Organocatalyzed enantioselective decarboxylative stereoablation reaction for the construction of 3,3′-disubstituted oxindoles using β-ketoacids and 3-halooxindoles

Article abstract of DOI:10.1021/jo302048v

An unprecedented method for the construction of optically active 3,3′-disubstituted oxindoles via an organocatalyzed decarboxylative stereoablation reaction has been developed. We describe the first asymmetric reaction between β-ketoacids and 3-halooxindoles utilizing an organocatalyst. This method allows for the formation of a variety of 3,3′-disubstituted oxindoles bearing a keto-carbonyl group, which are not easily accessible using other methodologies, in moderate to good yields with high enantioselectivities.

Full text of DOI:10.1021/jo302048v

Note
pubs.acs.org/joc
Organocatalyzed Enantioselective Decarboxylative Stereoablation
Reaction for the Construction of 3,3′-Disubstituted Oxindoles Using
β‑Ketoacids and 3‑Halooxindoles
Jian Zuo,†,‡,§ Yu-Hua Liao,†,‡,§ Xiao-Mei Zhang,† and Wei-Cheng Yuan*,†
†National Engineering Research Center of Chiral Drugs, Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences,
Chengdu 610041, China
‡University of Chinese Academy of Sciences, Beijing, 100049, China
S
* Supporting Information
ABSTRACT: An unprecedented method for the construction of
optically active 3,3′-disubstituted oxindoles via an organocatalyzed
decarboxylative stereoablation reaction has been developed. We
describe the first asymmetric reaction between β-ketoacids and 3-
halooxindoles utilizing an organocatalyst. This method allows for the
formation of a variety of 3,3′-disubstituted oxindoles bearing a keto-
carbonyl group, which are not easily accessible using other
methodologies, in moderate to good yields with high enantioselectivities.
different types of electrophiles (Scheme 1, reaction 2).5 Despite
he 3,3′-disubstituted oxindole unit, which bears a
Tquaternary stereogenic center at the C3 position, has
the substantial advances made in this research area, pursuing
alternative tactics for the construction of structurally diverse
oxindoles bearing a tetrasubstituted stereogenic center at C3
position is still in demand. In this context, taking advantage of a
suitable achiral 3,3′-disubstituted oxindole as an electrophilic
precursor for the asymmetric synthesis of chiral 3,3′-
disubstituted oxindole compounds has begun to emerge
recently.6,7 It is particularly noticeable that a significant example
of using 3-halooxindoles as electrophilic precursors via
stereoablative transformation8 for the synthesis of chiral C3-
quaternary oxindoles was reported in 2009 by the Stoltz group
(Scheme 1, reaction 3).6a Guided by Stoltz’s work, we recently
reported an organocatalytic enantioselective stereoablative
hydroxylation of 3-halooxindoles for the construction of 3-
substituted-3-hydroxy-2-oxindole derivatives (Scheme 1, reac-
tion 3).7
been recognized as a crucial fragment of a number of natural
products and medicinally important agents.1 The stereo-
controlled synthesis of 3,3′-disubstituted oxindole derivatives
has become the subject of enormous interest over the past
decades.2 Accordingly, a variety of asymmetric methods for the
construction of diverse 3,3′-disubstituted oxindoles by means of
metal catalysis and organocatalysis have been reported.3
However, among the various methods, the most common
approaches to 3,3′-disubstituted oxindole scaffolds involve
using isatins/isatinimines as electrophiles reacting with various
nucleophiles (Scheme 1, reaction 1)4 and applying 3-
monosubstituted oxindoles as nucleophiles reacting with
Scheme 1
Although the vast majority of the literature has described the
widespread application of the decarboxylative transformation of
malonic acid half thioesters (MAHTs) in the formation of
carbon−carbon bonds,9 a very small number of methods using
β-ketoacids as attractive surrogates of ketones via a
decarboxylation process for various asymmetric transformations
have been reported in the literature.10 Thus, the development
of a versatile decarboxylative reaction regarding β-ketoacids in
asymmetric synthesis is particularly appealing and highly
desired. On the basis of the progress with respect to the
enantioselective stereoablative reaction6a,8,11 and our recent
studies of the asymmetric stereoablation reaction,7 we
envisioned that a methyl ketone enolate, in situ generated
Received: September 27, 2012
© XXXX American Chemical Society
A
dx.doi.org/10.1021/jo302048v | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
a
from β-ketoacids via a decarboxylative process, should be able
to attack another putative intermediate, o-azaxylylene, in situ
generated from 3-halooxindoles, for installing a keto-carbonyl
group at the C3 position of an oxindole. Certainly, if the above
process proceeds under a somewhat appropriate asymmetric
environment, it will afford a type of chiral 3,3′-disubstituted
oxindole product (Scheme 2). In conjunction with our efforts
Table 1. Reaction Optimization
b
c
entry
cat.
solvent
base
yield (%)
ee (%)
Scheme 2. Strategy for the Decarboxylative Stereoablation
Reaction between β-Ketoacids and 3-Halooxindoles
1
A
B
C
D
E
F
G
H
I
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
THF
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Na2CO3
Cs2CO3
Et3N
94
94
94
74
94
93
94
85
94
67
88
76
85
59
91
50
94
91
43
−19
72
2
3
4
50
5
83
6
82
7
4
8
−33
−71
64
9
10
11
12
13
14
15
16
17
18
E
E
E
E
E
E
E
E
E
toluene
CHCl3
DCE
85
82
79
to explore asymmetric strategies for the construction of
structurally diverse oxindoles,12 we have investigated an
asymmetric decarboxylative stereoablation reaction between
β-ketoacids and 3-halooxindoles with cinchona alkaloid
derivatives as catalysts. Herein, we report our recent studies
on this subject.
toluene
toluene
toluene
toluene
toluene
90
27
85
K3PO4
K3PO4
87
d
90
a
Unless otherwise noted, reactions were carried out with 1a (0.1
We started our investigations with the reaction between
racemic 3-benzyl-3-bromooxindole (1a) and 3-oxo-3-phenyl-
propanoic acid (2a) in CH2Cl2 with potassium carbonate as
base using various cinchona alkaloids and their derivatives A−I
(Figure 1) as chiral catalysts. As shown in Table 1 (entries 1−
mmol), 2a (0.12 mmol), base (0.1 mmol), and catalyst (0.02 mmol) in
b
the solvent (1.0 mL) at room temperature for 5 h. Isolated yield.
c
d
Determined by chiral HPLC. Reaction was carried out in 2 mL of
toluene at room temperature for 15 h. Bn = benzyl; Bz = benzoyl.
afforded the best reactivity (94% yield) and a high
enantioselectivity (87%) (Table 1, entry 17). Higher
enantioselectivity, up to 90% ee for 3a, could be attained in
91% yield after 15 h at a lower substrate concentration (Table
1, entry 18).
With the optimized conditions in hand, we turned our focus
to the substrate scope and generality of the reaction. First, a
wide range of 3-substituted-3-bromooxindoles 1 were reacted
with 3-oxo-3-phenylpropanoic acid (2a) under the optimized
conditions, respectively (Table 2). The introduction of
electron-donating groups onto the phenyl ring of R and
incorporation into the 3-halooxindoles did not compromise the
reactivity nor significantly affect the selectivity (Table 2, entries
2−4). On the other hand, when electron-withdrawing groups
were introduced onto the phenyl ring of R, the reaction also
proceeded smoothly and gave the desired product with good
yield and ee value (Table 2, entries 5−9). Meanwhile, the
substrate 1j bearing a bulky naphthylmethyl group reacted well
with 2a and gave the desired product 3j in 95% yield with 89%
ee (Table 1, entry 10). High ee was also obtained when the
phenyl group was replaced with other aromatics such as
thiophene (Table 2, entry 11). 3-Halooxindoles containing
electron-withdrawing substitution on the oxindole core were
equally effective substrates (Table 2, entries 12 and 13).
Additionally, good yield and enantioselectivity could be
obtained even with a substrate bearing an allyl substituent at
the C3 position of the oxindole core (Table 2, entry 14).
Notably, the current reaction system is also effective for 3-
benzyl-3-chlorooxindole (1o), affording the corresponding
product 3a in 60% yield with 92% ee (Table 2, entry 15).
Acceptable results were also provided by using 3-phenyl-3-
Figure 1. Selected examples of examined catalysts.
9), the structures of the catalysts have a dramatic effect on the
enantioselectivity but a minor influence on the catalytic activity.
As a result, demethylated quinidine derivative E was proven to
be the most effective, giving the expected 3,3′-disubstituted 3a
in 94% yield with 83% ee (Table 1, entry 5). Meanwhile,
particular attention should be paid to the reaction with G as
catalyst because the product was obtained as a nearly racemic
mixture (Table 1, entry 7). By comparison, it was found that
the structural difference between catalysts E and G is that E
bears a C6′-OH but G contains a C6′-OMe (Figure 1). This
led us to speculate that the C6′-OH moiety of the catalyst was
crucial for the expected high enantioselectivity. Afterward,
solvent screening did not offer further improvement of the
enantioselectivity (Table 1, entries 10−13), but toluene gave a
relatively higher ee value (Table 1, entry 11). Further studies
showed that the base made a large impact on the yield and
enantioselectivity (Table 1, entries 14−17), and K3PO4
B
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Note
a
Table 2. Substrate Scope for 3-Halooxindoles
a
All reactions were performed by using 1 (0.1 mmol), 2a (0.12 mmol), K3PO4 (0.1 mmol), and E (0.02 mmol) in toluene (2.0 mL) at room
b
c
temperature for 15 h. Isolated yield. Determined by chiral HPLC.
chlorooxindole (1p) as a substrate (Table 2, entry 16).
Particularly, the absolute configuration of compound 3g was
determined as S by X-ray analysis (Figure 2), and the other
3,3′-disubstituted oxindole products in this work could be
tentatively assigned by analogy.13
Subsequently, a variety of β-ketoacids (2b−h) were further
subjected to the E-catalyzed decarboxylative stereoablation
reaction under the standard reaction conditions (Table 3).
Introduction of some substitutents, regardless of being
electron-rich or electron-deficient, onto the phenyl ring of 3-
C
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Note
Scheme 3. Proposed Reaction Pathway
Figure 2. X-ray structure of product 3g.
a
Table 3. Substrate Scope for β-Ketoacids
and the resulting carboxylate undergoes decarboxylation,
generating a methyl ketone enolate. Meanwhile, 3-halooxindole
1 is subjected to K3PO4, thus forming a putative o-azaxylylene
intermediate. Simultaneously, activation of the o-azaxylylene
intermediate and the methyl ketone enolate by the hydroxyl
and tertiary amine group of E derives a transition state T1
(Scheme 3). With the enantioselective induction from chiral
catalyst E, the S configuration for the 3,3′-disubstituted
oxindoles 3 is predominately generated via the enolate
attacking the si-face of the o-azaxylylene.
In conclusion, we have developed a new catalytic approach
toward optically active 3,3′-disubstituted oxindoles via an
organocatalyzed decarboxylative stereoablation process. The
current process adopts β-ketoacids and 3-halooxindoles as
substrates and a demethylated quinidine derivative as catalyst.
The reaction provides a practical and valuable catalytic entry for
the enantioselective construction of a variety of 3,3′-
disubstituted oxindoles bearing a keto-carbonyl group in
moderate to good yields (up to 95%) and with high
enantioselectivities (up to 92% ee), which are not easily
accessible using other methodologies. Particularly, the readily
available substrates, reagents, and catalysts, and a simple
protocol with mild conditions, are among the attractive features
of this reaction.
b
c
entry
2
3
yield (%)
ee (%)
1
2
3
4
5
6
7
R = 4-MeC6H4 (2b)
R = 4-MeOC6H4 (2c)
R = 4-BrC6H4 (2d)
R = 3-ClC6H4 (2e)
R = 2-naphthyl (2f)
R = 2-thiophenyl (2g)
R = Me (2h)
3o
3p
3q
3r
3s
3t
86
86
81
50
94
91
72
87
86
90
83
89
82
80
3u
a
All reactions were performed by using 1a (0.1 mmol), 2 (0.12
mmol), K3PO4 (0.1 mmol), and E (0.02 mmol) in toluene (2.0 mL) at
room temperature for 15 h. Isolated yield. Determined by chiral
HPLC.
b
c
oxo-3-phenylpropanoic acid allowed the reaction to proceed
well and provided the expected product with moderate to good
yield and good enantioselectivity (Table 3, entries 1−4).
Nevertheless, β-ketoacids with a 2-naphthyl (2f) and a 2-
thiophenyl group (2g) were also tolerated (Table 3, entries 5
and 6). We also investigated the decarboxylative stereoablation
process of alkyl-substituted β-ketoacid-like 3-oxobutanoic acid
(2h). This substrate was found to be suitable for this
asymmetric transformation and provided the desired product
3u with acceptable results (Table 3, entry 7).
So far as the possible reaction mechanism was concerned, we
tried to conduct some preliminary experiments to obtain some
useful information. When only substrate 2a and a catalytic
amount of catalyst E were subjected to our standard reaction
conditions, substrate 2a was almost completely decomposed
and significant amounts of acetophenone were generated. This
suggests that the methyl ketone enolate is liable to be formed
via decarboxylation from β-ketoacids. On the other hand, when
the reaction of substrate 1a, ethyl 3-oxo-3-phenylpropanoate,
and a catalytic amount catalyst E was performed with toluene as
solvent at room temperature for 15 h, the substrate 1a
disappeared and the reaction presented greatly complexity.
Therefore, based on the above-noted experimental results and
some relevant reports,10 we proposed the following possible
reaction pathway for the enantioselective decarboxylative
stereoablation reaction of β-ketoacids and 3-halooxindoles
with demethylated quinidine derivative E as catalyst (Scheme
3). The tertiary amine part of E deprotonates the β-ketoacid 2,
EXPERIMENTAL SECTION
■
General Experimental Procedure for the Enantiose-
lective Decarboxylative Stereoablation Reaction be-
tween β-Ketoacids and 3-Halooxindoles Catalyzed by
E. A solution of 3-halooxindole 1 (0.1 mmol), β-ketoacid 2
(0.12 mmol), K3PO4 (0.1 mmol), and catalyst E (0.02 mmol)
in toluene (2 mL) was stirred at room temperature for 15 h.
Then the reaction mixture was directly charged onto a silica gel
column and purified through flash chromatography to furnish
the corresponding products 3.
(S)-3-Benzyl-3-(2-oxo-2-phenylethyl)indolin-2-one
20
(3a). Pale yellow solid, 31.0 mg, yield 91%; 90% ee, [α]D
=
1
+112.3 (c 1.35, CHCl3); mp 158.4−159.7 °C. H NMR (300
MHz, CDCl3), δ (ppm): 3.10 (d, J = 12.8 Hz, 1H), 3.19 (d, J =
12.8 Hz, 1H), 3.78 (d, J = 18.3 Hz, 1H), 3.84 (d, J = 18.3 Hz,
1H), 6.72 (d, J = 7.8 Hz, 1H), 6.90−6.99 (m, 4H), 7.09−7.13
(m, 4H), 7.41 (t, J = 7.5 Hz, 2H), 7.52 (d, J = 7.5 Hz, 1H), 7.86
(d, J = 7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3), δ (ppm):
44.0, 44.7, 51.1, 109.8, 121.3, 123.0, 126.6, 127.5, 127.7, 127.8,
128.3, 130.2, 131.3, 133.0, 134.9, 136.2, 141.6, 181.7, 195.9.
HRMS (ESI-TOF) calcd for C23H19NNaO2 [M + Na]+:
D
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Note
20
1
364.1308; found: 364.1318. HPLC analysis: Chiralcel AD-H
column, 2-propanol/hexane = 50:50, flow rate 1.0 mL/min, λ =
254 nm, tmajor = 16.5 min, tminor = 7.4 min.
ee, [α]D = +95.3 (c 1.50, CHCl3); mp 147.8−149.6 °C. H
NMR (300 MHz, CDCl3), δ (ppm): 3.09 (d, J = 12.9 Hz, 1H),
3.16 (d, J = 12.9 Hz, 1H), 3.75 (d, J = 18.0 Hz, 1H), 3.83 (d, J
= 18.0 Hz, 1H), 6.73 (d, J = 7.8 Hz, 1H), 6.81−6.85 (m, 2H),
6.95−7.12 (m, 5H), 7.41−7.54 (m, 3H), 7.85−8.00 (m, 3H);
13C NMR (75 MHz, CDCl3), δ (ppm): 43.7, 44.9, 51.1, 109.9,
121.8, 123.0, 126.9, 128.0, 128.1, 128.4, 128.5, 128.8, 130.2,
131.0, 133.3, 136.2, 136.9, 141.4, 181.0, 195.8. HRMS (ESI-
TOF) calcd for C23H18ClNNaO2 [M + Na]+: 398.0918; found:
398.0928. HPLC analysis: Chiralcel AD-H column, 2-
propanol/hexane = 50:50, flow rate 1.0 mL/min, λ = 254
nm, tmajor = 17.9 min, tminor = 7.0 min.
(S)-3-(4-Methylbenzyl)-3-(2-oxo-2-phenylethyl)-
indolin-2-one (3b). Pale yellow solid, 30.9 mg, yield 87%;
20
90% ee, [α]D = +90.2 (c 1.45, CHCl3); mp 152.5−154.0 °C.
1H NMR (300 MHz, CDCl3), δ (ppm): 2.25 (s, 3H), 3.04 (d, J
= 12.9 Hz, 1H), 3.14 (d, J = 12.9 Hz, 1H), 3.75 (d, J = 18.0 Hz,
1H), 3.83 (d, J = 18.0 Hz, 1H), 6.74 (d, J = 7.8 Hz, 1H), 6.80
(d, J = 7.8 Hz, 2H), 6.90−7.12 (m, 5H), 7.41 (t, J = 7.5 Hz,
2H), 7.50−7.55 (m, 2H), 7.86 (d, J = 7.2 Hz, 2H); 13C NMR
(75 MHz, CDCl3), δ (ppm): 21.0, 44.0, 45.0, 51.1, 109.6,
121.6, 123.2, 127.8, 128.0, 128.4, 128.5, 130.2, 131.6, 131.7,
133.2, 136.2, 136.3, 141.4, 181.3, 195.9. HRMS (ESI-TOF)
calcd for C24H21NNaO2 [M + Na]+: 378.1465; found:
378.1474. HPLC analysis: Chiralcel AD-H column, 2-
propanol/hexane = 50:50, flow rate 1.0 mL/min, λ = 254
nm, tmajor = 27.7 min, tminor = 7.4 min.
(S)-3-(2-Chlorobenzyl)-3-(2-oxo-2-phenylethyl)-
indolin-2-one (3g). Pale yellow solid, 34.2 mg, yield 91%;
91% ee, [α]D20 = +41.4 (c 1.60, CHCl3); mp 81.8−83.6 °C. 1H
NMR (300 MHz, CDCl3), δ (ppm): 3.15 (d, J = 13.5 Hz, 1H),
3.51 (d, J = 13.5 Hz, 1H), 3.88 (s, 2H), 6.80−6.87 (m, 3H),
7.10−7.15 (m, 4H), 7.27 (t, J = 4.5 Hz, 1H), 7.41 (t, J = 7.5 Hz,
2H), 7.52 (d, J = 7.2 Hz, 1H), 7.84−7.87 (m, 2H), 7.96 (br s,
1H); 13C NMR (75 MHz, CDCl3), δ (ppm): 40.0, 44.3, 50.8,
109.7, 121.4, 123.6, 126.2, 128.0, 128.3, 128.5, 129.4, 131.0,
132.5, 133.2, 133.3, 134.9, 136.2, 141.3, 181.8, 195.9. HRMS
(ESI-TOF) calcd for C23H18ClNNaO2 [M + Na]+: 398.0918;
found: 398.0925. HPLC analysis: Chiralcel AD-H column, 2-
propanol/hexane = 50:50, flow rate 1.0 mL/min, λ = 254 nm,
tmajor = 16.2 min, tminor = 7.9 min.
(S)-3-(3-Methylbenzyl)-3-(2-oxo-2-phenylethyl)-
indolin-2-one (3c). Pale yellow solid, 32.0 mg, yield 90%; 89%
20
1
ee, [α]D = +94.6 (c 1.50, CHCl3); mp 152.5−154.0 °C. H
NMR (300 MHz, CDCl3), δ (ppm): 2.20 (s, 3H), 3.04 (d, J =
12.9 Hz, 1H), 3.15 (d, J = 12.9 Hz, 1H), 3.77 (d, J = 18.3 Hz,
1H), 3.84 (d, J = 18.3 Hz, 1H), 6.71−6.75 (m, 3H), 6.90−7.01
(m, 4H), 7.09−7.14 (m, 1H), 7.41 (t, J = 7.5 Hz, 2H), 7.51−
7.53 (m, 1H), 7.86 (d, J = 8.1 Hz, 3H); 13C NMR (75 MHz,
CDCl3), δ (ppm): 21.1, 44.1, 44.8, 51.1, 109.7, 121.3, 123.1,
127.3, 127.4, 127.5, 127.7, 127.9, 128.4, 131.1, 131.5, 133.1,
134.8, 136.3, 137.0, 141.6, 181.6, 195.9. HRMS (ESI-TOF)
calcd for C24H21NNaO2 [M + Na]+: 378.1465; found:
378.1474. HPLC analysis: Chiralcel AD-H column, 2-
propanol/hexane = 50:50, flow rate 1.0 mL/min, λ = 254
nm, tmajor = 16.1 min, tminor = 6.5 min.
(S)-3-(3-Bromobenzyl)-3-(2-oxo-2-phenylethyl)-
indolin-2-one (3h). Pale yellow solid, 39.9 mg, yield 95%;
91% ee, [α]D = +73.7 (c 1.90, CHCl3); mp 112.1−113.9 °C.
20
1H NMR (300 MHz, CDCl3), δ (ppm): 3.20 (d, J = 13.5 Hz,
1H), 3.50 (d, J = 13.5 Hz, 1H), 3.90 (s, 2H), 6.80−6.88 (m,
3H), 7.11−7.16 (m, 4H), 7.41−7.52 (m, 4H), 7.84−7.87 (m,
3H); 13C NMR (75 MHz, CDCl3), δ (ppm): 42.4, 44.3, 50.8,
109.7, 121.4, 123.7, 126.0, 126.8, 128.0, 128.5, 128.6, 131.0,
132.4, 132.8, 133.2, 135.1, 136.2, 141.4, 181.9, 195.9. HRMS
(ESI-TOF) calcd for C23H18BrNNaO2 [M + Na]+: 442.0413;
found: 442.0425. HPLC analysis: Chiralcel AD-H column, 2-
propanol/hexane = 50:50, flow rate 1.0 mL/min, λ = 254 nm,
tmajor = 16.4 min, tminor = 8.3 min.
(S)-3-(2-Methylbenzyl)-3-(2-oxo-2-phenylethyl)-
indolin-2-one (3d). Pale yellow solid, 33.1 mg, yield 93%;
89% ee, [α]D20 = +102.2 (c 1.55, CHCl3); mp 150.6−152.2 °C.
1H NMR (300 MHz, CDCl3), δ (ppm): 1.98 (s, 3H), 3.11 (d, J
= 13.5 Hz, 1H), 3.20 (d, J = 13.5 Hz, 1H), 3.81 (d, J = 18.0 Hz,
1H), 3.92 (d, J = 18.0 Hz, 1H), 6.71−6.84 (m, 3H), 7.00−7.14
(m, 5H), 7.41−7.53 (m, 4H), 7.84−7.87 (m, 2H); 13C NMR
(75 MHz, CDCl3), δ (ppm): 19.7, 40.1, 44.5, 50.8, 109.8,
121.4, 123.2, 125.2, 126.9, 127.9, 128.0, 128.5, 130.4, 130.9,
131.4, 133.2, 133.8, 136.3, 137.7, 141.5, 182.3, 195.9. HRMS
(ESI-TOF) calcd for C24H21NNaO2 [M + Na]+: 378.1465;
found: 378.1476. HPLC analysis: Chiralcel AD-H column, 2-
propanol/hexane = 50:50, flow rate 1.0 mL/min, λ = 254 nm,
tmajor = 13.3 min, tminor = 7.3 min.
(S)-3-(4-Chlorobenzyl)-3-(2-oxo-2-phenylethyl)-
indolin-2-one (3e). Pale yellow solid, 33.1 mg, yield 88%;
87% ee, [α]D20 = +99.9 (c 1.55, CHCl3); mp 82.2−84.1 °C. 1H
NMR (300 MHz, CDCl3), δ (ppm): 3.09 (d, J = 12.6 Hz, 1H),
3.15 (d, J = 12.6 Hz, 1H), 3.74 (d, J = 18.0 Hz, 1H), 3.83 (d, J
= 18.0 Hz, 1H), 6.71 (d, J = 7.8 Hz, 1H), 6.80 (d, J = 8.4 Hz,
2H), 6.96 (d, J = 7.5 Hz, 1H), 7.04−7.13 (m, 4H), 7.39−7.54
(m, 4H), 7.85−7.87 (m, 2H); 13C NMR (75 MHz, CDCl3), δ
(ppm): 43.5, 45.0, 51.2, 109.9, 121.8, 123.0, 127.8, 128.0, 128.1,
128.5, 128.9, 131.1, 131.5, 132.7, 133.3, 136.3, 141.5, 181.1,
195.8. HRMS (ESI-TOF) calcd for C23H18ClNNaO2 [M +
Na]+: 398.0918; found: 398.0925. HPLC analysis: Chiralcel
OD-H column, 2-propanol/hexane = 10:90, flow rate 1.0 mL/
min, λ = 254 nm, tmajor = 18.0 min, tminor = 16.5 min.
(S)-3-(2-Bromobenzyl)-3-(2-oxo-2-phenylethyl)-
indolin-2-one (3i). Pale yellow solid, 39.1 mg, yield 93%; 89%
20
1
ee, [α]D = +38.3 (c 1.85, CHCl3); mp 86.9−88.8 °C. H
NMR (300 MHz, CDCl3), δ (ppm): 3.08 (d, J = 12.9 Hz, 1H),
3.14 (d, J = 12.9 Hz, 1H), 3.75 (d, J = 18.0 Hz, 1H), 3.83 (d, J
= 18.0 Hz, 1H), 6.72 (d, J = 5.7 Hz, 1H), 6.84 (d, J = 7.5 Hz,
1H), 6.94−7.26 (m, 6H), 7.42 (t, J = 7.5 Hz, 3H), 7.52−7.54
(m, 1H), 7.85−7.88 (m, 2H); 13C NMR (75 MHz, CDCl3), δ
(ppm): 43.6, 44.8, 51.1, 109.9, 121.5, 121.7, 123.0, 127.9, 128.1,
128.5, 128.9, 129.1, 129.8, 130.9, 133.1, 133.2, 136.2, 137.1,
141.5, 181.0, 195.8. HRMS (ESI-TOF) calcd for
C23H18BrNNaO2 [M + Na]+: 442.0413; found: 442.0415.
HPLC analysis: Chiralcel AD-H column, 2-propanol/hexane =
50:50, flow rate 1.0 mL/min, λ = 254 nm, tmajor = 19.1 min,
tminor = 7.1 min.
(S)-3-(Naphthalen-1-ylmethyl)-3-(2-oxo-2-
phenylethyl)indolin-2-one (3j). Pale yellow solid, 37.2 mg,
20
yield 95%; 89% ee, [α]D = +113.3 (c 1.75, CHCl3); mp
176.4−178.3 °C. 1H NMR (300 MHz, CDCl3), δ (ppm): 3.54
(d, J = 13.8 Hz, 1H), 3.71 (d, J = 13.8 Hz, 1H), 3.82 (d, J =
18.0 Hz, 1H), 3.91 (d, J = 18.0 Hz, 1H), 6.72 (m, 3H), 7.12−
7.15 (m, 2H), 7.28−7.51 (m, 7H), 7.71−8.42 (m, 5H); 13C
NMR (75 MHz, CDCl3), δ (ppm): 39.5, 44.6, 51.1, 109.7,
121.3, 123.8, 124.5, 124.7, 125.3, 125.4, 127.7, 127.8, 127.9,
(S)-3-(3-Chlorobenzyl)-3-(2-oxo-2-phenylethyl)-
indolin-2-one (3f). Pale yellow solid, 31.9 mg, yield 85%; 89%
E
dx.doi.org/10.1021/jo302048v | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
128.3, 128.4, 129.1, 131.5, 131.7, 132.7, 133.2, 133.6, 136.3,
141.4, 182.0, 195.9. HRMS (ESI-TOF) calcd for C27H21NNaO2
[M + Na]+: 414.1465; found: 414.1476. HPLC analysis:
Chiralcel AD-H column, 2-propanol/hexane = 50:50, flow rate
1.0 mL/min, λ = 254 nm, tmajor = 16.2 min, tminor = 8.6 min.
(S)-3-(2-Oxo-2-phenylethyl)-3-(thiophen-2-ylmethyl)-
indolin-2-one (3k). Pale yellow solid, 29.9 mg, yield 86%;
MHz, CDCl3), δ (ppm): 2.37 (s, 3H), 3.09 (d, J = 12.9 Hz,
1H), 3.20 (d, J = 12.9 Hz, 1H), 3.75 (d, J = 18.0 Hz, 1H), 3.82
(d, J = 18.0 Hz, 1H), 6.71 (d, J = 7.8 Hz, 1H), 6.72−6.94 (m,
3H), 6.99 (d, J = 6.9 Hz, 1H), 7.06−7.13 (m, 4H), 7.20 (d, J =
8.1 Hz, 2H), 7.76 (d, J = 8.1 Hz, 2H), 8.29 (br, 1H); 13C NMR
(75 MHz, CDCl3), δ (ppm): 21.6, 44.3, 44.8, 51.2, 109.7,
121.5, 123.1, 126.7, 127.6, 127.8, 128.1, 129.1, 130.3, 131.5,
133.9, 134.9, 141.5, 144.0, 181.4, 195.5. HRMS (ESI-TOF)
calcd for C24H22NO2 [M + H]+: 356.1645; found: 356.1646.
HPLC analysis: Chiralcel OD-H column, 2-propanol/hexane
=10:90, flow rate 1.0 mL/min, λ = 254 nm, tmajor = 14.0 min,
tminor = 36.6 min.
(S)-3-Benzyl-3-(2-(4-methoxyphenyl)-2-oxoethyl)-
indolin-2-one (3p). Pale yellow solid, 31.8 mg, yield 86%;
86% ee, [α]D20 = +111.7 (c 1.50, CHCl3); mp 158.8−160.6 °C.
1H NMR (300 MHz, CDCl3), δ (ppm): 3.08 (d, J = 12.9 Hz,
1H), 3.18 (d, J = 12.9 Hz, 1H), 3.75−3.76 (m, 2H), 3.83 (s,
3H), 6.70 (d, J = 7.8 Hz, 1H), 6.85−6.98 (m, 6H), 7.07−7.13
(m, 4H), 7.84 (d, J = 9.0 Hz, 2H), 8.00 (br s, 1H); 13C NMR
(75 MHz, CDCl3), δ (ppm): 44.3, 44.6, 51.2, 55.4, 109.6,
113.6, 121.5, 123.2, 126.7, 127.6, 127.8, 129.5, 130.2, 130.3,
131.5, 135.0, 141.4, 163.5, 181.2, 194.4. HRMS (ESI-TOF)
calcd for C24H22NO3 [M + H]+: 372.1594; found: 372.1594.
HPLC analysis: Chiralcel AD-H column, 2-propanol/hexane =
40:60, flow rate 1.0 mL/min, λ = 254 nm, tmajor = 71.1 min,
tminor = 14.2 min.
20
89% ee, [α]D = +68.4 (c 1.40, CHCl3); mp 156.3−158.2 °C.
1H NMR (300 MHz, CDCl3), δ (ppm): 3.35 (d, J = 14.1 Hz,
1H), 3.42 (d, J = 14.1 Hz, 1H), 3.74 (d, J = 18.0 Hz, 1H), 3.87
(d, J = 18.0 Hz, 1H), 6.65 (d, J = 2.7 Hz, 1H), 6.79−6.83 (m,
2H), 6.96−7.18 (m, 4H), 7.39−7.77 (m, 4H), 7.87 (d, J = 7.5
Hz, 2H); 13C NMR (75 MHz, CDCl3), δ (ppm): 38.3, 44.9,
51.0, 109.7, 121.9, 123.3, 124.7, 126.4, 127.7, 128.0, 128.2,
128.6, 131.3, 133.3, 136.3, 136.4, 141.7, 180.7, 195.7. HRMS
(ESI-TOF) calcd for C21H18NO2S [M + H]+: 348.1053; found:
348.1050. HPLC analysis: Chiralcel AD-H column, 2-
propanol/hexane = 50:50, flow rate 1.0 mL/min, λ = 254
nm, tmajor = 13.9 min, tminor = 8.1 min.
(S)-3-Benzyl-4-chloro-3-(2-oxo-2-phenylethyl)indolin-
2-one (3l). Pale yellow solid, 34.2 mg, yield 91%; 82% ee,
20
1
[α]D = +112.5 (c 1.60, CHCl3); mp 191.2−192.4 °C. H
NMR (300 MHz, CDCl3), δ (ppm): 3.17 (d, J = 12.6 Hz, 1H),
3.56 (d, J = 12.6 Hz, 1H), 3.75 (d, J = 18.3 Hz, 1H), 4.52 (d, J
= 18.3 Hz, 1H), 6.50 (d, J = 7.8 Hz, 1H), 6.90−6.94 (m, 3H),
6.99−7.06 (m, 4H), 7.41−7.56 (m, 4H), 7.90−7.93 (m, 2H);
13C NMR (75 MHz, CDCl3), δ (ppm): 41.1, 44.2, 53.1, 108.2,
122.7, 126.7, 127.5, 127.6, 128.1, 128.5, 129.2, 129.5, 129.6,
133.3, 134.4, 136.0, 143.4, 180.1, 196.3. HRMS (ESI-TOF)
calcd for C23H19ClNO2 [M + H]+: 376.1099; found: 376.1088.
HPLC analysis: Chiralcel OD-H column, 2-propanol/hexane
=10:90, flow rate 1.0 mL/min, λ = 254 nm, tmajor = 11.6 min,
tminor = 19.7 min.
(S)-3-Benzyl-3-(2-(4-bromophenyl)-2-oxoethyl)-
indolin-2-one (3q). Pale yellow solid, 34.2 mg, yield 81%;
20
90% ee, [α]D = +69.4 (c 1.6, CHCl3); mp 212.8−214.6 °C.
1H NMR (300 MHz, CDCl3), δ (ppm): 3.08 (d, J = 12.9 Hz,
1H), 3.17 (d, J = 12.9 Hz, 1H), 3.75 (s, 2H), 6.71 (d, J = 7.8
Hz, 1H), 6.90−7.00 (m, 4H), 7.08−7.13 (m, 4H), 7.54 (d, J =
8.4 Hz, 2H), 7.70 (d, J = 8.4 Hz, 2H), 8.02 (br s, 1H); 13C
NMR (75 MHz, CDCl3), δ (ppm): 44.3, 44.9, 51.1, 109.7,
121.7, 123.1, 126.8, 127.7, 128.0, 128.5, 129.5, 130.3, 131.2,
131.8, 134.7, 135.0, 141.4, 181.0, 194.9. HRMS (ESI-TOF)
calcd for C23H19BrNO2 [M + H]+: 420.0594; found: 420.0584.
HPLC analysis: Chiralcel OD-H column, 2-propanol/hexane
=10:90, flow rate 1.0 mL/min, λ = 254 nm, tmajor = 13.8 min,
tminor = 20.8 min.
(S)-3-Benzyl-5-bromo-3-(2-oxo-2-phenylethyl)indolin-
2-one (3m). Pale yellow solid, 37.0 mg, yield 88%; 87% ee,
20
1
[α]D = +119.4 (c 1.75, CHCl3); mp 206.8−208.2 °C. H
NMR (300 MHz, CDCl3), δ (ppm): 3.08 (d, J = 12.9 Hz, 1H),
3.14 (d, J = 12.9 Hz, 1H), 3.81 (s, 2H), 6.60 (d, J = 8.1 Hz,
1H), 6.90−6.92 (m, 2H), 7.10−7.24 (m, 5H), 7.43−7.56 (m,
4H), 7.85−7.88 (m, 2H); 13C NMR (75 MHz, CDCl3), δ
(ppm): 44.3, 45.0, 51.4, 111.2, 114.2, 126.2, 127.0, 127.8, 128.0,
128.6, 128.8, 129.2, 130.3, 130.7, 133.4, 133.8, 134.3, 136.0,
140.7, 181.2, 195.7. HRMS (ESI-TOF) calcd for C23H19BrNO2
[M + H]+: 420.0594; found: 420.0583. HPLC analysis:
Chiralcel AD-H column, 2-propanol/hexane = 50:50, flow
rate 1.0 mL/min, λ = 254 nm, tmajor = 12.9 min, tminor = 6.4 min.
(S)-3-Benzyl-3-(2-(3-chlorophenyl)-2-oxoethyl)-
indolin-2-one (3r). Pale yellow solid, 18.8 mg, yield 50%; 83%
20
1
ee, [α]D = +92.4 (c 0.65, CHCl3); mp 156.7−158.4 °C. H
NMR (300 MHz, CDCl3), δ (ppm): 3.09 (d, J = 12.9 Hz, 1H),
3.17 (d, J = 12.9 Hz, 1H), 3.76 (s, 2H), 6.71 (d, J = 7.8 Hz,
1H), 6.89−7.02 (m, 4H), 7.10−7.15 (m, 4H), 7.36 (t, J = 7.8
Hz, 1H), 7.50 (d, J = 7.8 Hz, 1H), 7.62 (br s, 1H), 7.73 (d, J =
7.8 Hz, 1H), 7.82 (s, 1H); 13C NMR (75 MHz, CDCl3), δ
(ppm): 44.4, 45.1, 51.1, 109.6, 121.8, 123.1, 126.1, 126.9, 127.7,
128.0, 128.1, 129.9, 130.3, 131.2, 133.2, 134.6, 134.9, 137.8,
141.3, 180.7, 194.6. HRMS (ESI-TOF) calcd for C23H19ClNO2
[M + H]+: 376.1099; found: 376.1099. HPLC analysis:
Chiralcel OD-H column, 2-propanol/hexane =10:90, flow
rate 1.0 mL/min, λ = 254 nm, tmajor = 14.4 min, tminor = 12.9
min.
(S)-3-Allyl-3-(2-oxo-2-phenylethyl)indolin-2-one (3n).
20
Pale yellow solid, 26.2 mg, yield 90%; 89% ee, [α]D
=
1
+44.1 (c 1.20, CHCl3); mp 160.5−162.1 °C. H NMR (300
MHz, CDCl3), δ (ppm): 2.50−2.66 (m, 2H), 3.62−3.81 (m,
2H), 5.05−5.13 (m, 2H), 5.57−5.66 (m, 1H), 6.90−6.97 (m,
2H), 7.10 (d, J = 7.2 Hz, 1H), 7.18 (t, J = 7.5 Hz, 1H), 7.40 (t, J
= 7.6 Hz, 2H), 7.53 (t, J = 7.2 Hz, 1H), 7.86 (d, J = 7.2 Hz,
2H), 8.05 (br s, 1H); 13C NMR (75 MHz, CDCl3), δ (ppm):
42.6, 44.6, 49.6, 109.8, 119.6, 121.9, 122.6, 127.9, 128.0, 128.5,
131.5, 132.1, 133.2, 136.3, 141.4, 181.4, 196.0. HRMS (ESI-
TOF) calcd for C19H17NNaO2 [M + Na]+: 314.1151; found:
314.1156. HPLC analysis: Chiralcel AD-H column, 2-
propanol/hexane = 50:50, flow rate 1.0 mL/min, λ = 254
nm, tmajor = 10.9 min, tminor = 6.6 min.
(S)-3-Benzyl-3-(2-(naphthalen-2-yl)-2-oxoethyl)-
indolin-2-one (3s). Pale yellow solid, 36.7 mg, yield 94%; 89%
20
1
ee, [α]D = +138.1 (c 1.75, CHCl3); mp 178.2−179.9 °C. H
NMR (300 MHz, CDCl3), δ (ppm): 3.16 (d, J = 12.9 Hz, 1H),
3.26 (d, J = 12.9 Hz, 1H), 3.91 (d, J = 17.7 Hz, 1H), 3.99 (d, J
= 17.7 Hz, 1H), 6.73 (d, J = 7.8 Hz, 1H), 6.93−6.96 (m, 3H),
7.06−7.15 (m, 5H), 7.56−7.93 (m, 6H), 8.03 (s, 1H), 8.42 (s,
1H); 13C NMR (75 MHz, CDCl3), δ (ppm): 45.3, 46.1, 52.4,
(S)-3-Benzyl-3-(2-oxo-2-(p-tolyl)ethyl)indolin-2-one
20
(3o). Pale yellow solid, 30.6 mg, yield 86%; 87% ee, [α]D
=
1
+114.5 (c 1.40, CHCl3); mp 140.9−143.2 °C. H NMR (300
F
dx.doi.org/10.1021/jo302048v | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
110.6, 122.6, 124.2, 124.6, 127.7, 128.6, 128.7, 128.9, 129.4,
129.5, 130.5, 130.7, 131.3, 132.4, 133.2, 134.7, 135.9, 136.6,
142.4, 182.2, 196.9. HRMS (ESI-TOF) calcd for C27H22NO2
[M + H]+: 392.1645; found: 392.1641. HPLC analysis:
Chiralcel AD-H column, 2-propanol/hexane = 50:50, flow
rate 1.0 mL/min, λ = 254 nm, tmajor = 108.7 min, tminor = 10.4
min.
(S)-3-Benzyl-3-(2-oxo-2-(thiophen-2-yl)ethyl)indolin-
2-one (3t). Pale yellow solid, 31.6 mg, yield 91%; 82% ee,
[α]D20 = +73.9 (c 1.50, CHCl3); mp 173.4−175.3 °C. 1H NMR
(300 MHz, CDCl3), δ (ppm): 3.09 (d, J = 12.9 Hz, 1H), 3.20
(d, J = 12.9 Hz, 1H), 3.71 (s, 2H), 6.71−6.92 (m, 4H), 7.03−
7.12 (m, 6H), 7.57 (d, J = 4.8 Hz, 1H), 7.68 (m, 1H), 8.23 (br
s, 1H); 13C NMR (75 MHz, CDCl3), δ (ppm): 44.0, 45.3, 51.3,
109.7, 121.6, 123.4, 126.7, 127.6, 127.9, 128.0, 130.3, 131.0,
132.1, 133.8, 134.8, 141.4, 143.6, 181.0, 188.9. HRMS (ESI-
TOF) calcd for C21H18NO2S [M + H]+: 348.1053; found:
348.1057. HPLC analysis: Chiralcel AD-H column, 2-
propanol/hexane = 30:70, flow rate 1.0 mL/min, λ = 254
nm, tmajor = 16.3 min, tminor = 12.0 min.
Western Light Talent Culture Project, and Sichuan Youth
Science and Technology Foundation.
REFERENCES
■
(1) For selected reviews, see: (a) Dounay, A. B.; Overman, L. E.
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(S)-3-Benzyl-3-(2-oxopropyl)indolin-2-one (3u). Color-
20
less oil, 20.0 mg, yield 72%; 80% ee, [α]D = +54.0 (c 0.9,
CHCl3). 1H NMR (300 MHz, CDCl3), δ (ppm): 2.01 (s, 3H),
2.96 (d, J = 12.9 Hz, 1H), 3.06 (d, J = 12.9 Hz, 1H), 3.15 (d, J
= 17.7 Hz, 1H), 3.25 (d, J = 17.7 Hz, 1H), 6.69 (d, J = 7.8 Hz,
1H), 6.85 (t, J = 4.5 Hz, 2H), 6.95−7.00 (m, 2H), 7.05−7.14
(m, 4H), 8.15 (br s, 1H); 13C NMR (75 MHz, CDCl3), δ
(ppm): 30.1, 43.9, 49.4, 51.1, 109.7, 121.7, 123.2, 126.7, 127.6,
128.0, 130.2, 131.1, 134.8, 141.3, 181.0. HRMS (ESI-TOF)
calcd for C18H18NO2 [M + H]+: 280.1332; found: 280.1341.
HPLC analysis: Chiralcel AD-H column, 2-propanol/hexane =
30:70, flow rate 1.0 mL/min, λ = 254 nm, tmajor = 9.3 min, tminor
= 8.4 min.
(4) For selected examples, see: (a) Hanhan, N. V.; Sahin, A. H.;
Chang, T. W.; Fettinger, J. C.; Franz, A. K. Angew. Chem., Int. Ed.
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Y.-W.; Li, X.-C.; Zhong, L.-Z.; Peng, Y.-G. J. Org. Chem. 2012, 77,
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W.; Chen, Y.-C. Org. Lett. 2008, 10, 3583. (b) Duan, S.-W.; An, J.;
Chen, J.-R.; Xiao, W.-J. Org. Lett. 2011, 13, 2290. (c) Trost, B. M.; Xie,
J.; Sieber, J. D. J. Am. Chem. Soc. 2011, 133, 20611. (d) Bergonzini, G.;
Melchiorre, P. Angew. Chem., Int. Ed. 2012, 51, 971.
(6) (a) Ma, S.; Han, X.; Krishnan, S.; Virgil, S. C.; Stoltz, B. M.
Angew. Chem., Int. Ed. 2009, 48, 8037. (b) Peng, J.; Huang, X.; Cui, H.-
L.; Chen, Y.-C. Org. Lett. 2010, 12, 4260. (c) Guo, C.; Song, J.; Huang,
J.-Z.; Chen, P.-H.; Luo, S.-W.; Gong, L.-Z. Angew. Chem., Int. Ed. 2012,
51, 1046. (d) Song, L.; Guo, Q.-X.; Li, X.-C.; Tian, J.; Peng, Y.-G.
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Zhong, F.; Lu, Y. Org. Lett. 2012, 14, 3955.
(S)-3-(2-Oxo-2-phenylethyl)-3-phenylindolin-2-one
(3v):14 White solid, 22.6 mg, yield 69%; 77% ee, [α]D
=
20
1
+156.6 (c 1.13, CHCl3); mp 200.6−202.2 °C. H NMR (300
MHz, CDCl3), δ (ppm): 4.11 (d, J = 18.0 Hz, 1H), 4.20 (d, J =
18.0 Hz, 1H), 6.95−7.01 (m, 2H), 7.23−7.32 (m, 5H), 7.40−
7.53 (m, 5H), 7.87−7.90 (m, 2H), 8.23 (s, 1H); 13C NMR (75
MHz, CDCl3), δ (ppm): 46.8, 53.5, 110.1, 122.2, 124.4, 126.7,
127.6, 128.0, 128.3, 128.6, 128.7, 132.2, 133.3, 136.3, 139.4,
141.7, 180.3, 195.8. HPLC analysis: Chiralcel OD-H column, 2-
propanol/hexane = 10:90, flow rate 1.0 mL/min, λ = 254 nm,
tmajor = 45.6 min, tminor = 26.8 min.
(7) Liao, Y.-H.; Wu, Z.-J.; Han, W.-Y.; Zhang, X.-M.; Yuan, W.-C.
Chem.Eur. J. 2012, 18, 8916.
ASSOCIATED CONTENT
* Supporting Information
(8) For a review, see: Mohr, J. T.; Ebner, D. C.; Stoltz, B. M. Org.
Biomol. Chem. 2007, 5, 3571.
■
S
(9) Pan, Y.; Tan, C.-H. Synthesis 2011, 2044 and references therein..
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129, 11583. (b) Rohr, K.; Mahrwald, R. Org. Lett. 2011, 13, 1878.
(c) Yang, C.-F.; Shen, C.; Wang, J.-Y.; Tian, S.-K. Org. Lett. 2012, 14,
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X-ray crystallographic data (CIF file of 3g) and detailed spectral
data for products. This material is available free of charge via
the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: yuanwc@cioc.ac.cn
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Author Contributions
§These authors contributed equally.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We are grateful for financial support from National Basic
Research Program of China (973 Program) (2010CB833300),
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dx.doi.org/10.1021/jo302048v | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
Y.; Chen, W.-B.; Han, W.-Y.; Wu, Z.-J.; Zhang, X.-M.; Yuan, W.-C.
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L.; Zhang, X.-M.; Yuan, W.-C. Chem.Eur. J. 2012, 18, 6679. (i) Han,
Y.-Y.; Han, W.-Y.; Hou, X.; Zhang, X.-M.; Yuan, W.-C. Org. Lett. 2012,
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(13) See the Supporting Information for details of crystallographic
data.
(14) Ruce, J. M.; Sutcliffe, F. K. J. Chem. Soc. 1957, 4789.
H
dx.doi.org/10.1021/jo302048v | J. Org. Chem. XXXX, XXX, XXX−XXX