Synthesis of zwitterionic phosphapalladacycles: Unusual reactivity pattern of six-membered P,N-chelates

Article abstract of DOI:10.1021/acs.organomet.8b00224

A cyclometalation motif has been discovered in the unprecedented reaction of Pd(II) precursors with simple pentane-2,4-diyl based aminoalkyl-phosphines. The unique six-membered zwitterionic palladacycles can easily be synthesized in the presence of 1 molar equiv of oxidant in high yields in a pure form. A comparison between the analogous ligands of different tether lengths revealed that the formation of the zwitterionic palladacycles is the exclusive privilege of the six-membered rings.

Full text of DOI:10.1021/acs.organomet.8b00224

Communication
Cite This: Organometallics XXXX, XXX, XXX−XXX
Synthesis of zwitterionic phosphapalladacycles: unusual reactivity
pattern of six-membered P,N-chelates
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Laszlo Szi-Ferenc, Zsofia Csaszar, Gyorgy Lendvay, Attila Benyei, Szabolcs Balogh, Balazs Nanasi,
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Gergely Farkas,*,† and Jozsef Bakos*
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Department of Organic Chemistry, University of Pannonia, Egyetem u. 10, H-8200 Veszprem, Hungary
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Department of General and Inorganic Chemistry, University of Pannonia, Egyetem u. 10, H-8200 Veszprem, Hungary
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Institute of Materials and Environmental Chemistry, Hungarian Academy of Sciences, Magyar tudosok krt. 2., H-1117 Budapest,
Hungary
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Department of Physical Chemistry, University of Debrecen, Egyetem ter 1, H-4032 Debrecen, Hungary
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NMR Laboratory, University of Pannonia, Egyetem u. 10, H-8200 Veszprem, Hungary
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Egis Pharmaceuticals PLC, Kereszturi ut 30-38., H-1106 Budapest, Hungary
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* Supporting Information
ABSTRACT: A cyclometalation motif has been discovered in the
unprecedented reaction of Pd(II) precursors with simple pentane-
2,4-diyl based aminoalkyl-phosphines. The unique six-membered
zwitterionic palladacycles can easily be synthesized in the presence of
1 molar equiv of oxidant in high yields in a pure form. A comparison
between the analogous ligands of different tether lengths revealed
that the formation of the zwitterionic palladacycles is the exclusive
privilege of the six-membered rings.
eterobidentate ligands containing a combination of
examinations, which can make significant contribution to the
development of highly efficient catalytic systems.5 Moreover,
cyclopalladated complexes have shown extremely high activity
and selectivity in a number of catalytic transformations.6
Surprisingly, cyclometalated complexes of simple alkanediyl-
based P,N ligands are extremely rare.4c Furthermore, to the
best of our knowledge there is no example for the formation of
zwitterionic metallacycles by the sp3 CH activation of a P,N
ligand. However, the synthesis and catalytic application of
zwitterionic metal complexes exhibiting reversed polarity, i.e.
with a formal negative charge on the transition metal, are of
crucial importance.7 They may have unique catalytic features,
as they are able to accelerate oxidative addition owing to the
electron-rich metalate moiety (Figure 1, A−D).3b,8 Zwitter-
ionic palladate type complexes reported recently usually
contain an imidazole (e.g., Figure 1, B−D) or triazole unit
as the positively charged moiety.8,9
Hexclusively phosphorus and nitrogen donor atoms are
widely studied due to their diverse coordination behavior and
exceptional catalytic properties.1 Generally, their unique
catalytic features are attributed to the interplay of the steric
and electronic effects of their P and N donor-atoms at the
metal center. Indeed, the most frequent κ2-P,N coordination
mode of bidentate P,N systems ensures successful stereo-
electronic communication between the substrate and the
catalyst.2 In several cases, however, P,C chelation becomes
preponderant over P,N coordination, e.g., palladacycles can
form due to the rather unusual bonding interactions of
palladium with an ipso carbon atom of an aromatic ring (e.g.,
Figure 1, A, Pd complex of the chiral ligand MAP).3 Of
particular interest are P,N-ligated complexes where the
preliminary CH activation of the ligand at the transition-
metal center results in the formation of P,C-metallacycles.4
These types of reactions offer themselves for mechanistic
Herein we present evidence that the reaction of alkanediyl-
based P,N systems with Pd(II) can lead to the formation of
unique zwitterionic palladate type complexes with a κ2-P,C
coordination. Furthermore, we report on a facile synthetic
methodology for the preparation of these zwitterionic
palladacycles. In order to shed light on the possible CH2
linkage effects in the unusual complex formation reaction, we
extended our studies to P,N ligands of different tether length.
Figure 1. Examples of zwitterionic palladate type complexes
synthesized from MAP (A) and several imidazole derivatives (B−D).
Received: April 13, 2018
© XXXX American Chemical Society
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DOI: 10.1021/acs.organomet.8b00224
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Communication
Chiral ligands 1a−f (Scheme 1) were synthesized in an
optically pure form according to literature methods (1b−d)10
or to its slightly modified variant (1a,e,f).
Table 1. Selected Bond Lengths (Å) and Angles (deg) and
Torsion Angles (deg) of Complexes 2a,b Crystallized from
Acetone
2a
2b
Scheme 1. Synthesis of Alkanediyl-Based P,N Ligands
Pd1−Cl1
Pd1−Cl2
Pd1−P1
Pd1−C4
2.366(3)
2.373(2)
2.222(3)
2.079(8)
1.324(12)
124.2(10)
114.98(9)
120.9(8)
101.6(6)
176.3(9)
174(1)
2.369(5)
2.370(5)
2.219(5)
2.06(2)
1.31(3)
125(2)
108(2)
126(2)
101(1)
174(2)
174(2)
98(2)
C3−N1
C3−N1−C32
C32−N1−C36
C3−N1−C36
Pd1−C4−C3
C2−C3−N1−C36
C4−C3−N1−C32
Pd1−C4−C3−N1
In order to investigate the coordination chemistry of the
novel compounds, 1 equiv of chiral ligand 1a was added to the
suitably labile palladium precursor [Pd(COD)Cl2] in CH2Cl2
as solvent. After 1 h of stirring the reaction mixture turned dark
and palladium black appeared in the solution. Nevertheless, we
were able to isolate a yellow complex (2a, 10% yield) from the
reaction mixture that could be comprehensively characterized
in both the solid and solution phases.
Crystals of 2a suitable for X-ray structure analysis could be
obtained by slow evaporation of the solvent from a dilute
acetone solution of the complex. Strikingly, the X-ray structure
revealed a six-membered palladium chelate with P,Cσ
coordination (Figure 2). In contrast to compounds 1a−d,
94.2(9)
solution of the complex in chloroform that revealed the same
structural characteristics found for the acetone solvate (see the
Supporting Information).
Complex 2a has very low solubility in organic solvents such
as chloroform, dichloromethane, acetone, methanol, and THF.
On the other hand, DMSO-d6 offers complete solubility of the
complex; therefore, it was the solvent of choice for NMR
1
experiments. Compound 2a showed a relatively simple H
NMR spectrum indicative of one species present in solution.
Most importantly, the signal of the expected methyl protons in
the ligand backbone adjacent to the nitrogen did not appear in
the spectrum. Instead, two new diastereotopic methylene
signals were detected at 3.46 and 2.78 ppm, respectively,
indicating the presence of Pd−CH2 protons. The 31P signal of
2a at 42.44 ppm is out of the range (21.6−27.6 ppm) found for
six-membered [Pd(P,N)Cl2] chelates with a pentane-2,4-diyl
backbone.12 Furthermore, on comparison of the 13C{1H} and
13C DEPT NMR spectra a quaternary carbon signal (CN)
appeared at 184.81 ppm with a coupling constant of J(P,C) =
5.6 Hz. Additionally, the infrared spectrum of 2a recorded in a
KBr disk showed a very strong absorption band at 1591 cm−1
indicative of a CN double bond.
The full agreement of both the solid- and solution-phase
studies substantiates that compound 2a is a zwitterionic
iminium palladate type complex containing a Pd−C(sp3)
bond. This suggests that the reaction of the P,N compound
with the metal precursor leads to the dehydrogenation of the
ligand, furnishing two reducing equivalents (Pd(II) to Pd(0)),
and to the coordination of the resulting enamine functionality
in a η1 fashion.14 Although enamines are able to coordinate
through the nitrogen donor15 or through the π system of the
carbon−carbon double bond,16 complex 2a should be
considered as a metalated iminium compound with an M−C
bond.17
Figure 2. X-ray structures of complexes 2a (top) and 2b (bottom)
crystallized from acetone: ORTEP views at the 50% probability level
with a partial numbering scheme. Atom colors: gray, C; green, Cl;
orange, P; violet, N; blue, Pd.
pentane-2,4-diyl based P,N ligands with a secondary amino
functionality form stable six-membered P,N chelates or 12-
membered binuclear cycles with [Pd(COD)Cl2], as was
reported earlier.11,12
The palladium has a slightly distorted square planar
geometry, and the chelate ring is stabilized in a boat
conformation. The relatively long Pd1−C4 distance (2.079
Å), the wide Pd1−C4−C3 angle (101.53°), the pronounced
double-bond character of the N1−C3 bond (1.324 Å), and the
nearly full planarity at the nitrogen center support the iminium
character of the ligand (Table 1). Furthermore, the torsion
angle Pd1−C4−C3−N1 (94.2°) suggests a hyperconjugative
orbital overlap between the π system of the iminium moiety
and the Pd−C4 bond. This interaction might influence the
geometry of the chelate ring and also stabilize the boat
conformation.13 Single crystals of 2a were also obtained from a
To obtain more information on the reaction of ligand 1a and
1
[Pd(COD)Cl2], it was carefully monitored by H and 31P
NMR spectroscopy using CD2Cl2 as solvent. It has been
observed that the formation of the corresponding six-
membered P,N chelate takes place immediately, exhibiting a
single line in the 31P spectrum at 19.81 ppm. This complex
then starts to decompose, and after 1 h a significant amount of
new phosphorus species (ca. 20%) can be found in solution.
This experiment indicates that the six-membered P,N chelate is
an intermediate in the formation of 2a.
B
DOI: 10.1021/acs.organomet.8b00224
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Communication
In order to prevent the formation of Pd(0), the reaction of
ligands 1a−d with [Pd(COD)X2] (X = Cl, Br) was performed
in acetone in the presence of 1 equiv of benzoquinone.18 After
3 h of stirring at reflux temperature, the reaction mixtures were
analyzed by 1H NMR spectroscopy. The crude samples
contained a 1:1:1 mixture of 2a, hydroquinone, and cyclo-
octadiene, indicating the formation of the enamine complex as
a result of the benzoquinone reduction. On the basis of this
facile method, complexes 2a−d and 3a could readily be
prepared as bright yellow solids in high yields (65−80%)
without the formation of Pd black (Scheme 2). In addition, to
our surprise, these complexes are stable in air and they are not
moisture-sensitive.
It is generally accepted that the stability of the chelate
complexes follows the traditional order five- > six- > seven-
membered chelate rings. This order is in good agreement with
our experimental results: (i) ligand 1e forms the expected five-
membered P,N chelate ring, (ii) ligands 1a−d initially also
form six-membered P,N rings that are rapidly converted to P,C
chelates, and (iii) the combined effect of the N atom’s
hemilability and the reduced stability of the seven-membered
chelates results in the formation of a complex mixture in the
case of ligand 1f. It is also important to note that, in addition to
the length of the P−N linker, the steric nature of the
substituents on the nitrogen (tertiary vs secondary amine
group) strongly affects the stability of a chelate ring.20
Recently, it has also been demonstrated that the orientation
of the C−H bond in an optimum position relative to the metal
has a crucial role in CH-activation processes.21
Scheme 2. Synthesis of Zwitterionic Palladium Complexes
2a−d and 3a
Five-membered P,N chelates with secondary and tertiary
amine functionalities as well as six-membered P,N chelates
with secondary amine functionalities11,12 are more stable than
the six-membered P,N chelates formed by ligands 1a−d
bearing a tertiary amine moiety. This indicates that the
formation of reactive free coordination sites is hampered in the
former cases. Although the exact mechanism of the formation
of complexes 2a−d and 3a is unclear, our findings indicate that
(i) a suitably labile P,N-chelate and (ii) a properly tuned tether
ensuring the proximity and the ideal orientation of the
corresponding CH fragment are essential to initiate the
activation.
In summary, we have presented a facile method for the
synthesis of zwitterionic palladacycles. Five novel complexes
were isolated and structurally characterized in the unusual
reaction of [Pd(COD)Cl2] and pentane-2,4-diyl based amino-
alkyl phosphines. By addition of benzoquinone as an oxidant,
2a−d and 3a were readily obtained in high yield (65−80%).
These complexes are stable in air and are not moisture-
sensitive. The variation of the ligands’ tether length as well as a
change in their N substituent led to the conclusion that the
formation of the zwitterionic palladacycles is the exclusive
privilege of the pentane-2,4-diyl based systems with a tertiary
amino functionality. We are currently expanding the scope of
this ligand system in order to gain a closer look into the
mechanism of the activation process as well as to apply the
novel palladacycles in catalytic transformations.
According to 1H, 31P{1H}, and 13C{1H} NMR spectroscopy,
complexes 2a−d and 3a exhibit very similar characteristic
coupling patterns and chemical shifts that are fully consistent
with the zwitterionic iminium-palladate structure: i.e. with the
Pd metal bearing a formal negative charge. The thorough
NMR analysis also substantiated that all five six-membered
chelates have the same boat conformation in solution, as
deduced from the X-ray structure of 2a. Moreover, crystals of
2b suitable for X-ray analysis were grown by slow evaporation
of the acetone solvent (its structure is shown in Figure 2). A
comparison of the selected bond lengths, bond angles, and
torsion angles of 2a,b reveals that their structures are
analogous (Table 1).
In order to shed light on the structural features promoting
the dehydrogenation of the ligand, we compared the
coordination properties of several analogous alkanediyl-based
P,N systems with a tertiary amine functionality. In order to
evaluate the effect of the chelate ring size, directly analogous
alkanediyl-based aminoalkyl phosphines of different tether
length (1e,f) have been synthesized (Scheme 1). Ligand 1e (n
= 0) formed a stable five-membered P,N chelate (4e) that can
be proved by the characteristic chemical shifts and coupling
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.organo-
met.8b00224.
1
patterns in its H NMR spectrum. The yellow solid (4f)
Experimental details and characterization data of the
obtained with ligand 1f (n = 2) revealed nine broad signals in
its 31P NMR spectrum at room temperature in CDCl3,
suggesting the presence of several species in dynamic
equilibrium. These could arise from the different conforma-
tions of chelate species or from multinuclear complexes.19 As
the resonances of phosphorus in the 31P spectrum as well as
new compounds (PDF)
Cartesian coordinates for 2a_ac, 2a_CHCl3 (2a crystal-
lized from acetone and CHCl3, respectively) and 2d
(XYZ)
1
Accession Codes
the H NMR signals of the N-methyl protons in the major
components are remarkably shifted with respect to those of the
free ligand, it is reasonable to assume that both the N and P
atoms are involved in coordination. Nevertheless, during
complex formation no palladium black could be observed.
Furthermore, complexes 4e,f can be stored for days in
dichloromethane without any change in their composition.
CCDC 1834437−1834439 contain the supplementary crys-
tallographic 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.
C
DOI: 10.1021/acs.organomet.8b00224
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Communication
(13) Sriram, M.; Zhu, Y.; Camp, A. M.; Day, C. S.; Jones, A. C.
Organometallics 2014, 33, 4157−4164.
AUTHOR INFORMATION
Corresponding Authors
*E-mail for G.F.: gerifarkas@almos.uni-pannon.hu.
*E-mail for J.B.: bakos@almos.uni-pannon.hu.
■
(14) (a) Muzart, J. J. Mol. Catal. A: Chem. 2009, 308, 15−24.
(b) McCrindle, R.; Ferguson, G.; Arsenault, G. J.; McAlees, A. J. J.
Chem. Soc., Chem. Commun. 1983, 571−572. (c) Gamage, S. N.;
Morris, R. H.; Rettig, S. J.; James, B. R. J. Organomet. Chem. 1986,
309, C59−C62.
ORCID
Gergely Farkas: 0000-0002-4119-0918
Jozsef Bakos: 0000-0003-3502-6473
Notes
(15) Mazzarella, L.; Pellechia, C.; Mattia, C. A.; De Felice, V.; Puliti,
R. J. Coord. Chem. 1986, 14, 191−200.
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(16) (a) Ponti, P. P.; Baldwin, J. C.; Kaska, W. C. Inorg. Chem. 1979,
18, 873−875. (b) De Renzi, A.; Ganis, P.; Panunzi, A.; Vitagliano, A.;
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The authors declare no competing financial interest.
ACKNOWLEDGMENTS
(17) (a) Balacco, G.; Natile, G. J. Chem. Soc., Dalton Trans. 1990,
3021−3024. (b) Doran, S. L.; Brown, D. B.; Allen, C. W. J.
Organomet. Chem. 1988, 340, 111−118.
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We thank Mr. Bela Edes for skillful assistance in analytical
measurements and synthetic experiments. The research was
supported by the “National Excellence Program” in the
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(18) Grennberg, H.; Gogoll, A.; Backvall, J.-E. Organometallics 1993,
12, 1790−1793.
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framework of the projects TAMOP-4.2.4.A/2-11/1-2012-
(19) Romeo, R.; Scolaro, L. M.; Plutino, M. R.; Romeo, A.; Nicolo’,
F.; Del Zotto, A. Eur. J. Inorg. Chem. 2002, 2002, 629−638.
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Parsons, S.; Parkin, A.; Sadler, P. J. J. Chem. Soc., Dalton Trans. 2001,
1306−1318.
0001, VEKOP-2.3.2-16-2017-00013, and EFOP-3.6.1-16-
2016-00015 and by the Hungarian Scientific Research Fund
(OTKA K115539). The research was also supported by the
EU and cofinanced by the European Regional Development
Fund under the projects GINOP-2.3.2-15-2016-00008 and
GINOP-2.3.3-15-2016-00004.
(21) Calleja, J.; Pla, D.; Gorman, T. W.; Domingo, V.; Haffemayer,
B.; Gaunt, M. Nat. Chem. 2015, 7, 1009−1016.
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DOI: 10.1021/acs.organomet.8b00224
Organometallics XXXX, XXX, XXX−XXX