A modular assembly of chiral oxazolinylcarbene-rhodium complexes: Efficient phosphane-free catalysts for the asymmetric hydrosilylation of dialkyl ketones

Article abstract of DOI:10.1002/anie.200353133

A novel class of chiral bidentate ligands with a carbene and an oxazoline moiety is obtained by the coupling of N-arylimidazoles and a 2-bromooxazoline derivative. The rhodium complex 1 catalyzes the hydrosilylation of aryl alkyl ketones and otherwise problematic dialkyl ketones in high yields and good enantioselectivities (up to 95% ee).

Full text of DOI:10.1002/anie.200353133

Communications
Hydrosilylation Catalysts
A Modular Assembly of Chiral
Oxazolinylcarbene–Rhodium Complexes:
Efficient Phosphane-Free Catalysts for the
Asymmetric Hydrosilylation of Dialkyl Ketones**
Lutz H. Gade,* Vincent CØsar, and
StØphane Bellemin-Laponnaz*
The modular combination of a strongly bonded “anchor” unit
with a chiral stereodirecting structural element is an under-
lying principle in the development of many phosphane-
heteroatom-based chiral catalysts.[1] In the optimization of
their catalytic performance,the assembly of such systems in
essentially one step represents the ideal practical strategy.
Given their facile chemical accessibility and stability,the
replacement of phosphanes by N-heterocyclic carbenes and
their combination with chiral donor units such as oxazolines
provides an attractive alternative to the established catalytic
systems.
N-heterocyclic carbenes have emerged as a new family of
ligands for homogeneous catalysis.[2–4] However,despite the
numerous efforts to prepare chiral carbene complexes,[5] there
have been relatively few reports on highly enantioselective
[*] Prof. Dr. L. H. Gade,+ V. CØsar, Dr. S. Bellemin-Laponnaz
Laboratoire de Chimie OrganomØtallique et de Catalyse (UMR
7513)
Institut Le Bel, UniversitØ Louis Pasteur
4, rue Blaise Pascal, 67070 Strasbourg (France)
Fax: (+33)390-241-531
E-mail: gade@chimie.u-strasbg.fr
bellemin@chimie.u-strasbg.fr
[+] New address:
Anorganisch-Chemisches Institut
Universität Heidelberg
Im Neuenheimer Feld 270, 69120 Heidelberg (Germany)
[**] We thank the CNRS (France) and the Institut Universitaire de France
for support of this work and the Minist›re de L'Education Nationale
de la Recherche etde la Technologie for a Ph.D. grantto V.C.
Supportby BASF (Ludwigshafen) and Degussa (Hanau) is gratefully
acknowledged. We thank Dr. A. De Cian and N. Gruber for the X-ray
diffraction study.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
1014
ꢀ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/anie.200353133
Angew. Chem. Int. Ed. 2004, 43, 1014 –1014

Angewandte
Chemie
catalytic transformations using these systems. Notable exam-
ples include a chiral olefin metathesis catalyst reported by
Hoveyda and co-workers[6] as well as the development of
highly efficient asymmetric hydrogenation catalysts based on
carbene–oxazoline iridium complexes reported by Burgess
et al.[7] However,most examples of asymmetric catalysis using
chiral carbenes,such as the hydrosilylation of ketones,have
provided much lower enantioselection.[8–10]
We recently reported the synthesis of an achiral oxazo-
linyl-carbene ligand (A-B),which is easily obtained by a
direct linkage between the two heterocycles A and B.[11] This
Figure 1. Molecular structure of the rhodium complex 2c. Selected
bond lengths [Š] and angles [8]: Rh-N(1) 2.285(3), Rh-C(10) 2.001(4),
Rh-Br 2.6775(5), Rh-C(20) 2.231(4), Rh-C(21) 2.231(4), Rh-C(23)
2.084(4), Rh-C(24) 2.070(4); Br-Rh-N(1) 91.72(9), Br-Rh-C(10) 96.5(1),
N(1)-Rh-C(10) 77.0(1).
bromo ligand in the apical position.[15] The mesityl ring plane
is twisted almost orthogonally out of the plane of the central
À
molecular unit (C(10)-N(3)-C(11)-C(12) 81.68). The Rh C
modular approach,which assembles both the “anchor” and
the chiral directing unit(s) in a single coupling step,was
thought to be an efficient strategy for the development of
novel (chiral) catalysts. Based on this general consideration,
we report a chiral N-heterocyclic carbene derivative that is
highly efficient as a ligand for the Rh-catalyzed asymmetric
hydrosilylation of,in particular,dialkyl ketones.
The chiral oxazoline–carbene ligands were prepared by
reacting 2-bromo-4(S)-tert-butyl oxazoline with several imi-
dazole derivatives in THF at room temperature to generate
the corresponding aryl imidazolium salts 1a–d in good yields
(Scheme 1).[12,13] The steric demand at the ortho position of
bond lengths of 2.231(4) Š for the norbornadiene carbon
atoms in trans disposition to the carbene ligand are signifi-
cantly longer than those trans to the oxazoline-N donor atom
À
À
(Rh C(23) 2.084(4),Rh C(24) 2.070(4) Š). This is consistent
with the previously observed strong trans influence of the N-
heterocyclic carbene ligands.[16]
Recently,a number of very efficient phosphane-hetero-
donor-based catalysts for the stereoselective hydrosilylation
of ketones have been reported,notably by Fu and Tao [17] and
Evans et al.[18] Whereas aryl-alkyl-substituted ketones are
transformed with very high enantioselectivity,the application
of this catalytic reaction to unsymmetrical dialkyl ketones
remains a challenge. One goal of our work therefore was the
asymmetric hydrosilylation of such ketones with the new class
of rhodium complexes 2a–d. These complexes would repre-
sent the first carbene complexes to display high enantiose-
lectivity for this reaction.
We chose the hydrosilylation of acetophenone with
diphenylsilane as the reference reaction to test the potential
of the catalysts. Complexes 2a–d,which differ in the pattern
of the ortho-substituents at the aryl group and which were
used with a catalyst loading of 1.0 mol% in the presence of a
slight excess of AgBF4,gave the results displayed in Table 1.
The N-mesityl-substituted catalyst 2c (Table 1,entry 3) gave
the highest selectivity at 208C with 65% ee.[19] The formation
of the square-planar cationic rhodium species as active
Table 1: Asymmetric hydrosilylation of acetophenone with catalysts 2a–d
at room temperature.
Scheme 1. Synthesis of the catalysts 2a–d.
the N-phenyl substituent increases in the series from 1a to 1d.
The reaction of 1a–d with [{Rh(m-OtBu)(nbd)}2] generated in
situ leads to the corresponding N-heterocyclic complexes
2a–d in 80–89% yield.[14]
Crystals suitable for X-ray structure analysis were
obtained for complex 2c,and its molecular structure is
represented in Figure 1. The complex possesses a slightly
distorted square-pyramidal coordination geometry with the
Entry
Catalyst
Additive
ee [%]
Yield [%]
1
2
3
4
5
2a
2b
2c
2c
2d
AgBF4
AgBF4
AgBF4
none
0
90
82
90
53
89
31
65
13
20
AgBF4
Angew. Chem. Int. Ed. 2004, 43, 1014 –1014
www.angewandte.org
ꢀ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1015

Communications
Table 3: Asymmetric hydrosilylation of a series of dialkyl ketones with
catalyst 2c and AgBF4.
catalyst appears to be crucial since the use of compound 2c
without the silver salt gave both poor yield and enantiose-
lectivity (Table 1,entry 4). Lowering the reaction temper-
ature led to a significant increase in stereoselectivity,while,
remarkably,barely altering the activity of the catalysts. The
catalytic runs performed at À608C gave the best results,with
acetophenone being hydrosilylated cleanly giving the product
with an enantiomeric excess of 90% after a reaction time of
10 h. Similarly high enantioselectivities were obtained in the
reduction of a variety of aryl alkyl ketones under these
optimized reaction conditions (Table 2).
Entry
1
Ketone
ee [%]
Yield [%]
95
79
2
77
97
Table 2: Asymmetric hydrosilylation of aryl alkyl ketones with catalyst 2c
and AgBF4.
3
4
5
81
88
95
63[a]
53[b]
70[a]
Entry
1
Ketone
ee [%]
Yield [%]
92
90
6
89
96
2
3
4
91
89
88
99
93
92
[a] A conversion of >98% was observed by 1H NMR spectroscopy. The
moderate yield was due to the volatility of the products. [b] A conversion
of 85% was observed by 1H NMR spectroscopy.
In summary,we have reported a readily accessible,
efficient chiral N-heterocyclic carbene ligand for asymmetric
hydrosilylation of ketones. Moreover,the modular synthesis
of the oxazolinylcarbene ligands allows the facile access to a
large ligand library. Future work will explore the potential of
this class of C,N-heterodonor ligands in other stereoselective
catalytic reactions.[21]
5
91
90
Whereas the selectivity in the hydrosilylation of aryl alkyl
ketones is much higher than for previously reported chiral
carbene catalysts,it is nevertheless somewhat below that of
the most efficient phosphane-based systems with which values
of over 95% ee were obtained.[10,17,18,20] This may be related to
the absence of an aryl-directing group in complex 2c,the
principal stereodirecting function most probably being the
tert-butyl group in the oxazoline ring. We therefore probed
the efficiency of precatalyst 2c in the hydrosilylation of
unsymmetrical dialkyl ketones which have proved to be
difficult substrates for the known chiral catalysts,although
recent progress has been reported by Fu and co-workers.[17]
Carrying out the Rh-catalyzed transformation under condi-
tions identical to those described above gave the correspond-
ing secondary alcohols in high enantiopurity (Table 3). In
particular,the relatively high ee values obtained for the
ketones that do not contain an a-branching point is remark-
able (Table 3,entries 1 and 2) and makes this novel class of
chiral catalysts promising candidates for the further develop-
ment of this field aimed at the general application of this
methodology in stereoselective organic synthesis.
Experimental Section
General procedure for the hydrosilylation reaction (Table 2,entry 1):
A solution of 2c (5.9 mg,0.01 mmol) in CH 2Cl2 (0.3 mL) was added to
AgBF4 (2.3 mg,1.2 equiv) under a nitrogen atmosphere. After the
mixture had been stirred for 5 min,the red solution was filtered over a
bed of celite and rinsed with additional CH2Cl2 (0.2 mL). Acetophe-
none (117 mL,1.0 mmol) was added to this solution,the reaction
mixture was cooled to À608C,and diphenylsilane (210 mL,1.1 mmol)
was subsequently added dropwise over a period of 2 min. The bright
yellow reaction mixture was stirred at À608C for 10 h. A solution of
K2CO3 (2.0 mL) in methanol (0.1%) was then added and the resulting
mixture was stirred for 4 h at room temperature. After evaporation of
the solvents,the product ( S)-sec-phenethyl alcohol (112 mg,92%)
was purified by silica gel chromatography. GC analysis showed 90%
ee.
Crystal data for 2c: C26H33BrN3ORh, Mr = 586.39,orange crys-
tals,dimensions 0.25 ” 0.20 ” 0.20 mm,orthorhombic,space group
P212121, a = 9.7117(1), b = 13.7354(2), c = 18.3991(2) Š, U =
2454.33(5) Š3, Z = 4, 1calcd = 1.59 gcmÀ3, m = 2.347 mmÀ1, F(000) =
1192,number of data measured: 7139 (2.5 < q < 30.038) at 173 K,
number of data with I > 3s(I): 3461,number of variables: 289, R =
0.030, Rw = 0.048,GOF = 1.020,largest peak in final difference:
0.532 eŠÀ3. CCDC-221154 contains the supplementary crystallo-
1016
ꢀ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
Angew. Chem. Int. Ed. 2004, 43, 1014 –1014

Angewandte
Chemie
graphic data for this paper. These data can be obtained free of charge
via www.ccdc.cam.ac.uk/conts/retrieving.html (or from the Cam-
bridge Crystallographic Data Centre,12,Union Road,Cambridge
CB21EZ,UK; fax: ( + 44)1223-336-033; or deposit@ccdc.cam.ac.uk).
[15] Due to the arrangement of the ligands,a stereogenic center at
the metal atom is created leading to the existence of a possible
second diastereoisomer. However,we were not able to detect
any trace of the second diastereomer by classical spectroscopic
methods.
[16] Similar examples for the trans influence of carbene ligands,see:
a) A. R. Chianese,X. Li,M. C. Janzen,J. W. Faller,R. H.
Crabtree, Organometallics 2003, 22,1663; b) J. A. Loch,M.
Albrecht,E. Peris,J. Mata,J. W. Faller,R. H. Crabtree, Organo-
metallics 2002, 21,700; c) A. C. Hillier,H. M. Lee,E. D. Stevens,
S. P. Nolan, Organometallics 2001, 20,4246.
[17] Fu and Tao reported a new P,N ligand family giving high
enantioselectivities: B. Tao,G. C. Fu, Angew. Chem. 2002, 114,
4048; Angew. Chem. Int. Ed. 2002, 41,3892.
[18] Evans et al. reported a new P,S ligand family giving very high
activity and selectivity in Rh-catalyzed hydrosilylation: D. A.
Evans,F. E. Michael,J. S. Tedrow,K. R. Campos, J. Am. Chem.
Soc. 2003, 125,3534.
[19] The influence of the silane structure on the enantioselectivity of
the reaction was investigated and we found that the standard
reducing agent diphenylsilane gave the best results.
[20] a) R. Kuwano,M. Sawamura,J. Shirai,M. Takahashi,Y. Ito,
Bull. Chem. Soc. Jpn. 2000, 73,485,and references therein; b) Y.
Yamanoi,T. Imamoto, J. Org. Chem. 1999, 64,2988.
[21] Note added in proof (14.1.2004): While this work was in press an
efficient chiral biscarbene–rhodium hydrosilylation catalyst was
reported: W.-L. Duan,M. Shi,G. B. Rong, Chem. Commun.
2003,2916.
Received: October 22,2003 [Z53133]
Keywords: asymmetric catalysis · carbene ligands ·
.
hydrosilylation · ketones · rhodium
[1] a) G. Helmchem,A. Pfaltz, Acc. Chem. Res. 2000, 33,326; b) for
a general review,covering phosphane-oxazoline ligands in
catalysis,see: P. Braunstein,F. Naud, Angew. Chem. 2001, 113,
702; Angew. Chem. Int. Ed. 2001, 40,681.
[2] Reviews: a) W. A. Herrmann, Angew. Chem. 2002, 114,1342;
Angew. Chem. Int. Ed. 2002, 41,1290; b) D. Bourissou,O.
Guerret,F. Gabba ï,G. Bertrand, Chem. Rev. 2000, 100,39;
c) W. A. Herrmann,C. Köcher, Angew. Chem. 1997, 109,2257;
Angew. Chem. Int. Ed. Engl. 1997, 36,2162.
[3] Selected examples for palladium-catalyzed coupling reactions:
a) G. Altenhoff,R. Goddard,C. W. Lehmann,F. Glorius, Angew.
Chem. 2003, 115,3818; Angew. Chem. Int. Ed. 2003, 42,3690;
b) C. W. K. Gstöttmayr,V. P. W. Böhm,E. Herdtweck,M.
Grosche,W. A. Herrmann, Angew. Chem. 2002, 114,1421;
Angew. Chem. Int. Ed. 2002, 41,1363; c) G. A. Grasa,M. S.
Viciu,J. Huang,C. Zhang,M. L. Trudell,S. P. Nolan,
metallics 2002, 21,2866; d) D. S. McGuinness,K. J. Cavell,
Organometallics 2000, 19,741.
Organo-
[4] Selected examples of ruthenium-catalyzed olefin ring-closing
metathesis: a) T. Weskamp,F. J. Kohl,W. Hieringer,D. Gleich,
W. A. Herrmann, Angew. Chem. 1999, 111,2573; Angew. Chem.
Int. Ed. 1999, 38,2416; b) M. Scholl,T. M. Trnka,J. P. Morgan,
R. H. Grubbs, Tetrahedron Lett. 1999, 40,2247; c) J. Huang,
H. Z. Schanz,E. D. Stevens,S. P. Nolan, Organometallics 1999,
18,5375; d) L. Ackermann,A. Fürstner,T. Weskamp,F. J. Kohl,
W. A. Herrmann, Tetrahedron Lett. 1999, 40,4787.
[5] Review on N-heterocyclic carbene ligands in asymmetric
catalysis: M. C. Perry,K. Burgess, Tetrahedron: Asymmetry
2003, 14,951.
[6] J. J. Van Veldhuizen,S. B. Garber,J. S. Kingsbury,A. H. Hov-
eyda, J. Am. Chem. Soc. 2002, 124,4954.
[7] M. C. Perry,X. Cui,M. T. Powell,D. R. Hou,J. H. Reibenspies,
K. Burgess, J. Am. Chem. Soc. 2003, 125,113.
[8] Herrmann et al. obtained enantiomeric excesses of up to
32% ee: W. A. Herrmann,L. J. Goossen,C. Kocher,G. R. J.
Artus, Angew. Chem. 1996, 108,2580; Angew. Chem. Int. Ed.
Engl. 1996, 35,2805.
[9] Enders et al. reported maximum enantiomeric excesses of
44% ee in hydrosilylation catalysis with chiral N-heterocyclic
carbenes: a) D. Enders,H. Gielen,J. Runsink,K. Breuer,S.
Brode,K. Boehn, Eur. J. Inorg. Chem. 1998,913; b) D. Enders,
H. Gielen,J . Organomet. Chem. 2001, 617–618,70.
[10] a) For a review on asymmetric hydrosilylation,see: H. Nish-
iyama,K. Itoh, Catalytic Asymmetric Synthesis (Ed.: I. Ojima),
Wiley-VCH,New York, 2000,chap. 2.
[11] V. Cꢀsar,S. Bellemin-Laponnaz,L. H. Gade, Organometallics
2002, 21,5204.
[12] For the synthesis of the 2-bromo-oxazoline,see: A. I. Meyers,
K. A. Novachek, Tetrahedron Lett. 1996, 37,1747.
[13] We also recently reported a very efficient way to synthesize
trisoxazolines using 2-bromooxazoline,see: a) S. Bellemin-
Laponnaz,L. H. Gade, Chem. Commun. 2002,1286; b) S.
Bellemin-Laponnaz,L. H. Gade, Angew. Chem. 2002, 114,
3623; Angew. Chem. Int. Ed. 2002, 41,3473.
[14] C. Köcher,W. A. Herrmann, J. Organomet. Chem. 1997, 532,
261.
Angew. Chem. Int. Ed. 2004, 43, 1014 –1017
www.angewandte.org
ꢀ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1017