Catalytic Approach toward Chiral P,N-Chelate Complexes Utilizing the Asymmetric Hydrophosphination Protocol

Article abstract of DOI:10.1021/acs.inorgchem.9b03549

A synthetic procedure for obtaining a chiral P,N ligand was developed by exploiting the versatility of the asymmetric hydrophosphination protocol catalyzed by a phosphapalladacycle complex. The addition of the synthesized ligand to various metal sources led to the generation of chiral and enantioenriched chelate complexes, which can be useful prototypes for catalyst design in the future. The resulting coordination compounds were comprehensively characterized by solid-state (X-ray crystallography) and solution-based (one- and two-dimensional NMR spectroscopy) techniques and natural bond orbital (density functional theory) analysis to determine their structural and key electronic features.

Full text of DOI:10.1021/acs.inorgchem.9b03549

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Catalytic Approach toward Chiral P,N-Chelate Complexes Utilizing
the Asymmetric Hydrophosphination Protocol
́
David Katona, Yunpeng Lu, Yongxin Li, Sumod A. Pullarkat,* and Pak-Hing Leung*
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ABSTRACT: A synthetic procedure for obtaining a chiral P,N
ligand was developed by exploiting the versatility of the
asymmetric hydrophosphination protocol catalyzed by a phospha-
palladacycle complex. The addition of the synthesized ligand to
various metal sources led to the generation of chiral and
enantioenriched chelate complexes, which can be useful prototypes
for catalyst design in the future. The resulting coordination
compounds were comprehensively characterized by solid-state (X-
ray crystallography) and solution-based (one- and two-dimensional
NMR spectroscopy) techniques and natural bond orbital (density
functional theory) analysis to determine their structural and key
electronic features.
efficiently conveyed, including in the chemistry of chiral
INTRODUCTION
■
palladacycles11 (Figure 2). Because these cyclopalladated
Bidentate ligands and their stereochemical properties play a
crucial role in both asymmetric and nonasymmetric transition-
metal-mediated catalysis.1 Diphosphines, as bidentate ligands,
have been widely utilized in asymmetric synthesis, e.g.,
hydroformylation, asymmetric hydrogenation, allylic substitu-
tion, and hydrosilylation, because of their proven track record
in providing high selectivity.2 Apart from diphosphines, which
remain the most popular class of bidentates used in catalysis,
heterobidentate ligands, such as P,N ligands, also have played a
significant and emerging role in transition-metal catalyis.3 They
indeed have a proven record in several key transformations
such as asymmetric allylic alkylation (employing H8-MAP or
QUINAP),4 isomerization5 and asymmetric hydrogenation of
allylic alcohols,6 enantioselective hydroboration,3b,7 and even
in the asymmetric Heck reaction.8
Figure 2. Chiral palladacycles: versatile tools in asymmetric synthetic
protocols.
compounds play an important role in several asymmetric
transformations including Diels−Alder cycloadditions12 and,
more recently, in hydrophosphinations,11d,13 our aim was to
design a new P,N bidentate system based on the structure of
(R)-214 (Figure 2). Such a modification will then allow us,
from the point of catalyst design, to vary the metal center and
access and exploit a broader scale of oxidation states. It is
envisaged that by switching the coordinating moiety located in
the aryl backbone from an sp2 carbon atom to a sp2 nitrogen
atom, the electronic properties at the metal center will be
altered, and this can enhance its reactivity toward oxidative
addition.3b,15
In the case of BINAP9 and QUINAP10 (Figure 1), the key to
their efficiency lies in the rigid and predetermined spatial
arrangement that they provide around a certain metal center
upon coordination. This kind of steric block has been utilized
in numerous cases where chiral induction needed to be
Received: December 5, 2019
Figure 1. Chiral ligands for asymmetric catalysis including the new
P,N ligand synthesized by us.
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However, the synthesis of such chiral heterobidentate P,N
ligands traditionally requires tedious manipulations, including
multiple steps and resolution protocols that can adversely
impact the atom economy.3b,10a Although novel syntheses of
QUINAP have been reported by both Stoltz et al.16 and
Lassaletta et al.17 by using dynamic kinetic resolution and
dynamic kinetic asymmetric transformation, respectively, those
syntheses use racemic mixtures as starting materials.
In our case, however, by utilizing the asymmetric hydro-
phosphination reaction, the synthetic route produces an
enantioenriched P,N ligand from a truly achiral substrate.
Having obtained the enantioenriched P,N phosphine ligand,
we were able to generate a class of unreported complexes
incorporating the new P,N ligand system, such as enantiopure
dichloropalladium and -platinum complexes, and enantioen-
riched rhodium and iridium cyclooctadiene complexes. The
investigation of the structural, steric, and electronic behavior of
these complexes by one- and two-dimensional NMR spectros-
copy and X-ray crystallography was also undertaken. The
experimental results were supported by using density func-
tional theory (DFT) methods, such as structure optimization
and natural bond orbital (NBO) analysis, conducted to
provide insight into the π acidity of the P,N ligand. The
collected data on these model compounds can be useful for the
design and application of these complexes and their derivatives
in catalytic protocols.
Figure 3. Synthesis of the activated olefin for asymmetric hydro-
phosphination.
planned catalytic hydrophosphination reaction to proceed
smoothly.21 The hydrophosphination reaction was optimized
by using the dimethyl malonate derivative 5a as a substrate,
while both the (S)-2 and (R,R)-7 catalysts were employed21b,22
(Table 1). The resulting phosphine was treated with sulfur
upon completion of the reaction to obtain phosphine sulfides,
which could be handled easily to carry out high-performance
liquid chromatography (HPLC) and other measurements. As
aforementioned, based on our previous experience, we
expected that the phosphapalladacycle catalyst (S)-2 was not
suitable for the planned hydrophosphination of this substrate
because of the intramolecular pathway that the Michael-
addition process is known to undergo in this class of catalysts.
The presence of the aromatic nitrogen atom, in conjunction in
5a along with the newly introduced phosphine, can cause
catalyst poisoning at the palladium center via a strong P,N
chelation upon product formation.11d,23 We envisaged that for
this particular substrate the pincer-type metallacycle complex
(R,R)-7 would be a more suitable catalyst because it promotes
the catalytic hydrophosphination protocol in an intermolecular
fashion, thus precluding the chance of product chelation and
subsequent catalyst poisoning.24 However, to our surprise, the
(S)-2 complex indeed showed a good catalytic performance,
while the pincer type (R,R)-7 catalyst did not prove to be
successful in delivering either significant enantiomeric excess
(ee) or higher yield. The progress of the hydrophosphination
reactions was monitored by 31P{1H} NMR spectroscopy.
It was revealed during the optimization studies that the
optimum condition was when triethylamine (TEA) was used
as a base in dichloromethane (DCM) at −80 °C while using
(S)-2 as the catalyst (entry 8). In this instance, the
hydrophosphination reaction proceeded smoothly, providing
82% ee of the expected product with 65% yield. By close
monitoring of the yield and ee of the reaction, it was observed
that the conversion reached its maximum after 72 h. Increasing
the reaction temperature could not assist in the completion of
the reaction, but it caused proportionally lower ee in each case
(entries 9 and 10). We also concluded that the selectivity of
the reaction is sensitive to the concentration of the catalyst
(entry 11).
RESULTS AND DISCUSSION
■
Synthetic Scheme. Because we intended to apply
asymmetric hydrophosphination in a synthetic pathway to
generate the P,N ligand motif, it was necessary to synthesize
the activated olefin, which already incorporated an sp2 nitrogen
atom. The synthetic challenge, however, in attempting this is
that typically small bite-angle P,N heterobidentate ligands can
themselves disrupt the catalytic cycle of the palladium-
catalyzed asymmetric hydrophosphination reaction by forming
a chelate with the catalyst, thus disrupting the process by which
the phosphine substrate can be displaced from the metal center
by the nucleophilic diphenylphosphine moiety present in the
reaction system.11a,d,13 To design a suitable substrate to test
the performance of various known hydrophosphination
catalysts and to surmount the aforementioned challenge,
isoquinoline 3 was functionalized in the first position by a
selective radical formylation reported by Minisci et al. in
1986,18 which led to a cyclic acetal 3a (1,3,5-trioxane
derivative). After deprotection,19 the desired carbaldehyde 4
was isolated (Scheme 1).
Scheme 1. Synthetic Scheme for Functionalizing
Isoquinoline
During screening of the base, we found that the use of 1.0
equiv of TEA was necessary for catalysis to take place: The
reaction could not start either in the absence of a base or by
using a weaker base or a lower base loading (entries 13−15).
Another observation was that the application of a stronger
base, e.g., 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) led to a
racemic product mixture, although the reaction proceeded to
completion (entry 16). Another interesting fact that was
observed during the optimization studies was that the reaction
The aldehyde 4 was then successfully reacted with dialkyl
and diaralkyl malonates in condensation reactions,20 which
provided the activated olefin substrates (Figure 3).
It has been seen from previous studies conducted by us that
the presence of two −COOR moieties is essential to provide
the optimum activation, which allows the subsequently
B
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Table 1. Optimization and Application of the Hydrophosphination of Activated Olefins 5a−5d
a
c
e
entry
R
catalyst
base
solvent
T/°C
t/h
yield/%
ee/%
1
2
3
4
5
6
7
8
9
10
11
12
13
14
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Et
Pd(OAc)2
(R,R)-7
(R,R)-7
(S)-2
(S)-2
(S)-2
(S)-2
(S)-2
(S)-2
(S)-2
(S)-2
(R)-2
(S)-2
(S)-2
(S)-2
(S)-2
(S)-2
(S)-2
(S)-2
DCM
DCM
DCM
THF
25
25
2
18
24
55
17
22
72
72
72
72
66
72
66
57
50
76
69
44
86
65
99
72
75
60
0
0
0
−40
−80
−80
−80
−80
−80
−40
−60
−80
−80
−80
−80
−80
−80
−80
−80
−80
TEA
TEA
TEA
TEA
TEA
TEA
TEA
TEA
TEA
1.7
1.6
13
44
82
25
49
73
55
toluene
MeOH
acetone
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
b
d
NaOAc
TEA
DBU
TEA
d
15
16
17
18
19
72
264
216
288
60
58
NA
64
0
25
NA
61
iPr
TEA
Bn
TEA
b
a
c
d
5 mol % catalyst was loaded, unless otherwise noted. 10 mol % catalyst was loaded. 1 equiv of base was used unless otherwise noted. 10 mol %
base was used. Isolated yields.
e
can indeed proceed without the metal at room temperature
(RT) with the use of 1.0 equiv of TEA.
removal of residual reagents and additives before proceeding
with metal complexation. The residual solvent as well as TEA
was removed using a vacuum under inert conditions.
Diphenylphosphine was subsequently removed by trituration
with degassed hexane before filtration on a short Celite plug
under nitrogen. The obtained P,N ligand 8 was subsequently
added immediately to selected metal sources at low temper-
ature (−80 °C) to allow complexation without further
isolation.
With ligand 8 in hand, the complexation was carried out by
adding the corresponding metal sources to a DCM solution of
8 at −80 °C and then the mixture was allowed to reach RT
(Schemes 2 and 3). Chelation took place immediately in every
case: the ligand could coordinate to the various metal sources
employed, viz., Pd(MeCN)2Cl2, Pt(MeCN)2Cl2, [Rh(COD)-
Cl]2, and [Ir(COD)Cl]2 (COD = 1,5-cyclooctadiene), without
any difficulty providing square-planar d8 complexes.
However, the conversion was significantly slower than that
achieved by employing the palladium catalyst, and, as expected,
no stereoselectivity was achieved. This occurrence of a
background nonmetal-catalyzed hydrophosphination has been
observed by us previously for activated ligands and necessitates
conduction of the reaction at low temperature in order for the
metal-catalyzed pathway to dominate and provide enantiose-
lectivity.
Given that the formed P,N ligand bears an acidic proton on
the carbon atom adjacent to the chiral center, our concern was
that the acid−base equilibrium could occur in the basic
medium, and this could potentially lead to side reactions,
which would set back the progression of the main one and
impact stereodiscrimination. To exclude this scenario, 1.0
equiv of water was added to the reaction, but this had no
further effect on the reaction.
With the optimized conditions in hand, we applied the
reaction to different malonate derivatives by changing the R
group of the ester moiety (entries 17−19). In these cases, the
reactions were significantly slower compared to the hydro-
phosphination of 5a; moreover, in the case of diisopropyl
malonate 5c, there was no product at all. In the case of 5b, the
yield was satisfactory (58%), but the selectivity was low (25%).
Surprisingly, hydrophosphination of 5d performed relatively
well (64% yield and 61% ee), in spite of the presence of bulky
benzyl groups on the substrate.
Scheme 2. Complexation of Palladium 9 and Platinum 10
Metals with the P,N Ligand 8
Although we concluded that the progress of the reaction
stops after 3 days, as indicated by the presence of the
unreacted starting materials in the reaction mixture, the
addition of the metal source to form the metal P,N complex in
situ to facilitate isolation was not favorable. Adding Pd-
(MeCN)2Cl2 and letting the mixture warm up to RT had to be
avoided because the presence of metal and the higher
temperature under basic conditions accelerated the reaction
to total completion without selectivity. In light of this
observation, we developed a workup process to facilitate the
C
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a
Scheme 3. Reaction Scheme for Synthesizing Rh(COD) (13) and Ir(COD) (14) Complexes
a
S indicates solvent molecules.
Each coordination product exhibited characteristic signal(s)
in CDCl3 when 31P{1H} spectroscopy was used to monitor the
progress of the complexation. For palladium complex 9, a
sharp singlet could be observed at 52.1 ppm (CDCl3, 202
MHz). For complex 10, the main resonance signal was at 28.7
ppm with two satellites: at 19.3 ppm and at 38.2 ppm (1JPt−P
=
3826.9 Hz, CDCl3, 202 MHz) due to coupling between the
NMR-active 195Pt and 31P nuclei.25 Complexes 9 and 10 are
stable in air and resistant to moisture; however, they
decompose during column chromatography. In both cases,
the crude complex could be purified by recrystallization in a
DCM/diethyl ether system.
We also intended to synthesize P,N rhodium(I) and
iridium(I) complexes with a COD ancillary ligand and a
BF4− counterion in the outer coordinating sphere because this
formula proved to be more stable than their chlorotriphenyl-
phosphine counterparts (see Coordination Behavior of
Complexes, complexes 20 and 21). Before the addition to 8,
the chloro ligands of the [M(COD)Cl]2 sources were removed
by AgBF4 (by stirring in degassed DCM in the dark for 2 h).26
After filtration of intermediates 12a and 12b on short silica
plugs, ligand 8 was added at low temperature (Scheme 3). It
resulted in a singlet at 41.5 ppm in the case of the iridium
complex (14) and a doublet at 49.7 ppm with a 1JRh−P = 156.2
Hz (CDCl3, 202 MHz) coupling constant in the case of the
rhodium complex (13), which is in accordance with the
literature27
Structural Determination and Conformational Anal-
ysis. As revealed by X-ray crystallography, the chiral complex 9
was successfully recrystallized from the enantioenriched
mixture with a R absolute configuration [because the applied
catalyst was (S)-2; Figure 4]. The measured Flack’s parameter
of the complex was 0.03(4).28 The selected bond lengths,
angles, and torsion angles are compiled in Table 2.
The four bonds that include palladium are significantly
longer than the usual 1.5 Å C−C bond, which causes a slight
elongation of the five-membered chelate ring. The bite angle of
the P,N ligand is close to the preferred 90° in bidentate
complexes;1e,f,2d however, it shows that the shape of the metal
center differs from the ideal square-planar arrangement of the
low-spin d8 complexes. Another important observation is that
the Pd−Cl bond length in the position trans to the nitrogen
atom is significantly smaller than that in the analogous P,C
chloro dimer complexes.14a,21a
When the chelate ring is observed from the aspect of bond
angles, it can be seen that it has an envelope-like conformation
(similarly to the cyclopentane Cs conformer), which is
supported by the relatively large torsion angle (−24.17°)
observed within C10−C9−N1−Pd1. This indicates that C10 is
out of the mean coordination plane (m.c.pl., defined by P−
Pd−N atoms). Because this carbon atom bears the dimethyl
Figure 4. ORTEP image of complex (R)-9.
malonate moiety, the torsion values within C11−C10−P1−
C22 (158.60°) and especially within Pd1−P1−C10−C11
(80.58°) support the fact that the bulky malonate group is
positioned axially with respect to the m.c.pl. On the basis of
these observations, we concluded that the P,N complex 9 with
an R configuration prefers the δ conformation (Figure 5).
The structure of compound (R)-9 was investigated further in
solution by performing two-dimensional 1H−1H ROESY NMR
spectroscopy. The two-dimensional spectrum of the complex
can be seen in Figure 6.
According to the ROESY correlations, we can observe that
five major interactions are occurring in the complex.
Correlation A is not surprising at all because those protons
are in vicinal coupling to each other. Cross-peak B between Ha
and Hb is important; this means that, although the bulky
malonate moiety in the axial position can rotate along the C−
C bond, a steric block exists between that and the isoquinoline
ring. Cross-peak F [interaction of Hd and the ortho protons of
the axial phenyl group (Hax‑ortho)] can be explained by the
conformational changes in solution. Nonetheless, the spatial
proximity between Ha and the equatorial phenyl group’s ortho
protons (Heq‑ortho; C), Hb and the ortho protons of the axial
phenyl group (Hax‑ortho; D), and Hc and the ortho protons
equatorial phenyl group (Heq‑ortho; E) also confirm that the δ
conformation is more likely in solution. Furthermore, the NOE
signal E points at it unambiguously because if the λ
conformation had any probability of occurring in solution,
Hc would have had a correlation peak with the ortho protons
D
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Table 2. Selected Bond Lengths, Angles, and Torsion Angles Based on Crystallographic Analysis
bond
d/Å
bond
d/Å
Pd1−N1
Pd1−Cl1
C9−C10
C10−P1
bond
2.054(8)
2.370(3)
1.510(13)
1.849(10)
α/deg
Pd1−P1
Pd1−Cl2
C9−N1
2.200(3)
2.290(3)
1.344(12)
bond
α/deg
N1−Pd1−P1
P1−Pd1−Cl1
P1−Pd1−Cl2
C9−N1−Pd1−P1
C11−C10−P1−C22
83.20(2)
N1−Pd1−Cl1
N1−Pd1−Cl2
Cl1−Pd1−Cl2
C10−C9−N1−Pd1
Pd1−P1−C10−C11
95.40(3)
169.70(3)
92.11(12)
−24.17
173.48(11)
90.13(11)
−3.22
−158.60
80.58
major product. The coupling constants between the 31P
nucleus of the chelating ligand (P,N) and 195Pt were generally
1
high (1JPt−P1 = 3693.6 Hz in the case of cis-16 and JPt−P
=
3680.6 Hz for complex 17), which indicates strong bonding
between those atoms,29 although the coupling constant value
observed between the phosphorus nucleus of triphenylphos-
phine and the platinum center was slightly lower (1JPt−P2
=
3445.6 Hz). It is worth mentioning that we observed that the
concentrations of the dimer (17) and starting material (10)
slowly increased in the mixture with respect to the
coordination compound 16 (see the Supporting Information).
The P,C counterpart 18 (Figure 8), in contrast, showed a
dynamic equilibrium between cis and trans P1−Pd−P2
2
coordination (2JP1−P2,trans = 427.2 Hz and JP1−P2, cis = 26.5
Hz), although trans proved to be the favored arrangement
(19).
This can be explained by the difference between the trans
influences of the coordinating nitrogen and sp2 carbon atoms.
Phosphorus and carbon atoms are both at the end of the trans
influence series and have a strong labilizing effect30 compared
to the nitrogen atom. In a P,N complex, a trans P−M−P
arrangement is less favorable than P−M−N; hence, despite the
significant steric repulsion, we could observe the cis isomer
being formed. Regarding P,C coordination, carbon has an even
stronger labilizing effect at the trans position than phosphorus;
thus, P−M−P arrangement (trans) is still benign. Moreover, it
is also preferred from the point of view of steric effects.
To support this explanation, we investigated the difference
in π acidity between the coordinating carbon and nitrogen (as
part of the aromatic moieties) with the use of DFT calculations
performed by applying Gaussian 09.31 For this purpose, we
carried out NBO32 analysis on complexes 9, 10, and 18 and
examined the highest occupied molecular orbital (HOMO)−
lowest unoccupied molecular orbital (LUMO) interaction
energies between the metals’ corresponding d orbitals
(HOMO) and the aromatic CN and CC aromatic π*-
antibonding (LUMO) orbitals (Figure 9).
DFT calculations were performed by using the B3LYP
functional.33 On palladium and platinum atoms, the SDD
effective core potential was used. On other atoms, the 6-31G*
basis set was applied.34 The calculated interaction energies can
be seen in Table 3.
According to the analysis, the aforementioned interactions
are more significant in the case of palladacycle 18 than in that
of the P,N palladium complex 9, which means that the π
acidity of the coordinating carbo-aromatic naphthyl moiety is
more significant. This, in turn, explains the stronger trans
influence of the coordinating aromatic carbon observed in the
coordination study. In the case of platinum (complex 10), this
Figure 5. Preferred δ conformation of complex 9 shown by Sawhorse
and Newman projections.
of the axial phenyl group, which is clearly absent in the
spectrum.
Coordination Behavior of Complexes. Because the P,N
bidentate ligand was developed based on the analogous P,C
palladacycles, the change in the electronic effects of the
coordinating moiety has to be taken into consideration. In
order to scrutinize the difference in the trans influence between
the coordinating aromatic nitrogen and carbon atoms, we
compared the P,N system to its exact P,C analogue.21a The
study was carried out by adding 1.0 equiv of the coordinating
monodentate phosphine (PPh3) to P,N and P,C complexes at
RT, with stirring for 1 h in DCM. The reactions were
monitored by 31P{1H} NMR spectroscopy (DCM, 162 MHz;
Figures 7 and 8).
According to the determined coupling constants from
31P{1H} NMR spectroscopy, only cis coordination (the PPh3
ligand prefers the cis position to the phosphorus atom of the
chelate ligand) occurred when 9 and 10 complexes were the
2
starting materials [2JP1−P2 = 7.3 Hz (15); JP1−P2 = 13.3 Hz
(16)].25a
Nevertheless, in the case of platinum, the obtained 31P{1H}
NMR spectrum requires greater scrutiny: besides the starting
material (10) and the coordination of triphenylphosphine (cis-
16), significant dimerization occurred to give complex 17 as a
E
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Figure 6. 1H−1H ROESY NMR spectrum of the palladium complex (R)-9. Selected NOE interactions: A, Ha−Hc; B, Ha−Hb; C, Ha−H (equatorial
phenyl ortho protons); D, Hb−H (axial phenyl ortho protons); E: Hc−H (equatorial phenyl ortho protons); F: Hd−H (axial phenyl ortho
protons).
Figure 7. Investigations on the coordination behavior of 9 and 10 by adding triphenylphosphine to their solution. P1 is the P,N ligand’s
phosphorus atom, and P2 is the triphenylphosphine’s phosphorus atom.
energy is relatively high compared to its P,N palladium
analogue (9), but it can be explained by the difference between
the palladium and platinum atoms: platinum’s 5d atomic
orbitals are at higher energy levels and are more diffuse than
palladium’s 4d orbitals. Thus, they are able to donate more
efficiently to the heteroaromatic ligand’s antibonding orbitals.
To further investigate the electronic effects of the P,N ligand
in regard to other transition metals, we performed the same
experiment with rhodium and iridium complexes by adding 0.5
equiv of [Rh(ethylene)Cl]2 and [Ir(COD)Cl]2 to ligand 8 to
form the respective P,N complexes. We subsequently added
1.0 equiv of triphenylphosphine to the mixtures at RT, and
they were stirred for 1.0 h to observe the coordination
behavior (complexes 20 and 21 in Figure 10).
In the case of rhodium (20), the coupling between the three
NMR-active nuclei (103Rh and the two 31P nuclei) caused a
characteristic pattern (doublet of doublets) in the NMR
spectrum. The 31P−31P coupling constants were 2JP1−P2 = 41.6
F
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Figure 8. P,C palladium complex 18 (analogue of the P,N palladium complex) after the addition of triphenylphosphine.
with respect to the coordinating phosphorus atoms, which is
not surprising if we consider the electronic effects discussed
earlier. Nevertheless, as revealed by 31P{1H} NMR spectros-
copy, the lability and air sensitivity of complexes 20 and 21 are
higher than we could experience in the case of complexes 13
and 14.
As aforementioned in the Synthetic Scheme section,
conversion of the asymmetric hydrophosphination reached
its maximum and did not increase beyond a certain point. To
explain this observation, we hypothesized that the P,N
bidentate 8 formed can coordinate to the (S)-2 catalyst and
obstruct the progress of catalysis. In order to support our
hypothesis, we decided to add (R)-1 C,N palladacycle complex
in situ to the reaction mixture of the hydrophosphination of 5a
once the maximum conversion was attained (the conditions
were the same as those at entry 8 in Table 1; Figure 11).
Figure 9. Selected interacting d(Pt)−π*(CN) orbitals in complex
10.
Table 3. Sum of the d(Metal)−π*(Aromatic) Interaction
Energies in P,N and P,C Complexes
metal complex
E
d−π* interaction/kcal/mol
9
10
18
1.94
4.45
4.72
Figure 11. In situ addition of the (R)-1 chiral auxiliary to the forming
P,N ligand.
The resulting complex 22 could be isolated, and it was
recrystallized to obtain the pure R,R diastereomer (Figure 11).
The formation of this structure proved our hypothesis that the
bidentate P,N ligand was indeed able to undergo chelation
with catalysts possessing at least two free coordination sites.
From the coordination point of view, this structure also
proves our observations on the steric and electronic effects as
well; i.e., it is favorable that the two nitrogen atoms are in
pairwise trans position to the carbon and phosphorus atoms to
avoid the less favored P−Pd−C(sp2) arrangement.
Figure 10. Rhodium and iridium P,N complexes after the addition of
triphenylphosphine. P1 is the P,N ligand’s phosphorus atom, and P2
is the triphenylphosphine’s phosphorus atom.
Hz (75.2 ppm, doublet of doublets; 46.2 ppm, doublet of
doublets; 162 MHz, DCM), which are typical values when cis
coordination occurs.35 The 103Rh−31P couplings are also
1
consistent with the literature values: JRh−P1 = 200.3 Hz and
1JRh−P2 = 171.9 Hz, where P1 refers to the P,N ligand’s
phosphorus atom and P2 refers to the triphenylphosphine’s
phosphorus atom.27,35
CONCLUSION
■
A new class of chiral and enantioenriched P,N transition-metal
complexes was synthesized and investigated from conforma-
tional, coordination, and electronic points of view. The
synthesis of the P,N heterobidentate ligand was carried out
Complex 21 also showed cis coupling with 2JP1−P2= 32.8 Hz
(32.1 ppm, doublet; −30.3 ppm, doublet; 162 MHz, DCM)36
G
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(s), 122.49 (s), 52.92 (s, 1C, COOCH3), 52.45 (s, 1C, COOCH3).
HRMS (+ESI). Calcd for C15H14NO4 [(M + H)+]: m/z 272.0923.
Found: m/z 272.0923. Anal. Calcd for C15H13NO4: C, 66.41; H, 4.83;
N, 5.16. Found: C, 66.15; H, 4.15; N, 5.16.
catalytically by employing the phosphapalladacycle-catalyzed
asymmetric hydrophosphination protocol. By overcoming the
challenges posed by potential catalyst poisoning due to the
product chelation in the catalytic step, we obtained palladium,
platinum, rhodium, and iridium complexes, which can be
starting points for new catalyst designs in the future. With
rhodium and iridium complexes, we have also demonstrated
that this ligand system can be applicable for the synthesis of
metal complexes with less stable oxidation states. Conforma-
tional analysis revealed that the coordinated P,N ligand has a
well-defined spatial arrangement, while the coordination study
carried out on various metals showed that its electronic effects
differ from their P,C bidentate counterparts.
General Procedure for the Preparation of Diethyl,
Diisopropyl, and Dibenzyl 2-(Isoquinolin-1-ylmethylene)-
malonates (5b−5d). TiCl4 (2.0 mmol, 2.1 equiv) was dissolved in
1.5 mL of CCl4, and this solution was added dropwise to 12 mL of
tetrahydrofuran (THF) at 0 °C. When the yellow adduct appeared,
carbaldehyde 4 (0.95 mmol, 1.0 equiv) and the corresponding
malonate (0.95 mmol, 1.0 equiv) were dissolved in 2.0 mL of THF
and added to the TiCl4 solution dropwise. A THF solution of pyridine
(16.0 mmol, 16.6 equiv) was also added to the reaction mixture,
which then was stirred under nitrogen at 0 °C for 1 h and further at
RT until the reaction was complete. Upon completion, the reaction
mixture was quenched with 10.0 mL of H2O, and then 20.0 mL of
ethyl acetate and Na2CO3(aq) were added (to adjust the pH to
neutral), and the solution was extracted with ethyl acetate. The
organic layer was further washed with NaHCO3 and brine, then dried,
and evaporated. The resulting diester was the purified by column
chromatography on silica gel (5:1 to 1:1 n-hexane/ethyl acetate) to
obtain the pure product.
The information gained and collected in this study can play
an important role in the design of new heterobidentate chiral
P,N-type transition-metal catalysts. Investigation of the
catalytic activity of the synthesized complexes is still in
progress.
EXPERIMENTAL SECTION
■
Diethyl 2-(Isoquinolin-1-ylmethylene)malonate (5b). Yield: 29%,
1
3
brown oil. H NMR (500 MHz, CDCl3): δ 8.53 (d, JH−H = 5.6 Hz,
General Considerations. For the preparation and handling of
air-sensitive phosphines and complexes, positive nitrogen and argon
flows were used (standard Schlenk techniques). Solvents were
degassed previously for all reactions and measurements when
necessary. Reagents for carrying out synthetic steps were purchased
from Sigma-Aldrich, TCI, Strem, Alfa Aesar, and Acros Organics.
Purifications by flash column chromatography was carried out on a
Merck Silica Gel 60. For the NMR data, Bruker AV500 (1H, 500.1
MHz; 13C, 125.7 MHz; 19F, 470.6 MHz; 31P, 202.4 MHz), Bruker
AV400 and BBFO 400 (1H. 400.1 MHz; 13C, 100.6 MHz; 19F, 376.5
MHz; 31P, 162.0 MHz) instruments were used for the characterization
of new compounds and a study of the coordination. Chemical shifts
were reported in parts per million by using the internal standard
1H, ArH), 8.52 (s, 1H, ArH), 8.28 (d, 3JH−H = 8.5 Hz, 1H, ArH), 7.85
3
(d, JH−H = 8.0 Hz, 1H, CCHAr), 7.74−7.62 (m, 3H, ArH), 4.39
3
3
(q, JH−H = 7.2 Hz, 2H, OCH2CH3), 4.37 (q, JH−H = 7.2 Hz, 2H,
3
3
OCH2CH3), 4.22 (q, JH−H = 7.15 Hz, 1H), 1.38 (t, JH−H = 7.2 Hz,
3H, OCH2CH3), 1.31 (t, JH−H = 7.15 Hz, 3H, OCH2CH3), 1.24 (t,
3
3JH−H = 7.1 Hz, 1H). 13C NMR (126 MHz, CDCl3): δ 166.57 (1C,
CO), 164.05 (1C, CO), 150.44 (1C, NCCH), 142.21 (s),
136.47 (s), 135.52 (s), 131.17 (s), 130.32 (s), 128.12 (s), 127.68 (s),
127.48 (s), 123.99 (s), 122.29 (s), 61.90 (1C, COOCH2CH3), 61.34
(1C, COOCH2CH3), 14.16 (1C, COOCH2CH3), 14.03 (1C,
COOCH2CH3). HRMS (+ESI). Calcd for C17H18NO4 [(M + H)+]:
m/z 300.1236. Found: m/z 300.1236.
1
tetramethylsilane for H NMR measurements, CDCl3 for 13C NMR
Diisopropyl 2-(Isoquinolin-1-ylmethylene)malonate (5c). Yield:
38%, brown oil. 1H NMR (400 MHz, CDCl3): δ 8.52 (d, 3JH−H = 5.6
Hz, 1H, ArH), 8.47 (s, 1H, ArH), 8.29 (d, 3JH−H = 8.5 Hz, 1H, ArH),
measurements, external standard H3PO4 for 31P NMR measurements,
and CFCl3 for 19F NMR measurements. High-resolution mass
spectrometry (HRMS) data were recorded on a Waters Q-TOF
Premier spectrometer by using electrospray ionization (ESI) positive
mode. Elemental analysis was carried out on a PerkinElmer CHNS/O
series II 2400 EA instrument. The determination of ee was performed
on an Agilent 1200 series chromatograph with Daicel Chiralpack ID
and IF columns in an n-hexane−isopropyl alcohol solvent system.
Optical rotation measurements were performed on a Jasco P-1030
polarimeter using the D lines of sodium (589 nm) as the light source.
Caution! Perchlorate salts of metal complexes are dangerous because they
are potentially explosive. These chemicals must be handled with care.
Preparation of Dimethyl 2-(Isoquinolin-1-ylmethylene)-
malonate (5a). Carbadehyde 4 (5.60 mmol, 0.89 g, 1.0 equiv) and
dimethyl malonate (6.52 mmol, 0.86 g, 1.15 equiv) were dissolved in
40.0 mL of benzene and heated to reflux temperature. N-
Methylpiperidine (0.85 mmol, 0.08 g, 0.15 equiv) and benzoic acid
(0.42 mmol, 0.05 g, 0.075 equiv) were dissolved in 10.0 mL of
benzene and added to the boiling solution of the starting material and
malonate. The solution was refluxed overnight with the use of a
Dean−Stark apparatus and 4 Å molecular sieve. After the reaction was
complete, saturated aqueous sodium bicarbonate was added to the
solution and extracted with DCM. The combined organic layer was
washed with brine, dried, and evaporated. The residue was purified
with column chromatography on silica gel (4:1 to 2:1 n-hexane/ethyl
acetate) to afford the pure diester.
3
7.85 (d, JH−H = 7.6 Hz, 1H, ArH), 7.76−7.63 (m, 3H, ArH), 5.32
(hept, 3JH−H = 6.3 Hz, 1H, COOCH(CH3)2), 5.22 (hept, 3JH−H = 6.2
3
Hz, 1H, COOCH(CH3)2), 1.36 (d, JH−H = 6.3 Hz, 6H, COOCH-
3
(CH3)2), 1.32 (d, JH−H = 6.2 Hz, 6H, COOCH(CH3)2), 1.28−1.20
3
(m, 1H), 1.16 (d, JH−H = 6.3 Hz). 13C NMR (126 MHz, CDCl3): δ
166.00 (s, 1C, CO), 163.60 (s, 1C, CO), 150.66 (s, 1C, N
CCH), 142.05 (s), 136.44 (s), 134.92 (s), 131.97 (s), 130.27 (s),
128.04 (s), 127.63 (s), 127.45 (s), 124.09 (s), 122.16 (s), 69.59 (s),
69.54 (s, 1C, COOCH(CH3)2), 68.77 (s), 68.69 (s, 1C, COOCH-
(CH3)2), 21.78 (s, 2C, COOCH(CH3)2), 21.61 (s, 2C, COOCH-
(CH3)2). HRMS (+ESI). Calcd for C19H22NO4 [(M + H)+]: m/z
328.1549. Found: m/z 328.1548.
Dibenzyl 2-(Isoquinolin-1-ylmethylene)malonate (5d). Yield:
22%, brown solid. 1H NMR (500 MHz, CDCl3): δ 8.57 (s, 1H,
3
3
ArH), 8.33 (d, JH−H = 5.5 Hz, 1H, ArH), 8.26 (d, JH−H = 8.4 Hz,
3
1H, ArH), 7.84 (d, JH−H = 8.1 Hz, 1H, CCHAr), 7.74−7.58 (m,
3H, ArH), 7.42−7.33 (m, 5H, ArH), 7.33−7.26 (m, 6H, ArH), 5.35
(s, 2H, benzyl CH2), 5.34 (s, 2H, benzyl CH2). 13C NMR (126 MHz,
CDCl3): δ 166.44 (s, 1C, CO), 163.82 (s, 1C, CO), 150.07 (s,
1C, NCCH), 142.29 (s), 136.48 (s), 136.35 (s), 135.59 (s), 135.49
(s), 130.43 (s), 130.35 (s), 128.66 (s), 128.63 (s), 128.50 (s), 128.44
(s), 128.31 (s), 128.20 (s), 128.17 (s), 128.14 (s), 128.05 (s), 128.00
(s), 127.71 (s), 127.51 (s), 127.25 (s), 123.90 (s), 122.42 (s), 67.38
(s, 1C, benzyl CH2), 67.22 (s, 1C, benzyl CH2). HRMS (+ESI). Calcd
for C27H22NO4 [(M + H)+]: m/z 424.1549. Found: m/z 424.1549.
General Procedure for Catalytic Hydrophosphination on
Dialkyl and Diaralkyl 2-(Diphenylphosphorothioyl)-
(isoquinolin-1-ylmethylene)malonates (Optimization of Con-
ditions; 6a−6c). Diphenylphosphine (0.05 mmol, 9.31 mg, 1.0
equiv) was weighed into a Schlenk flask under positive nitrogen flow,
and 2.0 mL of the previously degassed solvent was added. The
1
Yield: 52%, yellow-brown solid. H NMR (500 MHz, CDCl3): δ
8.57 (s, 1H, ArH), 8.55 (d, 3JH−H = 5.5 Hz, 1H, ArH), 8.31 (d, 3JH−H
= 8.4 Hz, 1H, ArH), 7.87 (d, 3JH−H = 8.0 Hz, 1H, CCHAr), 7.78−
7.60 (m, 3H, ArH), 3.92 (s, 3H, COOCH3), 3.90 (s, 3H, COOCH3).
13C NMR (126 MHz, CDCl3): δ 167.22 (s, 1C, CO), 164.43 (s,
1C, CO), 150.11 (s, 1C, NCCH), 142.40 (s), 136.54 (s), 136.11
(s), 130.39 (s), 130.30 (s), 128.23 (s), 127.78 (s), 127.53 (s), 123.89
H
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2
1
malonate substrate (0.05 mmol, 1.0 equiv) and catalyst (0.0025
mmol, 0.05 equiv) were added to the solution, and then the required
temperature was adjusted. When the required temperature was
reached, a base (0.05 mmol, 1.0 equiv) was added dropwise to the
reaction mixture. The reaction was monitored by 31P{1H} NMR
spectroscopy. Upon completion of the reaction, excess sulfur was
added, the mixture was allowed to warm up, and the volatiles were
evaporated. The residue was purified by column chromatography on
silica gel (5:1 to 2:1 n-hexane/ethyl acetate) to obtain the pure
sulfurized phosphine product.
54.89 (d, JP−C = 3.0 Hz, 1C, CHCH(PPh2)Ar), 45.15 (d, JP−C
=
45.7 Hz, 1C, CHCH(PPh2)Ar). 31P{1H} NMR (202 MHz, CDCl3): δ
48.66 (s). HRMS (+ESI). Calcd for C39H33NO4PS [(M + H)+]: m/z
642.1868. Found: m/z 642.1865.
General Procedure for Generating P,N Dichloropalladium
and -Platinum Complexes [(R)-9 and (R)-10]. Diphenylphosphine
(0.17 mmol, 0.032 g, 1.0 equiv) was weighed into a Schlenk flask
under positive nitrogen flow, and 7.0 mL of the previously degassed
DCM was added. Substrate 5a (0.17 mmol, 0.046 g, 1.0 equiv) and
(S)-2 catalyst (0.0085 mmol, 0.005 g, 0.05 equiv) were added to the
solution, and then the mixture was cooled to −80 °C. When the
required temperature was reached, TEA (0.17 mmol, 0.017 g, 1.0
equiv) was added dropwise to the reaction mixture. After the reaction
reached the desired conversion, TEA and the solvent were removed
by using a nitrogen flow and vacuum, while the low temperature was
permanently maintained. The residue was then triturated four times
with degassed hexane to remove excess diphenylphosphine. The crude
material was redissolved in DCM and filtered through a short Celite
plug under Schlenk conditions. MCl2(MeCN)2 (0.17 mmol, 1.0
equiv) was then added to the free P,N ligand 8 at −80 °C, stirred for
1 h, and allowed to reach RT. Each of the resulting air-stable
complexes was filtered through a short Celite plug and recrystallized
from DCM with diethyl ether to afford enantiopure crystals.
Dimethyl 2-(Diphenylphosphorothioyl)(isoquinolin-1-ylmethyl)-
1
malonate (6a). Yield: 86%, pale-yellow solid. H NMR (500 MHz,
CDCl3): δ 8.40 (d, 3JH−H = 5.6 Hz, 1H, ArH), 8.11 (dd, 3JH−H = 11.6
3
and 7.0 Hz, 2H, ArH), 8.02 (d, JH−H = 8.3 Hz, 1H, ArH), 7.57 (d,
3JH−H = 8.1 Hz, 1H, ArH), 7.51−7.37 (m, 7H, ArH), 7.35 (d, 3JH−H
=
3
5.0 Hz, 1H, ArH), 7.04 (t, JH−H = 6.7 Hz, 1H, ArH), 6.91 (m, 2H,
ArH), 5.83 (t, 3JH−H, 3JH−P = 10.2 Hz, 1H, CHCH(PPh2)Ar), 5.28 (t,
3JH−H 2JH−P = 10.7 Hz, 1H, CHCH(PPh2)Ar), 3.37 (s, 3H,
,
COOCH3), 3.36 (s, 3H, COOCH3). 13C NMR (126 MHz,
2
CDCl3): δ 168.46−168.11 (m, 2C, CO), 155.43 (d, JP−C = 6.6
Hz, 1C, Ar, NCC(H)P), 141.29 (d, JP−C = 3.0 Hz, 1C), 135.90,
1
1
132.46 (d, JP−C = 9.7 Hz, 1C, Ar, PC6H5), 131.93 (d, JP−C = 10.1
Hz, 1C, Ar, PC6H5), 131.61 (s), 131.10 (s), 130.96 (s), 130.86 (s),
130.48 (s), 130.31 (s), 129.53 (s), 128.21 (d, JP−C = 12.0 Hz), 128.00
(s), 127.40 (s), 127.31 (s), 127.17 (s), 127.14 (s), 124.50 (s), 120.13
(R)-κ2-P,N-[Dimethyl 2-(diphenylphosphanyl)(isoquinolin-1-
ylmethyl)malonate]dichloropalladium(II) [(R)-9]. Yield: 85%, yellow
solid. [α]25D = −479 (c 1.0, CH2Cl2). 1H NMR (500 MHz, CDCl3): δ
9.79 (d, 3JH−H = 6.6 Hz, 1H, ArH, HCCHN), 8.29 (d, 3JH−H = 8.6
Hz, 1H, ArH), 8.02−7.86 (m, 7H, ArH), 7.81−7.70 (m, 2H, ArH),
7.59 (t, 3JH−H = 6.9 Hz, 2H, ArH), 7.53 (t, 3JH−H = 7.6 Hz, 2H, ArH),
2
(s), 54.40 (d, JP−C = 3.0 Hz, 1C, CHCH(PPh2)Ar), 52.63 (s, 2C,
1
COOCH3), 44.84 (d, JP−C = 47.3 Hz, 1C, CHCH(PPh2)Ar).
31P{1H} NMR (202 MHz, CDCl3) δ 48.73 (s). HRMS (+ESI). Calcd
for C27H25NO4PS [(M + H)+]: m/z 490.1242. Found: m/z 490.1240.
Anal. Calcd for C27H24NO4PS: C, 66.25; H, 4.94; N, 2.86. Found:
65.73; H, 4.80; N, 2.99.
3
3
7.48 (td, JH−P = 7.7 Hz, JH−H = 2.7 Hz, 2H, P−C6H5), 7.43 (td,
3JH−P = 7.7 Hz, JH−H = 2.5 Hz, 2H, PC6H5), 5.89 (dd, JP−H = 14.8
Hz, 3JH−H = 9.4 Hz, 1H, CHCH(PPh2)Ar), 4.49 (dd, 2JP−H = 15.6 Hz,
3JH−H = 9.4 Hz, 1H, CHCH(PPh2)Ar), 3.30 (s, 3H, COOCH3), 3.25
(s), 2.76 (s), 2.73 (s, 3H, COOCH3). 13C NMR (126 MHz, CDCl3):
3
3
Diethyl 2-(Diphenylphosphorothioyl)(isoquinolin-1-ylmethyl)-
malonate (6b). Yield: 58%, yellow solid. 1H NMR (500 MHz,
CDCl3): δ 8.39 (d, 3JH−H = 5.6 Hz, 1H, ArH), 8.10 (dd, 3JH−H = 12.1
3
δ 166.89 (s, 1C, Ar, HCCHN), 166.17 (d, JP−C = 12.0 Hz, 1C,
3
3
Hz, JH−H = 7.3 Hz, 2H, ArH), 8.05 (d, JH−H = 8.4 Hz, 1H, ArH),
CO), 161.97 (d, 3JP−C = 8.1 Hz, 1C, CO), 145.40 (s), 136.54 (s),
136.29 (d, 2JP−C = 11.3 Hz, 1C, Ar, NCC(H)P), 133.44 (s), 133.10
(d, JP−C = 2.8 Hz), 132.74 (d, JP−C = 2.9 Hz), 132.61 (d, 1JP−C = 10.5
7.57 (d, 3JH−H = 8.0 Hz, 1H, ArH), 7.53−7.36 (m, 7H, ArH), 7.34 (d,
3JH−H = 5.2 Hz, 1H, ArH), 7.05 (t, 3JH−H = 7.0 Hz, 1H, ArH), 6.94 (d,
3JH−H = 5.2 Hz, 2H, ArH), 5.85 (t, JH−H
,
3JH−P = 10.3 Hz, 1H
3
1
Hz, 1C, Ar, PC6H5), 129.93 (s), 129.71 (d, JP−C = 11.4 Hz, 1C, Ar,
PC6H5), 128.62 (d, JP−C = 12.1 Hz), 126.71 (d, JP−C = 10.6 Hz),
125.04 (d, JP−C = 53.6 Hz), 123.27 (s), 122.60 (d, JP−C = 56.0 Hz),
3
CHCH(PPh2)Ar), 5.22 (t, JH−H
,
2JH−P = 10.8 Hz, 1H,
CHCH(PPh2)Ar), 3.95−3.63 (m, 4H, COOCH2CH3), 1.10 (t,
3
3JH−H = 7.1 Hz, 3H, COOCH2CH3), 0.76 (t, JH−H = 7.0 Hz, 3H,
2
53.22 (s, 1C, COOCH3), 53.17 (d, JP−C = 5.3 Hz, 1C,
COOCH2CH3). 13C NMR (126 MHz, CDCl3): δ 167.79−167.08 (m,
1
CHCH(PPh2)Ar), 52.71 (s, 1C, COOCH3), 47.08 (d, JP−C = 30.4
2C, CO), 155.79 (d, 2JP−C = 6.0 Hz, 1C, Ar, NCC(H)P), 141.31
Hz, 1C, CHCH(PPh2)Ar), 30.93 (s), 29.69 (s). 31P{1H} NMR (202
1
(d, JP−C = 2.9 Hz), 135.86 (s), 132.45 (d, JP−C = 9.7 Hz, 1C, Ar,
MHz, CDCl3):
δ 52.13 (s). HRMS (+ESI). Calcd for
1
C27H25Cl2NO4PPd [(M + H)+]: m/z 635.9937. Found: m/z
635.9931. Anal. Calcd for C27H24Cl2NO4PPd: C, 51.09; H, 3.81; N,
2.21. Found: C, 48.51; H, 3.61; N, 2.03.
PC6H5), 132.03 (d, JP−C = 10.0 Hz, 1C, Ar, PC6H5), 131.50 (s),
130.78 (s), 129.49 (s), 128.11 (d, JP−C = 12.1 Hz), 127.34 (d, JP−C
=
12.2 Hz), 124.63 (s), 119.96 (s), 61.82 (s, 1C, COOCH2CH3), 61.41
(s, 1C, COOCH2CH3), 54.93 (d, 2JP−C = 2.8 Hz, 1C, CHCH(PPh2)-
(R)-κ2-P,N-[Dimethyl 2-(diphenylphosphaneyl)(isoquinolin-1-
1
ylmethyl)malonate]dichloroplatinum(II) [(R)-10]. Yield: 67%,
Ar), 44.80 (d, JP−C = 47.3 Hz, 1C, CHCH(PPh2)Ar), 13.71 (s, 1C,
brown solid. [α]25 = −43 (c 0.5, CH2Cl2). H NMR (500 MHz,
1
COOCH2CH3), 13.65 (s, 1C, COOCH2CH3). 31P{1H} NMR (202
MHz, CDCl3): δ 48.81 (s). HRMS (+ESI). Calcd for C29H29NO4PS
[(M + H)+]: m/z 518.1555. Found: m/z 518.1555.
D
CDCl3): δ 10.03 (d, 3JH−H = 6.7 Hz, 1H, ArH, HCCHN), 8.30 (d,
3JH−H = 8.5 Hz, 1H, ArH), 8.08−7.94 (m, 5H, ArH), 7.93 (s, ArH),
7.91 (s, 1H, ArH), 7.90 (s, 1H, ArH), 7.73 (m, 1H, ArH), 7.69 (d,
3JH−H = 6.8 Hz, 1H, ArH), 7.57 (m, 2H, ArH), 7.53−7.41 (m, 6H,
Dibenzyl 2-(Diphenylphosphorothioyl)(isoquinolin-1-ylmethyl)-
malonate (6c). Yield: 64%, yellow solid. 1H NMR (500 MHz,
CDCl3): δ 8.31 (d, 3JH−H = 5.6 Hz, 1H, ArH), 8.05 (dd, 3JH−H = 12.2
3
3
ArH), 5.83 (dd, JP−H = 12.3 Hz, JH−H = 9.9 Hz, 1H,
3
3
2
3
Hz, JH−H = 7.6 Hz, 2H, ArH), 7.97 (d, JH−H = 8.3 Hz, 1H, ArH),
CHCH(PPh2)Ar), 4.52 (dd, JP−H = 14.7 Hz, JH−H = 9.9 Hz, 1H,
CHCH(PPh2)Ar), 3.30 (s), 3.27 (s, 3H, COOCH3), 2.74 (s), 2.69 (s,
3H, COOCH3). 13C NMR (126 MHz, CDCl3): δ 166.98 (s, 1C, Ar,
7.58−7.27 (m, 14H, ArH), 7.25−7.19 (m, 2H, ArH), 7.15 (t, 3JH−H
=
3
7.4 Hz, 1H, ArH), 7.07 (t, JH−H = 7.5 Hz, 2H, ArH), 7.05 (s, 1H,
ArH), 6.92 (m, 2H, ArH), 6.83 (d, 3JH−H = 7.3 Hz, 2H, ArH), 5.87 (t,
3
HCCHN), 166.34 (d, JP−C = 12.2 Hz, 1C, CO), 162.84 (d,
3JH−H, 3JH−P = 10.4 Hz, 1H, CHCH(PPh2)Ar), 5.39 (t, 3JH−H, 2JH−P
=
3JP−C = 5.7 Hz, 1C, CO), 144.38 (s), 141.96 (s), 139.29 (s), 136.26
2
10.7 Hz, 1H, CHCH(PPh2)Ar), 4.85−4.77 (m, 2H, benzyl CH2),
(d, JP−C = 11.7 Hz, 1C, Ar, NCC(H)P), 135.95 (s), 133.18 (s),
4.72 (s, 2H, benzyl CH2). 13C NMR (126 MHz, CDCl3): δ 167.79−
132.94 (s), 132.66 (d, JP−C = 10.9 Hz, 1C, Ar, PC6H5), 132.45 (s),
1
2
1
167.08 (m, 2C, CO), 155.46 (d, JP−C = 6.2 Hz, 1C, Ar, N
130.16 (s), 129.50 (d, JP−C = 11.5 Hz, 1C, Ar, PC6H5), 128.51 (d,
JP−C = 12.4 Hz), 127.56 (d, JP−C = 48.2 Hz), 126.99 (d, JP−C = 8.7
Hz), 124.60 (d, JP−C = 62.1 Hz), 123.34 (s), 120.84 (d, JP−C = 63.8
Hz), 53.14 (s, 1C, COOCH3), 52.56 (s, 1C, COOCH3), 52.12 (d,
2JP−C = 4.3 Hz, 1C, CHCH(PPh2)Ar), 46.23 (d, 1JP−C = 37.1 Hz, 1C,
CHCH(PPh2)Ar), 33.82 (s), 31.93 (s), 29.70 (s), 29.36 (s), 22.69
(s), 14.12 (s). 31P{1H} NMR (202 MHz, CDCl3): δ 28.71 (s), 28.72
CC(H)P), 141.27 (d, JP−C = 3.0 Hz), 135.87 (s), 135.29 (s), 134.86
(s), 132.42 (d, 1JP−C = 9.4 Hz 1C, Ar, PC6H5), 132.08 (d, 1JP−C = 9.9
Hz, 1C, Ar, PC6H5), 131.48 (d, JP−C = 2.8 Hz), 130.80 (s), 130.32 (s),
129.46 (s), 128.35 (s), 128.19 (s), 128.07 (s), 127.99 (s), 127.94 (s),
127.90 (s), 127.87 (s), 127.36 (d, JP−C = 12.4 Hz), 127.09 (s), 124.58
(s), 120.03 (s), 67.30 (s, 1C, benzyl CH2), 67.12 (s, 1C, benzyl CH2),
I
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Inorg. Chem. XXXX, XXX, XXX−XXX

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Article
2
(d, 1JPt−P = 3826.9 Hz). HRMS (+ESI). Calcd for C27H25Cl2NO4PPt
[(M + H)+]: m/z 723.0546. Found: m/z 723.0544. Anal. Calcd for
C27H24Cl2NO4PPt: C, 44.83; H, 3.34; N, 1.94. Found: C, 44.67; H,
3.45; N, 2.10.
Hz, 1C, Ar, NCC(H)P), 132.72 (d, JP−C = 19.0 Hz, 1C, Ar,
2
PC6H5), 131.12 (d, JP−C = 9.0 Hz), 130.54 (s), 129.86 (d, JP−C
10.7 Hz, 1C, Ar, PC6H5), 129.50 (d, JP−C = 10.5 Hz), 129.01 (d, JP−C
=
= 9.9 Hz), 128.15 (s), 127.62 (s), 127.49 (s), 127.18−126.79 (m),
2
125.19 (s), 122.49 (d, JP−C = 46.8 Hz), 99.76 (s), 97.35 (d, JP−C
=
General Procedure for the Synthesis of P,N Rhodium and
Iridium 1,5-Cyclooctadiene Tetrafluoroborate Complexes (13
and 14). [M(COD)Cl]2 (0.04 mmol, 0.5 equiv) was dissolved in 5.0
mL of degassed DCM and stirred under nitrogen. AgBF4 (0.08 mmol,
1.0 equiv) was dissolved in degassed methanol, and this was added to
the DCM solution. This mixture was stirred at RT in the dark for 3 h.
The resulting M+(COD)−BF4 complex was filtered through a short
Celite plug under nitrogen and immediately added to the DCM
solution of P,N ligand 8 (0.08 mmol, 1.0 equiv; obtained in the
aforementioned way) at −80 °C, stirred for 1 h under nitrogen, and
allowed to reach RT. The formed (P,N)M+(COD)−BF4 complex was
filtered through a short Celite plug under Schlenk conditions, and the
solvent was removed by vacuum.
2
7.7 Hz, 1C, COD, HCCH), 96.87 (d, JP−C = 8.9 Hz, 1C, COD,
2
HCCH), 65.79 (d, JP−C = 10.4 Hz, 1C, COD, HCCH), 63.06
2
2
(d, JP−C = 13.8 Hz 1C, COD, HCCH), 55.28 (d, JP−C = 6.8 Hz,
1C, CHCH(PPh2)Ar), 53.43 (s, 1C, COOCH3), 52.86 (s, 1C,
1
COOCH3), 49.59 (s), 48.22 (d, JP−C = 30.3 Hz, 1C, CHCH(PPh2)-
Ar), 47.73 (s), 43.77 (d, J = 8.6 Hz), 36.80 (s), 32.60 (s), 31.91 (s),
29.68 (s), 29.34 (s), 28.94 (s), 25.75 (s), 25.14 (s), 23.24 (d, J = 4.3
Hz), 23.04 (s), 22.68 (s), 14.10 (s), 9.13 (s). 19F NMR (376 MHz,
CDCl3): δ −153.26 (s). 31P{1H} NMR (202 MHz, CDCl3): δ 41.49
−
(s). HRMS (+ESI). Calcd for C35H37NO4PIr [(M + H − BF4 )+]: m/
z 759.2090. Found: m/z 759.2097.
Preparation of [(R)-κ2-C2,N-1-[1-(Dimethylamino)ethyl]-
naphthyl][(R)-κ2-P,N-dimethyl 2-(diphenylphosphaneyl)-
(isoquinolin-1-ylmethyl)malonate]palladium(II) Perchlorate
[(R,R)-22]. Diphenylphosphine (0.08 mmol, 0.015 g, 1.0 equiv) was
weighed into a Schlenk flask under positive nitrogen flow, and 3.0 mL
of the previously degassed DCM was added. The malonate substrate
5a (0.08 mmol, 0.022 g, 1.0 equiv) and (S)-2 catalyst (0.004 mmol,
0.0025 g, 0.05 equiv) were added to the solution, and then the
mixture was cooled to −80 °C. When the required temperature was
reached, TEA (0.08 mmol, 0.009 g, 1.0 equiv) was added dropwise to
the reaction mixture. After completion of the reaction, the (R)-1
complex (0.08 mmol, 0.042 g, 1.0 equiv) was added, and the mixture
was allowed to warm to RT. The solution was washed with water and
brine, dried, and filtered through a short Celite plug, and then the
solvent was evaporated. The crude complex was recrystallized from
DCM with diethyl ether to afford diastereomerically pure crystals.
[κ2-P,N-[Dimethyl 2-(diphenylphosphanyl)(isoquinolin-1-
ylmethyl)malonate]][1,2,5,6-η-(1Z,5Z)-cycloocta-1,5-diene]-
rhodium(I) Tetrafluoroborate (13). Yield: crude brown solid. 1H
NMR (500 MHz, CDCl3): δ 8.18 (d, 3JH−H = 8.7 Hz, 1H, ArH), 8.07
(d, 3JH−H = 6.5 Hz, 1H, ArH), 7.96 (t, 3JH−3H = 9.1 Hz, 1H, ArH), 7.89
3
(d, JH−H = 6.4 Hz, 1H, ArH), 7.86 (d, JH−H = 8.3 Hz, 1H, ArH),
3
7.77 (d, JH−H = 7.3 Hz, 1H, ArH), 7.74−7.69 (m, 3H, ArH), 7.68−
7.63 (m, 1H, ArH), 7.55−7.49 (m, 1H, ArH), 7.48−7.38 (m, 5H,
3
3
ArH), 7.33−7.27 (m, 3H, ArH), 5.88 (dd, JP−H = 13.2 Hz, JH−H
=
=
3
2
8.1 Hz, 1H, CHCH(PPh2)Ar), 5.67 (dd, JH−H = 15.1 Hz, JRh−H
1.4 Hz, 2H, COD HC = CH), 4.65 (dd, 2JP−H = 15.0 Hz, 3JH−H = 8.1
Hz, 1H, CHCH(PPh2)Ar), 4.38 (d, 3JH−H = 55.1 Hz, 2JRh−H= 5.5 Hz,
2H, COD HCCH), 3.70−3.60 (m), 3.46 (s, 3H, COOCH3), 3.24−
3.14 (m, 1H), 2.81 (s, 3H, COOCH3), 2.74−2.53 (m, 2H, COD
CH2), 2.37 (m, 3H, COD CH2), 2.10−1.99 (m, 2H, COD CH2). 13
C
(R,R)-22 is a bright-yellow solid. Yield: 33%. [α]25 = −247 (c 2.0,
CH2Cl2). H NMR (500 MHz, CDCl3): δ 8.72 (d, JH−H = 6.1 Hz,
D
NMR (126 MHz, CDCl3): δ 167.26 (s, 1C, Ar, HCCHN), 166.16
1
3
3
3
(d, JP−C = 9.4 Hz, 1C, CO), 162.56 (d, JP−C = 9.3 Hz, 1C, C
3
2
1H, ArH, HCCHN), 8.32 (d, JH−H = 8.6 Hz, 1H, ArH), 8.25 (d,
O), 142.02 (s), 136.68 (s), 133.84−133.40 (m), 133.55 (d, JP−C
=
3JH−H = 6.1 Hz, 1H, ArH), 7.99 (d, 3JH−H = 8.2 Hz, 1H, ArH), 7.89−
1
10.8 Hz, 1C, Ar, NCC(H)P), 133.16 (d, JP−C = 10.8 Hz, 1C, Ar,
7.76 (m, 5H, ArH), 7.74 (d, 3JH−H = 8.1 Hz, 1H, ArH), 7.58−7.47 (m,
PC6H5) 132.51 (d, JP−C = 2.4 Hz), 132.33 (d, JP−C = 2.1 Hz), 130.07
3
2
1
5H, ArH), 7.47−7.40 (m, 3H, ArH), 7.30 (t, JH−H = 6.9 Hz, 2H,
(s), 129.63 (dd, JRh−C = 20.9 Hz, JP−C = 10.3 Hz, 1C, Ar, PC6H5),
128.01 (s), 128.00 (s), 127.68 (s), 127.09 (s), 127.02 (s), 126.97 (s),
124.62 (d, JP−C = 2.2 Hz), 124.45 (s), 124.32 (d, JP−C = 2.7 Hz),
114.05 (s), 109.30−108.82 (m, 1C, COD, HCCH), 107.50 (d, J =
3
ArH), 7.20 (d, JH−H = 8.4 Hz, 1H, ArH), 6.97−6.91 (m, 1H, ArH),
3
3
5.91 (dd, JH−P = 13.7 Hz, JH−H = 8.6 Hz, 1H, CHCH(PPh2)Ar),
4.74−4.60 (m, 2H, NCHCH3, CHCH(PPh2)Ar), 3.31 (s, 3H,
4
2
COOCH3), 3.28 (s), 3.19 (s), 3.13 (d, JP−H = 3.0 Hz, 3H,
7.8 Hz), 106.60−106.16 (m, 1C, COD, HCCH), 79.44 (dd, JP−C
NCH3), 3.09 (s, 3H, NCH3), 2.85 (s, 3H, COOCH3), 2.22 (d, 3JH−H
= 6.2 Hz, 3H, NCHCH3), 1.29 (s), 1.26 (s). 13C NMR (126 MHz,
= 10.8 Hz, 1JRh−C = 4.9 Hz, 1C, COD, HCCH), 78.07 (s), 76.47−
2
76.24 (m, 1C, COD, HCCH), 55.89 (d, JP−C = 8.4 Hz, 1C,
3
CDCl3): δ 166.60 (s, 1C, Ar, HCCH−N), 165.95 (d, JP−C = 11.3
CHCH(PPh2)Ar), 53.46 (s, 1C, COOCH3), 52.85 (s, 1C,
COOCH3), 47.75 (s), 47.59 (d, 1JP−C = 25.2 Hz, 1C, CHCH(PPh2)-
Ar), 35.55 (s), 33.81 (s), 31.91 (s), 30.88 (s), 29.34 (s), 29.14 (s),
28.97 (s), 26.03 (s), 22.67 (s), 18.36 (s), 14.10 (s), 9.13 (s), 1.00 (s).
19F NMR (376 MHz, CDCl3): δ −153.06 (s). 31P{1H} NMR (202
MHz, CDCl3): δ 49.69 (d, 1JRh−P = 156.2 Hz). HRMS (+ESI). Calcd
3
Hz, 1C, CO), 158.91 (d, JP−C = 5.4 Hz, 1C, CO), 150.18 (s),
146.55 (s), 142.29 (s), 137.27 (d, 2JP−C = 12.6 Hz, Ar, NCC(H)P),
1
137.02 (s), 135.44 (d, JP−C = 12.0 Hz, Ar, PC6H5), 133.17 (s),
133.07 (s), 132.96 (t, 1C, JP−C = 2.8 Hz, Ar), 131.81 (s), 130.06 (s),
129.96 (d, JP−C = 4.5 Hz, 1C, Ar), 129.01 (d, JP−C = 11.2 Hz, Ar,
PC6H5), 128.91 (d, JP−C = 3.9 Hz), 128.37 (s), 127.11 (d, JP−C = 6.0
Hz), 126.66 (d, JP−C = 7.2 Hz), 126.30 (s), 125.39 (s), 125.18 (s),
124.80 (s), 123.27 (s), 123.17 (s), 122.82 (s), 74.33 (d, JP−C = 2.8
1
−
for C35H37NO4PRh [(M + H − BF4 )+]: m/z 669.1515. Found: m/z
669.1519.
3
[κ2-P,N-Dimethyl 2-(diphenylphosphaneyl)(isoquinolin-1-
ylmethyl)malonate][1,2,5,6-η-(1Z,5Z)-cycloocta-1,5-diene]iridium-
(I) Tetrafluoroborate (14). Yield: crude dark-red solid. 1H NMR (500
2
Hz, 1C, NCH3), 55.02 (d, JP−C = 9.4 Hz, 1C, CHCH(PPh2)Ar),
53.23 (s, 1C, COOCH3), 52.89 (s, 1C, COOCH3), 52.09 (d, 3JP−C
=
2.4 Hz, 1C, NCH3), 47.29 (s, 1C, NCHCH3), 46.08 (d, 1JP−C = 32.3
Hz, 1C, CHCH(PPh2)Ar), 29.69 (s), 24.51 (s, 1C, NCHCH3).
31P{1H} NMR (202 MHz, CDCl3): δ 57.75 (s), 54.85 (s). HRMS
(+ESI). Calcd for C41H41ClN2O8PPd [(M + H)+]: m/z 861.1324.
Found: m/z 861.1301.
MHz, CDCl3): δ 8.49 (d, 3JH−H = 6.5 Hz, 1H, ArH), 8.20 (d, 3JH−H
=
8.7 Hz, 1H, ArH), 8.08 (d, 3JH−H = 6.4 Hz, 1H, ArH), 7.93 (d, 3JH−H
= 8.1 Hz, 1H, ArH), 7.83−7.79 (m, 2H, ArH), 7.72−7.61 (m, 4H,
3
ArH), 7.53 (d, JH−H = 3.9 Hz, 2H, ArH), 7.50−7.43 (m, 4H, ArH),
7.36 (d, 3JH−H = 5.2 Hz, 3H, ArH), 7.16 (s, ArH), 6.97 (d, 3JH−H = 9.2
3
3
Hz, 1H, ArH), 6.09 (dd, JP−H = 12.2 Hz, JH−H = 9.05 Hz, 1H,
CHCH(PPh2)Ar), 5.62 (s, 1H, COD HCCH), 5.36 (s, 1H, COD
ASSOCIATED CONTENT
* Supporting Information
■
2
3
sı
HCCH), 4.56 (dd, JP−H = 14.1 Hz, JH−H = 9.05 Hz, 1H,
CHCH(PPh2)Ar), 4.20 (s, 1H, COD HCCH), 3.82 (s, 1H, COD
HCCH), 3.42 (s), 3.40 (s, 3H, COOCH3), 3.19−3.10 (m), 2.73 (s,
3H, COOCH3), 2.58 (s, 4H, COD CH2), 2.32−2.16 (m, 2H, COD
CH2), 1.82−1.65 (m, 2H, COD CH2). 13C NMR (126 MHz,
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.inorgchem.9b03549.
General information, experimental methods, NMR
spectra, HPLC chromatograms, coordination study,
NBO analysis, XYZ coordinates for the optimized
geometries, and X-ray crystallographic data (PDF)
3
CDCl3): δ 167.03 (s, 1C, Ar, HCCHN), 166.09 (d, JP−C = 10.3
3
Hz, 1C, CO), 165.17 (d, JP−C = 7.4 Hz, 1C, CO), 164.54 (s),
2
142.34 (s), 136.85 (s), 134.22−133.81 (m), 133.62 (d, JP−C = 10.6
J
https://dx.doi.org/10.1021/acs.inorgchem.9b03549
Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
pubs.acs.org/IC
Article
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N. M. Bite angle effects of diphosphines in C−C and C−X bond
forming cross coupling reactions. Chem. Soc. Rev. 2009, 38 (4), 1099−
1118.
Accession Codes
CCDC 1968108, 1968110, and1968111 contain the supple-
mentary crystallographic data for this paper. These data can be
obtained free of charge via www.ccdc.cam.ac.uk/data_request/
cif, or by emailing data_request@ccdc.cam.ac.uk, or by
contacting The Cambridge Crystallographic Data Centre, 12
Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
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AUTHOR INFORMATION
Corresponding Authors
■
Sumod A. Pullarkat − Division of Chemistry and Biological
Chemistry, School of Physical and Mathematical Sciences,
Nanyang Technological University, Singapore 637371
Singapore; orcid.org/0000-0002-4150-2408;
Email: sumod@ntu.edu.sg
Pak-Hing Leung − Division of Chemistry and Biological
Chemistry, School of Physical and Mathematical Sciences,
Nanyang Technological University, Singapore 637371
Singapore; orcid.org/0000-0003-3588-1664;
Email: pakhing@ntu.edu.sg
Authors
́
David Katona − Division of Chemistry and Biological
Chemistry, School of Physical and Mathematical Sciences,
Nanyang Technological University, Singapore 637371
Singapore; orcid.org/0000-0001-7109-3716
Yunpeng Lu − Division of Chemistry and Biological Chemistry,
School of Physical and Mathematical Sciences, Nanyang
Technological University, Singapore 637371 Singapore;
orcid.org/0000-0003-2493-7853
Yongxin Li − Division of Chemistry and Biological Chemistry,
School of Physical and Mathematical Sciences, Nanyang
Technological University, Singapore 637371 Singapore;
orcid.org/0000-0002-7860-3237
́
2006, 17 (4), 560−565. (h) Dutartre, M.; Bayardon, J.; Juge, S.
Applications and stereoselective syntheses of P-chirogenic phosphorus
compounds. Chem. Soc. Rev. 2016, 45 (20), 5771−5794.
(3) (a) Togni, A. Planar-Chiral Ferrocenes: Synthetic Methods and
Applications. Angew. Chem., Int. Ed. Engl. 1996, 35 (13−14), 1475−
1477. (b) Guiry, P. J.; Saunders, C. P. The Development of Bidentate
P, N Ligands for Asymmetric Catalysis. Adv. Synth. Catal. 2004, 346
(5), 497−537. (c) Rokade, B. V.; Guiry, P. J. Axially Chiral P, N-
Ligands: Some Recent Twists and Turns. ACS Catal. 2018, 8 (1),
624−643. (d) Mothes, E.; Sentets, S.; Luquin, M. A.; Mathieu, R.;
Lugan, N.; Lavigne, G. New Insight into the Reactivity of Pyridine-
Functionalized Phosphine Complexes of Ruthenium(II) with Respect
to Olefin Metathesis and Transfer Hydrogenation. Organometallics
2008, 27 (6), 1193−1206. (e) Yang, H.; Gao, H.; Angelici, R. J.
Hydrogenation of Arenes under Mild Conditions Using Rhodium
Pyridylphosphine and Bipyridyl Complexes Tethered to a Silica-
Supported Palladium Heterogeneous Catalyst. Organometallics 2000,
19 (4), 622−629.
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.inorgchem.9b03549
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank Nanyang Technological University for enabling and
supporting our research [Grants M4080454 (NTU) and 2017-
T1-001-175-02 (MOE)] and for a SINGA scholarship
supporting D.K. in his studies. We also thank Li Xi-Rui for
providing the P,C analogue of our complexes for the
coordination study.
(4) (a) Wang, Y.; Guo, H.; Ding, K. Synthesis of novel N, P chiral
ligands for palladium-catalyzed asymmetric allylations: the effect of
binaphthyl backbone on the enantioselectivity. Tetrahedron: Asymme-
try 2000, 11 (20), 4153−4162. (b) Brown, J. M.; Hulmes, D. I.;
Guiry, P. J. Mechanistic and synthetic studies in catalytic allylic
alkylation with palladium complexes of 1-(2-diphenylphosphino-1-
naphthyl)isoquinoline. Tetrahedron 1994, 50 (15), 4493−4506.
(5) (a) Cahard, D.; Gaillard, S.; Renaud, J.-L. Asymmetric
isomerization of allylic alcohols. Tetrahedron Lett. 2015, 56 (45),
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