Mechanistic study of asymmetric Michael addition of malonates to enones catalyzed by a primary amino acid lithium salt

Article abstract of DOI:10.1016/j.tet.2013.09.066

A mechanistic study was carried out for the asymmetric Michael addition reaction of malonates to enones catalyzed by a primary amino acid lithium salt to elucidate the origin of the asymmetric induction. A primary β-amino acid salt catalyst, O-TBDPS β-hom

Full text of DOI:10.1016/j.tet.2013.09.066

Tetrahedron 69 (2013) 10003e10008
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Mechanistic study of asymmetric Michael addition of malonates to
enones catalyzed by a primary amino acid lithium salt
,
b
,
c
b
a,b
Masanori Yoshida a , Yuki Nagasawa , Ami Kubara , Shoji Hara
,
*
Masahiro Yamanaka c
,
*
a Division of Chemical Process Engineering, Faculty of Engineering, Hokkaido University, Kita 13-jo Nishi 8, Kita-ku, Sapporo, Hokkaido 060-8628, Japan
b Molecular Chemistry and Engineering Course, Graduate School of Chemical Sciences and Engineering, Hokkaido University, Kita 13-jo Nishi 8, Kita-ku,
Sapporo, Hokkaido 060-8628, Japan
c Department of Chemistry and Research Center for Smart Molecules, Faculty of Science, Rikkyo University, 3-34-1 Nishi-Ikebukuro, Toshima-ku,
Tokyo 171-8501, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 29 August 2013
Received in revised form 17 September 2013
Accepted 20 September 2013
Available online 27 September 2013
A mechanistic study was carried out for the asymmetric Michael addition reaction of malonates to
enones catalyzed by a primary amino acid lithium salt to elucidate the origin of the asymmetric in-
duction. A primary
enantioselectivity than that achieved with the corresponding catalysts derived from
acids for this reaction. Detailed studies of the transition states with DFT calculations revealed that the
lithium cation and carboxylate group of the -amino acid salt catalyst have important roles in achieving
high enantioselectivity in the Michael addition reaction of malonates to enones.
Ó 2013 Elsevier Ltd. All rights reserved.
b
-amino acid salt catalyst, O-TBDPS
b
-homoserine lithium salt, exhibited much higher
a
- and -amino
g
b
Keywords:
Organocatalysis
Asymmetric synthesis
Primary amino acid
Michael addition
DFT calculation
1. Introduction
much interest in the development of new chiral organocatalysts for
this reaction and elucidation of their reaction mechanisms.1,2,5
Since the rediscovery of a simple secondary
a
-amino acid,
L
-
We recently reported that a primary
TBDPS -homoserine lithium salt (1), was an effective catalyst for
the Michael addition reaction of dimethyl malonate (2) to 2-
cyclohexen-1-one (3) and that the -amino acid moiety was
necessary for obtaining Michael adduct 4 with high enantiose-
lectivity, since - and -amino acid salt analogues 5 and 6 resulted
in lower enantioselectivity than that from using the -amino acid
salt catalyst 1 (Scheme 1).6 After carrying out detailed optimiza-
tion of the reaction conditions with -amino acid salt catalyst 1,
b-amino acid salt, O-
proline, as a high-potential catalyst in catalytic asymmetric syn-
thesis, asymmetric organocatalysis has achieved explosive growth
as a result of efforts to develop unique catalysts.1 Asymmetric Mi-
b
b
chael addition reaction of carbon nucleophiles to a,b-unsaturated
ketones or enals is one of the synthetic methodologies that received
much benefit from the growth of organocatalysis, and it has be-
come a powerful tool for the carbonecarbon bond formation re-
a
g
b
action to create a carbon stereogenic center on the
carbonyl groups.2 As pioneering works in this reaction with orga-
nocatalysis, a rubidium salt of -proline and a chiral (2-pyrrolidyl)
b
-position of
b
we succeeded in obtaining various 1,5-ketoesters in high yields
(up to 92%) with high enantioselectivities (up to 97% ee); however,
L
alkyl ammonium hydroxide were discovered as effective catalysts
for the asymmetric Michael addition of malonates to enones by
Yamaguchi3 and Taguchi,4 respectively, in the early 1990s. Since
Michael addition reaction of malonates to enones provides 1,5-
ketoesters, which are synthetically useful substrates, there is
the function of the b-amino acid salt moiety in the Michael ad-
dition reaction to achieve high enantioselectivity remains elusive.
Although several reports about successful organocatalysis using
a
b
-amino acid catalyst have been published, there have been few
mechanistic studies compared with studies on organocatalysis
using an
-amino acid catalyst.7 In this context, we carried out
a mechanistic study with DFT calculations to determine why the
a
b
-
amino acid salt catalyst 1 is effective for obtaining 1,5-ketoesters
with high enantioselectivity in the Michael addition reaction of
* Corresponding authors. E-mail addresses: myoshida@eng.hokudai.ac.jp (M.
Yoshida), myamanak@rikkyo.ac.jp (M. Yamanaka).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.09.066

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M. Yoshida et al. / Tetrahedron 69 (2013) 10003e10008
90
80
70
60
50
40
30
20
10
Catalyst
loading
5 mol%
10 mol%
20 mol%
Scheme 1. Michael addition reaction of dimethyl malonate (2) to 2-cyclohexen-1-one
(3) catalyzed by a primary amino acid lithium salt (1, 5, and 6). Isolated yield and
0
2
4
Reaction time / h
8
16
24
enantiomeric excess of the (R)-enantiomer of Michael adduct
4 are shown in
parentheses.
Fig. 2. Effect of catalyst loading on the Michael addition reaction of malonate 2 to
enone 3. The Michael addition reaction was carried out with a mixed catalyst con-
sisting of 1 and the original amino acid (1:3), malonate 2 (1 mmol), and enone 3
(0.5 mmol) in DMSO/(CH2Cl)2 (1:2, 0.5 mL) at 25 ꢀC.
malonates to enones and why the catalyst exhibits higher enan-
tioselectivity than that of the a- and g-amino acid salt catalysts 5
and 6.
time (Fig. 2). These results indicate that a monomeric reactive
species would participate in the TS of the present Michael addition
reaction.
In our previous studies on a primary amino acid salt-catalyzed
Michael addition of malonates to enones,6,9 the use of a mixed
solvent consisting of a coordinative solvent (DMSO) and a low polar
solvent [(CH2Cl)2] was found to be essential to achieve high enan-
tioselectivity (Table 1). The solvent effect indicates that DMSO
would coordinate with the lithium cation to prevent aggregation of
the reactive species during the course of the reaction.
2. Results and discussion
To verify a reliable chemical model, it is necessary to determine
how many molecules of the catalyst participate in the transition
state (TS). Two typical mechanistic studies were carried out as
shown in Figs. 1 and 2.8 First, we examined the Michael addition
reaction of malonate 2 to enone 3 in the presence of a primary
amino acid lithium salt catalyst 1 with various enantiomeric ex-
cesses that were prepared from O-TBDPS (S)- and (R)- -homo-
b-
b
serines. A good linear relationship was obtained between the
enantiomeric excesses of Michael adduct 4 and catalyst 1 (Fig. 1).
We next studied the effects of catalyst loading on the Michael ad-
dition reaction. It was found that the reaction rates are roughly
proportional to the concentration of the catalyst at each reaction
Table 1
Solvent effect in the Michael addition of malonate 2 to enone 3 catalyzed by primary
amino acid salt 1a
Entry
Solvent
Yield (%)b
ee (%)c
100
80
1
2
3
4
5
6
7
8
9
DMSO
CH2Cl2
(CH2Cl)2
DMSO/CH2Cl2 (2:1)
DMSO/CH2Cl2 (1:1)
DMSO/CH2Cl2 (1:2)
DMSO/(CH2Cl)2 (2:1)
DMSO/(CH2Cl)2 (1:1)
DMSO/(CH2Cl)2 (1:2)
61
28
30
52
51
49
42
42
43
59
60
56
81
87
88
85
87
90
60
40
20
0
a
The Michael addition reaction was carried out with catalyst 1 (0.05 mmol),
malonate 2 (1 mmol), and enone 3 (0.5 mmol) in a solvent (1 mL) at 25 ꢀC for 24 h.
-20
-40
-60
-80
b
Isolated yield of 4 based on 3.
Determined by chiral HPLC analysis.
c
Based on these experimental mechanistic studies, DFT calcula-
tions10 were carried out at the B3LYP/6-311þþG**//B3LYP/6-31G*
level using monomeric imine models, where DMSO coordinates
with the lithium cation of the catalyst as an explicit solvent model
and TMS is used instead of TBDPS to reduce computational cost
(Fig. 3). We have previously proposed that the reaction would
proceed through the formation of imine intermediate 7 generated
from enone 3 and catalyst 1, in which the Lewis acidic lithium
cation of the catalyst would coordinate with the nitrogen atom of
imine and the oxygen atom of the carboxylate group to form
a stable six-membered ring structure.6a,9 DFTcalculations exhibited
-100
-100-80 -60 -40 -20 0 20 40 60 80 100
ee of (S)-catalyst / %
Fig. 1. Linear relationship between enantiomeric excess of the Michael adduct 4 and
O-TBDPS
out with a mixed catalyst consisting of 1 and the original amino acid (1:3, 0.1 mmol),
malonate 2 (1 mmol), and enone 3 (0.5 mmol) in DMSO/(CH2Cl)2 (1:2, 0.5 mL) at 25 ꢀ
for 24 h according to our previous report.6a Yields of 4 were ranged from 74 to 88%.
b-homoserine lithium salt catalyst. The Michael addition reaction was carried
C

M. Yoshida et al. / Tetrahedron 69 (2013) 10003e10008
10005
Fig. 3. Optimized structures of DMSO (L) coordinated (Z)- and (E)-7 (C, gray; O, red; N, blue; Li, purple; S, yellow; Si, sky-blue). Relative energies are shown in parentheses (B3LYP/6-
311þþG**//B3LYP/6-31G*).
noteworthy structural and energetic properties of imine 7. It was
found that the lithium cation coordinates with not only the nitro-
gen atom of imine and the oxygen atom of the carboxylate group
but also the oxygen atom of the siloxy group to form a stable bi-
cyclic structure. Furthermore, it was found that there is little dif-
ference in energy between the geometric isomers, (E)- and (Z)-7.
We then carried out DFT calculations for the TS of the present
(
b
TSa), and an enolate-coordinating model (
b
TSb), were explored.
TSrb, since
In the re-facial attacking TSs, TSra is more stable than
b
b
Lewis acidic lithium cation would favorably coordinate with the
oxygen atom of the siloxy group, which has a more negative charge
(ꢁ0.914) than that of the carbonyl group of enolate (ꢁ0.657). In
addition, in bTSrb, steric repulsion was observed between malo-
nate 2 and methylene groups of the cyclohexene moiety. Therefore,
TSrb is higher in energy than TSra. As for the si-facial attacking
TSs, in contrast, the enolate-coordinating model ( TSsb) is more
stable than the siloxy-coordinating model ( TSsa). Both of the ox-
ygen atoms of the carboxylate group can be used for hydrogen
bonding and coordination with the lithium cation in TSsb to
provide resonance stabilization of the carboxylate group, whereas
Michael addition reaction to reveal how the
b-amino acid salt
b
b
catalyst functions as an efficient asymmetric catalyst. As malonate 2
approaches imine 7 through hydrogen bonding with the carbox-
ylate group, (Z)- and (E)-7 lead to re-facial and si-facial attacking
b
b
TSs,
b
TSr, and
bTSs, respectively (Fig. 4). For these TSs, two types of
b
lithium cation coordination models, a siloxy-coordinating model
Fig. 4. Optimized structures of
bTS (C, gray; O, red; N, blue; Li, purple; S, yellow; Si, sky-blue; malonate 2, ball and stick model; imine 7, tube model). Relative energies are shown in
parentheses (B3LYP/6-311þþG**//B3LYP/6-31G*).

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M. Yoshida et al. / Tetrahedron 69 (2013) 10003e10008
there is no such stabilization effect in
b
TSsa. By comparison of the
the two geometric isomers of an imine, which was generated
from 2-cyclohexen-1-one and O-TBDPS -homoserine lithium
energy differences of these four diastereomeric transition struc-
tures, TSra and TSsb were determined as plausible TSs that give
major and minor enantiomers of Michael adduct 4, respectively. In
agreement with the experimental results, TSra leading to the
major enantiomer of Michael adduct 4 is the energetically most
favored. It was thus revealed that the carboxylate group of the
b
b
b
salt. DFT calculations of the TSs of conjugate addition of dimethyl
malonate to this imine indicated that the lithium cation and the
carboxylate group of the catalyst have important roles as an an-
chor to hold the stable bicyclic structure of the imine and as
a tether to grab an enolate of malonate to bring it close to the
prochiral center of the imine, respectively. By comparison with
b
b
-
amino acid salt catalyst has a role as a tether forming the stable
bicyclic structure of imine 7 and grabbing the enolate of malonate 2
to bring it close to the prochiral center.
DFT calculations of the TSs with
a- and g-amino acid salts, it was
revealed that O-TBDPS -homoserine lithium salt has an appro-
b
To obtain further detailed insight into the effect of tether length
on stereochemical control, DFT calculations of TSs of the Michael
priate length of the amino acid structure to achieve high enan-
tioselectivity in the Michael addition reaction of malonates to
enones.
addition reaction with
TS) were also carried out (Figs. 5 and 6). In
coordinating models ( TSa) were only optimized because the
shorter tether length of the -amino acid moiety is not sufficient to
form the enolate-coordinating models ( TSb). The energy difference
TSsa (Fig. 5,1.9 kcal/mol) was smaller than that
TSsb (Fig. 4, 2.7 kcal/mol). In a manner similar
-amino acid salt catalyst has
a long and flexible tether to form both siloxy-coordinating ( TSa)
and enolate-coordinating ( TSb) models (Fig. 6). In the re-facial
attacking models, the structural and energy differences between
TSra and TSrb are similar to those obtained from the -amino acid
salt catalyst. A great difference in transition structures compared
with the case of the -amino acid salt catalyst was found in the si-
facial attacking models ( TSs) as follows: the siloxy-coordinating
model ( TSsa) provides resonance stabilization of the carboxylate
group, whereas there is no such stabilization effect in the enolate-
coordinating model ( TSsb). In contrast to TS, TSsa is thus ener-
getically more favored than TSsb. Therefore, there is a very small
energy difference (0.1 kcal/mol) between TSra and TSsa. Those
smaller energy differences between the re- and si-facial attacking
models in both TS and TS can support the experimental result that
the Michael addition reaction with the - and -amino acid salt
a
- and
g-amino acid salt catalysts (
aTS and
g
a
TS, the siloxy-
a
4. Experimental
a
a
4.1. General
between
between
a
b
TSra and
TSra and
a
b
Solvents, dimethyl malonate (2), and 2-cyclohexen-1-one (3)
to the b-amino acid salt catalyst, the g
were used after purification by distillation. O-TBDPS b-homoserine
g
was prepared according to our previous report.6a 1H NMR
g
(400 MHz) and 13C NMR (100 MHz) spectra were recorded on
a JEOL JNM-ECX400P. Chemical shifts, d are referred to TMS (CDCl3).
g
g
b
Specific rotation was measured by a HORIBA SEPA-500. HPLC was
carried out using a JASCO PU-2089 Plus intelligent pump and a UV-
2075 Plus UV detector.
b
g
g
4.2. Michael addition reaction of dimethyl malonate (2) to 2-
cyclohexen-1-one (3) catalyzed by O-TBDPS b-homoserine
lithium salt (1) with various enantiomeric excesses (Fig. 1)
g
b
g
g
g
g
4.2.1. Preparation of catalysts. In a vial, ground LiOH mono hydrate
(42 mg, 1 mmol) was added to a solution of O-TBDPS (S)-b-
a
g
homoserine (1.43 g, 4 mmol) in MeOH (4 mL) at 0 ꢀC. After stirring
for overnight at room temperature, the reaction mixture was
concentrated under reduced pressure. The obtained white solid
was ground well and dried in vacuo to give a 1:3 mixture of O-
a
g
catalysts 5 and 6 resulted in lower enantioselectivities.
Finally, we carried out DFT calculations of the TSs with a real
system of O-TBDPS
facial attacking model (TBDPS_
attacking model (TBDPS_ TSsb) (Fig. 7). It was thus confirmed that
b
-homoserine lithium salt 1 and found that a re-
TBDPS (S)-b-homoserine lithium salt 1 and the original amino
b
TSra) is more stable than a si-facial
acid. The corresponding (R)-catalyst was also synthesized in the
same manner. The obtained (S)- and (R)-catalysts were mixed in
various proportions to give catalysts with various enantiomeric
excesses.
b
the results are in agreement with those obtained by using the O-
TMS catalyst model.
3. Conclusion
4.2.2. Michael addition reaction. In a 7 mL vial, dimethyl malo-
nate (2, 132 mg, 1 mmol) was added to a solution of the catalyst
obtained above (36 mg, 0.1 mmol) and 2-cyclohexen-1-one (3,
48 mg, 0.5 mmol) in DMSO/(CH2Cl)2 (1:2, 0.5 mL) at 25 ꢀC. After
By the present experimental and computational mechanistic
studies, it was found that there is little energy difference between
Fig. 5. Optimized structures of
aTS with (R)-enantiomer of catalyst 5 (C, gray; O, red; N, blue; Li, purple; S, yellow; Si, sky-blue; malonate 2, ball and stick model; imine, tube model).
Relative energies are shown in parentheses (B3LYP/6-311þþG**//B3LYP/6-31G*).

M. Yoshida et al. / Tetrahedron 69 (2013) 10003e10008
10007
Fig. 6. Optimized structures of gTS (C, gray; O, red; N, blue; Li, purple; S, yellow; Si, sky-blue; malonate 2, ball and stick model; imine, tube model). Relative energies are shown in
parentheses (B3LYP/6-311þþG**//B3LYP/6-31G*).
the reaction mixture was stirred for 24 h at 25 ꢀC, satd aq NaCl
(1 mL) was added to the vial, and extracted with Et2O
(1.5 mLꢂ4). The combined organic phase was dried over MgSO4,
filtered, and concentrated under reduced pressure. 3-[Bis(me-
thoxycarbonyl)methyl]cyclohexanone (4) was isolated by col-
umn chromatography (silica gel, hexane/Et2O 1:1) as oil. The
enantioselectivity was determined by HPLC analysis [Daicel
CHIRALPAK AS-H, 40% isopropanol/hexane, 0.7 mL/min, 218 nm;
tR (major)¼32.3 min, tR (minor)¼34.9 min]. The absolute con-
2.38e2.46 (2H, m), 2.50e2.59 (1H, m), 3.35 (1H, d, J 7.9 Hz), 3.75
(3H, s), 3.76 (3H, s); dC (CDCl3) 24.0, 28.3, 37.6, 40.5, 44.6, 52.07,
52.09, 56.1, 167.7, 167.8, 209.0.
4.3. Effect of catalyst loading on the Michael addition re-
action of dimethyl malonate (2) to 2-cyclohexen-1-one (3)
(Fig. 2)
figuration was determined by comparison of the specific rota-
Michael addition reactions were carried out in the same
manner as shown in 4.2.2 but with various catalyst loading of an
enantiopure 1:3 mixed catalyst consisting of 1 and the original
amino acid (5 mol %: 9 mg, 0.025 mmol, 10 mol %: 18 mg,
tion with that of our previous report.6a
[
a
]
þ8.9 (c 1.0, CHCl3,
26.0
589
91% ee); dH (CDCl3) 1.45e1.55 (1H, m), 1.63e1.75 (1H, m),
1.91e1.98 (1H, m), 2.04e2.12 (1H, m), 2.23e2.31 (2H, m),
Fig. 7. Optimized structures of TBDPS model of
bTS (C, gray; O, red; N, blue; Li, purple; S, yellow; Si, sky-blue; malonate 2, ball and stick model; imine, tube model). Relative energies
are shown in parentheses (B3LYP/6-311þþG**//B3LYP/6-31G*).

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M. Yoshida et al. / Tetrahedron 69 (2013) 10003e10008
Biomol. Chem. 2012, 10, 8322; (f) Mase, N.; Fukasawa, M.; Kitagawa, N.; Shi-
bagaki, F.; Noshiro, N.; Takabe, K. Synlett 2010, 2340; (g) Fleischer, I.; Pfaltz, A.
Chem.dEur. J. 2010, 16, 95; (h) Procopio, A.; Nino, A. D.; Nardi, M.; Oliverio, M.;
Paonessa, R.; Pasceri, R. Synlett 2010, 1849; (i) Maltsev, O. V.; Kucherenko, A. S.;
Zlotin, S. G. Eur. J. Org. Chem. 2009, 5134; (j) Riguet, E. Tetrahedron Lett. 2009, 50,
4283; (k) Yang, Y.-Q.; Zhao, G. Chem.dEur. J. 2008, 14, 10888; (l) Wascholowski,
V.; Knudsen, K. R.; Mitchell, C. E. T.; Ley, S. V. Chem.dEur. J. 2008, 14, 6155; (m)
Wang, Y.; Li, P.; Liang, X.; Ye, J. Adv. Synth. Catal. 2008, 350, 1383; (n) Ma, A.; Zhu,
S.; Ma, D. Tetrahedron Lett. 2008, 49, 3075.
0.05 mmol, 20 mol %: 36 mg, 0.1 mmol). Reactions were carried
out for 2, 4, 8, 16 or 24 h and stopped to isolate Michael adduct 4.
Acknowledgements
This work was supported by a Grant-in-Aid for Scientific Re-
search on Innovative Areas ‘Advanced Molecular Transformations
by Organocatalysts’ from MEXT, Japan (KAKENHI No. 24105501, No.
23105005) and MEXT-Supported Program for the Strategic Re-
search Foundation at Private Universities.
6. (a) Yoshida, M.; Narita, M.; Hara, S. J. Org. Chem. 2011, 76, 8513; (b) Yoshida, M.;
Kubara, A.; Hara, S. Chem. Lett. 2013, 42, 180.
7. (a) Kokotos, C. G. Org. Lett. 2013, 15, 2406; (b) Yang, H.; Wong, M. W. J. Org.
Chem. 2011, 76, 7399; (c) Armstrong, A.; Bhonoah, Y.; White, A. J. P. J. Org. Chem.
2009, 14, 5041; (d) Zhang, H.; Mitsumori, S.; Utsumi, N.; Imai, M.; Garcia-Del-
gado, N.; Mifsud, M.; Albertshofer, K.; Cheong, P. H.-Y.; Houk, K. N.; Tanaka, F.;
Supplementary data
ꢀ
Barbas, C. F., III. J. Am. Chem. Soc. 2008, 130, 875; (e) Dziedzic, P.; Cordova, A.
Tetrahedron: Asymmetry 2007, 18, 1033; (f) Davies, S. G.; Russell, A. J.; Sheppard,
ꢀ
R. L.; Smith, A. D.; Thomson, J. E. Org. Biomol. Chem. 2007, 5, 3190; (g) Cordova,
Supplementary data associated with this article (molecular ge-
ometries and energies obtained by DFT calculations) can be found.
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2013.09.066.
A.; Zou, W.; Dziedzic, P.; Ibrahem, I.; Reyes, E.; Xu, Y. Chem.dEur. J. 2006, 12,
5383; (h) Limbach, M. Tetrahedron Lett. 2006, 47, 3843; (i) Davies, S. G.; Shep-
perd, R. L.; Smith, A. D.; Thomson, J. E. Chem. Commun. 2005, 3802; (j) Buch-
€
schacher, P.; Cassal, J.-M.; Furst, A.; Meier, W. Helv. Chim. Acta 1977, 60, 2747.
8. (a) Xu, X.-Y.; Tang, Z.; Wang, Y.-Z.; Luo, S.-W.; Cun, L.-F.; Gong, L.-Z. J. Org. Chem.
2007, 72, 9905; (b) Blackmond, D. G. Angew. Chem., Int. Ed. 2005, 44, 4302; (c)
Mathew, S. P.; Iwamura, H.; Blackmond, D. G. Angew. Chem., Int. Ed. 2004, 43,
3317; (d) Schmidt, B.; Seebach, D. Angew. Chem., Int. Ed. Engl. 1991, 30, 1321; (e)
Puchot, C.; Samuel, O.; Dunach, E.; Zhao, S.; Agami, C.; Kagan, H. B. J. Am. Chem.
Soc. 1986, 108, 2353; (f) Duangdee, N.; Harnying, W.; Rulli, G.; Neudorfl, J.-M.;
Groger, H.; Berkessel, A. J. Am. Chem. Soc. 2012, 134, 11196; (g) Klussmann, M.;
Iwamura, H.; Mathew, S. P.; Wells, D. H., Jr.; Pandya, U.; Armstrong, A.; Black-
References and notes
1. Reviews and a book on organocatalysis: (a) MacMillan, D. W. C. Nature 2008,
455, 304; (b) Pellissier, H. Tetrahedron 2007, 63, 9267; (c) Dalko, P. I.; Moisan, L.
Angew. Chem., Int. Ed. 2004, 43, 5138; (d) Houk, K. N.; List, B. Acc. Chem. Res.
€
€
€
2004, 37, 487; (e) Berkessel, A.; Groger, H. Asymmetric Organocatalysis: From
mond, D. G. Nature 2006, 441, 621.
Biomimetic Concepts to Applications in Asymmetric Synthesis; Wiley-VCH:
Weinheim, Germany, 2005.
9. Yoshida, M.; Narita, M.; Hirama, K.; Hara, S. Tetrahedron Lett. 2009, 50, 7297.
10. All DFT calculations were performed with the Gaussian 09 package: Frisch, M.
J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.;
Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; Nakatsuji, H.; Caricato,
M.; Li, X.; Hratchian, H. P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.;
Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima,
T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, J. A., Jr.; Peralta, J. E.;
Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K. N.; Staroverov, V. N.;
Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar,
S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, J. M.; Klene, M.; Knox, J. E.; Cross, J.
B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev,
O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.; Moro-
kuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Dapprich,
2. Selected reviews on organocatalytic asymmetric Michael addition: (a) Dal-
pozzo, R.; Bartoli, G.; Bencivenni, G. Symmetry 2011, 3, 84; (b) Tsogoeva, S. B.
Eur. J. Org. Chem. 2007, 1701; (c) Almas¸ i, D.; Alonso, D. A.; Najera, C. Tetrahedron:
Asymmetry 2007, 18, 299; (d) Berner, O. M.; Tedeschi, L.; Enders, D. Eur. J. Org.
Chem. 2002, 1877.
3. Yamaguchi, M.; Shiraishi, T.; Hirama, M. J. Org. Chem. 1996, 61, 3520 and ref-
erences cited therein.
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4. Kawara, A.; Taguchi, T. Tetrahedron Lett. 1994, 35, 8805.
5. Organocatalytic Michael addition of malonates published recently: (a) Kim, J.-
H.; Park, E.-J.; Lee, H.-J.; Ho, X.-H.; Yoon, H.-S.; Kim, P.; Yun, H.; Jang, H.-Y. Eur. J.
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Org. Chem. 2013, 4337; (b) Swiderek, K.; Pabis, A.; Moliner, V. Org. Biomol. Chem.
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2012, 10, 5598; (c) Dudzinski, K.; Pakulska, A. M.; Kwiatkowski, P. Org. Lett.
€
S.; Daniels, A. D.; Farkas, O.; Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J.
Gaussian 09, Revision B.01; Gaussian: Wallingford, CT, 2009.
2012, 14, 4222; (d) Moritaka, M.; Miyamae, N.; Nakano, K.; Ichikawa, Y.; Kotsuki,
H. Synlett 2012, 2554; (e) Ghosh, S. K.; Dhungana, K.; Headley, A. D.; Ni, B. Org.