2-vinylindoles as the four-atom component in a catalytic [4+1] cycloaddition with a silylene-palladium species generated from (aminosilyl)boronic ester

Article abstract of DOI:10.1021/om200135u

The palladium-catalyzed silylene transfer to 2-alkenylindoles from a silylboronic ester bearing a diethylamino group on the silicon atom takes place efficiently, resulting in the formation of a 1-sila-3-cyclopentene ring fused with the indole ring. Further silylene transfer proceeds in the reaction of 2-(1-alkenyl)indoles, giving bissilylated tricyclic indoles in high yields.

Full text of DOI:10.1021/om200135u

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2-Vinylindoles As the Four-Atom Component in a Catalytic [4þ1]
Cycloaddition with a Silylene-Palladium Species Generated from
(Aminosilyl)boronic Ester
Kohei Masuda, Toshimichi Ohmura,* and Michinori Suginome*
Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku,
Kyoto 615-8510, Japan
S Supporting Information
b
ABSTRACT: The palladium-catalyzed silylene transfer to
2-alkenylindoles from a silylboronic ester bearing a diethylami-
no group on the silicon atom takes place efficiently, resulting in
the formation of a 1-sila-3-cyclopentene ring fused with the indole
ring. Further silylene transfer proceeds in the reaction of 2-(1-
alkenyl)indoles, giving bissilylated tricyclic indoles in high yields.
ilylene is a highly reactive divalent chemical species and is
utilized in the synthesis of organosilicon compounds. There-
The reaction of 2-(β-styryl)-N-methylindole (1a) with silyl-
boronic ester 210 (2.0 equiv), which has a diethylamino group on
the silicon atom, was carried out in C6D6 at 50 °C in the presence
of Pd(dba)2 (1.0 mol %) and PPh3 (1.2 mol %) (entry 1,
Table 1). The reaction gave aminoborane 4 in 55% yield after
12 h, indicating that a silylene equivalent was formed from 2
under the reaction conditions used. However, the expected
silylene-1,3-diene [4þ1] cycloaddition product 5a was not
observed in the products. We found that the reaction afforded
bissilylated indole 3a in 43% yield as a single diastereomer. The
formation of 3a took place more favorably using the palladium
catalyst bearing PMePh2 as a ligand (entry 2), whereas an ineffi-
cient formation of both 3a and 4a was observed in the reaction
with other phosphines, such as PMe2Ph and PMe3 (entries 3
and 4). The palladium catalyst bearing a single PMePh2 ligand
demonstrated a high catalyst capability (entry 2), although 3a
was formed in lower yields when other P/Pd ratios (0, 2, or 4)
were applied (entries 5-7). Finally, 3a was obtained in the
highest yield when the reaction was carried out using 2.5 equiv
of 2 in the presence of the Pd/PMePh2 (P/Pd = 1.2) catalyst
(entry 8).11
Various 2-alkenylindoles 1 were then reacted with 2 (2.5 equiv)
under the optimized catalyst conditions (Table 2). The bissilylative
cyclization took place efficiently with N-methyl-2-alkenylindoles
1b-d bearing both electron-donating and electron-withdrawing
aryl groups, giving the corresponding bissilylatied indoles 3b-d in
85-89% yields (entries 1-3). Indoles 1e and 1f, having ortho-
substituted aryls, also reacted with 2 under the above conditions to
give 3e and 3f, respectively, in high yields (entries 4 and 5). In
addition to β-styryl-substituted indoles, 1-propenyl-substituted 1g
underwent the bissilylation (entry 6). However, the reaction of
vinyl-substituted 1h was sluggish, and 3h was formed in low yield
when the reaction was carried out at room temperature (entry 7).
The methyl and chloro groups at the 5-position did not affect the
S
fore, much effort has been devoted to the efficient generation and
utilization of silylene.1 Successful silylene-based transformations have
been achieved using the kinetic stabilization technique, in which a
specially designed sterically bulky group is introduced onto the
silicon atom.2 An alternative strategy to utilize silylene in synthesis is
to use transition metal catalysts, which may be more versatile and
practical for application to the synthesis of organosilicon compounds.
Catalytic silylene transfer from relatively stable precursors, such as
silacyclopropane and hydrodisilane, to organic substrates has been
achieved in the presence of group 10 and 11 transition metal
catalysts.3-7 There is much more room to develop catalytic reactions
involving silylene, not only for exploring new silylene-based trans-
formation but also for establishing new routes to organosilicon
compounds that are difficult to obtain using conventional methods.
On the basis of our recent findings on catalytic silylene transfer
from (aminosilyl)boronic esters to 1-alkynes and 1,3-dienes,8 we
were interested in the reaction of the silylene species with
alkenes. Our particular attention has been focused on vinylated
heteroaromatic compounds because of their structural analogy to
1,3-dienes, which is expected to lead to unique bicyclic products
via silylene-1,3-diene [4þ1] cycloaddition (Scheme 1).8b,9 Here-
in, we describe the palladium-catalyzed reaction of (aminosilyl)-
boronic ester with 2-alkenylindoles. The C2-C3 double bond
conjugated to the alkenyl group was found to participate in the
[4þ1] cycloaddition with dearomatization of the indole.
Scheme 1. Catalytic Silylene Transfer to 1,3-Diene-Type
Substrate
Received: February 12, 2011
Published: February 21, 2011
r
2011 American Chemical Society
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COMMUNICATION
Table 1. Screening of Reaction Conditions in Bissilylative
Cyclization of 1aa
Table 2. Bissilylative Cyclization of 2-(1-Alkenyl)indoles 1a
entry
R1
R2
R3
time (h)
yield (%)b
1
4-MeC6H4
4-MeOC6H4
4-CF3C6H4
2-MeC6H4
2-ClC6H4
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Boc
H
H
H
H
H
H
H
Me
Cl
H
1b
1c
1d
1e
1f
15
5
85 (3b)
87 (3c)
89 (3d)
85 (3e)
91 (3f)
75 (3g)
24e (3h)
92 (3i)
85 (3j)
72 (3k)
2
3
4c
5
entry ligand ligand/Pd equiv of 2 yield of 3a (%)b yield of 4 (%)c
8
5
15
12
36
5
1
2
3
4
5
6
7
8
PPh3
1.2
1.2
1.2
1.2
0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.5
43
55
83
47
26
11
71
42
89
6
7d
1g
1h
1i
PMePh2
PMe2Ph
PMe3
70
H
35
8
Ph
13
9
Ph
1j
18
24
none
3
10
Ph
1k
PMePh2
PMePh2
PMePh2
2.4
4.8
1.2
65
a 1 (0.40 mmol), 2 (1.0 mmol), Pd(dba)2 (4.0 μmol), and PMePh2 (4.8
μmol) were stirred in toluene (0.8 mL) at 50 °C unless otherwise noted.
b Isolated yield based on 1. c 3 mol % of the catalyst was used. d At room
temperature using 1h (0.30 mmol) and 2 (0.60 mmol). e 1H NMR yield
based on 1h.
33
94 (91)d
a 1a (0.20 mmol), 2 (0.40-0.50 mmol), Pd(dba)2 (2.0 μmol), and
ligand (0-9.6 μmol) were stirred in C6D6 (0.2 mL) at 50 °C for 12 h.
b 1H NMR yield based on 1a. c 1H NMR yield based on 2. d Isolated yield
on a 0.4 mmol scale reaction in toluene.
prolonged reaction times. Although 5l was unstable to silica gel
chromatography, it could be converted to the more stable silole 6
by oxidation with tetrabromo-p-benzoquinone (p-bromanil) in
the presence of N,O-bis(trimethylsilyl)acetamide (BSA).8b,12,13
In sharp contrast to 2-alkenylindoles 1, no conversion was
observed in the reaction of 3-(β-styryl)-N-methylindole (7) with
2 under the identical conditions (eq 1).
Figure 1. ORTEP drawing of 3b at the 50% probability level. Hydrogen
atoms were omitted for the clarity.
Scheme 2. Reaction of R-Styryl Group-Substituted 1l
To obtain mechanistic insight into the bissilylation, deute-
rium-labeled indoles were subjected to the reaction (eqs 2 and 3).
No migration of the deuterium was observed in the reaction of
indole 1aD-1, which has a group (E)-β-deuterio-β-styryl group,
which gave 3aD-1 as a single diastereomer (eq 2). In contrast, the
reaction of 3-deuterioindole 1aD-2 proceeded with the migra-
tion of deuterium to the silicon atom that was introduced at the
β-position of the styryl group (eq 3).
bissilylation and gave 3i and 3j in good yields (entries 8 and 9). The
bissilylation was also applicable to N-Boc-substituted 1k to give 3k
in good yield (entry 10). It should be noted that all the bissilylated
compounds were formed as a single trans diastereomer, whose
stereochemistry was confirmed from NMR analysis and X-ray
structural analysis of 3b (Figure 1).
The reaction of N-Boc-2-(R-styryl)indole (1l) with 2 was then
examined (Scheme 2). The reaction proceeded smoothly even at
15 °C to give 5l in a quantitative yield, indicating that mono-
silylation took place selectively via silylene-1,3-diene [4þ1]
cycloaddition. The bissilylated product did not form even when
the reaction was carried out at higher temperatures or with
A possible mechanism of the bissilylative cyclization is shown
in Scheme 3. The silylene-palladium species B is formed through
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Scheme 3. Possible Reaction Mechanism
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oxidative addition of the Si-B bond of 2 to Pd(0), followed by
elimination of aminoborane 4 (Scheme 3, i).14,15 Stereospecific
formation of dihydrosilole 5 then takes place through silylene-
1,3-diene [4þ1] cycloaddition between B and 1 (Scheme 3, ii).8b
Sequentially, the second B reacts with 5 to form π-allylpalladium
C via oxidative addition of the allylic C-H bond. The conversion
of (hydride)(silylene)palladium C to the (hydrosilyl)palladium
complex D takes place,16 and then 3 is formed by reductive
elimination from D. This mechanism is consistent with both the
stereochemical course of the reaction and the results of the
deuterium labeling experiments.
In conclusion, we have established a new catalytic silylene-based
transformation utilizing silylboronic ester as a silylene source. In this
transformation, 2-alkenylindoles react with silylene as a four-atom
component in the [4þ1] cycloaddition, giving five-membered
silacycles fused with the indole. Remarkable bissilylative cyclization
takes place with high diastereoselectivity in the reaction of 2-(1-
alkenyl)indoles. The synthetic utility of the bissilylated indoles and
the applicability of the reaction to other alkenyl heteroaromatic
compounds are now under investigation in our laboratory.
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ꢀ
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(8) (a) Ohmura, T.; Masuda, K.; Suginome, M. J. Am. Chem. Soc.
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’ ASSOCIATED CONTENT
S
Supporting Information. Experimental details and char-
b
acterization data of the products. This material is available free of
charge via the Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: ohmura@sbchem.kyoto-u.ac.jp; suginome@sbchem.
kyoto-u.ac.jp.
(10) Ohmura, T.; Masuda, K.; Furukawa, H.; Suginome, M. Orga-
nometallics 2007, 26, 1291.
(11) An attempt to synthesize 5a failed even in the reaction of 1a
using 1.0 equiv of 2. The reaction gave 3a (38% based on 1a) and 4
(94%) with a small amount of 5a, which was detected in GC-MS analysis
of the crude mixture.
(12) Screening of some quinones including DDQ and p-chloranil
indicated that p-bromanil was the most suitable reagent for the oxidation
of 5l. For properties of activated quinines, see: Fujita, M.; Fukuzumi, S.;
Matsubayashi, G.; Otera, J. Bull. Chem. Soc. Jpn. 1996, 69, 1107.
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was carried out without BSA. For DDQ oxidation in the presence of
BSA, see: Ryu, I.; Murai, S.; Hatayama, Y.; Sonoda, N. Tetrahedron Lett.
1978, 19, 3455.
’ ACKNOWLEDGMENT
This work is supported by Grant-in-Aid for Young Scientists (A)
from Ministry of Education, Culture, Sports, Science and Technology,
Japan. K.M. acknowledges JSPS for fellowship support. The authors
thank Dr. Y. Nagata for helping with X-ray crystallographic analysis.
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