Palladium-Catalyzed Intramolecular C?H Arylation versus 1,5-Palladium Migration: A Theoretical Investigation

Article abstract of DOI:10.1002/asia.201800603

Theoretical investigations were carried out to elucidate the origin of chemoselectivity in the palladium-catalyzed reactions of 2-(dimethylphenylsilyl)phenyl triflates with or without an amino group at the 3-position. The selective formation of a 5,10-dihydrophenazasiline rather than a dibenzosilole from the substrate with an amino group at the 3-position could be successfully explained by proposing a new 1,5-palladium migration pathway that involves a neutral diorganopalladium(II) intermediate along with the subsequent formation of a low-energy amine-coordinated palladacycle intermediate prior to the C?N bond-forming process.

Full text of DOI:10.1002/asia.201800603

CHEMISTRY
AN ASIAN JOURNAL
www.chemasianj.org
Accepted Article
Title: Palladium-Catalyzed Intramolecular C-H Arylation vs. 1,5-
Palladium Migration: Theoretical Investigation
Authors: Nana Misawa, Tomohiro Tsuda, Ryo Shintani, Koichi
Yamashita, and Kyoko Nozaki
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To be cited as: Chem. Asian J. 10.1002/asia.201800603
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10.1002/asia.201800603
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Palladium-Catalyzed Intramolecular C–H Arylation vs. 1,5-
Palladium Migration: Theoretical Investigation
Nana Misawa,[a] Tomohiro Tsuda,[b] Ryo Shintani,*,[b] Koichi Yamashita,*,[c] and Kyoko Nozaki*,[a]
To the memory of Dr. Keiji Morokuma
Abstract: Theoretical investigations were carried out to elucidate the
origin of chemoselectivity in the palladium-catalyzed reactions of 2-
(dimethylphenylsilyl)phenyl triflates with or without an amino group at
the 3-position. The selective formation of a 5,10-dihydrophenazasiline
rather than a dibenzosilole from the substrate with an amino group at
the 3-position could be successfully explained by proposing a new
explore the mechanisms in detail for deeper understanding of
these reactions, and herein we describe our findings by
theoretical calculations.
Regarding the mechanistic investigation of 1,n-metal migration,
deuterium-labeling experiments are most widely utilized to
confirm the existence of such migration as reported in the
reactions involving 1,4-palladium,[3f–h,j] 1,4-rhodium,[4a,b,d,e,g,j,o] 1,5-
palladium,[6] or 1,5-rhodium migration.[5b–d] On the other hand,
elucidation of the exact mechanism of 1,n-metal migration itself
(how the migration takes place) relies on computational studies.
In this context, Mota and Dedieu theoretically investigated 1,n-
palladium migration processes using model systems (n = 3–6) by
proposing and comparing two possible pathways for each:
oxidative addition/reductive elimination pathway via palladium(IV)
and s-bond metathesis pathway maintaining palladium(II).[9,10] In
our present study, however, we found that neither of these
proposed pathways is likely to occur in the reaction of 3-amino-2-
1,5-palladium migration pathway that involves
diorganopalladium(II) intermediate along with the subsequent
formation of low-energy amine-coordinated palladacycle
a
neutral
a
intermediate prior to the C–N bond-forming process.
Introduction
Catalytic reactions involving 1,n-metal migration constitute a
powerful way of synthesizing structurally complex molecules from
relatively simple
precursors
through
a
C–H
bond
(dimethylphenylsilyl)phenyl
triflate
toward
a
5,10-
functionalization.[1] Among them, reactions with 1,4-migration[2] of
palladium[3] and rhodium[4] have been most widely explored, and
corresponding reactions with 1,5-migration have been
significantly less investigated.[5] In particular, effective utilization
of 1,5-palladium migration had been limited to only one catalytic
system[6] until our recent report where we described a palladium-
catalyzed asymmetric synthesis of silicon-stereogenic 5,10-
dihydrophenazasilines from prochiral 3-amino-2-(diarylsilyl)aryl
triflates through enantioselective 1,5-palladium migration [Eq.
(1)].[7] This reaction was in stark contrast to the related
asymmetric reaction of prochiral 2-(diarylsilyl)aryl triflates without
an amino group at the 3-position, which gave silicon-stereogenic
dibenzosiloles through intramolecular C–H arylation [Eq. (2)].[8]
The difference of the reaction outcome depending on the
presence or absence of an amino group in the substrate led us to
dihydrophenazasiline, and a 1,5-palladium migration pathway
involving a neutral diorganopalladium(II) intermediate is newly
proposed through theoretical calculations.
Y
Y
Pd(OAc)2 (5 mol%)
(R)-L1 (5.5 mol%)
R
R
R'HN
(1)
Si
Et3N (2.0 equiv)
Si
DMA, 100 °C
Y
Y
X
N
R'
SiMe3
X
OTf
up to 89% yield
up to 98% ee
PPh2
PPh2
SiMe3
(R)-L1
Y
Y
Pd(OAc)2 (5 mol%)
(R,Sp)-L2 (5.5 mol%)
R
R
(2)
Et2NH (2.0 equiv)
toluene, 50–70 °C
Si
Si
[a]
[b]
[c]
N. Misawa, Prof. Dr. K. Nozaki
Y
X
Department of Chemistry and Biotechnology
Graduate School of Engineering, The University of Tokyo
7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 (Japan)
E-mail: nozaki@chembio.t.u-tokyo.ac.jp
Me
X
Y
OTf
up to 99% yield
up to 98% ee
PCy2
PAr2
Fe
T. Tsuda, Prof. Dr. R. Shintani
Division of Chemistry, Department of Materials Engineering Science
Graduate School of Engineering Science, Osaka University
Toyonaka, Osaka 560-8531 (Japan)
E-mail: shintani@chem.es.osaka-u.ac.jp
Prof. Dr. K. Yamashita
Department of Chemical System Engineering
School of Engineering, The University of Tokyo
7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 (Japan)
E-mail: yamasita@chemsys.t.u-tokyo.ac.jp
(R,Sp)-L2: Ar = 3,5-Me2-4-MeOC6H2
Computational Details
All calculations were performed with the Gaussian 16 package.[11]
Geometrical optimizations were conducted in vacuum using the
DFT-B3LYP functional[12] including the D3 version of Grimme’s
empirical dispersion correction.[13] The LANL2DZ basis set with
Supporting information for this article is given via a link at the end of
the document.
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10.1002/asia.201800603
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the associated effective core potential was used for Pd, and the
standard 6-31G(d) basis set for other atoms. Frequency analyses
were carried out to confirm that each structure is a local minimum
(no imaginary frequency) or a transition state (only one imaginary
frequency). Intrinsic reaction coordinate (IRC) calculations of
some key transition states were performed to confirm the
connectivity of these transition states to the intermediates. The
energies were further estimated by single-point calculations using
the same level of theory as the geometry optimization, including
solvation effect by SCRF-CPCM model[14] using experimental
DMA solvent (ε = 37.8), zero-point correction, thermal correction,
and BSSE correction by counterpoise method of Boys and
Bernardi[15] in order to obtain more accurate results with B3LYP/6-
31G(d).[13d] The Gibbs free energies in DMA solvent (DG at 373.15
K and 1 atm) with single-point corrections are reported throughout
this paper.
A proposed catalytic cycle for the reaction of 1(H) to 2(H) is
illustrated in Scheme 1. Oxidative addition of 1(H) to palladium(0)
species gives arylpalladium(II) triflate A(H), which then undergoes
Ph
Ph
tBu
tBu
Pd(PPh3)4 (10 mol%)
Si
Si
(3)
Et2NH (3.0 equiv)
DMA, 100 °C, 47 h
OTf
1a (0.25 M)
2a: 81% yield
Ph
tBu
tBu Ph
Ph
tBu
H2N
H2N
Pd(PPh3)4 (10 mol%)
Si
Si
Si
(4)
Et2NH (3.0 equiv)
DMA, 100 °C, 47 h
N
H
OTf
1b (0.25 M)
Me
Si
3b: 79% yield
Me
Me
2b: 0% yield
Me
Me
Me
R
R
Pd(PPh3)2
Si
Si
(5)
or
Me2NH
DMA, 100 °C
N
H
OTf
1(H) (R = H)
1(N) (R = NH2)
2(H) (R = H)
2(N) (R = NH2)
3(N) (R = NH2)
Me
Si
Me
Me
Me
Results and Discussion
Si
Pd0
[Pd = Pd(PPh3)2]
OTf
1(H)
Initially, we experimentally compared reactions of simple and
structurally related substrates 1a and 1b under the same reaction
conditions using Pd(PPh3)4 as a catalyst with diethylamine as a
base in N,N-dimethylacetamide (DMA) at 100 °C [Eqs. (3) and
(4)]. As expected, while 1a gave dibenzosilole 2a in 81% yield, 1b
selectively gave 5,10-dihydrophenazasiline 3b in 79% yield with
no formation of corresponding dibenzosilole 2b. Based on these
results, we further simplified the structures of substrates and the
catalyst system as shown in Eq. (5) to carry out computational
studies to elucidate the detailed reaction pathways of these
reactions.[16]
2(H)
Me Me
Me Me
Si
Si
PdII
II
Pd
OTf
A(H)
B(H)
Me2NH2 OTf
Me2NH
Scheme 1. Proposed catalytic cycle for the reaction of 1(H) to give 2(H).
‡
Si
Pd
‡
OTf
HNMe2
Si
+
Pd
‡
20
II
Si
TS 1-A1(H)
11.2 kcal/mol
H
‡
–OTf
Si
10
Me2HN
Pd
+
–OTf
H2NMe2
TS B-2(H)
–3.1 kcal/mol
TS A2-B(H)
0.1 kcal/mol
II
Pd
OTf
0
-10
-20
-30
-40
-50
HNMe2
TS A1-A2(H)
–9.3 kcal/mol
0 kcal/mol
1(H)
Si
OTf
–16.4 kcal/mol
0
–17.6 kcal/mol
Pd
–18.6 kcal/mol
A1(H)
A2(H)
B(H)
HNMe2
Si
Si
+
Si
OTf
PdII
HNMe2
II
Pd
Pd
II
+
–OTf
HNMe2
H2NMe2 –OTf
–40.9 kcal/mol
2(H)
Si
0
Pd
+
H2NMe2 –OTf
Figure 1. Calculated reaction pathways from 1(H) to 2(H) (Pd = Pd(PPh3)2).
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‡
H2N
Si
Pd
40
30
20
10
0
OTf
HNMe2
‡
H2N
‡
H2N
TS 1-A1(N)
28.3 kcal/mol
Si
+
Si
II
Pd
‡
H
H2N
–OTf
Si
Pd
H2NMe2
TS B-2(N)
9.8 kcal/mol
Me2HN
TS A2-B(N)
12.1 kcal/mol
+
–OTf
II
Pd
OTf
HNMe2
TS A1-A2(N)
3.5 kcal/mol
0 kcal/mol
1(N)
H2N
–5.5 kcal/mol
–7.1 kcal/mol
A1(N)
H2N
-10
-20
-30
Si
A2(N)
–9.3 kcal/mol
B(N)
H2N
H2N
Si
+
OTf
0
Si
Si
Pd
II
OTf
PdII
HNMe2
Pd
HNMe2
–OTf
Pd
HNMe2
II
+
–26.9 kcal/mol
2(N)
H2NMe2 –OTf
H2N
Si
0
Pd
H2NMe2 –OTf
+
Figure 2. Calculated reaction pathways from 1(N) to 2(N) (Pd = Pd(PPh3)2).
Me
Si
Me
Me
Me
H2N
intramolecular C–H activation with the aid of amine base to give
diarylpalladium(II) B(H). Reductive elimination from this
intermediate takes place to give dibenzosilole 2(H) with
regeneration of the palladium(0) catalyst. Based on this proposed
catalytic cycle, we theoretically examined each step as shown in
the energy diagram in Figure 1. Initial oxidative addition of 1(H) to
Pd(PPh3)2 is exergonic by 16.4 kcal/mol via TS 1-A1(H) (DG‡ =
11.2 kcal/mol) to give arylpalladium(II) species A1(H). This then
undergoes conformational change and dissociation of triflate via
TS A1-A2(H) (–9.3 kcal/mol; DG‡ = 7.1 kcal/mol) to give cationic
arylpalladium(II) intermediate A2(H). Subsequent intramolecular
C–H activation with the aid of Me2NH gives intermediate B(H) (–
18.6 kcal/mol) through TS A2-B(H) (0.1 kcal/mol; DG‡ = 17.7
kcal/mol), and the C–C bond-forming reductive elimination
through TS B-2(H) (–3.1 kcal/mol; DG‡ = 15.5 kcal/mol) leads to
dibenzosilole 2(H) along with regeneration of palladium(0)
species. The overall process was found to be exergonic by 40.9
kcal/mol with relatively low activation barriers, indicating that the
conversion of 1(H) to 2(H) could proceed quite smoothly.
H2N
Si
0
Pd
[Pd = Pd(PPh3)2]
OTf
1(N)
2(N)
Me Me
Si
H2N
Me Me
H2N
Si
II
Pd
PdII
OTf
A(N)
B(N)
Me2NH2 OTf
Me2NH
Scheme 2. Proposed catalytic cycle for the reaction of 1(N) to give 2(N).
process is exergonic by 26.9 kcal/mol and the formation of 2(N)
would be feasible once the initial oxidative addition takes place,
but the fact that dibenzosilole 2b was not experimentally produced
at all in the reaction of 1b in Eq. (4) indicates that the reaction
Based on these results, we calculated the reaction pathways
from 1(N) to 2(N) and 3(N) to examine the effect of an amino
group at 3-position of 1(N). As shown in Scheme 2 and Figure 2,
a proposed catalytic cycle and the calculated reaction pathway
from 1(N) to 2(N) are essentially the same with those from 1(H) to
2(H) described above (Scheme 1 and Figure 1). However,
compared to the pathway from 1(H) to 2(H), the activation barrier
for initial oxidative addition step (1(N) ® A1(N)) is significantly
higher (DG‡ = 28.3 kcal/mol) and each of the subsequent steps
from oxidative adduct A1(N) to dibenzosilole 2(N) proceeds with
a comparable or somewhat higher activation barrier. The overall
pathway
from
oxidative
adduct
A1(N)
to
5,10-
dihydrophenazasiline 3(N) should be energetically more favorable.
A proposed catalytic cycle for the reaction of 1(N) to 3(N) is
summarized in Scheme 3. After oxidative addition of 1(N) to
palladium(0), resulting arylpalladium(II) triflate A(N) undergoes
1,5-palladium migration to give another arylpalladium(II) triflate
C(N). Intramolecular coordination of the amino group presumably
takes place to give intermediate D(N), deprotonation of which
leads to palladacycle E(N). Subsequent C–N bond-forming
reductive elimination gives 5,10-dihydrophenazasiline 3(N) to
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‡
‡
H2N
H2N
Si
Si
H2N
H
+
H
Si
H
+
Pd
Pd
–OTf
HNMe2
50
40
–OTf
HNMe2
Pd
IV
+
TS B’-C2(N)
TS A1-B’(N)
–OTf
HNMe2
40.9 kcal/mol
40.9 kcal/mol
B’(N)
36.8 kcal/mol
‡
H2N
‡
Si
+
Pd
H2N
30
II
NH2
‡
Si
II
‡
H2N
H
Si
–OTf
Si
19.8 kcal/mol
Pd
Me2HN
20
II
OTf
Pd
TS A2-C1(N)
HNMe2
TS A2-B(N)
12.1 kcal/mol
II
Pd
‡
H2N
H
TfO
+
HNMe2
–OTf
Si
NHMe2
10
0
II
Pd
TS B-C1(N)
4.4 kcal/mol
TS A1-A2(N)
3.5 kcal/mol
+
TS C1-C2(N)
0.8 kcal/mol
H
–OTf
HNMe2
–3.0 kcal/mol
C1(N)
–4.0 kcal/mol
C2(N)
–5.5 kcal/mol
–7.1 kcal/mol
-10
-20
A2(N)
H2N
–9.3 kcal/mol
A1(N)
NH2
H2N
B(N)
H2N
Si
Si
H2N
Si
Si
+
PdII
Si
+
Pd
OTf
PdII
HNMe2
II
TfO
–OTf
HNMe2
II
Pd
–OTf
Pd
II
HNMe2
HNMe2
+
H2NMe2 –OTf
Figure 3. Calculated 1,5-palladium migration pathways from A1(N) to C2(N) (Pd = Pd(PPh3)2).
Me Me
H2N
Me
Me
Me Me
Si
H2N
Si
Si
N
PdIV
OTf
H
path 1
Pd0
OTf
H
B’(N)
1(N)
3(N)
[Pd = Pd(PPh3)2]
Me Me
H2N
Me
Me
‡
H2N
H2N
Me
Me
Me
Me
Me Me
H2N
Si
path 2
Si
Si
Si
Si
PdII
H
HN PdII
H
PdII
OTf
PdII H
TfO
A(N)
PdII
OTf
A(N)
E(N)
OTf
TS A-C(N)
+
C(N)
Me2NH2 OTf
path 3
Me2NH
Me2NH2 OTf
– Me2NH
Me2NH
Me Me
H2N
Me
Me
– Me2NH2 OTf
Me Me
Si
H2N
Si
Si
+
PdII
H2N PdII
PdII
B(N)
OTf
OTf
C(N)
D(N)
Scheme 3. Proposed catalytic cycle for the reaction of 1(N) to give 3(N).
Scheme 4. Possible reaction pathways of 1,5-palladium migration from A(N) to
C(N) (Pd = Pd(PPh3)2).
regenerate palladium(0) species. Considering the common
intermediacy of oxidative adduct A(N) for both diarylpalladium
B(N) toward 2(N) and 1,5-palladium migration intermediate C(N)
toward 3(N), the key of this process is how the 1,5-palladium
migration proceeds from A(N). To elucidate the most plausible
mechanism of this 1,5-palladium migration step, we calculated
and compared several possible reaction pathways from A(N) to
C(N) (Figure 3).
According to the literature precedent,[9] two possible pathways,
i.e., oxidative addition/reductive elimination via palladium(IV)
(path 1 in Scheme 4) and s-bond metathesis maintaining
palladium(II) (path 2), have been proposed and theoretically
examined in the related 1,5-palladium migration processes. In
path 1, intramolecular oxidative addition of aryl C–H bond of
A1(N) to the arylpalladium(II) center leads to cationic
diarylpalladium(IV) hydride B’(N), and C–H bond-forming
reductive elimination in the opposite direction gives 1,5-palladium
migration intermediate C2(N). However, this reaction pathway
involves energetically unfavorable transition states TS A1-B’(N)
(40.9 kcal/mol; DG‡ = 48.0 kcal/mol) and TS B’-C2(N) (40.9
kcal/mol) via high-energy intermediate B’(N) (red path in Figure
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‡
H2N
‡
H2N
Si
Si
TfO
Pd
II
TfO
Pd
II
‡
HNMe2
HNMe2
10
5
Si
‡
TS C2-C3(N)
TS C3-C4(N)
4.9 kcal/mol
5.5 kcal/mol
Si
NH2
Pd
HN
Pd
+
II
H2NMe2 –OTf
TfO
2.5 kcal/mol
0
HNMe2
TS E-3(N)
–3.4 kcal/mol
C3(N)
TS C4-D(N)
H2N
–6.1 kcal/mol
-5
–4.0 kcal/mol
C2(N)
‡
Si
Pd
Si
NH2
TfO
-10
-15
-20
-25
-30
-35
II
+
II
Pd
H2N
Si
HNMe2
–12.8 kcal/mol
–OTf
C4(N)
TfO
HNMe2
II
Pd
TS D-E(N)
–21.4 kcal/mol
Si
NH2
HNMe2
TfO
Pd
II
–22.4 kcal/mol
–23.7 kcal/mol
HNMe2
E(N)
D(N)
Si
Si
–29.9 kcal/mol
3(N)
+
II
II
Pd
HN
Pd
H2N
+
H2NMe2 –OTf
Si
–OTf
HNMe2
N
H
0
Pd
+
H2NMe2 –OTf
Figure 4. Calculated reaction pathways from C2(N) to 3(N) (Pd = Pd(PPh3)2).
3), and cannot outcompete with the reaction pathway toward
dibenzosilole 2(N) via diarylpalladium(II) intermediate B(N)
(Figure 2). On the other hand, as for path 2, A1(N) first undergoes
the conformational change and dissociation of the triflate to give
A2(N) and successive s-bond metathesis takes place via four-
centered transition state TS A2-C1(N) (blue path in Figure 3),
followed by coordination of the triflate and the conformational
change, to reach 1,5-palladium migration intermediate C2(N).
Although this pathway was found to be energetically more
favorable than path 1, the transition sate energy of TS A2-C1(N)
(19.8 kcal/mol) is still higher than that of the highest transition
state from A2(N) to 2(N) (TS A2-B(N)) by 7.7 kcal/mol, which is
not consistent with the experimental outcome in Eq. (4). These
calculation results strongly indicate that previously proposed
reaction pathways for 1,5-palladium migration (paths 1 and 2) are
not operative in the reaction of 1(N) to 3(N).
As an alternative pathway, we also examined the possibility of
the involvement of neutral diarylpalladium(II) species B(N) in the
event of 1,5-palladium migration from A(N) (path 3 in Scheme 4),
and calculated the subsequent pathways from B(N) to find that
protodepalladation of B(N) in the opposite direction proceeds via
low-energy TS B-C1(N) (4.4 kcal/mol; DG‡ = 13.7 kcal/mol),
followed by coordination of the triflate and the conformational
change, to give 1,5-palladium migration intermediate C2(N)
(Figure 3). With this reasonable 1,5-palladium migration pathway,
we further investigated the remaining process from C2(N) to 3(N)
(Figure 4). Thus, the amino group on the benzene ring of C2(N)
ΔΔG‡
= 4.3 kcal/mol
Me
Me
Me
Si
Me Me
Me
H2N
H2N
Si
Si
via C(N), D(N), E(N)
N
H
II
Pd
2(N)
B(N)
3(N)
Scheme 5. Comparison of overall transition state energies from B(N) to 2(N)
and 3(N).
undergoes intramolecular coordination to palladium through the
rotation of the aryl C–Si bond via intermediates C3(N) and C4 (N)
to give lowest-energy intermediate D(N) (–23.7 kcal/mol).
Subsequent deprotonation by Me2NH leads to neutral
amidopalladium(II) species E(N), and reductive elimination from
this intermediate via TS E-3(N) gives product 3(N) along with
palladium(0) species.[17,18] The overall process from 1(N) to 3(N)
is exergonic by 29.9 kcal/mol, and it is worth mentioning that all
the calculated transition state energy levels from B(N) to 3(N)
described here were found to be lower than that of TS B-2(N)
(Scheme 5), which is consistent with the selective formation of
5,10-dihydrophenazasiline 3b from compound 1b without
producing dibenzosilole 2b [Eq. (4)].[19,20]
Conclusions
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[1]
For selected recent reviews on C–H bond functionalization: a) CH
Activation special issue (R. H. Crabtree, A. Lei, Eds.) in Chem. Rev. 2017,
117, Issue 13; b) C-H Bond Activation and Catalytic Functionalization I-
II (P. H. Dixneuf, H. Doucet, Eds.) in Topics in Organometallic Chemistry,
Springer, Cham, 2016.
In summary, we have theoretically examined the palladium-
catalyzed reactions of 2-(dimethylphenylsilyl)phenyl triflates to
elucidate the origin of chemoselectivity depending on the absence
(1(H)) or presence (1(N)) of an amino group at the 3-position. As
a result, for the reaction of 1(N), we have found that a new 1,5-
[2]
[3]
For reviews on 1,4-migration of palladium and rhodium: a) F. Shi, R. C.
Larock, Top. Curr. Chem. 2010, 292, 123; b) S. Ma, Z. Gu, Angew. Chem.
Int. Ed. 2005, 44, 7512.
palladium
migration
pathway
involving
neutral
diorganopalladium(II) intermediate B(N) is more plausible rather
than previously proposed pathways for related 1,5-palladium
migration. Through the overall energy diagram of this process, it
has also been indicated that the formation of low-energy amine-
coordinated palladacycle intermediate D(N) after the 1,5-
migration drives the reaction toward 5,10-dihydrophenazasiline
3(N) instead of dibenzosilole 2(N). The results obtained in this
study could be informative for the development of new catalytic
transformations involving 1,5-palladium migration or related
processes, which are currently under investigation in our
laboratory.
For selected examples: a) M. A. Campo, R. C. Larock, J. Am. Chem. Soc.
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Experimental Section
Procedure for Equation 3. A solution of compound 1a (32.5 mg, 70.0
µmol), Pd(PPh3)4 (8.1 mg, 7.0 µmol), and diethylamine (21.7 µL, 0.210
mmol) in DMA (0.28 mL) was stirred for 47 h at 100 °C under nitrogen.
After cooled to room temperature, this was diluted with Et2O and washed
with water. The organic layer was dried over MgSO4, filtered, and
concentrated under vacuum. The residue was purified by silica gel
preparative TLC with EtOAc/hexane = 1/50 to afford compound 2a (CAS
1116155-69-1) as a colorless oil (17.9 mg, 56.9 µmol; 81% yield). 1H NMR
3
3
(CDCl3): d 7.88 (d, JHH = 7.1 Hz, 2H), 7.85 (d, JHH = 7.8 Hz, 2H), 7.82-
7.76 (m, 2H), 7.46 (td, 3JHH = 7.6 Hz and 4JHH = 1.2 Hz, 2H), 7.39-7.30 (m,
5H), 1.07 (s, 9H). 13C NMR (CDCl3): d 148.8, 135.8, 135.3, 133.9, 133.0,
130.4, 129.6, 127.9, 127.5, 121.2, 26.9, 18.4.
Procedure for Equation 4. A solution of compound 1b (33.6 mg, 70.1
µmol), Pd(PPh3)4 (8.2 mg, 7.1 µmol), and diethylamine (21.7 µL, 0.210
mmol) in DMA (0.28 mL) was stirred for 47 h at 100 °C under nitrogen.
After cooled to room temperature, this was diluted with Et2O and washed
with water and then with saturated NaClaq. The organic layer was dried
over MgSO4, filtered, and concentrated under vacuum. The residue was
purified by silica gel preparative TLC with EtOAc/hexane = 1/10 to afford
compound 3b (CAS 2104795-25-5) as a white solid (18.3 mg, 55.5 µmol;
79% yield). 1H NMR (CDCl3): d 7.84-7.75 (m, 2H), 7.49 (dd, 3JHH = 7.4 Hz
and 4JHH = 1.2 Hz, 2H), 7.42-7.27 (m, 5H), 6.89 (t, 3JHH = 7.2 Hz, 2H), 6.80
[5]
For examples of 1,5-rhodium migration: a) M. Tobisu, J. Hasegawa, Y.
Kita, H. Kinuta, N. Chatani, Chem. Commun. 2012, 48, 11437; b) N.
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[6]
[7]
Y. Sato, C. Takagi, R. Shintani, K. Nozaki, Angew. Chem. Int. Ed. 2017,
56, 9211.
3
(d, JHH = 8.1 Hz, 2H), 6.55 (bs, 1H), 1.04 (s, 9H). 13C NMR (CDCl3): d
[8]
[9]
a) R. Shintani, H. Otomo, K. Ota, T. Hayashi, J. Am. Chem. Soc. 2012,
134, 7305; For a nonasymmetric precedent: b) M. Shimizu, K. Mochida,
T. Hiyama, Angew. Chem. Int. Ed. 2008, 47, 9760.
146.9, 136.4, 135.1, 130.4, 129.3, 127.9, 119.5, 115.2, 113.9, 27.4, 20.4.
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Acknowledgements
[10] For theoretical investigation on 1,4-rhodium migration via an oxidative
addition/reductive elimination pathway: K. Sasaki, T. Nishimura, R.
Shintani, E. A. B. Kantchev, T. Hayashi, Chem. Sci. 2012, 3, 1278.
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Bloino, B. G. Janesko, R. Gomperts, B. Mennucci, H. P. Hratchian, J. V.
Ortiz, A. F. Izmaylov, J. L. Sonnenberg, D. Williams-Young, F. Ding, F.
Lipparini, F. Egidi, J. Goings, B. Peng, A. Petrone, T. Henderson, D.
Ranasinghe, V. G. Zakrzewski, J. Gao, N. Rega, G. Zheng, W. Liang, M.
Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T.
Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreven, K. Throssell, J. A.
Montgomery, Jr., J. E. Peralta, F. Ogliaro, M. J. Bearpark, J. J. Heyd, E.
Support has been provided in part by a Grant-in-Aid for Scientific
Research (B) (16H04145), the Ministry of Education, Culture,
Sports, Science and Technology, Japan. The computations were
performed using workstation at Research Center for
Computational Science, National Institutes of Natural Sciences,
Okazaki, Japan.
Keywords: palladium • catalytic cycle • mechanism • 1,5-
migration • C-H activation
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N. Brothers, K. N. Kudin, V. N. Staroverov, T. A. Keith, R. Kobayashi, J.
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[17] An alternative pathway involving reductive elimination followed by
deprotonation was also examined to find that direct reductive elimination
from amine-coordinated cationic palladium species D(N) giving
protonated form of 3(N) goes through a higher-energy transition state
(11.0 kcal/mol; DG‡ = 34.7 kcal/mol). See the Supporting Information for
details.
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[19] The overall energy diagrams from 1(N) to 3(N) (Figures 2–4) do not
completely reproduce the experimental observations in ref 7, which
employs a different catalyst system.
[20] Geometry optimization including solvation effect by SCRF-CPCM model
using experimental DMA solvent (ε = 37.8) has also been carried out for
the dibenzosilole-forming pathway from oxidative adduct A2(N) to 2(N)
via 3(N) and the plausible 1,5-palladium migration pathway from A2(N)
to C1(N) via 3(N). See the Supporting Information for details.
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[16] The reaction of
a more structurally related substrate having a
dialkylphenylsilyl group instead of 1b also gave the corresponding 5,10-
dihydrophenazasiline selectively with no formation of a dibenzosilole.
See the Supporting Information for details.
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Entry for the Table of Contents (Please choose one layout)
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Selective formation a 5,10-
N. Misawa, T. Tsuda, R. Shintani,* K.
Yamashita,* and K. Nozaki*
dihydrophenazasiline from 3-amino-2-
(dimethylphenylsilyl)phenyl triflate
under palladium catalysis was
Page No. – Page No.
theoretically explained by proposing a
new 1,5-palladium migration pathway
that involves a neutral
diorganopalladium(II) intermediate
along with the subsequent formation
of a low-energy amine-coordinated
palladacycle prior to the C–N bond-
forming process.
Palladium-Catalyzed Intramolecular
C–H Arylation vs. 1,5-Palladium
Migration: Theoretical Investigation
Pd-catalyst
H2
N
Si
Si
H2N
Si
N
H
OTf
– H+
Pd
0
Pd
0
–
0
Pd
disfavored
H2N
–
H2N
H2N
favored
H+
Si
Si
II
– H+
Si
II
H
Pd
Pd
TfO
H
II
Pd
OTf
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