InCl3-catalyzed cross-coupling of alkyl trimethylsilyl ethers and allylsilanes via an in situ derived combined lewis acid of InCl3 and Me3SiI

Article abstract of DOI:10.1021/jo7015289

(Chemical Equation Presented) Direct C_sp3-C_sp3 coupling of various aliphatic trimethylsilyl ethers and allylsilanes is effectively catalyzed by InCl₃ and I₂. The transformation is thought to involve an in situ-derived combined Lewis acid of InCl₃ and Me₃SiI. The reaction can be used for the construction of quaternary-quaternary and quaternary-tertiary carbon-carbon bonds. This system enabled a highly chemoselective coupling to be conducted with a trimethylsilyl ether including an aryl halide moiety. Furthermore, couplings were possible using an alkynyltri-methylsilane and a trimethylsilyl ketene acetal.

Full text of DOI:10.1021/jo7015289

InCl3/I2-Catalyzed Cross-Coupling of Alkyl
Trimethylsilyl Ethers and Allylsilanes via an in
Situ Derived Combined Lewis Acid of InCl3 and
Me3SiI
Takahiro Saito, Yoshihiro Nishimoto, Makoto Yasuda, and
Akio Baba*
Department of Applied Chemistry, Center for Atomic and
Molecular Technologies (CAMT), Graduate School of
Engineering, Osaka UniVersity, 2-1 Yamadaoka, Suita,
Osaka 565-0871, Japan
FIGURE 1. Reverse of reactivity order.
important transformation protocol.4 Such a method would
circumvent the need for deprotection of silyl-derivatized hy-
droxyls and their subsequent transformation into good leaving
groups, such as halides and esters, in preparation for coupling.
As noted in Figure 1, our combined system involving indium
and silicon reversed the reactivity order of acetoxy and hydroxyl
moieties.5 In view of this situation, our group focused on the
direct substitution of siloxy moiety.
baba@chem.eng.osaka-u.ac.jp
ReceiVed July 12, 2007
A few direct couplings between silyl ethers and allylic silanes
which have been catalyzed by such the Lewis acids as Ph3CCl/
NaTFPB6 and Ti-fluoride complex have been reported.7
However, these elaborately prepared Lewis acid catalysts are
limited to the coupling with benzylic silyl ethers or silyl acetals
that form very stable carbocations. The coupling reaction
promoted readily by ZnCl2 has been reported, but is also limited
to the allylic silyl ethers.8 Simple tertiary aliphatic silyl ethers
have not been used in such couplings9 but would be of
considerable value in the construction of quaternary carbon
centers. Moreover, only a few reports of Csp3-Csp3 coupling
via simple tertiary aliphatic organic halides are known,10 given
their tendency to undergo the â-elimination.11 In this paper, we
wish to report the cross-coupling reaction of simple tertiary
aliphatic silyl ethers and allylsilanes catalyzed by InCl3 and I2
via a putative, in situ-derived combined Lewis acid of InCl3
and Me3SiI. Our system is very convenient and characteristically
works just when the both components are combined, while each
of them separately has no activity.
Direct Csp3-Csp3 coupling of various aliphatic trimethylsilyl
ethers and allylsilanes is effectively catalyzed by InCl3 and
I2. The transformation is thought to involve an in situ-derived
combined Lewis acid of InCl3 and Me3SiI. The reaction can
be used for the construction of quaternary-quaternary and
quaternary-tertiary carbon-carbon bonds. This system
enabled a highly chemoselective coupling to be conducted
with a trimethylsilyl ether including an aryl halide moiety.
Furthermore, couplings were possible using an alkynyltri-
methylsilane and a trimethylsilyl ketene acetal.
Metal-catalyzed cross-coupling is one of the most important
carbon-carbon bond-forming reactions in organic synthesis, and
its application to the use of inexpensive and readily available
substrates, such as alcohols1 and their derivatives, is of current
interest. However, this is a considerable challenge due to the
strength of RC-OR′ bond and the poor leaving ability of the
OR′ component. Recently, Gevorgyan et al.2 demonstrated that
a strong Lewis acid like B(C6F5)3 promoted the substitution of
the acetoxy group with carbon nucleophiles in high yield and
the substitution of the hydroxyl group in low yield, but the siloxy
group was not examined (Figure 1). Furthermore, Cho et al.3
reported that InBr3 itself also promoted the substitution of the
acetoxy group, but not the hydroxyl group. The leaving ability
is generally arranged in the following order: OAc > OH .
OSiMe3. However, direct substitution of siloxy groups, which
are widely utilized as protecting groups, would be a very
We have previously reported the direct allylation of alcohols
effectively catalyzed by the combined Lewis acid system of
InCl3/Me3SiBr.5 We therefore tried to apply the system to the
direct allylation of the simple tertiary aliphatic silyl ether 1a
(4) Greene, T. W.; Wuts, P. G. M. ProtectiVe Groups in Organic
Synthesis, 3rd ed.; John Wiley & Sons: New York, 1999.
(5) (a) Saito, T.; Nishimoto, Y.; Yasuda, M.; Baba, A. J. Org. Chem.
2006, 71, 8516-8522. (b) Saito, T.; Yasuda, M.; Baba, A. Synlett 2005,
1737-1739. (c) Yasuda, M.; Saito, T.; Ueba, M.; Baba, A. Angew. Chem.,
Int. Ed. 2004, 43, 1414-1416.
(6) Kira, M.; Hino, T.; Sakurai, H. Chem. Lett. 1992, 21, 555-558.
(7) For the asymmetric transformation of silyl ethers mediated by
titanium(IV) complexes, see: Braun, M.; Kotter, W. Angew. Chem., Int.
Ed. 2004, 43, 514-517.
(8) Yokozawa, T.; Furuhashi, K.; Natsume, H. Tetrahedron Lett. 1995,
36, 5243-5246.
(9) Dau-Schmidt, J.-P.; Mayr, H. Chem. Ber. 1994, 127, 205-212.
(10) (a) Tsuji, T.; Yorimitsu, H.; Oshima, K. Angew. Chem., Int. Ed.
2002, 41, 4137-4139. (b) Ohmiya, H.; Tsuji, T.; Yorimitsu, H.; Oshima,
K. Chem. Eur. J. 2004, 10, 5640-5648. (c) Hirano, K.; Fujita, K.; Yorimitsu,
H.; Shinokubo, H.; Oshima, K. Tetrahedron Lett. 2004, 45, 2555-2557.
(11) For recent reviews of Csp3-Csp3 coupling, see: (a) Frisch, A. C.;
Beller, M. Angew. Chem., Int. Ed. 2005, 44, 674-688. (b) Netherton, M.
R.; Fu. G. C. AdV. Synth. Catal. 2004, 346, 1525-1532.
(1) For recent reviews, see: (a) Tamaru, Y. Eur. J. Org. Chem. 2005,
2647-2656. (b) Muzart, J. Tetrahedron 2005, 61, 4179-4212.
(2) (a) Rubin, M.; Gevorgyan, V. Org. Lett. 2001, 3, 2705-2707. (b)
Schwier, T.; Rubin, M.; Gevorgyan, V. Org. Lett. 2004, 6, 1999-2001.
(3) Kim, S. H.; Shin, C.; Pae, A. N.; Koh, H. Y.; Chang, M. H.; Chung,
B. Y.; Cho, Y. S. Synthesis 2004, 1581-1584.
10.1021/jo7015289 CCC: $37.00 © 2007 American Chemical Society
Published on Web 10/03/2007
8588
J. Org. Chem. 2007, 72, 8588-8590

TABLE 1. Direct Coupling by Combined Lewis Acida
TABLE 2. Direct Allylation of Silyl Ethers by InCl3/Me3SiIa
entry
catalyst (mol %)
yield (%)
1
2
3
4
5
InCl3 (5) + Me3SiCl (20)
InCl3 (5) + Me3SiBr (20)
InCl3 (5) + Me3SiI (20)
InCl3 (5) + l2 (20)
l2 (20) or Me3SiI (20)
InCl3 (5)
32
34
61
76
0
6
0
7
8
9
10
AlCl3 (5) + I2 (20)
B(C6F5)3 (5) + I2 (20)
ZnCl2 (5) + I2 (20)
Yb(OTf)3 (5) + I2 (20)
0
0
27
26
a All reactions were carried out in dichloromethane (1 mL) with
allylsilane 2a (3.0 mmol) and silyl ether 1a (1.0 mmol) at rt.
with allylsilane 2a, and the desired product 3a was obtained in
only 34% yield (Table 1, entry 2). Using a combination of InCl3/
Me3SiI, which represents stronger Lewis acidity,5a increased the
yield up to 61% at room temperature in dichloromethane (entry
3). The highest yield (76%) was obtained by means of the
combination of InCl3 and I2, where Me3SiI is presumably
generated in situ from I2 and allylsilane 2a (entry 4).12 The sole
use of InCl3 or Me3SiI showed no activity (entries 5 and 6).
Representative Lewis acids such as AlCl3 and B(C6F5)3 were
ineffective, even in the presence of I2 (entries 7 and 8).
Interestingly, the milder acids, ZnCl2 and Yb(OTf)3,13 gave the
desired product in low yields (entries 9 and 10).
Direct coupling of a variety of silyl ethers 1 with allylsilanes
2 was investigated under the optimized conditions (Table 2).
The cyclic tertiary silyl ether 1b was allylated in good yield
(entry 1). The transformation of adamantyl silyl ether 1c into
the desired product 3c proceeded in 77% yield at 70 °C (entry
2). In the case of secondary ethers, norbornyl and benzylic
systems were easily allylated, and the former gave the product
3d as a single isomer (entries 3 and 4). Benzyl silyl ether 1f
was also allylated using the combined Lewis acid system,
although simple normal silyl ether 1g was unreactive (entries 5
and 6). These results strongly suggest that our system proceeds
through the SN1 mechanism including a carbocation. The tertiary
aliphatic silyl ether 1h was transformed to the corresponding
coupling products 3h, 4h, and 5h from allyl-, cynnamyl-, and
prenylsilane in 73, 66, and 81% yields, respectively (entries 7,
8, and 9). The reaction conditions are compatible with phthal-
imide moiety to give the allylated and prenylated products 3i
and 5i in moderate yields (entries 10 and 11). The formation of
carbon skeletons connecting two quaternary carbons was
accomplished by means of the InCl3/Me3SiI system (entries 9
and 11). Our system also tolerates the phenolic OH to give the
desired product 3j in 83% yield (entry 12). The silyl ethers
bearing chlorine and bromine moieties were transformed to the
desired products 3k and 3l without affecting the halide moieties
(entries 13 and 14).
a Reactions were carried out in dichloromethane (1 mL) with silyl ether
1 (1.0 mmol), silyl nucleophile 2 (3.0 mmol), I2 (0.2 mmol), and InCl3
(0.05 mmol) at rt unless otherwise stated. b Allylsilane (6 mmol). c 1,2-
Dichloroethane (2 mL) was used as a solvent. d Allylsilane (4 mmol).
e Allylsilane (5 mmol).
SCHEME 1. Chemoselective Allylation toward Iode-
Substituted Silyl Ether
Even when the silyl ether 1m including the iodine moiety
was used, our system selectively provided the silioxy-coupling
product 3m in 74% yield (Scheme 1). This transformation was
used to compliment allylation to the palladium-catalyzed
Hiyama-coupling reaction with the aryl iodide to give 6.14
(12) (a) Jung, M. E.; Blumenkopf, T. A. Tetrahedron Lett. 1978, 19,
3657-3660. (b) For a review of silicon Lewis acids, see: Dilman, A. D.;
Loffe, S. L. Chem. ReV. 2003, 103, 733-772.
(13) Yamanaka, M.; Nishida, A.; Nakagawa, M. Org. Lett. 2000, 2, 159-
161.
(14) Jeffery, T. Tetrahedron Lett. 2000, 41, 8445-8449.
J. Org. Chem, Vol. 72, No. 22, 2007 8589

SCHEME 2. Plausible Mechanism
SCHEME 3. Direct Coupling by Combined Lewis Acid of
InCl3/Me3SiBr
the mixture was added 3,7-dimethyl-3-trimethylsiloxyoctane 1a
(1.0 mmol) at room temperature. The mixture was stirred for 3 h
at room temperature and then quenched by saturated NaHCO3 aq
(30 mL). The mixture was extracted with diethyl ether (10 ×
3 mL). The collected organic layer was dried (MgSO4). The
evaporation of the ether solution gave the crude product which was
analyzed by NMR. The details of further purification performed
for the new compounds are described in the Supporting Information.
Scheme 2 proposes a plausible reaction route for the direct
coupling between silyl ether 1 and allylsilane 2a catalyzed by
InCl3/I2 combined system (Scheme 2). At first, I2 reacts with
2a to give Me3SiI12 which generates the combined Lewis acid
7. The Lewis acidity of the silicon center is enhanced by
coordination from iodine to indium trichloride. The C-O bond
of 1 is activated by the coordination from the siloxy oxygen to
the silicon center of the combined catalyst to form a carbocation
and hexamethyldisiloxane (8). Then, nucleophilic attack of 2a
on the carbocation gives the coupling product 3 with regenera-
tion of the combined catalyst (InCl3/Me3SiI). It is noted that
the low oxophilicity of the indium species aids in completing
the catalytic cycle.5,15 If stronger, the promoter species would
be trapped by siloxane. The fact that 7 is the true catalyst is
supported by the result of the reaction of 1a with 2a in the
presence of InCl3, Me3SiI and allyl iodide.16 In contrast to the
reaction with alcohols, Me3SiI is hardly decomposed because
of the absence of active proton, and the facile formation of Me3-
SiOSiMe3 8 may prevent the â-elimination, as seen for tertiary
alcohols or halides.
The benzylic silyl ether 1e coupled with the allylsilane 2a in
good yield under the mild combined Lewis acid of InCl3 and
Me3SiBr (Scheme 3). This system can be applied to other types
of nucleophiles. The alkynylsilane 2d gave the product 9 in an
R-addition manner. The coupling with trimethylsilyl ketene
acetal 2e smoothly proceeded to afford the desired ester 10 in
high yield.17
In conclusion, we have demonstrated the direct formation of
quaternary carbon centers by the direct coupling reaction
between tertiary aliphatic silyl ethers and allylsilanes by the
catalytic use of the indium-silicon combined system. The system
has high chemoselectivity for the coupling with silyl ether
moieties in contrast to Pd-catalyzed coupling.
Hiyama Cross-Coupling Reaction of 2a with 1m (Scheme 1).
A suspended solution of Bu4NOAc (7.5 mmol) and 4A MS in DMF
(6 mmol) was stirred for 1 h. To the stirred solution were added
Pd(dba)2 (0.12 mmol), PPh3 (0.54 mmol), 4-(4-iodophenyl)-2-
methyl-2-trimethylsiloxybutane 1m (3 mmol), and allyltrimethyl-
silane 2a (15 mmol). The reaction mixture was stirred at 60 °C for
40 h. After the mixture was cooled to room temperature, diethyl
ether (10 mL) was added and the resulting mixture filtered over
Celite. The filtrate was washed with water (10 mL) and dried over
MgSO4. The evaporation of the ether solution gave the crude
product which was analyzed by NMR. The details of further
purification performed for the new compounds are described in the
Supporting Information.
Allylation of 1e Using Combined Lewis Acid of InCl3/Me3SiBr
(Scheme 3). To a mixture of InCl3 (0.05 mmol) and 1-phenylethanol
1e (1.0 mmol) in CH2Cl2 (1 mL) was added allyltrimethylsilane
2a (2.0 mmol) and Me3SiBr (0.1 mmol) under nitrogen. The mixture
was stirred for 4 h at room temperature and then quenched with
saturated NaHCO3 aq (30 mL). The mixture was extracted with
diethyl ether (10 × 3 mL). The collected organic layer was dried
(MgSO4). The evaporation of the ether solution gave the crude
product which was analyzed by NMR. The details of further
purification performed for the new compounds are described in the
Supporting Information.
Acknowledgment. This work was supported by Grants-in-
Aid for Scientific Research on Priority Areas (No. 18065015,
“Chemistry of Concerto Catalysis” and No. 19027038, “Syn-
ergistic Effects for Creation of Functional Molecules”) and for
Scientific Research (No. 19550038) from the Ministry of
Education, Culture, Sports, Science and Technology, Japan.
M.Y. acknowledges financial support from Tokuyama Science
Foundation, Mitsubishi Chemical Corporation Fund, and Kansai
Research Foundation for Technology Promotion (KRF).
Experimental Section
Typical Procedure for Allylation of 1a (Table 1, Entry 3).
To a suspended solution of InCl3 (0.05 mmol) and allyltrimethyl-
silane 2a (3 mmol) in CH2Cl2 (1 mL) was added I2 (0.2 mmol). To
(15) (a) Yasuda, M.; Somyo, T.; Baba, A. Angew. Chem., Int. Ed. 2006,
45, 793-796. (b) Yasuda, M.; Yamasaki, S.; Onishi, Y.; Baba, A. J. Am.
Chem. Soc. 2004, 126, 7186-7187. (c) Yasuda, M.; Onishi, Y.; Ueba, M.;
Miyai, T.; Baba, A. J. Org. Chem. 2001, 66, 7741-7744.
(16) The reaction of 1a (1 mmol) with 2a (3 mmol) in the presence of
InCl3 (0.05 mmol), Me3SiI (0.2 mmol), and allyl iodide (0.2 mmol) at room
temperature afforded 3a in 59% yield.
Supporting Information Available: Reaction procedures and
spectroscopic details of new compounds. This material is available
free of charge via the Internet at http://pubs.acs.org.
(17) In cases of the alkynylsilane and the silyl enolate, InCl3/Me3SiBr
system was superior to InCl3/Me3SiI system.
JO7015289
8590 J. Org. Chem., Vol. 72, No. 22, 2007