Organocatalytic asymmetric michael addition of oxindoles to nitroolefins for the synthesis of 2,2-disubstituted oxindoles bearing adjacent quaternary and tertiary stereocenters

Article abstract of DOI:10.1021/jo301886j

A bifunctional thiourea-catalyzed Michael addition of activated indolin-3-ones to nitroolefins has been developed. The synthetically useful 2,2-disubstituted indolin-3-one derivatives with vicinal chiral quaternary-tertiary stereocenters were obtained in high yields with excellent stereoselectivities. The adduct can be readily transformed into a structurally interesting heterocyclic architecture by means of further synthetic elaboration.

Full text of DOI:10.1021/jo301886j

Note
pubs.acs.org/joc
Organocatalytic Asymmetric Michael Addition of Oxindoles to
Nitroolefins for the Synthesis of 2,2-Disubstituted Oxindoles Bearing
Adjacent Quaternary and Tertiary Stereocenters
Cheng-Yong Jin, Yao Wang, Yao-Zong Liu, Chao Shen, and Peng-Fei Xu*
State Key Laboratory of Applied Organic Chemistry and College of Chemistry and Chemical Engineering, Lanzhou University,
Lanzhou 730000, P. R. China
S
* Supporting Information
ABSTRACT: A bifunctional thiourea-catalyzed Michael addition of activated indolin-3-ones to nitroolefins has been developed.
The synthetically useful 2,2-disubstituted indolin-3-one derivatives with vicinal chiral quaternary−tertiary stereocenters were
obtained in high yields with excellent stereoselectivities. The adduct can be readily transformed into a structurally interesting
heterocyclic architecture by means of further synthetic elaboration.
ndolin-3-ones with a quaternary stereocenter at the 2-
position are commonly found in a wide range of biologically
activation modes via efficient combination of diverse
nucleophiles and electrophiles.6,7 Although the organocatalytic
Michael addition of highly reactive trisubstituted carbon
nucleophiles to nitroalkenes to generate quaternary carbons
are well-documented,8 to our knowledge, the organocatalytic
strategy exploiting 2-substituted indolin-3-ones as pronucleo-
philes to construct a quaternary carbon at the 2-position in a
highly stereocontrolled manner has not been reported. With
our ongoing interest in the study of indolin-3-one chemistry,9
we report here an efficient method for the synthesis of 2,2-
disubstituted oxindoles bearing adjacent quaternary and tertiary
stereocenters via a bifunctional thiourea-catalyzed the Michael
addition reaction of methyl 1-acetyl-3-oxoindoline-2-carbox-
ylate10 to nitroalkenes.
I
active natural alkaloids such as brevianamide A,1 austamide,2
and fluorocurine3 (Figure 1). Thus, the development of
Figure 1. Biologically active molecules containing indolin-3-ones with
a quaternary stereocenter at the 2-position.
Initially, the Michael addition reaction of methyl 1-acetyl-3-
oxoindoline-2-carboxylate 2 with β-nitrostyrene 3a in the
presence of catalyst 1a (10 mol %) in toluene was
investigated.11 To our delight, the Michael addition reaction
proceeded smoothly to afford the desired product 4a in
excellent yield and stereoselectivity (91% yield, 94% ee, 20:1
dr) after 30 h (Table 1, entry 1). Various promising
bifunctional base/Brønsted acid catalysts were tested (Table
1, entries 2−6), and it was found that the cinchonine- and
quinidine-derived bifunctional thiourea 1b, 1f, Takemoto
catalyst 1d, and amino acid-derived catalyst 1c could also
efficient methods for the construction of functionalized
indolin-3-one building blocks with structural complexity and
skeleton diversity would provide new opportunities for the
synthesis of new kinds of biologically active molecules. Despite
the fruitful achievements toward the enantioselective con-
struction of quaternary carbon-incorporated indolin-2-ones,4
the catalytic asymmetric synthesis of indolin-3-ones with a
quaternary center at the 2-position had been rarely explored,
and it remained a challenging task.5
The Michael addition reaction is one of the most
fundamental, yet important, methods for carbon−carbon
bond formation in modern organic synthesis. Over the past
decade, various organocatalytic asymmetric Michael addition
reactions have been developed by employing new catalysts and
Received: August 31, 2012
Published: November 20, 2012
© 2012 American Chemical Society
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The Journal of Organic Chemistry
Note
a
Table 1. Screening of the Reaction Conditions
b
c
entry
cat.
solvent
R3
R4
T (°C)
time (h)
yield (%)
dr
ee (%)
1
2
1a
1b
1c
1d
1e
1f
toluene
toluene
toluene
toluene
toluene
toluene
CH2Cl2
THF
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
i-Pr
Ac
Ac
Ac
Ac
Ac
Ac
Ac
Ac
Ac
Ac
Ac
Boc
Ac
0
0
30
30
30
30
30
30
24
72
24
42
42
42
42
91
91
93
92
90
92
90
<30
90
84
91
87
91
20:1
20:1
20:1
20:1
20:1
20:1
20:1
20:1
20:1
20:1
20:1
20:1
20:1
94
−92
92
3
0
4
0
−91
55
5
0
6
0
−93
95
7
1a
1a
1a
1a
1a
1a
1a
0
8
0
79
9
CHCl3
CH3OH
CH2Cl2
CH2Cl2
CH2Cl2
0
94
10
11
12
13
0
11
−10
0
94
95
0
91
a
Unless otherwise noted, the reactions were carried out with 2 (0.1 mmol), 3a (0.2 mmol), and catalyst 1 (0.01 mmol) in solvent (1.0 mL) at 0 °C.
Determined by H NMR spectroscopic analysis of the crude reaction mixture. Determined by HPLC on a chiral stationary phase.
b
c
1
give good results albeit with slightly lower enantioselectivities in
contrast to catalyst 1a. However, primary aminothiourea
catalyst 1e gave a significantly decreased enantioinduction.
Subsequently, the solvent effect was investigated, and CH2Cl2
was identified as the solvent of choice in comparison with the
protonic and polar solvents (Table 1, entries 7−10). When the
reaction temperature was dropped to −10 °C, no obviously
beneficial effect on the stereoselctivity and yield was observed
(Table 1, entry 11). Further optimization with modified
substrates also revealed that bulkyl isopropyl ester and N-
Boc-protected nucleophile were also suitable reaction partners.
With the reaction conditions optimized, we next examined
the substrate scope of the reaction (Table 2). The results
showed that a wide range of nitroalkenes could be used in this
reaction. Aromatic groups bearing electron-withdrawing or
-donating groups were well tolerated as well as aromatic rings
substituted in the para, meta and ortho positions. A
heteroaromatic group, such as furan, could also be successfully
employed to afford the desired product. Notably, despite the
structural difference of nitroalkenes, the Michael adducts were
obtained with excellent yields, dr values, and ee values in most
cases. However, the steric hindrance of the o-methoxy-
substituted aromatic ring of nitroolefin resulted in lower
diastereoselectivity compared with other substituted aromatic
substrates (8:1 dr, Table 2, entry 10). Alkyl substrates, on the
other hand, did not perform well in the reaction; n-butyl-
substituted nitroolefin proceeded slowly under the optimized
reaction conditions (Table 2, entry 17). However, with a
modification to our optimal method by raising the reaction
temperature to 20 °C, the Michael reaction proceeded well to
give the product in 87% yield, 20:1 dr, albeit with 75% ee.
Furthermore, indolin-2-ones with different substituents on the
aryl ring were also tolerated and afforded the desired products
with good results (Table 2, entries 18−20). The absolute and
relative configuration of the product was determined based on
single-crystal X-ray diffraction of 4e (see the Supporting
Information).12
As a further example illustrative of the power of this reaction,
the product 4e was readily converted to a structurally diverse
heterocyclic architecture. When 4e was reduced with Zn/HCl
in EtOH followed by treatment with AcCl/Et3N in CH2Cl2, the
desired substituted hexahydropyrrolo[3,2-b]indole 5 was
obtained in moderate yields and high enantioselectivity
(Scheme 1). The structure and configuration of 5 was
determined by X-ray diffraction (see the Supporting
Information).12
Based on the observed reactivity and experimental results of
these Michael addition reactions, we propose that the reaction
proceeds via a double activation model.13 As shown in Figure 2,
the thiourea moiety of the catalyst 1a interacts via hydrogen
bonding with the nitro group of the nitroalkene and enhances
its electrophilicity while the tertiary amine deprotonates an
acidic proton of the methyl 1-acetyl-3-oxoindoline-2-carbox-
ylate, generating a ternary complex. The proposed activation
model explains the stereochemical outcome of these Michael
reactions and why Si-face attack at the nitroolefin is favored.
11308
dx.doi.org/10.1021/jo301886j | J. Org. Chem. 2012, 77, 11307−11312

The Journal of Organic Chemistry
Note
a
readily converted to a structurally interesting heterocyclic
architecture without loss of enantioselectivities.
Table 2. Investigating the Scope of the Reaction
EXPERIMENTAL SECTION
■
Typical Procedure for Michael Addition of Methyl 1-Acetyl-
3-oxoindoline-2-carboxylate to Nitroolefins (Table 2). To a
solution of β-nitrostyrene 3a (30.0 mg, 0.2 mmol) and catalyst 1a (6.0
mg, 0.01 mmol) in dry CH2Cl2 (1.0 mL) was added methyl 1-acetyl-3-
oxoindoline-2-carboxylate 2 (24.0 mg, 0.1 mmol) at 0 °C. The
reaction mixture was stirred at 0 °C until 2 was consumed as
monitored by TLC. Then the reaction mixture was concentrated in
vacuo, and the residue was purified by flash column chromatography
on silica gel using petroleum ether/EtOAc as eluting reagent to afford
the desired product 4a 34.4 mg, in 90% yield. Unless otherwise
specified, all products were synthesized according to the typical
procedure.
c
time
(h)
ee
b
entry
R1
R2
yield (%)
dr
(%)
1
2
H
Ph
24
24
24
24
24
24
24
24
24
72
72
24
90 (4a)
99 (4b)
98 (4c)
94 (4d)
92 (4e)
95 (4f)
95 (4g)
93 (4h)
90 (4i)
90 (4j)
98 (4k)
95 (4l)
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
8:1
95
94
94
95
94
95
94
92
94
96
87
93
H
H
H
H
H
H
H
H
H
H
H
3-ClC6H4
3
4-ClC6H4
4
3-BrC6H4
5
4-BrC6H4
6
4-FC6H4
7
3-NO2C6H4
4-NO2C6H4
4-CF3C6H4
2-MeOC6H4
3-MeOC6H4
8
(S)-Methyl 1-acetyl-2-((S)-2-nitro-1-phenylethyl)-3-oxoindoline-
2-carboxylate (4a): 34.4 mg (90% yield); white solid; mp 146−148
°C; [α]2D0 = −222 (c 1.00, CHCl3, 95% ee); IR (KBr) 3418, 1751,
1710, 1672, 1610, 1552, 1474, 1374, 1321, 1256, 1200, 997, 754, 698,
673, 596 cm−1; 1H NMR (400 MHz, CDCl3) δ (ppm) 7.77 (d, J = 7.2
Hz, 1H), 7.52−7.48 (m, 1H), 7.17 (t, J = 7.6 Hz, 1H), 7.07−6.98 (m,
4H), 6.89 (d, J = 6.8 Hz, 2H), 5.95−5.85 (m, 1H), 5.11−5.01 (m,
2H), 3.73 (s, 3H), 2.30 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
(ppm) 193.1, 167.6, 166.0, 151.9, 137.8, 134.1, 128.4, 128.1, 127.8,
125.1, 124.6, 124.1, 114.3, 75.7, 75.1, 53.5, 45.4, 25.4; HRMS (ESI)
m/z calcd for [C20H22N3O6]+ [M + NH4]+ 400.1503, found 400.1490.
The enantiomeric excess was determined by HPLC with an OD-H
column (hexane/i-PrOH = 70:30), 1.0 mL/min; major enantiomer tR
= 8.2 min, minor enantiomer tR = 10.9 min.
9
10
11
12
>20:1
>20:1
3,4-(OCH2O)
C6H3
13
14
15
16
H
4-MeC6H4
3,4-(CH3)2C6H3
2-naphthyl
2-furyl
24
36
24
24
48
48
48
48
97 (4m) >20:1
96
92
93
90
75
90
91
91
H
93 (4n)
95 (4o)
93 (4p)
87 (4q)
94 (4r)
95 (4s)
88 (4t)
>20:1
>20:1
>20:1
>20:1
>20:1
16:1
H
H
d
17
H
n-Bu
18
19
20
5-Br
6-Cl
Ph
Ph
(S)-Methyl 1-Acetyl-2-((S)-1-(3-chlorophenyl)-2-nitroethyl)-3-ox-
oindoline-2-carboxylate (4b): 41.2 mg (99% yield); white solid; mp
120−122 °C; [α]2D0 = −199 (c 1.00, CHCl3, 94% ee); IR (KBr) 3411,
2955, 1754, 1713, 1665, 1608, 1553, 1472, 1376, 1344, 1246, 1202,
7-Me Ph
12:1
a
Unless otherwise noted, the reactions were carried out with 2 (0.1
mmol), 3 (0.2 mmol), and catalyst 1a (0.01 mmol) in 1.0 mL of
CH2Cl2 at 0 °C. Determined by H NMR spectroscopic analysis of
the crude reaction mixture. Determined by HPLC on a chiral
b
1
1
1082, 999, 946, 790, 764, 700, 588, 514 cm−1; H NMR (400 MHz,
c
CDCl3) δ (ppm) 7.78 (d, J = 7.6 Hz, 1H), 7.57−7.53 (m, 1H), 7.20 (t,
J = 7.6 Hz, 1H), 7.06−7.04 (m, 2H), 6.96−6.92 (m, 2H), 6.80 (d, J =
7.6 Hz, 1H), 5.92−5.88 (m, 1H), 5.09−4.98 (m, 2H), 3.73 (s, 3H),
2.35 (s, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 192.7, 167.7,
165.8, 151.8, 138.1, 136.2, 134.1, 129.4, 128.6, 125.2, 124.5, 124.4,
114.3, 75.3, 74.8, 53.6, 45.0, 25.4; HRMS (ESI) m/z calcd for
[C20H21ClN3O6]+ [M + NH4]+ 434.1113, found 434.1115. The
enantiomeric excess was determined by HPLC with an OD-H column
(hexane/i-PrOH = 80:20), 1.0 mL/min; major enantiomer tR = 12.6
min, minor enantiomer tR = 16.1 min.
d
stationary phase. The reaction was performed at 20 °C.
Scheme 1. Synthetic Transformation
(S)-Methyl 1-Acetyl-2-((S)-1-(4-chlorophenyl)-2-nitroethyl)-3-ox-
oindoline-2-carboxylate (4c): 40.8 mg (98% yield); white solid; mp
140−142 °C; [α]2D0 = −208 (c 1.00, CHCl3, 94% ee); IR (KBr) 3404,
2952, 1752, 1712, 1668, 1609, 1555, 1473, 1377, 1286, 1245, 1086,
984, 838, 764, 628, 527 cm−1; 1H NMR (400 MHz, CDCl3) δ (ppm)
7.78 (d, J = 7.2 Hz, 1H), 7.58−7.54 (m, 1H), 7.21 (t, J = 7.6 Hz, 1H),
7.07 (d, J = 8.4 Hz, 1H), 7.00 (d, J = 8.4 Hz, 2H), 6.85 (d, J = 8.0 Hz,
1H), 5.91−5.87 (dd, J = 2.8 Hz, 13.6 Hz, 1H), 5.11−4.96 (m, 2H),
3.72 (s, 3H), 2.34 (s, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm)
192.8, 167.7, 165.8, 151.9, 138.1, 134.3, 132.8, 129.2, 128.4, 125.3,
124.4, 114.5, 75.6, 74.9, 53.6, 44.9, 25.5; HRMS (ESI) m/z calcd for
[C20H21ClN3O6]+ [M + NH4]+ 434.1113, found 434.1114. The
enantiomeric excess was determined by HPLC with an OD-H column
(hexane/i-PrOH = 70:30), 1.0 mL/min; major enantiomer tR = 9.0
min, minor enantiomer tR = 11.4 min.
Figure 2. Proposed transition-state model in the Michael addition.
(S)-Methyl 1-Acetyl-2-((S)-1-(3-bromophenyl)-2-nitroethyl)-3-ox-
oindoline-2-carboxylate (4d): 43.2 mg (94% yield); white solid; mp
160−162 °C; [α]2D0 = −175 (c 1.00, CHCl3, 95% ee); IR (KBr) 3401,
2954, 1750, 1712, 1664, 1607, 1558, 1473, 1432, 1375, 1249, 1089,
In conclusion, we have developed a bifunctional base/
Brønsted acid-catalyzed asymmetric Michael addition reaction
of methyl 1-acetyl-3-oxoindoline-2-carboxylate to nitroolefins
affording indolin-3-ones with vicinal quaternary and tertiary
stereocenters in excellent yields with high diastereo- and
enantioselectivities. The corresponding product could be
1
1057, 986, 939, 900, 765, 700, 631, 588, 510 cm−1; H NMR (400
MHz, CDCl3) δ (ppm) 7.79 (d, J = 7.6 Hz, 1H), 7.57−7.53 (m, 1H),
7.22−7.18 (m, 2H), 7.05 (d, J = 8.0 Hz, 2H), 6.90 (t, J = 7.6 Hz, 2H),
5.90 (m, 1H), 5.07−4.97 (m, 2H), 3.73 (s, 1H), 2.35 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ (ppm) 192.7, 167.7, 165.8, 151.7, 138.1,
136.4, 131.5, 129.6, 125.3, 124.5, 124.4, 122.2, 114.3, 75.2, 74.8, 53.6,
11309
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Note
44.9, 25.4; HRMS (ESI) m/z calcd for [C20H21BrN3O6]+ [M +
NH4]+: 478.0608, found 478.0607. The enantiomeric excess was
determined by HPLC with an OD-H column (hexane/i-PrOH =
90:10), 1.0 mL/min; major enantiomer tR = 25.0 min, minor
enantiomer tR = 31.6 min.
solid; mp 50−52 °C; [α]2D0 = −55 (c 1.00, CHCl3, 94% ee); IR (KBr)
3413, 2959, 2923, 1757, 1715, 1675, 1609, 1557, 1472, 1434, 1376,
1326, 1285, 1248, 1169, 1123, 1068, 993, 847, 759, 630, 527 cm−1; 1H
NMR (400 MHz, CDCl3) δ (ppm) 7.79 (d, J = 7.6 Hz, 1H), 7.56−
7.52 (m, 1H), 7.29 (d, J = 9.2 Hz, 2H), 7.21 (t, J = 7.6 Hz, 1H), 7.07−
7.01 (m, 1H), 5.96−5.91 (dd, J = 3.2 Hz, 14 Hz, 1H), 5.19 (d, J = 10
Hz, 1H), 5.09−5.02 (m, 1H), 3.74 (s, 3H), 2.32 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ (ppm) 192.6, 167.8, 165.7, 151.7, 138.4, 138.2,
130.6 (q, J = 32.6 Hz), 128.4, 125.3, 125.1(q, J = 3.6 Hz), 124.5, 124.4,
123.7 (q, J = 272.5 Hz), 114.4, 75.3, 74.7, 53.7, 45.2, 25.4; HRMS
(ESI) m/z calcd for [C21H21F3N3O6]+ [M + NH4]+: 468.1377, found
468.1382. The enantiomeric excess was determined by HPLC with an
OD-H column (hexane/i-PrOH = 70:30), 1.0 mL/min; major
enantiomer tR = 7.7 min, minor enantiomer tR = 10.4 min.
(S)-Methyl 1-Acetyl-2-((S)-1-(4-bromophenyl)-2-nitroethyl)-3-ox-
oindoline-2-carboxylate (4e): 42.3 mg (92% yield); white solid; mp
150−152 °C; [α]2D0 = −185 (c 1.00, CHCl3, 94% ee); IR (KBr) 3408,
2950, 1752, 1712, 1667, 1609, 1554, 1473, 1376, 1285, 1244, 1073,
1006, 982, 835, 760, 628, 523, 417 cm−1; 1H NMR (400 MHz,
CDCl3) δ (ppm) 7.78 (d, J = 7.6 Hz, 1H), 7.57 (t, J = 7.6 Hz, 1H),
7.21 (t, J = 7.6 Hz, 1H), 7.15 (d, J = 8.0 Hz, 1H), 7.08 (d, J = 8.4 Hz,
1H), 6.79 (d, J = 8.0 Hz, 1H), 5.90−5.86 (dd, J = 2.8 Hz, 13.2 Hz,
1H), 5.09−4.96 (m, 2H), 3.73 (s, 3H), 2.34 (s, 3H); 13C NMR (100
MHz, CDCl3) δ (ppm) 192.8, 167.7, 165.8, 151.8, 138.2, 133.3, 131.4,
129.5, 125.3, 124.4, 122.5, 114.5, 75.6, 74.8, 53.6, 44.9, 25.5; HRMS
(ESI) m/z calcd for [C20H21BrN3O6]+ [M + NH4]+ 478.0608, found
478.0593. The enantiomeric excess was determined by HPLC with an
OD-H column (hexane/i-PrOH = 70:30), 1.0 mL/min; major
enantiomer tR = 9.2 min, minor enantiomer tR = 11.5 min.
(S)-Methyl 1-Acetyl-2-((S)-1-(2-methoxyphenyl)-2-nitroethyl)-3-
oxoindoline-2-carboxylate (4j): 37.1 mg (90% yield); white solid;
mp 170−172 °C; [α]2D0 = −120 (c 1.00, CHCl3, 96% ee); IR (KBr)
3415, 2924, 2848, 1757, 1717, 1663, 1603, 1556, 1471, 1378, 1253,
1
1121, 1022, 987, 921, 763, 603, 549, 515, 424 cm−1; H NMR (400
MHz, CDCl3) δ (ppm) 7.82 (d, J = 7.2 Hz, 1H), 7.55 (t, J = 7.2 Hz,
1H), 7.21 (t, J = 7.2 Hz, 1H), 7.12−7.07 (m, 3H), 6.80 (t, J = 7.2 Hz,
1H), 6.44 (d, J = 8.0 Hz, 1H), 5.71 (d, J = 10.8 Hz, 1H), 5.21−5.12
(m, 2H), 3.72 (s, 3H), 3.07 (s, 3H), 2.12 (s, 3H); 13C NMR (100
MHz, CDCl3) δ (ppm) 191.9, 167.4, 167.0, 156.8, 150.4, 136.7, 133.6,
129.7, 125.1, 124.8, 123.6, 122.6, 120.5, 114.3, 109.7, 74.4, 74.3, 53.5,
53.2, 45.7, 25.1; HRMS (ESI) m/z calcd for [C21H24N3O7]+ [M +
NH4]+ 430.1609, found 430.1597. The enantiomeric excess was
determined by HPLC with an OD-H column (hexane/i-PrOH =
73:30), 1.0 mL/min; major enantiomer tR = 8.8 min, minor
enantiomer tR = 11.3 min.
(S)-Methyl 1-Acetyl-2-((S)-1-(4-fluorophenyl)-2-nitroethyl)-3-ox-
oindoline-2-carboxylate (4f): 38.0 mg (95% yield); white solid; mp
130−132 °C; [α]2D0 = −126 (c 1.00, CHCl3, 95% ee); IR (KBr) 3415,
2957, 2924, 1754, 1714, 1670, 1608, 1553, 1511, 1473, 1376, 1345,
1
1232, 1162, 1106, 995, 843, 756, 629, 598, 533, 421 cm−1; H NMR
(400 MHz, CDCl3) δ (ppm) 7.78 (d, J = 7.6 Hz, 1H), 7.57−7.53 (m,
1H), 7.20 (t, J = 7.6 Hz, 1H), 7.06 (d, J = 8.0 Hz, 1H), 6.89 (t, J = 6.4
Hz, 2H), 6.71 (t, J = 8.4 Hz, 2H), 5.91−5.87 (dd, J = 2.8 Hz, 13.6 Hz,
1H), 5.11−4.97 (m, 2H), 3.73 (s, 3H), 2.33 (s, 3H); 13C NMR (100
MHz, CDCl3) δ (ppm) 192.9, 167.7, 165.9, 162.4 (d, J = 246.2 Hz),
151.8, 138.1, 130.0, 129.5, 125.2, 124.4, 124.3, 115.2 (d, J = 21.8 Hz),
114.4, 75.7, 75.0, 53.6, 44.7, 25.5; HRMS (ESI) m/z calcd for
[C20H21FN3O6]+ [M + NH4]+: 418.1409, found 418.1410. The
enantiomeric excess was determined by HPLC with an OD-H column
(hexane/i-PrOH = 70:30), 1.0 mL/min; major enantiomer tR = 9.1
min, minor enantiomer tR = 12.4 min.
(S)-Methyl 1-Acetyl-2-((S)-1-(3-methoxyphenyl)-2-nitroethyl)-3-
oxoindoline-2-carboxylate (4k): 40.4 mg (98% yield); white solid;
mp 154−156 °C; [α]2D0 = −171 (c 1.00, CHCl3, 87% ee); IR (KBr)
3413, 2962, 1755, 1713, 1663, 1609, 1553, 1473, 1377, 1284, 1254,
1
1163, 1057, 997, 888, 762, 704, 642, 592, 517, 402 cm−1; H NMR
(400 MHz, CDCl3) δ (ppm) 7.78 (d, J = 7.6 Hz, 1H), 7.55−7.51 (m,
1H), 7.18 (t, J = 7.6 Hz, 1H), 7.05 (d, J = 8.4 Hz, 1H), 6.91 (t, J = 8.0
Hz, 1H), 6.61−6.59 (dd, J = 2 Hz, 8.0 Hz, 1H), 6.48 (d, J = 6.8 Hz,
1H), 6.41 (s, 1H), 5.93−5.83 (m, 1H), 5.05−4.99 (m, 2H), 3.72 (s,
3H), 3.53 (s, 3H), 2.32 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
(ppm) 193.1, 167.6, 166.0, 159.2, 152.0, 137.9, 135.5, 129.1, 125.1,
124.6, 124.1, 114.4, 75.8, 75.0, 55.0, 53.5, 45.5, 25.5; HRMS (ESI) m/z
calcd for [C21H24N3O7]+ [M + NH4]+ 430.1609, found 430.1606. The
enantiomeric excess was determined by HPLC with an OD-H column
(hexane/i-PrOH = 70:30), 1.0 mL/min; major enantiomer tR = 9.0
min, minor enantiomer tR = 11.0 min.
(S)-Methyl 1-Acetyl-2-((S)-2-nitro-1-(3-nitrophenyl)ethyl)-3-ox-
oindoline-2-carboxylate (4g): 40.6 mg (95% yield); white solid; mp
122−124 °C; [α]2D0 = −120 (c 1.00, CHCl3, 94% ee); IR (KBr) 3420,
3046, 2956, 1754, 1667, 1608, 1554, 1534, 1472, 1435, 1377, 1348,
1
1248, 1089, 999, 945, 802, 763, 694, 632, 607, 519 cm−1; H NMR
(400 MHz, CDCl3) δ (ppm) 7.94 (d, J = 7.6 Hz, 1H), 7.83−7.81 (m,
1H), 7.76 (s, 1H), 7.55−7.51 (m, 1H), 7.35−7.33 (d, J = 8.0 Hz, 1H),
7.29−7.27(m, 1H), 7.22−7.18 (m, 1H), 7.05−7.01 (m, 1H), 5.99−
5.95 (dd, J = 3.2 Hz, 14.4 Hz, 1H), 5.25−5.22 (dd, J = 2.0 Hz, 11.6 Hz,
1H), 5.12−5.05 (m, 1H), 3.75 (s, 3H), 2.35 (s, 3H); 13C NMR (100
MHz, CDCl3) δ (ppm) 192.3, 167.9, 165.5, 151.6, 147.7, 138.3, 136.5,
134.1, 129.3, 125.5, 124.7, 124.3, 123.4, 122.5, 114.3, 75.0, 74.6, 53.7,
45.0, 25.3; HRMS (ESI) m/z calcd for [C20H21N4O8]+ [M + NH4]+
445.1354, found 445.1359. The enantiomeric excess was determined
by HPLC with an OD-H column (hexane/i-PrOH = 70:30), 1.0 mL/
min; major enantiomer tR = 15.8 min, minor enantiomer tR = 22.1 min.
(S)-Methyl 1-Acetyl-2-((S)-2-nitro-1-(4-nitrophenyl)ethyl)-3-ox-
oindoline-2-carboxylate (4h): 39.7 mg (93% yield); white solid; mp
160−162 °C; [α]2D0 = −129 (c 1.00, CHCl3, 92% ee); IR (KBr) 3432,
2956, 2925, 1750, 1704, 1665, 1606, 1557, 1526, 1474, 1377, 1530,
(S)-Methyl 1-Acetyl-2-((S)-1-(benzo[d][1,3]dioxol-5-yl)-2-nitroeth-
yl)-3-oxoindoline-2-carboxylate (4l): 40.5 mg (95% yield); white
solid; mp 82−84 °C; [α]2D0 = −174 (c 1.00, CHCl3, 93% ee); IR (KBr)
3412, 2960, 2901, 1758, 1714, 1675, 1608, 1555, 1472, 1377, 1239,
1
1039, 995, 934, 814, 752, 643, 591, 517, 421 cm−1; H NMR (400
MHz, CDCl3) δ (ppm) 7.78 (d, J = 7.6 Hz, 1H), 7.59−7.55 (m, 1H),
7.20 (t, J = 7.6 Hz, 1H), 7.13 (d, J = 8.4 Hz, 1H), 6.50−6.38 (m, 3H),
5.87 (t, J = 11.2 Hz, 1H), 5.82−5.76 (m, 2H), 5.02−4.94 (m, 2H),
3.71 (s, 3H), 2.36 (s, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm)
193.1, 167.7, 166.0, 152.0, 147.4, 147.4, 137.9, 127.6, 125.2, 124.5,
124.2, 121.4, 114.4, 107.8, 101.1, 76.0, 75.2, 53.5, 45.1, 25.5; HRMS
(ESI) m/z calcd for [C21H22N3O8]+ [M + NH4]+ 444.1401, found
444.1392. The enantiomeric excess was determined by HPLC with an
OD-H column (hexane/i-PrOH = 70:30), 1.0 mL/min; major
enantiomer tR = 12.0 min, minor enantiomer tR = 14.8 min.
(S)-Methyl 1-Acetyl-2-((S)-2-nitro-1-(p-tolyl)ethyl)-3-oxoindoline-
2-carboxylate (4m): 38.4 mg (97% yield); white solid; mp 124−126
°C; [α]2D0 = −229 (c 1.00, CHCl3, 96% ee); IR (KBr) 3409, 2951,
2924, 1752, 1713, 1663, 1609, 1554, 1473, 1377, 1245, 982, 760, 629,
529 cm−1; 1H NMR (400 MHz, CDCl3) δ (pp m) 7.77 (d, J = 7.6 Hz,
1H), 7.54−7.49 (m, 1H), 7.17 (t, J = 7.2 Hz, 1H), 7.03 (d, J = 8.0 Hz,
1H), 6.81−6.75 (m, 4H), 5.91−5.83 (m, 1H), 5.06−4.99 (m, 2H),
3.72 (s, 3H), 2.31 (s, 3H), 2.13 (s, 3H); 13C NMR (100 MHz, CDCl3)
δ (ppm) 193.1, 167.6, 166.1, 151.9, 138.1, 137.8, 130.9, 128.8, 127.7,
1
1289, 1250, 1207, 1112, 1001, 982, 857, 759, 699, 629, 599 cm−1; H
NMR (400 MHz, CDCl3) δ (ppm) 7.90 (d, J = 8.8 Hz, 1H), 7.82 (d, J
= 7.6 Hz, 1H), 7.59−7.54 (m, 1H), 7.23 (d, J = 7.2 Hz, 1H), 7.13(t, J
= 7.6 Hz, 2H), 7.06 (d, J = 8.4 Hz, 1H), 5.98−5.94 (dd, J = 3.2 Hz,
14.4 Hz, 1H), 5.27 (t, J = 3.2 Hz, 1H), 5.09−5.03 (m, 1H), 3.74 (s,
3H), 2.35 (s, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 192.3,
167.9, 165.5, 151.7, 147.7, 141.9, 138.5, 129.0, 125.5, 124.7, 124.2,
123.3, 114.4, 75.2, 74.6, 53.8, 45.2, 25.4; HRMS (ESI) m/z calcd for
[C20H21N4O8]+ [M + NH4]+ 445.1354, found 445.1365. The
enantiomeric excess was determined by HPLC with an OD-H column
(hexane/i-PrOH = 50:50), 1.0 mL/min; major enantiomer tR = 8.3
min, minor enantiomer tR = 16.3 min.
(S)-Methyl 1-Acetyl-2-((S)-2-nitro-1-(4-(trifluoromethyl)phenyl)-
ethyl)-3-oxoindoline-2-carboxylate (4i): 40.5 mg (90% yield); white
11310
dx.doi.org/10.1021/jo301886j | J. Org. Chem. 2012, 77, 11307−11312

The Journal of Organic Chemistry
Note
125.1, 124.6, 124.0, 114.4, 75.9, 75.2, 53.4, 45.1, 25.5, 20.9; HRMS
(ESI) m/z calcd for [C21H24N3O6]+ [M + NH4]+ 414.1660, found
414.1675. The enantiomeric excess was determined by HPLC with an
AD-H column (hexane/i-PrOH = 80:20), 1.0 mL/min; major
enantiomer tR = 12.1 min, minor enantiomer tR = 15.3 min.
1063, 995, 822, 704, 646, 601, 467 cm−1; 1H NMR (400 MHz,
CDCl3) δ (ppm) 7.87 (s, 1H), 7.58−7.56 (dd, J = 2.0 Hz, 8.8 Hz, 1H),
7.11−7.03 (m, 3H), 6.89 (d, J = 6.8 Hz, 3H), 5.86 (d, J = 10.8 Hz,
1H), 5.08−4.99 (m, 2H), 3.72 (s, 3H), 2.28 (s, 3H); 13C NMR (100
MHz, CDCl3) δ (ppm) 191.8, 167.4, 165.5, 150.7, 140.3, 133.8, 128.6,
128.3, 127.6, 126.0, 117.1, 115.8, 75.5, 53.6, 45.5, 25.4; HRMS (ESI)
m/z calcd for [C20H21BrN3O6]+ [M + NH4]+ 478.0611, found
478.0608. The enantiomeric excess was determined by HPLC with an
OD-H column (hexane/i-PrOH = 70:30), 1.0 mL/min; major
enantiomer tR = 7.8 min, minor enantiomer tR = 10.6 min.
(S)-Methyl 1-Acetyl-2-((S)-1-(3,4-dimethylphenyl)-2-nitroethyl)-3-
oxoindoline-2-carboxylate (4n): 38.1 mg (93% yield); white solid;
mp 158−160 °C; [α]2D0 = −175 (c 1.00, CHCl3, 92% ee); IR (KBr)
3403, 2954, 2924, 1747, 1708, 1676, 1607, 1556, 1475, 1434, 1376,
1321, 1248, 1203, 1109, 1056, 999, 941, 816, 757, 717, 640, 611, 514,
419 cm−1; 1H NMR (400 MHz, CDCl3) δ (ppm) 7.77 (d, J = 8.0 Hz,
1H), 7.52−7.48 (m, 1H), 7.16 (t, J = 7.6 Hz, 1H), 7.15 (d, J = 8.4 Hz,
1H), 6.73 (d, J = 7.6 Hz, 1H), 6.61 (s, 2H), 5.89−5.82 (dd, J = 9.2 Hz,
20 Hz, 1H), 5.04−4.97 (m, 2H), 3.72 (s, 3H), 2.30 (s, 3H), 2.02 (s,
3H), 1.95 (s, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 193.2,
167.5, 166.1, 151.9, 137.7, 136.6, 136.3, 131.2, 129.3, 125.0, 124.7,
123.9, 114.3, 75.9, 75.2, 53.4, 45.0, 25.4, 19.3, 19.2; HRMS (ESI) m/z
calcd for [C22H26N3O6]+ [M + NH4]+ 428.1816, found 428.1811. The
enantiomeric excess was determined by HPLC with an OJ-H column
(hexane/i-PrOH = 70:30), 1.0 mL/min; major enantiomer tR = 15.7
min, minor enantiomer tR = 10.7 min.
(S)-Methyl 1-Acetyl-6-chloro-2-((S)-2-nitro-1-phenylethyl)-3-ox-
oindoline-2-carboxylate (4s): 39.5 mg 95% yield; white solid; mp
136−138 °C; [α]2D0 = −172 (c 1.00, CHCl3, 91% ee); IR (KBr) 3401,
2990, 1752, 1711, 1605, 1559, 1553, 1432, 1372, 1273, 1247, 1080,
1
993, 948, 800, 705, 636, 460 cm−1; H NMR (400 MHz, CDCl3) δ
(ppm) 7.69 (d, J = 8 Hz, 1H), 7.16−7.13 (dd, J = 1.6 Hz, 8.0 Hz, 2H),
7.11−7.00 (m, 3H), 6.90 (d, J = 7.2 Hz, 2H), 5.89−5.84 (m, 1H),
5.05−5.00 (m, 2H), 3.72 (s, 3H), 2.30 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ (ppm) 191.7, 167.5, 165.6, 152.3, 144.5, 133.9, 128.6, 128.3,
127.8, 125.9, 124.8, 122.9, 114.7, 75.6, 53.6, 45.3, 25.5; HRMS (ESI)
m/z calcd for [C20H21ClN3O6]+ [M + NH4]+ 434.1113, found
434.1111. The enantiomeric excess was determined by HPLC with an
OD-H column (hexane/i-PrOH = 80:20), 1.0 mL/min; major
enantiomer tR = 9.6 min, minor enantiomer tR = 12.0 min.
(S)-Methyl 1-Acetyl-7-methyl-2-((S)-2-nitro-1-phenylethyl)-3-ox-
oindoline-2-carboxylate (4t): 34.8 mg 88% yield; white solid; mp
172−174 °C; [α]2D0 = −205 (c 1.00, CHCl3, 91% ee); IR (KBr) 3407,
2956, 2925, 1755, 1713, 1673, 1594, 1555, 1437, 1348, 1278, 1246,
1076, 1005, 972, 778, 615, 575 cm−1; 1H NMR (400 MHz, CDCl3) δ
(ppm) 7.57 (d, J = 7.6 Hz, 1H), 7.25 (d, J = 7.6 Hz, 1H), 7.12 (t, J =
7.6 Hz, 1H), 7.03 (t, J = 7.2 Hz, 1H), 6.95 (t, J = 6.8 Hz, 2H), 6.87 (s,
2H), 5.80−5.73 (dd, J = 10.0 Hz, 20.4 Hz, 1H), 5.03−4.95 (m, 2H),
3.77 (s, 3H), 2.12 (s, 3H), 1.70 (s, 3H); 13C NMR (100 MHz, CDCl3)
δ (ppm) 193.6, 169.7, 166.6, 152.9, 140.1, 133.9, 128.1, 127.9, 126.6,
125.5, 122.2, 74.8, 53.5, 47.5, 23.5, 19.2; HRMS (ESI) m/z calcd for
[C21H21N2O6]+ [M + H]+ 397.1396, found397.1394. The enantio-
meric excess was determined by HPLC with an OD-H column
(hexane/i-PrOH = 80:20), 1.0 mL/min; major enantiomer tR = 10.1
min, minor enantiomer tR = 14.8 min.
Experimental Procedure for the Synthesis of Compound 5. A 10
mL round-bottom flask with well-stirring was filled with zinc powder
(210.0 mg, 0.25 mmol), and then 4e (94% ee, 115.0 mg, 0.25 mmol)
and EtOH (2.5 mL) were added to the flask. After the mixture was
stirred at 35 °C for 10 min, 1.5 mL of 4 N HCl aq was added
dropwise. The contents were stirred at 35 °C until the reaction was
complete (about 4 h as monitored by TLC). After EtOH was removed
under reduced pressure, 3 N NaOH aq (5.0 mL) was added, and the
solution was stirred for 5 min. After being diluted with 5.0 mL of
CH2Cl2, the mixture was filtrated through a plug of Celite. The layers
were separated, and the aqueous layer was extracted with CH2Cl2 (3 ×
10 mL).The combined organic layers were washed with brine and
dried over anhydrous MgSO4 and concentrated. The crude mixture
was then dissolved in 2.0 mL of dry CH2Cl2, and then Et3N (55 μL,
0.38 mmol) was added to the solution at 0 °C. After 5 min, AcCl (20
μL, 0.25 mmol) was added dropwise. The mixture was stirred for 4 h
and then allowed to warm to room temperature. The solvent was
removed by a rotary evaporator and the residue was purified by flash
chromatography (petroleum/EtOAc = 2:1) to afford 53.0 mg of pure
5 (42% yield, 20:1 dr, 96% ee).
(S)-Methyl 1-Acetyl-2-((S)-1-(naphthalen-2-yl)-2-nitroethyl)-3-ox-
oindoline-2-carboxylate (4o): 41.0 mg (95% yield); white solid; mp
148−150 °C; [α]2D0 = −186 (c 1.00, CHCl3, 93% ee); IR (KBr) 3422,
2956, 1755, 1715, 1666, 1611, 1548, 1475, 1377, 1346, 1288, 1242,
1
1207, 1056, 1001, 950, 822, 756, 599, 480, 480 cm−1; H NMR (400
MHz, CDCl3) δ (ppm) 7.79 (d, J = 7.6 Hz, 1H), 7.64−7.61 (m, 1H),
7.55(s, 1H), 7.46 (d, J = 8.4 Hz, 1H), 7.39−7.32 (m, 4H), 7.09 (t, J =
7.6 Hz, 1H), 6.95 (d, J = 7.2 Hz, 1H), 6.83 (d, J = 8.4 Hz,1H), 6.00−
5.95 (dd, J = 3.2 Hz, 13.6 Hz, 1H), 5.28−5.12 (m, 2H), 3.74 (s, 3H),
2.23 (s, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 193.1, 167.7,
166.1, 151.8, 137.8, 132.8, 132.7, 131.5, 127.9, 127.6, 127.4, 126.3,
126.3, 125.1, 124.5, 124.1, 114.3, 75.9, 75.2, 53.5, 45.5, 25.4; HRMS
(ESI) m/z calcd for [C24H24N3O6]+ [M + NH4]+ 450.1660, found
450.1657. The enantiomeric excess was determined by HPLC with an
OD-H column (hexane/i-PrOH = 70:30), 1.0 mL/min; major
enantiomer tR = 17.0 min, minor enantiomer tR = 13.1 min.
(S)-Methyl 1-Acetyl-2-((S)-1-(furan-2-yl)-2-nitroethyl)-3-oxoindo-
line-2-carboxylate (4p): 34.6 mg (93% yield); white solid; mp 132−
134 °C; [α]2D0 = −181 (c 1.00, CHCl3, 90% ee); IR (KBr) 3411, 2965,
1751, 1710, 1675, 1606, 1555, 1474, 1375, 1284, 1206, 1148, 1081,
998, 940, 914, 755, 596, 516, 416 cm−1; 1H NMR (400 MHz, CDCl3)
δ (ppm) 7.77 (d, J = 7.6 Hz, 1H), 7.62−7.58 (m, 1H), 7.21 (t, J = 7.6
Hz, 2H), 6.90 (s, 1H), 6.08−6.04 (m, 2H), 5.82−5.78 (dd, J = 2.8 Hz,
14 Hz, 1H), 5.22 (d, J = 10.0 Hz, 1H), 5.01−4.91 (m, 1H), 3.72 (s,
3H), 2.43 (s, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 192.3,
167.6, 165.8, 151.4, 148.3, 142.4, 137.6, 125.4, 124.1, 114.3, 110.2,
109.8, 74.1, 53.5, 39.5, 25.5; HRMS (ESI) m/z calcd for
[C18H20N3O7]+ [M + NH4]+ 390.1296, found 390.1293. The
enantiomeric excess was determined by HPLC with an OD-H column
(hexane/i-PrOH = 70:30), 1.0 mL/min; major enantiomer tR = 8.4
min, minor enantiomer tR = 12.4 min.
(S)-Methyl 1-Acetyl-2-((S)-1-nitropentan-2-yl)-3-oxoindoline-2-
carboxylate (4q): 30.3 mg (87% yield); white solid; mp 156−158
°C; [α]2D0 = −140 (c 1.00, CHCl3, 75% ee); IR (KBr) 3432, 2964,
1755, 1707, 1669, 1607, 1552, 1473, 1377, 1338, 1262, 1104, 997, 760,
625, 591, 421 cm−1; 1H NMR (400 MHz, CDCl3) δ (ppm) 7.80−7.77
(dd, J = 2.8 Hz, 7.6 Hz, 2H), 7.29 (m, 1H), 5.73 (d, J = 14.8 Hz, 1H),
4.36−4.31 (dd, J = 6.8 Hz, 15.2 Hz, 1H), 3.86 (s, 1H), 3.68 (s, 3H),
2.55 (s, 3H), 1.30−1.16 (m, 4H), 1.08−1.00 (m, 1H), 0.75 (t, J = 7.2
Hz, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 193.4, 168.0, 166.3,
138.2, 125.4, 124.6, 75.3, 53.4, 39.2, 30.8, 25.5, 19.8, 13.9; HRMS
(ESI) m/z calcd for [C17H20NaN2O6]+ [M + Na]+ 371.1290, found
371.1293. The enantiomeric excess was determined by HPLC with an
OD-H column (hexane/i-PrOH = 70:30), 1.0 mL/min; major
enantiomer tR = 33.6 min, minor enantiomer tR = 40.0 min.
(3S,3aS,8bS)-Methyl 1,4-Diacetyl-3-(4-bromophenyl)-
1,2,3,3a,4,8b-hexahydropyrrolo[3,2-b]indole-3a-carboxylate (5).
48.0 mg (42% yield); white solid; mp 168−170 °C; [α]2D0 = +262 (c
1.00, CHCl3, 96% ee); IR (KBr) 2952, 2023, 1744, 1656, 1484, 1383,
1
1351, 1248, 1011, 988, 831, 759, 520 cm−1; H NMR (400 MHz,
CDCl3) δ (ppm) 7.79 (d, J = 7.6 Hz, 1H), 7.19−7.12 (m, 3H), 7.08−
7.04 (m, 1H), 6.83 (d, J = 8.0 Hz, 1H), 6.66 (d, J = 8.0 Hz, 1H), 5.94
(s, 1H), 4.66−4.63 (dd, J = 3.2 Hz, 7.6 Hz, 1H), 4.23−4.18 (dd, J = 8
Hz, 10.8 Hz, 1H), 3.76 (s, 3H), 3.73−3.70 (dd, J = 3.2 Hz, 10.8 Hz,
1H), 2.20 (s, 3H), 2.08 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
(ppm) 171.0, 170.9, 167.8, 141.0, 137.6, 131.3, 130.5, 130.2, 129.6,
(S)-Methyl 1-Acetyl-5-bromo-2-((S)-2-nitro-1-phenylethyl)-3-ox-
oindoline-2-carboxylate (4r): 43.2 mg 94% yield; white solid; mp
156−158 °C; [α]2D0 = −246 (c 1.00, CHCl3, 90% ee); IR (KBr) 3077,
2963, 1751, 1707, 1673, 1601, 1553, 1469, 1373, 1335, 1263, 1195,
11311
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The Journal of Organic Chemistry
Note
128.1, 124.3, 121.2, 112.5, 66.0, 53.6, 53.1, 48.8, 24.5, 22.8; HRMS
(ESI) m/z calcd for [C22H22BrN2O4]+ [M + H]+ 457.0766, found
457.0757. The enantiomeric excess was determined by HPLC with an
AD-H column (hexane/i-PrOH = 80:20), 1.0 mL/min; major
enantiomer tR = 12.8 min, minor enantiomer tR = 10.8 min.
Lett. 2008, 49, 6773. (g) Jiang, X.-X.; Zhang, Y.-F.; Liu, X.; Zhang, G.;
Wang, R. J. Org. Chem. 2009, 74, 5562. (h) Han, X.; Luo, J.; Liu, C.;
Lu, Y.-X. Chem. Commun. 2009, 2044. (i) Luo, J.; Xu, L.-W.; Lu, Y.-X.
Org. Lett. 2010, 12, 964. (j) Nemoto, T.; Obuchi, K.; Tamura, S.;
Fukuyama, T.; Hamada, Y. Tetrahedron Lett. 2011, 52, 6773.
(9) (a) Liu, Y.-Z.; Cheng, R.-L.; Xu, P.-F. J. Org. Chem. 2011, 76,
2884. (b) Liu, Y.-Z.; Zhang, J.; Xu, P.-F.; Luo, Y.-C. J. Org. Chem.
2011, 76, 7551.
(10) Collot, V.; Bourguignon, J. J. Heterocycles 1999, 51, 12.
(11) For selected reviews on the use of cinchona alkaloid/thiourea
catalysis, see: (a) Connon, S. J. Chem. Commun. 2008, 2499. (b) Song,
C. E. In Cinchona Alkaloids in Synthesis and Catalysis; Wiley-VCH:
Weinheim, 2009; (c) Takemoto, Y. Chem. Pharm. Bull. 2010, 58, 593.
(d) Yeboah, E. M. O.; Yeboah, S. O.; Sing, G. S. Tetrahedron 2011, 67,
1725. For selected recent examples of cinchona alkaloid/thiourea
catalysis, see: (e) Wang, Y.; Han, R.-G.; Zhao, Y.-L.; Yang, S.; Xu, P.-
F.; Dixon, D. J. Angew. Chem., Int. Ed. 2009, 48, 9834. (f) Zhang, H.;
Syed, S.; Barbas, C. F., III. Org. Lett. 2010, 12, 708. (g) Xie, H.; Zhang,
Y.; Zhang, S.; Chen, X.; Wang, W. Angew. Chem., Int. Ed. 2011, 50,
11773. (h) Curti, C.; Rassu, G.; Zambrano, V.; Pinna, L.; Pelosi, G.;
Sartori, A.; Battistini, L.; Zanardi, F.; Casiraghi, G. Angew. Chem., Int.
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ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental details, spectra data for the products, and X-ray
crystallographic data of 4e (CCDC 862138) and 5 (CCDC
862139) (CIF). This materia is available free of charge via the
Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: xupf@lzu.edu.cn.
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
(12) CCDC 862138 and 862139 contain the supplementary
crystallographic data for this paper. These data can be obtained free
of charge from The Cambridge Crystallographic Data Centre via www.
ccdc.cam.ac.uk/data_request/cif.
(13) McCooey, S. H.; Connon, S. J. Angew. Chem., Int. Ed. 2005, 44,
6367.
We are grateful for the NSFC (21032005, 20972058,
21172097), the National Basic Research Program of China
(No. 2010CB833203), and the “111” program from MOE of P.
R. China.
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