Complexation to [Ru(bpy)2]2+: The trick to functionalize 3,3′-disubstituted-2,2′-bipyridine

Article abstract of DOI:10.1016/j.tetlet.2012.11.089

While many papers reported the synthesis and chemical transformations of x,x′-disubstituted-2,2′-bipyridine with x = 4, 5 or 6, this is not the case when x = 3. Though, such 3,3′-disubstituted-2,2′- bipyridines would be a useful building block for the design of new original complexes. Here we report the results of our investigation concerning the synthesis of members of this family. This study led to the formation of several [(2,2′-bipyridine)₂Ru(3,3′-dialkylated-2,2′- bipyridine)]²⁺ complexes highlighting a surprising chemical behaviour of the 3,3′-disubstituted-2,2′-bipyridine ligand compared to its 4,4′, 5,5′ and 6,6′-homologues.

Full text of DOI:10.1016/j.tetlet.2012.11.089

Tetrahedron Letters 54 (2013) 840–842
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Complexation to [Ru(bpy)2]2+: the trick to functionalize
3,30-disubstituted-2,20-bipyridine
Pascal Guillo a, Olivier Hamelin a, , Jacques Pécaut b, Stéphane Ménage a
⇑
a Laboratoire de Chimie et Biologie des Métaux, UMR 5249-Université Grenoble, I-CNRS-CEA CEA Grenoble, 17 Avenue des Martyrs, 38054 Grenoble, France
b Laboratoire de Reconnaissance Ionique et Chimie de Coordination, Service de Chimie Inorganique et Biologique, (UMR E-3 CEA/UJF-Grenoble 1), INAC, 17 rue des Martyrs,
38054 Grenoble Cedex 9, France
a r t i c l e i n f o
a b s t r a c t
While many papers reported the synthesis and chemical transformations of x,x0-disubstituted-2,20-bipyr-
idine with x = 4, 5 or 6, this is not the case when x = 3. Though, such 3,30-disubstituted-2,20-bipyridines
would be a useful building block for the design of new original complexes. Here we report the results
of our investigation concerning the synthesis of members of this family. This study led to the formation
of several [(2,20-bipyridine)2Ru(3,30-dialkylated-2,20-bipyridine)]2+ complexes highlighting a surprising
chemical behaviour of the 3,30-disubstituted-2,20-bipyridine ligand compared to its 4,40, 5,50 and 6,60-
homologues.
Article history:
Received 6 September 2012
Revised 15 November 2012
Accepted 21 November 2012
Available online 10 December 2012
Keywords:
3,30-Disubstituted-2,20-bipyridine
Ruthenium complexes
Metalloligands
Ó 2012 Elsevier Ltd. All rights reserved.
Bipyridine and in particular 2,20-bipyridine is, to date, probably
the most widely used ligand in coordination chemistry mainly for
its availability, its robust redox stability and its relative ease of
functionalization.1 Literature contains countless examples of metal
(Ru,2,3 Fe,4 Ir,5 Os,3,6 Cu7 . . .) complexes bearing one or more of this
versatile building block. This enormous popularity of these classes
of compounds is driven by the wide range of applications mainly
related to their well defined redox and photophysical properties.8,9
However, while many papers report the synthesis and/or chemical
transformations of x,x0-dialkylated-2,20-bipyridine with x = 4,10–13
514–16 or 617,18, syntheses of 3,30-disubstituted-2,20-bipyridines
are still extremely challenging.19 The main difficulty is related to
the relative proximity of the nitrogen atom and the substituent
of the opposite ring. This often leads to side reactions when 3,30-
benzylic positions have to be functionalized.
R
1; R = R' = CO2H
2; R = R' = CO2Me
3; R = R' = CH2OH
N
a
b
N
R'
Scheme 1. Synthesis of 3,30-dihydroxymethyl-2,20-bipyridine. (a) N,N0-Dicyclohex-
ylcarbodiimide (DCC), MeOH, 3 h, 0 °C, 85%; (b) LiAlH4, reflux, 2.5 days, 70%.
to reduce its 3,30 homologue with LiAlH4 (LAH, 1.6 equiv room
temperature) yielded to very low conversion. Consequently, more
drastic conditions were required and the reduction of the 3,30 dies-
ter was achieved under reflux for 2.5 days using an excess of LAH
(3.5 equiv). Surprisingly, the presence of substituents (phenyl,
methyl and tert-butyl) at the 6,60 positions greatly enhanced the
reduction of the diesters. Only 2 h at room temperature in the pres-
ence of 1.6 equiv of LAH was needed to reduce the 6,60-diphenyl
homologue of 2 as reported by Hayashi and coll.19 Using sodium
In this Letter we report our investigations in the preparation of
ruthenium bis(2,20-bipyridine) complexes bearing various 3,30-
disubstituted-2,20-bipyridine as the third bidentate ligand. The
synthesized compounds could be useful building blocks to access
new families of polynuclear complexes.
bis(2-methoxyethoxy)aluminium hydride as
a more powerful
In order to synthesize 3,30-di(hydroxymethyl)-2,20-bipyridine
(3), the commercially available 2,20-bipyridine-3,30-dicarboxylic
acid (1) was first esterified using the standard procedure into its
corresponding methyl diester in good yield (Scheme 1).20 However,
in the next reduction step, while 3 equiv of NaBH4 efficiently re-
duced the 4,40 diester at room temperature in 3 h,13 our attempts
reducing agent in diethyl ether at 0 °C, diol 3 was formed in 84%
yield.21
The substitution of the two hydroxyl groups by two potential
leaving groups (chloride, tosylate, bromide) was also particularly
difficult. After several unsuccessful attempts to introduce tosylate
groups22,23 or chloride substituents using SOCl2, the substitution
of the two hydroxyl groups by bromide was investigated. Despite
24,25
our efforts using NBS and PPh3
or an aqueous solution of HBr
⇑
Corresponding author. Tel.: +33 4 38 78 91 08; fax: +33 4 38 78 91 24.
E-mail address: ohamelin@cea.fr (O. Hamelin).
at room temperature26–28 or at 110 °C29 the desired dibromo
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.11.089

P. Guillo et al. / Tetrahedron Letters 54 (2013) 840–842
841
product was never obtained properly. A similar behaviour was ob-
served by Meyer and coll. with 4,40-di(bromomethyl)-2,20-bipyri-
dine.30 The authors suggested that the problem was related to
the close proximity of the nitrogen atom of one pyridine to the
benzylic position of the second pyridine. In order to move away
these functions from one to the other, the complexation of the li-
gand by its bipyridine moiety with a cation as template was envis-
aged. However Van der Waals repulsions between substituents in
the 3,30-positions might prevent chelation by avoiding a near cis-
planar conformation required for an optimal coordination,. This
is not the case with small substituents such as methyl groups, car-
boxylic acids and methyl esters as reported by Wallis and co-work-
ers.31 Notably, in these systems, pyridine rings are displaced from
co-planarity by 30–35° and two diastereomeric forms (
, aS- , aS) could be obtained.
D, aR-K, aR/
K
D
Reaction of 3 with 1 equiv of Ru(bpy)2Cl2,6H2O in refluxing eth-
anol resulted in the formation of complex [Ru(bpy)23]2+ (4) in rea-
sonable yield (57%; Scheme 2). The reaction proved to be highly
stereoselective since a unique diastereomer was detected by 1H
NMR spectroscopy at room temperature. The relative configuration
K
, aR-(D, aS) was attributed by X-ray crystallography of a single
crystal obtained by the slow diffusion of diethyl ether into a solu-
tion of the complex in a 3:1 acetone–MeOH mixture (Fig. 1;
Table 1). It is worth to note that the same relative configuration
was observed by Ashby and coll. for the [(bpy)2Ru(3,30-diamino-
2,20-bipyridine]2+ complex.32 In addition, an important dihedral
angle of about 34° between the two pyridinyl moieties of the
disubstituted ligand was observed, highlighting a noticeable steric
strain between substituents. Moreover, two conformational forms,
differing only by the position of one of the hydroxymethyl substi-
tuent, were observed in the crystal (65:35 ratio). Once again, the
substitution of the two hydroxyl groups by bromide to form com-
pound 5 was problematic. In the standard conditions (HBr 48% at
reflux), the cyclic ether 6 was quantitatively formed as a result of
Figure 1. ORTEP view of 4, 5 and 11 cations.
a unique substitution of one hydroxyl group by a bromide followed
by direct intramolecular cyclization due to the proximity of the hy-
droxyl and bromide groups. A 46:54 mixture of 6 and 5 respec-
tively was however obtained when the reaction was carried out
with PBr3 in dichloromethane at room temperature. This problem
was addressed by adding a large excess of PBr3 (100 equiv) directly
into a highly concentrated refluxing solution of 4 in dichlorometh-
ane. In such conditions, a 5:95 mixture was obtained in favour of
the dibromo product. After purification, 5 was obtained in 70%
yield. Single crystals suitable for X-ray analysis were obtained by
the slow diffusion of diethyl ether in a solution of the complex in
a mixture of acetone and dichloromethane with a little amount
2+
of ethanol (Fig. 1). Surprisingly, a
K, aS-(D, aR) relative configura-
tion with a dihedral angle of 39.5° was determined underlining an
unexpected isomerization of the complex during the substitution
reaction. One may hypothesize the decoordination of the disubsti-
tuted ligand followed by a subsequent recoordination after confor-
mational isomerization around the C2–C20 axis to afford a more
stable isomer. The observed important dihedral angle is without
any doubt at the origin of the weak chelation of the disubstituted
ligand even if Ru–N bond lengths involving the disubstituted li-
gand are nearly identical to the Ru–Nbpy bonds (2.069 compared
to 2.054 and 2.062 Å, respectively).
N
N
OH
a
b
(bpy)2RuCl2 + 3
(bpy)2Ru
OH
4
2+
2+
N
N
Br
Br
N
N
(bpy)2Ru
(bpy)2Ru
+
O
95 : 5
5
6
2+
3+
With the objective to synthesize compound 8 as an interesting
metalloligand able to bind different metal cations, the substitution
of the two bromide by 1,2-bis(4-pyridyl)ethane (BPA) was then
investigated.
N
N
N
2
N
N
N
N
N
c
(bpy)2Ru
+
(bpy)2Ru
(bpy)2Ru
5
N
N
N
2
100 : 0
8
7
However, despite the use of a large excess of BPA (100 equiv),
the cyclic ammonium product 7 was obtained as the unique prod-
uct in good yield (78%). Despite the high concentration of BPA,
cyclization occurred faster than intermolecular substitution of
the remaining bromide by a second molecule of BPA. Similarly,
when 1,4,11-triazacyclononane was used as nucleophile, the corre-
sponding cyclic ammonium product 9 was formed, as detected by
mass spectrometry. Compound 10 could not be detected. Conse-
quently, in order to avoid such intramolecular cyclization, azide
and phthalimide were used as nucleophile. In anhydrous DMF at
0 °C, the desired products 11 and 12 were obtained in 62 and
87% yields, respectively. Slow diffusion of diethyl ether into a solu-
tion of complex 11 in a 3:1 acetone:dichloromethane mixture
afforded single crystals suitable for X-ray analysis. While an unex-
pected and unexplained isomerization was observed during the
NH
3+
2+
N
NH
NH
N
N
N
N
NH
NH
d
N
(bpy)2Ru
5
+
N
100 : 0
NH
10
9
2+
N
N
Nu
Nu
11; Nu = N3
12; Nu = Pht
e
5
(bpy)2Ru
Scheme 2. Complexes synthesis. (a) EtOH, reflux, 4 h, 57%; (b) PBr3 (large excess),
CH2Cl2, reflux, 87%; (c) 1,2-bis(4-pyridyl)ethane, K2CO3, acetone, reflux, 78%; (d)
1,4,11-triazacyclononane, K2CO3, acetone, reflux, 42%; (e) For 11: NaN3, anhydrous
DMF, 0 °C, 62%; For 12: potassium phthalimide, DMF, rt, 24 h, 60%.

842
P. Guillo et al. / Tetrahedron Letters 54 (2013) 840–842
Table 1
Selected crystallographic data for complexes [4][PF6]2, [5][PF6]2 and [11][PF6]2
Compound
2[4][PF6]2,0.39H2O
4[5][PF6]2,8Et2O
[11][PF6]2
Formula
Molecular weight
Colour
C73H74.78F24N12O7.39P4Ru2
2020.46
Orange
C160H184Br8F48N24O8P8 Ru4
4774.63
Orange
C32H26F12N12P2Ru
969.66
Orange
Crystal system
Space group
a [Å]
b [Å]
c [Å]
Monoclinic
P 21/c
24.5602(8)
12.6187(5)
25.7537(9)
90
Monoclinic
C 2/c
12.7396(4)
20.6339(7)
18.4614(5)
90
Monoclinic
P 2(1)/n
12.1165(2)
24.5613(5)
12.2965(2)
90
a
[°]
b [°]
99.881
104.783
92.3794(16)
c
[°]
90
7
90
4692.3(3)
90
3
V [Å]3
863.1(5)
656.25(12)
Z
4
1
4
R Indices
R1 = 0.0513, wR2 = 0.0997
R1 = 0.0309, wR2 = 0.0549
R1 = 0.0391, wR2 = 0.0780
P
P
P
P
R1 =
||F0| ꢀ |Fc||/ |F0| ; wR2 = { [w(F02 ꢀ Fc2)2]/ [w(F02)2]}1/2 with w = 1/[s2(F20) + (aP)2 + bP] and P = [2Fc2 + Max(F20, 0)]/3.
formation of the dibromo product 5 from diol 4, (from a
aS) to a , aS-( , aR) relative configuration), a similar behaviour
was observed during the substitution of the two bromides by azide
K, aR-(D,
References and notes
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In conclusion, we report here the results of our investigation
into the intriguing chemistry of 3,30-disubstituted-2,20-dipyridine
and related ruthenium based-complexes yielding the formation
of compounds of interest such as 7, 9, 11 and 12. To the difference
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Acknowledgment
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Supplementary data
Supplementary data (Crystallographic data for 4, 5 and 11 were
deposited at the Cambridge Crystallographic Data Centre (CCDC)
with the CCDC reference numbers: CCDC 858774 for [1][PF6]2,
CCDC 858775 for [5][PF6]2 and CCDC 858776 for [11][PF6]2) associ-
ated with this article can be found, in the online version, at http://
dx.doi.org/10.1016/j.tetlet.2012.11.089.