Synergistic Ligand Effect between N-Heterocyclic Carbene (NHC) and Bicyclic Phosphoramidite (Briphos) Ligands in Pd-Catalyzed Amination

Article abstract of DOI:10.1021/acs.organomet.8b00413

A synergistic ligand effect between NHC and phosphorus ligands in Pd-catalyzed Buchwald-Hartwig amination reactions was demonstrated with tunable π-acceptor bicyclic bridgehead phosphoramidite (briphos) ligands. The catalytic activity of NHC-Pd-L (L = phosphorus ligand) precatalysts depends on the electronic properties of L. A NHC-Pd-L catalyst with an N-cyclohexyl-substituted briphos ligand was found to be highly efficient. A series of C-N bond coupling reactions between primary or secondary amines and aryl chlorides were performed with high yields under mild reaction conditions.

Full text of DOI:10.1021/acs.organomet.8b00413

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Cite This: Organometallics XXXX, XXX, XXX−XXX
Synergistic Ligand Effect between N‑Heterocyclic Carbene (NHC)
and Bicyclic Phosphoramidite (Briphos) Ligands in Pd-Catalyzed
Amination
Miji Kim, Taeil Shin, Ansoo Lee, and Hyunwoo Kim*
Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Korea
S
* Supporting Information
ABSTRACT: A synergistic ligand effect between NHC and phosphorus
ligands in Pd-catalyzed Buchwald−Hartwig amination reactions was
demonstrated with tunable π-acceptor bicyclic bridgehead phosphoramidite
(briphos) ligands. The catalytic activity of NHC-Pd-L (L = phosphorus
ligand) precatalysts depends on the electronic properties of L. A NHC-Pd-L
catalyst with an N-cyclohexyl-substituted briphos ligand was found to be
highly efficient. A series of C−N bond coupling reactions between primary or
secondary amines and aryl chlorides were performed with high yields under
mild reaction conditions.
INTRODUCTION
■
The catalytic performance of transition metals highly depends
on the character of the ligands that bind to the central metal
atoms. Thus, the investigation of ligand effects has been one of
the major research topics in the field of transition-metal
catalysis. In recent years, N-heterocyclic carbenes (NHC) have
emerged as privileged ligands for transition-metal catalysis due
to their unique electronic and steric properties.1 The strong σ-
donor property of NHCs is reported to facilitate the oxidative
addition processes found to be rate determining in many
transition-metal catalysis.1,2 With this excellent ligand platform,
there has been much effort to improve the catalytic
performance of the NHC-based catalysts. In this context, the
cooperative ligand effect between NHC and additive ligands is
proposed to modulate the reactivity and selectivity of the
transition-metal catalysts.3 Organ and co-workers have
introduced pyridine-enhanced precatalyst preparation stabiliza-
tion and inhibition (PEPPSI) (Figure 1a).4 A significant
improvement in the catalytic performance has been achieved in
Pd-PEPPSI-catalyzed cross-coupling reactions even at ambient
temperature.4,5 In addition to the pyridine ligands, other
ligands with coordination atoms such as C, N, and P have been
used to develop NHC-PdII precatalysts for cross-coupling
reactions.6
Figure 1. (a) Pd-PEPPSI precatalyst, (b) Pd complex with IPr and a
phosphorus ligand, and (C) preparation of [PdCl2(IPr)L] (L =
briphos).
Among several types of ligands, phosphorus ligands caught
our attention because these classical ligands are suitable for the
electronic and steric tuning of ligand properties as well as
mechanistic investigation by 31P NMR spectroscopy (Figure
1b). Herrmann and Cazin prepared NHC-Pd-L complexes (L
= phosphines or phosphites), which are efficient precatalysts in
several cross-coupling reactions including the Suzuki−
Miyaura,7 Mizoroki−Heck,8 and Migita−Kosugi−Stille8 cou-
plings. In addition, we wanted to systematically investigate the
cooperative ligand effect between NHC and phosphorus
ligands in the same ligand platform. To perform this research,
we used bicyclic bridgehead phosphoramidite (briphos)
ligands, new types of tunable π-acceptor ligands (Figure
1c).9 Here we demonstrate the cooperative ligand effect of
Received: June 15, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/acs.organomet.8b00413
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NHC-Pd-briphos complexes and their applications to
Buchwald−Hartwig amination reactions.
of the 2,6-diisopropylphenyl groups in IPr to rotate by about
15° from an orthogonal orientation relative to the NHC plane
(Φ2 = 74.7° for Pd-1 and Φ1 = 75.3° for Pd-2 in Table 1). The
rotation of the NHC N substitutents results in a significant
increase in the %Vbur value (37.0 for Pd-1 and 36.2 for Pd-2 in
Table 1) in comparison with the calculated %Vbur value of IPr
(31.3 for [IrCl(IPr)(CO)2]). Cazin and co-workers reported
that the [PdCl2(IPr){P(OMe)3}] precatalyst with the highest
%Vbur value of 36.3 exhibited an excellent reactivity for the
Suzuki−Miyaura reaction among several [PdCl2(IPr){P-
(OR)3}] precatalysts.7b Thus, [PdCl2(IPr)(briphos)] com-
plexes have some beneficial structural features that make them
effective cross-coupling catalytsts.
Ligand Effect for C−N Bond Coupling Reactions. To
investigate the synergistic ligand effect between IPr and
briphos ligands, we carried out a coupling reaction between 4-
chlorotoluene and morpholine11 with several [PdCl2(IPr)(L)]
(L = PCy3, PPh3, P(OPh)3, briphos L1−L4, 3-chloropyridine
(3-ClPy)) and [PdCl(IPr)(η3-cinnamyl)] complexes (Table
2). The coupling reactions were performed at 80 °C for 30 min
RESULTS AND DISCUSSION
■
Synthesis and Characterization of [PdCl2(IPr)-
(briphos)]. A series of NHC-Pd-briphos complexes were
prepared from a reaction between [Pd(μ-Cl)Cl(IPr)]2 (IPr =
1,3-bis(2,6-diisopropylphenyl)-1,3-dihydro-2H-imidazol-2-yli-
dene) and briphos ligands with various substituents. According
to the reported procedure7b for the preparation of [PdCl2(IPr)
L] (L = PPh3, P(OR)3), [PdCl2(IPr)(briphos)] complexes
were successfully prepared in 73−84% yields (Figure 1c). The
structure of [PdCl2(IPr)(L2)] was determined by X-ray
crystallographic analysis, as shown in Figure 2.10 Two
Table 2. Catalyst Screening with the [PdCl2(IPr)(L)]
a
Complexes
b
entry
L
R in briphos
yield (%)
Figure 2. ORTEP representation of [PdCl2(IPr)(L2)] with 50%
probability ellipsoids. The two conformationally different structures
Pd-1 and Pd-2 were found in the unit cell. Hydrogen atoms are
omitted for clarity.
1
2
3
4
5
6
7
8
9
PCy3
PPh3
P(OPh)3
L1
L2
L3
3
28
66
99
99
99
97
99
83
3,5-(CH3)2C6H3
Cy
Ph
conformationally different structures, Pd-1 and Pd-2, were
identified, and their structural parameters are given in Table 1.
L4
3,5-F2C6H3
3-ClPy
η3-cinnamyl
Table 1. %Vbur Values and Selected Bond Lengths (Å) and
Bond Angles (deg) for Pd-1 and Pd-2
c
a
Conditions unless specified otherwise: 4-chlorotoluene (0.250
Pd-1
37.0
24.2
Pd-2
36.2
23.6
mmol), morpholine (0.275 mmol), KOtBu (0.375 mmol), and
[PdCl2(IPr)(L)] (1 mol %) were stirred in 1,2-dimethoxyethane
(DME, 0.25 mL) at 80 °C for 0.5 h. Yield of the isolated product.
[PdCl(IPr)(L)].
%Vbur of IPr
%Vbur of L2
Φ1
b
c
86.3
75.3
Φ2
74.7
83.0
90° − Φav
Pd−C
Pd−P
9.5
10.9
in the presence of 1 mol % of the Pd complex and 1.5 equiv of
KOtBu. In the cases where L is PCy3, PPh3, or P(OPh)3, the
reaction with P(OPh)3 had a better conversion in comparison
to that with PCy3 or PPh3, indicating that a more π accepting
phosphorus ligand provides a beneficial catalytic activity
(entries 1−3, Table 2). Indeed, such a favorable ligand effect
between the σ-donating NHC ligands and π-accepting
phosphorus ligands has also been found in several cross-
coupling reactions such as Suzuki coupling,12 a coupling
between alkenes and aldehydes,13 and a coupling of aryl
diarylboronic acids or anhydrides with aryl halides.14 Because
we developed the briphos ligands as tunable π-accepting
phosphorus ligands, [PdCl2(IPr)(briphos)] complexes were
tested for Buchwald−Hartwig amination reactions. As shown
in Table 2, all of the NHC-Pd-briphos complexes showed an
excellent yield (>97%) and were found to be as efficient as a
PEPPSI catalyst (entries 4−8, Table 2). The complex
[PdCl(IPr)(η3-cinnamyl)] showed a reduced yield of 83%
(entry 9, Table 2). To closely compare the ligand effects, we
2.020(3)
2.2667(8)
2.2887(8)
2.2961(8)
176.58(8)
90.33(8)
89.35(8)
86.36(3)
93.98(3)
178.50(3)
2.021(3)
2.2655(8)
2.2898(8)
2.2939(8)
172.36(9)
89.90(8)
89.06(8)
89.17(3)
91.82(3)
178.90(3)
Pd−Cl(1)
Pd−Cl(2)
C−Pd−P
C−Pd−Cl(1)
C−Pd−Cl(2)
P−Pd−Cl(1)
P−Pd−Cl(2)
Cl(1)−Pd−Cl(2)
Consistent with the previous structures, IPr and briphos
ligands are coordinated to the Pd center in a trans fashion.
However, the C−Pd−P bonds are slightly bent: the C−Pd−P
bond angles in Pd-1 and Pd-2 were found to be 176.58(8) and
172.36(9)°, respectively. These bent structures may be
attributed to the highly rigid and unsymmetrical nature of
the briphos ligand. Indeed, the briphos ligand L2 enables one
B
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then did the coupling reaction with 0.1 mol % of Pd
precatalysts. As shown in Figure 3, the experimental results
Figure 3. Conversion for the C−N bond formation with a 0.1 mol %
catalyst loading (isolated yields are given).
Figure 4. Proposed catalytic cycle.
indicated that the briphos ligands substituted with the 3,5-
dimethylphenyl (L1) and cyclohexyl (L2) groups were slightly
more efficient than L3, L4, or P(OPh)3. When 0.05 mol % of
Pd precatalysts were used, L2 was found to be more efficient
than the other briphos ligands L1, L3, and L4 because the
conversions with L1−L4 were measured to be 26, 58, 21, and
29%, respectively (Figure S1 in the Supporting Information).
According to the literature and our previous studies on the
electronic properties of ligands,9e,15 the order of the π-
accepting ligand property can be given as L4 > L3 > L2 =
P(OPh)3 > L1 > PPh3 > PCy3. Thus, efficient NHC-Pd-L
precatalysts for Buchwald−Hartwig amination reactions can be
developed by optimizing the π-accepting ability of the
phosphorus ligands. Moreover, additional ligand properties
such as a steric effect related to the %Vbur value can be
considered because L2 (%Vbur = 36.2, 37.0)16 is more efficient
than P(OPh)3 (%Vbur = 34.3),7b albeit with the same π-
accepting property.
Our experimental results show a synergistic ligand effect
between NHC and phosphorus ligands in the NHC-Pd-L
complexes. To understand the role of the additional ligand L,
we monitored a stoichiometric reaction by following the
31P{1H} NMR spectra. When [PdCl2(IPr)(briphos)] was
mixed with the starting materials at ambient temperature, the
31P NMR spectra showed that the briphos ligand was
completely dissociated from the complex, indicating the
generation of the NHC-Pd(0) complex which has been
proposed as the active catalytic species.1−3 Although the
synthesis of the NHC-Pd0-PPh3 complex has been reported,17
we were unable to synthesize the NHC-Pd0-briphos complex
probably due to its instability. We then proposed that the
binding ability of the phosphorus ligands may be related to the
catalytic activity because the easily removable ligand would
provide the active NHC-Pd0 species more efficiently. Thus, we
did a competition experiment to determine the relative binding
ability of the phosphorus ligands. Our competition experiment
showed that the order of the ligand binding ability was found
to be PPh3 > L2 > P(OPh)3 > L3 > L1 = L4. Because L1 and
L2 were found to be highly efficient, the binding strength is not
directly correlated to the catalyst activity (see the Supporting
Information). Thus, the electronic property of the ligand, not
its binding ability, is the major factor that determines the
catalytic activity of the NHC-Pd-P precatalysts.
aryl chloride to form a Pd(II) intermediate. Then, subsequent
processes such as the coordination of amine, deprotonation,
and reductive elimination occur to give the desired cross-
coupled product and NHC-Pd0 catalyst. In this catalytic cycle,
we propose that phosphorus ligand L can associate with the Pd
intermediates and dissociate to complete the catalytic reaction.
The role of the briphos ligands would be the stabilization of
the Pd intermediates to maintain the catalytic activity of the Pd
catalyst.
Reaction Scope for the C−N Bond Coupling
Reactions. Our results of the catalyst screening suggest that
[PdCl2(IPr)(L2)] is the most efficient among the NHC-Pd-L
catalysts. With this highly efficient catalyst [PdCl2(IPr)(L2)],
we have expanded the reaction scope to achieve several types
of C−N bond formations. Under our optimized reaction
conditions, 1.1 equiv of primary or secondary amine, 1.0 equiv
of aryl chloride, and 1 mol % of [PdCl2(IPr)(L2)] were mixed
in 1,2-dimethoxyethane (DME, 1 M) at 80 °C for 1 h. As
shown in Figure 5, most of the reactions proceeded to
completion to afford the desired coupled products in good
yields. In the case of morpholine (1−11), aryl chlorides with
various substituents such as methyl, methoxy, trifuloromethyl,
and cyano groups were used to provide the desired N-aryl
morpholines in good yields (87−99%) except for 2-
(fluorophenyl)morpholine (11, 53% yield). Other secondary
amines such as N-methylpiperazine, pyrrolidine, piperidine,
and diisooctylamine were successfully coupled with aryl
chlorides in good to excellent yields (80−96%) (12−17). In
addition, primary alkyl amines (18 and 19), 2,4,6-trimethylani-
line (20−22), and 2,6-diisopropylaniline (23) gave the desired
products in good yields (76−99%). Particularly, more
challenging reactions using aniline (24 and 25) and 4-
fluoroaniline (26) with aryl chlorides19 proceeded with high
yields, although an increased reaction time of 24 h and
temperature of 100 °C were required.
We have demonstrated that π-acceptor briphos ligands can
be combined with the NHC ligand in Pd-catalyzed Buchwald−
Hartwig amination reactions to develop highly efficient
catalysts. These types of synergistic ligand effects can be
applied to other Pd-catalyzed cross coupling reactions. As
shown in Figure 6, we compared the catalytic activities of the
NHC-Pd-L complexes in both the Buchwald−Hartwig reaction
and Suzuki−Miyaura reaction. In both reactions, 4-chloroto-
luene was used as the substrate. Interestingly, the catalyst
[PdCl2(IPr)(L)] showed quite different reaction outcomes.
While the catalyst [PdCl2(IPr)(L1)] was highly efficient in
both reactions, the catalyst [PdCl2(IPr)(L2)] or [PdCl2(IPr)-
On the basis of our experimental results, we propose a
catalytic cycle, as shown in Figure 4. Closely related to the
Organ model,18 the NHC-Pd0 species generated from the
NHC-Pd-L precursors is the active catalyst, which reacts with
C
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Figure 6. Reactivity comparison of the [PdCl2(IPr)(L)] complexes.
Suzuki−Miyaura reaction conditions: 4-chlorotoluene (0.250 mmol),
phenylboronic acid (0.262 mmol), KOtBu (0.375 mmol), and
[PdCl2(IPr)(L)] (1 mol %) were stirred in ethanol (EtOH, 0.500
mL) at room temperature for 1 h. The GC yields were calculated from
the averages of three runs.
The briphos ligand is an excellent ligand platform to
systematically investigate the synergistic ligand effect with
NHC ligand because the steric and electronic properties of
briphos can be readily modified and the reaction intermediates
can be identified by 31P{1H} NMR analysis. The concept of
the synergistic ligand effect may be applied to transition-metal-
catalyzed reactions, and thus briphos and NHC can be a useful
combination to develop highly efficient transition-metal
catalysts.
Figure 5. Scope for the [PdCl2(IPr)(L2)]-catalyzed C−N bond
formation. Conditions: aryl chloride (0.250 mmol), amine (0.275
mmol), KOtBu (0.375 mmol), and [PdCl2(IPr)(L2)] (1 mol %) were
stirred in DME (0.250 mL) at 80 °C for 1 h. For the synthesis of 11
and 24−26, the reaction was performed in 1,4-dioxane (0.250 mL) at
100 °C for 24 h. Isolated yields are shown.
EXPERIMENTAL SECTION
■
General Information. Commercially available compounds were
used without further purification or drying. The 1H NMR (400
MHz), 13C NMR (100 MHz), 19F NMR (376 MHz), and 31P NMR
(162 MHz) spectra were recorded on a Bruker Ascend 400 or a
Bruker Advance III HD spectrometer. The high-resolution mass
spectra (EA) were obtained on a Thermo Scientific FLASH 2000
series. GC analysis was performed on an Agilent 7890A instrument
using an HP-5 column (length 30 m, diameter 0.320 mm, film 0.25
μm).
{P(OPh)3}] was efficient only in the Buchwald−Hartwig
amination or Suzuki−Miyaura reaction, respectively.
CONCLUSIONS
■
We have demonstrated a synergistic ligand effect between
NHC and briphos ligands in Pd-catalyzed Buchwald−Hartwig
amination reactions. In our reaction screening, the optimal π-
accepting ligand L2 was found to be the most efficient among
the phosphorus ligands tested. The catalytic performance of
the NHC-Pd-L precatalysts for Buchwald−Hartwig amination
reactions depends on the steric and electronic properties of the
phosphorus ligand (L), not on the binding ability of the ligand.
We have shown that [PdCl2(IPr)(L2)] is a highly efficient
precatalyst for the coupling of primary or secondary amines
with aryl chlorides with high yields under mild reaction
conditions. Moreover, [PdCl2(IPr)(L1)] is found to be only
effective for both C−N and C−C bond forming cross
couplings. The reaction mechanism was proposed on the
basis of in situ 31P{1H} NMR analysis and competition
experiments.
Procedure for Synthesis of [PdCl2(IPr){briphos(R)}]. To a
20
stirred solution of [Pd(μ-Cl)Cl(IPr)]2 (0.29 mmol) in CH2Cl2 (6
mL) was added briphos(R)9 (0.58 mmol). The resulting solution was
stirred for 30 min at room temperature under a nitrogen atmosphere
and then concentrated in vacuo. Addition of pentane led to a
precipitate, which was filtered and dried under vacuum to afford the
desired product as a pale yellow powder (73−84%).
[PdCl2(IPr)(L1)], L1 = briphos(3,5-(CH3)2C6H3). Pale yellow powder
1
(81% yield). H NMR (400 MHz, CDCl3): δ (ppm) 7.46 (m, 2H),
7.26 (m, 4H), 7.11 (m, 2H), 7.00 (m, 6H), 6.90 (m, 2H), 6.63 (m,
1H), 6.55 (m, 2H), 5.15 (d, J = 8.6 Hz, 1H), 3.03 (m, 4H), 2.04 (s,
6H), 1.32 (d, J = 6.6 Hz, 12H), 1.05 (d, J = 6.9 Hz, 12H). 13C{1H}
NMR (100 MHz, CDCl3): δ (ppm) 169.2, 166.3, 149.8, 149.7, 146.6,
142.2, 142.1, 138.5, 135.0, 130.2, 129.1, 128.4, 127.0, 126.9, 126.6,
125.2, 125.1, 124.8, 124.7, 123.9, 123.2, 119.4, 119.3, 61.7, 28.7, 26.4,
23.2, 21.4. 31P{1H} NMR (162 MHz, CDCl3): δ (ppm) 81.0. Anal.
D
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Calcd for C48H54Cl2N3O2PPd: C, 63.13; H, 5.96; N, 4.60. Found: C,
62.89; H, 6.03; N, 4.44.
AUTHOR INFORMATION
Corresponding Author
*E-mail for H.K.: hwkim@kaist.edu.
ORCID
Hyunwoo Kim: 0000-0001-5030-9610
Notes
The authors declare no competing financial interest.
■
[PdCl2(IPr)(L2)], L2 = briphos(Cy). Pale yellow powder (73%
yield). 1H NMR (400 MHz, CDCl3): δ (ppm) 7.49 (m, 2H), 7.36 (m,
4H), 7.10 (m, 2H), 7.05 (m, 4H), 6.89 (m, 4H), 4.99 (d, J = 9.7 Hz,
1H), 3.52 (m, 1H), 3.16 (m, 4H), 1.48−1.39 (m, 5H), 1.45 (d, J = 6.7
Hz, 12H), 1.16−1.07 (m, 2H), 1.12 (d, J = 6.9 Hz, 12H), 0.87 (m,
3H). 13C{1H} NMR (100 MHz, CDCl3): δ (ppm) 170.1, 167.2,
150.5, 150.4, 146.8, 135.3, 130.2, 128.8, 128.2, 128.1, 126.0, 124.7,
124.7, 124.2, 123.0, 119.4, 119.3, 58.1, 58.0, 51.7, 32.4, 32.3, 28.8,
26.4, 25.3, 23.4. 31P{1H} NMR (162 MHz, CDCl3): δ (ppm) 87.3.
Anal. Calcd for C46H56Cl2N3O2PPd: C, 61.99; H, 6.33; N, 4.71.
Found: C, 61.63; H, 6.26; N, 4.59.
[PdCl2(IPr)(L3)], L3 = briphos(Ph). Pale yellow powder (84%
yield). 1H NMR (400 MHz, CDCl3): δ (ppm) 7.54 (m, 2H), 7.34 (m,
4H), 7.14−6.81 (m, 15H), 5.39 (d, J = 8.3 Hz, 1H), 3.07 (m, 4H),
1.33 (d, J = 6.6 Hz, 12H), 1.06 (d, J = 6.9 Hz, 12H). 13C{1H} NMR
(100 MHz, CDCl3): δ (ppm) 168.9, 166.0, 149.9, 149.8, 146.8, 142.7,
142.6, 135.2, 130.2, 129.2, 129.2, 127.0, 126.9, 126.4, 125.0, 124.9,
124.8, 124.7, 124.6, 124.2, 123.5, 119.4, 119.4, 60.5, 28.7, 26.4, 23.3.
31P{1H} NMR (162 MHz, CDCl3): δ (ppm) 80.8. Anal. Calcd for
C46H50Cl2N3O2PPd: C, 62.41; H, 5.69; N, 4.75. Found: C, 62.13; H,
5.56; N, 4.58.
ACKNOWLEDGMENTS
■
The authors are grateful for the financial support provided by
the C1 Gas Refinery Program (2016M3D3A1A01913256) and
the National Research Foundation of Korea
(2017R1A2B4002650). The authors thank Dr. Alan J. Lough
(University of Toronto) for his X-ray analysis.
REFERENCES
■
(1) For selected reviews, see: (a) Zhao, D.; Candish, L.; Paul, D.;
Glorius, F. N-Heterocyclic Carbenes in Asymmetric Hydrogenation.
ACS Catal. 2016, 6, 5978−5988. (b) Clavier, H.; Nolan, S. P. Percent
Buried Volume for Phosphine and N-heterocyclic Carbene Ligands:
Steric Properties in Organometallic Chemistry. Chem. Commun. 2010,
46, 841−861. (c) Kantchev, E. A. B.; O’Brien, C. J.; Organ, M. G.
Palladium Complexes of N-Heterocyclic Carbenes as Catalysts for
Cross-Coupling ReactionsA Synthetic Chemists Perspective.
Angew. Chem., Int. Ed. 2007, 46, 2768−2813.
[PdCl2(IPr)(L4)], L4 = briphos(3,5-F2C6H3). Pale yellow powder
1
(84% yield). H NMR (400 MHz, CDCl3): δ (ppm) 7.49 (m, 2H),
7.31 (m, 4H), 7.15 (m, 2H), 7.06−6.93 (m, 8H), 6.55 (m, 2H), 6.44
(m, 1H), 5.26 (d, J = 7.8 Hz, 1H), 3.05 (m, 4H), 1.37 (d, J = 6.6 Hz,
12H), 1.08 (d, J = 6.9 Hz, 12H). 13C{1H} NMR (100 MHz, CDCl3):
δ (ppm) 168.2, 165.3, 163.8, 161.5, 161.3, 149.6, 149.4, 146.5, 145.2,
134.8, 130.3, 129.5, 126.5, 126.3, 126.2, 124.9, 124.8, 124.0, 123.8,
119.5, 119.4, 110.0, 109.9, 109.7, 102.1, 101.9, 61.3, 28.7, 26.4, 23.2.
31P{1H} NMR (162 MHz, CDCl3): δ (ppm) 80.0. 19F{1H} NMR
(376 MHz, CDCl3): δ (ppm) −107.5. Anal. Calcd for
C46H48Cl2F2N3O2PPd: C, 59.98; H, 5.25; N, 4.56. Found: C, 59.78;
H, 5.38; N, 4.38.
General Procedure for the Amination of Aryl Chlorides. In a
nitrogen-filled glovebox, a mixture of [PdCl2(IPr)(L2)] (0.0025
mmol, 1 mol %), aryl chloride (0.250 mmol), and 1,2-dimethoxy-
ethane (DME, 0.250 mL) was placed in a screw-capped glass tube
containing a magnetic stirring bar. After the solution was stirred for 5
min, amine (0.275 mmol) and KOtBu (0.375 mmol) were added
successively. The tube was sealed and removed from the glovebox.
The resulting mixture was stirred at 80 °C for 1 h. After the mixture
was cooled to room temperature, the volatiles were evaporated under
reduced pressure. Purification by flash column chromatography on
silica gel with diethyl ether/pentane (1/50 to 1/10) as eluent gave the
desired products (1−26). For the synthesis of 11 and 24−26, 1,4-
dioxane was used as the solvent and the mixture was stirred at 100 °C
for 24 h. Compounds 1−26 have all been reported (see the
Supporting Information).
́
́
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Experimental and spectroscopic data and crystallo-
graphic details (PDF)
Accession Codes
CCDC 1539245 contains the supplementary crystallographic
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 Cam-
bridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
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Organometallics XXXX, XXX, XXX−XXX