A practical transformation of aldehydes into (E)-iodoalkenes with geminal dichromium reagents

Article abstract of DOI:10.1055/s-1999-2829

A catalytic cycle of a chromium salt in a stereoselective transformation of aldehydes to (E)-l-iodoalkenes using a geminal dichromium reagent, is assembled with zinc, Me₃SiCl, and NaI in dioxane.

Full text of DOI:10.1055/s-1999-2829

1268
LETTER
A Practical Transformation of Aldehydes into (E)-Iodoalkenes with Geminal
Dichromium Reagents
Kazuhiko Takai,* Tetsuya Ichiguchi, Shintaro Hikasa
Department of Applied Chemistry, Faculty of Engineering, Okayama University, Tsushima, Okayama 700-8530, Japan
Fax: +81-86-251-8094; E-mail: ktakai@cc.okayama-u.ac.jp
Received 17 May 1999
CHI3, cat. CrCl2, Mtl, Me3SiCl
Abstract: A catalytic cycle of a chromium salt in a stereoselective
transformation of aldehydes to (E)-1-iodoalkenes using a geminal
dichromium reagent, is assembled with zinc, Me3SiCl, and NaI in
dioxane.
Ph
Ph
I
CHO
THF, 25 °C, 24 h
1
Keywords: geminal dichromium reagent, iodoform, (E)-1-iodoalk-
ene, chromium(II), zinc
Iodoalkenes are important synthetic intermediates, espe-
cially for carbon-carbon bond formation under transition
metal catalysis. One method to access the iodoalkenes is
to use a geminal dichromium reagent derived from iodo-
form and CrCl2.1 The protocol provides (E)-iodoalkenes
with one-carbon homologation under mild conditions in
chemo- and stereoselective manners (eq. 1).2
O
CHI3 (2.0), CrCl2 (6.0)
CHO
THF, 0 °C, 1 h
O
I
75% (E / Z = 81 / 19 )
Equation 1
This transformation, however, requires 6-8 equiv of the
one-electron reductant, CrCl2 to obtain reasonable yields.
In order to assemble the catalytic cycle of chromium(II)
using a metal as a reductant, the reducing ability of the
metal should be stronger than that of chromium(II). How-
ever, it should be weak enough to leave the iodoform in-
tact, or at least the reduction rate of iodoform with the
metal should be considerably slower than that with chro-
mium(II). In 1996, Fürstner reported a chromium(II)-me-
diated coupling of halo olefins and aldehydes with a
catalytic amount of chromium(II) using manganese as a
reductant.3,4 In the procedure, an excess amount of
Me3SiCl was employed for conversion of O-CrLn to O-
SiMe3 to regenerate chromium(III) halide, which is easily
reduced with the metal. Here, several metal reductants are
examined to find an appropriate one that forms a catalytic
cycle for the formation of iodoalkene 1 (Table 1).
46% yield (run 4). Although alkene 2 and chloroalkene 4
were produced as byproducts and the E/Z ratio was 74/26,
the reaction could proceed with a catalytic amount of
CrCl2.
Further examination with a CrCl2-zinc system revealed
that the reaction completed within 1 h when 6 equiv of
zinc was used; Iodoalkene 1 and chloroalkene 4 were pro-
duced in 60% (E/Z = 80 / 20) and 8%, yields, respectively.
The formation of 4 could not be suppressed by addition of
sodium iodide, however the yield was slightly improved.6
The E/Z ratios of 1 depended on the solvent, and the ratio
was improved to 88 / 12 in dioxane.7 In addition, slow ad-
dition of a mixture of iodoform and an aldehyde in diox-
ane to a mixture of zinc, Me3SiCl, and a catalytic amount
of CrCl2 in dioxane improved both the yield and the E/Z
ratio markedly. Iodoalkene 1 was obtained in 80% yield
(E/Z = 96 / 4) by slow addition over a period of 4 h (eq. 2).
Magnesium and aluminum metals are very strong and re-
duce iodoform to give complex mixtures (Table 1, runs 1
and 2). In contrast, a combination of zinc (4.0 equiv) and
CrCl2 (0.08 equiv) afforded the desired iodoalkene 1 in
Synlett 1999, No. 8, 1268–1270 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
A Practical Transformation of Aldehydes into (E)-Iodoalkenes with Geminal Dichromium Reagents
1269
CHI3 (2.0), NaI (1.0)
CHI3, cat. CrCl3(thf)3
Zn, Me3SiCl
Zn (6.0), Me3SiCl (6.0)
Ph
R
R
Ph
+
RCHO
CHO
I
I
X
H
dioxane, 25 °C
4 h (slow addition)
1
dioxane, 25 °C
X = Cl and
CrCl2 (0.16)
CrCl3 (0.20)
80% (E / Z = 96 / 4)
82% (E / Z = 95 / 5)
84% (E / Z = 95 / 5)
CrCl3(thf)3 (0.20)
Equation 2
RCHO
CrX2
CrX2
I
C
CHI3
H
CrX2
2 CrX3
+
2 CrX3
R
4 CrX2
I
OCrX2
(X2Cr)2O
2 Me3SiCl
2 ZnX2
(Me3Si)2O
R
I
2 Zn
Scheme 1
A plausible mechanism of the CrCl2-zinc system is shown
in Scheme 1. The reduction of iodoform with 4 equiv of
chromium(II) gives a geminal dichromium reagent,8
which reacts with an aldehyde followed by elimination of
(X2Cr)2O to afford an iodoalkene. The produced (X2Cr)2O
is converted to chromium(III) halides with Me3SiCl, and
the chromium(III) is then reduced with zinc to reproduce
chromium(II). Two equiv. of both zinc and Me3SiCl are
necessary for this transformation.
ter the mixture was stirred at 25 °C for 40 min, a solution
of 3-phenylpropanal (0.27 g, 2.0 mmol) and iodoform (1.6
g, 4.0 mmol) in dioxane (20 mL) was added at 25 °C to the
mixture over a period of 4 h. The color of the mixture
gradually turned to red during the addition. The reaction
mixture was poured into water (50 mL) and organic layer
was extracted with hexane (3 x 30 mL). The organic ex-
tracts were washed with aqueous Na2S2O3 and brine, dried
over anhydrous MgSO4 and concentrated. Purification by
column chromatography on silica gel (hexane) gave 1-
iodo-4-phenyl-1-butene 1 in 84% yield (0.43 g, E/Z = 95/
5) as a colorless oil along with 1-chloro-4-phenyl-1-
butene (27 mg, 8%) and 4-phenyl-1-butene (5.3 mg, 2%).
Because chromium(III) is reduced with zinc to give chro-
mium(II), the reaction proceeded using a catalytic amount
of chromium(III). Both CrCl3 and CrCl3(thf)3 could be
used for the transformation (eq. 2), although the latter
gave normally better yields especially in small scale ex-
periments due to less hygroscopicity. The results with a
catalytic amount of CrCl3(thf)3 are summarized in Table 2.
Procedure B: Under an argon atmosphere, Me3SiCl (13
mL, 0.10 mol) was added at 25 °C to a suspension of
CrCl3 (0.63 g, 4.0 mmol), zinc (5.9 g, 90 mmol), and dried
NaI (3.0 g, 20 mmol) in dioxane (100 mL). After the mix-
ture was stirred at 25 °C for 40 min, a solution of 3-phe-
nylpropanal (2.7 g, 20 mmol) and iodoform (12 g, 30
mmol) in dioxane (50 mL) was added at 25 °C (water
bath) to the mixture over a period of 12 h. The reaction
mixture was poured into water (200 mL) and organic layer
was extracted with hexane (3 8x 100 mL). The organic ex-
tracts were washed with Na2SO4 and brine, dried over an-
hydrous MgSO4 and concentrated. Distillation of the
crude product gave 1-iodo-4-phenyl-1-butene 1 in 70%
yield (3.6 g, E/Z = 94/6) as a colorless oil along with 1-
chloro-4-phenyl-1-butene (0.20 g, 6%) and 4-phenyl-1-
butene (30 mg, 1%).
Under the standard reaction conditions (Table 1, run 1),
compounds were recovered in the following order: 1-
dodecene (90%); 1-dodecyne (92%); 1-chlorododecane
(93%); ethyl octanoate (94%); nonanenitrile (97%). In
contrast to a stoichiometric reaction with CrCl2, in which
nonanal diethylene acetal was recovered in 92% yield, the
acetal was recovered in only 50% yield under the catalytic
conditions and the acetal was converted to 1-iododecene
in 33% yield (E / Z = 90 / 10).
Typical Procedure
Procedure A: Under an argon atmosphere, Me3SiCl (1.5
mL, 12 mmol) was added at 25 °C to a suspension of
CrCl3(thf)3 (0.15 g, 0.40 mmol),11 zinc (0.78 g, 12 mmol),
and dried NaI (0.30 g, 2.0 mmol) in dioxane (20 mL). Af-
Synlett 1999, No. 8, 1268–1270 ISSN 0936-5214 © Thieme Stuttgart · New York

1270
K. Takai et al.
LETTER
(6) Sodium iodide was dried at 120 °C (2 Torr) for 1 day. Morita,
T.; Okamoto, Y.; Sakurai, H. J. Chem. Soc., Chem. Commun.
1978, 874. Olah, G. A.; Narang, S. C.; Gupta, B. G. B.;
Malhotra, R. Synthesis 1979, 61. See also, ref. 4.
(7) Evans, D. A.; Black, W. C. J. Am. Chem. Soc. 1993, 115,
4497. In contrast to the stoichiometric reaction in dioxane
where the reaction did not complete after 4 days, the catalytic
process completed within 4 h in the solvent.
Acknowledgement
We thank Dr. Alois Fürstner of the Max-Planck-Institut für Kohlen-
forschung for useful suggestions. Financial support by a Grant-in-
Aid for Scientific Research on Priority Area No. 283 from the Mi-
nistry of Education, Science, Sports and Culture of Japan is grate-
fully acknowledged
(8) Okazoe, T.; Takai, K.; Utimoto, K. J. Am. Chem. Soc. 1987,
109, 951; Takai, K.; Kataoka, Y.; Okazoe, T.; Utimoto, K.
Tetrahedron Lett. 1987, 28, 1443; Takai, K.; Shinomiya, N.;
Kaihara, H.; Yoshida, N.; Moriwake, T.; Utimoto, K. Synlett
1995, 963.
(9) Chromium(III) hexahydrate (99.995% purity) was purchased
from Aldrich Chemical Co. and dehydrated by treatment with
thionyl chloride. Pray, A. R. Inorg. Synth. 1954, 5, 153.
Chromium(III) chloride THF complex (97% purity) was
purchased from Aldrich Chemical Co.
References and Notes
(1) Takai, K.; Nitta, K.; Utimoto, K. J. Am. Chem. Soc. 1986, 108,
7408.
(2) For some representative application to total synthesis, see:
Nicolaou, K. C.; Bertinato, P.; Piscopio, A. D.; Chakraborty,
T. K.; Minowa, N. J. Chem. Soc., Chem. Commun. 1993, 619.
Kanda, Y.; Fukuyama, T. J. Am. Chem. Soc. 1993, 115, 8451.
Kende, A. S.; Koch, K.; Dorey, G.; Kaldor, I.; Liu, K. J. Am.
Chem. Soc. 1993, 115, 9842. See also ref. 7.
(10) Similar low geometrical selectivity of the produced olefin was
observed in iodomethylenation of cyclohexylideneacetal-
dehyde with the reagent derived from CHI3 and a stoichio-
metric amount of CrCl2.1
(3) A. Fürstner, N. Shi, J. Am. Chem. Soc. 1996, 118, 2533 and
12349.
(4) Beckman, R. K., Jr.; Hudack, R. A. Jr. J. Org. Chem. 1998, 63,
3524; Kuroboshi, M.; Tanaka, M.; Kishimoto, S.; Goto, K.;
Tanaka, H.; Torii, S. Tetrahedron Lett. 1999, 40, 2785.
(5) Chromium(II) chloride (99.9% purity) was purchased from
Aldrich Chemical Co. Zinc powder (99.9% purity) was
purchased from Merck Co. and activated by washing with 1M
hydrochloric acid, water, methanol, and ether, and dried in
vacuo.
Article Identifier:
1437-2096,E;1999,0,08,1268,1270,ftx,en;Y11399ST.pdf
Synlett 1999, No. 8, 1268–1270 ISSN 0936-5214 © Thieme Stuttgart · New York