Ni(0)-Catalyzed Three-Component Coupling Reaction of Tetrafluoroethylene and N-Sulfonyl-Substituted Imines with Silanes via Aza-Nickelacycles

Article abstract of DOI:10.1021/acs.orglett.8b03674

A nickel-catalyzed three-component coupling reaction of tetrafluoroethylene (TFE) and N-sulfonyl-substituted imines with silanes that furnishes a variety of fluorine-containing amines is disclosed. Stoichiometric experiments revealed that the aza-nickelac

Full text of DOI:10.1021/acs.orglett.8b03674

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Ni(0)-Catalyzed Three-Component Coupling Reaction of
Tetrafluoroethylene and N‑Sulfonyl-Substituted Imines with Silanes
via Aza-Nickelacycles
Hiroshi Shirataki, Takafumi Ono, Masato Ohashi,* and Sensuke Ogoshi*
Department of Applied Chemistry, Faculty of Engineering, Osaka University, Suita, Osaka 565-0871, Japan
S
* Supporting Information
ABSTRACT: A nickel-catalyzed three-component coupling
reaction of tetrafluoroethylene (TFE) and N-sulfonyl-sub-
stituted imines with silanes that furnishes a variety of fluorine-
containing amines is disclosed. Stoichiometric experiments
revealed that the aza-nickelacycles generated upon oxidative
cyclization of TFE and N-sulfonyl-substituted imines on Ni(0)
were identified as the key intermediates in this catalytic
reaction. A single-crystal X-ray diffraction analysis of such an aza-nickelacycle revealed that the O atom of the N-sulfonyl group
stabilizes the key intermediate via coordination to the nickel center.
rganofluorine species are widely employed in commer-
cial products owing to the unique properties endowed
reaction as we envisioned that they would (i) enhance the
coordination ability by back-donation from Ni(0) to the N-
sulfonyl-substituted imines and (ii) thermodynamically stabi-
lize the generated aza-nickelacycle by coordination of the O
atom of the N-sulfonyl group to the nickel center.11d,12
O
by the fluorine atom.1,2 Highly fluorinated organic compounds
have recently gained much attention due to their potential
applications as physiologically active compounds and in
advanced materials.1 Synthetic routes to highly fluorinated
organic compounds have been extensively explored, including
the straightforward transformation of industrially available
fluorine-containing feedstocks.3 For this approach, tetrafluoro-
ethylene (TFE) is an ideal starting material, given that it is
economical and environmentally friendly with negligible
global-warming potential.4 However, the conventional use of
TFE has been limited mostly to the preparation of
polytetrafluoroethylene (PTFE) and copolymers with other
alkenes.4a,b,5
The reaction conditions for the Ni-catalyzed three-
component coupling reaction of TFE and (E)-N-benzylidene
benzenesulfonamide (1a) with silanes were optimized on the
basis of a previous report.7d When a toluene solution of 1a and
Et3SiH was exposed to TFE (3.5 atm, > 3.0 equiv) in the
presence of Ni(cod)2 (10 mol %; cod = 1,5-cyclooctadiene)
and PtBu3 (10 mol %), followed by quenching with MeOH, N-
(2,2,3,3-tetrafluoro-1-phenylpropyl)benzenesulfonamide (2a)
was not obtained, even after 24 h at 100 °C (Table 1, entry
1); instead, N-benzylbenzenesulfonamide (3a) was generated
as an undesired product in 13% yield. By employing Ph2SiH2
instead of Et3SiH, 2a was obtained in 55% yield under
concomitant generation of 3a in 36% yield (entry 2).
Encouraged by this result, we studied the effect of the ligand
for the system using Ph2SiH2. The yield of the reaction with
PPh3 was comparable to that with PtBu3 (entry 3). When the
reaction was conducted in the presence of 20 mol % of PPh3,
the yield of 2a decreased (entry 4). Control experiments
showed that both Ni(cod)2 and PPh3 are necessary for this
catalytic reaction (entries 5 and 6). Thus, further optimizations
of the reaction conditions were carried out in the presence of
10 mol % of Ni(cod)2 and PPh3. Higher reaction temperatures
(120 °C) and increased partial pressure of TFE (5.0 atm, > 4.0
equiv) slightly increased the yield of 2a (entries 7 and 8).
Finally, the effect of different silanes was examined. While
tBu2SiH2 was ineffective due to its steric bulk, Et2SiH2 provided
Our research group has been focusing on the transformation
of TFE by oxidative cyclization with Ni(0) as the key reaction
step.6−8 Such oxidative cyclization can efficiently produce a
nickelacycle under concomitant formation of a C−C bond
from various combinations of two π-components, where the
generated nickelacycle serves as the key intermediate in such
multicomponent coupling reactions.9 Very recently, we have
disclosed a Ni-catalyzed three-component coupling reaction of
TFE and aldehydes with silanes via oxa-nickelacycle key
intermediates.7d Thus, the development of a catalytic system
involving reactions via aza-nickelacycle key intermediates is a
logical extension. Herein, we report a three-component
coupling reaction via an aza-nickelacycle generated from TFE
and imines. Although Ni-catalyzed three-component coupling
reactions have been reported with several combinations of two
π-components,10,11 the coupling of alkenes and imines remains
challenging given that the simultaneous coordination of
alkenes and imines, followed by oxidative cyclization, is
difficult. Thus, we began our investigation using N-sulfonyl-
substituted imines as model substrates for this catalytic
Received: November 16, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.8b03674
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Letter
yields of the desired products (2c: 51% and 2d: 62%; entries 3
and 4). Even though (E)-N-benzylidene-2-methylbenzenesul-
fonamide (1e) furnished the target product (2e) in 76% yield
after 24 h, 73% yield was obtained after 6 h (entry 5). The use
of (E)-N-benzylidene-2,4,6-trimethylbenzenesulfonamide (1f),
however, furnished the target product 2f in merely 38% yield.
Employing (E)-N-benzylidenemethanesulfonamide (1g) af-
forded the target product in 67% yield within 6 h (entry 7).
Neither (E)-N-benzylidenebenzenamine (1h) nor (E)-tert-
butyl benzylidenecarbamate (1i) generated the corresponding
target product (entries 8 and 9). N-Diphenylphosphine-
substituted imine 1j was ineffective, although it has been
reported to accelerate the oxidative cyclization of alkynes and
imines by thermodynamic stabilization of the generated aza-
nickelacycle (entry 10).12c,d These results revealed that the N-
sulfonyl group on the imines is essential for the catalytic
reaction.
Table 1. Optimization of the Reaction Conditions for the
Ni-Catalyzed Three-Component Coupling Reaction of TFE,
N-Sulfonyl-Substituted Imine 1a, and Silanes
a
yield (%)
entry
ligand
silane
temp (°C)
2a
3a
1
2
3
PtBu3
PtBu3
PPh3
PPh3
none
PPh3
PPh3
PPh3
PPh3
PPh3
Et3SiH
100
100
100
100
100
100
120
120
120
120
0
55
51
40
0
13
36
29
58
15
0
55
42
0
Ph2SiH2
Ph2SiH2
Ph2SiH2
Ph2SiH2
Ph2SiH2
Ph2SiH2
Ph2SiH2
tBu2SiH2
Et2SiH2
b
4
5
6
c
0
7
53
57
5
d
8
d
The scope and limitations of the catalytic reaction with
respect to N-sulfonyl-substituted imines were examined under
the optimal reaction conditions (Scheme 1).14 The reaction of
9
d
10
80
6
a
General conditions: Ni(cod)2 (0.010 mmol), ligand (0.010 mmol),
1a (0.10 mmol), silane (0.10 mmol), and toluene (0.5 mL). Based on
the ideal gas equation, an excess of TFE (3.5 atm) relative to 1a was
used; quenching agent: MeOH; yields determined by GC using n-
Scheme 1. Substrate Scope of the Ni-Catalyzed Three-
Component Coupling Reaction of TFE, N-Sulfonyl-
a,b
b
c
Substituted Imine 1, and Et2SiH2
hexadecane as the internal standard. 20 mol % of PPh3. Without
d
Ni(cod)2. 5.0 atm of TFE.
2a in 80% yield and improved the 2a/3a product ratio (entries
9 and 10). Thus, we concluded that the optimal reaction
conditions are those in entry 10.13
Under the optimal reaction conditions, we performed
reactions with a variety of N-substituted imines (Table 2).
The use of (E)-N-benzylidene-4-methylbenzenesulfonamide
(1b) instead of 1a afforded comparable results, furnishing the
target product (2b) in 70% yield (entry 2). Methoxy- and
trifluoromethyl-substituted imines 1c and 1d afforded lower
Table 2. Effect of the N-Substituent of the Imine on the Ni-
Catalyzed Three-Component Coupling Reaction of TFE,
a
Imines, and Et2SiH2
a
General conditions: Ni(cod)2 (0.05 mmol), PPh3 (0.05 mmol), 1
(0.50 mmol), Et2SiH2 (0.50 mmol), toluene (2.5 mL), and TFE (5.0
b
c
d
atm); quenching agent: MeOH. Isolated yield. Run for 12 h. Yield
estimated by 19F NMR analysis of the crude reaction mixture.
TFE, 1e, and Et2SiH2 afforded 2e in 73% isolated yield. The
reactions with methyl-substituted imines (1k, 1l, and 1m) were
completed within 12 h to furnish the corresponding amines
(2k, 2l, and 2m) in moderate to good yield; however,
trimethylphenylimine (1n) was not tolerated, and merely trace
amounts of 2n were detected by 19F NMR analysis of the crude
reaction mixture. Fluoro- (1o) and chloro-substituted imines
(1p) afforded the corresponding amines (2o and 2p), but
bromo-substituted imine 1q could not be used as the substrate
due to the undesired oxidative addition of Ni(0) to the C−Br
bond. The reaction with imine 1r, which carries an electron-
donating group, afforded the target product (2r) in 30% yield,
a
General conditions: Ni(cod)2 (0.010 mmol), PPh3 (0.010 mmol), 1
(0.10 mmol), Et2SiH2 (0.10 mmol), toluene (0.5 mL), and TFE (5.0
atm); quenching agent: MeOH; yields determined by 19F NMR
b
analysis using α,α,α-trifluorotoluene as the internal standard. Run for
6 h. Reaction conditions: Ni(cod)2 (0.0050 mmol), PPh3 (0.005
mmol), 1j (0.050 mmol), Et2SiH2 (0.050 mmol), toluene (0.5 mL),
and TFE (5.0 atm).
c
B
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Letter
while the reactions of imines with electron-withdrawing
groups, including ester, trifluoromethyl, and phenyl groups
(1s, 1t, and 1u) furnished the corresponding target products
(2s, 2t, and 2u) in 80%, 85%, and 78% yield, respectively.
Naphthylimines (1v and 1w) also underwent this catalytic
reaction to generate 2v and 2w. The p-boronate-substituted
amine 2x, which can be further used as a coupling agent, was
successfully prepared from the reaction with a p-boronate-
substituted imine (1x). Finally, the reaction with an aliphatic
cyclic imine (1y) resulted in the formation of the target
product 2y in 62% yield.14,15
analysis revealed that the O atom of the N-sulfonyl group
occupies the vacant coordination site on the nickel center of
another aza-nickelacycle monomer unit to stabilize the dimer
complex in the solid state (Figure 1). This result contrasts with
the findings of previous studies, where intramolecular
coordination of the O atom of the N-sulfonyl group and the
nickel center was observed.12
Then the scope and limitations of the catalytic reaction were
evaluated using a different industrially available fluorinated
olefin (Scheme 2).15 The present Ni(0)/PPh3 system catalyzed
Scheme 2. Ni-Catalyzed Three-Component Coupling
Reaction of Trifluoroethylene, 1e, and Et2SiH2
Figure 1. Molecular structure of syn-5 with thermal ellipsoids at 30%
probability (except for the organic substituents including the o-tolyl
and phenyl groups); selected hydrogen atoms have been omitted for
clarity.
the reaction of trifluoroethylene with 1e to generate the target
product 2-methyl-N-(2,3,3-trifluoro-1-phenyl)propyl)-
benzenesulfonamide (4) in 60% NMR yield (12:1 dr).
However, the major product (the diastereomer) could not
be isolated from the regioisomer, 2-methyl-N-(2,2,3-trifluoro-
1-phenyl)propyl)benzenesulfonamide.
Stoichiometric experiments were performed in order to gain
deeper insight into the reaction mechanism.16 A toluene
solution of Ni(cod)2, PPh3, and 1e was exposed to TFE (1.5
atm, > 6.8 equiv) at 60 °C to produce a five-membered aza-
nickelacycle dimer (syn-5) in 76% isolated yield (Scheme 3a).
The reaction of 1h with Ni(cod)2 and PPh3 under an
atmosphere of TFE (1.5 atm) produced octafluoronickelacy-
clopentane (7), which was generated via the oxidative
cyclization of two molecules of TFE, in 15% yield (Scheme
4). The molecular structure of 7 exhibits a distorted square-
Scheme 4. Stoichiometric Experiments with 1h and
Subsequent Reactions with Et2SiH2
Scheme 3. Stoichiometric Experiments with 1e for (a) the
Isolation of the Aza-nickelacycle and (b) Subsequent
Reactions with Et2SiH2
planar geometry in the solid state, as confirmed by single-
crystal X-ray diffraction analysis (Figure 2). The expected aza-
When the reaction was conducted under higher pressure of
TFE (5.0 atm, >18.7 equiv), the yield of syn-5 was reduced to
53% and (CF2CF2CF2CF2)Ni(PPh3)2 was produced as a
byproduct in 12% yield.7a,16 Indeed, monitoring the synthesis
of syn-5 by NMR analysis revealed the formation of an η2-N-
sulfonyl-substituted imine nickel complex (6) both in the
absence and presence of excess TFE.12a Subsequently,
treatment of syn-5 with Et2SiH2 in C6D6 at 120 °C for 2 h,
followed by quenching with MeOH, afforded 2e in 82% yield
(Scheme 3b). Based on these results, we propose that the
catalytic reaction proceeds via an aza-nickelacycle monomer or
dimer generated from TFE and the N-sulfonyl-substituted
imine.
Figure 2. Molecular structure of 7 with thermal ellipsoids at 30%
probability (except for the organic substituents of the PPh3); selected
hydrogen atoms have been omitted for clarity.
The molecular structure of syn-5 was unambiguously
determined by single-crystal X-ray diffraction analysis. This
C
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Letter
nickelacycles (8 or 9), formed by the oxidative cyclization of
TFE and 1h, were not obtained, while a η2-N-phenylimine
nickel complex (10) was observed by NMR analysis in C6D6
before exposure to TFE.12a In order to consider the possibility
of retro-oxidative cyclization, the reaction of 7 with Et2SiH2
was explored. However, the target product (2h) was not
obtained, even at 120 °C. These results indicate that the N-
sulfonyl groups on the imines are crucial to accelerate the
oxidative cyclization and generate the thermodynamically
stabilized aza-nickelacycle intermediates.
reaction product to give N-protonated amine, it was
unfortunately unsuccessful.
In conclusion, we have developed a nickel-catalyzed three-
component coupling reaction of TFE, N-sulfonyl-substituted
imines, and Et2SiH2. Detailed mechanistic studies revealed aza-
nickelacycles as key intermediates. The N-sulfonyl group on
the imines is crucial for this catalytic reaction by enhancing the
coordination ability of the imine to Ni(0) and stabilizing the
resulting aza-nickelacycle intermediates. The obtained prod-
ucts can subsequently be transformed into valuable trifluoro
allylic amines.
On the basis of these results, a plausible reaction mechanism
for the present nickel-catalyzed three-component coupling
reaction is proposed in Scheme 5. A simultaneous coordination
ASSOCIATED CONTENT
* Supporting Information
■
S
Scheme 5. Plausible Mechanism for the Ni-Catalyzed Three-
Component Coupling Reaction of TFE, N-Sulfonyl-
Substituted Imines, and Silanes
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.8b03674.
Detailed experimental procedures and spectral data for
all new compounds (PDF)
Accession Codes
CCDC 1879548−1879549 contain the supplementary crys-
tallographic data for this paper. These data can be obtained
free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by
emailing data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
AUTHOR INFORMATION
Corresponding Authors
■
of TFE and the N-sulfonyl-substituted imine with Ni(0) would
form η2:η2 nickel complex A. Then an oxidative cyclization
would produce an aza-nickelacycle monomer (B) and/or
dimer (syn-C or anti-C) as key intermediates, which would be
stabilized by coordination of the N-sulfonyl group. Afterward,
transmetalation of the silane with B, syn-C, or anti-C would
afford nickel hydride D. A reductive elimination on D would
afford E under concomitant regeneration of the Ni(0) species.
Finally, E could be protonated during the workup to give the
target product. Alas, all of our attempts to isolate E have
remained unsuccessful so far.
*E-mail: ogoshi@chem.eng.osaka-u.ac.jp.
*E-mail: ohashi@chem.eng.osaka-u.ac.jp.
ORCID
Masato Ohashi: 0000-0001-8718-2799
Sensuke Ogoshi: 0000-0003-4188-8555
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The reactivity of the reaction product 2k was studied in
order to demonstrate the utility of this catalytic reaction
(Scheme 6). The reaction of 2k with lithium diisopropyl amide
This work was partially supported by Grants-in-Aid for
Scientific Research (A) (A16H02276) and (B) (16KT0057
and 17H03057) from the Japan Society for the Promotion of
Science (JSPS).
Scheme 6. Utility of Fluorine-Containing Amines
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