Unusual NHC-Iridium(I) Complexes and Their Use in the Intramolecular Hydroamination of Unactivated Aminoalkenes

Article abstract of DOI:10.1002/chem.201600378

N-heterocyclic carbene (NHC) ligands with naphthyl side chains were employed for the synthesis of unsaturated, yet isolable [(NHC)Ir(cod)]⁺ (cod=1,5-cyclooctadiene) complexes. These compounds are stabilised by an interaction of the aromatic win

Full text of DOI:10.1002/chem.201600378

DOI: 10.1002/chem.201600378
Full Paper
&
Carbene Complexes
Unusual NHC–Iridium(I) Complexes and Their Use in the
Intramolecular Hydroamination of Unactivated Aminoalkenes**
GellØrt Sipos,[a] Arnold Ou,[a] Brian W. Skelton,[b] Laura Falivene,[c] Luigi Cavallo,*[c] and
Reto Dorta*[a]
Abstract: N-heterocyclic carbene (NHC) ligands with naph-
thyl side chains were employed for the synthesis of unsatu-
rated, yet isolable [(NHC)Ir(cod)]+ (cod=1,5-cyclooctadiene)
complexes. These compounds are stabilised by an interac-
tion of the aromatic wingtip that leads to a sideways tilt of
the NHCÀIr bond. Detailed studies show how the tilting of
such N-heterocyclic carbenes affects the electronic shielding
properties of the carbene carbon atom and how this is re-
flected by significant upfield shifts in the 13C NMR signals.
When employed in the intramolecular hydroamination,
these [(NHC)Ir(cod)]+ species show very high catalytic activi-
ty under mild reaction conditions. An enantiopure version of
the catalyst system produces pyrrolidines with excellent
enantioselectivities.
1. Introduction
donor ability and the high stability of their metal complexes
they represent powerful tools in modern homogeneous cata-
lyst development. Although dozens of monodentate NHCs
have been synthesised to date, only a few of them have so far
proven to be versatile as ancillary ligands. Data gathered so far
would indicate that NHCs with perpendicularly oriented aro-
matic side chains offer a uniquely useful steric environment as
exemplified by the very successful 1,3-bis(2,6-diisopropylphe-
nyl)imidazol-2-ylidene/1,3-bis(2,6-diisopropylphenyl)-4,5-dihy-
droimidazol-2-ylidene (IPr/SIPr) and 1,3-bis(dimesityl)-imidazol-
2-ylidene/1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-
ylidene (IMes/SIMes) ligand pairs.[5]
Homogeneous catalysis based on metal complexes where
bulky, monodentate ancillary ligands are used has gained enor-
mous significance in the last two decades because it often pro-
vides catalytic systems with superior performance. For exam-
ple, major developments in cross-coupling reactions have
often relied on substituting multiple ligands or ligand chelates
with a single, sterically demanding spectator ligand.[1] Al-
though the success of this approach is undeniable as it usually
generates highly active and unsaturated metal complexes as
catalytic species, rendering ligand systems overly bulky can
lead to catalyst decomposition through unwanted activations
of parts of the ligand that closely approach the metal centre.[2]
Within the growing class of bulky, monodentate ancillary li-
gands, Arduengo-type N-heterocyclic carbenes (NHCs) have
garnered increasing attention and have become ubiquitous li-
gands in transition-metal catalysis.[3–5] Due to their strong s-
In the past, we have identified NHCs with alkylated naphthyl
wingtips as viable and often superior alternatives to these li-
gands.[6] Incorporation of naphthalene units in NHC design had
been reported before, and offers the option of a relatively
straightforward introduction of a chiral element into the NHC
ligand structure.[7] In general, our ligands show increased reac-
tivity also under forcing reaction conditions, which would
point to a less ready deactivation of the catalyst through an
unwanted metal–ligand reactivity. Even within this new class
of NHCs, fine-tuning of the naphthyl side chain substituents of
the ligands seems to be important. For example, when used as
ligands in ruthenium metathesis, the particular substitution
pattern of the side chains rendered the catalyst system more
or less prone to decomposition through what appeared to be
ruthenium-mediated cyclometalation reactions.[6c] In another
study on their application to NHC–Pd catalysts, the special
steric bulk created by these ligands resulted in greatly im-
proved reactivity in the Suzuki–Miyaura coupling reaction of
sterically hindered aryls.[6d]
[a] G. Sipos, A. Ou, Prof. R. Dorta
School of Chemistry and Biochemistry
University of Western Australia
35 Stirling Highway
6009 Crawley, WA, (Australia)
E-mail: reto.dorta@uwa.edu.au
[b] Prof. B. W. Skelton
Centre for Microscopy, Characterisation and Analysis
University of Western Australia
35 Stirling Highway
6009 Crawley, WA, (Australia)
[c] Dr. L. Falivene, Prof. L. Cavallo
Kaust Catalysis Center, Physical Sciences and Engineering Division
King Abdullah University of Science and Technology
Thuwal 23955-6900 (Saudi Arabia)
Herein, we disclose studies that show how two representa-
tive members of our ligand systems (namely, ligands 1a and
1b in Scheme 1), although electronically very comparable to
the classical IPr/SIPr and IMes/SIMes ligands, are able to stabi-
[**] NHC=N-heterocyclic carbene.
Supporting information of this article can be found under http://dx.doi.org/
10.1002/chem.201600378.
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bination.[10f,11] Although monodentate NHCs have previously
been used in various iridium-catalysed transformations,[8b,d,e,12]
they have not been applied in the HA reaction of unactivated
aminoalkenes.[13] Here, we show how our special ligand archi-
tecture imparts unusually high reactivity and how we can
extend the use of our ligands to the asymmetric version of this
reaction, where systems based on iridium have been absent so
far.[14]
2. Results and Discussion
2.1. Synthesis and characterisation of the NHC–iridium com-
plexes
Scheme 1 shows the synthetic pathway to neutral NHC–Ir sys-
tems employing two representatives of our NHC ligand family
[i.e., 2-SICyNap (1a) and 2,7-SICyNap (1b)]. The [(NHC)Ir(cod)Cl]
complexes 2a and 2b were obtained in good overall yields by
reacting stoichiometric amounts of the free carbenes with
0.5 equivalents of [Ir(cod)Cl]2 (Scheme 1).[15] The syn and anti
isomers of compound 2a were separated by column chroma-
tography.
Scheme 1. Synthesis of neutral NHC–IrI complexes (cod=1,5-cycloocta-
diene).
lise formally three coordinate [NHC–Ir]+ systems through
weak, non-destructive interactions of their side chains with the
metal centre.[8] We also show why and how the tilted nature of
such NHC–M structures leads to significant upfield shifts in the
13C NMR signals. These unsaturated [NHC–Ir]+ species were
then used in the intramolecular hydroamination (HA) of simple
aminoalkenes,[9] where developments within the last decade
have established the usefulness of Group 9 metal complexes in
the intramolecular HA of electronically unbiased aminoal-
kenes.[10] Most notably, Hartwig et al. have developed cationic
rhodium systems that contain phosphorous-based ancillary li-
gands,[10b,g,i] whereas Stradiotto et al. have reported the use of
simple [Ir(cod)Cl]2 as the precatalyst.[10c,e] These developments
have broadened the scope of this simple and atom-economical
reaction as they employ relatively easy-to-handle, functional-
group-tolerant late-transition-metal catalysts for the construc-
tion of these important nitrogen heterocycles. Obviously, de-
veloping enantioselective versions of this transformation repre-
sents a particular challenge with any chiral ligand–metal com-
1
The H and the 13C NMR spectra of compounds anti-2a and
anti-2b exhibit two distinct sets of signals for each of the
naphthyl side chains (i.e., twenty carbon signals can be ob-
served). The two methylene carbon atoms of the imidazolidine
backbone are clearly distinguishable in these complexes (d=
54.8 and 54.4 ppm for anti-2a; d=54.5 and 54.0 ppm for anti-
2b). Also, the CH=CH fragments of the cod ligand are repre-
sented by four distinct sets of signals both in the 1H and
13C NMR spectra. Finally, the most characteristic resonance (of
the NHC) in the 13C NMR spectra is found at around d=
210 ppm.
The synthesis and full characterisation of complexes 2 (the
molecular structures of which are shown in Figure 1) set the
stage to evaluate the electronic properties of our NHC ligands
1a and 1b. The carbonyl complexes were accessed in high
yield by reacting compounds anti-2a and anti-2b with carbon
monoxide.[16] Somewhat expectedly, complexes anti-3a and
anti-3b showed Tolman electronic parameter (TEP) values very
Figure 1. Molecular structures of compounds (from left to right) anti-2a, anti-2b, anti-4a and anti-4b. For cationic complexes, the anion is omitted for clarity.
All hydrogen atoms are omitted for clarity and the cyclohexyl groups are represented differently for the same reason. Selected bond lengths [Š] and angles
[8]: for compound anti-2a: IrÀC1 2.034(1), IrÀC11 2.147(1), IrÀC12 2.147(1), IrÀC15 2.127(1), IrÀC16 2.094(1), IrÀCl 2.3645(3); Ir-C1-N2 120.70(9), Ir-C1-N5
131.31(9); for compound anti-2b: IrÀC1 2.052(5), IrÀC11 2.194(5), IrÀC12 2.173(6), IrÀC15 2.121(5), IrÀC16 2.113(6), IrÀCl 2.350(1); Ir-C1-N2 126.0(4), Ir-C1-N5
127.2(4); for compound anti-4a: IrÀC1 2.041(1), IrÀC11 2.178(1), IrÀC12 2.233(1), IrÀC15 2.101(1), IrÀC16 2.104(1), IrÀC51 2.981(1), IrÀC58 2.407(1), IrÀC58A
2.666(1); Ir-C1-N2 134.56(9), Ir-C1-N5 116.00(8); for compound anti-4b: IrÀC1 2.038(2), IrÀC11 2.181(2), IrÀC12 2.224(2), IrÀC15 2.091(2), IrÀC16 2.114(2), IrÀC51
2.591(1), IrÀC58 2.544(2), IrÀC58A 2.413(2); Ir-C1-N2 145.0(1), Ir-C1-N5 106.7(1).
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similar to the established SIMes/IMes and SIPr/IPr ligand pairs
(Table 1).[8c,15,17] However, we note that the second cyclohexyl
substituent (position 7) is rendering ligand 1b more electron-
donating, much in the same way as seen when going from the
saturated to the unsaturated NHC analogues of the standard li-
gands SIMes/IMes and SIPr/IPr.
Table 1. Carbonyl stretching frequencies for the complexes
[(NHC)Ir(CO)2Cl] and [(NHC)Ni(CO)3].
av
CO
NHC
n˜CO [cmÀ1
]
n˜ [cmÀ1
]
TEP [cmÀ1
]
2-SICyNap (1a)
2,7-SICyNap (1b)
SIPr[b]
2067.4, 1982.7
2066.5, 1981.3
2068.0, 1981.8
2066.8, 1981.0
2068.0, 1981.2
2066.4, 1979.8
2025.0
2023.9
2024.9
2023.9
2024.6
2023.1
2051.2[a]
2050.3[a]
2051.2
2050.2
2050.8
2049.6
Figure 2. Steric maps of the neutral complexes anti-2a and anti-2b and the
cationic complexes anti-4a and anti-4b. Isocontour lines are given in [Š].
IPr[b]
SIMes[b]
IMes[b]
compound anti-4b) and also impacts space occupation around
the metal centre. As evidenced by the steric quadrant maps
shown in Figure 2, the tilting results in a %VBur (percent buried
volume) of approximately 80% of the relevant quadrant and
leads to a significant increase in overall ligand bulk.
[a] Calculated with the formula: TEP=0.847”n˜av+336 [cmÀ1]. [b] Taken
from reference [17b].
The [(NHC)Ir(cod)Cl] complexes syn-2a, anti-2a and anti-2b
also gave us a very interesting entry into ligand degradation
problems mentioned in the introduction. In a recent paper, Al-
dridge et al. had studied the outcome of the reaction of
[(IPr)Ir(cod)Cl] with Na(BArf4),[18,19c] where abstraction of the
chloride led to a highly reactive metal species that underwent
ready CÀH activation and dehydrogenation of one of the iso-
propyl moieties of the wingtips. In stark contrast, halide ab-
straction on compounds syn-2a, anti-2a and anti-2b gave
deep red, crystalline materials where X-ray diffraction analyses
of compounds syn-4a, anti-4a and anti-4b confirmed the com-
position of the complexes as being [(NHC)Ir(cod)][PF6]
(Scheme 2).[20] Representations of compounds anti-4a and anti-
4b (Figure 1) reveal that cyclometalation does not occur and
in order to stabilise these formally 14-electron species,[21] one
of the aromatic wingtips approaches the metal centre and dis-
plays an arene–metal interaction that involves the C8 and C8a
carbon atoms of the naphthyl unit (C58 and C58A in the crys-
tallographic numbering; the IrÀC bond lengths are 2.407(1)/
2.666(1) Š for compound anti-4a and 2.544(2)/2.413(2) Š for
compound anti-4b) and leads to a pseudo-square-planar coor-
dination geometry.[22] As a consequence, the NHC ring is tilted
towards the side where the interaction occurs.[23] This affords
disparate Ir-C1-N2 and Ir-C1-N5 angles (namely, 134.56(8)/
116.00(8)8 for compound anti-4a and 145.0(1)/106.7(1)8 for
NMR spectroscopy indicated that the arene interaction
might not be present in solution. The proton spectra of com-
pounds anti-4a and anti-4b were highly simplified compared
to the parent neutral complexes and the two naphthyl rings
1
appeared to be identical on the H NMR time scale. Neverthe-
less, the 1H NMR analysis of the syn-4a isomer at 298 K
showed very broad signals, and a variable-temperature (VT)
analysis of compound anti-4b, although inconclusive, indicat-
ed that both the COD and the NHC ligand undergo fluxional
processes. More insightful information was gathered through
analyses of the 13C NMR spectra. The signals for the C8 and
C8a carbon atoms of the two naphthyl rings showed broad
singlets significantly upfield with respect to their neutral coun-
terparts (d(C8)=107.2/d(C8a)=126.0 ppm for anti-4a; d(C8)=
107.0/d(C8a)=123.6 for anti-4b), which would be expected
when binding interactions with the metal are present. Unusual-
ly large shifts were also measured for the carbene carbon
atoms, whose signals are positioned approximately 20 ppm
upfield from their neutral congeners (d=196.0 ppm for anti-
4a and d=188.1 ppm for anti-4b). At first sight, we attributed
these large shifts to the tilt of the N-heterocycle that is main-
tained in solution and influences the electronic environment of
the carbene carbon atom. Evidence for such a scenario came
from an experiment whereby compound anti-4b was dissolved
in CD3CN. A new, dissymmetric species (namely, [(anti-1b)Ir(-
cod)(CD3CN)][PF6]) was formed with NMR data mirroring the
ones seen for anti-2b and where the carbene carbon atom
was found at d=200.5 ppm.[24]
2.2. Computational analysis of tilted NHC–M compounds
To shed light on the origin of the upfield shift of the carbene
carbon atom NMR signals in our tilted structures, we per-
formed DFT NMR calculations.[16,25] We initially tested the com-
putational setup to reproduce the crystallographic geometry
and the experimental chemical shift, dC, of twelve monoden-
Scheme 2. Synthesis of cationic NHC–IrI complexes.
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tate and chelating NHC–M complexes described in the litera-
ture[23b,26] (see Figure S11 in the Supporting Information) plus
the free NHC ligand 1b and the corresponding protonated
form, 1b·H+. We selected these compounds because they rep-
resent pairs of related complexes presenting linear and bent
NHCÀM bonds, for which the crystallographic structure and
13C NMR data are available.
transition of electrons between occupied and virtual orbitals,
properly connected by symmetry, induced by the external
magnetic field (e.g., px!pz by 908 rotation around the y axis).
The amount of the shielding is inversely related to the energy
gap between these two orbitals, and it is directly related to
a proper overlap of the orbitals after rotation.[28] Correlation of
the paramagnetic term to the molecular properties thus
should focus on these two factors, which affect the paramag-
netic shielding.
To check for the validity of the chosen computational ap-
proach in reproducing the geometry of the complexes exam-
ined, we compared the main structural parameters from the
DFT optimisation, which is the MÀNHC bond length and the
M-C-N(NHC) angles, with the values of the crystallographic
structure (see Table S2 in the Supporting Information). The ex-
cellent agreement between the DFT-optimised and the crystal-
Because the sp term is dominated by transitions between
symmetry-related occupied and empty molecular orbitals
(MOs)[28] based on previous work,[27a] we focused on changes in
energy and shape of the filled and empty MOs corresponding
to the s and p* orbitals of the SeÀNHC bond at q=0 and
lographic parameters, with mean unsigned error on the MÀ 308.[16,28] Whereas the connection between the paramagnetic
NHC bond length of only 0.013 Š, and on the M-C-N1 and M-
C-N2 angles of 0.81 and 1.048, respectively, validate the meth-
odology we used to calculate the geometries of this series of
M–NHC complexes. To check for the validity of the chosen DFT
NMR protocol, we tested it to reproduce the experimental dC
values of the examined complexes. The excellent correlation
(R2 =0.93) between the DFT isotropic chemical shielding sC
values and the experimental dC values of the carbene carbon
atoms (see Figure S12 in the Supporting Information) validates
the DFT NMR part of the computational setup.
shielding and the energy gap between these MOs is quite
simple, the smaller the gap the larger the shielding, the re-
quired symmetry relation between the MOs is explained in Fig-
ure 4a. In the linear geometry, rotation of the MO induced by
an external magnetic field results in MOs having the same
symmetry and an optimal overlap, because the s-bonding MO
is mainly composed by px atomic orbitals (AOs) on both the
carbenic carbon atom and the Se atom (see Figures 4a and b).
At this point, we moved to decipher the origin of the upfield
shift due to the bending of the MÀNHC bond. To this end, we
used the model system NHCÀSe shown in Figure 3, because it
Figure 3. DFT-calculated chemical shielding versus the tilt angle for the
NHCÀSe bond.
was demonstrated that the NHCÀSe bond is a good mimic of
the NHCÀM bond.[25,27] Starting from a linear geometry, we
tilted the NHCÀSe bond by q=10, 20 and 308. For each struc-
ture we calculated the sC value of the carbene atom. Gratify-
ingly, also the sC values of the NHCÀSe system moves upfield
as the NHCÀSe bond is tilted (Figure 3), and the shift, approxi-
mately 10 ppm, is consistent with the experimental shift in the
NHC–M complexes we investigated. The strong correlation
(R2 =0.90) between the sC value and q indicates that the up-
field shift is essentially due to the tilting.
Decomposing the isotropic chemical shielding sC into dia-
(sd) and paramagnetic (sp) terms, sC =sd+sp, indicates that the
change in sC is due to the paramagnetic term sp that varies by
6.5 ppm from 0 to 308, whereas the diamagnetic term sd varies
by only 0.1 ppm. The paramagnetic shielding depends from
Figure 4. a) Schematic representation of the magnetic s!p* coupling.
b,c) Analysis of the MOs corresponding to the s and p* SeÀNHC bonds.
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This optimal overlap results in a strong magnetic coupling be-
tween the s and p* MOs, with strong paramagnetic deshield-
ing of the carbenic carbon atom. Differently, in the bent geom-
etry the same rotation results in a non-optimal overlap of the
MOs, due to the different composition of the s-bonding MO
on Se (see Figures 4a and c). Due to the tilting, hybridisation
of the Se atoms moves from a dominant participation of the px
AO to a mixture of px and py AOs, in order to orient the s-
bonding lobe on the Se towards the NHC (see Figure 4c). The
px component of the bonding lobe on the Se is still capable of
magnetic coupling with the p* MO by 908 rotation, whereas
the py component has not the proper symmetry, and thus
does not contribute to the paramagnetic shielding. The re-
duced amount of the px component in the NHCÀSe s bond on
going from a linear to a bent geometry results in weaker mag-
netic coupling between the s and p* MOs in the bent geome-
try and, consequently, in smaller paramagnetic deshielding and
upfield shift of the carbenic resonance. Extension of these con-
cepts to a NHC–M complex is straightforward.
catalyst even when increasing the catalyst loading tenfold (i.e.,
to 5 mol%).
Subsequently, a variety of substrates were tested with cata-
lyst anti-4b and the obtained results are summarised in
Table 2. For these reactions, we chose tBuOH as the solvent be-
cause not only did it show comparable reactivity with model
substrate 5a, but reactions with other substrates gave less sec-
ondary products that arise from isomerisation of the olefin
moiety. Examples of successfully ring-closed substrates include
a variety of electron-donating and -withdrawing benzyl groups
which are tolerated and lead to high yields of product at low
catalyst loadings of anti-4b (products 6–8 in Table 2). Sub-
strates with aliphatic groups on the nitrogen atom went
through the cyclisation smoothly (products 9 and 10 in
Table 2). Hydroamination of aryl amine (11 a), which was de-
scribed as a limitation for cationic rhodium systems,[10g] gave
the corresponding pyrrolidine (11 b) in good yield.
Table 2. Scope of the intramolecular HA reaction catalysed by compound
anti-4b.
Quantitatively, our analysis indicates that a bending of 308
of the NHCÀSe bond destabilises the M–NHC s-bonding MO
by 0.54 eV, whereas the NHCÀSe p* MO is stabilised by
0.24 eV, with a decrease of 0.78 eV of the energy gap between
them (Figure S13 in the Supporting Information). The represen-
tation of these MOs at q=0 and 308 (Figure 4) suggests that
destabilisation of the NHCÀSe s-bonding MO is due to a mis-
alignment of the in phase lobes on the NHC and the Se atom.
Differently, the NHCÀSe p* MO is less affected because the tilt-
ing does not reduce the overlap of the pz orbitals on the car-
bene carbon and Se atoms. The reduced energy gap between
the s and p* MOs should shift the carbene atom downfield.
However, the weight of the px atomic orbital on the Se atom
in the NHCÀSe s-bonding MO, which is the atomic orbital
having a proper symmetry relation for overlap with the NHCÀ
Se p* MOs after 908 rotation, is strongly reduced with tilting
(from 39 to 26%, see Figure 4). This translates into poorer
magnetic coupling and causes the observed upfield shift of
the carbene atom.[16]
Substrate
Product
Ir [mol%][a]
Yield [%][b]
5a R=CH2(C6H5) (Bn)
6a R=CH2(4-MeOC6H4)
7a R=CH2(4-ClC6H4)
8a R=CH2(4-NO2C6H4)
9a R=CH2(C6H11)
10a R=Me
5b
6b
7b
8b
9b
0.25
1.5
0.5
2
0.5
0.25
1.0
96
93
91
79
95
93
96
10b
11 b
11 a R=C6H5
12a
13a
12b
13b
0.5
1.0
88
86 (>99)[c]
2.3. Catalytic application in the intramolecular hydroamina-
tion reaction
14a
15a
14b
15b
1.5
1.0
95 (3:2)[d]
96 (3:2)[d]
The catalytic behaviour of complexes 4 was then explored in
the intramolecular HA reaction. In a first stage, we tested the
cationic complexes syn-4a, anti-4a and anti-4b with the
model substrate 5a and monitored their performance by using
1H NMR spectroscopy (Figure S8 in the Supporting Informa-
tion). Cyclisation occurred with a catalyst loading of 0.5 mol%
at room temperature and an especially impressive performance
was achieved with compound anti-4b, with full conversion at-
tained within approximately 3.5 min (turnover frequency (TOF)
of ꢀ3500 hÀ1). Generating the complex anti-4b in situ by
mixing equimolar amounts of anti-2b and AgPF6 in dichloro-
methane prior to adding substrate 5a replicated the results
seen for the preformed catalyst anti-4b. In stark contrast, by
using the similarly bulky and electronically analogous SIPr
ligand (i.e., [(SIPr)Ir(cod)Cl]+AgPF6) led to a totally inefficient
16a
17a
16b
17b
3.5
5
82[c]
traces
18a
18b
5
77[c]
[a] General conditions: 0.3 mmol substrate, compound anti-4b, 0.5 mL
tBuOH, 608C, 24 h. [b] Yields of isolated compounds. [c] 1H NMR yield by
using internal standard. [d] Diastereomeric ratio determined by 1H NMR
spectroscopy.
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The backbone of the substrate can be modified to include
a variety of substituents (compare 5 and 12–16 in Table 2) and
although the Thorpe–Ingold effect clearly helps cyclisation,
substrate 16a that lacks backbone substitution underwent cyc-
lisation smoothly with higher catalyst loadings (3.5 mol%). This
is in contrast to the simple [Ir(cod)Cl]2 system described by
Stradiotto et al.,[10e] which is not able to cyclise this type of
substrates. A higher catalyst loading of anti-4b was also
needed for the formation of the six-membered piperidine 18b.
Some limitations remain however under our chosen reaction
conditions. For example, the cyclisation of the internal alkene
17a only led to trace amounts of the expected product 17b,
and what anti-4b shares with [Ir(cod)Cl]2 is the inability to cy-
clise primary amines under these conditions (i.e., no additives).
Overall though, the results listed in Table 2 show that surpris-
ingly low catalyst loadings and mild reaction conditions can be
used in the intramolecular HA with catalyst anti-4b.
Table 3. Asymmetric intramolecular HA reaction catalysed by compound
(Ra,Ra,S,S)-19.[a]
2.4. Asymmetric intramolecular hydroamination reaction
An intriguingly simple possibility to further extend the utility
of our catalyst system arose from the fact that the NHCs used
above can rather easily be modified to produce enantiopure
ligand frameworks, as previously described by us.[29] To this
aim and to keep the overall catalytic system as similar as possi-
ble to anti-4a respectively anti-4b, we used a close relative of
ligand 1a that we had previously used in a palladium-cata-
lysed asymmetric a-arylation protocol.[29a] The corresponding
cationic complex (Ra,Ra,S,S)-19 (Table 3) was isolated in 52%
overall yield (over two steps) from the corresponding NHC salt.
The reactivity of compound 19 (for reasons unknown at pres-
ent) was significantly lower when compared to its immediate
counterpart anti-4a when monitoring the conversion of sub-
strate 5a. Furthermore and in contrast to anti-4b, catalyst 19
did not react smoothly with substrates in tBuOH. Nevertheless,
reactions run in dichloromethane showed that ready cyclisa-
tion occurs under mild conditions when raising the catalyst
loading. The enantioselectivities that we recorded with the
substrates chosen for this brief survey are excellent and
indeed, the enantiomeric excess (ee) values obtained for these
pyrrolidines are amongst the highest reported for the asym-
metric intramolecular HA of unactivated aminoolefins.[30] Fur-
thermore, the fact that the present system seems to be rather
insensitive to the nature of the nitrogen substitution (benzyl
or alkyl), bodes well for further development of this new chiral
catalyst platform.[31]
[a] General conditions: 0.3 mmol substrate, 19 (5 mol%), CH2Cl2 (0.5 mL),
78C, 24 h. Yields of isolated compounds. The ee was determined by
1H NMR spectroscopy. [b] 19 (2 mol%) was used, the ee was determined
by HPLC.
were able to gather with anti-4b in dichloromethane in the
presence of a stoichiometric amount of triethylamine is rele-
vant and noteworthy. Scheme 3 shows that anti-4b rapidly de-
composes in the presence of this simple tertiary amine in di-
chloromethane to give good isolated yields of the starting
chloride complex anti-2b, which is not catalytically active in
Scheme 3. Reactivity of Et3N with dichloromethane accelerated by complex
anti-4b.
the intramolecular HA reaction described here. It is known that
triethylamine (and other amines) can be alkylated by methyl-
ene chloride (Menshutkin reaction),[32] but the reaction is nor-
mally negligible due to its very slow reaction rate (half-live
over a month for triethylamine).[33] The reactivity in Scheme 3
shows that anti-4b is able to greatly accelerate this transfor-
mation.[34] Although more detailed information will have to be
gathered in the future with regards to similar reactivity with
amines that are substrates and/or products of the intramolecu-
lar HA protocol, it seems likely that this decomposition path-
way is operative to some degree in the overall catalytic trans-
formation described here.
2.5. Possible deactivation pathway of the [(NHC)Ir(cod)][PF6]
catalysts in dichloromethane
As outlined above, we did see some differences in the behav-
iour of both catalysts anti-4b and enantiopure (Ra,Ra,S,S)-19 in
terms of suitability of the solvent, with anti-4b performing
better in tBuOH than dichloromethane, especially for the less
reactive substrates. Although a more thorough investigation is
needed to fully understand how the solvent influences the
outcome of these HA reactions, a preliminary result that we
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Springer, Heidelberg, 2007; c) N-Heterocyclic Carbenes in Transition-
Metal Catalysis and Organocatalysis (Ed.: C. S. J. Cazin), Springer, Heidel-
berg, 2010; d) N-Heterocyclic Carbenes: From Laboratory Curiosities to Ef-
ficient Synthetic Tools (Ed.: S. Díez-Gonzµlez), RSC, Cambridge, 2011;
e) N-Heterocyclic Carbenes (Ed.: S. P. Nolan), Wiley-VCH, Weinheim, 2014.
For a short account, see: f) M. N. Hopkinson, C. Richter, M. Schedler, F.
Glorius, Nature 2014, 510, 485.
3. Conclusion
In conclusion, we have synthesised unusual [(NHC)Ir(cod)][PF6]
complexes where an additional binding interaction is present.
The interaction stabilises an otherwise very reactive 14-electron
IrI species and at the same time significantly increases the
steric bulk of the ligand, as quantified by steric quadrant
maps. The interaction also leads to a sideways tilt of the NHCÀ
M bond that translates into a large upfield shift of the carbene
carbon NMR signal. DFT calculations have allowed us to show
that this is a general phenomenon of such tilted NHCs. It can
be attributed to the paramagnetic component of the isotropic
shielding and is due to the misalignment of the bonding lobes
forming the NHCÀM s bond. The non-destructive nature of the
wingtip interaction is at the heart of the excellent performance
of the complexes when employed as catalysts in the intramo-
lecular HA reaction. Notably, first results employing an enantio-
pure version of our NHC gave a catalyst that provided excel-
lent enantioselectivities in the asymmetric version of this HA.
Because the catalytic results here are a first for the monoden-
tate NHC ligand class, further investigations will be needed to
understand how steric and electronic tuning of the NHC
moiety affects the catalytic performance. A major goal of these
studies will be to conjure up chiral catalyst systems that show
similarly high reactivity to complex anti-4b. Detailed mechanis-
tic studies will also be conducted to shed light onto the cata-
lytic reaction cycle and will have to take into account our pre-
liminary, intriguing data on solvent participation to catalyst de-
composition.
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[8] Examples of neutral [(NHC)Ir(cod)X] (X=anionic ligand) and [(NHC)Ir-
(cod)L]+ (L=neutral two-electron donor) complexes are abundant in
the literature. For overviews, see examples reviewed in references [3]
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Beller, Chem. Rev. 1998, 98, 675; b) K. C. Hultzsch, Adv. Synth. Catal.
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Acknowledgements
G.S. thanks the UWA for an International Postgraduate Re-
search Scholarship. R.D. thanks the Australian Research Council
for generous funding (FT130101713). The Centre for Microsco-
py, Characterisation & Analysis at the UWA is thanked for pro-
viding facilities and assistance. L.C. thanks the King Abdullah
University of Science and Technology for financial support.
Keywords: carbenes
hydroamination · heterocycles · iridium
·
density functional calculations
·
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this paper. These data are provided free of charge by The Cambridge
Crystallographic Data Centre.
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[16] See the Supporting Information for further details.
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[32] N. Menshutkin, Z. Phys. Chem. Stoechiom. Verwandtschaftsl. 1890, 6, 41.
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[20] CCDC 1433190 (syn-2a),
1433191 (anti-2a),
1433192 (anti-2b),
and
1433193 (anti-3b),
1433194 (syn-4a), 1433195 (anti-4a)
Received: January 27, 2016
1433196 (anti-4b) contain the supplementary crystallographic data for
Published online on April 5, 2016
Chem. Eur. J. 2016, 22, 6939 – 6946
www.chemeurj.org
6946
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim