Reaction of indium ate complexes with allylic compounds. Controlling S N2/SN2′ selectivity by solvents

Article abstract of DOI:10.1016/j.tetlet.2004.02.129

Vinyl and methylindium ate complexes (indates) were prepared and both the tendency of immigration and regioselectivity toward cinnamyl bromide were investigated. The vinyl group was more preferably transferred than the Me group, giving a regioisomeric mixture of S_N2 and S_N2′ products. The ratio of S_N2/S_N2′ selectivity can be controlled by solvents; in the presence of polar solvents, such as N-butylpyrrolidone (NBP) and THF, the S_N2′ product was mainly obtained, whereas the S_N2 product was selectively prepared in solutions containing hexane. The vinylindium compound, generated by the reaction of allylic-type diindium reagents with imine, was also converted to the corresponding vinyl indate, which was allowed to react with allyl chloride to give a three-component coupling product.

Full text of DOI:10.1016/j.tetlet.2004.02.129

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 3225–3228
Reaction of indium ate complexes with allylic compounds.
0
Controlling S 2/S 2 selectivity by solvents
N
N
*
Tsunehisa Hirashita, Yousuke Hayashi, Kazuma Mitsui and Shuki Araki
Omohi College, Graduate School of Engineering, Nagoya Institute of Technology, Gokiso-cho, Showa-ku, Nagoya 466-8555, Japan
Received 6 February 2004; revised 24 February 2004; accepted 26 February 2004
Abstract—Vinyl and methylindium ate complexes (indates) were prepared and both the tendency of immigration and regioselectivity
toward cinnamyl bromide were investigated. The vinyl group was more preferably transferred than the Me group, giving a regio-
0
0
isomeric mixture of S
N
2 and S
N
2 products. The ratio of S
N
2/S
solvents, such as N-butylpyrrolidone (NBP) and THF, the S
N
2 selectivity can be controlled by solvents; in the presence of polar
0
N
2 product was mainly obtained, whereas the S
N
2 product was
selectively prepared in solutions containing hexane. The vinylindium compound, generated by the reaction of allylic-type diindium
reagents with imine, was also converted to the corresponding vinyl indate, which was allowed to react with allyl chloride to give a
three-component coupling product.
Ó 2004 Elsevier Ltd. All rights reserved.
Organoindium reagents have been extensively applied
1
for carbon–carbon bond formation in the past decade.
the vinylindium compounds 1 are inert to electrophiles
such as carbonyl compounds and allylic halides due
to the poor nucleophilicity of the vinylic indium
bond. In order to exploit 1 for a further carbon–carbon
bond formation in the consecutive coupling reaction,
we examined a conversion of 1 into the corresponding
indates. The nucleophilicity of vinylindium 1 is con-
sidered to be strongly enhanced by ate-complexation.
As the study of vinylindium ate complexes remains
unexplored, we first prepared trimethylvinylindate
and examined an allylic substitution of cinnamyl bro-
Although initial studies focused on the reaction of
allylindium reagents, a broad range of alkyl organo-
indium compounds have recently been used for carbon–
carbon bond formation by the aid of transition metal
2
catalysts. In contrast, application of tetraorganoindium
ate complexes (indates) in organic synthesis has been
limited to the reduction of carbonyl compounds by
3
lithium indium tetrahydride, the addition to a,b-unsat-
urated compounds, and the substitution of allylic
4
5
7
halides by tetra(n-butyl)-, tetramethyl-, and allylindates.
mide as a model reaction. Trimethylvinylindate was
In the course of our study of organoindium reagents, we
found that vinylindium compounds 1 are prepared by
the reaction of allylic-type diindium reagents with
prepared by the reaction of methyllithium or methyl-
magnesium bromide with indium(III) halides, followed
by the addition of vinylmagnesium bromide (Eqs. 1 and
2).
6
carbonyl compounds or imines (Scheme 1). However,
1
1
2
L In
L
2
In
3MeM þ InX
! Me
In þ 3M X
ð1Þ
3
3
In
I
Br
InL
2
InL
2
2
2
Me In þ CH @CHM ! ½Me ðCH @CHÞInŠM ð2Þ
3
2
3
2
E
E
InL
2
The reaction of trimethylvinylindate with cinnamyl
bromide gave a mixture of coupling products 2a,b and
3a,b. The results are summarized in Table 1. The cou-
pling products were obtained totally in 33% yield (Table
1
Scheme 1. Preparation of vinylindium from allylic-type diindium.
1, entry 1). The vinyl group was preferably transferred
to cinnamyl bromide in the ratio of 82:18. Addition of
Keywords: Indium; Ate complex; Allylic alkylation.
*
0
Corresponding author. Tel./fax: +81-52-735-5206; e-mail: hirasita@
nitech.ac.jp
N-butylpyrrolidone (NBP) improved the total yield
0
(entry 2), where the S
N
2
reaction predominantly
040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.02.129

3226
T. Hirashita et al. / Tetrahedron Letters 45 (2004) 3225–3228
a
Table 1. The reaction of heteroindates with cinnamyl bromide
Ph
1
1
2
2
M[InR1R2
3
]
+
Ph
R
3
R M , R M
or
Ph
Br
R
or
InX
3
1
1
2
2
M[InR1
2
2a: R = Me
b: R = vinyl
c: R = Ph
3a: R = Me
3b: R = vinyl
3c: R = Ph
R M , 3R M
R ]
3
2
2
1
1
2
2
b
Entry
R M (mol %)
R M (mol %)
X
Solvent
THF
T
Yield (%)
Ratio
2:3
52:48
[
°C]
2
a
3a
2b
3b
a:b
18:82
23:77
71:29
1
2
3
4
5
6
7
8
9
MeMgBr (300)
MeMgBr (300)
MeMgBr (300)
MeLi (300)
VinylMgBr (100) Cl
VinylMgBr (100) Cl
)78
)78
)78
4
2
4
3
13
53
14
14
THF–NBP (3:1)
THF–NBP (3:1)
16
8
79:21
VinylMgBr (100)
VinylMgBr (100)
I
6025
58 :04 2:10 0
35
11:89
19:81
I
THF–Et
THF–Et
THF
2
O–hexane (1:5:5)
O (1:1)
0013
018
VinylMgBr (100) MeLi (300)
VinylMgBr (100) MeMgBr (300)
VinylMgBr (100) MeLi (300)
Cl
Cl
Cl
Cl
Cl
2
08
0
5
21
1
42:58
16:84
2:98
3
2
8
19
34:66
THF–Et
2
O–hexane (1:5:5)
O (4:7:3)
O (4:7:3)
01
032
38
40 49:51
c
d
e
MeLi (300)
PhLi (100)
PhLi (100)
MeLi (300)
THF–c-hexane–Et
THF–c-hexane–Et
2
8
3
16
21
68:32
62:38
59:41
61:39
c
d
b
2
040 10
9
a
1
1
2
2
Indate was prepared from InX
3
(1 mmol) and R M /R M at )78 or 0 °C, and the reactions were carried out with indate (1 mmol) and cinnamyl
bromide (1 mmol) at room temperature for 17 h.
Determined by GC analysis.
b
c
Yield of 2c.
Yield of 3c.
a:c.
d
e
proceeded giving 2b as a main product. NBP may pro-
mote the ate-complexation and/or activate the indate.
in the ate-complexation. The methyl group on the
indium atom was transferred more preferably than the
0
The use of InI
(
selectivity was highly improved but with a loss of the
3
in place of InCl
entry 3). In a solution containing hexane the S
3
gave similar results
phenyl group, where S
the methyl and the phenyl group; the methyl group was
N
2 /S
N
2 selectivity was different in
N
2
0
transferred with the S 2 mode, whereas the phenyl
N
8
group selectivity (a:b) (entry 4).
N
group was preferably introduced with the S 2 mode.
The tendency of immigration and the regioselectivity
was almost coincident, showing both indates are iden-
tical irrespective of the order of addition.
Next, the order of addition of the organometallic
reagents was inversed and the resulting ate complex was
subjected to the reaction with cinnamyl bromide. An
equal molar of vinylmagnesium bromide and InCl was
3
premixed (Eq. 3), followed by the addition of 3 equiv of
another organometallic compound (Eq. 4).
Tetramethylindate also showed the dependence on the
solvent for the regioselectivity and reactivity, as
observed in the reaction of trimethylvinylindate.
0
N
Tetramethylindate prepared in THF gave the S 2
product selectively (Table 2, entries 1–4). Again, the
indate prepared with MeLi as the complexing reagent
gave a higher yield than that with MeMgBr (entries 1
and 2). The S 2 selectivity was not further improved by
N
the addition of NBP (entry 3). NBP must be added at
low temperature to prevent a decrease of the yield
CH
2
@CHMgBr þ InCl
3
! CH
2
@CHInCl
2
þ MgBrX
ð3Þ
0
2
2
CH
2
@CHInCl
2
þ 3MeM ! ½Me
3
ðCH
2
@CHÞInŠM
ð4Þ
(entries 3 and 4). Trimethylindium scarcely reacted with
cinnamyl bromide under these conditions (entry 5). In
the absence of indium salts MeLi and MeMgBr gave the
product in 7% (2a:3a ¼ 71:29) and 17% (2a:3a ¼ 41:59)
yields, respectively. These results clearly support that the
present reaction proceeded via indium ate complexes.
This inversed addition did not essentially affect both the
0
group and the S 2 /S 2 selectivity (entries 1 vs 6 and 4
N
N
vs 7). Again, dependence of both the group and the
regioselectivity on the solvent was observed; high S
N
2
selectivity at the sacrifice of the group selectivity was
observed in the reaction using hexane as a co-solvent
Although the reaction of MgBr[InMe
0
4
] in ether–hexane
2 selectivity (entry 6),
did not reverse the S
2 /S
N
N
(
entry 7). The indate prepared by adding Grignard
reagents to triorganoindium gave lower yields than that
prepared by the treatment of MeLi as the complexing
reagent (entries 1, 4, and 6 vs 5 and 7). To compare the
effect of the inversed addition exactly, trimethylphenyl-
indate was prepared from MeLi and PhLi (entries 8 and
1
The presence of tetramethylindate was confirmed by H NMR
spectroscopy. Me
3
In prepared from InCl
3
and MeMgBr in THF
showed a singlet at d )0.10 ppm in C
6
D
6
at room temperature. By the
addition of MeMgBr (100 mol %) in THF, the singlet shifted to d
9). This procedure permits access to trimethylphenylin-
date independent of the organometals and solvents used
)0.32 ppm, which can be assigned to MgBr[InMe ]. MeMgBr
resonates at d )1.47 ppm.
4

T. Hirashita et al. / Tetrahedron Letters 45 (2004) 3225–3228
3227
a
Table 2. The effect of solvent on the reaction of tetramethylindate with cinnamyl bromide
Ph
Br
4MeM
InX3
M[InMe4]
2a + 3a
b
b
Entry
RM
X
Solvent
T [°C]
Yield (%)
Ratio
2
a
3a
2a:3a
1
2
3
4
MeMgBr
MeLi
MeLi
Cl
Cl
Cl
Cl
Cl
Cl
I
THF
)78
)78
)78
031
)78
)78
01
57
86
69
13
9
81:19
91:9
86:14
THF–Et
THF–Et
THF–Et
2
2
2
O (1:2)
O–NBP (1:4:1)
O–NBP (1:4:1)
11
MeLi
4
89:11
c
5
MeMgBr
MeMgBr
MeLi
THF–NBP (5:2)
6
38
1
19
86:14
67:33
d
6
7
Et
Et
2
O–hexane (1:1)
O–hexane (7:5)
2
80 1:99
a
Indate was prepared from InX
3
(1 mmol) and MeMgBr or MeLi (4 mmol) at )78 or 0 °C, and the reactions were carried out with cinnamyl bromide
(1 mmol) at room temperature for 17 h.
Determined by GC analysis.
MeMgBr (3 mmol) was used to form trimethylindium.
b
c
d
2
Indate was prepared in THF, then the solvent was removed under reduced pressure and Et O–hexane (1:1) was added.
Li[InMe
hexane (entry 7).
4
] exclusively afforded the S
N
2 product in ether–
Table 3. The reaction of tetramethylindate with cinnamyl alcohol
a
derivatives
Ph
X
+
Li[InMe4]
2a + 3a
This dramatic solvent effect prompted us to investigate
other reaction conditions for controlling the regioselec-
tivity. As it has been reported that leaving groups play
an important role to determine the regioselectivity in the
b
b
Entry
1
X
Solvent
Yield (%) 2a:3a
Cl
Br
I
Et
Et
Et
Et
Et
Et
2
2
2
2
2
2
O
O
O
O
O
O
53
78
<1:>99
0:100
c
2
8b;9
allylic substitution reaction,
we examined the reac-
3
4
5
6
7
8
9
80<1:>99
tion of tetramethylindate by employing various cinn-
amyl compounds with different leaving groups (Table 3).
The coupling occurred regioselectively at the a-position
OC(O)OEt
OP(O)(OEt)
26
73
22
0:100
4:96
2
OAc
Cl
<1:>99
37:63
91:9
of cinnamyl alcohol derivatives in Et O (Table 3, entries
2
THF–Et O (1:1) 72
2
1–5). The best results were obtained with cinnamyl
bromide and iodide. In contrast, the reaction in THF–
Et O showed diverse regioselectivity; cinnamyl chloride
2
Br
I
THF–Et
THF–Et
THF–Et
THF–Et
2
2
2
2
O (1:1) 95
O (1:1) 47
O (1:1) 59
O (1:1) 22
74:26
61:39
<1:>99
1
1
0OP(O)(OEt)
OAc
2
1
and acetate gave the S 2 product and cinnamyl bro-
N
0
a
mide, iodide, and phosphate gave the S
N
2 product.
All reactions were carried out with indate (0.5 mmol) and allylic
compound (0.5 mmol) in solvent (2 mL) at room temperature for 17 h.
The yield and ratio were determined by GC.
Ref. 4.
b
c
Finally, we applied the above results to the allylation of
vinylindium 1. Vinylindium 1 was treated with MeLi
and the resulting vinylindate was allowed to react with
allyl chloride, bromide, and iodide. Among them, allyl
chloride gave the best results; the desired homoallylic
amide 4 was obtained in moderate yield together with
5 and 6 (Table 4, entry 1). An excess addition of MeLi
improved the yield of 4 (entry 4). MeMgBr was capable
a
Table 4. The cascade reaction of diindium reagent with sulfonimine and allyl chloride
1
2
3
. In, PhCH=NSO
2
Ph
Ph
Ph
. MeM
R
+
I
Br
. CH
2
=CHCH
2
Cl
NHSO Ph
NHSO Ph
2
2
(
E:Z=53:47)
4
5
: R = CH
: R = H
2
CH=CH
2
6
Entry
MeM (mmol)
Solvent
Additive (mL)
Yield (%)
4
5
6
1
2
3
4
5
6
MeLi (1.5)
MeLi (3.0)
THF
THF
THF
––
––
47
58
40
18
21
30
6
7
MeMgBr (2.0)
MeMgBr (2. T0 HF
MeMgBr (2.0)
MeMgBr (2.0)
NBP (0.4)
601010
NBP (4)
––
23
)
NBP (2)
THF
NBP
58
66
13
14
10
0
a
All reactions were carried out in 3-bromo-1-iodopropene (0.5 mmol), imine (0.5 mmol), and indium (1.0 mmol) in solvent (2 mL) at room tem-
perature for 4 h and then RM was added at )78 °C, followed by the addition of equimolar allyl chloride corresponding to RM.

3228
T. Hirashita et al. / Tetrahedron Letters 45 (2004) 3225–3228
of activating 1 and the usefulness of NBP was again
observed (entries 3–6). The yield of 4 was improved by
increasing the amount of NBP and the reaction per-
1267–1269; (c) Fujiwara, N.; Yamamoto, Y. J. Org. Chem.
999, 64, 4095–4101; (d) Gelman, D.; Schumann, H.; Blum,
1
J. Tetrahedron Lett. 2000, 41, 7555–7558; (e) Blum, J.;
Katza, J. A.; Jabera, N.; Michman, M.; Schumann, H.;
Schutte, S.; Kaufmann, J.; Wassermann, B. C. J. Mol.
Catal. A: Chem. 2001, 165, 97–102; (f) Hirashita, T.;
Yamamura, H.; Kawai, M.; Araki, S. Chem. Commun.
à
formed in NBP gave the highest yield. Compound 5,
which came from protonation of 1, was found in all
cases, showing that a methyl group may be transferred
from the indate to allyl chloride, giving 1-butene, to
some extent, as shown in Table 1, and the resulting
vinylindium was protonated to give 5.
2
001, 387–388; (g) Takami, K.; Yorimitsu, H.; Shinokubo,
H.; Matsubara, S.; Oshima, K. Org. Lett. 2001, 3, 1997–
1999; (h) Legros, J.-Y.; Primault, G.; Fiaud, J.-C. Tetra-
hedron 2001, 57, 2507–2514; (i) P ꢀe rez, I.; Sestelo, J. P.;
Sarandeses, L. A. J. Am. Chem. Soc. 2001, 123, 4155–4160;
In summary, we have examined the reaction behavior of
mixed indates in the reaction with allylic compounds
and demonstrated that the group- and regioselectivity
can be efficiently controlled by the solvent. The reaction
of vinylic indate with allylic halide was applicable to the
cascade coupling of allylic-type diindium compounds
giving the linear homoallylic amines.
(
j) Jaber, N.; Gelman, D.; Schumann, H.; Dechert, S.;
Blum, J. Eur. J. Org. Chem. 2002, 1628–1632; (k) Pena, M.
A.; P ꢀe rez, I.; Sestelo, J. P.; Sarandeses, L. A. Chem.
Commun. 2002, 2246–2247; (l) Pena, M. A.; Sestelo, J. P.;
Sarandeses, L. A. Synthesis 2003, 780–784; (m) Wallner, O.
A.; Szab oꢀ , K. J. Org. Lett. 2003, 5, 2405–2408; (n) Takami,
K.; Mikami, S.; Yorimitsu, H.; Shinokubo, H.; Oshima, K.
J. Org. Chem. 2003, 68, 6627–6631.
3
. (a) Yamada, M.; Tanaka, K.; Araki, S.; Butsugan, Y.
Tetrahedron Lett. 1995, 36, 3169–3172; (b) Yamada, M.;
Horie, T.; Kawai, M.; Yamamura, H.; Araki, S. Tetrahe-
dron 1997, 53, 15685–15690; (c) Yamada, M.; Tanaka, K.;
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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.
4
5
6
7
. Araki, S.; Shimizu, T.; Jin, S.-J.; Butsugan, Y. Chem.
Commun. 1991, 824–825.
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Chem. 2003, 64, 172–177.
. Recently, allylic substitution using organoindium com-
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à
Cascade reaction of 3-bromo-1-iodoprop-1-ene with sulfonimine and
allyl chloride: To a mixture of sulfonimine (123 mg, 0.50 mmol),
indium (114 mg, 1.0mmol) in NBP (2 mL), 3-bromo-1-iodoprop-1-
ene (123 mg, 0.50 mmol) was added at room temperature and stirred
for 1 h. The resulted mixture was cooled with a dry ice–acetone bath
and MeMgBr (0.93 M in THF, 2.15 mL, 2.0 mmol) was added. After
the reaction mixture was stirred at this temperature for 10min, allyl
chloride (164 lL, 2.0mmol) was added and stirred at room temper-
ature for 17 h. The reaction was quenched with hydrochloric acid
(1 M, 2 mL) and the product was extracted with ether and washed
with water and brine. The ether layer was dried over Na SO and the
2
4
solvent was removed under reduced pressure. The product was
purified by chromatography on silica gel (EtOAc–hexane ¼ 1:15 then
EtOAc) to give a mixture of 4 and 5. The yields (4; 66%, 5; 14%) were
1
determined by H NMR analysis.