Fragmentation of Carbohydrate Anomeric Alkoxy Radicals: A New Synthesis of Chiral 1-Halo-1-iodo Alditols

Article abstract of DOI:10.1002/chem.200305294

Treatment of 1,2-fluorohydrins, 1,2-chlorohydrins, 1,2-bromohydrins, and 1,2-iodohydrins of the D-gluco, D-galacto, D-lacto, L-rhamno, D-allo, L-arabino, 3-deoxy-D-gluco, and 3,4-dideoxy-D-gluco families of carbohydrates with the (diacetoxyiodo)benzene/io

Full text of DOI:10.1002/chem.200305294

FULL PAPER
Fragmentation of Carbohydrate Anomeric Alkoxy Radicals: A New
Synthesis of Chiral 1-Halo-1-iodo Alditols
ConcepciÛn C. Gonzµlez,[a] Alan R. Kennedy,[b] Elisa I. LeÛn,[a]
ConcepciÛn Riesco-Fagundo,[a] and Ernesto Suµrez*[a]
Abstract: Treatment of 1,2-fluorohy-
drins, 1,2-chlorohydrins, 1,2-bromohy-
drins, and 1,2-iodohydrins of the d-
gluco, d-galacto, d-lacto, l-rhamno, d-
allo, l-arabino, 3-deoxy-d-gluco, and
3,4-dideoxy-d-gluco families of carbo-
hydrates with the (diacetoxyiodo)ben-
zene/iodine system afforded 1-fluoro-1-
iodo, 1-chloro-1-iodo, 1-bromo-1-iodo,
and 1,1-diiodo alditols, respectively, in
excellent yields. The reaction was ach-
ieved by radical fragmentation of the
C1ꢀC2 bond, triggered by the initially
formed anomeric alkoxy radical, and
subsequent trapping of the C2-radical
by iodine atoms. This methodology is
compatible with the stability of the
protective groups most frequently used
in carbohydrate chemistry. The poten-
tial utility of these 1-halo-1-iodo aldi-
tols as chiral synthons was evaluated
by their transformation into alk-1-enyl
iodides and in the Takai E-olefination
reaction.
Keywords: Halogen compounds ¥
alditols ¥ carbohydrates ¥ iodine ¥
radical reactions
Introduction
This situation is similar to that found for the synthesis of
the mixed halo-iodo species, 1-fluoro-1-iodo,[4] 1-chloro-1-
iodo,[5] and 1-bromo-1-iodo[6] compounds. Halogen exchange
by means of a Finkelstein reaction can be used to prepare
specific compounds.[7] Thus, the synthesis of 1-fluoro-1-iodo
compounds is generally accomplished from the more easily
available 1-fluoro-1-chloro or 1-fluoro-1-bromo deriva-
tives.[4] The oxidative decarboxylations of a-bromo- and a-
chlorobutyric acid with lead tetraacetate and iodine (modi-
fied Hunsdiecker reaction) to give 1-bromo-1-iodopropane
and 1-chloro-1-iodopropane, respectively, albeit in low yield,
have also been described.[8]
Methodology for the asymmetric synthesis of mixed
geminal haloiodides has scarcely been described in the liter-
ature, although the resolution of racemic chloro-iodo-acetic
acid through recrystallization of diastereomeric brucine salts
was described as early as 1927.[9] To the best of our knowl-
edge, the only previous syntheses of optically pure 1-fluoro-
1-iodide compounds by resolution of racemic mixtures was
reported by Bailey et al. and Myers et al.[10] The trapping of
highly enantiomerically enriched a-halo-2-phenylethylmag-
nesium chloride with trifluoroiodoethane afforded (S)-1-
chloro-1-iodo-2-phenylethane, with retention of configura-
tion.[11]
1,1-Dihaloalkanes, and in particular the highly reactive 1,1-
diiodoalkanes, are an important class of organic compounds
extensively used in organic synthesis.[1] Several methods for
the preparation of these compounds have been developed,[2]
among them the iodolysis of 1,1-bis(diisobutylalumino)al-
kanes,[2a] the alkylation of diiodomethyllithium or diiodome-
thylsodium with reactive electrophiles,[2b] treatment of 1,1-
bistrifluoromethylsulfonyloxy-alkanes with magnesium io-
dide,[2c and the oxidation of aldehyde hydrazones with io-
e]
dine.[2f,g] None of these is mild enough to be used with
highly functionalized or sensitive molecules. In consequence,
in the great majority of cases the 1,1-diiodoalkanes obtained
are derivatives of relatively simple hydrocarbons.[3]
[a] Prof. E. Suµrez, Dr. C. C. Gonzµlez, Dr. E. I. LeÛn,
C. Riesco-Fagundo
Instituto de Productos Naturales y AgrobiologÌa del C.S.I.C.
Carretera de La Esperanza 3
38206 La Laguna, Tenerife (Spain)
Fax :(+34)922-260-135
E-mail: esuarez@ipna.csic.es
[b] Dr. A. R. Kennedy
Since the synthetic utility of these compounds owes a
great deal to the ease and mildness with which they are pre-
pared, the need for a more general and practical synthesis
proved justified. Moreover, several products possessing this
1,1-halo-iodo grouping have been isolated from marine nat-
ural sources.[12]
Department of Pure and Applied Chemistry
University of Strathclyde
295 Cathedral Street, Glasgow G1 1XL, Scotland (UK)
E-mail: a.r.kennedy@strath.ac.uk
Supporting information for this article is available on the WWW
under http://www.chemeurj.org/ or from the author.
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5800 5809
Recently, the facile formation of glycopyran-1-O-yl and
glycofuran-1-O-yl radicals was achieved in our laboratories
by treatment of carbohydrate anomeric alcohols with hyper-
valent iodine reagents in the presence of iodine.[13] The reac-
tion presumably proceeds by homolytic fragmentation of an
and we now report full details of these experiments and
their extension to a number of new models.
Results and Discussion
We have synthesized 1,2-halohydrins of carbohydrates in
pyranose and furanose form as outlined in Table 1, Table 2,
and Table 3. 1,2-Fluorohydrins, 1,2-chlorohydrins, 1,2-bro-
mohydrins, and 1,2-iodohydrins were prepared from the cor-
responding 2-deoxy-hex-1-enitol by treatment with Select-
fluor,[16] N-chlorosuccinimide[17] or chloramine-T,[18] N-bro-
moacetamide,[19] and N-iodosuccinimide,[20] respectively. The
required 2-deoxy-hex-1-enitols were known compounds,
except for 2,6-anhydro-5-deoxy-4-O-pivaloyl-1,3-O-(tetraiso-
propyldisiloxane-1,3-diyl)-d-arabino-hex-5-enitol (1) and
2,6-anhydro-5-deoxy-1-O-(3,5-dinitrobenzoyl)-3,4-O-isopro-
pylidene-d-arabino-hex-5-enitol (2), which were prepared
from 2,6-anhydro-5-deoxy-d-arabino-hex-5-enitol by well es-
tablished procedures as described in the Supporting Infor-
mation. The fluorohydrin 3 was synthesized by treatment of
Scheme 1. Mechanism of alkoxy radical fragmentation (ARF): a) R1
O-alkyl; R2 = protective group. b) R1 = OC(O)-alkyl, halogen; R2
protective group.
=
=
alkyl hypoiodite intermediate.[14] The newly formed alkoxy
radical subsequently undergoes b-fragmentation of the C1ꢀ
C2 bond and gives rise to a C2 radical (Scheme 1). The
nature of the substituent at the 2-position may have a strong
influence on the ultimate fate of the radical. Indeed, when
the substituent is an ether group the radical is rapidly oxi-
dized by an excess of the hypervalent iodine reagent to give
an oxycarbenium ion (path a). This ion can be trapped inter-
or intramolecularly by nucleophiles, leading to a variety of
modified carbohydrate deriva-
tives with one carbon fewer.[13]
Table 1. Synthesis of 1-halo-1-iodo-d-arabinitol derivatives.[a]
The presence at C2 of a sub-
stituent with a more strongly
Entry
Substrate
t [h]
Product
Yield [%](dr)
electron-withdrawing
ability
(e.g., an ester group, path b)
should decrease the electron
density at this position and the
oxidation of the radical should
be more difficult. This offers
the possibility of competitive
trapping of the intermediate C2
radical by atoms of iodine from
the reaction medium. The a-io-
doalkyl esters thus formed are
difficult to synthesize by other
methods and may be interesting
chiral synthons.[13f]
Based on the above results,
we decided to carry out the
alkoxy radical fragmentation
(ARF) reaction with 2-deoxy-2-
halo carbohydrates in order to
develop an advantageous meth-
odology for the preparation of
1
2
3
4
5
6
7
8
9
3 R1 = F; R2 = Ac
1
3
19 R1 = F; R2 = Ac
96 (1:1)
95 (1:1)
99 (1:1)
92
94 (3:2)
84 (2:1)
91 (2:1)
91
4 R1 = Cl; R2 = Ac
5 R1 = Br; R2 = Ac
6 R1 = I; R2 = Ac
20 R1 = Cl; R2 = Ac
21 R1 = Br; R2 = Ac
22 R1 = I; R2 = Ac
1.5
0.75
1
0.5
1
7 R1 = F; R2 = TBDMS
8 R1 = Cl; R2 =TBDMS
9 R1 = Br; R2 = TBDMS
10 R1 = I; R2 = TBDMS
11 R1 = I; R2 = Bn
23 R1 = F; R2 = TBDMS
24 R1 = Cl; R2 = TBDMS
25 R1 = Br; R2 = TBDMS
26 R1 = I; R2 = TBDMS
27 R1 = I; R2 = Bn
1
2.5
86
10
11
12
13
12 R = F
13 R = Cl
14 R = Br
15 R = I
1
2.5
3
28 R = F
29 R = Cl
30 R = Br
31 R = I
84 (4:3)
85 (1:1)
82 (1:1)
80
4
14
15
16
16 R = Cl
17 R = Br
18 R = I
0.5
0.5
0.5
32 R = Cl
33 R = Br
34 R = I
83 (3:2)
92 (3:2)
69
1-halo-1-iodo-alditol
deriva-
tives. We have described the
obtained preliminary results in
[a] Halohydrin (1 mmol) in CH2Cl2 (50 mL) containing (diacetoxyiodo)benzene (1.5 mmol) and iodine
(1.5 mmol) was irradiated with two 80 W tungsten-filament lamps at reflux temperature.
a
previous communication,[15]
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E. Suµrez et al.
FULL PAPER
Table 2. Synthesis of 5-halo-5-iodo-d-arabinitol derivatives.[a]
cases complete consumption of
the starting material was ob-
served. In Table 1 we compare
the reactions of several halohy-
drins 3 15 of the 2-deoxy-2-
halo-glucopyranose type. The
reaction proceeded smoothly to
afford 1-halo-1-iodo-d-arabini-
tol derivatives 19 31 in excel-
lent yield. During each reaction
the integrity of the adjacent
stereogenic center was pre-
served and no generation of di-
astereoisomers at this carbon
atom were detected. As may be
expected, the level of diastereo-
selection achieved was very low
for the mixed halogen com-
pounds, which in the great ma-
jority of cases were obtained as
chromatographically insepara-
ble equimolar mixtures of iso-
mers. The mild reaction condi-
tions were fully compatible
with the acetate and TBDMS
protective groups (Table 1, en-
tries 1 8) and also with the b-
(1!4)-glycosidic linkage pres-
ent in the disaccharide deriva-
tives 12 15 (Table 1, entries 10
13). The results with iodohydrin
11 (Table 1, entry 9) indicate
that benzyl ethers also survive
the conversion well, in spite of
the recent use of the DIB/I2
system for the deprotection of
carbohydrate benzyl ethers.[24]
To extend the scope of the
Entry
Substrate
t [h]
Product
Yield [%](dr)
1
2
3
4
5
6
7
8
35 R1 = F; R2 = Ac
1
1.5
2
0.5
1
1
61 R1 = F; R2 = Ac
94 (1:1)
96 (3:2)
98 (3:2)
84
95 (1:1)
92 (1:1)
95 (1:1)
87
36 R1 = Cl; R2 = Ac
62 R1 = Cl; R2 = Ac
37 R1 = Br; R2 = Ac
38 R1 = I; R2 = Ac
63 R1 = Br; R2 = Ac
64 R1 = I; R2 = Ac
39 R1 = F; R2 = TBDMS
40 R1 = Cl; R2 = TBDMS
41 R1 = Br; R2 = TBDMS
42 R1 = I; R2 = TBDMS
65 R1 = F; R2 = TBDMS
66 R1 = Cl; R2 = TBDMS
67 R1 = Br; R2 = TBDMS
68 R1 = I; R2 = TBDMS
1
1.5
9
10
11
43 R = F
44 R = Cl
45 R = Br
0.5
1
0.5
(R,S)-69 R = F
70 R = Cl
71 R = Br
83 (1:1)[b]
91 (3:2)
95 (5:4)
12
13
14
15
16
17
18
46 R1 = F; R2 = Bn
1
1
1.5
1
1
(R,S)-72 R1 = F; R2 = Bn
(R,S)-73 R1 = Cl; R2 = Bn
(R,S)-74 R1 = Br; R2 = Bn
75 R1 = I; R2 = Bn
79 (3:2)[b]
92 (3:2)[b]
93 (3:2)[b]
90
47 R1 = Cl; R2 = Bn
48 R1 = Br; R2 = Bn
49 R1 = I; R2 = Bn
50 R1 = F; R2 = (NO2)2Bz[c]
51 R1 = Cl; R2 = (NO2)2Bz
52 R1 = Br; R2 = (NO2)2Bz
(R,S)-76 R1 = F; R2 = (NO2)2Bz
(R,S)-77 R1 = Cl; R2 = (NO2)2Bz
(R,S)-78 R1 = Br; R2 = (NO2)2Bz
92 (5:4)[b]
92 (2:1)[b]
93 (2:1)[b]
1.5
1
19
20
21
22
53 R = F
54 R = Cl
55 R = Br
56 R = I
1
3
3
0.5
79 R = F
70 (3:2)
65 (4:3)[b]
60 (1:1)
75
(R,S)-80 R = Cl
81 R = Br
82 R = I
described method further, we
investigated the feasibility of
applying this methodology to
the five-membered glucofura-
nose halohydrins 16 18. In
these three cases the reaction
proceeded analogously to give
a new set of halo-iodo-d-arabi-
23
24
25
26
57 R = F
58 R = Cl
59 R = Br
60 R = I
1
0.5
1
83 R = F
84 R = Cl
85 R = Br
86 R = I
96 (3:2)
92 (1:1)
92 (4:3)
84
0.5
[a] Halohydrin (1 mmol) in CH2Cl2 (50 mL) containing (diacetoxyiodo)benzene (1.5 mmol) and iodine
(1.5 mmol) was irradiated with two 80 W tungsten-filament lamps at reflux temperature. [b] R and S isomers
were separated by chromatography. [c] (NO2)2Bz = 3,5-dinitrobenzoyl.
no derivatives 32 34 with
very different protection pattern (Table 1, entries 14 16).
a
3,4,6-tri-O-acetyl-1,5-anhydro-2-deoxy-d-arabino-hex-1-enitol
with xenon difluoride,[21] followed by acid hydrolysis of the
anomeric fluoride, peracetylation, and subsequent selective
anomeric O-deacetylation with hydrazine acetate.[22] As de-
tected spectroscopically, the halohydrins were diastereoiso-
meric mixtures in most cases.[23]
The ARF reactions were performed under the conditions
stated in the tables, with (diacetoxyiodo)benzene (DIB) and
iodine in CH2Cl2 at reflux temperature and irradiation with
two 80 W tungsten-filament lamps. The reaction yields were
determined on chromatographically homogeneous halohy-
drin mixtures giving correct elemental analyses, and in all
A number of differently protected d-galactopyranose
halohydrins 35 60 (Table 2) were prepared in order to study
the influence of the intramolecular environments on the se-
lectivity of the fragmentation reaction. These compounds
provided a new series of 5-halo-5-iodo-d-arabinitol (1-halo-
1-iodo-d-lyxitol)[25] derivatives 61 86. In the examples
shown in the first 11 entries of Table 2 little if any diastereo-
selectivity was observed. Nevertheless, a modest increment
in the diastereoselectivity is observed as the steric demand
of the starting halohydrin increases (compare entries 1 or
6,7 versus 12 or 17,18 in Table 2). The mixed fluoro-iodo
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Chiral 1-Halo-1-iodo Alditols
5800 5809
Table 3. Synthesis of 1-halo-1-iodo compounds.[a]
(72), chloro-iodo (73), and bromo-iodo (74) derivatives
could now be separated by careful Chromatotron chroma-
tography. Unfortunately, none of these diastereoisomers
could be crystallized, and so we prepared the 3,5-dinitro-
benzoates 76 78 in order to establish the absolute configu-
rations at C1[25] by X-ray crystallographic analysis. Crystalli-
zation of the major isomers (R)-76, (R)-77, and (R)-78 from
n-hexane/EtOAc yielded colorless crystals suitable for X-
ray studies, which permitted the determination of the ste-
reochemistry as stated.[26]
Entry Substrate
t
Product
Yield
[%](dr)
[h]
1
2
3
4
87 R = F
88 R = Cl
89 R = Br
90 R = I
0.5 99 R = F
90 (1:1)
89 (1:1)
84 (1:1)
90
4
2
100 R = Cl
101 R = Br
0.5 102 R = I
The X-ray crystal structure of (R)-76 shows that the flu-
orine atom exhibits a nearly antiperiplanar disposition with
the oxygen at C2 (F-C1-C2-O torsion angle of 172.3o). The
observed deshielding of the C1 signal in the 13C NMR spec-
trum of the R isomer (dRꢀdS = 3.4 ppm) and principally
the differences between the 2J(F,C) in both isomers
(28.4 Hz for the R and 18.0 Hz for the S), from the X-ray
crystallographic data, permit the assignment of the C1 ster-
eochemistry in the closely related iodo-fluoro compound 72
[dRꢀdS = 2 ppm, 2J(F,C) ( R) = 29.8 Hz, 2J(F,C) ( S) =
17.2 Hz]. Although the differences are smaller in the case
of the fluoro-iodo compound 69 we tentatively assigned the
5
91
1
103
76
6
7
8
9
92 R = F
93 R = Cl
94 R = Br
95 R = I
0.5 104 R = F
1
1
96 (3:2)
73 (3:2)
87 (4:3)
82
105 R = Cl
106 R = Br
0.5 107 R = I
2
R stereochemistry to the isomer with the higher J(C,F) value.
The configurations at C1 of the chloro-iodo and bromo-
iodo series can now be assigned on the basis of the signifi-
cant deshielding of the C3 signal in the 13C NMR spectra of
the S isomers. The observed deshielding (dSꢀdR = 1.6
10
11
96 R1 = OAc; R2
=
0.5 108 R1 = OAc; R2 = OAc 94
109 R1 = H; R2 = OSiiPr3 90
OAc
97 R1 = H; R2
OSiiPr3
=
2
2.5 ppm for the mixed chloro-iodo and dSꢀdR
= 1.3
1.8 ppm for the bromo-iodo compound) is possibly due to
restricted rotation around the C1ꢀC2 bond. The use of the
sensitive cyclic carbonate as the protective group (Table 2,
entries 19 22) resulted in a significant reduction in the yield
of the fragmentation reaction. On the other hand, treatment
of 1,1,3,3-tetraisopropyldisiloxane-1,3-diyl (TIPDS) group
derivatives (Table 2, entries 23 26) proceeded efficiently
with high yield.
12[b]
98
2.5 110
69 (1:1)
[a] Halohydrin (1 mmol) in CH2Cl2 (50 mL) containing (diacetoxyiodo)benzene
(1.5 mmol) and iodine (1.5 mmol) was irradiated with two 80 W tungsten-fila-
ment lamps at reflux temperature. [b] Crude bromohydrin was used, two-step
yield.
Next, the reaction was examined with other types of car-
bohydrates or modified carbohydrates as substrates in order
to test the generality and applicability of this methodology
further. The results summarized in Table 3 showed that halo-
hydrins derived from hexenitols such as 3,4-di-O-acetyl-1,5-
anhydro-2,6-dideoxy-l-arabino-hex-1-enitol (Table 3, en-
tries 1 4) and 3-O-acetyl-1,5-anhydro-4,6-O-benzylidene-2-
deoxy-d-ribo-hex-1-enitol (Table 3, entry 5) and pentenitols
such as 3-di-O-acetyl-1,5-anhydro-4-deoxy-d-erythro-pent-4-
enitol (Table 3, entries 6 9) gave the corresponding 1-halo-
1-iodo compounds 99 107 in similar yields.
This process could also be applied successfully to 3-
deoxy and 3,4-dideoxy iodohydrins 96 and 97 (Table 3, en-
tries 10 and 11), which were synthesized from 4,6-di-O-
acetyl-1,5-anhydro-2,3-dideoxy-d-erythro-hex-1-enitol[27] and
1,5-anhydro-1,2,3,4-tetradeoxy-6-O-(triisopropylsilyl)-d-glyc-
ero-hex-1-enitol,[28] respectively. The obtained gem-diiodo al-
ditols 109 and 108 may be interesting chiral synthons when
the introduction of one or two stereogenic centers, respec-
tively, is required.
110. In this case the inherent instability of the tertiary halide
intermediate precluded isolation and so it was used without
purification in the fragmentation reaction.
The synthetic usefulness of these compounds as chiral
synthons has been assessed in the E-olefination of aldehydes
with chromium(ii) chloride. Our initial attempts to use these
1,1-diiodo compounds in a Takai[30] reaction were unsuccess-
ful, and only b-elimination products were isolated. These re-
sults, however, provide the possibility to obtain chiral vinyl
iodides from 1,1-diiodo compounds oxygenated at the a-po-
sition. For example, treatment of 1,1-diiodo 22 with the
chromium(ii) chloride/DMF complex afforded a mixture of
the corresponding (1Z)- and (1E)-1-iodo-d-erythro-pent-1-
enitol derivatives 111 in excellent yield and moderate dia-
stereoselectivity (Z/E 3:2) (Scheme 2). An iodo-chromium
carbenoid may be involved in this reaction, followed by
chromium-induced b-elimination of the oxygenated function
at C2. As far as we know, no examples of chromium-mediat-
ed b-elimination of 2-O-acetyl-1,1-diiodo compounds have
been reported until now.[31] Alk-1-enyl iodides are probably
the most widely used organic electrophiles in the Stille and
Suzuki coupling reactions.[32]
The reaction of the 2-C-hydroxymethyl branched carbo-
hydrate 98[29] (Table 3, entry 12) also proceeded effectively,
providing the 2-bromo-2-iodo-d-arabino-hexitol derivative
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E. Suµrez et al.
FULL PAPER
ance of the starting material was observed by TLC. The reaction mixture
was then heated to reflux for 0.5 h, poured into brine, and extracted with
EtOAc. The organic layer was dried and concentrated in vacuo. Column
chromatography of the residue (hexanes/EtOAc mixtures) afforded the
required fluorohydrin compounds. The fluorohydrin corresponding to
3,4,6-tri-O-acetyl-d-glucal 3 was prepared by the procedure described in
the Supporting Information.
General procedure for the synthesis of chlorohydrins: A solution of the
corresponding 2-deoxy-hex-1-enitol (1 mmol) in THF (45 mL) and H2O
(5 mL), containing N-chlorosuccinimide (2 mmol), was heated at reflux
for 8 h. The reaction mixture was then poured into water and extracted
with CH2Cl2. The organic layer was dried and concentrated in vacuo.
Column chromatography of the residue (hexanes/EtOAc mixtures) af-
forded the required chlorohydrin compounds. Alternatively, a solution of
the 2-deoxy-hex-1-enitol (1 mmol) in acetone (10 mL) and H2O (10 mL)
was cooled to 08C and chloramine-T trihydrate (1.5 mmol) and pyridini-
um p-toluenesulfonate (1.5 mmol) were added. The reaction mixture was
kept at this temperature for 5 min and was then stirred at room tempera-
ture for 1 h. The reaction mixture was poured into water and extracted
with EtOAc. Column chromatography of the residue (hexanes/EtOAc
mixtures) afforded the required iodohydrin compounds.
Scheme 2. Reactions of 1,1-diiodo compounds. a) CrCl2 (4 equiv), DMF
(4 equiv), THF, RT, 30 min, 89%, (Z/E 3:2); b) CrCl2 (3 equiv), hydrocin-
namaldehyde (Ph(CH2)2CHO; 1 equiv), DMF (3 equiv), THF, RT, 2.5 h,
70%.
On the other hand, the 2-deoxy-pentitol 108, when sub-
jected to the normal Takai reaction conditions in the pres-
ence of hydrocinnamaldehyde, gave the expected E olefin
112 in good yield (Scheme 2). It is worth noting the stability
of the highly sensitive formyl ester under the reaction condi-
tions.
General procedure for the synthesis of bromohydrins: A solution of the
corresponding 2-deoxy-hex-1-enitol (1 mmol) in THF (35 mL) and H2O
(4 mL), containing recently crystallized N-bromoacetamide (1.5 mmol),
was stirred at room temperature for 4 h. The reaction mixture was then
poured into water and extracted with CH2Cl2. The organic layer was
dried and concentrated in vacuo. Column chromatography of the residue
(hexanes/EtOAc mixtures) afforded the required bromohydrin com-
pounds.
The synthetic utility of the Takai reaction owes a great
deal to the ease with which the 1,1-diiodo compounds can
be synthesized. As a consequence of the difficulty in the
preparation of the 1,1-diiodo compounds of highly function-
alized substrates, this reaction, in the majority of cases, has
been used simply as an E-ethylenation of aldehydes with
diiodoethane.[33]
General procedure for the synthesis of iodohydrins: A solution of the
corresponding 2-deoxy-hex-1-enitol (1 mmol) in THF (10 mL) and H2O
(10 mL), containing N-iodosuccinimide (1.2 mmol), was stirred at room
temperature for 20 min. The reaction mixture was diluted with EtOAc,
poured into water, and extracted with EtOAc. The organic layer was
washed with 10% aqueous sodium thiosulfate, dried, and concentrated in
vacuo. Chromatotron chromatography of the residue (hexanes/EtOAc
mixtures) afforded the required iodohydrin compounds.
Conclusions
This new ARF reaction offers special advantages for the
synthesis of these gem-dihalocompounds, including the
ready accessibility of the starting materials, experimental
simplicity, high yields, and mild conditions compatible with
the stability of the protective groups most commonly used
in carbohydrate chemistry. It is hoped that these 1-halo-1-
iodo compounds will be powerful building blocks for organic
synthesis by virtue of the fact that the carbohydrate would
potentially be amenable to prior manipulation to provide
more specific or complex synthons.
General procedure for the synthesis of 1-halo-1-iodo compounds: A solu-
tion of the halohydrin (1 mmol) in CH2Cl2 (50 mL) containing (diacetoxy-
iodo)benzene (1.5 mmol) and iodine (1.5 mmol) was irradiated with two
80 W tungsten-filament lamps at reflux temperature. The reaction mix-
ture was then poured into water and extracted with CH2Cl2. The organic
layer was washed with 10% aqueous sodium thiosulfate, dried, and con-
centrated in vacuo. Chromatotron chromatography of the residue (hex-
anes/EtOAc mixtures) afforded the required halo-iodine compounds.
2,3,5-Tri-O-acetyl-1-deoxy-4-O-formyl-1,1-diiodo-d-arabinitol (22): Crys-
talline solid (92%): m.p. 109 1108C (from n-hexane/EtOAc); [a]D
=
+45 (c = 1.42); 1H NMR: d = 2.04 (s, 3H), 2.12 (s, 3H), 2.14 (s, 3H),
4.08 (dd, J = 5.9, 12.4 Hz, 1H), 4.27 (dd, J = 3.3, 12.4 Hz, 1H), 5.06 (d,
J = 7.5 Hz, 1H), 5.18 (m, 1H), 5.25 (dd, J = 3.0, 7.5 Hz, 1H), 5.76 (dd,
J = 3.0, 7.3 Hz, 1H), 7.98 (s, 1H) ppm; 13C NMR: d = ꢀ33.9 (CH), 20.6
(3îCH3), 61.5 (CH2), 68.6 (CH), 68.9 (CH), 73.4 (CH), 159.4 (CH), 169.3
(2îC), 170.4 (C) ppm; IR: n˜ = 3013, 1754 cmꢀ1; MS (70 eV, EI): m/z
(%): 542 (<1) [M]+, 482 (3), 207 (100); HRMS (EI): found 541.8989;
C12H16I2O8 calcd 541.8935; elemental analysis calcd (%) for C12H16I2O8
(542.1): C 26.59, H 2.98; found: C 26.72, H 2.82.
Experimental Section
General methods: Melting points were determined with a hot-stage appa-
ratus. Optical rotations were measured at the sodium line at ambient
temperature in CHCl3 solutions. IR spectra were recorded in CHCl3 solu-
tions unless otherwise stated. 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. Merck silica gel 60 PF (0.063 0.2 mm) was used for column chro-
matography. Circular layers of 1 mm of Merck silica gel 60 PF254 were
used on a Chromatotron for centrifugally assisted chromatography. Com-
mercially available reagents and 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 atmos-
phere. The spray reagents for TLC analysis were conducted with 0.5%
vanillin in H2SO4/EtOH (4:1) and further heating until development of
color.
2,3,5-Tris-O-[tert-butyl(dimethyl)silyl]-1-deoxy-4-O-formyl-1,1-diiodo-d-
1
arabinitol (26): Oil (91%): [a]D = +5.0 (c = 2.38); H NMR: d = 0.03
(s, 3H), 0.04 (s, 3H), 0.13 (s, 3H), 0.13 (s, 3H), 0.15 (s, 3H), 0.30 (s, 3H),
0.87 (s, 9H), 0.92 (s, 9H), 1.01 (s, 9H), 3.76 (dd, J = 4.8, 5.0 Hz, 1H),
3.76 (dd, J = 6.7, 11.6 Hz, 1H), 3.90 (dd, J = 2.8, 11.6 Hz, 1H), 4.07 (dd,
J = 1.9, 5.0 Hz, 1H), 5.22 (ddd, J = 2.8, 4.8, 6.7 Hz, 1H), 5.62 (d, J =
1.9 Hz, 1H), 8.09 (s, 1H) ppm; 13C NMR: d = ꢀ24.1 (CH), ꢀ5.3 (CH3),
ꢀ5.0 (CH3), ꢀ4.6 (CH3), ꢀ4.6 (CH3), ꢀ4.0 (CH3), ꢀ3.7 (CH3), 18.0 (C),
18.0 (C), 18.3 (C), 26.0 (9îCH3), 62.3 (CH2), 74.0 (CH), 74.4 (CH), 81.2
(CH), 160.7 (CH) ppm; IR: n˜ = 2930, 1726, 1110 cmꢀ1; MS (70 eV, EI):
m/z (%): 713 (15) [MꢀC3H9]+, 655 (9), 581 (100), 555 (84), 453 (44);
HRMS (EI): found: 713.0515; C21H43I2O5Si3 calcd 713.0508; elemental
analysis calcd (%) for C24H52I2O5Si3 (758.7): C 37.99, H 6.91; found: C
37.80, H 7.26.
General procedure for the synthesis of fluorohydrins: H2O (1.5 mL) and
F-TEDA-BF4 (Selectfluor, 1.5 mmol) were added to a solution of the cor-
responding 2-deoxy-hex-1-enitol (1 mmol) in nitromethane (8.5 mL), and
the mixture was stirred at room temperature (1 5 h) until the disappear-
5804
¹ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2003, 9, 5800 5809

Chiral 1-Halo-1-iodo Alditols
5800 5809
2,3,5-Tri-O-benzyl-1-deoxy-4-O-formyl-1,1-diiodo-d-arabinitol (27): Oil
(86%): [a]D
separated by careful column chromatography (hexanes/EtOAc 98:2).
Compound (S)-69: crystalline solid (40.8%): m.p. 40 41.58C (from n-
hexane/EtOAc); [a]D = +8.4 (c = 0.25); 1H NMR (C6D6): d = 0.01 (s,
3H), 0.02 (s, 3H), 0.06 (s, 6H), 0.94 (s, 9H), 0.95 (s, 9H), 1.71 (s, 3H),
3.74 (dd, J = 5.0, 11.1 Hz, 1H), 3.81 (dd, J = 5.7, 11.1 Hz, 1H), 4.24
(ddd, J = 4.0, 6.5 Hz, 3J(F,H) = 10.1 Hz, 1H), 5.46 (ddd, J = 5.0, 5.0,
5.0 Hz, 1H), 5.80 (dd, J = 4.0, 4.0 Hz, 1H), 6.82 (dd, J = 6.5 Hz, 2J(F,H)
= 11.1 Hz, 1H), 7.65 (s, 1H) ppm; 13C NMR (C6D6): d = ꢀ5.4 (CH3),
ꢀ5.3 (CH3), ꢀ4.7 (CH3), ꢀ4.6 (CH3), 18.4 (2îC), 20.3 (CH3), 25.9 (3î
CH3), 26.0 (3îCH3), 62.0 (CH2), 71.3 (CH), 72.0 (CH), 74.9 (1J(F,C) =
256.8 Hz, CH), 77.0 (2J(F,C) = 19.5 Hz, CH), 159.8 (CH), 168.7 (C); IR
(CCl4): n˜ = 1754, 1732, 1257, 1175 cmꢀ1; MS (70 eV, EI): m/z (%): 521
(16) [MꢀC4H9]+, 441 (8), 333 (10), 301 (14), 207 (13), 174 (16), 117 (81),
73 (100); HRMS (EI): found: 521.0691; C16H31FIO6Si2 calcd 521.0688;
elemental analysis calcd (%) for C20H40FIO6Si2 (578.6): C 41.51, H 6.97;
found: C 41.57, H 6.79.
=
+22.7 (c = 1.046); 1H NMR: d = 3.68 (dd, J = 4.4,
5.6 Hz, 1H), 3.67 (dd, J = 5.4, 5.4 Hz, 1H), 3.89 (dd, J = 5.2, 10.3 Hz,
1H), 4.11 (dd, J = 4.5, 5.6 Hz, 1H), 4.51 (d, J = 11.9 Hz, 1H), 4.55 (d, J
= 11.9 Hz, 1H), 4.71 (d, J = 11.1 Hz, 1H), 4.79 (d, J = 11.1 Hz, 1H),
4.83 (d, J = 10.7 Hz, 1H), 5.03 (d, J = 10.7 Hz, 1H), 5.19 (ddd, J = 4.8,
4.8, 4.8 Hz, 1H), 5.39 (d, J = 4.4 Hz, 1H), 7.26 7.46 (m, 15H), 8.03 (s,
1H) ppm; 13C NMR: d
=
ꢀ25.1 (CH), 67.2 (CH2), 72.6 (CH), 73.5
(CH2), 75.1 (CH2), 75.4 (CH2), 80.4 (CH), 83.9 (CH), 127.8 (5îCH),
128.3 (5îCH), 128.5 (5îCH), 137.3 (C), 137.5 (C), 137.7 (C), 159.9
(CH) ppm; IR: n˜ = 3016, 1726, 1174 cmꢀ1; MS (70 eV, EI): m/z (%): 595
(1) [MꢀPhCH2]+, 503 (0.5), 427 (0.5), 91 (100); HRMS (EI): found:
594.9494; C20H21I2O5 calcd 594.9479; elemental analysis calcd (%) for
C27H28I2O5 (686.3): C 47.25, H 4.11; found: C 47.29, H 4.02.
2,5-Di-O-acetyl-1-deoxy-4-O-formyl-1,1-diiodo-3-O-(2,3,4,6-tetra-O-
acetyl-b-d-galactopyranosyl)-d-arabinitol (31): Oil (80%): [a]D = +28.4
1
Compound (R)-69: amorphous solid (41.5%): [a]D = +4.5 (c = 0.22);
1H NMR: d = 0.05 (s, 3H), 0.06 (s, 3H), 0.13 (s, 3H), 0.14 (s, 3H), 0.89
(s, 9H), 0.93 (s, 9H), 2.09 (s, 3H), 3.69 (dd, J = 5.5, 11.3 Hz, 1H), 3.72
(c = 1.02); H NMR: d = 1.95 (s, 3H), 2.05 (s, 3H), 2.06 (s, 6H), 2.14 (s,
3H), 2.16 (s, 3H), 3.96 (dd, J = 6.6, 7.0 Hz, 1H), 4.02 (dd, J = 5.6,
12.4 Hz, 1H), 4.19 (dd, J = 7.0, 11.3 Hz, 1H), 4.30 (dd, J = 6.3, 11.3 Hz,
1H), 4.51 (dd, J = 2.7, 12.4 Hz, 1H), 4.56 (d, J = 8.0 Hz, 1H), 4.57 (dd,
J = 1.8, 4.7 Hz, 1H), 4.97 (dd, J = 3.5, 10.4 Hz, 1H), 5.04 (m, 1H), 5.17
(dd, J = 8.0, 10.4 Hz, 1H), 5.33 (dd, J = 1.8, 9.6 Hz, 1H), 5.36 (m, 1H),
5.37 (d, J = 9.7 Hz, 1H), 7.98 (s, 1H) ppm; 13C NMR: d = ꢀ27.6 (CH),
20.5 (CH3), 20.6 (CH3), 20.7 (2îCH3), 20.8 (CH3), 20.9 (CH3), 61.1
(CH2), 61.3 (CH2), 66.7 (CH), 68.8 (CH), 69.9 (CH), 70.9 (CH), 71.2
(CH), 73.9 (CH), 75.4 (CH), 101.6 (CH), 159.4 (CH), 169.1 (C), 169.8
(C), 170.0 (C), 170.1 (C), 170.2 (C), 170.4 (C) ppm; IR: n˜ = 3026, 1751,
1232, 1076 cmꢀ1; MS (FAB) m/z (%): 853 (100) [M+Na]+, 831 (42), 703
(49); HRMS (EI): found: 770.9581; C22H29I2O14 calcd 770.9647; elemental
analysis calcd (%) for C24H32I2O16 (830.3): C 34.72, H 3.88; found: C
34.75, H 3.91.
(dd, J
=
5.5, 11.3 Hz, 1H), 3.80 (ddd, J
= =
3.1, 6.6 Hz, 3J(F,H)
10.2 Hz, 1H), 5.11 (dd, J = 3.5, 6.6 Hz, 1H), 5.21 (ddd, J = 3.5, 5.5,
5.5 Hz, 1H), 6.85 (dd, J
=
3.1 Hz, 2J(F,H)
= 48.1 Hz, 1H), 8.11 (s,
1H) ppm; 13C NMR: d = ꢀ5.55 (CH3), ꢀ5.48 (CH3), ꢀ4.6 (CH3), ꢀ3.9
(CH3), 18.2 (2îC), 20.7 (CH3), 25.7 (3îCH3), 25.9 (3îCH3), 61.7 (CH2),
72.0 (2îCH), 73.6 (2J(F,C) = 21.1 Hz, CH), 78.0 (1J(F,C) = 256.0 Hz,
CH), 160.1 (CH), 169.1 (C) ppm; IR (CCl4): n˜
= 1760, 1734, 1222,
1173 cmꢀ1; MS (70 eV, EI): m/z (%): 521 (30) [MꢀC4H9]+, 441 (12), 415
(11), 333 (15), 301 (20), 174 (16), 117 (72), 73 (100); HRMS (EI): found:
521.0675; C16H31FIO6Si2 calcd 521.0688; elemental analysis calcd (%) for
C20H40FIO6Si2 (578.6): C 41.51, H 6.97; found: C 41.60, H 6.61.
(5RS)-1-O-Benzyl-5-deoxy-5-fluoro-2-O-formyl-5-iodo-3,4-O-isopropili-
dene-d-arabinitol (72): Diastereoisomeric mixture (3:2), separated by
careful Chromatotron chromatography (hexanes/EtOAc 98:2). Com-
1-Deoxy-3-O-formyl-1,1-diiodo-2-O-methyl-4,5-O-isopropylidene-d-ara-
binitol (34): Oil (69%): [a]D = +12 (c = 1.04); 1H NMR: d = 1.35 (s,
3H), 1.46 (s, 3H), 3.60 (dd, J = 3.0, 7.0 Hz, 1H), 3.72 (s, 3H), 3.85 (dd, J
= 5.3, 8.9 Hz, 1H), 4.02 (dd, J = 6.1, 8.9 Hz, 1H), 4.18 (ddd, J = 5.3,
6.1, 8.1 Hz, 1H), 5.14 (d, J = 7.0 Hz, 1H), 5.49 (dd, J = 3.0, 8.1 Hz,
1H), 8.09 (s, 1H) ppm; 13C NMR: d = ꢀ27.8 (CH), 25.4 (CH3), 26.7
(CH3), 62.0 (CH3), 66.8 (CH2), 72.6 (CH), 74.4 (CH), 84.3 (CH), 110.1
(C), 160.0 (CH) ppm; IR: n˜ = 2992, 2938, 1732 cmꢀ1; MS ( 70 eV, EI):m/z
(%): 470 (1) [M]+, 455 (22), 438 (6), 343 (8), 101 (100); HRMS (EI):
found: 469.9064; C10H16I2O5 calcd 469.9087; elemental analysis calcd (%)
for C10H16I2O5 (470.0): C 25.54, H 3.43; found: C 25.66, H 3.26.
1
pound (R)-72: Oil (42%); [a]D = +54 (c = 0.2); H NMR: d = 1.39 (s,
3H), 1.47 (s, 3H), 3.67 (ddd, J = 5.2, 5.2, 13.1 Hz, 2H), 4.41 (ddd, J =
4.9, 9.2 Hz, 3J(F,H) = 4.5 Hz, 1H), 4.52 (dd, J = 4.9, 5.2 Hz, 1H), 4.53
(d, J = 11.8 Hz, 1H), 4.56 (d, J = 11.8 Hz, 1H), 5.39 (ddd, J = 5.2, 5.2,
2
5.2 Hz, 1H), 6.84 (dd, J = 9.2 Hz, J(F,H) = 48.5 Hz, 1H), 7.29 7.37 (m,
5H), 8.09 (s, 1H) ppm; 13C NMR: d = 25.1 (CH3), 27.4 (CH3), 68.2
(CH2), 68.5 (CH), 73.4 (CH2), 73.6 (1J(F,C) = 268.4 Hz, CH), 74.5 (CH),
79.7 (2J(F,C)
= 29.8 Hz, CH), 109.4 (C), 127.7 (2îCH), 127.9 (CH),
128.5 (2îCH), 137.4 (C), 159.9 (CH) ppm; IR: n˜ = 3032, 1735, 1375,
1223, 1166 cmꢀ1; MS (70 eV, EI): m/z (%): 438 (1) [M]+, 423 (2), 380 (2),
185 (10), 147 (40), 91 (100); HRMS (EI): found: 438.0313; C16H20FIO5
calcd 438.0340; elemental analysis calcd (%) for C16H20FIO5 (438.2): C
43.83, H 4.60; found: C 43.78, H 4.67.
1,3,4-Tri-O-acetyl-5-deoxy-2-O-formyl-5,5-diiodo-d-arabinitol (64): Crys-
talline solid (84%): m.p. 122 1238C (from n-hexane/EtOAc); [a]D
=
+11 (c = 0.32); 1H NMR: d = 1.99 (s, 3H), 2.14 (s, 3H), 2.15 (s, 3H),
3.85 (dd, J = 7.6, 11.8 Hz, 1H), 4.29 (dd, J = 4.7, 11.8 Hz, 1H), 5.02 (dd,
J = 2.7, 8.4 Hz, 1H), 5.21 (dd, J = 1.2, 8.4 Hz, 1H), 5.24 (d, J = 2.7 Hz,
1H), 5.38 (ddd, J = 1.2, 4.7, 7.6 Hz, 1H), 7.97 (s, 1H) ppm; 13C NMR: d
1
Compound (S)-72: Oil (37%); [a]D = +13.1 (c = 0.13); H NMR: d =
1.42 (s, 3H), 1.54 (s, 3H), 3.58 (dd, J = 7.0, 9.8 Hz, 1H), 3.70 (dd, J =
5.3, 9.8 Hz, 1H), 4.39 (t, J = 6.3 Hz, 1H), 4.47 (ddd, J = 3.3, 6.3 Hz,
3J(F,H) = 24.3 Hz, 1H), 4.53 (s, 2H), 5.39 (ddd, J = 6.3, 6.3, 6.0 Hz,
1H), 6.92 (dd, J = 3.3 Hz, 2J(F,H) = 49.8 Hz, 1H), 7.28 7.39 (m, 5H),
8.09 (s, 1H) ppm; 13C NMR: d = 25.6 (CH3), 26.3 (CH3), 68.5 (CH2),
69.1 (CH), 71.6 (1J(F,C) = 261.1 Hz, CH), 73.7 (CH2), 76.3 (CH), 81.3
(2J(F,C) = 17.2 Hz, CH), 110.3 (C), 127.9 (2îCH), 128.2 (CH), 128.6
(2îCH), 136.9 (C), 159.9 (CH) ppm; IR: n˜ = 3032, 1733, 1372, 1220,
1169, 1134 cmꢀ1; MS (70 eV, EI): m/z (%): 438 (1) [M]+, 423 (3), 380 (1),
185 (7), 147 (19), 91 (100); HRMS (EI): found: 438.0349; C16H20FIO5
calcd 438.0340; elemental analysis calcd (%) for C16H20FIO5 (438.2): C
43.85, H 4.60; found: C 43.62, H 5.04.
=
ꢀ32.3 (CH), 20.6 (CH3), 20.7 (CH3), 20.8 (CH3), 62.0 (CH2), 67.2
(CH), 72.1 (CH), 73.4 (CH), 159.7 (CH), 169.1 (2îC), 170.3 (C) ppm;
IR: n˜
=
3027, 2953, 1753 cmꢀ1; MS (70 eV, EI): m/z (%): 482 (19)
[MꢀAcOH]+, 415 (10), 327 (59), 313 (100); HRMS (EI): found:
481.8750; C10H12I2O6 calcd 481.8723; elemental analysis calcd (%) for
C12H16I2O8 (542.1): C 26.59, H 2.98; found: C 26.82, H 2.64.
1,3,4-Tris-O-[tert-butyl(dimethyl)silyl]-5-deoxy-5,5-diiodo-2-O-formyl-d-
arabinitol (68): Oil (87%): [a]D = ꢀ6.4 (c = 1.43); 1H NMR: d = 0.07
(s, 3H), 0.08 (s, 3H), 0.15 (s, 3H), 0.22 (s, 3H), 0.24 (s, 3H), 0.35 (s, 3H),
0.91 (s, 18H), 0.98 (s, 9H), 3.74 (dd, J = 4.5, 11.5 Hz, 1H), 3.80 (dd, J =
4.3, 11.5 Hz, 1H), 3.90 (dd, J = 4.3, 6.4 Hz, 1H), 4.22 (dd, J = 3.4,
5.4 Hz, 1H), 5.08 (ddd, J = 4.3, 4.5, 5.4 Hz, 1H), 5.55 (d, J = 6.4 Hz,
1H), 8.08 (s, 1H) ppm; 13C NMR (100.6 MHz): d = ꢀ17.8 (CH), ꢀ5.4
(CH3), ꢀ5.2 (CH3), ꢀ4.3 (CH3), ꢀ3.5 (CH3), ꢀ3.4 (CH3), ꢀ3.2 (CH3),
18.2 (C), 18.3 (C), 18.7 (C), 25.9 (3îCH3), 26.1 (3îCH3), 26.5 (3îCH3),
61.2 (CH2), 70.4 (CH), 74.8 (CH), 81.7 (CH), 160.5 (CH) ppm; IR: n˜ =
3017, 1722, 1472, 1257, 1187 cmꢀ1; MS (70 eV, EI): m/z (%): 701 (1)
[MꢀC(CH3)3]+, 673 (1), 655 (1), 569 (3), 527 (2), 73 (100); HRMS (EI):
found: 701.0542; C20H43I2O2Si3 calcd 701.0508; elemental analysis calcd
(%) for C24H52I2O5Si3 (758.7): C 37.99, H 6.91; found: C 38.07, H 6.79.
(5RS)-1-O-Benzyl-5-chloro-5-deoxy-2-O-formyl-5-iodo-3,4-O-isopropyli-
dene-d-arabinitol (73): Diastereoisomeric mixture (3:2), separated by
careful Chromatotron chromatography (hexanes/EtOAc 98:2). Com-
pound (R)-73: Oil (52%); [a]D = +43 (c = 1.33); 1H NMR: d = 1.40
(s, 3H), 1.52 (s, 3H), 3.63 (dd, J = 6.9, 9.6 Hz, 1H), 3.67 (dd, J = 6.1,
9.7 Hz, 1H), 4.45 (dd, J = 5.9, 9.7 Hz, 1H), 4.50 (dd, J = 2.2, 5.8 Hz,
1H), 4.54 (s, 2H), 5.45 (m, 1H), 5.69 (d, J = 9.3 Hz, 1H), 7.29 7.36 (m,
5H), 8.10 (s, 1H) ppm; 13C NMR (50.3 MHz): d
= 25.3 (CH3), 25.8
(CH), 26.8 (CH3), 68.2 (CH2), 68.5 (CH), 73.3 (CH2), 74.2 (CH), 82.2
(CH), 109.3 (C), 127.7 (2îCH), 127.9 (CH), 128.4 (2îCH), 137.4 (C),
160.2 (CH) ppm; IR: n˜ = 1728 cmꢀ1; MS (70 eV, EI): m/z (%): 441/439
(2/5) [MꢀMe]+, 398/396 (0.3/1), 277/275 (2/6), 185 (12); HRMS (EI):
(5RS)-3-O-Acetyl-1,4-bis-O-[tert-butyl(dimethyl)silyl]-5-deoxy-5-fluoro-
2-O-formyl-5-iodo-d-arabinitol (69): Diastereoisomeric mixture (1:1),
5805
Chem. Eur. J. 2003, 9, 5800 5809
www.chemeurj.org
¹ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

E. Suµrez et al.
FULL PAPER
found: 440.9737; C15H1737ClIO5 calcd 440.9780; elemental analysis calcd
(%) for C16H20ClIO5 (454.7): C 42.27, H 4.43; found: C 42.47, H 4.17.
Crystal data and structure refinement for (R)-76: C16H16FIN2O10, Mt
=
542.21, monoclinic, space group P21, a = 7.9686 (1), b = 7.5629 (1), c =
17.7602 (3) ä, b = 102.262 (1), V = 1045.91 (3) ä3, Z = 2, 1calcd
=
Compound (S)-73: Oil (40%); [a]D = ꢀ25 (c = 0.5); 1H NMR: d =
1.42 (s, 3H), 1.58 (s, 3H), 3.59 (dd, J = 6.8, 9.8 Hz, 1H), 3.68 (dd, J =
5.9, 9.9 Hz, 1H), 4.42 (dd, J = 4.7, 5.9 Hz, 1H), 4.54 (d, J = 11.8 Hz,
1H), 4.55 (d, J = 11.8 Hz, 1H), 4.71 (dd, J = 6.5, 6.5 Hz, 1H), 5.53
(ddd, J = 6.1, 6.1, 6.1 Hz, 1H), 5.75 (d, J = 6.8 Hz, 1H), 7.30 7.38 (m,
1.722 Mgmꢀ3, m(MoKa) = 0.71073 ä, F(000) = 536, T = 150(2) K; color-
less crystal, 0.20î0.16î0.08 mm, collected reflections 27779. The struc-
ture was solved by direct methods, all hydrogen atoms were refined ani-
sotropically by use of full-matrix, least-squared based F2 to give R1
=
5H), 8.10 (s, 1H) ppm; 13C NMR (50.3 MHz): d
= 25.4 (CH), 25.6
0.0356, wR2 = 0.0726 for 6094 independently observed reflections (jFo j
>2s(jFo j)) and 274 parameters.
(CH3), 26.3 (CH3), 68.6 (CH2), 68.6 (CH), 73.6 (CH2), 76.7 (CH), 82.9
(CH), 110.4 (C), 127.8 (2îCH), 128.0 (CH), 128.6 (2îCH), 137.1 (C),
160.1 (CH) ppm; IR: n˜ = 1725 cmꢀ1; MS (70 eV, EI): m/z (%): 456/454
(0.2/0.6) [M]+, 441/439 (1/3), 277/275 (1/3), 185 (9); HRMS (EI): found:
454.0011; C16H2035ClIO5 calcd 454.0044; elemental analysis calcd (%) for
C16H20ClIO5 (454.7): C 42.27, H 4.43; found: C 42.35, H 4.27.
Compound (S)-76: Oil (40.3%): [a]D = ꢀ17.9 (c = 0.47); 1H NMR: d
= 1.46 (s, 3H), 1.60 (s, 3H), 4.46 (dd, J = 2.6, 6.5 Hz, 1H), 4.54 (dd, J =
7.5, 11.9 Hz, 1H), 4.73 (dd, J = 3.6, 11.9 Hz, 1H), 4.81 (ddd, J = 6.5,
3
6.5 Hz, J(F,H) = 15.8 Hz, 1H), 5.70 (ddd, J = 0.8, 3.6, 7.5 Hz, 1H), 6.76
(dd, J = 6.5 Hz, 2J(F,H) = 50.2 Hz, 1H), 8.17 (s, 1H), 9.13 (d, J =
2.1 Hz, 2H), 9.25 (dd, J = 2.1, 2.1 Hz, 1H) ppm; 13C NMR: d = 25.5
(CH3), 26.4 (CH3), 65.6 (CH2), 67.7 (CH), 68.2 (1J(F,C) = 257.7 Hz, CH),
75.2 (3J(F,C) = 3.2 Hz, CH), 81.3 (2J(F,C) = 18.0 Hz, CH), 111.7 (C),
122.7 (CH), 129.5 (2îCH), 133.0 (C), 148.7 (2îC), 159.9 (CH), 162.2
(C); IR n˜ = 3102, 2939, 1735, 1551, 1343, 1276, 1171 cmꢀ1; MS (70 eV,
EI): m/z (%): 527 (51) [MꢀCH3]+, 371 (16), 254 (12), 195 (100), 149
(31); HRMS (EI): found 526.9588; C15H13FIN2O10 calcd 526.9599; ele-
mental analysis calcd (%) for C16H16FIN2O10 (542.2): C 35.44, H 2.97, N
5.17; found: C 35.61, H 3.04, N 4.95.
(5RS)-1-O-Benzyl-5-bromo-5-deoxy-2-O-formyl-5-iodo-3,4-O-isopropyli-
dene-d-arabinitol (74): Diastereoisomeric mixture (3:2) separated by
careful Chromatotron chromatography. Compound (R)-74: Oil (56%);
[a]D = +38 (c = 0.64); 1H NMR: d = 1.41 (s, 3H), 1.54 (s, 3H), 3.62
(dd, J = 6.8, 9.8 Hz, 1H), 3.66 (dd, J = 6.3, 9.8 Hz, 1H), 4.50 (dd, J =
1.5, 5.9 Hz, 1H), 4.54 (s, 2H), 4.58 (dd, J = 6.0, 10.0 Hz, 1H), 5.41 (d, J
= 10.0 Hz, 1H), 5.50 (ddd, J = 1.3, 6.6, 6.6 Hz, 1H), 7.28 7.34 (m, 5H),
8.11 (s, 1H) ppm; 13C NMR: d = 6.3 (CH), 25.4 (CH3), 26.7 (CH3), 68.3
(CH2), 68.5 (CH), 73.4 (CH2), 74.6 (CH), 82.1 (CH), 109.4 (C), 127.8 (2î
CH), 127.9 (CH), 128.4 (2îCH), 137.5 (C), 160.2 (CH) ppm; IR: n˜
=
(5RS)-5-Chloro-5-deoxy-1-O-(3,5-dinitrobenzoyl)-2-O-formyl-5-iodo-3,4-
O-isopropylidene-d-arabinitol (77): Diastereoisomeric mixture (92%,
2:1), partially separated by careful Chromatotron chromatography (hex-
anes/EtOAc 85:15). Compound (R)-77: crystalline solid (67%): m.p.
1725 cmꢀ1; MS (70 eV, EI): m/z (%): 500/498 (<1) [M]+, 485/483 (3),
321/319 (3), 209/207 (15); HRMS (EI): found: 499.9565; C16H2081BrIO5
calcd 499.9518; elemental analysis calcd (%) for C16H20BrIO5 (499.1): C
38.50, H 4.04; found: C 38.72, H 3.98.
102.5 1048C (from n-pentane/EtOAc); [a]D
=
+28.6 (c = 0.22); 1H
Compound (S)-74: Oil (37%): [a]D = ꢀ12 (c = 0.73); 1H NMR: d =
1.42 (s, 3H), 1.58 (s, 3H), 3.61 (dd, J = 6.8, 9.9 Hz, 1H), 3.66 (dd, J =
6.2, 9.9 Hz, 1H), 4.46 (dd, J = 3.3, 6.1 Hz, 1H), 4.54 (d, J = 11.9 Hz,
1H), 4.55 (d, J = 11.9 Hz, 1H), 4.74 (dd, J = 6.1, 8.4 Hz, 1H), 5.44 (d, J
= 8.4 Hz, 1H), 5.54 (ddd, J = 3.5, 6.8, 6.8 Hz, 1H), 7.30 7.37 (m, 5H),
8.11 (s, 1H) ppm; 13C NMR: d = 6.1 (CH), 25.5 (CH3), 26.5 (CH3), 68.4
(CH2), 68.5 (CH), 73.5 (CH2), 76.4 (CH), 82.7 (CH), 110.2 (C), 127.8 (2î
NMR (400 MHz): d = 1.45 (s, 3H), 1.57 (s, 3H), 4.50 (ddd, J = 1.3, 1.3,
6.0 Hz, 1H), 4.60 (dd, J = 7.3, 12.1 Hz, 1H), 4.63 (dd, J = 5.8, 10.6 Hz,
1H), 4.75 (dd, J = 3.7, 11.9 Hz, 1H), 5.64 (d, J = 10.3 Hz, 1H), 5.76
(dddd, J = 1.3, 1.3, 3.7, 7.2 Hz, 1H), 8.19 (s, 1H), 9.14 (d, J = 2.1 Hz,
2H), 9.24 (dd, J = 2.3, 2.3 Hz, 1H) ppm; 13C NMR (100.6 MHz): d =
23.4 (CH), 25.3 (CH3), 26.5 (CH3), 65.9 (CH2), 67.6 (CH), 74.6 (CH), 82.6
(CH), 110.1 (C), 122.7 (CH), 129.5 (2îCH), 133.2 (C), 148.7 (2îC),
160.0 (CH), 162.2 (C) ppm; IR: n˜ = 3102, 1736, 1549 cmꢀ1; MS (70 eV,
EI): m/z (%): 545/543 (19/59) [MꢀMe]+, 433/431 (6/20), 405/403 (2/7),
347/345 (2/8), 277/275 (7/24), 195 (100); HRMS (EI): found: 544.9273;
C15H1337ClIN2O10 calcd 544.9274; elemental analysis calcd (%) for
C16H16ClIN2O10 (558.7): C 34.40, H 2.89, N 5.01; found: C 34.75, H 2.83,
N 4.74.
CH), 128.0 (CH), 128.6 (2îCH), 137.3 (C), 160.2 (CH) ppm; IR: n˜
=
1725 cmꢀ1; MS (70 eV, EI): m/z (%): 500/498 (<1) [M]+, 485/483 (1),
321/319 (2), 209/207 (9); HRMS (EI): found: 499.9483; C16H2081BrIO5
calcd 499.9518; elemental analysis calcd (%) for C16H20BrIO5 (499.1): C
38.50, H 4.04; found: C 38.67, H 3.93.
1-O-Benzyl-5-deoxy-2-O-formyl-5,5-diiodo-3,4-O-isopropylidene-d-arabi-
=
+29 (c = 1.88); 1H NMR: d = 1.40 (s,
Crystal data and structure refinement for (R)-77: C16H16ClIN2O10, Mt
=
nitol (75): Oil (90%): [a]D
558.66, monoclinic, space group P21, a = 8.0771 (1), b = 7.5186 (1), c =
3H), 1.54 (s, 3H), 3.60 (dd, J = 6.6, 9.9 Hz, 1H), 3.63 (dd, J = 6.4,
9.9 Hz, 1H), 4.50 (dd, J = 1.8, 5.9 Hz, 1H), 4.53 (s, 1H), 4.54 (s, 1H),
4.62 (dd, J = 5.9, 10.1 Hz, 1H), 4.91 (d, J = 10.1 Hz, 1H), 5.50 (ddd,
17.4913 (2) ä, b = 101.362 (1), V = 1041.40 (2) ä3, Z = 2, 1calcd
=
1.782 Mgmꢀ3, m(MoKa) = 0.71073 ä, F(000) = 552, T = 150(2) K; color-
less crystal, 0.45î0.42î0.32 mm, collected reflections 22552. The struc-
ture was solved by direct methods, all hydrogen atoms were refined ani-
J
=
1.8, 6.4, 6.6 Hz, 1H), 7.97 7.27 (m, 5H), 8.10 (s, 1H) ppm; 13C
NMR: d = ꢀ34.2 (CH), 25.5 (CH3), 26.7 (CH3), 68.2 (CH), 68.5 (CH2),
sotropically by use of full-matrix, least-squared based F2 to give R1
=
73.3 (CH2), 75.0 (CH), 82.6 (CH), 109.6 (C), 127.8 (2îCH), 127.8 (CH),
0.0162, wR2 = 0.0355 for 4757 independently observed reflections (jFo j
128.5 (2îCH), 137.4 (C), 160.3 (CH) ppm; IR: n˜
= 3010, 2938,
1724 cmꢀ1; MS (70 eV, EI): m/z (%): 546 (<1) [M]+, 531 (2), 91 (100);
HRMS (EI): found: 545.9393; C16H20I2O5 calcd 545.9400; elemental anal-
ysis calcd (%) for C16H20I2O5 (546.1): C 35.17, H 3.69; found: C 35.41,
H 3.60.
>2a(jFo j)) and 273 parameters.
Compound (S)-77: oil (33%): [a]D
=
+24.6 (c
=
0.24); 1H NMR
1.3, 1.3,
(400 MHz): d 1.47 (s, 3H), 1.60 (s, 3H), 4.51 (ddd, J
=
=
6.0 Hz, 1H), 4.55 (dd, J = 7.4, 11.7 Hz, 1H), 4.72 (dd, J = 4.0, 11.4 Hz,
1H), 4.82 (dd, J = 6.1, 9.8 Hz, 1H), 5.53 (d, J = 10.1 Hz, 1H), 5.77
(dddd, J = 1.3, 1.3, 4.0, 7.7 Hz, 1H), 8.20 (s, 1H), 9.14 (d, J = 2.1 Hz,
2H), 9.24 (dd, J = 2.1, 2.1 Hz, 1H) ppm; 13C NMR (100.6 MHz): d =
23.0 (CH), 25.6 (CH3), 26.6 (CH3), 65.7 (CH2), 67.6 (CH), 76.2 (CH), 82.9
(CH), 111.5 (C), 122.7 (CH), 129.6 (2îCH), 133.1 (C), 148.8 (2îC),
160.1 (CH), 162.2 (C) ppm; IR: n˜ = 3102, 1737, 1549 cmꢀ1; MS (70 eV,
EI): m/z (%): 545/543 (19/53) [MꢀMe]+, 433/431 (1/3), 277/275 (7/23),
195 (100); HRMS (EI): found: 544.9225; C15H1337ClIN2O10 calcd
544.9274; elemental analysis calcd (%) for C16H16ClIN2O10 (558.7): C
34.40, H 2.89, N 5.01; found: C 34.73, H 3.00, N 4.82.
(5RS)-5-Deoxy-1-O-(3,5-dinitrobenzoyl)-5-fluoro-2-O-formyl-5-iodo-3,4-
O-isopropylidene-d-arabinitol (76): Diastereoisomeric mixture (92%,
5:4), partially separated by careful Chromatotron chromatography (hex-
anes/EtOAc 85:15). Compound (R)-76: crystalline solid (51.3%): m.p.
122 1248C (from n-hexane/EtOAc); [a]D = +43.2 (c = 0.8); 1H NMR:
d = 1.43 (s, 3H), 1.52 (s, 3H), 4.48 (dd, J = 3.4, 5.7 Hz, 1H), 4.59 4.63
(m, 1H), 4.78 (dd, J = 3.4, 12.0 Hz, 1H), 5.70 5.71 (m, 2H), 6.87 (dd, J
= 8.8 Hz, 2J(F,H) = 48.7 Hz, 1H), 8.14 (s, 1H), 9.14 (d, J = 2.1 Hz,
2H), 9.25 (dd, J = 2.1, 2.1 Hz, 1H) ppm; 13C NMR (100 MHz): d = 25.2
(CH3), 27.2 (CH3), 65.7 (CH2), 67.2 (3J(F,C) = 3.2 Hz, CH), 71.6 (1J(F,C)
= 248.6 Hz, CH), 75.1 (CH), 80.3 (2J(F,C) = 28.4 Hz, CH), 110.2 (C),
122.7 (CH), 129.6 (2îCH), 133.2 (C), 148.7 (2îC), 159.7 (CH), 162.2
(C); IR n˜ = 3094, 2984, 1742, 1372, 1240, 1170 cmꢀ1; MS (70 eV, EI): m/z
(%): 527 (40) [MꢀMe]+, 415 (21), 195 (100), 149 (32); HRMS (EI):
found: 526.9603; C15H13FIN2O10 calcd 526.9599; elemental analysis calcd
(%) for C16H16FIN2O10 (542.2): C 35.44, H 2.97, N 5.17; found: C 35.71,
H 2.74, N 5.13.
(5RS)-5-Bromo-5-deoxy-1-O-(3,5-dinitrobenzoyl)-2-O-formyl-5-iodo-3,4-
O-isopropylidene-d-arabinitol (78): Diastereoisomeric mixture (93%,
2:1), partially separated by careful Chromatotron chromatography (hex-
anes/EtOAc 98:2!90:10). Compound (R)-78: crystalline solid (66%);
m.p. 99 1008C (from n-hexane/EtOAc); [a]D
=
+23 (c = 0.45); 1H
NMR: d = 1.46 (s, 3H), 1.58 (s, 3H), 4.52 (d, J = 5.8 Hz, 1H), 4.58 (dd,
J = 7.6, 11.7 Hz, 1H), 4.72 (dd, J = 6.1, 10.5 Hz, 1H), 4.73 (dd, J = 4.7,
5806
¹ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2003, 9, 5800 5809

Chiral 1-Halo-1-iodo Alditols
5800 5809
11.0 Hz, 1H), 5.32 (d, J = 10.8 Hz, 1H), 5.78 (dd, J = 3.6, 7.2 Hz, 1H),
5-Deoxy-4-O-(2,2-dimethylpropanoyl)-2-O-formyl-5-diiodo-1,3-O-(tetra-
isopropyldisiloxane-1,3-diyl)-d-arabinitol (86): Crystalline solid (84%):
m.p. 76.9 78.28C (from n-hexane/EtOAc); [a]D = ꢀ19 (c = 0.84); 1H
NMR: d = 1.01 1.30 (m, 28H), 1.31 (s, 9H), 3.76 (dd, J = 10.4, 10.4 Hz,
1H), 3.82 (dd, J = 5.9, 10.4 Hz, 1H), 4.17 (d, J = 8.5 Hz, 1H), 4.96 (dd,
J = 5.8, 10.3 Hz, 1H), 5.07 (dd, J = 1.8, 8.5 Hz, 1H), 5.56 (d, J =
1.9 Hz, 1H), 7.92 (s, 1H) ppm; 13C NMR: d = ꢀ27.9 (CH), 12.3 (CH),
13.2 (2îCH), 15.2 (CH), 17.0 (CH3), 17.1 (2îCH3), 17.3 (CH3), 17.4 (2î
CH3), 17.6 (CH3), 17.9 (CH3), 27.1 (3îCH3), 39.2 (C), 57.6 (CH2), 69.7
(CH), 71.1 (CH), 75.4 (CH), 160.2 (CH), 176.5 (C) ppm; IR: n˜ = 2948,
2869, 1727, 1725 cmꢀ1; MS (70 eV, EI): m/z (%): 699 (16) [MꢀC3H7]+, 57
(100); HRMS (EI): found: 699.0163; C20H37I2O7Si2 calcd 699.0167; ele-
mental analysis calcd (%) for C23H44I2O7Si2 (742.6): C 37.20, H 5.97;
found: C 37.29, H 5.69
8.20 (s, 1H), 9.13 (d, J
= 1.8 Hz, 2H), 9.24 (dd, J = 2.0, 2.0 Hz,
1H) ppm; 13C NMR: d = 3.6 (CH), 25.4 (CH3), 26.6 (CH3), 65.9 (CH2),
67.6 (CH), 74.8 (CH), 82.4 (CH), 110.2 (C), 122.6 (CH), 129.5 (2îCH),
133.2 (C), 148.7 (2îC), 160.1 (CH), 162.2 (C) ppm; IR: n˜ = 3100, 1731,
1549 cmꢀ1; MS (70 eV, EI): m/z (%): 589/587 (90) [MꢀMe]+, 477/475 (9),
321/319 (28), 195 (100); HRMS (EI): found: 588.8742; C15H1381BrIN2O10
calcd 588.8778; elemental analysis calcd (%) for C16H16BrIN2O10 (603.1):
C 31.86, H 2.67, N 4.64; found: C 31.95, H 2.51, N 4.51.
Crystal data and structure refinement for (R)-78: C16H16BrIN2O10, Mt
603.12, monoclinic, space group P21, a = 8.0662 (2), b = 9.0388 (3), c =
14.8243 (6) ä, b = 105.710 (2)o, V = 1040.45 (6) ä3, Z = 2, 1calcd
=
=
1.925 gcmꢀ3, m(MoKa) = 0.71073 ä, F(000) = 588, T = 150 (2) K; color-
less crystal, 0.55î0.40î0.25 mm, Rigaku AFC7-S diffractometer, collect-
ed reflections 6834. The structure was solved by direct methods, all non-
hydrogen atoms were refined anisotropically by use of full-matrix, least-
squared based on F2 to give R1 = 0.0247, wR2 = 0.0631 for 3585 inde-
pendently observed reflections (jFo j>2a(jFo j)) and 274 parameters.
2,3-Di-O-acetyl-1,5-dideoxy-4-O-formyl-1,1-diiodo-l-arabinitol (102): Oil
1
(90%): [a]D = ꢀ65 (c = 0.48); H NMR: d = 1.27 (d, J = 6.5 Hz, 3H),
2.14 (s, 3H), 2.16 (s, 3H), 5.02 (d, J = 7.8 Hz, 1H), 5.04 (dddd, J = 6.5,
6.5, 6.5, 6.7 Hz, 1H), 5.31 (dd, J = 2.8, 7.9 Hz, 1H), 5.64 (dd, J = 2.8,
6.7 Hz, 1H), 7.97 (s, 1H) ppm; 13C NMR: d = ꢀ32.9 (CH), 16.1 (CH3),
20.77 (CH3), 20.83 (CH3), 68.0 (CH), 71.8 (CH), 73.4 (CH), 159.7 (CH),
Compound (S)-78: Crystalline solid (34%): m.p. 129 129.58C (from n-
hexane/EtOAc); [a]D = ꢀ10 (c = 0.88); 1H NMR: d = 1.47 (s, 3H),
1.60 (s, 3H), 4.53 (d, J = 5.8 Hz, 1H), 4.55 (dd, J = 7.2, 11.7 Hz, 1H),
4.71 (dd, J = 4.0, 11.7 Hz, 1H), 4.83 (dd, J = 6.1, 10.5 Hz, 1H), 5.25 (d,
J = 10.8 Hz, 1H), 5.76 (dd, J = 4.0, 7.6 Hz, 1H), 8.20 (s, 1H), 9.13 (d, J
= 1.8 Hz, 2H), 9.24 (dd, J = 2.0, 2.0 Hz, 1H) ppm; 13C NMR: d = 3.3
(CH), 25.6 (CH3), 26.6 (CH3), 65.7 (CH2), 67.5 (CH), 76.1 (CH), 82.7
(CH), 111.2 (C), 122.7 (CH), 129.5 (2îCH), 133.2 (C), 148.7 (2îC),
160.1 (CH), 162.1 (C) ppm; IR: n˜ = 3101, 1728, 1549 cmꢀ1; MS (70 eV,
EI): m/z (%): 589/587 (20) [MꢀMe]+, 393/395 (14), 321/319 (35), 195
(57); HRMS (EI): found: 588.8747; C15H1381BrIN2O10 calcd 588.8778; ele-
mental analysis calcd (%) for C16H16BrIN2O10 (603.1): C 31.86, H 2.67, N,
4.64; found: C 31.97, H 2.64, N, 4.39.
169.3 (C), 169.6 (C) ppm; IR: n˜
=
3018, 2940, 1754, 1728 cmꢀ1; MS
(70 eV, EI): m/z (%): 485 (<1) [M+H]+, 439 (76), 269 (100); HRMS
(EI): found: 484.8932; C10H15I2O6 calcd 484.8958; elemental analysis
calcd (%) for C10H14I2O6 (484.0): C 24.81, H 2.92; found: C 24.92,
H 2.96.
2-O-Acetyl-3,5-O-benzylidene-1-deoxy-4-O-formyl-1,1-diiodo-d-ribitol
(103): Oil (76%): [a]D = +2.4 (c = 0.74); 1H NMR: d = 2.21 (s, 3H),
3.62 (dd, J = 9.5, 10.9 Hz, 1H), 4.01 (dd, J = 7.6, 9.3 Hz, 1H), 4.47 (dd,
J = 5.3, 10.9 Hz, 1H), 4.96 (dd, J = 2.6, 7.6 Hz, 1H), 5.12 (ddd, J = 5.3,
9.3, 9.5 Hz, 1H), 5.53 (s, 1H), 5.55 (d, J = 2.6 Hz, 1H), 7.40 7.42 (m,
3H), 7.46 7.48 (m, 2H), 7.95 (s, 1H) ppm; 13C NMR: d = ꢀ28.0 (CH),
20.9 (CH3), 65.3 (CH), 67.1 (CH2), 76.6 (CH), 78.9 (CH), 101.2 (CH),
126.9 (2îCH), 128.3 (2îCH), 129.3 (CH), 136.2 (C), 158.6 (CH), 159.5
(C) ppm; IR: n˜ = 3024, 1752, 1373, 1144, 1004 cmꢀ1; MS (70 eV, EI): m/z
(%): 546 (3) [M]+, 486 (2), 419 (9), 101 (100); HRMS (EI): found:
545.9064; C15H16I2O6 calcd 545.9036; elemental analysis calcd (%) for
C15H16I2O6 (546.1): C 32.99, H 2.95; found: C 32.88, H 2.67.
(5RS)-1-O-[tert-Butyl(dimethyl)silyl]-5-chloro-5-deoxy-2-O-formyl-5-
iodo-3,4-O-(oxomethylene)-d-arabinitol (80): Diastereoisomeric mixture
(65%, 4:3) separated by careful column chromatography (hexanes/
EtOAc 98:2); Compound (R)-80: crystalline solid; m.p. 130 1328C (from
n-hexane/EtOAc); [a]D = ꢀ4.8 (c = 0.44); 1H NMR: d = 0.1 (s, 6H),
0.89 (s, 9H), 3.69 (dd, J = 9.0, 9.5 Hz, 1H), 3.79 (dd, J = 5.7, 9.5 Hz,
1H), 5.09 (dd, J = 7.3, 10.0 Hz, 1H), 5.16 (d, J = 7.3 Hz, 1H), 5.38 (dd,
J = 5.7, 9.0 Hz, 1H), 5.64 (d, J = 10.0 Hz, 1H), 8.08 (s, 1H) ppm; 13C
NMR: d = ꢀ5.7 (CH3), ꢀ5.6 (CH3), 16.9 (CH), 18.2 (C), 25.6 (3îCH3),
59.4 (CH2), 68.8 (CH), 74.7 (CH), 81.8 (CH), 151.1 (C), 159.2 (CH); IR
(CCl4): n˜ = 1844, 1736, 1163, 1086 cmꢀ1; MS (79 eV, EI): m/z (%): 409/
407 (2/5) [MꢀC4H9]+, 319/317 (4/11), 245/243 (6/18), 190 (12), 117 (32),
103 (100); HRMS (EI): found: 406.9234; C9H1335ClIO6Si calcd 406.9215;
elemental analysis calcd (%) C13H22ClIO6Si (464.7): C 33.60, H 4.77;
found: C 33.66, H 4.63.
2,3-Di-O-acetyl-4-deoxy-1-O-formyl-4,4-diiodo-l-erythritol (107): Crys-
talline solid (82%): m.p. 60.9 61.18C (from n-hexane/EtOAc); [a]D
=
ꢀ52 (c = 1.31); 1H NMR: d = 2.11 (s, 3H), 2.22 (s, 3H), 4.15 (dd, J =
3.5, 12.5 Hz, 1H), 4.49 (dd, J = 2.4, 12.5 Hz, 1H), 5.10 (m, 1H), 5.10 (m,
1H), 5.34 (d, J = 2.9 Hz, 1H), 8.03 (s, 1H) ppm; 13C NMR: d = ꢀ31.5
(CH), 20.8 (2îCH3), 60.0 (CH2), 72.4 (CH), 73.8 (CH), 160.2 (CH), 169.1
(C), 169.2 (C) ppm; IR: n˜ = 3029, 2959, 1753 cmꢀ1; MS (70 eV, EI): m/z
(%): 470 (1) [M]+, 410 (47), 343 (29), 241 (100); HRMS (EI): found:
469.8680; C9H12I2O6 calcd 469.8723; elemental analysis calcd (%) for
C9H12I2O6 (470.0): C 23.00, H 2.57; found: C 23.15, H 2.42.
Compound (S)-80: crystalline solid; m.p. 73 758C (from n-hexane/
EtOAc); [a]D = ꢀ26.8 (c = 0.40); 1H NMR: d = 0.09 (s, 6H), 0.87 (s,
9H), 3.70 (dd, J = 9.0. 9.7 Hz, 1H), 3.79 (dd, J = 5.7, 9.7 Hz, 1H), 5.05
(dd, J = 2.9, 7.1 Hz, 1H), 5.20 (dd, J = 7.1, 8.5 Hz, 1H), 5.50 (ddd, J =
2.9, 5.7, 9.0 Hz, 1H), 5.71 (d, J = 8.5 Hz, 1H), 8.07 (s, 1H) ppm; 13C
NMR: d = ꢀ5.5 (CH3), ꢀ5.4 (CH3), 18.1 (C), 20.0 (CH), 25.7 (3îCH3),
60.1 (CH2), 68.3 (CH), 76.5 (CH), 82.4 (CH), 152.1 (C), 159.2 (CH); IR
(CCl4): n˜ = 1842, 1736, 1161, 1085 cmꢀ1; MS (70 eV, EI): m/z (%): 409/
407 (1/3) [MꢀC4H9]+, 319/317 (3/7), 245/243 (5/15), 190 (10), 117 (30),
103 (100); HRMS (EI): found: 316.9261; C7H1135ClIO2Si calcd 316.9264;
elemental analysis calcd (%) for C13H22ClIO6Si (464.7): C 33.60, H 4.77;
found: C 33.85, H 4.75.
3,5-Di-O-acetyl-1,2-dideoxy-4-O-formyl-1,1-diiodo-D-erythro-pentitol
(108): Oil (94%): [a]D
=
+5 (c = 0.44); 1H NMR: d = 2.05 (s, 3H),
2.06 (s, 3H), 2.65 (ddd, J = 9.9, 10.7, 15.2 Hz, 1H), 2.86 (ddd, J = 2.6,
3.6, 15.2 Hz, 1H), 4.14 (dd, J = 7.0, 12.1 Hz, 1H), 4.23 (dd, J = 4.0,
12.1 Hz, 1H), 4.93 (dd, J = 3.6, 10.7 Hz, 1H), 5.03 (ddd, J = 2.6, 3.5,
9.9 Hz, 1H), 5.39 (ddd, J = 3.5, 4.0, 7.0 Hz, 1H), 8.06 (s, 1H) ppm; 13C
NMR: d = ꢀ36.7 (CH), 20.6 (CH3), 20.7 (CH3), 47.7 (CH2), 61.6 (CH2),
70.0 (CH), 73.0 (CH), 159.6 (CH), 169.8 (C), 170.3 (C) ppm; IR: n˜
=
3025, 2945, 1738 cmꢀ1; MS (70 eV, EI): m/z (%): 484 (<1) [M]+, 357
(23), 209 (100); HRMS (EI): found: 483.8832; C10H14I2O6 calcd 483.8880;
elemental analysis calcd (%) for C10H14I2O6 (484.0): C 24.81, H 2.92;
found: C 25.05, H 2.90.
1-O-[tert-Butyl(dimethyl)silyl]-5-deoxy-2-O-formyl-5,5-diiodo-3,4-O-
(oxomethylene)-d-arabinitol (82): Crystalline solid (75%): m.p. 138.4
1,1-Diiodo-4-O-formyl-1,2,3-trideoxy-6-O-(triisopropylsilyl)-d-glycero-
pentitol (109): Oil (90%): [a]D = +0.6 (c = 1.08); 1H NMR: d = 1.05
(m, 21H), 1.80 (m, 1H), 1.89 (m, 1H), 2.38 (m, 2H), 3.75 (dd, J = 5.0,
10.6 Hz, 1H), 3.79 (dd, J = 5.6, 10.6 Hz, 1H), 5.05 (dddd, J = 4.9, 4.9,
4.9, 9.4 Hz, 1H), 5.15 (dd, J = 6.2, 6.2 Hz, 1H), 8.10 (s, 1H) ppm; 13C
NMR: d = ꢀ27.7 (CH), 11.9 (3îCH), 17.9 (6îCH3), 32.7 (CH2), 43.6
1
140.38C (from n-hexane/EtOAc); [a]D = ꢀ14 (c = 0.53); H NMR: d =
0.09 (s, 6H), 0.88 (s, 9H), 3.69 (dd, J = 9.0, 9.6 Hz, 1H), 3.75 (dd, J =
5.8, 9.7 Hz, 1H), 4.84 (d, J = 10.4 Hz, 1H), 5.15 (d, J = 6.9 Hz, 1H),
5.18 (dd, J = 6.9, 10.4 Hz, 1H), 5.44 (dd, J = 5.8, 8.8 Hz, 1H), 8.07 (s,
1H) ppm; 13C NMR: d = ꢀ42.8 (CH), ꢀ5.5 (CH3), ꢀ5.4 (CH3), 18.1 (C),
25.7 (3îCH3), 59.5 (CH2), 68.1 (CH), 75.4 (CH), 80.2 (CH), 151.3 (C),
159.3 (CH) ppm; IR: n˜ = 2955, 2931, 1833, 1814, 1731 cmꢀ1; MS (70 eV,
EI): m/z (%): 499 (4) [MꢀC4H9]+, 103 (100); HRMS (EI): found:
498.8576; C9H13I2O6Si calcd 498.8571; elemental analysis calcd (%) for
C13H22I2O6Si (556.2): C 28.06, H 3.99; found: C 28.14, H 3.75.
(CH2), 64.3 (CH2), 72.6 (CH), 160.7 (CH) ppm; IR: n˜ = 1721, 1185 cmꢀ1
;
MS (70 eV, EI): m/z (%): 541 (2) [M+H]+, 495 (35), 367 (4), 159 (100);
HRMS (EI): found: 541.0208; C15H31I2O3Si calcd 541.0132; elemental
analysis calcd (%) for C15H30I2O3Si (540.3): C 33.35, H 5.60; found: C
33.33, H 5.93.
5807
Chem. Eur. J. 2003, 9, 5800 5809
www.chemeurj.org
¹ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

E. Suµrez et al.
FULL PAPER
(1E)-3,5-Di-O-acetyl-1,2-dideoxy-4-O-formyl-1-iodo-d-erythro-pent-1-
enitol ((E)-111) and (1Z)-3,5-di-O-acetyl-1,2-dideoxy-4-O-formyl-1-iodo-
d-erythro-pent-1-enitol ((Z)-111): Dry, deoxygenated DMF (48 mL,
0.62 mmol) was added to a suspension of CrCl2 (76 mg, 0.62 mmol) in
dry, deoxygenated THF (2 mL), and the mixture was stirred at room tem-
perature under nitrogen for 30 min. A solution of compound 22 (82.4 mg,
0.15 mmol) in dry THF (1.5 mL) was then added, and stirring was contin-
ued at this temperature for 30 min. The reaction mixture was poured into
ice/water and extracted with EtOAc. The organic extracts were washed
with brine, dried, and evaporated. The residue was purified by column
chromatography (n-hexane/EtOAc, 90:10!80:20) to provide vinyl io-
dides (E)-111 (18.2 mg, 0.051 mmol, 34%) and (Z)-111 (29.8 mg,
0.084 mmol, 55%). Compound (E)-111: Oil, [a]D +52.5 (c = 1.14); 1H
NMR: d = 2.07 (s, 3H), 2.09 (s, 3H), 4.19 (dd, J = 12.4, 6.6 Hz, 1H),
4.26 (dd, J = 3.8, 12.4 Hz, 1H), 5.34 (ddd, J = 3.8, 4.6, 6.6 Hz, 1H), 5.42
(dd, J = 4.6, 7.4 Hz, 1H), 6.53 (dd, J = 7.4, 14.6 Hz, 1H), 6.65 (d, J =
14.6 Hz, 1H), 8.08 (s, 1H) ppm; 13C NMR (50.3 MHz): d = 20.7 (CH3),
20.8 (CH3), 61.4 (CH2), 70.2 (CH), 73.3 (CH), 83.8 (CH), 138.4 (CH),
Vol. 4 (Eds.: A. R. Katritzky, O. Meth-Cohn, C. W. Rees), Perga-
mon, Oxford, 1995, pp.2 40.
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159.7 (CH), 169.3 (C), 170.4 (C) ppm; IR: n˜ = 3024, 2943, 1734 cmꢀ1
;
MS (70 eV, EI): m/z (%): 356 (<1) [M]+, 313 (<1), 311 (<1), 229 (<1),
183 (100); HRMS (EI): found 355.9768; C10H13IO6 calcd 355.9757; ele-
mental analysis calcd (%) for C10H13IO6 (356.1): C 33.73, H 3.68; found:
C 33.61, H 3.92.
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2000, 41, 193 195.
Compound (Z)-111: Oil, [a]D ꢀ2.8 (c = 1.35); 1H NMR d = 2.07 (s,
6H), 4.18 (dd, J = 7.3, 12.1 Hz, 1H), 4.26 (dd, J = 4.0, 12.1 Hz, 1H),
5.49 (ddd, J = 4.0, 4.2, 7.3 Hz, 1H), 5.72 (dd, J = 4.2, 8.5 Hz, 1H), 6.32
(dd, J = 8.0, 8.5 Hz, 1H), 6.74 (d, J = 8.0 Hz, 1H), 8.10 (s, 1H) ppm;
13C NMR d = 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) ppm; IR:
n˜ = 3025, 2939, 1736 cmꢀ1; MS (70 eV, EI): m/z (%): 356 (1) [M]+, 229
(<1), 183 (100); HRMS (EI): found 355.9695; C10H13IO6 calcd 355.9698;
elemental analysis calcd (%) for C10H13IO6 (356.1): C 33.73, H 3.68;
found: C 33.58, H 4.07.
(1S,3E)-1-[(1R)-2-Acetyloxy-1-(formyloxy)ethyl]-6-phenyl-3-hexenyl ace-
tate (112): Dry, deoxygenated DMF (38 mL, 0.49 mmol) was added to a
suspension of CrCl2 (60 mg, 0.49 mmol) in dry, deoxygenated THF
(1 mL), and the mixture was stirred at room temperature under nitrogen
for 30 min. A solution of compound 108 (82 mg, 0.17 mmol) and hydro-
cinnamaldehyde (23 mg, 0.17 mmol) in dry THF (1 mL) was then added,
and stirring was continued at this temperature for 2.5 h. The reaction
mixture was poured into ice/water and extracted with EtOAc. The organ-
ic extracts were washed with brine, dried, and evaporated. The residue
was purified by column chromatography (n-hexane/EtOAc, 90:10) to
give compound 112 (41 mg, 0.12 mmol, 70%): Oil, [a]D +25.5 (c
=
1
1.71); H NMR d = 2.04 (s, 3H), 2.06 (s, 3H), 2.34 (m, 4H), 2.66 (dd, J
= 7.9, 7.9 Hz, 2H), 4.18 (dd, J = 7.2, 12.4 Hz, 1H), 4.32 (dd, J = 3.1,
12.4 Hz, 1H), 5.11 (ddd, J = 5.1, 5.1, 7.5 Hz, 1H), 5.29 (ddd, J = 3.7,
3.7, 7.2 Hz, 1H), 5.36 (ddd, J = 7.3, 7.3, 14.8 Hz, 1H), 5.56 (ddd, J =
7.2, 7.2, 14.7 Hz, 1H), 7.18 (m, 3H), 7.28 (m, 2H), 8.06 (s) ppm; 13C
NMR d = 20.7 (CH3), 20.8 (CH3), 33.5 (CH2), 34.2 (CH2), 35.6 (CH),
61.7 (CH), 71.0 (2îCH), 124.0 (CH), 125.8 (CH), 128.3 (2îCH), 128.5
(2îCH), 134.2 (CH), 141.6 (C), 159.9 (C), 170.0 (C), 170.6 (C) ppm; IR:
n˜ = 3027, 2938, 1732 cmꢀ1; MS (70 eV, EI): m/z (%): 348 (<1) [M]+, 289
(<1), 288 (<1), 243 (<1), 242 (<1), 228 (18), 182 (16), 109 (35), 91
(100); HRMS (EI): found 348.1499; C19H24O6 calcd 348.1573; elemental
analysis calcd (%) for C19H24O6 (348.4): C 65.50, H 6.94; found: C 65.83,
H 6.57.
Acknowledgement
This work was supported by the Investigation Programs nos. PPQ2000
0728, BQU2000 0650, and BQU2001 1665 of the DirecciÛn General de
InvestigaciÛn CientÌfica y Tÿcnica, Spain. C.R.-F. thanks the DirecciÛn
General de Universidades e InvestigaciÛn del Gobierno de Canarias for
a fellowship.
[21] W. Korytnyk, S. Valentekovic-Horvath, C. R. Petrie III, Tetrahedron
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with galactal and fucal derivatives gave only the equatorial fluorine
at C2 while glucal derivatives gave diastereoisomeric mixtures.
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5808
¹ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2003, 9, 5800 5809

Chiral 1-Halo-1-iodo Alditols
5800 5809
[25] Throughout this section the numbering of the dihaloalditols always
begins at the carbon bearing the halogens, although the correct
IUPAC systematic nomenclature has been used in the Experimental
Section and Supporting Information
Bernard, J. A. Pÿrez-Andrÿs, Angew. Chem. 1999, 111, 2528 2530;
Angew. Chem. Int. Ed. 1999, 38, 2384 2386; b) J. M. ConcellÛn, H.
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2002, 1839 1847.
[26] CCDC-212682 [(R)-76], CCDC-212683 [(R)-77], and CCDC-155002
[(R)-78] contain the supplementary crystallographic data for this
paper. These data can be obtained free of charge via www.ccdc.
cam.ac.uk/conts/retrieving.html (or from the Cambridge Crystallo-
graphic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK;
fax: (+44) 1223-336-033; or e-mail: deposit@ccdc.cam.ac.uk).
[27] The 3-deoxy-d-glucal precursor of 96 was prepared in two steps by
BF3-catalyzed rearrangement of commercially available tri-O-acetyl-
d-glucal, and LiAlH4 reduction of the hex-2-enopyranoside formed,
84% overall yield (R. J. Ferrier, Methods Carbohydr. Chem. 1972, 6,
307 311; B. Fraser-Reid, S. Y-K. Tam, B. Radatus, Can. J. Chem.
1975, 53, 2005 2016). A one-step method is available as well, also
starting from tri-O-acetyl-d-glucal, although with a lower yield of
58% (N. Greenspoon, E. Keinan, J. Org. Chem. 1988, 53, 3723
3731).
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Received: July 2, 2003 [F5294]
5809
Chem. Eur. J. 2003, 9, 5800 5809
www.chemeurj.org
¹ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim