An Alternative Procedure in the Takai Reaction Using Chromium(III) Chloride Hexahydrate as a Convenient Source of Chromium(II)

Article abstract of DOI:10.1081/SCC-120025182

An alternative procedure in the Takai reaction using chromium(III) chloride hexahydrate as the source of Cr(II) was performed. The use of zinc as Cr(III) reducer allowed us to carry out the iodovinylation of aldehydes in 63-99% yields. With the Garner and Dondoni aldehydes, these conditions along with a work-up using 4-t-butylpyridine allowed us to improve the yield of the corresponding vinyl iodide compared to the previous procedures.

Full text of DOI:10.1081/SCC-120025182

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An Alternative Procedure in the Takai Reaction Using
Chromium(III) Chloride Hexahydrate as a Convenient
Source of Chromium(II)
Jacques Augé a , Valérie Boucard a , Richard Gil a , Nadège Lubin-Germain a , Julien Picard a
& Jacques Uziel a
a Synthèse Organique Sélective et Chimie Organométallique , Cergy-Pontoise, France
Published online: 16 Aug 2006.
To cite this article: Jacques Augé , Valérie Boucard , Richard Gil , Nadège Lubin-Germain , Julien Picard & Jacques Uziel
(2003) An Alternative Procedure in the Takai Reaction Using Chromium(III) Chloride Hexahydrate as a Convenient Source of
Chromium(II), Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
33:21, 3733-3739, DOI: 10.1081/SCC-120025182
To link to this article: http://dx.doi.org/10.1081/SCC-120025182
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SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 21, pp. 3733–3739, 2003
An Alternative Procedure in the Takai Reaction
Using Chromium(III) Chloride Hexahydrate as a
Convenient Source of Chromium(II)
*
Jacques Auge, Valerie Boucard, Richard Gil,
´
Nadege Lubin-Germain, Julien Picard, and Jacques Uziel
´
Synthese Organique Selective et Chimie
´
tallique, Cergy-Pontoise, France
Organome
´
ABSTRACT
An alternative procedure in the Takai reaction using chromium(III)
chloride hexahydrate as the source of Cr(II) was performed. The use
of zinc as Cr(III) reducer allowed us to carry out the iodovinylation
of aldehydes in 63–99% yields. With the Garner and Dondoni
aldehydes, these conditions along with a work-up using 4-t-butyl-
pyridine allowed us to improve the yield of the corresponding vinyl
iodide compared to the previous procedures.
Key Words: Takai reaction; Chromium salts; Vinyl iodide.
Vinyl halides are useful building blocks for the synthesis of substi-
tuted olefins. Wittig olefination reactions represent one of the main
*Correspondence: Jacques Auge, Synthese Organique Selective et Chimie
´ ´
Organometallique, UMR 8123, 5 mail Gay-Lussac, Neuville-sur-Oise, 95031
´
Cergy-Pontoise, France; E-mail: jacques.auge@chim.u-cergy.fr.
3733
DOI: 10.1081/SCC-120025182
Copyright & 2003 by Marcel Dekker, Inc.
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´
Auge et al.
3734
methods for formation of vinyl halides.[1] Halogenation of carbon-metal
is also utilized, along with addition reactions to alkynes catalyzed by
transition metals.[2] Vinyl iodides are frequently formed via a Takai
reaction[3] specially in multistep total synthesis.[4] This efficient method
requires large amounts of chromium(II) chloride which is expensive
and not so easy to handle due to its hygroscopic character. In order
to produce vinyl iodides, we were interested to use the less expensive
chromium(III) chloride coupled with a reductive metal such as zinc or
manganese. Takai has recently proposed a catalyzed procedure relying on
the zinc reduction of CrCl3 and on the trimethylsilyl chloride cleavage
of the Cr–O bond regenerating CrCl3.[5] This process was formerly intro-
duced by Furstner and Shi[6] and applied later in other cases.[7]
¨
Unfortunately trimethylsilyl chloride is often incompatible with
elaborated molecules giving rise to various by-products.
We report herein the use of hexahydrated chromium(III) chloride,
which is the cheapest and the easiest to handle chlorochromium complex.
At high temperature and under vacuum, it was very easy to dehydrate
this complex. The deep green [Cr(H2O)4Cl2]Clꢀ2H2O complex became
light green at 110–120ꢁC, when it lost two molecules of water; to
eliminate the last molecules of water, it was necessary to heat at about
300ꢁC. The purple complex then obtained is characteristic of the
anhydrous chromium(III) chloride. This complex could be stored in
vials for several days.
We first studied the iodovinylation of benzaldehyde in THF with
manganese and zinc as the metal reducers (Sch. 1). The reaction carried
out with manganese during 18 h gave 2-iodovinylbenzene 1 in 73% yield
with an E/Z ratio of 12/1. The use of zinc gave better results in the Takai
reaction. First of all, the zinc reduction was more efficient as evidenced by
the rapid coloration change from purple (CrCl3) to deep grey or deep
green (complexed CrCl2). The nucleophilic addition of the organometallic
species was also faster since the reaction yield increased to 99% after only
4 h. It should be noted that, in this case, we observed the presence of (E )
2-chlorovinylbenzene 2 (7%) resulting from halogen exchange, and 92%
of 1 with an E/Z ratio of 9/1. In order to avoid the halogen exchange, we
have added 5 equiv. of sodium iodide. Although the chlorinated product
was not formed anymore, the yield of the reaction was lower (85%).
Since traces of chromium(III) strongly disturbed the 1H NMR
analysis owing to their paramagnetic character, we have developed a
work-up allowing an analysis of the crude mixture. To eliminate these
chromium complexes from the organic layer, the reaction was quenched
with a solution of hydrochloric acid 1N, followed by an addition of
EDTAꢀNa2 and ether. After stirring for 30 min, the EDTA-

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Alternative Procedure in the Takai Reaction
3735
CrCl3/Zn or Mn
Ph
Ph
+
PhCHO
CHI3
+
I
Cl
THF, r.t.
73-99 %
1
2
Scheme 1.
Table 1. Iodovinylation of aldehydes.
CrCl3/Zn
CHI3 NaI Time Yield
(equiv.) (equiv.) (equiv.) (equiv.) (h) (%)
Ratio
RCHO
E
Z
3
4
2
8
6
4
3
—
5
4
4
67 100 0
CHO
CHO
1.5
64
72
80 20
78 22
CHO
5
1.5
6
3
5
3
chromium(III) complex was completely dissolved in the aqueous layer.
We have thus shown that it was not necessary to use more than 1.5 equiv.
of iodoform. However 4 equiv. of CrCl3 per iodoform were necessary.
Our process has been tried with other aldehydes such as cyclo-
hexanecarboxaldehyde 3, 2-phenylacetaldehyde 4, and (ꢂ)-citronellal 5
(Table 1). We noted that the E/Z ratio depends on the starting aldehyde.
We obtained exclusively the E isomer with 3 and it was not necessary to
use sodium iodide to avoid the halogen exchange. We observed also
that the stereoselectivity did not vary with temperature. Dioxane as the
solvent did not bring about any improvement of the stereoselectivity as in
the previous protocol.[3]
For products sensitive in acidic conditions, the reaction mixture was
quenched by adding 4-t-butylpyridine then hydrolyzed by an aqueous
saturated sodium chloride solution. The added amine was used to chelate
the chromium(III) salts and liberate the expected products that were
bound to the chromium. These conditions were applied in the synthesis
of vinyl iodides derived from the acid-sensitive Garner aldehyde 7[8] and
from the formyl C-glycoside 8.[9]
When the original conditions described by Takai were used (2 equiv.
of CHI3 and 6 equiv. of CrCl2) we isolated 9 in only 32% yield.[10] Using

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´
Auge et al.
3736
Cl
I
O
H
CrCl3 / Zn
CHI3
+
N
O
N
O
N
O
THF, r.t.
66 %
Boc
Boc
Boc
7
9
10
85 : 15
(E / Z = 80 : 20)
Scheme 2.
OBn
OBn
H
CHI3
O
O
BnO
BnO
BnO
BnO
CrCl3/Zn/NaI
I
O
63%
OBn
OBn
8
11
Scheme 3.
the alternative procedure (CrCl3/Zn) and work-up with 4-t-butylpyridine
we were then able to obtain the vinylated derivatives in 66% yield (Sch. 2).
Nevertheless, we did not manage to avoid the formation of the chloro-
alkene 10, even after adding different amounts of sodium iodide. In the
catalytic conditions using TMSCl to regenerate chromium(III) species[5]
the reaction was sluggish.
When using the alternative procedure with the Dondoni aldehyde 8
(Sch. 3), we were able to prepare the corresponding vinyl iodide 11 with
63% yield. This result was advantageously compared with those obtained
from the original procedure and from the catalytic process (Table 2). No
chloroalkene was detected and the vinyl iodide 11 was isolated as a
mixture of (E) and (Z) isomers in the ratio 19:1 as indicated by its
NMR spectrum which exhibited two distinct coupling constants (14.6
and 9 Hz, respectively).
In summary, we have described an alternative procedure using
chromium(III) chloride hexahydrate, as a cheap and easy to handle
source of Cr(II) by dehydration and zinc reduction. In addition we
have developed efficient work-up procedures (with EDTAꢀNa2 or 4-t-

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Alternative Procedure in the Takai Reaction
Table 2. Iodovinylation of the Dondoni aldehyde 8.
3737
CHI3
RCHO (equiv.) (equiv.) (equiv.) (equiv.) (equiv.) (equiv.) (h) (%) E/Z
CrCl2 CrCl3
Zn
NaI TMSCl Time 11 Ratio
8
8
8
1.5
1.5
2
6
6
6
6
59 86/14
63 95/5
43 80/20
6
0.2
3
6
5
1
6
butylpyridine) in order to allow separation and removal of chromium
complexes from the final organic product. Overall, this procedure is
interesting for the iodovinylation of fragile aldehydes.
EXPERIMENTAL
Dehydration Procedure of Chromium(III)
Chloride Hexahydrate
In a Schlenk tube, chromium(III) chloride hexahydrate was warmed
under vacuum pump with a heat gun up to 110–120ꢁC. The deep green
complex became light green in a few seconds and some drops of water
appeared on the top of the Schlenk tube. The heating was carried out at
300ꢁC and prolonged until the appearance of the purple coloration. Then
the complex was left cooling to room temperature and placed under an
argon atmosphere. Anhydrous chromium(III) chloride was stored into
vials for several days.
Typical Procedure for Benzaldehyde Iodovinylation
In a first Schlenk tube, 6 mmol of anhydrous CrCl3 , 3 mmol of zinc,
and 5 mmol of dehydrated sodium iodide were placed under vacuum and
heated to 100ꢁC for 2–3 min. The solid mixture was stirred for 10 min
under vacuum. The mixture was then placed under an argon atmosphere.
Immediately after adding 10 mL of freshly distilled THF, the color turned
to green, which was an indication of the formation of CrCl2. In a second
Schlenk tube 1 mmol of benzaldehyde was added via a syringe into a
solution of 1.5 mmol of iodoform in 5 mL of THF. This resulting solution
was transferred via a canula into the first Schlenk tube. The reaction
mixture became brown and was stirred at room temperature during

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Auge et al.
3738
4 h. It was then hydrolyzed with a solution of hydrochloric acid 1 M; a
spatula of EDTAꢀNa2 was added and the mixture was extracted with
ether after stirring for 30 min. The organic layer was washed with a
saturated aqueous solution of NaCl, dried over MgSO4, and concentrated
under reduced pressure. The yellow–brown residue was purified by
flash silica gel column chromatography using cyclohexane as the eluent
affording 2-iodovinylbenzene in 85% yield.
Work-Up Modification for Iodovinylation of Compound 7
After completion of the reaction (16 h) and addition of 2 equiv.
of 4-t-butylpyridine, the mixture was stirred at room temperature for
30 min and then hydrolyzed with a saturated aqueous solution of
NaCl. After extraction with ethyl acetate, the organic layer was dried
over anhydrous magnesium sulfate and concentrated under reduced
pressure. Silica gel column chromatography (cyclohexane–ethyl acetate,
90/10 v/v) of the residue afforded an inseparable mixture of the vinyl
halides 9 and 10 in a global yield of 66%. NMR and MS data of these
compounds were in accordance with those of the literature.[11,12]
(R,E )-2,2-Dimethyl-3-tert-butoxycarbonyl-4-(2-iodoethen-1-yl)oxazo-
lidine (9). 1H NMR (CDCl3, 250 MHz): ꢀ 6.49 (dd, 1H, J 8 and 14 Hz), 6.3
(m, 1H), 4.3 (m, 1H), 3.95 (dd, 1H, J 6.2 and 8.8 Hz), 3.76 (dd, 1H, J 2
and 8.8 Hz). 13C NMR (CDCl3, 62.5 MHz): ꢀ 150.6, 143.2, 93.1, 79.1,
66.6, 60.6, 28.6, 27.4, 23.5. MS m/z: 338 (M-15)þ, 282, 57.
(R,E )-2,2-Dimethyl-3-tert-butoxycarbonyl-4-(2-chloroethen-1-yl)oxa-
zolidine (10). 1H NMR (CDCl3, 250 MHz): ꢀ 6.3 (m, 1H), 5.84 (dd, 1H, J
8 and 13 Hz), 4.3 (m, 1H), 4.06 (dd, 1H, J 7 and 8 Hz), 3.76 (m, 1H).
13C NMR (CDCl3, 62.5 MHz): ꢀ 150.6, 143.2, 93.1, 79.1, 66.6, 60.6, 28.6,
27.4, 23.5. MS m/z: 246 (M-15)þ, 190, 57.
(E)-3,7-Anhydro-4,5,6,8-tetra-O-benzyl-1,2-dideoxy-1-iodo-D-glycero-
D-gulo-oct-1-enitol (11). In a first Schlenk tube, 490 mg (3.09 mmol) of
anhydrous CrCl3 , 100 mg (1.53 mmol) of zinc, and 382 mg (2.55 mmol)
of dehydrated sodium iodide were placed under vacuum and heated to
100ꢁC for 2–3 min. The solid mixture was stirred for 10 min under
vacuum. The mixture was then placed under an argon atmosphere and
5 mL of freshly distilled THF was added. In a second Schlenk
tube 0.51 mmol (285 mg) of the aldehyde 8 was added via a syringe
into a solution of 0.78 mmol (305 mg) of iodoform in 5 mL of THF.
This resulting solution was transferred via a canula into the first
Schlenk tube. The reaction mixture became dark brown and was stirred

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Alternative Procedure in the Takai Reaction
3739
at room temperature during 6 h. After the addition of 1.02 mmol (150 mL)
of 4-t-butylpyridine, the mixture was stirred at room temperature for
30 min and then hydrolyzed with a saturated aqueous solution of NaCl
(20 mL). After extraction with ether, the organic layer was dried over
anhydrous magnesium sulfate and concentrated under reduced pressure.
Silica gel column chromatography (cyclohexane–ethyl acetate, 90/10 v/v)
of the residue afforded 217 mg (63%) of 11 in which the (E ) isomer largely
predominated (95%).
M.p: 94–95ꢁC. 1H NMR (CDCl3, 250 MHz): ꢀ 7.3 (m, 20H), 6.62 (dd,
1H, J 5.9 and 14.6 Hz, H2), 6.50 (d, 1H, J 14.6 Hz, H1), 4.84 (m, 4H, CH2
benzyl), 4.56 (m, 4H, CH2 benzyl), 3.65 (m, 5H), 3.44 (m, 1H), 3.30 (dd,
1H, J 9 Hz). 13C NMR (CDCl3, 62.5 MHz): ꢀ 142.54 (C2), 138.45, 137.98,
137.54, 128.53–127.70, 86.57, 81.58, 81.04, 80.48 (C1), 78.71, 77.96, 75.63,
75.27, 75.04, 73.5, 68.78.
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Stork, G.; Zhao, K. Tetrahedron Lett. 1989, 30, 2173; (c) Uenishi, J.;
Kawahama, R.; Shiga, Y.; Yonemitsu, O. Tetrahedron Lett. 1996,
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2. (a) Hua, R.; Shimada, S.; Tanaka, M. J. Am. Chem. Soc. 1998, 120,
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10. For a previous use of the Takai conditions with Garner aldehyde
see: Campbell, A.D.; Paterson, D.E.; Raynham, T.M.; Taylor,
R.J.K. J. Chem. Soc. Chem. Commun. 1999, 1599.
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12. Branquet, E.; Meffre, P.; Durand, P.; Le Goffic, F. Synth. Commun.
1998, 28, 613.
Received in the UK February 27, 2003

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