Diastereo- and enantioselective conjugate addition of α-substituted cyanoacetates to maleimides catalyzed by binaphthyl-based thiourea

Full text of DOI:10.1002/bkcs.10439

Note
DOI: 10.1002/bkcs.10439
BULLETIN OF THE
S. H. Kang and D. Y. Kim
KOREAN CHEMICAL SOCIETY
Diastereo- and Enantioselective Conjugate Addition of α-Substituted
Cyanoacetates to Maleimides Catalyzed by Binaphthyl-based Thiourea
*
Seong Hye Kang and Dae Young Kim
Department of Chemistry, Soonchunhyang University, Asan 336-745, Korea. *E-mail: dyoung@sch.ac.kr
Received April 24, 2015, Accepted May 17, 2015, Published online August 12, 2015
Keywords: Asymmetric catalysis, Organocatalysis, Michael addition, α-Cyanoacetates, Maleimides
The Michael addition reaction is widely recognized as one of
the most efficient and powerful methods for the C–C bonds
formation in organic synthesis.1 To date, various asymmetric
Michael addition reactions have been developed.2 Chiral
α-cyanoacetates bearing a quaternary stereogenic center are
an important class of substrates that serve as precursors of
the highly functionalized chiral compounds such as amino
acids and amino alcohols with simple functional group trans-
formation.3 Recently, organocatalytic enantioselective conju-
gate addition reactions of α-substituted cyanoacetates with
various Michael acceptors have been reported.4 Until now,
there are a few reports for the catalytic conjugate addition of
α-substituted cyanoacetates to maleimides using organocata-
lysts.5 Although these methods are satisfyingly efficient in
some extent, new organocatalytic conjugate addition of α-sub-
stituted cyanoacetates to maleimides is highly desired.
As part of our research program related to the development
of synthetic methods for the enantioselective construction of
stereogenic carbon centers,6 we recently reported the asym-
metric Michael addition reactions of active methines using
chiral catalysts.7 Herein, we wish to describe the conjugate
addition of α-substituted cyanoacetates with maleimide pro-
moted by binaphthyl-based organocatalysts.
To determine suitable reaction conditions for the catalytic
enantioselective Michael addition of α-substituted cyanoace-
tates, we initially investigated the reactions with N-phenylma-
leimide (2a) in the presence of 10 mol % binaphthyl-based
organocatalysts I–IV bearing both central and axial chiral ele-
ments (Figure. 1). As shown in Table 1, binaphthyl-based
(thio)urea catalysts I–III effectively promoted the reaction
in toluene with high enantioselectivities (entries 1–3,
Table 1). Replacement of urea function with squaramide (cat-
alyst IV) slightly decreased the enantioselectivity (entry 4, -
Table 1), and the highest enantioselectivities obtained with
the binaphthyl-based thiourea catalyst II. For further improve-
ment of selectivity, different solvents were then tested in the
presence of 10 mol % of catalyst II. Aprotic solvents such
as toluene, benzene, diethyl ether, THF, and dichloromethane
were well tolerated in this Michael addition without a signif-
icant decrease of enantioselectivities (76–96% enantiomeric
excesses [ee], entries 2 and 5–9, Table 1). Among the solvents
probed, toluene provided the best results (79% yield, 9:1 dr,
96% ee, entry 2, Table 1). The present catalytic system toler-
ates catalyst loading down to 5 mol %, and both the yields and
enantioselectivities were retained (entries 4 and 10–11,
Table 1).
With the optimized conditions in hand, we proceeded to
investigate the scope of the enantioselective conjugate addi-
tion of various α-substituted cyanoacetates 1 and N-phenyl-
maleimide (2a) in the presence of 5 mol % of binaphthyl-
based thiourea-tertiary amine catalyst II in toluene at room
temperature. The results of conjugate addition reaction are
summarized in Table 2. A range of electron-donating and elec-
tron-withdrawing substitutions on the aryl ring of the α-aryl
cyanoacetates 1 provided reaction products 3a–3e in high
yields (64–97%), high diastereoselectivities (7–9:1), and
excellent enantioselectivities (84–98%, entries 2–5,
Table 2). The α-heteroaryl cyanoacetate provided the products
with high selectivity (87% ee, entry 6, Table 2). Moderate yield
and selectivity were obtained when α-alkylsubstituted cyanoa-
cetateswereusedasthesubstrate(entry7,Table2).Anarylsub-
stitution on the N-arylmaleimides 2 provided corresponding
products 3h–3i in high yields and high enantioselectivities
(81–94%, entries 8–9, Table 2). Absolute configuration of pro-
ducts was determined by comparison either of the optical rota-
tion or chiral HPLC data with those of the reported ones.5
Although the reason for the observed enantioselectivity is
still unclear, we believe that a carbonyl group of the maleimide
is activated by the thiourea moiety through hydrogen bonding,
and the cyanoacetate moiety is activated by the basic nitrogen
atom intertiary amine(Figure 2). The attack fromthe si-face of
the enol form of cyanoacetate to the re-face of the maleimide
givesproduct3. Nevertheless, theprecisecatalytic mechanism
still requires further investigation.
In summary, we have developed efficient catalytic enantio-
selective Michael addition reactions of α-substituted cyanoa-
cetates 1 to maleimides 2 using binaphthyl-based thiourea
catalyst. The desired Michael products were obtained in high
yields and diastereoselectivities. Also, the excellent enantios-
electivities were observed (up to 98% ee). Further studies on
asymmetric reactions catalyzed by binaphthyl-based organo-
catalysts are underway in our laboratory.
Experimental
General. All commercial reagents and solvents were used
without purification. TLC analyses were carried out on pre-
coated silica gel plates with F254 indicator. Visualization
Correction added on 01 October 2015, after first online publication: ISSN (Print) has been corrected.
Bull. Korean Chem. Soc. 2015, Vol. 36, 2371–2374
© 2015 Korean Chemical Society, Seoul & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Wiley Online Library
2371

Note
BULLETIN OF THE
ISSN (Print) 0253-2964 | (Online) 1229-5949
KOREAN CHEMICAL SOCIETY
was accomplished by UV light (254 nm), I2, p-anisaldehyde,
ninhydrin, and phosphomolybdic acid solutionasanindicator.
Purification of reaction products was carried out by flash chro-
matography using Merck silica gel 60 (Darmstadt, Germany)
(230–400 mesh). 1H NMR and 13C NMR spectra were
recorded on a Jeol ECS 400 MHz NMR (Tokyo, Japan)
(400 MHz for 1H and 100 MHz for 13C). Chemical shift values
(δ) are reported in ppm relative to Me4Si (δ 0.0 ppm). Optical
rotations were measured on a JASCO-DIP-1000 digital polar-
imeter (Tokyo, Japan) with a sodium lamp. The ee were deter-
mined by HPLC. HPLC analysis was performed on Younglin
M9100 Series, measured at 230 nm using the indicated chiral
column.
Typical Procedure for the Michael Addition of Ethyl
2-Cyanoacetate 1a to N-Phenylmaleimide 2a. To a stirred
solution of N-phenylmaleimide (2a, 104 mg, 0.6 mmol, 1.2
equiv) and binaphthyl-modified thiourea II (1.7 mg, 2.5 μ
mol, 5 mol %) in toluene (1.0 mL) was added ethyl 2-
cyano-2-phenylacetate (1a, 95 mg, 0.5 mmol, 1.0 equiv) at
room temperature. The reaction mixture was stirred at room
temperature for 2 days. The reaction mixture was purified
by column chromatography (EtOAc:hexane:dichlomethane
= 1:8:6) to give the desired product (3a, 139 mg, 77%).
(R)-Ethyl 2-cyano-2-((S)-2,5-dioxo-1-phenylpyrrolidin-
25
3-yl)-2-phenylacetate (3a): ½αꢀD = −44:3 (c = 1, CHCl3); 1H
NMR (400 MHz, CDCl3) δ 7.669–7.627 (m, 2H), 7.52–7.39
(m, 6H), 7.32–7.29 (m, 2H), 4.43–4.23 (m, 3H), 2.85–2.78
(dd, J = 9.2, 18.6 Hz, 1H), 2.58–2.51 (dd, J = 6.4, 18.8 Hz,
1H), 1.32–1.30 (t, J = 7.0 Hz, 3H); 13C NMR (50 MHz,
CDCl3) δ 173.97, 172.88, 165.98, 131.21, 129.71, 129.67,
129.32, 129.09, 126.48, 115.86, 64.19, 55.44, 46.99, 31.65,
13.77; HPLC (70:30, n-hexane:i-PrOH, 220 nm, 1.0 mL/
Figure 1. Structures of organocatalysts.
Table 1. Optimization of the reaction conditions.a
Entry
Catalysts
Solvent
Time (h)
Yieldb (%)
drc
eed (%)
1
2
3
4
5
6
7
8
I
II
III
IV
II
II
II
II
II
II
II
PhMe
PhMe
PhMe
PhMe
PhH
p-xylene
Et2O
THF
5
5
5
5
5
5
7
7
9
80
79
24
55
64
93
45
70
55
77
35
1.9:1
9:1
1.3:1
1.5:1
9:1
16:1
9:1
9:1
94
96
88
89
94
80
83
76
69
98
90
9
CH2Cl2
PhMe
PhMe
3:1
9:1
9:1
10e
11f
48
72
a Reaction conditions: ethyl α-phenyl cyanoacetate (1a, 0.3 mmol), N-phenylmaleimide (2a, 0.36 mmol), catalyst (0.03 mmol), solvent (3.0 mL) at room
temperature.
b Isolated yield.
c Determined 1H NMR analysis of the crude mixture.
d Enantiopurity was determined by HPLC analysis using CHIRALPAK IA column.
e 5 mol % catalyst loading.
f 2.5 mol % catalyst loading.
Bull. Korean Chem. Soc. 2015, Vol. 36, 2371–2374
© 2015 Korean Chemical Society, Seoul & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.bkcs.wiley-vch.de 2372

BULLETIN OF THE
Note
KOREAN CHEMICAL SOCIETY
Table 2. Substrate scope.a
Entry
1, R
2, Ar
Time (days)
Yieldb (%)
drc
eed (%)
1
2
3
4
5
6
7
8
9
Ph
4-OMe–Ph
4-F–Ph
4-Cl–Ph
3-Cl–Ph
2-Thienyl
Bn
Ph
Ph
Ph
Ph
Ph
2
1
4
4
1
2
7
1
5
3a, 77
3b, 64
3c, 97
3d, 95
3e, 96
3f, 95
3g, 50
3h, 93
3i, 86
9:1
9:1
8:1
8:1
7:1
9:1
1.3:1
9:1
98
95
88
84
98
87
64
94
81
Ph
Ph
Ph
Ph
4-CN–Ph
4-OMe–Ph
20:1
a Reaction conditions: α-cyanoacetates 1 (0.3 mmol), maleimides 2 (0.36 mmol), catalyst (0.015 mmol), solvent (3.0 mL) at room temperature.
b Isolated yield.
c Determined 1H NMR analysis of the crude mixture.
d Enantiopurity was determined by HPLC analysis using CHIRALPAK IA (3a–3f, 3h,and 3i) and AD-H (3g) columns.
CHIRALPAK IA column, tR = 14.0 min (major), tR = 19.3
min (minor), 88% ee.
(R)-Ethyl 2-(4-chlorophenyl)-2-cyano-2-((S)-2,5-dioxo-
1-phenylpyrrolidin-3-yl)acetate (4d): ½αꢀ2D1 = −15:5 (c =
0.57, CHCl3); 1H NMR (400 MHz, CDCl3) δ 7.61–7.58 (m,
2H), 7.48–7.42 (m, 5H), 7.32–7.26 (m, 2H), 4.42–4.24
(m, 3H), 2.86–2.79 (dd, J = 9.6, 18.4 Hz, 1H), 2.56–2.50
(dd, J = 6.4, 18.4 Hz, 1H), 1.34–1.30 (t, J = 7.2 Hz, 3H);
HPLC (90:10, n-hexane:i-PrOH, 220 nm, 1.0 mL/min) CHIR-
ALPAK IA column, tR = 70.6 min (major), tR = 41.6 min
(minor), 84% ee.
Figure 2. Proposed stereochemical model.
(R)-Ethyl 2-(3-chlorophenyl)-2-cyano-2-((S)-2,5-dioxo-
min) CHIRALPAK IA column, tR = 17.1 min (major), tR =
25.8 min (minor), 98% ee.
(R)-Ethyl 2-cyano-2-((S)-2,5-dioxo-1-phenylpyrrolidin-
1-phenylpyrrolidin-3-yl)acetate (3e): ½αꢀ2D0 = −168:7 (c =
0.17, CHCl3); 1H NMR (400 MHz, CDCl3) δ 7.67–7.66 (m,
1H), 7.63–7.55 (m, 1H), 7.49–7.42 (m, 5H), 7.32–7.29 (m,
2H), 4.43–4.26 (m, 3H), 2.88–2.81 (dd, J = 9.6, 18.6 Hz,
1H), 2.57–2.51 (dd, J = 6.4, 18.0 Hz, 1H), 1.35–1.31 (t, J =
6.8 Hz, 3H); HPLC (70:30, n-hexane:i-PrOH, 220 nm, 1.0
mL/min) CHIRALPAK IA column, tR = 17.5 min (major),
tR = 14.8 min (minor), 98% ee.
3-yl)-2-(4-methoxyphenyl)acetate (3b): ½αꢀ2D4 = −68:1 (c =
1, CHCl3); 1H NMR (400 MHz, CDCl3) δ 7.56–7.54 (d, J =
8.8 Hz, 2H), 7.49–7.41 (m, 3H), 7.32–7.29 (m, 2H),
6.98–6.96 (d, J = 8.8 Hz, 2H), 4.41–4.22 (m, 3H), 3.842
(s, 3H), 2.85–2.78 (dd, J = 9.6, 18.4 Hz, 1H), 2.58–2.52 (dd,
J = 6.8, 18.6 Hz, 2H), 1.33–1.28 (t, J = 7.2 Hz, 3H); HPLC
(70:30, n-hexane:i-PrOH, 220 nm, 1.0 mL/min) CHIRAL-
PAK IA column, tR = 23.6 min (major), tR = 16.7 min (minor),
95% ee.
(R)-Ethyl 2-cyano-2-((S)-2,5-dioxo-1-phenylpyrrolidin-
3-yl)-2-(thiophen-2-yl)acetate (3f ): ½αꢀ2D2 = −27:4 (c = 1.09,
1
CHCl3); H NMR (400 MHz, CDCl3) δ 7.50–7.37 (m, 5H),
7.31–7.24 (m, 2H), 7.07–7.04 (m, 1H), 4.46–4.25 (m, 3H),
2.94–2.87 (dd, J = 9.6, 18.6 Hz, 1H), 2.73–2.67 (dd, J = 6.0,
18.6 Hz, 1H), 1.38–1.34 (t, J = 7.2 Hz, 3H); HPLC (70:30,
n-hexane:i-PrOH, 220 nm, 1.0 mL/min) CHIRALPAK IA
column, tR = 24.4 min (major), tR = 20.3 min (minor), 87% ee.
(S)-Ethyl 2-cyano-2-((S)-2,5-dioxo-1-phenylpyrrolidin-
(R)-Ethyl 2-cyano-2-((S)-2,5-dioxo-1-phenylpyrrolidin-
3-yl)-2-(4-fluorophenyl)acetate (3c): ½αꢀ2D4 = −108:1 (c = 1,
1
CHCl3); H NMR (400 MHz, CDCl3) δ 7.671–7.659 (m,
1H), 7.53–7.42 (m, 4H), 7.32–7.13 (m, 4H), 4.43–4.24
(m, 3H), 2.86–2.78 (dd, J = 9.6, 18.8 Hz, 1H), 2.56–2.50
(dd, J = 6.4, 18.4 Hz, 1H), 1.34–1.30 (t, J = 6.8 Hz, 3H);
HPLC (70:30, n-hexane:i-PrOH, 220 nm, 1.0 mL/min)
3-yl)-3-phenylpropanoate (3g): ½αꢀ2D2 = −179:5 (c = 0.22,
CHCl3); 1H NMR (400 MHz, CDCl3) δ (major + minor)
Bull. Korean Chem. Soc. 2015, Vol. 36, 2371–2374
© 2015 Korean Chemical Society, Seoul & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.bkcs.wiley-vch.de 2373

BULLETIN OF THE
Note
KOREAN CHEMICAL SOCIETY
22, 690; (c) Z.-w. Ma, Y. Wu, B. Sun, H.-l. Du, W.-m. Shi,
J.-c. Tao, Tetrahedron: Asymmetry 2013, 24, 7.
7.51–7.30 (m, 10H), 4.27–4.17 (m, 2H), 3.83–3.79 (d, J =
13.6 Hz, 0.5H), 3.56–3.51 (m, 2H), 3.40–3.37 (d, J = 13.2
Hz, 0.5H), 3.17–3.08 (m, 1H), 2.92–2.86 (dd, J = 6.0, 18.2
Hz, 0.5H), 2.79–2.73 (dd, J = 6.4, 18.4 Hz, 0.5H),
1.23–1.19 (m, 3H); HPLC (90:10, n-hexane:i-PrOH, 220
nm, 1.0 mL/min) CHIRALPAK AD-H column, tR = 45.2
min (major), tR = 99.8 min (minor), 64% ee.
6. For selected recent examples, see:(a) Y. K. Kang, S. M. Kim,
D. Y. Kim, J. Am. Chem. Soc. 2010, 132, 11847;
(b) H. W. Moon, D. Y. Kim, Tetrahedron Lett. 2010, 51, 2906;
(c) Y. K. Kang, D. Y. Kim, Curr. Org. Chem. 2010, 14, 917;
(d) S. H. Kang, B. K. Kwon, D. Y. Kim, Tetrahedron Lett.
2011, 52, 3247; (e) Y. K. Kang, K. H. Suh, D. Y. Kim, Synlett
2011, 22, 1125; (f ) H. W. Moon, D. Y. Kim, Bull. Korean Chem.
Soc. 2011, 32, 291; (g) H. J. Lee, Y. M. Chae, D. Y. Kim, Bull.
Korean Chem. Soc. 2011, 32, 2875; (h) H. J. Lee, S. H. Kang,
D. Y. Kim, Synlett 2011, 22, 1559; (i) H. J. Lee, S. H. Kang,
D. Y. Kim, Bull. Korean Chem. Soc. 2011, 32, 1125;
(j) H. J. Lee, J. H. Kim, D. Y. Kim, Bull. Korean Chem. Soc.
2011, 32, 785; (k) Y. K. Kang, H. H. Kim, K. O. Koh,
D. Y. Kim, Tetrahedron Lett. 2012, 53, 3811; (l) B. K. Kwon,
J. Y. Mang, D. Y. Kim, Bull. Korean Chem. Soc. 2012, 33,
2481; (m) H. J. Lee, D. Y. Kim, Tetrahedron Lett. 2012, 53,
6984; (n) H. J. Lee, S. B. Woo, D. Y. Kim, Tetrahedron Lett.
2012, 53, 3374; (o) H. W. Moon, D. Y. Kim, Bull. Korean Chem.
Soc. 2012, 33, 2845; (p) H. J. Lee, S. B. Woo, D. Y. Kim, Mole-
cules 2012, 17, 7523; (q) Y. J. Lim, D. Y. Kim, Bull. Korean
Chem. Soc. 2013, 34, 1955; (r) S. B. Woo, C. W. Suh,
K. O. Koh, D. Y. Kim, Tetrahedron Lett. 2013, 54, 3359;
(s) H. A. Lee, D. Y. Kim, Bull. Korean Chem. Soc. 2013, 34,
3539; (t) C. W. Suh, T. H. Han, D. Y. Kim, Bull. Korean Chem.
Soc. 2013, 34, 1623; (u) C. W. Suh, C. W. Chang, K. W. Choi,
Y. J. Lim, D. Y. Kim, Tetrahedron Lett. 2013, 54, 3651;
(v) Y. K. Kang, D. Y. Kim, Chem. Commun. 2014, 50, 222;
(w) C. W. Suh, S. B. Woo, D. Y. Kim, Asian J. Org. Chem.
2014, 3, 399; (x) C. W. Suh, D. Y. Kim, Org. Lett. 2014, 16, 5374.
7. For selected recent works using organocatalysts, see:
(a) S. H. Jung, D. Y. Kim, Tetrahedron Lett. 2008, 49, 5527;
(b) S. M. Kim, J. H. Lee, D. Y. Kim, Synlett 2008, 19, 2659;
(c) J. H. Lee, D. Y. Kim, Adv. Synth. Catal. 2009, 351, 1779;
(d) B. K. Kwon, D. Y. Kim, Bull. Korean Chem. Soc. 2009, 30,
1441; (e) H. W. Moon, D. Y. Kim, Bull. Korean Chem. Soc.
2011, 32, 291; (f ) H. J. Lee, J. H. Kim, D. Y. Kim, Bull. Korean
Chem. Soc. 2011, 32, 785; (g) H. J. Lee, S. H. Kang, D. Y. Kim,
Bull. Korean Chem. Soc. 2011, 32, 1125; (h) J. H. Lee, D. Y. Kim,
Bull. Korean Chem. Soc. 2012, 33, 3537; (i) H. J. Lee, S. B. Woo,
D. Y. Kim, Tetrahedron Lett. 2012, 53, 3374; (j) Y. J. Lim,
D. Y. Kim, Bull. Korean Chem. Soc. 2012, 33, 1825;
(k) H. W. Moon, D. Y. Kim, Bull. Korean Chem. Soc. 2012,
33, 2845; (l) J. Y. Lee, D. Y. Kim, Bull. Korean Chem. Soc.
2013, 34, 2569; (m) Y. K. Kang, H. J. Lee, H. W. Moon,
D. Y. Kim, RSC Adv. 2013, 3, 1332; (n) Y. K. Kang,
D. Y. Kim, Adv. Synth. Catal. 2013, 355, 3131; (o) M. H. Lee,
D. Y. Kim, Bull. Korean Chem. Soc. 2013, 34, 3891;
(p) J. H. Lee, D. Y. Kim, Bull. Korean Chem. Soc. 2013, 34,
1619; (q) D. Y. Kim, Bull. Korean Chem. Soc. 2013, 34, 3463;
(r) C. W. Suh, D. Y. Kim, Bull. Korean Chem. Soc. 2014, 35,
98; (s) H. J. Lee, D. E. Lee, D. Y. Kim, Bull. Korean Chem.
Soc. 2015, 36, 370; (t) C. W. Suh, H. J. Jeong, D. Y. Kim, Bull.
Korean Chem. Soc. 2015, 36, 406; (u) M. H. Kim, H. J. Jeong,
D. Y. Kim, Bull. Korean Chem. Soc. 2015, 36, 1155;
(v) H. J. Jeong, S. J. Kwon, D. Y. Kim, Bull. Korean Chem.
Soc. 2015, 36, 1516; (w) Y. S. Kim, S. J. Kwon, D. Y. Kim, Bull.
Korean Chem. Soc. 2015, 36, 1512.
(R)-Ethyl 2-cyano-2-((S)-1-(4-cyanophenyl)-2,5-dioxo-
pyrrolidin-3-yl)-2-phenylacetate (3h): ½αꢀ2D3 = −57:4 (c =
1, CHCl3); 1H NMR (400 MHz, CDCl3) δ 7.78–7.72 (m, 2H),
7.64–7.60 (m, 2H), 7.53–7.45 (m, 5H), 4.45–4.23 (m, 3H),
2.88–2.81 (dd, J = 9.2, 18.6 Hz, 1H), 2.59–2.53 (dd, J = 6.4,
18.8 Hz, 1H), 1.33–1.29 (t, J = 6.8 Hz, 3H); HPLC (70:30, n-
hexane:i-PrOH, 220 nm, 1.0 mL/min) CHIRALPAK IA col-
umn, tR = 18.5 min (major), tR = 23.4 min (minor), 94% ee.
(R)-Ethyl 2-cyano-2-((S)-1-(4-methoxyphenyl)-2-oxo-
pyrrolidin-3-yl)-2-phenylacetate (3i): ½αꢀ2D3 = −37:4 (c = 1,
1
CHCl3); H NMR (400 MHz, CDCl3) δ 7.65–7.63 (m, 2H),
7.49–7.43 (m, 3H), 7.22–7.14 (m, 2H), 6.99–6.93 (m, 2H),
4.41–4.23 (m, 3H), 3.81 (s, 3H), 2.82–2.75 (dd, J = 9.2,
18.6 Hz, 1H), 2.54–2.48 (dd, J = 6.4, 18.4 Hz, 1H),
1.32–1.29 (t, J = 6.8 Hz, 3H); HPLC (70:30, n-hexane:i-
PrOH, 220 nm, 1.0 mL/min) CHIRALPAK IA column, tR =
27.1 min (major), tR = 20.6 min (minor), 81% ee.
Acknowledgment. This research was supported by Soon-
chunhyang University Research Fund.
References
1. (a) J. Leonard, Contemp. Org. Synth. 1994, 1, 387;
(b) P. Perlmutter, Conjugate Addition Reactions in Organic Syn-
thesis, Pergamon, Oxford, 1992.
2. For recent reviews of asymmetric Michael reactions, see:
(a) N. Krause, A. Hoffmann-Röder, Synthesis 2001, 2001, 171;
(b) O. M. Berner, L. Tedeschi, D. Enders, Eur. J. Org. Chem.
2002, 2002, 1877; (c) J. Christoffers, A. Baro, Angew. Chem.
Int. Ed. 2003, 42, 1688; (d) S. B. Tsogoeva, Eur. J. Org. Chem.
2007, 2007, 1701; (e) D. Almasi, D. A. Alonso, D. Najera, Tetra-
hedron: Asymmetry 2007, 18, 299.
3. (a) M. D. Diaz-de-Villegas, J. A. Galvez, R. Badorrey, P. Lopez-
Ram-de-Viu, Adv. Synth. Catal. 2014, 356, 3261; (b) E. J. Park,
H. R. Kim, C. U. Joung, D. Y. Kim, Bull. Korean Chem. Soc.
2004, 25, 1451; (c) H. R. Kim, D. Y. Kim, Tetrahedron Lett.
2005, 46, 3115; (d) S. M. Kim, Y. K. Kang, M. J. Cho,
J. Y. Mang, D. Y. Kim, Bull. Korean Chem. Soc. 2007, 28, 2435.
4. For selected recent examples, see:(a) H. Li, J. Song, D. Deng,
Tetrahedron 2009, 65, 3139; (b) F. Marini, S. Sternativo,
F. Del Verme, L. Testaferri, M. Tiecco, Adv. Synth. Catal.
2009, 351, 103; (c) Y. Hasegawa, I. D. Gridnev, T. Ikariya,
Angew. Chem. Int. Ed. 2010, 50, 8157; (d) S. H. Eitel,
S. Jautze, W. Frey, Chem. Sci. 2013, 4, 2218; (e) P. Chauhan,
J. Kaur, S. S. Chimni, Chem. Asian J. 2013, 8, 328.
5. (a) Y.-H. Liao, X.-L. Jiu, Z.-J. Wu, X.-L. Du, X.-M. Zhang,
W.-C. Yuan, Adv. Synth. Catal. 2011, 353, 1720; (b) J.-J. Wang,
X.-J. Dong, W.-T. Wei, M. Yan, Tetrahedron: Asymmetry 2011,
Bull. Korean Chem. Soc. 2015, Vol. 36, 2371–2374
© 2015 Korean Chemical Society, Seoul & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.bkcs.wiley-vch.de 2374