The use of chiral BINAM NHC-Rh(III) complexes in enantioselective hydrosilylation of 3-oxo-3-arylpropionic acid methyl or ethyl esters

Article abstract of DOI:10.1021/jo062453d

Axially chiral BINAM N-heterocyclic carbene (NHC)-Rh-(III) complexes were applied in the enantioselective hydrosilylation of 3-oxo-3-arylpropionic acid methyl or ethyl esters. The reduction products 3-hydroxy-3-arylpropionic acid methyl or ethyl esters could be obtained in good yields with good to excellent enantioselectivities under mild conditions.

Full text of DOI:10.1021/jo062453d

compounds.2 In addition, enzymatic reductions of â-ketoesters
as well as aldol reactions can also efficiently provide optically
active â-hydroxy esters.3,4 Apart from those methods, biocata-
lytic deracemization5 and optical resolution of racemic â-
hydroxy esters6 also have been frequently employed. Herein
we report a new method to prepare optically active 3-hydroxy-
3-arylpropionic acid methyl or ethyl esters by enantioselective
hydrosilylation of 3-oxo-3-arylpropionic acid methyl or ethyl
esters using NHC-Rh complexes derived from optically active
1,1′-binaphthalenyl-2,2′-diamine (BINAM) and H8-BINAM for
the first time.
The Use of Chiral BINAM NHC-Rh(III)
Complexes in Enantioselective Hydrosilylation of
3-Oxo-3-arylpropionic Acid Methyl or
Ethyl Esters
Qin Xu,† Xingxing Gu,† Sijia Liu,† Qinyu Dou,† and
Min Shi*,†,‡
School of Chemistry & Molecular Engineering, East China
UniVersity of Science and Technology, 130 Meilong Road,
Shanghai 200237, China, and State Key Laboratory of
Organometallic Chemistry, Shanghai Institute of Organic
Chemistry, Chinese Academy of Sciences, 354 Fenglin Road,
Shanghai 200032, China
N-Heterocyclic carbenes (NHC), a flexible ligand, developed
rapidly in the latest decade due to their stability to air and
moisture and their strong σ-donor but poor π-acceptor abilities.7
Great effort has been made to conduct chiral NHC-metal
complexe-catalyzed reactions in an enantioselective way, and
this century has already witnessed remarkable achievements.8
NHC-Rh complexes have been known as effective catalysts for
enantioselective hydrosilylation of ketones to provide optically
active secondary alcohols in moderate to good enantiomeric
excesses under mild conditions.9 Previously, we also reported
the preparation of an axially chiral NHC-Rh(III) complex 1
derived from optically active 1,1-binaphthalenyl-2,2′-diamine
(BINAM) and demonstrated its high chiral induction ability in
mshi@mail.sioc.ac.cn
ReceiVed NoVember 29, 2006
(2) For recent reviews of asymmetric hydrogenation, see: (a) Tang, W.;
Zhang, X. Chem. ReV. 2003, 103, 3029. (b) McCarthy, M.; Guiry, P. J.
Tetrahedron 2001, 57, 3809. (c) Catalytic Asymmetric Synthesis; Ojima,
I., Ed.; Wiley-VCH: Weinheim, Germany, 2000. (d) ComprehensiVe
Asymmetric Catalysis; Jacobsen, E. N., Pfalts, A., Yamamoto, H., Eds.;
Springer: Berlin, Germany, 1999.
(3) (a) Davies, H. G.; Green, R. H.; Kelly, D. R.; Roberts, S. M. In
Biotransformations in PreparatiVe Organic Chemistry. The Use of Isolated
Enzymes and Whole Cell Systems in Synthesis; Academic Press: London,
UK, 1989; Chapter 3. (b) Rodriguez, S.; Kayser, M. M.; Stewart, J. D. J.
Am. Chem. Soc. 2001, 123, 1547. (c) Buque, E. M.; Chin-Joe, I.; Straathof,
A. J. J.; Jongejan, J. A.; Heijnen, J. J. Enzyme Microb. Technol. 2002, 31,
656.
(4) (a) Duthaler, R. O.; Herold, P.; Lottenbach, W.; Oertle, K.; Riediker,
M. Angew. Chem., Int. Ed. Engl. 1989, 28, 495. (b) Mioskowski, C.;
Solladie, G. Tetrahedron 1979, 36, 227. (c) Meyers, A. I.; Knaus, G.
Tetrahedron Lett. 1974, 15, 1333.
(5) (a) Azerad, R.; Buisson, D. In Microbial Reagents in Organic
Synthesis; Servi, S., Ed.; Kluwer Academic Publishers: Dordecht, The
Netherlands, 1992; p 421. (b) Nakamura, K.; Fuji, M.; Ida, Y. Tetrahedron:
Asymmetry 2001, 12, 3147. (c) Padhi, S. K.; Chadha, A. Tetrahedron:
Asymmetry 2005, 16, 2790.
Axially chiral BINAM N-heterocyclic carbene (NHC)-Rh-
(III) complexes were applied in the enantioselective hydrosi-
lylation of 3-oxo-3-arylpropionic acid methyl or ethyl esters.
The reduction products 3-hydroxy-3-arylpropionic acid meth-
yl or ethyl esters could be obtained in good yields with good
to excellent enantioselectivities under mild conditions.
(6) (a) Sharma, A.; Chattopadhyay, S. J. Mol. Catal. B: Enzym. 2000,
10, 531. (b) Xu, C.; Yuan, C. Tetrahedron 2005, 61, 2169.
(7) For reviews, see: (a) Herrmann, W. A. Angew. Chem., Int. Ed. 2002,
41, 1209. (b) Ce´sar, V.; Bellemin-Laponnaz, S.; Gade, L. H. Chem. Soc.
ReV. 2004, 33, 619.
Enantiopure â-hydroxy esters are important building blocks
for the synthesis of biologically active compounds and natural
products.1 Thus far, medicinal importance has spurred the
research of convenient and highly selective methods for the
synthesis of optically active â-hydroxy esters or their derivatives.
Metal-catalyzed asymmetric hydrogenation of â-ketoesters is
one of the most practical and efficient methods to obtain such
(8) For the asymmetric catalysis using chiral metal-NHC as catalyst to
achieve good to excellent enantioselectivities, see: (a) Seiders, T. J.; Ward,
D. W.; Grubbs, R. H. Org. Lett. 2001, 3, 3225. (b) Powell, M. T.; Hou, D.
R.; Perry, M. C.; Cui, X. H.; Burgess, K. J. Am. Chem. Soc. 2001, 123,
8878. (c) Perry, M. C.; Cui, X. H.; Powell, M. T.; Hou, D. R.; Reibenspies,
J. H.; Burgess, K. J. Am. Chem. Soc. 2003, 125, 113. (d) Van Veldhuizen,
J. J.; Garber, S. B.; Kingsbury, J. S.; Hoveyda, A. H. J. Am. Chem. Soc.
2002, 124, 4954. (e) Alexakis, A.; Winn, C. L.; Guillen, F.; Pytkowicz, J.;
Roland, S.; Mangeney, P. AdV. Synth. Catal. 2003, 345, 345. (f) Ce´sar, V.;
Bellemin-Laponnaz, S.; Gade, L. H. Chem. Soc. ReV. 2004, 33, 619. (g)
Lee, S.; Hartwig, J. F. J. Org. Chem. 2001, 66, 3402. (h) Perry, M. C.;
Burgess, K. Tetrahedron: Asymmetry 2003, 14, 951. (i) Van Veldhuizen,
J. J.; Gillingham, D. G.; Garber, S. B.; Kataoka, O.; Hoveyda, A. H. J.
Am. Chem. Soc. 2003, 125, 12502. (j) He, M.; Struble, J. R.; Bode, J. W.
J. Am. Chem. Soc. 2006, 128, 8418.
* Address correspondence to this author. Fax: 86-21-64166128.
† East China University of Science and Technology.
‡ Chinese Academy of Sciences.
(1) (a) Mori, K. Tetrahedron 1989, 45, 3233. (b) Girard, A.; Greck, C.;
Ferroud, D.; Genet, J. P. Tetrahedron Lett. 1996, 37, 7967. (c) Ali, I. S.;
Sudalai, A. Tetrahedron Lett. 2002, 43, 5435. (d) Wirth, D. D.; Miller, M.
S.; Boini, S. K.; Koenig, T. M. Org. Process Res. DeV. 2000, 4, 513. (e)
Hodgetts, K. J. Tetrahedron Lett. 2001, 42, 3763.
10.1021/jo062453d CCC: $37.00 © 2007 American Chemical Society
Published on Web 02/21/2007
2240
J. Org. Chem. 2007, 72, 2240-2242

FIGURE 1. Axially chiral NHC-Rh(III) complex 1 and 2.
SCHEME 1. Synthesis of Axially Chiral NHC-Rh(III)
Complex 2
FIGURE 2. ORTEP drawing of chiral NHC-Rh(III) Complex 2.
the hydrosilylation of ketones.10 However, to the best of our
knowledge, there has been no report on the enantioselective
hydrosilylation of â-ketoesters with NHC-Rh(III) complexes.
Therefore, we attempted to utilize axially chiral NHC-Rh(III)
complexes 1 and 2 in the enantioselective hydrosilylation of
3-oxo-3-arylpropionic acid methyl or ethyl esters to further
examine their catalytic abilities (Figure 1).
TABLE 1. Axially Chiral NHC-Rh(III) Complex 1 Catalyzed
Enantioselective Hydrosilylation of 4a
Results and Discussion. The synthesis of novel NHC-Rh-
(III) complex 2 was accomplished by use of the corresponding
dibenzimidazolium salt (R)-3 derived from optically active H8-
BINAM as the starting material and in a similar sequence for
the preparation of axially chiral NHC-Rh complex 1.11The
structure of compound 2 was determined unambiguously by an
X-ray diffraction. The ORTEP drawing of 2 is shown in
Figure 2.12
Initial studies of the influence of reaction conditions were
carried out with 3-oxo-3-phenylpropionic acid ethyl ester 4a
as a substrate and chiral NHC-Rh(III) complex 1 (2.0 mol %)
as a catalyst at room temperature (15 °C) in a variety of solvents.
We found that tetrahydrofuran (THF) is the best solvent among
dichloromethane, toluene, acetonitrile, and hexane to give the
corresponding (S)-3-hydroxy-3-phenylpropionic acid ethyl ester
5a in 81% yield and 95% ee within 72 h at room temperature
(15 °C) (Table 1, entries 1-5). Elevating the reaction temper-
ature to 45 °C, the ee value of 5a slightly decreased in THF
(Table 1, entry 6). By using complex 1 (1.0 mol %) as a catalyst
entry
solvent
time (h)
yield (%)a
ee (%)b
config.c
1d
2
3
THF
72
72
72
72
72
60
81
30
50
75
20
80
95
45
79
73
50
90
S
S
S
S
S
S
CH2Cl2
toluene
CH3CN
hexane
THF
4
5
6e
a Isolated yields. b Ee values were determined by HPLC on a Chiralcel
OD-H column. c Absolute stereochemistry was determined by comparison
of the sign of optical rotation to the literature value. d Using Cat. 1 (1.0
mol %) in this reaction, 5a was obtained in 48% yield and 95% ee under
otherwise identical conditions. e The reaction temperature is 45 °C.
in this reaction, 5a was obtained in 48% yield and 95% ee under
otherwise identical conditions (Table 1, entry 1).
Under these optimized reaction conditions, we subsequently
investigated the substrate scopes of the enantioselective hy-
drosilylation of 3-oxo-3-arylpropionic acid methyl or ethyl esters
4 using NHC-Rh(III) complexes 1 and 2. The results are
summarized in Table 2. As can be seen from Table 2, various
3-oxo-3-arylpropionic acid methyl or ethyl esters 4 can be
smoothly reduced to give the corresponding 3-hydroxy-3-
arylpropionic acid methyl or ethyl esters 5 in good to high yields
with >80% ee in most cases under mild conditions in spite of
4 with electron-rich, electron-neutral, and electron-poor sub-
stituents on the benzene ring. In addition, the position of
substituent on the benzene ring did not significantly affect the
ee of 5 under the catalysis of complex 1 or 2. Chiral NHC-Rh-
(III) complexes 1 and 2 gave the corresponding 3-hydroxy-3-
arylpropionic acid methyl or ethyl esters 5 in similar enanti-
oselectivities and chemical yields under identical condi-
tions.
(9) (a) Herrmann, W. A. Angew. Chem., Int. Ed. 2002, 40, 1290 and
references cited therein. (b) Herrmann, W. A.; Goossen, L. T.; Ko¨cher, C.;
Artus, G. R. J. Angew. Chem., Int. Ed. Engl. 1996, 35, 2805. (c) Enders,
D.; Gielen, H. J. Organomet. Chem. 2001, 617, 70. (d) Enders, D.; Gielen,
H.; Breuer, K. Tetrahedron: Asymmetry 1997, 8, 3571. (e) Enders, D.;
Gielen, H.; Runsink, J.; Breuer, K.; Brode, S.; Boehn, K. Eur. J. Inorg.
Chem. 1998, 913. (f) Gade, L. H.; Cesar, V.; Bellemin-Laponnaz, S. Angew.
Chem., Int. Ed. 2004, 43, 1014. (g) Chianese, A. R.; Crabtree, R. H.
Organometallics 2005, 24, 4432.
(10) Duan, W.-L.; Shi, M.; Rong, G.-B. Chem. Commun. 2003, 2916
and references cited therein.
(11) See the Supporting Information for the details on the preparation
of chiral NHC-Rh(III) complexes 1 and 2.
(12) The crystal data of NHC-Rh(III) complex 2 have been deposited in
CCDC, number 287294. Empirical formula: C38H37I2N4O2Rh. Formula
weight: 938.43. Crystal color, habit: colorless, prismatic. Crystal system:
monoclinic. Lattice type: primitive. Lattice parameters: a ) 9.843(2) Å,
b ) 19.500(4) Å, c ) 19.388(4) Å, R ) 90°, â ) 96.280(5)°, γ ) 90°, V
In conclusion, we have developed a fairly effective axially
chiral NHC-Rh(III) complex system for the enantioselective
hydrosilylation of various 3-oxo-3-arylpropionic acid methyl or
ethyl esters 4 for the first time. This work adds to the growing
) 3698.8(15) Å3. Space group: P2(1). Z ) 4. Dcalc ) 1.685 g/cm3. F000
)
1840. Diffractometer: Rigaku AFC7R. Residuals, R, Rw: 0.1014, 0.2643.
J. Org. Chem, Vol. 72, No. 6, 2007 2241

TABLE 2. Chiral Rh Complexe Catalyzed Enantioselective
Hydrosilylation of 3-Oxo-3-arylpropionic Methyl or Ethyl Esters
CH3CN (12 mL) under reflux for 24 h. After cooling, volatiles were
removed under reduced pressure and the residue was purified by a
flash column chromatography (eluent: hexane/ethyl acetate ) 1/1)
to give NHC-Rh(III) complex 2 as an orange solid. Yield: 51 mg
(27%). [R]20D 72 (c 0.25, CHCl3); IR (CH2Cl2) ν 3727, 3630, 2933,
1
2858, 1721, 1465, 1335, 1090, 743 cm-1; H NMR (300 MHz,
CDCl3, TMS) δ 1.35-1.57 (m, 8H, CH2), 1.93-2.05 (m, 4H, CH),
2.00 (s, 3H, CH3), 2.50-2.64 (m, 4H, CH), 4.36 (s, 6H, CH3), 6.73
(d, J ) 8.1 Hz, 2H, ArH), 7.04-7.11 (m, 2H, ArH), 7.21 (t, J )
7.2 Hz, 2H, ArH), 7.30 (t, J ) 8.1 Hz, 2H, ArH), 7.97 (d, J ) 8.1
Hz, 2H, ArH); 13C NMR (75 MHz, CDCl3) δ 22.0, 22.2, 24.96,
24.98, 27.1, 29.1, 38.0, 109.8, 111.5, 122.6, 123.2, 127.7, 129.9,
133.1, 134.7, 134.66, 134.69, 135.7, 136.3, 139.0; MS (EI) m/z
(%) 879 (M+ - OAc), 811 (M+ - I). Anal. Calcd for C38H37I2N4O2-
Rh: C 48.63, H 3.97, N 5.97. Found: 49.02, H 4.18, N 5.82%.
Rh
catalyst
yield
(%)a
ee
(%)
entry
4 (Ar/R)
config.b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
4a (C6H5/Et)
5a, 81
5a, 78
5b, 90
5b, 83
5c, 88
5c, 80
5d, 91
5d, 88
5e, 72
5e, 65
5f, 89
5f, 86
5g, 87
5g, 80
5h, 75
5h, 70
5i, 82
5i, 81
95c
80c
95d
99d
92e
92e
98c
99c
96d
90d
95e
96e
97e
97e
81d
84d
95e
92e
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
4a
4b (4-MeC6H4/Et)
4b
4c (2-MeC6H4/Et)
4c
4d (3-MeC6H4/Et)
4d
General Procedure for Rh-Catalyzed Enantioselective Hy-
drosilylation Reaction. Under an Ar atmosphere, 3-oxo-3-aryl-
propionic acid methyl or ethyl esters (0.5 mmol) and Ph2SiH2 (138
mg, 0.75 mmol) were added to a solution of NHC-Rh(III) complex
(0.01 mmol) in anhydrous THF (2 mL). The reaction mixture was
stirred at 15 °C for 72 h. The reaction was quenched by addition
of H2O (1 mL) and 0.5 N HCl (0.5 mL). The resulting aqueous
solution was stirred for 2-5 h at room temperature, extracted with
Et2O (2 × 10 mL), and dried over anhydrous Na2SO4. The solvent
was removed under reduced pressure and the residue was purified
by a flash column chromatography (eluent: pentane/Et2O ) 10/
1∼4/1) to give the corresponding 3-hydroxy-3-arylpropionic acid
methyl or ethyl esters. The enantiomeric excess of 3-hydroxy-3-
arylpropionic acid methyl or ethyl esters was determined by chiral
HPLC.
4e (2-MeOC6H4/Et)
4e
4f (4-BrC6H4/Et)
4f
4g (4-ClC6H4/Et)
4g
4h (2-ClC6H4/Et)
4h
4i (4-ClC6H4/Me)
4i
a Isolated yields. b Absolute stereochemistry was determined by com-
parison of the sign of specific rotation with those of literature values. c Ee
values were determined by HPLC on a Chiralcel OD-H column. d Ee values
were determined by HPLC on Chiralpak AS-H column. e Ee values were
determined by HPLC on Chiralpak AD-H column.
body of synthetic studies on the preparation of optically active
3-hydroxy-3-arylpropionic acid methyl or ethyl esters and also
shows new application of the chiral NHC-metal complexes
developed from this group, using BINAM or H8-BINAM as a
chiral skeleton. Efforts to elucidate the mechanistic details of
this catalytic system and to explore new types of NHC-metal
complexes are underway.
Acknowledgment. Financial support from Shanghai Mu-
nicipal Committee of Science and Technology (04JC14083 and
06XD14005), the National Natural Science Foundation of China
(203900502, 20472096, and 20672127), and the Cheung Kong
Scholar Program is greatly appreciated.
Supporting Information Available: Experimental details and
characterization data, chiral HPLC, and X-ray crystallographic files
in CIF format. This material is available free of charge via the
Internet at http://pubs.acs.org.
Experimental Section
Synthesis of NHC-Rh(III) Complex 2. A mixture of (R)-3
(156 mg, 0.20 mmol), [RhCl(COD)]2 (48 mg, 0.10 mmol), NaOAc
(132 mg, 0.80 mmol), and KI (66 mg, 0.40 mmol) was stirred in
JO062453D
2242 J. Org. Chem., Vol. 72, No. 6, 2007