Highly efficient desymmetrisation of a tricarbonylchromium 1,4-dibromonaphthalene complex by asymmetric Suzuki-Miyaura coupling

Article abstract of DOI:10.1039/c1cc10347d

Access to planar chiral complexes has been sought by catalytic desymmetrisation of a prochiral complex via asymmetric Suzuki-Miyaura cross-coupling. High selectivities of up to 98% ee were achieved using a bulky chiral palladium catalyst. The Royal Societ

Full text of DOI:10.1039/c1cc10347d

View Article Online / Journal Homepage / Table of Contents for this issue
Dynamic Article Links
ChemComm
Cite this: Chem. Commun., 2011, 47, 3739–3741
www.rsc.org/chemcomm
COMMUNICATION
Highly efficient desymmetrisation of a tricarbonylchromium
1,4-dibromonaphthalene complex by asymmetric Suzuki–Miyaura couplingwz
´
¨
Xavier Urbaneja, Audrey Mercier, Celine Besnard and E. Peter Kundig*
Received 18th January 2011, Accepted 10th February 2011
DOI: 10.1039/c1cc10347d
Access to planar chiral complexes has been sought by catalytic
desymmetrisation of a prochiral complex via asymmetric
Suzuki–Miyaura cross-coupling. High selectivities of up to
98% ee were achieved using a bulky chiral palladium catalyst.
Optically pure arene tricarbonylchromium complexes have found
wide applications in asymmetric synthesis, natural product
synthesis and as chiral ligands in asymmetric catalysis.1 Most
of the methods for their preparation involve the resolution of
racemic mixtures or stereoselective transformations. The inherent
limitation of these methodologies is the use of a stoichiometric
amount of chiral reagents or auxiliaries. Asymmetric catalysis
would provide a powerful alternative to circumvent these issues,
but surprisingly few examples of catalytic asymmetric induction
of planar chirality have been reported.2 An attractive possibility
is the desymmetrisation of prochiral complexes by a chiral
catalyst that discriminates between two enantiotopic groups.
This strategy was first investigated by Uemura and Hayashi,3a–c
and subsequently by Schmalz,3d,e using Pd-catalysed asymmetric
cross-coupling reactions. However, moderate enantioselectivities
and yields were achieved. More recently, Uemura et al. success-
fully developed an asymmetric gold(I)-catalysed process for the
synthesis of highly enantioenriched planar chiral isochromene
chromium complexes.2e
Scheme 1 Palladium-catalysed enantioselective desymmetrisation as
a route to enantioenriched planar chiral complexes.
an efficient enantioselective desymmetrisation of [Cr(CO)3(5,8-di-
bromonaphthalene)] (1) using a Suzuki–Miyaura cross-coupling
reaction (Scheme 1, path (b)).
We started this project by examining the coupling of complex
1 and PhB(OH)2 6a in toluene using KF as a base (Table 1).
These reaction conditions were based on those previously
employed in the efficient Suzuki–Miyaura coupling of
[Cr(5-bromonaphthalene)(CO)3] ((S)-3).6,7 Preliminary experiments
revealed that the bulky phosphoramidite ligand L* (Fig. 1),
that was successfully used in the enantioselective hydrogenolysis
reaction,4 was also well suited for this transformation. The
axial chirality as well as the central chirality on the amine part
Based on the efficient Pd-catalysed enantioselective
hydrogenolysis of [Cr(CO)3(5,8-dibromonaphthalene)] (1)
developed in our laboratory (Scheme 1, path (a)),4 the challenging
desymmetrisation via asymmetric C–C bond formation was
investigated with the objective of accessing a larger array of planar
chiral complexes than those obtainable by asymmetric hydro-
genolysis. Similar levels of asymmetric induction may be expected
considering that oxidative addition of the Pd(0) catalyst to 1 would
generate the common chiral palladium intermediate 2.5 This pivotal
precursor could then be advanced through various processes. We
here report the realization of this endeavour by the development of
Table 1 Optimisation of the asymmetric Suzuki–Miyaura coupling of
1 with PhB(OH)2 (6a)
Entry Solvent
t/h 1a (%) 4aa (%) 5aa (%) ee 4ab (%)
1
2
Toluene
7
4
4
20
18
12
87
5
13
5
66
12
62
66
66
22
1
33
21
29
91
91
93
90
98
Department of Organic Chemistry, University of Geneva,
Quai Ernest Ansermet 30, 1211 Geneva 4, Switzerland.
E-mail: Peter.Kundig@unige.ch
w This article is part of a ChemComm web-based themed issue on new
advances in catalytic C–C bond formation via late transition metals.
z Electronic supplementary information (ESI) available: Experimental
procedures and analytical data for the reported compounds. CCDC
806187. For ESI and crystallographic data in CIF or other electronic
format see DOI: 10.1039/c1cc10347d
Tol/H2Oc
Toluened
Toluened
Toluened
3
4e
5f
a
b
c
Determined by 1H NMR. Determined by chiral HPLC. 9 : 1
d
mixture. Reagent grade toluene.
e
f
2 mol% of PdL*. Reaction
carried out at 0 1C.
c
This journal is The Royal Society of Chemistry 2011
Chem. Commun., 2011, 47, 3739–3741 3739

View Article Online
Table 2 Asymmetric Suzuki–Miyaura coupling of 1 with representative
boronic acids
Fig. 1 Chiral phosphoramidite ligand used in this project.
and the steric bulk in the 3,30-positions were all essential
elements to achieve high levels of asymmetric induction.
The reaction in toluene at 10 1C resulted in high conversion of 1
after 7 h and delivered 66% of the coupled product (S)-4a in 91%
ee, along with 22% of the bisphenylated complex (entry 1).8,9
Several other solvents (e.g., DME, CH2Cl2, trifluorotoluene) were
examined but none of them outperformed the results shown in
entry 1. The use of water as a co-solvent was then envisaged to aid
in the solubilisation of the inorganic base and therefore enhance
the reaction rate. It was found, however, that this significantly
lowered the rate of reaction (entry 2). In sharp contrast, the use of
commercial reagent grade (non-dried) toluene allowed high
conversion in only 4 h (entry 3). Such water traces in toluene
provide a good compromise between solubilising KF in the
medium and avoiding KF to remain exclusively in the aqueous
phase,10 which would be detrimental to the reaction.11 Lowering
the catalyst loading to 2 mol% gave rise to a slightly less efficient
process and required longer reaction time (entry 4). Finally, the
reaction carried out at 0 1C afforded (S)-4a in similar yield (66%)
and greatly enhanced enantioselectivity of 98% after 18 h
(entry 5). Further decrease of the reaction temperature did not
improve this result (not shown).
Entry
RB(OH)2
t/h
1a (%)
4a (%)
5a (%)
ee 4b (%)
1
2
3
4
5
6
6b
6c
6d
6e
6f
10
7
23
10
17
10
5
1
6
1
9
9
63
67
55
65
62
72
32
33
39
34
29
19
92
93
95
91
98
92
6g
a
1
Determined by H NMR. Determined by chiral HPLC.
b
Thus the asymmetric Suzuki–Miyaura coupling involving 1
appears to have a relatively wide scope and proceeds under
mild reaction conditions since no decomplexation products
were detected. Moreover, the relatively close ee values
obtained in both hydrogenolysis and Suzuki–Miyaura based
desymmetrisation processes are consistent with our assumption
that the oxidative addition is the enantiodetermining step.
To gain more insight into the structure of the catalyst, the
cationic [Pd(Z3-allyl)(R,S,S)-L*][SbF6] (7) complex was
prepared and fully characterised by NMR spectroscopy and
X-ray diffraction. The 31P NMR spectrum exhibited two
singlets at d 143.1 and 145 ppm in a very nearly 1 : 1 ratio,
corresponding to two diastereoisomeric species.14 Fig. 2
depicts the (R,S,S,RPd)-7 diastereoisomer obtained upon
crystallisation from CH2Cl2–cyclohexane.15 The palladium
center features a slightly distorted square planar geometry.
Identification of a weak secondary Z2-interaction between the
palladium and one of the benzyl substituents is in line with
the work of Mezzetti and co-workers16 and indicates that the
phosphoramidite used in this study can function as a
bidentate ligand. Evaluation of the buried volume of the
phosphoramidite ligand L* revealed an exceptional high steric
Control experiments involving longer reaction times
indicated an increase in the enantiomeric purity of 4a during
the course of the reaction. A similar observation was made for the
parent hydrogenolysis reaction and thorough investigation had
revealed the presence of an in situ kinetic resolution.4b,12 Similarly,
1
monitoring experiments were conducted by means of H NMR
analysis and chiral HPLC for the asymmetric Suzuki–Miyaura
coupling (see ESIz). These experimental data clearly showed that
the minor enantiomer (R)-4a is converted faster into 5a resulting
in enrichment in (S)-4a, thereby supporting the presence of
substantial kinetic resolution in this process as well.
The effect of the tricarbonylchromium fragment was next
studied. A competition experiment between [Cr(CO)3(5,8-
dibromonaphthalene)] (1) and free 1,4-dibromonaphthalene showed
that their respective relative reactivities were about 8 : 1, indicating
significant rate enhancement by Cr(CO)3 complexation.13
With optimised conditions established, the generality of the
process was explored with a range of boronic acids (Table 2). The
temperature was adjusted to 10 1C to avoid long reaction times
with the sensitive chromium complexes. Electron-rich aromatic
boronic acids, such as p-MePhB(OH)2 and p-MeOPhB(OH)2,
performed well, affording the coupled products 4b,c in 92 and
93% ee, respectively (entries 1 and 2). However, their electron-
deficient counterpart displayed reduced reactivity although high
enantioselectivity was maintained (entry 3). (E)- and (Z)-Vinyl-
boronic acids were also tolerated, delivering compounds 4e,f in
satisfactory yields and with enantioselectivities of 91 and 98%,
respectively (entries 4 and 5). Finally, the introduction of an alkyl
unit was evaluated. Butylboronic acid was efficiently coupled to
give 4g in good yield and 92% ee (entry 6).
Fig. 2 Molecular structure of [Pd(Z3-allyl)(1,2-Z-Ph-L*-kP)-L*)]+
((R,S,S,RPd)-7), determined by X-ray crystallography, showing an
1,2-Z-phenyl interaction.
c
3740 Chem. Commun., 2011, 47, 3739–3741
This journal is The Royal Society of Chemistry 2011

View Article Online
(f) A. R. Pape, K. P. Kaliappan and E. P. Kundig, Chem. Rev., 2000,
¨
100, 2917; (g) C. Bolm and K. Muniz, Chem. Soc. Rev., 1999, 28, 51.
2 For a review, see: (a) M. Ogasawara and S. Watanabe, Synthesis,
2009, 1761; (b) M. Ogasawara and S. Watanabe, Synthesis, 2009,
3177; For more recent examples, see: (c) M. Ogasawara, S.
Watanabe, K. Nakajima and T. Takahashi, J. Am. Chem. Soc.,
2010, 132, 2136; (d) E. Bergin, D. L. Hughes and C. J. Richards,
Tetrahedron: Asymmetry, 2010, 21, 1619; (e) M. Murai, J. Uenishi
and M. Uemura, Org. Lett., 2010, 12, 4788.
3 (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, 437, 129; (c) K. Kamikawa, K. Harada
and M. Uemura, Tetrahedron: Asymmetry, 2005, 16, 1419;
(d) B. Gotov and H. G. Schmalz, Org. Lett., 2001, 3, 1753;
(e) A. Bottcher and H. G. Schmalz, Synlett, 2003, 1595.
4 (a) E. P. Kundig, P. D. Chaudhuri, D. House and G. Bernardinelli,
¨
Angew. Chem., Int. Ed., 2006, 45, 1092; (b) A. Mercier, X. Urbaneja,
Scheme 2 Access to both enantiomers of 8a by using the same chiral
ligand (S,R,R)-L*.
W. C. Yeo, P. D. Chaudhuri, G. R. Cumming, D. House,
G. Bernardinelli and E. P. Kundig, Chem.–Eur. J., 2010, 16, 6285.
¨
congestion in the first coordination sphere of the palladium
center (%VBur = 55.4%).17
5 For a similar concept, see: (a) S. J. Byrne, A. J. Fletcher,
P. Hebeisen and M. C. Willis, Org. Biomol. Chem., 2010, 8, 758;
(b) M. C. Willis, L. H. W. Powell, C. K. Claverie and S. J. Watson,
Angew. Chem., Int. Ed., 2004, 43, 1249.
Finally, the potential complementarity of our two
desymmetrising processes was illustrated with the synthesis
of both enantiomers of [Cr((5-phenyl)naphthalene)(CO)3] (8a)
using the phosphoramidite ligand with identical absolute
configuration (Scheme 2). Indeed, performing the asymmetric
hydrogenolysis followed by a Suzuki–Miyaura cross-coupling
reaction6 using Fu’s catalytic system18 delivered enantiomer
(S)-8a in 97% ee and 62% overall yield. Inverting the order of
the sequence, namely the asymmetric Suzuki–Miyaura
coupling followed by hydrogenolysis, afforded the opposite
enantiomer (R)-8a with similar enantioselectivity. In both
cases, the transformations were performed without erosion
of enantioselectivity.
6 G. R. Cumming, G. Bernardinelli and E. P. Kundig, Chem.–Asian J.,
2006, 1, 459.
¨
7 Chromium naphthalene complexes easily undergo haptotropic
slippage of the metal unit coordinated to the aromatic ring, often
leading to the decomplexation of the compounds. To avoid this
side process, polar solvents, heating over 40 1C and the presence of
oxygen must be avoided. For some leading references, see:
(a) H. C. Jahr, M. Nieger and K. H. Dotz, Chem.–Eur. J., 2005,
11, 5333; (b) Y. F. Oprunenko, Russ. Chem. Rev., 2000, 69, 683;
(c) E. P. Kundig, V. Desobry, C. Grivet, B. Rudolph and
¨
S. Spichiger, Organometallics, 1987, 6, 1173.
8 The absolute configuration of 4a, and by analogy 4b–g, was
assigned based on X-ray diffraction analysis of compound 3
obtained by asymmetric hydrogenolysis, and corroborated by the
further transformation of both compounds into 8a.
In conclusion, we have demonstrated that prochiral
complex 1 could be successfully desymmetrised via asymmetric
C–C bond formation. The enantioselective Suzuki–Miyaura
coupling proved to be general, affording good yields and
excellent enantioselectivities with an array of aryl-, vinyl-
and even alkylboronic acids. These results are in close
agreement with our assumption that the oxidative addition
determines the stereochemical outcome of the reaction.
Combining the two desymmetrisation processes would allow
the access to a wide variety of planar chiral compounds with
complete stereocontrol. Further studies will focus on the
isolation and identification of a relevant reactive intermediate
(e.g., oxidative addition product) in order to get more insight
into the origin of the asymmetric induction.
9 Among all the inorganic bases surveyed,K3PO4 and Cs2CO3
showed similar efficiency in terms of reactivity and enantio-
selectivity. Nevertheless, KF was kept as the base of choice
considering its lower price (3.65 USD molꢀ1).
10 The solubility of water in toluene is 0.53 g Lꢀ1 at 25 1C.
11 These results are in line with those reported by Wright:
S. W. Wright, D. L. Hageman and L. D. McClure, J. Org. Chem.,
1994, 59, 6095.
12 Kinetic resolution in a related desymmetrisation process was first
described by Gotov and Schmalz (ref. 3d).
13 For competitive experiments of a halobenzene chromium complex
and its free ligand towards radical dehalogenation, see: H. C. Lin,
Q. Chen, L. D. Cao, L. Yang, Y. D. Wu and C. Z. Li, J. Org.
Chem., 2006, 71, 3328.
14 The absolute configuration at Pd was assigned using the conven-
tion suggested by Faller and Sarantopoulos: J. W. Faller and
N. Sarantopoulos, Organometallics, 2004, 23, 2008.
15 Crystal data for 2(7)ꢁC7H14: C109H94N2O4P2Sb2F12Pd2, M =
We thank the Swiss National Science Foundation and the
University of Geneva for financial support. We are particularly
grateful to P. Romanens for technical assistance and A. Pinto
for NMR measurements.
2242.18, T = 170 K, MoKa, tetragonal, P43212, a = 12.593(1) A,
c = 59.124(6) A, V = 9376.1(14) A3, Z = 4, m = 1.06 mmꢀ1
,
dx = 1.588 g cmꢀ3, Flack parameter x = 0.09(2), R = 0.044,
oR = 0.097. CCDC 806187.
16 I. S. Mikhel, H. Ruegger, P. Butti, F. Camponovo, D. Huber and
A. Mezzetti, Organometallics, 2008, 27, 2937.
Notes and references
17 (a) H. Clavier and S. P. Nolan, Chem. Commun., 2010, 46, 841. The
buried volume %VBur was calculated using the SambVca software:
(b) A. Poater, B. Cosenza, A. Correa, S. Giudice, F. Ragone,
V. Scarano and L. Cavallo, Eur. J. Inorg. Chem., 2009, 1759.
18 (a) A. F. Littke, C. Y. Dai and G. C. Fu, J. Am. Chem. Soc., 2000,
122, 4020; For the preparation and use of air-stable
[(t-Bu)3PH][BF4], see: (b) M. R. Netherton and G. C. Fu,
Org. Lett., 2001, 3, 4295.
1 For reviews, see: (a) M. Rosillo, G. Dominguez and J. Perez-Castells,
Chem. Soc. Rev., 2007, 36, 1589; (b) Transition Metal Arene
p-Complexes in Organic Synthesis and Catalysis, in Topics in
Organometallic Chemistry, ed. E. P. Kundig, Springer Verlag,
¨
Heidelberg, 2004, vol. 7; (c) E. P. Kundig and S. H. Pache, Sci. Synth.,
¨
2003, 2, 155; (d) A. Salzer, Coord. Chem. Rev., 2003, 242, 59;
(e) S. E. Gibson and H. Ibrahim, Chem. Commun., 2002, 2465;
c
This journal is The Royal Society of Chemistry 2011
Chem. Commun., 2011, 47, 3739–3741 3741