Synthesis of tridentate ligands based on chiral diamines and their application to enantioselective Friedel-Crafts alkylation of indoles with nitroalkenes

Article abstract of DOI:10.1002/cjoc.201090243

A new type of chiral tridentate ligands were prepared and their Zn complexes were examined for the asymmetric Friedel-Crafts alkylation of indoles with nitroalkenes, which gave rise to good yields and moderate enantioselectivities.

Full text of DOI:10.1002/cjoc.201090243

FULL PAPER
Synthesis of Tridentate Ligands Based on Chiral Diamines and
Their Application to Enantioselective Friedel-Crafts Alkylation
of Indoles with Nitroalkenes
Wu, Meia,b(吴梅)
Wang, Shoufenga(王寿峰)
Xia, Chungua(夏春谷)
Sun, Wei*,a(孙伟)
a State Key Laboratory for Oxo Synthesis and Selective Oxidation, Lanzhou Institute of Chemical Physics, Chinese
Academy of Sciences, Lanzhou, Gansu 730000, China
b Graduate School of the Chinese Academy of Sciences, Beijing 100039, China
A new type of chiral tridentate ligands were prepared and their Zn complexes were examined for the asymmet-
ric Friedel-Crafts alkylation of indoles with nitroalkenes, which gave rise to good yields and moderate enantioselec-
tivities.
Keywords Friedel-Crafts alkylation, N ligands, indoles, nitroalkenes, asymmetric catalysis
Introduction
we have designed and prepared a series of new types of
tridentate ligands based on chiral diamines, which could
be subjected to asymmetric F-C alkylation reaction of
indoles with nitroalkenes.
Asymmetric Friedel-Crafts (F-C) alkylation of in-
dole derivatives with electron-deficient alkenes is an
extremely powerful reaction in the organic synthesis for
the formation of valuable N-heterocycles derivatives1
and has attracted considerable attention in the past few
years.2 The substrates which are suitable for the F-C
reaction involve alkylidene malonates,3 β,γ-unsaturated
α-ketoesters,4 acyl phosphonates,5 acyl heterocyclic
compounds6 and nitroalkenes.7 Among these kinds of
electron-deficient acceptors, nitroalkenes have attracted
considerable interest and witnessed significant progress
since nitro functional group is a strongly electron-with-
drawing group that allows subsequent versatile trans-
formation. Recently, comparative attention is being paid
to nitroalkenes which have achieved asymmetric F-C
alkylation with indoles, and extensive progress has been
accomplished in this direction. After pioneering work
which led to the SalenAlCl catalyst,8 thioureas,9 phos-
phoric acids,10 bis-sulfonamides,7a zinc,7d-7h and cop-
per11 catalysts have since been successfully applied to
F-C reaction of indoles with nitroalkenes. Among these
catalyst systems, various bisoxazoline-metal complexes
have been used as chiral Lewis acids in asymmetric F-C
reaction of five- or six-membered heterocycles to give
the corresponding alkylation products in good yields
and high ee values. Moreover, bis-sulfonamides have
been reported as the catalyst for asymmetric F-C reac-
tion.7a Recently, we have successfully synthesized a
series of new chiral tetradentate nitrogen ligands to-
gether with their manganese complexes, which exhibit
rapid, highly enantioselective epoxidation of various
α,β-enones.12 Encouraged by these conceptual strategies,
Results and discussion
These chiral tridentate ligands 3a— 3e were synthe-
sized with 2a— 2e and the corresponding Grignard re-
agents. The experimental procedure is shown in Scheme
1. Similarly, chiral tridentate ligand 3f was prepared
with 2f and PhMgBr as shown in Scheme 1.
Initially, we evaluated the enantioselective F-C reac-
tion of indole and nitroalkene 4a with the catalyst gen-
erated in situ with ligand 3a and Zn(OTf)2, and found
that the corresponding F-C reaction product was ob-
tained in an 80% yield and a 27% ee using CH2Cl2 as
solvent at room temperature for 24 h. Subsequently, we
examined a series of metallic salts with chiral ligand 3a
and the results are shown in Table 1, the combination of
ligand 3a with Fe(OTf)2 or Cu(OAc)2 in CH2Cl2 gave
no product. Cu(OTf)2 and (CuOTf)2•Ph showed the
similar ee values and catalytic activity with that of
Zn(OTf)2. Employing Mn(OTf)2 as a metal source,
lower yield and ee value were observed. Nearly racemic
product was obtained when AgOTf or NiCl2•6H2O was
used (Table 1, Entries 6 and 8).
With Zn(OTf)2 as the metallic salt and 3a as ligand,
we next studied the effects of solvent. When CH3OH or
Et2O was applied, no reaction occurred. Using toluene
as the solvent gave the product in higher yield but
slightly low enantioselectivity. The reactivity and
stereoselectivity decreased dramatically when the reac-
*
E-mail: wsun@licp.cas.cn; Tel.: 0086-931-4968278; Fax: 0086-931-8277088
Received December 15, 2009; revised March 24, 2010; accepted April 1, 2010.
Project supported by the National Natural Science Foundation of China (Nos. 20873166, 20625308).
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© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2010, 28, 1424— 1428

Enantioselective Friedel-Crafts Alkylation of Indoles with Nitroalkenes
Scheme 1 The synthesis of ligands 3a—3f
Table 2 Effect of solvents on asymmetric F-C reactiona
Entry
Solvent
Dichloromethane
Methanol
Yieldb/%
80
eec/%
1
2
3
4
5
27
N.R.
57
Acetone
13
23
Diethyl ether
Toluene
N.R.
90
a All reactions were performed with nitroalkene (0.2 mmol), in-
dole (0.2 mmol) in 1.0 mL of CH2Cl2 in the presence of 6 mol%
ligand 3a and 5 mol% Zn(OTf)2 at room temperature. b Isolated
yield. c Determined by HPLC using a Chiralcel OD-H column.
Table 3 Effect of chiral ligands on the Zn(OTf)2 catalyzed F-C
reactiona
Entry
Ligand
3a
T/℃
r.t.
Yieldb/%
80
eec/%
27
27
28
43
54
51
28
8
1
2
3
4
5
6
7
8
9
3b
r.t.
89
3c
r.t.
88
3d
r.t.
94
Table 1 Asymmetric F-C reaction catalyzed by ligand 3a and a
variety of metallic saltsa
3d
0
82
3d
－10
－20
r.t.
79
3d
57
3e
64
3f
r.t.
84
23
a All reactions were performed with nitroalkene (0.2 mmol), in-
dole (0.2 mmol) in 1.0 mL of CH2Cl2 in the presence of 6 mol%
ligands 3a—3f and 5 mol% Zn(OTf)2. b Isolated yield. c Deter-
mined by HPLC using a Chiralcel OD-H column.
Entry
Metallic salt
Zn(OTf)2
Cu(OTf)2
Mn(OTf)2
Fe(OTf)2
Yieldb/%
80
eec/%
27
1
2
3
4
5
6
7
8
78
25
54
14
synthesized ligands 3b—3f and examined the influence
of the substituted groups R1 on the yields and ee values
of the reactions. It can be seen that both the 3b and 3c
gave the similar ee values but slightly high catalytic
activity to the catalyst system with ligand 3a (Table 3,
Entries 1—3). Subsequently, the effect of group of
pyridine (R2) on the yields and ee values was investi-
gated. Higher yield and ee value were obtained when R2
was larger substituted group methyl (Table 3, Entry 4)
at room temperature. Ligand 1e bearing phenyl group
on the R2 led to low ee (Table 3, Entry 8). Ligand 1f
derived from (1R,2R)-1,2-diphenyl-ethanediamine was
also investigated in the F-C alkylation of indole and
nitroalkene, only 23% ee was observed (Table 3, Entry
9). In light of these results, the ligand 3d was found to
N.R.
80
(CuOTf)2•Ph
AgOTf
24
7
32
Cu(OAc)2
N.R.
NiCl2•6H2O
63
2
a All reactions were performed with nitroalkene (0.2 mmol), in-
dole (0.2 mmol) in 1.0 mL of CH2Cl2 in the presence of 6 mol%
ligand and 5 mol% metallic salts at room temperature. b Isolated
yield. c Determined by HPLC using a Chiralcel OD-H column.
tion was carried out in acetone (Table 3). Therefore,
dichloromethane was optimal in terms of both enanti-
oselectivity and yield.
To further optimize the reaction conditions, we
Chin. J. Chem. 2010, 28, 1424— 1428
© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
1425

Wu et al.
FULL PAPER
be the best ligand. With Zn(OTf)2 as metallic salt and
3d as ligand, we also examined the influence of the re-
action temperature on the ee value. We were pleased to
find that the product was obtained in 54% ee when tem-
perature was lowered to 0 ℃ (Table 3, Entry 5). When
the reaction was performed at －10 ℃, a slightly de-
creased ee was observed (Table 3, Entry 6). Lowering
temperature to －20 ℃, both the chemical reaction
activity and enantioselectivity reduced dramatically.
Based on the discussion above, we can conclude that the
reaction should perform in the presence of Zn(OTf)2 and
ligand 3d in dichloromethane at 0 ℃ for 48 h.
asymmetric F-C alkylation reaction of indoles with ni-
troalkenes, showing satisfactory yields and moderate
enantioselectivity. Further applications of these ligands
on other asymmetric reactions are underway in our
laboratory.
Experimental
General remarks
Commercially available compounds were used
without further purification. Solvents were dried ac-
cording to standard methods. Column chromatography
was carried out using silica gel (200—300 mesh). The
1H NMR spectra and 13C NMR spectra were recorded
on a Bruker Avance III 400MHz spectrometer. The ena-
tionmeric excesses were determined by chiral HPLC
analysis using Waters 1525 instrument. 1a and 1b were
prepared according to literature method.13,14
Under the optimized reactions, we explored the
limitations and scope by using various nitroalkenes and
indoles, and the results are summarized in Table 4. We
found that moderate enantioselectivities were achieved
when the nitroalkenes with electron-withdrawing and
slender electron-donating substituted groups were in-
volved (Table 4, Entries 3—5). However, the nitroal-
kene with strong electron-donating substitute afforded
the product with significantly decreased enantioselectiv-
ity (Table 4, Entry 6). When 2-substituted nitroalkene
was used, a comparative ee was accomplished with that
of 4-substituted nitroalkenes (Table 4, Entry 3). When
the substituent of indole such as 4b and 4g were se-
lected as substrate, lower ee values were obtained (Ta-
ble 4, Entries 2, 7).
General procedure for the preparation of 3a— 3f
To the solution of RMgBr (30 mmol) in Et2O was
added 2a—2f and the solution was stirred for 12 h at
room temperature. Saturated NH4Cl was added to
quench the reaction and the organic layer was separated
and dried over anhydrous Na2SO4. The mixture was
directly separated by silica gel chromatography with
petroleum ether/ethyl acetate (V∶V＝3∶1) as eluent.
The product was obtained with 58%—71% yield as a
colorless solid.
Table 4 Asymmetric F-C reaction of various substratesa
3a: Colorless solid; [α]2D0 －64.5 (c 0.1, CHCl3);
1H NMR (CDCl3, 400 MHz) δ: 8.51 (d, J＝4.8 Hz, 1H,
ArH), 7.76 (d, J＝8.4 Hz, 2H, ArH), 7.56 (t, J＝7.6 Hz,
1H, ArH), 7.39—7.24 (m, 7H, ArH), 7.13 (t, J＝6.0 Hz,
1H, ArH), 7.04 (d, J＝7.6 Hz, 1H, ArH), 5.54 (s, 1H,
NH), 4.98 (s, 1H, CH), 2.72 (s, 1H, CH), 2.42 (s, 3H,
CH3), 2.19—2.07 (m, 3H, CH), 1.60 (t, J＝12.8 Hz, 2H,
CH), 1.13—0.96 (m, 4H, CH); 13C NMR (CDCl3, 100
MHz) δ: 162.28, 148.67, 143.02, 142.07, 137.27, 136.55,
129.54, 128.87, 128.06, 127.68, 127.32, 121.97, 121.84,
64.35, 58.07, 57.42, 32.72, 31.21, 24.63, 24.31, 21.5＋7;
HRMS (ESI-MS) calcd for C25H29N3O2S [M＋H] :
436.2053, found 436.2056.
Entry Substrate R1 R2
R3
Yieldb/% eec/%
1
2
4a
4b
4c
4d
4e
4f
H
CH3
H
H
H
H
H
H
H
Br
Ph
Ph
82
90
86
76
60
67
56
54
47
50
54
57
36
36
3
2-Cl-C6H4
4-CH3-C6H4
4-F-C6H4
4-OCH3-C6H4
Ph
3b: Colorless solid; [α]2D0 －64.9 (c 0.1, CHCl3);
1H NMR (CDCl3, 400 MHz) δ: 8.50 (d, J＝4.0 Hz, 1H,
ArH), 7.76 (d, J＝8.0 Hz, 2H, ArH), 7.56 (t, J＝8.0 Hz,
1H, ArH), 7.27—7.24 (m, 4H, ArH), 7.13—7.11 (m, 1H,
ArH), 7.04 (d, J＝8.0 Hz, 1H, ArH), 6.90 (d, J＝8.8 Hz,
2H, ArH), 5.60 (s, 1H, NH), 4.93 (s, 1H, CH), 3.81 (s,
3H, OCH3), 2.69 (d, J＝7.2 Hz, 1H, CH), 2.41 (s, 3H,
CH3), 2.20—2.07 (m, 4H, CH), 1.60 (t, J1＝14.0 Hz,
J2＝16.4 Hz, 2H, CH), 1.16—0.92 (m , 3H, CH); 13C
NMR (CDCl3, 100 MHz) δ: 162.62, 159.03, 148.62,
143.01, 137.25, 136.53, 134.00, 129.53, 129.13, 127.32,
121.89, 121.74, 114.24, 63.64, 58.07, 57.19, 55.25,
32.73, 31.16, 24.66, 24.31, 21.57; HRMS (ESI-MS)
calcd for C26H31N3O3S [M＋H]＋ : 466.2159, found
466.2157.
4
H
5
H
6
7d
H
4g
H
a All reactions were performed with nitroalkene (0.2 mmol), in-
dole (0.2 mmol) in 1.0 mL of CH2Cl2 in the presence of Zn(OTf)2
c
and ligand 3d at 0 ℃ for 48 h. b Isolated yield. Determined by
HPLC using a Chiralcel OD-H, AD-H or AS column. d Performed
at room temperature.
Conclusion
In summary, a new type of tridentate ligands (3a—3f)
were successfully designed and synthesized. The tri-
dentate ligands and Zn(OTf)2 were applied to the
3c: Colorless solid; [α]2D0 －53.4 (c 0.1, CHCl3);
1426
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© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2010, 28, 1424— 1428

Enantioselective Friedel-Crafts Alkylation of Indoles with Nitroalkenes
1H NMR (CDCl3, 400 MHz) δ: 8.53 (d, J＝4.4 Hz, 1H,
ArH), 7.78 (d, J＝8.4 Hz, 2H, ArH), 7.61—7.58 (m, 5H,
ArH), 7.57—7.41 (m, 4H, ArH), 7.36—7.32 (m, 1H,
ArH), 7.26—7.11 (m, 4H, ArH), 5.56 (s, 1H, NH), 5.04
(s, 1H, CH), 2.77 (t, J＝9.6 Hz, 1H, CH), 2.41 (s, 3H,
CH3), 2.36—2.10 (m, 3H, CH), 1.64—1.53 (m, 2H, CH),
1.21—0.93 (m, 4H, CH); 13C NMR (CDCl3, 100 MHz)
δ: 162.21, 148.76, 143.05, 140.61, 140.49, 137.33,
136.64, 129.56, 128.77, 128.44, 127.56, 127.31, 127.04,
122.05, 121.84, 64.11, 58.07, 57.49, 32.68, 31.22, 24.61,
24.32, 21.57; HRMS (ESI-MS) calcd for C31H33N3O2S
[M＋H]＋: 512.2366, found 512.2360.
mixture was cooled to 0 ℃ and then nitroalkene was
added. After 10 min indole was added and the mixture
was stirred for 48 h. The mixture was directly separated
by silica gel chromatography with petroleum ether/ethyl
acetate (V∶V＝10∶1) as eluent.
3-(2-Nitro-1-phenylethyl)-1H-indole
This is a
known compound.7d [α]D20 ＋16.3 (c 0.42, CH2Cl2); 1H
NMR (CDCl3, 400 MHz) δ: 8.07 (s, 1H, NH), 7.42 (d,
J＝6.4 Hz, 1H, ArH), 7.33—7.21 (m, 5H, ArH), 7.20—
7.14 (m, 1H, ArH), 7.06 (t, J＝8.0 Hz, 1H, ArH), 6.98
(d, J＝2.0 Hz, 1H, ArH), 5.17 (t, J＝8.0 Hz, 1H, CH),
5.04 (dd, J＝12.4, 7.6 Hz, 1H, CH), 4.92 (dd, J＝12.4,
8.4 Hz, 1H, CH); 13C NMR (CDCl3, 100 MHz) δ:
139.18, 136.47, 128.90, 127.75, 127.54, 126.08, 122.66,
121.61, 119.92, 118.90, 114.35, 111.39, 79.52, 41.54.
The ee value was determined by chiral HPLC on a Dai-
cel Chiralcel OD-H col－umn (hexane/2-propanol, V∶V
3d: Colorless solid; [α]2D0 －65.0 (c 0.1, CHCl3);
1H NMR (CDCl3, 400 MHz) δ: 7.75 (d, J＝3.6 Hz, 2H,
ArH), 7.44 (t, J＝8.0 Hz, 1H, ArH), 7.36—7.26 (m ,7H,
ArH), 6.98 (d, J＝7.6 Hz, 1H, ArH), 6.83 (d, J＝7.6 Hz,
1H, ArH), 5.57 (s, 1H, NH), 4.93 (s, 1H, CH), 2.72—
2.68 (m, 1H, CH), 2.53 (s, 3H, CH3), 2.41 (s, 3H, CH3),
2.19—2.09 (m, 3H, CH), 1.63—1.55 (m, 2H, CH), 1.16
—0.92 (m, 4H, CH); 13C NMR (CDCl3, 100 MHz) δ:
161.57, 157.36, 142.98, 142.35, 137.38, 136.72, 129.50,
128.77, 128.11, 127.57, 127.32, 121.49, 118.76, 64.28,
58.11, 57.39, 32.61, 31.22, 24.69, 24.46, 24.30, 21.5＋4;
HRMS (ESI-MS) calcd for C26H31N3O2S [M＋H] :
450.2210, found 450.2215.
1
＝70∶30, 1.0 mL•min , 254 nm, tmajor＝21.18 min,
tminor＝19.57 min).
2-Methyl-3-(2-nitro-1-phenylethyl)-1H-indole
This is a known compound.7d [α]D20 －8.3 (c 0.48,
1
CH2Cl2); H NMR (CDCl3, 400 MHz) δ: 7.83 (s, 1H,
NH), 7.36 (d, J＝7.6 Hz, 1H, ArH), 7.31—7.19 (m, 6H,
ArH), 7.09 (t, J＝7.6 Hz, 1H, ArH), 7.01 (t, J＝7.6 Hz,
1H, ArH), 5.23—5.07 (m, 3H, CH), 2.34 (s, 3H, CH3);
13C NMR (CDCl3, 100 MHz) δ: 139.49, 135.38, 132.84,
128.75, 127.28, 127.05, 126.82, 121.30, 119.71, 118.56,
110.69, 108.81, 78.60, 40.43, 11.95. The ee value was
determined by chiral HPLC on a Daicel Chiralcel AS
column (hexane/2-propanol, V∶V＝94∶6, 1.0 mL•
3e: Colorless solid; [α]2D0 －153.2 (c 0.1, CHCl3);
1H NMR (CDCl3, 400 MHz) δ: 8.01 (d, J＝6.8 Hz, 2H,
ArH), 7.73 (d, J＝6.4 Hz, 2H, ArH), 7.60—7.26 (m,
10H, ArH), 7.11 (d, J＝8.0 Hz, 2H, ArH), 6.91 (d, J＝
6.8 Hz, 1H, ArH), 5.43 (s, 1H, NH), 5.01 (s, 1H, CH),
2.71—2.68 (m, 1H, CH), 2.26 (s, 3H, CH3), 2.19—2.09
(m, 3H, CH), 1.61—1.57 (m, 2H, CH), 1.26—1.09 (m,
4H, CH); 13C NMR (CDCl3, 100 MHz) δ: 161.73,
155.98, 143.01, 142.38, 139.17, 137.24, 137.06, 129.48,
129.02, 128.86, 128.72, 128.19, 127.66, 127.27, 126.91,
120.40, 118.49, 64.36, 58.17, 57.59, 32.59, 31.26, 24.69,
24.31, 21.43; HRMS (ESI-MS) calcd for C31H33N3O2S
[M＋H]＋: 512.2366, found 512.2359.
－1
min , 254 nm, tmajor＝27.60 min, tminor＝30.78 min).
3-[1-(2-Chlorophenyl)-2-nitroethyl]-1H-indole
This is a known compound.7d [α]D20 ＋35.8 (c 0.55,
1
CH2Cl2); H NMR (CDCl3, 400 MHz) δ: 8.08 (s, 1H,
NH), 7.43—7.41 (m, 2H, ArH), 7.32 (d, J＝8.0 Hz, 1H,
ArH), 7.23—7.04 (m, 6H, ArH), 5.73 (t, J＝8.0 Hz, 1H,
CH), 5.01—4.91 (m, 2H, CH); 13C NMR (CDCl3, 100
MHz) δ: 136.45, 133.82, 130.12, 128.96, 128.83, 127.27,
126.16, 122.76, 121.96, 120.01, 118.90, 113.20, 113.39,
77.70, 37.94. The ee value was determined by chiral
HPLC on a Daicel Chiralcel OD-H column (hex-
3f: Colorless solid; [α]2D0 －60.0 (c 0.1, CHCl3); 1H
NMR (CDCl3, 400 MHz) δ: 8.53 (d, J＝4.4 Hz, 1H,
ArH), 7.50 (t, J＝8.8 Hz, 1H, ArH), 7.39—6.80 (m,
21H, ArH), 6.42 (s, 1H, NH), 4.57 (s, 1H, CH), 4.34 (d,
J＝8.0 Hz, 1H, CH), 3.56—3.31 (m, 2H, CH), 2.33 (s,
3H, CH3); 13C NMR (CDCl3, 100 MHz) δ: 161.41,
156.01, 148.61, 142.61, 141.13, 138.61, 138.13, 137.05,
136.47, 129.57, 129.05, 128.77, 128.50, 128.30, 127.94,
127.74, 127.70, 127.48, 127.16, 125.38, 121.97, 120.34,
115.43, 64.57, 63.93, 63.37, 21.45; HRMS (ESI-MS)
calcd for C33H31N3O2S [M＋H]＋ : 534.2210, found
534.2215.
－1
ane/2-propanol, V∶V＝70∶30, 1.0 mL•min , 254 nm,
tmajor＝25.07 min, tminor＝16.48 min).
3-[1-(4-Methylphenyl)-2-nitroethyl]-1H-indole
This is a known compound.7d [α]D20 ＋7.8 (c 0.49,
1
CH2Cl2); H NMR (CDCl3, 400 MHz) δ: 7.99 (s, 1H,
NH), 7.43 (d, J＝7.6 Hz, 1H, ArH), 7.28 (d, J＝8.4 Hz,
1H, ArH), 7.20—7.03 (m, 6H, ArH), 6.93 (d, J＝2.4 Hz,
1H, ArH), 5.12 (t, J＝8.0 Hz, 1H, CH), 5.00 (dd, J＝
12.4, 7.6 Hz, 1H, CH), 4.88 (dd, J＝12.4, 8.4 Hz, 1H,
CH), 2.28 (s, 3H, CH3); 13C NMR (CDCl3, 100 MHz) δ:
137.25, 136.53, 136.22, 129.64, 127.67, 126.16, 122.66,
121.62, 119.93, 118.98, 114.57, 111.45, 79.69, 41.25,
21.09. The ee value was determined by chiral HPLC on
a Daicel Chiralcel OD-H co－lumn (hexane/2-propanol,
Typical procedure for the asymmetric F-C alkylation
reaction
To an oven-dried Schlenk tube were added ligand 3d
(2.4 µmol) and Zn(OTf)2 (2 µmol) under nitrogen, fol-
lowed by addition of dichloromethane (1 mL). The mix-
ture was stirred at room temperature for 3 h. The
1
V∶V＝70∶30, 1.0 mL•min , 254 nm, tmajor＝16.06
min, tminor＝17.95 min).
Chin. J. Chem. 2010, 28, 1424— 1428
© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
1427

Wu et al.
FULL PAPER
3-[1-(4-Fluorophenyl)-2-nitroethyl]-1H-indole
(b) Sheng, Y. F.; Zhang, A. J.; Zheng, S. L.; You, S. L. Chin.
J. Org. Chem. 2008, 28, 605 (in Chinese).
(c) You, S. L.; Cai, Q.; Zeng, M. Chem. Soc. Rev. 2009, 38,
2190.
This is a known compound.7d [α]D20 ＋20.7 (c 0.35,
1
CH2Cl2); H NMR (CDCl3, 400 MHz) δ: 8.08 (s, 1H,
NH), 7.39 (d, J＝8.0 Hz, 1H, ArH), 7.33 (d, J＝8.4 Hz,
1H, ArH), 7.30—7.23 (m, 2H, ArH), 7.19 (t, J＝7.2 Hz,
1H, ArH), 7.07 (t, J＝7.6 Hz, 1H, ArH), 7.01—6.95 (m,
3H, ArH), 5.15 (t, J＝8.0 Hz, 1H, CH), 5.03 (dd, J＝
12.4, 7.2 Hz, 1H, CH), 4.88 (dd, J＝12.4, 8.4 Hz, 1H,
CH); 13C NMR (CDCl3, 100 MHz) δ: 163.29, 160.84,
136.50, 134.96, 134.92, 129.40, 129.32, 125.93, 122.81,
121.45, 120.04, 118.83, 115.92, 115.70, 114.21, 111.46,
79.53, 40.86. The ee value was determined by chiral
HPLC on a Daicel Chiralcel OD-H column (hex-
3
(a) Zhuang, W.; Hausen, T.; Jrgensen, K. A. Chem. Com-
mun. 2001, 347.
(b) Zhou, J.; Tang, Y. J. Am. Chem. Soc. 2002, 124, 9030.
(c) Zhou, J.; Tang, Y. Chem. Commun. 2004, 432.
(d) Zhou, J.; Ye, M. C.; Huang, Z. Z.; Tang, Y. J. Org.
Chem. 2004, 69, 1309.
(e) Liu, Y. L.; Shang, D. J.; Zhou, X.; Liu, X. H.; Feng, X.
M. Chem. Eur. J. 2009, 15, 2055.
－1
4
5
6
7
Jensen, K. B.; Thorhauge, J.; Hazell, R. G.; Jrgensen, K. A.
Angew. Chem., Int. Ed. 2001, 40, 160.
ane/2-propanol, V∶V＝70∶30, 1.0 mL•min , 254 nm,
tmajor＝22.44 min, tminor＝27.32 min).
Evans, D. A.; Scheidt, K. A.; Frandrick, K. R.; Lam, H. W.;
Wu, J. J. Am. Chem. Soc. 2003, 125, 10780.
Bandini, M.; Melloni, A.; Tommasi, S.; Umani-Ronchi, A.
Helv. Chim. Acta 2003, 86, 3753.
3-[1-(4-Methoxyphenyl)-2-nitroethyl]-1H-indole
This is a known compound.7d [α]D20 ＋11.6 (c 0.57,
1
CH2Cl2); H NMR (CDCl3, 400 MHz) δ: 8.07 (s, 1H,
NH), 7.43 (d, J＝8.0 Hz, 1H, ArH), 7.35 (d, J＝8.4 Hz,
1H, ArH), 7.25—7.23 (m, 2H, ArH), 7.19 (t, J＝8.0 Hz,
1H, ArH), 7.07 (t, J＝7.6 Hz, 1H, ArH), 7.02 (d, J＝2.0
Hz, 1H, ArH), 6.85 (d, J＝6.8 Hz, 2H, ArH), 5.14 (t,
J＝8.0 Hz, 1H, CH), 5.05 (dd, J＝12.4, 7.6 Hz, 1H,
CH), 4.90 (dd, J＝12.4, 8.4 Hz, 1H, CH), 3.77 (s, 3H,
OCH3); 13C NMR (CDCl3, 100 MHz) δ: 158.91, 136.52,
131.17, 128.81, 126.11, 122.70, 121.43, 119.94, 119.01,
114.83, 114.28, 111.34, 79.75, 55.25, 40.86. The ee
value was determined by chiral HPLC on a Daicel
Chiralcel OD-H col－umn (hexane/2-propanol, V∶V＝
(a) Zhuang, W.; Hazell, R. G.; Jørgensen, K. A. Org. Bio-
mol. Chem. 2005, 3, 2566.
(b) Herrera, R. P.; Sgarzani, V.; Bernardi, L.; Ricci, A.
Angew. Chem., Int. Ed, 2005, 44, 6576.
(c) Singh, P. K.; Bisai, A.; Singh, V. K. Tetrahedron Lett.
2007, 48, 1127.
(d) Jia, Y. X.; Zhu, S. F.; Yang, Y.; Zhou, Q. L. J. Org.
Chem. 2006, 71, 75.
(e) Lu, S. F.; Du, D. M.; Xu, J. X. Org. Lett. 2006, 8, 2115.
(f) Han, L.; Lu, S. F.; Xu, J. X.; Du, D. M. Chem. Asian J.
2008, 3, 1111.
1
70∶30, 1.0 mL•min , 254 nm, tmajor＝20.72 min, tminor
＝22.83 min).
(g) Yuan, Z. L.; Lei, Z. Y.; Shi, M. Tetrahedron: Asymmetry
2008, 19, 1339.
5-Bromo-3-(2-nitro-1-phenylethyl)-1H-indole
This is a known compound.7d [α]D20 －19.7 (c 0.54,
1
CH2Cl2); H NMR (CDCl3, 400 MHz) δ: 8.17 (s, 1H,
(h) Lin, S. Z.; You, T. P. Tetrahedron 2009, 65, 1010.
Bandini, M.; Garelli, A.; Rovinetti, M.; Tommasi, S.;
Umani-Ronchi, A. Chirality 2005, 17, 522.
(a) Fleming, E. M.; McCabe, T.; Connon, S. J. Tetrahedron
Lett. 2006, 47, 7037.
NH), 7.54 (s, 1H, ArH), 7.35—7.19 (m, 7H, ArH), 7.05
(d, J＝2.0 Hz, 1H, ArH), 5.11 (t, J＝8.0 Hz, 1H, CH),
5.01 (dd, J＝12.4, 8.0 Hz, 1H, CH), 4.91 (dd, J＝12.4,
8.0 Hz, 1H, CH); 13C NMR (CDCl3, 100 MHz) δ:
138.65, 135.05, 129.04, 127.82, 127.76, 127.64, 125.63,
122.72, 121.43, 113.98, 113.22, 112.85, 79.38, 41.27.
The ee value was determined by chiral HPLC on a Dai-
cel Chiralcel AD-H col－umn (hexane/2-propanol, V∶V
8
9
(b) Ganesh, M.; Seidel, D. J. Am. Chem. Soc. 2008, 130,
16464.
10 (a) Itoh, J.; Fuchibe, K.; Akiyama, T. Angew. Chem., Int. Ed.
2008, 47, 4016.
1
＝90∶10, 1.0 mL•min , 254 nm, tmajor＝16.04 min,
(b) Sheng, Y. F.; Li, G. Q.; Kang, Q.; Zhang, A. J.; You, S.
L. Chem. Eur. J. 2009, 15, 3351.
tminor＝14.71 min).
11 (a) Singh, P. K.; Bisai, A.; Singh, V. K. Tetrahedron Lett.
2007, 48, 1127.
References
1
(a) Olah, G. A.; Khrisnamurti, R.; Prakash, G. K. S. In
Comprehensive Organic Synthesis, Vol. III, 1st ed., Eds.:
Trost, B. M.; Fleming, I., Pergamon, Oxford, 1991, p. 293.
(b) Roberts, R. M.; Khalaf, A. A. Friedel-Crafts Alkylation
Chemistry. A Century of Discovery, Marcel Dekker, New
York, 1984.
(b) Yokoyama, N.; Arai, T. Chem. Commun. 2009, 3285.
12 Wu, M.; Wang, B.; Wang, S. F.; Xia, C. G.; Sun, W. Org.
Lett. 2009, 11, 3622.
13 Ng, K.; Somanathan, R.; Walsh, P. J. Tetrahedron: Asym-
metry 2001, 12, 1719.
14 Liu, P. N.; Gu, P. M.; Wang, F.; Tu, Y. Q. Org. Lett. 2004,
6, 169.
2
(a) Poilsen, T. B.; Jørgensen, K. A. Chem. Rev. 2008, 108,
2903.
(E0912151 Pan, B.)
1428
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