Chiral Co(II) complex catalyzed asymmetric Michael reactions of β-ketoamides to nitroolefins and alkynones

Article abstract of DOI:10.1016/j.tetlet.2014.05.067

The catalytic enantioselective Michael additions of cyclic β-ketoamides to nitroolefins and alkynones were accomplished in the presence of chiral N,N′-dioxide-Co(II) complexes. The desired adducts were obtained in high yields (up to 98%) with excellent en

Full text of DOI:10.1016/j.tetlet.2014.05.067

Tetrahedron Letters 55 (2014) 3797–3801
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Tetrahedron Letters
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Chiral Co(II) complex catalyzed asymmetric Michael reactions
of b-ketoamides to nitroolefins and alkynones
⇑
⇑
Zuliang Zhang, Xiaohua Liu , Zhen Wang, Xiaohu Zhao, Lili Lin, Xiaoming Feng
Key Laboratory of Green Chemistry & Technology Ministry of Education, College of Chemistry, Sichuan University, Chengdu 610064, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 26 March 2014
Revised 4 May 2014
Accepted 15 May 2014
Available online 21 May 2014
The catalytic enantioselective Michael additions of cyclic b-ketoamides to nitroolefins and alkynones
were accomplished in the presence of chiral N,N0-dioxide–Co(II) complexes. The desired adducts were
obtained in high yields (up to 98%) with excellent enantioselectivities (up to 97% ee).
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
Asymmetric catalysis
Michael reaction
b-Ketoamides
Nitroolefins
Alkynones
Introduction
quaternary stereocenters. Chiral organocatalysts are generally
utilized to promote these enantioselective processes. For instance,
In the past decade, the Michael reaction of carbon nucleophiles
,b-unsaturated compounds has been found to be attractive for
the construction of new carbonAcarbon bonds.1,2 A wide variety of
chiral proline derivatives were used for the b-ketoamide addition
to
,b-unsaturated aldehydes,4d,e and chiral multifunctional
thiourea catalysts were efficient for the cascade reaction between
b-ketoamide and
,b-unsaturated ketones4f,g,l, or formal [3+3]
cyclization between amide and
,b-unsaturated acyl cyanides.4m
Chiral squaramide bearing cinchonine unit promoted the addition
between cyclobutanone derivatives with an amide moiety and
nitroalkenes in high diastereo- and enantioselectivities.4i However,
extending the Michael donors and developing the efficient
catalyst system for the Michael reactions of b-ketoamides are still
desirable.
In recent years, the application of the less expensive and more
abundant early transition metals gains momentum for the intro-
duction of asymmetric centers in molecules. Nevertheless, the total
number of chiral cobalt complex mediated asymmetric processes
still remains small compared to other metals.5,6j As excellent chiral
ligands, N,N0-dioxide-metal complexes have shown powerful cata-
lytic capability in many different types of reactions owing to their
easily tunable electronic and steric chiral scaffolds.6 On our going
work, we develop chiral N,N0-dioxide–Co(II) complex catalysts for
to
a
a
b-diketones, b-ketoesters, as well as
a
-substituted-1,3-dicarbon-
a
yls3 have been extensively and successfully used as the nucleo-
philes in such reactions. In contrast to the Michael reaction of
b-diketones and b-ketoesters, the conjugate addition using b-keto-
a
amides as the nucleophile is interesting.4 Using
a,b-unsaturated
aldehydes or ketones as the electrophiles, a Michael-initiated cycli-
zation can occur. For example, Rodriguez and co-workers utilized
the electrophilic and nucleophilic property of simple b-ketoamides
to realize a multicomponent domino reaction, furnishing highly
functionalized 2,6-diazabicylco[2,2,2]octane skeleton.4a,l Coopera-
tive participation of the amido group of b-ketoamides can be
employed to construct azaspirocyclic derivatives,4c,m and spiroa-
minals.4g The modified b-ketoamides containing an acidic methane
group and pendant nucleophilic substituent with a,b-unsaturated
carbonyl compounds can perform diverse stereodivergent catalytic
one-pot addition/cyclization/annulation sequence to synthesize
quinolizidine derivatives,4d,e oxzaine and oxazolidine derivatives,4f
as well as other tetracyclic alkaloid derivatives.4b In addition, the
the asymmetric Michael additions of
a-substituted b-ketoamides.
direct asymmetric addition of
a-substituted b-ketoamides with
Both nitroolefins and alkynones are tolerable in the process, fur-
other Michael acceptors provides an easy synthetic route to
nishing the desired nitro-derivatives with vicinal quartery–tertiary
carbon centers and
a,b-unsaturated enone derivatives, respec-
tively. High enantioselectivities are obtained for the two kinds
of Michael donors, although the diastereoselectivities or Z/E selec-
tivities are moderate. The Z/E adducts of alkynones underwent
⇑
Corresponding authors. Tel./fax: +86 28 8541 8249.
E-mail addresses: liuxh@scu.edu.cn (X. Liu), xmfeng@scu.edu.cn (X. Feng).
http://dx.doi.org/10.1016/j.tetlet.2014.05.067
0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.

3798
Z. Zhang et al. / Tetrahedron Letters 55 (2014) 3797–3801
isomerization to afford the E-isomers and chloride derivatives by
the treatment with HCl. Thermodynamically stable E-adduct could
be obtained in high enantioselectivity after isomerization with
TsOH.
(Table 1, entries 8–15). The screening of chiral amino acids back-
bone of ligands indicated that L1 (derived from -pipecolic acid)
gave higher enantioselectivities than the ligand L2 (derived from
-proline) and the ligand L6 (derived from -ramipril) (Table 1,
L
L
L
entry 8 vs entry 9, 10). The amide subunits of the ligands also play
a crucial role in the enantiocontrol. Comparing to the aryl substi-
tuted amide moieties, the introduction of diphenylmethyl group
obviously increased the ee value to 97% and 84% ees for the two
diastereomeric products (Table 1, entry 11 vs entry 8). Meanwhile,
the diastereoselection of the reaction reversed although the dr
value was not satisfied in the presence of chiral L3–Co(BF4)2ꢀ6H2O
complex. However, both the yield and the enantioselectivity of the
reaction significantly decreased when N,N0-dioxides L4 and L5
bearing other sterically hindered alkyl amide moieties were used
as the ligands (Table 1, entries 12, 13). Ligand L7 derived from
2,6-diisopropylaniline accelerated the reaction with satisfied
enantioselectivity inferior to that of the ligand L3 (Table 1, entry
14). Further optimization of the reaction conditions is in vain for
the improvement of the diastereoselectivity of the reaction. Other
ordinary solvents gave both low yield and enantioselectivity, and
CH2Cl2 was the most suitable (Table 1, entries 15–19). Thus, the
optimized experimental conditions are as follows: 10 mol % of
L3–Co(BF4)2ꢀ6H2O (1.2:1) as the catalyst and CH2Cl2 as the solvent.
Under the optimized reaction conditions (Table 1, entry 7), the
scope of nitroolefins and b-ketoamides was examined and the
Results and discussion
Initially, we examined various metal salts coordinated with chi-
ral N,N0-dioxide L1 in situ to catalyze the Michael reaction of N-
tert-butyl-1-oxo-2,3-dihydro-1H-indene-2-carboxamide (1a) to
nitroolefin (2a) in CH2Cl2 at 0 °C. As shown in Table 1, Sc(OTf)3
did not promote the reaction at all (Table 1, entry 1). Other lantha-
nides such as Y(OTf)3, Gd(OTf)3, and Lu(OTf)3 could mediate the
reaction but in low reactivities and inefficient selectivities (Table 1,
entries 2–4). When using Hf(OTf)4 as the metal precursor, the reac-
tion could get 2.0/1 diastereoselectivity, 50%/19% ees, but the yield
was very low (Table 1, entry 5). The combination of nickel salts
with L1 could afford the Michael adduct 3a with delightful yield
and enantioselectivity but with poor diastereoselectivity (Table 1,
entries 6, 7). And Ni(BF4)2ꢀ6H2O was superior to Ni(OTf)2 in terms
of stereoselectivity. To our delight, the enantioselectivity could be
further improved when Co(BF4)2ꢀ6H2O was used as the center
metal, and 89% and 66% ees were obtained for the major and minor
diastereomers, respectively (Table 1, entry 8). Encouraged by the
initial results, various N,N0-dioxide ligands were then tested
Table 1
a
Optimization of the Michael addition of b-ketoamide (1a) to nitroolefin (2a)
Ph
O
*
L-metal
O
O
NO2
*
(1.2: 1, 10 mol%)
NO2
NHtBu
Ph
O
CH2Cl2, 0-30oC
NH Bu
t
3a
1a
2a
n
n
L1 R = 2,6-diethylphenyl,n = 2
L2 R = 2,6-diethylphenyl,n = 1
L3 R = diphenylmethyl,n = 2
L4 R = tBu, n = 2
N
N
O
N
N
O
O
O
O
O
O
N
H
O
N
L5 R = 1-adamantly, n = 2
L7 R = 2,6-diisopropylphenyl,n = 2
N
N
H
R
H
R
H
R
R
R =2,6-diethylphenyl
L6
Entry
Ligand
Metal
Solvent
Yieldb (%)
D.r.c
eed (%)
1
L1
L1
L1
L1
L1
L1
L1
L1
L2
L6
L3
L4
L5
L7
L3
L3
L3
L3
L3
Sc(OTf)3
Y(OTf)3
Gd(OTf)3
Lu(OTf)3
Hf(OTf)4
Ni(OTf)2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CHCl3
n.r.
50
51
19
8
n.d.
1/1
n.d.
27/7
0/0
2e
3e
4e
5e
6
1/1.4
1.6/1
2.0/1
1/1
1/1.7
1/1.6
1/2
1/1.9
1.7/1
4/1
44/22
50/19
60/77
64/85
66/89
37/75
36/64
97/84
40/50
6/60
94/58
78/51
68/38
18/<5
58/69
88/52
84
87
88
84
57
84
87
75
80
46
81
33
64
25
7
8
9
Ni(BF4)2ꢀ6H2O
Co(BF4)2ꢀ6H2O
Co(BF4)2ꢀ6H2O
Co(BF4)2ꢀ6H2O
Co(BF4)2ꢀ6H2O
Co(BF4)2ꢀ6H2O
Co(BF4)2ꢀ6H2O
Co(BF4)2ꢀ6H2O
Co(BF4)2ꢀ6H2O
Co(BF4)2ꢀ6H2O
Co(BF4)2ꢀ6H2O
Co(BF4)2ꢀ6H2O
Co(BF4)2ꢀ6H2O
10
11
12
13
14
15
16
17
18
19
1/1
1/1.3
2.1/1
1/1.2
1/1.2
1/1
THF
Toluene
CH3OH
Et2O
1.8/1
a
Unless otherwise noted, the reactions were carried out with the ligand L (12 mol %), metal (10 mol %), 1a (0.1 mmol), and 2a (0.12 mmol) in solvent (0.6 mL) at 0 °C for
2 days and then at 30 °C for 1 day.
b
Isolated yield; n.r. = no reaction.
c
Determined by 1H NMR analysis, n.d. = not determined.
d
Determined by chiral HPLC analysis.
e
The reaction was carried out at 0 °C for 2 days, and the yield was determined by 1H NMR analysis (using CH2Br2 as internal standard).

Z. Zhang et al. / Tetrahedron Letters 55 (2014) 3797–3801
3799
Table 2
Asymmetric Michael additions of b-ketoamides 1 with nitroolefins 2a
O
R2
L3
-Co(BF4)2· 6H2O
NO2
NO2
O
NHtBu
R2
(1.2: 1, 10 mol%)
o
O
+
R1
O
,
CH2Cl2 0-30
C
R1
1
NHtBu
2
3
Entry
R1
R2
Yieldb (%)
D.r.c
eed (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
H
H
H
H
H
H
H
H
5-Cl
5-Cl
5-F
5-Cl
5-Br
5,6-(OMe)2
6-F
6-Cl
6-Me
Ph
4-FC6H4
84(3a)
94(3b)
91(3c)
82(3d)
96(3e)
98(3f)
96(3g)
98(3h)
51(3i)
84(3j)
97(3k)
98(3l)
94(3m)
92(3n)
95(3o)
98(3p)
92(3q)
63/37
62/38
66/34
66/34
65/35
62/38
66/34
66/34
54/46
72/28
67/33
65/35
63/37
69/31
67/33
61/39
57/43
97/84
96/77
96/73
97/74
96/77
94/85
96/90
97/82
93/72
86/55
96/62
96/69
96/66
97/70
96/71
93/55
94/82
4-ClC6H4
4-BrC6H4
4-PhC6H4
3-BrC6H4
3-ClC6H4
3,4-Cl2C6H3
2-BrC6H4
2-Furanyl
4-BrC6H4
4-BrC6H4
4-BrC6H4
4-BrC6H4
4-BrC6H4
4-BrC6H4
Ph
a
Unless otherwise noted, reactions were carried out with L3 (12 mol %), Co(BF4)2ꢀ6H2O (10 mol %), 1 (0.1 mmol), 2 (0.12 mmol) in CH2Cl2 (0.6 mL) at 0 °C for 2 days and
then at 30 °C for 1 day.
b
Isolated yield.
c
Determined by 1H NMR analysis.
d
Determined by chiral HPLC analysis.
results are summarized in Table 2. The electron-withdrawing sub-
stituents on the b-aryl group of nitroolefins had no obvious
effects on the enantioselectivity and reactivity of the reaction
(Table 2, entries 2–8). However, 2-bromophenyl substituted nitro-
alkene suffered moderate reactivity albeit the enantioselectivity
was satisfied (93% and 72% ee for the two diastereomers; Table 2,
entries 9), probably due to the hindrance of the substituent.
2-(2-Nitrovinyl)furan reacted with 5-chloro-substiuted b-ketoamide
smoothly, generating the corresponding product 3j with
improved dr value and slightly decreased enantioselectivity
(72:28 dr, 86% and 55% ee; Table 2, entry 10). Next, a variety of
dihydro-inden-1-one based b-ketoamides was examined in the
reaction. Both electron-withdrawing and electron-donating
substituents on the aromatic ring of the indenone scaffold were
tolerated with high yields and good enantioselectivities (93–97%
ees for the major diastereomer; entries 11–17). The outcome
Table 3
Asymmetric Michael additions of b-ketoamides 1 with alkynones 4a
O
L1 or L7-Co(BF ) 6H O
·
O
4
2
2
O
O
R2
(1.2: 1, 10 mol%)
O
+
R1
O
CH2Cl2
R2
N
H
4 Å MS, 0 o
C
R1
NHtBu
5
4
1
Entry
R1
R2
Yieldb (%)
Z/Ec
ee of Z/E isomersd (%)
1
2
3
4
5
6
7
8
9
H
H
H
H
H
H
H
4-Me
3-CF3
4-CF3
4-OMe
99(98)(5a)
94(94)(5b)
98(97)(5c)
99(96)(5d)
97(92)(5e)
95(80)(5f)
94(89)(5g)
92(98)(5h)
94(97)(5i)
93(82)(5j)
74/26(55/45)
71/29(60/40)
69/31(58/42)
75/25(64/36)
75/25(68/32)
78/22(62/38)
72/28(47/53)
65/35(63/37)
79/21(62/38)
69/31(52/48)
90/79(94/96)
91/80(97/95)
90/77(97/94)
84/69(97/97)
86/72(96/93)
89/75(96/95)
90/84(97/97)
84/75(95/92)
93/80(95/94)
92/85(93/94)
5-F
5-Br
6-Me
6-Cl
6-F
H
H
H
H
10
a
Unless otherwise noted, reactions were carried out with ligand L1 or L7 (12 mol %), Co(BF4)2ꢀ6H2O (10 mol %), 1 (0.1 mmol), 4 (0.12 mmol) and MS (4 Å, 30 mg) in CH2Cl2
(1.0 mL) at 0 °C for 24 h. The data in parentheses were the results using the ligand L7 instead.
b
Isolated yield.
c
Determined by 1H NMR analysis.
d
Determined by chiral HPLC analysis.

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Z. Zhang et al. / Tetrahedron Letters 55 (2014) 3797–3801
Table 4
Z/E adduct in the presence of HCla
tBu
NH
Cl
O
O
O
O
O
O
tBu
tBu
N
H
N
H
R1
R1
R1
conc. HCl
O
O
CH2Cl2,10 o
C
O
Ar
dr
Ar
Ar
8
5
>95:5
E-5
Entry
Z/E-5 (ee %)
R1
Ar
Ph
8 Yieldb % (ee %)c
E-5 Yieldb % (ee %)c
1
2
3
55/45(94/96)
52/48(93/94)
64/36(97/97)
H
H
6-Me
53(97)(8a)
38(96)(8b)d
60(95)(8c)
32(94)(E-5a)
43(94)(E-5j)
26(92)(E-5d)
4-OMeC6H4
Ph
a
b
c
Reaction conditions: HCl (37.5% w/w) (0.2 mL), CH2Cl2 (1.0 mL), 10 °C, 24 h.
Isolated yield.
Determined by chiral HPLC analysis.
d
The absolute configuration was determined by X-ray analysis.
tested other chiral N,N0-dioxide–Co(BF4)2ꢀ6H2O complexes, in an
attempt to improve the enantioselectivity further. Chiral N,N0-diox-
Table 5
Z/E adduct in the presence of TsOHa
ide L7, prepared from L-pipecolic acid and 2,6-diisopropylaniline
O
O
was subjected to the reaction, exhibiting even higher enantioselec-
tivities compared with the ligand L3. Although the Z/E-selectivity
dropped a little, excellent enantioseletivities (92–97% ees) were
achieved for each diastereomer (Table 3, data in the parentheses).
The acid mediated isomerization of (Z)-enones enables the for-
mation of thermodynamically stable E-adduct.6i,9b We found that
the treatment of the mixture of Michael adducts Z/E-5 with con-
centrated HCl gave another mixture of the chloro addition products
8 and E-5 isomers (Table 4). Considering the isolated yield of the
two products, we think that Z-isomer preferred to undergo the
addition of HCl. Nevertheless, the organic acid such as p-toluene-
sulfonic acid (TsOH) mainly promoted the isomerization process
to form the E-5 isomer (Table 5). The optical purity of the resulted
E-5 isomer was maintained, indicating that the Z/E-5 had a same
stereo-arrangement at the quaternary center. Finally, the absolute
configuration of the chloro addition products 8b was unambigu-
ously determined to be (R,R) by single-crystal X-ray diffraction
(Fig. 1) 10. Therefore, the chiral carbon of the corresponding Z/E-
enone 5 was characterized as (R)-configuration.
O
O
N
H
R1
R1
TsOH
HN
O
O
Ar
Ar
Z/E-5
E-5
Entry
Z/E-5 (ee %)
R1
Ar
Ph
Yieldb (%)
eec (%)
1
2
3
55/45(94/96)
52/48(93/94)
64/36(97/97)
H
H
6-Me
91(E-5a)
94(E-5j)
87(E-5d)
96
94
94
4-OMeC6H4
Ph
a
b
c
Reaction conditions: TsOH (0.01 mmol), CH2Cl2 (1.0 mL), 10 °C, 24 h.
Isolated yield.
Determined by chiral HPLC analysis.
related to the diastereoselectivity is not satisfied in most of the
investigated cases.
Compared with nitroolefins, the asymmetric conjugate addition
of alkynones is relatively rare.7–9 Next, we attached the b-ketoa-
mide templates to alkynones in the identified N,N0-dioxide–
Co(BF4)2ꢀ6H2O complex catalysts. Chiral ligand L3 bearing alkyl
substituted amide subunits were inferior to the aryl substituted
partner L1 related to the enantioselectivity and Z/E-selectivity. It
was found that high yields, moderate Z/E-selectivity, and high
enantioselectivity of Z-isomers could be obtained for different
alkynones in the presence of N,N0-dioxide L1–Co(BF4)2ꢀ6H2O cata-
lyst, indicating that electronic effect has no major role in control-
ling Z/E and enantioselectivity of the reaction (65:35–79:21 Z/E
ratio, 84–93% ees; Table 3). The thermodynamically unstable
Z-isomers were produced as the major products. We have also
Conclusions
In summary, we have developed chiral cobalt(II) complexes of
N,N0-dioxides for the enantioselective Michael reaction of cyclic
b-ketoamides. The addition of a variety of useful active nitroalkane
derivatives underwent the reaction to give nitro-derivatives with
vicinal quaternary–tertiary chiral centers in high enantioselectivi-
ties. Alkynones also performed the reaction well, affording the
enone derivatives donating quaternary carbon centers in high
enantioselections for both Z- and E-isomers. Further application
of this catalyst system to other reactions is in progress.
O
Cl
O
O
O
NH
(R,R)
Figure 1. X-ray crystallographic structure of 8b.

Z. Zhang et al. / Tetrahedron Letters 55 (2014) 3797–3801
3801
Rodriguez, J. Org. Lett. 2012, 14, 4686; (i) Mailhol, D.; Sanchez Duque, M. M.;
Raimondi, W.; Bonne, D.; Constantieux, T.; Coquerel, Y.; Rodriguez, J. Adv.
Synth. Catal. 2012, 354, 3523; (j) De Fusco, C.; Meninno, S.; Tedesco, C.; Lattanzi,
A. Org. Biomol. Chem. 2013, 11, 896; (k) Yin, C. K.; Cao, W. D.; Lin, L. L.; Liu, X. H.;
Feng, X. M. Adv. Synth. Catal. 2013, 355, 1924; (l) Sanchez Duque, M. M.; Basle,
O.; Genisson, Y.; Plaquevent, J.-C.; Bugaut, X.; Constantieux, T.; Rodriguez, J.
Angew. Chem., Int. Ed. 2013, 52, 14143; (m) Goudedranche, S.; Bugaut, X.;
Constantieux, T.; Bonne, D.; Rodriguez, J. Chem.-Eur. J. 2014, 20, 410.
Acknowledgments
We appreciate the National Natural Science Foundation of
China (Nos. 21321061, and 21222206) for financial support. We
also thank the State Key Laboratory of Biotherapy for HRMS
analysis.
5. Pellissier, H.; Clavier, H. Chem. Rev. 2014, 114, 2775.
6. For examples and reviews on chiral N,N0-dioxide as ligands in catalytic
asymmetric reactions, see: (a) Liu, X. H.; Lin, L. L.; Feng, X. M. Acc. Chem. Res.
2011, 44, 574; (b) Liu, X. H.; Lin, L. L.; Feng, X. M. Org. Chem. Front. 2014, 1, 298;
(c) Huang, S.-X.; Ding, K.-L. Angew. Chem., Int. Ed. 2011, 50, 7734; (d) Malkov, A.
Supplementary data
Supplementary data associated with this article can be found,
in the online version, at http://dx.doi.org/10.1016/j.tetlet.2014.
05.067.
ˇ
´
V.; Kocovsky, P. Eur. J. Org. Chem. 2007, 29; (e) Wang, Z.; Yang, Z. G.; Chen, D. H.;
Liu, X. H.; Lin, L. L.; Feng, X. M. Angew. Chem., Int. Ed. 2011, 50, 4928; (f) Zhou, L.;
Liu, X. H.; Ji, J.; Zhang, Y. H.; Hu, X. L.; Lin, L. L.; Feng, X. M. J. Am. Chem. Soc.
2012, 134, 17023; (g) Zheng, K.; Lin, L. L.; Feng, X. M. Acta Chim. Sinica 2012, 70,
1785; (h) Zhao, J. N.; Liu, X. H.; Luo, W. W.; Xie, M. S.; Lin, L. L.; Feng, X. M.
Angew. Chem., Int. Ed. 2013, 52, 3473; (i) Wang, Z.; Zhang, Z. L.; Yao, Q.; Liu, X.
H.; Cai, Y. F.; Lin, L. L.; Feng, X. M. Chem.-Eur. J. 2013, 19, 8591; (j) Cao, W. D.;
Liu, X. H.; Wang, W. T.; Lin, L. L.; Feng, X. M. Org. Lett. 2011, 13, 600; (k) Xie, M.
S.; Wu, X. X.; Wang, G.; Lin, L. L.; Feng, X. M. Acta Chim. Sinica 2014. http://
dx.doi.org/10.6023/A13121253.
References and notes
1. (a) Steven, A.; Overman, L. E. Angew. Chem., Int. Ed. 2007, 46, 5488; (b) Li, C.-J.;
Trost, B. M. Proc. Natl. Acad. Sci. U.S.A. 2008, 105, 13197.
2. For reviews on the asymmetric Michael reaction, see: (a) Tsogoeva, S. B. Eur. J.
´
7. For selected examples, see: (a) Bella, M.; Jørgensen, K. A. J. Am. Chem. Soc. 2004,
126, 5672; (b) Wang, X.; Kitamura, M.; Maruoka, K. J. Am. Chem. Soc. 2007, 129,
1038; (c) Lan, Q.; Wang, X.; Maruoka, K. Tetrahedron Lett. 2007, 48, 4675; (d)
Chen, Z.; Furutachi, M.; Kato, Y.; Matsunaga, S.; Shibasaki, M. Angew. Chem., Int.
Ed. 2009, 48, 2218; (e) Poulsen, T. B.; Bernardi, L.; Bell, M.; Jørgensen, K. A.
Angew. Chem., Int. Ed. 2006, 45, 6551.
8. For Z-selective racemic conjugate addition, see: (a) Jia, C.; Lu, W.; Oyamada, J.;
Kitamura, T.; Matsuda, K.; Irie, M.; Fujiwara, Y. J. Am. Chem. Soc. 2000, 122,
7252; (b) Grossman, R. B.; Comesse, S.; Rasne, R. M.; Hattori, K.; Delong, M. N. J.
Org. Chem. 2003, 68, 871; (c) Shi, Z.; He, C. J. Org. Chem. 2004, 69, 3669; (d)
Mueller, A. J.; Jennings, M. P. Org. Lett. 2007, 9, 5327.
9. (a) Misaki, T.; Kawano, K.; Sugimura, T. J. Am. Chem. Soc. 2011, 133, 5695; (b)
Wang, Z.; Chen, Z. L.; Bai, S.; Li, W.; Liu, X. H.; Lin, L. L.; Feng, X. M. Angew.
Chem., Int. Ed. 2012, 51, 2776; (c) Uraguchi, D.; Ueki, Y.; Sugiyama, A.; Ooi, T.
Chem. Sci. 2013, 4, 1308.
10. CCDC-991899 (8b) contains the supplementary crystallographic data of the
adduct for this Letter. These data can be obtained free of charge from the
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_
request/cif.
Org. Chem. 2007, 1701; (b) Almas xi, D.; Alonso, D. A.; Najera, C. Tetrahedron:
Asymmetry 2007, 18, 299; (c) Vicario, J. L.; Badıa, D.; Carrillo, L. Synthesis 2007,
2065; (d) MacMillan, D. W. C. Nature 2008, 455, 304; (e) Asymmetric
Organocatalysis, (special issue, Ed.: B. List), Top. Curr. Chem. 2009, 291, 1–
456.; (f) Bertelsen, S.; Jørgensen, K. A. Chem. Soc. Rev. 2009, 38, 2178.
´
3. (a) Capuzzi, M.; Perdicchia, D.; Jorgensen, K. A. Chem.-Eur. J. 2008, 14, 128; (b)
Rigby, C. L.; Dixon, D. J. Chem. Commun. 2008, 3798; (c) Yu, Z. P.; Liu, X. H.;
Zhou, L.; Lin, L. L.; Feng, X. M. Angew. Chem., Int. Ed. 2009, 48, 5195; (d)
Akiyama, T.; Katoh, T.; Mori, K. Angew. Chem., Int. Ed. 2009, 48, 4226; (e)
Boddaert, T.; Coquerel, Y.; Rodriguez, J. Adv. Synth. Catal. 2009, 351, 1744; (f)
Yang, J. J.; Li, W. J.; Jin, Z. C.; Liang, X. M.; Ye, J. X. Org. Lett. 2010, 12, 5218.
4. (a) Liéby-Muller, F.; Constantieux, T.; Rodriguez, J. J. Am. Chem. Soc. 2005, 127,
17176; (b) Pilling, A. W.; Boehmer, J.; Dixon, D. J. Angew. Chem., Int. Ed. 2007, 46,
5428; (c) Pilling, A. W.; Böehmer, J.; Dixon, D. J. Chem. Commun. 2008, 832; (d)
Franzén, J.; Fisher, A. Angew. Chem., Int. Ed. 2009, 48, 787; (e) Zhang, W.;
Franzén, J. Adv. Synth. Catal. 2010, 352, 499; (f) Jin, Z. C.; Wang, X.; Huang, H. C.;
Liang, X. M.; Ye, J. X. Org. Lett. 2011, 13, 564; (g) Sanchez Duque, M. M.; Basle,
O.; Isambert, N.; Gaudel-Siri, A.; Genisson, Y.; Plaquevent, J.-C.; Rodriguez, J.;
Constantieux, T. Org. Lett. 2011, 13, 3296; (h) Mohanan, K.; Coquerel, Y.;