[Pd(IPr*)(acac)CI]: An easily synthesized, bulky precatalyst for C-N bond formation

Article abstract of DOI:10.1021/om300205c

A very straightforward synthesis of [Pd(IPr*)(acac)Cl] has been developed from commercially available Pd(acac)₂ and the easily prepared IPr*·HCl (acac = acetylacetonate; IPr* = N,N′-bis(2,6-bis(diphenylmethyl)-4-methylphenyl)imidazol-2-ylidene). The reactivity of the resulting complex [Pd(IPr*)(acac)Cl] (1) as a highly active Pd^II precatalyst for the Buchwald-Hartwig arylamination coupling has been explored. A wide range of substrates with varying electronic and steric demands of both coupling partners has been screened successfully. The chemoselectivity of the reaction was also explored by using aryl heterodihalides.

Full text of DOI:10.1021/om300205c

Article
pubs.acs.org/Organometallics
[Pd(IPr*)(acac)Cl]: An Easily Synthesized, Bulky Precatalyst for C−N
Bond Formation
Sebastien Meiries, Anthony Chartoire, Alexandra M. Z. Slawin, and Steven P. Nolan*
EaStCHEM School of Chemistry, University of St. Andrews, St. Andrews KY16 9ST, U.K.
S
* Supporting Information
ABSTRACT: A very straightforward synthesis of [Pd(IPr*)(acac)Cl] has been developed from commercially available
Pd(acac)2 and the easily prepared IPr*·HCl (acac = acetylacetonate; IPr* = N,N′-bis(2,6-bis(diphenylmethyl)-4-methylphenyl)-
imidazol-2-ylidene). The reactivity of the resulting complex [Pd(IPr*)(acac)Cl] (1) as a highly active PdII precatalyst for the
Buchwald−Hartwig arylamination coupling has been explored. A wide range of substrates with varying electronic and steric
demands of both coupling partners has been screened successfully. The chemoselectivity of the reaction was also explored by
using aryl heterodihalides.
of the IPr* ligand onto palladium was achieved through a facile
ligand exchange between IPr*·HCl and Pd(acac)2 as described
in the literature3m and afforded [Pd(IPr*)(acac)Cl] (1) as a
well-defined compound (Scheme 1).
INTRODUCTION
■
Palladium-catalyzed arylamination has become an important and
widely employed method for the formation of C−N bonds.1 In
comparison to reports of phosphine-based ligands2 commonly
used for this reaction, considerably fewer studies have appeared
using N-heterocyclic carbene (NHC) based ligands.1d,3 However,
unlike their phosphine analogues, Pd-NHC complexes are now
well-known for their significant air and moisture stability, which
renders them very user friendly. Their catalytic activity for the
oxidative addition of aryl halides is related to their strong σ-
donating properties.4 Their steric hindrance also facilitates
reductive elimination and presumably helps stabilize the Pd-
centered 12-electron reactive intermediate.5 Sterically demanding
ancillary ligands can kinetically stabilize highly reactive low-valent
transition metals and permit high catalytic activity.6 Spectacular
reactivity was attributed to a “flexible steric bulk” in which the
ligands can adjust toward incoming substrates, while enabling the
stabilization of a low-valent active intermediate.7 Similarly, bulky
NHCs, in which the carbene center sits in the middle of a large
bowl-shaped cavity, have also provided interesting results.8 In this
context, the bulky precatalyst [Pd(IPr)(acac)Cl] developed by
Nolan et al.3m proved to be very efficient for the catalytic
Buchwald−Hartwig arylamination reaction. In an effort to test
whether more sterically demanding ligands would lead to
improved catalytic performance, the preparation of the bulkier
[Pd(IPr*)(acac)Cl] and a subsequent study of its catalytic
reactivity in arylamination is reported here.
Compound 1 proved to be both air- and moisture-stable, and
suitable crystals for X-ray diffraction were successfully grown by
slow diffusion of hexane into a saturated C6D6 solution of the
complex (Figure 1).10 The Pd1−C1 bond length is longer than
in the case of the [Pd(IPr)(acac)Cl] analogue3q (2.019(10) Å
for 1 and 1.9694(17) Å for [Pd(IPr)(acac)Cl]). This
presumably is due to the high steric hindrance brought about
by the IPr* ligand. On the other hand, the Pd−O and Pd−Cl
bond lengths are quite similar to those for the [Pd(IPr)(acac)-
Cl] complex. The structure of 1 adopts a slightly distorted
square planar geometry. Finally, the percent buried volume of
IPr* in the Pd system was calculated using the web application
SambVca.11 Unsurprisingly, with a percent buried volume of
42.2%,12 IPr* was found to be larger than IPr (%VBur
=
34.7%)13 in the [Pd(NHC)(acac)Cl] motif.
The catalytic properties of 1 in Buchwald−Hartwig
arylamination were explored by screening several base/solvent
systems (Table 1). The results gave preliminary guidelines
showing that several bases (NaOtBu, KOH, NaOH, Cs2CO3,
K3PO4) were inefficient for the coupling. The nature of the
solvent proved to have a minor effect on the conversion of the
reaction but was important for the complete dissolution of both
precatalyst 1 and the base. Comparable efficiencies were
obtained with potassium tert-amylate, potassium tert-butoxide,
RESULTS AND DISCUSSION
■
Multigram quantities of IPr*·HCl were successfully prepared as
Received: March 13, 2012
Published: March 26, 2012
described by Marko
́
et al. (Scheme 1).9 Ultimately, the binding
© 2012 American Chemical Society
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Scheme 1. Synthesis of [Pd(IPr*)(acac)Cl]
shown in Table 2. These preliminary data clearly demonstrated
that the catalytic arylamination displayed the best efficiency with
the system LiHMDS/1,4-dioxane14 (entries 3, 6, 9, and 12) and
further studies were conducted with this optimized system
(Tables 3 and 4).
The catalyst loading, the reaction time, and the temperature
of the reaction were thoroughly screened by using a
combination of sterically and electronically demanding
substrates. A first set of reactions was conducted with 1.0
mol % catalyst 1 at room temperature (Table 3), allowing for
the coupling to proceed with great efficiency in short reaction
times.15 Under these conditions, the couplings of hindered
substrates (entries 1 and 5), deactivated aryl halides (entries 3
and 6), and heterocyclic halides (entries 2 and 4) were
successfully achieved. However, less reactive and more hindered
substrates gave only modest conversions after 18 h using these
particular conditions.
A simple increase in temperature had a dramatic effect on the
efficiency of the amination, permitting the coupling of more ch-
allenging substrates that failed under milder conditions (Table 4).
More rapid conversions16 and good to excellent isolated yields
were obtained for various substrates at lower catalyst loadings. A
first scope was conducted at 50 °C (Table 4) and enabled us to
highlight the excellent catalytic activity of 1 for the coupling of
reasonably challenging bromides (entries 1−3). However, at the
same temperature, aryl chlorides (entries 6−8) required higher
catalyst loading (1.0 mol %) to be successfully coupled.
Figure 1. Molecular structure of 1. Hydrogens have been omitted for
clarity. Selected bond lengths (Å) and angles (deg): Pd1−C1,
2.019(10); Pd1−O73, 2.043(7); Pd1−O75, 2.063(7); Pd1−Cl1,
2.282(3); C1−Pd1−O73, 92.2(3); O73−Pd1−O75, 92.9(3); C1−
Pd1−Cl1, 88.2(3); O75−Pd1−Cl1, 86.7(2).
and lithium bis(trimethylsilyl)amide, depending on the solvent
used (Table 1, entries 1, 4, and 9).
Although lower catalyst loadings and lower temperatures
could be successfully used with various coupling partners, the
selected optimized conditions (0.4 mol % of catalyst loading at
110 °C in 1,4-dioxane) were generally applied to a wide
number of substrates (Table 5). Hindered aryl halides (entries
4, 6, and 8) and amines (entries 3, 5, 6, 8, and 10) were
successfully coupled under these conditions. Heterocyclic
(entries 9 and 10), electron-rich (entries 7 and 8), and
electron-deficient (entries 11 and 12) aryl halides also proved
to be suitable partners. The demonstrated reactivity is on par
with that of Pd-PEPPSI-IPent3j,17 catalyst. An important
example is the good isolated yield obtained for the challenging
coupling of both sterically and electronically disfavored
2-chloro-5-methoxy-1,3-dimethylbenzene with the very hindered
2,6-diisopropylaniline under these conditions (Table 5, entry 8).
However, it is to be noted that methyl halobenzoates failed to
couple with amines, as the undesired amidation reaction first
occurred.
Table 1. First Screening of Base/Solvent System for
Amination with [Pd(IPr*)(acac)Cl]
a
b
entry
solvent
toluene
base
GC conversn (%)
1
2
3
4
5
6
7
8
9
KOtAm
KOtAm
KOtAm
KOtBu
KOtBu
KOtBu
37
5
dimethoxyethane
1,4-dioxane
toluene
10
45
5
dimethoxyethane
1,4-dioxane
toluene
17
21
34
37
LiHMDS
LiHMDS
LiHMDS
dimethoxyethane
1,4-dioxane
a
Reagents and conditions: 4-chloroanisole (0.50 mmol), morpholine
The Buchwald−Hartwig arylamination is a very powerful
synthetic tool for the preparation of a wide range of biologically
active molecules.18 However, its synthetic applications could be
significantly increased if the reaction could be applied in a
completely chemoselective manner. This aspect is underex-
plored in the literature,3a,19 and therefore we proposed
examining the reactivity of several aryl groups bearing
heterodihalides (Table 6). Excellent selectivities were obtained
(0.55 mmol), Pd precatalyst 1 (0.50 mol %), solvent (0.5 mL), base
(0.55 mmol), room temperature, 24 h. Conversion to coupling
product based on starting aryl halide determined by GC.
b
To further determine the optimal base/solvent system, each set
of conditions (Table 1, entries 1, 4, and 9) was used in the
coupling of other challenging aryl halides with N-morpholine, as
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a
Table 2. Further Screening toward Optimized Conditions
a
Table 3. Arylamination Reactions at Room Temperature
CONCLUSION
■
The utility of [Pd(IPr*)(acac)Cl] (1) as an easily synthesized
and well-defined precatalyst has been highlighted for the
arylamination of various substrates. Beyond its air and moisture
stability and its easy preparation,20 this very bulky NHC-
bearing precatalyst can be efficiently used for the coupling of
sterically and electronically challenging substrates with useful
chemoselectivity when heterodihalides are employed. In some
cases, [Pd(IPr*)(acac)Cl] (1) appears to have catalytic activity
similar to that of its earlier generation [Pd(IPr)(acac)Cl]
congener.21 Nevertheless, it was also successfully employed for
a much wider range of coupling substrates at lower catalyst
loadings or lower temperatures.
EXPERIMENTAL SECTION
■
All aryl halides and amines were used as purchased, except for 2-
chloro-5-methoxy-1,3-dimethylbenzene (Table 5, entry 8), which was
prepared by methylation of the corresponding 4-chloro-3,5-dimethyl-
phenol. Anhydrous 1,4-dioxane and toluene and the bases (NaOtBu,
KOtBu, Na2CO3, K3PO4, Cs2CO3, K2CO3, NaOH, KOH) were used
as received and stored in a glovebox. 1,2-Dimethoxyethane (DME)
was distilled on sodium/benzophenone, degassed, and stored in a
glovebox. Pd(acac)2 was purchased from UMICORE and stored under
atmospheric conditions. Flash column chromatography was performed
a
Reagents and conditions: aryl halide (0.50 mmol), amine (0.55
mmol), Pd precatalyst 1 (1.0 mol %), 1,4-dioxane (0.5 mL), LiHMDS
b
(0.55 mmol), room temperature. Isolated yield after chromatography
c
d
on silica gel; average of two runs. Reaction time of 3 h. Reaction
1
on silica gel with 60 Å pore diameter and 40−63 μm particle size. H
e
time of 18 h. Chloronaphtalene was purchased and used as a mixture
and 13C nuclear magnetic resonance (NMR) spectra were recorded on
a Bruker 400 or 300 MHz spectrometer at ambient temperature in
CDCl3 without TMSCl as internal standard. NMR peaks were
assigned by using COSY and HSQC experiments, except in the case of
[Pd(IPr*)(acac)Cl] (1), where an HMBC experiment was necessary.
Elemental analyses were performed at London Metropolitan
University, 166−220 Holloway Road, London N7 8DB, U.K. High-
resolution mass spectrometry was performed by the EPSRC National
Mass Spectrometry Service Centre (NMSSC), Grove Building Extn.,
Swansea University, Singleton Park, Swansea SA2 8PP, U.K.
of 1- and 2-isomers and resulted in the isolation of the corresponding
cross-product as a separable 9.6:1 mixture of isomers that were fully
characterized.
for the coupling of chloroiodo (entry 1) and bromochloro aryls
(entries 2−6) with diverse amines. In each case only a single
adduct was detected with excellent GC conversions and iso-
lated with good to excellent yields. Surprisingly, no coup-
ling was observed between p-bromoiodobenzene and
2,6-dimethylaniline. Other substrates such as 2,3- and 2,4-
dichlorotoluenes were also subjected to the same conditions to
determine the influence of the methyl group on the selectivity of
the reaction. Although couplings occurred at both positions with
some encouraging selectivities, inseparable mixtures of isomers
were obtained.
Procedure for the Synthesis of [Pd(IPr*)(acac)Cl] (1). In a
Schlenk flask equipped with a magnetic stirring bar were added
IPr*·HCl (950 mg, 1.00 mmol) and Pd(acac)2 (225 mg, 0.74 mmol)
in dry 1,4-dioxane (15 mL) under an atmosphere of nitrogen. The
reaction mixture was then refluxed for 24 h. This time has not yet been
optimized. After this time, dioxane was evaporated, the crude product
was dissolved in DCM, the solution was filtered on a pad of silica
covered with Celite, and the pad was eluted with DCM. After
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a
Table 4. Arylamination Screening of Various Substrates with 0.2−1.0 mol % of [Pd(IPr*)(acac)Cl] at 50 °C
a
b
Reagents and conditions: aryl halide (0.50 mmol), amine (0.55 mmol), 1,4-dioxane (0.5 mL), LiHMDS (0.55 mmol), 50 °C. Isolated yield after
c
d
e
chromatography on silica gel; average of two runs. Reaction time of 3 h. Reaction time of 18 h. Reaction time of 43 h.
evaporation of the solvents, the complex was triturated with pentane,
and then the supernatant was decanted. After drying under high
vacuum, the pure complex was obtained as a yellow powder (811 mg,
17.6 (CH3), 18.2 (2 × CH3), 111.7 (CHAr), 118.1 (CHAr), 122.3
(CIVAr), 125.5 (CHAr), 126.9 (CHAr), 128.5 (CHAr), 130.2 (CHAr),
135.5 (CIVAr), 138.7 (CIVAr), 144.1 (CIVAr).
1
95%). H NMR (400 MHz, CDCl3): δ 7.26−7.00 (m, 32H, HAr),
N-Methyl-N-phenylpyridin-2-amine (Table 3, Entries 2 and 4;
Table 4, Entries 4 and 5). The general procedure yielded the pure
arylamine as a yellow oil. Data were in full agreement with those
reported in the literature.2,23 1H NMR (400 MHz, CDCl3): δ 3.49
(3H, s, CH3), 6.54 (1H, dt, J = 8.7, 0.8 Hz, CHpyr), 6.59 (1H, ddd, J =
6.9, 4.9, 0.8 Hz, CHpyr), 7.17−7.30 (4H, m, CHpyr + CHAr), 7.35−7.41
(2H, m, CHAr), 8.26 (1H, ddd, J = 5.1, 2.1, 1.0 Hz, 3-CHpyr). 13C{1H}
NMR (100 MHz, CDCl3): δ 38.1 (N−CH3), 108.9 (CHpyr), 112.9
(CHpyr), 125.1 (CHAr), 126.0 (CHAr), 129.4 (CHAr), 136.3 (CHpyr),
146.6 (CIVAr), 147.6 (CHpyr), 158.6 (2-CIVpyr).
6.84−6.69 (m, 12H, HAr), 5.87 (s, 4H, CH), 5.10 (s, 1H, CHacac), 4.93
(s, 2H, CHIm), 2.24 (s, 6H, CH3), 2.06 (s, 3H, CH3acac), 0.72 (s, 3H,
CH3acac). 13C{1H} NMR (100 MHz, CDCl3): δ 186.9 (C−Oacac),
185.5 (C−Oacac), 154.7 (NCN), 144.0 (CAr), 142.4 (CAr), 139.0 (CAr),
135.2 (CAr), 130.8 (CAr, b), 129.7 (CAr), 128.2 (CAr), 127.9 (CAr),
126.4 (CAr), 126.2 (CAr), 124.4 (CHIm), 100.3 (CHacac), 50.9 (CH),
27.3 (CH3acac), 26.3 (CH3acac), 21.8 (CH3). Anal. Calcd for
C74H63ClN2O2Pd: C, 77.01; H, 5.50; N, 2.43. Found: C, 77.16; H,
5.41; N, 2.36.
4-(4-Methoxyphenyl)morpholine (Table 3, Entries 3 and 6; Table 4,
Entry 3; Table 5, Entry 7). The general procedure yielded the pure
arylamine as a white solid. Data were in full agreement with those
reported in the literature.3j,24 1H NMR (400 MHz, CDCl3): δ 3.01
(4H, m, 2 × N−CH2), 3.74 (3H, s, O−CH3), 3.82 (4H, m, 2 × O−
CH2), 6.86 (4H, m, HAr). 13C{1H} NMR (100 MHz, CDCl3): δ 50.3
(2 × N−CH2), 55.0 (O−CH3), 66.6 (2 × O−CH2), 114.0 (CHAr),
117.3 (CHAr), 145.3 (N−CIVAr), 153.5 (O−CIVAr).
Buchwald−Hartwig Cross-Coupling of Aryl Halides with
Primary and Secondary Amines: General Procedure. In a
glovebox,22 a glass vial was charged with LiHMDS (0.55 mmol),
equipped with a magnetic stir bar, and sealed with a screw cap fitted
with a septum. The vial was then loaded with the neat amine (0.55
mmol) and the aryl halide (0.50 mmol) outside the glovebox. Finally, a
premade solution of [Pd(IPr*)(acac)Cl] (1) in anhydrous solvent
(prepared in a glovebox)22 was subsequently injected at room
temperature under argon, and the reaction mixture was stirred until
completion, as indicated by GC chromatography. After the reaction
reached completion, the mixture was diluted with a minimum amount
of dichloromethane and directly loaded onto silica gel to be purified by
flash column chromatography (silica gel, diethyl ether in pentane).
The reported yields are the results of two runs. In the case of solid
starting materials, the solid was quickly added to the vial containing
LiHMDS outside the glovebox and the vial was purged using classical
Schlenk techniques.
2,6-Dimethyl-N-(o-tolyl)aniline (Table 3, Entry 1; Table 4, Entry 6;
Table 5, entry 3). The general procedure yielded the pure arylamine as
a white solid. Data were in full agreement with those reported in the
literature.3m 1H NMR (400 MHz, CDCl3): δ 2.34 (6H, s, 2 × CH3),
2.48 (3H, s, CH3), 5.06 (1H, bs, NH), 6.32 (1H, dd, J = 7.6, 1.0 Hz,
HAr), 6.86 (1H, td, J = 7.6, 1.0 Hz, HAr), 7.12 (1H, td, J = 8.0, 1.3 Hz,
HAr), 6.20−6.30 (4H, m, HAr). 13C{1H} NMR (100 MHz, CDCl3): δ
4-(Naphthalen-1-yl)morpholine (Table 3, Entry 5). The general
procedure yielded the pure arylamine as a separable mixture of two
isomers (154 mg, 72% and 16 mg, 8%) as white and pinkish solids,
respectively. Data were in full agreement with those reported in the
literature for both isomers.24a,25 1H NMR (400 MHz, CDCl3): δ 3.15
(4H, app t, J = 4.6 Hz, 2 × N−CH2), 4.03 (4H, app t, J = 4.6 Hz, 2 ×
O−CH2), 7.13 (1H, dd, J = 7.4, 0.8 Hz, 2-CHAr), 7.47 (1H, app t, J =
8.2 and 7.4 Hz, 3-CHAr), 7.50−7.59 (2H, m, 7-CHAr + 8-CHAr), 7.64
(1H, d, J = 8.2 Hz, 4-CHAr), 7.90 (1H, m, 6-CHAr), 8.30 (1H, m, 9-
CHAr). 13C{1H} NMR (100 MHz, CDCl3): δ 53.4 (2 × N−CH2),
67.3 (2 × O−CH2), 114.6 (CHAr), 123.3 (CHAr), 123.7 (CHAr), 125.4
(CHAr), 125.8 (CHAr), 128.4 (CHAr), 128.7 (CIVAr), 134.7 (CIVAr),
149.3 (N−CIVAr).
4-(Naphthalen-2-yl)morpholine (Table 3, Entry 5). 1H NMR (400
MHz, CDCl3): δ 3.28 (4H, app t, J = 4.8 Hz, 2 × N−CH2), 3.93 (4H,
app t, J = 4.8 Hz, 2 × O−CH2), 7.14 (1H, d, J = 2.6 Hz, 2-CHAr), 7.27
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a
Table 5. Arylamination using [Pd(IPr*)(acac)Cl] at 110 °C
Table 6. Chemoselective Arylamination of Various
Dihalides
a
a
Reagents and conditions: aryl dihalide (0.50 mmol), amine (0.55
mmol), 1,4-dioxane (0.5 mL), LiHMDS (0.55 mmol), Pd precatalyst 1
b
(0.4 mol %), 110 °C. Isolated yield after chromatography on silica
c
d
gel, average of two runs. Reaction time of 3 h. Reaction time of 18 h.
agreement with those reported in the literature.2q 1H NMR (400
MHz, CDCl3): δ 2.25 (6H, s, CH3), 3.31 (3H, s, N−CH3), 6.57 (2H,
vbs, HAr), 6.82 (1H, app tt, J = 7.2, 1.0 Hz, HAr), 7.27−7.33 (5H, m,
HAr). 13C{1H} NMR (100 MHz, CDCl3): δ 17.9 (CH3), 36.9 (N−
CH3), 110.8 (CHAr), 115.9 (CHAr), 126.8 (CHAr), 128.8 (CHAr),
129.1 (CHAr), 137.7 (Me-CIVAr), 144.0 (N−CIVAr), 148.0 (N−CIVAr).
4-(2-Methoxyphenyl)morpholine (Table 4, Entry 6). The general
procedure yielded the pure arylamine as a colorless oil. Data were in
full agreement with those reported in the literature.2 1H NMR (400
MHz, CDCl3): δ 3.08 (4H, m, 2 × N−CH2), 3.87 (3H, s, OCH3),
3.90 (4H, m, 2 × O−CH2), 6.87−6.90 (1H, m, HAr), 6.93−6.95 (2H,
m, HAr), 7.00−7.06 (2H, m, HAr). 13C{1H} NMR (100 MHz, CDCl3):
δ 51.0 (N−CH2), 55.2 (CH3), 67.0 (O−CH2), 111.1 (CHAr), 117.8
(CHAr), 120.9 (CHAr), 123.0 (CHAr), 141.0 (O−CIVAr), 152.1 (N−
CIVAr).
a
Reagents and conditions: aryl halide (0.50 mmol), amine (0.55
mmol), Pd precatalyst 1 (0.4 mol %), 1,4-dioxane (0.5 mL), LiHMDS
(0.55 mmol), 110 °C. Isolated yield after chromatography on silica
gel; average of two runs. Reaction time of 3 h. Reaction time of 18 h.
b
c
d
4-(p-Tolyl)morpholine (Table 5, Entries 2 and 13). The general
procedure yielded the pure arylamine as a white solid. Data were in full
agreement with those reported in the literature.7 1H NMR (400 MHz,
CDCl3): δ 2.33 (3H, s, CH3), 3.15 (4H, m, 2 × N−CH2), 3.90 (4H,
m, 2 × O−CH2), 6.87−6.90 (2H, m, HAr), 7.13−7.16 (2H, m, HAr).
13C{1H} NMR (100 MHz, CDCl3): δ 20.3 (CH3), 49.8 (2 × N−
CH2), 66.8 (2 × O−CH2), 115.9 (CHAr), 129.4 (Me-CIV), 129.6
(CHAr), 149.1 (N−CIVAr).
Bis(2,6-dimethylphenyl)amine (Table 5, Entry 5). The general
procedure yielded the pure arylamine as a white solid. Data were in full
agreement with those reported in the literature.28 1H NMR (400 MHz,
CDCl3): δ 2.11 (12H, s, 4 × CH3), 4.89 (1H, bs, NH), 6.94 (2H, dd,
J = 6.8, 1.3 Hz, p-HAr), 7.08 (4H, app bd, J = 7.9 Hz, m-HAr). 13C{1H}
NMR (100 MHz, CDCl3): δ 19.1 (CH3), 121.7 (CHAr), 128.9
(CHAr), 129.5 (CIVAr), 141.7 (CIVAr).
N-(2,6-Diisopropylphenyl)-2,6-dimethylaniline (Table 5, Entry 6).
The general procedure yielded the pure arylamine as a colorless oil.
Data were in full agreement with those reported in the literature.2,3c,10
1H NMR (400 MHz, CDCl3): δ 1.26 (6H, s, 2 × CH3), 1.29 (6H, s,
2 × CH3), 2.13 (6H, s, 2 × CH3), 3.31 (2H, m, 2 × Me2CH), 4.95 (1H,
bs, NH), 6.87 (1H, bt, J = 7.6 Hz, HAr), 7.09 (2H, bd, J = 7.7 Hz, HAr),
7.24−7.31 (3H, m, HAr). 13C{1H} NMR (100 MHz, CDCl3): δ 19.3
(CH3), 23.4 (CH3), 28.0 (Me2CH), 119.6 (CHAr), 123.2 (CHAr),
(1H, dd, J = 9.0, 2.6 Hz, 3-CHAr), 7.32 (1H, ddd, J = 7.9, 6.8, 1.4 Hz,
7-CHAr), 7.43 (1H, ddd, J = 8.2, 6.8, 1.4 Hz, 4-CHAr), 7.70−7.78 (3H,
m, 6-CHAr). 13C{1H} NMR (100 MHz, CDCl3): δ 49.8 (2 × N−
CH2), 66.9 (2 × O−CH2), 110.1 (CHAr), 118.9 (CHAr), 123.5
(CHAr), 126.3 (CHAr), 126.8 (CHAr), 127.4 (CHAr), 128.7 (CIVAr),
128.8 (CHAr), 134.5 (CIVAr), 149.1 (N−CIVAr).
N-Methyl-N-phenylaniline (Tables 4 and 5, Entry 1). The general
procedure yielded the pure arylamine as a yellowish oil. Data were in
full agreement with those reported in the literature.26 1H NMR (400
MHz, CDCl3): δ 3.39 (3H, s, N−CH3), 7.01−7.06 (2H, m, HAr),
7.09−7.12 (4H, m, HAr), 7.32−7.39 (4H, m, HAr). 13C{1H} NMR
(100 MHz, CDCl3): δ 40.2 (CH3), 120.4 (o-CHAr), 121.2 (p-CHAr),
129.1 (m-CHAr), 149.0 (N−CIVAr).
4-(2,6-Dimethylphenyl)morpholine (Table 4, Entry 2; Table 5,
Entry 4). The general procedure yielded the pure arylamine as a white
solid. Data were in full agreement with those reported in the
literature.3c,d,g,27 1H NMR (400 MHz, CDCl3): δ 2.43 (6H, s, 2 ×
CH3), 3.16 (4H, app t, J = 4.6 Hz, 2 × N−CH2), 3.87 (4H, app t, J =
4.6 Hz, 2 × O−CH2), 7.02−7.09 (2H, m, HAr). 13C{1H} NMR (100
MHz, CDCl3): δ 19.5 (CH3), 49.9 (2 × N−CH2), 68.0 (2 × O−CH2),
125.2 (CHAr), 128.9 (Me-CIV), 136.7 (CHAr), 147.7 (N−CIV).
N-2,6-Trimethyl-N-phenylaniline (Table 4, Entry 5). The general
procedure yielded the pure arylamine as a white solid. Data were in full
3406
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Organometallics
Article
124.8 (CHAr), 125.6 (CIVAr), 129.5 (CHAr), 138.8 (CIVAr), 143.1
(CIVAr), 144.1 (CIVAr).
HAr), 7.24 (1H, ddd, J = 7.9, 1.5, 0.9 Hz, HAr), 7.37 (1H, dd, J = 7.9,
1.5 Hz, HAr). 13C{1H} NMR (100 MHz, CDCl3): δ 51.6 (N−CH2),
67.0 (O−CH2), 120.2 (CHAr), 123.8 (CHAr), 127.6 (CHAr), 128.7
(Cl−CIVAr), 130.6 (CHAr), 148.9 (N−CIVAr).
2-Chloro-N-methyl-N-phenylaniline (Table 6, Entry 7). The
general procedure yielded the pure arylamine as a yellowish oil.
Data were in full agreement with those reported in the literature.32 1H
NMR (400 MHz, CDCl3): δ 3.32 (3H, s, CH3), 6.68 (2H, bd, J = 7.9
Hz, HAr), 6.84 (1H, bt, J = 7.3 Hz, HAr), 7.27 (3H, m, HAr), 7.35 (2H,
m, HAr), 7.56 (1H, bd, J = 7.9 Hz, HAr). 13C{1H} NMR (100 MHz,
CDCl3): δ 38.9 (CH3), 113.5 (CHAr), 117.8 (CHAr), 127.3 (CHAr),
128.1 (CHAr), 128.9 (CHAr), 130.1 (CHAr), 130.9 (CHAr), 133.5 (Cl−
CIVAr), 145.3 (N−CIVAr), 148.5 (N−CIVAr). HRMS (ESI+): found m/z
[M + H]+ 218.0731, calcd for C13H13NCl 218.0731.
N-(2,6-Diisopropylphenyl)-4-methoxy-2,6-dimethylaniline (Table 5,
Entry 8). The general procedure yielded the pure arylamine as an
1
orange oil. H NMR (400 MHz, CDCl3): δ 1.18 (6H, s, 2 × CH3),
1.21 (6H, s, 2 × CH3), 2.09 (6H, s, 2 × CH3), 3.16 (2H, m, 2 ×
Me2CH), 3.83 (3H, s, OCH3), 4.72 (1H, bs, NH), 6.63 (2H, bs, J =
7.6 Hz, HAr), 7.09−7.19 (3H, m, HAr). 13C{1H} NMR (100 MHz,
CDCl3): δ 19.5 (CH3), 23.5 (CH3), 27.8 (Me2CH), 55.3 (OCH3),
114.4 (CHAr), 123.0 (CHAr), 123.4 (CHAr), 129.8 (Me-CIVAr), 136.5
(N−CIVAr), 139.7 (N−CIVAr), 141.5 (iPr−CIVAr), 153.9 (MeO-CIVAr).
HRMS (ESI+): found m/z [M + H]+ 312.2325, calcd for C21H30ON
312.2322.
N-Methyl-N-phenylpyridin-3-amine (Table 5, Entry 9). The
general procedure yielded the pure arylamine as a yellowish oil.
Data were in full agreement with those reported in the literature.10 1H
NMR (400 MHz, CDCl3): δ 3.34 (6H, s, 2 × CH3), 7.05−7.11 (3H,
m, m-CHAr + p-CHAr), 7.14 (1H, partially hidden dd, J = 8.5, 4.6 Hz,
4-CHpyr), 7.23 (1H, ddd, J = 8.5, 2.7, 1.4 Hz, 5-CHpyr), 7.30−7.37
(2H, m, o-CHAr), 8.15 (1H, dd, J = 4.6, 1.4 Hz, 6-CHpyr), 8.33 (1H, d,
J = 2.7 Hz, 2-CHpyr). 13C{1H} NMR (100 MHz, CDCl3): δ 39.9 (N−
CH3), 122.3 (m-CHAr), 123.2 (4-CHpyr), 123.4 (p-CHAr), 124.7 (5-
CHpyr), 129.5 (o-CHAr), 140.6 (2-CHpyr), 141.1 (6-CHpyr), 145.0 (N−
CIVpyr), 147.8 (N−CIVAr).
ASSOCIATED CONTENT
■
S
* Supporting Information
Figures giving 1H and 13C NMR spectra for all compounds and
a CIF file giving crystallographic data for 1. This material is
available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: snolan@st-andrews.ac.uk.
■
N-(2,6-Dimethylphenyl)pyridin-3-amine (Table 5, Entry 10). The
1
general procedure yielded the pure arylamine as a white solid. H
NMR (400 MHz, CDCl3): δ 2.21 (6H, s, 2 × CH3), 5.53 (1H, bs,
NH), 6.65 (1H, ddd, J = 8.3, 2.7, 1.3 Hz, 5-CHpyr), 7.04 (1H, dd, J =
8.3, 4.8 Hz, 4-CHpyr), 7.13 (3H, m, CHAr), 8.00 (1H, dd, J = 4.8, 1.3
Hz, 6-CHpyr), 8.05 (1H, d, J = 2.7 Hz, 2-CHpyr). 13C{1H} NMR (100
MHz, CDCl3): δ 18.2 (CH3), 118.9 (5-CHpyr), 123.7 (4-CHpyr), 126.3
(CHAr), 128.6 (CHAr), 135.9 (Me-CIVAr), 136.5 (2-CHpyr), 136.8 (N−
CIVpyr), 139.3 (6-CHpyr), 142.5 (N−CIVAr).
4-(Methyl(phenyl)amino)benzonitrile (Table 5, Entries 11 and 12).
The general procedure yielded the pure arylamine as a brownish oil.
Data were in full agreement with those reported in the literature.3a,2k,29
1H NMR (400 MHz, CDCl3): δ 3.37 (3H, s, CH3), 6.73−6.77 (2H, m,
HAr), 7.20−7.32 (3H, m, HAr), 7.40−7.48 (4H, m, HAr). 13C{1H}
NMR (100 MHz, CDCl3): δ 39.9 (CH3), 99.0 (NC-CIVAr), 113.60
(CHAr), 120.1 (CN), 126.0 (CHAr), 126.2 (CHAr), 129.9 (CHAr),
133.0 (CHAr), 146.5 (N−CIVAr), 151.7 (N−CIVAr).
N-(4-Chlorophenyl)-2′,6′-dimethylaniline (Table 6, Entries 1 and 4).
The general procedure yielded the pure arylamine as a yellowish solid.
Data were in full agreement with those reported in the literature.19 1H
NMR (400 MHz, CDCl3): δ 2.25 (6H, s, 2 × CH3), 5.21 (1H, bs,
NH), 6.45−6.50 (2H, m, HAr), 7.12−7.21 (5H, m, HAr). 13C{1H}
NMR (100 MHz, CDCl3): δ 18.2 (CH3), 114.5 (CHAr), 122.6 (Cl−
CIVAr), 126.1 (CHAr), 128.6 (CHAr), 129.1 (CHAr), 135.9 (Me−CIVAr),
137.7 (N−CIVAr), 144.9 (N−CIVAr).
4-(4-Chlorophenyl)morpholine (Table 6, Entry 3). The general
procedure yielded the pure arylamine as a white solid. Data were in full
agreement with those reported in the literature.13,30 1H NMR (400
MHz, CDCl3): δ 3.12 (4H, m, 2 × N−CH2), 3.86 (4H, m, 2 × O−
CH2), 6.81−6.86 (2H, m, HAr), 7.20−7.26 (2H, m, HAr). 13C{1H}
NMR (100 MHz, CDCl3): δ 49.3 (N−CH2), 66.7 (O−CH2), 116.9
(CHAr), 124.8 (Cl−CIVAr), 129.0 (CHAr), 149.9 (N−CIVAr).
4-Chloro-N-(2,6-dimethylphenyl)-2-methylaniline (Table 6, Entry 5).
The general procedure yielded the pure arylamine as a white solid. 1H
NMR (400 MHz, CDCl3): δ 2.22 (6H, s, 2 × CH3), (3H, s, CH3),
4.94 (1H, bs, NH), 6.10 (1H, d, J = 8.7 Hz, HAr), 6.95 (1H, bdd, J =
8.7, 2.6 Hz, HAr), 7.11−7.20 (4H, m, HAr). 13C{1H} NMR (100 MHz,
CDCl3): δ 17.4 (CH3), 18.1 (CH3), 112.7 (CHAr), 122.5 (Cl−CIVAr),
124.0 (CIVAr), 125.9 (CHAr), 126.6 (CHAr), 128.6 (CHAr), 129.9
(CHAr), 135.5 (CIVAr), 138.2 (CIVAr), 142.8 (CIVAr). HRMS (ESI+):
found m/z [M + H]+ 246.1042, calcd for C15H17NCl 246.1044.
4-(2-Chlorophenyl)morpholine (Table 6, Entry 6). The general
procedure yielded the pure arylamine as a colorless oil. Data were in
full agreement with those reported in the literature.31 1H NMR (400
MHz, CDCl3): δ 3.06 (4H, m, 2 × N−CH2), 3.88 (4H, m, 2 × O−
CH2), 7.00 (1H, dt, J = 7.9, 1.5 Hz, HAr), 7.04 (1H, dd, J = 8.0, 1.5 Hz,
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We gratefully acknowledge the EC for funding through the
seventh framework programme SYNFLOW. We thank the
EPSRC National Mass Spectrometry Service Center in Swansea
for mass spectroscopic analyses. Johnson Matthey (Dr. Chris
Barnard) and Umicore (Dr. Ralf Karch) are thanked for their
generous gifts of materials. S.P.N. is a Royal Society Wolfson
Research Merit Award holder.
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