, J¼10.8, 5.8 Hz), 4.11 (1H, dd, J¼8.7, 5.9 Hz), 4.22 (1H, d,
J¼11.7 Hz), 4.50 (1H, d, J¼12.1 Hz), 4.53 (1H, d, J¼12.1 Hz), 4.60 (1H,
d, J¼11.7 Hz), 5.22 (1H, ddd, J¼5.4, 5.4, 5.4 Hz), 5.90 (1H, dd, J¼13.5,
8.6 Hz), 6.24 (1H, d, J¼13.5 Hz), 7.27–7.35 (10H, m), 8.08 (1H, s); 13C
NMR (125.7 MHz) dC 67.7 (CH2), 70.9 (CH2), 72.9 (CH), 73.3 (CH2),
76.1 (CH), 123.4 (CH), 127.7–128.4 (10ꢃCH), 129.8 (CH), 137.4 (C),
4.4.9. (Z)-5-O-Acetyl-1,2-dideoxy-1-fluoro-4-O-formyl-3-O-
137.6 (C), 160.2 (CH); MS m/z (rel intensity) 271/269 (MþꢂC7H7,<1/
(2,3,4,6-tetra-O-acetyl-b-D-galactopyranosyl)-D-erythro-pent-
37
<1), 183/181 (1/2), 91 (100); HRMS m/z calcd for C13
H ClO4
14
1-enitol (25Z) and (E)-5-O-acetyl-1,2-dideoxy-1-fluoro-4-O-
271.0551, found 271.0548. Anal. Calcd for C20H21ClO4: C, 66.65; H,
5.88. Found: C, 66.72; H, 5.97.
formyl-3-O-(2,3,4,6-tetra-O-acetyl-b-D-galactopyranosyl)-D-
erythro-pent-1-enitol (25E)
Yield 79%, Z/E dr: 3:1. Compound 25Z: crystalline solid, mp
121.5–122.2 ꢀC (from n-hexane–EtOAc); [
þ9.2 (c 0.62); IR
1749 cmꢂ1 1H NMR dH 1.97 (3H, s), 2.03 (3H, s), 2.06 (3H, s), 2.07
4.4.7. (Z)-3,5-Di-O-benzyl-1-bromo-1,2-dideoxy-4-O-formyl-
erythro-pent-1-enitol (19Z) and (E)-3,5-di-O-benzyl-1-bromo-1,2-
dideoxy-4-O-formyl- -erythro-pent-1-enitol (19E)
D
-
a]
D
;
D
(3H, s), 2.14 (3H, s), 3.89 (1H, ddd, J¼6.7, 6.7, 0.6 Hz), 4.06 (1H, dd,
J¼12.1, 7.1 Hz), 4.08 (1H, dd, J¼11.6, 4.1 Hz), 4.13 (1H, dd, J¼11.3,
6.9 Hz), 4.35 (1H, dd, J¼12.1, 3.3 Hz), 4.58 (1H, d, J¼8.0 Hz), 4.78
(1H, dd, J¼9.2, 5.3 Hz), 5.00 (1H, dd, J¼10.5, 3.4 Hz), 5.04 (1H, ddd,
3JFH¼39.9 Hz, J¼9.2, 4.3 Hz), 5.18 (1H, dd, J¼10.5, 8.0 Hz), 5.29 (1H,
Yield 81%, Z/E dr: 7:3. Compound 19Z. The isolated vinyl bro-
mide was contaminated with ca. 8% of vinyl iodide 20Z that could
not be completely removed by chromatography, nevertheless
a small analytical sample was obtained. Oil, IR 1727 cmꢂ1; 1H NMR
dH 3.66 (1H, dd, J¼10.6, 4.4 Hz), 3.69 (1H, dd, J¼10.5, 5.9 Hz), 4.51
(1H, d, J¼11.6 Hz), 4.56 (1H, d, J¼11.8 Hz), 4.63 (1H, d, J¼11.8 Hz),
4.66 (1H, d, J¼11.6 Hz), 4.72 (1H, dd, J¼8.9, 5.5 Hz), 5.41 (1H, ddd,
J¼5.5, 5.0, 4.4 Hz), 6.24 (1H, dd, J¼8.8, 7.4 Hz), 6.61 (1H, d, J¼7.3 Hz),
7.32–7.41 (10H, m), 8.17 (1H, s); 13C NMR (125.7 MHz) dC 68.1 (CH2),
71.0 (CH2), 72.9 (CH), 73.3 (CH2), 75.0 (CH), 113.4 (CH), 127.6–128.4
(10ꢃCH), 131.5 (CH), 137.6 (C), 137.7 (C), 160.3 (CH); MS m/z (rel
intensity) 325 (MþꢂBr, <1), 315/313 (<1/<1), 227/225 (1/1), 91
(100); HRMS m/z calcd for C20H21O4 325.1440, found 325.1431. Anal.
Calcd for C20H21BrO4: C, 59.27; H, 5.22. Found: C, 59.25; H, 5.57.
Compound 19E. The isolated vinyl bromide was contaminated with
ca. 3% of vinyl iodide 20E that could not be completely removed by
2
m), 5.37 (1H, dd, J¼3.4, 0.6 Hz), 6.55 (1H, dd, JFH¼83.1 Hz,
J¼4.8 Hz), 8.05 (1H, s); 13C NMR dC 20.5 (CH3), 20.55 (CH3), 20.62
(CH3), 20.64 (CH3), 20.7 (CH3), 61.3 (CH2), 61.8 (CH2), 67.0 (CH), 68.7
4
(CH), 70.8 (CH), 71.0 (CH), 71.4 (CH, JFC¼2.2 Hz), 72.1 (CH,
2
3JFC¼6.4 Hz), 102.0 (CH), 108.3 (CH, JFC¼2.1 Hz), 150.2 (CH,
1JFC¼264.4 Hz), 159.7 (CH), 169.4 (C), 170.1 (C), 170.2 (C), 170.37 (C),
170.42 (C); 19F NMR dF ꢂ123.7 (dd, 2JFH¼82.6 Hz, 3JFH¼36.7 Hz); MS
m/z (rel intensity) 491 (MþꢂOCHO, <1), 476 (<1), 348 (<1), 331
(19), 189 (100); HRMS m/z calcd for C21H28FO12 491.1565, found
491.1560. Anal. Calcd for C22H29FO14: C, 49.26; H, 5.45. Found: C,
49.40; H, 5.32. Compound 25E: oil, [
a
]
D þ5.7 (c 0.14); IR 1736 cmꢂ1
;
1H NMR dH 1.98 (3H, s), 2.05 (3H, s), 2.06 (3H, s), 2.07 (3H, s), 2.16
(3H, s), 3.88 (1H, ddd, J¼6.8, 6.8, 0.5 Hz), 4.09 (1H, dd, J¼11.7,
6.0 Hz), 4.09 (1H, dd, J¼11.7, 6.0 Hz), 4.14 (1H, dd, J¼11.4, 7.2 Hz),
4.24 (1H, dd, J¼8.3, 5.2 Hz), 4.38 (1H, dd, J¼12.2, 3.1 Hz), 4.55 (1H, d,
J¼7.7 Hz), 5.01 (1H, dd, J¼10.5, 3.5 Hz), 5.20 (1H, dd, J¼10.5, 7.9 Hz),
5.22 (1H, m), 5.37 (1H, dd, J¼3.5, 0.5 Hz), 5.48 (1H, ddd,
3JFH¼16.8 Hz, J¼11.2, 8.3 Hz), 6.75 (1H, dd, 1JFH¼82.0 Hz, J¼11.2 Hz),
8.06 (1H, s); 13C NMR dC 20.5 (2ꢃCH3), 20.6 (2ꢃCH3), 20.7 (CH3),
61.5 (CH2), 61.6 (CH2), 67.0 (CH), 68.7 (CH), 70.7 (CH), 71.0 (CH), 71.8
chromatography, nevertheless
a small analytical sample was
obtained. Oil, IR 1727 cmꢂ1
;
1H NMR dH 3.63 (1H, dd, J¼10.6,
4.3 Hz), 3.70 (1H, dd, J¼10.6, 5.5 Hz), 4.09 (1H, dd, J¼8.3, 5.7 Hz),
4.39 (1H, d, J¼11.8 Hz), 4.49 (1H, d, J¼12.1 Hz), 4.52 (1H, d,
J¼12.1 Hz), 4.60 (1H, d, J¼11.7 Hz), 5.22 (1H, ddd, J¼5.2, 5.2, 5.2 Hz),
6.33 (1H, dd, J¼13.7, 8.3 Hz), 6.36 (1H, d, J¼13.7 Hz), 7.26–7.35 (10H,
m), 8.08 (1H, s); 13C NMR (125.7 MHz) dC 67.7 (CH2), 71.0 (CH2), 72.6
(CH), 73.3 (CH2), 77.4 (CH), 110.9 (CH), 127.7–128.4 (10ꢃCH), 133.9
(CH), 137.3 (C), 137.6 (C), 160.2 (CH); MS m/z (rel intensity) 325
(MþꢂBr, <1), 315/313 (<1/<1), 227/225 (2/2), 91 (100); HRMS m/z
calcd for C20H21O4 325.1440, found 325.1451. Anal. Calcd for
C20H21BrO4: C, 59.27; H, 5.22. Found: C, 59.21; H, 5.55.
4
3
(CH, JFC¼3.2 Hz), 75.6 (CH, JFC¼12.9 Hz), 101.3 (CH), 108.9 (CH,
2JFC¼12.9 Hz), 152.7 (CH, 1JFC¼264.4 Hz), 159.6 (CH), 169.4 (C), 170.1
(C), 170.2 (C), 170.4 (C), 170.5 (C); 19F NMR dF ꢂ122.4 (dd,
2JFH¼82.6 Hz, 3JFH¼13.8 Hz); MS m/z (rel intensity) 491 (MþꢂOCHO,
<1), 476 (<1), 431 (<1), 331 (31), 189 (100); HRMS m/z calcd for
C21H28FO12 491.1565, found 491.1559. Anal. Calcd for C22H29FO14: C,
49.26; H, 5.45. Found: C, 49.32; H, 5.54.
4.4.8. (Z)-3,5-Di-O-benzyl-1,2-dideoxy-4-O-formyl-1-iodo-
erythro-pent-1-enitol (20Z) and (E)-3,5-di-O-benzyl-1,2-dideoxy-4-
O-formyl-1-iodo- -erythro-pent-1-enitol (20E)
D-
D
Yield 81%, Z/E dr: 3:1. Compound 20Z: oil, [
a
]
D ꢂ15.8 (c 2.12); IR
4.4.10. (Z)-5-O-Acetyl-1-chloro-1,2-dideoxy-4-O-formyl-3-O-
1727 cmꢂ1
;
1H NMR dH 3.66 (1H, dd, J¼10.4, 6.4 Hz), 3.70 (1H, dd,
(2,3,4,6-tetra-O-acetyl-b-D-galactopyranosyl)-D-erythro-pent-1-
J¼10.6, 5.8 Hz), 4.45 (1H, d, J¼11.8 Hz), 4.47 (1H, dd, J¼8.6, 5.9 Hz),
4.50 (1H, d, J¼12.1 Hz), 4.58 (1H, d, J¼12.1 Hz), 4.59 (1H, d,
J¼11.8 Hz), 5.35 (1H, ddd, J¼5.3, 5.3, 5.3 Hz), 6.28 (1H, dd, J¼8.0,
8.0 Hz), 6.69 (1H, d, J¼8.0 Hz), 7.28–7.35 (10H, m), 8.10 (1H, s); 13C
NMR (125.7 MHz) dC 68.1 (CH2), 71.0 (CH2), 72.8 (CH), 73.3 (CH2),
79.2 (CH), 87.8 (CH), 127.6–128.4 (10ꢃCH), 137.5 (CH), 137.6 (C),
137.7 (C), 160.3 (CH); MS m/z (rel intensity) 361 (MþꢂBn, <1), 325
(<1), 273 (5), 91 (100); HRMS m/z calcd for C13H14IO4 360.9937,
found 360.9946. Anal. Calcd for C20H21IO4: C, 53.11; H, 4.68. Found:
C, 53.42; H, 4.87. Compound 20E. The material isolated was con-
taminated with ca. 20% of the isomer 20Z that could not be re-
enitol (26Z) and (E)-5-O-acetyl-1-chloro-1,2-dideoxy-1-fluoro-4-O-
formyl-3-O-(2,3,4,6-tetra-O-acetyl-b-D-galactopyranosyl)-D-
erythro-pent-1-enitol (26E)
Yield 81%, Z/E dr: 2:1. Compound 26Z: oil, [
a
]
D
ꢂ11.7 (c 1.03);
IR 1747 cmꢂ1 1H NMR dH 1.97 (3H, s), 2.03 (3H, s), 2.06 (3H, s),
;
2.07 (3H, s), 2.13 (3H, s), 3.89 (1H, dd, J¼6.7, 6.3 Hz), 4.06 (1H,
dd, J¼12.2, 7.2 Hz), 4.07 (1H, dd, J¼6.5 Hz, not observed), 4.10
(1H, dd, J¼11.1, 6.9 Hz), 4.34 (1H, dd, J¼12.1, 3.1 Hz), 4.58 (1H, d,
J¼8.1 Hz), 4.83 (1H, dd, J¼8.5, 4.9 Hz), 5.00 (1H, dd, J¼10.8,
3.6 Hz), 5.18 (1H, dd, J¼10.8, 8.1 Hz), 5.33 (1H, m), 5.37 (1H, d,
J¼3.1 Hz), 5.96 (1H, dd, J¼8.5, 7.2 Hz), 6.26 (1H, d, J¼7.2 Hz), 8.05
(1H, s); 13C NMR (125.7 MHz) dC 20.5 (CH3), 20.6 (2ꢃCH3), 20.7
(2ꢃCH3), 61.3 (CH2), 61.8 (CH2), 66.9 (CH), 68.7 (CH), 70.7 (CH),
moved chromatographically. Oil, IR 1728 cmꢂ1
(1H, dd, J¼10.6, 4.2 Hz), 3.69 (1H, dd, J¼10.6, 5.6 Hz), 4.06 (1H, dd,
;
1H NMR dH 3.62

E.I. Leo´n et al. / Tetrahedron 64 (2008) 10706–10713
10711
71.1 (CH), 71.2 (CH), 75.3 (CH), 102.1 (CH), 122.3 (CH), 128.0 (CH),
O-(2,3,4,6-tetra-O-acetyl-
enitol (28E)
Yield 93%, Z/E dr: 3:2. Compound 28Z: crystalline solid, mp
99.6–101.6 ꢀC (from n-hexane–EtOAc); [
D ꢂ20.9 (c 1.85); IR (neat)
1747 cmꢂ1 1H NMR dH 1.97 (3H, s), 2.04 (3H, s), 2.07 (3H, s), 2.08
b-D-galactopyranosyl)-D-erythro-pent-1-
159.6 (CH), 169.4 (C), 170.0 (C), 170.2 (C), 170.35 (C), 170.39 (C);
MS (FAB) m/z (rel intensity) 577/575 (MþþNa, 4/10), 331 (65),
37
207/205 (7/20); HRMS m/z calcd for C22
H
ClNaO14 577.1114,
a]
29
found 577.1093. Anal. Calcd for C22H29ClO14: C, 47.79; H, 5.29.
Found: C, 47.52; H, 5.66. Compound 26E. The material isolated
was contaminated with ca. 15% starting material 22 that could
not be completely removed by chromatography, nevertheless
;
(3H, s), 2.14 (3H, s), 3.90 (1H, dd, J¼6.9, 6.5 Hz), 4.07 (1H, dd, J¼12.1,
7.2 Hz), 4.106 (1H, d, J¼6.9 Hz), 4.11 (1H, d, J¼6.9 Hz), 4.34 (1H, dd,
J¼12.1, 3.3 Hz), 4.58 (1H, dd, J¼8.5, 5.2 Hz), 4.61 (1H, d, J¼8.0 Hz),
5.01 (1H, dd, J¼10.5, 3.4 Hz), 5.18 (1H, dd, J¼10.5, 7.9 Hz), 5.34 (1H,
ddd, J¼7.2, 5.2, 3.3 Hz), 5.37 (1H, d, J¼3.4 Hz), 6.36 (1H, dd, J¼8.2,
8.1 Hz), 6.57 (1H, d, J¼7.9 Hz), 8.05 (1H, s); 13C NMR (125.7 MHz) dC
20.5 (CH3), 20.7 (4ꢃCH3), 61.2 (CH2), 61.7 (CH2), 66.9 (CH), 68.7
(CH), 70.7 (CH), 71.1 (2ꢃCH), 82.1 (CH), 86.4 (CH), 102.1 (CH), 137.0
(CH), 159.5 (CH), 169.4 (C), 170.1 (C), 170.2 (C), 170.3 (C), 170.4 (C);
MS (FAB) m/z (rel intensity) 667 (MþþNa, 2), 331 (23), 297 (18);
HRMS m/z calcd for C22H29INaO14 667.0500, found 677.0494. Anal.
Calcd for C22H29IO14: C, 41.01; H, 4.54. Found: C, 41.15; H, 4.47.
a
small analytical sample was obtained. Oil, IR (CHCl3)
1751 cmꢂ1 1H NMR dH 1.98 (3H, s), 2.050 (3H, s), 2.055 (3H, s),
;
2.07 (3H, s), 2.16 (3H, s), 3.87 (1H, dd, J¼6.5, 6.4 Hz), 4.03 (1H,
m), 4.106 (1H, d, J¼6.4 Hz), 4.109 (1H, d, J¼6.7 Hz), 4.31 (1H, dd,
J¼6.0, 6.0 Hz), 4.35 (1H, dd, J¼12.3, 3.2 Hz), 4.55 (1H, d,
J¼8.1 Hz), 5.00 (1H, dd, J¼10.6, 3.5 Hz), 5.19 (1H, dd, J¼10.7,
7.9 Hz), 5.22 (1H, m), 5.37 (1H, d, J¼3.2 Hz), 5.97 (1H, dd, J¼13.3,
7.4 Hz), 6.36 (1H, dd, J¼13.3, 1.1 Hz), 8.06 (1H, s); 13C NMR
(125.7 MHz) dC 20.5 (CH3), 20.6 (4ꢃCH3), 61.4 (2ꢃCH2), 67.0
(CH), 68.7 (CH), 70.7 (CH), 71.0 (CH), 71.7 (CH), 78.3 (CH), 101.5
(CH), 123.6 (CH), 128.9 (CH), 159.6 (CH), 169.3 (C), 170.0 (C),
170.2 (C), 170.4 (2ꢃC); MS (FAB) m/z (rel intensity) 555/553
Compound 28E: oil, [
a]
þ20 (c 0.09); IR 1749 cmꢂ1
;
1H NMR dH
D
1.98 (3H, s), 2.06 (3H, s), 2.07 (3H, s), 2.08 (3H, s), 2.17 (3H, s), 3.72
(1H, dd, J¼6.7, 6.0 Hz), 4.09 (1H, dd, J¼12.1, 7.1 Hz), 4.11 (2H, d,
J¼6.6 Hz), 4.26 (1H, dd, J¼4.7, 4.7 Hz), 4.33 (1H, dd, J¼12.3, 3.1 Hz),
4.56 (1H, d, J¼7.8 Hz), 5.00 (1H, dd, J¼10.5, 3.4 Hz), 5.20 (1H, dd,
J¼10.3, 7.9 Hz), 5.22 (1H, ddd, J¼7.9, 4.7, 3.1 Hz), 5.37 (1H, d,
J¼3.3 Hz), 6.58 (1H, d, J¼4.6 Hz), 6.59 (1H, s), 8.06 (1H, s); 13C NMR
(125.7 MHz) dC 20.5 (CH3), 20.7 (3ꢃCH3), 20.8 (CH3), 61.3 (CH2), 61.4
(CH2), 66.9 (CH), 68.7 (CH), 70.7 (CH), 70.9 (CH), 71.3 (CH), 81.5
(CH), 81.6 (CH), 101.6 (CH), 140.8 (CH), 159.6 (CH), 169.4 (C), 170.1
(C), 170.2 (C), 170.4 (2ꢃC); MS m/z (rel intensity) 644 (Mþ, <1), 584
(<1), 297 (100); HRMS m/z calcd for C22H29IO14 644.0602, found
644.0577. Anal. Calcd for C22H29IO14: C, 41.01; H, 4.54. Found: C,
41.36; H, 4.33.
(MþþH, 1/2), 331 (2), 207/205 (16/6); HRMS m/z calcd for
37
C22
H ClO14 555.1295, found 555.1292. Anal. Calcd for
30
C22H29ClO14: C, 47.79; H, 5.29. Found: C, 47.67; H, 5.60.
4.4.11. (Z)-5-O-Acetyl-1-bromo-1,2-dideoxy-4-O-formyl-3-O-
(2,3,4,6-tetra-O-acetyl-
b-D-galactopyranosyl)-D-erythro-pent-
1-enitol (27Z) and (E)-5-O-acetyl-1-bromo-1,2-dideoxy-4-O-
formyl-3-O-(2,3,4,6-tetra-O-acetyl-b-D-galactopyranosyl)-D-
erythro-pent-1-enitol (27E)
Yield 92%, Z/E dr: 4:1. Compound 27Z. The isolated vinyl bro-
mide was contaminated with ca. 11% of vinyl iodide 28Z that could
not be completely removed by chromatography, nevertheless
a small analytical sample was obtained. Oil, IR 1747 cmꢂ1; 1H NMR
dH 1.97 (3H, s), 2.03 (3H, s), 2.05 (3H, s), 2.07 (3H, s), 2.13 (3H, s),
3.89 (1H, dd, J¼6.5, 6.5 Hz), 4.07 (1H, dd, J¼11.9, 7.3 Hz), 4.10 (1H, d,
J¼7.2 Hz), 4.11 (1H, d, J¼7.3 Hz), 3.84 (1H, dd, J¼12.1, 3.3 Hz), 4.59
(1H, d, J¼8.0 Hz), 4.56 (1H, dd, J¼8.4, 5.0 Hz), 5.0 (1H, dd, J¼10.5,
3.3 Hz), 5.18 (1H, dd, J¼10.3, 8.0 Hz), 5.34 (1H, ddd, J¼7.6, 4.2,
4.2 Hz), 5.36 (1H, d, J¼3.5 Hz), 6.26 (1H, dd, J¼8.6, 7.4 Hz), 6.42 (1H,
d, J¼7.3 Hz), 8.05 (1H, s); 13C NMR (125.7 MHz) dC 20.5 (CH3), 20.6
(4ꢃCH3), 61.2 (CH2), 61.7 (CH2), 66.9 (CH), 68.7 (CH), 70.7 (CH),
71.08 (2ꢃCH), 77.7 (CH), 102.1 (CH), 111.8 (CH), 131.1 (CH), 159.6
(CH), 169.4 (C), 170.0 (C), 170.1 (C), 170.3 (C), 170.4 (C); MS (FAB) m/z
4.4.13. (Z)-3,5-Di-O-acetyl-1,2-dideoxy-1-fluoro-4-O-formyl-
threo-pent-1-enitol (33Z) and (E)-3,5-di-O-acetyl-1,2-dideoxy-1-
fluoro-4-O-formyl- -threo-pent-1-enitol (33E)
D-
D
Yield 84%, Z/E dr: 1:1. Compound 33Z: oil, [
a
]
D þ140.7 (c 0.17); IR
1744 cmꢂ1
;
1H NMR dH 2.06 (6H, s), 4.12 (1H, dd, J¼12.2, 6.4 Hz),
3
4.33 (1H, dd, J¼12.2, 3.6 Hz), 4.85 (1H, ddd, JFH¼39.3 Hz, J¼9.0,
4.9 Hz), 5.37 (1H, ddd, J¼6.4, 6.4, 3.6 Hz), 5.95 (1H, dd, J¼9.0,
6.4 Hz), 6.57 (1H, dd, 2JFH¼81.8 Hz, J¼4.9 Hz), 8.11 (1H, s); 13C NMR
3
dC 20.6 (CH3), 20.8 (CH3), 61.9 (CH2), 64.8 (CH, JFC¼4.6 Hz), 70.9
(CH, 4JFC¼1.8 Hz), 105.8 (CH, 2JFC¼2.0 Hz), 151.1 (CH, 1JFC¼268.8 Hz),
159.8 (CH), 169.4 (C), 170.4 (C); 19F NMR dF ꢂ119.1 (dd, 2JFH¼82.8 Hz,
3JFH¼41.1 Hz); MS m/z (rel intensity) 247 (MþꢂH, <1), 203 (13), 189
(7), 160 (30), 130 (34), 117 (100); HRMS m/z calcd for C10H12FO6
247.0618, found 247.0625. Anal. Calcd for C10H13FO6: C, 48.39; H,
(rel intensity) 620/618 (MþþNaꢂH, 5/5), 539/537 (1/1), 331 (100),
81
251/249 (26/26); HRMS m/z calcd for C22
H BrNaO14 620.0540,
28
found 620.0547. Anal. Calcd for C22H29BrO14: C, 44.23; H, 4.89.
Found: C, 44.13; H, 5.07. Compound 27E. The isolated vinyl bromide
was contaminated with ca. 8% of vinyl iodide 28E that could not be
completely removed by chromatography, nevertheless a small an-
5.28. Found: C, 48.10; H, 5.59. Compound 33E: oil, [
a
]
D þ17.3 (c 1.8);
IR 1736 cmꢂ1 1H NMR dH 2.05 (3H, s), 2.06 (3H, s), 4.05 (1H, dd,
;
J¼12.1, 6.3 Hz), 4.37 (1H, dd, J¼12.1, 3.9 Hz), 5.35 (2H, m), 5.47 (1H,
alytical sample was obtained. Oil, IR 1749 cmꢂ1
;
1H NMR dH 1.98
dd, J¼9.3, 6.1 Hz), 6.84 (1H, dd, JFH¼81.4 Hz, J¼11.1 Hz), 8.10 (1H,
2
(3H, s), 2.06 (6H, s), 2.07 (3H, s), 2.16 (3H, s), 3.87 (1H, dd, J¼6.7,
6.7 Hz), 4.10 (1H, m), 4.110 (1H, d, J¼6.7 Hz), 4.113 (1H, d, J¼6.7 Hz),
4.28 (1H, dd, J¼6.1, 5.7 Hz), 4.34 (1H, dd, J¼12.6, 3.1 Hz), 4.56 (1H, d,
J¼8.0 Hz), 5.01 (1H, dd, J¼10.3, 3.4 Hz), 5.20 (1H, dd, J¼10.5, 7.8 Hz),
5.23 (1H, m), 5.37 (1H, d, J¼3.5 Hz), 6.25 (1H, dd, J¼13.4, 6.9 Hz),
6.50 (1H, s), 8.06 (1H, s); 13C NMR (125.7 MHz) dC 20.5 (CH3), 20.7
(4ꢃCH3), 61.3 (CH2), 61.4 (CH2), 66.9 (CH), 68.7 (CH), 70.6 (CH), 71.0
(CH), 71.4 (CH), 79.6 (CH), 101.5 (CH), 111.1 (CH), 132.9 (CH), 159.6
(CH), 169.4 (C), 170.0 (C), 170.2 (C), 170.4 (2ꢃC); 620/618
s); 13C NMR dC 20.6 (CH3), 20.9 (CH3), 61.7 (CH2), 67.4 (CH,
3JFC¼14.6 Hz), 70.8 (CH, 4JFC¼3.1 Hz), 106.4 (CH, 2JFC¼13.2 Hz), 154.6
1
(CH, JFC¼266.7 Hz), 159.7 (CH), 169.6 (C), 170.3 (C); 19F NMR dF
ꢂ119.6 (dd, 2JFH¼82.8 Hz, 3JFH¼15.1 Hz); MS m/z (rel intensity) 203
(MþꢂHCO2, 18), 189 (8), 160 (35), 130 (50), 117 (100); HRMS m/z
calcd for C9H12FO4 203.0720, found 203.0672. Anal. Calcd for
C10H13FO6: C, 48.39; H, 5.28. Found: C, 48.30; H, 5.56.
4.4.14. (Z)-3,5-Di-O-acetyl-1-chloro-1,2-dideoxy-4-O-formyl-
threo-pent-1-enitol (34Z) and (E)-3,5-di-O-acetyl-1-chloro-1,2-
dideoxy-4-O-formyl- -threo-pent-1-enitol (34E)
Yield 96%, Z/E dr: 1:1. Compound 34Z: oil, [
D-
(MþþNaꢂH, 4/4), 539/537 (1/1), 331 (100), 251/249 (17/17); HRMS
81
m/z calcd for C22
H
BrNaO14 620.0540, found 620.0547. Anal. Calcd
D
28
for C22H29BrO14: C, 44.29; H, 4.90. Found: C, 44.03; H, 5.23.
a
]D þ36.4 (c 0.40); IR
1737 cmꢂ1; 1H NMR dH 2.07 (3H, s), 2.08 (3H, s), 4.10 (1H, dd, J¼12.1,
6.7 Hz), 4.34 (1H, dd, J¼12.1, 4.1 Hz), 5.42 (1H, ddd, J¼5.8, 5.8,
3.6 Hz), 5.74 (1H, dd, J¼8.5, 7.6 Hz), 6.00 (1H, dd, J¼8.6, 5.9 Hz), 6.32
(1H, dd, J¼7.2, 0.9 Hz), 8.10 (1H, s); 13C NMR (125.7 MHz) dC 20.65
4.4.12. (Z)-5-O-Acetyl-1,2-dideoxy-4-O-formyl-1-iodo-3-O-
(2,3,4,6-tetra-O-acetyl-
b-D-galactopyranosyl)-D-erythro-pent-1-
enitol (28Z) and (E)-5-O-acetyl-1,2-dideoxy-4-O-formyl-1-iodo-3-

10712
E.I. Leo´n et al. / Tetrahedron 64 (2008) 10706–10713
(CH3), 20.7 (CH3), 61.8 (CH2), 67.7 (CH), 70.5 (CH), 124.3 (CH), 125.5
(CH), 159.7 (CH), 169.3 (C), 170.4 (C); MS m/z (rel intensity) 229
(MþꢂCl, 5), 103 (100), HRMS m/z calcd for C10H13O6 229.0746,
found 229.0740. Anal. Calcd for C10H13ClO6: C, 45.38; H, 4.95.
355.9770. Anal. Calcd for C10H13IO6: C, 33.73; H, 3.68. Found: C,
33.62; H, 3.67.
4.4.17. (Z)-3,5-O-Benzylidene-1,2-dideoxy-4-O-formyl-1-iodo-D-
Found: C, 45.41; H, 5.11. Compound 34E: oil, [
a
]
þ2.2 (c 0.27); IR
erythro-pent-1-enitol (40Z) and (E)-3,5-O-benzylidene-1,2-
D
1740 cmꢂ1; 1H NMR dH 2.07 (3H, s), 2.09 (3H, s), 4.05 (1H, dd, J¼12.1,
6.7 Hz), 4.36 (1H, dd, J¼12.2, 3.6 Hz), 5.33 (1H, ddd, J¼6.3, 5.9,
3.5 Hz), 5.52 (1H, dd, J¼7.7, 5.9 Hz), 5.87 (1H, dd, J¼13.5, 7.7 Hz),
6.42 (1H, d, J¼13.5 Hz), 8.10 (1H, s); 13C NMR (125.7 MHz) dC 20.6
(CH3), 20.8 (CH3), 61.7 (CH2), 70.0 (CH), 70.4 (CH), 125.7 (CH), 126.6
dideoxy-4-O-formyl-1-iodo-D-erythro-pent-1-enitol (40E)
Yield 91%, Z/E dr: 3:2. Compound 40Z: crystalline solid, mp
73.9–74.6 ꢀC (from n-hexane–AcOEt); [
a]
ꢂ60.5 (c 0.81); IR
D
1733 cmꢂ1
;
1H NMR dH 3.84 (1H, dd, J¼10.5, 10.5 Hz), 4.41 (1H,
dd, J¼10.8, 5.3 Hz), 4.65 (1H, dd, J¼8.9, 8.8 Hz), 5.14 (1H, ddd,
J¼9.9, 9.8, 5.6 Hz), 5.64 (1H, s), 6.36 (1H, dd, J¼8.0, 8.0 Hz), 6.66
(1H, d, J¼8.0 Hz), 7.38 (3H, m), 7.51 (2H, m), 8.04 (1H, s); 13C
NMR (125.7 MHz) dC 64.8 (CH), 67.7 (CH2), 81.1 (CH), 87.8 (CH),
101.2 (CH), 126.1 (2ꢃCH), 128.3 (2ꢃCH), 129.3 (CH), 136.8 (C),
140.5 (CH), 159.4 (CH); MS m/z (rel intensity) 360 (Mþ, <1), 314
(4), 233 (<1), 208 (7), 107 (100); HRMS m/z calcd for C13H13IO4
359.9859, found 359.9840. Anal. Calcd for C13H13IO4: C, 43.36; H,
3.64. Found: C, 43.55; H, 3.48. Compound 40E: crystalline solid,
(CH), 159.6 (CH), 169.4 (C), 170.3 (C); MS m/z (rel intensity) 266/264
37
(Mþ, <1/<1), 229 (8), 103 (100); HRMS m/z calcd for C10
H ClO6
13
266.0371, found 266.0341. Anal. Calcd for C10H13ClO6: C, 45.38; H,
4.95. Found: C, 45.31; H, 5.11.
4.4.15. (Z)-3,5-Di-O-acetyl-1-bromo-1,2-dideoxy-4-O-formyl-
threo-pent-1-enitol (35Z) and (E)-3,5-di-O-acetyl-1-bromo-1,2-
dideoxy-4-O-formyl- -threo-pent-1-enitol (35E)
D-
D
Yield 84%, Z/E dr: 3:2. Compound 35Z. The isolated vinyl
bromide was contaminated with ca. 4% of vinyl iodide 36Z that
could not be completely removed by chromatography, never-
mp 100.2–100.6 ꢀC (from n-hexane–AcOEt); [
a
]
þ11.6 (c 0.51);
D
IR 1735 cmꢂ1
;
1H NMR dH 3.70 (1H, dd, J¼10.5, 10.5 Hz), 4.28
(1H, dd, J¼9.6, 2.4 Hz), 4.44 (1H, dd, J¼10.8, 5.3 Hz), 4.93 (1H,
ddd, J¼10.0, 9.6, 5.4 Hz), 5.56 (1H, s), 6.63 (1H, d, J¼2.2 Hz), 6.64
(1H, s), 7.39 (3H, m), 7.49 (2H, m), 8.05 (1H, s); 13C NMR
(125.7 MHz) dC 65.7 (CH), 67.7 (CH2), 80.7 (CH), 81.8 (CH), 101.3
(CH), 126.2 (2ꢃCH), 128.3 (2ꢃCH), 129.4 (CH), 136.8 (C), 140.5
(CH), 159.3 (CH); MS m/z (rel intensity) 360 (Mþ, <1), 314 (4),
233 (<1), 208 (2), 107 (100); HRMS m/z calcd for C13H13IO4
359.9859, found 359.9845. Anal. Calcd for C13H13IO4: C, 43.36; H,
3.64. Found: C, 43.42; H, 3.53.
theless
a
small analytical sample was obtained. Oil, IR
1740 cmꢂ1
;
1H NMR dH 2.07 (3H, s), 2.08 (3H, s), 4.10 (1H, dd,
J¼12.1, 6.7 Hz), 4.34 (1H, dd, J¼12.1, 3.9 Hz), 5.44 (1H, m), 5.92
(1H, dd, J¼8.4, 5.7 Hz), 6.10 (1H, dd, J¼8.3, 7.6 Hz), 6.54 (1H, dd,
J¼7.5, 0.8 Hz), 8.10 (1H, s); 13C NMR dC 20.7 (CH3), 20.8 (CH3),
61.8 (CH2), 69.9 (CH), 70.4 (CH), 113.7 (CH), 128.7 (CH), 159.7
(CH), 169.3 (C), 170.4 (C); MS m/z (rel intensity) 229 (MþꢂBr, 1),
81 (100); HRMS m/z calcd for C10H13O6 229.0712, found
229.0691. Anal. Calcd for C10H13BrO6: C, 38.86; H, 4.24. Found: C,
38.81; H, 4.33. Compound 35E. The isolated vinyl bromide was
contaminated with ca. 3% of vinyl iodide 36Z that could not be
completely removed by chromatography, nevertheless a small
4.4.18. 5-O-[tert-Butyl(dimethyl)silyl]-1,2-dideoxy-4-O-formyl-1-
iodo-D-threo-pent-1-enitol (42EZ) and 5-O-[tert-butyl(dimethyl)
silyl]-1,2-dideoxy-3-O-formyl-1-iodo-D-threo-pent-1-enitol (43EZ)
analytical sample was obtained. Oil, IR 1736 cmꢂ1
;
1H NMR dH
Yield 85%, Z/E dr: 3:7, the four products were isolated as two
mixtures (42E, 43E and 42Z, 43Z) that could not be separated. In-
separable mixture of compounds 42E and 43E (71%, 68:32): IR 3611,
3468, 1727 cmꢂ1; MS m/z (rel intensity) 387 (MþþH, 5), 341 (3), 73
(100); HRMS m/z calcd for C12H23IO4Si 387.0489, found 387.0466.
Anal. Calcd for C12H23IO4Si: C, 37.31; H, 6.00. Found: C, 37.34; H, 6.04.
Compound 42E: 1H NMR dH ꢂ0.07 (3H, s), ꢂ0.06 (3H, s), 0.86 (9H, s),
2.06 (1H, br s), 3.47 (1H, dd, J¼11.0, 4.9 Hz), 3.57 (1H, dd, J¼11.0,
4.8 Hz), 3.99 (1H, dd, J¼4.6, 4.6 Hz), 4.76 (1H, ddd, J¼4.8, 4.8, 4.8 Hz),
6.24 (1H, d, J¼14.5 Hz), 6.36 (1H, dd, J¼14.4, 5.2 Hz), 7.50 (1H, s); 13C
NMR (125.7 MHz) dC ꢂ5.5 (2ꢃCH3), 18.3 (C), 25.9 (3ꢃCH3), 62.0
(CH2), 73.3 (CH), 74.6 (CH), 79.1 (CH), 144.3 (CH), 159.9 (CH). Com-
pound 43E: 1H NMR dH ꢂ0.07 (3H, s), ꢂ0.06 (3H, s), 0.86 (9H, s), 2.06
(1H, br s), 3.33 (2H, d, J¼4.2 Hz), 3.37 (1H, ddd, J¼6.3, 4.2, 4.2 Hz),
5.34 (1H, dd, J¼7.0, 6.3 Hz), 6.29 (1H, d, J¼14.6 Hz), 6.42 (1H, dd,
J¼14.6, 7.4 Hz), 7.46 (1H, s); 13C NMR (125.7 MHz) dC ꢂ5.5 (2ꢃCH3),
18.3 (C), 25.9 (3ꢃCH3), 63.2 (CH2), 72.1 (CH), 75.3 (CH), 82.5 (CH),
140.5 (CH), 159.4 (C). Inseparable mixture of compounds 42Z and
43Z (14%, 57:43): IR 3592, 3468, 1727 cmꢂ1; MS (FAB) m/z (rel in-
tensity) 409 (MþþNa, 1), 391 (4). Anal. Calcd for C12H23IO4Si: C,
37.31; H, 6.00. Found: C, 37.63; H, 5.71. Compound 42Z: 1H NMR dH
ꢂ0.05 to 0.10 (6H, s), 0.91 (9H, s), 2.86 (1H, d, J¼4.6 Hz), 3.89 (1H, dd,
J¼11.0, 3.7 Hz), 3.93 (1H, dd, J¼11.0, 5.0 Hz), 4.74 (1H, ddd, J¼7.8, 4.6,
3.4 Hz), 5.04 (1H, ddd, J¼4.9, 3.7, 3.4 Hz), 6.35 (1H, dd, J¼7.8, 7.8 Hz),
6.51 (1H, d, J¼7.8 Hz), 8.14 (1H, s); 13C NMR (125.7 MHz) dC ꢂ5.5 to
ꢂ5.4 (2ꢃCH3), 18.2 (C), 25.8 (3ꢃCH3), 62.4 (CH2), 74.0 (CH), 74.4
(CH), 84.7 (CH), 139.1 (CH), 160.4 (CH). Compound 43Z: 1H NMR dH
ꢂ0.05 to 0.10 (6H, s), 0.91 (9H, s), 2.50 (1H, d, J¼6.5 Hz), 3.67 (1H, dd,
J¼10.2, 5.9 Hz), 3.69 (1H, dd, J¼10.2, 4.8 Hz), 3.86 (1H, dddd, J¼6.5,
5.9, 4.8, 4.8 Hz), 5.68 (1H, dd, J¼8.3, 4.8 Hz), 6.42 (1H, dd, J¼8.2,
8.1 Hz), 6.65 (1H, d, J¼8.0 Hz), 8.12 (1H, s); 13C NMR (125.7 MHz) dC
ꢂ5.5 to ꢂ5.4 (2ꢃCH3), 18.2 (C), 25.8 (3ꢃCH3), 63.0 (CH2), 72.2 (CH),
76.2 (CH), 86.6 (CH), 136.2 (CH), 159.9 (C).
2.07 (3H, s), 2.10 (3H, s), 4.06 (1H, dd, J¼12.1, 6.4 Hz), 4.36 (1H,
dd, J¼12.1, 4.0 Hz), 5.33 (1H, ddd, J¼6.1, 6.1, 6.1 Hz), 5.49 (1H, dd,
J¼7.2, 6.1 Hz), 6.15 (1H, dd, J¼13.7, 7.6 Hz), 6.56 (1H, d,
J¼13.7 Hz), 8.10 (1H, s); 13C NMR (125.7 MHz) dC 20.6 (CH3), 20.8
(CH3), 61.6 (CH2), 70.1 (CH), 71.3 (CH), 113.2 (CH), 130.6 (CH),
159.5 (CH), 169.4 (C), 170.3 (C); MS m/z (rel intensity) 229
(MþꢂBr, 2), 81 (100); HRMS m/z calcd for C10H13O6 229.0712,
found 229.0681. Anal. Calcd for C10H13BrO6: C, 38.86; H, 4.24.
Found: C, 39.03; H, 4.35.
4.4.16. (Z)-3,5-Di-O-acetyl-1,2-dideoxy-4-O-formyl-1-iodo-
threo-pent-1-enitol (36Z) and (E)-3,5-di-O-acetyl-1,2-dideoxy-
4-O-formyl-1-iodo- -threo-pent-1-enitol (36E)
Yield 90%, Z/E dr: 1:1. Compound 36Z: crystalline solid, mp
45.9–47.5 ꢀC (from n-hexane–EtOAc);
þ51.6 (c 1.12); IR
1740 cmꢂ1 1H NMR dH 2.069 (3H, s), 2.072 (3H, s), 4.09 (1H, dd,
D-
D
[a]
D
;
J¼12.0, 6.7 Hz), 4.34 (1H, dd, J¼12.0, 3.9 Hz), 5.44 (1H, ddd, J¼6.7,
5.8, 3.9 Hz), 5.72 (1H, dd, J¼8.3, 5.8 Hz), 6.24 (1H, dd, J¼8.2, 8.2 Hz),
6.70 (1H, d, J¼8.0 Hz), 8.09 (1H, s); 13C NMR (125.7 MHz) dC 20.67
(CH3), 20.74 (CH3), 61.7 (CH2), 70.2 (CH), 74.1 (CH), 88.1 (CH), 134.7
(CH), 159.7 (C), 169.3 (C), 170.4 (C); MS m/z (rel intensity) 357
(MþþH, 3), 356 (Mþ, 1), 311 (15), 297 (80), 183 (100); HRMS m/z
calcd for C10H13IO6 355.9757, found 355.9794. Anal. Calcd for
C10H13IO6: C, 33.73; H, 3.68. Found: C, 33.86; H, 3.66. Compound
36E: oil, [
a
]
D ꢂ14.2 (c 0.94); IR 1739 cmꢂ1; 1H NMR dH 2.07 (3H, s),
2.10 (3H, s), 4.05 (1H, dd, J¼12.1, 6.3 Hz), 4.35 (1H, dd, J¼12.1,
4.0 Hz), 5.33 (1H, ddd, J¼6.3, 6.2, 4.0 Hz), 5.45 (1H, dd, J¼6.4,
6.2 Hz), 6.48 (1H, dd, J¼14.6, 7.0 Hz), 6.64 (1H, d, J¼14.6 Hz), 8.09
(1H, s). 13C NMR (125.7 MHz) dC 20.6 (CH3), 20.7 (CH3), 61.6 (CH2),
69.9 (CH), 73.0 (CH), 83.4 (CH), 138.4 (CH), 159.6 (CH), 169.3 (C),
170.3 (C); MS m/z (rel intensity) 356 (Mþ, 1), 310 (3), 297 (3), 229
(<1), 183 (100); HRMS m/z calcd for C10H13IO6 355.9757, found

E.I. Leo´n et al. / Tetrahedron 64 (2008) 10706–10713
10713
terscience: New York, NY, 2002; (d) Kohei, T.; Miyaura, N. Top. Curr. Chem.
2002, 219, 1–9.
3. (a) Barluenga, J.; Moriel, P.; Aznar, F.; Valde´s, C. Org. Lett. 2007, 9, 275–278; (b)
Delhi, J. R.; Legros, J.; Bolm, C. Chem. Commun. 2005, 973–986.
4. (a) Stanforth, S. P. In Comprehensive Organic Functional Group Transformations II;
Katritzky, A. R., Taylor, R. J., Eds.; Elsevier: Oxford, 2005; Vol. 2, p 561; (b) van
Steenis, J. H.; van der Gen, A. J. Chem. Soc., Perkin Trans. 1 2002, 2117–2133; (c)
Maryanoff, B. E. Chem. Rev. 1989, 89, 863–927.
5. (a) Kim, K.-M.; Park, I.-H. Synthesis 2004, 2641–2644; (b) Barluenga, J.; Campos,
P. J.; Gonza´lez, J. M.; Sua´rez, J. L. J. Org. Chem. 1991, 56, 2234–2237; (c) Bando-
dakar, B. S.; Nagendrappa, G. Synthesis 1990, 843–844; (d) Grattan, T. J.;
Whitehurst, J. S. J. Chem. Soc., Perkin Trans. 1 1990, 11–18; (e) Croft, A. P.; Bartsch,
R. A. J. Org. Chem. 1983, 48, 876–879; (f) Tremmling, M. J.; Hopper, S. P.; Men-
delowitz, P. L. J. Org. Chem. 1978, 43, 3076–3077; (g) Eckes, L.; Hanack, M. Syn-
thesis 1978, 217–219; (h) Strobach, D. R.; Boswell, G. A. J. Org. Chem.1971, 36, 818–
820; (i) Erickson, K. L.; Markstein, J.; Kim, K. J. Org. Chem. 1971, 36, 1024–1030; (j)
Hoff, M. C.; Greenlee, W.; Boord, C. E. J. Am. Chem. Soc. 1951, 73, 3329–3336.
6. (a) Dolbier, W. R., Jr.; Alty, A. C.; Phanstiel, O., IV. J. Am. Chem. Soc. 1987, 109,
3046–3050; (b) Daub, G. W.; Zuckermann, R. N.; Johnson, W. S. J. Org. Chem.
1985, 50, 1599–1602; (c) Bergmann, F.; Kalmus, A.; Breuer, E. J. Am. Chem. Soc.
1958, 40, 4540–4543.
4.4.19. (Z,E)-3-O-Acetyl-1,2-dideoxy-4-O-formyl-1-iodo-D-glycero-
tetra-1-enitol (45ZE)
Yield 86%, Z/E dr: 3:2. Inseparable mixture of compounds 45Z
and 45E: Oil, IR 1732 cmꢂ1; MS m/z (rel intensity) 284 (Mþ, 7), 238
(1), 225 (41), 196 (58), 111 (100); HRMS m/z calcd for C7H9IO4
283.9546, found 283.9565. Anal. Calcd for C7H9IO4: C, 29.60; H,
3.19. Found: C, 29.77; H, 3.16. Compound 45Z: 1H NMR dH 2.10 (3H,
s), 4.28 (1H, dd, J¼11.9, 6.2 Hz), 4.38 (1H, dd, J¼11.9, 3.6 Hz), 5.71
(1H, ddd, J¼7.9, 6.2, 3.6 Hz), 6.33 (1H, dd, J¼7.9, 7.9 Hz), 6.64 (1H, d,
J¼8.0 Hz), 8.08 (1H, s); 13C NMR (50.3 MHz) dC 20.8 (CH3), 62.9
(CH2), 74.0 (CH), 86.5 (CH), 135.5 (CH), 160.3 (CH), 169.7 (C). Com-
pound 45E: 1H NMR dH 2.10 (3H, s), 4.18 (1H, dd, J¼11.8, 6.5 Hz),
4.32 (1H, dd, J¼11.9, 4.0 Hz), 5.40 (1H, ddd, J¼6.6, 6.6, 3.9 Hz), 6.52
(1H, dd, J¼14.6, 6.7 Hz), 6.62 (1H, d, J¼14.6 Hz), 8.04 (1H, s); 13C
NMR (50.3 MHz) dC 20.8 (CH3), 63.1 (CH2), 72.6 (CH), 82.6 (CH),
139.2 (CH), 160.3 (CH), 169.7 (C).
7. (a) Concello´n, J. M.; Rodrı´guez-Solla, H. Chem. Soc. Rev. 2004, 33, 599–609; (b)
Concello´n, J. M.; Rodrı´guez-Solla, H.; Huerta, M.; Pe´rez-Andre´s, J. A. Eur. J. Org.
Acknowledgements
´
´
´
Chem. 2002, 1839–1847; (c) Concellon, J. M.; Bernard, P. L.; Perez-Andres, J. A.
Angew. Chem., Int. Ed. 1999, 38, 2384–2386.
8. (a) Ram, R. N.; Manjot, T. P. Org. Lett. 2008, 11, 2243–2246; (b) Bejot, R.; Tis-
serand, S.; Reddy, L. M.; Barma, D. K.; Baati, R.; Falck, J. R.; Mioskowski, C.
Angew. Chem., Int. Ed. 2005, 44, 2008–2011; (c) Nakagawa, M.; Saito, A.; Ya-
mamoto, N.; Taguchi, T. Tetrahedron Lett. 2005, 46, 5257–5261; (d) Baati, R.;
Barma, D. K.; Krishna, U. M.; Falck, J. R.; Mioskowski, C. Tetrahedron Lett. 2002,
43, 959–961; (e) Baati, R.; Barma, D. K.; Falck, J. R.; Mioskowski, C. J. Am. Chem.
Soc. 2001, 123, 9196–9197.
This work was supported by the Investigation Programmes nos.
´
CTQ2004-06381 and CTQ2007-67492/BQU of the Direccion Gen-
´
´
´
eral de Investigacion Cientıfica y Tecnica, Spain. C.R.-F. thanks the
´
´
Direccion General de Investigacion del Gobierno de Canarias for
a fellowship. N.R.P. thanks the Program I3P-CSIC for a fellowship.
The helpful suggestions of Professor Jose´ M. Concello´n (University
of Oviedo) regarding the SmI2 experiments are gratefully
acknowledged.
´
´
´
9. (a) Gonzalez, C. C.; Kennedy, A. R.; Leon, E. I.; Riesco-Fagundo, C.; Suarez, E.
Chem.dEur. J. 2003, 9, 5800–5809; (b) Gonza´lez, C. C.; Kennedy, A. R.; Leo´ n, E.
I.; Riesco-Fagundo, C.; Sua´rez. Tetrahedron Lett. 2003, 44, 6347–6350; (c)
´
´
´
Gonzalez, C. C.; Kennedy, A. R.; Leon, E. I.; Riesco-Fagundo, C.; Suarez, E. Angew.
Chem., Int. Ed. 2001, 113, 2388–2390.
´
´
10. Concellon, J. M.; Rodrıguez-Solla, H.; Bardales, E.; Huerta, M. Eur. J. Org. Chem.
2003, 1775–1778.
References and notes
11. (a) Fu¨rstner, A. Chem. Rev. 1999, 99, 991–1045; (b) Takai, K.; Kataoka, Y.; Okazoe,
T.; Utimoto, K. J. Am. Chem. Soc. 1987, 109, 951–953; (c) Takai, K.; Utimoto, K.;
Nitta, K. J. Am. Chem. Soc. 1986, 108, 7408–7410.
12. (a) Takai, K.; Kokumai, R.; Nobunaka, T. Chem. Commun. 2001, 1128–1129; (b)
Wolf, R.; Steckhan, E. J. Chem. Soc., Perkin Trans. 1 1986, 733–739.
13. Hiyama, T. Organofluorine Compounds: Chemistry and Applications; Springer:
Berlin, 2000.
1. Stanforth, S. P. In Comprehensive Organic Functional Group Transformations II;
Katritzky, A. R., Taylor, R. J., Eds.; Elsevier: Oxford, 2005; Vol. 2, p 1025.
2. (a) Nicolaou, K. C.; Bulger, P. G.; Sarlah, D. Angew. Chem., Int. Ed. 2005, 44,
4442–4489; (b) Metal-Catalyzed Cross-Coupling Reactions, 2nd ed.; de Mei-
jere, A., Diederich, F., Eds.; Wiley-VCH: Weinheim, 2004; (c) Handbook of
Organopalladium Chemistry for Organic Synthesis; Negishi, E., Ed.; Wiley In-