Ferrocenyl (P,N)-diphosphines incorporating pyrrolyl, imidazolyl or benzazaphospholyl moieties: Synthesis, coordination to group 10 metals and performances in palladium-catalyzed arylation reactions

Article abstract of DOI:10.1016/j.jorganchem.2013.03.025

Three novel symmetrical ferrocenyl diphosphines with tertiary phosphorus atoms holding respectively nitrogen-containing heterocyclic derivatives of pyrrole, imidazole and benzazaphosphole were synthesized and characterized. Up to now, integration of heteroaromatic fragments, or more generally hetero-cycles, as substituents on the tertiary phosphines of symmetrical ferrocenyl diphosphines has been limited to the furyl motif. Their coordination to palladium and platinum group 10 transition metals was exemplified, and analyzed using single crystal X-ray diffraction. The performances obtained in palladium-catalyzed copper-free Sonogashira and Suzuki cross-coupling reactions using bromoarenes and chloroarenes are reported for the most efficient system. The unprecedented combination of a tert-butyl group and of an imidazolyl motif on the phosphorus atoms led to an air-stable ferrocenyl diphosphine, which allowed in combination with 0.1-0.2 mol% of palladium to generate catalytic systems able to couple some activated chloroarenes and most of the bromoarenes examined.

Full text of DOI:10.1016/j.jorganchem.2013.03.025

Accepted Manuscript
Ferrocenyl (P,N)-diphosphines incorporating pyrrolyl, imidazolyl or
benzazaphospholyl moieties: synthesis, coordination to group 10 metals and
performances in palladium-catalyzed arylation reactions
Fatima Allouch, Nikolay V. Vologdin, Hé lè ne Cattey, Nadine Pirio, Daoud Naoufal,
Ali Kanj, Radomyr V. Smaliy, Aleksandr Savateev, Anatoly Marchenko, Anastasia
Hurieva, Heorgii Koidan, Aleksandr N. Kostyuk, Jean-Cyrille Hierso
PII:
S0022-328X(13)00210-6
10.1016/j.jorganchem.2013.03.025
JOM 17935
DOI:
Reference:
To appear in: Journal of Organometallic Chemistry
Received Date: 30 January 2013
Revised Date: 10 March 2013
Accepted Date: 13 March 2013
Please cite this article as: F. Allouch, N.V. Vologdin, H. Cattey, N. Pirio, D. Naoufal, A. Kanj, R.V.
Smaliy, A. Savateev, A. Marchenko, A. Hurieva, H. Koidan, A.N. Kostyuk, J.-C. Hierso, Ferrocenyl (P,N)-
diphosphines incorporating pyrrolyl, imidazolyl or benzazaphospholyl moieties: synthesis, coordination to
group 10 metals and performances in palladium-catalyzed arylation reactions, Journal of Organometallic
Chemistry (2013), doi: 10.1016/j.jorganchem.2013.03.025.
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Graphical Abstract

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Highlights
♦ Synthesis of the first ferrocenyl diphosphines holding N-containing heterocyclic motifs ♦ X-ray
characterization of their palladium and platinum dichloride complexes ♦ Palladium-catalyzed copper-
free Sonogashira and Suzuki cross-coupling reactions using bromoarenes and chloroarenes

ACCEPTED MANUSCRIPT
Ferrocenyl (P,N)-diphosphines incorporating pyrrolyl, imidazolyl or
benzazaphospholyl moieties: synthesis, coordination to group 10
metals and performances in palladium-catalyzed arylation reactions
Fatima Alloucha,b, Nikolay V. Vologdina, Hélène Catteya, Nadine Pirioa,*, Daoud Naoufalb, Ali Kanjb,
Radomyr V. Smaliyc, Aleksandr Savateevc, Anatoly Marchenkoc, Anastasia Hurievac, Heorgii Koidanc,
Aleksandr N. Kostyukc,* and Jean-Cyrille Hiersoa,*
a Université de Bourgogne, Institut de Chimie Moléculaire de l’Université de Bourgogne, UMR-CNRS 6302,
9 avenue Alain Savary, 21078 Dijon, France
b Université Libanaise, Laboratoire de Chimie de Coordination Inorganique et Organométallique,
Campus Universitaire R. Hariri -Faculté des Sciences, Beyrouth - Hadath, Lebanon
c Institute of Organic Chemistry, National Academy of Sciences of Ukraine,
Murmanska St. 5, 02094 Kiev, Ukraine
Corresponding authors:
Tél: (+33)3 80396107 – Fax: (+33)3 80393682 (J.-C.H)
jean-cyrille.hierso@u-bourgogne.fr
Nadine.pirio@u-bourgogne.fr
a.kostyuk@enamine.net
March 10th 2013
REVISED VERSION
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Abstract
Three novel symmetrical ferrocenyl diphosphines with tertiary phosphorus atoms holding
respectively nitrogen-containing heterocyclic derivatives of pyrrole, imidazole and benzazaphosphole
were synthesized and characterized. Up to now, integration of heteroaromatic fragments, or more
generally heterocycles, as substituents on the tertiary phosphines of symmetrical ferrocenyl
diphosphines has been limited to the furyl motif. Their coordination to palladium and platinum group
10 transition metals was exemplified, and analyzed using single crystals X-ray diffraction. The
performances obtained in palladium-catalyzed copper-free Sonogashira and Suzuki cross-coupling
reactions using bromoarenes and chloroarenes are reported for the most efficient system. The
unprecedented combination of a tert-butyl group and of an imidazolyl motif on the phosphorus
atoms led to an air-stable ferrocenyl diphosphine, which allowed in combination with 0.1 to 0.2
mol% of palladium to generate catalytic systems able to couple some activated chloroarenes and
most of the bromoarenes examined.
Keywords: Ferrocene • Diphosphine • Heteroaromatic • Palladium • X-ray structure • Cross-
coupling
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1. Introduction
The discovery of ferrocene and the elucidation of its “sandwich” structure initiated an era of
development for organometallic chemistry in the history of chemical science [1]. The selective
functionalization of the ferrocene backbone with donor atoms (P, N, S, Se, etc.) has generated many
chiral and achiral molecules which are, among other applications, much beneficial as stabilizing
ligands for transition metals. Such species have shown for instance important applications in
palladium-catalyzed organic synthesis reactions [2]. Based on the impetus provided by the
applications of the simple diphosphine 1,1'-bis(diphenylphosphino)ferrocene (dppf), investigations
directed towards the synthesis of new ferrocene-based ligands —sterically and/or electronically
modified either at the ferrocenyl backbone or at the donor atoms— are of fundamental and applied
interest [2a]. Accordingly, a variety of dppf derivatives has been designed and is available for
applications in homogeneous metal catalysis (Scheme 1) [3]. Nevertheless, despite the various
symmetrical ferrocenyl diphosphine incorporating tertiary phosphines produced and employed as
ligands for transition metals, such species are mostly restricted to phosphorus donor atoms
substituted with fairly classical aryl and alkyl moieties, as shown in Scheme 1 (left).
Scheme 1. Typical symmetrical ferrocenyl diphosphine employed as ligand in palladium-catalysis.
To the best of our knowledge, the incorporation of heteroaromatic fragments, or more generally
heterocycles, as substituents on the tertiary phosphines of symmetrical ferrocenyl diphosphines has
been limited to the furyl motif, which though led to unique catalytic performances [4,5]. For
instance, the ligand 1,1'-bis[di(5-methyl-2-furyl)phosphino]ferrocene (1 in Scheme 1, right) reported
by some of us was found to promote nucleophilic allylic amination of allylic acetate at room
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temperature with excellent turnover frequencies [6]. In the presence of 0.01 mol% [Pd/1] catalyst
the coupling of aniline with allyl acetate occurred at a turnover frequency TOF above 10,000 h−1
leading to a complete conversion of substrates with 96% selectivity in monoallylamine. Under the
same conditions, dppf as the ligand gave a conversion of 60% after 40 h at room temperature, TOF
150 h−1. Combined with palladium, diphosphine 1 has also provided an efficient and selective
catalytic system for the Heck reaction using hydroxylated styrenes and bromoarenes in a
straightforward stilbenes synthesis which circumvents the use of protective groups [7]. The
combination in 1 of the steric hindrance from ferrocenyl backbone and of strong electron-
withdrawing effect from the four furyl substituents on phosphorus donors clearly outperforms the
existence of only one of these features in the parent ligands dppf and P(2-furyl)3 tested in the same
reaction [7]. With the view to further study the features and catalytic performances of ferrocenyl
diphosphines incorporating phosphorus atoms substituted with heteroaromatic motifs, in the
present work the novel ferrocenyl diphosphines 2, 3 and 4 (Scheme 2), bearing respectively nitrogen-
containing heterocycles of pyrrole, imidazole and benzazaphosphole type were synthesized and
characterized. Their coordination to palladium and platinum group 10 transition metals was
exemplified, and the performances obtained in palladium-catalyzed copper-free Sonogashira and
Suzuki cross-coupling reactions using bromoarenes and chloroarenes are reported.
2. Results and discussion
One of the remaining challenges offered by palladium-catalyzed cross-coupling arylation reactions
is the activation of more reluctant carbon-chloride bonds with robust non air-sensitive ligands [8].
Metal-catalyzed activation of the C–Cl bond of organic chlorides can be promoted by the presence of
electron donating fragments in the vicinity of the metal. We thus envisioned that in addition to the
heterocyclic substituent attached to phosphorus donor atoms, the introduction of a bulky electron-
rich alkyl group, such as tert-butyl, on this phosphine group might be helpful for promoting oxidative
addition of C−Cl bond onto palladium [8]. On the other hand, due to the predictable heterocyclic π-
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delocalization offered to phosphorus lone pairs, we anticipated for the resulting ferrocenyl
diphosphines (2 and 3 in Scheme 2) a weaker basicity and thus a better stability toward atmospheric
oxidation than the one observed for classical trialkyl phosphines such as P(t-Bu)3. It is noteworthy
that such mixed tertiary phosphines incorporating in addition to the metallocenic fragment both an
alkyl and N-heterocyclic groups are unprecedented. Pioneering works on 1,1'-
bis[phosphino]ferrocene compounds Fe(C5H4PR1PR2)2 with two different substituents at the
phosphorus atom have been limited to aryl/alkyl groups: R1 = Ph/R2 = t-Bu [9], R1= Ph/R2=i-Pr [10], and
R1 = Ph/R2 = Me [11]. The simple synthetic pathways we choose does not involve any asymmetric
induction step, therefore the resulting ligands were expected to be obtained as diastereomeric
mixtures (rac/meso due to asymmetric phosphorus), which may eventually be resolved by fractional
crystallization [11]. Finally, we were also interested in introducing a tertiary P-heterocyclic
substituent on ferrocene backbone, and a novel heterophosphole of benzazaphosphole type was
chosen (4 in Scheme 2) [12].
Scheme 2. Ferrocenyl (P,N)-diphosphines 2, 3 and 4, P-substituted with N-heterocycles.
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2.1. Synthesis and characterization of ferrocenyl diphosphines incorporating N-heterocyclic moieties
The synthesis of ferrocenyl diphosphine was conducted by dilithiation of the ferrocene followed
by quenching with halophosphines ClPR2 (Scheme 2) as early reported by Bishop et al. to yield the
1,1'-bis(diphenylphosphino)ferrocene (dppf) [13]. The chlorophosphine precursors A, B, and C of
ClPR2 type were synthesized following the routes depicted in Scheme 3.
E
E
E
1) n-BuLi
PCl3
NMe2
Cl
P
P
N
R
2)
N
R
N
R
NMe2
t-Bu
Cl
t-Bu
P
(A), E = CH, R = t-Bu
(B), E = N, R = Me
t-Bu
Me
PCl3
N
P
-Me2NH
N
P
NMe2
NMe2
N
P
Me
Me2N
Me2N
Me
NMe2
Cl
NMe2
(C)
Scheme 3. Synthesis of pyrrolyl, imidazolyl and benzazaphospholyl chlorophosphines A, B, and C.
The ferrocenyl diphosphines 2-4 were isolated by crystallization as mixture of diastereomers with
various diastereomeric excess depending on the species and the conditions, as summarized in Table
1. Our success in further improving diastereomeric excess by fractional crystallization was limited
since co-crystallization systematically occurred despite our efforts. However, this was not considered
as detrimental for our subsequent synthetic applications since we focused on testing achiral
palladium-catalyzed cross-coupling reactions. After diastereomeric separation further resolution of
the chiral species (rac) we formed would be of interest to develop asymmetric cross-coupling
reactions. The chemical shifts δ for the phosphorus atoms of 2-4 were found ranging between −15
and −30 ppm [14], the imidazolyl group contributes to a greater shielding of phosphorus signal (−29.0
ppm) compared to the pyrrolyl group (−15.6 ppm). A 31P NMR δ chemical shift around −25 ppm was
found for the diastereomeric forms of compound 4 holding benzazaphospholyl groups.
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Table 1.
Ratio of diastereomers 2-4 from fractional crystallization and corresponding 31P NMR shifts.
δ 31P NMR D1/D2
Diphosphines Crystallization
Total
yield
Cryst. 1
Crystallization
crop 2 –
Enrichment
D1:D2
Total
yield
Cryst. 2
crop 1 –
Enrichment
D1:D2
(ppm)
2
3
4
90:10
62:38
80:20
55%
52%
33%
/
/
−15.6 / −15.1a
−28.8 / −29.0b
−24.9 / −23.3b
22:78
58:42
20%
39%
Solvent: aCDCl3, bC6D6.
2.2. Coordination of ferrocenyl (P,N)-diphosphines to group 10 metals
Due to the presence of several nitrogen and phosphorus donors on the ferrocenyl ligands 2-4 we
were eager to check whether phosphorus coordination is prevailing, or if the presence of nitrogen
atoms may perturb the Pd/P soft-soft Pearson acid/base preference. The complex [PdCl2(2)] in which
palladium is embedded into a classical chelating coordination to phosphorus atoms (Fig. 1), was
obtained from reacting the dimeric precursor [Pd(II)Cl2(η3-C3H5)] with diphosphine 2 (diastereomer
mixture 90:10) in dichloromethane. After evaporation and treating the residue with diethylether, 31P
1
and H NMR indicated that only a single diastereomer was obtained in a final yield of 58%, as
evidenced by a single phosphorous signal at 32.45 ppm, and from one set of signal for H-Cp at 4.12,
4.19, 4.27 and 4.30 ppm. Methyl protons from t-Bu groups on phosphorus atoms are detected as a
doublet centered at 1.31 ppm (2JPH= 15.9 Hz), N-methyl groups are found at 1.60 ppm and pyrrolyl
protons gave signals at 6.41, 6.94 and 8.1 ppm. Single crystals suitable for X-ray diffractions studies
allowed us to determine the absolute configuration of the rac-[PdCl2(2)] complex isolated (Ortep in
Fig. 1). We consequently assumed that the diasteromeric phosphine crop used for coordination to
palladium was (rac)-90:(meso)-10.
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The molecular structure of rac-[PdCl2(2)] is of non-crystallographic C2 symmetry with a distortion
of the metallocene backbone. The sandwich conformation is staggered with a torsion angle P1-Ct1-
Ct2-P2 of –40.67(8) ° (Ct1 and Ct2 are the centroids of Cp rings). The conformation of the phosphine
groups places the t-Bu groups roughly perpendicular to the Cp rings in exo position relative to
ferrocene backbone, pyrrolyl groups are in endo position. The palladium center is in a distorted
square planar environment with a P1-Pd-P2 bite angle of 101.93(3) ° and a Cl1-Pd-Cl2 angle of
86.18(3) °.
Fig. 1 Molecular structure of R,R-[PdCl2(2)] (S,S-enantiomer is equally present in the unit cell),
hydrogen atoms and solvent molecules are omitted for clarity. Selected bond lengths (Å) and angles
(°): Pd−P1 2.3135(8), Pd−P2 2.3100(8), Pd−Cl1 2.3529(8), Pd−Cl2 2.3296(9), P1-Pd-P2 101.93(3), P1-
Pd-Cl1 169.53(3), P2-Pd-Cl2 173.50(3), Cl1-Pd-Cl2 86.18(3), Fe−Ct1 1.631(3), Fe−Ct2 1.632(3); Ct1-Fe-
Ct2 175.97(16), P1-Ct1-Ct2-P2 –40.67(8).
The complex [PdCl2(3)] (Fig. 2) was obtained from reacting [PdCl2(PhCN)2] in stoichiometric
amount with diphosphine 3 (diastereomer mixture 62:38) in dichloromethane. In the crude mixture
this ratio was conserved. After evaporation and treating the residue with diethyl ether, the complex
was crystallized and diastereomeric resolution led to isolate rac-[PdCl2(3)] in 45% yield, with a
1
corresponding δ 31P NMR at 22.7 ppm and H NMR δ H-Cp at 3.91, 4.16, 4.38 and 4.81 ppm. We
easily deduced that the original diasteromeric phosphine crop used for coordination to palladium
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was (rac)-62:(meso)-38 since the obtained yield (45% ) of the complex is more than 38 %. (The X-ray
structure characterization (see Ortep in Fig. 2) revealed features comparable to rac-[PdCl2(2)].
However, this complex presents a torsion angle P1-Ct1-Ct2-P2 equal to –28.96(9) °, and in contrast to
rac-[PdCl2(2)], the imidazolyl groups adopt two different orientations with respect to the ferrocene
backbone (Pd…C18 = 3.933 (4) and Pd…C26 = 3.605 (4)) and hence the C2 axis is lost in this solid state
conformation.
Fig. 2 Molecular structure of R,R-[PdCl2(3)] (S,S-enantiomer is equally present in the unit cell),
hydrogen atoms and solvent molecules are omitted for clarity. Selected bond lengths (Å) and angles
(°): Pd−P1 2.3190(9), Pd−P2 2.3100(9), Pd−Cl1 2.3547(9), Pd−Cl2 2.3425(9), P1-Pd-P2 98.62(3), P1-Pd-
Cl1 83.39(3), P2-Pd-Cl2 91.92(3), Cl1-Pd-Cl2 86.35(3), Fe−Ct1 1.637(3), Fe−Ct2 1.633(3); Ct1-Fe-
Ct2 177.34(17), P1-Ct1-Ct2-P2 –28.96(9).
The synthesis of the related rac-[PtCl2(3)] was also easily achieved from reacting in stoichiometric
amount PtCl2(PhCN)2 with diphosphine 3. Crystals suitable for X-Ray diffraction were isolated in 61%
yields from a pentane/dichloromethane mixture. 31P NMR in CD2Cl2 indicates a signal at 5.2 ppm with
1
a JPtP of 3604 Hz typical of a cis-coordination of chelating phosphorus atoms with chloride atoms in
trans position [15]. The complex rac-[PtCl2(3)] is isostructural with rac-[PdCl2(3)] complex with no C2
axis in this solid state conformation (for instance Pt…C18 = 3.638 (4) and Pt…C26 = 4.035 (4)).
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Fig. 3 Molecular structure of R,R-[PtCl2(3)] (S,S-enantiomer is equally present in the unit cell),
hydrogen atoms and solvent molecules are omitted for clarity. Selected bond lengths (Å) and angles
(°): Pt−P1 2.2788(12), Pt−P2 2.2863(13), Pt−Cl1 2.3486(13), Pt−Cl2 2.3598(12), P1-Pt-P2 98.74(5), P1-
Pt-Cl1 92.65(4), P2-Pt-Cl2 84.13(4), Cl1-Pt-Cl2 84.63(4), Fe−Ct1 1.631(4) , Fe−Ct2 1.637(4); Ct1-Fe-
Ct2 177.1(2), P1-Ct1-Ct2-P2 –28.84(12).
The complex [PdCl2(4)] (Fig. 4) was obtained from reacting [PdCl2(PhCN)2] in stoichiometric
amount with diphosphine 4 (Scheme 2) from a diastereomer mixture 58:42 in dichloromethane. In
the crude mixture this ratio was conserved with the presence of two phosphorus signals in NMR at
28.95 and 32.92 ppm. Crystals were obtained by slow diffusion of pentane in a solution of the
complex in CHCl3 (87% yield, major isomer 58%). This complex presents a pseudo-symetry plane, the
[PdCl2(4)] molecule structure conformation is meso. The sandwich conformation is staggered with a
torsion angle P1-Ct1-Ct2-P2 equal to –21.3(4). The conformation of the phosphorus atoms places the
planar benzazaphospholyl groups roughly perpendicular to the Cp rings in exo position relative to
ferrocene backbone.
Finally, the synthesis of the platinum complex [PtCl2(4)] was also achieved in very good yield (86%)
from dichloro(1,5-cyclooctadiene) platinum(II) as a mixture of diastereomers (major isomer 58%).
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The phosphorous 31P NMR signal from the major isomer signal is found at 8.14 ppm with a high 1JPtP
=
1
3626 Hz constant (minor isomer 10.20 ppm, JPtP = 3622 Hz), attesting for a cis-coordination of
chelating phosphorus atoms.
Pd
Fig. 4 Molecular structure of R,S-[PdCl2(4)], hydrogen atoms and solvent molecules are omitted for
clarity. Selected bond lengths (Å) and angles (°): Pd−P1 2.26(2), Pd−P2 2.2443(9), Pd−Cl1 2.348(1),
Pd−Cl2 2.340(1), P1-Pd-P2 96.8(5), P1-Pd-Cl1 84.2(5), P2-Pd-Cl2 86.52(4), Cl1-Pd-Cl2 92.22(3), Fe−Ct1
1.650(4) , Fe−Ct2 1.643(4); Ct1-Fe-Ct2 179.2(2), P1-Ct1-Ct2-P2 –21.3(4).
2.3. Cross-coupling reactions catalyzed by palladium/ferrocenyl diphosphine complexes
In order to assess the influence of the novel ferrocenyl (P,N)-diphosphines bearing heterocyclic
groups on palladium-catalyzed cross-coupling reactions we started our investigations with the
arylation of terminal alkynes by using in situ formed precatalyst [PdCl2(3)] under copper-free
conditions. Among palladium-catalyzed C−C bond formation this reaction is known to be significantly
ligand-dependent [16], and rather challenging. The palladium-catalyzed arylation of terminal alkynes
in the absence of copper render the activation of alkynes even more difficult (since no Cu→Pd
transmetalation step of acetylide occurs), but is preferable to obviate the formation of undesired
alkyne dimerization side-products [17]. In preliminary screening experiments the coupling of phenyl
acetylene with aryl iodides was easily achieved in 20 h in the presence of 4 mol% of catalyst (Table 2,
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entries 1 and 2). Interestingly, when 3-bromo-1-iodobenzene is used, thus in the presence of both a
bromo and an iodo function on the substrate, the cross-coupling selectively occurred at the more
reactive C−I bond. We then examined the coupling reactions using aryl bromide substrates in the
presence of a lower catalyst loading at 1 mol%. Bromobenzene and 4-trifluorobromobenzene were
quantitatively coupled within 20 h (Table 2, entries 3 and 4). Under the same experimental
conditions the coupling of 4-bromoacetophenone was found less effective with a yield of 77% after
20 h (entry 5).
Table 2.
Palladium-catalyzed copper-free arylation of phenyl acetylene from aryl halides using [PdCl2(3)].a
entry
1
aryl halide
product
Pd/3
loading (%)
yieldb
(%)
4
4
>95
>95
2
3
4
5
1
1
1
>95
>95
77
6
7
4
1
1
1
44
>95
29
8
9
<5
a Conditions: catalyst [PdCl2(PhCN)2]/3 (0.01 to 0.04 mmol) , aryl halide (1 mmol), phenyl acetylene (2
mmol), Cs2CO3 (2 mmol), DMF, 100 °C, 20 h under Ar. b Average of two or more runs determined by
GC and GC-MS (±5%).
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The electron-rich 4-bromoanisole was converted in a moderate 44% yield by using 4 mol% of catalyst
(entry 6). The cross-coupling of aryl chlorides was also tested with chlorobenzene and substrates
holding electron-donating or electron-withdrawing groups in para position. The non-substituted
chlorobenzene was efficiently coupled (yield >95%, entry 7), while the functionalization of aryl
chloride significantly hampers the reactivity of these species by using [PdCl2(3)]. The presence of one
donating t-Bu group on the phosphorus atoms is apparently insufficient to ensure very fast oxidative
addition of electron-rich aryl halides on palladium under our conditions. This might possibly be due
to the electron-withdrawing effect of the imidazolyl group. Nevertheless, we tested the arylation of
chlorobenzene following Suzuki-Miyaura reaction, this cross-coupling reaction being known to be
generally less-demanding than copper-free arylation of alkynes due to preformed organometallic
reactive nucleophile.
Various aryl chlorides were tested and the optimization of catalyst loading at 0.2 mol% was found
appropriate for such couplings. As reported in Table 3, under these conditions the coupling of
chlorobenzene was efficiently achieved (entry 1). In contrast to alkyne arylation reactions,
substitution on aryl chlorides did not completely inhibit the coupling. For instance, electron-deficient
4-trifluoromethylchlorobenzene was converted in 82% yield (entry 2). Conversely, the presence of
the electron-donating methoxy group was a severe limitation when positioned on the aryl chloride
with only 7% yield of coupling product (entry 3). The coupling of 4-metoxyphenyl boronic acid to
chlorobenzene was also tested but was unsuccessful (entry 4). In contrast, 4-cyano-4'-
methoxybiphenyl was obtained in satisfactory 72% yield under these low palladium loading
conditions at 100 °C (entry 5).
These results in phenyl arylation from aryl chlorides position fairly favorably ferrocenyl
diphosphine 3 among the numerous auxiliary ligands used for Suzuki cross-coupling, in particular if is
considered that this phosphine can be kept under air [18].
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Table 3.
Palladium-catalyzed arylation of aryl boronic acids from aryl chlorides.a
entry
1
aryl chloride
product
Pd/L
loading (%)
0.2
yield b
(%)
>95
2
3
4
5
6
0.2
0.2
0.2
0.2
0.2
82
7
<5
76
100
7
8
0.2
0.2
26
26
9
0.2
<5
10
0.2%
>95c
11
0.2%
6c
a Conditions: catalyst [PdCl2(PhCN)2]/3 (0.002 mmol) , aryl halide (1 mmol), aryl boronic acid (2
mmol), K2CO3 (2 mmol), DMF, 100 °C, 20 h under Ar. b Average of two or more runs determined by
GC, GC-MS and NMR (±5%). c Catalyst [PdCl2(PhCN)2]/4 (0.002 mmol).
Such type of cross-coupling reactions has been much less studied with heteroaryl chlorides. Due to
the usual prevalence of phosphorus coordination over nitrogen coordination in group 10 metal
complexes, as confirmed from our X-ray structure characterizations, we hypothesized that
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heteroaromatic substrates containing nitrogen or other donor atoms should not bring undesired
coordinative perturbation to our catalytic systems. The results of our investigation of the Suzuki
coupling reaction of a selection of heteroaromatic substrates are reported in Table 3, entries 6 to 9.
The quantitative coupling of 3-bromopyridine indeed proceeded easily. However, the coupling of
chloroheteroarenes was found more difficult and only moderate conversions of 3-cyano-2-
chloropyridine (26% yield) and 6-methoxy-3-chloropyridazine (26% yield) were obtained in 20 h. The
five membered-ring 2-chlorothiazole was found poorly reactive (entry 9). We also tested the coupling
of chloroarenes with [Pd/4] (see for instance Table 3, entries 10 and 11) but we obtained either
similar or inferior performances. Clearly, the robustness and steric and electronic features of these
ligands are demonstrated to be useful in homogeneous catalysis but activating organic chlorides
remains a limitation.
3. Summary and conclusions
Three novel ferrocenyl (P,N)-diphosphines 2, 3 and 4 incorporating phosphorus atoms substituted
with N-heteroaromatic pyrrolyl, imidazolyl or benzazaphospholyl motifs have been synthesized and
characterized, completing the previously reported two sole examples of symmetrical ferrocenyl
diphosphines holding heteroaromatic groups (furyl heterocycles). The group 10 coordination
complexes formed from coordination of these diphosphines display a classical chelating (P,P)-
behavior, even though two to four accessible nitrogen donors are present on the modified
ferrocenes. An apparent preference for crystallization of the rac-diastereomer has been observed in
some cases. In the solid state the diphosphines are not air-sensitive (no phosphine oxide formed
after several months under air) despite the presence on the phosphorus atoms of an electron-rich t-
Bu group. In the palladium-catalyzed arylation of terminal alkynes and phenyl boronic acids the
influence of ligand 3 has been specifically examined showing that arene and heteroarene bromides
are suitable substrates, while only activated chlorides can be efficiently employed in the presence of
0.2 to 1.0 mol% catalyst. Further works aiming at exploring the properties of these ligands might
15

ACCEPTED MANUSCRIPT
address copper coordination chemistry possibly via nitrogen atoms and related Ullmann catalysis as
arylation reactions.
4. Experimental
All procedures with air and moisture sensitive compounds were performed under an atmosphere
of dry argon in oven or flame-dried glassware. Solvents were purified and dried by standard
1
methods. H spectra were recorded on a Bruker Avance DRX 500 (500.13 MHz) or Varian VXR-300
(299.94 MHz) spectrometer. 13C NMR spectra were recorded on a Bruker Avance DRX 500 (125.75
MHz) spectrometer. 31P NMR spectra were recorded on a Varian VXR-300 (80.95 MHz) spectrometer.
1
Chemical shifts (δ) are reported in parts per million downfield relative to internal TMS (for H, 13C)
and external 85% H3PO4 (for 31P). Coupling constants are reported in hertz. Chromatography was
performed on silica gel Gerudan SI60. Elemental analyses were performed at the “Micro analytical
laboratory of the Institute of Organic Chemistry of the National Academy of Sciences of Ukraine”.
Alternatively, the identity and purity (≥95%) of the compounds were established at the “Plateforme
d’Analyses Chimiques et de Synthèse Moléculaire de l’Université de Bourgogne” using high-resolution
mass spectrometry and multinuclear NMR. The exact mass of the complexes was obtained on a
Bruker micrOTOF-Q ESI-MS. 1H (300.13, 500.13, or 600.13MHz), 13C (75.5, 125.8, or 150.9 MHz), and
31P (121.5, 202.5, or 242.9 MHz) NMR spectra were recorded on a Bruker 300 Avance, a Bruker 500
Avance DRX spectrometer, or on a Bruker 600 Avance II spectrometer at ICMUB. X-ray analysis of
compounds were conducted with intensity data collected on a Bruker-Nonius APEX II diffractometer
equipped with an Oxford Cryosystem low-temperature device operating at 115 K. 1-tert-butylpyrrol-
3-ylphosphorous dichloride [19] and dimethylaminophosphole [20] were synthesized following
literature procedures. Coupling product yields were determined by GC, GC-MS and NMR. The rac or
meso configuration was determined when possible after selective crystallization of a palladium
complex from a single diastereomer, determination of the yield, X-ray diffraction and 31P/1H NMR of
the crystals.
4.1. Synthesis of chlorophosphines (A), (B) and (C)
4.1.1. tert-Butylchloro(1-tert-butyl)-1H-pyrrol-3-ylphosphine, A
To a solution of 14.3 g of 1-tert-butylpyrrol-3-ylphosphorous dichloride (14.3 g, 63.8 mmol) in 60
mL of diethyl ether was added dropwise over 30 min under dry argon tert-butylmagnesium chloride
(46 mL in 1.6 M solution in diethyl ether, 0.0736 mol). The mixture was then heated under reflux for
1 hour. After the solvent was removed in vacuum, and 200 mL of dry benzene was added to the
16

ACCEPTED MANUSCRIPT
residue (alternatively less toxic toluene can be used in 300 mL), and insoluble parts were filtered,
washed with benzene (2x30 mL). The filtrate was concentrated under vacuum and distilled. The crop
boiling between 79 and 90 °C at 0.05 mmHg was collected. A second distillation between 83 and 85
°C at 0.05 mmHg, gives the phosphine A as a colorless oil in 34% yield (5.2 g, 21.1 mmol).
1
Chlorophosphine A is very sensitive to air and moisture. H NMR (C6D6, δ ppm) 7.02 (m, 1H, pyrrol),
6.59 (m, 2H, pyrrol), 1.21 (d, 9H, 3JPH = 14 Hz, t-BuP), 0.99 (s, 9H, t-BuN). 31P NMR (C6D6, δ ppm) 100.7.
13C NMR (C6D6, δ ppm) 124.9 (d, 2JCP = 49.0 Hz, C2), 119.7 (s, C5), 115.4 (d, 1JCP = 34.0 Hz, C3), 111.8 (d,
2JCP = 8.8 Hz, C4), 54.7 (s, N-C(CH3)), 34.1 (d, 1JCP = 26.4 Hz, P-C(CH3)), 30.0 (s, N-C(CH3)), 25.5 (d, 2JCP
=
17.1 Hz, P-C(CH3)).
4.1.2. tert-Butylchloro(1-methyl)-1H-imidazol-2-ylphosphine, B
To a solution of imidazole (3.24 g, 39.5 mmol) in 55 mL of THF maintained at –90 °C under argon
was added dropwise, over 10 min, 16 mL of a solution of n-BuLi 2.5 M in hexane (40 mmol). The
reaction mixture was warmed up and stirred for 30 min at –70 °C. After cooling back to –80 °C a
solution of dimethylamino-tert-butylchlorophosphine (6.23 g, 39.5 mmol) in 10 mL of hexane was
added dropwise over 10 min. The reaction mixture was warmed up and stirred for 30 min at 20 °C.
After solvent evaporation under vacuum, the resulting yellow suspension was cooled to –30 °C and 9
g of dimethylamine (200 mmol) was added. After 10 min stirring the mixture was evaporated to
dryness and the residue was treated with 60 mL of hot pentane (glassware in a boiling water bath).
The non-soluble solid residue was filtered off under argon and rinsed twice with 30 mL of pentane.
The filtrate was evaporated and the oily residue was distilled (b. p. 75-85 °C/0.05 mmHg) to give the
target tert-butyl-(1-methyl)-1H-imidazol-2-yl-dimethylaminophosphine in 73% yield (6.18 g, 29.0
mmol). 1H NMR (C6D6, δ ppm): 1.40 (d, 9H, J = 14 Hz, C(CH3)3), 2.64 (d, 6H, J = 8 Hz, N(CH3)2), 3.16 (s,
3H, NCH3), 6.47 (s, 1H, Im), 7.24 (s, 1H, Im). 31P NMR (C6D6, δ ppm): 50.0. 13C NMR (C6D6): δ (ppm)
27.2 (d, J = 18 Hz, C(CH3)3), 32.75 (d, J = 15Hz, NCH3), 35.5 (d, J = 13 Hz, C(CH3)3), 43.2 (d, J = 15 Hz,
N(CH3)2), 121.9 (C-5), 129.1 (d, J = 1 Hz, C-4), 147.6 (d, J = 13 Hz, C-2).
The tert-butyl-(1-methyl)-1H-imidazol-2-yl-dimethylaminophosphine is easily converted in
chlorophosphine B. To a solution of tert-butyl-(1-methyl)-1H-imidazol-2-yl-dimethylaminophosphine
(6.18 g, 29 mmol) in 10 mL benzene (alternatively less-toxic toluene can be used in 15 mL amount)
was added to phosphorous trichloride (8.0 g, 60 mmol) at 20 °C. The reaction mixture was stirred for
1 h, then the solvent was first removed under vacuum (14 mmHg), and distillation gave as a second
fraction (b. p. 80-82 °C/0.05 mmHg) 5.81 g of chlorophosphine B (98%, 28.4 mmol). 1H NMR (C6D6, δ
ppm): 1.39 (d, 9H, J = 15 Hz, C(CH3)3), 3.08 (s, 3H, NCH3), 6.31 (s, 1H, Im), 7.17 (s, 1H, Im). 31P NMR
(C6D6, δ ppm): 79.7. 13C NMR (C6D6, δ ppm): 25.6 (d, J = 19 Hz, C(CH3)3), 33.1 (d, J = 14Hz, NCH3), 34.6
17

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(d, J = 24 Hz, C(CH3)3), 123.85 (C-5), 130.4 (C-4), 144.65 (J = 40 Hz, C-2). Elemental analysis C8H14ClN2P
(204.64): calcd. Cl 17.32, N 13.69, P 15.14 found: Cl 16.87, N 13.51, P 15.19.
4.1.3. 3-Chloro-5-methyl-3H-benzo[1,3]azaphosphol-2-yldimethylamine, C
To a solution of dimethylaminophosphole [20] (3.37 g, 14 mmol) in 5 mL of benzene was added
phosphorous trichloride (5.9 g, 43 mmol). The reaction mixture was stirred at 25 °C for 3 h. The
phosphorous trichloride excess and benzene were then evaporated under vacuum (14 mmHg).
Dimethylaminodichlorophosphine was removed under a lower pressure vacuum of 0.05 mmHg. The
residue was then distilled (b. p. 130-140 °C/0.05 mmHg) to give C as deep red crystals (3.09 g, yield
1
95%). H NMR (C6D6, δ ppm): 1.97 (s, 3H, CH3), 2.64 (br s, 3H, N(CH3)2), 2.75 (br s, 3H, N(CH3)2), 6.88
(d, 1H, J = 8 Hz, HAr), 7,16 (br s, 1H, HAr), 7.33 (d, 1H, J = 8 Hz, HAr). 31P NMR (C6D6, δ ppm): 57.4. 13C
NMR (C6D6, δ ppm) 20.3, 37.5 (br s, N(CH3)2), 40.8 (br s, N(CH3)2), 119.5 (CH), 130.46 (d, J = 16 Hz),
130.48 (d, J = 29 Hz, CH), 131.2 (d, J = 5 Hz), 134.3 (CH), 160.1 (d, J = 5 Hz), 174.9 (d, J = 33 Hz, CN).
Elemental analysis C10H12ClN2P (226.64): calcd. Cl 15.64, N 12.36, P 13.67 found: Cl 15.17, N 12.27, P
13.41.
4.2. Synthesis of 1,1'-bis(tert-Butyl(1-tert-butyl)-1H-pyrrol-3-ylphosphanyl) ferrocene (2)
To a solution of ferrocene (1.0 g, 5.4 mmol) and N,N,N,N-tetramethylethylenediamine (TMEDA, 2
mL, 12.8 mmol) in 40 mL of hexane was added dropwise at 0 °C a solution of n-BuLi 1.6 M in hexane
(7.9 mL, 12.8 mmol). The reaction mixture was allowed to warm and stirred overnight at room
temperature. A solution of chlorophosphine A (2.66 g, 10.8 mmol) in 30 mL of hexane was added
dropwise to the red suspension of ferrocenyl dilithium salt at –40°C. The reaction mixture was
allowed to warm and stirred at room temperature for 3 h. The mixture was then filtered through
Celite®, the filtrate was evaporated to dryness and the residue was dried under vacuum at 60 °C for
TMEDA removal. The resulting solid was twice crystallized from a 2:3 vol. mixture of CH2Cl2/hexane
to yield 1.8 g of diphosphine 2 (3 mmol, 55%). The major diastereomer (rac) is obtained in 9:1 ratio.
1H NMR (CDCl3, ppm): δ 0.90 (d, 18H, 2JPH = 12 Hz, PC(CH3)3), minor isomer 1.05 (d, 2JPH = 12 Hz), 1.55
(s, 18H, NC(CH3)3), minor isomer 1.49, 3.67 (br s, 2H, Cp), 3.92 (br s, 2H, Cp), 3.99 (br s, 2H, Cp), 4.26
(br s, 2H, Cp), 6.36 (m, 2H, pyrrol), 6.91 (m, 2H, pyrrol), 7.15 (m, 2H, pyrrol). 31P{1H} NMR (CDCl3): δ –
15.6 ppm (minor isomer –15.1). 13C{1H} NMR (CDCl3): δ 27.0 (d, 2C, 2JPc = 15.0 Hz, PC(CH3)3), 29.80 (s,
NC(CH3)3), 44.60 (s, PC(CH3)3), 53.76 (s, NC(CH3)3), 66.89 (s, Cp), 67.89 (s, Cp), 71.03 (d, Cp, J = 7.5 Hz),
74.71 (d, Cp, J = 7.5 Hz), 76.24 (s, Cp), 112.20 (s, pyrrol), 117.38 (m, pyrrol), 125.34 (s, pyrrol), 126.07
(s, pyrrol). C36H56FeN2P2 (634.64): calcd. C 68.13 , H 8.89, N 4.41, found: C 68.22, H 8.56, N 4.48.
18

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4.3. Synthesis of 1,1'-bis(tert-Butyl(1-methyl)-1H-imidazol-2-ylphosphanyl)ferrocene (3)
To a suspension of ferrocene (4.26 g, 23 mmol) and TMEDA (51 mmol) in 110 mL of hexane
maintained at 0 °C was added via syringe a solution of 20.5 mL of n-BuLi at 2.5 M in hexane (51
mmol). The reaction mixture was allowed to warm up and stirred overnight at 20 °C. The resulting
red-orange precipitate was filtered under argon, rinsed twice with 20 mL hexane and was dried
under vacuum (5.11 g, 71%). This ferrocene dilithium salt (2.73 g, 8.7 mmol) was dispersed in 50 mL
of toluene at 5 °C, and a solution of chlorophosphine B (3.12 g, 15.3 mmol) in 12 mL of toluene was
added. The reaction mixture was stirred for 1 h, and the precipitate was filtered off under argon. The
filtrate was evaporated in high vacuum to dryness. The reddish-brown oil residue was treated with
90 mL of degassed hot pentane. The solution was filtered under argon, the solid residue was washed
with pentane (2x15 mL) and the gathered liquid phase filtrate was evaporated to 70 mL to precipitate
2.08 g of the targeted ferrocenyl diphosphine as a 1.6:1 mixture of diastereoisomers (total yield
52%). The mother solution was concentrated to 20 mL, and then crystals formed at 18 °C were
separated to give 710 mg of a 1:3.6 mixture of diastereoisomers (total yield 20%). Major isomer (rac):
m. p. 160-161 °C. 1H NMR (C6D6): δ (ppm) 1.10 (d, 9H, 2JPH = 14.0 Hz, C(CH3)3), 3.47 (s, 3H, NCH3), 3.86
(2H, Cp), 3.97 (s, 2H, Cp), 4.03 (s, 2H, Cp), 5.49 (s, 2H, Cp), 6.51 (ps, 2H, Im), 7.38 (s, 2H, Im). 31P NMR
(C6D6): δ (ppm) –28.8. 13C NMR (C6D6): δ (ppm) δ 27.54 (d, J = 15 Hz, C(CH3)3), 31.6 (d, J = 4Hz, NCH3),
33.7 (d, J = 23 Hz, C(CH3)3), 71.1 (d, J = 10 Hz, Cp), 71.69 (Cp), 74.7(d, J = 6 Hz, Cp), 77.1(s, Cp), 77.4(s,
Cp), 121.8 (s, ImC-5), 130.1 (s, ImC-4), 146.5 (d, J = 4Hz, ImC-2). Minor isomer (meso). 1H NMR (C6D6):
δ(ppm) 1.11 (d, 9H, J = 12 Hz, C(CH3)3), 3.54 (s, 3H, NCH3), 3.82 (s, 2H, Cp), 3.94 (s, 2H, Cp), 4.03 (s,
2H, Cp), 5.54 (s, 2H, Cp), 6.51 (s, 2H, Im), 7.37 (s, 2H, Im). 31P NMR (C6D6): δ (ppm) –29.0. 13C NMR
(C6D6): δ 27.5 (d, J = 15Hz, C(CH3)3), 31.6 (d, J = 5Hz, NCH3), 33.6 (d, J = 20Hz, C(CH3)3), 73.2 (d, J =
6.3Hz, Cp), 74.7 (d, J = 6.3Hz, Cp), 77.8 (s, Cp), 78.1 (s, Cp), 121.8 (ImC-5), 130.1 (ImC-4), 146.56 (d, J =
6.3Hz, ImC-2). Elemental analysis N, 10.72; C, 59.77; H, 6.89 Found: N, 10.01; C, 59.19; H, 6.82
(residual toluene solvent). HR-MS (C26H37N4FeP2) ESI: [M+H]+ m/z theo = 523.18374, exp =523.18306,
δ 1.297 ppm.
4.4. Synthesis of 1,1’-bis((2-dimethylamino)-5-methyl-benzo[1,3]azaphosphol-3-yl-)ferrocene (4)
A solution of chlorophosphine C (3.10 g, 13.7 mmol) in 35 mL of degassed benzene was added to a
dark red suspension of ferrocene dilithium salt (2.36 g, 7.5 mmol) in 70 mL of degassed benzene at 5
°C. The reaction mixture was allowed to warm up and was stirred overnight at 20 °C. The precipitate
was filtered off under argon and washed twice with 20 mL of benzene. The filtrate was evaporated to
dryness. The residue was crystallized from 55 mL of degassed benzene. After 72 h at 20 °C, the
crystals formed were collected to give 1.3 g of 4 as a 1:4 mixture of diastereoisomers (total yield
19

ACCEPTED MANUSCRIPT
33%). The mother liquor was then concentrated to 20 mL and the precipitate formed was collected
and crystallized to give 1.5 g of 4 as a 1:1.4 mixture of diastereoisomers (yield 39%). Major isomer:
31P NMR (C6D6, δ ppm): –24.9. 1H NMR (C6D6, δ ppm): 2.19 (s, 6H, CH3), 2.74 (s, 12H, N(CH3)2), 3.63 (s,
2H, Cp), 4.05 (s, 2H, Cp), 4.28 (s, 2H, Cp), 4.43 (s, 2H, Cp), 7.06-7.09 (m, 2H, HAr), 7.53 (br s, 2H, HAr),
7.61 (m, 2H, HAr). Minor isomer: 31P NMR (C6D6, δ ppm): –23.3. 1H NMR (C6D6, δ ppm): 2.25(s, 6H,
CH3), 2.77 (s, 12H, N(CH3)2), 3.79 (s, 1H, Cp), 4.05 (s, 1H, Cp), 4.18 (s, 1H, Cp), 4.33 (s, 1H, Cp), 7.06-
7.09 (m, 2H, HAr), 7.53 (br s, 2H, HAr), 7.59-7.62 (m, 2H, HAr). For the diastereoisomers: 13C NMR (C6D6,
δ ppm): 20.83, 20.89 (CH3), 39.0, (NCH3), 70.4 (d, J = 4 Hz), 70.6 (d, J = 4 Hz), 71.23, 71.58, 74.97,
75.09, 75.13, 75.33, 119.3 (CH), 119.4 (CH), 129.77 (d, J = 7.5 Hz), 129.71 (d, J = 7.5 Hz), 129.97 (d, J =
24 Hz), 130.08 (d, J = 21 Hz), 130. 67 (d, J = 6.3 Hz), 130.62 (d, J = 5 Hz), 131.14 (CH), 131.21 (CH),
159.49 (d, J = 5 Hz), 159.65 (d, J = 5 Hz, N-CAr), 177.93 (d, J = 18 Hz, CN), 178.07 (d, J = 18 Hz, CN).
Elemental analysis N, 9.89: C, 63.60; H, 5.65; Found: N, 8.59, C, 60.78, H, 5.64. HR-MS (C30H33N4FeP2)
ESI: [M+H]+ m/z theo = 567.15244, exp = 567.15149, δ 1.673 ppm.
1
N. B.: For all the compounds above described and characterized at IOC-NASU, H NMR was conducted
on Bruker Avance DRX 500 (500.13 MHz) or Varian VXR-300 (299.94 MHz) spectrometer; 13C NMR
spectra were recorded on a Bruker Avance DRX 500 (125.75 MHz) spectrometer; 31P NMR spectra
were recorded on a Varian VXR-300 (121.42 MHz) spectrometer.
4.5. Synthesis of the palladium complex [PdCl2(2)]
To a solution of 0.50 g of ferrocenyl diphosphine 2 (0.83 mmol, 90:10 rac/meso) in 15 mL of
freshly distilled CH2Cl2 was added 0.15 g of palladium η3-allyl chloride dimer (0.41 mmol). The
reaction mixture was stirred overnight and the solvent was evaporated. The brown oily residue was
treated with 5 mL of Et2O and the resulting precipitate was collected by filtration and dried. Single
crystals of rac-[PdCl2(2)] suitable for X-ray diffraction were obtained by slow diffusion of pentane in a
saturated solution of complex in CH2Cl2 (0.38 g, 0.48 mmol, yield 58%). 1H NMR (CDCl3, 300 MHz, 300
K): δ 1.31 (d, 18H, 2JPH = 15.9 Hz, PC(CH3)3), 1.60 (s, 18H, NC(CH3)3), 4.12 (br s, 2H, Cp), 4.19 (br s, 2H,
Cp), 4.27 (br s, 2H, Cp), 4.30 (br s, 2H, Cp), 6.41 (m, 2H, pyrrol), 6.94 (m, 2H, pyrrol), 8.11 (m, 2H,
pyrrol). 31P{1H} NMR (CDCl3): δ 32.5 ppm. 13C{1H} NMR (CDCl3): δ 30.23 (s, PC(CH3)3), 30.74 (s,
NC(CH3)3), 30.81 (s, PC(CH3)3), 40.82 (s, PC(CH3)3), 55.83 (s, NC(CH3)3), 67.91 (s, Cp), 71.24 (s, Cp),
74.86 (d, Cp, J = 7.5Hz), 75.18 (d, Cp, J = 7.5Hz), 86.14 (s, Cp), 111.79 (s, pyrrol), 113.15 (m, pyrrol),
119.43 (s, pyrrol), 132.69 (s, pyrrol). C36H56FeN2P2PdCl2 (811.53): calcd. C 53.28, H 6.96; found: C
53.42, H 6.65. HR-MS (ESI) analysis were unsatisfactory.
20

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4.6. Synthesis of the palladium complex [PdCl2(3)]
To a solution of 0.05 g of ferrocenyl diphosphine 3 (0.095 mmol, 62:38 rac/meso) in 5 mL of
freshly distilled toluene was added 0.036 g of bis(benzonitrile) palladium dichloride (0.095 mmol).
The reaction mixture was stirred for 4 hours at room temperature, filtrated on silica, and the solvent
was removed from the filtrate to give [PdCl2(3)] as a red powder (0.05 g, 0.007 mmol, yield 75 %).
Single crystals of rac-[PdCl2(3)] suitable for X-ray diffraction were obtained by slow evaporation of a
solution of the complex in CH2Cl2 (0.03 g, 0.0042 mmol, total yield 45%). 1H NMR (C6D6, 600 MHz, 300
K, δ ppm): 1.56 (d, 18 H, 3JPH = 16 Hz, C(CH3)3), 3.91 (s, 2H, Cp), 4.16 (s, 2H, Cp), 4.38 (s, 2H, Cp), 4.50
(s, 6H, NCH3), 4.81 (s, 2H, Cp), 7.21 (s, 2H, lm), 7.22 (s, 2H, lm). 31P {1H} NMR (C6D6, 242 MHz, 300 k, δ
ppm): 22.72. 13C {1H} NMR (C6D6, 150 MHz, 300 K, δ ppm): 29.36 (s, C(CH3)3), 29.91 (s, NCH3), 40.6 (s,
Cipso(CH3)3), 71.51 (s, Cp), 74.3 (m, Cp), 76.23 (m, Cp), 78.43 (s, Cp), 125.31 (d, JPC = 7 Hz, lm), 129.71
(d, JPC = 7 Hz, lm). N.B: NMR in CD2Cl2 or CDCl3 of 3 gives an oxide product at 25.22 ppm due to the
sensitiveness of the diphosphine in solution. Anal Calcd for C26H36N4P2FePdCl2: C 44.63, H 5.19, N
8.01; found C 44.63, H 5.18, N 8.00. HR-MS (C26H36N4ClFeP2Pd) ESI: [M-Cl]+ m/z theo = 663.04919, exp
= 663.05048, δ 3.364 ppm.
4.7. Synthesis of the platinum complex [PtCl2(3)]
To a solution of 0.10 g of ferrocenyl diphosphine 3 (0.19 mmol, 62:38 rac/meso) in 5 mL of freshly
distilled CH2Cl2 was added 0.090 g of bis(benzonitrile) platinum dichloride (0.19 mmol). The reaction
mixture was stirred at room temperature overnight, then the solvent was evaporated and the
resulting red powder was treated with 5 mL of Et2O. The red precipitate was isolated by filtration and
dried under vacuum to give [PtCl2(3)] as a red solid (0.14 g, 0.17 mmol, yield 94 %). Orange single
crystals of rac-[PtCl2(3)] suitable for X-ray diffraction analysis were obtained by slow diffusion of
1
pentane in a solution of the complex in CH2Cl2 (0.09 g, 0.11 mmol, yield 61 %). H NMR (CD2Cl2, 600
MHz, 300 K, δ ppm): 1.24 (d, 18 H, 3JPH = 16 Hz, C(CH3)3), 4.28 (s, 2H, Cp), 4.56 (s, 2H, Cp), 4.57 (s, 2H,
Cp), 4.62 (s, 6H, NCH3), 4.63 (s, 2H, Cp), 7.17 (s, 2H, lm), 7.2 (s, 2H, lm). 31P {1H} NMR (CD2Cl2, 242
MHz, 300 K, δ ppm): 5.2 (1JPtP = 3604 Hz). 13C {1H} NMR (CD2Cl2, 121 MHz, 300 K, δ ppm): 28.9 (s,
C(CH3)3), 38.0 (s, NCH3), 40.9 (s, C(CH3)3), 72.3 (s, Cp), 74.3 (t, J = 5 Hz, Cp), 76.3 (m, Cp), 78.1 (s, Cp),
125.7 (s, lm), 129.6 (d, JPC = 7 Hz, lm), 137.4 (C-ipso, lm), 137.9 (C-ipso, lm). Quaternary carbons of Cp
were not detected. Unsatisfactory elemental analysis was obtained, presumably due to residual
solvent in the crystals. HR-MS (C26H36N4P2FePtCl) ESI [M-Cl]+ m/z theo = 752.10954, exp = 752.11157,
δ 2.698 ppm.
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4.8. Synthesis of the palladium complex [PdCl2(4)]
To a solution of 0.10 g of ferrocenyl phosphine 4 (0.17 mmol, 42:58, N.B.: from this mixture
rac/meso attribution could not be determined since co-crystallization occurs even for single crystals
crops, as checked by 31P NMR of the crystals) in 5 mL of freshly distilled CH2Cl2 was added 0.067 g of
bis(benzonitrile) palladium dichloride (0.17 mmol). The reaction mixture was stirred at room
temperature overnight, then the solvent was evaporated and the resulting red powder was treated
with 5mL of Et2O. The red precipitate was isolated by filtration and dried in vacuum to give [PdCl2(4)]
(0.11 g, 0.15 mmol, yield 87%) as a mixture of diastereomers corresponding to the starting ligand 4
(42:58). Crystals were obtained by slow diffusion of pentane in a solution of the complex in CHCl3
(0.08 g, 0.1 mmol, total yield 66%). Major isomer (58%): 1H (CD2Cl2, 600 MHz, 300 K, δ ppm): 2.49 (s,
6H, CH3), 3.71 (br s, 12H, NMe2), 4.03 (s, 2H, Cp), 4.28 (s, 2H, Cp), 4.82 (s, 2H, Cp), 5.08 (s, 2H, Cp),
7.18 (d, 2H, JAB = 8 Hz, CHAr), 7.37 (d, 2H, JAB = 8 Hz, CHAr), 7.63 (d, 2H, JPH = 7 Hz, CHAr). 31P {1H} (CD2Cl2,
242 MHz, 300 K, δ ppm): 28.95 ppm. 13C {1H} (CD2Cl2, 150 MHz, 300 K, δ ppm): 21.49 (s, CH3), 72.35 (s,
Cp), 72.95 (t, J = 8 Hz, Cp), 77.29 (t, J = 3 Hz, Cp), 77.73 (s, Cp), 120.87 (s, CH), 130.13 (t, J = 9 Hz),
132.75 (d, J = 6 Hz, C-ipso CCH3), 135.36 (s, CH), 156.57 (C-ipso, CN), 168 (C-ipso, CP). Minor isomer
(42%): 1H (CD2Cl2, 600 MHz, 300 K, δ ppm): 2.51 (s, 6H, CH3), 3.16 (br s, 12H, NMe2), 4.39 (s, 2H, Cp),
4.59 (s, 2H, Cp), 4.66 (s, 2H, Cp), 4.81 (s, 2H, Cp), 7.13 (d, 2H, JAB = 8 Hz, CHAr), 7.13 (d, 2H, JAB = 8 Hz,
CHAr), 7.87 (br s, 2H, CHAr). 31P {1H} (CD2Cl2, 242 MHz, 300 K, δ ppm): 32.92 ppm.13C {1H} (CD2Cl2, 150
MHz, 300 K, δ ppm): 21.36 (s, CH3), 72.68 (t, J = 3 Hz, Cp), 74.40 (s, Cp), 74.64 (t, J = 7 Hz, Cp), 75.71 (t,
J = 3 Hz, Cp), 120.72 (s, CH), 129.82 (t, J = 9 Hz, CH), 133.09 (d, J = 6 Hz, C-ipso, CCH3), 135.05 (s, CH),
155 (C-ipso, CN), 167 (C-ipso, CP). Quaternary carbons of Cp and (CH3)2N were not detected. Anal
Calcd for C30H32N4P2FePdCl2: C 48.45, H 4.34, N 7.53; found: C 48.28, H 3.94, N 7.12. HR-MS
(C30H33N4Cl2FeP2Pd) ESI: [M+H]+ m/z theo = 742.99445, exp = 742.99695, δ 4.472 ppm.
4.9. Synthesis of the platinum complex [PtCl2(4)]
To a solution of 0.10 g of ferrocenyl phosphine 4 (0.17 mmol, 58:42) in 5 mL of freshly distilled
CH2Cl2 was added 0.066 g of dichloro(1,5-cyclooctadiene)platinum(II) (0.17 mmol). The reaction
mixture was stirred at room temperature overnight, then the solvent was evaporated and the
resulting orange powder was treated with 5mL of Et2O. The orange precipitate was isolated by
filtration and dried in vacuum to give [PtCl2(4)] (0.12 g, 0.14 mmol, yield 86%) as a mixture of
1
diastereomers corresponding to the starting ligand 4 (42:58). Major isomer (58 %): H (CD2Cl2, 600
MHz, 300 K, δ ppm): 2.47 (s, 6H, CH3), 3.78 (br s, 12H, NMe2), 3.98 (s, 2H, Cp), 4.31 (s, 2H, Cp), 4.76 (s,
2H, Cp), 5.03 (s, 2H, Cp), 7.17 (d, 2H, JAB = 8 Hz, CHAr), 7.34 (d, 2H, JAB = 8 Hz, CHAr), 7.54 (d, 2H, JPH = 7
Hz, CHAr). 31P {1H} (CD2Cl2, 242 MHz, 300 K, δ ppm): 8.14 (1JPtP = 3626 Hz). 13C {1H} (CD2Cl2, 150 MHz,
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300 K, δ ppm): 21.50 (s, CH3), 72.22 (d, J = 16 Hz, Cp), 73.03 (d, J = 8 Hz, Cp), 71.91 (d, J = 6 Hz, Cp),
76.97 (d, J = 8 Hz, Cp), 120.67 (d, J = 4 Hz, CH), 130.14 (d, J = 15 Hz), 132.88 (d, J = 11 Hz, C-ipso CCH3),
135.42 (s, CH), 156.78 (C-ipso, CN). Minor isomer (42%): 1H (CD2Cl2, 600 MHz, 300 K, δ ppm): 2.49 (s,
6H, CH3), 3.15 (br s, 12H, NMe2), 4.37 (s, 2H, Cp), 4.56 (s, 2H, Cp), 4.57 (s, 2H, Cp), 4.74 (s, 2H, Cp),
7.12 (d, 2H, JAB = 8 Hz, CHAr), 7.29 (d, 2H, JAB = 8 Hz, CHAr), 7.74 (br s, 2H, CHAr). 31P {1H} (CD2Cl2, 242
MHz, 300 K, δ ppm): 10.20 (1JPtP = 3622 Hz).13C {1H} (CD2Cl2, 150 MHz, 300 K, δ ppm): 21.37 (s, CH3),
73.10 (d, J = 8 Hz, Cp), 74.00 (d, J = 13 Hz, Cp), 74.48 (d, J = 7 Hz, Cp), 74.95 (d, J = 9 Hz, Cp), 120.57 (d,
J = 5 Hz, CH), 129.85 (d, J = 15 Hz, CH), 132.58 (d, J = 11 Hz, C-ipso, CCH3), 135.03 (s, CH), 156,78 (C-
ipso, CN). Quaternary carbon of Cp and C-P and (CH3)2N were not detected. HR-MS (ESI) analysis
were unsatisfactory. Anal Calcd for C30H32N4P2FePtCl2: C 43.29, H 3.87; found: C 42.02, H 4.32.
4.10. Catalytic cross-coupling reactions
Copper-free alkyne arylation. An oven-dried Schlenk flask was charged with the acetylenic
compound (2 mmol), 1:1 [PdCl2(PhCN)2]/ligand (1 mol %), Cs2CO3 (2 mmol), and the aryl halide (1
mmol). A magnetic stirring bar was added, and the flask was purged. 5 ml of DMF was then added.
1
The reaction was heated at 100 °C for 20 h. Reactions were monitored by GC, GC-MS and H NMR,
and yields were calculated from NMR and GC.
Suzuki-Miyaura arylation. An oven-dried Schlenk flask was charged with the aryl boronic acid (2
mmol), 1:1 [PdCl2(PhCN)2]/ligand (0.2 mol %), K2CO3 (2 mmol), and the aryl halide (1 mmol). A
magnetic stirring bar was added, and the flask was purged and placed under inert atmosphere. 5 ml
of DMF was then added. The reaction was heated to 100 °C for 20 h. Reactions were monitored by
GC, GC-MS and 1H NMR and yields were calculated from NMR and GC.
Acknowledgments
Cooperation between the institutes IOC-NASU and ICMUB (UMR-CNRS 6302) was funded by the
CNRS and the Ukrainian Academy of Sciences (NASU) via PICS program 2010-2012 (n° 5424,
coordinator C. Danilovic) which are sincerely and gratefully acknowledged. The “Conseil Régional de
Bourgogne” supported also this work through the programs 3MIM, and PARI IME-SMT08 with a PhD
grant for F. A. shared with the Lebanese Foundation “Azm et Saada”. Cooperation between the
“Université de Bourgogne” and the “Université Libanaise” benefited of a CEDRE program 2010-2012
(project 09 SCI F 33/L 50), P. Meunier is acknowledged for that.
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Appendix A. Supplementary material
CCDC 922383 – 922386 contain the supplementary crystallographic data for this paper. These data
can be obtained free of charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
Appendix B. Supplementary data
Supplementary data associated with this article can be found, in the online version, at
http://dx.doi.org/
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References
[1] (a) A. Togni, T. Hayashi (Eds), Ferrocenes, Homogeneous Catalysis, Organic Synthesis, Material
Science, VCH, Weinheim, 1995;
(b) P. Štĕpnička (Ed), Ferrocenes: Ligands, Materials and Biomolecules, John Wiley & Sons Ltd,
Chichester, 2008;
(c) L.-X. Dai, X.-L. Hou (Eds), Chiral Ferrocenes in Asymmetric Catalysis: Synthesis and
Applications, Wiley–VCH, 2010;
[2] (a) A. Fihri, P. Meunier, J.-C. Hierso, Coord. Chem. Rev. 251 (2007) 2017;
(b) R. G. Arrayás, J. Adrio, J. C. Carretero, Angew. Chem. Int. Ed. 45 (2006) 7674;
(c) R. C. J. Atkinson, V. C. Gibson, N. J. Long, Chem. Soc. Rev. 33 (2004) 313;
(d) N. Debono, A. Labande, E. Manoury, J.-C. Daran, R. Poli, Organometallics 29 (2010) 1879;
(e) L. E. Hagopian, A. N. Campbell, J. A. Golen, A. L. Rheingold, C. Nataro, J. Organomet. Chem.
691 (2006) 4890;
(f) A. Jakob, B. Milde, P. Ecorchard, C. Schreiner, H. Lang, J. Organomet. Chem. 693 (2008) 3821;
(g) M. Lohan, B. Milde, S. Heider, J. M. Speck, S. Krauße, D. Schaarschmidt, T. Rüffer, H. Lang,
Organometallics 31 (2012) 2310.
(i) A. N. Cammidge, K. V. L. Crépy, Chem. Commun. 2000, 1723.
[3] In ref. 2(a) Table 1 summarizes the ferrocenyl diphosphines analogous to dppf and their reported
palladium-catalyzed applications until 2008.
[4] B. C. Hamann, J. F. Hartwig, J. Am. Chem. Soc. 120 (1998) 3694.
[5] A. Fihri, J.-C. Hierso, A. Vion, D. H. Nguyen, M. Urrutigoïty, P. Kalck, R. Amardeil, P. Meunier, Adv.
Synth. Catal. 347 (2005) 1198.
[6] J.-C. Hierso, A. Fihri, R. Amardeil, P. Meunier, H. Doucet, M. Santelli, Tetrahedron 61 (2005) 9759.
[7] M. Chalal, D. Vervandier-Fasseur, P. Meunier, H. Cattey, J.-C. Hierso, Tetrahedron 68 (2012) 3899.
[8] A. F. Littke, G. C. Fu, Angew. Chem. Int. Ed. 41 (2002) 4176.
[9] (a) I. R. Butler, W. R. Cullen, T.-J. Kim, F. W. B. Einstein, T. Jones, J. Chem. Soc. Chem. Commun.
(1984) 719;
(b) W. R. Cullen, T.-J. Kim Organometallics 4 (1985) 346.
[10] L.-K. Liu, J.-C. Chen, Bull. Inst. Chem. Acad. Sinica 38 (1991) 43.
[11] G. E. Herberich, S. Moss, Chem. Ber. 128 (1995) 689.
[12] A. Marchenko, A. Hurieva, H. Koidan, V. Rampazzi, H. Cattey, N. Pirio, A. N. Kostyuk, J.-C. Hierso,
Organometallics 31 (2012) 5986.
25

ACCEPTED MANUSCRIPT
[13] J.-J. Bishop, A. Davison, M. L. Katcher, D. W. Lichtenberg, R. E. Merrill, J. C. Smart, J. Organomet.
Chem. 27 (1971) 241
[14] In comparison the diphosphines 1,1’-bis(di-tert-butylphosphino)ferrocene and the furyl-
containing 1,1’-bis(di-2-furylphosphino)ferrocene have been attributed 31P NMR δ = 27.08 (C6D6)
and −64.92 (CDCl3) ppm, respectively.
[15] J. Roger, S. Mom, M. Beaupérin, S. Royer, P. Meunier, V. V. Ivanov, H. Doucet, J.-C. Hierso,
ChemCatChem 2 (2010) 296.
[16] H. Doucet, J.-C. Hierso, Angew. Chem. Int. Ed. 46 (2007) 834.
[17] (a) M. Beaupérin, A. Job, H. Cattey, S. Royer, P. Meunier, J.-C. Hierso, Organometallics 29 (2010)
2815;
(b) A. S. Batsanov, J. C. Collings, , I. J. S. Fairlamb, J. P. Holland, J. A. K. Howard, Z. Lin, T. B.
Marder, A. C. Parsons, R. M. Ward, J. Zhu, J. Org. Chem. 70 (2005) 703;
(c) D. Gelman, S. L. Buchwald, Angew. Chem. Int. Ed. 42 (2003) 5993.
(d) J.-C. Hierso, CR Chimie, 2013 in press.
[18] (a) N. T. S. Pham, M. Van Der Sluys, C. W. Jones, Adv. Synth. Catal. 348 (2006) 609;
(b) M. Lamblin, L. Nassar-Hardy, J.-C. Hierso, E. Fouquet, F.-X. Felpin, Adv. Synth. Catal. 352
(2010) 33.
[19] A. A. Chaikovskaya, Y. V. Dmitriv, P. S. Ivonin, A. M. Pinchuk, A. A. Tolmachev, Heteroatom
Chem. 16 (2005) 599.
[20] A. P. Marchenko, G. N. Koidan, A. N. Hurieva, A. S. Merkulov, A. M. Pinchuk, A. N. Kostyuk,
Tetrahedron 66 (2010) 3668.
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