Synthesis of 1,1-dibromo-1-alkenes from partially and unprotected aldoses

Article abstract of DOI:10.1016/S0040-4039(02)00149-1

Partially and unprotected aldoses react with dibromomethylenetriphenylphosphorane, generated in situ from dibromomethyltriphenylphosphonium bromide in the presence of zinc, to give corresponding unsaturated Wittig adducts in good yields.

Full text of DOI:10.1016/S0040-4039(02)00149-1

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 1847–1849
Synthesis of 1,1-dibromo-1-alkenes from partially and
unprotected aldoses
Franck Dolhem, Catherine Li e` vre* and Gilles Demailly
Laboratoire de Chimie des Glucides, Universit e´ de Picardie Jules Verne, 33 Rue Saint-Leu, F-80039 Amiens, France
Received 10 January 2002; revised 18 January 2002; accepted 21 January 2002
Abstract—Partially and unprotected aldoses react with dibromomethylenetriphenylphosphorane, generated in situ from dibro-
momethyltriphenylphosphonium bromide in the presence of zinc, to give corresponding unsaturated Wittig adducts in good yields.
©
2002 Elsevier Science Ltd. All rights reserved.
1
,1-Dibromo-1-alkenes are versatile intermediates in
and zinc, to give the corresponding E unsaturated Wittig
products with good yields and stereoselectivity.
9
organic synthesis. These dibromocompounds have been
often used for the synthesis of acetylenics and more
recently in coupling reactions.
1,2
3
We have extended the use of zinc to generate in situ the
dibromomethylenetriphenylphosphorane in order to syn-
thesize 1,1-dibromo-1-alkenes from aldoses whereon
there are few reports.
4,5
The Wittig-type reaction has been employed as a
convenient method to their synthesis and the well-known
conditions are the Corey–Fuchs conditions. Recently,
1
6
Rassat described the synthesis of acetylenics via 1,1-
We now report herein an efficient method for olefination
of aldoses having free hydroxyl groups to 1,1-dibromo-1-
alkenes precursors of glyco-1-ynitols. The reaction of
dibromo-1-alkenes from aromatic and aliphatic alde-
hydes. These dibromocompounds were prepared by the
condensation of aldehydes with dibromomethylene-
triphenylphosphorane generated in situ from dibro-
2-deoxy-5-O-trityl-
D
-ribofuranose
1
with dibro-
momethyltriphenylphosphonium bromide in the presence
of zinc in refluxing 1,4-dioxane led to (2R,3R) 6,6-
dibromo-1-O-trityl-hex-5-ene-1,2,3-triol 2 (Scheme 1).
4,7
momethyltriphenylphosphonium
bromide
tBuOK. Moreover Chapleur described the synthesis of
,1-dibromo-1-alkenes from lactones. In this case, the
and
8
1
dibromomethylenetriphenylphosphorane was generated
by reaction of tBuOK in THF on an excess of bro-
momethyltriphenylphosphonium bromide.
2
PPh3 + CBr4
Ph PCBr ,Br + PPh
3 3 3
CH Cl
2
2
H O
2
In a preceding communication, we reported the reaction
of partially and unprotected aldoses with methyl bro-
moacetate or bromoacetonitrile, tri-n-butylphosphine
Ph PCHBr , Br
3
2
Scheme 2.
TrO
O
TrO
OH
Br
Br
OH
Ph3PCHBr2, Br (4 eq.)
Zn (4 eq.)
,4-dioxane rfx 40 min
yield : 90%
1
HO
HO
2
1
Scheme 1.
Keywords: dibromoalkenes; aldoses; dibromomethyltriphenylphosphonium bromide; ylid.
*
0
Corresponding author. Fax: +33 (0) 3 22 82 75 61; e-mail: catherine.lievre@sc.u-picardie.fr
040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)00149-1

1
848
F. Dolhem et al. / Tetrahedron Letters 43 (2002) 1847–1849
Table 1. Reaction of partially and unprotected aldoses with dibromomethyltriphenylphosphonium bromide (4 equiv.) in
presence of zinc (4 equiv.) in refluxing 1,4-dioxane
1
1
NMR and mass were used to establish the structure of
olefin 2. Indeed, the NMR spectra exhibited three charac-
teristic peaks: 134.8 and 90.5 ppm attributed, respec-
tively to C- and C- and 6.48 ppm attributed to H- .
a fourfold excess of zinc. This phosphonium salt was
4,10
obtained under a modified Ramirez procedure
(Scheme 2) and isolated. Moreover it must be recrystal-
5
6
5
Ph PCHBr , Br + Zn
Ph P=CBr + ZnBr2
3 2
3
2
Good yields of 2 were obtained using a fourfold excess
of dibromomethyltriphenylphosphonium bromide and
10
Scheme 3.

F. Dolhem et al. / Tetrahedron Letters 43 (2002) 1847–1849
1849
lized and its structure has been confirmed by NMR and
the financial support. This work was also supported by
the ‘Conseil r e´ gional de Picardie’.
1
0
mass. When zinc’s activation is not sufficient, the
reaction needs a larger excess of both reagents to bring
it to completion. The zinc needs to be prepared by the
oxydo-reduction reaction of zinc chloride by lithium or
sodium.
References
1. Corey, E. J.; Fuchs, P. L. Tetrahedron Lett. 1972, 13,
A series of dibromoolefins has been obtained under our
3769–3772.
optimized conditions (Table 1): the yields were excellent
2. de Meijere, A.; Kozhuskov, S.; Haumann, T.; Boese, R.;
Puls, C.; Cooney, M. J.; Scott, L. T. Chem. Eur. J. 1995,
1, 124–131.
3. (a) Shen, W.; Wang, L. J. Org. Chem. 1999, 64, 8873–
8879; (b) Shen, W. Synlett 2000, 737–739.
with 2,3:5,6-di-O-isopropylidene-a-
90%), and slightly lower with partially and unprotected
substrates (44 to 77%). These yields are satisfactory on
the free aldoses: 60% from deoxy- -glucose 9 and 48%
from -ribose 19. On the other substrates, a deprotection
D
-mannofuranose 3
(
D
D
4. Ramirez, F.; Desai, N. B.; McKelvie, N. J. Am. Chem.
of hydroxyl groups takes place when the reaction time
is too long. This degradation was attributed to the
Soc. 1962, 84, 1745–1747.
5. Maryanoff, B. E.; Reitz, A. B. Chem. Rev. 1989, 89,
863–927.
formation of ZnBr during the reaction. Under Rassat’s
2
conditions: dibromomethyltriphenylphosphonium bro-
mide with tBuOK in THF, the dibromoolefins cannot be
formed from aldoses when a free hydroxyl group is
present. But, it is possible on the 2,3:5,6-di-O-isopropy-
6. Michel, P.; Gennet, D.; Rassat, A. Tetrahedron Lett.
1999, 40, 8575–8578.
7. Wolkoff, P. Can. J. Chem. 1975, 53, 1333–1335.
8. Lakhrissi, Y.; Taillefumier, C.; Chr e´ tien, F.; Chapleur, Y.
Tetrahedron Lett. 2001, 42, 7265–7268.
9. (a) Li e` vre, C.; Fr e´ chou, C.; Demailly, G. Tetrahedron
Lett. 1995, 36, 6467–6470; (b) Le Mignot, V.; Li e` vre, C.;
Fr e´ chou, C.; Demailly, G. Tetrahedron Lett. 1998, 39,
983–984; (c) Li e` vre, C.; Fr e´ chou, C.; Demailly, G. Carbo-
hyd. Res. 1997, 303, 1–15.
10. Preparation of dibromomethyltriphenylphosphonium bro-
mide: carbon tetrabromide* (16.4 g, 49.4 mmol) was
added to a solution of triphenylphosphine (26 g, 99.1
mmol) in methylene chloride (240 mL). The solution was
stirred for 15 min at room temperature. Water (8 mL)
was added to this resulting red reaction. After 15 min of
vigorous magnetic stirring, the aqueous layer was sepa-
lidene-a- -mannofuranose 3, to obtain olefin 4 in similar
D
yield (89%).
The mildness of our conditions allowed us to form the
dibromoolefins on aldoses having free hydroxyl groups.
This is due to the formation of the dibromomethylene-
triphenylphosphorane in situ from the corresponding
phosphonium salt and zinc (Scheme 3). In this way, usual
Wittig’s parasite reactions were avoided.
In summary, an easy direct access to 1,1-dibromo-1-alke-
nes derivatives from partially or unprotected aldoses is
now available. At present, we continue our studies to
synthesize acetylenics from these 1,1-dibromoolefins.
rated of CH Cl . The organic layer was dried and evapo-
2 2
rated at reduced pressure to syrup. The salt was
precipitated by addition of acetonitrile. The yellow pow-
der obtained was filtered, dried under vacuum and recrys-
General procedure for the preparation of 1,1-dibromo-1-
alkenes
tallized from dry acetonitrile** at 20
h at reflux
temperature. The solution was filtered hot and the dibro-
momethyltriphenylphosphonium bromide *** recrystal-
lized was filtered and dried under vacuum.
The anhydrous 1,4-dioxane (15 mL) was added to a
mixture of zinc (3.19 mmol, 4 equiv.), dibromomethyl-
triphenylphosphonium bromide (3.19 mmol, 4 equiv.)
and sugar (0.79 mmol). The mixture was stirred under
an argon atmosphere and allowed to 60°C to reflux. When
the substrate had completely reacted (TLC), the mixture
was filtered and concentrated in vacuum to afford a
residue, which was purified by flash chromatography.
*: CBr
**: Acetonitrile must be freshly distillate on CaCl
must be a colorless solid.
4
.
2
***: The salt was stable at least 6 months if stored at
−20°C under an inert atmosphere.
13
NMR C (CDCl , 75 MHz): 30.12 (d, J=48 Hz), 116.70
3
(d, J=87.7 Hz), 130.68 (d, J=12.8 Hz), 134.98 (d, J=9.8
Hz), 136.40 (d, J=2 Hz). FAB-MS (nitrobenzylalcohol
+
+
matrix): C H Br P m/z: 433, C H BrP m/z: 353,
C H16P m/z: 275.
19
19
16
2
19 15
+
Acknowledgements
1
1. Bouhlel, E.; Rathke, M. W. Synth. Commun. 1991, 21,
The authors thank the French Ministry of Research for
133–136.