Synthesis of highly enantiomerically enriched planar chiral ruthenium complexes via Pd-catalysed asymmetric hydrogenolysis

Article abstract of DOI:10.1039/b910977c

Key elements in this communication are a very efficient microwave synthesis of [RuCp(naphthalene)][PF₆], the precursor of [RuCp(CH ₃CN)₃][PF₆], and a Pd-catalysed asymmetric hydrogenolysis to afford planar chira

Full text of DOI:10.1039/b910977c

View Online / Journal Homepage / Table of Contents for this issue
This article was published as part of the
2
009 ‘Catalysis in Organic
Synthesis’ web theme issue
Showcasing high quality research in organic chemistry
Please see our website
(
http://www.rsc.org/chemcomm/organicwebtheme2009)
to access the other papers in this issue.

COMMUNICATION
www.rsc.org/chemcomm | ChemComm
Synthesis of highly enantiomerically enriched planar chiral ruthenium
complexes via Pd-catalysed asymmetric hydrogenolysiswz
Audrey Mercier, Wee Chuan Yeo, Jingyu Chou, Piyali Datta Chaudhuri, Gerald Bernardinelli
´
and E. Peter Kundig*
¨
Received (in Cambridge, UK) 4th June 2009, Accepted 21st July 2009
First published as an Advance Article on the web 5th August 2009
DOI: 10.1039/b910977c
4
,5
Key elements in this communication are a very efficient
scarce attention in terms of applications in catalysis.
6
5
microwave synthesis of [RuCp(naphthalene)][PF ], the precursor
6
Both cationic (Z -arene)ruthenium and neutral(Z -indenyl)
6
of [RuCp(CH CN) ][PF ], and a Pd-catalysed asymmetric
3
ruthenium species are more resistant than [Cr(Z -arene)(CO) ]
3
6
3
hydrogenolysis to afford planar chiral ruthenium complexes
with high levels of enantioselectivity using a bulky chiral
phosphoramidite ligand.
complexes to oxidative, thermal and photolytic cleavage of the
metal–arene bond. To date, enantiopure members of planar
chiral Ru sandwich complexes have been synthesised either via
5
chiral precursors or by resolution via (semi)-preparative
6
HPLC. To the best of our knowledge, catalytic desymmetri-
Efficient access to optically pure planar chiral complexes is of
interest in asymmetric synthesis and catalysis. The complexes
can notably serve as the chiral source in asymmetric reactions
and as catalysts or chiral ligands in a variety of organic
sation processes have been applied exclusively to prochiral
6
7
3
[Cr(Z -arene)(CO) ] complexes.
Before investigating dibromonaphthalene complexes of
Ru(II), we deemed it important to further develop an efficient
access to multi-gram quantities of starting material. We thus
revisited the synthetic protocol of the pivotal precursor
1
transformations. The most widely applied strategies to access
enantiomerically enriched forms of these compounds
are based either on resolution of racemates or on diastereo-
selective and enantioselective reactions. These approaches
require a stoichiometric amount of chiral reagents or
auxiliaries. A very attractive alternative, recently developed
in our laboratory, is the Pd-catalysed enantioselective hydro-
[RuCp(CH
CN) ][PF ] (4a). In 2004, we reported an
3 3 6
operationally safe and simple method for the synthesis of
8
4a that avoids the use of both highly toxic thallium
a
8
b
8b,c
reagents and photolytic quartz apparatus.
The procedure
2
genolysis of the prochiral chromium complex 1 (Scheme 1).
still suffers from practical limitations, notably a long reaction
time and large excess of naphthalene. Focusing on the
Cp–arene exchange, we now find that using microwave
We here report on the first application of this desymmetrisation
5
6
process to the isoelectronic [Ru(Z -C R )(Z -5,8-dibromo-
5
5
9
naphthalene)][PF
5
6
] (5) as well as to the neutral analogues
irradiation allows us to reduce the amount of naphthalene
5
[
Ru(Z -C
5
R
5
)(Z -4,7-dibromoindene)] (6).
from 10 to 2 equivalents. More importantly, the reaction time
can be drastically shortened from 3 days to 15 minutes!
This reaction was carried out conveniently on a 10 mmol
scale, leading to 3.7 g of [RuCp(naphthalene)][PF ] (8) after
6
purification (Scheme 2).y
This new efficient preparation removes
a bottleneck
in the preparation of the widely used catalyst
1
0
[RuCp(CH
3
CN)
3
][PF
6
].
We also note that it can be
more convenient to use the air-stable catalyst precursor
[
RuCp(naphthalene)][PF
6
] (8) in place of the air-sensitive
1
1
[
RuCp(CH CN) ][PF ] (4a).
3
3
6
Scheme 1 Palladium-catalysed asymmetric hydrogenolysis of complex 1.
Complexes 5a, b and 6a, b were synthesised starting from
RuCp(CH CN) ][PF ] (4a) and [RuCp*(CH CN) ][PF ]
[
3
In contrast to planar chiral ferrocenes and chromium
1
3
3
6
3
3
6
13,14
1
4b), respectively, according to literature procedures.
2
(
complexes, ruthenium sandwich complexes have received
Similarly, complex 6c was prepared from 4c (Scheme 3).
Initial desymmetrisation studies started with cationic
5
6
[
Ru(Z -C
(Table 1). The optimal conditions developed for chromium
complex 1 were applied first. LiBH was employed as the
hydride source and DABCO was used as the borane scavenger
5
R
5
6
)(Z -5,8-dibromonaphtahlene)][PF ] (5) as substrates
Department of Organic Chemistry, University of Geneva,
Quai Ernest Ansermet 30, 1211 Geneva 4, Switzerland.
E-mail: Peter.Kundig@unige.ch
4
w This article is part of a ChemComm ‘Catalysis in Organic Synthesis’
web-theme issue showcasing high quality research in organic
chemistry. Please see our website (http://www.rsc.org/chemcomm/
organicwebtheme2009) to access the other papers in this issue.
z Electronic supplementary information (ESI) available: Experimental
details for the reported compounds and spectroscopic data (28 pages).
CCDC 735050. For ESI and crystallographic data in CIF or other
electronic format see DOI: 10.1039/b910977c
1
5
3
to prevent the formation of the BH –ligand adduct.
The reaction of 5a in DME gave only moderate conversion
and asymmetric induction (Table 1, entry 1). Using dichloro-
methane, adjusting the temperature to ꢀ50 1C and the amount
of LiBH to one equivalent afforded mono-halogenated 9a in
4
This journal is ꢁc The Royal Society of Chemistry 2009
Chem. Commun., 2009, 5227–5229 | 5227

Table 1 Palladium-catalysed asymmetric hydrogenolysis of cationic
complexes
a
LiBH
T/1C (eq.)
4
5
(%)
9
(%)
10
(%)
ee 9
c
(%)
b
b
b
Entry
5
t/h
d,e
1
5a
5a
5b
5b
5b
ꢀ20
ꢀ50
ꢀ40
ꢀ40
ꢀ40
2
1
1.5
1.5
1.5
1.7
1.7
3.0
4.0
2.5
27
2
0
0
0
56
75
92
88
90
17
19
8
12
10
74
90
96
99
97
Scheme 2 Improved protocol for the synthesis of 4a via microwave-
d,f
2
g
assisted Cp–arene exchange.
3
g
4
h
5
a
Reaction conditions (unless otherwise stated): 0.2 mmol of 5, LiBH
added dropwise as a DME solution, 0.025 M in dry and degassed
4
b
1
Determined by H NMR. Determined by H NMR in the
c
1
CH
2
Cl
2
.
1
8 d
presence of [n-Bu
e
4
N][D-TRISPHAT].
Reaction carried out in DME. 3% of decomplexation product.
20 mol% of L*, no DABCO.
f
g
h
2
.5 mol% [Pd(allyl)Cl]
Pd(allyl)Cl] , 4 mol% L*; 92% isolated yield of a 9 : 1 mixture
of 9: 10.
2
.
Run on 3 mmol of 5; 0.5 mol%
[
2
Scheme 3 Synthesis of cationic and neutral complexes 5 and 6
(DCE = dichloroethane).
9
0% ee with an excellent selectivity between 9a and the over-
reduced complex 10a (Table 1, entry 2). With complex 5b,
bearing the bulky, electron-rich Cp* ligand, the optimal
temperature for the desymmetrisation was ꢀ40 1C. After 3 h,
full conversion and high 9b/10b selectivity were attained and
the ee reached 96% (Table 1, entry 3). Taking advantage of the
kinetic resolution at play in this reaction, 9b can be obtained in
Scheme 4 Suzuki–Miyaura coupling of 9b. ORTEP view of the
crystal structure of (S)-13b.
was achieved, affording 11a in up to 96% ee along with a good
1
9
1a/12a ratio (Table 2, entries 3 and 4). Complex 6b,
1
incorporating the bulky, electron-rich Cp* ligand, was proved
more problematic. 11b was obtained in 68% ee, with a 2 : 1
ratio between 11b and 12b (Table 2, entry 5). The reaction was
9
9% enantiomeric excess, albeit at the expense of a larger
amount of over-reduced complex 10b (Table 1, compare
entries 3 and 4, faster conversion of the minor enantiomer
Table 2 Pa alladium-catalysed asymmetric hydrogenolysis of neutral
complexes
1
6
(
R)-9 into 10 leads to further enrichment in (S)-9). When the
reaction was performed on a larger scale (3 mmol), as low as
mol% of Pd and 4 mol% of chiral ligand were sufficient to
achieve complete conversion and high enantioselectivity
Table 1, entry 5). Attempts to separate complexes 9 and 10
1
(
were not successful. Conversion of 9b into 13b by a micro-
wave-assisted cross-coupling reaction was performed without
erosion of enantioselectivity (Scheme 4). Separation of 13b
from remaining 10b posed no problem. The (S) absolute
configuration of 13b, and by analogy 9b, was determined via
6
(%)
11
(%)
12
(%)
ee 11
(%)
b
b
b
c
Entry
6
Solvent T/1C t/h
1
7
X-ray crystallographic analysis.
1
2
3
4
5
6
6a DME
6a Toluene
6a Toluene ꢀ10
6a Toluene ꢀ20
6b Toluene ꢀ20
6c Toluene ꢀ20
10
10
1.5
1.5
2.5
18.0
22.5
24.0
0
0
2
0
0
3
30
65
72
72 (72)
69 (62)
77 (71)
70
35
26
28
31
20
96
89
91
96
68
78
We next tested this desymmetrisation procedure on the
neutral analogues 6. These are more stable and easier to
handle than the cationic derivatives (Table 2). Reaction
conditions had to be modified from those optimal for 5. The
d
d
d
temperature was raised to 10 1C, Pd(dba)
2
was used in place of
a
Reaction conditions (unless otherwise stated): 0.1 mmol of 6, LiBH
4
[
Pd(allyl)Cl] and the solvent was changed to DME.
2
,
added dropwise as a DME solution, 0.025 M in dry and degassed
Substantial over-reduction to give 12a remained a problem,
however (Table 2, entry 1). In toluene the 11a/12a selectivity
was improved (Table 2, entry 2). At ꢀ20 1C complete conversion
b
solvent. Determined by H NMR. Determined by chiral HPLC.
1
c
d
Isolated yield after flash chromatography.
5
228 | Chem. Commun., 2009, 5227–5229
This journal is ꢁc The Royal Society of Chemistry 2009

0
also carried out with 6c (R = Me, R = CF
3
), isosteric to 6c
22, 1038; (e) S. Bonnet, J. Li, M. A. Siegler, L. S. von Chrzanowski,
A. L. Spek, G. van Koten and R. J. M. K. Gebbink, Chem.–Eur. J.,
2
0
and isoelectronic to 6a. Complex 11c was obtained with an
intermediate 78% ee (Table 2, entry 6), indicating that both
steric and electronic properties affect the enantioselectivity
outcome of the process. This trend had not been observed
for the cationic complexes.
2009, 15, 3340.
6
7
C. E. Garrett and G. C. Fu, J. Am. Chem. Soc., 1998, 120, 7479.
(a) M. Uemura, H. Nishimura and T. Hayashi, Tetrahedron Lett.,
1993, 34, 107; (b) M. Uemura, H. Nishimura and T. Hayashi,
J. Organomet. Chem., 1994, 473, 129; (c) B. Gotov and
H. G. Schmalz, Org. Lett., 2001, 3, 1753; (d) A. Bottcher and
H. G. Schmalz, Synlett, 2003, 1595; (e) K. Kamikawa, K. Harada
and M. Uemura, Tetrahedron: Asymmetry, 2005, 16, 1419.
In conclusion, we have established a convenient, high
yield, microwave-assisted synthesis for the preparation of
8
9
(a) E. P. Ku
01; (b) T. P. Gill and K. R. Mann, Organometallics, 1982, 1, 485;
c) B. M. Trost and C. M. Older, Organometallics, 2002, 21, 2544.
D. Adam, Nature, 2003, 421, 571.
¨
ndig and F. R. Monnier, Adv. Synth. Catal., 2004, 346,
[
3 3 6
RuCp(CH CN) ][PF ] (4a) from readily available ruthenocene.
9
(
We have also developed the first catalytic desymmetrisation of
ruthenium complexes and demonstrated the generality of the
Pd-catalysed asymmetric enantioselective hydrogenolysis.
Studies are ongoing in our laboratory to apply these planar
chiral complexes as chiral ligands in asymmetric catalysis.
Financial support by the Swiss National Science Foundation
and the University of Geneva is acknowledged with thanks.
We are grateful to M. Berthod, P. Buchgraber, D. Linder and
C. Mazet for helpful discussions and technical assistance.
10 (a) B. M. Trost, F. D. Toste and A. B. Pinkerton, Chem. Rev.,
001, 101, 2067; Recent reports; (b) E. C. Hansen and D. S. Lee,
2
J. Am. Chem. Soc., 2005, 127, 3252; (c) H. Saburi, S. Tanaka and
M. Kitamura, Angew. Chem., Int. Ed., 2005, 44, 1730;
(d) B. M. Trost and A. C. Gutierrez, Org. Lett., 2007, 9, 1473;
(e) F. C. Pigge, R. Dhanya and E. R. Hoefgen, Angew. Chem., Int.
Ed., 2007, 46, 2887; (f) S. Constant, S. Tortoioli, J. Muller and
J. Lacour, Angew. Chem., Int. Ed., 2007, 46, 2082.
1
1
1 (a) A. Labonne, T. Kribber and L. Hintermann, Org. Lett., 2006,
8
, 5853; (b) T. Kribber, A. Labonne and L. Hintermann, Synthesis,
007, 2809; (c) A. Labonne, L. Zani, L. Hintermann and C. Bolm,
Notes and references
2
J. Org. Chem., 2007, 72, 5704; (d) D. Linder, F. Buron, S. Constant
and J. Lacour, Eur. J. Org. Chem., 2008, 5778.
2 B. Steinmetz and W. A. Schenk, Organometallics, 1999, 18, 943.
y See caution note on the use of Al powder in the microwave
experiments (ESI).
1
(a) C. Bolm and K. Muniz, Chem. Soc. Rev., 1999, 28, 51;
b) A. R. Pape, K. P. Kaliappan and E. P. Kundig, Chem. Rev.,
000, 100, 2917; (c) A. Salzer, Coord. Chem. Rev., 2003, 242, 59;
d) Transition Metal Arene p-Complexes in Organic Synthesis and
Catalysis: Topics in Organometallic Chemistry, ed. E. P. Kundig,
13 (a) R. C. Cambie, S. A. Coulson, L. G. Mackay, S. J. Janssen,
P. S. Rutledge and P. D. Woodgate, J. Organomet. Chem., 1991,
409, 385; (b) S. P. Nolan, K. L. Martin, E. D. Stevens and
P. J. Fagan, Organometallics, 1992, 11, 3947.
14 A. R. Kudinov, P. V. Petrovskii, Y. T. Struchkov, A. I. Yanovskii
and M. I. Rybinskaya, J. Organomet. Chem., 1991, 421, 91.
(
2
(
¨
¨
Springer Verlag, Heidelberg, 2004, vol. 7; (e) M. Ogasawara and
S. Watanabe, Synthesis, 2009, 1761.
15 The manuscript regarding the use of DABCO as BH
Pd–phosphoramidite–LiBH asymmetric hydrogenolysis of Ar–Br
3
-scavenger in
2
3
E. P. Kundig, P. D. Chaudhuri, D. House and G. Bernardinelli,
Angew. Chem., Int. Ed., 2006, 45, 1092.
¨
4
bonds in arene chromium complexes is in preparation.
(a) Ferrocenes, ed. T. Hayashi and A. Togni, VCH, Weinheim,
Germany, 1995; (b) T. J. Colacot, Chem. Rev., 2003, 103, 3101;
16 Kinetic resolution: (a) H. B. Kagan and J. C. Fiaud, Top.
Stereochem., 1988, 18, 249; (b) J. M. Keith, J. F. Larrow and
E. N. Jacobsen, Adv. Synth. Catal., 2001, 343, 5; (c) For racemic
(
c) G. C. Fu, Acc. Chem. Res., 2004, 37, 542; (d) R. G. Arrayas,
J. Adrio and J. C. Carretero, Angew. Chem., Int. Ed., 2006, 45,
674; (e) M. Ogasawara, S. Watanabe, K. Nakajima and
[RuCp*(5-bromonaphthalene)][PF
6
], a selectivity factor S of 3.5
was found at ꢀ40 1C.
6
17 Crystal data for (S)-13: (C26H27Ru)(PF ), M = 585.5, T = 150 K,
7
T. Takahashi, Pure Appl. Chem., 2008, 80, 1109.
(a) R. M. Moriarty, U. S. Gill and Y. Y. Ku, J. Organomet. Chem.,
4
MoKa, orthorhombic, space group P2
1
2
1
2
1
, a = 7.1897(3),
3
b = 16.1402(7), c = 20.8063(13) A, U = 2414.4(2) A , Z = 4,
˚
˚
1988, 350, 157; (b) J. W. Janetka and D. H. Rich, J. Am. Chem.
ꢀ
3
ꢀ1
Soc., 1997, 119, 6488; (c) A. J. Pearson and M. V. Chelliah, J. Org.
Chem., 1998, 63, 3087; (d) F. C. Pigge, S. Y. Fang and N. P. Rath,
Tetrahedron Lett., 1999, 40, 2251; (e) E. Matsushima,
N. Komatsuzaki, Y. Ajioka, M. Yamamoto, H. Kikuchi,
Y. Takata, N. Dodo, K. Onitsuka, M. Uno and S. Takahashi,
Bull. Chem. Soc. Jpn., 2001, 74, 527; (f) F. C. Pigge and
J. J. Coniglio, Curr. Org. Chem., 2001, 5, 757.
(a) R. Pasch, U. Koelle, B. Ganter and U. Englert, Organo-
metallics, 1997, 16, 3950; (b) N. Komatsuzaki, H. Kikuchi,
M. Yamamoto, M. Uno and S. Takahashi, Chem. Lett., 1998,
D
c
= 1.611 g cm , m = 0.774 mm , F(000) = 1184, 23 582
reflections were measured of which 5188 are unique (Rint = 0.029)
and 4261 are observed (I 4 4s). Final R-values are R (I 4 4s) =
0.019, wR (I 4 4s) = 0.020 (308 parameters, 5188 unique), Flack
1
2
parameter ꢀ0.03(3). CCDC 735050.
18 J. Lacour, C. Ginglinger, F. Favarger and S. Torche-Haldimann,
Chem. Commun., 1997, 2285. The tris(tetrachlorobenzenediolato)
phosphate(V) salt was used as a NMR chiral shift reagent to
determine the enantiopurity of chiral cationic complexes 9. We thank
5
4
Prof. J. Lacour for the generous gift of [n-Bu N][D-TRISPHAT].
4
45; (c) K. Kamikawa, M. Furusyo, T. Uno, Y. Sato, A. Konoo,
G. Bringmann and M. Uemura, Org. Lett., 2001, 3, 3667;
d) K. Kamikawa, K. Norimura, M. Furusyo, T. Uno, Y. Sato,
A. Konoo, G. Bringmann and M. Uemura, Organometallics, 2003,
19 For racemic [RuCp(4-bromoindene)], a selectivity factor S of 5 was
found at ꢀ20 1C.
(
20 P. G. Gassman, J. W. Mickelson and J. R. Sowa, J. Am. Chem.
Soc., 1992, 114, 6942.
This journal is ꢁc The Royal Society of Chemistry 2009
Chem. Commun., 2009, 5227–5229 | 5229