Zinc-Catalyzed Dehydrogenative Silylation of Indoles

Article abstract of DOI:10.1021/acs.organomet.7b00382

A unique Lewis acid/base system consisting of zinc triflate and pyridine was found to act as an effective catalyst for making an N(indolyl)-Si bond in a dehydrogenative fashion. Execution in a nitrile medium brings out the best performance of the Zn-pyridine system, which enables participation of flexible pieces of indoles and hydrosilanes, thereby giving diverse N-silylindoles in high to excellent yields. The Zn-pyridine system in the nitrile solvent is also applicable to the corresponding C-silylation in the case that the nitrogen atom of indoles has a substituent. Pyrrole, carbazole, arylamine, and thiophene substrates other than indoles undergo the dehydrogenative N- and/or C-silylation as well. Mechanistic studies showed that the role of the zinc Lewis acid is to activate the hydrosilane. The rate-determining step of the present reaction was found to be involved in the stage of the indolyl-H bond cleavage, on the basis of kinetic isotope effect experiments. Kinetic studies indicated that the indole-based dehydrogenative N-silylation is first-order in indole, second-order in each of hydrosilane and zinc triflate, and positive and negative fractional orders in pyridine.

Full text of DOI:10.1021/acs.organomet.7b00382

Article
pubs.acs.org/Organometallics
Zinc-Catalyzed Dehydrogenative Silylation of Indoles
Kyohei Yonekura, Yoshihiko Iketani, Masaru Sekine, Tomohiro Tani, Fumiya Matsui, Daiki Kamakura,
and Teruhisa Tsuchimoto*
Department of Applied Chemistry, School of Science and Technology, Meiji University, 1-1-1 Higashimita, Tama-ku, Kawasaki,
214-8571, Japan
S
* Supporting Information
ABSTRACT: A unique Lewis acid/base system consisting of zinc triflate and
pyridine was found to act as an effective catalyst for making an N(indolyl)−Si
bond in a dehydrogenative fashion. Execution in a nitrile medium brings out the
best performance of the Zn−pyridine system, which enables participation of
flexible pieces of indoles and hydrosilanes, thereby giving diverse N-silylindoles
in high to excellent yields. The Zn−pyridine system in the nitrile solvent is also
applicable to the corresponding C-silylation in the case that the nitrogen atom
of indoles has a substituent. Pyrrole, carbazole, arylamine, and thiophene
substrates other than indoles undergo the dehydrogenative N- and/or C-
silylation as well. Mechanistic studies showed that the role of the zinc Lewis acid is to activate the hydrosilane. The rate-
determining step of the present reaction was found to be involved in the stage of the indolyl−H bond cleavage, on the basis of
kinetic isotope effect experiments. Kinetic studies indicated that the indole-based dehydrogenative N-silylation is first-order in
indole, second-order in each of hydrosilane and zinc triflate, and positive and negative fractional orders in pyridine.
emerged in succession.8−12 However, among the studies
INTRODUCTION
■
released thus far, effectively catalyzing both N- and C-silylation
Silylindoles are one of the important structural motifs in the
field of organic synthesis. For example, N- and C-silylindoles
have been widely used as synthetic intermediates for
is limited to the ruthenium complex of Tatsumi and Ohki,5,8b,13
the synthesis of which requires three steps.14 We therefore
envisioned that a readily available catalytic system applicable to
constructing valuable organic molecules such as natural
products and biologically active compounds1 as well as
both the N- and C-silylation would be an attractive and
optoelectronic materials.2 The most common way to synthesize
powerful synthetic tool when requiring silylindoles. Herein, we
report that a zinc salt along with a pyridine base in a nitrile
the silylindole includes preparation of indolylmetals with strong
medium, all of which are commercially available, effectively
metallic bases such as Li−Bu, K−N(SiMe3)3, and Na−H
(met−base), followed by adding halosilanes (X−SiR3).3 This
catalyzes both of the dehydrogenative N- and C-silylation of
indoles. We also disclose that the trinary zinc−pyridine−nitrile
system is applicable to the dehydrogenative silylation of other
aromatic molecules including pyrroles and carbazoles as well as
arylamines and thiophenes.
strategy, however, results in the coproduction of stoichiometric
amounts of wastes including met−X and H−base. Requiring
the handling of the moisture-sensitive reagents, met−base and
X−SiR3, should be also disadvantageous. Moreover, indoles
with base or nucleophile (e.g., Bu−) sensitive functional groups
are incompatible with the reaction conditions.
RESULTS AND DISCUSSION
■
In contrast to such traditional strategy, dehydrogenative
coupling of the indolyl−H and H−Si bonds coproducing only
H2 gas would be an ideal process to introduce the silyl group
onto the indole framework. In fact, significant progress has
recently been made on the dehydrogenative silylation of
indoles. In 2008, Falck disclosed the first dehydrogenative
silylation of indoles, where an iridium complex acts as a catalyst
to silylate the C2 of indoles.4 The ruthenium-catalyzed C3-
silylation of indoles has been also reported by Oestreich as well
as Tatsumi and Ohki research groups.5 Different from these C-
silylation reactions, as a preliminary communication, we
reported in 2012 the first practical dehydrogenative synthesis
of N-silylindoles, which are produced uniquely with the aid of a
zinc Lewis acid catalyst.6,7 After its publication, the
dehydrogenative N- and C-silylation of indoles catalyzed
mainly by transition metals such as Fe, Ru, Rh, and Ir have
We first investigated suitable reaction conditions for the
dehydrogenative N-silylation of indole (1a) with methyldiphe-
nylsilane (2a) (Table 1). When In(OTf)3 (10 mol %) was used
as a catalyst, the treatment of 1a and 2a in EtCN at 80 °C for
15 h provided only a small amount of N-(methyldiphenylsilyl)-
indole (3aa), along with a significant quantity of indoline (4)
(entry 1).15 Other triflate salts of Bi, Cu, Ag, Sc, and Mg metals
gave no improvements in the yield of 3aa (Bi, Cu, Sc, and Mg:
< 1%, Ag: 5%). In marked contrast, Zn(OTf)2 exhibited a
remarkable catalytic activity, and 3aa was thus obtained in an
almost quantitative yield. However, 4 was formed again in 1%
yield (entry 2). Inspired by this result, other zinc Lewis acid
Received: May 23, 2017
© XXXX American Chemical Society
A
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reduced further to 1 mol % without significant lowering of the
yield (entry 18). A catalytic use of pyridine (50 mol %) is also
possible (entry 19).
Table 1. Lewis Acid Catalyzed Dehydrogenative N-Silylation
of Indole with Methyldiphenylsilane
a,b
As shown separately in Figure 1, there seems to be an
important correlation between the basicity of the organic base
c
yield (%)
3aa
entry
Lewis acid (mol %)
organic base (pKa value)
4
1
In(OTf)3 (10)
Zn(OTf)2 (10)
Zn(ONf)2 (10)
Zn(NTf2)2 (10)
Zn(OAc)2 (10)
ZnF2 (10)
none
4
13
1
2
none
99
84
18
<1
<1
<1
<1
52
<1
<1
23
46
81
>99
99
52
97
93
3
none
<1
3
4
none
5
none
<1
<1
<1
<1
3
6
none
7
ZnCl2 (10)
none
8
ZnBr2 (10)
none
Figure 1. Yield (%) of 3aa as a function of pKa values of organic bases.
9
Zn(OTf)2 (5)
Zn(OTf)2 (5)
Zn(OTf)2 (5)
Zn(OTf)2 (5)
Zn(OTf)2 (5)
Zn(OTf)2 (5)
Zn(OTf)2 (5)
Zn(OTf)2 (5)
Zn(OTf)2 (5)
Zn(OTf)2 (1)
Zn(OTf)2 (5)
none
and the reaction rate.17 The yield of 3aa decreases when using
either of stronger or weaker organic bases than those with a pKa
value of approximately 5, like pyridine and 3-MeO−pyridine. A
stronger base such as Et3N might impair the catalytic activity of
Lewis acid Zn(OTf)2, possibly by strong coordination to the
zinc center. By contrast, a weaker base such as 3-Cl−pyridine
might not have sufficient ability to form an active zinc complex
and to stabilize a key intermediate (see discussion based on
Figure 3, Table 3, and Scheme 8 for a possible role of an
organic base).
10
11
12
13
14
15
16
17
18
19
DBU (12.4)
Et3N (10.8)
DMAP (9.7)
2,6-Lut (6.7)
4-t-BuPy (6.0)
Py (5.3)
3-MeOPy (4.9)
3-ClPy (2.8)
Py (5.3)
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
d
Py (5.3)
a
Reagents (unless otherwise noted): 1a (0.40 mmol), 2a (0.48 mmol),
With the promising reaction conditions in hand, we next
examined the scope of the N-silylation. In order to avoid
overlapping, only the structures of the N-silylindoles that have
not emerged in the preceding communication6 are collected in
Table 2, and the experimental results that should be noted here
are as follows. No troublesome side-reactions such as reductive
cleavage of the Bn−O bond18 of 1c as well as reduction of the
ester functionality19 of 1d were observed. The dehydrogenative
silylation occurred at not only the indolyl nitrogen atom but
also the phenolic and alcoholic hydroxy groups under the
reaction conditions, thereby giving 3ea and 3fa in high yields.
In addition to the OH group, the amino group of 1g underwent
silylation, but a standard quenching with a NaHCO3 aqueous
solution was found to hydrolyze the constructed Ph2MeSi−NH
bond to afford 3ga with the silyl group only at the indolyl
nitrogen atom. The hydrolysis can be prevented by altering the
quenching agent simply to Et3N. However, in order to obtain
3ga′ safely, subsequent careful handling is needed: Column
chromatography on silica gel completely decomposed 3ga′ to
3ga, but filtration on a short alumina pad followed by
recrystallization was found to be effective, albeit still causing
the partial hydrolysis from 87% NMR yield to 66% isolated
yield. Heteroaryl-substituted indoles also reacted well with 2a
to afford 3ha and 3ia in high yields. The N-silylation is
applicable to indoles 1 with an electron-withdrawing halogeno
group (3ja and 3ka). However, more electron-poor indoles do
not participate in this strategy. Thus, no N-silylindoles were
formed in the reaction of 5-nitroindole (1l) and 3-
benzoylindole (1m); see Figure 2 wherein incompatible indole
substrates with the dehydrogenative N-silylation are collected.
Lewis acid [40 μmol (10 mol %), 20 μmol (5 mol %), 4.0 μmol (1 mol
%)], organic base (0.40 mmol), EtCN (0.40 mL). Abbreviations: Tf
= SO2CF3; Nf = SO2C4F9; Ac = COMe; DBU = 1,8-
b
diazabicyclo[5.4.0]undec-7-ene; DMAP = 4-(Me2N)−pyridine; 2,6-
c
Lut = 2,6-lutidine; Py = pyridine. Determined by GC using n-decane
as an internal standard. Due to overlapping of GC peaks of n-decane
1
and 3-MeOPy, the yields for entry 16 were determined by H NMR.
d
Performed with pyridine (0.20 mmol).
catalysts were tested continuously. The nonaflate and
triflylimide salts also catalyzed the N-silylation, albeit in slower
reaction rates (entries 3 and 4). Zinc acetate and a series of zinc
halides, however, were totally inactive (entries 5−8). With
Zn(OTf)2 as a promising catalyst, a survey of solvents other
than EtCN was conducted and indicated that only nitrile
medium is friendly to this reaction, with EtCN leading to the
best yield of 3aa: No 3aa was formed at all in the use of other
solvents such as N,N-dimethylformamide, nitromethane, 1,4-
dioxane, dibutylether, 1,2-dichloroethane, chlorobenzene, tol-
uene, and cyclohexane. The effect of adding organic bases was
next examined with the intention of reducing the catalyst
loading and of inhibiting the formation of 4. Just lowering of
the catalytic amount from 10 to 5 mol % without an organic
base made the N-silylation much slower (entry 9). Adding 1.0
mol equiv of DBU, Et3N, DMAP, and 2,6-lutidine instead had
detrimental effects, but the exclusive and quantitative formation
of 3aa could be achieved when pyridine was used (entries 10−
15).16 The N-silylation was also accelerated effectively by 3-
MeO−pyridine but not by 3-Cl−pyridine (entries 16 and 17).
In the presence of pyridine, the amount of Zn(OTf)2 can be
B
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HSiMe2Bn, HSiMe2t-Bu, HSi(i-Pr)3, and H2SiMePh, and the
details are also collected in our communication.6
Table 2. Zinc-Catalyzed Dehydrogenative N-Silylation of
Indoles
a
Besides the synthesis of N-silylindoles, preparing N-
silylpyrroles 3pa and 3qa as well as N-silylbenzo[c]carbazole
3ra is achievable (Schemes 1 and 2).20 However, no desired
Scheme 1. Zinc-Catalyzed Dehydrogenative N-Silylation of
Pyrroles
Scheme 2. Zinc-Catalyzed Dehydrogenative N-Silylation of
10-Bromobenzo[c]carbazole
products were unfortunately obtained from 7-azaindole (1n)
and pyrazole (1o), probably due in part to their low
nucleophilicity (Figure 2). It should be noted that in all the
cases indicated in Table 2 and Schemes 1 and 2, no reduction
of indole, pyrrole, and carbazole rings was observed as a side
reaction.9,10,15
As already observed in the synthesis of 3ga′, the present N-
silylation is applicable to the nitrogen atom of aniline itself (1s),
other than the nitrogen atom as a member of aromatic rings
(Scheme 3). Here again, the alumina-filtration−recrystallization
sequence was used to isolate 3sa, due to the instability of the
silylamino moiety. Moreover, 3ta and 3ua could be derived
successfully from less nucleophilic arylamines but were isolated
directly by column chromatography on alumina and silica gel,
respectively, without using the alumina-filtration−recrystalliza-
tion procedure, thus showing that the stability of N-silylaryl-
amines against hydrolysis would largely depend on the electron
density of the nitrogen atom.
a
Reagents (unless otherwise noted): 1 (0.40 mmol), 2a (0.48−0.96
mmol), Zn(OTf)2 (20 μmol), pyridine (0.40 mmol), EtCN (0.40
mL). Yields of isolated 3 based on 1 are provided. See the
Experimental Section for further details. PrCN instead of EtCN
b
was used as a solvent.
Since substrates used for the dehydrogenative N-silylation
are indoles 1 and hydrosilanes 2, the reaction is considered to
start with the activation of either 1 or 2. As already disclosed in
Table 1, the reaction is significantly accelerated by pyridine but
in fact proceeds even in the absence of pyridine, strongly
indicating that the zinc salt, not pyridine, would be a key starter
Figure 2. Incompatible substrates with the zinc-catalyzed dehydrogen-
ative N-silylation.
This reaction can be equally well applied to a range of
hydrosilanes other than 2a, for instance, HSiMe2Ph, HSiEt3,
C
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Scheme 3. Zinc-Catalyzed Dehydrogenative N-Silylation of
Arylamines
Scheme 5. Zinc-Catalyzed H/D Exchange Reaction Between
2a-d and 2b
proceeded over Zn(OAc)2 and ZnBr2 that are inactive catalysts
for the dehydrogenative coupling (see entries 5 and 8 of Table
1). These results indicate that the activation of 2 by the zinc salt
is a significant step for the successful dehydrogenative coupling.
After stirring a 10:1 mixture of 2a and Zn(OTf)2 in CD3CN at
30 °C for 36 h, Zn(OTf)2 was confirmed by 19F NMR
spectroscopy and thus recovered almost quantitatively (98.4%),
indicating that Zn(OTf)2 undergoes no reduction by hydro-
silanes under the conditions.24
Next, in order to confirm whether the N-silylation of indoles
proceeds in a dehydrogenative fashion, we performed a
trapping experiment of the hydrogen gas (Scheme 6). The
Scheme 6. Trapping Experiment of a Hydrogen Gas
of the reaction. Some NMR spectroscopic studies provided
valuable insight into the mechanistic aspects of the reaction.
We first investigated the possibility of whether Zn(OTf)2 can
activate indoles 1. One possible scenario may be formation of
N-zinc−indole species 5 and/or 5′ via deprotozincation,21,22
which may be assisted by pyridine. However, on monitoring 1H
NMR spectra after mixing 1a, Zn(OTf)2, and pyridine in
varying ratios [1a/Zn(OTf)2/pyridine = 1−2:1:0−3] at 80 °C
for 1−20 h in CD3CN,23 no disappearance or decrease of the
N−H signal of 1a was observed (Scheme 4). Thus, there might
be no positive reason to propose a route starting with the
activation of 1 by Zn(OTf)2.
palladium-catalyzed hydrogenation of trans-stilbene (6) was
thus carried out for capturing the hydrogen gas that could be
evolved from the reaction of 1a with 2a.25 As expected, 1,2-
diphenylethane (7) was formed in an excellent yield of 98%.
Conducting kinetic isotope effect (KIE) experiments also
provides us with important information for discussing the
reaction mechanism (Scheme 7; see the Experimental Section
for the experimental details). Treating 2,3-dimethylindole (1b)
Scheme 4. NMR Studies with the Intention of Monitoring N-
Zinc−Indole Species
Scheme 7. Kinetic Isotope Effect Experiments
We then examined another possibility whether Zn(OTf)2 can
activate hydrosilanes 2. When a 1:1 mixture of DSiMePh2 (2a-
d, 99%-d) and HSiMe2Ph (2b) was subjected to 10 mol % of
Zn(OTf)2 in CD3CN, the H/D exchange between 2a-d and 2b
was observed even at 30 °C, thereby forming DSiMe2Ph (2b-d)
accompanied by a gradual decrease of the D-content of 2a-d
(Scheme 5). In contrast to this, no H/D exchange reaction
D
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Figure 3. Dependence of the initial reaction rate on the concentration of (a) 2,3-dimethylindole [1b], (b) HSiMePh2 [2a], (c) Zn(OTf)2
[Zn(OTf)2], and (d) pyridine [pyridine].
with HSiMePh2 (2a) or DSiMePh2 (2a-d) under the standard
reaction conditions revealed that the value of the KIE (kH/kD)
is 1.0, suggesting that the H−Si bond activation would not be
the rate-determining step (Scheme 7a). This result is nicely
E
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Table 3. Observation of H NMR Signals of Pyridine
Article
a
1
b
chemical shift (ppm) of pyridine
entry
chemicals included
Py
α-H
β-H
γ-H
7.68
Solvent: CDCl3
8.62
1
2
3
7.29
Py/Zn (6:1)
8.57 (0.05)
8.57 (0.05)
Solvent: CD3CN
8.57
7.40 (0.11)
7.40 (0.11)
7.84 (0.16)
7.84 (0.16)
Py/CH3CN/Zn (6:6:1)
4
5
Py
7.33
7.73
Py/Zn (6:1)
8.48 (0.09)
7.51 (0.18)
7.99 (0.26)
a
b
1H NMR spectra were recorded at 30 °C on 500 MHz with tetramethylsilane as an internal standard. Py = pyridine. Zn = Zn(OTf)2. The values in
the parentheses show the difference from the chemical shift given by measuring only pyridine.
consistent with the findings of Scheme 5, which showed that
the activation of the H−Si bond by Zn(OTf)2 requires no
heating, whereas heating over 80 °C is necessary for the
progress of the reaction. Therefore, the rate-determining step
should appear in the different stage. As thus expected, the kH/
kD value of more than 2.0 was observed in the reaction of 1b or
1b-d (>95%-d) with 2a, implying that the N−H bond cleavage
of indole 1 is likely to be the rate-determining step (Scheme
7b).
We next investigated the dependence of the initial reaction
rate on the concentration of indole 1b [1b], hydrosilane 2a
[2a], Zn(OTf)2 [Zn(OTf)2], and pyridine [pyridine], and the
concentration of product 3ba to estimate the initial rate was
determined by GC analysis (Figure 3; see the Experimental
Section for the experimental details).26 We first examined how
varying [1b] from 0.2 to 1 M affects the initial rate, while
keeping [2a] at 1.2 M, [Zn(OTf)2] at 0.1 M, and [pyridine] at
1 M (Figure 3a-1). Plotting ln(initial rate) versus ln[1b] gave a
straight line with a slope of 1.10, showing that the
dehydrogenative silylation is a first-order dependence on [1b]
and thus implying that a single molecule of 1b is involved in the
rate-determining step (Figure 3a-2).27 This result supports the
observation in the KIE experiments (Scheme 7) that the stage
involving the N(indolyl)−H bond cleavage is the rate-
determining step.
Similar kinetic experiments for other species were
successively performed. The kinetic analysis depending on
[2a] (0.1−1.2 M) and [Zn(OTf)2] (0.02−0.1 M) indicated a
second-order dependence on each of 2a and Zn(OTf)2 (Figure
3b,c), thus implying that two molecules of 2a and Zn(OTf)2
respectively are present in the rate-determining step. Since, as
disclosed in Scheme 5, Zn(OTf)2 works to activate hydrosilane
2, the change in order at 0.5 M of 2a would be attributed to the
consideration that, under the condition of including more than
5 mol equiv of 2a to Zn(OTf)2, the amount of 2a that
Zn(OTf)2 can activate as a catalyst reaches saturation.
On the other hand, the initial rate depending on [pyridine]
showed a positive response at the concentration below 0.6 M
but became negative at the concentration higher than 0.6 M
(Figure 3d-1). The plot of ln(initial rate) versus ln[pyridine]
thus yielded two straight lines with different slopes: 0.67 for
[pyridine] ≤ 0.6 M and −0.41 for [pyridine] ≥ 0.6 M (Figure
3d-2). First, the positive slope value implies that pyridine is
involved in the rate-determining step, and a possible
explanation why the value is not close to an integer and thus
is 0.67 is as follows: As already shown in Table 1, the silylation
proceeds well even without pyridine, only in the nitrile medium
(RCN). This may imply that RCN with a coordinating nitrogen
atom like pyridine can perform the same role as pyridine under
the reaction conditions. Therefore, considering that pyridine
and RCN may participate to the rate-determining step, with a
ratio of roughly 7:3, respectively, under the system using
pyridine in RCN, the meaning of the 0.67 value should be able
to be understood. Second, the negative slope value based on
the decrease of the initial rate implies that an inactive species
inhibiting the N-silylation is likely to be derived from extra
coordination of pyridine to a promoter at the higher
concentration. Additional NMR studies seem to be useful to
discuss this matter (Table 3). Thus, on measuring a 6:1 mixture
of pyridine and Zn(OTf)2 in noncoordinating solvent CDCl3
1
with H NMR spectroscopy, new signals appeared with the
disappearance of original pyridine signals (entries 1 and 2).
Adding the same quantity of CH3CN as that of pyridine to this
mixture led to no further change (entry 3); importantly, no
shift in the proton signal of CH3CN was also observed
compared to its original. The signal of each pyridine proton was
shifted larger, albeit in a large excess of CD3CN (525 or 88 mol
equiv of CD3CN to Zn(OTf)2 or pyridine, respectively; entries
4 and 5). These results interestingly represent that, even in the
nitrile medium, pyridine coordinates most predominately to
Zn(OTf)2 to give Zn−pyridine species.28 Closely related to
this, the broken-order changing from positive to negative in
Figure 3d-2 suggests that an active Zn−pyridine species is
generated at [pyridine] ≤ 0.6 M, that an inactive one is formed
at [pyridine] ≥ 0.6 M, and that an equilibrium between the two
Zn−pyridine species may exist before the rate-determining
step.29 An important aspect to be aware of here is that the
difference between the two slope values is 1.08 [= 0.67 −
(−0.41)], which would mean that the numerical difference of
the coordinating pyridine molecule between the two zinc−
pyridine species is 1. Herewith, considering that the active
zinc−pyridine species at the lower [pyridine] undergoes the
coordination of one pyridine molecule at the higher [pyridine]
to give the inactive species as a catalytic resting state, the
numeric difference in the broken-order should be rationally
understood.
Combining all of the kinetic studies, an experimental rate law
for the zinc-catalyzed dehydrogenative silylation of 1b with 2a
in the presence of pyridine is represented by
d[3ba]
dt
= k[1b][2a]2[Zn(OTf)2]2[pyridine]0.67
([pyridine] ≤ 0.6 M)
(1)
which is valid at [pyridine] ≤ 0.6 M and implies that one
molecule of 1b and two molecules of each of 2a and Zn(OTf)2
participate to the rate-determining step. The order in pyridine
F
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is not an integer, but pyridine has been reasonably discussed to
be involved in the rate-determining step.
as dimer form 12 to possibly stabilize each other.34 The
N(indolyl)−Si bond formation successively occurs via the
substitution of one L in 12 by indole 1 to give possible
intermediate 13, which includes one molecule of 1, and two
molecules of each of 2 and 8, thus being nicely consistent with
the results of the kinetic studies (see Figure 3). Finally, the
N(indolyl)−H bond cleavage in 13 as the rate-determining step
(RDS) yields N-silylindole 3 and the H2 gas, and then
regenerates active zinc species 8 and complex 11.
On the basis of the proposed mechanism, we developed the
following working hypothesis: If the reaction proceeds via the
formation of 11 or 12 with the electrophilic silicon atom, then
use of N-substituted indoles instead of N-unsubstituted indoles
1 should lead to C3-silylation by 11 or 12 reacting with the
intrinsic most nucleophilic C3-site of indoles.35
In order to agree with the mechanistic studies conducted so
far, a proposed mechanism would be required to satisfy the
following aspects: (1) No deprotozincation of indole 1 occurs.
(2) A zinc Lewis acid activates hydrosilane 2. (3) The reaction
is accompanied by the evolution of the H2 gas. (4) The N−H
bond cleavage of 1 is involved in the rate-determining step. (5)
The reaction is first-order in 1, second-order in both 2 and
Zn(OTf)2, and positive-order in pyridine at its low
concentration. (6) RCN partially plays the same role as
pyridine. (7) Pyridine coordinates predominately to a zinc salt
even in a nitrile medium. (8) Active and inactive two states of
zinc−pyridine species exist. (9) Their difference is one
molecule of coordinating pyridine.
Taking the above aspects (1)−(9) as well as important refs
into consideration, we propose a more reasonable reaction
mechanism for the N-silylation (Scheme 8) compared to that
In order to test our working hypothesis, the dehydrogenative
C3-silylation of 1-methylindole (14a) with 2a was carried out
under the same reaction conditions as those for synthesizing N-
silylindole 3aa (Table 4). Although the first attempt provided
Scheme 8. Proposed Reaction Mechanism
Table 4. Zinc-Catalyzed Dehydrogenative C3-Silylation of 1-
Methylindole with Methyldiphenylsilane
a
organic
base
conv.
b
yield
b
entry X in ZnX2 RCN
T (°C)
(%)
(%)
1
OTf
EtCN
EtCN
PrCN
PrCN
PrCN
PrCN
PrCN
PrCN
PrCN
PrCN
PrCN
PrCN
PrCN
Py
80
100
115
130
130
130
130
130
130
130
130
130
130
5
15
25
48
51
58
<1
10
35
54
66
85
80
1
15
24
45
44
48
<1
2
2
OTf
Py
3
OTf
Py
4
OTf
Py
5
ONf
NTf2
NTf2
NTf2
NTf2
NTf2
NTf2
NTf2
NTf2
Py
6
Py
7
DMAP
4-MeOPy
2-MePy
4-MePy
4-MePy
4-MePy
4-MePy
8
9
24
50
63
85
80
10
11
12
13
c
d
a
Reagents: 14a (0.40 mmol), 2a (0.48 mmol for entries 1−10, 0.60
mmol for entries 11−13), ZnX2 (20 μmol), organic base (0.40 mmol),
b
c
1
depicted in the preceding communication.6 To begin with, a
zinc salt immediately reacts with pyridine to form catalytically
active zinc−pyridine complex 8 {ZnII(pyridine)n = [ZnII]},
which is the starting point of the catalytic cycle but allows the
additional coordination of pyridine at its higher concentration
to give inactive complex ZnII(pyridine)n+1 (9) as a catalytic
resting state. The next for active complex 8 is the encounter
with hydrosilane 2 to afford 10,30 the silicon center of which
then becomes more electrophilic. The electrophilic character
can be appeased by the coordination of pyridine and partially
RCN (L), which would consequently lead to enhancing the
zinc−hydride31 character as shown as 11: Its form may be
drawn instead as 11′, as previously proposed.30a,b In this regard,
a silylium ion supported by pyridines or nitriles has reportedly
been known to give a stable silylpyridinium or -nitrilium ion,
respectively.32,33 In accordance with the findings that the
hydrogen atoms on 2 are mutually exchangeable with the aid of
Zn(OTf)2 (see Scheme 5) and that the reaction is second-order
in both 2 and Zn(OTf)2 (see Figure 3b,c), complex 11 can exist
RCN (0.40 mL). Determined by H NMR. Reaction time = 24 h.
d
Reaction time = 36 h.
desired product 15aa only in a small amount (entry 1), raising
the reaction temperature to 100 °C improved the reaction rate,
and gave 15aa in 15% yield (entry 2). Following the
replacement of the solvent from EtCN (bp = 97 °C) to
PrCN (bp = 116 °C), further increasing the reaction
temperature led to a higher yield of 15aa (entries 3 and 4).
Switching the catalyst to Zn(ONf)2 gave no improvement, but
the yield was slightly higher with Zn(NTf2)2 (entries 5 and 6).
Under the conditions of catalyst Zn(NTf2)2 in PrCN at 130 °C
for 15 h, the screening of organic bases revealed that the choice
of 4-methylpyridine (γ-picoline) seems to be suitable (entries
6−10). Finally, the higher loading of 2a by going from 1.2 to
1.5 mol equiv and the reaction time of 24 h were adopted,
thereby raising the yield of 15aa to 85% (entries 11−13).
Having established the efficient reaction conditions, we next
explored the scope of the dehydrogenative C-silylation (Table
G
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Article
5). A 1-methylindole with a methoxy or bromo group at the
C5-position was silylated dehydrogenatively, similar to 14a
benzyl group on the nitrogen atom of indoles can be readily
removed under acidic conditions even at room temperature,36
15fa was safely obtained in a high yield. HSiMe2Ph (2b) and
HSiMe2Bn (2c) other than 2a also reacted with 14a to give
15ab and 15ac in good yields, respectively. Besides indole
derivatives, other heteroarenes participated in this protocol as
well. In the reaction of 1-hexylpyrrole (14g), a mixture of
regioisomers 15ga was formed, albeit in a high β-selectivity.
Silylthiophene 15ha can be successfully prepared on the basis
of this strategy. Both of the two H−Si bonds of H2SiPh2 (2d)
are also available for the dehydrogenative C-silylation of 14a
and 1-hexylindole (14i) to get diindolylsilanes 15ad and 15id
in 73 and 58% yields, respectively (Scheme 9).
Table 5. Zinc-Catalyzed Dehydrogenative C-Silylation of
a
Indoles and Other Heteroarenes
Scheme 9. Zinc-Catalyzed Dehydrogenative C3-Silylation of
1-Alkylindoles with H2SiPh2
In contrast to the successful experiments shown in Table 5
and Scheme 9, no C-silylation unfortunately proceeded when
using less nucleophilic (hetero)arenes such as N-EWG−indoles
14j and 14k (EWG = electron-withdrawing group) as well as
benzothiophene (14l), benzofuran (14m), and N,N-dimethy-
laniline37 (14n) (Figure 4). In order to gain mechanistic insight
Figure 4. Incompatible substrates in the zinc-catalyzed dehydrogen-
ative C-silylation.
a
Reagents (unless otherwise noted): 14 (0.40 mmol), 2 (0.60 mmol),
Zn(NTf2)2 (20 μmol), γ-picoline (0.40 or 0.80 mmol), PrCN (0.40
mL). Yields of isolated 15 based on 14 are shown here. 4-MePy: the
molar equivalent of γ-picoline used. See the Experimental Section for
into the dehydrogenative C-silylation as well, KIE experiments
were again performed but at 115 °C in BuCN (bp = 140 °C)
instead of at 130 °C in PrCN (bp = 115−117 °C) as the
standard reaction conditions, in terms of the reproducibility
(Scheme 10; see the Experimental Section for the experimental
details). Thus, the kH/kD value for the reaction of 14a with 2a
or 2a-d was 1.1, and that for the reaction of 14a or 14a-d (95%-
d) with 2a was 2.4. These results suggest that the stage related
to the cleavage of the C3(indolyl)−H bond is the rate-
determining step. This result is nicely consistent with that for
the N-silylation discussed in Scheme 7.
b
further details. Performed with Zn(OTf)2 (5 mol %) as a catalyst and
c
TMPDA (0.40 mmol) as an organic base. Performed with 14h (1.2
mmol) and 2a (0.40 mmol). The yield of isolated 15ha is based on 2a.
(15ba and 15ca). Under the same reaction conditions as those
used for preparing 15aa, 1,2-dimethylindole (14d) reacted
similarly with 2a but sluggishly, providing 15da in 40% yield.
Since the nucleophilicity of 14d that has one more electron-
donating methyl group than 14a will be somewhat higher than
that of 14a, the slower reaction might be due to steric
hindrance induced by the C2-methyl group. After rescreening
of a zinc catalyst and an organic base, the combination of
Zn(OTf)2 and N,N,N′,N′-tetramethyl-1,3-propanediamine
(TMPDA) for the reaction of 14d turned out to be more
effective, giving 15da in 77% yield. The Zn(OTf)2−TMPDA
system, however, did not work for 2,3′-biindole 14e with the
bulkier 3-indolyl group, which again reacted with 2a under the
standard reaction conditions using the Zn(NTf2)2−γ-picoline
system, albeit in a low yield (15ea). In spite of the fact that the
CONCLUSION
■
We have demonstrated herein that the combination of a zinc
Lewis acid and pyridine base in a nitrile is an effective and
practical catalytic system to connect indoles and hydrosilanes
dehydrogenatively. Our method features a broad range of
substrate coverage with a high functional group tolerance. In
contrast to other methods catalyzed by rather rare and
expensive transition metals, the use of the ubiquitous zinc
metal for the catalyst is an advantage of our system in terms of
H
DOI: 10.1021/acs.organomet.7b00382
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Article
further purification. Elemental analysis was performed for some
selected products.
Scheme 10. Kinetic Isotope Effect Experiments
Zinc-Catalyzed Dehydrogenative N-Silylation of Indoles
with Methyldiphenylsilane: A General Procedure for Table 2.
Zn(OTf)2 (7.27 mg, 20.0 μmol) was placed in a 20 mL Schlenk tube,
which was heated at 80 °C in vacuo for 15 min. The tube was cooled
down to room temperature and filled with argon. EtCN or PrCN (0.40
mL) was added to the tube, and the mixture was then stirred at room
temperature for 3 min. To this were added 1 (0.400 mmol), 2a (0.480,
0.600, or 0.960 mmol), and pyridine (31.6 mg, 0.400 mmol), and the
resulting mixture was stirred at 80, 90, or 120 °C. After the time
specified in Table 2, unless otherwise noted, the following workup
procedure was performed. Thus, a saturated NaHCO3 aqueous
solution (0.5 mL) was added to the mixture, and the aqueous phase
was extracted with EtOAc (5 mL × 3). The combined organic layer
was washed with brine (1 mL) and then dried over anhydrous sodium
sulfate (Na2SO4). Filtration and evaporation of the solvent followed by
purification gave product 3. Unless otherwise noted, products 3
1
synthesized here were fully characterized by H and 13C{1H} NMR
spectroscopy, and HRMS.
2,3-Dimethyl-1-methyldiphenylsilyl-1H-indole (3ba). The title
compound was synthesized using reagents and conditions of 1b
(0.400 mmol), 2a (0.480 mmol), Zn(OTf)2 (20.0 μmol), pyridine
(0.400 mmol), EtCN (0.40 mL), 90 °C, and 24 h, and was isolated by
column chromatography on alumina (hexane). Compound 3ba has
already appeared in the literature,9a and its spectral and analytical data
are in good agreement with those reported. Accordingly, 13C{1H}
supporting and promoting sustainable chemistry. Moreover,
high availability of all of the zinc salt, pyridine base, and nitrile
solvent as commercial sources will also enhance the utility of
our protocol. Mechanistic studies revealed that the reaction
starts with the activation of the H−Si bond by the zinc Lewis
acid, and the rate-determining step is the indolyl−H bond
cleavage. The pyridine base that significantly accelerates the
reaction rate plausibly works to form the active zinc species and
to stabilize the silicon center of the hydrosilane−zinc key
intermediate. Further application of the Zn−pyridine−nitrile
system to other transformations is in progress in our
laboratory.38
1
NMR data were omitted here. White solid, mp 80−81 °C. H NMR
(400 MHz, CDCl3) δ 1.08 (s, 3H), 2.05 (s, 3H), 2.21 (s, 3H), 6.73−
6.85 (m, 2H), 7.00−7.07 (m, 1H), 7.32−7.58 (m, 11H). HRMS (FD)
calcd for C23H23NSi M+, 341.1594. Found m/z 341.1622. Anal. Calcd
for C23H23NSi: C, 80.89; H, 6.79; N, 4.10. Found: C, 80.84; H, 6.71;
N, 4.00.
6-Benzyloxy-1-methyldiphenylsilyl-1H-indole (3ca). The title
compound was synthesized using reagents and conditions of 1c
(0.400 mmol), 2a (0.480 mmol), Zn(OTf)2 (20.0 μmol), pyridine
(0.400 mmol), EtCN (0.40 mL), 80 °C, and 15 h, and was isolated by
column chromatography on silica gel (hexane/EtOAc = 40/1). White
EXPERIMENTAL SECTION
■
1
solid, mp 95−96 °C. H NMR (500 MHz, CDCl3) δ 0.97 (s, 3H),
General Remarks. All manipulations were conducted with a
standard Schlenk technique under an argon atmosphere. NMR spectra
(1H, 400 and 500 MHz; 13C{1H}, 100 and 125 MHz) were taken
using tetramethylsilane as an internal standard. Analytical GC was
performed with a capillary column coated with 5% phenyl
polysilphenylene-siloxane (30 m × 0.25 mm × 0.25 μm) or 5%
diphenyl- and 95% dimethylpolysiloxane (30 m × 0.25 mm × 0.25
μm) and with FID detector, using nitrogen as carrier gas. Quantitative
analyses by GC were performed using a standard curve method. GC−
MS analyses were performed with a capillary column coated with 5%
phenyl polysilphenylene-siloxane (30 m × 0.25 mm × 0.25 μm) or 5%
diphenyl- and 95% dimethylpolysiloxane (30 m × 0.25 mm × 0.25
μm) by electron ionization at 70 eV using helium as carrier gas.
Preparative recycling gel permeation chromatography (GPC) was
performed with a highly cross-linked polystyrene/divinylbenzene
packed column using chloroform as eluent. HRMS were obtained by
a magnetic sector or FD-TOF. All melting points were determined on
a micro hot stage apparatus and are uncorrected. Elemental analysis
was performed using a Vario EL III elemental analysis instrument.
Propionitrile (EtCN), and butyronitrile (PrCN) were distilled under
argon from P2O5 just prior to use. Hydrosilanes 2, pyrroles, 2-
methoxythiophene (14h), and pentanenitrile (BuCN) were stored
over molecular sieves 4 Å (MS 4 Å) under argon. Aniline (1s), 3,5-
bis(trifluoromethyl)aniline (1t), pyridine, and other organic bases
were stored over KOH pellets under argon. The following zinc salt and
substrates were synthesized according to the respective literature
methods: Zn(NTf2)2,39 5-(2,5-dimethylpyrrol-1-yl)-1H-indole (1h),40
2-(benzofuran-2-yl)-1H-indole (1i),41 3-benzoyl-1H-indole (1m),42 2-
(4-fluorophenyl)-1H-pyrrole (1q),43 DSiMePh2 (2a-d),44 1,1′-dimeth-
yl-1H,1′H-2,3′-biindole (14e),45 1-hexyl-1H-pyrrole (14g),46 and 1-
hexylindole (14i).47 Unless otherwise noted, other substrates and
reagents were commercially available and used as received without
4.73 (s, 2H), 6.53 (d, J = 3.2 Hz, 1H), 6.59 (d, J = 2.0 Hz, 1H), 6.83
(dd, J = 8.6, 2.3 Hz, 1H), 6.90 (d, J = 3.2 Hz, 1H), 7.24−7.33 (m, 5H),
7.36−7.42 (m, 4H), 7.44−7.54 (m, 7H). 13C{1H} NMR (125 MHz,
CDCl3) δ −2.7, 70.4, 99.3, 105.1, 110.9, 120.9, 126.0, 127.4, 127.7,
128.3, 128.4, 130.2, 130.5, 133.3, 134.9, 137.4, 141.3, 154.8. HRMS
(FD) calcd for C28H25NOSi M+, 419.1700. Found m/z 419.1719.
Anal. Calcd for C28H25NOSi: C, 80.15; H, 6.01; N, 3.34. Found: C,
79.75; H, 6.01; N, 3.28.
3-Acetyloxy-1-methyldiphenylsilyl-1H-indole (3da). The title
compound was synthesized using reagents and conditions of 1d
(0.400 mmol), 2a (0.600 mmol), Zn(OTf)2 (20.0 μmol), pyridine
(0.400 mmol), EtCN (0.40 mL), 90 °C, and 24 h, and was isolated by
column chromatography on silica gel (hexane/EtOAc = 20/1).
Viscous pale yellow oil. 1H NMR (400 MHz, CDCl3) δ 1.05 (s,
3H), 2.32 (s, 3H), 6.97−7.07 (m, 2H), 7.07−7.15 (m, 2H), 7.36−7.43
(m, 4H), 7.47 (tt, J = 7.4, 1.6 Hz, 2H), 7.50−7.56 (m, 5H). 13C{1H}
NMR (100 MHz, CDCl3) δ −2.4, 20.9, 114.1, 117.6, 119.9, 120.3,
122.3, 123.9, 128.3, 130.7, 132.5, 133.0, 134.9, 137.9, 168.6. HRMS
(FD) calcd for C23H21NO2Si M+, 371.1336. Found m/z 371.1342.
1-Methyldiphenylsilyl-4-[(methyldiphenylsilyl)oxy]-1H-indole
(3ea). The title compound was synthesized using reagents and
conditions of 1e (0.400 mmol), 2a (0.960 mmol), Zn(OTf)2 (20.0
μmol), pyridine (0.400 mmol), EtCN (0.40 mL), 80 °C, and 15 h, and
was isolated by column chromatography on silica gel (hexane/EtOAc
= 40/1). White solid, mp 158−159 °C. 1H NMR (400 MHz, CDCl3)
δ 0.77 (s, 3H), 1.04 (s, 3H), 6.39−6.46 (m, 1H), 6.65 (d, J = 3.2 Hz,
1H), 6.70−6.78 (m, 2H), 6.85 (d, J = 3.4 Hz, 1H), 7.35−7.49 (m,
12H), 7.49−7.54 (m, 4H), 7.69−7.76 (m, 4H). 13C{1H} NMR (100
MHz, CDCl3) δ −2.6, −2.5, 102.8, 107.9, 109.1, 122.0, 125.1, 127.9,
128.2, 130.0, 130.1, 130.5, 133.3, 134.4, 134.9, 136.1, 142.6, 148.3.
HRMS (FD) calcd for C34H31NOSi2 M+, 525.1939. Found m/z
I
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Article
525.1925. Anal. Calcd for C34H31NOSi2: C, 77.67; H, 5.94; N, 2.66.
Found: C, 77.53; H, 5.80; N, 2.64.
CDCl3) δ 0.73 (s, 3H), 6.65 (d, J = 0.9 Hz, 1H), 6.89−6.96 (m, 2H),
6.98 (s, 1H), 7.07−7.20 (m, 4H), 7.22−7.29 (m, 4H), 7.32 (tt, J = 7.3,
1.9 Hz, 2H), 7.38−7.43 (m, 1H), 7.49−7.54 (m, 4H), 7.64 (dt, J = 7.8,
0.9 Hz, 1H). 13C{1H} NMR (100 MHz, CDCl3) δ −0.95, 105.5, 110.2,
111.3, 115.3, 120.6, 120.7, 120.8, 122.4, 122.8, 124.0, 127.8, 128.6,
129.9, 130.8, 134.6, 134.67, 134.74, 143.0, 150.1, 154.2. HRMS (FD)
calcd for C29H23NOSi M+, 429.1543. Found m/z 429.1556. Anal.
Calcd for C29H23NOSi: C, 81.08; H, 5.40; N, 3.26. Found: C, 80.73;
H, 5.19; N, 3.18.
1-Methyldiphenylsilyl-3-{2-[(methyldiphenylsilyl)oxy]ethyl}-1H-
indole (3fa). The title compound was synthesized using reagents and
conditions of 1f (0.400 mmol), 2a (0.960 mmol), Zn(OTf)2 (20.0
μmol), pyridine (0.400 mmol), EtCN (0.40 mL), 90 °C, and 24 h, and
was isolated by column chromatography on silica gel (hexane/EtOAc
= 40/1). Viscous colorless oil. 1H NMR (400 MHz, CDCl3) δ 0.55 (s,
3H), 1.00 (s, 3H), 2.98 (t, J = 7.2 Hz, 2H), 3.92 (t, J = 7.2 Hz, 2H),
6.80 (s, 1H), 6.93−7.00 (m, 1H), 7.00−7.08 (m, 2H), 7.28−7.47 (m,
13H), 7.48−7.54 (m, 8H). 13C{1H} NMR (100 MHz, CDCl3) δ −3.0,
−2.4, 28.8, 63.7, 113.9, 115.2, 118.9, 119.6, 121.4, 127.8, 128.2, 129.2,
129.7, 130.5, 131.6, 133.5, 134.4, 134.9, 136.1, 140.9. HRMS (FD)
calcd for C36H35NOSi2 M+, 553.2252. Found m/z 553.2249.
5-Amino-1-methyldiphenylsilyl-1H-indole (3ga). The title com-
pound was synthesized using reagents and conditions of 1g (0.400
mmol), 2a (0.960 mmol), Zn(OTf)2 (20.0 μmol), pyridine (0.400
mmol), EtCN (0.40 mL), 80 °C, and 15 h, and was isolated by column
chromatography on silica gel (hexane/EtOAc = 4/1). White solid, mp
123−124 °C. 1H NMR (500 MHz, CDCl3) δ 1.02 (s, 3H), 3.46 (br s,
2H), 6.42 (dd, J = 3.2, 0.9 Hz, 1H), 6.44 (dd, J = 8.6, 2.3 Hz, 1H), 6.89
(dt, J = 8.6, 0.7 Hz, 1H), 6.91 (d, J = 3.2 Hz, 1H), 6.93 (dd, J = 2.3, 0.6
Hz, 1H), 7.35−7.41 (m, 4H), 7.45 (tt, J = 7.4, 1.7 Hz, 2H), 7.49−7.55
(m, 4H). 13C{1H} NMR (125 MHz, CDCl3) δ −2.5, 104.3, 105.6,
112.2, 114.3, 128.2, 130.5, 132.1, 132.8, 133.5, 134.9, 135.2, 139.9.
HRMS (FD) calcd for C21H20N2Si M+, 328.1390. Found m/z
328.1390. Anal. Calcd for C21H20N2Si: C, 76.78; H, 6.14; N, 8.53.
Found: C, 76.55; H, 5.87; N, 8.46.
1-Methyldiphenylsilyl-5-[N-(methyldiphenylsilyl)amino]-1H-in-
dole (3ga′). The title compound was synthesized using reagents and
conditions of 1g (0.400 mmol), 2a (0.960 mmol), Zn(OTf)2 (20.0
μmol), pyridine (0.400 mmol), EtCN (0.40 mL), 80 °C, and 15 h. The
following workup procedure was conducted after stirring at 80 °C for
15 h. A mixture of benzene/Et3N (10/1, 10 mL) was added to the
reaction mixture, and the resulting solution was filtered through a pad
of Celite, which was then washed with a mixture of benzene/Et3N
(10/1). Evaporation of the solvent and filtration through 1 cm alumina
covered with Celite (benzene/EtOAc = 10/1) and then evaporation of
the solvent followed by recrystallization from pentane/EtOAc at −20
°C provided 3ga′. White solid, mp 182−184 °C. 1H NMR (400 MHz,
C6D6) δ 0.69 (s, 3H), 0.71 (s, 3H), 3.50 (br s, 1H), 6.39 (dd, J = 3.0,
0.7 Hz, 1H), 6.47 (dd, J = 8.6, 2.4 Hz, 1H), 6.87 (d, J = 3.2 Hz, 1H),
6.97−7.09 (m, 6H), 7.10−7.20 (m, 8H), 7.36−7.42 (m, 4H), 7.63−
7.69 (m, 4H). 13C{1H} NMR (100 MHz, C6D6) δ −2.64, −2.61,
105.3, 107.7, 114.2, 114.5, 128.4, 128.6, 129.9, 130.5, 132.0, 133.7,
134.1, 135.1, 135.2, 135.5, 137.1, 140.7. HRMS (FD) calcd for
C34H32N2Si2 M+, 524.2099. Found m/z 524.2074. Anal. Calcd for
C34H32N2Si2: C, 77.81; H, 6.15; N, 5.34. Found: C, 77.65; H, 6.03; N,
5.30.
5-(2,5-Dimethylpyrrol-1-yl)-1-methyldiphenylsilyl-1H-indole
(3ha). The title compound was synthesized using reagents and
conditions of 1h (0.400 mmol), 2a (0.600 mmol), Zn(OTf)2 (20.0
μmol), pyridine (0.400 mmol), EtCN (0.40 mL), 80 °C, and 24 h, and
was isolated by recrystallization from hexane/EtOAc after column
chromatography on silica gel (hexane/EtOAc = 40/1). White solid,
mp 154−155 °C. 1H NMR (500 MHz, CDCl3) δ 1.10 (s, 3H), 2.01 (s,
6H), 5.88 (s, 2H), 6.62 (dd, J = 3.2, 0.9 Hz, 1H), 6.81 (dd, J = 8.6, 2.0
Hz, 1H), 7.05 (d, J = 3.2 Hz, 1H), 7.13 (d, J = 8.6 Hz, 1H), 7.40−7.47
(m, 5H), 7.50 (tt, J = 7.4, 1.7 Hz, 2H), 7.54−7.60 (m, 4H). 13C{1H}
NMR (125 MHz, CDCl3) δ −2.5, 13.1, 104.8, 105.4, 113.8, 120.2,
121.9, 128.4, 129.3, 130.7, 131.7, 131.9, 132.9, 133.0, 134.9, 139.7.
HRMS (FD) calcd for C27H26N2Si M+, 406.1860. Found m/z
406.1861. Anal. Calcd for C27H26N2Si: C, 79.76; H, 6.45; N, 6.89.
Found: C, 79.46; H, 6.27; N, 6.69.
5-Fluoro-1-methyldiphenylsilyl-1H-indole (3ja). The title com-
pound was synthesized using reagents and conditions of 1j (0.400
mmol), 2a (0.600 mmol), Zn(OTf)2 (20.0 μmol), pyridine (0.400
mmol), EtCN (0.40 mL), 80 °C, and 36 h, and was isolated by
recycling GPC after column chromatography on silica gel (hexane/
1
EtOAc = 80/1). White solid, mp 94−95 °C. H NMR (400 MHz,
CDCl3) δ 1.04 (s, 3H), 6.56 (dd, J = 3.2, 0.7 Hz, 1H), 6.73 (td, J = 9.0,
2.6 Hz, 1H), 6.98 (dd, J = 8.9, 4.4 Hz, 1H), 7.03 (d, J = 3.2 Hz, 1H),
7.24−7.29 (m, 1H), 7.36−7.44 (m, 4H), 7.45−7.54 (m, 6H). 13C{1H}
NMR (100 MHz, CDCl3) δ −2.6, 105.3 (d, J = 4.8 Hz), 105.5 (d, J =
23.0 Hz), 109.7 (d, J = 25.9 Hz), 114.3 (d, J = 9.6 Hz), 128.4, 130.7,
132.3 (d, J = 10.1 Hz), 133.0, 133.3, 134.9, 137.0, 158.1 (d, J = 235.3
Hz). HRMS (FD) calcd for C21H18FNSi M+, 331.1187. Found m/z
331.1184. Anal. Calcd for C21H18FNSi: C, 76.10; H, 5.47; N, 4.23.
Found: C, 75.93; H, 5.43; N, 4.20.
5-Chloro-1-methyldiphenylsilyl-1H-indole (3ka). The title com-
pound was synthesized using reagents and conditions of 1k (0.400
mmol), 2a (0.600 mmol), Zn(OTf)2 (20.0 μmol), pyridine (0.400
mmol), EtCN (0.40 mL), 80 °C, and 36 h, and was isolated by
recycling GPC after column chromatography on silica gel (hexane/
1
EtOAc = 80/1). White solid, mp 106−107 °C. H NMR (400 MHz,
CDCl3) δ 1.04 (s, 3H), 6.54 (d, J = 3.0 Hz, 1H), 6.93 (dd, J = 8.7, 2.1
Hz, 1H), 6.96−7.03 (m, 2H), 7.36−7.43 (m, 4H), 7.45−7.54 (m, 6H),
7.59 (d, J = 2.1 Hz, 1H). 13C{1H} NMR (100 MHz, CDCl3) δ −2.6,
104.8, 114.7, 120.1, 121.8, 125.9, 128.4, 130.7, 132.8, 132.9, 134.8,
138.9 (one carbon signal is missing due to overlapping). HRMS (FD)
calcd for C21H18ClNSi M+, 347.0892. Found m/z 347.0897. Anal.
Calcd for C21H18NSi: C, 72.50; H, 5.22; N, 4.03. Found: C, 72.34; H,
5.12; N, 3.99.
Zinc-Catalyzed Dehydrogenative N-Silylation of Pyrroles
with Methyldiphenylsilane (Scheme 1). Synthesis of 3pa and 3qa
was carried out in a manner similar to the general procedure described
in the section above (“Zinc-Catalyzed Dehydrogenative N-Silylation of
Indoles with Methyldiphenylsilane: A General Procedure for Table
2”). As shown below, products 3pa and 3qa were fully characterized by
1H and 13C{1H} NMR spectroscopy and HRMS.
3-Heptyl-1-methyldiphenylsilyl-1H-pyrrole (3pa). The title com-
pound was synthesized using reagents and conditions of 1p (0.400
mmol), 2a (0.480 mmol), Zn(OTf)2 (20.0 μmol), pyridine (0.400
mmol), EtCN (0.40 mL), 80 °C, and 15 h, and was obtained as a
mixture with 4% of the disiloxane derived from 2a, which was
determined by 1H NMR, after purification by column chromatography
on silica gel (hexane/EtOAc = 80/1) and recycling GPC. Accordingly,
the yield of 3pa in Table 2 was determined by subtracting a yield of
the disiloxane from a yield of the mixture. Colorless oil. 1H NMR (400
MHz, CDCl3) δ 0.87 (t, J = 7.0 Hz, 3H), 0.92 (s, 3H), 1.19−1.36 (m,
8H), 1.45−1.62 (m, 2H), 2.45 (t, J = 7.7 Hz, 2H), 6.19 (dd, J = 2.6, 1.5
Hz, 1H), 6.47−6.53 (m, 1H), 6.64 (t, J = 2.4 Hz, 1H), 7.35−7.41 (m,
4H), 7.42−7.50 (m, 6H). 13C{1H} NMR (100 MHz, CDCl3) δ −2.8,
14.1, 22.7, 27.0, 29.2, 29.5, 31.0, 31.9, 111.9, 121.4, 124.6, 127.8, 128.1,
130.4, 133.8, 134.8. HRMS (FD) calcd for C24H31NSi M+, 361.2220.
Found m/z 361.2203.
2-(4-Fluorophenyl)-1-methyldiphenylsilyl-1H-pyrrole (3qa). The
title compound was synthesized using reagents and conditions of 1q
(0.400 mmol), 2a (0.600 mmol), Zn(OTf)2 (20.0 μmol), pyridine
(0.400 mmol), EtCN (0.40 mL), 90 °C, and 24 h, and was isolated by
recycling GPC after column chromatography on silica gel (hexane/
EtOAc = 60/1). Pink solid, mp 77 °C. 1H NMR (500 MHz, CDCl3) δ
0.49 (s, 3H), 6.28 (d, J = 2.0 Hz, 2H), 6.63 (t, J = 2.3 Hz, 1H), 6.73−
6.80 (m, 2H), 6.99−7.05 (m, 2H), 7.33−7.38 (m, 4H), 7.38−7.46 (m,
6H). 13C{1H} NMR (125 MHz, CDCl3) δ −1.9, 110.3, 112.8, 114.4
2-(Benzofuran-2-yl)-1-methyldiphenylsilyl-1H-indole (3ia). The
title compound was synthesized using reagents and conditions of 1i
(0.400 mmol), 2a (0.600 mmol), Zn(OTf)2 (20.0 μmol), pyridine
(0.400 mmol), PrCN (0.40 mL), 120 °C, and 72 h, and was isolated
by recycling GPC after column chromatography on silica gel (hexane/
1
EtOAc = 40/1). White solid, mp 42−43 °C. H NMR (400 MHz,
J
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(d, J = 21.0 Hz), 127.6, 128.1, 130.3, 131.6 (d, J = 3.6 Hz), 131.8 (d, J
= 8.4 Hz), 134.65, 134.71, 138.6, 162.1 (d, J = 246.5 Hz). HRMS
(FD) calcd for C23H20FNSi M+, 357.1344. Found m/z 357.1340. Anal.
Calcd for C23H20FNSi: C, 77.27; H, 5.64; N, 3.92. Found: C, 77.25; H,
5.43; N, 3.90.
spectral and analytical data are in good agreement with those reported.
Accordingly, 13C{1H} NMR data were omitted here. White solid, mp
113−114 °C. 1H NMR (500 MHz, C6D6) δ 0.46 (s, 3H), 6.79 (tt, J =
7.2, 1.3 Hz, 2H), 6.95−7.05 (m, 8H), 7.12−7.18 (m, 6H), 7.66−7.75
(m, 4H). HRMS (FD) calcd for C25H23NSi M+, 365.1594. Found m/z
365.1605.
Zinc-Catalyzed Dehydrogenative N-Silylation of 10-
Bromobenzo[c]carbazole with Methyldiphenylsilane (Scheme
2). Synthesis of 3ra was carried out in a manner similar to the general
procedure described in the section above (“Zinc-Catalyzed Dehydro-
genative N-Silylation of Indoles with Methyldiphenylsilane: A General
Procedure for Table 2”). As shown below, product 3ra was fully
Zinc-Catalyzed H/D Exchange Reaction Between DSiMePh2
(2a-d) and HSiMe2Ph (2b) (Scheme 5). Zn(OTf)2 (7.27 mg, 20.0
μmol) was placed in a 20 mL Schlenk tube, which was heated at 80 °C
in vacuo for 15 min. The tube was cooled down to room temperature
and filled with argon. CD3CN (0.4 mL) that had been dried over MS 3
Å was added to the tube, and the mixture was then stirred at room
temperature for 3 min. To this were added DSiMePh2 (2a-d, 99%-d)
(39.9 mg, 0.200 mmol) and HSiMe2Ph (2b) (27.3 mg, 0.200 mmol).
The resulting mixture was stirred at 30 °C for 10 s or 12, 24, or 36 h,
and approximately 10 μL of the solution was then transferred through
a cannula into an NMR tube equipped with an adapter connected to a
dual vacuum/argon manifold. The solution in the NMR tube was
diluted with CD3CN (0.5 mL) dried over MS 3 Å and then analyzed
1
characterized by H and 13C{1H} NMR spectroscopy and HRMS.
10-Bromo-7-methyldiphenylsilyl-7H-benzo[c]carbazole (3ra).
The title compound was synthesized using reagents and conditions
of 1r (0.800 mmol), 2a (1.20 mmol), Zn(OTf)2 (40.0 μmol), pyridine
(0.800 mmol), PrCN (0.40 mL), 110 °C, and 48 h, and was isolated
by recrystallization from hexane/EtOAc after column chromatography
on silica gel (hexane/EtOAc = 40/1). White solid, mp 200−201 °C.
1H NMR (400 MHz, CDCl3) δ 1.21 (s, 3H), 6.91 (d, J = 8.9 Hz, 1H),
7.18−7.24 (m, 2H), 7.38−7.44 (m, 4H), 7.44−7.54 (m, 3H), 7.54−
7.61 (m, 5H), 7.70 (ddd, J = 8.4, 6.9, 1.3 Hz, 1H), 7.90 (dt, J = 8.2, 0.6
Hz, 1H), 8.67−8.77 (m, 2H). 13C{1H} NMR (100 MHz, CDCl3) δ
−0.9, 113.7, 115.4, 115.8, 117.8, 122.9, 123.6, 124.3, 126.4, 127.0,
127.1, 128.6, 128.9, 129.0, 129.1, 129.4, 130.8, 133.8, 134.9, 142.5,
143.1. HRMS (FD) calcd for C29H22BrNSi M+, 491.0699. Found m/z
491.0724. Anal. Calcd for C29H22NSi: C, 70.73; H, 4.50; N, 2.84.
Found: C, 70.38; H, 4.18; N, 2.81.
1
1
by H NMR. A part of each H NMR spectrum is collected in Figure
5, where the septet peak at 4.38 ppm corresponds to the hydrogen on
the SiMe2Ph group, and the quartet peak at 4.88 ppm corresponds to
the hydrogen on the SiMePh2 group.
Zinc-Catalyzed Dehydrogenative N-Silylation of Arylamines
with Methyldiphenylsilane (Scheme 3). Unless otherwise noted,
synthesis of 3sa−3ua was carried out in a manner similar to the
general procedure described in the section above (“Zinc-Catalyzed
Dehydrogenative N-Silylation of Indoles with Methyldiphenylsilane: A
General Procedure for Table 2”).
N-Methyldiphenylsilylaniline (3sa). The title compound was
synthesized using reagents and conditions of 1s (0.400 mmol), 2a
(0.600 mmol), Zn(OTf)2 (20.0 μmol), pyridine (0.400 mmol), EtCN
(0.40 mL), 80 °C, and 15 h. The following workup procedure was
conducted after stirring at 80 °C for 15 h. A mixture of Et2O/Et3N
(10/1, 10 mL) was added to the reaction mixture, and the resulting
solution was filtered through a pad of Celite, which was then washed
with a mixture of Et2O/Et3N (10/1). Evaporation of the solvent and
filtration through 1 cm of alumina covered with Celite (benzene/
EtOAc = 10/1), and then evaporation of the solvent followed by
recrystallization from pentane/EtOAc at −20 °C provided 3sa.
Compound 3sa has already appeared in the literature,9a and its
spectral and analytical data are in good agreement with those reported.
Accordingly, 13C{1H} NMR data were omitted here. White solid, mp
76−77 °C. 1H NMR (400 MHz, C6D6) δ 0.65 (s, 3H), 3.51 (br s, 1H),
6.54−6.60 (m, 2H), 6.68 (tt, J = 7.3, 1.0 Hz, 1H), 6.94−7.02 (m, 2H),
7.11−7.22 (m, 6H), 7.54−7.64 (m, 4H). HRMS (FD) calcd for
C19H19NSi M+, 289.1281. Found m/z 289.1295. Anal. Calcd for
C19H19NSi: C, 78.84; H, 6.62; N, 4.84. Found: C, 78.89; H, 6.49; N,
4.83.
3,5-Bis(trifluoromethyl)-N-methyldiphenylsilylaniline (3ta). The
title compound was synthesized using reagents and conditions of 1t
(0.400 mmol), 2a (0.480 mmol), Zn(OTf)2 (20.0 μmol), pyridine
(0.400 mmol), PrCN (0.40 mL), 110 °C, and 48 h, and was isolated
by column chromatography on alumina (hexane/EtOAc = 8/1).
Compound 3ta has already appeared in the literature,9a and its spectral
and analytical data are in good agreement with those reported.
Accordingly, 13C{1H} NMR data were omitted here. Pale yellow oil.
1H NMR (400 MHz, CDCl3) δ 0.82 (s, 3H), 4.20 (br s, 1H), 6.97 (s,
Figure 5. 1H NMR spectra after (a) 10 s, (b) 12 h, (c) 24 h, and (d)
36 h of mixing at 30 °C.
Trapping Experiment of a Hydrogen Gas (Scheme 6): A
Procedure for Synthesis of 1,2-Diphenylethane (7). A two-
chamber glass equipment was used for this experiment. First,
Zn(OTf)2 (29.0 mg, 80.0 μmol) was placed in one chamber, which
is referred to as Chamber A, and the glassware was heated at 150 °C in
vacuo for 2 h. The glassware was cooled down to room temperature
and filled with argon. The other chamber, which is referred to as
Chamber B, was charged with 10% Pd/C (4.26 mg, 4.00 μmol), trans-
stilbene (6) (72.1 mg, 0.400 mmol) and EtCN (0.40 mL). To
Chamber A were then added, in order, EtCN (1.0 mL), 1a (187 mg,
1.60 mmol), pyridine (127 mg, 1.60 mmol), and 2a (377 mg, 1.90
mmol). After stirring at 80 °C for 15 h, the resulting solution was
treated separately for subsequent workup. Regarding the solution in
the Chamber A, a saturated NaHCO3 aqueous solution (1 mL) was
added, and the aqueous phase was extracted with EtOAc (10 mL × 3).
The combined organic layer was washed with brine (2 mL) and then
dried over anhydrous Na2SO4. Filtration through a pad of Celite and
evaporation of the solvent followed by column chromatography on
silica gel (hexane/EtOAc = 80/1) provided 3aa in 98% yield (493
mg). Compound 3aa has already appeared in the preceding
communication.6 Its spectral and analytical data are thus collected
there. With respect to the solution in the Chamber B, its filtration
through a pad of Celite and evaporation of the solvent provided 1,2-
diphenylethane (7) in 98% yield (71.9 mg) as a pure form.
(CAUTION: The Celite pad should not be dried up after the
2H), 7.15 (s, 1H), 7.36−7.49 (m, 6H), 7.56−7.65 (m, 4H). HRMS
(FD) calcd for C21H17F6NSi M+, 425.1029. Found m/z 425.1032.
N,N-Diphenyl-N-methyldiphenylsilylamine (3ua). The title com-
pound was synthesized using reagents and conditions of 1u (0.400
mmol), 2a (0.480 mmol), Zn(OTf)2 (20.0 μmol), pyridine (0.400
mmol), PrCN (0.40 mL), 110 °C, and 48 h, and was isolated by
column chromatography on silica gel (hexane/Et2O/Et3N = 45/5/2).
Compound 3ua has already appeared in the literature,9a and its
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filtration due to possible ignition of the activated Pd/C.) 1,2-
Diphenylethane is commercially available, and spectral and analytical
data of 7 are in good agreement with those obtained from the
1
commercial 1,2-diphenylethane. Accordingly, only H NMR data are
provided here. 1H NMR (400 MHz, CDCl3) δ 2.92 (s, 4H), 7.14−7.23
(m, 6H), 7.25−7.32 (m, 4H).
Synthesis of 2,3-Dimethyl-1H-indole-1-d (1b-d). Compound
1b-d used for the kinetic isotope effect experiments was synthesized
according to the modified literature procedure.9a Under an argon
atmosphere, a flame-dried 20 mL Schlenk tube was charged with 2,3-
dimethylindole (325 mg, 2.24 mmol) and CH3OD (1.00 mL, 24.7
mmol), and the resulting solution was stirred at room temperature for
1 h. The solvent was evaporated, and the process was repeated a
further three times. After removal of the solvent under reduced
pressure, 2,3-dimethylindole-1-d (1b-d) was isolated by sublimation
(90 °C/1.0 kPa) in 87% yield (286 mg) with a deuterium content of
1
97 or 95%, as determined by H or 13C{1H} NMR, respectively. On
Figure 7. Plots of the yield of 3ba against the reaction time for the
dehydrogenative N-silylation of 1b or 1b-d with 2a.
the basis of these values, the deuterium content of 1b-d was considered
to be >95%. Compound 1b-d as a white solid (mp 101−102 °C) was
fully characterized by 1H and 13C{1H} NMR spectroscopy and HRMS,
as follows: 1H NMR (400 MHz, C6D6) δ 1.83 (d, J = 0.7 Hz, 3H), 2.13
(d, J = 0.7 Hz, 3H), 7.00−7.10 (m, 1H), 7.19−7.28 (m, 2H), 7.52−
7.61 (m, 1H). 13C{1H} NMR (100 MHz, C6D6) δ 8.5, 11.1, 106.9,
110.3, 118.4, 119.4, 121.2, 130.0, 130.1, 135.6. HRMS (FD) calcd for
C10H10DN M+, 146.0949. Found m/z 146.0952.
Kinetic Isotope Effect Experiments (Scheme 7). The reactions
shown in Scheme 7 were carried out in the same way as described in
the section above (“Zinc-Catalyzed Dehydrogenative N-Silylation of
Indoles with Methyldiphenylsilane: A General Procedure for Table
2”). The N-silylation of 2,3-dimethylindole (1b) or 2,3-dimethylin-
dole-1-d (1b-d) with HSiMePh2 (2a) or DSiMePh2 (2a-d) was thus
performed using reagents and conditions of 1b or 1b-d (1b was
sublimated at 90 °C/1.0 kPa prior to use; 0.400 mmol), 2a or 2a-d
(0.480 mmol), Zn(OTf)2 (20.0 μmol), pyridine (0.400 mmol), EtCN
(0.40 mL), 80 °C, and 1−6 h, and the yields of product 3ba after 1, 2,
3, 4, 5, and 6 h were determined by GC using n-decane as an internal
standard. Compound 3ba has already emerged herein, and its spectral
and analytical data are thus collected above (“2,3-Dimethyl-1-
methyldiphenylsilyl-1H-indole (3ba)”). The reaction rate was obtained
by plotting the yield of 3ba against the reaction time. Figure 6
Catalyzed Dehydrogenative N-Silylation of Indoles with Methyldiphe-
nylsilane: A General Procedure for Table 2”).
Figure 3a. The N-silylation of 2,3-dimethylindole (1b) with
HSiMePh2 (2a) was performed using reagents and conditions of 1b
(0.0800, 0.160, 0.240, 0.320, and 0.400 mmol), 2a (0.480 mmol),
Zn(OTf)2 (40.0 μmol), pyridine (0.400 mmol), EtCN (0.40 mL), 80
°C, and 10−60 min, and the concentrations of product 3ba after 10,
20, 30, 40, 50, and 60 min were estimated for each reaction depending
on the amount of 1b used and based on yields of 3ba determined by
GC using n-decane as an internal standard. Compound 3ba has already
emerged herein, and its spectral and analytical data are thus collected
above (“2,3-Dimethyl-1-methyldiphenylsilyl-1H-indole (3ba)”). The
reaction rates at the initial stage (10−60 min) of the each reaction
were obtained by plotting the concentration of 3ba against the
reaction time (see the Supporting Information). The initial rates
obtained were then plotted with respect to the concentration of 1b as
shown in Figure 3a-1.
Figure 3b. The N-silylation of 2,3-dimethylindole (1b) with
HSiMePh2 (2a) was performed using reagents and conditions of 1b
(0.400 mmol), 2a (0.0500, 0.100, 0.160, 0.200, 0.300, 0.400, and 0.480
mmol), Zn(OTf)2 (40.0 μmol), pyridine (0.400 mmol), EtCN (0.40
mL), 80 °C, and 10−60 min, and the concentrations of product 3ba
after 10, 20, 30, 40, 50, and 60 min were estimated for each reaction
depending on the amount of 2a used and based on yields of 3ba
determined by GC using n-decane as an internal standard. Compound
3ba has already emerged herein, and its spectral and analytical data are
thus collected above (“2,3-Dimethyl-1-methyldiphenylsilyl-1H-indole
(3ba)”). The reaction rates at the initial stage (10−60 min) of the each
reaction were obtained by plotting the concentration of 3ba against
the reaction time (see the Supporting Information). The initial rates
obtained were then plotted with respect to the concentration of 2a as
shown in Figure 3b-1.
Figure 3c. The N-silylation of 2,3-dimethylindole (1b) with
HSiMePh2 (2a) was performed using reagents and conditions of 1b
(0.400 mmol), 2a (0.480 mmol), Zn(OTf)2 (8.00, 12.0, 16.0, 24.0,
32.0, and 40.0 μmol), pyridine (0.400 mmol), EtCN (0.40 mL), 80 °C,
and 10−60 min, and the concentrations of product 3ba after 10, 20,
30, 40, 50, and 60 min were estimated for each reaction depending on
the amount of Zn(OTf)2 used and based on yields of 3ba determined
by GC using n-decane as an internal standard. Compound 3ba has
already emerged herein, and its spectral and analytical data are thus
collected above (“2,3-Dimethyl-1-methyldiphenylsilyl-1H-indole
(3ba)”). The reaction rates at the initial stage (10−60 min) of the
each reaction were obtained by plotting the concentration of 3ba
against the reaction time (see the Supporting Information). The initial
rates obtained were then plotted with respect to the concentration of
Zn(OTf)2 as shown in Figure 3c-1.
Figure 6. Plots of the yield of 3ba against the reaction time for the
dehydrogenative N-silylation of 1b with 2a or 2a-d.
indicates the result for the reaction of 1b with 2a or 2a-d. The slope
value of each line in Figure 6 is 6.5 or 6.4, respectively, thus showing
that the value of the kH/kD is approximately 1.0 (= 6.5/6.4). Figure 7
shows the result for the reaction of 1b or 1b-d with 2a. The slope value
of each line in Figure 7 is 6.5 or 3.0, respectively, thus showing that the
value of the kH/kD is approximately 2.2 (= 6.5/3.0).
Kinetic Studies for the Dehydrogenative N-Silylation of
Indoles (Figure 3). Reactions to obtain Figure 3a-1,b-1,c-1,d-1 were
carried out in the same way as described in the section above (“Zinc-
Figure 3d. The N-silylation of 2,3-dimethylindole (1b) with
HSiMePh2 (2a) was performed using reagents and conditions of 1b
(0.400 mmol), 2a (0.480 mmol), Zn(OTf)2 (40.0 μmol), pyridine
(0.0200, 0.0400, 0.0800, 0.160, 0.240, 0.320, 0.400, and 0.800 mmol),
L
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EtCN (0.40 mL), 80 °C, and 10−60 min, and the concentrations of
product 3ba after 10, 20, 30, 40, 50, and 60 min were estimated for
each reaction depending on the amount of pyridine used and based on
yields of 3ba determined by GC using n-decane as an internal
standard. Compound 3ba has already emerged herein, and its spectral
and analytical data are thus collected above (“2,3-Dimethyl-1-
methyldiphenylsilyl-1H-indole (3ba)”). The reaction rates at the
initial stage (10−60 min) of the each reaction were obtained by
plotting the concentration of 3ba against the reaction time (see the
Supporting Information). The initial rates obtained were then plotted
with respect to the concentration of pyridine as shown in Figure 3d-1.
Zinc-Catalyzed Dehydrogenative C-Silylation of Indoles and
Other Heteroarenes with Hydrosilanes: A General Procedure
for Table 5. Zn(NTf2)2 (12.5 mg, 20.0 μmol) or Zn(OTf)2 (7.27 mg,
20.0 μmol) was placed in a 20 mL Schlenk tube, which was heated at
80 °C in vacuo for 15 min. The tube was cooled down to room
temperature and filled with argon. PrCN (0.40 mL) was added to the
tube, and the mixture was then stirred at room temperature for 3 min.
To this were added 14 (0.400 or 1.20 mmol), 2 (0.400 or 0.600
mmol), and an organic base (0.400 or 0.800 mmol), and the resulting
mixture was stirred at 130 °C. After the time specified in Table 5, a
saturated NaHCO3 aqueous solution (0.5 mL) was added to the
mixture, and the aqueous phase was extracted with EtOAc (5 mL × 3).
The combined organic layer was washed with brine (1 mL) and then
dried over anhydrous Na2SO4. Filtration and evaporation of the
solvent followed by purification gave product 15. Unless otherwise
(s, 3H), 3.68 (s, 3H), 6.87−6.92 (m, 1H), 7.08−7.15 (m, 2H), 7.28−
7.42 (m, 7H), 7.54−7.60 (m, 4H). 13C{1H} NMR (100 MHz, CDCl3)
δ −1.01, 13.5, 29.6, 100.3, 108.7, 119.3, 120.5, 121.5, 127.8, 129.1,
133.2, 135.2, 138.1, 138.3, 144.8. HRMS (FD) calcd for C23H23NSi
M+, 341.1594. Found m/z 341.1611.
1,1′-Dimethyl-3-methyldiphenylsilyl-1H,1′H-2,3′-biindole (15ea).
The title compound was synthesized using reagents and conditions of
14e (0.400 mmol), 2a (0.600 mmol), Zn(NTf2)2 (20.0 μmol), γ-
picoline (0.800 mmol), PrCN (0.40 mL), 130 °C, and 45 h, and was
isolated by recycling GPC after column chromatography on silica gel
(hexane/Et3N/EtOAc = 20/4/1). Pale yellow solid, mp 237−239 °C.
1H NMR (400 MHz, CDCl3) δ 0.46 (s, 3H), 3.51 (s, 3H), 3.57 (s,
3H), 6.45 (s, 1H), 6.93−7.01 (m, 1H), 7.04−7.13 (m, 3H), 7.16−7.25
(m, 6H), 7.26−7.41 (m, 6H), 7.41−7.48 (m, 2H). 13C{1H} NMR
(100 MHz, CDCl3) δ −1.8, 30.7, 32.5, 104.6, 106.9, 109.2, 109.3,
119.4, 119.85, 119.93, 121.1, 121.7, 122.1, 127.1, 127.4, 128.3, 128.6,
128.6, 130.8, 133.5, 134.8, 135.1, 136.3, 138.3, 138.5, 138.8, 142.9.
HRMS (FD) calcd for C31H28N2Si M+, 456.2016. Found m/z
456.2029.
1-Benzyl-3-methyldiphenylsilyl-1H-indole (15fa). The title com-
pound was synthesized using reagents and conditions of 14f (0.400
mmol), 2a (0.600 mmol), Zn(NTf2)2 (20.0 μmol), γ-picoline (0.400
mmol), PrCN (0.40 mL), 130 °C, and 36 h, and was isolated by
column chromatography on silica gel (hexane/Et3N/EtOAc = 160/8/
1). White solid, mp 107−108 °C. 1H NMR (400 MHz, CDCl3) δ 0.87
(s, 3H), 5.32 (s, 2H), 6.98−7.05 (m, 1H), 7.06−7.12 (m, 3H), 7.15
(td, J = 7.7, 1.1 Hz, 1H), 7.22−7.41 (m, 10H), 7.44 (d, J = 8.2 Hz,
1H), 7.55−7.62 (m, 4H). 13C{1H} NMR (100 MHz, CDCl3) δ −2.3,
50.2, 105.8, 110.0, 119.8, 121.8, 122.5, 126.6, 127.6, 127.8, 128.8,
129.2, 133.4, 135.1, 137.25, 137.28, 137.5, 138.2. HRMS (FD) calcd
for C28H25NSi M+, 403.1751. Found m/z 403.1764. Anal. Calcd for
C28H25NSi: C, 83.33; H, 6.24; N, 3.47. Found: C, 83.07; H, 5.84; N,
3.50.
1-Methyl-3-dimethylphenylsilyl-1H-indole (15ab). The title com-
pound was synthesized using reagents and conditions of 14a (0.400
mmol), 2b (0.600 mmol), Zn(NTf2)2 (20.0 μmol), γ-picoline (0.800
mmol), PrCN (0.40 mL), 130 °C, and 24 h, and was isolated by
column chromatography on silica gel (hexane/Et3N = 20/1).
Compound 15ab has already appeared in the literature,5,9b and its
spectral and analytical data are in good agreement with those reported.
Therefore, only 1H NMR data are provided here. 1H NMR (400 MHz,
CDCl3) δ 0.60 (s, 6H), 3.78 (s, 3H), 7.02 (s, 1H), 7.04−7.10 (m, 1H),
7.19−7.26 (m, 1H), 7.29−7.38 (m, 4H), 7.54−7.63 (m, 3H).
3-Benzyldimethylsilyl-1-methyl-1H-indole (15ac). The title com-
pound was synthesized using reagents and conditions of 14a (0.400
mmol), 2c (0.600 mmol), Zn(NTf2)2 (20.0 μmol), γ-picoline (0.800
mmol), PrCN (0.40 mL), 130 °C, and 24 h, and was isolated by
recycling GPC after column chromatography on silica gel (hexane/
Et3N/EtOAc = 80/4/1). Colorless oil. 1H NMR (400 MHz, CDCl3) δ
0.30 (s, 6H), 2.40 (s, 2H), 3.78 (s, 3H), 6.95−7.00 (m, 3H), 7.05 (tt, J
= 7.3, 1.5 Hz, 1H), 7.11 (ddd, J = 7.9, 7.0, 1.0 Hz, 1H), 7.16 (tt, J =
7.4, 1.7 Hz, 2H), 7.22−7.27 (m, 1H), 7.34 (dt, J = 8.2, 0.9 Hz, 1H),
7.59 (dt, J = 7.9, 0.9 Hz, 1H). 13C{1H} NMR (100 MHz, CDCl3) δ
−2.4, 26.9, 32.8, 107.2, 109.4, 119.3, 121.5, 121.9, 123.9, 128.0, 128.3,
132.7, 135.7, 138.4, 140.2. HRMS (FD) calcd for C18H21NSi M+,
279.1438. Found m/z 279.1426. Anal. Calcd for C18H21NSi: C, 77.36;
H, 7.57; N, 5.01. Found: C, 77.47; H, 7.32; N, 5.16.
1-Hexyl-3-methyldiphenylsilyl-1H-pyrrole (β-15ga). The title
compound was synthesized using reagents and conditions of 14g
(0.400 mmol), 2a (0.600 mmol), Zn(NTf2)2 (20.0 μmol), γ-picoline
(0.400 mmol), PrCN (0.40 mL), 130 °C, and 24 h, and was isolated
by recycling GPC after column chromatography on silica gel (hexane/
Et3N/EtOAc = 160/8/1). Colorless oil. 1H NMR (400 MHz, CDCl3)
δ 0.73 (s, 3H), 0.85−0.90 (m, 3H), 1.20−1.35 (m, 6H), 1.75 (quint, J
= 7.2 Hz, 2H), 3.85 (t, J = 7.3 Hz, 2H), 6.26 (dd, J = 2.3, 1.4 Hz, 1H),
6.65 (t, J = 1.8 Hz, 1H), 6.77 (t, J = 2.3 Hz, 1H), 7.29−7.39 (m, 6H),
7.53−7.58 (m, 4H). 13C{1H} NMR (100 MHz, CDCl3) δ −2.4, 14.0,
22.5, 26.4, 31.3, 31.5, 49.5, 112.4, 114.5, 122.1, 127.6, 128.7, 128.9,
135.0, 138.2. HRMS (FD) calcd for C23H29NSi M+, 347.2064. Found
m/z 347.2075. MS (GC−MS, EI) calcd for C23H29NSi M+, 347.
1
noted, products 15 synthesized here were fully characterized by H
and 13C{1H} NMR spectroscopy and HRMS and/or MS.
1-Methyl-3-methyldiphenylsilyl-1H-indole (15aa). The title com-
pound was synthesized using reagents and conditions of 14a (0.400
mmol), 2a (0.600 mmol), Zn(NTf2)2 (20.0 μmol), γ-picoline (0.400
mmol), PrCN (0.40 mL), 130 °C, and 24 h, and was isolated by
column chromatography on silica gel (hexane/Et3N/EtOAc = 160/4/
1). Compound 15aa has already appeared in the literature,5,9b and its
spectral and analytical data are in good agreement with those reported.
In the case of 15aa, data of 1H NMR and elemental analysis are
1
provided here. H NMR (500 MHz, CDCl3) δ 0.86 (s, 3H), 3.77 (s,
3H), 6.95 (s, 1H), 7.03 (t, J = 7.4 Hz, 1H), 7.23 (t, J = 7.7 Hz, 1H),
7.31−7.44 (m, 7H), 7.43 (d, J = 8.0 Hz, 1H), 7.58 (dd, J = 8.0, 1.1 Hz,
4H). Anal. Calcd for C22H21NSi: C, 80.68; H, 6.46; N, 4.28. Found: C,
80.37; H, 6.36; N, 4.20.
5-Methoxy-1-methyl-3-methyldiphenylsilyl-1H-indole (15ba).
The title compound was synthesized using reagents and conditions
of 14b (0.400 mmol), 2a (0.600 mmol), Zn(NTf2)2 (20.0 μmol), γ-
picoline (0.400 mmol), PrCN (0.40 mL), 130 °C, and 24 h, and was
isolated by column chromatography on silica gel (hexane/Et3N/
1
EtOAc = 160/8/1). White solid, mp 121−122 °C. H NMR (400
MHz, CDCl3) δ 0.85 (s, 3H), 3.62 (s, 3H), 3.74 (s, 3H), 6.80 (d, J =
2.3 Hz, 1H), 6.87 (dd, J = 8.7, 2.3 Hz, 1H), 6.94 (s, 1H), 7.22 (d, J =
9.2 Hz, 1H), 7.30−7.41 (m, 6H), 7.55−7.63 (m, 4H). 13C{1H} NMR
(100 MHz, CDCl3) δ −2.4, 33.0, 55.7, 104.2, 104.5, 109.9, 111.6,
127.8, 129.1, 133.7, 133.9, 135.1, 137.4, 138.2, 154.0. HRMS (FD)
calcd for C23H23NOSi M+, 357.1543. Found m/z 357.1549.
5-Bromo-1-methyl-3-methyldiphenylsilyl-1H-indole (15ca). The
title compound was synthesized using reagents and conditions of 14c
(0.400 mmol), 2a (0.600 mmol), Zn(NTf2)2 (20.0 μmol), γ-picoline
(0.400 mmol), PrCN (0.40 mL), 130 °C, and 36 h, and was isolated
by column chromatography on silica gel (hexane/Et3N/EtOAc = 160/
1
8/1). White solid, mp 159−160 °C. H NMR (400 MHz, CDCl3) δ
0.86 (s, 3H), 3.75 (s, 3H), 6.91 (s, 1H), 7.21 (d, J = 8.7 Hz, 1H),
7.28−7.43 (m, 7H), 7.51 (d, J = 1.8 Hz, 1H), 7.53−7.60 (m, 4H).
13C{1H} NMR (100 MHz, CDCl3) δ −2.4, 33.0, 105.0, 110.8, 113.1,
124.57, 124.62, 127.9, 129.3, 134.8, 135.0, 136.8, 137.4, 138.9. HRMS
(FD) calcd for C22H20BrNSi M+, 405.0543. Found m/z 405.0546.
1,2-Dimethyl-3-methyldiphenylsilyl-1H-indole (15da). The title
compound was synthesized using reagents and conditions of 14d
(0.400 mmol), 2a (0.600 mmol), Zn(OTf)2 (20.0 μmol), TMPDA
(0.400 mmol), PrCN (0.40 mL), 130 °C, and 24 h, and was isolated
by column chromatography on silica gel (hexane/Et3N/EtOAc = 160/
8/1). Colorless oil. 1H NMR (400 MHz, CDCl3) δ 0.92 (s, 3H), 2.14
M
DOI: 10.1021/acs.organomet.7b00382
Organometallics XXXX, XXX, XXX−XXX

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Article
Found m/z (relative intensity) 347 (47) [M]+, 332 (100), 197 (34),
150 (38), 105 (27), 55 (13).
following reagents and conditions: 14a (distillated by Kugelrohr at 100
°C/40.0 Pa prior to use) or 14a-d (0.400 mmol), 2a or 2a-d (0.600
mmol), Zn(NTf2)2 (40.0 μmol), γ-picoline (0.400 mmol), BuCN
(0.40 mL), 115 °C, and 0.5−3 h. The yields of product 15aa after 0.5,
1-Hexyl-2-methyldiphenylsilyl-1H-pyrrole (α-15ga). The title
compound could not be obtained as a pure form even after
purification by silica gel column chromatography and recycling GPC.
Accordingly, the formation of α-15ga was confirmed by comparison of
its MS data with that of the β-isomer (β-15ga) presented above, in
which the two MS data quite resemble each other. MS (GC−MS, EI)
calcd for C23H29NSi M+, 347. Found m/z (relative intensity) 347 (6)
[M]+, 332 (3), 197 (28), 150 (100), 105 (12), 55 (5).
1
1, 1.5, 2, 2.5, and 3 h were determined by H NMR using MeNO2 as
an external standard. Compound 15aa has already emerged herein,
and its spectral and analytical data are thus collected there (“1-Methyl-
3-methyldiphenylsilyl-1H-indole (15aa)”). The reaction rate was
obtained by plotting the yield of 15aa against the reaction time.
Figure 8 indicates the result for the reaction of 14a with 2a or 2a-d.
2-Methoxy-5-methyldiphenylsilylthiophene (15ha). The title
compound was synthesized using reagents and conditions of 14h
(1.20 mmol), 2a (0.400 mmol), Zn(NTf2)2 (20.0 μmol), γ-picoline
(0.400 mmol), PrCN (0.40 mL), 130 °C, and 24 h, and was isolated
by Kugelrohr bulb-to-bulb distillation (140 °C/200 Pa). White solid,
1
mp 57−58 °C. H NMR (400 MHz, CDCl3) δ 0.81 (s, 3H), 3.89 (s,
3H), 6.30 (d, J = 3.7 Hz, 1H), 6.89 (d, J = 3.7 Hz, 1H), 7.25−7.44 (m,
6H), 7.49−7.60 (m, 4H). 13C{1H} NMR (100 MHz, CDCl3) δ −2.5,
60.4, 105.9, 120.5, 127.8, 129.6, 135.0, 135.6, 136.0, 172.8. HRMS
(FD) calcd for C18H18OSSi M+, 310.0842. Found m/z 310.0839.
Zinc-Catalyzed Dehydrogenative C-Silylation of 1-Alkylin-
doles with Diphenylsilane (H2SiPh2) (Scheme 9). Syntheses of
15ad and 15id were carried out in a manner similar to the general
procedure described in the section above (“Zinc-Catalyzed Dehydro-
genative C-Silylation of Indoles and Other Heteroarenes with
Hydrosilanes: A General Procedure for Table 5”). As shown below,
1
products 15ad and 15id were fully characterized by H and 13C{1H}
NMR spectroscopy, and HRMS.
Figure 8. Plots of the yield of 15aa against the reaction time for the
dehydrogenative C-silylation of 14a with 2a or 2a-d.
Bis(1-methyl-1H-indol-3-yl)diphenylsilane (15ad). The title com-
pound was synthesized using reagents and conditions of 14a (1.60
mmol), 2d (0.400 mmol), Zn(NTf2)2 (20.0 μmol), γ-picoline (0.400
mmol), PrCN (0.40 mL), 130 °C, and 24 h, and was isolated by
column chromatography on silica gel (hexane/Et3N/EtOAc = 160/8/
1) followed by decantation (hexane and/or hexane/Et2O). White
solid, mp 246 °C. 1H NMR (400 MHz, CDCl3) δ 3.75 (s, 6H), 6.95−
7.03 (m, 4H), 7.19−7.25 (m, 2H), 7.28−7.44 (m, 10H), 7.66−7.73
(m, 4H). 13C{1H} NMR (100 MHz, CDCl3) δ 32.9, 104.6, 109.3,
119.5, 121.5, 123.0, 127.7, 129.1, 133.4, 135.9, 136.7, 138.7, 138.9.
HRMS (FD) calcd for C30H26N2Si M+, 442.1860. Found m/z
442.1836.
The slope value of each line in Figure 8 is 6.0 or 5.6, respectively, thus
showing that the value of the kH/kD is approximately 1.1 (= 6.0/5.6).
Figure 9 shows the result for the reaction of 14a or 14a-d with 2a. The
Bis(1-hexyl-1H-indol-3-yl)diphenylsilane (15id). The title com-
pound was synthesized using reagents and conditions of 14i (1.60
mmol), 2d (0.400 mmol), Zn(NTf2)2 (20.0 μmol), γ-picoline (0.400
mmol), PrCN (0.40 mL), 130 °C, and 42 h, and was isolated by
column chromatography on silica gel (hexane/Et3N/EtOAc = 160/8/
1). Yellow oil. 1H NMR (400 MHz, CDCl3) δ 0.84 (t, J = 6.6 Hz, 6H),
1.20−1.33 (m, 12H), 1.79 (quint, J = 7.1 Hz, 4H), 4.06 (t, J = 7.3 Hz,
4H), 6.96 (ddd, J = 7.8, 6.9, 0.9 Hz, 2H), 7.06 (s, 2H), 7.19 (ddd, J =
8.0, 7.1, 0.9 Hz, 2H), 7.27−7.45 (m, 10H), 7.70 (dt, J = 6.3, 1.5 Hz,
4H). 13C{1H} NMR (100 MHz, CDCl3) δ 14.0, 22.5, 26.6, 30.0, 31.3,
46.5, 104.3, 109.5, 119.3, 121.2, 123.1, 127.7, 129.0, 133.6, 135.9,
136.9, 138.0, 138.1. HRMS (FD) calcd for C40H46N2Si M+, 582.3430.
Found m/z 582.3415.
Figure 9. Plots of the yield of 15aa against the reaction time for the
dehydrogenative C-silylation of 14a or 14a-d with 2a.
Synthesis of 1-Methyl-1H-indole-3-d (14a-d). Compound 14a-
d used for the kinetic isotope effect experiments was synthesized
according to the literature procedure48 and isolated by Kugelrohr bulb-
to-bulb distillation (100 °C/40.0 Pa) in 66% yield with a deuterium
content of 95%, as determined by 1H and 13C{1H} NMR. Compound
slope value of each line in Figure 9 is 6.0 or 2.5, respectively, thus
showing that the value of the kH/kD for the reaction of 14a or 14a-d
with 2a is approximately 2.4 (= 6.0/2.5).
1
14a-d as a colorless oil was fully characterized by H and 13C{1H}
NMR spectroscopy and HRMS, as follows: 1H NMR (400 MHz,
CDCl3) δ 3.79 (s, 3H), 7.05 (s, 1H), 7.11 (ddd, J = 8.0, 6.9, 0.9 Hz,
1H), 7.22 (ddd, J = 8.2, 7.0, 1.0 Hz, 1H), 7.33 (d, J = 8.2 Hz, 1H), 7.63
(dt, J = 7.9, 0.9 Hz, 1H). 13C{1H} NMR (100 MHz, CDCl3) δ 32.8,
100.7 (t, J = 26.4 Hz), 109.2, 119.2, 120.8, 121.4, 128.3, 128.7, 136.6.
HRMS (FD) calcd for C9H8DN M+, 132.0792. Found m/z 132.0794.
Kinetic Isotope Effect Experiments (Scheme 10). Other than
being performed at 115 °C in BuCN, the reactions shown in Scheme
10 were carried out in the same way as those in Table 5. The C-
silylation of 1-methylindole (14a) or 1-methylindole-3-d (14a-d) with
HSiMePh2 (2a) or DSiMePh2 (2a-d) was thus performed using the
ASSOCIATED CONTENT
■
S
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.organo-
met.7b00382.
1H and 13C{1H} NMR spectra, and plots of the initial
rate data for Figure 3 (PDF)
N
DOI: 10.1021/acs.organomet.7b00382
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
T.; Hiyama, T. Chem. Lett. 2015, 44, 1065−1067. (Ir, C-silylation).
(h) Hua, Y.; Jung, S.; Roh, J.; Jeon, J. J. Org. Chem. 2015, 80, 4661−
4671. (Ir, N-silylation; Rh, intramolecular C-silylation). (i) Lee, K.-s.;
Katsoulis, D.; Choi, J. ACS Catal. 2016, 6, 1493−1496. (Rh, C-
silylation). (j) Yin, Q.; Klare, H. F. T.; Oestreich, M. Angew. Chem., Int.
Ed. 2016, 55, 3204−3207. (Fe, C-silylation). (k) Chen, Q.-A.; Klare,
H. F. T.; Oestreich, M. J. Am. Chem. Soc. 2016, 138, 7868−7871.
AUTHOR INFORMATION
Corresponding Author
*E-mail: tsuchimo@meiji.ac.jp. Fax: (+81) 44-934-7228.
ORCID
Kyohei Yonekura: 0000-0002-5019-6166
Teruhisa Tsuchimoto: 0000-0002-3780-8439
Notes
■
{Brønsted acid: [H(OEt2)2]+[BArF ]− [ArF = C6H3-3,5-(CF3)2], C-
4
silylation}. (l) Omann, L.; Oestreich, M. Organometallics 2017, 36,
767−776. (Ru, C-silylation). See also the following reviews: (m) Xu,
Z.; Huang, W.-S.; Zhang, J.; Xu, L.-W. Synthesis 2015, 47, 3645−3668.
(n) Cheng, C.; Hartwig, J. F. Chem. Rev. 2015, 115, 8946−8975.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
(o) Bahr, S.; Oestreich, M. Angew. Chem., Int. Ed. 2017, 56, 52−59.
̈
Financial support by Grants-in-Aid for Scientific Research (No.
24550123 and 15K05505) from the Ministry of Education,
Culture, Sports, Science and Technology is gratefully acknowl-
edged. We greatly appreciate Prof. Dr. Go Hirai at Kyushu
University, Japan, and Prof. Dr. Mikiko Sodeoka at RIKEN,
Japan, for their helpful support in HRMS measurements.
(9) For B(C6F5)3-catalyzed sequential Si−N dehydrogenative
coupling/hydrogenation to give N-silylindolines, see (a) Greb, L.;
Tamke, S.; Paradies, J. Chem. Commun. 2014, 50, 2318−2320. In
contrast to ref 9a, just prior to submitting this manuscript, catalyst
B(C6F5)3 has been reported to be effective for the selective
dehydrogenative C-silylation of indoles: (b) Han, Y.; Zhang, S.; He,
J.; Zhang, Y. J. Am. Chem. Soc. 2017, 139, 7399−7407.
REFERENCES
(10) For B(C6F5)3-mediated stoichiometric Si−N dehydrogenative
coupling, but complicated by simple reduction of an indole ring, see
Curless, L. D.; Clark, E. R.; Dunsford, J. J.; Ingleson, M. J. Chem.
Commun. 2014, 50, 5270−5272.
(11) Dehydrogenative N-silylation of nitrogen-containing substrates
other than indoles has also been the focus of research. For selected
■
(1) For selected examples, see (a) Yang, C.-G.; Liu, G.; Jiang, B. J.
Org. Chem. 2002, 67, 9392−9396. (b) Smith, A. B., III; Cui, H. Org.
Lett. 2003, 5, 587−590. (c) Kim, M.; Vedejs, E. J. Org. Chem. 2004, 69,
7262−7265. (d) Giordano, L.; Vermeij, R. J.; Jares-Erijman, E. A.
Arkivoc 2005, 268−281. (e) Buszek, K. R.; Brown, N.; Luo, D. Org.
Lett. 2009, 11, 201−204. (f) Brown, D. A.; Mishra, M.; Zhang, S.;
Biswas, S.; Parrington, I.; Antonio, T.; Reith, M. E. A.; Dutta, A. K.
Bioorg. Med. Chem. 2009, 17, 3923−3933. (g) Poisson, J.; Wharf, I.;
Bohle, D. S.; Barsan, M. M.; Gu, Y.; Butler, I. S. J. Organomet. Chem.
2010, 695, 2557−2561. (h) Carter, D. S.; Cai, H.-Y.; Lee, E. K.; Iyer,
P. S.; Lucas, M. C.; Roetz, R.; Schoenfeld, R. C.; Weikert, R. J. Bioorg.
Med. Chem. Lett. 2010, 20, 3941−3945.
́
recent reports, see (a) Perez, M.; Caputo, C. B.; Dobrovetsky, R.;
Stephan, D. W. Proc. Natl. Acad. Sci. U. S. A. 2014, 111, 10917−10921.
(b) Li, Q.; Driess, M.; Hartwig, J. F. Angew. Chem., Int. Ed. 2014, 53,
8471−8474. (Ir). (c) Bellini, C.; Carpentier, J.-F.; Tobisch, S.; Sarazin,
Y. Angew. Chem., Int. Ed. 2015, 54, 7679−7683. (d) Anga, S.; Sarazin,
Y.; Carpentier, J.-F.; Panda, T. K. ChemCatChem 2016, 8, 1373−1378.
(12) Dehydrogenative C-silylation of carbon frameworks other than
indoles has also been the focus of research. For selected recent reports,
see (a) Choi, G.; Tsurugi, H.; Mashima, K. J. Am. Chem. Soc. 2013,
135, 13149−13161. (Ir). (b) Takada, K.; Hanataka, T.; Namikoshi,
T.; Watanabe, S.; Murata, M. Adv. Synth. Catal. 2015, 357, 2229−
2232. (Ru). (c) Zhang, Q.-W.; An, K.; Liu, L.-C.; Yue, Y.; He, W.
(2) For selected reports, see (a) Liang, Y.; Zhang, S.; Xi, Z. J. Am.
Chem. Soc. 2011, 133, 9204−9207. (b) Shimizu, M.; Mochida, K.;
Hiyama, T. J. Phys. Chem. C 2011, 115, 11265−11274.
(3) For selected reports of N-silylation, see (a) Amat, M.; Hadida, S.;
Sathyanarayana, S.; Bosch, J. J. Org. Chem. 1994, 59, 10−11.
(b) Frenzel, A.; Klingebiel, U.; Luttke, W.; Pieper, U. J. Organomet.
̈
Angew. Chem., Int. Ed. 2015, 54, 6918−6921. (Rh). (d) Wubbolt, S.;
̈
Chem. 1994, 476, 73−76. (c) Terada, M.; Yokoyama, S.; Sorimachi, K.;
Uraguchi, D. Adv. Synth. Catal. 2007, 349, 1863−1867. (d) Im, G.-Y.
J.; Bronner, S. M.; Goetz, A. E.; Paton, R. S.; Cheong, P. H.-Y.; Houk,
K. N.; Garg, N. K. J. Am. Chem. Soc. 2010, 132, 17933−17944.
(e) Wales, S. M.; Walker, M. M.; Johnson, J. S. Org. Lett. 2013, 15,
2558−2561 and ref 1. For C-silylation, see. (f) Saulnier, M. G.;
Gribble, G. W. J. Org. Chem. 1982, 47, 757−761.
Oestreich, M. Angew. Chem., Int. Ed. 2015, 54, 15876−15879. (Ru).
(e) Shibata, T.; Shizuno, T.; Sasaki, T. Chem. Commun. 2015, 51,
7802−7804. (Rh). (f) Leifert, D.; Studer, A. Org. Lett. 2015, 17, 386−
389. (g) Wakaki, T.; Kanai, M.; Kuninobu, Y. Org. Lett. 2015, 17,
1758−1761. (Ir). (h) Murai, M.; Takami, K.; Takeshima, H.; Takai, K.
Org. Lett. 2015, 17, 1798−1801. (Ir). (i) Ma, Y.; Wang, B.; Zhang, L.;
Hou, Z. J. Am. Chem. Soc. 2016, 138, 3663−3666. (j) Gu, J.; Cai, C.
Chem. Commun. 2016, 52, 10779−10782. (Cu). (k) Mitsudo, K.;
Tanaka, S.; Isobuchi, R.; Inada, T.; Mandai, H.; Korenaga, T.;
Wakamiya, A.; Murata, Y.; Suga, S. Org. Lett. 2017, 19, 2564−2567
(Rh)..
(4) Lu, B.; Falck, J. R. Angew. Chem., Int. Ed. 2008, 47, 7508−7510.
(5) Klare, H. F. T.; Oestreich, M.; Ito, J.-i.; Nishiyama, H.; Ohki, Y.;
Tatsumi, K. J. Am. Chem. Soc. 2011, 133, 3312−3315.
(6) Tsuchimoto, T.; Iketani, Y.; Sekine, M. Chem. - Eur. J. 2012, 18,
9500−9504.
(13) Pilarski and co-workers have reported C2-silylation of indoles in
the presence of a ruthenium catalyst, which also promotes competitive
and non-competitive N-silylation of a specific substrate, albeit in a
rather low yield: Devaraj, K.; Sollert, C.; Juds, C.; Gates, P. J.; Pilarski,
L. T. Chem. Commun. 2016, 52, 5868−5871.
(14) Ohki, Y.; Takikawa, Y.; Sadohara, H.; Kesenheimer, C.;
Engendahl, B.; Kapatina, E.; Tatsumi, K. Chem. - Asian J. 2008, 3,
1625−1635.
(15) The partial reduction of indoles to indolines reportedly occurs
as a general trend under acid catalysis. For example, see (a) Pigge, F.
C.; Fang, S.; Rath, N. P. J. Organomet. Chem. 1998, 559, 131−140.
(b) Yato, M.; Homma, K.; Ishida, A. Tetrahedron 2001, 57, 5353−
5359. (c) Tan, M.; Zhang, Y. Tetrahedron Lett. 2009, 50, 4912−4915.
(16) In addition to 3aa, other N-silylindoles and an N-silylpyrrole can
be practically synthesized on a preparative scale. For these results, see
ref 6.
(7) Prior to our study on the dehydrogenative N-silylation of indoles
(see ref 6), Hartwig and co-workers have reported that a ruthenium
catalyst couples indoles and H2SiEt2 to give N-(SiHEt2)indoles as
proposed synthetic intermediates, which are subsequently utilized for
Ir-catalyzed site-selective borylation in one-pot. However, there is no
indication that the N-silylindoles have been isolated to ascertain their
structures: Robbins, D. W.; Boebel, T. A.; Hartwig, J. F. J. Am. Chem.
Soc. 2010, 132, 4068−4069.
(8) (a) Itagaki, S.; Kamata, K.; Yamaguchi, K.; Mizuno, N. Chem.
Commun. 2012, 48, 9269−9271. (Rh, N-silylation). (b) Konigs, C. D.
̈
F.; Muller, M. F.; Aiguabella, N.; Klare, H. F. T.; Oestreich, M. Chem.
̈
Commun. 2013, 49, 1506−1508. (Ru, N-silylation). (c) Cheng, C.;
Hartwig, J. F. Science 2014, 343, 853−857. (Rh, C-silylation).
(d) Sunada, Y.; Soejima, H.; Nagashima, H. Organometallics 2014, 33,
5936−5939. (Fe, C-silylation). (e) Toutov, A. A.; Liu, W.-B.; Betz, K.
N.; Fedorov, A.; Stoltz, B. M.; Grubbs, R. H. Nature 2015, 518, 80−84.
(KOt-Bu, C-silylation). (f) Cheng, C.; Hartwig, J. F. J. Am. Chem. Soc.
2015, 137, 592−595. (Ir, C-silylation). (g) Minami, Y.; Komiyama,
(17) For pKa values of organic bases, see (a) Mohajer, D.;
Karimipour, G.; Bagherzadeh, M. New J. Chem. 2004, 28, 740−747.
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Article
(b) Oss, M.; Kruve, A.; Herodes, K.; Leito, I. Anal. Chem. 2010, 82,
2865−2872. (c) Zhang, S. J. Comput. Chem. 2012, 33, 2469−2482.
(18) For an example of the Lewis acid-catalyzed reduction of the
Bn−O bond with hydrosilanes, see Gevorgyan, V.; Rubin, M.; Benson,
S.; Liu, J.-X.; Yamamoto, Y. J. Org. Chem. 2000, 65, 6179−6186.
(19) For the reduction of the ester functional groups by hydrosilanes
under Lewis acid catalysis, see Sakai, N.; Usui, Y.; Moriya, T.; Ikeda,
R.; Konakahara, T. Eur. J. Org. Chem. 2012, 2012, 4603−4608.
(20) For the experimental results on the dehydrogenative silylation of
simple pyrrole and carbazole, see ref 6.
(21) For an example of forming an N-metal−indole from a mixture of
an indole, a Lewis acid and an organic base, see Guidotti, S.; Camurati,
I.; Focante, F.; Angellini, L.; Moscardi, G.; Resconi, L.; Leardini, R.;
Nanni, D.; Mercandelli, P.; Sironi, A.; Beringhelli, T.; Maggioni, D. J.
Org. Chem. 2003, 68, 5445−5465.
(22) For reports on preparing an N-zinc−indole, see (a) Powers, J.
C.; Meyer, W. P.; Parsons, T. G. J. Am. Chem. Soc. 1967, 89, 5812−
5820. (b) Abu-Safieh, K. A.; Khanfar, M. A.; El-Barghouthi, M. I.; Ali,
B. F. J. Chem. Crystallogr. 2014, 44, 330−336.
(23) Solutions of 1a, Zn(OTf)2 and pyridine were prepared in
CD3CN in the following ratios: 1:1:0, 1:1:1, 1:1:3, 2:1:2, and 2:1:3.
(24) We have previously reported that Zn(OTf)2 can be recovered
without the reduction by the hydrosilane after performing the zinc-
catalyzed cyanation of indoles with the system of MeNO2 and
H2SiPh2, and the recovered Zn(OTf)2 can then be used for other zinc-
catalyzed reaction. See Nagase, Y.; Sugiyama, T.; Nomiyama, S.;
Yonekura, K.; Tsuchimoto, T. Adv. Synth. Catal. 2014, 356, 347−352.
(25) Experimental details, including the glassware used, are given in
the Experimental Section.
(33) In spite of some efforts on monitoring 29Si NMR spectra after
mixing 2a, Zn(OTf)2, EtCN and pyridine in varying ratios [2a/
Zn(OTf)2/EtCN/pyridine = 1:1:0−2:0−1] at 30 °C for 5 min in
CDCl3 or CD3CN, we presently have no positive results for the
formation of silylpyridinium or -nitrilium ions.
(34) Oestreich’s group has proposed a similar four-centered cyclic
form consisting of two molecules of each of a hydrosilane and a boron
Lewis acid in the hydrosilylation of carbonyl compounds catalyzed by a
boron Lewis acid: Rendler, S.; Oestreich, M. Angew. Chem., Int. Ed.
2008, 47, 5997−6000.
(35) (a) Gotta, M. F.; Mayr, H. J. Org. Chem. 1998, 63, 9769−9775.
(b) Pratihar, S.; Roy, S. J. Org. Chem. 2010, 75, 4957−4963.
(c) Tsuchimoto, T.; Iwabuchi, M.; Nagase, Y.; Oki, K.; Takahashi, H.
Angew. Chem., Int. Ed. 2011, 50, 1375−1379. (d) Nomiyama, S.;
Hondo, T.; Tsuchimoto, T. Adv. Synth. Catal. 2016, 358, 1136−1149.
(36) Watanabe, T.; Kobayashi, A.; Nishiura, M.; Takahashi, H.; Usui,
T.; Kamiyama, I.; Mochizuki, N.; Noritake, K.; Yokoyama, Y.;
Murakami, Y. Chem. Pharm. Bull. 1991, 39, 1152−1156.
(37) For the dehydrogenative C-silylation of aniline derivatives, see
refs 8c, 8i−k, 8o, and 12i.
(38) We have already disclosed that the zinc−pyridine−nitrile system
is applicable to the dehydrogenative silylation and borylation of
alkynes: (a) Tsuchimoto, T.; Fujii, M.; Iketani, Y.; Sekine, M. Adv.
Synth. Catal. 2012, 354, 2959−2964. (b) Tsuchimoto, T.; Utsugi, H.;
Sugiura, T.; Horio, S. Adv. Synth. Catal. 2015, 357, 77−82.
(39) For the synthesis of Zn(NTf2)2, see (a) Lebold, T. P.; Leduc, A.
B.; Kerr, M. A. Org. Lett. 2009, 11, 3770−3772. For the spectral and
analytical data of Zn(NTf2)2, see (b) Koller, R.; Stanek, K.; Stolz, D.;
Aardoom, R.; Niedermann, K.; Togni, A. Angew. Chem., Int. Ed. 2009,
48, 4332−4336. Zn(NTf2)2 can be synthesized easily by the literature
method, but is also commercially available.
(26) The initial rate method performed here provides an estimate
based on the data possibly including outliers, and the objective of the
investigation is to gain insight into the rate law and consequently the
mechanism, not to quantitatively determine a rate constant.
(27) For the relationship of the experimentally determined rate order
and the change in molecularity between the resting state and the rate-
determining step, see (a) Smith, M. B. March’s Advanced Organic
ChemistryReactions, Mechanisms, and Structure, 7th ed.; Wiley:
Hoboken, 2013; pp 278−285. (b) Cowley, R. E.; Golder, M. R.;
Eckert, N. A.; Al-Afyouni, M. H.; Holland, P. L. Organometallics 2013,
32, 5289−5298.
(40) Macor, J. E.; Chenard, B. L.; Post, R. J. J. Org. Chem. 1994, 59,
7496−7498.
(41) For the synthesis of 1i, see (a) Shriner, R. L.; Ashley, W. C.;
Welch, E. Org. Synth., Coll. 1955, 3, 725−727. (b) Joshi, K. C.; Jain, R.;
Garg, S. J. Indian Chem. Soc. 1985, 62, 388−390. (c) Slatt, J.; Bergman,
̈
J. Tetrahedron 2002, 58, 9187−9191. For the spectral and analytical
data of 1i, see (d) Tsuchimoto, T.; Matsubayashi, H.; Kaneko, M.;
Nagase, Y.; Miyamura, T.; Shirakawa, E. J. Am. Chem. Soc. 2008, 130,
15823−15835.
(42) For the synthesis of 1m, see (a) Okauchi, T.; Itonaga, M.;
Minami, T.; Owa, T.; Kitoh, K.; Yoshino, H. Org. Lett. 2000, 2, 1485−
1487. For the spectral and analytical data of 1m, see (b) Gu, L.; Jin,
C.; Liu, J.; Zhang, H.; Yuan, M.; Li, G. Green Chem. 2016, 18, 1201−
1205.
(28) For reports on zinc−N-ligand complexes derived from
Zn(OTf) , see (a) Borner, J.; Florke, U.; Doring, A.; Kuckling, D.;
̈
̈
̈
2
Jones, M. D.; Herres-Pawlis, S. Sustainability 2009, 1, 1226−1239.
(b) Comerford, J. W.; Hart, S. J.; North, M.; Whitwood, A. C. Catal.
Sci. Technol. 2016, 6, 4824−4831.
(43) For the synthesis of 1q, see (a) Miralles, N.; Romero, R. M.;
Fernandez, E.; Muniz, K. Chem. Commun. 2015, 51, 14068−14071.
́
(29) On the basis of the observation of a broken-order in substrate,
the formation of active and inactive species and the existence of an
equilibrium between the two species have been reportedly suggested:
Hauwert, P.; Boerleider, R.; Warsink, S.; Weigand, J. J.; Elsevier, C. J. J.
Am. Chem. Soc. 2010, 132, 16900−16910.
̃
(b) Wen, J.; Zhang, R.-Y.; Chen, S.-Y.; Zhang, J.; Yu, X.-Q. J. Org.
Chem. 2012, 77, 766−771. For the spectral and analytical data of 1q,
see (c) Du, W.; Zhao, M.-N.; Ren, Z.-H.; Wang, Y.-Y.; Guan, Z.-H.
Chem. Commun. 2014, 50, 7437−7439.
(44) Rendler, S.; Oestreich, M.; Butts, C. P.; Lloyd-Jones, G. C. J.
Am. Chem. Soc. 2007, 129, 502−503.
(45) Li, Y.-X.; Ji, K.-G.; Wang, H.-X.; Ali, S.; Liang, Y.-M. J. Org.
Chem. 2011, 76, 744−747.
(30) For selected examples with respect to the activation of
hydrosilanes by Lewis acids (L.A.) via the formation of an Si−H···
L.A. complex, see (a) Parks, D. J.; Blackwell, J. M.; Piers, W. E. J. Org.
Chem. 2000, 65, 3090−3098. (b) Das, S.; Addis, D.; Zhou, S.; Junge,
K.; Beller, M. J. Am. Chem. Soc. 2010, 132, 1770−1771. (c) Nikonov,
G. I.; Vyboishchikov, S. F.; Shirobokov, O. G.; Simionescu, R. Eur. J.
Inorg. Chem. 2014, 2014, 2896−2901.
(31) Treatment of zinc complexes with hydrosilanes has been
reported to give zinc hydrides: (a) Bette, V.; Mortreux, A.; Savoia, D.;
Carpentier, J.-F. Adv. Synth. Catal. 2005, 347, 289−302. (b) Mukherjee,
D.; Thompson, R. R.; Ellern, A.; Sadow, A. D. ACS Catal. 2011, 1,
698−702.
(32) For reports on the formation of silylpyridinium and/or
-nitrilium ions from hydrosilanes under Lewis acidic conditions, see
(a) Bahr, S. R.; Boudjouk, P. J. Am. Chem. Soc. 1993, 115, 4514−4519.
(b) Kira, M.; Hino, T.; Sakurai, H. Chem. Lett. 1993, 22, 153−156.
(c) Gandhamsetty, N.; Park, S.; Chang, S. J. Am. Chem. Soc. 2015, 137,
15176−15184.
(46) For the synthesis of 14g, see (a) Heaney, H.; Ley, S. V. J. Chem.
Soc., Perkin Trans. 1 1973, 499−500. For the spectral and analytical
data of 14g, see (b) Lanni, E. L.; Locke, J. R.; Gleave, C. M.; McNeil,
A. J. Macromolecules 2011, 44, 5136−5145.
(47) For the synthesis of 14i, see (a) Qi, T.; Qiu, W.; Liu, Y.; Zhang,
H.; Gao, X.; Liu, Y.; Lu, K.; Du, C.; Yu, G.; Zhu, D. J. Org. Chem. 2008,
73, 4638−4643. For the spectral and analytical data of 14i, see
(b) Bahn, S.; Imm, S.; Mevius, K.; Neubert, L.; Tillack, A.; Williams, J.
̈
M. J.; Beller, M. Chem. - Eur. J. 2010, 16, 3590−3593.
(48) Ibaceta-Lizana, J. S. L.; Jackson, A. H.; Prasitpan, N.; Shannon,
P. V. R. J. Chem. Soc., Perkin Trans. 2 1987, 1221−1226.
P
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