Cu(OTf)2-catalyzed asymmetric friedel-crafts alkylation reaction of indoles with arylidene malonates using bis(sulfonamide)-diamine ligands

Article abstract of DOI:10.1021/jo400747d

A highly efficient Cu-catalyzed asymmetric Friedel-Crafts alkylation reaction of indoles with arylidene malonates using simple, stable, and easily prepared bis-sulfonamide diamine ligands was developed. The desired products were obtained in up to 99% yiel

Full text of DOI:10.1021/jo400747d

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Article
Cu(OTf)2-Catalyzed Asymmetric Friedel-Crafts Alkylation Reaction of
Indoles with Arylidene Malonates Using Bis(sulfonamide)-Diamine Ligands
Jing Wu, Dongping Wang, Fan Wu, and Boshun Wan
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/jo400747d • Publication Date (Web): 03 May 2013
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Cu(OTf)2-Catalyzed Asymmetric Friedel-Crafts Alkylation Reaction of Indoles
with Arylidene Malonates Using Bis(sulfonamide)-Diamine Ligands
Jing Wu, Dongping Wang, Fan Wu, and Boshun Wan*
Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian
116023, China
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*E-mail: bswan@dicp.ac.cn
ABSTRACT
A highly efficient Cu-catalyzed asymmetric Friedel-Crafts alkylation reaction of
indoles with arylidene malonates using simple, stable and easily prepared
bis-sulfonamide diamine ligands was developed. The desired products were obtained
with up to 99% yield and 96% ee.
INTRODUCTION
Chiral indole architectures have been identified as privileged compounds due to their
common occurrence in a wide variety of medicinal chemistry lead compounds as well
as bioactive nature products.1 During the past decades, asymmetric Friedel-Crafts
alkylation reaction of indoles is one of the most powerful methodologies to provide
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optical active indole derivatives.2 Meanwhile, enantioselective Friedel-Crafts
alkylation of indoles with alkylidene malonates is intriguing. In 2001, C2-symmetric
chiral bis(oxazoline) 1-Cu(II) catalyst was used in the pioneering work of Jørgensen
and coworkers3 providing good yields and moderate enantioselectives. Subsequently,
impressive improvement was achieved by Tang’s group4 using pseudo-C3-symmetric
tris(oxazoline) ligand 2 in which an additional oxazoline moiety coordinated with the
copper center in an apical position affording high enantioselectivities (up to 93% ee).
Furthermore, Reiser et al.5 disclosed that meticulously tuning the ratio of
azabis(oxazoline) ligand 3/Cu(II) played a vital role in obtaining excellent
enantioselectivity in this reaction. Heteroarylidenemalonate-derived bis(oxazoline)
4-Cu(II) developed by Fu et al.6 could also serve as an efficient catalyst for this
transformation. Recently, Feng et al.7 found that N, N’-dioxide scandium(III)
complexes could effectively promote asymmetric Friedel-Crafts alkylation of indoles
with arylidene malonates. Although tremendous efforts have been devoted and
considerable progress have been made, the catalysts involved therein were limited to
bis- or trisoxazoline8-Cu(II) complexes and N, N’-dioxide9 5-scandium(III) complexes.
Given the great utility of this reaction, exploring efficient alternative catalysts
especially developing simple, stable, readily available chiral ligands is still highly
desirable.
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Scheme 1. Ligands Reported in the Asymmetric Friedel-Crafts Alkylation of
Indoles with Alkylidene Malonates
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Our recently developed chiral bis-sulfonamide diamine ligands, as a type of
simple, cheap, easily prepared and stable ligands, with their metal complexes were
described to be effective catalysts for enantioselective and diastereoselctive Henry
reaction10 as well as asymmetic Friedel-Crafts addition of indole to nitroalkenes11.
As a part of our continuing interest and ongoing research in making bis-sulfonamide
diamine ligands as structurally versatile and widely applicable ligands, we
demostrated herein the highly effective Cu-catalyzed asymmetric Friedel-Crafts
alkylation reaction of indoles with arylidene malonates using bis-sulfonamide diamine
ligands affording the products with up to 99% yield and 96% ee.
Scheme 2. Bis(sulfonamide)-diamine Ligands
RESULTS AND DISCUSSION
In order to determine the optimal reaction condition, initial studies were conducted
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between model substrates of indole 6a and benzylidene malonate 7a. Some
representative results were summarized in Table 1. Treatment of this reaction with
different copper salts revealed that only Cu(OTf)2 and Cu(ClO4)2·6H2O promoted the
reaction with promising results in the presence of bis-sulfonamide diamine ligand L1
derived from (1R,2R)-1,2-diphenylethylenediamine. Cu(OTf)2 displayed greater
competence in comparison to Cu(ClO4)2·6H2O providing desired product with 90%
yield and 60% ee (Table 1, entries 1 and 2). Further optimization of the reaction
condition focusing on screening the structure of bis-sulfonamide diamine ligands
indicated that different substituents R1 and R2 of the bis-sulfonamide diamine ligand
had a dramatic effect on both the reactivity and enantioselectivity of this
transformation (Table 1, entries 3–6). To our disappointment, when ligand L2 with R2
as phenyl group was used which showed the best performance in the previous work of
asymmetic Friedel-Crafts addition of indole to nitroalkenes, only racemic product was
obtained with 73% yield (Table 1, entry 3). Better results were observed when
substituent R2 was alkyl group (Table 1, entries 1, 4, 5, 6). Delightedly, significant
enhancement of the enantioselectivity was obtained when substituent R2 as benzyl
group was employed, providing the desired product with 95% yield and 82% ee
(Table 1, entry 6). Sequential investigation on modifying the substituent R1 group
indicated that the ligand containing (1R,2R)-cyclohexane-1,2-diamine moiety or
(1S,2S)-1,2-diphenylethylenediamine moiety showed poor induction on the level of
enantioselctivity (Table 1, entries 7 and 8). Evaluation on the effect of solvents
showed that alcohol was more appropriate solvent and isobutyl alcohol turned out to
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be the best choice (Table 1, entry 13). Subsequently, decreasing the temperature to
0 °C slightly improved the enantioselectivity (Table 1, entry 15). Further
improvement of the enantioselectivity was observed when meticulously tuning the
ligand/metal ratio to 1.1/1.0 (Table 1, entry 16).
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Table 1. Optimization of Reaction Conditionsa
Entry
1
Ligand
L1
X in CuX2
OTf
Solvent
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
MeOH
iPrOH
nPrOH
nBuOH
iBuOH
Yield (%)
90
Ee (%)b
60
2
L1
ClO4
OTf
96
38
3
L2
73
0
4
L3
OTf
97
13 (-)
69
5
L4
OTf
98
6
L5
OTf
95
82
7
L6
OTf
89
0
8
L7
OTf
99
30
9
L5
OTf
86
59
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13
L5
OTf
99
77
L5
OTf
99
86
L5
OTf
99
83
L5
OTf
98
89
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L5
L5
L5
OTf
OTf
OTf
tBuOH
iBuOH
iBuOH
97
99
98
78
92
95
15 c
16 c d
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a Unless otherwise noted, all reactions were performed with indole 6a (0.25 mmol)
and benzylidene malonate 7a (0.3 mmol) with 5 mol % catalyst {CuX2 (5 mol %),
b
ligand (according to the metal/ligand ratio)} in 1 mL solvent for 6–12 h.
Determined by chiral HPLC analysis. c The reaction was performed at 0 °C. The
d
reaction was performed when ligand/metal ratio was 1.1/1.0.
With the optimized reaction conditions established, we next sought to explore the
generality of this transformation. Various structurally different arylidene malonates
and indoles were evaluated (Table 2). Both electronic property and steric hindrance
on arylidene malonate was tolerated (Table 2, entries 8a–8m). The reaction proceed
smoothly and afforded the corresponding products in excellent yields and
enantioselectivities, regardless of electron-withdrawing or electron-donating groups
on the para- (Table 2, 8b–8g), meta- (Table 2, 8h–8j) or ortho-position (Table 2,
8k–8m) of the phenyl ring in arylidene malonate. In addition, disubstituted,
condensed-ring and heterocyclic arylidene malonates also served as competent
substrates for this transformation albeit with slightly lower enantioselctivities (Table 2,
8n–8p). Unfortunately, when ethylidene malonate was employed, the reaction
proceeded with 98% yield and only 34% ee (Table 2, 8q). Meanwhile, the substituents
on the indolyl scaffold were investigated. High yields and enantioselectivities were
achieved in the case of indoles containing electron-withdrawing or electron-donating
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groups at 5, 6 or 7 position (Table 2, 8r–8u).
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Table 2. Cu-Catalyzed Asymmetric Friedel-Crafts Alkylation of Indoles 6 with
Various Arylidiene Malonates 7 a,b,c
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a
Unless otherwise noted, all reactions were performed with indole 6 (0.25
mmol) and aryldiene malonate 7 (0.3 mmol) with 5 mol% Cu(OTf)2, and 5.5
b
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mol% L5 in 1 mL solvent at 0 °C. Determined by chiral HPLC analysis.
Determined to be S by comparison of optical rotation with that in ref 5a.
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To elucidate the mechanism and clarify the observed sense of asymmetric
induction, we tried to cultivate the single crystal of bis-sulfonamide diamine ligand
L5/Cu(II) complex in various solvents but failed. Fortunately, we examined the
composition of catalyst by ESI-MS and found that the MS peak at 998.2078 could be
assigned as [L5-Cu(OTf)]+ (m/z calculated for [C47H50N4O7S3CuF3]+: 998.2084, (See
supporting information). Subsequently, control experiment of N-methyl indole with
benzylidene malonate 7a was conducted under the optimal reaction condition to
produce the corresponding product 8v with 95% yield and only 64% ee (Scheme 3),
which indicated that the indolic proton play a vital role for the enantioselectivity. In
addition, screening of the ligands showed that (1R,2R)-1,2-diphenylethylenediamine
moiety is indispensible to achieve excellent yield and enantioselectivity while ligand
containing (1R,2R)-cyclohexane-1,2-diamine moiety only provided racemic product
(Table 1, entry 7). Notably, phenyl group as substituent R2 also gave racemic product
(Table 1, entry 3). In contrast, i-Pr (L1, 60% ee), Me (L4, 69% ee), Bn (L5, 82% ee)
or even t-Bu (L3, 13% ee) group as substituent R2 all showed induction ability of
enantioselectivity (Table 1, entries 1, 4, 5 and 6). These results revealed that the
additional sp3 carbon in R2 group directly connecting to the backbone of ligand had a
great impact on the enantioselectivity. Meanwhile, benzyl group was optimal R2
substituent and arylidene malonates were more suitable substrates, this might suggest
that a π-π stacking was existed between aryl group of arylidene malonate and benzyl
group R2 of L5. Furthermore, it is noteworthy that the optimal solvent isobutyl
alcohol not only accelerated the reaction but also increased the enatioselectivities.12
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Tang’s group4c proved that alcohol was involved in the H-transfer step of catalytic
circle to acceletate the reaction and coordinated to copper center in the active
transistion state. We presume that alcohol play the same role in this transformation.
Scheme 3. Control Experiment of N-methyl indole with Benzylidene Malonate
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Based on the above results and analysis, a plausible working model was proposed,
as shown in Figure 1. We envision that catalyst L5-Cu(OTf)2 acts in a bifunctional
way. A weak hydrogen bond is formed between indolic proton and the nitrogen atom
which linkes with the tosyl substituent. As a result, the ability of this nitrogen atom
coordinating with Cu(II) center diminishes. A distorted octahedral geometry at copper
center4c is taken into consideration in which the remaining three nitrogen atoms of
ligand L5 take three coordinate positions where one nitrogen atom in apical space and
both carboxyl moieties of arylidene malonate occupy two equatorial positions with
isobutyl alcohol coordinate in the another apical position. Arylidene malonate is
activated by chelating to Cu(II) center. In addition, the π-π stacking between aryl
group of arylidene malonate and benzyl group R2 of L5 turned the arylidene malonate
in a fixed position. One phenyl group of (1R,2R)-1,2-diphenylethylenediamine moiety
shields the back of arylidene malonate, thus directing the indole to attack on the Re
face and provide the product with the configuration of S.
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Figure 1. Proposed Transition State Model of Catalyst L5-Cu(OTf)2
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To further demonstrate the synthetic potential of this strategy, benzylidene
malonate (5 mmol, 1.24g) was conducted under optimal reaction condition with lower
catalyst loading (2.5 mol%). It is noteworthy that the product was obtained by simple
filtration as a white solid with 90% yield and 98% ee (Scheme 4).
Scheme 4. Reaction Carried out on a Large Scale
CONCLUSIONS
In summary, we have developed a highly efficient Cu-catalyzed asymmetric
Friedel-Crafts alkylation reaction of indoles with arylidene malonates using simple,
stable and easily prepared bis-sulfonamide diamine ligands. Several substrates of
arylidene malonates and indoles with various substituents were investigated, and the
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corresponding products were obtained in excellent yields and with high ee. Moreover,
a gram scale experiment was performed. Excellent yield and ee with simple process
illustrated the practical aspects.
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EXPERIMENTAL SECTION
General Considerations. All reactions were carried out under an atmosphere of
argon using standard Schlenk techniques, unless otherwise noted. H NMR and 13C
1
NMR spectra were recorded 400 and 100 MHz respectively using CDCl3 as solvent.
1
Tetramethylsilane (δ = 0) or CDCl3 (δ = 7.27) serves as the internal standard for H
13
NMR and CDCl3 (77.16 ppm) for C NMR. Coupling constants (J) are reported in
Hz and refer to apparent peak multiplications. The abbreviations s, d, t, q, and m stand
for singlet, doublet, triplet, quartet, and multiplet in that order. Optical rotations were
measured with MCP 200. HRMS data were obtained with Micromass HPLC-Q-TOF
mass spectrometer. Flash column chromatography was performed on silica gel
(300−400 mesh). TLC analysis was performed using silica gel GF254 and visualized
by fluorescence quenching under UV light. The enantiomeric excesses were
determined by HPLC analysis with chiral DAICEL CHIRALCEL AD-H, OJ-H,
OD-H and AS-H column
Commercially available reagents were used throughout without further
purification. All solvents were purified according to the standard procedures.
General Procedure for the Asymmetric Friedel-Crafts Alkylation Reaction:
Under argon atmosphere, bis(sulfonamide)-diamine ligand (10.8 mg, 0.0138 mmol,
5.5 mol%) and Cu(OTf)2 (4.5 mg, 0.0125 mmol, 5 mol%) were dissolved in i-BuOH
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(1 mL), and the mixture was stirred at room temperature in a 25 mL Schlenk tube for
2 h to give the catalyst. After putting it into a freezer with the temperature of 0 °C,
this mixture was added aryldiene malonate (0.3 mmol, 1.2 equiv). After stirred for 15
min, indole was added (0.25 mmol, 1.0 equiv). The reaction was stirred at 0 °C and
monitored by TLC. When the reaction was finished (about 2–12 h), the solvent was
evaporated under reduced pressure. The crude residue was purified by column
chromatography (CH2Cl2/Petroleum ether = 1:1) to afford the desired product.
(S)-Ethyl 2-ethoxycarbonyl-3-(3-indolyl)-3-phenyl propanoate (8a). 5a
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Following the general procedure, the compound was obtained as white solid: 90 mg,
98% yield and 95% ee; [α]20 = +63.4 (c 1.0, CH2Cl2); [lit.5a: [α]25 = +65.4 (c 1.0,
D
D
1
CH2Cl2) for 99% ee;] Rf = 0.3 (petroleum ether/EtOAc = 4/1); H NMR (400 MHz,
CDCl3) δ 8.04 (s, 1H), 7.55 (d, J = 7.9 Hz, 1H), 7.37 (d, J = 7.5 Hz, 2H), 7.29 (d, J =
8.1 Hz, 1H), 7.23 (t, J = 7.6 Hz, 2H), 7.19 – 7.09 (m, 3H), 7.03 (t, J = 7.5 Hz, 1H),
5.08 (d, J = 11.8 Hz, 1H), 4.29 (d, J = 11.8 Hz, 1H), 4.05 – 3.93 (m, 4H), 1.00 (q, J =
7.3 Hz, 6H); 13C NMR (101 MHz, CDCl3) δ 168.2, 168.0, 141.5, 136.3, 128.5, 128.3,
126.9, 122.4, 121.0, 119.7, 119.6, 117.2, 111.1, 61.6, 61.5, 58.5, 43.0, 13.91, 13.88.
HPLC: Daicel Chiralcel OD-H column, Hexanes/i-PrOH = 88/12, UV = 254 nm, flow
rate: 1.0 mL/min), t1 = 12.5 min (maj.), t2 = 14.9 min.
(S)-Ethyl 2-ethoxycarbonyl-3-(3-indolyl)-3-(p-methylphenyl) propanoate (8b). 5a
Following the general procedure, the compound was obtained as white solid: 95 mg,
white solid in 85% yield and 96% ee; [α]20 = +52.5 (c 0.8, CH2Cl2); [lit.5a: [α]25
=
D
D
+26.7 (c 0.5, CH2Cl2) for 94% ee;] Rf = 0.35 (petroleum ether/EtOAc = 8/1); 1H NMR
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(400 MHz, CDCl3) δ 8.10 (s, 1H), 7.55 (d, J = 7.9 Hz, 1H), 7.24 (d, J = 7.9 Hz, 3H),
7.12 – 7.08 (m, 2H), 7.03 – 7.00 (m, 3H), 5.04 (d, J = 11.8 Hz, 1H), 4.28 (d, J = 11.8
Hz, 1H), 4.02 – 3.95 (m, 4H), 2.23 (s, 3H), 1.03 (t, J = 7.1 Hz, 3H), 0.96 (t, J = 7.1 Hz,
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3H); C NMR (101 MHz, CDCl3) δ 168.3, 168.1, 138.5, 136.3, 136.3, 129.1, 128.1,
126.88, 122.2, 121.0, 119.5, 119.5, 117.1, 111.1, 61.54, 61.51, 58.5, 42.6, 21.1, 13.9,
13.8. HPLC: Daicel Chiralcel OD-H column, Hexanes/i-PrOH = 90/10, UV = 254 nm,
flow rate: 0.5 mL/min), t1 = 33.9 min, t2 = 36.4 min (maj.).
(S)-Ethyl 2-ethoxycarbonyl-3-(3-indolyl)-3-(p-methoxylphenyl) propanoate (8c). 5b
Following the general procedure, the compound was obtained as white solid: 95 mg,
96% yield and 90% ee; [α]20 = +67.0 (c 1.0, CH2Cl2); [lit.5b: [α]25 = +53.3 (c 1.0,
D
D
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CH2Cl2) for 84% ee;] Rf = 0.22 (petroleum ether/EtOAc = 8/1); H NMR (400 MHz,
CDCl3) δ 8.05 (s, 1H), 7.52 (d, J = 7.9 Hz, 1H), 7.27 (d, J = 7.7 Hz, 3H), 7.17 – 7.07
(m, 2H), 7.02 (t, J = 7.4 Hz, 1H), 6.76 (d, J = 7.3 Hz, 2H), 5.03 (d, J = 11.7 Hz, 1H),
4.24 (d, J = 11.7 Hz, 1H), 4.00 (q, J = 7.0 Hz, 4H), 3.72 (s, 3H), 1.04 (t, J = 7.1 Hz,
13
3H), 0.98 (t, J = 7.0 Hz, 3H); C NMR (101 MHz, CDCl3) δ 168.2, 168.0, 158.4,
136.4, 133.7, 129.3, 126.8, 122.3, 120.8, 119.59, 119.57, 117.4, 113.8, 111.1, 110.1,
61.6, 61.5, 58.7, 55.3, 42.2, 14.0, 13.9. HPLC: Daicel Chiralcel OD-H column,
Hexanes/i-PrOH = 88/12, UV = 254 nm, flow rate: 0.9 mL/min), t1 = 17.7 min, t2 =
21.0 min (maj.);
(S)-Ethyl 2-ethoxycarbonyl-3-(3-indolyl)-3-(p-chlorophenyl) popanoate (8d). 5a
Following the general procedure, the compound was obtained as white solid: 93 mg,
92% yield and 90% ee; [α]20 = +44.7 (c 1.0, CH2Cl2); [lit.5a: [α]25 = +48.2 (c 1.0,
D
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CH2Cl2) for 98% ee;] Rf = 0.31 (petroleum ether/EtOAc = 4/1); H NMR (400 MHz,
CDCl3) δ 8.12 (s, 1H), 7.48 (d, J = 7.8 Hz, 1H), 7.30 – 7.27 (m, 3H), 7.20 – 7.18 (m,
2H), 7.13 – 7.11 (m, 2H), 7.03 (t, J = 7.4 Hz, 1H), 5.06 (d, J = 11.7 Hz, 1H), 4.25 (d,
J = 11.7 Hz, 1H), 4.08 – 3.93 (m, 4H), 1.05 (t, J = 7.0 Hz, 3H), 0.98 (t, J = 7.0 Hz,
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3H); C NMR (101 MHz, CDCl3) δ 168.0, 167.8, 140.1, 136.4, 132.6, 129.7, 128.6,
126.6, 122.5, 121.0, 119.8, 119.3, 116.6, 111.2, 61.7, 58.3, 42.3, 14.0, 13.9. HPLC:
Daicel Chiralcel OD-H column, Hexanes/i-PrOH = 88/12, UV = 254 nm, flow rate:
0.5 mL/min), t1 = 20.1 min, t2 = 21.9 min (maj.);
(S)-Ethyl 2-ethoxycarbonyl-3-(3-indolyl)-3-(p-fluorophenyl) popanoate (8e). 6c
Following the general procedure, the compound was obtained as white solid: 93 mg,
97% yield and 91% ee; [α]20 = +79.9 (c 1.0, CH2Cl2); [lit.6c: [α]25 = -77.3 (c 0.2,
D
D
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CH2Cl2) for 83% ee;] Rf = 0.29 (petroleum ether/EtOAc = 4/1); H NMR (400 MHz,
CDCl3) δ 8.05 (s, 1H), 7.49 (d, J = 7.8 Hz, 1H), 7.37 – 7.27 (m, 3H), 7.21 – 7.09 (m,
2H), 7.03 (t, J = 7.0 Hz, 1H), 6.92 (t, J = 7.9 Hz, 2H), 5.07 (d, J = 11.6 Hz, 1H), 4.23
(d, J = 11.6 Hz, 1H), 4.04 – 3.97 (m, 4H), 1.09 – 0.96 (m, 6H); 13C NMR (101 MHz,
CDCl3) δ 168.0, 167.9, 161.8 (d, JC-F = 245.4 Hz), 137.3 (d, JC-F = 3.3 Hz), 136.4,
129.9 (d, JC-F = 8.0 Hz), 126.7, 122.5, 120.9, 119.7, 119.4, 117.0, 115.3 (d, JC-F = 21.3
Hz), 111.2, 61.7, 61.6, 58.6, 42.3, 14.0, 13.9. HPLC: Daicel Chiralcel AS-H column,
Hexanes/i-PrOH = 90/10, UV = 254 nm, flow rate: 1.0 mL/min), t1 = 19.1 min (maj.),
t2 = 27.8 min;
(S)-Ethyl 2-ethoxycarbonyl-3-(3-indolyl)-3-(p-trifluoromethylphenyl) popanoate
(8f). 5b Following the general procedure, the compound was obtained as white solid:
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105 mg, 97% yield and 89% ee; [α]20D = +45.1 (c 1.0, CH2Cl2); [lit.5b: [α]25D = +15.2
(c 0.5, CH2Cl2) for 90% ee;] Rf = 0.37 (petroleum ether/EtOAc = 4/1); 1H NMR (400
MHz, CDCl3) δ 8.13 (s, 1H), 7.49 – 7.45 (m, 5H), 7.31 – 7.29 (m, 1H), 7.19 – 7.13 (m,
2H), 7.05 – 7.03 (m, 1H), 5.15 (d, J = 11.5 Hz, 1H), 4.30 (d, J = 11.6 Hz, 1H), 4.00 –
3.99 (m, 4H), 1.01 – 0.99 (m, 6H); 13C NMR (101 MHz, CDCl3) δ 167.8, 167.7, 145.8,
136.4, 129.0, 128.7, 126.5, 125.5(q, JC-F = 4.0 Hz), 122.7, 121.2, 112.0, 119.2, 116.2,
111.3, 61.80, 61.77, 58.05, 42.70, 13.86. HPLC: Daicel Chiralcel OJ-H column,
Hexanes/i-PrOH = 90/10, UV = 254 nm, flow rate: 1.0 mL/min), t1 = 21.3 min, t2 =
27.1 min (maj.);
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(S)-Ethyl 2-ethoxycarbonyl-3-(3-indolyl)-3-(p-nitrophenyl) popanoate (8g). 5b
Following the general procedure, the compound was obtained as yellow solid: 95 mg,
93% yield and 91% ee; [α]20 = +9.3 (c 1.0, CH2Cl2); [lit.5b: [α]25 = +6.9 (c 1.0,
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CH2Cl2) for 80% ee;] Rf = 0.26 (petroleum ether/EtOAc = 4/1); H NMR (400 MHz,
CDCl3) δ 8.18 (s, 1H), 8.10 (d, J = 8.7 Hz, 2H), 7.55 (d, J = 8.7 Hz, 2H), 7.47 (d, J =
8.0 Hz, 1H), 7.32 (d, J = 8.2 Hz, 1H), 7.22 (d, J = 2.3 Hz, 1H), 7.16 (t, J = 7.3 Hz,
1H), 7.05 (t, J = 7.3 Hz, 1H), 5.20 (d, J = 11.6 Hz, 1H), 4.32 (d, J = 11.6 Hz, 1H),
4.07 – 3.99 (m, 4H), 1.07 (t, J = 7.1 Hz, 3H), 1.01 (t, J = 7.1 Hz, 3H); 13C NMR (101
MHz, CDCl3) δ 167.6, 167.5, 149.4, 146.8, 136.3, 129.3, 126.4, 123.8, 122.8, 121.3,
120.1, 119.0, 115.5, 111.4, 61.9, 57.8, 42.6, 14.0, 13.9. HPLC: Daicel Chiralcel AS-H
column, Hexanes/i-PrOH = 90/10, UV = 254 nm, flow rate: 1.0 mL/min), t1 = 33.4
min (maj.), t2 = 49.3 min;
(S)-Ethyl 2-ethoxycarbonyl-3-(3-indolyl)-3-(m-methoxylphenyl) popanoate (8h). 7a
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Following the general procedure, the compound was obtained as white solid: 98 mg,
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99% yield and 96% ee; [α]20D = +52.5 (c 0.8, CH2Cl2); [lit.7a: [α]27D = -49.6 (c 0.222,
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CH2Cl2) for 92% ee;] Rf = 0.26 (petroleum ether/EtOAc = 4/1); H NMR (400 MHz,
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CDCl3) δ 8.14 (s, 1H), 7.57 (d, J = 7.9 Hz, 1H), 7.25 (d, J = 8.3 Hz, 1H), 7.17 – 7.06
(m, 3H), 7.02 (t, J = 7.4 Hz, 1H), 6.96 (d, J = 7.7 Hz, 1H), 6.91 (s, 1H), 6.67 (dd, J =
8.1, 2.1 Hz, 1H), 5.05 (d, J = 11.9 Hz, 1H), 4.29 (d, J = 11.9 Hz, 1H), 4.03 – 3.94 (m,
13
4H), 3.71 (s, 3H), 1.03 (t, J = 7.1 Hz, 3H), 0.95 (t, J = 7.1 Hz, 3H); C NMR (101
MHz, CDCl3) δ 168.3, 168.1, 159.7, 143.3, 136.4, 129.5, 126.9, 122.4, 121.2, 120.8,
119.7, 119.5, 116.9, 114.4, 112.1, 111.3, 61.68, 61.65, 58.5, 55.3, 43.0, 14.0, 13.9.
HPLC: Daicel Chiralcel OD-H column, Hexanes/i-PrOH = 90/10, UV = 254 nm, flow
rate: 1.0 mL/min), t1 = 21.6 min, t2 = 28.1 min (maj.);
(S)-Ethyl 2-ethoxycarbonyl-3-(3-indolyl)-3-(m-methylphenyl) popanoate (8i). 7a
Following the general procedure, the compound was obtained as white solid: 89 mg,
94% yield and 91% ee; [α]20 = +53.1 (c 0.8, CH2Cl2); [lit.7a: [α]26 = -60.5 (c 0.2,
D
D
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CH2Cl2) for 90% ee;] Rf = 0.29 (petroleum ether/EtOAc = 4/1); H NMR (400 MHz,
CDCl3) δ 8.08 (s, 1H), 7.57 (d, J = 7.9 Hz, 1H), 7.26 (d, J = 8.1 Hz, 1H), 7.20 – 7.07
(m, 5H), 7.03 (t, J = 7.5 Hz, 1H), 6.94 (d, J = 7.3 Hz, 1H), 5.04 (d, J = 11.9 Hz, 1H),
4.29 (d, J = 11.9 Hz, 1H), 4.03 – 3.93 (m, 4H), 2.25 (s, 3H), 1.01 (t, J = 7.1 Hz, 3H),
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0.96 (t, J = 7.1 Hz, 3H); C NMR (101 MHz, CDCl3) δ 168.0, 167.8, 141.2, 137.6,
136.0, 128.8, 128.0, 127.3, 126.6, 124.9, 122.0, 120.8, 119.3, 119.2, 116.8, 110.8,
61.3, 61.2, 58.3, 42.6, 21.3, 13.6, 13.6. HPLC: Daicel Chiralcel AS-H column,
Hexanes/i-PrOH = 90/10, UV = 254 nm, flow rate: 1.0 mL/min), t1 = 17.8 min (maj.),
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t2 = 19.9 min;
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(S)-Ethyl 2-ethoxycarbonyl-3-(3-indolyl)-3-(m-bromophenyl) popanoate (8j). 6a
Following the general procedure, the compound was obtained as white solid: 109 mg,
98% yield and 93% ee; [α]20 = +55.7 (c 1.0, CH2Cl2); [lit.7a: [α]25 = +24.0 (c 0.2,
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CH2Cl2) for 99% ee;] Rf = 0.37 (petroleum ether/EtOAc = 4/1); H NMR (400 MHz,
CDCl3) δ 8.15 (s, 1H), 7.56 – 7.44 (m, 2H), 7.35 – 7.21 (m, 3H), 7.18 – 7.00 (m, 4H),
5.04 (d, J = 11.7 Hz, 1H), 4.25 (d, J = 11.7 Hz, 1H), 4.09 – 3.91 (m, 4H), 1.07 – 0.96
(m, 6H); 13C NMR (101 MHz, CDCl3) δ 167.9, 167.8, 144.0, 136.3, 131.4, 130.0,
127.1, 126.6, 122.5, 122.5, 121.2, 119.8, 119.3, 116.3, 111.3, 61.7, 58.2, 42.6, 13.94,
13.85. HPLC: Daicel Chiralcel OD-H column, Hexanes/i-PrOH = 88/12, UV = 254
nm, flow rate: 0.9 mL/min), t1 = 12.0 min, t2 = 15.1 min (maj.);
(S)-Ethyl 2-ethoxycarbonyl-3-(3-indolyl)-3-(o-chlorophenyl) popanoate (8k). 7a
Following the general procedure, the compound was obtained as oil: 99 mg, 99%
yield and 92% ee; [α]20D = +51.6 (c 0.8, CH2Cl2); [lit.7a: [α]25D = +22.6 (c 0.5, CH2Cl2)
for 90% ee;] Rf = 0.26 (petroleum ether/EtOAc = 4/1); 1H NMR (400 MHz, CDCl3) δ
8.14 (s, 1H), 7.68 (d, J = 7.9 Hz, 1H), 7.39 (d, J = 7.7 Hz, 1H), 7.31 (d, J = 7.9 Hz,
1H), 7.25 (d, J = 8.1 Hz, 1H), 7.18 – 6.99 (m, 5H), 5.66 (d, J = 11.7 Hz, 1H), 4.40 (d,
J = 11.7 Hz, 1H), 4.07 – 3.88 (m, 4H), 1.02 (t, J = 7.1 Hz, 3H), 0.94 (t, J = 7.1 Hz,
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3H); C NMR (101 MHz, CDCl3) δ 168.0, 167.7, 139.2, 136.1, 134.1, 130.0, 129.1,
127.9, 127.0, 126.8, 122.3, 122.1, 119.7, 119.6, 115.8, 111.2, 61.7, 61.6, 57.7, 38.7,
13.83, 13.79. HPLC: Daicel Chiralcel OD-H column, Hexanes/i-PrOH = 90/10, UV =
254 nm, flow rate: 1.0 mL/min), t1 = 15.8 min, t2 = 23.9 min (maj.);
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(S)-Ethyl 2-ethoxycarbonyl-3-(3-indolyl)-3-(o-methylphenyl) popanoate (8l). 6b
Following the general procedure, the compound was obtained as white solid: 95 mg,
98% yield and 94% ee; [α]20 = -51.9 (c 0.8, CH2Cl2); [lit. 6b: [α]25 = +11.2 (c 0.2,
D
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CH2Cl2) for 90% ee;] Rf = 0.43 (petroleum ether/EtOAc = 4/1); H NMR (400 MHz,
CDCl3) δ 8.07 (s, 1H), 7.61 (d, J = 7.9 Hz, 1H), 7.36 (d, J = 7.6 Hz, 1H), 7.26 – 7.21
(m, 1H), 7.17 – 7.01 (m, 5H), 6.95 (d, J = 2.4 Hz, 1H), 5.32 (d, J = 11.8 Hz, 1H), 4.34
(d, J = 11.8 Hz, 1H), 3.98 (q, J = 7.1 Hz, 2H), 3.88 (q, J = 7.1 Hz, 2H), 2.45 (s, 3H),
13
0.99 (t, J = 7.1 Hz, 3H), 0.89 (t, J = 7.1 Hz, 3H); C NMR (101 MHz, CDCl3) δ
168.5, 168.0, 140.2, 136.4, 136.1, 130.8, 126.8, 126.6, 126.4, 126.1, 122.5, 122.1,
119.6, 119.4, 116.5, 111.1, 61.6, 61.5, 58.6, 38.1, 20.1, 13.8, 13.7. HPLC: Daicel
Chiralcel OD-H column, Hexanes/i-PrOH = 90/10, UV = 254 nm, flow rate: 0.8
mL/min), t1 = 11.6 min, t2 = 14.2 min (maj.);
(S)-Ethyl 2-ethoxycarbonyl-3-(3-indolyl)-3-(o-methoxylphenyl) popanoate (8m).
uknown compound; Following the general procedure, the compound was obtained as
white solid: 97 mg, 98% yield and 90% ee; [α]20D = +22.9 (c 0.8, CH2Cl2); Rf = 0.29
(petroleum ether/EtOAc = 4/1); MP 94−96 °C; 1H NMR (400 MHz, CDCl3) δ 8.08 (s,
1H), 7.68 (d, J = 7.8 Hz, 1H), 7.31 (dd, J = 7.5, 1.2 Hz, 1H), 7.23 (d, J = 8.1 Hz, 1H),
7.16 (d, J = 2.3 Hz, 1H), 7.12 – 7.02 (m, 3H), 6.86 – 6.76 (m, 2H), 5.47 (d, J = 11.8
Hz, 1H), 4.55 (d, J = 11.8 Hz, 1H), 3.98 – 3.91 (m, 4H), 3.81 (s, 3H), 0.98 (t, J = 7.1
Hz, 3H), 0.92 (t, J = 7.1 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 168.6, 168.3, 157.2,
135.9, 129.9, 129.1, 127.9, 127.2, 121.9, 120.6, 119.5, 119.3, 116.5, 111.04, 110.98,
61.4, 61.3, 57.0, 55.5, 36.8, 13.9, 13.8. HPLC: Daicel Chiralcel OD-H column,
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Hexanes/i-PrOH = 90/10, UV = 254 nm, flow rate: 0.8 mL/min), t1 = 15.9 min, t2 =
23.0 min (maj.); HRMS (ESI, m/z ) Calculated for [C23H25NO5+Na]+ 418.1630, found
418.1642.
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(S)-Ethyl 2-ethoxycarbonyl-3-(3-indolyl)-3-(3,4-dichlorophenyl) propanoate (8n).
7a
Following the general procedure, the compound was obtained as white solid: 104
mg, 96% yield and 83% ee; [α]20 = +40.0 (c 0.8, CH2Cl2); [lit.7a: [α]25 = -42.8 (c
D
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0.208, CH2Cl2) for 83% ee;] Rf = 0.34 (petroleum ether/EtOAc = 4/1); 1H NMR (400
MHz, CDCl3) δ 8.16 (s, 1H), 7.49 (d, J = 8.0 Hz, 1H), 7.45 (d, J = 1.9 Hz, 1H), 7.31
(dd, J = 8.2, 2.9 Hz, 2H), 7.22 (dd, J = 8.3, 2.0 Hz, 1H), 7.19 – 7.13 (m, 2H), 7.06 (t, J
= 7.4 Hz, 1H), 5.05 (d, J = 11.6 Hz, 1H), 4.24 (d, J = 11.6 Hz, 1H), 4.08 – 3.99 (m,
4H), 1.10 (t, J = 7.1 Hz, 3H), 1.00 (t, J = 7.1 Hz, 3H)； 13C NMR (101 MHz, CDCl3)
δ 167.7, 167.6, 142.0, 136.3, 132.4, 130.9, 130.4, 130.3, 127.9, 126.4, 122.7, 121.1,
120.0, 119.2, 115.9, 111.3, 110.1, 61.9, 61.8, 58.0, 42.0, 14.0, 13.9. HPLC: Daicel
Chiralcel AS-H column, Hexanes/i-PrOH = 95/5, UV = 254 nm, flow rate: 1.0
mL/min), t1 = 33.5 min (maj.), t2 = 39.0 min;
(S)-Ethyl 2-ethoxycarbonyl-3-(3-indolyl)-3-(2-naphthly) propanoate (8o). 7a
Following the general procedure, the compound was obtained as white solid: 100 mg,
96% yield and 90% ee; [α]20D = +45.5 (c 0.8, CH2Cl2); [lit.7a: [α]25D = -38.4 (c 0.320,
1
CH2Cl2) for 80% ee;] Rf = 0.14 (petroleum ether/EtOAc = 4/1); H NMR (400 MHz,
CDCl3) δ 8.06 (s, 1H), 7.86 (s, 1H), 7.81 – 7.67 (m, 3H), 7.58 (d, J = 7.9 Hz, 1H),
7.49 – 7.36 (m, 3H), 7.28 (d, J = 8.1 Hz, 1H), 7.23 (s, 1H), 7.12 (t, J = 7.5 Hz, 1H),
7.01 (t, J = 7.5 Hz, 1H), 5.27 (d, J = 11.8 Hz, 1H), 4.42 (d, J = 11.8 Hz, 1H), 4.02 (q,
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J = 7.1 Hz, 2H), 3.98 – 3.89 (m, 2H), 1.01 (t, J = 7.1 Hz, 3H), 0.92 (t, J = 7.1 Hz, 3H);
13C NMR (101 MHz, CDCl3) δ 168.2, 168.0, 139.0, 136.3, 133.5, 132.6, 128.2, 128.0,
127.7, 126.9, 126.69, 126.66, 126.1, 125.7, 122.4, 121.2, 119.7, 119.5, 117.0, 111.1,
61.7, 61.6, 58.4, 43.0, 13.90, 13.87. HPLC: Daicel Chiralcel AD-H column,
Hexanes/i-PrOH = 80/20, UV = 254 nm, flow rate: 1.0 mL/min), t1 = 20.8 min (maj.),
t2 = 22.9 min;
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(S)-Ethyl 2-ethoxycarbonyl-3-(3-indolyl)-3-(2-thienyl) propanoate (8p). 6a
Following the general procedure, the compound was obtained as white solid: 91 mg,
98% yield and 75% ee; [α]20D = +51.1 (c 1.0, CH2Cl2); [lit.6a: [α]25D = +62.0 (c 0.25,
1
CH2Cl2) for 99% ee;] Rf = 0.34 (petroleum ether/EtOAc = 4/1); H NMR (400 MHz,
CDCl3) δ 8.12 (s, 1H), 7.63 (d, J = 7.9 Hz, 1H), 7.31 (d, J = 8.1 Hz, 1H), 7.19 – 7.12
(m, 2H), 7.12 – 7.04 (m, 2H), 6.99 (d, J = 3.2 Hz, 1H), 6.87 – 6.85 (m, 1H), 5.40 (d, J
= 11.4 Hz, 1H), 4.32 (d, J = 11.4 Hz, 1H), 4.17 – 4.06 (m, 2H), 3.94 (q, J = 7.1 Hz,
13
2H); C NMR (101 MHz, CDCl3) δ 167.9, 167.6, 145.9, 136.3, 126.5, 126.5, 125.2,
124.4, 122.4, 121.7, 119.8, 119.5, 116.6, 111.2, 61.8, 61.6, 59.5, 38.1, 14.0, 13.7.
HPLC: Daicel Chiralcel OD-H column, Hexanes/i-PrOH = 95/5, UV = 254 nm, flow
rate: 1.0 mL/min), t1 = 30.5 min, t2 = 33.2min (maj.);
(S)-Ethyl 2–ethoxycarbony–3–(3–indoly)-3–methylpropanoate (8q). 6a
Following the general procedure, the compound was obtained as colorless oil: 74 mg,
98% yield and 34% ee; [α]20 = -1.0(c 1.1, CH2Cl2); [lit.6a: [α]25 = +1.5 (c 0.2,
D
D
1
CH2Cl2) for 34% ee;] Rf = 0.34 (petroleum ether/EtOAc = 4/1); H NMR (400 MHz,
CDCl3) δ 8.23 (s, 1H), 7.69 (d, J = 7.8 Hz, 1H), 7.33 (d, J = 8.0 Hz, 1H), 7.18 (t, J =
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7.3 Hz, 1H), 7.12 (t, J = 7.4 Hz, 1H), 7.02 (d, J = 2.2 Hz, 1H), 4.24 (q, J = 7.1 Hz,
2H), 3.92 (q, J = 7.1 Hz, 3H), 3.83 (d, J = 9.9 Hz, 1H), 1.48 (d, J = 6.9 Hz, 3H), 1.28
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(t, J = 7.1 Hz, 3H), 0.93 (t, J = 7.1 Hz, 3H); C NMR (101 MHz, CDCl3) δ 168.9,
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168.7, 136.3, 126.4, 122.0, 121.6, 119.3, 119.3, 117.9, 111.3, 61.4, 61.2, 58.8, 31.8,
19.8, 14.2, 13.7. HPLC: Daicel Chiralcel OD-H column, Hexanes/i-PrOH = 90/10,
UV = 254 nm, flow rate: 0.7 mL/min), t1 = 14.3 min (maj.), t2 = 16.4min;
(S)–Ethyl 2–ethoxycarbonyl–3–[3–(5-methylindolyl)]–3–phenylpropanoate (8r). 6a
Following the general procedure, the compound was obtained as white solid: 94 mg,
99% yield and 93% ee; [α]20 = +36.0 (c 1.0, CH2Cl2); [lit.6a: [α]25 = +24.0 (c 0.5,
D
D
1
CH2Cl2) for 97% ee;] Rf = 0.29 (petroleum ether/EtOAc = 4/1); H NMR (400 MHz,
CDCl3) δ 8.25 (s, 1H), 7.34 (d, J = 7.7 Hz, 2H), 7.30 (s, 1H), 7.19 (t, J = 7.5 Hz, 2H),
7.16 – 7.07 (m, 3H), 6.91 (d, J = 8.3 Hz, 1H), 5.01 (d, J = 11.8 Hz, 1H), 4.24 (d, J =
11.8 Hz, 1H), 3.99 – 3.92 (m, 4H), 2.35 (s, 3H), 0.99 – 0.94 (m, 6H); 13C NMR (101
MHz, CDCl3) δ 168.1, 168.0, 141.6, 134.6, 128.6, 128.4, 128.2, 127.0, 126.7, 123.8,
121.1, 119.0, 116.4, 110.7, 61.5, 61.4, 58.6, 42.9, 21.6, 13.83, 13.80. HPLC: Daicel
Chiralcel OD-H column, Hexanes/i-PrOH = 85/15, UV = 254 nm, flow rate: 0.9
mL/min), t1 = 10.9 min, t2 = 13.1 min (maj.);
(S)–Ethyl 2–ethoxycarbonyl–3–[3–(5-methoxyindolyl)]–3–phenylpropanoate (8s). 5a
Following the general procedure, the compound was obtained as white solid: 98 mg,
99% yield and 96% ee; [α]20 = +12.1 (c 1.0, CH2Cl2); [lit.5a: [α]25 = +11.3 (c 1.0,
D
D
1
CH2Cl2) for 89% ee;] Rf = 0.29 (petroleum ether/EtOAc = 4/1); H NMR (400 MHz,
CDCl3) δ 7.99 (s, 1H), 7.36 (d, J = 7.4 Hz, 2H), 7.25 – 7.21 (m, 2H), 7.16 – 7.11 (m,
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3H), 6.96 (d, J = 2.2 Hz, 1H), 6.78 (dd, J = 8.8, 2.3 Hz, 1H), 5.02 (d, J = 11.8 Hz, 1H),
4.26 (d, J = 11.8 Hz, 1H), 4.03 – 3.95 (m, 4H), 3.77 (s, 3H), 1.02 – 0.97 (m, 6H); 13C
NMR (101 MHz, CDCl3) δ 168.2, 168.0, 154.0, 141.5, 131.5, 128.5, 128.3, 127.2,
126.9, 121.7, 116.8, 112.6, 111.8, 101.3, 61.6, 61.5, 58.5, 55.9, 43.0, 13.9. HPLC:
Daicel Chiralcel OD-H column, Hexanes/i-PrOH = 85/15, UV = 254 nm, flow rate:
0.9 mL/min), t1 = 14.9 min, t2 = 18.2 min (maj.);
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(S)–Ethyl 2–ethoxycarbonyl–3–[3–(7-chloroindolyl)]–3–phenylpropanoate (8t). 6a
Following the general procedure, the compound was obtained as white solid: 95 mg,
95% yield and 95% ee; [α]20D = +47.8 (c 1.0, CH2Cl2); [lit.6a: [α]25D = +60.0 (c 0.25,
1
CH2Cl2) for 98% ee;] Rf = 0.31 (petroleum ether/EtOAc = 4/1); H NMR (400 MHz,
CDCl3) δ 8.10 (s, 1H), 7.43 (d, J = 8.5 Hz, 1H), 7.33 (d, J = 7.5 Hz, 2H), 7.29 – 7.21
(m, 3H), 7.18 – 7.12 (m, 2H), 6.99 (dd, J = 8.5, 1.6 Hz, 1H), 5.03 (d, J = 11.8 Hz, 1H),
13
4.26 (d, J = 11.8 Hz, 1H), 4.04 – 3.95 (m, 4H), 1.00 (t, J = 7.1 Hz, 6H); C NMR
(101 MHz, CDCl3) δ 168.1, 167.8, 141.2, 136.7, 128.5, 128.3, 128.2, 127.0, 125.4,
121.7, 120.4, 120.3, 117.3, 111.1, 61.7, 61.6, 58.4, 42.8, 13.9. HPLC: Daicel
Chiralcel OD-H column, Hexanes/i-PrOH = 88/12, UV = 254 nm, flow rate: 0.8
mL/min), t1 = 11.2 min, t2 = 13.1 min (maj.);
(S)–Ethyl 2–ethoxycarbonyl–3–[3–(7-methylindolyl)]–3–phenylpropanoate (8u). 6b
Following the general procedure, the compound was obtained as white solid: 92 mg,
97% yield and 81% ee; [α]20 = +74.3 (c 0.8, CH2Cl2); [lit.6b: [α]25 = +23.5 (c 0.2,
D
D
CH2Cl2) for 99% ee;] Rf = 0.57 (petroleum ether/EtOAc = 4/1); 1H NMR (400 MHz,
CDCl3) δ 8.02 (s, 1H), 7.40 – 7.35 (m, 3H), 7.27 – 7.06 (m, 4H), 7.00 – 6.87 (m, 2H),
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5.07 (d, J = 11.9 Hz, 1H), 4.30 (d, J = 11.8 Hz, 1H), 4.04 – 3.94 (m, 4H), 2.40 (s, 3H),
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8
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1.00 (q, J = 7.2 Hz, 6H); C NMR (101 MHz, CDCl3) δ 168.2, 168.0, 141.6, 135.9,
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128.4, 128.3, 126.8, 126.3, 122.9, 120.7, 120.2, 119.8, 117.6, 117.2, 61.6, 61.5, 58.5,
43.1, 16.6, 13.9. HPLC: Daicel Chiralcel OD-H column, Hexanes/i-PrOH = 80/20,
UV = 254 nm, flow rate: 0.6 mL/min), t1 = 9.4min, t2 = 10.9 min (maj.);
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(S)–Ethyl 2–ethoxycarbonyl–3–[3–(N-methylindolyl)]–3–phenylpropanoate (8v). 7a
Following the general procedure, the compound was obtained as white solid: 92 mg,
95% yield and 64% ee; [α]20D = +47.0 (c 0.8, CH2Cl2); [lit.7a: [α]25D = +11.8 (c 0.25,
CH2Cl2) for 45% ee;] Rf = 0.28 (petroleum ether/EtOAc = 4/1); 1H NMR (400 MHz,
CDCl3) δ 7.55 (d, J = 7.9 Hz, 1H), 7.36 (d, J = 7.4 Hz, 2H), 7.27 – 7.08 (m, 5H), 7.06
– 6.98 (m, 2H), 5.06 (d, J = 11.8 Hz, 1H), 4.27 (d, J = 11.8 Hz, 1H), 4.04 – 3.92 (m,
13
4H), 3.71 (s, 3H), 1.01 – 0.99 (m, 6H); C NMR (101 MHz, CDCl3) δ 168.1, 168.0,
141.8, 137.1, 128.5, 128.3, 127.3, 126.8, 125.8, 121.9, 119.6, 119.1, 115.5, 109.2,
61.5, 61.5, 58.6, 43.0, 32.9, 13.90, 13.87. HPLC: Daicel Chiralcel OD-H column,
Hexanes/i-PrOH = 90/10, UV = 254 nm, flow rate: 1.0 mL/min), t1 = 25.7min (maj.),
t2 = 32.7 min;
ACKNOWLEDGMENTS
Financial support from the National Basic Research Program of China
(2010CB833300) is gratefully acknowledged.
Supporting Information
13
1H, C spectra, HRMS Spectra, Copy of HPLC for racemic and chiral compounds.
This material is available free of charge via the Internet at http://pubs.acs.org.
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8259. (b) Jin, W.; Li, X. C.; Wan, B. S. J. Org. Chem. 2011, 76, 484.
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