Functionalized chiral ionic liquids as highly efficient asymmetric organocatalysts for michael addition to nitroolefins

Article abstract of DOI:10.1002/anie.200600048

(Chemical Equation Presented) Catalytic combination: By combining the advantages of organocatalysts and ionic liquids, a functionalized chiral ionic liquid such as 1 can act as a highly efficient and reusable organocatalyst for the asymmetric Michael addition reaction of ketones and aldehydes with nitroalkenes.

Full text of DOI:10.1002/anie.200600048

Angewandte
Chemie
employed as chiral additives indeed helped to induce
moderate enantioselectivity in some cases, such as in photo-
[
5]
[6]
isomerization, the Baylis–Hillman reaction, and Michael
[
7]
additions, the full potential of CILs in asymmetric synthesis
still remains undisclosed. Compared to the extensive works
[
8]
on the achiral ionic-liquid catalysts, essentially no highly
efficient catalyst of the CIL type has been reported up to now.
Here, we present our recent discovery of a new class of
distinctly functionalized CILs that act as highly efficient
asymmetric organocatalysts.
This work was inspired by the extraordinary success of
chiral pyrrolidines and imidazolines as highly enantioselective
[
9]
Chiral Ionic Liquids
organocatalysts (Scheme 1, left and middle). Since the
DOI: 10.1002/anie.200600048
Functionalized Chiral Ionic Liquids as Highly
Efficient Asymmetric Organocatalysts for
Michael Addition to Nitroolefins**
Scheme 1. Privileged organic catalysts.
Sanzhong Luo,* Xueling Mi, Long Zhang, Song Liu,
Hui Xu, and Jin-Pei Cheng*
[
10]
seminal works of List et al. and MacMillan and co-work-
[
11]
ers, a great number of pyrrolidine- and imidazoline-type
asymmetric organocatalysts have been reported. The cyclic
five-membered secondary amine structure of these com-
pounds is now regarded as one of the “privileged” backbones
for asymmetric catalysis. Thus, our design for functional-
ized CILs (for example, 2a in Scheme 1) comprises such a
“privilieged” chiral pyrrolidine unit covalently tethered to an
IL moiety, so that the former can serve as a catalytic site and
the latter as both the phase tag and a chiral-induction group.
Previous studies have shown that the use of ionic liquids as
reaction media or phase tags for organocatalysts facilitated
catalyst recycling and offered enhanced reactivity and enan-
Ionic liquids, especially functional ionic liquids (FIL; or task-
specific ionic liquids, TSIL), have received growing attention
recently due to their tuneable features for various chemical
tasks and their advantages as reusable homogeneous sup-
ports, reaction media, and reagents with “green” creden-
[
9a]
[
1]
tials. In general, FILs are designed and synthesized by
attachment of functional groups onto the side chains of ionic
liquids. Such chemical functionalization usually enhances the
versatility of ionic liquids, thereby leading to a large number
[
1i,2]
of diverse FILs with improved properties.
progress along this line has been made with the development
Important
[
3]
[12]
of chiral ionic liquids (CILs). Following the initial work of
Seddon and co-workers, a number of CILs were employed
as chiral-resolution reagents, chiral solvents, or chiral addi-
tioselectivity. In this work, we envisaged that ionic-liquid-
[
4]
type organocatalysts such as 2a would still maintain the
unique properties of an ionic liquid and would also serve as an
efficient catalyst for judiciously selected reactions. The role of
imidazolium as a chiral-induction group may be rationalized
by considering that 1) the bulky and planar organic cation
may impart space shielding to the reaction intermediate and
) the proximity of the ionic-liquid unit to the active site may
create a microenvironment that is favorable for the reaction.
In fact, the high polarity and ionic character of the ILs exert
[
3c]
tives. Although it has been shown that chiral ionic liquids
[
*] Dr. S. Luo, H. Xu, Prof. Dr. J.-P. Cheng
Centre for Molecular Science
Institute of Chemistry
2
Chinese Academy of Sciences
Beijing, 100080 (P.R. China)
Fax: (+86)10-6255-4449
E-mail: luosz@iccas.ac.cn
chengjp@mail.most.gov.cn
[
1i,13]
synergistic effects on many organic reactions.
A series of the pyrrolidine-type CILs were synthesized
from the “chiral pool” using l-proline as a starting material
(Scheme 2). The synthetic procedures were quite straightfor-
ward and afforded the product (for example, 2a) in 45% total
yield from l-proline. All the CILs obtained are viscous liquids
at room temperature and are soluble in moderately polar
solvents, such as chloroform, dichloromethane, and methanol,
but insoluble in less polar solvents, such as diethyl ether, ethyl
acetate, and hexane. These properties, together with the
straightforward synthesis, suffice for practical applications in
asymmetric synthesis.
X. Mi, L. Zhang, S. Liu, Prof. Dr. J.-P. Cheng
Department of Chemistry and State-key Laboratory of Elemento-
organic Chemistry
Nankai University
Tianjin, 300071 (P.R. China)
Fax: (+86)10-5888-1878
[
**] This work was supported by the Natural Science Foundation of
China (grant nos.: NSFC 20452001, 20421202, and 20542007), the
Ministry of Science and Technology (MoST), and the Institute of
Chemistry, Chinese Academy of Sciences (ICCAS). We thank Prof. D.
Wang, Prof. Q. H. Fan, and Dr. L. Liu for the HPLC instrument.
We next examined the applications of these CILs in
asymmetric catalysis, where the asymmetric Michael reaction
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
Angew. Chem. Int. Ed. 2006, 45, 3093 –3097
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3093

Communications
Table 1: The effect of chiral ionic-liquid catalysts in asymmetric Michael
[
a]
additions of cyclohexanone and trans-b-nitrostyrene.
[
b]
[c]
[d]
Entry
Catalyst
t [h]
Yield [%]
syn/anti
ee [%]
1
2
1
18
10
20
8
97
99
99
100
97
99
96
86
97
100
40
97:3
99:1
99:1
99:1
97:3
96:4
97:3
98:2
97:3
96:4
96:4
97:3
94:6
91
98
97
99
94
91
93
87
97
94
82
89
70
2a
2a
2b
2b
2b
2b
2c
3a
3b
3c
4a
4b
[
e]
3
4
5
6
7
8
9
0
1
2
3
[
[
[
f]
8
g]
h]
24
48
12
20
16
12
18
18
1
1
1
1
Scheme 2. Synthesis of functionalized chiral ionic liquids. Conditions:
a) LiAlH , THF, 75%; b) 1. Boc O, NaOH; 2. TosCl, pyridine, 90% for
86
25
4
2
2
steps; c) NaH, imidazole, 83%; d) nBuBr, toluene, 708C, 93%;
[
a] TFA=trifluoroacetic acid. [b] Yield of isolated product. [c] Deter-
e) HCl/EtOH; then sat. NaHCO , 90%; f) NaX, acetone/acetonitrile,
3
1
mined by H NMR spectroscopy. [d] Determined by HPLC analysis
chiralcel AD-H column). [e] 10 mol% of catalyst was used. [f]–
h] Second, third, and fourth reuses of the catalyst, respectively.
room temperature. Boc=tert-butoxycarbonyl, THF=tetrahydrofuran,
Tos =toluene-4-sulfonyl.
(
[
was selected as our initial focus. As one of the most important
carbon–carbon bond-forming reactions, Michael addition has
been the subject of considerable research efforts aimed at
developing efficient asymmetric catalysts, especially environ-
[
12d,h]
media.
For example, 40 mol% of l-proline was required
to catalyze cyclohexanone addition to nitrostyrene in ionic
liquids with 75% yield after 60 h (d.r. = 95:5 and 75% ee for
the syn diastereomer).
[
14]
[12h]
mentally friendly, metal-free organocatalysts.
Proline
These observations, together with
[
15]
derivatives such as pyrrolidinyltetrazole, aminomethylpyr-
the comparatively lower efficiencies of non-ionic-liquid
pyrrolidine–imidazole conjugate 1 (Table 1, entry 1), clearly
indicate the critical role of the ionic-liquid moieties for
asymmetric catalysis. Overall, pyrrolidine–imidazolium bro-
mide and tetrafluoroborate, 2a and 2b, respectively, demon-
strate the best performances with nearly quantitative yields
and high diastereoselectivity (syn/anti = 99:1) and enantiose-
lectivity (98% ee).
In general, the reactions were carried out in neat mixtures
with 15 mol% of catalyst and 5 mol% of TFA as the co-
catalyst. (These were observed to be the optimal conditions;
see the Supporting Information.) A reduction in the amount
of catalyst (2a) to 10 mol% resulted in a relatively slow
reaction but still gave quantitative yield and 97% ee within
20 h (Table 1, entry 3). This result is comparable to that of the
experiment by Kotsuki and co-workers with a pyrrolidine–
[
16]
[17]
rolidine, and 2,2’-bipyrrolidine have been shown to serve
as useful asymmetric catalysts for the Michael addition of
ketones or aldehydes. Recently, Kotsuki and co-workers
developed a pyrrolidine–pyridine conjugate base as a highly
[
18]
selective catalyst for Michael reactions of ketones. Wang
[
19]
[20]
et al.
and Hayashi et al.
have independently reported
excellent catalysts for the asymmetric Michael reaction of
aldehydes. Intrigued by the success of chiral pyrrolidines as
asymmetric Michael addition catalysts, we investigated pyr-
rolidine-type CILs in the Michael addition of cyclohexanone
to trans-b-nitrostyrene.
As can be seen from the results summarized in Table 1, all
synthesized CILs catalyzed the asymmetric Michael addition.
The corresponding catalytic and enantioselective activities
varied significantly with different ionic-liquid units. With
regard to the ionic-liquid-cation moiety, CILs with an
imidazolium core (2a–c and 4a) are superior to their 2’-
methyl counterparts (3a–c and 4b) in terms of both activities
and enantioselectivities (Table 1, entries 2–13). Incorporation
of a protic group in the side chain of the cation, as in 4a and
[
18]
pyridine catalyst (24 h, 95%, syn/anti 98:2, 99% ee). In
agreement with previous reports,
catalyst was essential in our catalytic system. In the absence of
co-catalyst, the reaction became very sluggish and only
afforded 33% yield after 40 h.
[
16,17]
the use of an acidic co-
4
b, led to a decrease in both the catalytic activity and
The synthetic functionalized CILs still maintained the
biphasic property of ionic liquids and could be easily recycled
by precipitation with diethyl ether. Recycled CIL 2b was
directly used in the next run and demonstrated identical
activity with slightly decreased selectivities (Table 1, entry 5;
Table 2, entry 1). Loss of activity was observed for the third
and fourth reuse of the CIL, but excellent yields and ee values
could still be achieved (Table 1, entries 6 and 7; Table 2,
entry 1).
selectivity (Table 1, entries 12 and 13). As for the anion, while
the swap of Br to BF4 provided comparable catalysts with
slightly enhanced activities (Table 1, entry 2 versus 4 and
entry 9 versus 10), the exchange of Br for PF6 had a
detrimental effect on both the activities and selectivities
À
À
À
À
(
Table 1, entries 8 and 11). The functionalized CILs tested in
this work performed much better than previously reported
chiral pyrrolidine catalysis in ionic liquids as the reaction
3
094 www.angewandte.org
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2006, 45, 3093 –3097

Angewandte
Chemie
Table 2: CIL-catalyzed asymmetric Michael addition to nitroalkenes.
[
a]
[b]
[c]
[a]
[b]
[c]
Entry
1
Product
CIL
t [h] Yield [%]
syn/anti
ee [%]
Entry Product
7
CIL t [h] Yield [%]
syn/anti
ee [%]
2a
12
10
10
24
92
100
92
98:2
99:1
96:4
97:3
95
99
94
93
2a 42
2b 24
99
99
98:2
99:1
94
97
2
2
2
b
b
b
[
[
d]
e]
93
2
3
4
2a
12
12
99
100
99:1
99:1
96
99
8
9
2a 80
2b 60
61
87
75:25
63:37
83/80
79/82
2
b
2a
15
10
76
94
98:2
98:2
96
96
2a 12
2b 12
77
83
–
–
45
43
2
b
2a
16
12
94
99
99:1
99:1
92
95
10
2a 24
2b 24
57
92
83:17
85:15
79/81
76/80
2
b
5
6
2a
20
12
94
99
99:1
99:1
94
95
11
12
2a 96
2b 96
51
70
–
–
89
86
2
b
2a
12
10
99
99
99:1
99:1
95
97
2a 60
2b 60
73
100
90:10
90:10
77
72
2
b
1
[
[
a] Yield of isolated product. [b] Determined by H NMR spectroscopy. [c] Determined by HPLC analysis (chiralpak AD-H or AS-H columns). [d] and
e] Second and third reuses of the catalyst, respectively.
We next probed the scope of the reaction for a variety of
In the presence of 2a, the reaction of acetone with cyclic
nitroolefin afforded the desired Michael adducts with high
yields and good enantioselectivities (Table 2, entry 9, syn:
76% ee, anti: 80% ee).
Michael donors and nitroalkenes with the identified optimal
catalysts 2a and 2b (Table 2). The reactions worked
extremely well with cyclohexanone to generate Michael
adducts in nearly quantitative yields, high diastereoselectiv-
ities (d.r. ꢀ 97:3), and excellent enantioselectivities (92–99%
ee). Both electron-rich and electron-deficient nitrostyrenes
were excellent Michael acceptors for cyclohexanone (Table 2,
entries 1–7). With regard to the Michael donors, the reaction
with cyclopentanone occurred smoothly and showed moder-
ate diastereoselectivity and enantioselectivity for both dia-
stereomers (Table 2, entry 8). Acetone also served as an
efficient Michael donor to produce the desired adduct with
good yield and moderate enantioselectivity (Table 2, entry 9).
Our preliminary studies demonstrated that CILs 2a and
2b could also catalyze the Michael addition of aldehydes
(Table 2, entries 11 and 12). Under the optimized conditions,
the addition of isobutyraldehyde to trans-b-nitrostyrene gave
the desired adduct in good yields and up to 89% ee (Table 2,
entry 11). Valeraldehyde also worked well to afford the
desired product with quantitative yield and moderate selec-
tivity (Table 2, entry 12, syn/anti = 90:10, 72% ee). In most of
the cases examined, CIL tetrafluoroborate 2b performed
slightly better than CIL bromide 2a.
Angew. Chem. Int. Ed. 2006, 45, 3093 –3097
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
3095

Communications
The relative and absolute configurations of the Michael
adducts were determined by H NMR spectroscopic analysis
Keywords: asymmetric catalysis · ionic liquids ·
Michael addition · nitroalkenes · organocatalysis
.
1
and comparison of the optical rotations with those of known
compounds. The high diastereoselectivities and excellent
enantioselecitivities of CIL catalysis in the Michael additions
reported here may be explained by the concept of an acyclic
synclinal transition state, as proposed by Seebach and
[1] For reviews, see: a) J. H. Davis, Chem. Lett. 2004, 33, 1072 – 1077;
b) P. Wasserscheid, W. Keim, Angew. Chem. 2000, 112, 3926 –
3946; Angew. Chem. Int. Ed. 2000, 39, 3772 – 3789; c) T. Welton,
[
21]
[15–20]
Chem. Rev. 1999, 99, 2071 – 2083; d) R. Sheldon, Chem.
Commun. 2001, 2399 – 2407; e) J. Dupont, R. F. de Souza,
P. A. Z. Suarez, Chem. Rev. 2002, 102, 3667 – 3692; f) J. S.
Wikes, J. Mol. Catal. A 2004, 214, 11 – 17; g) T. Welton, Coord.
Chem. Rev. 2004, 248, 2459 – 2477; h) C. E. Song, Chem.
Commun. 2004, 1033 – 1043; i) N. Jain, A. Kumar, S. Chauhan,
S. M. S. Chauhan, Tetrahedron 2005, 61, 1015 – 1060.
Golinski and in other previous studies.
In this model,
the ionic-liquid moiety would effectively shield the Si face of
the enamine double bond in the ketone donor and the
reaction would occur through
a
Re–Re approach
[
22]
(
Scheme 3).
The ionic and highly polar nature of the
imidazolium group may also contribute in the transition state
and this feature is currently under investigation.
[
2] Z. Fei, T. J. Geldbach, D. Zhao, P. J. Dyson, Chem. Eur. J. 2006,
12, 2122 – 2130.
[
3] For reviews, see: a) C. Baudequin, J. Baudoux, J. Levillain, D.
Cahard, A.-C. Gaumont, J.-C. Plaquevent, Tetrahedron: Asym-
metry 2003, 14, 3081 – 3093; b) J. Ding, D. W. Armstrong,
Chirality 2005, 17, 281 – 292; c) C. Baudequin, D. BrØgeon, J.
Levillain, F. Guillen, J.-C. Plaquevent, A.-C. Gaumont, Tetrahe-
dron: Asymmetry 2005, 16, 3921 – 3945.
[
[
[
4] M. J. Earle, P. B. McCormac, K. R. Seddon, Green Chem. 1999,
1, 23 – 25.
Scheme 3. Transition-state model for ketone donors.
5] J. Ding, V. Desikan, X. Han, T. L. Xiao, R. Ding, W. S. Jenks,
D. W. Armstrong, Org. Lett. 2005, 7, 335 – 337.
6] B. PØgot, G. Vo-Thanh, A. Loupy, Tetrahedron Lett. 2004, 45,
6425 – 6428.
In summary, we have developed a novel asymmetric
catalytic system with functionalized CILs and demonstrated
their potential as highly efficient asymmetric organocatalysts
for Michael reactions. The pyrrolidine–ionic-liquid conju-
gates have several noteworthy features: 1) they can very
efficiently catalyze the Michael additions for a broad range of
Michael donors (both ketones and aldehydes) and Michael
acceptors (nitroolefins) with high yields (up to 100%),
excellent enantioselectivity (up to 99% ee), and very good
diastereoselectivity (syn/anti up to 99:1); 2) the ionic-liquid
moiety can not only act as a phase tag to facilitate recycling
and reuse of the catalyst but can also function as an efficient
chiral-induction group to ensure high selectivity; and 3) the
modular and tuneable features of ionic liquids promise
further developments. Further improvements of the present
catalysts (reusability) and the application of the CILs to other
types of reactions are currently underway in our laboratory.
[7] Z. Wang, Q. Wang, Y. Zhang, W. Bao, Tetrahedron Lett. 2005, 46,
657 – 4660.
[
4
8] For achiral ionic-liquid catalysts, see: acidic catalysts: a) A. Cole,
J. Jensen, I. Ntai, K. Loan, T. Tran, K. Weaver, D. Forbes, J.
Davis, J. Am. Chem. Soc. 2002, 124, 5962 – 5963; b) Y. Gu, F. Shi,
Y. Deng, Catal. Commun. 2003, 4, 597 – 601; c) D. C. Forbes, K. J.
Weaver, J. Mol. Catal. A 2004, 214, 129 – 132; d) Y. Gu, F. Shi, Y.
Deng, J. Mol. Catal. A 2004, 212, 71 – 75; e) J. Gui, H. Ban, X.
Cong, X. Zhang, Z. Hu, Z, Sun, J. Mol. Catal. A 2005, 225, 27 –
3
2
1; f) J. Gui, Y. Deng, Z. Hu, Z. Sun, Tetrahedron Lett. 2004, 45,
681 – 2683; g) D. Li, F. Shi, J. Peng, S. Guo, Y. Deng, J. Org.
Chem. 2004, 69, 3582 – 3585; h) S. Kitaoka, K. Nobuoka, Y.
Ishikawa, Chem. Commun. 2004, 1902 – 1903; i) Z. Fei, D. Zhao,
T. J. Geldbach, R. Scopelliti, P. J. Dyson, Chem. Eur. J. 2004, 10,
4886 – 4893; basic catalysts: j) B. C. Ranu, S. Banerjee, Org. Lett.
2005, 7, 3049 – 3052; k) S. Abelló, F. Medina, X. Rodríguez, Y.
Cesteros, P. Salagre, J. E. Sueiras, D. Tichit, B. Coq, Chem.
Commun. 2004, 1906 – 1907; l) A. Zhu, T. Jiang, D. Wang, B.
Han, L. Liu, J. Huang, J. Zhang, D. Sun, Green Chem. 2005, 7,
514 – 517; nucleophilic catalysts: m) D. W. Kim, C. E. Song, D. Y.
Chi, J. Am. Chem. Soc. 2002, 124, 10278 – 10279; n) D. W. Kim,
C. E. Song, D. Y. Chi, J. Org. Chem. 2003, 68, 4281 – 4285;
o) D. W. Kim, Y. S. Choe, D. Y. Chi, Nucl. Med. Biol. 2003, 30,
3
4
45 – 350; p) D. W. Kim, D. Y. Chi, Angew. Chem. 2004, 116,
89 – 491; Angew. Chem. Int. Ed. 2004, 43, 483 – 485; q) L.-W.
Experimental Section
Typical experimental procedure: Nitrostyrene (37 mg, 0.25 mmol)
and 2b (12 mg, 15 mol%) were mixed with cyclohexanone (0.5 mL,
Xu, Y. Gao, J.-J. Yin, L. Li, C.-G. Xia, Tetrahedron Lett. 2005, 46,
5317 – 5320; r) B. C. Ranu, S. S. Dey, Tetrahedron 2004, 60, 4183 –
4
5
8
mmol) at room temperature. After stirring at room temperature for
h, the homogeneous reaction mixture was diluted with ethyl ether to
188; s) L.-W. Xu, J.-W. Li, S.-L. Zhou, C.-G. Xia, New J. Chem.
2004, 28, 183 – 184.
precipitate the catalyst. The organic layer was separated and loaded
onto a silica gel column for purification, to afford the Michael adduct
[9] For selected reviews of organocatalysis, see: a) P. I. Dalko, L.
Moisan, Angew. Chem. 2004, 116, 5248 – 5286; Angew. Chem.
Int. Ed. 2004, 43, 5138 – 5175; b) A. Berkessel, H. Groger,
Asymmetric Organocatalysis, Wiley-VCH, Weinheim, 2005; c) J.
Seayad, B. List, Org. Biomol. Chem. 2005, 3, 719 – 724; d) S. T.
Handy, Chem. Eur. J. 2003, 9, 2938.
(61 mg, 99%) as a white solid: syn/anti 99:1, 99% ee (by HPLC on a
chiralpak AD-H column, l = 254 nm, eluent iPrOH/hexane (10:90),
À1
flow rate = 0.5 mLmin ; t = 21.4 (minor), 27.2 min (major)). The
R
catalyst was used directly for the next run after removing the residual
solvent.
[
10] B. List, R. A. Lerner, C. F. Barbas III, J. Am. Chem. Soc. 2000,
122, 2395.
Received: January 5, 2006
Published online: April 4, 2006
[11] K. A. Ahrendt, C. J. Borths, D. W. C. MacMillan, J. Am. Chem.
Soc. 2000, 122, 4243 – 4244.
3
096 www.angewandte.org
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2006, 45, 3093 –3097

Angewandte
Chemie
ˇ
[
12] a) P. Kotrusz, I. Kmentova, B. Gotov, S. Toma, E. Sol cˇ µniovµ,
Chem. Commun. 2002, 2510 – 2511; b) T.-P. Loh, L.-C. Feng, H.-
Y. Yang, J.-Y. Yang, Tetrahedron Lett. 2002, 43, 8741 – 8743;
c) N. S. Chowdari, D. B. Ramachary, C. F. Barbas III, Synlett
2003, 1906 – 1909; d) P. Kotrusz, S. Toma, H.-G. Schmalz, A.
Adler, Eur. J. Org. Chem. 2004, 1577 – 1583; e) H. M. Guo, L. F.
Cun, L. Z. Gong, A. Q. Mi, Y. Z. Jiang, Chem. Commun. 2005,
1450 – 1452; f) P. Kotrusz, S. Alemayehu, T. Toma, H. G.
Schmalz, A. Adler, Eur. J. Org. Chem. 2005, 4904 – 4911; g) A.
Córdova, Tetrahedron Lett. 2004, 45, 3949 – 3952; h) M. S.
Rasalkar, M. K. Potdar, S. S. Mohile, M. M. Salunkhe, J. Mol.
Catal. A 2005, 235, 267 – 270; i) X. L. Mi, S. Z. Luo, J.-P. Cheng, J.
Org. Chem. 2005, 70, 2338 – 2341; j) R. T. Dere, R. R. Pal, P. S.
Patil, M. M. Salunkhe, Tetrahedron Lett. 2003, 44, 5351 – 5353.
13] a) S. T. Handy, Curr. Org. Chem. 2005, 9, 959 – 988; b) J.
Habermann, S. Ponzi, S. V. Ley, Mini-Rev. Org. Chem. 2005, 2,
[
[
1
25 – 137.
14] For a review, see: a) J. Christoffers, A. Baro, Angew. Chem. 2003,
15, 1726 – 1728; Angew. Chem. Int. Ed. 2003, 42, 1688 – 1690.
1
For imidazoline-type organocatalysts for Michael additions, see:
b) N. Halland, P. S. Aburel, K. A. Jørgensen, Angew. Chem.
2004, 116, 1292 – 1297; Angew. Chem. Int. Ed. 2004, 43, 1272 –
1277, and references therein; c) M. T. H. Fonseca, B. List,
Angew. Chem. 2004, 116, 4048 – 4050; Angew. Chem. Int. Ed.
004, 43, 3958 – 3960; d) Y. Hayashi, H. Gotoh, T. Tamura, H.
Yamaguchi, R. Masui, M. Shoji, J. Am. Chem. Soc. 2005, 127,
6028 – 16029.
2
1
[
15] a) A. J. A. Cobb, D. A. Longbottom, D. M. Shaw, S. V. Ley,
Chem. Commun. 2004, 1808 – 1809; b) A. J. A. Cobb, D. M.
Shaw, D. A. Longbottom, J. B. Gold, S. V. Ley, Org. Biomol.
Chem. 2005, 3, 84 – 96; c) C. E. T. Mitchell, A. J. A. Cobb, S. V.
Ley, Synlett 2005, 611 – 614.
[
16] a) B. List, P. Pojarliev, H. J. Martin, Org. Lett. 2001, 3, 2423 –
2425; b) J. M. Betancort, C. F. Barbas III, Org. Lett. 2001, 3,
3737 – 3740; c) N. Mase, R. Thayumanavan, F. Tanaka, C. F.
Barbas III, Org. Lett. 2004, 6, 2527; d) J. M. Betancort, K.
Sakthivel, R. Thayumanavan, F. Tanaka, C. F. Barbas III, Syn-
thesis 2004, 1509 – 1521.
[
17] a) A. Alexakis, O. Andrey, Org. Lett. 2002, 4, 3611 – 3614; b) O.
Andrey, A. Alexakis, G. Bernardinelli, Org. Lett. 2003, 5, 2559 –
2561; c) O. Andrey, A. Alexakis, A. Tomassini, G. Bernardinelli,
Adv. Synth. Catal. 2004, 346, 1147 – 1168.
[
[
[
18] T. Ishii, S. Fujioka, Y. Sekiguchi, H. Kotsuki, J. Am. Chem. Soc.
2004, 126, 9558 – 9559.
19] W. Wang, J. Wang, H. Li, Angew. Chem. 2005, 117, 1393 – 1395;
Angew. Chem. Int. Ed. 2005, 44, 1369 – 1371.
20] Y. Hayashi, H. Gotoh, T. Hayashi, M. Shoji, Angew. Chem. 2005,
117, 4284 – 4287; Angew. Chem. Int. Ed. 2005, 44, 4212 – 4215.
[
[
21] D. Seebach, J. Golinski, Helv. Chim. Acta 1981, 64, 1413 – 1423.
22] For aldehyde donors, anti-enamine intermediates would be
formed and the reactions would occur through
approach.
a Si–Si
[
15–17]
Angew. Chem. Int. Ed. 2006, 45, 3093 –3097
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org 3097