Calcium-BINOL: A novel and efficient catalyst for asymmetric Michael reactions

Article abstract of DOI:10.1016/S0040-4039(01)01736-1

A new calcium-BINOL catalyst has been developed for asymmetric Michael addition reactions of enones and enals. This inexpensive monometallic catalyst functions not only as a Lewis acid but also acts as a Br?nsted base.

Full text of DOI:10.1016/S0040-4039(01)01736-1

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 8515–8517
Calcium-BINOL: a novel and efficient catalyst for asymmetric
†
Michael reactions
G. Kumaraswamy,* M. N. V. Sastry and Nivedita Jena
Gas-Based Chemicals, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Received 28 June 2001; revised 28 August 2001; accepted 14 September 2001
Abstract—A new calcium-BINOL catalyst has been developed for asymmetric Michael addition reactions of enones and enals.
This inexpensive monometallic catalyst functions not only as a Lewis acid but also acts as a Brønsted base. © 2001 Elsevier
Science Ltd. All rights reserved.
Recently, Shibasaki et al. have developed most impres-
sive asymmetric Michael reactions catalysed by unique
heterobimetallic catalysts. These lanthanoid-alkali
metal hybrids of BINOL function presumably as both
Brønsted bases and Lewis acids. A synergistic coopera-
tion of the two different metals in the complex pro-
motes formation of the desired products in up to 98%
amount of EtOH was found to accelerate the reaction
and increase yields and ee’s. The reaction proceeded
sluggishly without EtOH, whereas more than 0.1 ml (5
mole equivalent to (R)-(+)-BINOL used) of EtOH
showed a deleterious effect on optical purity. 10 mol%
of the Ca-BINOL catalyst also gave a satisfactory yield
with a slightly reduced ee. A Li-BINOL (LiOH+
BINOL) complex also gave the Michael adduct 5 with
1
ee.
2
8% ee in 85% yield. The supernatant toluene solution
2
Based on a recent report, we have initiated a study of
of the catalyst (R)-2 gave the adduct 5 in 80% yield
with 30% ee and the precipitate as a basic catalyst also
gave 40% ee with 90% yield indicating that the active
catalyst was the precipitate itself. Thus, we carried out
the Michael reactions using all the (R)-2 as the cata-
calcium complexes for activation of Michael acceptors.
Herein, we disclose a new enantioenriched, calcium-
BINOL catalyst, which is envisioned to function not
only as a Brønsted base but also by controlling the
orientation of the enones and enals. This hypothesis
was initially tested on trans-chalcone 3 and dimethyl
malonate 4 using 15 mol% of a catalyst prepared from
4
lyst. Next, we examined the generality of the reaction
and our results are shown in Table 1. Cyclic and acyclic
enones gave Michael adducts in excellent yields with
moderate ee’s (entries 1–6). Enals also gave good yields
of products albeit with lower ee (entry 8). The nature of
the ester group of the malonate affected the ee of the
BINOL and Ca(OH) in THF. Although the reaction
2
produced the Michael adduct 5 in good yield, no sig-
nificant ee was observed (3% ee). After considerable
experimentation, we successfully generated a calcium-
3
BINOL catalyst (R)-2 using CaCl2 for the activation
t
of Michael acceptors as shown in Scheme 1.
a) K OBu
OH
OH
O
O
2KCl
Ca
ethanol
The effect of solvents and temperature were investi-
gated. After screening a variety of solvents (THF 0%
ee; THF:toluene (3:7) 10% ee; C H CF 9% ee; DME
b) CaCl2
(R) -1
(R) -2
6
5
3
0
% ee; CH Cl 24% ee) toluene was found to give the
2 2
O
best results at −15°C (ambient temp. 20% ee). A small
Ph
Ph
a) (R) -2 (15 mol% )
3
CH(CO Me)2
2
O
+
Ph
O
O
Ph
*
Keywords: calcium-BINOL; Michael reactions; Brønsted base; Lewis
b) toluene, -15°C
acid.
H CO
3
OCH3
24 h
5
4
*
Corresponding author. Tel.: +91-40-7171382; fax: +91-40-7173757;
e-mail: gkswamy iict@yahoo.co.in
IICT Communication No. 4837.
–
†
Scheme 1.
0
040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01736-1

8
516
G. Kumaraswamy et al. / Tetrahedron Letters 42 (2001) 8515–8517
a
Table 1. Asymmetric Michael addition of malonates to enones and enols
Entry Enones/enals Malonate Adductsc
25
D
Yield(%)b %ee d,e
[α]
O
O
CH(CO Me)2
1)
2
+ 14
Ph
Ph
9
0
42 (S)
CH2(CO2Me)2
Ph
Ph
*
(
c=2, CHCl3)
O
O
O
CH(CO -i-Pr)
2
2
2)
H C
3
Ph
+ 8
85
CH (CO -i-Pr)
2
2
2
H C
3
Ph
*
( c=2, CHCl3)
O
3
)
CH2(CO2 Me)2
+ 33
88(R) f
7
5
*
CH(CO Me)2
2
( c=5, CHCl3)
O
O
4
)
)
7
6
87 (R)
CH2(CO2Et)2
+ 30
*
CH(CO Et)2
2
( c=5, CHCl3)
O
O
O
5
CH2(CO2-i-Pr)2
68
55
24 (S) f
-
6
CH(CO -i-Pr)
2
( c=5, CHCl3)
*
O
2
6
)
CH2(CO2-i-Pr)2
2
1.3(R)
+
1
2
CH(CO -i-Pr)2
*
(
c=5, CHCl3)
O
O
7
)
PhSH
0
80
60
0
SPh
O
8)
O
CH(CO -i-Pr)
31.25(S)
2
+5
H
CH3 CH2(CO2-i-Pr)2
H
CH3
*
( c=2, CHCl3)
a
b
c
d
e
f
All reactions were carried out on a 2 mmol scale except entries 3, 5 and 6 which were carried out on a 10 mmol scale.
Isolated yields based on enones or enals.
All the adducts gave satisfactory analytical data.
Enantiomeric excess (ee) values were determined by optical rotation and comparison of values from known literature.
Absolute configurations were assigned by comparison of specific rotations with literature value.
6
6
Absolute configuration and ee values were determined by chemical correlation to known compounds using decarboxylation and methylation.7
product. Higher optical yields were obtained using Me
or Et esters with cyclic enones. In the cases of acyclic
enones and enals, the diisopropyl ester gave a better ee
than the methyl or ethyl esters. Thiophenol as a donor
gave a racemic product with 80% yield (entry 7).
ery Programme of IICT to G.K. Thanks are also due to
UGC (New Delhi) for the award of JRF fellowships to
M.N.V.S. and N.J. We also gratefully acknowledge the
Gerchem Laboratory Pvt Ltd., Hyderabad for providing
R-(+)-BINOL.
In conclusion, we have succeeded in developing a substi-
tute for La(O-i-Pr) . Although, the Al-Li-BINOL cata-
lyst gave Michael adducts with good ee’s, because of its
3
References
sensitivity to moisture, it is not amenable for large-scale
applications. To the best of our knowledge, this new
Ca-BINOL catalyst is the first of its kind. Calcium is not
only an eco-friendly metal but is also inexpensive and
readily available. Tuning the catalyst to achieve higher
ee’s is under progress in our laboratory.
5
1. (a) For a review, see: Shibasaki, M.; Sasai, H.; Arai, T.
Angew. Chem., Int. Ed. Engl. 1997, 36, 1236; (b) Mat-
sunaga, S.; Ohshima, T.; Shibasaki, M. Tetrahedron Lett.
2
000, 41, 8473; (c) Kim, Y. S.; Matsunaga, S.; Das, J.;
Sekine, A.; Ohshima, T.; Shibasaki, M. J. Am. Chem. Soc.
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. Ikegami, S.; Yamada, Y. M. A. Tetrahedron Lett. 2000,
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2
2
4
Acknowledgements
3. (a) Without CaCl2 the reaction proceeded yielding a
racemic product. (b) The reaction of 3 with 4 was also
carried out with CaO+H O; CaH +H O and Ca(OAc) but
We are grateful to the Director, IICT for his constant
encouragement, and for the award of Prolog to Discov-
2
2
2
2
the product was found to be racemic.

G. Kumaraswamy et al. / Tetrahedron Letters 42 (2001) 8515–8517
8517
4
. A typical procedure for Michael addition of dimethyl
malonate 4 to chalcone 3: To a mixture of (R)-(+)-BINOL
wise via a syringe. The reaction mixture was stirred at
−15°C for 24 h. The reaction was quenched with 2N
HCl (5 ml) and extracted with EtOAc and dried over
anhydrous Na SO . After concentration, the residue was
(
0
100 mg, 0.35 mmol, 15 mol%) and pot.t-butoxide (78 mg,
.69 mmol), abs. ethanol (6 ml) was added at room
temperature under an argon atmosphere. After stirring for
h, ethanol was evaporated under reduced pressure and to
2
4
subjected to column chromatography over aluminium
oxide (neutral) (hexane:EtOAc 9:1) gave 565 mg of a white
1
25
the residue, solid CaCl (90%) (46.3 mg, 0.42 mmol) was
solid (90% yield, [h]D +14 (c 2, CHCl3).
2
added. Then, the solid was dried under vacuum (1 mmHg,
5. The production of a chiral binaphthol compound using a
non-rare earth metal complex, US Patent 6,090,969
(Nagase and Co. Ltd., Osaka, Japan).
15 min) followed by the addition of abs. ethanol (6 ml).
The white suspension was stirred for 5 h at ambient
temperature and then subsequent evaporation of ethanol
under reduced pressure gave a white solid powder. To this
solid catalyst, toluene (15 ml) and abs. EtOH (0.1 ml) were
added sequentially under argon atmosphere and the mix-
ture was stirred for 12 h at ambient temperature. This
reaction mixture was cooled at −15°C for 15 min followed
by addition of a toluene solution (0.5 ml) of chalcone (485
mg, 2.3 mmol) at the same temperature. After 15 min,
dimethyl malonate (368 mg, 2.7 mmol) was added drop-
6. (a) Yamaguchi, M.; Shiraishi, T.; Hirama, M. Angew.
Chem., Int. Ed. Engl. 1993, 32, 1176; (b) Sasai, H.; Arai,
T.; Satow, Y.; Houk, K. N.; Shibasaki, M. J. Am. Chem.
Soc. 1995, 117, 6194; (c) Yamaguchi, M.; Shiraishi, T.;
Hirama, M. J. Org. Chem. 1996, 61, 3520; (d) Manickam,
G.; Sundarajan, G. Tetrahedron: Asymmetry 1997, 8, 2271.
7. Posner, G. H.; Weitzberg, M.; Hamill, T. G.; Asirvatham,
E.; Cun-Heng, H.; Clardy, J. Tetrahedron 1986, 42,
2919.