Synthesis of Phosphanylferrocenecarboxamides Bearing Guanidinium Substituents and Their Application in the Palladium-Catalyzed Cross-Coupling of Boronic Acids with Acyl Chlorides

Article abstract of DOI:10.1002/ejic.201600461

Phosphanylferrocene donors bearing polar guanidinium substituents, namely acylguanidinium chloride, [Ph₂PfcCONHC(NH₂)NH₂]Cl (1), and amidoguanidinium chloride, [Ph₂PfcCONHCH₂CH₂NHC(NH₂)NH₂]Cl (2; fc = ferrocene-1,1′-diyl), have been prepared and characterized. As functional phosphane donors, they were employed in the synthesis of Pd^IIcomplexes bearing 2-[(dimethylamino)methyl-κN]phenyl-κC¹(L^NC) and η³-allyl supporting ligands, [(L^NC)PdCl(L-κP)] and [(η³-C₃H₅)PdCl(L-κP)] (L = 1 and 2), respectively. These defined complexes as well as their surrogates generated in situ from the respective palladium(II) precursor and the phosphanylferrocene ligand were evaluated as catalysts for the coupling of boronic acids with acyl chlorides to give ketones in an aqueous biphasic system. The coupling reaction proceeded best with a simple catalyst formed from Pd(OAc)₂and ligand 2, which (at 0.2 mol-% Pd loading) produced substituted benzophenones from benzoyl chlorides and benzeneboronic acids in very good yields. These yields could then be further improved by a proper choice of the reaction partners. Analogous reactions involving aliphatic substrates generally afforded lower yields.

Full text of DOI:10.1002/ejic.201600461

DOI: 10.1002/ejic.201600461
Full Paper
Palladium Catalysts
Synthesis of Phosphanylferrocenecarboxamides Bearing
Guanidinium Substituents and Their Application in the
Palladium-Catalyzed Cross-Coupling of Boronic Acids with Acyl
Chlorides
Hana Charvátová,[a] Ivana Císařová,[a] and Petr Štěpnička*[a]
Abstract: Phosphanylferrocene donors bearing polar guanidin- respective palladium(II) precursor and the phosphanylferrocene
ium substituents, namely acylguanidinium chloride, [Ph2PfcCO- ligand were evaluated as catalysts for the coupling of boronic
NHC(NH2)NH2]Cl (1), and amidoguanidinium chloride, acids with acyl chlorides to give ketones in an aqueous biphasic
[Ph2PfcCONHCH2CH2NHC(NH2)NH2]Cl (2; fc = ferrocene-1,1′- system. The coupling reaction proceeded best with a simple
diyl), have been prepared and characterized. As functional catalyst formed from Pd(OAc)2 and ligand 2, which (at 0.2 mol-
phosphane donors, they were employed in the synthesis of PdII % Pd loading) produced substituted benzophenones from
complexes bearing 2-[(dimethylamino)methyl-κN]phenyl-κC1 benzoyl chlorides and benzeneboronic acids in very good
(LNC) and η3-allyl supporting ligands, [(LNC)PdCl(L-κP)] and [(η3- yields. These yields could then be further improved by a proper
C3H5)PdCl(L-κP)] (L = 1 and 2), respectively. These defined com- choice of the reaction partners. Analogous reactions involving
plexes as well as their surrogates generated in situ from the aliphatic substrates generally afforded lower yields.
Introduction
The guanidine moiety in its native or protonated (i.e., guanidin-
ium) form is an integral part of many important naturally occur-
ring and biologically active compounds.[1] Because of their
highly polar and hydrophilic nature, guanidine substituents
have also been employed as modifying moieties in the prepara-
tion of water-soluble phosphane ligands suitable for use in tran-
sition-metal-catalyzed organic reactions performed in aqueous
media.[2] Representative examples of such compounds include
hydrophilic triphenylphosphane derivatives equipped with
guanidinium substituents (type A and B in Scheme 1),[3] analo-
gous donors with guanidinopropyl groups (C in Scheme 1),[4]
and guanidinium-tagged BINAP (D in Scheme 1).[5,6] Related
acylguanidine derivatives (e.g., E and F in Scheme 1) have been
also reported, being studied as constituents of supramolecular
transition-metal catalysts.[7]
As a continuation of our work focused on the preparation of
phosphanylferrocenecarboxamides bearing polar substituents
at the amide nitrogen atom and their catalytic applications in
aqueous reaction media,[8] we decided to employ the approach
outlined above and prepare phosphanylferrocene donors pos-
Scheme 1. Examples of phosphane donors with guanidinium substituents.
sessing terminal guanidinium groups.
Although there appears to be no reports in the literature
describing the application of such an approach to the prepara-
tion of functionalized phosphanylferrocene donors,[9] com-
pounds in which guanidine or guanidinium moieties are cova-
[a] Charles University in Prague,
lently attached to the ferrocene moiety are not unprecedented.
Hlavova 2030, 12840 Prague 2, Czech Republic
E-mail: stepnic@natur.cuni.cz
Supporting information and ORCID(s) from the author(s) for this article are
available on the WWW under http://dx.doi.org/10.1002/ejic.201600461.
For example, simple N-(ferrocenylmethyl)guanidinium salts[10]
and other guanidines with bridging ferrocene groups have
been extensively studied as sensors for anions, cations, and
Eur. J. Inorg. Chem. 0000, 0–0
1
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
amino acids.[11] More recently, a series of (ferrocenylmethyl)- ciently removed by evaporation and must be washed out by
and (ferrocenylcarbonyl)guanidinium chlorides were studied as repeated extractions of the reaction mixture with water. Follow-
complexing agents for carboxylate anions,[12] and in another ing evaporation (at 25 °C), the crude product containing trieth-
report Siemeling and co-workers[13] demonstrated that ferro- ylamine hydrochloride was taken up in THF in which most of
cenebis(guanidines) of the type [Fe{η5-C5H4NC(NR2)2}2] are su- the NEt3·HCl remained undissolved and then purified by col-
perbases capable of N,Fe,N coordination to PdII.
umn chromatography. The yield of this one-step procedure is
typically ca. 50 %.
In this contribution we describe the synthesis and structural
characterization of two new guanidinium-modified phosphanyl-
ferrocene ligands (1 and 2 in Scheme 2) that differ in the nature
of the functional pendant (acylguanidinium vs. alkylguanidin-
ium salts) and the presence of an aliphatic spacer. Furthermore,
we report the results of a catalytic evaluation of these ligands
in the palladium-catalyzed cross-coupling of acyl chlorides with
arylboronic acids to afford ketones.
Scheme 2. Target (phosphanylferrocenylacyl)guanidinium salts 1 and 2.
Scheme 4. Alternative syntheses of ligand 2 {HOBt = 1-hydroxybenzotriazole,
EDC = 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide}.
Results and Discussion
Synthesis of the Ligands and Complexes Thereof
As an alternative (route B in Scheme 4), phosphane 2 was
obtained by the guanylation of phosphanylamine 4 with 1H-
pyrazole-1-carboximidamide hydrochloride.[18,19] Amine 4 was
accessed by the reaction of 3 with 1,2-diaminoethane and is
better stored in the form of the more stable hydrochloride
4·HCl, which is easily prepared by the addition of methanolic
HCl and can be converted back into the free amine through the
reaction with triethylamine (the crystal structure of 4·HCl was
determined and is discussed in the Supporting Information).
Notably, the synthesis of 4 had to be carried out in a relatively
dilute solution and with an excess of the diamine to avoid the
formation of the bis(amide) (Ph2PfcCONHCH2)2 (fc = ferrocene-
1,1′-diyl), which cannot be easily separated from 4 by chroma-
tography due to similar retention characteristics [note that
amidation of Hdpf with 1,2-diaminoethane in the presence of
HOBt/EDC could not be used to prepare 4 directly as it affords
the above-mentioned bis(amide) as the sole product[20]]. The
overall yield achieved by route B was slightly lower (ca. 45 %)
than that obtained by the direct route A, but the two-step pro-
cedure is more practical, mainly because of easier product isola-
tion.
Compound 1 was obtained (Scheme 3) by the reaction of acyl-
benzotriazole 3[14] with guanidine generated in situ from its
hydrochloride and NaOH. The intermediate acylguanidine was
purified by column chromatography and immediately con-
verted into the more stable and better-crystallizing hydrochlor-
ide by the addition of HCl. Amorphous hydrochloride 1 ob-
tained by simple evaporation was then treated with methanol,
which induced the rapid separation of air-stable, red microcrys-
talline solvate 1·1/2MeOH in 69 % yield.
Scheme 3. Synthesis of 1 from acylbenzotriazole 3.
Ligand 2 possessing an alkylguanidinium pendant and an
extended amidoalkyl spacer group was synthesized by two dif-
The electrospray ionization (ESI) mass spectra of 1 and 2
ferent methods. The first one (route A in Scheme 4) made use confirmed the formulation through the peaks arising from the
of the standard amide coupling reaction[15] between 1′-(di- respective cations (i.e., [M – Cl]+). The NMR spectra show reso-
phenylphosphanyl)ferrocene-1-carboxylic acid (Hdpf)[16] and N- nances typical of the (diphenylphosphanyl)ferrocenyl moiety
(2-aminoethyl)guanidine hydrochloride liberated from the re- along with those of the functional pendants. Thus, the signals
spective dihydrochloride[17] with 1 mol-equiv. of triethylamine. of the 1,2-ethanediyl linker in 2 are observed as a multiplet
However, for solubility reasons, the coupling reaction had to be (δH = 3.29–3.50 ppm) in the 1H NMR spectrum and a pair of
carried out in a mixture of DMF and dichloromethane, which singlets at δC = 38.98 and 41.03 ppm in the 13C NMR spectrum.
complicated the isolation of the product. Because the product The 13C NMR signals of the amide and guanidinium carbon at-
decomposes at elevated temperatures, DMF cannot be effi- oms in 1 are observed at δC = 155.12 and 171.38 ppm, respec-
Eur. J. Inorg. Chem. 0000, 0–0
www.eurjic.org
2
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
tively, and those of 2 appear at δC = 157.72 and 172.34 ppm. Catalytic Experiments
The presence of these polar moieties is further manifested by
Suzuki–Miyaura-type cross-coupling reactions of acyl chlorides
with organoboron reagents represent an alternative synthetic
route towards ketones (Scheme 6),[21] which becomes particu-
larly useful when conventional methods such as the Friedel–
Crafts acylation or the oxidation of secondary alcohols cannot
be utilized due to their generally low functional-group toler-
ance. This reaction, advantageously performed in aqueous reac-
tion media, was chosen to evaluate the catalytic potential of
the newly prepared ligands and their complexes.
characteristic vibrations in the IR spectra (see the Exp. Sect.).
Finally, the 31P NMR resonances observed at δP = –19.0 ppm
(in DMSO) and –17.5 ppm (in CDCl3) for 1 and 2, respectively,
corroborate the presence of intact phosphane groups in both
compounds.
Compounds 1 and 2 were employed in the synthesis of PdII
complexes with auxiliary [2-(dimethylamino-κN)methyl]phenyl-
κC1 (LNC) and η3-allyl ligands by bridge-cleavage reactions of
the respective dinuclear precursors (Scheme 5). The resulting
complexes were isolated as air-stable solids, but – like the free
ligands – they tended to retain residual solvents in their struc-
tures and could not be purified by crystallization.
Scheme 6. Cross-coupling reactions of boronic acids with acyl chlorides to
give ketones (note that screening experiments were performed in benzene/
water).
All the catalytic reactions were performed with an excess
(1.2 equiv.) of acyl chloride as this can be partially hydrolyzed
in the reaction mixture and in the presence of a stoichiometric
amount of Na2CO3 as base. The initial experiments aimed at
finding the best catalyst were performed in a C6D6/water mix-
ture for the cross-coupling of benzoyl chloride (9a) with 4-
fluorophenylboronic acid (10f) to give 4-fluorobenzophenone
(11f), which allowed easy monitoring by 19F NMR spectroscopy.
The coupling reactions were performed at 50 °C for 1 h using
both the defined (5–8) and in situ generated (pre)catalysts at
the same 0.2 mol-% palladium loading (Table 1).
An inspection of the data in Table 1 shows that with the
exception of compound 8, the defined LNCPdII and (η3-allyl)PdII
complexes are more active catalysts than their in situ generated
analogues. Furthermore, the results reveal that catalysts based
on ligand 2 perform consistently better than their respective
counterparts containing donor 1.
Changing the reaction solvent to pure water reduced the
yield of the coupling product for all the defined catalysts. The
most significant decrease, by as much as 56 %, was noted in
the case of complex 8. Lowering the reaction temperature to
25 °C also had a detrimental effect on the reaction outcome
(see the results for catalyst 6).
Scheme 5. Synthesis of PdII complexes 5–8.
The presence of the supporting ligands in 5–8 was mani-
fested by signals in their 1H NMR spectra arising from the ortho-
palladated benzylamine (two broad singlets from the CH2 and
NMe2 protons and four multiplets from the aromatic protons)
and the π-coordinated allyl ligand (five more or less broadened
signals). The signals in the 31P NMR spectra shift to lower field
upon coordination, to δP ≈ 32–33 ppm for complexes 5 and 6
and to δP ≈ 13–15 ppm for 7 and 8. Finally, the ESI+ mass
spectra of 5–8 show fragment ions resulting from the simulta-
Next, we evaluated the catalysts generated in situ from palla-
neous elimination of HCl and the Pd-bound chloride (i.e., [M – dium(II) acetate as a common metal precursor for various Pd-
Cl – HCl]+).
catalyzed organic reactions. Indeed, the reaction mediated by
Table 1. Results of the screening experiments.[a]
Catalyst
Yield of 11f [%][b]
Catalyst
Yield of 11f [%][b]
[(LNC)PdCl]2/1
5
33
[(LNC)PdCl]2/2
6
75
78 (71[c]
43
)
)
90 (70,[c] 55[d]
96
)
[(η3-C3H5)PdCl]2/1
7
[(η3-C3H5)PdCl]2/2
8
95 (77[c]
62
85 (29[c]
98
98
)
Pd(OAc)2/1[e]
Pd(OAc)2/1[f]
Pd(OAc)2
Pd(OAc)2/2[e]
Pd(OAc)2/2[f]
78
68[g]
[a] Reagents and conditions: 9a (3.0 mmol), 10f (2.5 mmol), Na2CO3 (2.5 mmol), catalyst (0.2 mol-% Pd), C6D6/water (3 mL:3 mL), 50 °C, unless noted otherwise.
[b] Determined by integration of the 19F NMR spectrum. [c] Reaction in pure water. [d] Reaction at 25 °C. [e] Pd/ligand = 1:1.2. [f] Pd/ligand = 1:2.2. [g]
Reaction in the absence of any supporting ligand.
Eur. J. Inorg. Chem. 0000, 0–0
www.eurjic.org
3
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
this salt alone afforded a decent 68 % yield of 11f under the cf. Entries 2–4 and 16–18 in Table 2). In the case of the products
standard conditions. However, the addition of ligand 2 to the 4-methoxy- and 4-chlorobenzophenone, the reactions of the
reaction system markedly improved the yield of the coupling
product (at both 1:1.2 and 1:2.2 Pd/ligand ratios), yielding prac-
tically complete conversion of the boronic acid 10f into benzo-
phenone 11f. Similar experiments with ligand 1 provided some-
what conflicting results. An addition of 1.2 equiv. of ligand 1 to
Pd(OAc)2 slightly decreased the yield of the coupling product,
whereas the reaction in the presence of 2.2 equiv. of 1 afforded
an approximately 10 % better yield of 11f than that obtained
without any added supporting ligand [i.e., with Pd(OAc)2 alone;
see Table 1].
respective substituted boronic acids with 9a also gave better
yields than the coupling of 10a with substituted benzoyl chlor-
ides (Entries 5, 7, 19, 20). An inverted situation was observed
for the reactions leading to 4-nitrobenzophenone (11j); the re-
action involving substituted acyl chloride 9j and 10a afforded
a better yield by nearly 50 % (on the absolute scale) than the
reaction between the substituted boronic acid 10j and 9a. This
difference, however, very likely reflects the low solubility of 10j
in the reaction mixture that prevents efficient coupling.
The formal transposition of the substituent becomes particu-
larly important in the case of “difficult” substrates. This is exem-
plified by the reactions leading to trans-chalcone (11l) and par-
ticularly to 1,3-diphenylpropanone (11m). Thus, the former
product was isolated in 71 % yield from the reaction of styryl-
boronic acid (10l) with 9a and in a lower 60 % yield from the
reaction between cinnamoyl chloride (9l) and phenylboronic
acid (10a). The product 11m, in which one of the coupled
carbon atoms is sp3-hybridized, ensued in a 25 % yield from the
reaction of 3-phenylpropionyl chloride (9m) with 10a, whereas
the reaction performed in an “inverted” manner did not afford
any desired product. Generally lower yields were noted also in
the coupling reactions producing 2-benzoylfuran (11n) and 2-
benzoylthiophene (11o).
The scope of the coupling reaction was studied next by us-
ing variously substituted substrates and the most efficient (and
easy-to-prepare) catalyst, generated in situ from Pd(OAc)2 and
1.2 equiv. of ligand 2 (Table 2).
Table 2. Summary of the reaction scope tests.[a]
Entry
Acyl chloride (R1)
Boronic acid (R2)
Product
Yield [%][b]
1
2
3
4
5
6
7
8
Ph (9a)
9a
9a
9a
9a
9a
9a
9a
9a
9a
9a
9a
9a
9a
9a
Ph (10a)
2-MeC6H4 (10b)
3-MeC6H4 (10c)
4-MeC6H4 (10d)
4-MeOC6H4 (10e)
4-FC6H4 (10f)
4-ClC6H4 (10g)
4-BrC6H4 (10h)
4-AcC6H4 (10i)
4-O2NC6H4 (10j)
4-NCC6H4 (10k)
(E)-styryl (10l)
PhCH2CH2 (10m)
2-furyl (10n)
2-thienyl (10o)
Ph (10a)
11a
11b
11c
11d
11e
11f
11f
11h
11i
91
80
82
76
62
95
97
60[c]
21
8
It is also noteworthy that the presence of the less reactive
C–Cl and C–F bonds in the substrate does not interfere with
the coupling reactions producing benzophenones (Entries 6, 7,
20). In contrast, the cross-coupling reaction of the substrate 10h
featuring the more reactive C–Br bond competes with the self-
coupling reaction that leads to 4-benzoyl-4′-bromobiphenyl,
albeit in minor amounts (see Entry 8).
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
11j
11k
11l
4
71
0
11m
11n
11o
11b
11c
11d
11e
11g
11j
12
43
64
94
87
57
87
56
60
25
21
26
2-MeC6H4 (9b)
3-MeC6H4 (9c)
4-MeC6H4 (9d)
4-MeOC6H4 (9e)
4-ClC6H4 (9g)
4-O2NC6H4 (9j)
(E)-styryl (9l)
PhCH2CH2 (9m)
2-furyl (9n)
2-thienyl (9o)
Undoubtedly, the coupling of boronic acids with acyl chlor-
ides involves the use of relatively expensive chemicals com-
pared with those employed in conventional ketone synthesis.
However, the reaction shows good tolerance towards a range
of functional groups, proceeds selectively and with relatively
low environmental impact owing to the smaller amount of
waste produced and the easy hydrolysis of acyl chlorides (com-
pared with other substrates with environmentally persistent C–
halogen bonds). Thus, the reaction appears suitable for the syn-
thesis of fine chemicals, predominantly unsaturated ketones.
Such compounds, both naturally occurring and artificially
made,[22] show a range of biological activities.
10a
10a
10a
10a
10a
10a
10a
10a
11l
11m
11n
11o
10a
[a] Reagents and conditions: acyl chloride (3.0 mmol), boronic acid (2.5 mol),
Na2CO3 (2.5 mmol), toluene/water (3 mL:3 mL), catalyst generated in situ
from Pd(OAc)2 (0.2 mol-% Pd) and 1.2 equiv. of 2, 50 °C, 1 h. [b] Isolated
yields. The average of two independent runs is given. [c] 4-Benzoyl-4′-bromo-
biphenyl was also isolated in ca. 15 % yield.
In the present work we utilized the coupling reaction to pre-
pare 4,4′-dichlorobenzophenone (11gg), which was in turn con-
verted into acaricide chlorfenethol (12, Scheme 7). The reaction
of 4-chlorobenzoyl chloride (9g) with 4-chlorophenylboronic
acid (10g) proceeded reproducibly and in an essentially quanti-
tative yield under the standard reaction conditions. The ketone
was subsequently treated with methylmagnesium bromide to
provide the target compound 12 in a yield exceeding 95 % over
the two steps.
Under the optimized reaction conditions, the unsubstituted
benzophenone 11a was obtained in 91 % isolated yield. The
yields of the substituted products were similar or lower, de-
pending on the type of substituent and also on its source (bor-
onic acid vs. acyl chloride). For example, the reactions between
the isomeric tolylboronic acids with benzoyl chloride 9a fur-
nished the corresponding methylbenzophenones in rather simi-
lar yields of ca. 80 %, whereas those performed with toluyl
chlorides and 10a produced better yields of the 3- and 4-meth-
ylbenzophenones (by slightly over 10 % on the absolute scale)
Next, the aroylboronation reaction was used to synthesize
(E)-1-(4-methoxyphenyl)-3-[4-(trifluoromethyl)phenyl]prop-2-en-
but a considerably lower yield of the 2-methyl isomer (by 16 %; 1-one (11ep, Scheme 8), a chalcone showing antimalarial[23]
Eur. J. Inorg. Chem. 0000, 0–0
www.eurjic.org
4
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
molecule of 11ep is twisted, which is best demonstrated by the
torsion angles C4–C1–C2–C3 163.6(1)°, O1–C1–C2–C3 –17.7(2)°
and C1–C2–C3–C11 174.7(1)°, which reflect the departure from
an all-in-plane conformation. As a result, the planes of the benz-
ene rings are mutually rotated by 47.82(6)°.
Conclusions
Phosphanylferrocene donors 1 and 2 bearing guanidinium sub-
stituents represent new entries among ferrocenylphosphanes
equipped with highly polar functional pendants. They are ac-
cessible reproducibly and in good yields from readily available
starting materials and are air-stable. However, they cannot be
easily purified by crystallization and are isolated in a nonsolv-
ated form (or as defined solvates). Although the polar groups
present in 1 and 2 do not suffice to make these ligands and
their complexes particularly water-soluble, they render them
suitable for application in biphasic reaction media. This was
demonstrated in the Pd-catalyzed cross-coupling reaction of
arylboronic acids with benzoyl chlorides in an aqueous biphasic
reaction medium. The reactions selectively afforded benzo-
phenones in good to excellent yields. The experiments per-
formed with differently substituted substrates revealed that
their outcome depends on the properties of the reaction part-
ners (e.g., reactivity and solubility) and thus demands a judi-
cious choice of reagents from pairs with mutually transposed
functional groups [R1COCl + R2B(OH)2 vs. R2COCl + R1B(OH)2].
In addition, the results have implications for ligand design as
the catalysts generated from acylguanidinium donor 1 show
inferior catalytic performance to those generated with ligand 2
possessing an extended alkylguanidinium pendant attached to
the phosphanylferrocene moiety through an amide linkage. On
the whole, however, the activities of the catalysts obtained from
Pd(OAc)2 and ligand 1 or 2 are somewhat lower than those
previously achieved with phosphanylferrocene donors with
simple urea tags[8f] or amidourea pendants,[8e] which is particu-
larly important in reactions with less reactive substrates.
Scheme 7. Synthesis of chlorfenethol (12).
and other biological activities.[24] In this case, however, the cou-
pling reaction between acyl chloride 9e and boronic acid 10p
required a higher temperature (80 °C) to achieve a reasonable
yield of slightly over 50 % during 1 h (at 50 °C the coupling
product was isolated in ca. 40 % yield after 24 h).
Scheme 8. Synthesis of chalcone 11ep.
Chalcone 11ep was characterized by spectroscopic methods,
and its crystal structure was determined by single-crystal X-ray
diffraction analysis (Figure 1; selected crystallographic data are
given in the Supporting Information).
Experimental Section
Materials and Methods: All manipulations were carried out under
argon by using standard Schlenk techniques. Compound 3,[14]
Hdpf,[16] and N-(2-aminoethyl)guanidine dihydrochloride[17] were
prepared according to literature procedures. All other chemicals
were obtained from commercial sources (Sigma–Aldrich and Alfa-
Aesar) and used as received. Triethylamine and 1,2-diaminoethane
were dried by the addition of sodium metal and freshly distilled.
Methanol, tetrahydrofuran, and dichloromethane were dried using
a PureSolv MD5 solvent purification system (Innovative Technology,
USA). Solvents for chromatography were utilized as received (analyt-
ical grade, Lachner, Czech Republic). Anhydrous DMF was pur-
chased from Sigma–Aldrich. C6D6 and toluene utilized for catalytic
experiments were used without any additional purification. NMR
spectra were recorded with a Varian UNITY Inova 400 spectrometer
(1H, 399.95; 13C, 100.58; and 31P, 161.90 MHz) at 25 °C. Chemical
shifts (δ in ppm) are referenced to SiMe4 as internal standard (1H
and 13C) and 85 % aqueous H3PO4 as external standard (31P). In
addition to the usual notation of NMR signal multiplicity, “vt” and
Figure 1. PLATON plot of the molecular structure of chalcone 11ep. Ellipsoids
are drawn at the 50 % probability level. Selected distances [Å] and angles
[°]: C1–O1 1.226(2), C1–C4 1.485(2), C1–C2 1.489(2), C2–C3 1.333(2), C3–C11
1.469(2), C7–O2 1.368(2); O1–C1–C2/C4 120.6(1)/120.7(1), C1–C2–C3 119.5(1).
The geometric parameters describing the molecular geome-
try of 11ep fall within the common ranges[25] and compare well
with the data reported for 4′-methoxychalcone.[26] The “vq” are used to denote virtual triplets and virtual quartets arising
Eur. J. Inorg. Chem. 0000, 0–0
www.eurjic.org
5
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
from the AA′BB′ and AA′BB′X spin system formed by the protons at
tributed into four centrifugation tubes, diluted with chloroform, wa-
the C- and P-subsituted cyclopentadienyl ring, respectively. IR spec- ter, and brine (3 + 6 + 15 mL for each tube), and shaken well. After
tra were recorded with an FTIR Nicolet Magna 760 instrument in centrifugation at 6000 rpm for 2 min, the aqueous layer was re-
the range 400–4000 cm–1. Electrospray ionization (ESI) mass spectra
of samples dissolved in HPLC-grade methanol were recorded with
a Bruker Esquire 3000 instrument. Elemental analyses were deter-
mined by the standard combustion method using a PE 2400 Series
II CHNS/O Elemental Analyzer (Perkin–Elmer). The amount of resid-
ual solvent (if present) was verified by NMR analysis. CCDC 1475365
(for 4) and 1475366 (for 11ep) contain the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre.
moved and the organic layer washed similarly with water and then
with brine. Then, it was dried with anhydrous magnesium sulfate,
and the solvents were evaporated under vacuum at temperatures
not exceeding 25 °C. (Caution! Higher temperatures cause decom-
position.) The crude product was taken up with THF and filtered
through a PTFE syringe filter (0.45 μm) to remove insoluble triethyl-
amine hydrochloride. The filtrate was concentrated again (T < 25 °C)
to leave a residue that was purified by chromatography through a
short column on silica gel using ethyl acetate/methanol (4:1) as
eluent. Unreacted Hdpf was eluted first followed by a tailing band
due to 2. Hydrochloride 2 obtained after solvent removal was re-
peatedly treated with chloroform and concentrated, and finally
dried under vacuum to give 2·2/5CHCl3 as an orange foam (305 mg,
Synthesis of N-[Amino(imino)methyl]-1′-(diphenylphosphan-
yl)ferrocene-1-carboxamide Hydrochloride (1): An argon-flushed
reaction flask was charged with guanidinium hydrochloride
(382 mg, 4.0 mmol), sodium metal (92 mg, 4.0 mmol), and anhy-
drous THF (10 mL). Degassed water (0.8 mL, 5 mmol) was added to
the suspension followed by a solution of 3 (515 mg, 1.0 mmol) in
THF (10 mL). During the addition, the red color due to the benzotri-
azolyl derivative changed to orange. The resulting mixture was
stirred for 15 min and then filtered through a PTFE syringe filter
(0.45 μm pore size), and the solvents were evaporated under vac-
uum. The crude product was purified by column chromatography
on silica gel using dichloromethane/methanol (10:1) as eluent. The
first two bands containing unreacted 3 and Hdpf were discarded
and the following, orange tailing band containing the product, was
collected. The eluate was treated with methanolic HCl (1.1 equiv.),
and the solvents were evaporated. Methanol (5 mL) was added to
the residue, causing immediate separation of red microcrystals,
which were filtered off, washed with methanol, and dried under
vacuum. The mother liquor was concentrated and crystallized simi-
larly. The combined yield of 3·1/2MeOH was 350 mg (69 %). The
amount of clathrated methanol decreased upon prolonged storage
1
52 %). H NMR (CDCl3): δ = 2.75 (br. s, 2 H, NH), 3.29–3.50 (m, 4 H,
CH2), 4.04 (vq, J′ = 1.8 Hz, 2 H, fc), 4.12 (vt, J′ = 1.7 Hz, 2 H, fc), 4.37
(vt, J′ = 1.7 Hz, 2 H, fc), 4.76 (vt, J′ = 1.8 Hz, 2 H, fc), 7.0 (br. s, 1 H,
NH), 7.23–7.33 (m, 10 H, PPh2), 7.5 (br. s, 1 H, NH), 7.69 (br. s, 1 H,
NH), 7.96 (br. s, 1 H, NH) ppm. 13C{1H} NMR (CDCl3): δ = 38.89 (s, 1
C, CH2), 41.03 (s, 1 C, CH2), 69.60 (s, 2 C, CH fc), 72.37 (s, 2 C, CH fc),
73.25 (s, 2 C, CH fc), 74.39 (d, JPC = 14 Hz, 2 C, CH fc), 75.40 (s, 1 C,
2
C-P fc), 77.54 (d, JPC = 8 Hz, 1 C, C-CO fc), 128.30 (d, JPC = 7 Hz, 4
C, CHmeta PPh2), 128.72 (s, 2 C, CHpara PPh2), 133.44 (d, 3JPC = 20 Hz,
1
4 C, CHortho PPh2), 138.34 (d, JPC = 9 Hz, 2 C, Cipso PPh2), 157.72 [s,
1 C, NHC(NH)NH2], 172.34 [s, 1 C, fcC(O)NH] ppm. 31P{1H} NMR
(CDCl3): δ = –17.5 (s) ppm. IR (Nujol): ν = 3150 (br., s), 1625 (s), 1535
˜
(s), 1302 (s), 1241 (w), 1192 (m), 1160 (m), 1121 (w), 1092 (w), 1068
(w), 1027 (m), 999 (w), 932 (w), 912 (w), 889 (w), 833 (m), 743 (s),
723 (w), 697 (s), 635 (br., m), 497 (s), 453 (m) cm–1. MS (ESI+): m/z =
499 [M + H]+, 521 [M + Na]+. C26H28ClFeN4OP·2/5CHCl3 (582.54):
calcd. C 54.43, H 4.91, N 9.62; found C 54.69, H 5.01, N 9.55.
1
under vacuum. H NMR (DMSO): δ = 4.16 (vq, J′ = 1.8 Hz, 2 H, fc),
4.44 (vt, J′ = 2.1 Hz, 2 H, fc), 4.59 (vt, J′ = 1.8 Hz, 2 H, fc), 5.12 (vt,
J′ = 2.1 Hz, 2 H, fc), 7.28–7.34 (m, 4 H, PPh2), 7.36–7.42 (m, 6 H,
PPh2), 8.36 (br. s, 2 H, NH2), 8.74 (br. s, 2 H, NH2), 11.52 (s, 1 H, NH)
ppm. 13C{1H} NMR (DMSO): δ = 70.21 (s, 2 C, CH fc), 72.93 (s, 1 C,
C-CO fc), 73.10 (d, JPC = 4 Hz, 2 C, CH fc), 73.50 (s, 2 H, CH fc), 74.06
(d, JPC = 14 Hz, 2 C, CH fc), 78.23 (d, JPC = 10 Hz, 1 C, C-P fc), 128.31
(d, 2JPC = 7 Hz, 4 C, CHmeta PPh2), 128.70 (s, 2 C, CHpara PPh2), 132.94
(d, 3JPC = 20 Hz, 4 C, CHortho PPh2), 137.76 (d, 1JPC = 11 Hz, 2 C, Cipso
PPh2), 155.12 [s, 1 C, NHC(NH2)NH2], 171.38 [s, 1 C, fcC(O)NH] ppm.
Synthesis of Amine 4: A solution of 3 (129 mg, 0.25 mmol) in
anhydrous THF (4 mL) was added dropwise (over ca. 15 min) to a
solution of 1,2-diaminoethane (0.27 mL, 4 mmol) in the same sol-
vent (5 mL) while stirring and cooling with ice. The resulting mix-
ture was stirred at 0 °C for 45 min and then at room temperature
for another 15 min before being concentrated under reduced pres-
sure. The residue was repeatedly dissolved in toluene and concen-
trated at 50 °C to remove unreacted 1,2-diaminoethane and then
purified by column chromatography (silica gel; dichloromethane/
methanol, 5:1). The second, dominant band due to the product was
collected and concentrated to afford 4·1/6CH2Cl2 as an orange
31P{1H} NMR (DMSO): δ = –19.0 (s) ppm. IR (Nujol): ν = 3320 (br.,
˜
m), 3140 (br., m), 1686 (s), 1619 (s), 1559 (s), 1434 (m), 1419 (w),
1342 (w), 1307 (w), 1278 (s), 1191 (w), 1149 (s), 1093 (w), 1065 (w),
1051 (w), 1033 (m), 928 (w), 872 (w), 842 (m), 827 (s), 743 (s), 698
(s), 639 (br., m), 532 (m), 498 (s), 452 (w), 416 (w) cm–1. MS (ESI+):
m/z = 456 [M – Cl]+, 397 [PPh2fcCO]+. C24H23ClFeN3OP·1/2MeOH
(507.75): calcd. C 57.95, H 4.96, N 8.28; found C 57.97, H 4.63, N
8.28.
1
glassy solid. Yield: 102 mg, 87 %. H NMR (CDCl3): δ = 1.63 (s, 2 H,
3
3
NH2), 2.87 (t, JHH = 5.9 Hz, 2 H, CH2), 3.38 (t, JHH = 5.9 Hz, 2 H,
CH2), 4.08 (vq, J′ = 1.8 Hz, 2 H, fc), 4.20 (vt, J′ = 1.9 Hz, 2 H, fc), 4.43
3
(vt, J′ = 1.8 Hz, 2 H, fc), 4.60 (vt, J′ = 1.9 Hz, 2 H, fc), 6.29 (t, JHH
=
5.1 Hz, 1 H, NH), 7.31–7.40 (m, 10 H, PPh2) ppm. 13C{1H} NMR
(CDCl3): δ = 41.63 (s, 1 C, CH2), 42.17 (s, 1 C, CH2), 69.48 (d, JPC
=
Preparation of N-(2-{[Amino(imino)methyl]amino}ethyl)-1′-(di-
phenylphosphanyl)ferrocene-1-carboxamide Hydrochloride (2)
by Route A: A two-necked reaction flask equipped with a stirring
bar was charged with Hdpf (414 mg, 1.0 mmol) and HOBt (162 mg,
1.2 mmol), flushed with argon, and sealed with a rubber septum.
2 Hz, 2 C, CH fc), 71.48 (s, 2 C, CH fc), 72.81 (d, JPC = 4 Hz, 2 C, CH
2
fc), 74.35 (d, JPC = 14 Hz, 2 C, CH fc), 128.28 (d, JPC = 7 Hz, 4 C,
3
CHmeta PPh2), 128.74 (s, 2 C, CHpara PPh2), 133.45 (d, JPC = 20 Hz, 4
1
C, CHortho PPh2), 138.39 (d, JPC = 9 Hz, 2 C, Cipso PPh2), 170.14 [s, 1
C, fcC(O)NH] ppm; signals due to the ferrocene Cipso are probably
Dry dichloromethane was introduced (20 mL) followed by the drop- obscured by the solvent resonance. 31P{1H} NMR (CDCl3): δ = –16.9
wise addition of EDC (0.2 mL, 1.2 mmol). The resulting orange solu-
tion was transferred through a cannula to a mixture of (2-amino- 1618 (s), 1541 (s), 1437 (w), 1300 (s), 1220 (w), 1193 (m), 1161 (m),
(s) ppm. IR (Nujol): ν = 3314 (br., s), 3069 (br., s), 1650 (s),
˜
ethyl)guanidine dihydrochloride (176 mg, 1.0 mmol), dry DMF
(8 mL), and triethylamine (0.14 mL, 1.0 mmol). After stirring at room
temperature overnight, the dichloromethane was removed from the
1093 (m), 1069 (m), 1027 (s), 998 (w), 889 (w), 832 (s), 697 (m),
634 (m), 495 (s), 453 (m) cm–1. MS (ESI+): m/z = 457 [M + H]+.
C25H25FeN2OP·1/6CH2Cl2 (470.44): calcd. C 64.25, H 5.43, N 5.96;
reaction mixture (suspension) under vacuum. The residue was dis- found C 64.61, H 5.43, N 5.94.
Eur. J. Inorg. Chem. 0000, 0–0
www.eurjic.org
6
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
Synthesis of Hydrochloride 4·HCl: Free amine 4 was converted
into its hydrochloride by dissolution in a mixture of dichloro-
methane/methanol (5:1) followed by the addition of methanolic HCl
(1.1 equiv.). After stirring for 15 min, the mixture was concentrated
to afford 4·HCl·1/6CH2Cl2 as an orange foam in quantitative yield.
ric solvate 6·9/5CH2Cl2 as an orange solid (34 mg, 71 %). 1H NMR
(CDCl3): δ = 2.2 (br. s, 4 H, NH), 2.80 [s, 6 H, N(CH3)2], 3.34–3.52 (m,
4 H, CH2), 4.12 (s, 2 H, NCH2C6H4), 4.36 (s, 2 H, fc), 4.43 (s, 2 H, fc),
4.66 (s, 2 H, fc), 5.07 (s, 2 H, fc), 6.22 (t, J = 7.2 Hz, 1 H, C6H4), 6.37
(t, J = 7.7 Hz, 1 H, C6H4), 6.82 (t, J = 7.5 Hz, 1 H, C6H4), 7.00 (d, J =
3
3
1H NMR (DMSO): δ = 2.86 (t, JHH = 6.3 Hz, 2 H, CH2), 3.37 (q, JHH 6.8 Hz, 1 H, C6H4), 7.27–7.54 (m, 10 H, PPh2), 8.05 (br. s, 2 H, NH)
≈ 6.1 Hz, 2 H, CH2), 3.4 (vbr. s, 3 H, NH3), 4.06 (vq, J′ = 1.8 Hz, 2 H,
fc), 4.15 (vt, J′ = 1.9 Hz, 2 H, fc), 4.40 (vt, J′ = 1.8 Hz, 2 H, fc), 4.77 (br., m), 3100 (br., m), 1637 (s), 1578 (w), 1535 (s), 1436 (w), 1300
ppm. 31P{1H} NMR (CDCl3): δ = 32.7 (s) ppm. IR (Nujol): ν = 3250
˜
(vt, J′ = 1.9 Hz, 2 H, fc), 7.28–7.34 (m, 4 H, PPh2), 7.35–7.40 (m, 6 H,
(m), 1245 (w), 1182 (m), 1164 (m), 1098 (m), 1060 (w), 1028 (m), 992
(w), 972 (w), 844 (m), 743 (s), 695 (s), 628 (w), 543 (w), 521 (m), 506
(m), 477 (m) cm–1. MS (ESI+): m/z = 738 [M – HCl – Cl]+.
C35H40Cl2FeN5OPPd·9/5CH2Cl2 (963.71): C 47.85, H 4.61, N 7.92;
found C 47.48, H 4.78, N 7.55.
3
PPh2), 8.08 (t, JHH = 5.7 Hz, 1 H, NH) ppm. 13C{1H} NMR (DMSO):
δ = 38.05 (s, 1 C, CH2), 69.06 (s, 2 C, CH fc), 71.17 (s, 2 C, CH fc),
72.56 (d, JPC = 4 Hz, 2 C, CH fc), 73.44 (d, JPC = 15 Hz, 2 C, CH fc),
76.70 (d, JPC = 9 Hz, 1 C, C-P fc), 76.94 (s, 1 C, C-CO fc), 128.21 (d,
2JPC = 7 Hz, 4 C, CHmeta PPh2), 128.55 (s, 2 C, CHpara PPh2), 132.92
(d, 3JPC = 19 Hz, 4 C, CHortho PPh2), 138.23 (d, 1JPC = 11 Hz, 2 C, Cipso
PPh2), 168.85 [s, 1 C, fcC(O)NH] ppm; one CH2 resonance is obscured
by the solvent signal. 31P{1H} NMR (DMSO): δ = –18.3 (s) ppm. IR
Preparation of Complex 7: Dimeric precursor [PdCl(η3-C3H5)]2
(9.1 mg, 0.025 mmol) and 1·1/2MeOH (25.4 mg, 0.050 mmol) were
allowed to react in dichloromethane/methanol, as described for 5.
An analogous isolation procedure afforded solvate 7·7/3CH2Cl2 as
(Nujol): ν = 3250 (br., m), 1633 (s), 1541 (s), 1437 (m), 1305 (s), 1162
˜
1
an orange solid (30 mg, 69 %). H NMR (CDCl3): δ = 1.8 (br. s, 1 H,
(s), 1187 (s), 1070 (w), 1027 (m), 997 (w), 835 (m), 749 (m), 724 (s),
702 (s), 634 (w), 570 (s), 534 (m), 499 (s) cm–1. MS (ESI+): m/z = 457
[M – Cl]+. C25H26ClFeN2OP·1/6CH2Cl2 (506.90): calcd. C 59.63, H 5.24,
N 5.53; found C 59.77, H 5.47, N 5.46.
NH), 2.70–3.05 (br. m, 2 H, allyl CH2), 3.86 (br. s, 1 H, allyl CH2), 4.17
(s, 2 H, fc), 4.45 (s, 2 H, fc), 4.69 (s, 2 H, fc), 4.81 (br. s, 1 H, allyl CH2),
5.26 (s, 2 H, fc), 5.68 (quint, JHH = 10.3 Hz, 1 H, allyl CH), 7.30–7.70
(m, 10 H, PPh2), 8.5 (br. s, 1 H, NH), 8.8 (br. s, 2 H, NH), 10.9 (br. s, 1
Synthesis of 2 from 4 (Route B): A solution prepared by dissolving
amine 4 (320 mg, 0.70 mmol) in THF (30 mL) was added to a mix-
ture of 1H-pyrazole-1-carboximidamide hydrochloride (103 mg,
0.70 mmol) and anhydrous triethylamine (0.098 mL, 0.70 mmol) in
the same solvent (30 mL). The resulting orange solution was stirred
at room temperature overnight. The resulting white precipitate
(NEt3·HCl) was removed by filtration through a PTFE syringe filter
(0.45 μm pore size). The crude product obtained after concentration
under vacuum was dissolved in THF (minimum amount), filtered,
and concentrated again. The residue was purified by flash column
chromatography on silica gel using ethyl acetate/methanol (4:1) as
eluent. The dominant orange band of the product was collected,
and the solvents were evaporated under vacuum at 25 °C. Then the
product was repeatedly treated with chloroform and concentrated
to remove the reaction solvent to give 4·2/5CHCl3 as an orange
foam (217 mg, 53 %). The analytical data are the same as for the
product obtained by route A (see Scheme 4).
H, NH2) ppm. 31P{1H} NMR (CDCl3): δ = 13.4 (s) ppm. IR (Nujol): ν =
˜
3300 (br., m), 3150 (br., m), 3070 (m), 1697 (s), 1571 (m), 1436 (w),
1279 (s), 1153 (m), 1098 (m), 1031 (w), 829 (m), 749 (m), 696 (m),
628 (w), 519 (m), 500 (m), 468 (w) cm–1. MS (ESI+): m/z = 602 [M –
HCl – Cl]+. C27H28Cl2FeN3OPPd·7/3CH2Cl2 (872.80): C 43.72, H 3.94,
N 5.60; found C 43.78, H 3.94, N 5.47.
Synthesis of Complex 8: Complex 8 was prepared and isolated
similarly to complex 7 from [PdCl(η3-C3H5)]2 (9.1 mg, 0.025 mmol)
and 2 (26.7 mg, 0.050 mmol) to give nonstoichiometric solvate
1
8·7/3CH2Cl2 (31 mg, 68 %) as an orange solid. H NMR (CDCl3): δ =
2.63 (br. s, 1 H, NH), 2.8 (br. s, 1 H, allyl CH2), 3.05 (br. s, 1 H, allyl
CH2), 3.35–3.55 (m, 4 H, CH2), 3.84 (br. s, 1 H, allyl CH2), 4.08 (s, 2 H,
fc), 4.31 (s, 2 H, fc), 4.56 (s, 2 H, fc), 4.77 (br. s, 1 H, allyl CH2), 4.99
(s, 1 H, fc), 5.66 (quint, JHH = 10.3 Hz, 1 H, allyl CH), 7.1 (br. s, 2 H,
NH2), 7.32–7.65 (m, 10 H, PPh2), 7.92 (br. s, 1 H, NH), 8.09 (br. s, 1 H,
NH) ppm. 31P{1H} NMR (CDCl3): δ = 14.7 (s) ppm. IR (Nujol): ν = 3300
˜
(br., m), 3100 (br., m), 1640 (s), 1540 (s), 1437 (w), 1301 (s), 1240 (w),
1183 (m), 1167 (s), 1097 (s), 1070 (w), 1029 (s), 999 (w), 963 (w), 912
(w), 836 (m), 733 (s), 695 (s), 669 (w), 628 (w), 518 (s), 503 (s), 468
(s) cm–1. MS (ESI+): m/z = 645 [M – HCl – Cl]+. C29H33Cl2FeN4OPPd·
7/3CH2Cl2 (915.87): C 44.37, H 4.36, N 7.03; found C 44.04, H 4.41, N
6.90.
Synthesis of Complex 5: [Pd(LNC)Cl]2 (13.8 mg, 0.025 mmol) and
1·1/2MeOH (25.4 mg, 0.050 mmol) were dissolved in a mixture of
dichloromethane/methanol (3 mL:3 mL). The resultant orange solu-
tion was stirred for 30 min, and the solvents were evaporated to
leave a residue that was purified by flash column chromatography
on silica gel using dichloromethane/methanol (5:1) as eluent. Sub-
sequent concentration afforded 5·1/4CH2Cl2 as an orange amor-
phous solid (33 mg, 85 %). 1H NMR (CDCl3): δ = 2.85 [s, 6 H,
PdN(CH3)2], 4.14 (s, 2 H, NCH2C6H4), 4.50 (s, 2 H, fc), 4.58 (s, 2 H, fc),
4.93 (s, 2 H, fc), 5.38 (s, 2 H, fc), 6.22 (t, JHH = 7.2 Hz, 1 H, C6H4), 6.38
(t, JHH = 7.3 Hz, 1 H, C6H4), 6.83 (t, JHH = 7.1 Hz, 1 H, C6H4), 7.01 (d,
JHH = 6.6 Hz, 1 H, C6H4), 7.31–7.38 (m, 4 H, PPh2), 7.38–7.45 (m, 2
H, PPh2), 7.50–7.59 (m, 4 H, PPh2), 8.2–8.9 (m, 4 H, NH), 11.0 (br. s,
General Procedure for the Catalytic Experiments: A Schlenk tube
was charged with acyl chloride 9 (3.0 mmol), boronic acid 10
(2.5 mmol), anhydrous sodium carbonate (2.5 mmol), and the re-
spective catalyst [0.2 mol-% of a defined complex or 0.2 mol-% of
palladium(II) acetate and 1.2 equiv. of the ligand]. The reaction ves-
sel was flushed with argon and sealed with a rubber septum. Tolu-
ene and water (3 mL each) were introduced, and the reaction flask
was heated at 50 °C in the dark with continuous stirring for 1 h.
Then the reaction mixture was diluted with diethyl ether (ca.
20 mL), and the aqueous layer was discarded. The organic layer was
1 H, NH) ppm. 31P{1H} NMR (CDCl3): δ = 32.1 (s) ppm. IR (Nujol): ν =
˜
3200 (m), 1690 (s), 1619 (s), 1570 (s), 1436 (m), 1343 (w), 1305 (w),
1278 (s), 1151 (m), 1099 (m), 1060 (w), 1029 (m), 993 (m), 972 (w),
932 (w), 844 (m), 829 (m), 746 (s), 695 (s), 664 (w), 629 (w), 536
(m), 521 (m), 503 (m) cm–1. MS (ESI+): m/z = 695 [M – HCl – Cl]+.
C33H35Cl2FeN4OPPd·1/4CH2Cl2 (776.26): calcd. C 50.61, H 4.54, N
7.10; found C 50.65, H 4.53, N 7.00.
washed successively with 3
M HCl (2 × 20 mL), 5 % KOH (4 × 20 mL),
and brine (2 × 20 mL), dried with magnesium sulfate, and concen-
trated. The coupling product was isolated by chromatography on
silica gel using ethyl acetate/hexane as eluent (30:1, 10:1, or 5:1
depending on the polarity of the product). Characterization data
Synthesis of Complex 6: Complex 6 was prepared similarly starting
from [Pd(LNC)Cl]2 (13.8 mg, 0.025 mmol) and
2
(26.7 mg, for the products of the catalyzed reactions are presented in the
0.050 mmol). Isolation as described above afforded nonstoichiomet- Supporting Information.
Eur. J. Inorg. Chem. 0000, 0–0
www.eurjic.org
7
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
2000, 602, 158–169; d) P. Wasserscheid, H. Waffenschmidt, P. Machnitzki,
K. W. Kottsieper, O. Stelzer, Chem. Commun. 2001, 451–452.
H. Dibowski, F. P. Schmidtchen, Tetrahedron 1995, 51, 2325–2330.
P. Guerreiro, V. Ratovelomanana-Vidal, J.-P. Genêt, P. Dellis, Tetrahedron
Lett. 2001, 42, 3423–3426.
For examples of structurally related donors with aminopyrimidinyl sub-
stituents, see: a) Y. Sun, A. Hienzsch, J. Grasser, E. Herdtweck, W. R. Thiel,
J. Organomet. Chem. 2006, 691, 291–298; b) S. Farsadpour, L. T. Ghoo-
chany, Y. Sun, W. R. Thiel, Eur. J. Inorg. Chem. 2011, 4603–4609.
For representative examples, see: a) T. Šmejkal, B. Breit, Angew. Chem.
Int. Ed. 2008, 47, 311–315; Angew. Chem. 2008, 120, 317; b) T. Šmejkal,
B. Breit, Angew. Chem. Int. Ed. 2008, 47, 3946–3949; Angew. Chem. 2008,
120, 4010; c) L. Diab, T. Šmejkal, J. Geier, B. Breit, Angew. Chem. Int. Ed.
2009, 48, 8022–8026; Angew. Chem. 2009, 121, 8166; d) T. Šmejkal, D.
Gribkov, J. Geier, M. Keller, B. Breit, Chem. Eur. J. 2010, 16, 2470–2478; e)
D. Fuchs, G. Rousseau, L. Diab, U. Gellrich, B. Breit, Angew. Chem. Int. Ed.
2012, 51, 2178–2182; Angew. Chem. 2012, 124, 2220.
a) J. Schulz, I. Císařová, P. Štěpnička, J. Organomet. Chem. 2009, 694,
2519–2530; b) J. Tauchman, I. Císařová, P. Štěpnička, Organometallics
2009, 28, 3288–3302; c) J. Schulz, I. Císařová, P. Štěpnička, Organometal-
lics 2012, 31, 729–738; d) J. Tauchman, B. Therrien, G. Süss-Fink, P. Štěp-
nička, Organometallics 2012, 31, 3985–3994; e) H. Solařová, I. Císařová,
P. Štěpnička, Organometallics 2014, 33, 4131–4147; f) K. Škoch, I. Císař-
ová, P. Štěpnička, Organometallics 2015, 34, 1942–1956.
a) P. Štěpnička (Ed.), Ferrocenes: Ligands, Materials and Biomolecules,
Wiley, Chichester, 2008, pp. 1–277; b) P. Štěpnička in Patai's Chemistry of
Functional Groups (Eds.: I. Marek, Z. Rappoport), Wiley, Chichester, 2013,
pp. 103–154.
a) P. D. Beer, M. G. B. Drew, D. K. Smith, J. Organomet. Chem. 1997, 543,
259–261; b) Á. Lorenzo, E. Aller, P. Molina, Tetrahedron 2009, 65, 1397–
1401.
a) F. Otón, A. Tárraga, P. Molina, Org. Lett. 2006, 8, 2107–2110; b) F. Otón,
A. Espinosa, A. Tárraga, C. Ramírez de Arellano, P. Molina, Chem. Eur. J.
2007, 13, 5742–5752; c) A. Sola, R. A. Orenes, M. Á. García, R. M. Clara-
munt, I. Alkorta, J. Elguero, A. Tárraga, P. Molina, Inorg. Chem. 2011, 50,
4212–4220; d) A. Sola, A. Tárraga, P. Molina, Dalton Trans. 2012, 41, 8401–
8409.
a) C. L. Beck, S. A. Berg, A. H. Winter, Org. Biomol. Chem. 2013, 11, 5827–
5835; b) C. L. Beck, A. H. Winter, J. Org. Chem. 2014, 79, 3152–3158.
L. R. R. Klapp, C. Bruhn, M. Leibold, U. Siemeling, Organometallics 2013,
32, 5862–5872.
P. Štěpnička, H. Solařová, I. Císařová, J. Organomet. Chem. 2011, 696,
3727–3740.
Preparation of 4,4′-Dichlorobenzophenone (11gg): Ketone 11gg
was prepared according to the general procedure described above
and was isolated as a white solid in yields of 95 and 97 % (two
independent runs). 1H NMR (CDCl3): δ = 7.45–7.49 (m, 4 H, Ar), 7.70–
7.75 (m, 4 H, Ar) ppm. 13C{1H} NMR (CDCl3): δ = 128.78 (s, 4 C, Ar),
131.32 (s, 4 C, Ar), 135.52 (s, 2 C, Cipso Ar), 139.17 (s, 2 C, Cipso Ar),
194.23 (s, 1 C, CO) ppm. The analytical data are in agreement with
literature values.[27]
[4]
[5]
[6]
[7]
Preparation of 1,1-Bis(4-chlorophenyl)ethanol (12): Methylmag-
nesium bromide (0.75 mL of 1
M in dibutyl ether) was added to a
solution of 11gg (125.5 mg, 0.50 mmol) in anhydrous THF (15 mL).
The reaction mixture was stirred for 2 h and then quenched by the
addition of saturated aqueous NH4Cl. The organic layer was washed
with saturated aqueous NaHCO3 and brine, dried with MgSO4, and
the solvents were evaporated. Subsequent column chromatography
(silica gel; dichloromethane/methanol, 10:1) and concentration af-
forded alcohol 12 as a yellowish liquid. Yield: 131 mg (98 %). 1H
NMR (CDCl3): δ = 1.92 (s, 3 H, CH3), 2.16 (s, 1 H, OH), 7.26–7.35 (m,
8 H, Ar) ppm. 13C{1H} NMR (CDCl3): δ = 30.82 (s, 1 C, CH3), 75.54 (s,
1 C, CH), 127.26 (s, 4 C, Ar), 128.39 (s, 4 C, Ar), 133.06 (s, 2 C, Cipso
Ar), 146.04 (s, 2 C, Cipso Ar) ppm. The NMR parameters are in agree-
ment with literature data.[28]
[8]
[9]
Synthesis of Chalcone 11ep: 4-Methoxybenzoyl chloride (256 mg,
1.5 mmol), (E)-[4-(trifluoromethyl)styryl]boronic acid (270 mg,
1.25 mmol), and Na2CO3 (131 mg, 1.25 mmol) were allowed to react
in the presence of a catalyst generated in situ from palladium(II)
acetate (0.56 mg, 2.5 μmol) and 2 (1.2 equiv. with respect to Pd).
The reaction was performed in a mixture of toluene and water
(6 mL each) at 80 °C, and the coupling product was isolated as a
yellowish solid by column chromatography as specified above.
Yield: 194 mg (51 %), 202 mg (53 %). 1H NMR (CDCl3): δ = 3.90 (s,
3 H, OMe), 6.97–7.02 (m, 2 H, Ar), 7.57–7.82 (m, 6 H, Ar, CH=CH),
8.02–8.07 (m, 2 H, Ar) ppm. 13C{1H} NMR (CDCl3): δ = 55.55 (s, 1 C,
[10]
[11]
1
[12]
[13]
[14]
[15]
[16]
[17]
[18]
[19]
[20]
[21]
[22]
OMe), 113.99 (s, 2 C, Ar), 123.87 (q, JFC = 272 Hz, 1 C, CF3), 124.11
3
(s, 1 C, CH=CH), 125.87 (q, JFC = 4 Hz, 2 C, Ar), 128.41 (s, 2 C, Ar),
130.71 (s, 1 C, Cipso Ar), 130.92 (s, 2 C, Ar), 131.69 (q, 2JFC = 32 Hz, 1
4
C, Cipso Ar), 138.50 (q, JFC = 2 Hz, 1 C, Cipso C6H4), 141.88 (s, 1 C,
CH=CH), 163.73 (s, 1 C, Cipso Ar), 188.19 (s, 1 C, CO) ppm. Analytical
data are in accordance with literature data.[29]
a) A. El-Faham, F. Albericio, Chem. Rev. 2011, 111, 6557–6602; b)
C. A. G. N. Montalbetti, V. Falque, Tetrahedron 2005, 61, 10827–10852.
J. Podlaha, P. Štěpnička, J. Ludvík, I. Císařová, Organometallics 1996, 15,
543–550.
I. Matulková, H. Solařová, P. Štěpnička, I. Císařová, T. Janda, P. Němec, I.
Němec, Opt. Mater. 2015, 42, 39–46.
M. S. Bernatowicz, Y. Wu, G. R. Matsueda, J. Org. Chem. 1992, 57, 2497–
2502.
A. R. Katritzky, B. V. Rogovoy, ARKIVOC 2005, 49–87, and references cited
therein.
Acknowledgments
Financial support from the Czech Science Foundation (project
no. 13-08890S) is gratefully acknowledged.
Keywords: Phosphane ligands · N,P ligands · Ferrocene ·
Cross-coupling · Palladium
P. Štěpnička, J. Schulz, I. Císařová, K. Fejfarová, Collect. Czech. Chem. Com-
mun. 2007, 72, 453–467.
M. Blangetti, H. Rosso, C. Prandi, A. Deagostino, P. Venturello, Molecules
2013, 18, 1188–1213.
[1] a) R. G. S. Berlinck, Nat. Prod. Rep. 1996, 13, 377–409; b) R. G. S. Berlinck,
A. C. B. Burtuloso, M. H. Kossuga, Nat. Prod. Rep. Nat. Prod. Rev. 2008, 25,
919–954; c) R. G. S. Berlinck, A. C. B. Burtoloso, A. E. Trindade-Silva, S.
Romminger, R. P. Morais, K. Bandeira, C. M. Mizuno, Nat. Prod. Rep. 2010,
27, 1871–1907.
[2] a) F. Joó, Aqueous Organometallic Catalysis, Kluwer, Dordrecht, 2001; b)
B. Cornils, W. Herrmann (Eds.), Aqueous-Phase Organometallic Catalysis,
2nd ed., Wiley-VCH, Weinheim, 2004; c) C.-J. Li, Chem. Rev. 2005, 105,
3095–3165; d) R. N. Butler, A. G. Coyne, Chem. Rev. 2010, 110, 6302–
6337; e) K. H. Shaughnessy, Chem. Rev. 2009, 109, 643–710.
For selected reviews, see: a) S.-B. Wu, C. Long, E. J. Kennelly, Nat. Prod.
Rep. 2014, 31, 1158–1174; b) P. Singh, A. Anand, V. Kumar, Eur. J. Med.
Chem. 2014, 85, 758–777; c) D. K. Mahapatra, S. K. Bharti, V. Asati, Eur. J.
Med. Chem. 2015, 98, 69–114; d) Z. Rozmer, P. Perjesi, Phytochem. Rev.
2016, 15, 87–120; e) S. Baggett, E. P. Mazzola, E. J. Kennelly, Stud. Nat.
Prod. Chem. 2005, 32, 721–771.
A. Batagin-Neto, F. C. Lavarda, Med. Chem. Res. 2014, 23, 580–586.
a) V. Kumar, S. Kumar, M. Hassan, H. Wu, R. K. Thimmulappa, A. Kumar,
S. K. Sharma, V. S. Parmar, S. Biswal, S. V. Malhotra, J. Med. Chem. 2011,
54, 4147–4159; b) B. Mathew, G. E. Mathew, G. Uçar, I. Baysal, J. Suresh,
J. K. Vilapurathu, A. Prakasan, J. K. Suresh, A. Thomas, Bioorg. Chem. 2015,
62, 22–29; c) J. W. Choi, B. K. Jang, N. Cho, J.-H. Park, S. K. Yeon, E. J. Ju,
[23]
[24]
[3] a) A. Hessler, O. Stelzer, H. Dibowski, K. Worm, F. P. Schmidtchen, J. Org.
Chem. 1997, 62, 2362–2369; b) O. Herd, A. Hessler, M. Hingst, P. Mach-
nitzki, M. Tepper, O. Stelzer, Catal. Today 1998, 42, 413–420; c) P. Mach-
nitzki, M. Tepper, K. Wenz, O. Stelzer, E. Herdtweck, J. Organomet. Chem.
Eur. J. Inorg. Chem. 0000, 0–0
www.eurjic.org
8
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
Y. S. Lee, G. Han, A. N. Pae, D. J. Kim, K. D. Park, Bioorg. Med. Chem. 2015,
23, 6486–6496.
[28] H. Namai, H. Ikeda, N. Kato, K. Mizuno, J. Phys. Chem. A 2007, 111, 4436–
4442.
[25] F. H. Allen, O. Kennard, D. G. Watson, L. Brammer, A. G. Orpen, R. Taylor,
[29] K. R. A. Abdellatif, H. H. A. Elshemy, A. A. Azoz, Bioorg. Chem. 2015, 63,
J. Chem. Soc., Perkin Trans. 2 1987, S1–S19.
13–23.
[26] Refcode KORROY in the Cambridge Structural Database, version 5.37 of
November 2015 with updates up to January 2016.
[27] M. L. N. Rao, V. Venkatesh, P. Dasgupta, Tetrahedron Lett. 2010, 51, 4975–
4980.
Received: April 21, 2016
Published Online: ■
Eur. J. Inorg. Chem. 0000, 0–0
www.eurjic.org
9
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
Palladium Catalysts
Phosphanylferrocene ligands 1 and 2
bearing guanidinium pendants have
been prepared and utilized as donors
in PdII complexes and in the Pd-cata-
lyzed cross-coupling of arylboronic ac-
ids with benzoyl chlorides to give
benzophenones. Consistently better
results were achieved with ligand 2
possessing an extended alkylguanidin-
ium moiety appended to the phos-
phanylferrocene unit through an
amide moiety.
H. Charvátová, I. Císařová,
P. Štěpnička* ..................................... 1–10
Synthesis of Phosphanylferrocene-
carboxamides Bearing Guanidinium
Substituents and Their Application
in the Palladium-Catalyzed Cross-
Coupling of Boronic Acids with Acyl
Chlorides
DOI: 10.1002/ejic.201600461
Eur. J. Inorg. Chem. 0000, 0–0
www.eurjic.org
10
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim