Ruthenium(II)-Catalyzed Regioselective 1,2-Hydrosilylation of N-Heteroarenes and Tetrel Bonding Mechanism

Article abstract of DOI:10.1021/acscatal.1c01148

An efficient regioselective dearomatization of N-heteroarenes using a ruthenium precatalyst [Ru-(p-cymene)(PCy3)Cl2] 1 is achieved. Reactions were performed under mild and neat conditions. A wide variety of N-heteroarenes undergo the addition of silanes in the presence of precatalyst 1, leading to exclusive N-silyl-1,2-dihydroheteroarene products. This catalytic method displays a broad substrate scope; quinolines, isoquinolines, benzimidazoles, quinoxalines, pyrazines, pyrimidines, and pyridines undergo highly selective 1,2-dearomatization. Both electron-donating and electron-withdrawing substituents on N-heteroaromatics are well tolerated in this protocol. Mechanistic studies indicate the presence of [Ru-(p-cymene) (PCy3)HCl] 4 in the reaction mixture, which may be the resting state of the catalyst. The complete catalytic cycle as revealed from density functional theory (DFT) studies show that the product formation is governed by N → Si tetrel bonding. Initially, PCy3 dissociates from 1, and further reaction of [(p-cymene)RuCl2] 20 with silane generates the catalytically active intermediate [(p-cymene)RuHCl] 7. Heteroarene coordinates with 7, and subsequent dearomative 1,3-hydride transfer to the C2 position of the heteroaryl ligand generates an amide-ligated intermediate in which the reaction of silane occurs through a tetrel bonding and provides a selective pathway for 1,2-addition. DFT studies also revealed that ruthenium-catalyzed 1,4-hydroboration of pyridines is a facile process with a free energy barrier of 3.2 kcal/mol, whereas a pathway for the 1,2-hydroboration product is not observed due to the steric effects exerted by methyl groups on pinacolborane (HBpin) and p-cymene. Notably, enabled by the amine-amide inter-conversion of the coordinated heteroarene ligand, the +2 oxidation state of ruthenium intermediates remains unchanged throughout the catalytic cycle.

Full text of DOI:10.1021/acscatal.1c01148

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Research Article
Ruthenium(II)-Catalyzed Regioselective 1,2-Hydrosilylation of
N‑Heteroarenes and Tetrel Bonding Mechanism
Deepak Behera, Subramanian Thiyagarajan, Puthannur K. Anjalikrishna, Cherumuttathu H. Suresh,*
and Chidambaram Gunanathan*
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ABSTRACT: An efficient regioselective dearomatization of N-heteroarenes
using a ruthenium precatalyst [Ru-(p-cymene)(PCy3)Cl2] 1 is achieved.
Reactions were performed under mild and neat conditions. A wide variety of
N-heteroarenes undergo the addition of silanes in the presence of precatalyst
1, leading to exclusive N-silyl-1,2-dihydroheteroarene products. This catalytic
method displays a broad substrate scope; quinolines, isoquinolines,
benzimidazoles, quinoxalines, pyrazines, pyrimidines, and pyridines undergo
highly selective 1,2-dearomatization. Both electron-donating and electron-
withdrawing substituents on N-heteroaromatics are well tolerated in this
protocol. Mechanistic studies indicate the presence of [Ru-(p-cymene)
(PCy3)HCl] 4 in the reaction mixture, which may be the resting state of the
catalyst. The complete catalytic cycle as revealed from density functional
theory (DFT) studies show that the product formation is governed by N → Si tetrel bonding. Initially, PCy3 dissociates from 1, and
further reaction of [(p-cymene)RuCl2] 20 with silane generates the catalytically active intermediate [(p-cymene)RuHCl] 7.
Heteroarene coordinates with 7, and subsequent dearomative 1,3-hydride transfer to the C2 position of the heteroaryl ligand
generates an amide-ligated intermediate in which the reaction of silane occurs through a tetrel bonding and provides a selective
pathway for 1,2-addition. DFT studies also revealed that ruthenium-catalyzed 1,4-hydroboration of pyridines is a facile process with a
free energy barrier of 3.2 kcal/mol, whereas a pathway for the 1,2-hydroboration product is not observed due to the steric effects
exerted by methyl groups on pinacolborane (HBpin) and p-cymene. Notably, enabled by the amine−amide inter-conversion of the
coordinated heteroarene ligand, the +2 oxidation state of ruthenium intermediates remains unchanged throughout the catalytic cycle.
KEYWORDS: hydrosilylation, ruthenium, 1,2-regioselectivity, N-heteroarenes, dearomatization, catalysis, tetrel bonding
reduction of aromatic rings and the formation of different
regioisomers that are difficult to separate.6 Alternatively,
catalytic hydrogenation of quinolines is also achieved by
using an excess amount of silanes and boranes, which resulted
in over-reduction and provided tetrahydroquinoline products.7
Thus, the development of transition-metal-catalyzed regiose-
lective reduction of N-heteroaromatics under mild conditions
is highly desirable.
The selective hydrosilylation and hydroboration of N-
heteroarenes provide N-sila and bora-functionalized molecules,
which are key intermediates for further functionalization. In
the last decade, transition-metal-catalyzed regioselective hydro-
boration of N-heteroarenes is reported (Scheme 1).8−10
However, hydroboration reaction on pyridine and quinoline
INTRODUCTION
■
Partial hydrogenation of N-heteroaromatic compounds is an
essential strategy in synthetic chemistry because of their
widespread application in the synthesis of natural products,
bioactive molecules, and various drug molecules.1 There are a
number of biological transformations in which regioselective
dearomatization occurs through oxidation or reduction
reactions facilitated by microbes and enzymes present in
nature.2 Regioselective dearomatization of heteroaromatic
compounds is a challenging task in synthetic chemistry due
to the high resonance energy of aromatic rings and the
formation of different regioisomers, and thus, it requires an
efficient catalytic system to overcome these challenges.3,4 In
conventional organic synthesis, selective hydrogenation of N-
heteroaromatic rings has been achieved using alkali metal
hydrides, which suffers from serious drawbacks such as lack of
selectivity, harsh reaction conditions, and generation of
copious hazardous waste.5 Hydrogenation reaction is the
simplest and economical way to reduce aromatic rings.
Unfortunately, hydrogenation of heteroaromatic molecules
was performed under harsh conditions, which leads to over-
Received: March 12, 2021
Revised: April 16, 2021
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strategy under mild reaction conditions for regioselective 1,2-
hydrosilylation of N-heteroaromatics is highly desirable.
We have reported catalytic hydroelementation reactions
such as hydroboration of carbonyl compounds,18 olefins,19
deoxygenative hydroboration of carboxylic acids,20 imines, and
nitriles,21 and also hydrosilylation of aldehydes,22 using a
readily available, simple dinuclear ruthenium complex [Ru(p-
cymene)Cl2]2. Using mono- and dinuclear ruthenium catalysts,
multicomponent synthesis of borasiloxanes directly from
pinacolborane, silane, and water was reported.23 Using
phosphine-ligated mononuclear ruthenium catalyst 1, we
have developed an efficient regioselective 1,4-hydroboration
of pyridines.24 Very recently, our group demonstrated the
ruthenium-catalyzed selective hydroboronolysis of ethers.25 In
continuation of our interest in hydroelementation and selective
dearomatization reactions, herein, we report the ruthenium-
catalyzed regioselective 1,2-hydrosilylation of N-heteroaro-
matic compounds (Scheme 1). Surprisingly, a selectivity
reversal from 1,4-addition to 1,2-addition is observed in the
dearomatization of N-heteroarenes when electrophile changed
from borane to silane. Mechanistic studies using density
functional theory (DFT) calculations indicate that tetrel
bonding is responsible for the observed selective 1,2-hydro-
silylation of heteroaromatic compounds. To understand the
origin of selectivity reversal, DFT studies were also performed
on ruthenium-catalyzed hydroboration of pyridines. Notably,
all the attempts to locate the transition state for 1,2-
hydroboration of pyridine are failed, suggesting that the
reaction is regioselective toward 1,4-addition of pinacolborane
(HBpin) on pyridines as observed experimentally.24 However,
DFT calculations using a “reduced model” suggest that steric
effects exerted by the methyl groups on HBpin and p-cymene
are responsible for the regioselective 1,4-hydroboration of
pyridines.
Scheme 1. Catalytic Regioselective Hydroboration and
Hydrosilylation of N-Heteroarenes
RESULTS AND DISCUSSION
■
Initial investigation on catalytic dearomatization by hydro-
silylation was carried out using quinoline (0.5 mmol, 1 equiv)
and phenylsilane (0.6 mmol, 1.2 equiv) in the presence of
1
precatalyst 1 (2 mol %) at room temperature. After 12 h, H
NMR analysis of the reaction mixture indicated the selective
formation of 1,2-hydrosilylation product 2a in 78% yield
(Table 1, entry 1). Increasing the reaction time to 24 h
resulted in a significant improvement in the yield of 2a (Table
1, entry 2). Quantitative formation of quinoline 1,2-hydro-
silylation product 2a was observed upon performing the
reaction at 60 °C (Table 1, entry 3). When the phenylsilane
was reduced to 1 equiv, the yield of 2a diminished to 91%
(Table 1, entry 4). Similarly, reducing catalyst load to 1 mol %
also provided a lower yield (90%, Table 1, entry 5). The use of
diethylsilane in this catalytic hydrosilylation reaction was
tested, which provided product 2b in quantitative yield (Table
1, entry 6). However, diphenylsilane failed to react (Table 1,
entry 7). A control experiment was performed in the absence
of a catalyst that confirmed the necessity of catalyst in this
transformation (Table 1, entry 8).
Under the optimized reaction conditions, different quinoline
derivatives were subjected to regioselective 1,2-hydrosilylation
reactions, which are found to provide good to excellent yields
(Scheme 2). Electron-donating groups such as methyl- and
methoxy-substituted quinolines reacted with both phenylsilane
and diethylsilane and delivered the products 2c−g in
quantitative yield with exclusive regioselectivity. Interestingly,
substrates provided a mixture of 1,2- and 1,4-addition
products.10 On the other hand, selective hydrosilylation of
N-heteroaromatics also developed recently. Harrod and co-
workers have reported the first homogeneous catalytic
hydrosilylation of pyridines using titanium catalyst with
moderate regioselectivity.11 The groups of Nikonov and
Oestreich have independently developed ruthenium-catalyzed
1,4-selective hydrosilylation of N-heteroarenes.12,13 In contrast,
1,2-selective hydrosilylation of N-heteroarenes was less
developed, and there are only three notable reports known
in the literature. Harder and co-workers developed a calcium
complex for catalytic regioselective dearomatization of
pyridines with a limited substrate scope.14 In 2016, Chang
and co-workers reported an Ir(II)-catalyzed 1,2-hydrosilylation
of N-heteroaromatic compounds.15 Recently, Nikonov re-
ported the Zn(II)-catalyzed hydrosilylation and hydroboration
of N-heteroarenes with a narrow substrate scope and longer
reaction time.16 Very recently, the Wang group demonstrated
1,2-selective hydrogenation of quinolines using ammonia-
borane as a reducing agent.17 Despite these notable enticing
signs of progress, the 1,2-selective hydrosilylation of N-
heteroarenes remains underdeveloped. Thus, devising a new
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Table 1. Optimization of the Reaction Conditions for the
1,2-Selective Hydrosilylation of Quinoline Catalyzed by 1
Scheme 2. Ruthenium-Catalyzed 1,2-Selective
Hydrosilylation of Quinolines
a
a
b
entry 1 (mol %)
silane (equiv)
temp (°C) time (h) yield (%)
1
2
3
4
5
6
7
8
2
2
2
2
1
2
2
PhSiH3 (1.2)
PhSiH3 (1.2)
PhSiH3 (1.2)
PhSiH3 (1.0)
PhSiH3 (1.2)
Et2SiH2 (1.5)
Ph2SiH2 (1.0)
PhSiH3 (1.2)
RT
RT
60
60
60
60
60
60
12
24
18
18
24
18
18
18
78
81
99
91
90
99
n.r
n.r
a
Reaction conditions: quinoline (0.5 mmol), silane, and precatalyst 1
were stirred at room temperature or 60 °C under closed conditions.
b
1
Yield was determined by H NMR analysis of the reaction mixture
using cyclohexane as an internal standard.
halogen-substituted quinolines were well tolerated in this
reaction condition, which provided the products 2h−p in
excellent yields. However, the reaction is sensitive to the steric
hindrance on quinolines. When 2-methyl quinoline and 8-
methyl quinoline were reacted with phenylsilane, no reaction
occurred. The reaction also tested with excess silane. However,
no formation of products 2q and 2r was observed. Apparently,
steric hindrance from the proximal methyl group adjacent to
nitrogen in the ring prevented the reaction in these substrates.
Also, 5-nitro quinoline was unsuccessful in this catalysis due to
the solubility problem.
To diversify ruthenium-catalyzed regioselective 1,2-hydro-
silylation using precatalyst 1, various N-heteroarenes were
subjected in this catalytic protocol (Scheme 3). Substituted
pyridines such as 3-methylpyridine, 3-methoxypyridine, and 4-
benzylpyridine underwent exclusive 1,2-dearomatization and
provided products 3a−c in 41, 85, and 50% yields, respectively.
The reaction of 3-pyridyl acetate resulted in the mixture of
products with incomplete conversion of the starting material
due to the presence of sensitive and competing ester
functionality. When pyrazine was reacted under the standard
condition with diethylsilane, regioselective 1,2-hydrosilylation
occurred on both nitrogen centers, leading to the formation of
1,2,3,4-tetrahydropyrazine product 3d in 40% yield. Notably,
2-methyl pyrazine provided regioselective double-1,2-hydro-
silylation product 3e in quantitative yield. 4-Methyl pyrimidine
also underwent double hydrosilylation (3f, 81% yield). Benzo-
fused five-member heterocycle 1-methylbenzimidazole pro-
vided 1,2-hydrosilylation product 3g quantitatively. When
isoquinoline was reacted with diethylsilane, regioselective 1,2-
hydrosilylation product 3h was obtained in quantitative yield;
however, a similar reaction with phenylsilane exclusively
resulted in the formation of bis(dihydroisoquinoline) product
3m. The formation of such double-addition product with
isoquinoline was also observed in other catalytic systems.10b,14
Remarkably, contrary to the 2-methylquinoline, 1-methyl
isoquinoline reacted with diethylsilane, and exclusive 1,2
hydrosilylation product 3i was observed in which 1,2-addition
occurred on nitrogen and methyl-substituted aryl carbon (see
2q in Schemes 2 and 3). In the case of quinoxaline and 6-
chloro quinoxaline, quantitative formation of products 3j and
3k occurred. The reaction of acridine with phenylsilane
a
Reaction conditions: substrate (0.5 mmol, 1 equiv), PhSiH3 (0.6
mmol, 1.2 equiv), or Et2SiH2 (0.75 mmol, 1.5 equiv) and precatalyst 1
(2 mol%) were stirred at 60 °C for 18 h. The yield was calculated by
1H NMR analysis using cyclohexane as an internal standard. CDCl3
(0.3 mL) was used. 2 equiv of PhSiH3 was used. Not detected.
b
c
d
provided 1,4-addition product 3l exclusively with 83% yield,
as 1,2-addition is not favored on this substrate.
Toward understanding the reaction mechanism, a stoichio-
metric experiment using precatalyst 1 with phenylsilane (5
equiv) was carried out, and the reaction was monitored by
1
NMR spectroscopy. The H NMR spectrum of the reaction
mixture was recorded after 15 min, showing the formation of
ruthenium monohydride intermediate 4, which resonated a
characteristic doublet at δ −7.84 ppm (JPH = 49.2 Hz) as well
as a doublet at δ 59.70 ppm (JPH = 50.6 Hz) in 31P NMR
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Scheme 3. Ruthenium-Catalyzed Regioselective 1,2-
Hydrosilylation of N-Heterocycles
Scheme 4. Mechanistic Investigations for Ruthenium-
Catalyzed Regioselective 1,2-Hydrosilylation of N-
a
Heteroarenes
a
Reaction conditions: substrate (0.5 mmol, 1 equiv), silane (1.25
mmol, 2.5 equiv), and 2 mol% of precatalyst 1 were stirred at 60 °C
1
for 18 h and the yield was calculated by H NMR analysis using
b
cyclohexane as an internal standard. 1.5 equiv of silane was used.
d
cReaction performed using 0.3 mL of CDCl3. C6D6 (0.3 mL) was
used.
attain these dearomatization reactions. Further, the reaction
was also monitored by 31P NMR; no signals that correspond to
quinoline-coordinated ruthenium intermediate or dissociation
of chloride ligands were observed. Only a minor amount of
dissociated free phosphine ligand (PCy3) from catalyst 4 was
observed.
(Scheme 4a). Unfortunately, repeated experiments were
performed to obtain the single crystals for X-ray analysis of
complex 4, which remained unsuccessful so far. When
precatalyst 1 reacted with quinoline (2 equiv), no reaction
was observed (1H and 31P NMR) after 15 min both at room
temperature and at 60 °C (Scheme 4b). Reaction of catalyst 1
with phenylsilane (5 equiv) and quinoline (2 equiv) resulted in
the same ruthenium hydride intermediate 4 (observed after 15
min) in NMR analysis: 1H NMR doublet at δ −7.84 ppm (JPH
= 49.5 Hz) as well as in 31P NMR doublet at δ 59.70 ppm (JPH
= 46.8 Hz) and formation of product 2a (Scheme 4c). When
intermediate 4 employed as a catalyst, the formation of desired
1,2-hydrosilylation product 2a was observed in 81% yield
under standard reaction conditions. This experiment indicates
the involvement of Ru−H intermediate in the catalytic
hydrosilylation of heteroarenes (Scheme 4d). The reaction of
isolated intermediate 4 with quinoline in the absence of silane
1H NMR monitoring of this reaction indicated the
persistence of the intermediate 4 throughout the reaction
(Figure 1). These experiments indicate the facile reaction of
silane with precatalyst 1 to provide intermediate 4, which may
be a catalyst resting state. Notably, while precatalyst 1 does not
react with quinoline directly, it reacts with silane to provide the
intermediate 4, which then reacts with quinoline in the
presence of silane, leading to the formation of regioselective
1,2-addition product.
Further, a plausible mechanism for the reaction26 is derived
using DFT calculation at M06L/BS1/SMD level,27 where BS1
stands for a mixed basis set (LanL2DZ for Ru and 6-31G** for
other atoms). At first, PCy3 dissociation from [Ru-(p-cymene)
(PCy3)Cl2] 1 is invoked to produce the active dichloro
complex.28 The dissociation occurs with a free energy change
of 14.6 kcal/mol. The Si−H bond of PhSiH3 interacts with the
1
was performed (Scheme 4e). The H NMR spectrum of the
crude reaction mixture indicated the absence of 1,3-hydride
shift on quinoline, which indicates the necessity of silane to
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1
Figure 1. H NMR monitoring: the stoichiometric reaction of quinoline with phenylsilane and precatalyst 1.
Ru(II) center of [Ru-(p-cymene)Cl2] to yield the intermediate
5 (Figure 2). TS1 represents a four-center transition state for
an exchange reaction, which describes the transition of hydride
from silicon to ruthenium along with the simultaneous transfer
of chloride from ruthenium to silicon. The activation free
energy (ΔG#) for the chloro-hydride ligand exchange is 27.8
kcal/mol. The intermediate 6 formed at this step has a weak
interaction between the chloro of silylchloride and Ru(II). An
active hydride complex [Ru-(p-cymene)HCl] (7) is formed by
the dissociation of chlorophenylsilane (8) from 6. Notably,
intermediate 7 was observed in mass spectral analysis, and we
have previously established its involvement in the anti-
Markovnikov hydroboration of alkenes.19
The second stage of the reaction occurs when the 16-
electron complex 7 gets coordinated with an N-heteroaromatic
system such as quinoline, leading to the formation of 9 with
the coordination free energy −9.5 kcal/mol. The hydride
migration (1,3-hydride shift) to ortho position of quinoline is
feasible for 9 by passing through TS2 with ΔG# 21.1 kcal/mol
(Figure 3). The 16-electron Ru(II) complex 10 could be
coordinated with PCy3, or it may undergo further reaction
with PhSiH3.
The third stage of the reaction considers the formation of
complex 11 (Figure 4). In 11, one of the Si−H bonds shows a
significant interaction with the ruthenium center. Also, the Si−
N distance at 1.96 Å suggests noncovalent tetrel bonding
between Si and N. The σ-donation from the lone pair electrons
on the N-center of dihydroquinoline in 10 to the hole region in
phenylsilane leads to tetrel bonding (Figure 5). The hyper-
valent penta-coordinate characteristic29 is developed on Si in
11 with the typical trigonal bipyramidal geometry.29 The Si−H
bond of 11 cleaves by liberating a hydride ligand to the metal
center (12) through an early transition state TS3 with ΔG# 2.3
kcal/mol. The Si atom in TS3 mimics the characteristics of the
central atom of an SN2 type transition state. The very low
barrier for the Si−H bond cleavage can be attributed to the N
→ Si tetrel bonding interaction in TS3. In 12, N-silyl-1,2-
Figure 2. Ru(II)chloride to Ru(II) hydride exchange reaction.
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noncovalent interactions in metal complex catalysis.31 The
existence of neutral penta-, hexa-, and even hepta-coordinated
species containing N → Si dative bonding32 is reported in the
literature in the fields of crystal engineering and supra-
molecular chemistry.33,34 The significance of tetrel bonding in
the Ru(II)-catalyzed hydrosilylation of N-heteroarenes is
revealed for the first time here. Figure 4 can be regarded as
one of the rare examples of a “tetrel bonding energy profile”,
which connects the tetrel-bonded reactant, TS and product.
Previously, Gunanathan et al. reported the [Ru(p-cymene)-
Cl2(P(Cy)3)]-catalyzed regioselective 1,4-hydroboration of
pyridines using pinacolborane (HBpin).24 A DFT study on
the mechanism of this reaction is performed to compare it with
the regioselective 1,2-hydrosilylation of heteroarenes. The
active form of the catalyst for the 1,4-hydroboration is
expected to be [Ru(p-cymene)Cl2], formed by the dissociation
of the bulky PCy3 ligand from the catalyst. Similar to 5, the
Ru(II) dichloro species forms an adduct with HBpin with a
binding energy of −5.9 kcal/mol. In the adduct, one of the
chloro ligands is exchanged for the hydride group of HBpin,
resulting in the formation of Ru(II)hydrido complex [Ru(p-
cymene)HCl] and ClBpin (Figure 6). The ΔG# for the
Figure 3. Mechanism for a 1,3-hydride shift.
Figure 4. Mechanism for the hydrosilylation of quinoline driven by
tetrel bonding.
Figure 6. Ru(II) chloride to Ru(II) hydride exchange reaction.
Figure 5. Hole and σ regions for tetrel bonding: illustration using
molecular electrostatic potential on electron density iso-surface 0.006
a.u.
reaction is found to be 8.3 kcal/mol, much lower than that
required for a similar exchange reaction given in Figure 2 for
the hydrosilylation reaction. The reaction is endergonic by 1.5
kcal/mol. Both HBpin and ClBpin can form a zwitterionic
adduct with pyridine by the coordinate N → B bonding
interaction. The HBpin...Py complex 16 formation is ender-
gonic (4.7 kcal/mol) with a complexation energy of −8.4 kcal/
mol, whereas ClBpin...Py complex 17 formations showed
exergonic characteristic (1.6 kcal/mol) with a complexation
energy of −15.2 kcal/mol (Figure S1; Supporting Informa-
tion). Since the energetics support the spontaneous formation
of ClBpin...Py complex, we assume that this adduct reacts with
the [Ru(p-cymene)HCl] complex. The Cl of ClBpin...Py is
anionic in nature and coordinates with Ru(II) to yield the
dihydroquinoline (2a) is coordinated with [Ru-(p-cymene)-
HCl], 7. Dissociation of 2a, the final product from 12, liberates
the catalytically active hydride complex [Ru-(p-cymene)HCl],
7. Ru remains in +2 oxidation state throughout the catalytic
cycle, and p-cymene ligand adopts the hapticity η6. In the
figures, magenta, orange, green, and aqua blue are Ru, Cl, Si,
and N, respectively.
Tetrel bonding is considered as a powerful noncovalent
bonding between electron donors and the carbon group 14
elements where the positive electrostatic potential is localized
over the tetrel atom.30 In a recent review, Guedes da Silva et al.
have discussed the importance of tetrel bonding and other
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complex 18 as given in Figure 7. The chloro unit migrates to
Ru(II) with the simultaneous exchange of hydride ligand from
Scheme 5. Proposed Catalytic Cycle for Regioselective 1,2-
Hydrosilylation of N-Heteroarenes and Free Energy
Changes
Figure 7. Mechanism for the hydroboration of pyridine.
Ru(II) to the fourth position of pyridine. The transition state
for this reaction is depicted in Figure 7, and the free energy
barrier is found to be 3.2 kcal/mol. The products of the
reaction are 1,4-dihydropyridine adduct of HBpin and the
active form of the catalyst is [Ru(p-cymene)Cl2]. The reaction
is exergonic by 12.3 kcal/mol. All attempts to locate a
transition state for the formation of 1,2-dihydropyridine adduct
of HBpin is failed, suggesting that the reaction is regioselective
toward 1,4-hydroboration of the pyridine. It may be noted that
when we conducted a study by substituting all methyl groups
in HBpin by H and also used benzene moiety instead of p-
cymene for the metal complex, we could locate a transition
state for the 1,2-hydroboration product, which showed lower
barrier height than the 1,4-hydroboration reaction. The results
from this “reduced” model suggest that steric effects exerted by
the methyl groups of HBpin and p-cymene units are
responsible for the promotion of the regioselective 1,4-
hydroboration reactions.
On the basis of experimental observations, DFT calculations,
and our previous reports on catalytic hydroboration and
hydrosilylation of different functional groups,18−25 the
plausible reaction mechanism for regioselective 1,2-hydro-
silylation of N-heteroaromatic compounds is proposed in
Scheme 5. DFT studies indicate the dissociation of phosphine
ligand from the catalyst 1, leading to the formation of dichloro
ruthenium intermediate 20, which upon reaction with
phenylsilane generates 7. Further quinoline coordination to 7
results in 9, which then undergoes intramolecular dearomative
1,3-hydride transfer to the C2 position of the heteroaryl ligand
to produce the Ru-amide intermediate 10. The reaction of 10
with silane occurs via unique tetrel bonding and results in Si−
H and Ru interaction, and subsequent sigma bond metathesis
in 11 leads to the formation of amine coordinated Ru
monohydride species 12. The dissociation of 1,2-hydro-
silylation product (2a) from 12 regenerates the catalytically
active intermediate 7 and completes one loop in a catalytic
cycle. The reaction of complex 1 with phenylsilane leads to the
formation of ruthenium hydride intermediate 4 as observed by
1H NMR analysis (Scheme 4a), and the presence of 4 is also
observed throughout the catalysis on monitoring the reaction
progress, indicating perhaps that it could be a catalyst resting
state. Notably, all the ruthenium intermediates in the catalytic
cycle remain in +2 oxidation state, which is enabled by the in
situ interconversion of amine−amide ligation of heteroar-
omatic motifs.
CONCLUSIONS
■
In summary, a highly regioselective method for 1,2-
dearomative hydrosilylation of N-heteroarenes using the
simple and readily accessible ruthenium precatalyst 1 is
reported. Various N-heteroarenes are subjected to catalysis
under this condition, and the corresponding regioselective 1,2-
hydrosilylation products are observed in good to excellent
yields with exclusive selectivity. The formation of a PCy3-
coordinated Ru−H intermediate 4 was identified from a
stoichiometric experiment, which may be regarded as the
resting state of the catalyst. DFT studies indicate that
dissociation of PCy3 from 4 yields the catalytically active
complex [Ru-(p-cymene)HCl] 7, which upon coordination
with quinoline leads to the 1,3-hydride transfer reaction. The
amide complex formed in the reaction undergoes N → Si tetrel
bonding with the phenylsilane to yield the N-silyl-1,2-
dihydroquinoline. On the contrary, the steric effects exerted
by the methyl groups on HBpin and p-cymene coordinated
with ruthenium are found to be responsible for 1,4-hydro-
boration of pyridines catalyzed by the same precatalyst 1.
Remarkably, this selective catalytic hydrosilylation of N-
heteroarenes proceeds under neat, activator-free, and mild
reaction conditions, which make the protocol complete atom
economical and environmentally benign.
5891
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ACS Catal. 2021, 11, 5885−5893

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pubs.acs.org/acscatalysis
Research Article
P. Quinoline, Quinazoline and Acridone Alkaloids. Nat. Prod. Rep.
2000, 17, 603−620.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acscatal.1c01148.
■
sı
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AUTHOR INFORMATION
Corresponding Authors
■
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Authors
Deepak Behera − School of Chemical Sciences, National
Institute of Science Education and Research, HBNI,
Bhubaneswar 752050, India
Subramanian Thiyagarajan − School of Chemical Sciences,
National Institute of Science Education and Research, HBNI,
Bhubaneswar 752050, India; orcid.org/0000-0002-
0735-5686
Puthannur K. Anjalikrishna − Chemical Sciences and
Technology Division, CSIR-National Institute for
Interdisciplinary Science and Technology,
Thiruvananthapuram 695019, India; Academy of Scientific
and Innovative Research (AcSIR), Ghaziabad 201002, India
Complete contact information is available at:
https://pubs.acs.org/10.1021/acscatal.1c01148
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
C.G. thanks SERB New Delhi (EMR/2016/002517), DAE,
and NISER for financial support. D.B. thanks DST for an
inspire fellowship. S.T. thanks UGC for a research fellowship.
C.H.S. is grateful to CSIR for funding. P.K.A. is thankful to
UGC, Government of India, for providing Senior Research
Fellowship.
DEDICATION
■
Dedicated to Prof. T. K. Chandrashekar on the occasion of his
65th birthday with our best wishes.
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