Indium(III) salt promoted intramolecular addition of allylsilanes to unactivated alkynes

Article abstract of DOI:10.1055/s-2006-947348

In the presence of a stoichiometric or catalytic amount of a Lewis acidic indium(III) salt, allylsilanes reacted intramolecularly with unactivated terminal alkynes to give cyclized products in good to high yields. The fact that the reaction proceeded in a

Full text of DOI:10.1055/s-2006-947348

LETTER
1883
Indium(III) Salt Promoted Intramolecular Addition of Allylsilanes to
Unactivated Alkynes
I
ndium(III)-Promo
a
tedIntram
o
t
lecular
s
Allylatio
u
n
of
A
lkyneskiyo Miura,*a Naoki Fujisawa,a Sayaka Toyohara,a Akira Hosomi*b
a
Department of Chemistry, 21st Century COE, Graduate School of Pure and Applied Sciences, University of Tsukuba, and CREST, Japan
Science and Technology Corporation (JST), Tsukuba, Ibaraki 305-8571, Japan
Fax +81(29)8536503; E-mail: miura@chem.tsukuba.ac.jp
b
Faculty of University Evaluation and Research, National Institution for Academic Degrees and University Evaluation, Kodaira, Tokyo
187-8587, Japan
E-mail: hosomi@chem.tsukuba.ac.jp
Received 22 April 2006
E
E
E
E
Abstract: In the presence of a stoichiometric or catalytic amount of
a Lewis acidic indium(III) salt, allylsilanes reacted intramolecularly
with unactivated terminal alkynes to give cyclized products in good
to high yields. The fact that the reaction proceeded in a trans-addi-
tion mode suggests a reaction mechanism via electrophilic activa-
tion of the triple bond by the indium salt.
InCl3
Sn
InCl2
– SnCl
E = MeO2C, Sn = SnBu3
SnCl
Sn
InCl2
E
E
E
E
Key words: alkynes, catalysis, cyclizations, indium, silicon
– InCl3
H+
Allylsilanes are valuable as storable and controllable car-
bon nucleophiles for highly selective carbon–carbon bond
formation and functionalization.1 It is well known that
they react smoothly with polarized carbon–carbon multi-
ple bonds and carbon–heteroatom single and multiple
bonds under catalysis by a Lewis acid; however, their re-
E
E
Scheme 1
actions with unactivated (non-polarized) carbon–carbon jected to the reaction with several commercially available
multiple bonds have been less explored.1–5 A recent study indium(III) salts. As a result, it turned out that a stoichio-
has disclosed that electrophilic transition-metal catalysts metric amount of In(OTf)3 was quite effective in the
are quite effective in such reactions.5
intramolecular allylation of 1a to methylenecyclopentane
2a (Equation 1). A catalytic amount of In(OTf)3 also pro-
moted the cyclization efficiently. InCl3 was inferior to
In(OTf)3 in rate-accelerating ability; however, elongation
of the reaction time led to quantitative formation of 2a.
Use of less Lewis acidic indium salts resulted in no
cyclization.
Previously we have reported the InCl3-promoted intra-
molecular allylation and allylstannylation of unactivated
alkynes with allylstannanes (Scheme 1).6 These reactions
proceed probably via stepwise mechanisms involving the
formation of an allylindium intermediate by transmetala-
tion and subsequent intramolecular cis-allylindation of
the triple bond. Our attention was next focused on the use
of allylsilanes instead of allylstannanes with the intention
of an environmentally more benign synthetic method. In
addition, we were interested in whether the intramolecular
reaction of allylsilanes proceeds via a similar mechanism.
We herein report that Lewis acidic indium salts work as
effective promoters of intramolecular addition of allyl-
silanes to unactivated alkynes.
SiAlEt2
cat. CuCN
E
E
MeONa
Cl
+
CH2E2
Cl
MeOH
70%
THF
95%
E = CO2Me
Si = SiMe2Ph
E
1) NaH, DMF
E
E
2) HC≡CCH2Br
E
Si
Si
92%
Initially, allylsilane 1a, bearing an alkynyl group, was
selected as a substrate. It could be easily prepared from di-
methyl malonate in three steps (61% total yield) as shown
in Scheme 2. The second step is a ring-opening reaction of
an electronically activated vinylcyclopropane with
PhMe2SiAlEt2.7 Allylsilane 1a thus obtained was sub-
1a, E:Z = ca. 5:1
Scheme 2
The results of the InX3-promoted reaction of other allyl-
silanes are summarized in Table 1. Allylsilanes bearing a
SiMe3 or SiPh3 group, 1b,c, showed similar reactivities as
1a did (entries 1–4). Allylsilane 1d was converted into 2d
in high yield, but with no or low diastereoselectivity (en-
tries 5 and 6). A catalytic amount of In(OTf)3 is enough
SYNLETT 2006, No. 12, pp 1883–1886
0
1
.0
8
.2
0
0
6
Advanced online publication: 24.07.2006
DOI: 10.1055/s-2006-947348; Art ID: U04606ST
© Georg Thieme Verlag Stuttgart · New York

1884
K. Miura et al.
LETTER
E
E
E
E
InX3 (1.0 equiv)
MeCN, r.t., 4 h
E
E
SiMe2Ph
1a, E:Z = ca. 5:1
E = MeO2C
2a
3
X, Yield of 2a (%): OTf, 99 (79);a Cl, 65 (99);b
F, 0; OAc, 0; acac, 0; OH, 0
a With 0.2 equiv of In(OTf)3
b For 24 h.
Figure 1
presence of these indium salts (entries 9–12). Deuterated
allylsilane 1h was quantitatively cyclized to 2h with high
Z-selectivity (entries 13 and 14). This result indicates that
the present allylation proceeds in a trans-addition mode
unlike the InCl3-promoted intramolecular allylation with
allylstannanes.
Equation 1
for an efficient cyclization of 1b–d (entries 1, 3, and 5).
The In(OTf)3-promoted cyclization of methallylsilane 1e
was not so efficient because of competitive formation of
desilylated product 3 (Table 1, entry 7; Figure 1).8,9 In
contrast, use of InCl3 as promoter suppressed the desilyla-
tion to give 2e in high yield (entry 8).9 Allylsilanes bear-
ing an internal alkyne moiety, 1f,g, were unreactive in the
The trans-allylation suggests the formation of E-vinylin-
dium species 4 from 1a (Scheme 3). A plausible path to 4
involves electrophilic activation of the triple bond by InX3
Table 1 InX3-Promoted Cyclization of Allylsilanes 1a
R3
E
E
R3
InX3 (1.0 equiv)
E
Si
E
MeCN, r.t.
4 h (X = OTf)
or 24 h (X = Cl)
R1
R1
R2
R2
1: E = MeO2C
2
Entry
Allylsilane
X in InX3
Yield (%)b
Si
R1
H
R2
H
R3
H
1
SiMe3
1b
1b
1c
1c
1d
1d
1e
1e
1f
OTf
Cl
98 (89)
2c
3d
4
76
SiPh3
H
H
H
OTf
Cl
87 (99)
86
5e
6e
7f
8f
9
SiMe2Ph
SiMe2Ph
SiMe2Ph
SiMe2Ph
SiMe2Ph
Me
H
H
H
OTf
Cl
93 (88)
99
Me
H
H
OTf
Cl
52 (60)
94
H
Me
Ph
D
OTf
Cl
0
10
1f
0
11
H
H
1g
1g
1h
1h
OTf
Cl
0
12
0
13g
14g
H
H
OTf
Cl
99 (89)
99
a Unless otherwise noted, all reactions were carried out with 1 (0.300 mmol), InX3 (0.300 or 0.060 mmol), and MeCN (1.5 mL) at r.t.
b The result with 0.2 equiv of In(OTf)3 is shown in parentheses.
c The reaction was carried out for 4 h.
d The catalytic reaction was carried out for 24 h.
e The isomeric ratios of 2d are as follows: X = OTf (1 equiv), cis:trans = 50:50; X = OTf (0.2 equiv), cis:trans = 56:44; X = Cl (1 equiv),
cis:trans = 32:68.
f The yields of 3 are as follows: X = OTf (1 equiv), 32%; X = OTf (0.2 equiv), 39%; X = Cl (1 equiv), 6%.
g The D-content of 1h was 92% D. The D-content of 2h ranged from 88% to 90% D. In all cases, the Z-selectivity of 2h was more than 90%.
Synlett 2006, No. 12, 1883–1886 © Thieme Stuttgart · New York

LETTER
Indium(III)-Promoted Intramolecular Allylation of Alkynes
Typical Procedure
1885
and subsequent nucleophilic attack of the allylsilane
moiety from the side opposite to the coordinated InX3.10
An efficient cyclization with a catalytic amount of
In(OTf)3 is indicative of the presence of a proton donor
(HY) in the reaction system. The proton donor should be
used for protonation of vinylindium 4 to 2 and regenera-
tion of In(OTf)3. The In(OTf)3-catalyzed cyclization of 1a
in CD3CN afforded 2a with no D-content. Additionally,
the stoichiometric cyclization of 1a with InX3 (X = OTf,
Cl) in CD3CN followed by quenching with DCl–D2O re-
sulted in low D-content (14–16% D). These results indi-
cate that MeCN does not work as proton donor, and that
vinylindium 4 mostly undergoes protonation before an
aqueous work-up.11 Adventitious water may cause the in
situ protonation.12
Under a nitrogen atmosphere, allylsilane 1a (108 mg, 0.300 mmol)
was added to a mixture of In(OTf)3 (169 mg, 0.300 mmol) and
MeCN (1.5 mL, freshly distilled from CaH2) at r.t. The mixture was
stirred for 4 h and quenched with sat. aq NaHCO3. The extract with
t-BuOMe was dried over Na2SO4 and evaporated. Purification of
the crude product by silica gel column chromatography (hexane–
EtOAc 30:1) gave methylenecyclopentane 2a (66.6 mg, 0.297
mmol) in 99% yield. Identification of 2a was based on the com-
parison of its spectral data with those previously reported.5b
Acknowledgment
This work was partly supported by Grants-in-Aid for Scientific
Research from the Ministry of Education, Culture, Sports, Science,
and Technology, Government of Japan.
References and Notes
InX3
InX3
E
(1) (a) Miura, K.; Hosomi, A. In Main Group Metals in Organic
Synthesis, Vol. 2; Yamamoto, H.; Oshima, K., Eds.; Wiley-
VCH: Weinheim Germany, 2004, Chap. 10, 409.
(b) Hosomi, A. Acc. Chem. Res. 1988, 21, 200.
(2) For Lewis acid promoted allylsilylations of alkynes and
alkenes, see: (a) Yamamoto, Y.; Asao, N. Bull. Chem. Soc.
Jpn. 2000, 73, 1071. (b) Jung, I. N.; Yoo, B. R. Synlett 1999,
519.
1a
E
Si
InX2
HY
– InX3
+
+
2a
XSi
YSi
E
E
(3) Yamaguchi, M.; Sotokawa, T.; Hirama, M. Chem. Commun.
1997, 743.
4
(4) Miura, K.; Saito, H.; Nakagawa, T.; Hondo, T.; Tateiwa, J.;
Sonoda, M.; Hosomi, A. J. Org. Chem. 1998, 63, 5740.
(5) (a) Fernández-Rivas, C.; Méndez, M.; Echavarren, A. M. J.
Am. Chem. Soc. 2000, 122, 1221. (b) Fernández-Rivas, C.;
Méndez, M.; Nieto-Oberhuber, C.; Echavarren, A. M. J.
Org. Chem. 2002, 67, 5197. (c) Méndez, M.; Echavarren, A.
M. Eur. J. Org. Chem. 2002, 15.
Scheme 3
We examined internal quenching of vinylindium 4 with
D2O and CD3OD. The In(OTf)3-promoted cyclization of
1a in the presence of D2O (2 equiv) resulted in 14% D-
content of the cyclized product (r.t., 4 h, 81%). The low D-
content seems due to competitive protonation with adven-
titious water. Use of a large excess (20 equiv) of D2O
completely suppressed the cyclization. In the presence of
a large excess of CD3OD, the In(OTf)3-promoted reaction
of 1a gave the cyclized product in low yield, but with
moderate D-content and high E-selectivity (Equation 2).
(6) Miura, K.; Fujisawa, N.; Hosomi, A. J. Org. Chem. 2004, 69,
2427.
(7) (a) Fugami, K.; Oshima, K.; Utimoto, K.; Nozaki, H. Bull.
Chem. Soc. Jpn. 1987, 60, 2509. (b) The original method, in
which CuCN was not used, resulted in low reproducibility.
Use of the copper catalyst achieved high yield of the desired
adduct with good reproducibility.
(8) The competitive desilylation is attributable to higher
nucleophilicity of the methallylsilane moiety. See: Hagen,
G.; Mayr, H. J. Am. Chem. Soc. 1991, 113, 4954.
(9) (a) The formation of Me3SiOTf is expected in the In(OTf)3-
promoted reaction (Scheme 3). A strong Brønsted acid
generated by reaction of In(OTf)3 or Me3SiOTf with
adventitious water [e.g., TfOH, H2O·In(OTf)3] would cause
the competitive desilylation. In the case of InCl3, its
moderate Lewis acidity and water-tolerance may suppress
the generation of a strong Brønsted acid causing the
desilylation, see ref. 9b. Me3SiCl, a by-product, can be a
source of HCl, which has enough ability to desilylate
allylsilanes. However, hydrolysis of Me3SiCl is expected to
be slower than that of Me3SiOTf, a strong Lewis acid. The
slow generation of HCl from Me3SiCl may allow the
efficient cyclization of 1e with InCl3. (b) Babu, S. A. Synlett
2002, 531.
D
In(OTf)3 (1.0 equiv)
CD3OD (30 equiv)
DCl–D2O
E
E
1a
MeCN, r.t., 48 h
44%, 66% D, E:Z = >9:1
44% recovery of 1a
Equation 2
In conclusion, we have demonstrated that Lewis acidic
indium salts, In(OTf)3 and InCl3, are valuable for electro-
philic activation of unactivated alkynes followed by in-
tramolecular allylation with allylsilanes. It is noteworthy
that the allylation mechanism is different from that for the
InCl3-promoted reaction with allylstannanes (Scheme 1
vs. Scheme 3).6 The scope and limitations of the present
allylation are under further investigation.
Synlett 2006, No. 12, 1883–1886 © Thieme Stuttgart · New York

1886
K. Miura et al.
LETTER
(10) For synthetic reactions involving electrophilic activation of
alkynes by an indium salt, see: (a) Tsuchimoto, T.; Maeda,
T.; Shirakawa, E.; Kawakami, Y. Chem. Commun. 2000,
1573. (b) Tsuchimoto, T.; Hatanaka, K.; Shirakawa, E.;
Kawakami, Y. Chem. Commun. 2003, 2454.
(c) Tsuchimoto, T.; Matsubayashi, M.; Kaneko, M.;
Shirakawa, E.; Kawakami, Y. Angew. Chem. Int. Ed. 2005,
44, 1336. (d) Sakai, N.; Annaka, K.; Konakahara, T. Org.
Lett. 2004, 6, 1527. (e) Takita, R.; Fukuta, Y.; Tsuji, R.;
Ohshima, T.; Shibasaki, M. Org. Lett. 2005, 7, 1363.
(11) In the InCl3-promoted reaction of allylstannanes (Scheme 1
and ref. 6), a similar vinylindium species survived under
almost the same conditions, and could be deuterated with
good D-content. The present InCl3-promoted reaction
should form Me3SiCl as well as the cyclized products.
Me3SiCl is more sensitive toward hydrolysis than Bu3SnCl,
a by-product of the reaction of allylstannanes. HCl generated
from Me3SiCl and adventitious water may cause the in situ
protonation of vinylindium 4.
(12) We tried the In(OTf)3-promoted reaction of 1a using CaH2
(1 equiv) as a dehydration agent; however, treatment of the
reaction mixture with DCl–D2O resulted in low D-content
(<5%) of 2a.
Synlett 2006, No. 12, 1883–1886 © Thieme Stuttgart · New York