The first asymmetric synthesis of chiral ruthenium tris(bipyridine) from racemic ruthenium bis(bipyridine) complexes

Article abstract of DOI:10.1016/S0040-4039(00)00230-6

The first 'one-pot' asymmetric synthesis of ruthenium tris(bipyridine) derivatives starting from corresponding racemic ruthenium bis(bipyridine) complexes is described. This is achieved through the stereocontrolled formation of reactive intermediates derived from (R)-(+)- or (S)-(-)-methyl p-tolyl sulfoxide, which can be easily converted to the products with a retention of configuration at the metal center. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)00230-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 2617–2620
The first asymmetric synthesis of chiral ruthenium tris(bipyridine)
from racemic ruthenium bis(bipyridine) complexes
Dusan Hesek,a Yoshihisa Inoue,a,∗ Hitoshi Ishida,a Simon R. L. Everitt a and
Michael G. B. Drew b
aInoue Photochirogenesis Project, ERATO, JST, 4-6-3 Kamishinden, Osaka 560-0085, Japan
bDepartment of Chemistry, The University of Reading, Whiteknights, Reading RG6 6AD, UK
Received 13 December 1999; revised 24 January 2000; accepted 4 February 2000
Abstract
The first ‘one-pot’ asymmetric synthesis of ruthenium tris(bipyridine) derivatives starting from corresponding
racemic ruthenium bis(bipyridine) complexes is described. This is achieved through the stereocontrolled formation
of reactive intermediates derived from (R)-(+)- or (S)-(−)-methyl p-tolyl sulfoxide, which can be easily converted to
the products with a retention of configuration at the metal center. © 2000 Elsevier Science Ltd. All rights reserved.
Keywords: asymmetric synthesis; chirality; sulfoxides; ruthenium.
Optically active ruthenium tris(bipyridine) complexes are important synthetic targets,1 yet their prepa-
ration through diastereoselective synthetic methods is only rarely found in the literature, requiring highly
preorganized ligands which are not readily modified.2 The ∆- and Λ-isomers of [Ru(bpy)3]2+ are most
commonly prepared using a racemic synthesis, followed by a chiral resolution technique.3 Alternatively,
it is possible to prepare a racemic ruthenium bis(bipyridine) complex, which is then resolved, and
used to prepare optically active [Ru(bpy)3]2+ derivatives.4 However, these ruthenium bis(bipyridine)
precursors are not easily handled, and their scope may be limited by this problem. For instance, cis-
or trans-Ru(dmbpy)2Cl2 (1) (dmbpy=4,40-dimethyl-2,20-bipyridine) and Ru(bpy)2Cl2 (2) (bpy=2,20-
bipyridine) have only poor solubility, and the polar protic or harsh acidic reaction conditions required
to dissolve 1 or 2 may result in racemization. Attempts to resolve 2 into its ∆- and Λ-isomers are
not encouraging,5 and the direct preparation of enantiopure materials from resolved 2 seems unlikely
to succeed in the near future. We have recently reported that chromatographically resolved cis-∆-
and cis-Λ-[Ru(bpy)2(DMSO)(Cl)]+ react with bpy nucleophiles to give the corresponding ruthenium
tris(bpy) products with almost complete retention (96% ee) of chirality at the metal center.6,7 However,
this procedure, when using optically resolved ruthenium bis(bipyridine) complexes by HPLC, is not
∗
Corresponding author. Department of Molecular Chemistry, Osaka University, 2-1 Yamadaoka, Suita 565 0871, Japan.
Tel: +81 6 6879 7920; fax: +81 6 6879 7923; e-mail: inoue@chem.eng.osaka-u.ac.jp (Y. Inoue)
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00230-6
tetl 16510

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of real practical use as only a mg-scale sample is available for the synthesis. In order to simplify
this method, we have developed the first asymmetric synthesis of novel, diastereomerically enriched
ruthenium bis(bpy) p-tolyl sulfoxide ligands, derived from 1 and 2. In this reaction8 cis- or trans-
Ru(dmbpy)2Cl2 (1) with either (R)-(+)-methyl p-tolyl sulfoxide (3) or (S)-(−)-methyl p-tolyl sulfoxide
(4) leads to the preferential formation of cis-∆-[Ru(dmbpy)23(Cl)]Cl (5) or cis-Λ-[Ru(dmbpy)24(Cl)]Cl
(7), along with the formation of corresponding minor diastereomers cis-Λ-[Ru(dmbpy)23(Cl)]Cl (6) or
cis-∆-[Ru(dmbpy)24(Cl)]Cl (8), respectively. The highest des were observed in dipolar aprotic solvents
such as DMF (e.g. 5 of 59.5% de from 3), which slightly decreased when the reaction was carried out
in a refluxing polar protic solvent (e.g. 5 of 29.5% de from 3 in MeOH, or 23.0% de in MeOH:AcOH,
10:1). This important result8 led us to investigate whether chiral Ru(bpy)3 complexes could be prepared
in a similar manner, particularly as the conventional synthetic methods were handicapped by difficulties
such as the low reactivity and solubility of the Ru(bpy)2 complexes used in the reaction.
In this paper, we wish to report that these new diastereomerically enriched precursors can be in situ
converted to optically active [Ru(bpy)3]2+ complexes without the need for isolation or resolution, making
them potentially invaluable in the syntheses of new optically active ruthenium tris(bipyridine) complexes
(Scheme 1).
Scheme 1.
Ultimately, reaction to 5 and 6 could be carried out smoothly by treating an alcohol solution of
1 with 3 followed by warming to 60°C for a few hours, thereby affording 5 and 6 in quantitative
yields. The isolation of these light sensitive sulfoxide precursors is not necessary as the unresolved,
diastereomerically enriched mixture 5 and 6 can be readily converted by a ‘one-pot’ process to other
complexes through the nucleophilic substitution of the sulfoxide and chloride ligands under very mild
conditions (e.g. 20–30 min, refluxing MeOH). We have proposed that the mechanism of ligand exchange
involves the establishment of the intermediate species 9, in which the structure is intramolecularly

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stabilized by bonding of the S–O group (Scheme 1), following the dissociation of Cl− from 5 or 6. This
intermediate 9 retains the stereochemical information at the octahedral metal center during the thermally
induced formation of ruthenium tris(bipyridine) complexes.
The absolute configuration of ruthenium tris(bipyridine) complexes can be determined by X-ray
diffraction methods if one of the ligands contains known chiral centers. For this reason, both of the
∆- and Λ-isomers of [Ru(dmbpy)2(4,40-bis[(R)-(+)-α-phenylethylamido]-2,20-bipyridine)]Cl2 (12 and
13) were synthesized from a diastereomerically enriched mixture of cis-∆-[Ru(dmbpy)23(Cl)]Cl (5) and
cis-Λ-[Ru(dmbpy)23(Cl)]Cl (6) prepared in situ (5:6=61:38, 23.2% de) reacting with the 4,40-bis[(R)-
(+)-α-phenylethylamido]-2,20-bipyridine nucleophile (10).† This gave products for which retention of
chirality at the metal center was observed (12:13=58:42, 16.0% de; starting material 5:6=23.0% de).
Similar diastereoselectivities were seen for the reaction of cis-∆-[Ru(bpy)23(Cl)]Cl (16) and cis-Λ-
[Ru(bpy)23(Cl)]Cl (17) with 10 affording cis-∆-[Ru(bpy)210]Cl2 (18) and cis-Λ-[Ru(bpy)210]Cl2 (19),
although with a small decrease in selectivity (9.0% de). The decrease in diastereoselectivity was also seen
when the opposite enantiomer 4,40-bis[(S)-(−)-α-phenylethylamido]-2,20-bipyridine (11) was employed
yielding a diastereomeric mixture of cis-Λ-[Ru(bpy)211]Cl2 (20) and cis-∆-[Ru(bpy)211]Cl2 (21). From
the X-ray structure9 of 13 (the details will be reported elsewhere), in the chiral spacegroup P21, we were
able to fully assign the absolute configuration of the separated species. In combination with the HPLC
retention times, it was then possible to assign the correct stereochemistry to the CD spectra of 18 and
19, as shown in Fig. 1. The two CD spectra in CH3CN are not mirror image reflections of one another,
as they are a diastereomeric, rather than an enantiomeric, pair. We considered that the stereochemistry
at the metal center is influenced by the chiral centers of the nucleophile as it approached the metal,
as both of the chiral auxiliary bearing bipyridines 4,40-bis[(R)-(+)-α-phenylethylamido]-2,20-bipyridine
(10) and 4,40-bis[(S)-(−)-α-phenylethylamido]-2,20-bipyridine (11) had been found to react with cis-
∆-[Ru(dmbpy)23(Cl)]Cl (5) and cis-∆-[Ru(bpy)23(Cl)]Cl (16) to give products whose diastereomeric
preferences showed only retention of stereochemistry at the metal center. However, in order to clarify
the situation we synthesized 12, 13 and 14, or 15 from racemic cis-Ru(dmbpy)2Cl2 (1) by a direct
process, simply by reacting the starting material with 10 or 11, respectively. The products from this
reaction showed Cotton effects in the CD spectrum, but chiral HPLC resolution of the product mixture
demonstrated that only racemic (1:1) mixtures had been formed. This meant that the observed de arose
through the retention of the chirality of the sulfoxide precursors (5 and 7), and not as a function
of the chiral centers on the bipyridine nucleophile. Importantly, we were also able to carry out the
diastereoselective synthesis of 12 or 14 in a ‘one-pot’ process.
When racemic cis-Ru(bpy)2Cl2 (2) was reacted with (R)-(+)-methyl p-tolyl sulfoxide 3, and dmbpy
subsequently added to the reaction mixture, [Ru(bpy)2(dmbpy)]Cl2 (22) was formed as the expected ∆-
isomer with an increased de of 26.7%, as determined by HPLC. The Λ-isomer 23 could also be prepared
following the same procedure, but using (S)-(−)-methyl p-tolyl sulfoxide 4 instead of 3, and resulting in
products with de=28.0% (see Scheme 1).
In conclusion, we have demonstrated for the first time an ability to control the chirality at the metal
center in ruthenium tris(bipyridine) complexes through the use of chiral σ-bonded sulfoxide precursors.
When (R)-(+)-methyl p-tolyl sulfoxide 3 reacts with racemic 1 or 2, an excess of the ∆-isomer, both for
the sulfoxide precursor, and for the Ru(bpy)3 product, is observed. The complimentary synthesis of the
†
Derivatives 10 and 11 are prepared from the 4,40-dicarboxylic acid (Fluka), which is converted to the diacid chloride; this is
quantitatively quenched with (R)- or (S)-α-phenylethylamine.

2620
Fig. 1. CD spectra for 20 and 21 measured in CD3CN
Λ-isomer is achieved when the (S)-(−)-sulfoxide 4 is used. This asymmetric synthesis represents the first
direct approach to optically active ruthenium tris(bipyridine) complexes to be reported.
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