Phenylalanine-a biogenic ligand with flexible η6- and η6:κ1-coordination at ruthenium(ii) centres

Article abstract of DOI:10.1039/c3dt50589h

The reaction of (S)-2,5-dihydrophenylalanine 1 with ruthenium(iii) chloride yields the μ-chloro-bridged dimeric η⁶-phenylalanine ethyl ester complex 3, which can be converted into the monomeric analogue, η⁶:κ¹-phenylalanine ethyl ester complex 12, under basic conditions. Studies were carried out to determine the stability and reactivity of complexes bearing η⁶- and η⁶: κ¹-chelating phenylalanine ligands under various conditions. Reaction of 3 with ethylenediamine derivatives N-p-tosylethylenediamine or 1,4-di-N-p-tosylethylenediamine results in the formation of monomeric η⁶:κ¹-phenylalanine ethyl ester complexes 14 and 15, which could be saponified yielding complexes 16 and 17 without changing the inner coordination sphere of the metal centre. The structure of η⁶:κ¹-phenylalanine complex 17 and an N-κ¹-phenylalanine complex 13 resulting from the reaction of 3 with an excess of pyridine were confirmed by X-ray crystallography.

Full text of DOI:10.1039/c3dt50589h

View Article Online
View Journal
Dalton
Transactions
Accepted Manuscript
This is an Accepted Manuscript, which has been through the RSC Publishing peer
review process and has been accepted for publication.
Dalton
Transactions
Volume 39 | Number 3 | 21 January 2010 | Pages 657–964
Accepted Manuscripts are published online shortly after acceptance, which is prior
to technical editing, formatting and proof reading. This free service from RSC
Publishing allows authors to make their results available to the community, in
citable form, before publication of the edited article. This Accepted Manuscript will
be replaced by the edited and formatted Advance Article as soon as this is available.
An international journal of inorganic chemistry
www.rsc.org/dalton
To cite this manuscript please use its permanent Digital Object Identifier (DOI®),
which is identical for all formats of publication.
More information about Accepted Manuscripts can be found in the
Information for Authors.
Please note that technical editing may introduce minor changes to the text and/or
graphics contained in the manuscript submitted by the author(s) which may alter
content, and that the standard Terms & Conditions and the ethical guidelines
that apply to the journal are still applicable. In no event shall the RSC be held
responsible for any errors or omissions in these Accepted Manuscript manuscripts or
any consequences arising from the use of any information contained in them.
ISSN 1477-9226
COMMUNICATION
PAPER
Bu et al.
Manzano et al.
Zinc(ii)-boron(iii)-imidazolate
Experimental and computational study framework (ZBIF) with unusual
of the interplay between C–H/p and
anion–p interactions
pentagonal channels prepared from
deep eutectic solvent
1477-9226(2010)39:1;1-K
www.rsc.org/dalton
Registered Charity Number 207890

Page 1 of 12
Dalton Transactions
View Article Online
TOC graphic
Depending on the reaction conditions, phenylalanine derived ruthenium(II) half-sandwich complexes
show a rich reactivity and coordination chemistry, which can be utilised for selective derivatisations.

Dalton Transactions
Page 2 of 12
View Article Online
CREATED USING THE RSC ARTICLE TEMPLATE (VER. 3.1) - SEE WWW.RSC.ORG/ELECTRONICFILES FOR DETAILS
ARTICLE TYPE
www.rsc.org/xxxxxx | XXXXXXXX
Phenylalanine - a biogenic ligand with flexible η6- and η6:κ1-
coordination at ruthenium(II) centres†
Thomas Reiner,a,b Dominik Jantke,c Xiaohe Miao,c Alexander N. Marziale,c Florian Kiefer,a Jörg
Eppinger*c
5
Received (in XXX, XXX) Xth XXXXXXXXX 201X, Accepted Xth XXXXXXXXX 201X
First published on the web Xth XXXXXXXXX 201X
DOI: 10.1039/b000000x
The reaction of (S)ꢀ2,5ꢀdihydrophenylalanine 1 with ruthenium(III) chloride yields the ꢀꢀchloroꢀbridged dimeric η6ꢀ
phenylalanine ethyl ester complex 3, which can be converted into the monomeric analogue, η6:κ1ꢀphenylalanine ethyl ester
10 complex 12 under basic conditions. Studies were carried out to determine stability and reactivity of complexes bearing η6ꢀ and
η6:κ1ꢀchelating phenylalanine ligands under various conditions. Reaction of 3 with ethylenediamine derivatives Nꢀpꢀ
tosylethylenediamine or 1,4ꢀdiꢀNꢀpꢀtosylethylenediamine results in the formation of monomeric η6:κ1ꢀphenylalanine ethyl ester
complexes 14 and 15, which could be saponified yielding complexes 16 and 17 without changing the inner coordination sphere
of the metal centre. The structure of η6:κ1ꢀphenylalanine complex 17 and a Nꢀκ1ꢀphenylalanine complex 13 resulting from the
15 reaction of 3 with an excess of pyridine were confirmed by XꢀRay crystallography.
O
Introduction
The well established stability of d6 ꢀ sandwich complexes
HN
Cl
NH
O
towards oxygen, water or even under physiological
conditions1 has triggered widespread interest for the
20 application of such systems as biological probes2,3 as well as
pharmacologically active compounds (A, B).4,5,6 In particular,
the labelling of aromatic side chains of unprotected amino
acids and peptides by introduction of CpM and Cp*Mꢀ
moieties (M = d6ꢀmetal cation) has been an active field with
25 pivotal contributions by the groups of Moriart7, Pearson,8
Sheldrick9 and others.10 Conversion to halfꢀsandwich
complexes adds a further dimension to the chemistry of these
systems due to the introduction of potentially labile
coordination sites. Ward and coꢀworkers recently tailored the
30 labile coordination sphere of rhodium halfꢀsandwich
conjugates to generate an artificial enzyme.11 In particular
ruthenium(II) η6ꢀarene half sandwich complexes found a large
variety of applications.12 The in vivo and in vitro cytotoxic
activities of this class of compounds has recently triggered
35 intense research activity targeting the design of selective
organometallic anticancer agents (C).13,14 Further wellꢀ
documented applications include building blocks for
Ru
N
Ru
Cl
N
Cl
Cl
PTA
O
Cl
A Salmain5
B Dyson6
H
O
PF6
Ru
N
Ru
Ts
Ph
Cl
H2N
Cl
NH2
NH2
Ph
C Sadler13
D Noyori16
NH3Cl
O
Ru
Cl
Cl
Ts
NH
Ru
N
2
EtO
Cl
Ph
Ph
E Wills17
F Beck23
Fig. 1 Various η6ꢀarene Ru(II) half sandwich complexes applied in
the selective inhibition of enzymes (A), biological probes (B), tumour
therapy (C) or catalysis (D, E). Complex (F) represents the only
45 Ru(II) halfꢀsandwich complex with η6ꢀcoordination of an amino acid
side chain and unprotected amino group.
supramolecular
structures,15
catalysts
for
transfer
hydrogenations (D, E),16,17,18 hydrogenations19 or CꢀC
40 couplings20. Half sandwich ruthenium complexes were also
successfully converted into catalytically active metal centres
of organometallic enzyme hybrids.21 Ruthenium η6ꢀarene
complexes with pendant carboxylic,22 amine3,9,23 (F) or
alcohol24 functions have been synthesized. Side chains
50 containing a coordinating moiety such as an alcohol,25 amide15
or carbene26 group offer an easy entry to η6:κ1ꢀarenes which
provide a hemilabile tether at the metal centre. Multiple
synthetic endeavours focused on the preparation of complexes
a Technische Universität München, Department Chemie, Lichtenbergstr.
4, Dꢀ85747 Garching, Germany.
b
Present address: Department of Radiology, Memorial SloanꢀKettering
Cancer Center, 1275 York Avenue, New York, New York 10065, USA.
c
King Abdullah University of Science and Technology (KAUST)
Division of Physical Sciences & Engineering and KAUST Catalysis
Center (KCC), Thuwal 23955ꢀ6900, Saudi Arabia, Eꢀmail:
jorg.eppinger@kaust.edu.sa; Tel: (+) 996 2 808ꢀ2414.
with
a chiral tether, targeting asymmetric induction in
†
Electronic supplementary material available. CCDC reference
55 catalysis.17,23 However, examples of η6ꢀruthenium complexes
numbers 721712–721713. For crystallographic data in CIF see
DOI: 10.1039/b000000x/
with biogenic amino acids are scarce.9,23
This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00 | 1

Page 3 of 12
Dalton Transactions
View Article Online
Hence, we became interested in synthesis and exploration of
complexes that feature biogenic amino acids. We present the
synthesis of various novel η6ꢀphenylalanine, η6:κ1ꢀ
phenylalanine and η6:κ1ꢀphenylalanine ethyl ester complexes
of ruthenium(II). The distinct coordination behaviour of side
chain and external donors and complex stabilities are
COO
NH3
1) HCl, tBuOH
Cl
H3N
Cl
.
2) RuCl3 xH2O
Ru
2
Cl
5
5 (69%)
2
1
evaluated by H NMR, 13C NMR and 15N NMR spectroscopy.
50 Scheme 2 Synthesis of η6ꢀarene ruthenium complex 5 from 2,5ꢀ
XꢀRay crystallography supports the spectroscopic results.
t
dihydroꢀLꢀphenylglycine in BuOH.
Results
complexes 3, 4 and 6 reveal strong bands between 1741 and
1746 cmꢀ1, which correspond to the respective CO stretching
frequencies.30 While IR sprectra of 6 in chloroform solution
55 exhibit one carbonyl absorption at 1741 cmꢀ1, preparations in
KBr display two sharp bands in the carbonyl region at 1734
cmꢀ1 and 1726 cmꢀ1. The same two bands are present in nujol,
hence halide exchange during sample preparation can be ruled
out as possible reason for the double band structure. In
60 agreement with the IR measurements described above 13C
MAS NMR spectra of 6 exhibited a double set of signals for
ꢀ, ꢁ and carboxyl carbons. Hence, we assume that in the solid
state packing effects and / or different hydrogen bonding
patterns lead to different orientations and electron density for
10 The particular orientation of carboxylic acid and amino
moieties, which is characteristic for αꢀamino acids, is well
suited to chelate cationic metal centres. Hence, a decrease in
binding affinity of these functionalities is essential to prevent
chelation and thus deactivation of metal centre binding sites.
15 Beck et al. recently described an elegant procedure avoiding
tedious protection/deprotection strategies by a simple in situ
protonation (amino group) and esterification (carboxy group)
in acidic solutions.24 Using this strategy, the dihydro derivates
127 and 228, which were prepared from the artificial amino acid
20 Lꢀphenylglycine as well as the biogenic amino acid Lꢀ
phenylalanine, respectively, can be converted with
ruthenium(III) chloride hydrate in refluxing ethanol to the
1
65 the carboxylic acid function. The H and 13C NMR spectra of
corresponding η6ꢀarene ruthenium(II) complexes
previously described 424 in high yields (scheme 1).
3
and
the dimeric complexes 3, 4 and 5 only show a single set of
signals. 1H NMR spectra of 6 recorded in CDCl3 show two
multiplets (at 4.69 ppm and 4.06 ppm) for the prochiral NH2
protons. This confirms coordination of the amine to the metal
70 centre. In contrast, the ammonium resonances of 3, 4 and 5
are observed as broad singlets between 8.92 and 8.77 ppm.
Complex 6 is only slightly soluble in most organic solvents
other that DMSOꢀd6, where it decomposes and the η6ꢀ
cordinated arene is lost. Decomposition is faster in the
75 presence of 4% triethylamine in DMSO, whereas in the
presence of 4% HCl in DMSO η6ꢀarene coordination is
retained and no decomposition was detected within 48 h,
however, the metal centre’s inner coordination sphere is
altered.
R
1) HCl / AcOEt
R'
.
Cl
Cl
Ru Ru
Cl
R
2) RuCl3 xH2O
n
n
R'
R
Cl
n
R'
-
+
+
+
-
-
(90%)
(78%)
1 n = 1,
2 n = 0,
3
4
n = 1,
n = 0,
R = COO , R' = NH3
R = COOEt, R' = NH3 Cl
-
+
R = COO , R' = NH3
R = COOEt, R' = NH3 Cl
25 Scheme 1 Synthesis of η6ꢀarene ruthenium complexes 3 and 424.
tBuOH esters are unstable under the strongly acidic reaction
conditions. Hence, changing the reaction medium from
t
HCl/AcOEt to BuOH prevents formation of the carboxylic
acid ester. Also, the high proton concentration disfavours
30 coordination of the carboxylic acid group. Nevertheless,
O
1) HCl, tBuOH
2) RuCl3 . n H2O
O
O
OH
.
reaction of 2,5ꢀdihydroꢀphenylglycine 2 with RuCl3 n H2O in
Ru
t
NH3
the presence of BuOH does not lead to the expected pendant
NH2
Cl
Cl
η6ꢀhalf sandwich amino acid. Instead, we observe
decarboxylation of phenylglycine at the αꢀCH position,
35 resulting in the formation of the dimeric ꢁꢀchloroꢀbridged η6ꢀ
benzylammonium ruthenium(II) complex 5 (scheme 2), which
has been synthesized via a different route earlier.29 The
combination of an ammonium function and an electron
withdrawing η6ꢀcoordinated Ru(II) centre at the aromatic side
40 chain leads to an highly electron deficient αꢀcarbon, which is
known to favour decarboxylation under acidic conditions and
elevated temperatures. Correspondingly, decarboxylation does
not take place if 2,5ꢀdihydroꢀphenylalanine 1 is used as the η6ꢀ
arene precursor (scheme 3). In this case, monomeric η6:κ1ꢀ
45 phenylalanine complex 6 was isolated in 54% yield as a bright
1
6
(52%)
80 Scheme 3 Synthesis of η6:κ1ꢀarene ruthenium complex 6 from 2,5ꢀ
dihydroꢀLꢀphenylalanine in tꢀbutanol.
Addition of HCl leads to protonation of the amine tether and
concomitant dissociation of amine and metal centre. This
results in the formation of 6DMSO, the first example of a nonꢀ
85 derivatized η6ꢀarene phenylalanine ligand coordinated to a
half sandwich Ru(II) complex (scheme 4). 13C NMR spectra
of 6DMSO exhibited a single set of signals for all carbons, the
1
ammonium signal in H NMR spectra was observed as a broad
singlet at 8.72 ppm. The specific optical rotation of 6DMSO was
22
yellow powder. Spectroscopic data indicate that despite the 90 determined to be [α]D +44.0 (c 0.58 in HCl / DMSO = 1 /
25), indicating racemization of the phenylalanine ligand to be
unlikely under reaction conditions.
acidic reaction conditions the side chain amino function
coordinates to the metal centre, while the carboxylic acid
function is protonated. IR spectra of the ruthenium(II)
2
|
Journal Name, [year], [vol], 00–00
This journal is © The Royal Society of Chemistry [year]

Dalton Transactions
Page 4 of 12
View Article Online
45 complexes 6, 9 and 10 suggest that the η6:κ1ꢀcoordination
mode of the amine tether is responsible for the observed
instability.
O
OH
O
HClaq
Et3N
decomp.
NH3
Cl
Ru
Cl
(DMSO)
(DMSO)
NH2
OH
Cl
Ru
Cl
Cl
DMSO
6DMSO
Cl
Cl
Cl
Ru Ru
Cl
NH3
6
Et3N
Ru
Cl
(DMSO)
H3N
Cl
Scheme 4 Reactivity of 6 under acidic (HCl) and basic (Et3N)
Cl
NH2
Cl
conditions.
9
11
NHAc
To understand the role of the pendant amine group of complex
6 in η6ꢀarene dissociation, two model compounds were
Cl
Cl
Ru Ru
Cl
NHAc
Et3N
Ru
Cl
(DMSO)
5
synthesized:
the
previously
reported
ammonium
AcHN
Cl
Cl
DMSO
functionalized complex 931,32 and its acetamide analogue 10.
Both complexes were obtained from their 2,4ꢀdihydro
cyclohexadiene derivatives as brown and ochre powders in
10
10DMSO
Scheme 6 Reactivity under basic conditions depends on the side
chain functionality of complexes 9 and 10.
+
high yields (9: 88 % 10: 92 %). In case of 9, the NH3
1
10 resonance was observed as a broad singlet at 8.15 ppm in H
NMR spectra. The amide signal of 10 resonates 2.37 ppm
downfield from the free ligand at 7.94 ppm.
50
Complex 9; 100% DMSO-d6; stable
9
9
9
9
11
11
DMSO / 4% Et3N; 40 min
11
11
I
I
I
II
Scheme 5 Synthesis of η6ꢀarene ruthenium complex 931,32 and 10 via reꢀ
aromatization of cyclohexadiene derivatives 733 and 8.
DMSO / 4% Et3N; 7h
II
11
11
I
I
I
15 Both complexes 9 and 10 form deep red solutions in DMSOꢀ
d6 and are stable in solution under aerobic conditions for days.
Upon addition of triethylamine, the colour of complex 9
instantly changes from red to yellow. This colour change is
indicative for the formation of complex 11 (scheme 6), which
20 was characterized recently.34 In 1H NMR spectra, the
ammonium signal of complex 9 is replaced by a NH2
resonance at 4.39 ppm. Resonances of the η6ꢀcoordinated
arene ring are shifted upfield by up to 0.5 ppm, indicating a
more electron deficient metal centre and a changed Ru(II)
DMSO / 4% Et3N; 24h
II
1H (ppm)
Fig. 2 Decomposition of complex 9 (1H NMR, 400 MHz, Et3N / DMSOꢀ
d6 = (1 / 25)). Within minutes, the amine tether coordinates to the metal
centre, forming complex 11 and thus initiating the decomposition. I:
unisolated intermediate. II: free 2ꢀphenyletylamine.
25 coordination sphere. When triethylamine is added to
a
55 Correspondingly, complex 3, which has a protonated (= nonꢀ
coordinating) ammonium moiety, can be converted cleanly
into the respective monomeric complex through addition of
nucleophiles. Reaction with triphenylphosphine in a mixture
of methanol and dichloromethane yielded adduct 3PPh3, which
60 was highly soluble in polar media, in nearꢀquantitative yield
(97 %, scheme 7). No coordination of the pendant amino
solution of 10 in DMSOꢀd6, 1H NMR as well as 13C NMR
signals of 10 do not change. Therefore, only the primary
amine tether is able to coordinate to the metal centre in the
presence of triethylamine / DMSO (scheme 6). Complex 11 is
30 highly unstable and approximately 20 % of complex 11
1
decomposed after 40 min in solution (figure 2). In H NMR,
+
decomposition intermediate I can be observed after just
group was detected. The NH3 resonance is observed as a
minutes. While compound
I is not fully characterized,
broad singlet at 8.77 ppm. The deep red solid is stable for
days in protic or coordinating organic solvents such as
65 methanol and DMSO without apparent decomposition. When
observed NMR shifts suggest that the phenyl ring remains
35 metalꢀcoordinated. Arene signals are shifted upfield (6.4 ppm
– 5.5 ppm) in comparison to nonꢀcoordinated arenes. Beside
these signals, we observe free 2ꢀphenylethylamine II, and
after 24 h, the decomposition was found to be complete
(figure 2). This finding is in accordance with observations
40 made for η6:κ1ꢀcoordinated complex 6, which is unstable in
DMSOꢀd6 and highly unstable in DMSOꢀd6 containing Et3N.
Protonated amine functions result in the prevention of
decomposition (following HCl addition to complex 6 or 9 as
isolated from synthesis). The combined observations from
triethylamine was added to
a
suspension of
3
in
dichloromethane, the colour of the reaction mixture changed
from red to bright yellow within 2 h, resulting from the
formation of η6:κ1ꢀcoordinated complex 12. The ethyl ester
70 group markedly increases solubility of complex 12 in nonꢀ
coordinating organic solvents as compared to complex 6.
This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00 | 3

Page 5 of 12
Dalton Transactions
View Article Online
COOEt
NH
Table 1 Crystallographic data for complexes 13 and 17
Cl H3N
EtOOC
Cl
2 PPh3
3Cl
13
C26H30Cl2N4O2Ru
602.51
Orthorhombic
P212121
0.17 х 0.1 х 0.08
9.008(2)
9.554(2)
31.245(6)
90
17
C44H68N6O12Ru2S6
1267.54
Triclinic
P1
0.15 х 0.11 х 0.09
10.390(1)
12.136(1)
12.916(1)
103.591(8)
111.663(9)
108.650(8)
1313.9(2)
1
Ru
(MeOH/CH2Cl2)
2
formula
formula wt
cryst system
space group
cryst size (mm)
a (Å)
Ru
Cl
Cl
Cl
Cl
PPh3
3
3PPh3 (97%)
Cl
H3N
Cl
Cl
10 Et3N
COOEt
Ru
Ru
Ru
Cl
b (Å)
c (Å)
α (deg)
β (deg)
(CH2Cl2)
2
EtOOC
NH2
Cl
Cl
12 (33%)
3
3
90
90
2688.9(9)
4
γ (deg)
Cl
V (Å3)
Cl
H3N
py
py
Ru
10 py, h
ν
py
NH2
Z
Cl
EtOOC
(iPrOH)
2
Dcalc (g cmꢀ3)
no. of indep rflns
no. of params
R1 (I > 2σ(I))
wR2 (all data)
goodness of fit
1.488
4868
318
0.0323
0.0957
1.184
1.602
8457
626
0.0410
0.0910
1.003
EtOOC
13 (11%)
Scheme 7 Reactivity of dinuclear η6ꢀarene complex 3 towards different
nucleophiles.
1
In the H NMR spectrum, two signals were observed for the
30 Diamine chelates of Ru(II) halfꢀsandwich complexes have
become particularly popular since Noyori and Ikariya
described this type of complex as the prototype M/NH acid
base synergy catalyst in 1995.36 We therefore reacted the
dimeric complex 3 with ethylenediamine derivatives Nꢀpꢀ
35 tosylethylenediamine and 1,4ꢀdiꢀNꢀpꢀtosylethylenediamine,
yielding chelate complexes 14 and 15 respectively (Scheme
8). Triethylamine was added to neutralize the hydrochloric
acid formed. The basic conditions again lead to the
coordination of the αꢀamino group tether. Complexes 14 and
40 15 possess markedly different solubility properties. Whereas
complex 14 can be dissolved in dicloromethane and purified
by washing with water, the monocationic37 complex 15 is
highly soluble in aqueous solution. In order to remove
triethylammonium chloride from 15, the complex was
45 dissolved in cold dry tetrahydrofurane and the remaining salt
was filtered off.
Both complexes 14 and 15 are stable towards daylight and air.
When dissolved in a mixture of acetonitrile, water and
triethylamine, their ethyl ester functionality can be saponified
50 without changing the inner coordination sphere of the metal
centre, leading to bright yellow complexes 16 and 17 in good
yields. While complex 15 dissolves in water as well as in
dichloromethane, the zwitterion 17 is insoluble in
dichloromethane and only slightly soluble in water. It
55 crystallizes readily from DMSO at room temperature. Both
complexes 14 and 16 display a single set of signals in NMR
spectra, as the αꢀCH carbon is their only chiral centre.
However, for complexes 15 and 17, which contain an
unsymmetrically substituted diamine ligand, the ruthenium
60 metal centre becomes a second stereocentre, resulting in
formation of diastereomeric compounds. Hence, NMR spectra
of 17 recorded in DMSOꢀd6 / CD3COOD (9 / 1) show the
expected two diastereomers with R and S configuration of the
Ru(II) centre. 13CꢀNMR resonances corresponding to (RRu/Sαꢀ
65 CH)ꢀαꢀCH and (SRu/SαꢀCH)ꢀαꢀCH carbons appear as 1:1:1
triplets, each separated by 0.1 ppm (10 Hz), a feature only
observed for complex 17. These triplets may result from slow
diastereotopic NH2 protons (triplet at 4.57 ppm and multiplet
at 3.82 ppm). Complex 12 shares the typical instability in
protic (methanol) and coordinating (DMSO) solvents of the
other η6:κ1ꢀcoordinated complexes. In presence of an excess
of pyridine, complex 3 rapidly decomposes into several
products, two of which were characterized. Complex 13
10 (figure 3) was crystallized from the reaction mixture in 11 %
yield, confirming the observations for η6: κ 1ꢀcoordinated
complexes described above. The ligand no longer coordinates
via a η6 – mode but is only bound through the amine side
chain to the Ru(II) centre. The octahedral coordination
15 geometry is completed by two axial chloride and three
meridional pyridine ligands. Standard crystallographic data
are compiled in table 1. The Ruꢀamine (RuꢀN4) (2.1640(3) Å)
bond is longer than the other Ruꢀ Npyridine distances (2.053(3)ꢀ
2.102(3) Å) (figure 3), indicating a higher RuꢀN bond energy
20 for the pyridine ligands. Correspondingly a second species
could be crystallized from the reaction mixture: the octahedral
complex [(py)4RuCl2], which had been structurally
characterized before.35
5
25 Fig. 3 ORTEP representation of complex 13 (50 % thermal
ellipsoids). Selected bond lengths (Å): RuꢀN1 2.102(3), Ruꢀ
N2 2.053(3), RuꢀN3 2.090(3), RuꢀN4 2.164(3).
4
|
Journal Name, [year], [vol], 00–00
This journal is © The Royal Society of Chemistry [year]

Dalton Transactions
Page 6 of 12
View Article Online
Ts
HN
O
O
O
Et3N
6 eq. Et3N
(EtOH)
Ru
N
Ru
N
0.5 eq.
3
Et3NH
Ts
N
Ts N
NH2
O
NH2
(AcN / H2O )
HN
Ts
Ts
Ts
14 (73%)
16 (64%)
O
H2N
HN
O
O
6 eq. Et3N
(EtOH)
Et3N
0.5 eq.
3
Ru
Cl
Ru
Ts
N
(AcN / H2O )
NH2
O
Ts
N
NH2
NH2
NH2
Ts
15 (62%)
17 (60%)
Scheme 8 Conversion of 3 with ethylenediamine ligands, yielding complexes 14 and 15. Saponification with triethylamine leads to complexes 16
and 17.
protonꢀdeuterium exchange at the αꢀCH position. When 45 clearly be identified at 1738 and 1736 cmꢀ1, respectively. The
recorded in DMSOꢀh6 / CH3COOH (9 / 1), only a singlet was
observed for (SRu/SαꢀCH)ꢀαꢀCH and for (RRu/SαꢀCH)ꢀαꢀCH. All
IR spectra of complexes 16 and 17 show bands corresponding
5
to a free carboxylate moiety at 1610 and 1619 cmꢀ1 instead.
1
amineꢀbound hydrogen atoms show different HꢀNMR shifts,
which were all assigned by 1H,1HꢀCOSY experiments. For
complexes 14-17, two magnetically inequivalent protons were
observed that are coupling to the αꢀnitrogen.
10 For complex 15, a 1H15NꢀHSQC NMRꢀspectrum could be
obtained in CDCl3 (Fig. 4). It confirms the data collected in
1H, 1H1HꢀCOSY and 13C NMR spectra. 1H15NꢀHSQC NMR
data show four inequivalent nitrogen atoms. Each of these
nitrogen atoms is connected to two distinct proton resonances.
15 These findings are in agreement with formation of two
diastereomers. Each diastereomer is represented by two
signals on the 15N axis indicating two protonated nitrogen
atoms per stereoisomer. The tosylated nitrogen does not give a
signal which confirms its anionic
/ deprotonated state.
20 Overall, NMR data confirm configurational stability of the η6:
κ1ꢀconfiguration on the NMR time scale as well as formation
of ((SRu/SαꢀCH)ꢀ and the (RRu/SαꢀCH)ꢀdiastereomers due to
coordination of the ꢀꢀnitrogen at the Ru centre.
Fig.
5 ORTEP representation of complex 17 (50 % thermal
ellipsoids). Selected bond lengths (Å) and angles (deg) (RRu/SαꢀCH):
50 Ru1ꢀC1 2.094(11), Ru1ꢀC2 2.173(10), Ru1ꢀC3 2.175 (9), Ru1ꢀC4
2.167(11), Ru1ꢀC5 2.167(11), Ru1ꢀC6 2.191(11), Ru1ꢀN1 2.153(8),
Ru1ꢀN2 2.103(9), Ru1ꢀN3 2.079(9), C9ꢀO1 1.205 (12), C9ꢀO2
1.226(13), Ru1ꢀN1ꢀC8 110.8(6) Ru1ꢀN2ꢀC10 111.3(6) (SRu/SαꢀCH):
Ru2ꢀC19 2.126(12), Ru2ꢀC20 2.151(12), Ru2ꢀC21 2.172(11), Ru2ꢀ
55 C22 2.240(9), Ru2ꢀC23 2.195 (11), Ru2ꢀC24 2.158 (11), Ru2ꢀN4
2.148(9), Ru2ꢀN5 2.137(8), Ru2ꢀN6 2.130(8), C27ꢀO5 1.325(16),
C27ꢀO6 1.211(11), Ru2ꢀN4ꢀC26 111.4(5) Ru2ꢀN5ꢀC28 111.7(6).
25
{6.9, -1.0}
{7.2, -0.1}
{5.8, -1.0}
{5.4, -0.1}
15N
(ppm)
{5.7, 13.2}
{6.4, 15.3}
{4.3, 13.2}
{3.6, 15.3}
30
The molecular structure of complex 17 was confirmed by
60 single crystal diffraction analysis (figure 5). Standard
crystallographic data are compiled in table 1. The λꢀ(SRu, Sαꢀ
CH)ꢀ and δꢀ(RRu, SαꢀCH) configurations of complex 17 coꢀ
crystallized from DMSO with four solvent molecules per unit
cell. The crystal structure was solved in space group P1 with
65 both complexes in the unit cell showing the original S
stereochemsitry at the αꢀposition of the phenylalanine ligand
(figure 5).38 Both the tosylated nitrogens (sum of bond angles
for N3 358.6°; N6 357.3°) and the carboxylic groups (CꢀO
35
1H (ppm)
Fig. 4 1H15NꢀHSQC of complex 15 (500 MHz, 25°C, CDCl3, natural
abundance).
40 The basic nature of the coordinated nitrogen and the different
ligands and available counter ions lead to the formation of a
cationic ruthenium complex in case of 15 and an anionic
complex in case of 16. In infrared spectra of complexes 14
and 15, bands corresponding to ethyl ester functionalities can
bond length from 1.205(12) to 1.325(16)Å) are in the monoꢀ
70 anionic state. Since no other anions are present in the unit
cell, both primary amine functions (N1, N2) have two NꢀH
This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00 | 5

Page 7 of 12
Dalton Transactions
View Article Online
bonds. The RuꢀN distances of the tethers (Ru1ꢀN1, 2.153(8);
Ru2ꢀN4 2.148(8) ) are slightly elongated in comparison with
through η6:κ1ꢀligand coordination and is evident from the Xꢀ
ray structure of complex 17) induces this instability is
Å
the other RuꢀN bonds. This indicates some conformational 60 supported by the observation that addition of nucleophiles to
strain generated by the relatively short tether when
coordinated to the metal centre. An analysis of the crystal
structure reveals, that this strain induces a tilt of C1 towards
the metal centre. The respective planes form an angle of
dimeric complex 3 results in clean formation of the respective
monomeric complexes, as long as the primary ammonium
group remains protonated. Under basic conditions, however,
the complex decomposes rapidly. Isolation of complex 13 and
5
10.1(6)° (C2, C3, C4, C5 and C6 vs. C1, C2 and C6). The 65 [(py)4RuCl2] from the conversion with 10 eq. of pyridine
crystal structure further reveals some intermolecular
provides further insight into the decomposition pathway: the
donor ligand first facilitates decoordination of the arene
ligand (complex 13). Excess of donors to formation of the
terminal product [(L)4RuCl2] (L= donor ligand, e.g. py,
10 interactions. The two diastereomeric complexes within one
unit cell show a typical offꢀcantered parallel displaced πꢀ
stacking interaction39 between the η6ꢀcoordinated phenyl
rings. Diastereomeric complexes of neighbouring unit cells 70 DMSO, …).
pair in an antiparallel orientation via hydrogen bonding
15 interaction between the two Ruꢀcoordinated NH2ꢀmoieties and
the negatively charged carboxylate groups (see supplementary
figure S2 and supplementary tables S3 ꢀ S5 for details). The
A marked increase in stability is observed, if the chloride
anions are replaced by chelating ethylenediamineꢀderived
ligands (complexes 14 – 16). This stabilisation takes place
despite coordination of the amine tether to the metal centre
observed hydrogen bonding interactions further confirm the 75 and is independent of the protonation state and charge of the
protonation/deprotonation of the functionalities involved.
diamineꢀligand (monoꢀ or diꢀanionic). Hence, electronic
effects are not a likely cause for the stabilisation observed.
We therefore assume that the increased stability is a result of
steric shielding of the metal centre by the chelating ligands,
80 which prevents donor coordination.
20
Discussion
Amino acids are attractive ligands for transition metal
complexes since the combine sustainability, intrinsic chirality,
In summary, intramolecular coordination of a nucleophilic
tether promotes decomposition of ruthenium(II) η6ꢀarene half
sandwich complexes. Responsible are two factors: the ring
strain induced and availability of additional donor ligands.
85 Correspondingly, three elements can lead to increased
stability: (i) appropriate tether length, (ii) masking of the
donor (via protonation or temporary protecting groups) or (iii)
steric shielding of the metal centre by chelating ligands. We
therefore derive the following guidelines for applications of
90 tethered half sandwich complexes: first, during derivatisations
and bioconjugation of the tether nucleophile, excess of donors
and donor solvents should be avoided, if basic conditions are
required. Second, for most bioengineering and medical
applications, neutral to basic conditions as well as an excess
95 of donors ligands can not be excluded11. Hence tethers, which
induce strain after coordination (e.g. by forming a fiveꢀ
membered ring) should be avoided. Alternatively, chelating
ligands may be introduced to protect the metal centre. Third,
for catalytic applications, the tether may provide protons (as
100 e.g. required by the outer sphere mechanism in
hydrogenations and transfer hydrogenations)41 and induce
enantioselectivity by formation of diastereomeric transition
states. However, both functions require coordination of the
tether to the metal centre and steric shielding would also
105 diminish catalytic activity. A longer tether, which does not
induce much strain or a tether with two metal binding donor
moieties that prevent coordination of additional donors should
be applied. This reasoning may explain the remarkable
performance of the tethered ruthenium(II) half sandwich
110 hydrogenation catalyst developed by Wills and others (figure
1E)17, which combine these design elements.
low costs and
a
high degree of functionalization.4
25 Ruthenium(II) η6ꢀarene half sandwich complexes have found
numerous applications including artificial enzymes, reporters,
and biomedical research.12 Therefore it is important to
investigate their reactivity in the presence of biogenic
functional groups. Our study provides clear guidelines for the
30 synthesis, stability and application of such complexes.
Synthesis from the respective 2,5ꢀdihydro amino acid
precursors is straightforward. η6ꢀcoordination of the metal
centre to phenylglycine results in acidification and subsequent
decarboxylation at the Cα, if the carboxylic moiety is not
35 protected as an ester. For all other cases, the Cα configuration
is maintained and no racemisation was detected under
synthesis conditions. While it is obvious, that optimal
enantioselectivities require enantiopure catalyst precursors it
was shown recently, that also cytotoxicity of η6ꢀarene half
40 sandwich complexes strongly depends on the chirality of the
ligand.40 Correspondingly, any synthetic strategy targeting the
carboxylic moiety of a coordinated phenylglycine ligand
should avoid acidic conditions.
Our data reveal surprisingly fast decomposition for several η6ꢀ
45 arene ruthenium(II) complexes in the presence of an excess of
nucleophiles. Notably, decomposition does also proceed in the
dark. The combined observations from complexes 3, 6, and 9 ꢀ
12 suggest that a η6:κ1ꢀcoordination mode of the amine tether
is responsible for the observed instability. The strain resulting
50 from coordination of the tether may induce ring slippage,
which temporarily opens
a
coordination site. Donor
coordination may lock the phenylethylamine ligand in a η4:κ1ꢀ
coordination, which would be in agreement with the signals
observed for intermediate I along a suggested decomposition
55 pathway 9 ꢀ 11 ꢀ I ꢀ II (2ꢀphenylethylamine). Here,
successive DMSO coordination leads to fast decoordination of
the arene. The hypothesis that ring strain (which is induced
Conclusion
Based on the appropriate synthetic conditions, the novel and
known phenyl alanine and phenyl glycine derived η6ꢀarene
6
|
Journal Name, [year], [vol], 00–00
This journal is © The Royal Society of Chemistry [year]

Dalton Transactions
Page 8 of 12
View Article Online
and tethered η6:κ1ꢀarene ruthenium(II) complexes are
accessible. The coordination behaviour of the flexible amine
tether strongly depends on reaction conditions. Protonation
leads to a decoordination of the tether, which can be reversed
under basic conditions. The strain induced by the tether,
which is also confirmed by the solid state structure of
compound 17, makes these complexes surprisingly unstable
under basic conditions, particularly in the presence of
coordinating nucleophiles. Excess of base can hence quickly
(doublet), t (triplet), m (multiplet), br (broad). For cases
where diastereomers are formed, signal assignments for
distinct spin systems are marked with a tilde (~).
5
60 Procedures
.
[(η6-PheOEt)RuCl2]2
2 HCl (3). (R)ꢀ2,5ꢀdihydrophenylꢀ
alanine 1 (1.02 g, 6.12 mmol) was stirred with 16 mL of a
solution of HClconc. in ethyl acetate (approx. 2M) for 1 h. To
10 lead to loss of the η6–coordinated ligand. Reaction with
ethylenediamine derivatives gave
η6:κ1ꢀphenylalanine
.
this suspension, RuCl3 n H2O (400 mg, 1.53 mmol) and 60
65 mL of ethanol were added and the resulting mixture was
heated to 80°C for 16 h. The resulting suspension was cooled
to ꢀ78°C, the precipitate filtered off, washed with cold ethanol
and dichloromethane (each 2 x 5 mL) and dried under reduced
pressure. Pure product 3 (553 mg, 0.69 mmol, 90%) was
70 obtained as an orange powder. – elemental analysis: calcd (%)
for C22H32Cl6N2O4Ru2: C 32.9, H 4.0, N 3.5; found: C 32.9, H
4.0, N 3.4; IR (KBr): νmax/cmꢀ1 1724vs (CO), 1487s, 1250s,
1073w, 856w; 1H NMR (400 MHz, DMSOꢀd6): δ (ppm) =
ruthenium(II) complexes, which are stable under mild
saponification conditions. Hence, the ester protecting group,
which is required to achieve good synthetic yields, can be
15 converted into a free carboxylate. This opens the possibility
for further derivatisation of the amino acid derived η6:κ1ꢀ
ruthenium(II) complexes. The stabilities and instabilities
documented here provide as a guideline to design tethered as
well as donorꢀfunctionalized complexes for future
20 applications, e.g. as pharmaceutically, catalytically active
compounds or contrast agents.
+
8.92 (s, 6H, NH3 ), 6.08ꢀ5.87 (m, 10H, CareneH), 4.39 (dd,
3
3
75 JH,H = 6.8 Hz, JH,H = 6.8 Hz, 2H, CαH), 4.23ꢀ4.14 (m, 4H,
3
CH2CH3), 3.05ꢀ2.90 (m, 4H, CβH2), 1.17 (t, JH,H = 7.0 Hz,
6H, CH2CH3); 13C NMR (100.5 MHz, DMSOꢀd6): δ (ppm) =
168.3 (COO), 97.9 / 88.5 / 88.1 / 87.6 / 87.4 / 85.6 (Carene),
62.1 (CH2CH3), 51.8 (CαH), 33.8 (CβH2), 13.9 (CH2CH3).
80
Experimental
25 Materials and Methods
[(η6-PheOEt)RuCl2(PPh3)] (3PPh3). To a suspension of [(η6ꢀ
PheOEt)RuCl2]2 2 HCl 3 (39 mg, 0.05 mmol) in a solution of
.
Commercially available solvents and reagents were purified
methanol / dichloromethane (4 mL, MeOH / DCM = 1 / 1),
triphenylphosphine (31 mg, 0.12 mmol) was added and the
85 mixture stirred at r.t. for 1.5 h, the solvent evaporated under
reduced pressure. Then the residue was redissolved in
dichloromethane (1.5 mL) and diethylether (9 mL) was added.
The precipitate was filtered off and washed with diethylether
and hexane. Pure product 3PPh3 (62.8 mg, 0.09 mmol, 97%)
90 was obtained as a red solid. – elemental analysis: calcd (%)
for C29H31Cl3NO2PRu: C 52.5, H 4.7, N 2.1; found: C 52.3, H
according to literature procedures. All reactions were carried
.
out in degassed solvents under an argon atmosphere. RuCl3
n
H2O and triphenylꢀphosphine were obtained from Sigma
30 Aldrich and used without further purification. Nꢀacetylꢀ1,4ꢀ
cyclohexadieneꢀ1ꢀethylamine 842 was prepared similar to the
route previously reported. 2,5ꢀdihydroꢀLꢀphenylalanine 1,27
.
[(η6ꢀphenylglycineOEt)RuCl2]2
2
HCl 4,23 1,4ꢀ
cyclohexadieneꢀ1ꢀethylammonium chloride 7,33 1,4ꢀdiꢀpꢀ
35 tosylethylenediamine,43 Nꢀpꢀtosylethylenediamine,44 and [(η6ꢀ
1
4.6, N 2.1; IR (KBr): νmax/cmꢀ1 1744vs (CO); H NMR (400
C6H5(CH2)2NH3 ) RuCl2]2 2 HCl 931,32 were prepared as
+
.
+
MHz, DMSOꢀd6): δ (ppm) = 8.77 (br s, 3 H, NH3 ), 7.62 (m, 6
previously reported.
H, CPPh3H), 7.32 (m, 9 H, CPPh3H), 6.02 (m, 1 H, CorthoHa),
95 5.80 (m, 1 H, CorthoHb), 5.28 (m, 1 H, CmetaHa), 5.18 (m, 1 H,
CmetaHb), 4.60 (m, 1 H, CαH), 4.46 (m, 1 H, CorthoH), 4.10 (m,
2 H, CH2CH3), 3.53 (m, 1 H, CβHaHb), 3.40 (m, 1 H, CβHaHb),
1.03 (m, 3 H, CH2CH3); 13C NMR (100.5 MHz, DMSOꢀd6): δ
(ppm) = 168.2 (COO), 134.2 (d, JPC = 9.2 Hz, CPPh3), 133.1
Physical Measurements
40 Elemental analyses were obtained from the Microanalytical
Laboratory
of
Technische
Universität
München.
Spectroscopic data were recorded on the following
instruments: IR spectra: Jasco FT/IRꢀ460 PLUS (KBR pallets 100 (d, JPC = 56.9 Hz, CPPh3), 130.5 (s, CPPh3), 128.3 (d, JPC = 9.2
/ nujol / CHCl3 in KBr cell); optical rotations: PerkinꢀElmer
45 Polarimeter 341; mass spectra: Thermo Electron LCQ classic.
MAS NMR spectra: Bruker Avance 300 (13C NMR 75.43
MHz), T = 300 K; NMR spectra: JEOL JNMꢀGX 400 (1H
NMR 400.13 MHz, 13C NMR 100.53 MHz, 31P NMR 161.8 105
MHz), T = 300 K, or BRUKER DRX 500 (1H NMR 500.13
50 MHz, 13C NMR 125.76 MHz), T = 300 K. Signals were
calibrated to the residual proton resonance and to the natural
Hz, CPPh3), 105.2 / 90.8 / 90.6 / 88.5 / 87.7 / 82.8 (Carene), 63.1
(CH2CH3), 53.3 (CαH), 33.8 (CβH2), 14.1 (CH2CH3); 31P NMR
(161.8 MHz, CDCl3): δ (ppm) = 29.52 (s); MS (ESI): m/z (%)
= 592.1 ([MꢀHꢀ2Cl]+) (100), 627.9 ([MꢀCl]+) (35).
[(η6-benzylammonium)RuCl2]2Cl2 (5). (R)ꢀ2,5ꢀdihydroꢀ
phenylglycine 2 (1.17 g, 7.65 mmol) was added to 20 mL of a
solution of HClconc. in tertꢀbutyl alcohol (approx. 2M).
:
.
abundance 13C resonance of the solvent (DMSOꢀd6 , δH = 2.50
Thereafter, RuCl3 n H2O (400 mg, 1.53 mmol) in 70 mL of
ppm and δC = 39.52 ppm; CDCl3, δH = 7.26 ppm and δC
=
110 tertꢀbutyl alcohol were added and the resulting mixture heated
at 80°C for 16 h. The precipitate formed was filtered off,
washed with cold ethanol and dichloromethane (each 2 x 5
77.16 ppm). For 31P spectra, H3PO4 was used as an external
55 standard. Signal multiplicities are abbreviated as: s (singlet), d
This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00 | 7

Page 9 of 12
Dalton Transactions
View Article Online
mL) and the residue dried under reduced pressure. Pure
product 5 (320 mg, 0.51 mmol, 66%) was obtained as an
ochre powder. elemental analysis: calcd (%) for
accordance with literature.39
60
–
[(η6-2’-phenylethylammonium)RuCl2]2Cl2 (9). To a stirred
solution of 1,4ꢀcyclohexadieneꢀ1ꢀethylammonium chloride 7
(1.10 g, 6.90 mmol) in a solution of HClconc in ethyl acetate
C14H20Cl6N2Ru2: C 26.6, H 3.2, N 4.4; found: C 26.9, H 3.4,
N 4.3; IR (KBr): νmax/cmꢀ1 3052 vs, 2912 vs, 1594 s, 1489 s,
1455 m, 1384 m, 1203 w, 1111 w, 1088 w, 876 s; 1H NMR
5
.
(20 mL, approx. 2 M), RuCl3 n H2O (300 mg, 1.15 mmol)
(400 MHz, DMSOꢀd6): δ (ppm) = 8.80 (br s, 3 H, NH3+), 6.23 65 and ethanol (40 mL) were added and the resulting solution
3
3
(d, JH,H = 6.0, 2 H, CorthoH), 6.13 (t, JH,H = 5.8, 2 H, CmetaH),
heated for 16 h at 80°C. The suspension was reduced to half
the volume in vacuo, cooled to ꢀ10°C for 48 h, the precipitate
filtered off and subsequently washed with cold pentane and
ethanol (each 3 x 5 mL) and dried under reduced pressure.
70 Pure product 9 (332 mg, 0.50 mmol, 88%) was obtained as a
5.98 (t, JH,H = 5.6 1 H, CparaH), 3.81 (s, 2 H, CH2); 13C NMR
3
10 (100.5 MHz, DMSOꢀd6): δ (ppm) = 93.4 / 89.3 / 87.3 / 86.9
(Carene), 40.6 (CH2).
[(η6:κ1-PheOH)RuCl2] (6). (R)ꢀ2,5ꢀdihydrophenylalanine 1
brown powder.
–
elemental analysis: calcd (%) for
(1.00 g, 6.25 mmol) was added to 20 mL of a solution of
15 HClconc. in tertꢀbutyl alcohol (approx. 2M). Thereafter, RuCl3
C16H24Cl6N2Ru2: C 29.5, H 3.6, N 4.3; found: C 29.15, H 3.7,
.
N 4.25; IR (KBr): νmax/cmꢀ1 1583 s, 1485 s, 1455 vs, 1423 s,
n H2O (342 mg, 1.25 mmol) in 100 mL of tertꢀbutyl alcohol
1143 s, 1024 w, 996 w, 945 w, 854 s; 1H NMR (400 MHz,
was added and the resulting mixture heated to 80°C for 16 h. 75 DMSOꢀd6): δ (ppm) = 8.15 (s, 3 H, NH3+), 6.02 (t, JH,H = 5.8
3
3
The formed precipitate was filtered off, washed with 2ꢀ
propanol (2 x 10 mL) and dried under reduced pressure. Pure
20 product 6 (438 mg, 1.30 mmol, 52%) was obtained as a
Hz, 2 H, CmetaH), 5.90 (d, JH,H = 5.6 Hz, 2 H, CorthoH), 5.86
3
+
(t, JH,H = 5.6 Hz, 1 H, CparaH), 3.16 (m, 2 H, CH2CH2NH3 ),
2.78 (t, JH,H = 7.6 Hz, 2 H, CH2CH2NH3+); 13C NMR (100.5
3
yellow powder.
–
elemental analysis: calcd (%) for
MHz, DMSOꢀd6): δ (ppm) = 101.1 / 87.6 / 87.2 / 84.9 (Carene),
+
+
C9H11Cl2NO2Ru: C 32.1, H 3.3, N 4.15, Cl 21.0; found: C 80 37.8 (CH2CH2NH3 ), 30.4 (CH2CH2NH3 ).
32.1, H 3.7, N 4.1, Cl 20.9; IR (KBr): νmax/cmꢀ1 1747vs and
1
1739vs (CO); H NMR (400 MHz, CDCl3): δ (ppm) = 5.85 (t,
[(η6-N-Acetyl-2’-phenylethylamine)RuCl2]2 (10). To
a
3
3
25 1 H, JHH = 5.4 Hz, CmetaHa), 5.80 (t, 1 H, JHH = 5.6 Hz,
stirred solution of Nꢀacetylꢀ1,4ꢀcyclohexadieneꢀ1ꢀethylamine
3
.
CmetaHb), 5.63 (d, 1 H, JHH = 5.8 Hz, CorthoHa), 5.52 (t, 1 H,
8 (1.14 g, 6.90 mmol) in ethanol (50 mL), RuCl3 n H2O (300
3JHH = 5.8 Hz, CparaH), 5.39 (d, 1 H, JHH = 5.8 Hz, CorthoHb), 85 mg, 1.15 mmol) was added and the resulting solution heated
3
4.75ꢀ4.62 (m, 2 H, CαH / NHaHb), 4.06 (m, 1 H, NHaHb), 3.14
to reflux for 16 h. The suspension was reduced to half the
volume in vacuo, cooled to ꢀ10°C for 48 h, filtered and the
precipitate washed with cold pentane and ethanol (each 3 x 5
mL) and thereafter the residual solvent removed under
2
(dd, 1 H, JHH = 13.3 Hz, 3JHH = 6.2 Hz, CβHaHb), 2.84 (dd, 1
2
3
30 H, JHH = 12.9 Hz, JHH = 12.0 Hz, CβHaHb); 13C NMR (12
kHz, CPMAS, HPDEC, 4mm ZrO2 rotor): δ (ppm) = 171.4 /
168.6 (CO), 104.1 / 97.2 / 95.3 / 93.4 / 77.0 / 74.4 / 70.9 / 90 reduced pressure. Pure product 10 (355 mg, 0.55 mmol, 92%)
68.9 (Carene / CαH), 40.2 / 39.1 (CβH2).
was obtained as an ochre powder. – elemental analysis: calcd
(%) for C20H26Cl4N2O2Ru2: C 35.8, H 3.9, N 4.2; found: C
35.4, H 3.9, N 4.1; IR (KBr): νmax/cmꢀ1 1643 vs (CO), 1567br,
1446s, 1376s, 1297vs, 1254w, 1194w, 1153w, 1103w; 1H
35 [(η6-PheOH)RuCl2(Me2SO)]2 (6DMSO). [(η7ꢀPheOH)RuCl2]2 6
(20 mg, 0.06 mmol) was dissolved in
a solution of
concentrated hydrochloric acid and
dimethylsulfoxide (520 ꢁL, HCl/DMSOꢀd6 = 1/25) and stirred
deuterated 95 NMR (400 MHz, DMSOꢀd6): δ (ppm) = 7.94 (m, 1 H, NH),
3
5.98 (t, JH,H = 5.6 Hz, 2 H, CmetaH), 5.76 (m, 3 H, CorthoH,
3
until the complex was completely dissolved, before product
CparaH), 3.34 (m, 2 H, CH2CH2NH), 2.56 (t, JH,H = 6.8 Hz, 2
40 complex 6DMSO (quantiative) was analyzed in NMR. – [α]D
H, CH2CH2NH), 1.78 (s, 3 H, CH3); 13C NMR (100.5 MHz,
DMSOꢀd6): δ (ppm) = 169.4 (CONH), 104.3 / 88.3 / 86.0 /
22
1
+44.0 (c = 0.58 g/ml in HClconc / DMSO = 1 / 25); H NMR
+
(400 MHz, DMSOꢀd6): δ (ppm) = 8.72 (br s, 3 H, NH3 ), 6.05ꢀ 100 84.0 (Carene), 38.0 (CH2CH2NH), 32.8 (CH2CH2NH), 22.6
3
5.96 (m, 3 H, CareneH), 5.88 (d, 1 H, JH,H = 5.8 Hz, CorthoH),
(CH3).
3
5.84 (t, 1 H, JH,H = 5.6 Hz, CareneH), 4.28 (m, 1 H, CHCH2),
3
45 2.95 (d, 1 H, JH,H = 6.6 Hz, CHCH2); 13C NMR (100.5 MHz,
[(η6:κ1-C6H5(CH2)2NH2)RuCl2] (11). In a standard NMR
tube, [(η6ꢀC6H5(CH2)2NH2)RuCl2] 9 (20 mg, 0.03 mmol) was
105 dissolved in a solution of triethylamine and deuterated
dimethylsulfoxide (520 ꢁL, Et3N/DMSOꢀd6 = 1/25) and
immediately analyzed. 1H NMR (400 MHz, DMSOꢀd6): δ
DMSOꢀd6): δ (ppm) = 169.8 (COO), 98.4 / 88.7 / 88.3 / 87.8 /
87.7 / 85.8 (Carene), 52.1 (CH), 33.9 (CHCH2).
N-acetyl-1,4-cyclohexadiene-1-ethylamine
50 cyclohexadieneꢀ1ꢀethylammonium chloride 7 (0.56 g, 3.50
mmol) was dissolved in a mixture of acetic anhydride and
pyridine (4 mL, acetic anhydride / pyridine = 3 / 1) and stirred 110 (m, 2 H, NH2), 3.59 (t, 2 H, JHH = 5.2 Hz, CH2CH2NH2), 2.67
at 0°C for 2 h. Thereafter, the solvent was evaporated under
reduced pressure, the residue redissolved in water (5 mL) and
55 extracted with dichloromethane (3 x 5 mL). The organic phase
was dried over MgSO4 and the solvent removed under reduced
(8).
1,4ꢀ
3
3
(ppm) = 5.74 (t, 2 H, JHH = 5.4 Hz, CmetaH), 5.47 (t, 1 H, JHH
3
= 5.4 Hz, CparaH), 5.29 (d, 2 H, JHH = 5.4 Hz, CorthoH), 4.39
3
3
(t, 2 H, JHH = 6.2 Hz, CH2CH2NH2).
.
[(η6:κ1-PheOEt)RuCl2] (12). [(η6ꢀPheOEt)RuCl2]2 2 HCl 3
(100 mg, 0.12 mmol) was suspended in dichloromethane (3
pressure. Pure product 8 (0.54 g, 3.36 mmol, 96%) was 115 mL). After addition of triethylamine (174 ꢂL, 1.24 mmol), the
obtained as a yellowish solid. Spectroscopic data are in
reaction mixture was stirred at room temperature for 2 h,
8
|
Journal Name, [year], [vol], 00–00
This journal is © The Royal Society of Chemistry [year]

Dalton Transactions
Page 10 of 12
View Article Online
filtered, the solid washed with a small amount of cold
evaporated under reduced pressure. The crude compound was
dichloromethane and dried under reduced pressure to give a 60 dissolved in dichloromethane, precipitated by adding
bright yellow powder 12 (30 mg, 0.08 mmol, 33%). –
elemental analysis: calcd (%) for C11H15Cl2NO2Ru: C 36.2, H
4.1, N 3.8; found: C 35.8, H 4.1, N 3.55; IR (KBr): νmax/cmꢀ1
1734vs and 1726vs (CO), 1575w, 1384w, 1288s, 1263s,
diethylether, washed with diethylether and hexane and dried
in vacuo to give the yellow solid 15 (yield: 81.3 mg, 0.15
5
mmol, 62%) as mixture of diastereomers. – elemental
.
analysis: calcd (%) for C20H28ClN3O4RuS H2O requires C
1206s; νmax(nujol)/cmꢀ1 1733vs and 1725vs (CO); 65 42.8, H 5.4, N 7.5, Cl 6.3; found: C 42.3, H 5.4, N 7.3, Cl 6.1;
1
νmax(CHCl3)/cmꢀ1 1741vs (CO); H NMR (400 MHz, DMSOꢀ
IR (KBr): νmax/cmꢀ1 1736vs (CO), 1263vs, 1133vs, 1079vs,
3
1
d6): δ (ppm) = 6.03 (t, 1 H, JH,H = 5.6 Hz, CmetaHa), 5.91 (t, 1
832s, 662s; H NMR (400 MHz, CDCl3): δ (ppm) = 7.74 (d, 4
3
3
3
3
10 H, JH,H = 5.4 Hz, CmetaHb), 5.50 (t, 1 H, JH,H = 5.6 Hz,
H, JH,H = 7.9 Hz, CTsH / CTsH), 7.28 (d, 2 H, JH,H = 7.8 Hz
CTsH / CTsH), 7.21 (m, 1 H, CH2NHaHb), 6.77 (m, 1 H, CH2ꢀ
3
CparaH), 5.37 (d, 1 H, JH,H = 5.4 Hz, CorthoHb), 5.26 (d, 1 H,
3JH,H = 5.8 Hz, CorthoHa), 4.69 (m, 1 H, CαH), 4.57 (t, 1 H, 70 ÑHaHb), 6.66 (m, 1 H, CmetaHa), 6.56 (m, 1 H, CmetaHa), 6.44
3JHH = 10.4 Hz, NHaHb), 4.30 (q, 2 H, JH,H = 7.1 Hz,
(m, 1 H, CαHNHaHb), 6.03 (t, 1 H, JH,H = 5.5 Hz, CmetaHb),
3
3
2
3
CH2CH3), 3.82 (m, 1 H, NHaHb), 3.28 (dd, 1 H, JH,H = 14.1
5.88 (t, 1 H, JH,H = 5.4 Hz, CmetaHb), 5.77 (m, 1 H, CH2ꢀ
3
2
3
15 Hz, JH,H = 6.2 Hz, CβHaHb), 2.96 (dd, 1 H, JH,H = 14.1 Hz,
ÑHaHb), 5.73 (m, 1 H, CαHÑHaHb), 5.60 (d, 1 H, JH,H = 5.4
3JH,H = 11.2 Hz, CβHaHb), 1.34 (t, 3 H, JH,H = 7.0 Hz,
Hz, CorthoHb), 5.58 (m, 1 H, CorthoHa), 5.54 (d, 1 H, 3JH,H = 5.7
3
CH2CH3); 13C NMR (100.5 MHz, CDCl3): δ (ppm) = 169.9 75 Hz, CorthoHa), 5.48 (d, 1 H, JH,H = 5.7 Hz, CorthoHb), 5.41 (m,
3
3
(COO), 99.9 / 93.9 / 93.4 / 78.5 / 75.8 / 72.4 (Carene), 68.1
(CH2CH3), 63.0 (CαH), 39.1 (CβH2), 14.3 (CH2CH3).
1 H, CH2NHaHb), 5.20 (dd, 1 H, JH,H = 4.4 Hz, 3JH,H = 4.4 Hz,
3
CparaH), 5.11 (dd, 1 H, JH,H = 4.5 Hz, 3JH,H = 4.5 Hz, CparaH),
20
4.84 (m, 2 H, CαH / CαH), 4.25 (m, 5 H, CH2CH3 / CH2CH3 /
3
[(η6:κ1-PheOEt)Ru(enTs2)] (14). Triethylamine (103 ꢁL,
CαHÑHaHb), 3.61 (m, 1 H, CαHNHaHb), 3.28 (dd, 1 H, JH,H
=
2
3
0.74 mmol) was added to
a
suspension of [(η6ꢀ 80 5.5 Hz, JH,H = 14.5 Hz, CβHaHb), 3.25 (dd, 1 H, JH,H = 5.6
.
3
PheOEt)RuCl2]2 2 HCl 3 (100 mg, 0.14 mmol) and N,N'ꢀdiꢀ
pꢀtosylethylenediamine (101 mg, 0.24 mmol) in ethanol (15
Hz, 2JH,H = 14.2 Hz, CβHaHb), 2.93 (dd, 1 H, JH,H = 13.1 Hz,
2JH,H = 13.1 Hz, CβHaHb), 2.74ꢀ2.53 (m, 8 H, CH2CH2
CH2CH2), 2.67 (m, 1 H, CβHaHb), 2.43 (s, 6 H, CTsCH3), 1.34
/
25 mL) and refluxed for 80 min. The solvent was evaporated
under reduced pressure; the crude compound was dissolved in
3
3
(t, 3 H, JH,H = 7.0 Hz, CH2CH3), 1.33 (t, 3 H, JH,H = 6.9 Hz,
dichloromethane (30 mL) and extracted with distillated water 85 CH2CH3); 13C NMR (100.5 MHz, DMSOꢀd6): δ (ppm) =
and brine (each 3 x 30 mL). The organic phase was dried over
MgSO4 and the solvent removed under reduced pressure to
30 give the yellow product 14 (yield: 131 mg, 0.20 mmol, 73%).
– elemental analysis: calcd (%) for C27H33N3O6RuS2: C 49.1,
170.5 / 170.4 (COO / CÕÕ), 141.3 / 141.1 / 140.9 / 140.7
(CTsSO2 / CTsSÕ2), 129.5 / 129.3 (CTsH / CTsH), 126.3 / 126.0
(CTsH / CTsH), 105.1 / 104.5 (CareneCH2 / CareneCH2), 94.7 /
93.0 / 90.8 / 90.2 / 80.0 / 77.7 / 77.3 / 74.5 / 70.2 / 69.5 / 68.1
H 5.0, N 6.4; found: C 49.0, H 5.0, N 5.9; IR (KBr): νmax/cmꢀ1 90 / 67.1 (CareneH / CareneH / CαH / CαH), 61.4 (CH2CH3
/
1
1738vs (CO), 1261vs, 1133vs, 1091vs, 814vs, 662s; H NMR
CH2CH3), 50.2 / 46.2 / 46.1 (NCH2 / ÑCH2), 36.9 / 36.8
3
(400 MHz, CDCl3): δ (ppm) = 7.67 (d, 4 H, JH,H = 7.9 Hz,
(CβH2 / CβH2), 20.9 / 20.8 (CTsCH3 / CTsCH3), 14.0 (CH2CH3 /
CH2CH3); 1H,15NꢀHSQC (500 MHz, CDCl3): {6.9, ꢀ1.0} /
{5.8, ꢀ1.0} / {7.2, ꢀ0.1} / {5.4, ꢀ0.1} (CH2NHaHb / CH2NHaHb
3
35 CTsH), 7.19 (m, 4 H, CTsH), 5.89 (t, 1 H, JH,H = 5.4 Hz,
3
CmetaHa), 5.67 (t, 1 H, JH,H = 5.4 Hz, CmetaHb), 5.44 (d, 1 H,
3JH,H = 7.0 Hz, CorthoHa), 5.42 (d, 1 H, 3JH,H = 6.2 Hz, 95 / CH2ÑHaHb / CH2ÑHaHb), {5.7, 13.2} / {4.3, 13.2} / {6.4,
3
C
orthoHb), 4.80 (t, 1 H, JH,H = 5.6 Hz, CparaH), 4.75 (m, 1 H,
15.3} / {3.6, 15.3} (CHNHaHb / CHNHaHb / CHÑHaHb /
3
CαH), 4.36 (m, 1 H, CHNHaHb), 4.20 (q, 2 H, JH,H = 7.2 Hz,
40 CH2CH3), 3.60 (m, 1 H, CHNHaHb), 3.26 (dd, 1 H, JH,H
CHÑHaHb); MS (ESI): m/z (%) = 508.1 ([M+H]+) (80),
2
=
1050.9 ([2M+HCl+H]+) (100).
3
13.7 Hz, JH,H = 5.8 Hz, CβHaHb), 2.70ꢀ2.34 (m, 5H, NCH2 /
CβHaHb), 2.33 (s, 6 H, CTsCH3), 1.27 (t, 3 H, JH,H = 6.9 Hz, 100 [(η6:κ1-PheO-)Ru(enTs2)] HNEt3
2 H2O (16). [(η6:κ1ꢀ
3
+
.
CH2CH3); 13C NMR (100.5 MHz, CDCl3): δ (ppm) = 170.1
(COO), 141.5 / 141.4 (CTsCH3), 140.8 / 140.1 (CTsSO2), 129.4
45 / 129.3 / 126.9 / 126.6 (CTsH), 103.4 (CareneCH2), 93.3 / 91.8 /
80.3 / 77.3 / 69.3 (CareneH), 67.5 (CαH), 62.3 (CH2CH3), 53.0 /
PheOEt) Ru(enTs2)] 14 (72 mg, 0.11 mmol) was dissolved in
a mixture of triethylamine, water and acetonitrile (10 mL,
Et3N:H2O:AcN = 1:1:4.5) and stirred at room temperature for
16 h before removing volatiles under reduced pressure. The
52.2 (NCH2), 38.4 (CβH2), 21.4 (CTsCH3), 14.1 (CH2CH3); MS 105 crude product was dissolved in dichloromethane (20 mL) and
(ESI): m/z (%) = 662.1 ([M+H]+) (100), 1322.6 ([2M+H]+)
(45).
extracted with distilled water (3 x 10 mL). The aqueous phase
was lyophilized, giving the bright yellow solid 16 (yield: 39.8
mg, 0.07 mmol, 64%). – elemental analysis: calcd (%) for
50
[(η6:κ1-PheOEt)Ru(enTs)]Cl (15). Triethylamine (103 ꢁL,
C31H44N4O6RuS2 2 H2O: C 48.4, H 6.3, N 7.0; found: C 47.9,
.
0.74 mmol) was added to
PheOEt)RuCl2]2 2 HCl 3 (100 mg, 0.14 mmol) and Nꢀpꢀ
a
suspension of [(η6ꢀ 110 H 5.9, N, 7.0; IR (KBr): νmax/cmꢀ1 1610s (CO), 1259s, 1131vs,
.
1
1091vs, 815s, 661s; H NMR (400 MHz, CDCl3): δ (ppm) =
3
tosylethylenediamine (59 mg, 0.24 mmol) in ethanol (15 mL)
55 and refluxed for 80 min. The solvent was evaporated under
reduced pressure, the crude product suspended in sodiumꢀ
dried tetrahydrofurane and left at ꢀ20°C for 16 h. 115 JH,H = 5.4 Hz, CorthoHb), 4.80 (t, 1 H, JH,H = 5.4 Hz, CparaH),
Triethylammoniumchloride was filtered off and the filtrate
7.69 (m, 4 H, CTsH), 7.19 (d, 4 H, JH,H = 7.5 Hz, CTsH), 5.89
3
3
(t, 1 H, JH,H = 5.4 Hz, CmetaHa), 5.72 (t, 1 H, JH,H = 5.2 Hz,
3
CmetaHb), 5.43 (d, 1 H, JH,H = 5.4 Hz, CorthoHa), 5.39 (d, 1 H,
3
3
3
4.61 (m, 1 H, CαH), 4.33 (t, 1 H, JH,H = 10.4 Hz, CαHNHaHb),
This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00 | 9

Page 11 of 12
Dalton Transactions
View Article Online
3.31 (m, 1 H, CαHNHaHb), 3.27 (m, 1 H, CβHaHb), 3.04 (q, 6
radiation (λ = 0.71073 Å, graphite monochromator). A Cryojet
Controller from Oxford Diffractions allowed measurements at
3
2
H, JH,H = 6.1 Hz, NꢀCH2CH3), 2.75 (dd, 1H, JH,H = 12.4 Hz,
3JH,H = 12.8 Hz, CβHaHb), 2.58 (m, 2 H, NCH2CH’2N’), 2.50 60 150 K. The absorption correction (empirical) of the Oxford
(m, 2 H, NCH2CH’2N’), 2.35 (s, 6 H, CTsCH3), 1.27 (t, 9 H,
3JH,H = 7.0 Hz, NCH2CH3); 13C NMR (100.5 MHz, CDCl3): δ
Xcalibur3 data set was carried out using the program CrysAlis
RED (Oxford Diffraction Ltd). The structures were solved by
Direct Methods and refined by leastꢀsquares and difference
Fourier analysis, using leastꢀsquares cycles based on F2 with
5
(ppm) = 175.3 (COO), 141.2 / 141.1 / 141.0 (CTsCH3
/
CTsSO2), 129.3 / 127.0 / 126.9 (CTsH), 106.2 (CareneCH2), 92.8
/ 91.6 / 79.4 / 77.0 / 71.6 (Carene), 69.7 (CαH), 52.8 / 52.2 65 the SHELXTL software package.[45] All the hydrogen atoms
(NCH2CH’2N’), 45.4 (N(CH2CH3)3), 39.7 (CβH2), 21.5
were geometrically fixed and refined using a riding model.
CCDCꢀ721713 (for 13) and CCDCꢀ721712 (for 17) contain
the supplementary crystallographic data for this paper. These
10 (CtosylCH3), 9.0 (N(CH2CH3)3); MS (ESI): m/z (%) = 634.1
([M+H]+) (100).
data
can
be
obtained
free
of
charge
via
[(η6:κ1-Phe)Ru(enTs)] (17). [(η6:κ1ꢀPheOEt)Ru(enTs)]Cl 15 70 http://www.ccdc.cam.ac.uk/conts/retrieving.html (or from the
(44 mg, 0.08 mmol) was dissolved in
a
mixture of
CCDC, 12 Union Road, Cambridge CB21EZ, UK; Fax: +44ꢀ
1223ꢀ336033; Eꢀmail: deposit@ccdc.cam.ac.uk).
15 triethylamine, water and acetonitrile (7 mL, Et3N:H2O:AcN =
1:1:4.5) and stirred at room temperature for 16 h before
removing volatiles under reduced pressure. The residue was
washed with diethylether, dichloromethane and methanol,
giving the citric powder 17 (yield: 22.8 mg, 39.8 mg, 0.05
Acknowledgedemts
75 The authors thank Dr. Andreas O. Frank for help with NMR
spectra and both Prof. Dr. Horst Kessler and Prof. Dr. Thomas
F. Fässler for helpful discussions. This work was supported by
KAUSTꢀGCR (FIC/2010/07) and the KAUST baseline fund
(J.E.). We thank the Elitenetzwerk Bayern (graduate
80 fellowship for T.R. and A.N.M.) and the IDK NanoCat for
funding.
20 mmol, 60%).
–
elemental analysis: calcd (%) for
.
C18H23N3O4RuS 4 H2O: C 39.3, H 5.7, N 7.6; found: C 39.3,
H 5.0, N 7.2; IR (KBr): νmax/cmꢀ1 1619s and 1597s (CO),
1399s, 1385s, 1247s, 1126s, 1092vs, 834vs, 593s; 1H NMR
3
(400 MHz, CDCl3): δ (ppm) = 7.66 / 7.64 (d, 2 H, JH,H = 7.5
3
25 Hz, d, 2 H, JH,H = 7.0 Hz, CTsH / CTsH), 7.30 / 7.28, (d, 2 H,
3JH,H = 6.2 Hz, d, 2 H, JH,H = 7.1 Hz, CTsH / CTsH), 6.49 (m,
3
3
2 H, CH2NHaHb / CH2NHaHb), 5.97 (t, 1 H, JH,H = 5.4 Hz,
3
References
CmetaHa), 5.94 (t, 1 H, JH,H = 5.0 Hz, CmetaHa), 5.87 (t, 1 H,
3JH,H = 5.0 Hz, CmetaHb), 5.72 (t, 1 H, JH,H = 4.1 Hz, CmetaHb),
3
1
(a) G. Winkhaus, H. Singer, J. Organomet. Chem. 1967, 7, 487ꢀ491;
(b) G. Winkhaus, H. Singer, M. Kricke, Z. Naturforsch. 1966, 21b,
1109ꢀ1110; (c) R. Zelonka, M.C. Baird, J. Organomet. Chem. 1972,
44, 383ꢀ389; (d) R.A. Zelonka, M.C. Baird, Can. J. Chem. 1972, 50,
3063ꢀ3072; (e) M.A. Bennett, G.B. Robertson, A.K. Smith, J.
Organomet. Chem. 1972, 43, C41ꢀC43; (f) M.A. Bennett, A.K.
Smith, J. Chem. Soc. Dalton Trans. 1974, 233ꢀ241; (g) A.N.
Nesmeyanov, A.Z. Rubezhov, J. Organomet. Chem. 1979, 164, 259ꢀ
275; (h) T. Arthur, T.A. Stephenson, J. Organomet. Chem. 1981,
208, 369ꢀ387; (i) E. L. Muetterties, J. R. Bleeke, E. J. Wucherer,
Chem. Rev. 1982, 82, 499ꢀ525; (j) R. M. Moriarty, U. S. Gill, Y. Y.
Ku, J. Organomet.. Chem. 1988, 350, 157ꢀ190; (k) M.A. Bennett,
Coord. Chem. Rev. 1997, 166, 225ꢀ254.
3
3
30 5.53 (d, 1 H, JH,H = 6.2 Hz, CorthoHa), 5.51 (d, 1 H, JH,H = 5.8
3
Hz, CorthoHb), 5.45 (d, 1 H, JH,H = 5.8 Hz, CorthoHa), 5.26 (d, 1
3
3
H, JH,H = 5.4 Hz, CorthoHb), 5.10 (t, 1 H, JH,H = 5.2 Hz,
3
CparaH), 5.04 (t, 1 H, JH,H = 5.4 Hz, CparaH), 4.79 (m, 2 H,
CαHNHaHb), 4.71 (m, 2 H, CαHꢀÑHaHb), 4.61 / 4.26 (m, 2 H,
35 CH2NHaHb / CH2ÑHaHb), 4.26 (m, 2 H, CαH / CαH), 3.61 (m,
2 H, CHÑHaHb), 3.52 (m, 2 H, CαHNHaHb), 3.13 (dd, 1 H,
2JH,H = 13.7 Hz, JH,H = 5.8 Hz, CβHaHb), 3.05 (dd, 1 H, JH,H
3
2
3
= 13.7 Hz, JH,H = 6.2 Hz, CβHaHb), 2.68 (m, 1 H, CβHaHb),
2.50 (m, 1 H, CβHaHb), 2.60 (m, 2 H, CH2CH2NHaHb
/
/
2
3
4
D. B. Grotjahn, Coord. Chem. Rev. 1999, 190ꢃ192, 1125ꢀ1141.
R. Krämer, Angew. Chem. Int. Ed. 1996, 35, 1197ꢀ1199.
40 CH2CH2ÑHaHb), 2.20 (m,
2
H, CH2CH2NHaHb
CH2CH2ÑHaHb); 13C NMR (100.5 MHz, 90 % DMSOꢀd6, 10
% CD3COOD): δ (ppm) = 173.1 / 173.0 (COO / CÕÕ), 141.3
(a) K. Severin, R. Bergs, W. Beck, Angew. Chem. Int. Ed. 1998, 37,
1634ꢀ1654; (b) G. Jaouen, A. Vessières, Acc. Chem. Res. 1993, 26,
361ꢀ369; (c) P. KöpfꢀMaier, H. Köpf, Chem. Rev. 1987, 87, 1137ꢀ
1152; (d) R. Alberto, J. Organomet. Chem. 2007, 692, 1179ꢀ1186; (e)
D. S. Williams, G. E. Atilla, H. Bregman, A. Arzoumanian, P. S.
Klein, E. Meggers, Angew. Chem. Int. Ed. 2005, 44, 1984ꢀ1987; (f)
H. Bregman, P.J. Carroll, E. Meggers, J. Am. Chem. Soc. 2006, 128,
877ꢀ884; (g) J. É. Debreczeni, A. N. Bullock, G. E. Atilla, D. S.
Williams, H. Bergman, S. Knapp, E. Meggers, Angew. Chem. Int. Ed.
2006, 45, 1580ꢀ1585; (h) C. Streu, E. Meggers, Angew. Chem. Int.
Ed. 2006, 45, 5645ꢀ5648; (i) A. L. Noffke, A. Habtemariam, A. M.
Pizarro, P. J. Sadler, Chem. Commun. 2012, 48, 5219ꢀ5346.
P. Haquette, B. Talbi, S. Canaguier, S. Dagorne, C. Fosse, A. Martel,
G. Jaouen, M. Salmain, Tetrahedron Lett. 2008, 49, 4670ꢀ4673.
W. H. Ang, E. Daldini, L. JuilleratꢀJeanneret, P. J. Dyson, Inorg.
Chem. 2007, 46, 9048ꢀ9050.
/ 141.1 / 141.0 (CTsCH3 / CTsCH3), 129.7 / 129.4 (CTsSO2
CTsSÕ2), 126.5 126.2 (CTsH CTsH), 108.1 106.9
/
/
/
/
45 (CareneCH2 / CareneCH2), 94.7 / 93.3 / 90.8 / 90.2 / 79.8 / 77.7 /
76.2 / 74.5 (CareneH / CareneH), 71.9 / 71.8 / 71.7 / 71.5 / 71.4 /
71.3 (CαH / CαH), 70.6 / 70.0 (CareneH / CareneH), 50.3 / 46.7 /
46.5 (NCH2 / ÑCH2), 38.2 / 38.0 (CβH2 / CβH2), 21.0 (CTsCH3
/ CTsCH3); MS (ESI): m/z (%) = 480.2 ([M+H]+) (100).
50
Crystal structure determinations†
5
6
7
Crystals suitable for singleꢀcrystal Xꢀray analysis of complex
13 were grown from the reaction solution at room temperature
within several days. Complex 17 was crystallized in a solution
55 of DMSOꢀd6 (approx 40 mg/mL) at room temperature within
several days. Diffraction data were collected on an Oxford
Xcalibur3 and Nonius Kappa CCD diffractometer using MoKα
R. M. Moriarty, Y.ꢀY. Ku, U. S. Gill, Chem. Commun. 1987, 1837ꢀ
1838.
8
9
A. J. Pearson, K. Lee, J. Org. Chem. 1994, 59, 2304ꢀ2313.
(a) W. S. Sheldrick, A. Gleichmann, J. Organomet. Chem. 1994, 470,
183ꢀ187; (b) A. J. Gleichmann, J. M. Wolff, W. S. Sheldrick, J.
10
|
Journal Name, [year], [vol], 00–00
This journal is © The Royal Society of Chemistry [year]

Dalton Transactions
Page 12 of 12
View Article Online
Chem. Soc., Dalton Trans. 1995, 1549ꢀ1554; (c) J. M. Wolff, A. J.
Gleichmann, C. Schmidt, W. S. Sheldrick, J. Inorg. Biochem. 1995,
59, 219; (d) J. M. Wolff, W. S. Sheldrick, J. Organomet. Chem.
1997, 531, 141ꢀ149; (e) J. M. Wolff, W. S. Sheldrick, Chem. Ber.
Recueil 1997, 130, 981ꢀ988; (f) D. A. Herebian, C. S. Schmidt, W. S.
Sheldrick, C. van Wüllen, Eur. J. Inorg. Chem. 1998, 1991ꢀ1998. (g)
R. Stodt, S. Gencaslan, A. Frodl, C. Schmidt, W. S. Sheldrick, Inorg.
Chim. Acta 2003, 355, 242ꢀ253; (h) R. Stodt, S. Gencaslan, I. M.
Müller, W. S. Sheldrick, Eur. J. Inorg. Chem. 2003, 1873ꢀ1882.
10 (a) R. S. Koefod, K. R. Mann, J. Am. Chem. Soc. 1990, 112, 7287–
7293; (b) J. W. Janetka, D. H. Rich, J. Am. Chem. Soc. 1995, 117,
10585–10586; (c) R. M. Fairchild, K. T. Holman, Organometallics
2007, 26, 3049ꢀ3053.
22 R. Stodt, S. Gencaslan, I.M. Müller, W.S. Sheldrick, Eur. J. Inorg.
Chem. 2003, 1873ꢀ1882.
23 H. Dialer, P. Mayer, K. Polborn, W. Beck, Eur. J. Inorg. Chem.
2001, 1051ꢀ1055
24 (a) J. Soleimannejad, A. Sisson, C. White, Inorg. Chim. Acta 2003,
352, 121ꢀ128; (b) G. Marconi, H. Baier, F.W. Heinemann, P. Pinto,
H. Pritzkow, U. Zenneck, Inorg. Chim. Acta 2003, 352, 188ꢀ200; (c)
J. Soleimannejad, C. White, Organometallics 2005, 24, 2538ꢀ2541.
25 T. Ohnishi, Y. Miyaki, H. Asano, H. Kurosawa, Chem. Lett. 1999,
28, 809ꢀ810.
26 (a) B. Çetinkaya, S. Demir, I. Özdemir, L. Toupet, D. Sémeril, C.
Bruneau, P.H. Dixneuf, New J. Chem. 2001, 25, 519ꢀ521; (b) B.
Çetinkaya, S. Demir, I. Özdemir, L. Toupet, D. Sémeril, C. Bruneau,
P.H. Dixneuf, Chem. Eur. J. 2003, 9, 2323ꢀ2330; (c) I. Özdemir, S.
Demir, Bekir Çetinkaya, L. Toupet, R. Castarlenas, C. Fischmeister,
P.H. Dixneuf, Eur. J. Inorg. Chem. 2007, 2862ꢀ2869.
27 A. Skolaut, J. Rétey, Arch. Biochem. Biophys. 2001, 393, 187ꢀ191.
28 G. Zvilichovsky, V. Gurvich, Tetrahedron 1995, 51, 5479ꢀ5490.
29 (a) T. Reiner, M. Waibel, A. N. Marziale, D. Jantke, F. J. Kiefer, T.
F. Fässler, J. Eppinger, J. Organomet. Chem. 2010, 695, 2667ꢀ2672
(b) T. Reiner, D. Jantke, A. Raba, A. N. Marziale, J. Eppinger, J.
Organomet. Chem. 2009, 694, 1934ꢀ1937.
30 Due to decarboxylation, the IR spectrum of 5 does not exhibit any
CO bond stretching frequencies.
31 Y. Miyaki, T. Onishi, H. Kurosawa, Inorg. Chim. Acta 2000, 300ꢃ
302, 369ꢀ377.
32 C. Scolaro, T. J. Geldbach, S. Rochat, A. Dorcier, C. Gossens, A.
Bergamo, M. Cocchietto, I. Tavernelli, G. Sava, U. Rothilsberger, P.
J. Dyson, Organometallics, 2006, 25, 756ꢀ765.
33 R. Grewe, H.ꢀW. Otto, Chem. Ber. 1959, 92, 644ꢀ651.
34 M. Melchart, A. Habtemariam, O. Novakova, S. A. Moggach, F. P.
A. Fabbiani, S. Parsons, V. Brabec, P. J. Sadler, Inorg. Chem. 2007,
46, 8950ꢀ8962.
11 (a) T. K. Hyster, L. Knörr, T. R. Ward, T. Rovis, Science 2012, 338,
500ꢀ503; (b) D. Häusinger, F. Hollmann, N. J. Turner, T. R. Ward,
Nature Chem. 2013, 5, 93ꢀ99.
12 B. Therrien, Coord. Chem. Rev. 2009, 253, 493ꢀ519.
13 (a) R.H. Fish, G. Jaouen, Organometallics 2003, 22, 2166ꢀ2177; (b)
R.E. Morris, R.E. Aird, P. del S. Murdoch, H. Chen, J. Cummings,
N.D. Hughes, S. Parsons, A. Parkin, G. Boyd, D.I. Jodrell, P.J.
Sadler, J. Med. Chem. 2001, 44, 3616ꢀ3621; (c) R.E. Aird, J.
Cummings, A.A. Ritchie, M. Muir, R.E. Morris, H. Chen, P.J. Sadler,
D.I. Jodrell, Br. J. Cancer 2002, 86, 1652ꢀ1657. (d) S.J. Dougan, P. J.
Sadler, Chimia 2007, 61, 704ꢀ715; (e) R. Schuecker, R.O. John, M.A.
Jakupec, V.B. Arion, B.K. Keppler, Organometallics 2008, 27, 6587ꢀ
6595; (f) W.F. Schmid, R.O. John, V.B. Arion, M.A. Jakupec, B.K.
Keppler, Organometallics 2007, 26, 6643ꢀ6652.
14 (a) A. F. A. Peacock, A. Habtemariam, R. Fernandez, V. Walland, F.
P. A. Fabbiani, S. Parsons, R. E. Aird, D. I. Jodrell, P. J. Sadler, J.
Am. Chem. Soc. 2006, 128, 1739ꢀ1748; (b) A. F. A. Peacock, S.
Parsons, P. J. Sadler, J. Am. Chem. Soc. 2007, 129, 3348ꢀ3357; (c) H.
Kostrhunova, J. Florian, O. Novakova, A. F. A. Peacock, P. J. Sadler,
V. Brabec, J. Med. Chem. 2008, 51, 3635ꢀ3643; (d) J. C. Gray, A.
Habtemariam, M. Winnig, W. Meyerhof, P. J. Sadler, J. Biol. Inorg.
Chem. 2008, 13, 1111ꢀ1120.
35 (a) W.ꢀT. Wong, T.ꢀC. Lau, Acta Cryst. Sect. C 1994, C50, 1406ꢀ
1407; (b) M. R. J. Elsegood, D. A. Tocher, Acta Cryst. Sect. C 1995,
C51, 40ꢀ42.
15 K. Severin, Chem. Commun. 2006, 3859ꢀ3867.
36 For recent reviews see: (a) A. Robertson, T. Matsumoto, S. Ogo,
Dalton Trans. 2011, 40, 10304ꢀ10310; (b) T. Ikariyy, Top.
Organomet. Chem. 2011, 37, 31ꢀ35.
16 K.ꢀJ. Haack, S. Hashiguchi, A. Fujii, T. Ikariya, R. Noyori, Angew.
Chem. Int. Ed. 1997, 36, 285ꢀ288.
17 (a) J. Hannedouche, G. J. Clarkson, M. Wills, J. Am. Chem. Soc.
2004, 126, 986ꢀ987; (b) A. M. Hayes, D. J. Morris, G. J. Clarkson,
M. Wills, J. Am. Chem. Soc. 2005, 127, 7318ꢀ7319; (c) D. J. Morris,
A. M. Hayes, M. Wills, J. Org. Chem. 2006, 71, 7035ꢀ7044; (d) D. S.
Matharu, G. J. Clarkson, D. J. Morris and M. Wills, Chem. Commun.
2006, 3232; (e). 10) F. K. Cheung, M. A. Graham, F. Minissi and M.
Wills, Organometallics 2007, 26, 5346ꢀ51; (f) M. Wills, D. S.
Matharu and J. E. D. Martins, Chemistry; An Asian Journal 2008, 3,
1374ꢀ1383; (g) K. E. Jollis, A. ZanottiꢀGerosa, F. Hancock, A. Dyke,
D. M. Grainger, J. A. Medlock, H. G. Nedden, J. J. M. Le Paih, S. J.
Roseblade, A. Seger, V. Sivakumar, D. J. Morris, M. Wills, Adv.
Synth. Catal. 2012, 2545ꢀ2555; (h) J. Li, Y. Tang, Q. Wang, X. Li, L.
Cun, X. Zhang, J. Zhu, L. Li, J. Deng, J. Am. Chem. Soc. 2012, 134,
18522ꢀ18525; (i) K. M. Steward, M. T. Corbett, C. G. Goodman, J. S.
Johnson, J. Am. Chem. Soc. 2012, 134, 20197ꢀ20206.
37 Coordination to the metal centre increases the NꢀH acidity enough to
promote deprotonation of sulphonamides (pKa approx. 16 for nonꢀ
coordinated NꢀH in DMSO) under reaction conditions while primary
amines remain protonated (pKa > 40 for nonꢀcoordinated NꢀH in
DMSO). For pKa values of amines coordinated to late transition
metals compare: A. N. Marziale, E. Herdtweck, J. Eppinger, S.
Schneider, Inorg. Chem. 2009, 48, 3699ꢀ3709 and references cited
therein.
38 The crystal structure of compound 17 can be solved in space groups
P1 (no inversion of chirality at the αꢀCH) or space group Pꢀ1 (partial
inversion of chirality at the αꢀCH). Using space group Pꢀ1, however,
leads to higher Rꢀvalues and implies significant disordering. The
solvent molecules cannot be refined in space group Pꢀ1.
39 G.B. McGaughey, M. Gagné, A. K. Rappé, J. Biol. Chem. 1998,
15458ꢀ15463.
40 K. J. Kilpin, S. M. Cammack, C. M. Clavel, P. J. Dyson, Dalton
Trans. 2013, 42, 2008ꢀ2014
41 S. E. Clapham, A. Hadzovic, R. H. Morris, Coord. Chem. Rev. 2004,
248, 2201ꢀ2237.
42 S. Sugasawa, R. Tachikawa, Tetrahedron 1958, 4, 205ꢀ212.
43 Y. Fukudome, H. Naito, T. Hata, H. Urabe, J. Am. Chem. Soc. 2008,
130, 1820ꢀ1821.
18 (a) W. Baratta, W.A. Herrmann, R.M. Kratzer, P. Rigo,
Organometallics 2000, 19, 3664ꢀ3669; (b) W. Baratta, E. Herdtweck,
W.A. Herrmann, P. Rigo, J. Schwarz, Organometallics 2002, 21,
2101ꢀ2106; (c) S. Gladiali, E. Alberico, Chem. Soc. Rev. 2006, 35,
226ꢀ236; (d) T. Reiner, F. N. Naraschewski, J. Eppinger,
Tetrahedron: Asymmetry 2009, 20, 362ꢀ367.
19 C. Daguenet, R. Scopelliti, P.J. Dyson, Organometallics 2004, 23,
4849ꢀ4857.
44 A. Dijksman, J.M. Elzinga, Y.ꢀX. Li, I. W. C. E. Arends, R. A.
Sheldon, Tetrahedron: Asymmetry 2002, 13, 879ꢀ884.
45 Bruker AXS Shelxtl, Version 6.14, 2000.
20 (a) L. Ackermann, A. Althammer, R. Born, Angew. Chem. Int. Ed.
2006, 45, 2619ꢀ2622; (b) A. Fürstner, L. Ackermann, Chem. Comm.
1999, 95ꢀ96.
21 (a) M. Creus, A. Pordea, T. Rossel, A. Sardo, C. Letondor, A.
Ivanova, I. LeTrong, R. E. Stenkamp, T. R. Ward, Angew. Chem. Int.
Ed. 2008, 47, 1400ꢀ1404; (b) J. Steinreiber, T. R. Ward, Coord.
Chem. Rev. 2008, 252, 751ꢀ766; (c) T. Reiner, D. Jantke, A. N.
Marziale, A. Raba. J. Eppinger, ChemistryOpen, doi:
10.1002/open.201200044.
This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00 | 11