New phosphine-functionalized NHC ligands: Discovery of an effective catalyst for the room-temperature amination of aryl chlorides with primary and secondary amines

Article abstract of DOI:10.1021/om400684n

We report convenient and high-yielding syntheses of new phosphine-functionalized dihydroimidazolium salts and demonstrate their utility as ligand precursors for Buchwald-Hartwig amination. Several examples of the general formula [1-Mes-3-{2-(PR₂)phenyl}imidazolidin-2-ylium][BF ₄] have been prepared, where phosphines of varying steric and electronic properties (R = Ph (9), Cy (10), 1-Ad (11)) are tethered by an o-phenylene group. The synthesis was not adaptable to N-aryl groups other than mesityl, giving unexpected phosphonium salt species instead. The synthesis was adapted to flexible benzyl-linked variants of the formula [1-Ar-3-{2-(PCy ₂)benzyl}imidazolidin-2-ylium][BF₄], which allowed more steric variation of the dihydroimidazolium N-aryl group (Ar = Mes (21), Dipp (22)). A preliminary study of these hybrid NHC/P ligands in Buchwald-Hartwig amination catalysis (in situ precatalyst formation) revealed 11 to be the most active of the series. Premixing the isolated free NHC ligand 1-Mes-3-{2-(PAd₂)phenyl}imidazolidin-2-ylidene (23) with [Pd(cinnamyl)Cl]₂ provided a highly active precatalyst that performed well at room temperature and 1 mol % catalyst loading. The system was shown to have an unprecedented ability to arylate both primary alkylamines (monoarylation) and secondary dialkylamines with aryl chlorides at room temperature. Electron-rich and -poor aryl and heteroaryl halides, as well as those featuring ortho substitution, were well tolerated, while substrates featuring both primary and secondary amine groups were selectively arylated at the NH₂ position. Furthermore, a preliminary examination of performance in ammonia arylation and acetone α-arylation showed promising results, giving good conversion and high selectivity for monoarylation in both cases.

Full text of DOI:10.1021/om400684n

Article
pubs.acs.org/Organometallics
New Phosphine-Functionalized NHC Ligands: Discovery of an
Effective Catalyst for the Room-Temperature Amination of Aryl
Chlorides with Primary and Secondary Amines
Craig A. Wheaton, John-Paul J. Bow, and Mark Stradiotto*
Department of Chemistry, Dalhousie University, 6274 Coburg Road, P.O. Box 15000, Halifax, Nova Scotia, Canada B3H 4R2
S
* Supporting Information
ABSTRACT: We report convenient and high-yielding syn-
theses of new phosphine-functionalized dihydroimidazolium
salts and demonstrate their utility as ligand precursors for
Buchwald−Hartwig amination. Several examples of the general
formula [1-Mes-3-{2-(PR2)phenyl}imidazolidin-2-ylium][BF4]
have been prepared, where phosphines of varying steric and
electronic properties (R = Ph (9), Cy (10), 1-Ad (11)) are
tethered by an o-phenylene group. The synthesis was not
adaptable to N-aryl groups other than mesityl, giving
unexpected phosphonium salt species instead. The synthesis
was adapted to flexible benzyl-linked variants of the formula
[1-Ar-3-{2-(PCy2)benzyl}imidazolidin-2-ylium][BF4], which
allowed more steric variation of the dihydroimidazolium N-
aryl group (Ar = Mes (21), Dipp (22)). A preliminary study of these hybrid NHC/P ligands in Buchwald−Hartwig amination
catalysis (in situ precatalyst formation) revealed 11 to be the most active of the series. Premixing the isolated free NHC ligand 1-
Mes-3-{2-(PAd2)phenyl}imidazolidin-2-ylidene (23) with [Pd(cinnamyl)Cl]2 provided a highly active precatalyst that performed
well at room temperature and 1 mol % catalyst loading. The system was shown to have an unprecedented ability to arylate both
primary alkylamines (monoarylation) and secondary dialkylamines with aryl chlorides at room temperature. Electron-rich and
-poor aryl and heteroaryl halides, as well as those featuring ortho substitution, were well tolerated, while substrates featuring both
primary and secondary amine groups were selectively arylated at the NH2 position. Furthermore, a preliminary examination of
performance in ammonia arylation and acetone α-arylation showed promising results, giving good conversion and high selectivity
for monoarylation in both cases.
Our recent research efforts have been directed in part toward
palladium-catalyzed C−N cross-coupling (i.e., Buchwald−
Hartwig amination, BHA), which has emerged as a broadly
useful methodology for the construction of aniline derivatives.2
Early pioneering work by the groups of Buchwald and Hartwig
focused primarily on monodentate phosphine as well as simple
bis(phosphine) ligands.2a,b In the ensuing years, important
advances in the field by these and other research groups have
come from the development and/or application of more
intricately designed bidentate ligands that enhance catalytic
performance. In particular, practical catalysts for BHA can
largely be attributed to the development of biaryl mono-
phosphine ligands by Buchwald that exhibit κ2P,C-bidentate
INTRODUCTION
■
Late-transition-metal catalysis plays a central role in modern
chemical synthesis, in facilitating otherwise challenging or
impossible bond-forming reactions at low loadings and with
high activity and selectivity.1 Indeed, it is not an overstatement
to say that late-metal catalysis has revolutionized the way in
which chemists think about constructing organic molecules on
benchtop and industrial scales, enabling the streamlined
synthesis of many target molecules under mild conditions
without the need for stoichiometric reagents, protecting groups,
or preactivated substrates.1 In this regard, the continued
development of late-transition-metal catalysis can be viewed as
contributing positively toward the establishment of more
sustainable chemical protocols. While the early development
of late-transition-metal catalysis involved the study of
complexes featuring relatively simple ancillary coligands (e.g.,
PPh3), the ability of more elaborate ligand sets to provide vastly
improved catalytic performance has been demonstrated in
diverse applications. Such observations have given rise to the
burgeoning domain of ancillary ligand design within the field of
late-transition-metal catalysis.
4
ligation3 (including BuBrettPhos), and use of κ2P,P-bis-
(phosphine) ligands by Hartwig,2b including the JosiPhos
family of ligands (Figure 1).5 Recent work from our group has
built upon this foundation through the development of the
DalPhos family of ligands, which include potentially hetero-
bidentate P,N (e.g., Mor-DalPhos, Figure 1)6 and P,O (e.g.,
t
Received: July 12, 2013
© XXXX American Chemical Society
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shown new reactivity profiles and many useful applications in
catalysis.12
Although no such phosphine-functionalized NHC ligands
have been applied in BHA, various examples have been
synthesized for use in other applications. Among these are a
number of examples with different linkers between the NHC
and phosphine groups, including designs with alkyl,13 benzyl,14
anthracene,15 and phenylene16 linkers, as well as some chiral
examples,17 and recently a directly linked N-phosphanyl
NHC.18 Additionally, there are examples of hybrid pincer-
type ligands containing both types of donor groups.19 It is
notable that the vast majority of these phosphine-functionalized
NHC ligands incorporate a diphenylphosphino donor frag-
ment; the application of bulkier and more electron rich
phosphines in this capacity remains underexplored.
Herein we report the synthesis and characterization of two
types of phosphine-functionalized dihydroimidazolium salts, in
which the two groups are linked by either an o-phenylene or a
benzyl group. The unexpected formation of unusual new types
of phosphonium salts is also reported. Notably, a variant that
incorporates a bis(1-adamantyl)phosphino donor group is
shown to give highly active catalysts for BHA, resulting in the
first single-ligand catalyst system capable of room-temperature
amination of unactivated aryl chlorides involving both primary
and secondary alkylamines.
Figure 1. Selection of phosphine and NHC ligands employed in
Buchwald−Hartwig amination catalysis and functionalized NHC
ligands employed in previous studies and in this study.
OTips-DalPhos)7 variants that have proven useful in a range of
challenging BHA applications.
N-heterocyclic carbenes (NHCs) represent a complementary
class of ancillary ligands that have proven to be particularly
effective in BHA chemistry. Of particular importance are the
(NHC)Pd(cinnamyl)Cl precatalyst complexes developed by
Nolan and co-workers, where the NHC is the saturated
monodentate SIPr (Figure 1)8 or alternatively the more
sterically encumbered IPr*.9 These catalysts are notable for
excellent performance in the arylation of secondary amine and
primary aniline substrates at room temperature and/or low
catalyst loadings. Additionally, Organ and co-workers have
developed the highly active PEPPSI precatalysts featuring an
unsaturated monodentate NHC coligand, such as IPr or
IPent.10 These catalysts also offer excellent performance in the
arylation of secondary amines and primary anilines and are
notable for their ease of preparation and handling. Despite the
established utility of (hetero)bidentate phosphine-based
ancillary ligands (vide supra), a careful survey of the literature
reveals that the application of conceptually related hetero-
bidentate NHCs has received relatively little attention in BHA
chemistry.
In this context, we were motivated to examine analogous
heterobidentate NHC ligands for application in BHA
chemistry. Encouraged by the remarkable reactivity properties
exhibited by catalysts featuring Mor-DalPhos, we recently
developed a heterobidentate ligand variant featuring an NHC in
place of the phosphorus donor group.11 However, these
morpholino-tethered NHC ligands performed rather poorly
in BHA in comparison with both their monodentate NHC
counterparts and Mor-DalPhos. The high lability of the Pd−
N(morpholino) bond and the accompanying diminished steric
demands of the ligand represent possible sources of poor
performance.
RESULTS AND DISCUSSION
■
Dihydroimidazolium Salt Syntheses. As an extension of
our previous work on morpholine-functionalized NHC
ligands,11 we have chosen to pursue a directly analogous ligand
design in which an o-phenylene group rigidly links the
phosphine and NHC donors. A series of NHC−phosphine
ligands of this type have been prepared previously by Zhou and
co-workers.16 However, the reported synthetic route is low-
yielding and inconvenient and is limited to diphenylphosphino
derivatives. We therefore sought to develop a more convenient
and flexible synthetic route similar to what we developed
previously for the synthesis of morpholino-functionalized NHC
ligands.11 Such morpholine-functionalized NHC ligands are
prepared from o-bromoiodobenzene, whereby the ligand is
generated through two palladium-catalyzed C−N cross-
coupling steps. Adapting this methodology to the phosphine-
functionalized NHCs sought after herein requires the
installation of the diamine moiety in the first step, even though
its presence in the second step creates a potential chemo-
selectivity challenge (i.e., inter-/intramolecular C−N versus
intermolecular C−P bond formation). Installation of the
diamine was accomplished easily using the conditions for
selective cross-coupling of dihalogenated benzenes established
by Jørgensen and co-workers,20 giving 1−3 in high yield and
purity within 30 min (Scheme 1).
Our preliminary examination of the C−P cross-coupling step
focused initially on the N-mesityl diamine 1. Under standard
C−P cross-coupling conditions, both PPh2 and PCy2 groups
could be selectively installed with negligible formation of
competing C−N intermolecular or intramolecular cross-
coupling products, giving compounds 4 and 5, respectively.
In the case of P(1-Ad)2 installation, some minor products,
presumed to be due to undesired C−N coupling, were formed.
Nonetheless, under our standard conditions, compound 6 was
isolated in 62% yield. We then examined the cyclization step
using the established protocol employing triethyl orthoformate
as the precarbenic unit.21 With no precautions to exclude air
In the present study, we have adapted our approach by
targeting related phosphine-functionalized NHC ligands
(Figure 1). We reasoned that the improved ligating ability of
a phosphine relative to an amine would enforce a rigid chelate
geometry, reminiscent of bis(phosphines) and related ligands.
The resulting increase in steric hindrance could contribute in
part to facilitating C−N bond-forming reductive elimination,
which often represents the rate-limiting step in BHA chemistry.
This research direction is also inspired by the development of
[Pd(NHC)(PR3)] complexes by Cazin and Nolan, which have
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Single-crystal X-ray diffraction studies revealed 12 to be the
phosphonium salt depicted in Scheme 1 and Figure 2.
Scheme 1. Three-Step Synthesis of Dihydroimidazolium
Salts 9−11 and Phosphonium Salts 12 and 13
a
Figure 2. Molecular structure of the cation of 12 with most H atoms
omitted and ellipsoids drawn at the 50% probability level.
Evidently, the reduced steric hindrance of this system versus
that of 11 enabled nucleophilic attack of the phosphino group
at the C2 site of the dihydroimidazolium after cyclization had
occurred. The newly formed P−C bond is in the range
expected for a single bond (P(1)−C(29) = 1.895(1) Å), while
the N−C bond lengths also indicate single-bond character
(N(2)−C(29) = 1.479(2) Å; N(1)−C(29) = 1.464(2) Å),
rather than the bond order of 1.5 expected for a
dihydroimidazolium species. These metrical data along with
spectroscopic data support the assignment of this compound as
a phosphonium salt. This unique compound represents, to our
knowledge, the first example of a β-diamino phosphonium salt.
This potential precursor to unique phosphorus ylides, such as
those studied by Bertrand and co-workers,22 remains an
interesting avenue for future exploration.
We then attempted to synthesize a bulkier variant of 11
containing an N-Dipp (Dipp = 2,6-diisopropylphenyl) group.
Installation of the P(1-Ad)2 moiety was readily achieved, giving
8 in moderate yield. However, the standard conditions
employed previously for cyclization to the dihydroimidazolium
salt consistently gave a mixture of two major products in
approximately a 1:1 ratio. One of these features a 31P NMR
resonance consistent with the desired dihydroimidazolium salt
(δ 14.2), while the 31P NMR resonance of the other appears at
δ 32.3, suggesting a phosphonium salt. Longer reaction times or
higher reaction temperatures did not change the ratio of
products significantly; however, we found that a lower
temperature and shorter reaction time gave only the latter
compound, which was identified as the phosphonium salt 13 by
determination of the X-ray structure (Figure 3). This product,
which retains one ethoxy group from the orthoformate,
presumably results from nucleophilic attack of the phosphine
at the orthoformate carbon at an intermediate stage of the
cyclization, thereby blocking the already sterically hindered
amine from undergoing conversion to the target dihydroimi-
dazolium salt. All C−heteroatom bonds are in the single-bond
range, again indicating a +5 oxidation state of the phosphorus
and phosphonium salt character (P(1)−C(27) = 1.876(2) Å;
N(1)−C(27) = 1.446(2) Å; O(1)−C(27) = 1.416(2) Å). To
our knowledge, 13 represents the first example of a β-amino-β-
alkoxy phosphonium salt.
a
Conditions: (i) 1.05 equiv of N-aryl-1,2-diaminoethane, 1.4 equiv of
NaOtBu, 0.5 mol % of Pd2(dba)3, 2 mol % of Xantphos, toluene
([ArI] = 1 M), 110 °C, 30 min; (ii) 2 mol % of Pd(OAc)2, 2.4 mol %
of DiPPF, toluene ([ArBr] = 0.25 M), 1/1/1.4 ArCl/HPR2/NaOtBu;
(iii) 2 mol % of Pd(OAc)2, 2.4 mol % of DiPPF, 1,4-dioxane ([ArBr] =
0.25 M), 1/1/1.4 ArCl/HP(1-Ad)2/Cs2CO3; (iv) CH(OEt)3, 1.2
equiv of NH4BF4, 110-120 °C, 0.5−1 h; (v) CH(OEt)3, 1.2 equiv of
NH4BF4, 80 °C, 10 min.
and moisture from the reaction, the three dihydroimidazolium
salts 9−11 were isolated in high yield. The 31P NMR chemical
shifts are indicative of neutral phosphines (9, −18.2 ppm; 10,
−16.5 ppm; 11, 14.2 ppm), while new aromatic peaks
corresponding to the dihydroimidazole C2 position were
observed in the 1H NMR spectra (7.74−7.82 ppm).
Compound 11 was isolated in very high purity, while 9 and
10 were isolated in ca. 80% purity, as determined by integration
of the 31P NMR spectra, with minor byproducts exhibiting
downfield chemical shifts around δ 25 and 39, respectively.
Performing this cyclization step under an atmosphere of N2
gave the same result, ruling out phosphine oxide formation as
the source of these impurities. As such, we attribute the
impurities observed in the synthesis of 9 and 10 as likely
corresponding to the formation of a phosphonium salt,
analogous to 12 and 13 (vide infra).
Given the superior yield and purity of the P(1-Ad)2 variant
11 in the cyclization reaction, we sought to prepare further
derivatives featuring this bulky phosphine group. We found the
less bulky precursor 7 to be inaccessible under our standard P−
C coupling conditions, giving instead the tetrahydroquinoxaline
product of intramolecular amination. By modifying the
conditions (Cs2CO3, 1,4-dioxane), the desired phosphine 7
was obtained in 53% yield. Standard cyclization conditions then
cleanly afforded a new compound (12) in high yield, but with
NMR signatures that deviated significantly from those of the N-
mesityl variant 11. Specifically, the 31P NMR chemical shift of
the N-phenyl species 12 (δ 36.2) is downfield of the bulkier N-
mesityl analogue, while the newly installed CH functionality is
shifted upfield to δ 6.61 in the 1H NMR spectrum. Notably, this
latter proton resonance exhibited a P−H coupling constant of
24.3 Hz, indicating a close proximity of the phosphine moiety.
Given the novelty of phosphonium salt 13, we chose to
demonstrate the generality of this synthesis for simpler variants
not containing the dangling NHDipp group. To this end, the
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Having established that our synthetic route to phosphine-
functionalized dihydroimidazolium salts is not highly amenable
to steric variation at the N-aryl group, we sought to prepare
variants with greater separation between the phosphine and
dihydroimidazoium groups, by employing a benzyl linker.
Although Zhou and co-workers have disclosed a similar ligand
framework, the report featured an unsaturated NHC and is
limited to PPh2 donor fragments.14b Our synthetic route to
such ligands is depicted in Scheme 3.
Scheme 3. Synthesis of the Phosphine-Functionalized
Dihydroimidazolium Salts 21 and 22
Figure 3. Molecular structure of the cation of 13 with most H atoms
omitted and ellipsoids drawn at the 50% probability level.
a
phosphine precursor 15 was prepared using our established
synthetic methodology from the diarylamine 14 (Scheme 2).
a
Scheme 2. Synthesis of the Phosphonium Salt 16
a
Conditions: (i) 2 mol % of Pd(OAc)2, 2.4 mol % of DiPPF, toluene
a
Conditions: (i) 1.0 equiv of N-aryl-1,2-diaminoethane, toluene, room
([ArBr] = 0.25 M), 1/1/1.4 ArCl/HPCy2/NaOtBu; (ii) CH(OEt)3,
1.2 equiv of NH4BF4, 110 °C, 20 min.
temperature, 1 h; (ii) 2.0 equiv of NaBH4, anhydrous EtOH, room
temperature, 19 h; (iii) 2 mol % of Pd(OAc)2, 2.4 mol % of DiPPF,
toluene ([ArBr] = 0.25 M), 1/1.1/1.4 ArCl/HPCy2/NaOtBu; (iv) N2
atmosphere, CH(OEt)3, 1.2 equiv of NH4BF4, 110 °C, 15 min.
Treating this with acid and triethyl orthoformate under
standard cyclization conditions gave 16, a simplified analogue
of the phosphonium salt 13. Spectroscopic characteristics of
this compound are similar to 13, with a downfield signal in the
31P NMR spectrum at δ 39.5. The connectivity within this
compound was verified by determination of the X-ray crystal
structure (Figure 4). The metrical parameters found in 16
(P(1)−C(25) = 1.857(2) Å; N(1)−C(25) = 1.453(3) Å;
O(1)−C(25) = 1.409(3) Å) are similar to those of 13, albeit
with a noticeable reduction in the P−C distance of 0.019(4) Å
that can be attributed to the reduced steric repulsion from the
smaller PCy2 group in 16.
Starting from 2-bromobenzaldehyde, the diamine precursors
17 and 18 were prepared via reductive amination in moderate
yield. The PCy2 group was efficiently installed by using the
standard Pd-catalyzed coupling methodology, providing 19 and
20 in excellent yield. Unfortunately, the bulkier P(1-Ad)2
variants could not be prepared in an analogous manner,
which we attribute to a high susceptibility of the benzylamine
site to intermolecular arylation under the reaction conditions.
Under our standard benchtop conditions, attempts to cyclize
either 19 or 20 to the corresponding dihydroimidazolium salts
gave an intractable mixture of products. However, when the
reaction flask was purged of oxygen by sparging the reaction
mixture with N2 prior to heating under dynamic N2 flow, the
desired dihydroimidazolium salts 21 and 22 could be obtained.
It should be noted that a short reaction time was necessary to
prevent phosphonium salt formation, where heating at 110 °C
for 15 min was found to be optimal. The X-ray crystal structure
of 21 was obtained (Figure 5), thereby confirming the identity
of this expected dihydroimidazolium salt in the solid state.
Catalytic Studies. With these new phosphine-function-
alized saturated NHC precursors in hand, we sought to
determine their potential utility as ancillary ligands in the BHA
of aryl chlorides. We chose to restrict our survey to the five
dihydroimidazolium salts 9−11, 21, and 22. The initial
screening study was conducted with deprotonation and
complexation of the NHC precursors carried out in situ (see
the Experimental Section for more details), in order to identify
the most promising candidate for more careful examination.
Coupling between chlorobenzene and a representative series of
amines (octylamine, aniline, and morpholine) was surveyed,
and the results of this preliminary study are given in Table 1. In
a comparison of the structurally related series 9−11, it is
Figure 4. Molecular structure of the cation of 16, with most hydrogen
atoms omitted and ellipsoids drawn at the 50% probability level.
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NMR spectrum at δ 245.1 is consistent with a primarily NHC
character for this compound. Mixing 23, a colorless compound,
with [Pd(cinnamyl)Cl]2 (a yellow compound with low
solubility in THF) in precisely a 1:1 ratio of ligand to metal
in THF gave initially a light red solution, which gradually
changed to a very dark red-brown over the course of
approximately 30 min. The resulting material, which is
presumed to be composed of species of the additive general
formula 23·Pd(cinnamyl)Cl, was isolated after 1 h by removal
of volatiles under vacuum. This material proved not to be
composed of a single, well-defined species on the basis of
1
solution NMR data; rather, the H NMR spectrum is very
broad and featureless. However, the catalytic performance of
this precatalyst mixture proved to be vastly superior to in situ
precatalyst generation. With a catalyst loading of 2 mol %
(toluene, NaOtBu), it was observed that coupling between
chlorobenzene and octylamine proceeded rapidly at ambient
temperature, giving 85% yield after 15 min and >99% yield
within 3 h, with complete monoarylation selectivity (Table 2).
Figure 5. Molecular structure of 21, with most hydrogen atoms
omitted and ellipsoids drawn at the 50% probability level.
Table 1. Preliminary BHA Screening of Palladium Catalysts
Generated in Situ from Newly Prepared
Table 2. Optimization of Conditions for Arylation of
a
Dihydroimidazolium Salts
a
Octylamine with Chlorobenzene
amt of Pd (mol %)
solvent
toluene
base
GC yeld (%)
b
2
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
KOtBu
>99
GC yield (%)
1
toluene
toluene
toluene
DME
84
45
7
LH+BF4
octylamine
aniline
morpholine
−
0.5
0.1
0.5
0.5
0.5
0.5
0.5
0.5
0
9
0
16
20
14
6
2
75
91
59
64
3
33
8
72
83
69
22
63
46
92
10
11
21
22
1,4-dioxane
toluene
DME
50
20
KOtBu
a
1,4-dioxane
DME
KOtBu
Reagents and conditions: PhCl (0.25 mmol), amine (0.3 mmol),
LiHMDS
LiHMDS
NaOtBu (0.35 mmol), toluene (0.5 mL). Yields determined from GC
data, calibrated using authentic samples and employing dodecane as an
internal standard.
1,4-dioxane
a
Reagents and conditions: PhCl (0.25 mmol), amine (0.3 mmol), base
(0.35 mmol), solvent (0.5 mL), 24 h. Yields determined from GC data,
calibrated using authentic samples and using dodecane as an internal
standard. Reaction time 3 h.
evident that the nature of the phosphine significantly alters the
catalytic properties. The least bulky and less donating PPh2
variant exhibits virtually no activity, while going to the slightly
bulkier and more electron rich PCy2 derivative provides a
significant enhancement, giving 75% yield in the arylation of
aniline. The more sterically encumbered P(1-Ad)2 variant 11
proved better still, giving 91% yield in the arylation of aniline.
Neither of the more flexible analogues 21 and 22 performed
better than 11 for the arylation of primary amines, although 21
gave the best result for arylation of morpholine, albeit at only
50% yield. On the basis of these observations, we selected 11
for a more detailed study.
b
The conversions were considerably reduced at lower catalyst
loading, to only 45% at 0.5 mol %. Therefore, we optimized
conditions at this catalyst loading and found that the best yields
were obtained in 1,4-dioxane solvent using LiHMDS base,
which gave a yield of 92%.
It is well established that catalyst systems that are highly
active and selective for monoarylation of primary alkylamines
tend to function poorly for the arylation of secondary
amines.5g,23 In this context, we examined the arylation of
morpholine using the precatalyst mixture 23·Pd(cinnamyl)Cl
under ambient-temperature conditions. This reaction proved to
be slow in comparison to the octylamine reaction, giving only
56% yield after 3 h using 2 mol % catalyst loading. Therefore,
optimization of conditions for arylation of morpholine was
performed (Table 3). Optimal conditions proved to be DME
solvent and NaOtBu base, giving a 99% yield in only 1 h at
ambient temperature.
Prior to initiating further catalytic studies, we carried out a
preliminary survey of the coordination chemistry of this new
ligand system. The dihydroimidazolium salt 11 could be readily
deprotonated with NaHMDS to cleanly generate the
corresponding phosphine-functionalized free NHC 23 in high
yield. This compound exhibits somewhat broadened resonances
1
in the H, 31P, and 13C NMR spectra. The 31P NMR signature
is shifted downfield by approximately 5 ppm to δ 19.5 (C6D6)
relative to 11, which may indicate a weak interaction between
the phosphine and carbene groups (i.e., phosphorus ylide
Having established conditions for room-temperature aryla-
tion of these two distinct classes of amines using 23·
Pd(cinnamyl)Cl, we then studied the performance of this
character). However, the appearance of a broad peak in the 13
C
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selectivity, generating appreciable quantities of diarylation
product. For the arylation of morpholine, only SIPr and 23
performed well, where SIPr reached quantitative yield in less
than 1 h, while 23 reached 93% yield in 1 h and 99% after 24 h.
Notably, within this series of ligands, only 23 afforded a catalyst
capable of highly efficient arylation of both octylamine and
morpholine at room temperature.
Table 3. Optimization of Conditions for Arylation of
Morpholine with Chlorobenzene
a
solvent
toluene
base
yime (h)
GC yield (%)
No previous reports utilizing Pd(NHC)(cinnamyl)Cl or
PEPPSI have demonstrated a single catalyst that can
accommodate both of these classes of substrates at ambient
temperature. In particular, these catalyst types readily arylate
secondary amines or primary anilines at ambient temperature,
while primary alkylamines require elevated temperatures and/
or the use of ortho-substituted aryl halides.8−10 The coupling of
simple unhindered alkylamines with sterically unbiased and
unactivated aryl chlorides is notably absent from these reports.
Conversely, Hartwig has shown the JosiPhos system to be
highly effective for (hetero)arylation of primary amines at very
low catalyst loadings, while the system is ineffective for
arylation of secondary amines under similar conditions.5 The
CyPF-tBu/Pd[P(o-Tol)3]2 system is highly active for amination
of aryl tosylates at room temperature;5f however, the only
reported use of JosiPhos for amination of a (hetero)aryl
chloride at room temperature employed CyPF-tBu/Pd(OAc)2,
which coupled octylamine and 2-chloropyridine in high yield
within 5 h.5f Buchwald’s BrettPhos ligand has also displayed
excellent performance in monoarylation of primary amines with
aryl chlorides, as demonstrated using methylamine as
substrate,25 but this too is ineffective for BHA with secondary
amines. On the basis of these observations we conclude that 23
offers an unprecedented ability to accommodate primary and
secondary amine substrates in BHA at room temperature.
Encouraged by the unique ability of this new phosphine-
functionalized NHC to enable the selective room-temperature
BHA of both octylamine and morpholine, we sought to further
explore the scope of this system for the arylation of primary
(Table 5) and secondary amines (Table 6). Unhindered
primary alkylamines were all coupled efficiently with chlor-
obenzene (24a−c) using the optimized room-temperature
catalytic conditions. The arylation of methylamine was
conducted using only 1.4 equiv of the amine, with 96% isolated
yield achieved, and no diarylation product was observed.
Arylation of a dialkylhydrazine to give 24d was effective only
with the use of NaOtBu base. Bulkier alkylamines were not as
well tolerated, giving low to moderate yields of cross-coupling
products (24e,f) at room temperature. Efficient room-temper-
ature arylation of aniline (24g) demonstrates the applicability
of this protocol for unhindered arylamines, while the sterically
demanding DippNH2 could only be arylated at 65 °C,
providing a good yield of 24h. The amination of activated
aryl chlorides with octylamine proved extremely facile at
ambient temperature. Amination of 2-chloropyridine went to
completion in less than 1 min and gave rise to a noticeable
exotherm within seconds of amine addition. An isolated yield of
91% was achieved using the standard conditions, which was
improved to 96% with the use of NaOtBu base. At a catalyst
loading of 0.25 mol %, 60% of the 2-chloropyridine substrate is
consumed after 60 s (calibrated GC), corresponding to a
turnover frequency (TOF) of ca. 14000 h−1. To our knowledge,
this represents the highest TOF reported at room temperature
for the arylation of octylamine or any similar nucleophilic
primary alkylamine. For comparison, this is roughly 2 orders of
magnitude faster than the coupling of the same substrates using
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
KOtBu
3
3
1
3
3
1
1
56
58
99
31
79
5
THF
DME
1,4-dioxane
N,N-DMF
DME
DME
NaHMDS
85
a
Reagents and conditions: 2 mol % Pd, PhCl (0.25 mmol),
morpholine (0.3 mmol), base (0.35 mmol), solvent (0.5 mL). Yields
determined from GC data, calibrated using authentic samples and
employing dodecane as an internal standard.
catalyst system in direct comparison to a representative series of
commercially available ligands. These include examples known
to be highly effective in the arylation of primary amines (Mor-
DalPhos,6 CyPF-tBu5) or secondary amines (SIPr),8 as well as
BippyPhos, which has shown utility for arylation of both
primary and secondary amines.24 Additionally, we have
included Buchwald’s biaryl ligand tBuBrettPhos, which
performs extremely well in a broad range of challenging C−
N and C−O cross-coupling reactions.4 All ligands were treated
in the same manner as 23, whereby premixing the ligand with
[Pd(cinnamyl)Cl]2 in THF for 1 h, followed by solvent
evaporation, was undertaken to give the precatalyst mixtures.
BHA reactions were then carried out at ambient temperature,
with GC yields determined at 1 and 24 h reaction times (Table
4). For arylation of octylamine, we found that 23, Mor-
DalPhos, and CyPF-tBu all performed well, giving high
conversions of 95% or greater after 24 h. The NHC-phosphine
ligand 23 gave the most rapid conversion, reaching 98% after
only 1 h. SIPr provided high conversion also but suffered poor
Table 4. Comparison between the Phosphine-Functionalized
NHC Ligand 23 and Representative Commercially Available
Ligands in the Arylation of Morpholine and Octylamine
octylamine GC yield
morpholine GC yield
a
b
(%)
(%)
ligand
1 h
24 h
1 h
24 h
23
98
87
15
13
13
2
>99
>99
93
31
100
0
99
47
Mor-DalPhos
SIPr
c
76
CyPF-tBu
BippyPhos
tBuBrettPhos
95
22
12
3
53
0
52
0
a
Reagents and (standard) conditions: 1 mol % Pd, PhCl (0.25 mmol),
HNR2 (0.3 mmol), LiHMDS (0.35 mmol), 1,4-dioxane (0.5 mL).
b
Calibrated GC yields. Reagents and conditions: 1 mol % Pd, PhCl
(0.25 mmol), HNR2 (0.3 mmol), NaOtBu (0.35 mmol), DME (0.5
c
mL). Calibrated GC yields. Reaction gives complete consumption of
aryl chloride and 3:1 ratio of monoarylation to diarylation.
F
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Table 5. Amination of (Hetero)aryl Chlorides with Primary
Amines under Mild Conditions
Table 6. Amination of (Hetero)aryl Chlorides with
Secondary Dialkylamines under Mild Conditions
a
a
a
Reagents and (standard) conditions: (hetero)aryl halide (1.0 mmol),
HNR2 (1.2 mmol), NaOtBu (1.4 mmol), DME (2 mL). Temperature
and unoptimized reaction time indicated in parentheses. Isolated
b
yields; average of two runs. Used 1.4 equiv of HNMe2 as a 2 M
solution in THF.
In additional to the cross-coupling experiments discussed
above, we have taken a preliminary look at some more
challenging substrates to demonstrate the chemoselectivity of
the 23·Pd(cinnamyl)Cl precatalyst system. In particular, two
substrates bearing both a primary and secondary amine
functional group were subjected to arylation employing the
optimized conditions for primary amines (Scheme 4); in both
cases the system was completely selective for amination at the
primary amine site.
a
Reagents and (standard) conditions: (hetero)aryl halide (1.0 mmol),
H2NR (1.2 mmol), LiHMDS (1.4 mmol), 1,4-dioxane (2 mL).
Isolated yields; average of two runs. Temperature and unoptimized
reaction time indicated in parentheses. The base is NaOtBu (1.4
mmol).
b
the JosiPhos/Pd(OAc)2 system.5e Amination of the activated 4-
chlorobenzotrifluoride by using 23·Pd(cinnamyl)Cl gave only
hydrodehalogenation with LiHMDS base but was similarly
facile when NaOtBu base was employed, providing 24j in 96%
yield in less than 5 min. Additionally, the system tolerates ortho
substitution (24k) as well as electronic deactivation (24l).
A narrow scope of secondary amines was also examined using
23·Pd(cinnamyl)Cl as the precatalyst. Small cyclic and acyclic
secondary amines are coupled efficiently under the standard
conditions (25a−c). The arylation of dimethylamine was
performed similarly to that of methylamine, whereby a 2 M
THF solution was employed using only 1.4 equiv of the amine.
Interestingly, amination of activated aryl chlorides with
morpholine did not provide the same rate enhancement seen
for amination with octylamine, although high yields of coupling
products were obtained (25d,e). Furthermore, ortho sub-
stitution (25f) and electronic deactivation (25g) were not as
well tolerated with secondary amines. Amination of 2-
chlorotoluene required heating to 65 °C for 22 h to provide
a 73% yield of 25f, while amination of 4-chloroanisole
proceeded slowly at room temperature, giving a moderate
yield of 25g after 48 h.
Scheme 4. Room-Temperature Chemoselectivity Studies
Demonstrating Selectivity for Primary over Secondary
Amines
a
a
Conditions: PhCl (1.0 mmol), amine (1.2 mmol), LiHMDS (1.4
mmol). Temperature and unoptimized reaction time indicated in
parentheses.
The selective monoarylation of ammonia5b,6 and the mono-
α-arylation of acetone26 with the unactivated and sterically
unbiased aryl halides and pseudohalides remain highly
challenging transformations, for which only a handful of
catalyst systems have proven effective. We therefore undertook
a preliminary examination of the performance of 23·Pd-
G
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dried over Na/benzophenone, distilled, and stored over 4 Å molecular
sieves. Benzene-d6 (Cambridge Isotopes) was degassed by using at
least three repeated freeze−pump−thaw cycles and stored over 4 Å
molecular sieves for 24 h prior to use. Other deuterated solvents
(CDCl3, DMSO-d6) were used with air- and moisture-stable
compounds and were used as received. N-(2,4,6-Trimethylphenyl)-
1,2-ethanediamine,27 N-(2,6-diisopropylphenyl)-1,2-ethanediamine,27
(cinnamyl)Cl in these challenging cross-coupling reactions
(Scheme 5). The system proved highly effective for amination
Scheme 5. Selective Monoarylation of Ammonia and
Acetone
29
N-(2-bromophenyl)morpholine,28 and [Pd(cinnamyl)Cl]2 were
prepared according to literature procedures. All other materials were
obtained from commercial sources (Sigma-Aldrich, Alfa Aesar, Strem)
and used without further purification. NMR spectra were collected on
1
a Bruker spectrometer at a frequency of 500 MHz for H and 126
MHz for 13C experiments, at ambient temperature, and referenced to
residual solvent signals. Peak assignments were made with the aid of
COSY, DEPT-135, and HSQC experiments. Mass spectrometric data
were acquired by Mr. Xiao Feng (Mass Spectrometry Laboratory,
Dalhousie University). Single-crystal X-ray diffraction data were
collected by Dr. Robert McDonald and Dr. Michael Ferguson (X-
ray Crystallography laboratory, University of Alberta).
of chlorobenzene with ammonia, giving an 88% yield of
monoarylation product and 13:1 product ratio of mono- to
diarylation products, as determined by GC analysis. This yield
and selectivity is competitive with those of Mor-DalPhos, and
ammonia monoarylation therefore represents an interesting
potential application of this ligand that is deserving of further
study. It was also found that the system performed well in the
mono-α-arylation of acetone with chlorobenzene, whereby a
GC yield of 64% was achieved. Notably, this is the first example
of an NHC-based catalyst system exhibiting a high selectivity
for monoarylation in either of these transformations.
Synthesis and Characterization. Synthesis of N1-{2-bromo-
phenyl}-N2-Mes-1,2-ethanediamine (1). Pd2(dba)3 (46 mg, 0.05
mmol), Xantphos (116 mg, 0.2 mmol), NaOtBu (1.34 g, 14 mmol),
and 10 mL of toluene were combined in a 20 dram catalysis vial. The
vial was sealed with a cap containing a PTFE septum and removed
from the glovebox. Bromoiodobenzene (2.83 g, 1.28 mL, 10 mmol)
and N-mesityl-1,2-diaminoethane (1.87 g, 10.5 mmol) were then
injected using a syringe. The resulting reaction mixture was heated to
110 °C with vigorous stirring for 30 min. After it was cooled, the
mixture was filtered through a bed of silica, which was then washed
down with CH2Cl2 (40 mL). Removal of solvent and prolonged drying
in vacuo afforded the product as a beige crystalline solid in >99% yield
(3.32 g, 9.96 mmol). 1H NMR (500 MHz, CDCl3): δ 7.46 (dd, J = 7.9,
1.5 Hz, 1H, 3-Ph), 7.20 (td, J = 7.7, 1.3 Hz, 1H, 5-Ph), 6.86 (s, 2H, m-
Mes), 6.68 (dd, J = 8.2, 1.3 Hz, 1H, 4-Ph), 6.61 (td, J = 7.6, 1.3 Hz,
1H, 6-Ph), 4.79 (t, J = 5.0 Hz, 1H, NH), 3.38 (q, J = 5.6 Hz, 2H,
CH2), 3.24 (dd, J = 6.5, 5.0 Hz, 2H, NHCH2), 3.10 (s, 1H, NH), 2.29
(s, 6H, o-CH3 Mes), 2.25 (s, 3H, p-CH3 Mes). 13C{1H} NMR (126
MHz, CDCl3): δ 145.1, 142.8, 132.6 (3-Ph), 132.0, 130.4, 129.6 (m-
Mes), 128.6 (5-Ph), 118.1 (4-Ph), 111.5 (6-Ph), 110.2, 47.5 (CH2),
44.3 (CH2), 20.7 (p-CH3 Mes), 18.4 (m-CH3 Mes). HRMS (ESI/[M
+ H]+): calcd for C17H22BrN2 333.0961, found 333.0956.
CONCLUSION
■
In summary, a straightforward and high-yielding three-step
method for the preparation of phosphine-functionalized
dihydroimidazolium salts has been established. The bulkiest
example, which incorporated a bis(1-adamantyl)phosphine
donor group (11), proved most promising for application in
Buchwald−Hartwig amination catalysis. This new ligand
demonstrates unprecedented activity for the monoarylation of
primary nucleophilic alkylamines, as well as the ability to couple
alternative amine classes (i.e., primary alkyl- and arylamines,
secondary dialkylamines) at ambient temperature. The 23·
Pd(cinnamyl)Cl catalyst system also exhibits chemoselectivity,
with a demonstrated preference for primary over secondary
amines. Such selectivity is further highlighted by the excellent
performance in a preliminary examination of the monoarylation
of both ammonia and acetone. This is the first example of a
bidentate NHC-phosphine system ligand with high activity in
Buchwald−Hartwig amination, and we believe that these
findings show this class of ligands to be promising and worthy
of further consideration by other researchers in the field. Our
continuing studies in this area will examine the utility of
phosphine-functionalized NHC ligands in other challenging
metal-catalyzed reactions and will aim to gain an improved
understanding of the coordination chemistry of this new ligand
system.
Synthesis of N1-{2-bromophenyl}-N2-Dipp-1,2-ethanediamine
(2). This was prepared similarly to 1 from bromoiodobenzene (1.41
g, 5.00 mmol) and N-2,6-diisopropylphenyl-1,2-diaminoethane (1.10
g, 5.0 mmol). Purification by flash chromatography (10/1 hexanes/
EtOAc) afforded a pale yellow oil, which crystallized upon standing for
1
several hours. Yield: 81% (1.51 g, 4.03 mmol). H NMR (500 MHz,
CDCl3): δ 7.47 (dd, J = 7.9, 1.5 Hz, 1H, 3-Ph), 7.20 (td, J = 7.7, 1.3
Hz, 1H, 5-Ph), 7.11 (ov m, 3H, m+p-Dipp), 6.71 (dd, J = 8.2, 1.3 Hz,
1H, 6-Ph), 6.61 (td, J = 7.6, 1.3 Hz, 1H, 4-Ph), 4.90 (t, J = 5.4 Hz, 1H,
NH), 3.46 (q, J = 5.5 Hz, 2H, CH2), 3.29 (sp, J = 6.9 Hz, 2H,
CH(CH3)2), 3.17 (t, J = 5.6 Hz, 2H, CH2), 3.11 (br s, 1H, NH), 1.22
(d, J = 6.9 Hz, 12H, CH(CH3)2). 13C{1H} NMR (126 MHz, CDCl3):
δ 144.9, 143.1, 142.6, 132.6 (3-Ph), 128.6 (5-Ph), 124.4 (p-Dipp),
123.7 (m-Dipp), 118.2 (4-Ph), 111.6 (6-Ph), 110.2, 50.4 (CH2), 44.2
(CH2), 27.8 (CH(CH3)2), 24.5 (CH(CH3)2). HRMS (ESI/[M +
H]+): calcd for C20H28BrN2 375.1430, found 375.1413.
Synthesis of N1-{2-bromophenyl}-N2-Ph-1,2-ethanediamine (3).
This was prepared similarly to 1 from bromoiodobenzene (1.41 g, 5.00
mmol) and N-phenyl-1,2-diaminoethane (695 mg, 5.10 mmol).
Filtration of the reaction mixture through a bed of silica and removal
of volatiles in vacuo afforded the title compound as a light yellow-
EXPERIMENTAL SECTION
■
General Considerations. Unless otherwise stated, all manipu-
lations were conducted under an inert N2 atmosphere of dinitrogen
using standard Schlenk methods or within an mBraun glovebox
apparatus, using glassware that was oven-dried at 120 °C and
evacuated while hot prior to use. Toluene, benzene, hexanes, and
pentane were deoxygenated and dried by sparging with dinitrogen gas,
followed by passage through a double-column solvent purification
system purchased from mBraun Inc. THF, 1,4-dioxane, and DME were
1
orange oil in 98% yield (1.43 g, 2.48 mmol). H NMR (500 MHz,
CDCl3): δ 7.46 (d, J = 7.9 Hz, 1H, 3-Ph), 7.26−7.17 (ov m, 3H, m-
NPh + 5-Ph), 6.78 (t, J = 7.3 Hz, 1H, 6-Ph), 6.72−6.67 (ov m, 3H, o
+p-NPh), 6.63 (t, J = 7.6 Hz, 1H, 4-Ph), 4.53 (br s, 1H, NH), 3.89 (br
s, 1H, NH), 3.48−3.42 (ov m, 4H, CH2). 13C{1H} NMR (126 MHz,
CDCl3): δ 147.9, 144.9, 132.7 (3-Ph), 129.5 (m-Ph), 128.6 (5-Ph),
118.3 (4-Ph), 118.0 (6-Ph), 113.2 (o-Ph), 111.6 (p-Ph), 110.2, 43.24
H
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(CH2), 43.10 (CH2). HRMS (ESI/[M + H]+): calcd for C14H16BrN2
291.0491, found 291.0493.
130.1 (s), 129.5 (s, m-Mes), 116.3 (d, J = 16.2 Hz), 115.4 (s, 5-Ph),
110.2 (d, J = 2.9 Hz, 3-Ph), 48.2 (s, NCH2), 44.7 (s, NCH2), 41.8 (d, J
= 11.4 Hz, CH2 Ad), 37.1 (d, J = 18.1 Hz, CH2 Ad), 37.0 (s,
quaternary Ad), 28.9 (d, J = 9.0 Hz, CH Ad), 20.7 (p-CH3 Mes), 18.6
(o-CH3 Mes). 31P{1H} NMR (202 MHz, CDCl3): δ 3.3 (s). HRMS
(ESI/[M + H]+): calcd for C37H52N2P 555.3863, found 555.3873.
Synthesis of N1-{2-(PAd2)phenyl}-N2-Ph-1,2-ethanediamine (7).
This compound was prepared similarly to 6 (Condition B) from 3
(580 mg, 2.0 mmol). Flash chromatography (20/1 hexanes/EtOAc)
provided the compound as a white powder in 53% yield (547 mg, 1.07
mmol). 1H NMR (500 MHz, CDCl3): δ 7.52 (dt, J = 7.6, 2.0 Hz, 1H,
6-Ph), 7.23 (ddd, J = 8.3, 7.1, 1.3 Hz, 1H, 4-Ph), 7.19−7.15 (m, 2H,
m-NPh), 6.72−6.65 (ov m, 3H, p-NPh + 3-Ph + 5-Ph), 6.62−6.60 (m,
2H, o-NPh), 5.99 (dt, J = 13.1, 6.4 Hz, 1H, NH), 3.92 (s, 1H, NH),
3.43 (q, J = 5.8 Hz, 2H, NCH2), 3.35 (t, J = 5.3 Hz, 2H, NCH2), 1.99−
1.97 (m, 6H, Ad), 1.90 (m, 12H, Ad), 1.67 (s, 12H, Ad). 13C{1H}
NMR (126 MHz, CDCl3): δ 154.3 (d, J = 20.3 Hz), 148.2 (s), 136.9
(d, J = 2.6 Hz, 6-Ph), 130.4 (s, 4-Ph), 129.4 (s, m-NPh), 117.6 (s),
116.6 (d, J = 15.4 Hz), 115.7 (s), 113.1 (s, p-NPh), 110.8 (d, J = 2.7
Hz, 3-Ph), 43.4 (d, J = 1.3 Hz, NCH2), 42.8 (s, NCH2), 41.8 (d, J =
11.3 Hz, CH2 Ad), 37.1 (d, J = 17.8 Hz, quaternary Ad), 37.0 (s, CH2
Ad), 28.9 (d, J = 8.9 Hz, CH Ad). 31P{1H} NMR (202 MHz, CDCl3):
δ 3.2 (s). HRMS (ESI/[M + H]+): calcd for C34H46N2P 513.3393,
found 513.3414.
Synthesis of N1-{2-(PPh2)phenyl}-N2-Mes-1,2-ethanediamine (4).
Pd(OAc)2 (4.5 mg, 0.02 mmol) and DiPPF (10 mg, 0.024 mmol)
were combined in a 2 dram catalysis vial with 4 mL of toluene. After
the mixture was stirred for 5 min, NaOtBu was added (135 mg, 1.4
mmol), followed by diphenylphosphine (186 mg, 1.0 mmol). The vial
was sealed with a cap containing a PTFE septum and removed from
the glovebox. Compound 1 (333 mg, 1.00 mmol) was added via
syringe. The vial was then heated to 110 °C with vigorous stirring for
1
21 h, at which point complete conversion was confirmed by H and
31P NMR of an aliquot of the reaction mixture. The cooled reaction
mixture was then filtered through a bed of silica and washed down
with CH2Cl2 (20 mL). The solution was concentrated, and the
resulting crude material was purified by flash chromatography (5/1
hexanes/EtOAc), giving the product as a yellow oil in 88% yield (388
1
mg, 0.885 mmol). H NMR (500 MHz, CDCl3): δ 7.35−7.32 (ov m,
10H, o+m+p-PPh2), 7.27 (ddd, J = 8.2, 7.2, 1.6 Hz, 1H, 4-Ph), 6.80−
6.78 (ov m, 3H, 6-Ph + m-Mes), 6.71 (dd, J = 8.2, 5.2 Hz, 1H, 3-Ph),
6.67 (t, J = 7.4 Hz, 1H, 5-Ph), 5.12 (br q, J = 6.4 Hz, 1H, NH), 3.33
(br q, J = 5.4 Hz, 2H, CH2), 3.10 (dd, J = 6.4, 4.8 Hz, 2H, CH2), 2.22
(s, 3H, p-CH3 Mes), 2.11 (s, 6H, o-CH3 Mes). 13C{1H} NMR (126
MHz, CDCl3): δ 151.2 (d, J = 18.1 Hz), 143.0, 135.6 (d, J = 7.3 Hz),
134.6 (d, J = 1.9 Hz, 6-Ph), 133.8 (d, J = 8.8 Hz, m-PPh2), 131.8, 130.8
(4-Ph), 130.4, 129.5 (m-Mes), 128.9 (p-PPh2), 128.7 (d, J = 7.1 Hz, o-
PPh2), 119.8 (d, J = 7.3 Hz), 117.7 (d, J = 1.8 Hz, 5-Ph), 110.5 (d, J =
2.2 Hz, 3-Ph), 47.6 (CH2), 44.5 (CH2), 20.7 (p-CH3 Mes), 18.3 (o-
CH3 Mes). 31P{1H} NMR (202 MHz, CDCl3): δ −22.0 (s). HRMS
(ESI/[M + H]+): calcd for C29H32N2P 439.2298, found 439.2282.
Synthesis of N1-{2-(PCy2)phenyl}-N2-Mes-1,2-ethanediamine (5).
This was prepared similarly to 4 from 1 (1.00 g, 3.00 mmol) and
dicyclohexylphosphine (615 mg, 3.1 mmol). After a 17 h reaction time,
filtration of the cooled reaction mixture through a bed of silica and
removal of volatiles in vacuo gave the title compound as a light red oil
Synthesis of N1-{2-(PAd2)phenyl}-N2-Dipp-1,2-ethanediamine (8).
This compound was prepared similarly to 4 from 2 (375 mg, 1.0
mmol) and bis(1-adamantyl)phosphine (302 mg, 1.0 mmol).
Purification by flash chromatography gave the compound as a light
1
yellow powder in 56% yield (334 mg, 0.56 mmol). H NMR (500
MHz, CDCl3): δ 7.54 (dt, J = 7.5, 2.0 Hz, 1H, 6-Ph), 7.23 (t, J = 7.7
Hz, 1H, 4-Ph), 7.12−7.06 (ov m, 3H, m+p-Dipp), 6.70−6.65 (ov m,
2H, 5-Ph + 3-Ph), 6.20 (dt, J = 13.0, 6.2 Hz, 1H, NH), 3.39−3.32 (ov
m, 4H, NCH2 + CH(CH3)2), 3.22 (s, 1H, NH), 3.13 (t, J = 5.6 Hz,
2H, NCH2), 2.06−1.96 (ov m, 6H, Ad), 1.91 (ov m, 12H, Ad), 1.68
(br s, 12H, Ad), 1.25 (d, J = 6.8 Hz, 12H, CH(CH3)2). 13C{1H} NMR
(126 MHz, CDCl3): δ 154.8 (d, J = 20.1 Hz), 143.0 (s), 142.9 (s),
136.7 (d, J = 2.5 Hz, 6-Ph), 130.3 (s, 4-Ph), 123.9 (s, p-Dipp), 123.6
(s, m-Dipp), 116.3 (d, J = 16.3 Hz), 115.4 (5-Ph), 110.4 (d, J = 2.8 Hz,
3-Ph), 51.2 (NCH2), 44.9 (s, NCH2), 41.7 (d, J = 11.6 Hz, CH2 Ad),
37.0 (d, J = 18.3 Hz, quaternary Ad), 36.9 (CH2 Ad), 28.8 (d, J = 8.7
Hz, CH Ad), 27.6 (CH(CH3)2), 24.5 (CH(CH3)2). 31P{1H} NMR
(202 MHz, CDCl3): δ 3.4 (s). HRMS (ESI/[M + H]+): calcd for
C40H58N2P 597.4332, found 597.4358.
1
in high purity and >99% yield (1.348 g, 2.99 mmol). H NMR (500
MHz, CDCl3): δ 7.25−7.19 (m, 2H, 4-Ph + 6-Ph), 6.83 (s, 2H, m-
Mes), 6.69 (td, J = 7.4, 1.0 Hz, 1H, 5-Ph), 6.65 (dd, J = 8.2, 4.9 Hz,
1H, 3-Ph), 5.67 (br s, 1H, NH), 3.34 (br m, 2H, CH2), 3.18 (t, J = 5.7
Hz, 3H, CH2), 2.26 (s, 6H, o-CH3 Mes), 2.24 (s, 3H, p-CH3 Mes),
1.96−1.86 (ov m, 4H, Cy), 1.77 (m, 2H, Cy), 1.71−1.56 (br ov m, 6H,
Cy), 1.32−1.05 (ov m, 10H). 13C{1H} NMR (126 MHz, CDCl3): δ
153.9 (d, J = 18.7 Hz), 143.3, 133.4 (6-Ph), 131.6, 130.2 (4-Ph), 129.5
(m-Mes), 117.0 (d, J = 13.6 Hz), 116.5 (5-Ph), 110.3 (3-Ph), 48.0
(NCH2), 44.8 (NCH2), 33.1 (d, J = 9.1 Hz, CH Cy), 30.6 (d, J = 16.2
Hz, CH2 Cy), 28.9 (d, J = 7.1 Hz, CH2 Cy), 27.3 (d, J = 12.8 Hz, CH2
Cy), 27.1 (d, J = 8.0 Hz, CH2 Cy), 26.5 (CH2 Cy), 20.7 (p-CH3 Mes),
18.5 (o-CH3 Mes); one quaternary carbon signal associated with the
Mes group is not observed. 31P{1H} NMR (202 MHz, CDCl3): δ
−26.6. HRMS (ESI/[M + H]+): calcd for C29H44N2P 451.3237, found
451.3237.
Synthesis of [1-Mes-3-{2-(PPh2)phenyl}imidazolidin-2-ylium][BF4]
(9). In air, compound 4 (365 mg, 0.832 mmol), NH4BF4 (105 mg, 1.0
mmol), 3 mL of CH(OEt)3, and a stir bar were combined in a 2 dram
vial. The open vial was heated to 120 °C for 1 h with vigorous stirring,
resulting in the formation of a yellow oil which separated from the
reaction mixture. After the mixture was cooled to ambient temper-
ature, the solvent was decanted from the oil and 4 mL of diethyl ether
was added. Stirring for 1 h provided a fine white powder, which was
collected by filtration and washed with additional diethyl ether (2 × 2
mL). The product was taken up in CH2Cl2 and filtered. Removal of
volatiles from the resulting clear solution afforded a white powder in
94% yield. Examination of the material by NMR revealed it to be
Synthesis of N1-{2-(PAd2)phenyl}-N2-Mes-1,2-ethanediamine (6).
Condition A. This procedure is similar to that used to prepare 4, from
1 (333 mg, 1.0 mmol) and bis(1-adamantyl)phosphine (302 mg, 1.0
mmol). Purification by flash chromatography (20/1 hexanes/EtOAc)
provided the compound as a light yellow powder in 62% yield.
Condition B. Pd(OAc)2 (9.0 mg, 0.04 mmol) and DiPPF (20 mg,
0.048 mmol) were combined in a 2 dram catalysis vial with 1,4-dioxane
(8 mL). After the mixture was stirred for 5 min, Cs2CO3 (912 mg, 2.8
mmol) was added, followed by 1 (667 mg, 2.0 mmol) and bis(1-
adamantyl)phosphine (605 mg, 2.0 mmol). The reaction mixture was
heated to 120 °C for 72 h, followed by the workup procedure
described for condition A. This provided the title compound in 66%
yield (734 mg, 1.32 mmol). 1H NMR (500 MHz, CDCl3): δ 7.53 (d, J
= 7.8 Hz, 1H, 6-Ph), 7.22 (t, J = 7.8 Hz, 1H, 4-Ph), 6.83 (s, 2H, m-
Mes), 6.68−6.63 (ov m, J = 7.1 Hz, 2H, 3-Ph + 5-Ph), 6.11 (dt, J =
13.1, 6.3 Hz, 1H, NH), 3.34 (q, J = 5.7 Hz, 2H, CH2), 3.23 (s, 1H,
NH), 3.18 (t, J = 5.8 Hz, 2H, CH2), 2.27 (s, 6H, o-CH3), 2.24 (s, 3H,
p-CH3), 2.03−1.96 (ov m, 6H, Ad), 1.93−1.87 (ov m, 12H, Ad), 1.68
(s, 12H, Ad). 13C{1H} NMR (126 MHz, CDCl3): δ 154.8 (d, J = 20.3
Hz), 143.4 (s), 136.8 (d, J = 2.3 Hz, 6-Ph), 131.5 (s), 130.4 (s, 4-Ph),
1
∼80% pure by integration of 31P NMR resonances. H NMR (500
MHz, CDCl3): δ 7.92 (ddd, J = 7.9, 4.4, 1.0 Hz, 1H, 3-Ph), 7.74 (d, J =
1.6 Hz, 1H, NCHN+), 7.56 (td, J = 7.7, 1.5 Hz, 1H, 4-Ph), 7.39 (ov m,
J = 7.8 Hz, 7H, o+p-PPh2 + 5-Ph), 7.22 (td, J = 8.0, 1.5 Hz, 4H, m-
PPh2), 6.94−6.92 (m, 3H, 6-Ph + m-Mes), 4.55 (dd, J = 12.2, 9.4 Hz,
2H, NCH2), 4.28 (dd, J = 12.2, 9.4 Hz, 2H, NCH2), 2.28 (s, 3H, p-
CH3 Mes), 2.26 (s, 6H, m-CH3 Mes). 13C{1H} NMR (126 MHz,
CDCl3): δ 158.1 (d, J = 4.3 Hz, NCHN+), 140.6 (s), 138.6 (d, J = 22.3
Hz), 135.4 (s), 134.6 (s, 6-Ph), 134.4 (d, J = 15.3 Hz), 134.0 (d, J =
8.1 Hz), 133.8 (d, J = 19.6 Hz, m-PPh2), 131.6 (s, 4-Ph), 130.7 (s, 5-
Ph), 130.0 (s, m-Mes), 130.0 (d, J = 7.0 Hz, o-PPh2), 129.3 (d, J = 7.2
Hz, p-PPh2), 128.0 (d, J = 1.8 Hz, 3-Ph), 53.0 (d, J = 5.9 Hz, NCH2),
51.7 (s, NCH2), 21.0 (s, p-CH3 Mes), 17.5 (o-CH3 Mes). 31P{1H}
NMR (202 MHz, CDCl3): δ −18.2 (s).
I
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Synthesis of [1-Mes-3-{2-(PCy2)phenyl}imidazolidin-2-ylium][BF4]
(10). This was prepared similarly to 11 (see below) from 5 (318 mg,
0.706 mmol), with a reaction time of 15 min. The product was
obtained as a white powder in 94% yield (365 mg, 0.666 mmol), which
was determined to be approximately 80% pure by integration of 31P
NMR resonances. 1H NMR (500 MHz, CDCl3): δ 7.84 (ddd, J = 8.0,
3.9, 1.2 Hz, 1H, 3-Ph), 7.80 (d, J = 2.7 Hz, 1H, NCHN+), 7.59 (dt, J =
7.6, 1.7 Hz, 1H, 6-Ph), 7.54 (td, J = 7.7, 1.4 Hz, 1H, 4-Ph), 7.47 (td, J
= 7.5, 1.2 Hz, 1H, 5-Ph), 6.99 (d, J = 0.4 Hz, 2H, m-Mes), 4.69 (dd, J
= 12.3, 9.3 Hz, 2H, NCH2), 4.44 (dd, J = 12.2, 9.4 Hz, 2H, NCH2),
2.44 (s, 6H, m-CH3 Mes), 2.32 (s, 3H, p-CH3 Mes), 1.87−1.65 (ov m,
10H, Cy), 1.46−1.30 (ov m, 4H, Cy), 1.18−1.06 (ov m, 6H, Cy),
0.98−0.89 (ov m, 2H, Cy). 13C{1H} NMR (126 MHz, CDCl3): δ
157.6 (d, J = 7.4 Hz, NCHN+), 141.7 (d, J = 23.2 Hz), 140.8 (s), 135.7
(s), 134.2 (d, J = 3.8 Hz, 6-Ph), 131.9 (d, J = 23.3 Hz), 131.6 (s, 4-Ph),
130.2 (s), 130.1 (s, m-Mes), 129.7 (s, 5-Ph), 127.3 (d, J = 3.0 Hz, 3-
Ph), 54.3 (d, J = 6.2 Hz, NCH2), 51.6 (s, NCH2), 34.2 (d, J = 11.3 Hz,
CH Cy), 30.8 (d, J = 17.2 Hz, CH2 Cy), 29.4 (d, J = 7.3 Hz, CH2 Cy),
26.9 (d, J = 13.0 Hz, CH2 Cy), 26.8 (d, J = 8.2 Hz, CH2 Cy), 26.1 (s,
CH2 Cy), 21.1 (s, p-CH3 Mes), 18.0 (d, J = 4.0 Hz Hz, p-CH3 Mes).
31P{1H} NMR (202 MHz, CDCl3): δ −16.5 (s).
Synthesis of [1-Mes-3-{2-(PAd2)phenyl}imidazolidin-2-ylium][BF4]
(11). In air, compound 6 (1.55 g, 2.79 mmol) and NH4BF4 (351 mg,
3.35 mmol) were combined in a 4 dram vial. A 10 mL portion of
CH(OEt)3 was added, and the open vial was heated to 110 °C with
vigorous stirring for 30 min. The resulting white precipitate was
collected by filtration and washed copiously with diethyl ether (5 × 5
mL). The product was taken up in CH2Cl2 and filtered through a
sintered glass frit. Solvent was removed from the resulting clear
solution, providing the product as a beige powder in 98% yield (1.79 g,
2.74 mmol). 1H NMR (500 MHz, CDCl3): δ 7.89−7.86 (m, 2H, 3-Ph
+ 6-Ph), 7.82 (d, J = 3.2 Hz, 1H, NCHN+), 7.58 (td, J = 7.7, 1.1 Hz,
1H, 4-Ph), 7.46 (td, J = 7.6, 1.2 Hz, 1H, 5-Ph), 7.00 (s, 2H, m-Mes),
4.72 (dd, J = 12.3, 9.3 Hz, 2H, NCH2), 4.43 (dd, J = 12.2, 9.4 Hz, 2H,
NCH2), 2.48 (s, 6H, o-CH3 Mes), 2.32 (s, 3H, p-CH3 Mes), 1.92−1.90
(m, 12H, Ad), 1.83−1.81 (m, 6H, Ad), 1.66 (m, 12H, Ad). 13C{1H}
NMR (126 MHz, CDCl3): δ 157.2 (d, J = 7.0 Hz), 142.4 (d, J = 25.2
Hz), 140.8 (s), 137.4 (d, J = 2.0 Hz, 6-Ph), 135.9 (s), 131.9 (s, 4-Ph),
130.7 (d, J = 28.5 Hz), 130.4 (s), 130.2 (s, m-Mes), 128.7 (s, 5-Ph),
127.7 (d, J = 3.1 Hz, 3-Ph), 54.3 (d, J = 5.8 Hz, NCH2), 51.6 (s,
NCH2), 42.2 (d, J = 11.4 Hz, CH2 Ad), 37.6 (d, J = 21.3 Hz,
quaternary Ad), 36.7 (s, CH2 Ad), 28.7 (d, J = 9.0 Hz, CH Ad), 21.2
(s, p-CH3 Mes), 18.1 (s, o-CH3 Mes). 31P{1H} NMR (202 MHz,
CDCl3): δ 14.2 (s).
CDCl3): δ 7.54 (t, J = 7.9 Hz, 1H, 5-Ph), 7.49 (t, 3JHH = 3JPH = 7.5 Hz,
1H, 3-Ph), 7.09−7.03 (m, 3H, o+m-Dipp), 6.96 (td, J = 7.5, 3.5 Hz,
1H, 4-Ph), 6.86 (dd, J = 8.5, 3.4 Hz, 1H, 6-Ph), 6.19 (d, J = 4.0 Hz,
1H, PCH+), 4.35−4.29 (m, 1H, OCH2), 4.17−4.07 (m, 1H, OCH2),
3.92−3.77 (m, 2H, NCH2), 3.27 (sp, J = 6.8 Hz, 2H, CH(CH3)2),
3.18−3.06 (m, 2H, NCH2), 2.51−2.49 (m, 3H, Ad), 2.22−2.17 (m,
6H, Ad), 2.11 (s, 10H, Ad), 1.91−1.83 (m, 3H, Ad), 1.79 (br s, 6H,
Ad), 1.76−1.67 (m, 3H, Ad), 1.30 (t, J = 7.0 Hz, 3H, OCH2CH3), 1.20
(d, J = 6.8 Hz, 6H, CH(CH3)2), 1.17 (d, J = 6.8 Hz, 6H, CH(CH3)2).
13C{1H} NMR (126 MHz, CDCl3): δ 155.0 (d, J = 8.3 Hz), 143.1 (s),
142.6 (s), 136.9 (d, J = 1.2 Hz, 5-Ph), 131.7 (d, J = 4.4 Hz, 3-Ph),
124.2 (s, p-Dipp), 123.6 (s, m-Dipp), 119.6 (d, J = 10.1 Hz, 4-Ph),
110.7 (d, J = 6.5 Hz, 6-Ph), 97.6 (d, J = 71.3 Hz), 90.7 (d, J = 63.7 Hz,
PCH+), 69.4 (d, J = 4.3 Hz, OCH2), 49.9 (s, NCH2), 49.0 (d, J = 6.2
Hz, NCH2), 43.4 (d, J = 24.7 Hz, quaternary Ad), 41.0 (d, J = 26.2 Hz,
quaternary Ad), 37.2 (d, J = 2.6 Hz, CH2 Ad), 36.9 (d, J = 2.5 Hz, CH2
Ad), 35.9 (s, CH2 Ad), 35.4 (s, CH2 Ad), 27.9 (d, J = 9.7 Hz, CH Ad),
27.7 (d, J = 9.4 Hz, CH Ad), 27.6 (s, CH(CH3)2), 24.5 (s,
CH(CH3)2), 24.4 (s, CH(CH3)2), 15.6 (s, OCH2CH3). 31P{1H} NMR
(202 MHz, CDCl3): δ 32.3 (s).
Synthesis of 2-Bromo-N-phenylbenzenamine (14). This was
prepared similarly to 1 from bromoiodobenzene (566 mg, 2.0
mmol) and aniline (186 mg, 2 mmol). After a reaction time of 15
min at 110 °C, the reaction mixture was cooled to ambient
temperature, filtered through a bed of silica, and washed down with
DCM (10 mL). Removal of volatiles afforded the title compound as a
light yellow liquid in 97% yield (482 mg, 1.94 mmol). NMR data
closely match previously reported values for this compound.30 1H
NMR (500 MHz, CDCl3): δ 7.53 (dd, J = 8.0, 1.5 Hz, 1H), 7.35−7.31
(m, 2H), 7.26 (dd, J = 8.2, 1.5 Hz, 1H), 7.19−7.15 (m, 3H), 7.05 (tt, J
= 7.4, 1.1 Hz, 1H), 6.75 (ddd, J = 8.0, 7.2, 1.6 Hz, 1H), 6.10 (br s,
1H).
Synthesis of 2-Dicyclohexylphosphino-N-phenylbenzenamine
(15). This was prepared similarly to 4 from 14 (248 mg, 1.0 mmol)
and dicyclohexylphosphine (198 mg, 1.0 mmol), with a reaction time
of only 30 min at 110 °C. Purification by flash chromatography (20/1
hexanes/EtOAc) gave the product as a light yellow solid in 91% yield
(333 mg, 0.91 mmol). 1H NMR (500 MHz, CDCl3): δ 7.32 (ddd, J =
7.6, 2.8, 1.5 Hz, 1H, 6-Ph), 7.30−7.25 (m, 3H, 3-Ph + m-NPh), 7.21
(td, J = 7.7, 1.4 Hz, 1H, 4-Ph), 7.16 (br d, J = 11.1 Hz, 1H, NH), 7.13
(dd, J = 8.5, 1.0 Hz, 2H, o-NPh), 6.94 (tt, J = 7.3, 1.1 Hz, 1H, p-NPh),
6.87 (td, J = 7.4, 1.2 Hz, 1H, 5-Ph), 1.93 (tq, J = 11.8, 2.9 Hz, 2H, Cy),
1.88−1.85 (m, 2H, Cy), 1.77−1.73 (m, 2H, Cy), 1.71−1.61 (m, 6H,
Cy), 1.34−1.03 (m, 10H, Cy). 13C{1H} NMR (126 MHz, CDCl3): δ
149.2 (d, J = 18.3 Hz), 143.2 (s), 133.5 (s, 6-Ph), 129.6 (s, 4-Ph),
129.3 (s, m-NPh), 121.4 (s, p-NPh), 120.5 (d, J = 12.8 Hz), 119.6 (s,
5-Ph), 119.1 (s, o-NPh), 115.7 (s, 3-Ph), 32.9 (d, J = 9.4 Hz, Cy CH),
30.5 (d, J = 16.2 Hz, Cy CH2), 28.8 (d, J = 6.8 Hz, Cy CH2), 27.4 (d, J
= 12.5 Hz, Cy CH2), 27.1 (d, J = 7.9 Hz, Cy CH2), 26.5 (s, Cy CH2).
31P{1H} NMR (202 MHz, CDCl3): δ −24.4 (s). HRMS (ESI/[M +
Synthesis of Phosphonium Salt 12. This was prepared similarly to
11 from 7, giving the phosphonium salt compound in 91% yield (243
1
mg, 0.91 mmol). H NMR (500 MHz, CDCl3): δ 7.75 (t, J = 7.3 Hz,
1H, 5-Ph), 7.70 (t, J = 7.9 Hz, 1H, 4-Ph), 7.42 (dd, J = 8.8, 7.3 Hz, 2H,
m-NPh), 7.29 (dd, J = 8.3, 3.4 Hz, 1H, 3-Ph), 7.25 (td, J = 7.6, 2.9 Hz,
1H, 6-Ph), 7.10−7.04 (ov m, 3H, o+p-NPh), 6.61 (d, J = 24.2 Hz, 1H,
PCH+), 3.97 (t, J = 6.8 Hz, 2H, NCH2), 3.76 (td, J = 6.8, 1.6 Hz, 2H,,
NCH2), 2.21−2.18 (m, 6H, Ad), 2.05−1.98 (m, 12H, Ad), 1.74−1.68
(m, 12H, Ad). 13C{1H} NMR (126 MHz, CDCl3): δ 155.4 (d, J = 15.6
Hz), 144.1 (s), 136.3 (s, 4-Ph), 132.6 (s, 5-Ph), 130.1 (s, m-NPh),
123.6 (d, J = 8.1 Hz, 6-Ph), 122.9 (s, p-NPh), 117.6 (d, J = 5.7 Hz, 3-
Ph), 117.3 (s, o-NPh), 88.6 (br s, PCH+), 51.9 (s, NCH2), 51.3 (d, J =
3.5 Hz, NCH2), 42.7 (d, J = 14.9 Hz, quaternary Ad), 38.2 (s, CH2
Ad), 35.7 (s, CH2 Ad), 27.9 (d, J = 9.1 Hz, CH Ad). 31P{1H} NMR
(202 MHz, CDCl3): δ 36.2 (s).
H]+): calcd for C24H32NP 366.2345, found 366.2339.
Synthesis of Phosphonium Salt 16. In air, compound 15 (258 mg,
0.706 mmol) was combined with NH4BF4 (89 mg, 0.85 mmol), 3 mL
of CH(OEt)3, and a stir bar in a 4 dram vial. The open vial was heated
to 110 °C with vigorous stirring for 20 min, at which point an orange
oil was observed to have separated. Upon cooling, 5 mL of diethyl
ether was added to encourage complete precipitation. The supernatant
was decanted, and the oil was washed with diethyl ether (3 × 2 mL).
The resulting solid material was taken up in CH2Cl2 and filtered.
Evaporation of the solvent afforded 267 mg of the product as a light
yellow powder. The collected supernatant and washings were left to
stand for 24 h, resulting in crystallization of a further 64 mg of product,
giving a combined yield of 92% (331 mg, 0.650 mmol). 1H NMR (500
Synthesis of Phosphonium Salt 13. In air, diamine compound 8
(50 mg, 0.084 mmol) was combined with NH4BF4 (10 mg, 0.095
mmol), 1 mL of CH(OEt)3, and a stir bar in a 1 dram vial. The open
vial was heated to 80 °C with vigorous stirring for 10 min. The
resulting white precipitate was separated by decanting and then
washed with diethyl ether (3 × 2 mL). The powder was taken up in
CH2Cl2 and filtered through a sintered-glass frit, and the volatiles were
removed to provide 13 mg of the title compound. The collected
supernatant and washings were left to stand for 24 h, which resulted in
the crystallization of an additional 16 mg of material, giving a
3
3
MHz, CDCl3): δ 7.53 (t, JHH = JPH = 7.9 Hz, 1H, 3-Ph), 7.50−7.44
(ov m, 3H, 5-Ph + m-NPh), 7.41−7.35 (m, 3H, o+p-NPh), 6.99 (td, J
= 7.5, 3.4 Hz, 1H, 4-Ph), 6.64 (dd, J = 8.5, 3.4 Hz, 1H, 6-Ph), 6.17 (d, J
= 1.9 Hz, 1H, PCH+), 3.88 (dq, J = 9.3, 7.1 Hz, 1H, OCH2CH3), 3.48
(dq, J = 9.1, 7.1 Hz, 1H, OCH2CH3), 3.33−3.25 (m, 1H, Cy), 2.92
(qt, J = 13.3, 2.9 Hz, 1H, Cy), 2.30−2.27 (m, 1H, Cy), 2.16−2.05 (m,
3H, Cy), 1.98−1.94 (m, 2H, Cy), 1.86−1.66 (m, 7H, Cy), 1.55 (qt, J =
1
combined yield of 47% (29 mg, 0.039 mmol). H NMR (500 MHz,
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13.0, 3.1 Hz, 1H, Cy), 1.46−1.34 (m, 3H, Cy), 1.28 (qt, J = 13.0, 3.3
Hz, 1H, Cy), 1.14−1.10 (m, 1H, Cy), 1.05 (t, J = 7.0 Hz, 3H,
OCH2CH3), 1.01−0.91 (m, 1H, Cy). 13C{1H} NMR (126 MHz,
CDCl3): δ 155.3 (d, J = 10.2 Hz), 139.2 (d, J = 7.3 Hz), 136.8 (s, 5-
Ph), 132.1 (d, J = 5.0 Hz, 3-Ph), 130.5 (s, m-NPh), 128.5 (s, p-NPh),
127.7 (s, o-NPh), 120.7 (d, J = 10.3 Hz, 4-Ph), 112.0 (d, J = 7.4 Hz, 6-
Ph), 98.1 (d, J = 74.0 Hz), 89.4 (d, J = 71.5 Hz, PCH+), 70.1 (d, J = 5.9
Hz, OCH2CH3), 30.4 (d, J = 6.0 Hz, Cy CH), 30.1 (d, J = 2.4 Hz, Cy
CH), 26.8 (d, J = 3.9 Hz, Cy CH2), 26.7 (d, J = 8.8 Hz, Cy CH2), 26.6
(d, J = 8.5 Hz, Cy CH2), 26.4 (d, J = 3.7 Hz, Cy CH2), 25.8 (d, J = 4.6
Hz, Cy CH2), 25.6 (d, J = 14.2 Hz, Cy CH2), 25.5 (s, Cy CH2), 25.3
(d, J = 4.2 Hz, Cy CH2), 25.2 (s, Cy CH2), 25.1 (d, J = 13.6 Hz, Cy
CH2), 15.4 (s, OCH2CH3). 31P{1H} NMR (202 MHz, CDCl3): δ 39.5
(s).
NCH2), 2.29 (s, 6H, o-CH3 Mes), 2.25 (s, 3H, p-CH3 Mes), 1.97−1.91
(ov m, 4H, Cy), 1.84−1.45 (ov m, 8H, Cy), 1.36−1.00 (ov m, 10H,
Cy). 13C{1H} NMR (126 MHz, CDCl3): δ 147.1 (d, J = 24.5 Hz),
144.0 (s), 133.8 (d, J = 20.0 Hz), 133.0 (d, J = 3.4 Hz, 3-Ph), 131.0
(s), 129.8 (s), 129.7 (d, J = 6.5 Hz, 6-Ph), 129.4 (s, m-Mes), 128.8 (s,
5-Ph), 126.5 (s, 4-Ph), 52.6 (d, J = 21.3 Hz, PhCH2), 49.1 (s, NCH2),
48.4 (s, NCH2), 34.1 (d, J = 12.1 Hz, CH Cy), 30.7 (d, J = 17.1 Hz,
CH2 Cy), 29.2 (d, J = 8.1 Hz, CH2 Cy), 27.3 (d, J = 12.3 Hz, CH2 Cy),
27.2 (d, J = 7.6 Hz, CH2 Cy), 26.5 (s, CH2 Cy), 20.7 (s, p-CH3 Mes),
18.6 (s, o-CH3 Mes). 31P{1H} NMR (202 MHz, CDCl3): δ −16.2 (s).
HRMS (ESI/[M + H]+): calcd for C30H46N2P 465.3393, found
465.3384.
Synthesis of N1-(2-(PCy2)benzyl)-N2-Dipp-ethane-1,2-diamine
(20). This was prepared similarly to 19 from 18 (1.168 g, 3.00
mmol), giving the compound as a light orange oil, which crystallized
upon standing to give a light orange crystalline solid in 85% yield
(1.292 g, 2.55 mmol). 1H NMR (500 MHz, CDCl3): δ 7.47 (d, J = 8.1
Hz, 1H, 3-Ph), 7.41 (dd, J = 7.3, 3.8 Hz, 1H, 6-Ph), 7.32 (t, J = 7.2 Hz,
1H, 5-Ph), 7.26 (t, J = 7.0 Hz, 1H, 4-Ph), 7.10−7.02 (m, 3H, m+p-
Dipp), 4.10 (s, 2H, PhCH2), 3.34 (sp, J = 6.8 Hz, 2H, CH(CH3)2),
2.99 (t, J = 5.6 Hz, 2H, NCH2), 2.85 (t, J = 5.6 Hz, 2H, NCH2), 1.95−
1.90 (m, 4H, Cy), 1.78−1.51 (m, 8H, Cy), 1.36−1.26 (m, 2H, Cy),
1.23 (d, J = 6.8 Hz, 12H, CH(CH3)2), 1.18−0.98 (m, 8H, Cy).
13C{1H} NMR (126 MHz, CDCl3): δ 143.8 (s), 142.6 (s), 133.8 (d, J
Synthesis of N1-(2-bromobenzyl)-N2-Mes-ethane-1,2-diamine
(17). 2-Bromobenzaldehyde (2.77 g, 15.0 mmol) was combined with
N-mesityl-1,2-diaminoethane (2.67 g, 15.0 mmol) in 60 mL of toluene
and stirred at ambient temperature for 1 h. The mixture was then dried
with sodium sulfate and filtered, and the volatiles were removed under
reduced pressure, giving the crude imine condensation product as a
pale yellow oil. This material was dissolved in 60 mL of anhydrous
ethanol, and sodium borohydride (1.14 g, 30 mmol) was added slowly
with stirring over approximately 15 min. After the reaction mixture was
stirred for 19 h, it was quenched with 60 mL of water and extracted
with CH2Cl2 (3 × 60 mL). The combined organic extracts were dried
with sodium sulfate, filtered, and evaporated to dryness under reduced
pressure, giving the desired compound as a light brown oil in 77%
yield (4.032 g, 12.1 mmol). 1H NMR (500 MHz, CDCl3): δ 7.57 (d, J
= 8.0 Hz, 1H, 6-Ph), 7.41 (dd, J = 7.6, 1.4 Hz, 1H, 3-Ph), 7.31 (t, J =
7.5 Hz, 1H, 4-Ph), 7.15 (td, J = 7.6, 1.5 Hz, 1H, 5-Ph), 6.84 (s, 2H, m-
Mes), 3.93 (s, 2H, PhCH2), 3.08 (t, J = 5.6 Hz, 2H, NCH2), 2.85 (t, J
= 5.6 Hz, 2H, NCH2), 2.29 (s, 6H, o-CH3 Mes), 2.25 (s, 3H, p-CH3
Mes). 13C{1H} NMR (126 MHz, CDCl3): δ 143.8 (s), 139.3 (s),
132.9 (s, 6-Ph), 131.2 (s), 130.3 (s, 3-Ph), 129.7 (s), 129.5 (s, m-Mes),
128.7 (s, 5-Ph), 127.5 (s, 4-Ph), 124.1 (s), 53.6 (s, PhCH2), 49.2 (s,
NCH2), 48.3 (s, NCH2), 20.7 (s, p-CH3 Mes), 18.6 (s, o-CH3 Mes).
HRMS (ESI/[M + H]+): calcd for C18H24BrN2 347.1117, found
347.1115.
= 19.4 Hz), 133.1 (s, 3-Ph), 133.1 (s), 129.6 (d, J = 6.1 Hz, 6-Ph),
128.8 (s, 5-Ph), 126.6 (s, 4-Ph), 123.6 (s, m-Dipp), 123.6 (s, p-Dipp),
52.7 (d, J = 21.9 Hz, PhCH2), 51.4 (s, NCH2), 49.1 (s, NCH2), 34.1
(d, J = 12.1 Hz, CH Cy), 30.8 (d, J = 17.2 Hz, CH2 Cy), 29.2 (d, J =
8.0 Hz, CH2 Cy), 27.7 (s, CH(CH3)2), 27.3 (d, J = 12.5 Hz, CH2 Cy),
27.2 (d, J = 8.1 Hz, CH2 Cy), 26.5 (s, CH2 Cy), 24.5 (s, CH(CH3)2).
31P{1H} NMR (202 MHz, CDCl3): δ −16.3 (s). HRMS (ESI/[M +
H]+): calcd for C33H52N2P 507.3863, found 507.3852.
Synthesis of [1-Mes-3-{2-(PCy2)benzyl}imidazolidin-2-ylium][BF4]
(21). In air, compound 20 (0.500 g, 1.08 mmol) was combined with
ammonium tetrafluoroborate (0.124 g, 1.18 mmol) and 3 mL of
triethyl orthoformate in a 2 dram vial. The vial was sealed, and the
reaction mixture was sparged with N2 for 15 min. Under a constant
flow of N2, the vial was heated to 110 °C with vigorous stirring for 15
min at 110 °C. After the mixture was cooled, the resulting precipitate
was collected on a sintered-glass frit and washed with diethyl ether (3
× 2 mL). The product was then dissolved in CH2Cl2, filtered, and
dried under reduced pressure, resulting in a light yellow powder in a
Synthesis of N1-(2-bromobenzyl)-N2-Dipp-ethane-1,2-diamine
(18). This was prepared similarly to 17 from 2-bromobenzaldehyde
(2.77 g, 15.0 mmol) and N-2,6-diisopropylphenyl-1,2-diaminoethane
(3.305 g, 15.0 mmol), giving the product in 72% yield (4.203 g, 10.8
1
1
mmol). H NMR (500 MHz, CDCl3): δ 7.60 (d, J = 8.0 Hz, 1H, 3-
yield of 82% (498 mg, 0.89 mmol). H NMR (500 MHz, CDCl3): δ
Ph), 7.47 (dd, J = 7.6, 1.2 Hz, 1H, 6-Ph), 7.34 (t, J = 7.1 Hz, 1H, 5-
Ph), 7.17 (td, J = 7.7, 1.4 Hz, 1H, 4-Ph), 7.14−7.07 (m, 3H, m+p-
Dipp), 3.98 (s, 2H, PhCH2), 3.37 (sp, J = 6.8 Hz, 2H, CH(CH3)2),
3.05 (dd, J = 6.4, 4.7 Hz, 2H, NCH2), 2.94 (dd, J = 6.5, 4.6 Hz, 2H,
NCH2), 1.27 (d, J = 6.9 Hz, 12H, CH(CH3)2). 13C{1H} NMR (126
MHz, CDCl3): δ 143.6 (s), 142.5 (s), 139.3 (s), 132.9 (s, 3-Ph), 130.2
(s, 6-Ph), 128.7 (s, 4-Ph), 127.5 (s, 5-Ph), 124.0 (s), 123.7 (s, p-Dipp),
123.6 (s, m-Dipp), 53.5 (s, PhCH2), 51.2 (s, NCH2), 49.1 (s, NCH2),
27.7 (s, CH(CH3)2), 24.4 (s, CH(CH3)2). HRMS (ESI/[M + H]+):
calcd for C21H30BrN2 389.1587, found 389.1580.
7.94 (s, 1H), 7.55−7.47 (ov m, 2H), 7.41−7.37 (ov m, 2H), 6.91 (s,
2H), 5.14 (s, 2H), 4.15−4.04 (m, 4H), 2.27 (s, 6H), 2.26 (s, 3H),
1.96−1.82 (ov m, 4H), 1.80−1.45 (ov m, 8H), 1.34−0.87 (ov m,
10H). 13C{1H} NMR (126 MHz, CDCl3): δ 157.9 (d, J = 4.6 Hz,
NCHN+), 140.4 (s), 138.4 (d, J = 24.4 Hz), 135.6 (s), 135.3 (d, J =
22.4 Hz), 133.7 (d, J = 3.3 Hz, 5-Ph), 131.6 (d, J = 5.5 Hz, 3-Ph),
130.6 (s), 130.0 (s, Ph), 130.0 (s, m-Mes), 129.1 (s, Ph), 51.2 (d, J =
22.0 Hz, PhCH2), 51.1 (s, NCH2), 48.5 (d, J = 1.4 Hz, NCH2), 33.4
(d, J = 11.5 Hz, CH Cy), 30.4 (d, J = 16.7 Hz, CH2 Cy), 28.9 (d, J =
7.1 Hz, CH2 Cy), 27.1 (d, J = 12.5 Hz, CH2 Cy), 27.0 (d, J = 7.4 Hz,
CH2 Cy), 26.3 (s, CH2 Cy), 21.1 (s, p-CH3 Mes), 17.9 (s, m-CH3
Mes). 31P{1H} NMR (202 MHz, CDCl3): δ −16.2 (s).
Synthesis of N1-(2-(PCy2)benzyl)-N2-Mes-ethane-1,2-diamine
(19). Pd(OAc)2 (13.5 mg, 0.06 mmol, 2 mol %) and DiPPF (30
mg, 0.072 mmol, 2.4 mol %) were combined in a 4 dram vial with 6.0
mL of toluene stirred for 5 min. NaOtBu (0.4036 g, 4.2 mmol),
dicyclohexylphosphine (0.7112 mL, 3.3 mol), and 6 mL of additional
toluene were then added. The mixture was sealed with a cap
containing a PTFE septum, the vial was removed from the glovebox,
and 17 (1.051 g, 3.0 mmol) was injected with a syringe. The mixture
was heated to 110 °C with stirring for 23 h. After it was cooled, the
reaction mixture was then filtered through a bed of silica, which was
washed down with 20 mL of 10/1 CH2Cl2/MeOH, and concentrated
under reduced pressure. Purification by flash chromatography (20/1
CH2Cl2/MeOH) afforded the product as a light orange oil in 96%
yield. 1H NMR (500 MHz, CDCl3): δ 7.49 (d, J = 7.5 Hz, 1H, 3-Ph),
7.40 (dd, J = 7.0, 3.7 Hz, 1H, 6-Ph), 7.32 (t, J = 7.1 Hz, 1H, 5-Ph),
7.27 (t, J = 7.3 Hz, 1H, 4-Ph), 6.83 (s, 2H, m-Mes), 4.10 (s, 2H,
PhCH2), 3.06 (t, J = 5.7 Hz, 2H, NCH2), 2.82 (t, J = 5.7 Hz, 2H,
Synthesis of [1-Dipp-3-{2-(PCy2)benzyl}imidazolidin-2-ylium][BF4]
(22). This was prepared similarly to 21 from 20 (300 mg, 0.593
mmol), affording the dihydroimidazolium salt product in 65% yield
1
(233 mg, 0.385 mmol). H NMR (500 MHz, DMSO-d6): δ 9.08 (s,
1H, NCHN+), 7.68−7.62 (m, 1H), 7.53−7.49 (m, 3H), 7.48−7.43 (m,
1H), 7.38 (d, J = 7.8 Hz, 2H, m-Dipp), 5.10 (s, 2H, PhCH2), 4.13 (t, J
= 10.8 Hz, 2H, NCH2), 3.92 (t, J = 10.8 Hz, 2H, NCH2), 2.99 (sp, J =
6.8 Hz, 2H, CH(CH3)2), 2.02 (t, J = 11.4 Hz, 2H, Cy), 1.91 (d, J =
12.1 Hz, 2H, Cy), 1.78−1.47 (m, 8H, Cy), 1.38−1.29 (m, 2H, Cy),
1.25 (d, J = 6.9 Hz, 6H, CH(CH3)2), 1.23 (d, J = 6.8 Hz, 6H,
CH(CH3)2), 1.22−1.15 (m, 2H, Cy), 1.14−0.99 (m, 4H, Cy), 0.98−
0.88 (m, 2H, Cy). 13C{1H} NMR (126 MHz, DMSO-d6): δ 159.0 (s,
NCHN+), 146.4 (s), 139.0 (d, J = 24.5 Hz), 134.7 (d, J = 23.0 Hz),
133.5 (d, J = 2.7 Hz), 130.8 (s), 130.3 (s), 130.1 (d, J = 5.1 Hz), 129.6
(s), 128.6 (s), 124.7 (s, m-Dipp), 53.2 (s, NCH2), 50.3 (d, J = 24.3 Hz,
K
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Table 7. Crystal Data and Refinement Details for 12, 13, 16, and 21
12
13
16
21
empirical formula
formula wt
temp (K)
wavelength (Å)
cryst syst
space group
a (Å)
C35H44BF4N2P
610.50
C43H62BF4N2OP
740.73
C27H37BF4NOP
509.36
C31H44BF4N2P
562.46
173(2)
173(2)
173(2)
173(2)
1.54178
orthorhombic
Pbca
1.54178
1.54178
0.71073
monoclinic
P21/n
triclinic
orthorhombic
P212121
P1
̅
11.3006(2)
19.9760(3)
13.2786(2)
90
10.63530(10)
13.9417(2)
14.0006(2)
100.1680(10)
100.5580(10)
97.8890(10)
1977.63(4)
2
8.6050(5)
14.4373(8)
21.6605(12)
90
12.8487(4)
13.8907(4)
34.2663(9)
90
b (Å)
c (Å)
α (deg)
β (deg)
90.0860(10)
90
90
90
γ (deg)
V (Å3)
90
90
2997.52(8)
4
2690.9(3)
4
6115.8(3)
8
Z
ρcalcd (Mg m−3
)
1.353
1.244
1.257
1.222
μ (mm−1
)
1.259
1.059
0.150
1.187
cryst size (mm3)
0.52 × 0.18 × 0.14
4.00−70.20
54617
0.23 × 0.20 × 0.11
3.27−70.09
61462
0.53 × 0.20 × 0.14
1.70−26.37
46620
0.39 × 0.22 × 0.03
2.58−70.25
174379
θ range (deg)
no. of rflns collected
no. of indep rflns (R(int))
GOF on F2
5509 (0.0381)
1.043
7080 (0.0303)
1.057
5486 (0.0498)
1.062
5775 (0.1560)
1.013
a
final R indices (I > 2σ(I))
R1 = 0.0398
wR2 = 0.1071
R1 = 0.0410
wR2 = 0.1083
R1 = 0.0448
wR2 = 0.1266
R1 = 0.0478
wR2 =0.1297
0.454, −0.521
R1 = 0.0414
wR2 = 0.1098
R1 = 0.0500
wR2 = 0.1160
0.625, −0.338
R1 = 0.0510
wR2 = 0.1320
R1 = 0.0678
wR2 = 0.14480
0.505, −0.381
a
R indices (all data)
largest peak, hole (e Å−3
)
0.557, −0.386
a
R1 = ∑||Fo| − |Fc||/∑|Fo|. wR2 = [∑[w(Fo − Fc2)2]/∑[w(Fo )2]]1/2. w = 1/[σ2(Fo ) + (mP)2 + nP], where P = (Fo + 2Fc2)/3.
2
2
2
2
PhCH2), 48.0 (s, NCH2), 32.6 (d, J = 12.1 Hz, CH Cy), 29.9 (d, J =
16.9 Hz, CH2 Cy), 28.5 (d, J = 7.8 Hz, CH2 Cy), 27.9 (s, CH(CH3)2),
26.5 (d, J = 12.4 Hz, CH2 Cy), 26.3 (d, J = 7.7 Hz, CH2 Cy), 26.0 (s,
CH2 Cy), 24.8 (s, CH(CH3)2), 23.8 (s, CH(CH3)2). 31P{1H} NMR
(202 MHz, DMSO-d6): δ −17.0 (s).
mmol, 1.3 mg, 1 mol %) was added. After the mixture was stirred for
an additional 5 min, NaOtBu (0.35 mmol), PhCl (0.25 mmol), and
amine (0.3 mmol) were added sequentially. The vial was sealed with a
cap containing a PTFE septum, removed from the glovebox, and
heated to 110 °C with vigorous stirring. After 24 h, the reaction
mixture was cooled to ambient temperature and an aliquot was
removed, filtered through silica with CH2Cl2, and analyzed by GC.
Representative Procedure for Preparation of Precatalyst
Mixtures. Freshly prepared NHC-P compound 23 (400 mg, 0.708
mmol) was dissolved in 4 mL of THF. The resulting colorless solution
was added dropwise to a rapidly stirred suspension of [Pd(cinnamyl)-
Cl]2 in THF over a 10 min period, giving initially a light red solution.
Stirring was continued for 1 h, and over this time the solution
gradually became very dark red. Removal of solvent in vacuo gave the
precatalyst mixture 23·Pd(cinnamyl)Cl as a red powder.
Procedure for Arylation of Primary Amines (Table 5). A 0.0050 M
stock solution of precatalyst mixture 23·Pd(cinnamyl)Cl was prepared
by dissolving 32.8 mg of the precatalyst in 8.00 mL of 1,4-dioxane.
Stock solutions were freshly prepared as required and used within 1 h.
A 2.00 mL portion of the stock solution was added to a 1 dram
catalysis vial containing LiHMDS (234 mg, 1.4 mmol), and the
mixture was stirred for 5 min. The vial was sealed with a cap
containing a PTFE septum and removed from the glovebox. The aryl
halide and primary amine were then added sequentially using a
syringe, and the reaction mixture was stirred at ambient temperature
(65 °C for 24h). Upon completion of the reaction, the mixture was
filtered through a bed of silica and washed through with CH2Cl2.
Removal of volatiles gave the arylamine product, which was purified by
flash chromatography in silica if necessary. Reported isolated yields are
an average of two runs. In some instances, the procedure was modified
with the use of NaOtBu base (135 mg, 1.4 mmol), as noted in Table 5.
Procedure for Arylation of Secondary Amines (Table 6). A 0.0050
M stock solution of precatalyst mixture 23·Pd(cinnamyl)Cl was
prepared by dissolving 32.8 mg of the precatalyst in 8.00 mL of DME.
Then 2.00 mL of freshly prepared stock solution was added to a 1
dram catalysis vial containing NaOtBu (135 mg, 1.4 mmol) and the
1-Mes-3-{2-(PAd2)phenyl}imidazolidin-2-ylidene (23). The dihy-
droimidazolium salt 11 (800 mg, 1.23 mmol) was combined with 1
equiv of NaHMDS (225 mg, 1.23 mmol) in a 4 dram vial. An 8 mL
portion of THF was added, and the resulting mixture was stirred at
ambient temperature for 1 h. The reaction mixture was then filtered
through Celite and concentrated to approximately 0.5 mL. Addition of
pentane (5 mL) precipitated the product as a beige solid. This was
decanted, washed with pentane (3 × 3 mL), and dried in vacuo,
yielding 578 mg of the product as a beige powder. A further 62 mg of
material crystallized from the collected washings upon standing for 24
1
h, giving a total yield of 92% (640 mg, 1.13 mmol). H NMR (500
MHz, C6D6): δ 7.86 (d, J = 7.3 Hz, 1H, 6-Ph), 7.70 (br s, 1H, 3-Ph),
7.21 (t, J = 7.4 Hz, 1H, 4-Ph), 7.14 (t, J = 7.4 Hz, 1H, 5-Ph), 6.83 (s,
2H, m-Mes), 4.18 (br m, 2H, NCH2), 3.49 (br m, 2H, NCH2), 2.40 (s,
6H, o-CH3 Mes), 2.15−2.09 (ov m, 15H, p-CH3 Mes + Ad), 1.87 (br s,
6H, Ad), 1.63 (br s, 12H, Ad). 13C{1H} NMR (126 MHz, C6D6): δ
245.1 (br s, NCN), 137.1 (s, 6-Ph), 136.3 (s), 130.1 (s, 4-Ph), 130.0
(d, J = 4.3 Hz, 3-Ph), 129.4 (s, m-Mes), 125.2 (br s, 5-Ph), 54.5 (d, J =
19.0 Hz, NCH2), 51.8 (s, NCH2), 42.6 (d, J = 13.0 Hz, CH2 Ad), 37.6
(d, J = 25.2 Hz, quaternary Ad), 37.3 (s, CH2 Ad), 29.3 (d, J = 8.5 Hz,
CH Ad), 21.1 (s, p-CH3 Mes), 18.6 (s, o-CH3 Mes). Four quaternary
aromatic carbon resonances are not observed due to the broad
resonances associated with this compound. A broad Ccarbene peak at
245.1 is only observed upon the application of substantial line
broadening to improve the signal to noise ratio. 31P{1H} NMR (202
MHz, C6D6): δ 19.5 (s).
Details of Catalytic Studies. Procedure for Preliminary
Screening Studies (Table 1). The dihydroimidazolium salt (0.01
mmol, 4 mol %) and NaHMDS (0.01 mmol, 1.8 mg) were combined
in a 1 dram catalysis vial with a stir bar and 0.50 mL of toluene. The
mixture was stirred for 5 min, and then [Pd(cinnamyl)Cl]2 (0.0025
L
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Organometallics
Article
mixture was stirred for 5 min. The vial was sealed with a cap
containing a PTFE septum and removed from the glovebox. The aryl
halide and secondary amine were then added sequentially using a
syringe, and the reaction mixture was stirred at ambient temperature
(65 °C for 25f). Upon completion, the reaction mixture was filtered
through a bed of silica and washed through with CH2Cl2. Removal of
volatiles gave the arylamine product, which was purified by flash
chromatography if necessary. Reported isolated yields are an average of
two runs.
Biography
Procedure for Monoarylation of Ammonia. Using a modification
of the literature procedure,6g 4.1 mg of the precatalyst mixture 23·
Pd(cinnamyl)Cl (0.005 mmol, 2 mol %) was combined in a 1 dram
catalysis vial with NaOtBu (48.1 mg, 0.50 mmol) and 0.5 mL of 1,4-
dioxane. The mixture was stirred for 5 min, and chlorobenzene (25.4
μL, 0.25 mmol) was added. The vial was sealed with a cap containing a
PTFE septum and removed from the glovebox. A 2.5 mL portion of a
0.5 M solution of ammonia in 1,4-dioxane (1.25 mmol, 5 equiv) was
added with a syringe. The vial was heated to 110 °C with stirring for
30 min, at which time the reaction was complete. Calibrated GC
analysis, with calibration using authentic samples and measurements
relative to dodecane as an internal standard, was used to determine the
yield of product and the ratio of monoarylation to diarylation.
Procedure for Mono-α-arylation of Acetone. Using a modification
of the general procedure,26e 4.1 mg of the precatalyst mixture 23·
Pd(cinnamyl)Cl (0.005 mmol, 2 mol %) was combined in a 1 dram
catalysis vial with a catalytic amount of NaOtBu and 0.5 mL of DME.
After the mixture was stirred for 5 min, Cs2CO3 (163 mg, 0.5 mmol),
chlorobenzene (25.4 μL, 0.25 mmol), and 0.50 mL of dry acetone
were added. The vial was sealed, removed from the glovebox, and
heated to 90 °C for 1.5 h. GC analysis of an aliquot, with calibration
using authentic samples and measurements relative to dodecane as an
internal standard, then revealed 94% consumption of PhCl and 64%
yield of monoarylation product.
Details of X-ray Crystallographic Studies. Crystals of 12 and
13 were grown by slow diffusion of diethyl ether into a DCM solution
of the compound. Crystals of 16 and 21 were grown by slow diffusion
of hexanes into a DCM solution of the compound. Crystallographic
data were obtained at 173(2) K, on either a Bruker PLATFORM/
SMART 1000 CCD diffractometer or a Bruker D8/APEX II CCD
diffractometer using graphite-monochromated Mo Kα radiation (λ =
0.71073 Å) for 16 and Cu Kα radiation (λ = 1.54178 Å) for 12, 13,
and 21. Unit cell parameters were determined and refined on all
reflections. Data reduction and correction for Lorentz−polarization
were performed using Saint-plus,31 and scaling and absorption
correction were performed using the SADABS software package.32
Structure solution by direct methods and least-squares refinement on
F2 were performed using the SHELXTL software suite.33 Non-
hydrogen atoms were refined with anisotropic displacement
parameters, while hydrogen atoms were placed in calculated positions
and refined with a riding model. Multiscan absorption correction was
employed in all cases. Structural figures were generated with ORTEP-
3.34 The BF4 anion of 21 is poorly ordered, and three fluorines have
been modeled as positionally disordered over two sites in a 77:23 ratio.
All other atoms in all structures are well ordered. Crystallographic data
are given in Table 7.
Mark Stradiotto completed his Honours B.Sc. (Applied Chemistry,
1995) and Ph.D. (Organometallic Chemistry, 1999) degrees in the
Department of Chemistry at McMaster University (Canada), after
which he moved to the University of California at Berkeley as a
Natural Sciences and Engineering Research Council of Canada
Postdoctoral Fellow. In September of 2001, Mark joined the
Department of Chemistry at Dalhousie University as an Assistant
Professor, where he is now the Alexander McLeod Professor of
Chemistry. Mark has served on the Editorial Advisory board of
Organometallics and has received a number of awards in recognition of
his excellence in teaching and research, including most recently the
Strem Chemicals Award for Pure or Applied Inorganic Chemistry.
ACKNOWLEDGMENTS
■
We thank the Natural Sciences and Engineering Research
Council of Canada for a Discovery Grant to M.S., the Killam
Trusts for a Research Professorship to M.S. and a Postdoctoral
Fellowship to C.A.W., and Dalhousie University for their
generous support of this work.
REFERENCES
■
(1) (a) Nicolaou, K. C.; Bulger, P. G.; Sarlah, D. Angew. Chem., Int.
Ed. 2005, 44, 4442−4489. (b) Hashmi, A. S. K.; Hutchings, G. J.
Angew. Chem., Int. Ed. 2006, 45, 7896−7936. (c) Schrock, R. R.;
Hoveyda, A. H. Angew. Chem., Int. Ed. 2003, 42, 4592−4633.
(d) Trnka, T. M.; Grubbs, R. H. Acc. Chem. Res. 2001, 34, 18−29.
(2) (a) Wolfe, J. P.; Wagaw, S.; Marcoux, J.-F.; Buchwald, S. L. Acc.
Chem. Res. 1998, 31, 805−818. (b) Hartwig, J. F. Acc. Chem. Res. 1998,
31, 852−860. (c) Raders, S. M.; Moore, J. N.; Parks, J. K.; Miller, A.
D.; Leißing, T. M.; Kelley, S. P.; Rogers, R. D.; Shaughnessy, K. H. J.
Org. Chem. 2013, 78, 4649−4664. (d) Hao, X.; Yuan, J.; Yu, G.-A.;
Qiu, M.-Q.; She, N.-F.; Sun, Y.; Zhao, C.; Mao, S.-L.; Yin, J.; Liu, S.-H.
J. Organomet. Chem. 2012, 706, 99−105. (e) Chen, L.; Yu, G.-A.; Li,
F.; Zhu, X.; Zhang, B.; Guo, R.; Li, X.; Yang, Q.; Jin, S.; Liu, C.; Liu, S.-
H. J. Organomet. Chem. 2010, 695, 1768−1775. (f) Doherty, S.;
Knight, J. G.; McGrady, J. P.; Ferguson, A. M.; Ward, N. A. B.;
Harrington, R. W.; Clegg, W. Adv. Synth. Catal. 2010, 352, 201−211.
(g) Li, J.; Cui, M.; Yu, A.; Wu, Y. J. Organomet. Chem. 2007, 692,
3732−3742.
ASSOCIATED CONTENT
* Supporting Information
■
S
Figures giving NMR spectra of all reported compounds, text
giving NMR data, and CIF files giving X-ray crystallographic
data. This material is available free of charge via the Internet at
http://pubs.acs.org.
(3) (a) Wolfe, J. P.; Buchwald, S. L. Angew. Chem., Int. Ed. 1999, 38,
2413−2416. (b) Buchwald, S. L.; Mauger, C.; Mignani, G.; Scholz, U.
Adv. Synth. Catal. 2006, 348, 23−39.
(4) See for example: (a) Bruno, N. C.; Buchwald, S. L. Org. Lett.
2013, 15, 2876−2879. (b) Su, M.; Buchwald, S. L. Angew. Chem., Int.
Ed. 2012, 51, 4710−4713. (c) Salvi, L.; Davis, N. R.; Ali, S. Z.;
Buchwald, S. L. Org. Lett. 2012, 14, 170−173.
(5) (a) Klinkenberg, J. L.; Hartwig, J. F. J. Am. Chem. Soc. 2010, 132,
11830−11833. (b) Vo, G. D.; Hartwig, J. F. J. Am. Chem. Soc. 2009,
131, 11049−11061. (c) Shen, Q.; Hartwig, J. F. Org. Lett. 2008, 10,
AUTHOR INFORMATION
Corresponding Author
*E-mail for M.S.: mark.stradiotto@dal.ca.
Notes
■
The authors declare no competing financial interest.
M
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Article
4109−4112. (d) Shen, Q.; Ogata, T.; Hartwig, J. F. J. Am. Chem. Soc.
2008, 130, 6586−6596. (e) Shen, Q.; Shekhar, S.; Stambuli, J. P.;
Hartwig, J. F. Angew. Chem., Int. Ed. 2005, 44, 1371−1375. (f) Ogata,
T.; Hartwig, J. F. J. Am. Chem. Soc. 2008, 130, 13848−13849.
(g) Hartwig, J. F. Acc. Chem. Res. 2008, 41, 1534−1544.
(17) (a) Hodgson, R.; Douthwaite, R. E. Curr. Org. Chem. 2005, 690,
5822−5831. (b) Focken, T.; Raabe, G.; Bolm, C. Tetrahedron:
Asymmetry 2004, 15, 1693−1706.
(18) Nagele, P.; Herrlich, U.; Rominger, F.; Hofmann, P.
̈
Organometallics 2012, 32, 181−191.
(19) (a) Liu, X.; Braunstein, P. Inorg. Chem. 2013, 52, 7367−7379.
(b) Steinke, T.; Shaw, B. K.; Jong, H.; Patrick, B. O.; Fryzuk, M. D.
Organometallics 2009, 28, 2830−2836.
(6) (a) Alsabeh, P. G.; Lundgren, R. J.; McDonald, R.; Johansson
Seechurn, C. C. C.; Colacot, T. J.; Stradiotto, M. Chem. Eur. J. 2013,
19, 2131−2141. (b) Lundgren, R. J.; Stradiotto, M. Aldrichim. Acta
2012, 45, 59−65. (c) Tardiff, B. J.; Stradiotto, M. Eur. J. Org. Chem.
2012, 2012, 3972−3977. (d) Tardiff, B. J.; McDonald, R.; Ferguson,
M. J.; Stradiotto, M. J. Org. Chem. 2012, 77, 1056−1071. (e) Lundgren,
R. J.; Hesp, K. D.; Stradiotto, M. Synlett 2011, 2443−2458.
(f) Lundgren, R. J.; Stradiotto, M. Angew. Chem., Int. Ed. 2010, 49,
8686−8690. (g) Lundgren, R. J.; Peters, B. D.; Alsabeh, P. G.;
Stradiotto, M. Angew. Chem., Int. Ed. 2010, 49, 4071−4074.
(h) Lundgren, R. J.; Sappong-Kumankumah, A.; Stradiotto, M.
Chem. Eur. J. 2010, 16, 1983−1991.
(20) Larsen, S. B.; Bang-Andersen, B.; Johansen, T. N.; Jørgensen, M.
Tetrahedron 2008, 64, 2938−2950.
(21) Benhamou, L.; Chardon, E.; Lavigne, G.; Bellemin-Laponnaz, S.;
́
Cesar, V. Chem. Rev. 2011, 111, 2705−2733.
(22) (a) Vignolle, J.; Donnadieu, B.; Bourissou, D.; Soleilhavoup, M.;
Bertrand, G. J. Am. Chem. Soc. 2006, 128, 14810−14811. (b) Canac,
Y.; Conejero, S.; Soleilhavoup, M.; Donnadieu, B.; Bertrand, G. J. Am.
Chem. Soc. 2006, 128, 459−464.
(23) (a) Valente, C.; Çalimsiz, S.; Hoi, K. H.; Mallik, D.; Sayah, M.;
Organ, M. G. Angew. Chem., Int. Ed. 2012, 51, 3314−3332. (b) Surry,
D. S.; Buchwald, S. L. Chem. Sci. 2010, 2, 27−50. (c) Fors, B. P.;
Buchwald, S. L. J. Am. Chem. Soc. 2010, 132, 15914−15917.
(24) Withbroe, G. J.; Singer, R. A.; Sieser, J. E. Org. Process Res. Dev.
2008, 12, 480−489.
(7) Lavery, C. B.; McDonald, R.; Stradiotto, M. Chem. Commun.
2012, 48, 7277−7279.
(8) (a) Navarro, O.; Marion, N.; Mei, J.; Nolan, S. P. Chem. Eur. J.
2006, 12, 5142−5148. (b) Marion, N.; Navarro, O.; Mei, J.; Stevens, E.
D.; Scott, N. M.; Nolan, S. P. J. Am. Chem. Soc. 2006, 128, 4101−4111.
(9) (a) Meiries, S.; Speck, K.; Cordes, D. B.; Slawin, A. M. Z.; Nolan,
S. P. Organometallics 2013, 32, 330−339. (b) Chartoire, A.; Boreux, A.;
Martin, A. R.; Nolan, S. P. RSC Adv. 2013, 3, 3840−3843.
(c) Chartoire, A.; Frogneux, X.; Nolan, S. P. Adv. Synth. Catal.
2012, 354, 1897−1901. (d) Meiries, S.; Chartoire, A.; Slawin, A. M. Z.;
Nolan, S. P. Organometallics 2012, 31, 3402−3409. (e) Chartoire, A.;
Frogneux, X.; Boreux, A.; Slawin, A. M. Z.; Nolan, S. P. Organometallics
2012, 31, 6947−6951.
(25) Fors, B. P.; Watson, D. A.; Biscoe, M. R.; Buchwald, S. L. J. Am.
Chem. Soc. 2008, 130, 13552−13554.
(26) (a) Alsabeh, P. G.; Stradiotto, M. Angew. Chem., Int. Ed. 2013,
52, 7242−7246. (b) Li, P.; Lu, B.; Fu, C.; Ma, S. Adv. Synth. Catal.
̈
2013, 355, 1255−1259. (c) Crawford, S. M.; Alsabeh, P. G.;
Stradiotto, M. Eur. J. Org. Chem. 2012, 2012, 6042−6050.
(d) Ackermann, L.; Mehta, V. P. Chem. Eur. J. 2012, 18, 10230−
10233. (e) Hesp, K. D.; Lundgren, R. J.; Stradiotto, M. J. Am. Chem.
Soc. 2011, 133, 5194−5197.
(27) Marshall, C.; Ward, M. F.; Skakle, J. M. Synthesis 2006, 1040−
1044.
(10) (a) Hoi, K. H.; Coggan, J. A.; Organ, M. G. Chem. Eur. J. 2012,
19, 843−845. (b) Hoi, K. H.; C
A. C.; Organ, M. G. Chem. Eur. J. 2011, 18, 145−151. (c) Hoi, K. H.;
alimsiz, S.; Froese, R. D. J.; Hopkinson, A. C.; Organ, M. G. Chem.
̧alimsiz, S.; Froese, R. D. J.; Hopkinson,
(28) Wolfe, J.; Buchwald, S. J. Org. Chem. 1997, 62, 6066−6068.
(29) Auburn, P. R.; Mackenzie, P. B.; Bosnich, B. J. Am. Chem. Soc.
1985, 107, 2033−2046.
(30) Lakshmi Kantam, M.; Venkanna, G. T.; Sridhar, C.; Sreedhar,
B.; Choudary, B. M. J. Org. Chem. 2006, 71, 9522−9524.
(31) SAINT-Plus, Version 7.23a; Data Reduction and Correction
Program; Bruker AXS Inc., Madison, WI, 2004.
C
̧
Eur. J. 2011, 17, 3086−3090. (d) Organ, M. G.; Abdel-Hadi, M.;
Avola, S.; Dubovyk, I.; Hadei, N.; Kantchev, E. A. B.; O’Brien, C. J.;
Sayah, M.; Valente, C. Chem. Eur. J. 2008, 14, 2443−2452.
(11) Wheaton, C. A.; Stradiotto, M. Can. J. Chem. 2013, 91, 755−
762.
(32) Sheldrick, G. M. SADABS, Area-Detector Absorption Correction,
(12) (a) Broggi, J.; Jurcik, V.; Songis, O.; Poater, A.; Cavallo, L.;
Slawin, A. M. Z.; Cazin, C. S. J. J. Am. Chem. Soc. 2013, 135, 4588−
4591. (b) Hartmann, C. E.; Jurcik, V.; Songis, O.; Cazin, C. S. J. Chem.
Commun. 2013, 49, 1005−1007. (c) Schmid, T. E.; Jones, D. C.;
Songis, O.; Diebolt, O.; Furst, M. R. L.; Slawin, A. M. Z.; Cazin, C. S. J.
Dalton Trans. 2013, 42, 7345−7353. (d) Jurcik, V.; Schmid, T. E.;
Dumont, Q.; Slawin, A. M. Z.; Cazin, C. S. J. Dalton Trans. 2012, 41,
12619−12623. (e) Diebolt, O.; Jurcik, V.; da Costa, R. C.; Braunstein,
P.; Cavallo, L.; Nolan, S. P.; Slawin, A. M. Z.; Cazin, C. S. J.
Organometallics 2010, 29, 1443−1450. (f) Fantasia, S.; Nolan, S. P.
Chem. Eur. J. 2008, 14, 6987−6993.
v2.10; Universitat Gottingen, Gottingen, Germany, 1999.
̈
̈
̈
(33) Sheldrick, G. M. Acta Crystallogr., Sect. A 2007, 64, 112−122.
(34) Burnett, M. N.; Johnson, C. K. ORTEP-III: Oak Ridge Thermal
Ellipsoid Plot Program for Crystal Structure Illustrations, Oak Ridge
National Laboratory Report ORNL-6895, 1996.
(13) Salem, H.; Schmitt, M.; Herrlich nee
́
Blumbach, U.; Kuhnel, E.;
̈
Brill, M.; Nagele, P.; Bogado, A. L.; Rominger, F.; Hofmann, P.
̈
Organometallics 2013, 32, 29−46. (b) Cabeza, J. A.; Damonte, M.;
Garcia-Alvarez, P.; Kennedy, A. R.; Perez-Carreno, E. Organometallics
2011, 30, 826−833. (c) Yang, C.; Lee, H. M.; Nolan, S. P. Org. Lett.
2001, 3, 1511−1514.
(14) (a) Ho, C.-C.; Chatterjee, S.; Wu, T.-L.; Chan, K.-T.; Chang, Y.-
W.; Hsiao, T.-H.; Lee, H. M. Organometallics 2009, 28, 2837−2847.
(b) Wang, A.-E.; Xie, J.-H.; Wang, L.-X.; Zhou, Q.-L. Tetrahedron
2005, 61, 259−266. (c) Cabeza, J. A.; Damonte, M.; Garcia-Alvarez,
P.; Hernan
327−334.
́
dez-Cruz, M. G.; Kennedy, A. R. Organometallics 2012, 31,
(15) (a) Abdellah, I.; Lepetit, C.; Canac, Y.; Duhayon, C.; Chauvin,
R. Chem. Eur. J. 2010, 16, 13095−13108. (b) Bappert, E.; Helmchen,
G. Synlett 2004, 1789−1793.
(16) Zhong, J.; Xie, J.-H.; Wang, A.-E.; Zhang, W.; Zhou, Q.-L.
Synlett 2006, 1193−1196.
N
dx.doi.org/10.1021/om400684n | Organometallics XXXX, XXX, XXX−XXX