Synthesis of an amidosulfonate-tagged biphenyl phosphine and its application in the Suzuki-Miyaura reaction affording biphenyl-substituted amino acids in water

Article abstract of DOI:10.1016/j.jorganchem.2015.01.020

An amidosulfonate-tagged phosphinobiphenyl, viz triethylammonium 2-(dicyclohexylphosphino)-4′-{[(sulfonatomethyl)amino]carbonyl}biphenyl (3), was prepared in two steps from 2-(dicyclohexylphosphino)biphenyl-4′-carboxylic acid and fully characterized including the crystal structure determination. As a highly polar phosphine ligand, compound 3 was employed in the Pd-catalyzed Suzuki-Miyaura cross-coupling of N-Boc protected 4-bromo and 4-chlorophenylalanine with aromatic boronic acids to afford the corresponding biphenyls in aqueous N,N-dimethylformamide or pure water. The coupling was demonstrated to proceed very well and without the loss of the Boc protecting group when the bromo-substituted substrate is reacted in the presence of 1 mol.% of Pd/3 catalyst in water at 40 °C. Reactions with boronic acids bearing electron-withdrawing substituents and, mainly, those with the less reactive chlorophenylalanine substrate required slightly higher reaction temperature and more catalyst to achieve similar results.

Full text of DOI:10.1016/j.jorganchem.2015.01.020

Journal of Organometallic Chemistry xxx (2015) 1e8
Contents lists available at ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Synthesis of an amidosulfonate-tagged biphenyl phosphine and its
application in the SuzukieMiyaura reaction affording biphenyl-
substituted amino acids in water
*
ꢀ
ꢀ
ꢀ
ꢁ
ꢀ
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Jirí Schulz, Ivana Císarova, Petr Stepnicka
Department of Inorganic Chemistry, Faculty of Science, Charles University in Prague, Hlavova 2030, 128 40 Prague, Czech Republic
a r t i c l e i n f o
a b s t r a c t
An amidosulfonate-tagged phosphinobiphenyl, viz triethylammonium 2-(dicyclohexylphosphino)-40-
{[(sulfonatomethyl)amino]carbonyl}biphenyl (3), was prepared in two steps from 2-(dicyclohex-
ylphosphino)biphenyl-40-carboxylic acid and fully characterized including the crystal structure deter-
mination. As a highly polar phosphine ligand, compound 3 was employed in the Pd-catalyzed Suzuki
eMiyaura cross-coupling of N-Boc protected 4-bromo and 4-chlorophenylalanine with aromatic boronic
acids to afford the corresponding biphenyls in aqueous N,N-dimethylformamide or pure water. The
coupling was demonstrated to proceed very well and without the loss of the Boc protecting group when
the bromo-substituted substrate is reacted in the presence of 1 mol.% of Pd/3 catalyst in water at 40 ꢀC.
Reactions with boronic acids bearing electron-withdrawing substituents and, mainly, those with the less
reactive chlorophenylalanine substrate required slightly higher reaction temperature and more catalyst
to achieve similar results.
Article history:
Received 6 January 2015
Received in revised form
22 January 2015
Accepted 23 January 2015
Available online xxx
Dedicated to Professor Georg Süss-Fink on
the occasion of his 65th birthday.
Keywords:
Biphenyl phosphines
Phosphinoamides
Sulfonates
© 2015 Elsevier B.V. All rights reserved.
Palladium
SuzukieMiyaura cross-coupling
Amino acids
Introduction
of organic transformations [2]. In order to perform metal-catalyzed
reactions in water, one naturally has to ensure sufficient solubility
Environmental and economic concerns have recently raised
the demand for the implementation of highly efficient and
environmentally benign approaches toward the synthesis of
organic compounds. Since catalysts can be advantageously
employed to increase the rate and selectivity of chemical re-
actions (thereby decreasing the energy consumption and waste
production) [1], significant attention is currently being paid to the
search for new efficient and practically applicable catalytic pro-
cesses. Among various approaches introduced to date, a particular
attention has been devoted to the development of catalytic re-
actions proceeding in water or aqueous mixtures (solutions or
biphasic mixtures).
of the particular transition metal catalysts in the aqueous solvent
used, typically by means of water-soluble ligands. The design of
such donors for catalytic applications, most often phosphines, is
also well established, relying predominantly on modifications of
the successful ligands through the introduced hydrophilic sub-
stituents among which the highly polar sulfonato moieties play a
prominent role [3].
Monophosphines combining the sterically demanding
biphenyl-2-yl backbone with an electron rich phosphine substitu-
ent (typically dialkylphosphine) emerged as a class of versatile li-
gands affording active catalytic systems for SuzukieMiyaura biaryl
coupling [4,5]. Particular derivatives sulfonated at the biphenyl
moiety allowed to perform this reaction in water [6] while car-
boxylic acid 1 (Scheme 1) and amidation reactions were employed
to conjugate the 2-(dicyclohexyl)biphenyl ligating moiety with
glucosamine [7] or to immobilize it covalently onto amine-
substituted polymers [8] or aminopropylated silica gel [9] with
retention of its favorable catalytic properties. In order to prepare
further molecular donors, we decided to convert acid 1 into an
Water as a reaction medium is not only attractive due to its low
price, relatively easy recycling and non-toxic nature, but also owing
to its unique physicochemical properties that may alter the course
* Corresponding author. Fax: þ420 221 951 253.
ꢀ
ꢀ
ꢀ
E-mail address: stepnic@natur.cuni.cz (P. Stepnicka).
http://dx.doi.org/10.1016/j.jorganchem.2015.01.020
0022-328X/© 2015 Elsevier B.V. All rights reserved.
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2
J. Schulz et al. / Journal of Organometallic Chemistry xxx (2015) 1e8
amidophosphine was isolated in the form of stoichiometric solvate
3$1/2CH3CO2Et in a very good overall yield (80% over the two
steps).
The compound was characterized by multinuclear NMR spec-
troscopy, IR spectroscopy, electrospray-ionization mass spectrom-
etry and by elemental analysis. The 1H NMR spectra of 3 show two
sets of complicated multiplets attributable to the cyclohexyl sub-
stituents and the biphenyl moiety. Also seen are the discrete signals
due to the amide proton and its bonded methylene group (dH 8.65
(t) and 4.16 (d) with 3JHH of 6.3 Hz, respectively), and the resonances
of the ethyl groups in the Et3Nþ cation. The 13C NMR spectra sup-
port the formulation, displaying ten distinct resonances due to the
biphenyl unit, the signals of the CH2 linker (dC 55.84) and the Et3Nþ
cation as well as those of the phosphorus-bound cyclohexyl groups
in a typical pattern [13]. The presence of the amide unit is clearly
manifested by a 13C NMR resonance at dC 165.31 and by amide
Scheme 1.
anionic amidosulfonate 3 (Scheme 1), making use of the approach
which we have recently employed in the preparation of water-
soluble phosphinoferrocene donors [10]. In this contribution, we
describe the synthesis of a novel (dicyclohexylphosphino)biphenyl
amidophosphine ligand 3 [11] possessing a water-solubilizing
anionic amidosulfonate tag and its application as a ligand for Pd-
catalyzed biaryl coupling of various aromatic boronic acids with
halogen-substituted N-protected phenylalanine in water.
bands in the IR spectrum (amide I: 1655 cmꢁ1
1544 cmꢁ1). The IR spectrum further display strong characteristic
, amide II:
bands of the terminal sulfonate group (i.e., ns(SO3) at 1042 cmꢁ1
,
and nas(SO3) at 1159 cmꢁ1).
Single crystals of unsolvated 3 suitable for X-ray diffraction
analysis were obtained from hot acetonitrile. The compound crys-
tallizes with the symmetry of the monoclinic space group C2/c. Its
molecular structure is depicted in Fig. 1 and the selected geometric
parameters are presented in Table 1.
Results and discussion
The benzene rings constituting the biphenyl moiety in the
amidosulfonate anion of 3 are mutually rotated by ca. 58ꢀ (see
Table 1), presumably because of the presence of the bulky dicy-
clohexylphosphino moiety in the position adjacent to the pivotal
C1eC11 bond. A similar twisting can be found in the crystal
Syntheses and structural characterization
The target compound was prepared (Scheme 2) from 2-(dicy-
clohexylphosphino)biphenyl-40-carboxylic acid (1) using the active
ester method [12]. In the first step, the acid was converted to the
respective pentafluorophenyl ester via treatment with penta-
fluorophenol in the presence of N-(3-dimethylaminopropyl)-N0-
ethylcarbodiimide hydrochloride (EDC$HCl) and 4-(dimethyla-
mino)pyridine in dichloromethane. As a second step, the active
ester was reacted with aminomethanesulfonic acid in a mixture of
N,N-dimethylformamide, dichloromethane and triethylamine con-
structure
of
2-(dicyclohexylphosphino)-40-(dimethylamino)-
biphenyl (twist angle: 55ꢀ) [14]. Nonetheless, the phosphine sub-
stituent in 3 appears to be attached without any significant torsion
at its parent aromatic ring as indicated by the torsion angle
C1eC11eC12eP of ꢁ1.9(2)ꢀ. The substituents at the phosphorus
atom are directed away from the parent benzene ring C(11e26) so
that the PeC17 and PeC23 bond intersect the ring plane at
72.32(8)ꢀ and 32.98(8)ꢀ, respectively. The cyclohexane rings adopt
chair conformations, which is manifested by the ring puckering
taining
a
catalytic amount of 4-(dimethylamino)pyridine.
Following crystallization from hot ethyl acetate, the
parameters [15]: Q ¼ 0.576(2) Å,
q
¼ 177.8(2)ꢀ and Q ¼ 0.569(2) Å,
q
¼ 5.5(2)ꢀ for the rings C(17e22) and C(23e29), respectively.
(Note: the ideal chair is characterized by
bonds assume equatorial positions, further minimizing a possible
steric strain.
q
¼ 0/180ꢀ.) Both PeC
The amide plane constituted by the atoms C7, N1 and O1 is also
twisted with respect to its bonding benzene ring though only by ca.
16ꢀ. The C8 atom lies in this plane (the distance of C8 from the
amide plane is 0.001(2) Å) but its sulfonate substituent is oriented
away (cf. the angle between the C8eS bond and the amide plane of
66.2(2)ꢀ and the torsion angle C7eN1eC8eS being 96.5(2)ꢀ), which
in turn diverts both functional substituents (PR2 and SO3) into
roughly opposite positions with respect to the central biphenyl
moiety.
The triethylammonium cation assumes the usual geometry [16]
and is connected to the amidosulfonate anion via the N2eH2/O3
hydrogen bond (Fig. 2). The sulfonate moiety is further involved in
hydrogen bonding to the amide proton in an adjacent amidosul-
fonate moiety related by the crystallographic inversion. As the
result, the solid-state structure is built up from hydrogen-bonded
aggregates constituted by two amidosulfonate anions and two
Et3NHþ cations (see Fig. 2), that are further interlinked only by the
soft CeH/O3S interactions. It is also noteworthy, that the different
hydrogen-bonding interactions differentiate the SeO bonds within
the terminal sulfonate moiety. The distance between the sulfur
atom and oxygen O3 forming a charge-supported hydrogen bond to
Scheme 2. Synthesis of amidophosphine 3.
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J. Schulz et al. / Journal of Organometallic Chemistry xxx (2015) 1e8
3
Fig. 1. PLATON plot of the molecular structure of 3. The displacement ellipsoids enclose the 30% probability level. The N2eH2N/O3 hydrogen bond is indicated by a dotted line.
the triethylammonium cation is slightly yet statistically signifi-
cantly elongated (SeO3 z 1.47 Å) compared to the remaining two
SeO distances (SeO2/4 z 1.45 Å) pertaining to the oxygen atoms
employed in O/HeN bonding (O2) or not involved in secondary
binding in the crystal state (O4). Consistently, the N2/O3 distance
is by ca. 0.1 Å shorter (stronger) than the N1/O2 contact (2.1760(2)
vs. 2.866(2) Å).
Because of an easy monitoring by 1H NMR spectroscopy, the
initial screening experiments were performed with 4-
methoxyphenylboronic acid (5e) [20] and aryl chloride 4a which
enables for a better differentiation of the influence of the individual
reaction parameters owing to is relatively lower reactivity. The
reactions were performed at 100 ꢀC and over short reaction times in
order to avoid unwanted removal of the Boc protecting group,
which proceeds in parallel with the coupling process affecting
either 5e or the formed 6e and thus diminishes the yield of the
desired coupling product 6e.
Catalytic evaluation
The first experiments were carried out in pure water and with
Palladium-catalyzed SuzukieMiyaura cross-coupling evolved as
a versatile synthetic tool and has accordingly found numerous
applications in organic synthesis [17]. It tolerates a wide range of
functional groups and is relatively easy to carry out under practi-
cally applicable, moderate reactions conditions and often with
commercially available starting materials. Importantly, it can be
advantageously performed in aqueous media due to the hydrolytic
stability of many organoboron reagents [18], which led us to eval-
uate the newly prepared amidophosphine ligand 3 in this particular
type of cross-coupling reaction. For testing, we chose the biaryl
coupling of aryl boronic acids with N-Boc protected [19], racemic
phenylalanines halogenated in position 4 of the benzene ring (4a
various bases in the presence of catalyst generated from [PdCl(h3
-
C3H5)]2 and ligand 3 at Pd:P molar ratio of 1:1. The NMR yields
determined after 4 h at 100 ꢀC (Table 2) revealed a pronounced
effect of the base additive on the reaction outcome, reflecting very
likely both the efficiency of the base in the cross-coupling reaction
itself and the rate at which the base promotes removal of the
protecting group. Alkali metal acetates (NaeCs; entries 1e4)
showed rather similar efficacy (24e34% yields of 6e), while the
yield achieved in the reaction with KHCO3 was exactly the half of
that obtained with the corresponding “normal” salt (cf. entries 2
and 5). The results obtained with the alkali metal phosphates
and 4b) as the model substrates leading to biphenyl-substituted a-
amino acids (Scheme 3).
Table 1
Selected interatomic distances and angles for 3 (in Å and deg).a
C1eC2
C4eC7
C7eO1
C7eN1
N1eC8
C8eS
SeO2
SeO3
SeO4
PeC12
PeC17
PeC23
N2eC31
N2eC33
N2eC35
1.391(2)
1.499(2)
1.227(2)
1.351(2)
1.439(2)
1.793(2)
1.451(1)
1.469(1)
1.450(1)
1.849(2)
1.873(2)
1.858(2)
1.497(2)
1.507(2)
1.501(3)
41
58.36(8)
42
15.5(2)
122.5(2)
120.9(1)
113.0(1)
112.93(8)
113.07(7)
112.28(7)
100.49(8)
100.52(7)
105.54(8)
ꢁ1.9(2)
O1eC7eN1
C7eN1eC8
N1eC8eS
O2eSeO3
O2eSeO4
O3eSeO4
C12ePeC17
C12ePeC23
C17ePeC23
C1eC11eC12eP
C31eN2eC33
C31eN2eC35
C33eN2eC35
113.9(2)
109.7(1)
113.6(1)
Fig. 2. View of the hydrogen bonded dimers in the structure of 3. For clarity, only the
NH hydrogens are shown. Hydrogen bond parameters are as follows: N1eH1N/O2i,
N1/O2i ¼ 2.866(2) Å, angle at H1N ¼ 158ꢀ; N2eH2N/O3, N2/O3 ¼ 2.760(2) Å,
angle at H2N ¼ 156ꢀ; i. (1/2 ꢁ x, 5/2 ꢁ y, 2 ꢁ z).
a
Definitions: 41 is the dihedral angle subtended by the least-squares benzene
planes C(1e6) and C(11e16) while 42 denotes the dihedral angle between the
amide plane (C7, O1 and N1) and its bonding benzene ring C(1e6).
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4
J. Schulz et al. / Journal of Organometallic Chemistry xxx (2015) 1e8
Table 3
Influence of the reaction solvent on the model cross-coupling reaction.a
Entry
Solvent
Water
1H NMR yield [%]
1
2
3
4
5
6
7
8
46
32
34
20
89
77
37
63
45
34
Dioxane
Dioxane-water (1:1 v/v)
Dimethylformamide
Dimethylformamide/water (1:1 v/v)
Dimethylformamide/water (1:1 v/v)b
Propionitrile
Propionitrile/water (1:1 v/v)
Propanol
Propanol/water (1:1 v/v)
Scheme 3. SuzukieMiyaura cross-coupling of N-protected amino acids 4 with boronic
acids 5.
9
10
a
Conditions: 4a (0.5 mmol), 5e (0.65 mmol), K3PO4 (2.0 mmol), [PdCl(
mol) and ligand 3 (10.0
mol) in water (3 mL), 4 h at 100 ꢀC. For details, see
Experimental section.
h
3-C3H5)]2
(5.0
m
m
(entries 6e8) differed significantly more. Whereas no coupling
product was detected in the reaction mixture containing Li3PO4, the
corresponding potassium salts afforded the best yield among the
bases tested (46%). Finally, the yields obtained with KOH or KOt-Bu,
which is hydrolyzed in situ to the former base, were ca. 26%,
whereas potassium acetate, commonly used in this type of re-
actions, surprisingly failed to provide any coupling product.
The influence of the reaction solvent was evaluated next
(Table 3) using potassium phosphate as the base and the same
catalytic system at 100 ꢀC for 4 h. Changing the reaction medium
from water (46% yield) to pure dioxane and dioxane-water (1:1)
decreased the yield of 6e by approximately 10% (compare entries
1e3 in Table 3). Although the reaction in pure N,N-dime-
thylformamide (DMF) afforded a rather disappointing result (20%
yield), addition of water to this solvent markedly increased the
catalytic efficacy even at a shorter reaction time (2 h; cf. entries
4e6). On the other hand, reactions performed in propionitrile and
1-propanol ensued in comparably lower yields, similar to those
achieved in water. Addition of water to these solvents had an
opposite effect: The yield obtained in aqueous propionitrile was
markedly better than in the pure organic solvent whereas the
addition of water to 1-propanol reduced the yield of 6e from 45% in
pure solvent to 34% for the aqueous mixture (entries 7e10). These
results together with the fact that the yields achieved in dioxane
and aqueous dioxane are practically the same, implicate an “indi-
vidual” effect of the added water for a particular solvent and, hence,
the need for testing all possible combinations.
b
The reaction time was reduced to 2 h.
Table 4
Influence of the palladium source on the model cross-coupling reaction.a
Entry
Palladium saltb
1H NMR yield [%]
1
2
3
4
5
6
7
Pd(OAc)2
Pd(OAc)2
PdCl2
51
30
62
54
66
89
8
c
[PdCl2(cod)]
[LNCPdCl]2
[PdCl(
[Pd2(dba)3]
h
3-C3H5)]2
a
Conditions: 4a (0.5 mmol), 5e (0.65 mmol), K3PO4 (2.0 mmol), palladium pre-
cursors (2 mol.% Pd) and ligand 3 (2 mol.%; Pd:P ¼ 1:1) in water-dimethylformamide
(3 mL, 1:1 v/v), 4 h at 100 ꢀC. For details, see Experimental section.
b
Legend: dba ¼ dibenzylideneacetone, cod ¼ h5
:h
5-cycloocta-1,5-diene, LNC ¼ 2-
[(dimethylamino-kN)methyl]phenyl-k
C1.
c
4 mol.% of 3 were used (Pd:P ¼ 1:2).
product to 30%. The yield of 6e achieved with palladium(II) chloride
was by ca. 10% better than with the acetate salt and thus similar to
that obtained with [(LNC)PdCl]2 possessing an auxiliary ortho-pal-
ladated N,N-dimethylbenzylamine ligand. The “ligated” palladiu-
m(II) dichloride surrogate, [PdCl2(cod)], performed similarly to
Pd(OAc)2. The best result (89% of 6e) was obtained with the catalyst
generated from 3 and (p -
-allyl)palladium chloride dimer, [PdCl(h3
A subsequent examination of various palladium precursors has
shown that the palladium source also plays a vital role in deter-
mining the efficacy of the Pd/3 catalyst (Table 4). For instance,
palladium(II) acetate, a very typical palladium source for various
cross-coupling reactions, provided a 51% yield of 6e at 2 mol.%
loading and Pd:P ratio of 1:1. Increasing the amount ligand to two
equivalents with respect to Pd decreased the yield of the coupling
C3H5)]2. In contrast, catalyst generated from [Pd2(dba)3] as an
imminent source of Pd(0) performed by far the worst, furnishing
only an 8% yield of 6e under the standard reaction conditions.
Having established that the catalytic system generated from 3
and [PdCl(h-C3H5)]2 efficiently mediates the coupling of the model
substrates in aqueous DMF in the presence of potassium phosphate,
we next turned to testing of different substrates under these con-
ditions. The results summarized in Table 5 indicate that the cross-
coupling reaction with the more reactive substrate 4b proceeds
very well even at 40 ꢀC and with 1 mol.% of in situ generated Pd-
catalyst, resulting in complete conversions to the target product
6e within 4 h. A shorter reaction time (2 h) lowered the yield only
slightly (cf. entries 1 and 2). When 4b was replaced with the cor-
responding aryl chloride 4a, the reaction not only required a higher
catalyst loading (2 mol.% of Pd) but also a higher reaction temper-
ature (100 ꢀC/4 h in N,N-dimethylformamide) to achieve similar
results (entry 3). This trend was reproduced also in the case of
couplings with unsubstituted phenylboronic acid 5a (entries 4 and
5).
Table 2
Evaluation of various bases in the model cross-coupling reaction.a
Entry
Base
1H NMR yield [%]
1
2
3
4
5
6
7
8
Na2CO3
K2CO3
Rb2CO3
Cs2CO3
KHCO3
Li3PO4
Na3PO4
K3PO4
KOH
28
34
24
28
17
0
21
46
27
25
0
9
10
11
The reaction was affected also by substituents at the aromatic
ring of the boronic acid component. Substitution leading to
increased steric demands around the reaction site (2-Me) as well as
electron-withdrawing substituents (4-CN and 4-NO2) reduced the
KOt-Bu
KOAc
a
Conditions: 4a (0.5 mmol), 5e (0.65 mmol), base (2.0 mmol), [PdCl(
mol) and ligand 3 (10.0
mol) in water (3 mL), 4 h at 100 ꢀC. For details, see
Experimental section.
h
3-C3H5)]2
(5.0
m
m
yield of the respective coupling products even at
a higher
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J. Schulz et al. / Journal of Organometallic Chemistry xxx (2015) 1e8
5
Table 5
Synthesis of pentafluorophenyl 2-(dicyclohexylphosphino)biphenyl-
40-carboxylate (2)
The results of screening of various substrates.a
Entry Aryl halide Boronic acid T
Time Product 1H NMR yield (isolated
(ꢀC) (h)
yield) [%]
(X)
(R)
A two-necked flask was charged with acid 1 (1.48 g, 3.75 mmol),
pentafluorophenol (1.17 g, 5.63 mmol), N-(3-dimethylamino-
propyl)-N0-ethylcarbodiimide hydrochloride (EDC$HCl; 1.08 g,
5.63 mmol) and 4-(dimethylamino)pyridine (0.12 g, 0.94 mmol),
flushed with argon and sealed with a rubber septum. Anhydrous
dichloromethane (50 mL) was introduced via a syringe and the
resulting mixture was stirred at room temperature overnight. The
reaction was terminated by addition of distilled water (25 mL), the
layers were separated, and the aqueous phase was extracted with
dichloromethane (2 ꢂ 25 mL). The combined organic layers were
washed with brine (25 mL) and dried over magnesium sulfate.
Then, the solvents were removed under vacuum, and the solid
residue was purified by column chromatography (silica gel, ethyl
acetate/hexanes, 1:15 v/v) to afford analytically pure penta-
fluorophenyl 2-(dicyclohexylphosphino)biphenyl-40-carboxylate as
a white solid. Yield of 2: 1.93 g (92%).
1
2
3
4
5
6
7
8
9
10
4b (Br)
4b (Br)
4a (Cl)
4b (Br)
4a (Cl)
4b (Br)
4b (Br)
4b (Br)
4b (Br)
4b (Br)
5e (4-MeO) 40
5e (4-MeO) 40
5e (4-MeO)b 100
4
2
4
4
4
4
4
4
4
4
6e
6e
6e
6a
6a
6b
6c
6d
6f
100 (94)
92
89
100 (96)
86
5a (H)
40
100
60
40
40
5a (H)b
5b (2-Me)c
5c (3-Me)
5d (4-Me)
5f (4-CN)c
72
100 (83)
100 (85)
89
60
5g (4-NO2)c 60
6g
91
a
Conditions: 4a or 4b (0.5 mmol), boronic acid (0.55 mmol), K3PO4 (2.0 mmol),
3-C3H5)]2 (2.5
mol; 1 mol.% Pd) and 3 (5.0 mol) in 3 mL of water unless
specified otherwise.
[PdCl(
h
m
m
b
Reaction performed with [PdCl(
(10.0 mol) in 3 mL of water-dimethylformamide (1:1 v/v).
Reaction performed with [PdCl( mol;
3-C3H5)]2 (5.0
(10.0 mol) in 3 mL of water.
h
3-C3H5)]2 (5.0
m
mol;
2
mol.% Pd) and
3
m
c
h
m
2
mol.% Pd) and
3
m
1H NMR (CDCl3):
d 0.98e1.31 (m, 10H), 1.54e1.78 (m, 10H), and
1.82e1.91 (m, 2H, PCy2); 7.28e7.30 (m, 1H), 7.38e7.49 (m, 4H),
7.62e7.68 (m, 1H), and 8.19e8.22 (m, 2H, C12H8). 13C{1H} NMR
temperature (60 ꢀC) and with 2 mol.% of the catalyst. In contrast,
methyl substituents in position 3 or 4 of the aromatic ring did not
affect the coupling, the respective coupling products being ob-
tained with full NMR and good isolated yields.
(CDCl3):
d
26.35 (2C), 27.10 (2C), 27.20 (d, JPC ¼ 6 Hz, 2C), 29.20 (d,
JPC ¼ 8 Hz, 2C), 30.41 (d, JPC ¼ 16 Hz, 2C), and 34.55 (d, JPC ¼ 10 Hz,
2C) (PCy2); 125.22, 127.47, 128.80, 129.87 (d, JPC ¼ 6 Hz), 130.00,
1
131.21 (d, JPC ¼ 4 Hz), 133.32 (C12H8); 138.0 (dm, JFC ¼ 253 Hz),
139.5 (dm, 1JFC ¼ 253 Hz), 141.5 (dm, 1JFC ¼ 252 Hz, C6F5); 149.10 (d,
Conclusion
JPC ¼ 29 Hz), 149.65 (d, JPC ¼ 5 Hz), 162.61 (C]O). 19F NMR (CDCl3):
3
The newly designed and synthesized amidosulfonate
3
d
ꢁ162.7 (m, 2 F, Fmeta of C6F5), ꢁ158.5 (t, JFF ¼ 22 Hz, 1 F, Fpara of
C6F5), ꢁ152.6 (m, 2 F, Fortho of C6F5). 31P{1H} NMR (CDCl3):
d
ꢁ12.6
combining the bulky (dicyclohexylphoshino)biphenyl coordinating
moiety with an anionic amidosulfate solubilizing tag gives rise to
an active palladium catalyst for SuzukieMiyaura cross-coupling of
N-Boc protected 4-halophenylalanines with aromatic boronic acids.
A thorough survey of the reaction parameters revealed the need for
a careful optimization of the reaction conditions such as the sol-
vent, base additive and palladium source to ensure good yields of
the coupling products in the aforementioned reaction. Under the
optimized conditions, the biaryl coupling could be performed with
high to complete conversions and very good isolated yields in water
or a 1:1 water-N,N-dimethylformamide mixture over practical re-
action times and with negligible loss of the target product due to
unwanted removal of the amine protecting group.
(s). IR (Nujol): 2935 s, 2920 m, 2893 w, 2857 m, 1760 vs, 1604 w,
1521 vs, 1476 vw, 1446 w, 1254 m, 1239 s, 1183 m, 1147 v, 1051 vs,
1021 m, 1003 s, 991 s, 851 m, 755 s, 701 w cmꢁ1. MS (ESIþ): m/z
583.1 ([M þ Na]þ), 561.2 ([M þ H]þ). Anal. Calcd. for C31H30PO2F5: C
66.42, H 5.39%. Found: C 66.66, H 5.41%.
Preparation of triethylammonium 2-(dicyclohexylphosphino)-40-
{[(sulfonatomethyl)amino]carbonyl}biphenyl (3)
A reaction flask equipped with a stirring bar was charged with
active ester 2 (0.56 g, 1.0 mmol), aminomethanesulfonic acid
(0.17 g, 1.5 mmol) and 4-(dimethylamino)pyridine (6 mg,
0.05 mmol), flushed with argon and sealed with a septum. The solid
educts were suspended in the mixture of anhydrous N,N-dime-
thylformamide (10 mL), dichloromethane (2 mL) and triethylamine
(2 mL), and the reaction mixture was stirred overnight. The
resulting transparent solution was evaporated to dryness and the
crude product was isolated by flash chromatography (silica gel,
dichloromethane/methanol/triethylamine, 20:1:1 v/v). Subsequent
crystallization from hot ethyl acetate afforded solvated salt
3,½AcOEt as a white crystalline solid. Yield 0.55 g (87%).
Experimental
Materials and methods
2-(Dicyclohexylphosphino)biphenyl-40-carboxylic acid (1) was
prepared according to the literature procedure [8]. Dichloro-
methane was dried over potassium carbonate and distilled under
argon. Distilled water was saturated with argon prior to the cata-
lytic experiments. Anhydrous N,N-dimethylformamide (Sigma-
eAldrich) and other solvents (Lachner, Czech Republic) were used
as received. 1H NMR spectra were recorded at 25 ꢀC on a Varian
UNITY Inova 400 spectrometer (1H 399.95 MHz, 13C{1H}
100.58 MHz, 19F 376.29 MHz, and 31P{1H} 161.90 MHz). Chemical
1H NMR (DMSO-d6):
d 0.86e1.29 (m, 10H, PCy2), 1.17 (t,
3JHH ¼ 7.3 Hz, 9H, CH3 of Et3NHþ), 1.42e1.2 (m, 2H), 1.53e1.68 (m,
8H), and 1.80e1.89 (m, 2H, PCy2); 3.09 (q, 3JHH ¼ 7.3 Hz, 6H, CH2 of
3
Et3NHþ), 4.16 (d, JHH ¼ 6.3 Hz, 2H, SCH2N), 7.24e7.32 (m, 3H),
7.39e7.46 (m, 2H), 7.62e7.67 (m,1H), 7.87e7.93 (m, 2H,C12H8); 8.65
shifts (
13C), external neat CFCl3
31P). Electrospray ionization mass spectra (ESI-MS) were recorded
d
/ppm) are given relative to internal tetramethylsilane (1H;
19F), or to external 85% aqueous H3PO4
(t, 3JHH ¼ 6.3 Hz, 1H, NH). 13C{1H} NMR (DMSO-d6):
d 8.60 (9C, CH3
(
of Et3NHþ), 25.91 (2C), 26.37 (2C), 26.46 (d, JPC ¼ 5 Hz, 2C), 28.96 (d,
JPC ¼ 9 Hz, 2C), 30.14 (d, JPC ¼ 18 Hz, 2C), and 34.02 (d, JPC ¼ 15 Hz,
2C) (PCy2); 45.70 (6C, CH2 of Et3NHþ), 55.84 (SCH2N), 126.49,
127.08, 128.55, 129.68 (d, JPC ¼ 5 Hz), 130.20 (d, JPC ¼ 5 Hz), 132.39,
132.89 (d, JPC ¼ 3 Hz), 133.58 (d, JPC ¼ 23 Hz), 145.16 (d, JPC ¼ 6 Hz),
and 149.13 (d, JPC ¼ 29 Hz) (C12H8); 165.31 (C]O). 31P{1H} NMR
(
with Bruker Esquire 3000 or Finnigan LCQ Deca spectrometers
using solutions in HPLC-grade methanol. Infrared spectra were
collected on a Thermo Nicolet AVATAR 370 FT-IR instrument in the
range 400e4000 cmꢁ1
.
The samples were diluted with
spectroscopy-grade KBr and the spectra were recorded in diffuse
reflectance (DRIFT) mode.
(DMSO-d6):
d
ꢁ13.1 (s). IR (KBr): 3318 m, 3046 w, 3001 w, 2968 w,
2926 vs, 2848 s, 2758 v, 2684 m, 2558 w, 2519 w, 2489 w, 1655 s,
Please cite this article in press as: J. Schulz, et al., Journal of Organometallic Chemistry (2015), http://dx.doi.org/10.1016/
j.jorganchem.2015.01.020

6
J. Schulz et al. / Journal of Organometallic Chemistry xxx (2015) 1e8
1610 w, 1583 w, 1544 s, 1503 m, 1476 m, 1470 m, 1449 m, 1389 m,
1329 s, 1287 m, 1254 m, 1201 vs, 1159 vs, 1042 vs, 1009 m, 854 m,
749 s, 740 mw, 662 m, 611 m, 528 s, 501 m cmꢁ1. MS (ESIꢁ): m/z
485.9 ([M ꢁ HNEt3]ꢁ). Anal. Calcd. for C32H49PO4N2S,½AcOEt: C
64.53, H 8.44, N 4.43%. Found: C 64.16, H 8.33, N 4.48%.
layer was analyzed by NMR spectroscopy. For isolation of the
coupling product, the aqueous layer was extracted with ethyl ac-
etate (2 ꢂ 5 mL) and the combined organic layers were washed
with brine (10 mL), dried over MgSO4 and evaporated under
reduced pressure. The products were purified by column chro-
matography over silica gel column using dichloromethane-
methanol (20:1 v/v) as the eluent and, following evaporation
under reduced pressure, were isolated as white solids. Amino
acids 6 often tend to retain traces of dichloromethane used during
the chromatography, which cannot be removed even upon pro-
longed evacuation. The amount of the residual solvent was always
verified by NMR analysis.
Synthesis of racemic N-Boc-4-chlorophenylalanine (4a)
Racemic 4-chlorophenylalanine (10.0 g, 50 mmol) and sodium
hydroxide (6.0 g, 150 mmol) were dissolved in distilled water
(150 mL) in a round-bottom flask equipped with a stirring bar and a
dropping funnel. The reaction mixture was cooled in ice and a so-
lution of di-tert-butyl dicarbonate (13.1 g, 60 mmol) in tetrahy-
drofurane (150 mL) was slowly introduced from the dropping
funnel. The resulting mixture was allowed to warm to room tem-
perature and then stirred overnight. The resulting solution was
transferred into a separatory funnel and washed twice with diethyl
ether (100 mL). The aqueous phase was acidified with 3 M aqueous
citric acid to pH 4e5 and the obtained suspension was extracted
with dichloromethane (3 ꢂ 150 mL). The combined organic extracts
were washed with brine, dried over anhydrous MgSO4, filtered and
evaporated under reduced pressure to give 4a as a white solid.
Yield: 13.8 g (92%).
Analytical data for the cross-coupling products 6
Rac-2-{[(tert-butyloxy)carbonyl]amino}-3-(biphenyl-4-yl)propionic
acid (6a)
White solid. 1H NMR (DMSO-d6):
d 1.33 (s, 9H, CH3), 2.78e3.09
(m, 2H, CH2), 4.01e4.17 (m, 1H, CH), 7.14 (d, 3JHH ¼ 8.4 Hz, 1H, NH),
7.33e7.37 (m, 3H, C12H8), 7.43e7.47 (m, 2H, C12H8); 7.57e7.59 (m,
2H, C12H8), 7.63e7.65 (m, 2H, C12H8), 12.62 (br s, 1H, CO2H). 13C{1H}
NMR (DMSO-d6):
d 28.1, 36.0, 55.1, 78.1, 126.4, 126.5, 127.2, 127.3,
1H NMR (DMSO-d6):
d 1.32 (s, 9H, CMe3), 2.74e3.05 (m, 2H,
128.9, 129.7, 134.5, 137.3, 138.2, 140.0, 155.5, 173.6. MS (ESIꢁ): m/z
340.0 ([M ꢁ H]ꢁ). The data are in accordance with the literature
[21].
CH2), 3.97e4.12 (m, 1H, CH), 7.11 (d, 3JHH ¼ 8.5 Hz, 1H, NH), 7.27 (d,
3JHH ¼ 8.4 Hz, 2H, C6H4); 7.33 (d, 3JHH ¼ 8.4 Hz, 2H, C6H4),12.64 (br s,
1H, CO2H). 13C{1H} NMR (DMSO-d6):
d 28.03 (9C, CMe3), 35.66
(CH2), 54.84 (CH), 77.98 (CMe3), 127.94 (2C), 130.90 (2C), and 136.99
(C6H4); 155.33 (C]O), 173.27 (CO2H). One of the C6H4 carbons was
not found. MS (ESIꢁ): m/z 299.1 ([M ꢁ H]ꢁ). Anal. Calcd. for
Rac-2-{[(tert-butyloxy)carbonyl]amino}-3-(20-methylbiphenyl-4-
yl)propionic acid (6b)
Colorless viscous oil. 1H NMR (DMSO-d6):
d 1.33 (s, 9H, CH3),
C
14H18ClNO4: C 56.09, H 6.05, N 4.67%. Found: C 55.99, H 6.07, N
2.22 (s, 3H, CH3), 2.78e3.12 (m, 2H, CH2), 4.03e4.21 (m, 1H, CH),
7.12e7.19 (m, 2H, C12H8 and NH), 7.20e7.36 (m, 7H, C12H8),12.65 (br
4.60%.
s, 1H, CO2H). 13C{1H} NMR (DMSO-d6):
d 20.15 (CH3), 28.13 (9C,
Synthesis of racemic N-Boc-4-bromophenylalanine (4b)
CH3), 36.19 (CH2), 55.00 (CH), 78.00 (CMe3), 125.88, 127.14, 128.67,
128.95, 129.45, 130.29, 134.66, 136.66, 139.22, 141.11 (C12H8); 155.45
(C]O),173.60 (CO2H). MS (ESIꢁ): m/z 354.0 ([M ꢁ H]ꢁ). Anal. Calcd.
for C21H25NO4,0.1CH2Cl2: C 69.64, H 6.98, N 3.85%. Found: C 69.62,
H 7.05, N 3.64%.
Compound 4b was prepared similarly to 4a starting from
racemic 4-bromophenylalanine (5.0 g, 20.4 mmol) and sodium
hydroxide (2.5 g, 61.2 mmol) in distilled water (75 mL), and di-tert-
butyl dicarbonate (5.4 g, 24.7 mmol) in tetrahydrofurane (75 mL),
and was isolated as a white solid. Yield 6.1 g (87%).
1H NMR (DMSO-d6):
d 1.32 (s, 9H, CH3), 2.70e3.04 (m, 2H, CH2),
Rac-2-{[(tert-butyloxy)carbonyl]amino}-3-(30-methylbiphenyl-4-
3
3.97e4.12 (m, 1H, CH), 7.11 (d, JHH ¼ 8.4 Hz, 1H, NH), 7.21 (d,
yl)propionic acid (6c)
3JHH ¼ 8.3 Hz, 2H, Ph), 7.47 (d, 3JHH ¼ 8.3 Hz, 2H, Ph); 12.64 (br s, 1H,
White solid. 1H NMR (DMSO-d6):
d 1.33 (s, 9H, CH3), 2.37 (s, 3H,
CO2H). 13C{1H} NMR (DMSO-d6):
d 28.02 (9C, CH3), 35.70 (CH2),
CH3), 2.78e3.08 (m, 2H, CH2), 4.01e4.16 (m, 1H, CH), 7.09e7.18 (m,
2H, C12H8 and NH), 7.29e7.37 (m, 3H, C12H8), 7.39e7.47 (m, 2H,
54.77 (CH), 77.98 (CMe3), 119.4, 130.86 (2C), 131.3 (2C), 137.4 (C6H4),
155.3 (C]O), 173.2 (CO2H). MS (ESIꢁ): m/z 343.0 ([M ꢁ H]ꢁ). Anal.
Calcd. for C14H18BrNO4: C 48.85, H 5.27, N 4.07%. Found: C 48.81, H
5.19, N 3.85%.
C
12H8), 7.53e7.59 (m, 2H, C12H8), 12.64 (br s, 1H, CO2H). 13C{1H}
NMR (DMSO-d6):
d 21.07 (CH3), 28.09 (9C, CH3), 36.00 (CH2), 55.09
(CH), 78.01 (CMe3), 123.57, 126.35, 127.13, 127.81, 128.72, 129.58,
137.18, 137.93, 138.27, 139.91 (C12H8); 155.42 (C]O), 173.51 (CO2H).
MS (ESIꢁ): m/z 354.0 ([M
21H25NO4,0.05CH2Cl2: C 70.29, H 7.03 N 3.90%. Found: C 70.53, H
7.07, N 3.77%.
ꢁ
H]ꢁ). Anal. Calcd. for
SuzukieMiyaura cross-coupling of protected amino acids 4a and 4b
with boronic acids 5
C
The respective palladium precursor (5
mmol of Pd) and ligand 3
(2.9 mg, 5 mol; unless noted otherwise) were placed into a
Schlenk tube and dissolved in dichloromethane (0.5 mL). The
mixture was stirred for 15 min and then evaporated under vac-
m
Rac-2-{[(tert-butyloxy)carbonyl]amino}-3-(40-methylbiphenyl-4-
yl)propionic acid (6d)
uum. The appropriate protected halogenated amino acid
4
White solid. 1H NMR (DMSO-d6):
d 1.32 (s, 9H, CH3), 2.33 (s, 3H,
(0.50 mmol), boronic acid (0.55 mmol) and base (2.0 mmol) were
added to the Schlenk tube, and the reaction vessel was degassed
by three vacuumeargon cycles, filled with argon and sealed with a
rubber septum. Degassed solvent (3 mL) was introduced and the
reaction vessel was placed into a pre-heated oil bath. After stirring
for 4 h, the reaction was terminated by cooling in ice and simul-
taneous addition of 3 M aqueous HCl (3 mL), ethyl acetate (3 mL)
and mesitylene (0.50 mmol; an internal standard). The organic
CH3), 2.76e3.08 (m, 2H, CH2), 4.01e4.16 (m, 1H, CH), 7.12 (d,
3JHH ¼ 8.3 Hz, 1H, NH), 7.24e7.26 (m, 2H, C12H8), 7.30e7.32 (m, 2H,
C
12H8), 7.51e7.56 (m, 4H, C12H8), 12.63 (br s, 1H). 13C{1H} NMR
(DMSO-d6):
d 20.64 (CH3), 28.14 (9C, CH3), 36.05 (CH2), 55.16 (CH),
78.05 (CMe3), 126.14, 126.31, 129.48, 129.64, 136.48, 136.99, 137.10,
138.11 (C12H8); 155.47 (C]O), 173.57 (CO2H). MS (ESIe): m/z 354.0
([M ꢁ H]ꢁ). Anal. Calcd. for C21H25NO4: C 70.96, H 7.09, N 3.94%.
Found: C 71.23, H 7.31, N 3.51%.
Please cite this article in press as: J. Schulz, et al., Journal of Organometallic Chemistry (2015), http://dx.doi.org/10.1016/
j.jorganchem.2015.01.020

J. Schulz et al. / Journal of Organometallic Chemistry xxx (2015) 1e8
7
Rac-2-{[(tert-butyloxy)carbonyl]amino}-3-(40-methoxybiphenyl-4-
diffractions and R ¼ 6.57% and wR ¼ 9.88% for all data. Extremes on
yl)propionic acid (6e)
the residual electron density map were 0.33 and ꢁ0.42e Åꢁ3
.
White solid. 1H NMR (DMSO-d6):
d
1.33 (s, 9H, CH3), 2.75e3.08
Geometric data and all structural drawings were obtained with
a recent version of the PLATON program [24]. The numerical values
are rounded with respect to their estimated standard deviations
(ESDs) given with one decimal. Parameters pertaining to atoms in
constrained positions are given without ESDs.
(m, 2H, CH2), 3.79 (s, 3H, CH3O), 3.99e4.16 (m, 1H, CH), 6.99e7.02
3
(m, 2H, C6H4), 7.07 (d, JHH ¼ 8.4 Hz, 1H, NH), 7.29e7.31 (m, 2H,
C6H4); 7.51e7.53 (m, 2H, C6H4), 7.56e7.59 (m, 2H, C6H4), 12.67 (br s,
1H, CO2H). 13C{1H} NMR (DMSO-d6):
d 28.15 (9C, CH3); 36.06 (CH2),
55.14 (CH3O), 55.23 (CH); 78.02 (CMe3), 114.31, 125.89, 127.55,
129.63, 132.37, 136.57, 137.86 (C12H8); 155.4 (C]O), 158.74
(CeOMe), 173.61 (CO2H). MS (ESIe): m/z 370.0 ([M ꢁ H]ꢁ). The data
are in agreement with the literature [22].
Acknowledgments
This research was financially supported by the Czech Science
Foundation (Project No. 13-08890S).
Rac-2-{[(tert-butyloxy)carbonyl]amino}-3-(40-cyanobiphenyl-4-yl)
Appendix A. Supplementary data
propionic acid (6f)
White solid. 1H NMR (DMSO-d6):
d 1.32 (s, 9H, CH3), 2.80e3.14
(m, 2H, CH2), 4.02e4.18 (m, 1H, CH), 7.16 (d, 3JHH ¼ 8.4 Hz, 1H, NH),
7.39 (d, 3JHH ¼ 8.3 Hz, 2H, C12H8), 7.68 (d, 3JHH ¼ 8.3 Hz, 2H, C12H8),
7.85e7.92 (m, 4H, C12H8), 12.57 (br s, 1H, CO2H). 13C{1H} NMR
CCDC 1040352 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge from
The Cambridge Crystallographic Data Centre via the Internet at
http://www.ccdc.cam.ac.uk.
(DMSO-d6): d 28.04 (9C, CH3), 35.98 (CH2), 54.93 (CH), 77.99 (CMe3),
109.71, 118.81 (C^N), 126.73, 127.24, 129.87, 132.73, 136.16, 138.84,
144.37 (C12H8); 155.39 (C]O), 173.41 (CO2H). MS (ESIꢁ): m/z 365.0
([M ꢁ H]ꢁ). Anal. Calcd. for C21H22N2O4,0.05CH2Cl2: C 68.21, H 6.01,
N 7.56%. Found: C 67.90, H 6.12, N 6.93%.
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d 1.32 (s, 9H, CH3),
2.80e3.14 (m, 2H, CH2), 4.02e4.18 (m,1H, CH), 7.17 (d, 3JHH ¼ 8.5 Hz,
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3
1H, NH), 7.40e7.43 (d, JHH ¼ 8.2 Hz, 2H, C12H8), 7.72e7.74 (d,
3JHH ¼ 8.2 Hz, 2H, C12H8), 7.94e7.76 (m, 2H, C12H8), 8.28e8.31 (m,
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5359;
2H, C12H8), 12.63 (br s, 1H, CO2H). 13C{1H} NMR (DMSO-d6):
d 28.08
(9C, CH3), 35.99 (CH2), 54.91 (CH), 78.0 (CMe3), 123.99, 126.93,
127.49,129.93,135.72,139.21,146.36,146.42 (C12H8); 155.39 (C]O),
173.38 (CO2H). MS (ESIꢁ): m/z 385.0 ([M ꢁ H]ꢁ). Anal. Calcd. for
C
20H22N2O6,0.1CH2Cl2: C 61.13, H 5.67, N 7.10. %. Found: C 61.33, H
5.64, N 6.97%.
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X-ray crystallography
Single crystals of 3 suitable for X-ray diffraction analysis were
obtained
from
hot
acetonitrile
(colorless
plate,
0.06 ꢂ 0.29 ꢂ 0.48 mm3). The diffraction data (qmax ¼ 27.5ꢀ; data
completeness: 100%) were collected with a Nonius Kappa CCD
diffractometer equipped with an APEX-II CCD detector (Bruker) and
a Cryostream Cooler (Oxford Cryosystems) at 150(2) K using
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[8] K. Glegoła, E. Framery, K.M. Pietrusiewicz, D. Sinou, Adv. Synth. Catal. 348
(2006) 1728.
graphite monochromated MoK
were corrected for absorption using routines included in the
diffractometer software.
a
radiation (
l
¼ 0.71073 Å). The data
The structure was solved by direct methods (SHELXS97) and
refined by full-matrix least squares based on F2 (SHELXL97) [23]. All
non-hydrogen atoms were refined with anisotropic displacement
parameters. Hydrogen atoms residing at the nitrogen atoms (NH
protons) were identified on the difference electron density map
and refined as riding atoms with Uiso(H) ¼ 1.2 Ueq(N). Hydrogens
bonding to the carbon atoms were included in their calculated
positions and refined analogously. Relevant crystallographic data
and structure refinement parameters for 3 are as follows.
[9] R. Sayah, K. Glegoła, E. Framery, V. Dufaud, Adv. Synth. Catal. 349 (2007) 373.
ꢀ
ꢀ
ꢁ
ꢀ
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[10] J. Schulz, I. Císarova, P. Stepnicka, Organometallics 31 (2012) 729.
ꢀ
ꢀ
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C
32H49N2O4PS (588.76 g molꢁ1), monoclinic, space group C2/c
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b
m
¼ 109.110(2)ꢀ, V ¼ 6344.0(5) Å, Z ¼ 8, Dcalc ¼ 1.233 g cmꢁ3
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according to the Io ꢃ 2
s(Io) criterion. The refinement converged (D/
s
< 0.001 for 364 parameters) with R ¼ 4.08% for the observed
Please cite this article in press as: J. Schulz, et al., Journal of Organometallic Chemistry (2015), http://dx.doi.org/10.1016/
j.jorganchem.2015.01.020

8
J. Schulz et al. / Journal of Organometallic Chemistry xxx (2015) 1e8
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Please cite this article in press as: J. Schulz, et al., Journal of Organometallic Chemistry (2015), http://dx.doi.org/10.1016/
j.jorganchem.2015.01.020