Microwave assisted enantioselective Michael addition reaction using BINOL-Al-Li catalyst

Article abstract of DOI:10.1081/SCC-120015397

Enantioselective (S)-BINOL-Al-Li catalyzed Michael reaction of malonates and thiols with cyclic enones are achieved with high enantioselectivity in a remarkably lesser reaction time using microwaves.

Full text of DOI:10.1081/SCC-120015397

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MICROWAVE ASSISTED ENANTIOSELECTIVE MICHAEL
ADDITION REACTION USING BINOL–Al–Li CATALYST
a
a
S. Narasimhan & S. Velmathi
a
Centre for Natural Products, SPIC Science Foundation, 111, Mount Road, Guindy, Chennai,
00 032, India
6
Published online: 23 Aug 2006.
To cite this article: S. Narasimhan & S. Velmathi (2002): MICROWAVE ASSISTED ENANTIOSELECTIVE MICHAEL ADDITION
REACTION USING BINOL–Al–Li CATALYST, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 32:24, 3791-3795
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SYNTHETIC COMMUNICATIONS
Vol. 32, No. 24, pp. 3791–3795, 2002
MICROWAVE ASSISTED
ENANTIOSELECTIVE MICHAEL
ADDITION REACTION USING
BINOL–Al–Li CATALYST
S. Narasimhan* and S. Velmathi
Centre for Natural Products, SPIC Science Foundation
111, Mount Road, Guindy, Chennai-600 032, India
ABSTRACT
Enantioselective (S)-BINOL–Al–Li catalyzed Michael reac-
tion of malonates and thiols with cyclic enones are achieved
with high enantioselectivity in a remarkably lesser reaction
time using microwaves.
Key Words: Microwave irradiation; Michael reaction;
Enantioselectivity; Heterobimetallic catalyst
INTRODUCTION
Conjugate addition reactions of carbon nucleophiles to a,b-unsatu-
rated carbonyl compounds are among the most widely used methods for
[
1]
[2]
C–C bond formation in organic syntheses. Recently Shibasaki and his
co-workers introduced a new class of aluminium based BINOL complexes
as effective catalysts for Michael addition reactions of malonate esters
*Corresponding author. E-mail: narasim3_@hotmail.com or narasimhan_s@
yahoo.com
3
791
DOI: 10.1081/SCC-120015397
Copyright & 2002 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
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2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
3
792
NARASIMHAN AND VELMATHI
to cyclic enones. But the reactions require long reaction times for com-
pletion (72h).
[
3]
In recent years, microwave mediated organic reactions have gained
importance providing the advantages of short reaction times, reduced
amount of solvent and eco-friendly nature of the process. This, coupled
with the significance of Michael reaction in asymmetric C–C bond
formation, prompted us to study enantioselective Michael addition reaction
under microwave irradiation.
RESULTS AND DISCUSSION
We describe here the use of microwave technology in asymmetric
Michael addition of malonates to cyclic a,b-unsaturated ketones in the
presence of S-BINOL–Al–Li catalyst (Sch. 1).
[
4]
[
4]
We adopted a similar procedure reported by Shibasaki for preparing
the heterobimetallic catalyst (which contains two different metal ions, Al
and Li for coordinating with the reactants after each catalytic cycle).
Typically a mixture of cyclohexenone and diethylmalonate was irradiated
with microwaves in a domestic microwave oven (IFB model 750 W). After
cooling to room temperature, the product was isolated (See Experimental).
The experiment was performed with a number of different substrates and the
results are presented in the table. Interestingly the reaction was complete
within a short period of time (2–15 min) retaining high enantioselectivity
(>98%). Although many reports are available on the catalytic asymmetric
Michael addition using malonate derivatives, the same using thiols as sub-
strates has not been explored in detail. The only catalyst that has shown
reasonably good enantioselectivity in the asymmetric C–S bond formation
[
5]
was made from Lanthanum–sodium–BINOL (LSB). However, the reac-
tion required longer reaction times (from 20 min to 43 h). Hence we explored
MWI ¼ Microwave irradiation
Scheme 1.

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BINOL–Al–Li CATALYST REACTION
3793

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794
NARASIMHAN AND VELMATHI
Scheme 2.
the reaction using BINOL–Al–Li under microwave conditions. It was
gratifying to note that the addition was complete in a remarkably less
time (2min) with moderate enantioseletivity (31%). The results are pre-
sented in Table 1 (Sch. 2).
In conclusion, the BINOL–Al–Li catalyst can be effectively used
to promote the asymmetric Michael addition of malonates and
thiols under microwave activation in short reaction times and with high
enantioselectivity.
EXPERIMENTAL
Reactions were conducted under nitrogen atmosphere in an oven-
dried flask closed with a septum. BINOL–Al–Li catalyst was prepared
[
from S-BINOL and LiAlH by the literature procedure. To 0.5 mmol of
4]
4
BINOL–Al–Li catalyst generated in situ, 5 mmol of 2-cyclohexenone
(
490 mg, 5 mmol) and diethyl malonate (800 mg, 5 mmol) were added. The
reaction mixture was kept under microwave irradiation for the stipulated
period of time (See Table 1). The progress of the reaction was monitored by
tlc. When all of the malonate had reacted, the reaction mixture was
quenched with 1N HCl and extracted with ethyl acetate. The organic layer
was washed successively with saturated NaHCO solution, brine and dried
3
over anhydrous Na SO . Removal of the solvent under reduced pressure
2
4
gave a syrupy mass, which on flash column chromatography (using 230–400
mesh type silica gel, Hexane : ethyl acetate (98 : 2) as eluant) gave the prod-
0
D
ꢀ
uct as a colorless oil (1.1 g, 90% yield, [ꢀŠ ¼ À3.5 ee ¼ 98%).
ACKNOWLEDGMENT
The authors thank Prof. T. R. Govindachari for his encouragement
and S.V thanks CSIR for financial assistance.

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BINOL–Al–Li CATALYST REACTION
REFERENCES
. Perlmutter, P. Conjugate Addition Reactions in Organic Synthesis;
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Pergamon Press: Oxford, 1992: Tetrahedron Organic Chemistry
Series, Vol. 9.
. Shibasaki, M.; Sasai, H.; Arai, T. Angew. Chemie. Int. Ed. 1997, 36,
2
1236–1256.
3
4
. Caddick, S. Tetrahedron 1995, 51, 10403.
. Shibasaki, M.; Arai, T.; Sasai, H.; Aoe, K.; Okamura, Date, T. Angew.
Chemie. Int. Ed. 1996, 35, 104.
5. Mori, E.; Arai, T.; Sasai, H.; Shibasaki, M. J. Am. Chem. Soc. 1998,
1
20, 4043.
. Yamaguchi, M.; Shiraishi, A.; Hirama, M. Angew. Chemie. Int. Ed.
993, 32, 1176.
6
1
Received in the USA December 9, 2001

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2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.