Reaction of 1,2-dihalogen substituted arenes with lanthanum metal: A new generation method of benzyne

Article abstract of DOI:10.1016/S0040-4039(02)00958-9

A new generation method of benzyne has been developed. When 1,2-dihalogen substituted arenes were allowed to react with lanthanum metal in the presence of dienes, Diels-Alder products between benzyne and dienes were formed in moderate to good yields.

Full text of DOI:10.1016/S0040-4039(02)00958-9

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 4911–4913
Reaction of 1,2-dihalogen substituted arenes with lanthanum
metal: a new generation method of benzyne
Hiroshi Kawabata, Toshiki Nishino, Yutaka Nishiyama* and Noboru Sonoda*
Department of Applied Chemistry, Faculty of Engineering, Kansai University, Suita, Osaka 564-8680, Japan
Received 17 April 2002; accepted 20 May 2002
Abstract—A new generation method of benzyne has been developed. When 1,2-dihalogen substituted arenes were allowed to react
with lanthanum metal in the presence of dienes, Diels–Alder products between benzyne and dienes were formed in moderate to
good yields. © 2002 Elsevier Science Ltd. All rights reserved.
The use of lanthanoid salts and organolanthanoid com-
pounds in organic synthesis has been steadily increasing
in recent years. In particular; low-valent, trivalent, and
thalene (2), which is a Diels–Alder product of benzyne
and furan, was obtained in almost quantitative yield
(Scheme 1). Although the reaction efficiently proceeded
at lower reaction temperature (at 0°C: 100%), in the
1
tetravalent lanthanoid compounds have been widely
used as versatile reagents in organic reaction. Up to
1
0,11
absence of iodine, the reaction did not occur.
2
3
now the direct use of cerium, samarium, and
4
ytterbium metals has been developed; however, to the
In order to know the reactivity of other lanthanoid
metals, 1-chloro-2-iodobenzene was allowed to react
with various lanthanoid metals in the presence of excess
amount of furan (30 equiv.) at 25°C for 4 h, and these
results are shown in Table 1. Although the use of Ce,
Pr, Nd, and Yb led to the formation of 2, the yield was
decreased. In the case of samarium metal, which is
widely used in organic synthesis, the yield of 2 was very
low owing to the formation of various complex prod-
best of our knowledge, there are no reports on the
direct use of lanthanum metal in organic synthesis.
Recently, we have succeeded in the first direct use of
5
lanthanum metal as a reducing agent, which is a
relatively stable metal under aerobic conditions and has
the largest redox potential among the lanthanoid
metals, in organic synthesis. In connection with a study
on the direct use of lanthanum metal in organic synthe-
sis, we found that generation of benzyne from 1,2-
dihalogen substituted arenes was accomplished by the
efficient transfer of available electrons from the lan-
a
Table 1. Effect of lanthanoid metal
6
thanum metal.
I
Metal, cat. I2
THF
O
+
O
When 1-chloro-2-iodobenzene (1) was treated with an
Cl
9
equivalent amount of lanthanum metal in the presence
1
2
of an excess amount of furan (30 equiv.) under a
nitrogen
atmosphere,
1,4-dihydro-1,4-epoxynaph-
Yield (%)b
Yield (%)b
Metal
Metal
La (1 mmol)
La
Ce
Pr
Nd
Sm
Eu
Gd
100
89
77
59
Trace
0
Tb
Dy
Ho
Er
Tm
Yb
Lu
0
0
0
0
0
Cl
cat.
O
I2 (0.04 mmol)
O
THF (10 ml)
+
I
1
25 °C, 4 h
2
(
1 mmol)
(30 mmol)
1
00 %
54
0
0
Scheme 1.
a
Reaction conditions: 1-chloro-2-iodobenzene (1 mmol), furan (30
mmol), metal (1 mmol), I2 (0.04 mmol) and THF (10 ml) at 25°C
*
Corresponding authors. Tel.: +81-6-6368-1121; fax: +81-6-6339-
026; e-mail: nishya@ipcku.kansai-u.ac.jp
for 4 h.
GC yield.
b
4
0
040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)00958-9

4
912
H. Kawabata et al. / Tetrahedron Letters 43 (2002) 4911–4913
ucts. In the reaction of other lanthanoid metals, the
reaction did not proceed, and 1 was recovered. To
understand the scope and limitation of the reaction,
Table 3. Reaction of various 1-chloro-2-iodobenzene
a
derivatives
1
-fluoro-, 1-bromo-2-iodobenzene, and 1,2-diiodoben-
zene instead of 1-chloro-2-iodobenzene were treated
with lanthanum metal in the presence of furan, and the
results are shown in Table 2. For every o-halogen
substituted iodobenzene, the Diels–Alder adducts 2
were obtained in moderate yields; however, the yields
were slightly decreased compared with that of 1-chloro-
2-iodobenzene, owing to the formation of fluoro-,
bromo- and iodobenzene, reductive deiodination prod-
ucts, as by-products. In the case of 2-trifluoromethane-
sulfonyl-1-iodobenzene, the reaction did not proceed at
all. The treatment of o-halogen substituted iodobenzene
with lanthanum metal in the presence of 2-methylfuran
or cyclopentadiene was examined. In contrast to the
case of furan, the Diels–Alder addition efficiently pro-
ceeded to form the Diels–Alder products in moderate to
good yields, by the use of 1-bromo-2-iodobenzene
instead of 1-chloro-2-iodobenzene (Scheme 2). In the
case of isoprene, the yield of product was low owing to
the formation of various complex products. Similarly,
various benzyne derivatives was successfully generated
by the reaction of 1,2-, 1,3-, 1,4-dichloro-6-iodoben-
zene, 4-chloro-3-iodotoluene, and 4-chloro-3-iodoan-
isole with lanthanum metal, and the corresponding
a
Reaction conditions: substrate (1 mmol), furan (30 mmol), La (1
mmol), I (0.04 mmol) and THF (10 ml) at 25°C for 4 h.
2
b
GC yield.
some experiments. 1-Chloro-2-iodobenzene was treated
with lanthanum metal in the presence of
trimethylchlorosilane giving 1-chloro-2-trimethylsilyl-
benzene 3 in 58% yield (Scheme 3). In addition, the
treatment of 1,4,5-trichloro-2-iodobenzene (4) with lan-
thanum metal in the presence of an excess amount of
1
,4-dihydro-1,4-epoxynaphthalenes were obtained in
relatively high yields (Table 3).
furan followed by quenching with DCl/D O instead of
2
HCl/H O provided a C-deuterated product (5) (Scheme
2
13
By this method, reductive deiodinated products were
formed as by-products. From these results, we specu-
lated that benzyne was formed via elimination of the
halogen anion from the 2-halogen substituted phenyl
anion (6). In order to gain information on the reaction
pathway for the generation of benzyne, we carried out
4). At the present time, while the reaction pathway for
the generation of benzyne is not shown in detail, a
reaction pathway including a phenyl anion species is
strongly suggested (Scheme 5). Transfer of two elec-
trons from lanthanum metal or low-valent lanthanum
species, which were generated in situ by the reaction of
lanthanum metal with iodine, to 1,2-dihalogen substi-
tuted benzenes, followed by elimination of the iodine
anion forms the corresponding phenyl anion species (6).
The halogen anion was easily eliminated from 6 to form
a
Table 2. Reaction of various 1-halogeno-2-iodobenzene
X
La, cat. I2
THF
O
+
O
I
2
La ( 1 mmol )
I2 ( 0.04 mmol )
I
SiMe3
Cl
+
Me3SiCl
1 mmol
Entry
X
Yield (%)b
THF (10 ml ) , 25 °C, 4 h
Cl
3
1
2
3
4
5
F
80
100
87
82
0
1
mmol
58 %
Cl
Br
I
Scheme 3.
OTf
La (1 mmol )
I2 (0.04 mmol )
a
Reaction conditions: 1-halogeno-2-iodobenzene (1 mmol), furan (30
mmol), La (1 mmol), I (0.04 mmol) and THF (10 ml) at 25°C for
Cl
I
O
2
+
4
h.
THF (10 ml )
25 °C, 4 h
Cl
Cl
b
GC yield.
4
1
mmol
30 mmol
Cl
Cl
D (H)
Cl
Cl
Cl
DCl
O
+
O
65 %
100 %
23 %
5
30 % (D/H = 50/50)
29 %
Scheme 2. Reaction of 1-bromo-2-iodobenzene with various
dienes.
Scheme 4.

H. Kawabata et al. / Tetrahedron Letters 43 (2002) 4911–4913
4913
e-
e-
Yanada, K.; Fujita, T. Tetrahedron Lett. 1996, 37, 9313;
(e) Yanada, R.; Negoro, N.; Yanada, K.; Fujita, T.
Tetrahedron Lett. 1997, 38, 3271; (f) Ding, Z.-B.; Wu,
S.-H. Youji Huaxue 1997, 17, 165; (g) Wang, L.; Zhang,
Y. Tetrahedron 1998, 54, 11129. See also Ref. 2a.
. Taniguchi, Y.; Takaki, K.; Fujiwara, Y. In Reviews on
Heteroatom Chemistry; Oae, S., Ed.; MYU: Tokyo, 1995;
Vol. 12, p. 163.
. (a) Nishino, T.; Nishiyama, Y.; Sonoda, N. Heteroatom
Chem. 2000, 11, 81; (b) Nishino, T.; Nishiyama, Y.;
Sonoda, N. Heteroatom Chem. 2002, 13, 131; (c) Nishino,
T.; Watanabe, T.; Okada, M.; Nishiyama, Y.; Sonoda,
N. J. Org. Chem. 2002, 67, 966; (d) Nishino, T.;
Nishiyama, Y.; Sonoda, N. Tetrahedron Lett. 2002, 43,
I
La or Lan+
La or Lan+
-
I-
X
X
X
6
4
5
-
X -
Scheme 5. Plausible reaction path.
the corresponding benzyne intermediate. In the case of
,2-dihalogeno benzenes substituted electron-withdraw-
ing group, it seems likely that elimination of the halo-
gen anion from 6 was suppressed owing to the stability
of the phenyl anion, giving the corresponding deiodina-
tion product.
1
3689.
6
. Since Wittig showed a generation method of benzyne by
the reaction of o-dihalogen substituted benzene with
7
lithium metal, many methods of generating benzyne
In summary, we have found that an efficient transfer of
available electrons from lanthanum metal successfully
achieved the generation of benzyne from o-dihalogen
substituted benzene. Further work on application and
elucidation of the reaction pathway are now in
progress.
8
have been developed.
7
8
. (a) Wittig, G.; Pohmer, L. Angew. Chem. 1960, 72, 564;
(
b) Wittig, G.; Pohmer, L. Chem. Ber. 1956, 89, 1334.
. (a) Kitamura, T.; Yamane, M.; Inoue, K.; Todaka, M.;
Fukatsu, N.; Meng, Z.; Fujiwara, Y. J. Am. Chem. Soc.
1999, 121, 11674; (b) Kitamura, T.; Fukatsu, N.; Fuji-
wara, Y. J. Org. Chem. 1998, 63, 8579; (c) Kitamura, T.;
Yamane, M. J. Chem. Soc., Chem. Commun. 1995, 983;
Acknowledgements
(
d) Hoffman, R. W. Dehydrobenzene and Cycloalkynes;
Academic Press: New York, 1967; (e) Gilchrist, T. L. In
The Chemistry of Functional Groups; Patai, S.; Rappo-
port, Z., Eds.; Wiley: Chichester, 1983; Chapter 11; (f)
Hart, H. In The Chemistry of Triple-Bonded Functional
Groups, Supplement C2; Patai, S., Ed.; Wiley: Chichester,
We thank the Santoku Co. for supplying the lanthanum
metal. This research was supported in part by a Grant-
in-Aid for Scientific Research from the Ministry of
Education, Science, Culture and Sports, Government of
Japan.
1994; Chapter 18; (g) Himeshima, Y.; Sonoda, T.;
Kobayashi, H. Chem. Lett. 1983, 1211 and references
cited therein.
9
. Lanthanum metal was commercially available high-grade
product and was used after powderization (ca. 40 mesh).
References
1
1
0. We have already shown that the addition of a catalytic
amount of iodine dramatically enhanced the reductive
dimerization of carbonyl compounds or imine with lan-
thanum metal. See Ref. 5.
1
. For recent reviews, see: (a) Kagan, H. B. New J. Chem.
1
990, 14, 453; (b) Curran, D. P.; Fevig, T. L.; Jasperse, C.
P.; Totleben, M. J. Synlett 1992, 943; (c) Molander, G. A.
Chem. Rev. 1992, 92, 29; (d) Kobayashi, S. Synlett 1994,
1. In the reaction used ytterbium or samarium metal, it was
disclosed that various reactions were promoted by the
addition of a catalytic amount of methyl iodide or iodine;
however, the mechanism of the effect of methyl iodide or
6
89; e) Komochi, Y.; Kubo, T. J. Syn. Org. Chem. Jpn.
1
994, 52, 285; (f) Imamoto, T. Lanthanides in Organic
Synthesis; Academic Press: New York, 1994; (g) Mat-
suda, Y. J. Syn. Org. Chem. Jpn. 1995, 53, 987; (h)
Molander, G. A.; Harris, C. R. Chem. Rev. 1996, 96, 307;
12
iodine was not explained.
1
2. (a) Hou, Z.; Tamamine, K.; Aoki, O.; Shiraishi, H.;
(
i) Ito, Y.; Fujiwara, Y.; Yamamoto, T. Kikan Kagaku
Sousetsu: Organic Synthesis by Means of Lanthanoids No.
7; Gakkai Press Center, 1998; (j) Kobayashi, S. Lan-
Fujiwara, Y.; Taniguchi, H. J. Org. Chem. 1988, 53,
6077; (b) Yanada, R.; Negoro, N.; Okaniwa, M.; Taga,
3
T.; Yanada, K.; Fujita, T. Synlett 1999, 537; (c) Wang,
L.; Zhou, L.; Zhang, Y. Synlett 1999, 1065; (d) Taluldar,
S.; Fang, J.-M. J. Org. Chem. 2001, 66, 330. See also
Refs. 2a and 2b.
thanide: Chemistry and Use In Organic Synthesis;
Springer: Berlin, 1999 and references cited therein.
2
. (a) Imamoto, T.; Kusumoto, T.; Hatanaka, Y.;
Yokoyama, M. Tetrahedron Lett. 1982, 23, 1353; (b)
Fukuzawa, S.; Fujinami, T.; Sakai, S. J. Chem. Soc.,
Chem. Commun. 1986, 475; (c) Fukuzawa, S.; Sumimoto,
N.; Fujinami, T.; Sakai, S. J. Org. Chem. 1990, 55, 1328.
. (a) Yanada, R.; Bessho, K.; Yanada, K. Chem. Lett.
1
3. At present, the formation pathway of 1,3,4-trichloroben-
zene has not been explained; however, it was suggested
that 1,3,4-trichlorobenzene was formed by the hydrogen
abstraction of the phenyl radical, which was generated in
situ by the one-electron transfer from lanthanum metal to
1,4,5-trichloro-2-iodobenzene (4), followed by the elimi-
3
1
994, 1279; (b) Yanada, R.; Bessho, K.; Yanada, K.
Synlett 1995, 443; (c) Yanada, R.; Bessho, K.; Yanada,
K. Synlett 1995, 1261; (d) Yanada, R.; Negoro, N.;
−
nation of I from THF as a solvent.