An efficient copper-aluminum hydrotalcite catalyst for asymmetric hydrosilylation of ketones at room temperature

Article abstract of DOI:10.1021/ol800616p

(Chemical Equation Presented) A catalyst system consisting of a copper-aluminum hydrotalcite-chiral diphosphine ligand effects asymmetric hydrosilylation of several ketones, using polymethylhydrosiloxane (PMHS) as the stoichiometric reducing agent at room temperature, with moderate-to-excellent enantioselectivities. The catalyst is recovered by simple centrifugation, and the efficiency of the catalyst remains almost unaltered even after several cycles.

Full text of DOI:10.1021/ol800616p

ORGANIC
LETTERS
2
008
Vol. 10, No. 14
979-2982
An Efficient Copper-Aluminum
Hydrotalcite Catalyst for Asymmetric
Hydrosilylation of Ketones at Room
Temperature
2
,
†
†
M. Lakshmi Kantam,* Soumi Laha, Jagjit Yadav, Pravin R. Likhar,
†
†
†
Bojja Sreedhar, Shailendra Jha, Suresh Bhargava, M. Udayakiran, and
‡
§
†
†
B. Jagadeesh
Indian Institute of Chemical Technology, Hyderabad-500007, India, Department of
Chemistry, JadaVpur UniVersity, Kolkata, India, and School of Applied Sciences, RMIT
UniVersity, Melbourne, Australia
mlakshmi@iict.res.in
Received April 24, 2008
ABSTRACT
A catalyst system consisting of a copper-aluminum hydrotalcite-chiral diphosphine ligand effects asymmetric hydrosilylation of several
ketones, using polymethylhydrosiloxane (PMHS) as the stoichiometric reducing agent at room temperature, with moderate-to-excellent
enantioselectivities. The catalyst is recovered by simple centrifugation, and the efficiency of the catalyst remains almost unaltered even after
several cycles.
The development of asymmetric catalytic systems is a major
challenge because of its importance in synthetic organic
chemistry and fine chemicals manufacturing. Enantiomeri-
technical simplicity, much effort has been placed upon the
asymmetric hydrosilylation of a wide range of substrates,
normally using Rh- or Ti-based catalysts.
1
7
cally pure chiral alcohols have numerous applications in the
Recently the use of copper, a less expensive base metal,
and polymethylhydrosiloxane (PMHS), an inexpensive,
2
3
field of pharmaceuticals, agrochemicals, flavors, and fra-
4
grances, and they can be obtained by asymmetric hydro-
5
6
(5) (a) Noyori, R. Asymmetric Catalysis in Organic Synthesis; Wiley:
New York, 1994. (b) Noyori, R.; Ohkuma, T. Angew. Chem., Int. Ed. 2001,
40, 41. (c) Mikami, K.; Wakabayashi, K.; Aikawa, K. Org. Lett. 2006, 8,
genation or transfer hydrogenation of carbonyl compounds.
However, due to exceedingly mild reaction conditions and
1
517. (d) Ohkuma, T.; Utsumi, N.; Watanabe, M.; Tsutsumi, K.; Arai, N.;
Murata, K. Org. Lett. 2007, 9, 2565. (e) Ohkuma, T.; Koizumi, M.; Muniz,
K.; Hilt, G.; Kabuto, C.; Noyori, R. J. Am. Chem. Soc. 2002, 124, 6508. (f)
Shimizu, H.; Igarashi, D.; Kuriyama, W.; Yusa, Y.; Sayo, N.; Saito, T.
Org. Lett. 2007, 9, 1655. (g) Hamilton, R. J.; Berger, S. H. J. Am. Chem.
Soc. 2006, 128, 13700.
†
Indian Institute of Chemical Technology.
Jadavpur University.
RMIT University.
‡
§
(
1) For recent reviews: (a) Ohkuma, T.; Kitamura, M.; Noyori, R. In
Catalytic Asymmetric Synthesis, 2nd ed.; Ojima, I., Ed.; Wiley-VCH: New
York, 2000; Chapter 1, pp 1-110. (b) Tang, W.; Zhang, X. Chem. ReV.
(6) (a) Liu, P. N.; Deng, J. G.; Tu, Y. Q.; Wang, H. Chem. Commun.
2004, 2070. (b) Fujii, A.; Hashiguchi, S.; Uematsu, N.; Ikariya, T.; Noyori,
R. J. Am. Chem. Soc. 1996, 118, 2521. (c) Sterk, D.; Stephen, M.; Mohar,
B. Org. Lett. 2006, 8, 5935. (d) Yang, J. W.; List, B. Org. Lett. 2006, 8,
5653. (e) Zaitsev, A. B.; Adolfsson, H. Org. Lett. 2006, 8, 5129. (f) Matharu,
D. S.; Morris, D. J.; Clarkson, G. J.; Wills, M. Chem. Commun. 2006, 3232.
(g) Liu, G.; Yao, M.; Zhang, F.; Gao, Y.; Li, H. Chem. Commun. 2008,
347.
2
003, 103, 3029.
(
2) Astleford, B. A.; Weigel, L. O. In Chirality in Industry II; Collins,
A. N., Ed.; Wiley: New York, 1997; p 99.
(
(
3) Sheldon, R. A. Chirotechnology; Dekker: New York, 1993.
4) (a) Rossiter, K. J. Chem. ReV. 1996, 96, 3201. (b) Boelens, M.
Perfum. FlaVor 1993, 18, 2.
10.1021/ol800616p CCC: $40.75
Published on Web 06/19/2008
 2008 American Chemical Society

nontoxic polymer coproduct of the silicone industry as the
stoichiometric reducing agent, has opened up a new perspec-
tive to asymmetric hydrosilylation.
containing different ratios of Cu:Al, such as 2:1, 2.5:1, and 3:1,
15
were prepared according to the literature procedure (see
Supporting Information) and screened in the presence of PMHS
using 4-methylacetophenone as a model substrate. Catalyst A
(Cu:Al ) 3:1) was found to be more active than catalyst B
(Cu:Al ) 2.5:1) and catalyst C (Cu:Al ) 2:1). The effect of
organic solvents and chiral ligands on the asymmetric hydrosi-
lylation of 4-methylacetophenone was also examined (see Table
1). A significant decrease in the rate of reaction and a small
Buchwald described a highly enantioselective 1,4-reduc-
tion of R,ꢀ-unsaturated esters and ꢀ-substituted enones, using
an active catalyst generated in situ from the CuCl/NaO-t-
8
Bu/chiral diphosphine ligand and PMHS. The effectiveness
of copper for hydrosilylation of carbonyl compounds was
9
reported by Lipshutz and his group. Their subsequent studies
led to the development of highly enantioselective hydrosi-
lylation of ketones based on CuCl/NaO-t-Bu and chiral
1
0
diphosphine ligands. Besides copper alkoxides, copper
fluoride and copper(II) acetate also catalyze the asymmetric
hydrosilylation of ketones in the presence of a BINAP ligand
Table 1. Screening of Reaction Parameters for the Asymmetric
Hydrosilylation of 4-Methylacetophenone at Room Temperature
a
1
1
under homogeneous conditions.
Industry favors the catalytic process induced by a hetero-
geneous catalyst over the homogeneous one in view of its
ease of handling, simple workup, and regenerability. Re-
cently, Lipshutz reported copper-in-charcoal, and we reported
nanocrystalline copper(II) oxide for asymmetric hydrosily-
b
entry catalyst
ligand
BINAP
BINAP
BINAP
BINAP
BIPHEP
BINAM
time (h) yield (%)
91
ee (%)
1
2
3
4
5
6
7
8
9
1
1
Cat A
Cat A
Cat B
Cat C
Cat A
Cat A
Cat A
Cat A
Cat A
Cat A
Cat A
Cat A
9
83
83 , 75
12
lation reactions. Layered double hydroxides or hydrotalcite-
like compounds (HTs) have received much attention in view
of their potential applications as adsorbents, anion exchang-
c
d
c
d
c
d
24 , 5
12
21 , 87
56
80
80
81
78
-
12
72
1
3
12
44
ers, and most importantly, as catalysts. As part of our
ongoing research aimed at the development of solid catalysts
24
14
1
4
bisoxazoline 24
trace
-
10
15
52
for asymmetric synthesis, we herein present the results on
the use of Cu-Al hydrotalcite catalyst for the asymmetric
hydrosilylation of ketones to chiral secondary alcohols in
good yields with excellent enantiomeric excess (ee) at room
temperature using BINAP as a chiral auxiliary and PMHS
as the stoichiometric reducing agent (Scheme 1).
BINOL
BINAP
BINAP
BINAP
BINAP
24
24
24
12
2
-
e
75
68
78
80
f
0
1
g
h
12
87
a
Reaction conditions: 4-methylacetophenone (1 mmol), PMHS (4
mmol), Cu-Al hydrotalcite (10 mg), solvent (3 mL), chiral ligand (7 mg).
b
c
d
e
Isolated yields, Reaction at - 40 °C. Reaction at 60 °C. THF was
f
g
h
used. CH2Cl2 was used. Ether was used. 2 equiv of PhSiH3 was used.
Copper content (wt %): Cat A ) 34.11; Cat B ) 47.15; Cat C ) 46.07.
Scheme 1
amount of reduced product were obtained using polar solvents
such as THF. Nonpolar solvents such as toluene produced S-1-
(4-methylphenyl)ethanol in excellent yields and enantiomeric
excess (ee) at room temperature. Among the different chiral
ligands screened (Figure 1), commercially available BINAP
To identify and develop the best copper catalyst for the
asymmetric hydrosilylation of ketones, a series of hydrotalcites
(
7) (a) Gade, L. H.; Cesar, V.; Bellemin-Laponnaz, S. Angew. Chem.,
Int. Ed. 2004, 43, 1014. (b) Duan, W.-L.; Shi, M.; Rong, G. B. Chem.
Commun. 2003, 2916. (c) Evans, D.; Micheal, A. F. E.; Tedrow, J. S.;
Campos, K. R. J. Am. Chem. Soc. 2003, 125, 3534. (d) Yun, J.; Buchwald,
S. L. J. Am. Chem. Soc. 1999, 121, 5640. (e) Halterman, R. L.; Ramsey,
T. M.; Chen, Z. J. Org. Chem. 1994, 59, 2642. (f) Riant, O.; Mostefai, N.;
Courmarcel, J. Synthesis 2004, 2943.
(
8) (a) Appella, D. H.; Moritani, Y.; Shintani, R.; Ferreira, E. M.;
Buchwald, S. L. J. Am. Chem. Soc. 1999, 121, 9473. (b) Moritani, Y.;
Appella, D. H.; Jurkauskas, V; Buchwald, S. L J. Am. Chem. Soc. 2000,
1
22, 6797.
(
9) Lipshutz, B. H.; Chrisman, W.; Noson, K. J. Organomet. Chem.
2
001, 624, 367.
Figure 1. Different chiral ligands used.
(
10) (a) Lipshutz, B. H.; Noson, K.; Chrisman, W. J. Am. Chem. Soc.
2
2
001, 123, 12917. (b) Lipshutz, B. H.; Lower, A.; Noson, K. Org. Lett.
002, 4, 4045. (c) Lipshutz, B. H.; Noson, K.; Chrisman, W.; Lower, A.
J. Am. Chem. Soc. 2003, 125, 8779.
11) (a) Sirol, S.; Courmarcel, J.; Mostefai, N.; Riant, O. Org. Lett. 2001,
, 4111. (b) Lee, D.-W.; Yun, J. Tetrahedron Lett. 2004, 45, 5415.
gave excellent yields and ee’s greater than R-(+)-2,2′-bis(diphe-
nylphosphino)-6,6′-dimethoxy-1,1′-biphenyl (BIPHEP). The use
(
3
2980
Org. Lett., Vol. 10, No. 14, 2008

of bidentate nitrogen-based ligands gave poor yields, and the
ee’s decreased significantly (Table 1, entries 5 and 6). Although
phenylsilane is an active reductant, the inexpensive and
nontoxic polymer siloxane PMHS has been used in this work.
Eventually, the catalytic system consisting of catalyst A,
BINAP as the chiral auxiliary, and PMHS as the stoichio-
metric reducing agent in the presence of toluene was chosen
for the asymmetric hydrosilylation of an array of aryl alkyl
ketones at room temperature. The results are listed in Table
Conversely, the presence of an electron-donating group
at the para-position (Table 2, entry 13) has little effect on
enantioselectivity but requires longer reaction time for full
conversion. Another important observation is the dependence
of enantiomeric excess on the position of the substituent
group (irrespective of electron-withdrawing or electron-
donating) of the acetophenone. The ee value was highest
when the substituent group was present at the para-position
of the acetophenone rather than at the meta-position, which
in turn was higher than at the ortho-position (Table 2, entries
2
. Acetophenone is hydrosilylated cleanly with good ee
2
-7). This demonstrates the ability of steric hindrance of
meta- and ortho-substituents to modify the enantiomeric
excess of the reaction, which is in contrast to the recently
reported asymmetric hydrogenation of aryl ketones catalyzed
by copper catalyst reported by Shimizu et al., where the
obtained ee was highest in the case of ortho-substituted
Table 2. Asymmetric Hydrosilylation of Prochiral Ketones
Catalyzed by Cu-Al Hydrotalcite and BINAP at Room
Temperature
5
f
substrates. Sterically demanding 2-acetonaphthone and
-acetonaphthone (Table 2, entries 20 and 21) also afforded
1
good yields with excellent enantioselectivity. When the
methyl group of the aryl alkyl ketone is substituted with an
ethyl group, the asymmetric hydrosilylation reaction still gave
excellent enantioselectivity, albeit with moderate yields
(
Table 2, entries 17 and 18). It is significant to note that
different substituents like fluoro, bromo, chloro, and nitro
Table 2, entries 2-8 and 10) were not affected during the
(
hydrosilylation reaction.
Catalyst-recycling experiments were also carried out, using
4
-methylacetophenone as a model substrate. As can be seen
in Table 3, the catalyst A was used for three cycles without
a
Table 3. Method for Recycling Catalyst A
b
c
run
time (h)
yield (%)
ee (%)
1
2
3
9
9
9
91
85
83
83
80
81
a
Reaction conditions: 4-methylacetophenone (1 mmol), PMHS (4
mmol), Cu-Al hydrotalcite (10 mg), toluene (3 mL), BINAP (7 mg).
b
c
Isolated yields. Absolute configurations were determined to be (S).
loss of activity and selectivity. No reaction occurred when
the reaction was conducted with the filtrate obtained after
removal of the solid catalyst. This indicates that the active
catalyst species was not leached out of the solid catalyst.
a
Reaction conditions: substrate (1 mmol), PMHS (4 mmol), Cu-Al
b
(12) (a) Lipshutz, B. H.; Frieman, B. A.; Tomaso, A. E., Jr Angew. Chem.
Int. Ed. 2006, 45, 1259. (b) Kantam, M. L.; Laha, S.; Yadav, J.; Likhar,
P. R.; Sreedhar, B.; Choudary, B. M. AdV. Synth. Catal. 2007, 349, 1797.
hydrotalcite (10 mg), toluene (3 mL), BINAP (7 mg). Isolated yields.
Absolute configurations were determined to be S.
c
(
13) (a) Sels, B. F.; De Vos, D.; Jacobs, P. A. Catal. ReV. 2001, 43,
4
43. (b) Choudary, B. M.; Madhi, S.; Chowdari, N. S.; Kantam, M. L.;
Sreedhar, B. J. Am. Chem. Soc. 2002, 124, 14127. (c) Climent, M. J.; Corma,
A.; Iborra, S.; Velty, A. J. Catal. 2004, 221, 474.
(
Table 2, entry 1). Introduction of an electron-withdrawing
group at the para-position produced an increase in ee, and a
shorter reaction time was required for completion of the
reaction (Table 2, entries 2, 5, 8, 9, 11, and 18).
(14) (a) Choudary, B. M.; Kantam, M. L.; Ranganath, K. V. S.;
Mahender, K.; Sreedhar, B J. Am. Chem. Soc. 2004, 126, 3396. (b)
Choudary, B. M.; Ranganath, K. V. S.; Pal, U.; Kantam, M. L; Sreedhar,
B J. Am. Chem. Soc. 2005, 127, 13167.
Org. Lett., Vol. 10, No. 14, 2008
2981

Atomic absorption spectroscopy (AAS) was employed to
determine the copper content of the catalyst A, and it was
found to be 34.11 wt %. The leaching of the metal after the
first cycle was determined by AAS and was found to be
negligible (0.0149%).
Scheme 2
.
Possible Mechanism of Asymmetric Hydrosilylation
Catalyzed by Cu-HT
The plausible mechanism of hydrosilylation may be through
the formation of copper hydride species from the reduction of
ligated Cu-Al hydrotalcite by PMHS. At this stage, we are
not sure whether the active catalytic species is copper(I) or
11b
copper(II) hydride. X-ray photoelectron spectroscopic (XPS)
investigations of fresh Cu-HT and Cu-Al hydrotalcite treated
with the BINAP ligand at the Cu 2p level shows 2p3/2 lines at
9
34.3 and 934.4 eV, respectively. This corresponds to a +2
16
oxidation state (Figure 2).
hydrotalcite, is used for the asymmetric hydrosilylation of
ketones. A high level of ee can be obtained by using an
inexpensive and nontoxic reducing agent such as PMHS at
room temperature using commercialy available BINAP as
the chiral auxiliary. The catalyst can be activated by the
hydrosilylating reagent itself and thus obviates the need to
use alkoxide bases.
In conclusion, enantioselective hydrosilylation of ketones
to afford chiral secondary alcohols with good yields and
excellent enantioselectivities using Cu-Al hydrotalcite and
BINAP in the presence of PMHS as the stoichiometric
18
reducing agent is reported. No inorganic base was required
for the activation of the catalyst.
Figure 2. XPS high-resolution narrow scans of Cu 2p3/2 for (a)
Acknowledgment. Soumi Laha and Jagjit Yadav thank
CSIR, India, for their fellowships.
fresh Cu-HT, (b) Cu-HT treated with BINAP, (c) recovered
catalyst under inert conditions, and (d) recovered catalyst at normal
conditions.
Supporting Information Available: General experimental
procedures and characterization data of products. This
material is available free of charge via the Internet at
http://pubs.acs.org.
However, XPS spectra of the recovered catalyst after the
reaction under inert conditions show Cu 2p3/2 peaks at 933.1
eV, which correspond to Cu in the +1 oxidation state. The
copper hydride species reacts with the ketone, resulting in
the formation of copper alkoxide, and subsequently under-
goes σ-bond metathesis with the organosilane to afford the
OL800616P
(
18) Representative Procedure for the Asymmetric Hydrosilylation
of Ketones by Cu-Al hydrotalcite: Cu-Al hydrotalcite (0.010 g) and
S)-BINAP (0.01 mmol, 0.007 g) were placed in a dried Schlenk tube
(
8a,11b
silyl ether (Scheme 2).
The XPS spectra of the recovered
containing dry toluene (3 mL) at room temperature and stirred for 1 h under
a nitrogen atmosphere. PMHS (4 mmol, 0.24 mL) was then added dropwise
and allowed to stir for 30 min. To the reaction mixture, ketone (1 mmol)
was added, and stirring was continued. After completion of the reaction
catalyst at normal conditions show the 2p3/2 peak at 934.3
eV, which corresponds to Cu in the +2 oxidation state only.
This is probably due to the reoxidation of Cu(I) to Cu(II)
(
monitored by TLC), the reaction mixture was centrifuged to separate the
1
7
catalyst and washed several times with ether. The catalyst was reused for
another cycle after vacuum drying. The reaction mixture was quenched with
water and transferred to a round-bottom flask with the aid of Et2O (10 mL),
and then tetrabutylammonium fluoride (TBAF) (1.0 M in THF, 1.2 mL)
was added. The reaction mixture was stirred vigorously for 0.5 h. The layers
were separated, and the aqueous layer was extracted with ether. The
combined organic layers were dried over MgSO4, and the solvent was
removed under reduced pressure. The residue was purified by silica gel
flash column chromatography (eluent: hexane/ethyl acetate) to afford the
desired product.
under normal conditions.
The present protocol has several advantages. A heteroge-
neous and recyclable catalyst, namely, copper- aluminum
(
(
(
15) Velu, S.; Swamy, C. S. Appl. Catal., A 1996, 145, 141.
16) Tsoncheva, T.; Vankova, S.; Mehandjiev, D. Fuel 2003, 82, 755.
17) Choudary, B. M.; Sridhar, C.; Kantam, M. L.; Venkanna, G. T.;
Sreedhar, B. J. Am. Chem. Soc. 2005, 127, 9948.
2982
Org. Lett., Vol. 10, No. 14, 2008