Thioether-based anchimeric assistance for asymmetric coordination chemistry with ruthenium(ii) and osmium(ii)

Article abstract of DOI:10.1039/c3dt00015j

(R)-4-(Alkylthiomethyl)-5,5-dimethyl-2-(2′-hydroxyphenyl) -2-oxazolines are demonstrated to be highly suitable chiral auxiliaries for the two-step conversion of the half-sandwich complex [Ru(η⁶-C ₆H₆)(bpy)Cl]Cl, bpy = 2,2′

Full text of DOI:10.1039/c3dt00015j

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Thioether-based anchimeric assistance for asymmetric
coordination chemistry with ruthenium(II) and
osmium(II)†
Cite this: Dalton Trans., 2013, 42, 5623
Received 3rd January 2013,
Accepted 7th March 2013
Liang-An Chen,a Xiaobing Ding,a Lei Gong*a and Eric Meggers*a,b
DOI: 10.1039/c3dt00015j
www.rsc.org/dalton
(R)-4-(Alkylthiomethyl)-5,5-dimethyl-2-(2’-hydroxyphenyl)-2-ox-
Arene half-sandwich complexes such as [Ru(η6-C6H6)(bpy)-
azolines are demonstrated to be highly suitable chiral auxiliaries Cl]Cl (1), with bpy = 2,2′-bipyridine, are readily available in a
for the two-step conversion of the half-sandwich complex [Ru(η6- single step from the reaction of [{Ru(η6-C6H6)Cl(μ-Cl)}2] with
C6H6)(bpy)Cl]Cl, bpy = 2,2’-bipyridine, into Δ-configured ruthe- bpy and reported examples of the thermal displacement of the
nium polypyridyl complexes. The tailored thioether substituent at benzene moiety by other coordinating ligands hint towards
the oxazoline ring is essential for this conversion and not only complex 1 being an interesting starting complex for asym-
promotes the removal of the benzene moiety but also controls metric coordination chemistry.7,8 However, when we initially
the absolute metal-centered configuration. Applied to osmium, reacted ruthenium half-sandwich complex
1
with the
this strategy resulted in the first highly asymmetric synthesis of recently established salicyloxazoline auxiliary (S)-4-isopropyl-2-
Δ-[Os(bpy)3](PF6)2.
(2′-hydroxyphenyl)-2-oxazoline (2a)9 under optimized conditions
in the presence of bpy (1.2 eq.) and Et3N (10 eq.) in EtOH at
95 °C for 12 hours, we obtained the two diastereomers Λ-3a
and Δ-3a with an overall yield of only 27% and a disappointing
diastereomeric ratio of just 2 : 1 in favor of the Λ-diastereomer
(Scheme 1 and Table 1, entry 1). Fortuitously, when we instead
employed the oxazoline ligand 2b in which the isopropyl sub-
stituent is replaced by a methylthiomethyl group, under the
same reaction conditions Δ-3b was obtained diastereoselec-
tively with a d.r. of 11 : 1 in 61% yield (Table 1, entry 2).
Subsequently, in order to further improve yields and
diastereoselectivity of this transformation, the modified auxili-
aries 2c–h were synthesized and evaluated (Table 1, entries
3–8). It turned out that the oxazoline 2g, bearing two methyl
groups at the 5-position and a CH2SBn group at position 4,
provided the best results by affording Δ-3g in a yield of 82%
and a diastereomeric ratio of 24 : 1, the latter of which could
be further improved to >100 : 1 upon precipitation from
CH2Cl2–Et2O.
More than 100 years after Alfred Werner’s initial demon-
stration of metal-centered chirality in octahedral cobalt(III)
complexes, the synthetic control of chirality-at-metal remains a
formidable challenge.1 However, for many applications in the
life sciences, such as the design of metal-based nucleic acid
binders or enzyme inhibitors, optically pure metal complexes
are desired.2,3 To tackle this problem, our laboratory recently
developed a class of bidentate ligands that can serve as chiral
auxiliaries or even catalysts for the asymmetric synthesis of
octahedral ruthenium polypyridyl complexes.4,5 From a practi-
cal point of view, an important consideration is the identifi-
cation of suitable ruthenium complex precursors which are
not only synthetically readily accessible without specialized
equipment but also emenable to the following asymmetric
coordination chemistry in high yields and with high stereo-
control.6 We here wish to report our progress towards the
efficient asymmetric synthesis of ruthenium and osmium com-
plexes starting from simple η6-benzene half-sandwich com-
plexes (Fig. 1).
aCollege of Chemistry and Chemical Engineering, Xiamen University, Xiamen
361005, People’s Republic of China. E-mail: meggers@chemie.uni-marburg.de,
meggers@xmu.edu.cn, gongl@xmu.edu.cn; Tel: +86 592 2185821
bFachbereich Chemie, Philipps-Universität Marburg, Hans-Meerwein-Straße,
35043 Marburg, Germany
†Electronic supplementary information (ESI) available: Procedures and analyti-
cal data. CCDC 887598 and 917694. For ESI and crystallographic data in CIF or
other electronic format see DOI: 10.1039/c3dt00015j
Fig. 1 Asymmetric synthesis of polypyridyl complexes (M = Ru, Os) starting
from readily accessible η6-benzene half-sandwich precursors.
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Fig. 2 Crystal structure of the salicyloxazoline complex Δ-3g. Only one out of
two independent complex cations is shown. A solvent molecule and the hex-
afluorophosphate counterion are omitted for clarity. ORTEP drawing with 50%
probability thermal ellipsoids.
Scheme 1 Replacement of η6-coordinated benzene by chiral salicyloxazoline
auxiliaries. See Table 1 for more details.
Table 2 Diastereoselectivity of the conversion 2g→Δ-3g as function of the
reaction conditionsa
Table 1 Diastereoselective replacement of η6-coordinated benzene as a func-
Entry Solvent
Conc.
Temp., time
Yield d.r.b
tion of the substituents at the oxazoline ligandsa
1
2
3
4
5
6
7
EtOH
EtOH
EtOH
MeOCH2CH2OH
HOCH2CH2OH
DMF
2.5 mM 95 °C,c 12 h
82%
79%
76%
42%
24 : 1
15 : 1
21 : 1
10 : 1
3.5 : 1
—
95 °C,c 12 h
Auxiliaries 2a–h
25 mM
2.5 mM 80 °C,c 12 h
2.5 mM 120 °C, 2 h
Entry
R
R′
Main product
Yield
d.r.b
100 mM
2.5 mM 95 °C, 12 h
2.5 mM 95 °C, 12 h
120 °C, 1.5 h 69%
n.d.d
n.d.d
1
2
3
4
5
6
7
8
2a
2b
2c
2d
2e
2f
iPr
H
H
Ph
CH3
CH3
CH3
CH3
H
Λ-3a
Δ-3b
Δ-3c
Δ-3d
Δ-3e
Δ-3f
Δ-3g
Δ-3h
27%
61%
59%
74%
71%
67%
82%
31%
1 : 2
CH2SCH3
CH2SCH3
CH2SCH3
CH2SiPr
CH2StBu
CH2SBn
CH2CH2SCH3
11 : 1
19 : 1
22 : 1
16 : 1
8 : 1
MeOCH2CH2OMe
—
a Reaction conditions: half-sandwich complex 1, auxiliary 2g (1.1 eq.),
bpy (1.2 eq.), and Et3N (10 eq.) under the given conditions and in the
dark. b Diastereomeric ratios Δ-3g : Λ-3g as determined by 1H-NMR.
2g
2h
24 : 1c c Performed in a sealed vial. d n.d. = no product detected.
2.3 : 1
a Reaction conditions: Half sandwich complex 1 (2.5 mM), auxiliary
(1.1 eq.), bpy (1.2 eq.), and Et3N (10 eq.) in EtOH at 95 °C for 12 h in
the dark. b Diastereomeric ratios Δ : Λ as determined by 1H-NMR. c The
d.r. could be further improved to >100 : 1 upon precipitation of a
CH2Cl2 solution of Δ-3g with excess Et2O.
It is worth noting, that this reaction requires protic solvents
with EtOH providing better results compared to methoxyetha-
nol and ethylene glycol, whereas DMF or 1,2-dimethoxyethane
did not yield any detectable amounts of the desired product
(Table 2). The necessity for protic solvents is unclear but con-
sistent with reported thermal replacements of η6-coordinated
A crystal structure of the ruthenium complex Δ-3g is shown benzene moieties which were typically performed in MeOH or
in Fig. 2 and confirms the initially by means of CD spectro- EtOH.7,8
scopy assigned metal-centered Δ-configuration and an R-con-
Studies by Mann and co-workers indicated that the thermal
figuration at the oxazoline stereocenter.10 In addition to the displacement of η6-bound arene ligands proceed through
two bpy ligands, the salicyloxazolinate is coordinated in a intermediates with reduced hapticity.11 Accordingly, with
bidentate fashion through the phenolate oxygen and the ox- respect to the reaction between half-sandwich complex 1 and
azoline nitrogen, whereas the thioether group is not involved the thioether ligand 2g, it can be assumed that initially the
in any direct interaction. This is significant because the data chloride of 1 is substituted by either the thioether or phenol-
in Table 1 reveal that the thioether not only effects the overall ate, followed by a sequential decrease in benzene hapticity
yield of the benzene substitution but also switches the diastereo- (η6→η4→η2) going along will a concomitant increase in denti-
selectivity from Λ (Table 1, entry 1) to Δ (Table 1, entries 2–8), city (1→2→3) of 2g until the intermediates I and II are formed.
thus exerting an effect that is analogous to the well-established Under the applied reaction conditions of protic solvent and
anchimeric assistance (neighboring group participation) in high temperature these intermediates should be in a fast equi-
organic chemistry.
librium through pentacoordinated complexes. Previous DFT
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Scheme 2 Proposed mechanism for the thioether-assisted diastereoselective
formation of Δ-3g. L = EtOH (n = 1) or chloride (n = 0).
calculations with related complexes suggest that the observed
main diastereomer Δ-(R)-3g is then formed through the fast
reaction of bpy with the less stable, more reactive intermediate
II (Scheme 2).12
Scheme 3 Asymmetric synthesis of Δ-[Os(bpy)3](PF6)2. Osmium(II) complex 4
was used as chloride salt, whereas Δ-5 and Δ-6 were isolated as PF6 salts. aYield
and e.r. value after an additional precipitation.
We next evaluated this new method for the asymmetric syn-
thesis of a tris-heteroleptic ruthenium polypyridyl complex by
reacting half-sandwich complex 1 first with 5,5′-dimethyl-2,2′-
bipyridine (dmb) in the presence of auxiliary 2g under basic
conditions, followed in a separate reaction step by the TFA-
induced replacement of the chiral auxiliary with 1,10-phen-
anthroline (phen) to afford Δ-[Ru(bpy)(dmb)(phen)](PF6)2 in an
overall yield of 86% and 98 : 2 e.r. (see ESI† for more details).
Finally, we applied the developed thioether-assisted
method to asymmetric osmium(II) coordination chemistry. The
formidable challenge of this task relates to the high inertness
of coordinative bonds to osmium(II) and it is therefore not sur-
prising that, to the best of our knowledge, no efficient asym-
metric synthesis of chiral osmium(II) complexes bearing solely
achiral ligands has been reported until today. Most relevant
for this work, Bailar et al. published the (R,R)-(+)-tartrate-
mediated asymmetric synthesis of [Os(bpy)3]2+, albeit with a
low enantiomeric ratio of just 70 : 30.13
Fig. 3 Crystal structure of the osmium(II) complex Δ-5 which was crystallized as
a tetraphenylborate salt. The counterion is omitted for clarity. ORTEP drawing
with 50% probability thermal ellipsoids.
An initial screening of the auxiliary ligands of Table 1
revealed that oxazoline 2d, bearing two methyl groups at the
5-position and a CH2SCH3 group at position 4, provided the
best results. Accordingly, the osmium half-sandwich complex
4 was reacted with 2d in the presence of bpy and an excess of We assume that upon removal of the salicyloxazoline auxiliary,
K2CO3 in ethylene glycol at 150 °C for 3 h to provide Δ-5 in a Δ-[Os(bpy)2(acac-H)]+ forms as an intermediate, thus blocking
yield of 53% and with 11 : 1 d.r. (Scheme 3 and Fig. 3). Precipi- vacant coordination sites and thereby preventing racemization.
tation of in acetone dissolved Δ-5 with Et2O afforded the
In conclusion, we here revealed that 2-(2′-hydroxyphenyl)-
complex as a single diastereomer. The chiral auxiliary was sub- oxazolines with tailored thioether substituents at the 4-posi-
sequently removed by TFA-induced substitution of the salicyl- tion (Sox) are capable of thermally replacing the benzene
oxazoline against bpy to afford Δ-[Os(bpy)3](PF6)2 (Δ-6) in a moiety of the ruthenium half-sandwich complex [Ru(η6-C6H6)-
yield of 55% and with a satisfactory e.r. of 84 : 1 (Scheme 3). It (bpy)Cl]Cl and, in the presence of a polypyridyl ligand (pp), to
is noteworthy that acetylacetone (acac) as a solvent gave the afford in a stereoselective fashion the complexes Δ-[Ru(bpy)-
best results with the highest e.r. value for this reaction step. (pp)(Sox-H)]PF6, latter of which can be converted acid-induced
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under retention of configuration to Δ-[Ru(bpy)(pp)(pp′)]-
(PF6)2.14 The thioether substituent exerts a neighboring group
effect which is essential for achieving high yields and high dia-
stereoselectivity. This synthetic route is attractive for the con-
venient asymmetric synthesis of non-racemic ruthenium
polypyridyl complexes starting with readily accessible ruthe-
nium benzene half-sandwich complexes as demonstrated for
the enantioselective synthesis of one representative tris-hetereo-
leptic ruthenium polypyridyl complex. Finally, this study
culminated in what we believe is the first example of a highly
asymmetric synthesis of an osmium(II) polypyridyl complex.
5 (a) E. Meggers, Chem.–Eur. J., 2010, 16, 752; (b) L. Gong,
Z. Lin, K. Harms and E. Meggers, Angew. Chem., Int. Ed.,
2010, 49, 7955.
6 For an example of a recently reported novel ruthenium pre-
cursor complex, see: R. Vadavi, E. D. Conrad,
D. I. Arbuckle, T. S. Cameron, E. Essoun and
M. A. S. Aquino, Inorg. Chem., 2011, 50, 11862.
7 For examples of the thermal displacement of η6-coordi-
nated arenes in ruthenium half-sandwich complexes, see
for example: (a) D. A. Freedman, D. E. Janzen and
K. R. Mann, Inorg. Chem., 2001, 40, 6009; (b) X. L. Lu,
J. J. Vittal, E. R. T. Tiekink, G. K. Tan, S. L. Kuan, L. Y. Goh
and T. S. A. Hor, J. Organomet. Chem., 2004, 689, 1978;
(c) D. E. Janzen, X. Wang, P. W. Carr and K. R. Mann, Inorg.
Chim. Acta, 2004, 357, 3317; (d) D. A. Freedman, S. Kruger,
C. Roosa and C. Wymer, Inorg. Chem., 2006, 45, 9558;
(e) S. Y. Ng, J. Tan, W. Y. Fan, W. K. Leong, L. Y. Goh and
R. D. Webster, Eur. J. Inorg. Chem., 2007, 3827; (f) K.-L. Wu,
H.-C. Hsu, K. Chen, Y. Chi, M.-W. Chung, W.-H. Liu and
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H. M. Najafabadi, Y. Xu, K. Nonomura, L. Sun and L. Kloo,
Dalton Trans., 2011, 40, 8361.
8 For examples of diastereoselective coordination chemistry
with η6-benzene ruthenium half-sandwich complexes, see:
(a) M. Seitz, A. Kaiser, D. R. Powell, A. S. Borovik and
O. Reiser, Adv. Synth. Catal., 2004, 346, 737; (b) L. Gong,
C. Müller, M. A. Celik, G. Frenking and E. Meggers, New
J. Chem., 2011, 35, 788.
9 (a) L. Gong, S. P. Mulcahy, K. Harms and E. Meggers, J. Am.
Chem. Soc., 2009, 131, 9602; (b) L. Gong, S. P. Mulcahy,
D. Devarajan, K. Harms, G. Frenking and E. Meggers, Inorg.
Chem., 2010, 49, 7692.
Acknowledgements
We are grateful for support from the National Science Foun-
dation of P. R. China, the “National Thousand Plan” Foun-
dation of P. R. China, and the “985 Program” of the Chemistry
and Chemical Engineering disciplines of Xiamen University.
Notes and references
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rules, the formal assignment of the absolute stereo-
chemistry at the oxazoline moiety depends on the presence
and location of the sulfur in the substituent at the 4-posi-
tion, leading to the following formal assignments of the
major stereoisomers of the formed ruthenium complexes:
Λ-S (3a), Δ-R (3b–g), and Δ-S (3h).
4 For reviews on asymmetric coordination chemistry, see:
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wards. For example, when reacting Δ-3b in MeCN (50 mM)
with bpy (15 eq.) and TFA (5 eq.) in a sealed vial at 110 °C
for 2 hours, the auxiliary 2b was isolated in a yield of 92%
and an e.r. >99%.
5626 | Dalton Trans., 2013, 42, 5623–5626
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