Photochemical and radical initiator-induced reaction of allylic indium compounds

Article abstract of DOI:10.1016/j.tetlet.2004.11.056

Intramolecular cyclization of allylic radicals generated from allylindium compounds both by photolysis or by the reaction of radical initiators was examined. The photolysis of allylic indium compounds, prepared from 8-bromo- or 8-iodooct-1,6-dienes and powdered indium metal, led to the formation of the 5-exo-trig products. Benzoyl peroxide as a radical initiator was also effective for the cyclization. In contrast, the radical initiators with oxidizing nature, such as tert-butyl hypochlorite, induced iodocyclization producing iodomethylcyclopentane via an oxidation of the iodide on the indium atom.

Full text of DOI:10.1016/j.tetlet.2004.11.056

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 289–292
Photochemical and radical initiator-induced reaction
of allylic indium compounds
Tsunehisa Hirashita, Jiro Tanaka, Ayumi Hayashi and Shuki Araki*
Omohi College, Graduate School of Engineering, Nagoya Institute of Technology, Gokiso-cho, Showa-ku, Nagoya 466-8555, Japan
Received 1 October 2004; revised 5 November 2004; accepted 10 November 2004
Available online 26 November 2004
Abstract—Intramolecular cyclization of allylic radicals generated from allylindium compounds both by photolysis or by the reaction
of radical initiators was examined. The photolysis of allylic indium compounds, prepared from 8-bromo- or 8-iodooct-1,6-dienes
and powdered indium metal, led to the formation of the 5-exo-trig products. Benzoyl peroxide as a radical initiator was also effective
for the cyclization. In contrast, the radical initiators with oxidizing nature, such as tert-butyl hypochlorite, induced iodocyclization
producing iodomethylcyclopentane via an oxidation of the iodide on the indium atom.
Ó 2004 Elsevier Ltd. All rights reserved.
1
. Introduction
tolytic cleavage of a carbon–indium bond in organo-
indium compounds and subsequent intramolecular
additions to carbon–carbon double bonds. A similar
reaction mediated by radical initiators was also exam-
ined to compare with the photochemical reaction.
Organoindium compounds have hitherto been devel-
1
oped as nucleophilic reagents in organic synthesis.
Addition to the unsaturated bond in carbonyl com-
pounds and imines is a typical reaction of allylindium re-
agents, giving the corresponding homoallylic alcohols
2
3
and amines, respectively. Alkynes, allenes, and cyclo-
4
propenes also undergo allylindation to afford allylated
2. Photochemical reactions
products, where a suitably introduced hydroxy group
exerts a significant effect for both acceleration and
stereoselectivity of the allylation. However, an addition
to carbon–carbon double bonds without a proper acti-
vation, such as substitution by electron-withdrawing
Diene 1a and indium were refluxed in THF for 3h giving
allylic indium A, which was then irradiated with a high-
pressure mercury lump (100W, Pyrex filter) in THF to
afford the 5-exo-cyclization product 2 in 51% yield
(entry 1, Table 1). The corresponding 6-endo-cyclization
product was not obtained. In order to estimate the
amount of 2 formed via a pyrolytic course, the allylic
indium compound A was quenched with 1N HCl prior
to the irradiation, leading to the corresponding proton-
ated product 3 in 11% yield together with a small
amount of 2 (3%) (entry 2). These results indicate that
the present cyclization was induced by the photolysis
of A and the thermal decomposition is negligible. The
protolysis of allylindium compounds generally proceeds
selectively at the c-position to give the corresponding
5
groups or introduction of a hydroxy group adjacent
6
to the double bond, has not been attained owing to
the low nucleophilicity of organoindium compounds.
Recently, indium-mediated radical reactions have been
reported, involving single electron transfer (SET) reac-
tions caused by metallic indium or reactions of organo-
7
indium reagents with organic radicals. Although
photolysis of organometallic compounds leading to or-
ganic radicals is documented for organocobalt com-
8
pounds,
photochemical reactions dealing with
9
organoindium compounds remains unexplored. Here
we first report a generation of organic radicals by a pho-
protonated products in good yields. The low yield of
3 in entry 2 may be attributed to a decomposition/poly-
merization of A in a significant amount under the reflux-
ing conditions. Therefore, the allylic indium compound
was next prepared at room temperature by changing
bromide 1a to the more reactive iodide 1b. The disap-
pearance of metallic indium was observed by mixing
Keywords: Indium; Radical; Photolysis; Cyclization.
*
Corresponding author. Tel./fax: +81527355206; e-mail: araki@
ach.nitech.ac.jp
0
040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.11.056

290
T. Hirashita et al. / Tetrahedron Letters 46 (2005) 289–292
Table 1. Intramolecular cyclization of allylindium compounds A, B
In2X3
hν
X
A,B
In
h
ν
or ∆
EtO2C
CO2Et
EtO2C
CO2Et
CO2Et
H•
THF
EtO2C
CO2Et
EtO2C
CO2Et
3
1
1
a: X = Br
A: X =Br
b: X = I
B: X = I
N
2
O
O•
N
EtO2C
EtO2C
CO2Et
+
+
5
TEMPO
EtO2C
CO2Et
EtO C
2
CO Et
EtO2C
CO2Et
2
2
Scheme 1. Possible mechanism for the photochemical radical
cyclization.
2
3
4
Entry Substrate Conditions
Products and yield
cis:trans)
(
minution in the yield of 2. The chemical nature of A is
distinct from conventional allylic indium reagents; for
example, the reaction of A with benzaldehyde did not
give the corresponding homoallylic alcohol at all.
1
2
3
4
5
1a
1a
1b
1b
1a
rfx, 3h ! hm, rt, 36h 2: 51% (85:15)
rfx, 4h
rt, 2h ! hm, rt, 24h
rt, 2h
2: 3%, 3: 11%
2: 34% (93:7), 4: 24%
3: 18%, 4: 10%
2: 16% (57:43), 4: 61%
a
rt, 2h ! hm, rt, 20h
a
With LiI.
The most plausible mechanism is depicted in Scheme 1;
the irradiation of A or B causes a homolytic cleavage of
the In–C bond and the resulting radical attacks the car-
bon–carbon double bond intramolecularly in a 5-exo-
trig fashion leading to the cyclopentylmethyl radical,
which abstracts hydrogen from the solvent THF to pro-
duce 2. The presence of the radical intermediate was
confirmed by an experiment using 2,2,6,6-tetramethylpi-
1
b at room temperature for 2h, and the resulting solu-
tion was irradiated for 24h to produce 2 in 34% yield to-
gether with the dimer 4 in 24% yield (entry 3).
Quenching B by 1M HCl furnished protolysis product
3
in 18% yield and the dimer 4 in 10% yield (entry 4).
1
0
The reaction of allylic indium derived from 1a in the
presence of LiI at room temperature gave rise to the di-
mer 4 predominantly (61% yield) and 2 was obtained
only in 16% yield (entry 5). Although the reasons are un-
clear for the increase of the yield of 4 and for the de-
crease of the stereoselectivity of 2 in entry 5, the above
results show that refluxing during the preparation of
the allylic indium reagents is not responsible for the di-
peridin-1-oxyl (TEMPO): the photolysis of allylic in-
dium A in the presence of TEMPO gave 5 in 17% yield.
Next, similar dienes 6 and 7 were subjected to the
photochemical intramolecular cyclization reaction un-
der the identical conditions. The results are summarized
in Table 2. Diene 6, in which a methyl group was intro-
duced at the reactive site, also gave the corresponding
a
Table 2. Photochemical reaction of allylic indium compounds derived from 6 and 7
Entry
Substrate
t (h)
Product and yield (%)
Br
1
23
EtO2C
CO2Et
EtO2C
CO2Et
EtO2C
CO2Et
8:33
9
:6
6
I
2
20
22
N
Tos
10:42 (51:49)
N
N
b
b
Tos
Tos
2
7
11:19
c
3
7
10:32 (63:37)
N
Tos
2:4
1
a
b
c
Allylindium compounds, prepared from diene 6 or 7 in THF at reflux, were irradiated in THF (30mL).
Diastereomeric ratio in the crude product.
InI was used instead of In.

T. Hirashita et al. / Tetrahedron Letters 46 (2005) 289–292
291
cyclization product 8 in moderate yield (entry 1, Table
). In the case of tosyl amide 7, the 5-exo-cyclization
product 10 was formed in 42% yield along with the
dimer 11 in 19% yield (entry 2). When the allylic indium
compound prepared with InI in place of In gave 10 in
L
In
2
L'
B
EtO2C
CO2Et
32% yield with a small amount of the dehydrogenated
product 12 (4% yield).
B'
oxidant
I+
B or B'
3
. Radical initiator-induced reactions
InL2
1b
I
The reaction of oraganoindium compounds with organ-
7
e
13
ic radicals provides a new organic radicals. To com-
pare with the above-mentioned photo-induced radical
cyclization, the radical initiator-mediated reaction of
allylic indium B was performed. A solution of B in
THF was treated with tert-butyl hypochlorite at 60°C
to give iodomethylcyclopentane 13 in 37% yield as a sin-
gle diastereomer (entry 1, Table 3). The cyclization
product 2 obtained in the photochemical reaction was
not found. It is noted that the starting iodide 1b was ob-
tained in 11% yield, although 1b disappeared completely
after the preparation of B. As the source of iodine atom
in 13 is restricted to the iodide of the allylic indium ses-
quiiodide B, 1b is considered to be reproduced from B.
These phenomena were closely resemble to the iodin-
EtO C
2
2
CO Et
Scheme 2. Possible mechanism for the iodocyclization.
By prolonging the reaction time to 5h, tert-butyl hypo-
chlorite gave 13 exclusively in 53% yield (entry 2). The
same reaction in DMF also proceeded (entry 3). The
reaction performed at room temperature increased
the ratio of 1b (entry 4). Allylic indium derived from
InI also gave the cyclization product 13 (entry 5). The
reaction in the presence of TEMPO or galvinoxyl gave
1
3 (entries 6 and 7), indicating that the reaction proc-
1
1
eeded via an ionic path. Other oxidizing agents, such
as benzoyl peroxide (BPO), potassium ferricyanide,
NCS, and N-iodosuccinimide (NIS), were also effective
ation of cyclopropylindium, where the iodine atom
on the indium is transferred to the cyclopropane in the
presence of oxidants, such as tert-butyl hypochlorite
and N-chlorosuccinimide (NCS). It is considered that
the iodide on the indium atom was oxidized to iodonium
for the iodocyclization (entries 8–12). With I , no cycli-
2
zation occurred (entry 13). Refluxing of B in THF with-
out additives gave 13 in 26% yield (entry 14), showing
that an ionic cleavage of In–I bond in B occurred also
by pyrolysis. Exposure of 1b to tert-butyl hypochlorite
0
ion, which attacked the terminal olefin bond of B (B )
and the resulting iodonium intermediate underwent the
intermolecular cyclization to give 13 (Scheme 2). The
reactions of allylic indium B were examined by changing
the oxidizing agents. The results are summarized in
Table 3.
0
gave a mixture of the chlorinated products 14 and 14
0
(
26%, 14:14 = 62:38), and 13 was not formed; therefore,
13 is considered to be formed via allylic indium B, and
not directly from 1b and t-BuOCl.
Cl
Table 3. Iodocyclization of the allylic indium compound B
Cl
t-BuOCl ( 200 mol %)
+
I
1b
additive
THF, 60 ºC, 2 h
+
1b
EtO2C
CO2Et
EtO2C
CO2Et
B
conditions
EtO2C
CO2Et
1
4
14'
13
2
6% (62:38)
Entry Additive (mol%)
T
t (h) Yield (%)
1b
37 11
1
3
1
2
3
4
5
6
7
8
9
1
1
1
1
1
t-BuOCl (150)
t-BuOCl (200)
t-BuOCl (200)
t-BuOCl (200)
t-BuOCl (200)
60°C
60°C
60°C
rt
2
5
5
53
47
0
0
Consequently, treatment of allylic indium B with oxidi-
zing agents caused the iodocyclization. In order to sup-
press the oxidation of the iodide on the indium atom,
the reactions of allylindium A, derived from allylic bro-
mide 1a, with other radical initiators such as Et B were
3
examined (Table 4). To a solution of allylic indium A,
Et B was added and the mixture was stirred at room
temperature, giving 2 and 3 in low yields (entry 1).
The yield of 2 scarcely increased by increasing the reac-
tion time (entry 2). As the amounts of 2 obtained in en-
tries 1 and 2 were coincident to that formed during the
preparation of A as is shown in Table 1, it is concluded
that the radical cyclization did not proceed by the com-
a
3
31 17
35 Trace
29 Trace
b
60°C
60°C
2
t-BuOCl (200), TEMPO (200)
2
t-BuOCl (200), galvinoxyl (140) 60°C
BPO (300)
BPO (300), TEMPO (200)
2
11
39
35
28
32
0
5
6
0
5
rt
20
22
63
2
rt
3
0
1
2
3
4
K
3
[Fe(CN)
6
] (400)
rt
NCS (200)
NIS (200)
60°C
60°C 15
rt
rfx
13 17
15
26 Trace
I
2
(200)
16
14
0
—
a
DMF was used instead of THF.
InI was used instead of In.
b
binational use of allylic indium A and Et B. On the
3

292
T. Hirashita et al. / Tetrahedron Letters 46 (2005) 289–292
Table 4. Reaction of allylic indium compound A with radical initiators
the intramolecular iodocyclization of the allylic indium
sesquiiodide occurred via oxidation of the iodide in
the allylic indium compound. Although organic stann-
anes have hitherto been used as a radical source, their
use should be avoided in view of green chemistry. The
present radical process by means of photochemical
and radical initiator-induced reactions of allylindium
compounds can serve as another radical process and ex-
pands the possibility of the organoindium chemistry.
Further application of other organic indium compounds
is currently underway.
initiator
conditions
A (or 1a)
2
+
3
Entry
Initiator (mol%)
Conditions
Yield (%)
2
(cis:trans)
3
1
2
3
Et
Et
3
B (10)
B (100)
30min, rt
5h, rt
5
8
1
3
0
0
0
0
3
BPO (150)
BPO (150)
AIBN (150)
rfx, 14h
rfx, 14h
rfx, 5h
57 (85:15)
25 (44:56)
Trace
a,b
4
5
6
(t-BuO)
2
(150)
rfx, 16h
0
a
Reaction of 1a without indium.
The starting bromide 1a was recovered (71%).
b
Acknowledgements
This work was partially supported by a Grant-in-Aid for
Scientific Research (No. 14340195) from the Ministry of
Education, Science, Sport and Culture, Japan.
other hand, when allylic indium A was refluxed with
BPO for 14h, 2 was formed in 57% yield (entry 3), albeit
the reaction of B led to the formation of 13 even at room
temperature (entry 8, Table 3). Heating of allylic bro-
mide 1a with BPO led to the formation of 2 in 25% yield
and the rest of 1a was recovered (entry 4). This fact indi-
cates that the radical cyclization proceed from both 1a
and allylic indium A, and the latter is much faster than
References and notes
1
2
. (a) Cintas, P. Synlett 1995, 1087–1096; (b) Marshall, J. A.
Chemtracts—Org. Chem. 1997, 10, 481–496; (c) Li, C.-J.;
Chan, T.-H. Tetrahedron 1999, 55, 11149–11176; (d)
Araki, S.; Hirashita, T. In Main Group Metals in Organic
Synthesis; Yamamoto, H., Oshima, K., Eds.; Wiley-VCH:
Weinheim, 2004; Vol. 1, pp 323–386.
. (a) Araki, S.; Imai, A.; Shimizu, K.; Butsugan, Y.
Tetrahedron Lett. 1992, 33, 2581–2582; (b) Araki, S.;
Imai, A.; Shimizu, K.; Yamada, M.; Mori, A.; Butsugan,
Y. J. Org. Chem. 1995, 60, 1841–1847.
0
the former. As initiators, 2,2 -azobisisobutyronitrile
(AIBN) and di-tert-butyl peroxide were not effective
for the cyclization (entries 5 and 6).
A plausible reaction mechanism is illustrated in Scheme
3
. Benzoyl radical abstracts indium from A to liberate
the allyl radical, which undergoes the intramolecular
cyclization, as the case of photochemical reaction, giving
the cyclopentylmethyl radical. This radical intermediate
could be trapped by TEMPO to give 5 in 57% yield.
3. Araki, S.; Usui, H.; Kato, M.; Butsugan, Y. J. Am. Chem.
Soc. 1996, 118, 4699–4700.
4
. (a) Araki, S.; Nakano, H.; Subburaj, K.; Hirashita, T.;
Shibutani, K.; Yamamura, H.; Kawai, M.; Butsugan, Y.
Tetrahedron Lett. 1998, 39, 6327–6330; (b) Araki, S.;
Shiraki, F.; Tanaka, T.; Nakano, H.; Subburaj, K.;
Hirashita, T.; Yamamura, H.; Kawai, M. Chem. Eur. J.
In summary, a homolytic cleavage of the C–In bond in
allylic indium compounds was realized by both photo-
lysis and by the action of radical initiators, and the
resulting allylic radicals undergo the intramolecular
cyclization in a 5-exo-trig mode to afford vinylcyclopent-
anes. When initiators with oxidizing nature, such as
tert-butyl hypochlorite, BPO, and NCS, were involved,
2001, 7, 2784–2790.
. Araki, S.; Horie, T.; Kato, M.; Hirashita, T.; Yamamura,
5
H.; Kawai, M. Tetrahedron Lett. 1999, 40, 2331–2334.
6. Araki, S.; Kamei, T.; Igarashi, Y.; Hirashita, T.; Yamam-
ura, H.; Kawai, M. Tetrahedron Lett. 1999, 40, 7999–8002.
. (a) Miyabe, H.; Naito, T. Org. Biomol. Chem. 2004, 2,
267–1270; (b) Miyabe, H.; Ueda, M.; Nishimura, A.;
7
1
Naito, T. Tetrahedron 2004, 60, 4227–4235; (c) Yanada,
R.; Koh, Y.; Nishimori, N.; Matsumura, A.; Obika, S.;
Mitsuya, H.; Fujii, N.; Takemoto, Y. J. Org. Chem. 2004,
L
In
Br
6
9, 2417–2422; (d) Yanada, R.; Obika, S.; Nishimori, N.;
Yamauchi, M.; Takemoto, Y. Tetrahedron Lett. 2004, 45,
2331–2334; (e) Takami, K.; Mikami, S.; Yorimitsu, H.;
Shinokubo, H.; Oshima, K. Tetrahedron 2003, 59, 6627–
PhCOO
EtO2C
CO2Et
-
PhCOOInL2
EtO2C
CO2Et
6
635.
. (a) Patel, V. F.; Pattenden, G. Tetrahedron Lett. 1987, 28,
451–1454; (b) Patel, V. F.; Pattenden, G. J. Chem. Soc.,
A
8
9
1
H
2
5
Chem. Commun. 1987, 871; (c) Branchaud, B. P.; Meier,
M. S.; Choi, Y. Tetrahedron Lett. 1988, 29, 167–170.
. Araki, S.; Shimizu, T.; Johar, P. S.; Jin, S.-J.; Butsugan, Y.
J. Org. Chem. 1991, 56, 2538.
0. Beckwith, A. L. J.; Bowry, V. W.; Ingold, K. U. J. Am.
Chem. Soc. 1992, 114, 4983–4992.
EtO2C
CO2Et
1
TEMPO
Scheme 3. Possible mechanism for the radical initiator-induced radical
cyclization.
11. Araki, S.; Kenji, O.; Shiraki, F.; Hirashita, T. Tetrahedron
Lett. 2002, 43, 8033–8035.