Synthesis of 9,9′-biphenanthryl-10,10′-bis(oxazoline)s and their preliminary evaluations in the Friedel-Crafts alkylations of indoles with nitroalkenes

Article abstract of DOI:10.1016/j.tet.2008.11.083

Chiral 9,9′-biphenanthryl-10,10′-bis(oxazoline)s 6a-d were firstly prepared. These new chiral compounds were evaluated as ligands for the Friedel-Crafts alkylations of indoles with nitroalkenes, excellent yields and modest to good enantioselectivities were achieved.

Full text of DOI:10.1016/j.tet.2008.11.083

Tetrahedron 65 (2009) 1010–1016
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis of 9,90-biphenanthryl-10,100-bis(oxazoline)s and their preliminary
evaluations in the Friedel–Crafts alkylations of indoles with nitroalkenes
*
Shuang-zheng Lin, Tian-pa You
Department of Chemistry, University of Science and Technology of China, Hefei 230026, China
a r t i c l e i n f o
a b s t r a c t
Chiral 9,90-biphenanthryl-10,100-bis(oxazoline)s 6a–d were firstly prepared. These new chiral com-
pounds were evaluated as ligands for the Friedel–Crafts alkylations of indoles with nitroalkenes, ex-
cellent yields and modest to good enantioselectivities were achieved.
Article history:
Received 17 September 2008
Received in revised form 18 November 2008
Accepted 26 November 2008
Available online 30 November 2008
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
9,90-Biphenanthryl-10,100-bis(oxazoline)s
Indoles
Nitroalkenes
Friedel–Crafts alkylations
1. Introduction
hindrances of the aryl units, are seldom used for the asymmetric
reactions except for the parent biphenanthrol (Fig. 2, 4, R1¼
Biaryl compounds, especially the chiral 1,10-binaphthyl com-
pounds, are among the most widely used ligands in asymmetric
synthesis. Some binaphthyl ligands are illustrated in Figure 1.
A search of the literature revealed that the parent binaphthyl
ligands (Fig. 1, 1–3, R¼H) do not lead to satisfactory enantiose-
lectivities in some catalytic asymmetric reactions. In these cases,
high selectivities are often obtained when large substituted
groups (Fig. 1, 1–3, RsH) are introduced into the 3,30-positions
of the parent ligands.1 The coordination atoms of these ligands
are embedded within chiral pockets created by the hindrances of
the large R substituents. However, 9,90-biphenanthryl ligands
(Fig. 2, 4), in which the chiral pockets are created by the
R2¼H, X¼OH).2
R2
R1
X
X
Ph
Ph
OH
OH
R1
R2
X=OH, NH2, COOH, PPh2, etc.
5
4
R
R
R
Figure 2. Biphenanthryl ligands.
OH
OH
R'
R'
COOH
COOH
+ N
The studies of the 9,90-biphenanthrol as a chiral ligand
have not revealed significant advantages over the 1,10-
binaphthols (1).2 In contrast, the vaulted biaryl ligand 5 is
superior to binaphthols 1 in many reactions.3 We conceived
that 9,90-biphenanthryl ligands (substituted or unsubstituted)
would be good chiral ligands in some reactions. Herein we
would like to report the synthesis of 9,90-biphenanthryl-
10,100-bis(oxazoline)s (Fig. 3, 6) and their preliminary evalu-
ations as ligands for the Friedel–Crafts alkylations of indoles
with nitroalkenes.
R
R
R
3
2
1
Figure 1. Some binaphthyl ligands.
* Corresponding author. Tel.: þ86 551 3606944.
E-mail address: lins@mail.ustc.edu.cn (T.-pa You).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.11.083

S.-z. Lin, T.-pa You / Tetrahedron 65 (2009) 1010–1016
1011
Br
Br
iii, iv, v
i, ii
O
O
O
R
R
R
R
Br
CHO
CH3
N
N
N
N
8
9
10
O
Br
O
Br
COOH
vii, viii
R2
7
vi
H
N
6
OH
Figure 3. Biphenanthryl bis(oxazoline)s and binaphthryl bis(oxazoline)s.
R1
11
12
2. Results and discussion
Br
O
xi
ix, x
2.1. Preparations of biphenanthryl bis(oxazoline)s
N
R1
Due to (a) the high enantioselectivities in the asymmetric ca-
talysis mediated by the 1,10-binaphthryl-2,20-bis(oxazoline)s (Fig. 3,
7),4 (b) the facile preparations of oxazolines from natural amino-
acids (Scheme 1, a),5 and (c) the easy conversions to other func-
R2
13
R2
O
R1
R1
a R1=i-Pr, R2=H
6
N
N
O
R
NH2
1=Ph, R2=H
b R
R
HO
O
c R1=Bn, R2=H
HO
d R1=R2=Ph
O
NH2
R2
a
Scheme 2. Preparations of biphenanthryl bis(oxazoline)s. Reagents and conditions: (i)
n-BuLi (1.1 equiv), Et2O, rt, 1 h; then Me2SO4 (2 equiv), Et2O, reflux, 5 h, 99%; (ii) NBS
(1.1 equiv), CH3CN, rt in dark, 24 h, 92%; (iii) NBS (1.01 equiv), BPO (0.02 equiv), CCl4,
reflux, 7 h; (iv) CaCO3 (5 equiv), dioxane/H2O (1:1), reflux, 10 h, 92% (2 steps); (v) PCC
(1.3 equiv), CH2Cl2, 2 h, 84%; (vi) 2-methyl-2-butene (7.3 equiv), NaClO2 (8.7 equiv),
NaH2PO4$2H2O (6.9 equiv), t-BuOH/H2O (2:1), rt, 24 h; (vii) SOCl2, reflux, 5 h; (viii)
Et3N (3.1 equiv), aminoalcohol (1.0 equiv), THF, overnight; (ix) SOCl2 (10.2 equiv),
CH2Cl2, rt, 24 h; (x) NaOH (2.0 equiv), THF/MeOH (3:1), reflux, 5 h; (xi) activated Cu
powder (10.0 equiv), pyridine, reflux, 24 h.
d
b
O
R
R'
NH2
N
O
R'
R'
OH
c
OH
R'
R'
Scheme 1.
attention as ligands in coordination chemistry and asymmetric
catalysis.5 Recently, bis(oxazoline)s were reported to be used in the
Friedel–Crafts alkylations of indoles with nitroalkenes, and satis-
factory enantioselectivities were reported.10 As the indole skeleton
is one of the privileged structures in medicinal chemistry and 2-
indolyl-1-nitro derivatives are useful intermediates for the syn-
tional groups from oxazolines (Scheme 1, b–d),5b we try to prepare
the 9,90-biphenanthryl-10,100-bis(oxazoline)s (6) and explore their
applications as ligands in catalytic asymmetric reactions.
The synthetic sequence of biphenanthryl bis(oxazoline)s is
outlined in Scheme 2.
thesis of tryptamines and 1,2,3,4-tetrahydro-b
-carbolines,11 the
The commercial available 9-bromophenanthrene (8) was
treated with n-BuLi, and then methylated with dimethyl sulfate to
form 9-methylphenanthrene first, which was brominated to give 9-
bromo-10-methylphenanthrene (9). This compound was converted
to 10-bromophenanthrene-9-carbaldehyde (10) after bromination,
hydrolysis, and oxidation. The aldehyde intermediate 10 was
smoothly oxidized with sodium chlorite to afford 10-bromophe-
nanthrene-9-carboxylic acid (11).6 The yields of oxidations using
transition metal oxides were uniformly low for this step.7 With the
acid 11 in hand, the oxazolines 13 could be easily prepared by the
classical methods.5 The Ullmann reactions of 13 led to the bis(oxa-
zoline)s 6.8 We were unable to separate the diastereomers by
column chromatography. Fortunately, the major diastereomers,
which were supposed to be S-axial configurational, could be
obtained by recrystallization.9
reactions of indoles and nitroalkenes mediated by the biphe-
nanthryl bis(oxazoline)s were investigated.
At the outset, the alkylation of indole (14a) with trans-b-nitro-
styrene (15a) was performed in different solvents at room tem-
perature catalyzed by different Lewis acids and ligands, and the
results are summarized in Table 1.
When Cu(OTf)2, Mg(OTf)2, or Ba(OTf)2 was employed as a Lewis
acid (Table 1, entries 1, 3, and 4), and the bis(oxazoline) 6a was used
as a ligand, the reaction took place very slowly in chloroform. On
the contrast, the reaction mediated by Zn(OTf)2 was carried out
smoothly (Table 1, entry 2), giving the product 3-(2-nitro-1-phe-
nylethyl)-1H-indole (16aa) in an excellent yield (>99%) and modest
enantioselectivity (59% ee). When the reaction was catalyzed by
La(OTf)3 or Sm(OTf)3 (Table 1, entries 5 and 6), the enantiomeric
excess of the product was zero, though the yield was excellent
(>99%). The other three biphenanthryl bis(oxazoline)s (6b–d) were
also examined, but the ees of the products were all inferior to 6a
(Table 1, entries 7–9). This may indicate different properties of
these bulky biphenanthryl ligands compared to other type of
bis(oxazoline)s, since the bis(oxazoline)s ligands bearing phenyl
groups on the oxazoline rings usually gave better results than the
2.2. Friedel–Crafts alkylation reactions of indoles and
nitroalkenes
With the four biphenanthryl bis(oxazoline)s (6a–d) in hand, we
tried to evaluate them as ligands for catalytic asymmetric reactions.
C2-symmetric bis(oxazoline)s have received
a great deal of

1012
S.-z. Lin, T.-pa You / Tetrahedron 65 (2009) 1010–1016
Table 1
Table 2
Alkylation reactions of indole with trans-
b
-nitrostyrenea
Scope of the alkylations of indoles with nitroalkenesa
R3
Ph
R1
10 mol% cat.
10 mol% Zn(OTf)2
R1
*
*
R3
NO2
Ph
NO2
11 mol% ligand
11 mol% 6a
+
+
solvent
r.t.
NO2
N
H
Et2O, r.t.
NO2
N
N
N
R2
H
R2
16
14
15
14a
15a
16aa
Entry
Lewis acid
Solvent
Ligand
Time (h)
Yieldb (%)
eec (%)
Entry Indole R1
R2 R3
Product Yieldb (%) eec (%)
1d
2
Cu(OTf)2
Zn(OTf)2
Mg(OTf)2
Ba(OTf)2
La(OTf)3
Sm(OTf)3
Zn(OTf)2
Zn(OTf)2
Zn(OTf)2
Zn(OTf)2
Zn(OTf)2
Zn(OTf)2
Zn(OTf)2
Zn(OTf)2
Zn(OTf)2
Zn(OTf)2
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CH2Cl2
CCl4
ClCH2CH2Cl
PhCH3
Et2O
THF
CH3CN
6a
6a
6a
6a
6a
6a
6b
6c
6d
6a
6a
6a
6a
6a
6a
6a
24
24
24
24
18
18
24
24
24
24
24
48
72
20
72
48
<5
>99
<5
d
59
d
d
0
1
2
3
4
5
6
7
8
14a
14a
14a
14a
14a
14a
14a
14a
14a
14a
14a
14a
14a
14a
14a
14a
14b
14c
14d
14e
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Ph (15a)
4-F-Ph (15b)
16aa
16ab
16ac
16ad
16ae
16af
16ag
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
d
63 (67)
57
62
60
57
60
46
48
55
50
53
41
79 (85)
67
d
3d
4d
5
4-Cl-Ph (15c)
4-Br-Ph (15d)
4-O2N-Ph (15e)
4-Me-Ph (15f)
4-MeO-Ph (15g)
<5
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
d
6
7
8
9
10
11
12
13
14
15e
16
0
17
41
38
59
47
52
58
63
d
10
3,4,5-(MeO)3-Ph (15h) 16ah
9
4-HO-Ph (15i)
2-Br-Ph (15j)
1-Naphthyl (15k)
2-Furyl (15l)
n-Pr (15m)
i-Pr (15n)
t-Bu (15o)
c-hex (15p)
16ai
16aj
16ak
16al
16am
16an
16ao
16ap
16ba
16ca
16da
16ea
10
11
12
13
14
15d
16
17
18
19
20
>99
>99
>99
>99
>99
>99
39
55
40
60
a
Me Ph (15a)
The reactions were performed at rt using 0.1 equiv of Lewis acid, 0.11 equiv of
2-Me
5-Br
5-MeO
H
H
H
Ph (15a)
Ph (15a)
Ph (15a)
ligand, 1 equiv of indole (14a), and 2 equiv of trans-b-nitrostyrene (15a) under N2
atmosphere.
b
56
Isolated yield.
c
a
Determined by chiral HPLC. The absolute configuration is S, see Ref. 10b.
Estimated by TLC.
No reaction.
The reactions were performed at rt using 0.1 equiv of Zn(OTf)2, 0.11 equiv of 6a,
d
e
1 equiv of indole, and 2 equiv of nitroalkene under N2 atmosphere.
b
Isolated yield.
c
Determined by chiral HPLC. The values in the parentheses are the enantiose-
lectivities of the products obtained at 0 ꢀC.
d
isopropyl substituted ones in the reactions of indoles and nitro-
alkenes.10 Thus, the complex of Zn(OTf)2 and bis(oxazoline) 6a was
found to be the best catalyst here. Different solvents were then
screened under this condition (Table 1, entries 10–16). The reaction
in diethyl ether gave the best result, the conversion was completed
within 20 h and excellent yield (>99%) was obtained, but the ee
was still modest (63%).
No reaction.
Br-, and 5-MeO-indole gave modest enantioselectivities (Table 2,
entries 17, 19, and 20), while 2-methylindole gave lower ee value
because of the existence of steric hindrance (Table 2, entry 18).
To optimize the reaction conditions further, we screened other
parameters such as additives, temperature, and catalyst loading.
When water or molecular sieve was employed as an additive, the
enantioselectivity was decreased to 55% ee or 32% ee, respectively.
The enantiomeric excess was improved only slightly (65%) if the
catalyst loading was increased to 15%, while the ee was decreased
to 57% when 5% catalyst loading was used for the reaction. Low
reaction temperature did not bring much benefit. The enantiose-
lectivity was improved slightly to 67% ee, while a long reaction time
of 72 h was needed for a complete conversion.
3. Conclusion
In conclusion, biphenanthryl bis(oxazoline)s 6a–d were firstly
prepared. These new chiral compounds were employed as ligands
for the Friedel–Crafts alkylations of indoles with nitroalkenes, ex-
cellent yields and modest to good enantioselectivities were ach-
ieved. The enantioselectivity was highly affected by the steric
hindrance between the substrates. Unlike the results induced by
other types of bis(oxazoline)s ligands,10 unbranched aliphatic
nitroalkene 15m gave much better enantioselectivity than the rigid
nitrostyrenes in our experiments. Further evaluations of these
biphenanthryl bis(oxazoline)s and the preparations and evalua-
tions of other chiral ligands containing biphenanthryl unit are still
in progress in our laboratory.
The scope of the alkylations of indoles with nitroalkenes was
explored at room temperature under the optimal conditions, and
the results are summarized in Table 2.
Firstly, the para-substituted nitrostyrenes were screened, ex-
cellent yields and modest enantioselectivities were achieved in all
cases (Table 2, entries 1–9). Comparable results were obtained
when other aryl nitroalkenes were examined (Table 2, entries 10–
12). The best result was achieved when this reaction was extended
to unbranched aliphatic nitroalkene 15m, the enantioselectivity
was 79% ee, which was further enhanced to 85% ee when the re-
action was conducted at 0 ꢀC (Table 2, entry 13). However, the
enantioselectivity was significantly decreased with enhanced steric
hindrance when branched aliphatic nitroalkenes were employed in
this reaction. 3-Methyl-1-nitrobut-1-ene (15n) gave 67% ee (Table
2, entry 14), cyclohexyl-substituted nitroalkene 15p gave 39% ee
(Table 2, entry 16), and the reaction of 3,3-dimethyl-1-nitrobut-1-
ene (15o) with indole was completely restrained (Table 2, entry 15).
The substituent effect on the indole ring was also studied. 1-Me-, 5-
4. Experimental section
4.1. General
All reactions were conducted in oven-dried glassware. NMR
spectra were measured on a Bruker 300 MHz (or 400 MHz) spec-
trometer. Chemical shifts were reported in parts per million relative
to internal tetramethylsilane. High resolution mass spectroscopy
(HRMS) was performed on a Micromass GCT mass spectrometer.
Column chromatography was carried out on silica gel (200–400
mesh) using petroleum ether (bp 60–90 ꢀC) and EtOAc as eluents.
The enantiomeric excess of the products was determined by chiral

S.-z. Lin, T.-pa You / Tetrahedron 65 (2009) 1010–1016
1013
HPLC. All solvents were purified before use. PCC,12 (S)-valinol,13 (S)-
phenylglycinol,13 (S)-phenylalaninol,13 nitroalkenes,14 metal tri-
flates,15 and 2-methyl-2-butene16 were prepared according to the
literature procedures. Other reagents were purchased from vendors
and used without further purification. N2 was used without further
purification.
(10 mL) for 5 h, SOCl2 was then removed by rotary evaporation.
The residue was dissolved in 20 mL of dry THF, added dropwise to
a 20 mL THF solution of Et3N (1.5 mL, 10.8 mmol) and (S)-valinol
(0.36 g, 3.5 mmol) at 0 ꢀC. The mixture was allowed to stir over-
night at room temperature. After removal of THF, the residue was
dispersed in 1 M HCl and EtOAc. The organic phase was separated
and the aqueous phase was extracted twice with EtOAc. The or-
ganic layers were combined, concentrated, and chromatographed
on silica gel to give (S)-10-bromo-N-(1-hydroxy-3-methylbutan-2-
yl)phenanthrene-9-carboxamide (12a) (1.25 g, 3.24 mmol, 92.5%
yield).
4.2. General procedures for the preparation of biphenanthryl
bis(oxazoline)s
4.2.1. 9-Methylphenanthrene17
Under N2 atmosphere, 9-bromophenanthrene (8) (2.57 g,
10.0 mmol) was dissolved in 50 mL of dry Et2O. Cooled by ice-bath,
n-BuLi (2.5 M in hexane, 4.4 mL, 11.0 mmol) was slowly added to
the reactants in 10 min. Stirring was continued at room tempera-
ture for 1 h before recooled to 0 ꢀC. Then Me2SO4 (1.8 mL, 2.5 g,
19.8 mmol) was added carefully in 30 min. After addition, the re-
action was refluxed for 5 h. After cooling, 100 mL of NH3$H2O was
added, the mixture was stirred for 1 h, and then poured in sepa-
ratory funnel. The ether phase was separated and the water phase
was extracted twice by Et2O. The organic phases were combined
and dried with MgSO4. After evaporation of the solvent and
recrystallized from hexane, 9-methylphenanthrene was obtained
as white solid (1.9 g, 9.88 mmol, 99% yield).
4.2.5. (S)-2-(10-Bromophenanthren-9-yl)-4-isopropyl-4,5-
dihydrooxazole (13a)
(S)-10-Bromo-N-(1-hydroxy-3-methylbutan-2-yl)phenanthrene-
9-carboxamide (12a) (1.25 g, 3.24 mmol) and SOCl2 (2.4 mL,
33.1 mmol) were stirred in dry CH2Cl2 (30 mL) for 24 h at room
temperature. After carefully addition of 20 mL of water, the organic
layer was separated and the aqueous layer was extracted twice with
CH2Cl2. The organic extracts were combined, washed successively
with saturated aqueous NaHCO3 and water, dried over MgSO4.
Removal of the solvent gave (S)-10-bromo-N-(1-chloro-3-methyl-
butan-2-yl)phenanthrene-9-carboxamide as a crude product. This
residue was dissolved in dry THF (45 mL) and then a 15 mL MeOH
solution of NaOH (0.26 g, 6.5 mmol) was added. The mixture was
refluxed for 5 h. The solvent was removed by rotary evaporation,
and the residue was dispersed in CH2Cl2 and brine. The organic
layer was separated and the aqueous layer was extracted twice with
CH2Cl2. The organic extracts were combined, dried, concentrated,
and purified by chromatography to give (S)-2-(10-bromophe-
4.2.2. 9-Bromo-10-methylphenanthrene (9)17
9-Methylphenanthrene (1.9 g, 9.88 mmol) and NBS (1.93 g,
10.8 mmol) were dissolved in 30 mL of CH3CN, the mixture was
stirred in dark at ambient temperature for 24 h. Then the reaction
was ceased by addition of 100 mL of 1 M NaOH. The organics were
extracted with CH2Cl2 and dried with MgSO4. Purification by col-
umn chromatography gave 9-bromo-10-methylphenanthrene as
a white solid (2.47 g, 9.1 mmol, 92% yield).
nanthren-9-yl)-4-isopropyl-4,5-dihydrooxazole
(13a)
(1.15 g,
8.67 (d,
3.13 mmol, 96.5% yield). 1H NMR (300 MHz, CDCl3)
d
J¼7.5 Hz, 2H), 8.48 (dd, J¼7.5, 2.1 Hz, 1H), 7.90 (d, J¼7.8 Hz, 1H),
7.75–7.59 (m, 4H), 4.70–4.61 (m, 1H), 4.40–4.30 (m, 2H), 2.13–2.02
(m, 1H), 1.20 (d, J¼6.6 Hz, 3H), 1.12 (d, J¼6.9 Hz, 3H); 13C NMR
4.2.3. 10-Bromophenanthrene-9-carbaldehyde (10)7a
9-Bromo-10-methylphenanthrene (2.47 g, 9.1 mmol), NBS
(1.64 g, 9.2 mmol), and BPO (44 mg, 0.18 mmol) were refluxed in
CCl4 (25 mL) for 7 h. Then the solvent was evaporated under re-
duced pressure. The residue was refluxed with CaCO3 (5.5 g,
55.0 mmol) in 30 mL dioxane and 30 mL H2O for 10 h. After
cooling, excess diluted hydrochloric acid was added to dissolve
residual CaCO3. Extracted with CH2Cl2, dried with MgSO4, purified
by column chromatography, the alcohol product was gained as
a white solid (2.41 g, 8.4 mmol, 92% yield). This alcohol was oxi-
dized with PCC in CH2Cl2 to give aldehyde 10 (2.0 g, 7.0 mmol, 84%
yield) as a white solid. Total yield 70%. 1H NMR (300 MHz, CDCl3)
(75 MHz, CDCl3) d 162.7, 131.6, 130.4, 129.8, 129.7, 129.0, 128.8,
128.5, 127.9, 127.8, 127.5, 126.1, 123.8, 123.0, 122.8, 73.8, 71.1, 33.2,
19.5, 19.3.
4.2.6. (S)-2-(10-Bromophenanthren-9-yl)-4-phenyl-4,5-
dihydrooxazole (13b)
Yield from 10-bromophenanthrene-9-carbaldehyde (10) was
82.1%. 1H NMR (300 MHz, CDCl3)
d 8.73–8.70 (m, 2H), 8.52 (dd,
J¼7.5, 1.5 Hz, 1H), 7.99 (d, J¼7.5 Hz, 1H), 7.80–7.70 (m, 3H), 7.64 (t,
J¼7.2 Hz, 1H), 7.57 (d, J¼7.2 Hz, 2H), 7.45 (t, J¼7.5 Hz, 2H), 7.36 (t,
J¼7.2 Hz, 1H), 5.71 (t, J¼9.9 Hz, 1H), 5.04 (dd, J¼10.2, 8.4 Hz, 1H),
d
10.91 (s, 1H), 8.72 (d, J¼8.1 Hz, 1H), 8.71–8.63 (m, 3H), 7.86–7.66
4.49 (t, J¼9.0 Hz, 1H); 13C NMR (75 MHz, CDCl3)
d 164.1, 141.9, 131.6,
130.3, 129.7, 128.9, 128.6, 128.4, 127.9, 127.8, 127.5, 127.1, 126.0,
123.9, 123.0, 122.8, 75.1, 70.9.
(m, 4H); 13C NMR (75 MHz, CDCl3)
d
195.7, 133.1, 132.5, 130.3,
130.0, 129.9, 129.6, 128.9, 128.8, 128.5, 128.2, 127.9, 125.6, 123.0,
122.9.
4.2.7. (S)-4-Benzyl-2-(10-bromophenanthren-9-yl)-4,5-
dihydrooxazole (13c)
4.2.4. (S)-10-Bromo-N-(1-hydroxy-3-methylbutan-2-yl)-
phenanthrene-9-carboxamide (12a)
Yield from 10-bromophenanthrene-9-carbaldehyde (10) was
To a mixture of 10-bromophenanthrene-9-carbaldehyde (10)
(1.0 g, 3.5 mmol) and tert-butyl alcohol (60 mL) was added 2-
methyl-2-butene (2.7 mL, 25.5 mmol). A 30 mL of aqueous solu-
tion of NaClO2 (80%, 3.44 g, 30.4 mmol) and NaH2PO4$2H2O
(3.76 g, 24.1 mmol) was added dropwise over a period of 15 min.
This resulted in a clear solution, which was allowed to stir for 24 h
at room temperature. The t-BuOH was removed by rotary evapo-
ration and the mixture was treated with 20 mL of H2O and washed
with two portions of 20 mL hexane. The aqueous layer was then
acidified to pH 1 and extracted with EtOAc (3ꢁ30 mL). The organic
extracts were combined, dried over MgSO4, and concentrated by
rotary evaporation to afford the crude 10-bromophenanthrene-9-
carboxylic acid (11). This crude product was refluxed in SOCl2
84.0%. 1H NMR (300 MHz, CDCl3)
d 8.68–8.64 (m, 2H), 8.47 (dd,
J¼7.5, 1.5 Hz, 1H), 7.72–7.65 (m, 4H), 7.56 (t, J¼7.5 Hz, 1H), 7.34–7.24
(m, 5H), 4.91–4.81 (m, 1H), 4.59 (t, J¼9.0 Hz, 1H), 4.36 (t, J¼8.1 Hz,
1H), 3.37 (dd, J¼13.8, 5.7 Hz, 1H), 3.05 (dd, J¼13.8, 8.1 Hz, 1H); 13C
NMR (75 MHz, CDCl3) d 163.4, 138.0, 131.7, 130.3, 129.8, 129.7, 129.0,
128.9, 128.6, 128.0, 127.8, 127.6, 126.8, 126.2, 123.9, 123.0, 122.9,
72.4, 68.8, 41.7, 31.0.
4.2.8. (4S,5R)-2-(10-Bromophenanthren-9-yl)-4,5-diphenyl-4,5-
dihydrooxazole (13d)
Yield from 10-bromophenanthrene-9-carbaldehyde (10) was
80.7%; 1H NMR (400 MHz, CDCl3)
(d, J¼8.0 Hz, 1H), 8.12 (dd, J¼5.8, 2.8 Hz, 1H), 7.66–7.65 (m, 4H),
d
8.61 (d, J¼3.5 Hz, 2H), 8.48

1014
S.-z. Lin, T.-pa You / Tetrahedron 65 (2009) 1010–1016
7.53–7.52 (m, 4H), 7.44–7.41 (m, 4H), 7.37–7.32 (m, 2H), 5.64 (d,
4.3. General procedures for the catalytic asymmetric
Friedel–Crafts alkylation reactions
J¼9.5 Hz, 1H), 5.56 (d, J¼9.5 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d
163.3, 141.5, 139.6, 131.6, 130.3, 129.7, 129.0, 128.9, 128.63, 128.59,
128.3, 127.92, 127.87, 127.8, 127.5, 127.0, 126.3, 125.9, 124.1, 123.0,
122.8, 89.8, 79.4.
4.3.1. (S)-3-(2-Nitro-1-phenylethyl)-1H-indole (16aa)10
To
a dried Schlenk tube were added Zn(OTf)2 (4 mg,
0.011 mmol) and biphenanthryl bis(oxazoline)s 6a (7 mg,
0.012 mmol) under N2 atmosphere, followed by addition of Et2O
(0.5 mL). The solution was stirred at room temperature for 2 h
4.2.9. (S)-10,100-Bis[(S)-4-isopropyl-4,5-dihydrooxazol-2-yl]-9,90-
biphenanthrene (6a)
A mixture of (S)-2-(10-bromophenanthren-9-yl)-4-isopropyl-
4,5-dihydrooxazole (13a) (1.0 g, 2.72 mmol) and 1.73 g (27.2 mmol)
of freshly activated copper powder18 in 5.0 mL of freshly distilled
pyridine was refluxed for 24 h. After cooled, the mixture was di-
luted with CH2Cl2 and washed with aqueous ammonia repeatedly
until the copper had been completely removed. The organic portion
was washed with water and dried over MgSO4. The solvent was
removed in vacuo and the residue was chromatographed to give
a mixture of bis(oxazoline)s diastereomers. This mixture was
recrystallized twice from Et2O to give the major diastereomer, (S)-
under N2 atmosphere and trans-b-nitrostyrene (15a) (33 mg,
0.22 mmol) was added. The mixture was stirred for 15 min before
the indole (14a) (13 mg, 0.11 mmol) was added. After the reaction
was complete (monitored by TLC), the mixture was chromato-
graphed on silica gel column to afford the product (S)-3-(2-nitro-1-
phenylethyl)-1H-indole (16aa) (30 mg, quant.) as an oil: 63% ee
[Daicel Chiralcel OD column, n-hexane/i-PrOH¼70:30, 1.0 mL/min,
254 nm; t1¼15.04 min (major), t2¼19.24 min]; 1H NMR (300 MHz,
CDCl3)
d
7.95 (s, 1H), 7.38 (d, J¼8.4 Hz, 1H), 7.15–7.03 (m, 7H), 6.92
(t, J¼7.5 Hz, 1H), 6.72 (d, J¼1.8 Hz, 1H), 5.01 (t, J¼7.8 Hz, 1H), 4.84
10,100-bis[(S)-4-isopropyl-4,5-dihydrooxazol-2-yl]-9,90-biphenan-
(dd, J¼12.6, 7.5 Hz, 1H), 4.73 (dd, J¼12.6, 8.7 Hz); 13C NMR (75 MHz,
26
threne (6a), as a white solid (0.33 g, 0.57 mmol). Yield 42.0%; [
a
]
CDCl3) d 139.3, 136.5, 128.9, 127.8, 127.5, 126.1, 122.6, 121.8, 119.9,
D
ꢂ207.2 (c 1.02, CHCl3). 1H NMR (400 MHz, CDCl3)
d
8.78 (t, J¼8.7 Hz,
118.9, 114.1, 111.5, 79.5, 41.6.
4H), 8.19 (d, J¼8.3 Hz, 2H), 7.73–7.71 (m, 2H), 7.67–7.64 (m, 4H),
7.58 (d, J¼8.4 Hz, 2H), 7.39–7.37 (m, 2H), 3.72 (dd, J¼9.3, 1.4 Hz, 2H),
3.52–3.45 (m, 2H), 3.40 (t, J¼8.1 Hz, 2H), 1.01–0.95 (m, 2H), 0.50 (t,
4.3.2. 3-[1-(4-Fluorophenyl)-2-nitroethyl]-1H-indole (16ab)10
Yield >99%; 57% ee [Daicel Chiralcel OD column, n-hexane/i-
PrOH¼70:30, 1.0 mL/min, 254 nm; t1¼16.40 min (major),
J¼6.9 Hz, 12H); 13C NMR (100 MHz, CDCl3)
d 162.1, 135.5, 130.9,
130.8, 130.3,129.7,128.8,127.6,127.2,127.1,127.0,126.7,122.6,122.3,
73.2, 70.0, 32.8, 19.1, 18.5; HRMS calcd for C40H36N2O2 (Mþ)
576.2777, found 576.2781.
t2¼21.13 min]; 1H NMR (300 MHz, CDCl3)
d 8.11 (s, 1H), 7.36 (d,
J¼7.8 Hz, 1H), 7.26–7.12 (m, 4H), 7.03 (t, J¼7.5 Hz, 1H), 6.91 (t,
J¼8.7 Hz, 2H), 6.86 (d, J¼2.1 Hz, 1H), 5.10 (t, J¼8.1 Hz, 1H), 4.95 (dd,
J¼12.6, 7.5 Hz, 1H), 4.80 (dd, J¼9.9, 8.7 Hz, 1H); 13C NMR (75 MHz,
4.2.10. (S)-10,100-Bis[(S)-4-phenyl-4,5-dihydrooxazol-2-yl]-9,90-
CDCl3)
d
162.1 (d, J¼244 Hz), 136.6, 135.2, 129.5, 129.4, 126.0, 122.8,
biphenanthrene (6b)
121.6, 120.0, 118.9, 115.9, 115.7, 114.1, 111.6, 79.6, 40.9.
26
White solid; 39.0% yield; [
(400 MHz, CDCl3)
a]
ꢂ116.8 (c 1.02, CHCl3). 1H NMR
D
d
8.85 (d, J¼8.2 Hz, 2H), 8.76 (d, J¼8.2 Hz, 2H),
4.3.3. 3-[1-(4-Chlorophenyl)-2-nitroethyl]-1H-indole (16ac)10
Yield >99%; 62% ee [Daicel Chiralcel OD column, n-hexane/i-
PrOH¼70:30, 1.0 mL/min, 254 nm; t1¼18.71 min (major),
8.26 (d, J¼7.8 Hz, 2H), 7.80 (t, J¼6.9 Hz, 2H), 7.72 (t, J¼7.0 Hz, 2H),
7.64 (d, J¼7.2 Hz, 2H), 7.60 (dd, J¼8.3, 0.7 Hz, 2H), 7.37 (t, J¼7.0 Hz,
2H), 7.01 (t, J¼7.4 Hz, 2H), 6.84 (t, J¼7.7 Hz, 4H), 6.62 (d, J¼7.5 Hz,
4H), 5.01 (t, J¼9.8 Hz, 2H), 4.23 (dd, J¼10.2, 8.3 Hz, 2H), 3.38 (t, d,
t2¼24.04 min]; 1H NMR (300 MHz, CDCl3)
d 8.04 (s, 1H), 7.34 (d,
J¼7.8 Hz, 1H), 7.22–7.11 (m, 6H), 7.02 (t, J¼7.5 Hz, 1H), 6.79 (d,
J¼8.5 Hz, 2H); 13C NMR (100 MHz, CDCl3)
d 163.6, 141.8,135.7,130.9,
J¼2.4 Hz, 1H), 5.05 (t, J¼7.8 Hz, 1H), 4.89 (dd, J¼12.6, 7.5 Hz, 1H),
130.8, 130.5, 129.6, 128.8, 128.1, 127.8, 127.40, 127.37, 127.1, 126.92,
126.87, 126.5, 122.9, 122.5, 74.0, 70.5; HRMS calcd for C46H32N2O2
(Mþ) 644.2464, found 644.2468.
4.75 (dd, J¼12.6, 8.7 Hz, 1H); 13C NMR (75 MHz, CDCl3)
d 137.9,
136.5, 133.2, 129.1, 129.0, 125.9, 122.7, 121.7, 120.0, 118.7, 113.6, 111.6,
79.2, 40.9.
4.2.11. (S)-10,100-Bis[(S)-4-benzyl-4,5-dihydrooxazol-2-yl]-9,90-
4.3.4. 3-[1-(4-Bromophenyl)-2-nitroethyl]-1H-indole (16ad)10
Yield >99%; 60% ee [Daicel Chiralcel OD column, n-hexane/i-
PrOH¼70:30, 1.0 mL/min, 254 nm; t1¼19.90 min (major),
biphenanthrene (6c)
26
White solid; 40.3% yield; [
(400 MHz, CDCl3)
a
]
D
ꢂ63.4 (c 1.02, CHCl3). 1H NMR
d
8.80 (t, J¼8.4 Hz, 4H), 8.13 (d, J¼7.6 Hz, 2H),
t2¼26.03 min]; 1H NMR (300 MHz, CDCl3)
d 8.08 (s, 1H), 7.31–7.26
7.72–7.65 (m, 8H), 7.44 (t, J¼7.5 Hz, 2H), 7.12–7.10 (m, 6H), 6.76 (dd,
J¼7.5, 1.8 Hz, 4H), 4.11–4.05 (m, 2H), 3.71 (t, J¼8.8 Hz, 2H), 3.41 (dd,
J¼8.4, 6.8 Hz, 2H), 2.41 (dd, J¼13.6, 5.1 Hz, 2H), 1.56 (dd, J¼13.9,
(m, 3H), 7.20 (d, J¼8.1 Hz, 1H), 7.11–7.04 (m, 3H), 6.96 (t, J¼7.5 Hz,
1H), 6.82 (d, J¼2.1 Hz, 1H), 5.01 (t, J¼7.8 Hz, 1H), 4.89 (dd, J¼12.3,
7.5 Hz, 1H), 4.74 (dd, J¼12.6, 8.7 Hz, 1H); 13C NMR (75 MHz, CDCl3)
9.5 Hz, 2H); 13C NMR (100 MHz, CDCl3)
d
162.6, 138.3, 136.1, 131.0,
d 138.5, 136.7, 132.1, 129.6, 126.0, 122.9, 121.7, 121.6, 120.1, 118.8,
130.2, 129.5, 129.0, 128.8, 128.4, 127.8, 127.3, 127.0, 126.9, 126.7,
126.2,122.7,122.6, 71.1, 68.2, 40.8; HRMS calcd for C48H36N2O2 (Mþ)
672.2777, found 672.2776.
113.8, 111.6, 79.3, 41.1.
4.3.5. 3-[2-Nitro-1-(4-nitrophenyl)ethyl]-1H-indole (16ae)10
Yield >99%; 57% ee [Daicel Chiralcel OD column, n-hexane/i-
PrOH¼70:30, 1.0 mL/min, 254 nm; t1¼37.48 min (major),
4.2.12. (S)-10,100-Bis[(4S,5R)-4,5-diphenyl-4,5-dihydrooxazol-2-
yl]-9,90-biphenanthrene (6d)
t2¼48.29 min]; 1H NMR (300 MHz, CDCl3)
d 8.15 (s, 1H), 8.03 (d,
26
White solid; 39.8% yield; [
a
]
57.4 (c 1.02, CHCl3). 1H NMR
J¼7.8 Hz, 2H), 7.38 (d, J¼8.1 Hz, 2H), 7.26 (d, J¼8.1 Hz, 2H), 7.11 (t,
J¼7.8 Hz, 1H), 6.98 (t, J¼7.5 Hz, 1H), 6.92 (s, 1H), 5.17 (t, J¼7.8 Hz,
1H), 4.98 (dd, J¼12.6, 7.2 Hz, 1H), 4.87 (dd, J¼12.6, 9.0 Hz, 1H); 13C
D
(400 MHz, CDCl3)
d
8.90 (d, J¼8.1 Hz, 2H), 8.79 (d, J¼8.2 Hz, 2H),
8.44 (d, J¼7.7 Hz, 2H), 7.87 (t, J¼7.6 Hz, 2H), 7.80 (t, J¼7.7 Hz, 2H),
7.70 (d, J¼7.8 Hz, 2H), 7.64 (t, J¼7.6 Hz, 2H), 7.37 (t, J¼7.6 Hz,
2H), 7.13 (t, J¼7.5 Hz, 2H), 7.05–6.98 (m, 6H), 6.87 (t, J¼7.7 Hz, 4H),
6.80 (d, J¼7.5 Hz, 4H), 6.64 (d, J¼7.3 Hz, 4H), 4.81 (d, J¼10.0 Hz, 2H),
NMR (75 MHz, CDCl3) d 146.9, 136.7, 128.9, 125.8, 124.3, 123.2, 121.8,
120.5, 118.6, 113.1, 111.8, 78.9, 41.4.
4.59 (d, J¼10.0 Hz, 2H); 13C NMR (100 MHz, CDCl3)
d
163.0, 141.3,
4.3.6. 3-[1-(4-Methylphenyl)-2-nitroethyl]-1H-indole (16af)10
Yield >99%; 60% ee [Daicel Chiralcel OD column, n-hexane/i-
PrOH¼70:30, 1.0 mL/min, 254 nm; t1¼13.28 min (major),
139.3, 135.5, 131.0, 130.7, 129.8, 129.0, 128.4, 128.3, 128.0, 127.6,
127.5, 127.1, 127.0, 126.7, 126.0, 123.1, 122.5, 88.9, 78.8; HRMS calcd
for C58H40N2O2 (Mþ) 796.3090, found 796.3096.
t2¼15.80 min]; 1H NMR (300 MHz, CDCl3)
d 7.87 (s, 1H), 7.39 (d,

S.-z. Lin, T.-pa You / Tetrahedron 65 (2009) 1010–1016
1015
J¼7.8 Hz, 1H), 7.20–7.09 (m, 4H), 7.05–6.99 (m, 3H), 6.78 (d,
J¼2.4 Hz, 1H), 5.07 (t, J¼8.1 Hz, 1H), 4.91 (dd, J¼12.3, 7.5 Hz, 1H),
4.79 (dd, J¼12.6, 8.7 Hz, 1H), 2.23 (s, 3H); 13C NMR (75 MHz, CDCl3)
142.3, 136.4, 125.8, 122.9, 122.6, 120.0, 118.7, 111.7, 111.5, 110.5, 107.4,
78.0, 35.8.
d
137.2, 136.6, 134.3, 129.6, 127.7, 126.2, 122.6, 121.7, 119.9, 118.9,
4.3.13. 3-(1-Nitromethylbutyl)-1H-indole (16am)10
114.4, 111.5, 79.7, 41.3, 21.0.
Yield >99%; 79% ee [Daicel Chiralcel OD column, n-hexane/i-
PrOH¼90:10, 1.0 mL/min, 254 nm; t1¼25.45 min, t2¼27.39 min
4.3.7. 3-[1-(4-Methoxyphenyl)-2-nitroethyl]-1H-indole (16ag)10
Yield >99%; 46% ee [Daicel Chiralcel OD column, n-hexane/i-
PrOH¼70:30, 1.0 mL/min, 254 nm; t1¼16.74 min (major),
(major)]; 1H NMR (300 MHz, CDCl3)
d
8.01 (s, 1H), 7.59 (d, J¼7.8 Hz,
1H), 7.26 (d, J¼7.5 Hz, 1H), 7.19–7.08 (m, 2H), 6.87 (d, J¼2.4 Hz, 1H),
4.65–4.53 (m, 2H), 3.81–3.71 (m, 1H), 1.87–1.63 (m, 2H), 1.33–1.20
t2¼19.95 min]; 1H NMR (300 MHz, CDCl3)
d
8.07 (s, 1H), 7.43 (d,
(m, 3H); 13C NMR (75 MHz, CDCl3)
d 136.6, 126.3, 122.3, 122.1, 119.7,
J¼7.8 Hz, 1H), 7.33 (d, J¼8.1 Hz, 1H), 7.25–7.16 (m, 3H), 7.06 (t,
J¼7.5 Hz,1H), 6.99 (d, J¼2.1 Hz,1H), 6.84 (dd, J¼6.9, 2.1 Hz, 2H), 5.13
(t, J¼7.8 Hz, 1H), 5.03 (dd, J¼12.3, 7.5 Hz, 1H), 4.88 (dd, J¼12.3,
118.7, 114.1, 111.7, 80.6, 36.1, 34.7, 20.4, 13.8.
4.3.14. 3-(1-Isopropyl-2-nitroethyl)-1H-indole (16an)11
8.4 Hz, 1H), 3.76 (s, 3H); 13C NMR (75 MHz, CDCl3)
d
159.1, 136.7,
Yield >99%; 67% ee [Daicel Chiralcel AD-H column, n-hexane/i-
PrOH¼90:10, 1.0 mL/min, 254 nm; t1¼8.77 min, t2¼9.81 min
131.5, 129.0, 126.3, 122.8, 121.6, 120.1, 119.2, 115.0, 114.5, 111.5, 79.9,
55.4, 41.1.
(major)]; 1H NMR (300 MHz, CDCl3)
d 8.02 (s, 1H), 7.58 (d,
J¼7.8 Hz, 1H), 7.27 (d, J¼7.8 Hz, 1H), 7.19–7.08 (m, 2H), 6.87 (d,
J¼2.4 Hz, 1H), 4.78–4.64 (m, 2H), 3.67–3.60 (m, 1H), 2.17–2.06 (m,
1H), 0.96 (d, J¼6.6 Hz, 3H), 0.87 (d, J¼6.9 Hz, 3H); 13C NMR
4.3.8. 3-[2-Nitro-1-(3,4,5-trimethoxyphenyl)ethyl]-1H-indole
(16ah)
Yield >99%; 48% ee [Daicel Chiralcel OD column, n-hexane/i-
PrOH¼70:30, 1.0 mL/min, 254 nm; t1¼15.80 min (major),
(75 MHz, CDCl3) d 136.4, 127.0, 122.3, 119.7, 119.1, 113.2, 111.5, 78.8,
42.7, 30.9, 20.7, 20.1.
t2¼23.37 min]; 1H NMR (300 MHz, CDCl3)
d 8.55 (s, 1H), 7.47 (d,
J¼7.8 Hz, 1H), 7.28 (d, J¼8.1 Hz, 1H), 7.15 (t, J¼7.2 Hz, 1H), 7.06 (t,
J¼7.2 Hz, 1H), 6.95 (d, J¼2.1 Hz, 1H), 6.55 (s, 2H), 5.11 (t, J¼8.1 Hz,
1H), 5.00 (dd, J¼12.6, 7.5 Hz, 1H), 4.89 (dd, J¼12.6, 8.9 Hz, 1H), 3.80
4.3.15. 3-(1-Cyclohexyl-2-nitroethyl)-1H-indole (16ap)10
Yield >99%; 39% ee [Daicel Chiralcel OD column, n-hexane/i-
PrOH¼90:10, 1.0 mL/min, 254 nm; t1¼29.02 min, t2¼31.12 min
(s, 3H), 3.74 (s, 6H); 13C NMR (75 MHz, CDCl3)
d
153.5, 137.4, 136.7,
(major)]; 1H NMR (300 MHz, CDCl3)
d
8.09 (s, 1H), 7.59 (d, J¼7.8 Hz,
135.2, 126.1, 122.5, 121.9, 119.8, 118.7, 113.9, 111.6, 105.2, 79.6, 60.8,
56.2, 41.9.
1H), 7.31 (d, J¼7.8 Hz, 1H), 7.23–7.09 (m, 2H), 6.93 (s, 1H), 4.80 (dd,
J¼12.0, 6.3 Hz, 1H), 4.70 (t, J¼9.3 Hz, 1H), 3.70–3.62 (m, 1H), 1.84–
1.62 (m, 5H), 1.26–0.84 (m, 6H); 13C NMR (75 MHz, CDCl3)
d 136.5,
4.3.9. 3-[1-(4-Hydroxyphenyl)-2-nitroethyl]-1H-indole (16ai)
Yield >99%; 55% ee [Daicel Chiralcel OD column, n-hexane/i-
PrOH¼70:30, 1.0 mL/min, 254 nm; t1¼13.64 min, t2¼14.48 min
127.0, 122.4, 119.8, 119.2, 113.5, 111.5, 78.7, 42.0, 40.7, 31.3, 30.6, 29.8,
26.3.
(major)]; 1H NMR (300 MHz, CDCl3)
d
7.90 (s, 1H), 7.28 (d, J¼8.1 Hz,
4.3.16. 1-Methyl-3-(2-nitro-1-phenylethyl)-1H-indole (16ba)10
Yield >99%; 55% ee [Daicel Chiralcel OD column, n-hexane/i-
PrOH¼90:10, 1.0 mL/min, 254 nm; t1¼41.70 min, t2¼45.74 min
1H), 7.08–6.86 (m, 4H), 7.70 (d, J¼7.5 Hz, 1H), 6.61–6.57 (m, 2H),
6.50 (dd, J¼8.1, 2.1 Hz, 1H), 6.12 (s, 1H), 4.89 (t, J¼8.1 Hz, 1H), 4.72
(dd, J¼12.6, 7.8 Hz, 1H), 4.61 (dd, J¼12.6, 8.4 Hz, 1H); 13C NMR
(major)]; 1H NMR (300 MHz, CDCl3)
d
7.42 (d, J¼7.8 Hz, 1H), 7.31–
(75 MHz, CDCl3)
d
156.1, 141.3, 136.5, 130.1, 126.1, 122.6, 121.8, 120.1,
7.14 (m, 7H), 7.03 (t, J¼6.9 Hz, 1H), 6.79 (s, 1H), 5.13 (t, J¼8.1 Hz, 1H),
119.9, 118.8, 114.9, 114.7, 113.9, 111.6, 79.5, 41.4.
4.97 (dd, J¼12.3, 7.5 Hz, 1H), 4.85 (dd, J¼12.6, 8.7 Hz, 1H), 3.62 (s,
3H); 13C NMR (75 MHz, CDCl3)
d 139.6, 137.4, 128.9, 127.8, 127.5,
4.3.10. 3-[1-(2-Bromophenyl)-2-nitroethyl]-1H-indole (16aj)
Yield >99%; 50% ee [Daicel Chiralcel OD column, n-hexane/i-
PrOH¼70:30, 1.0 mL/min, 254 nm; t1¼12.94 min, t2¼18.93 min
126.6, 126.4, 122.3, 119.5, 119.0, 112.9, 109.6, 79.6, 41.6, 32.8.
4.3.17. 2-Methyl-3-(2-nitro-1-phenylethyl)-1H-indole (16ca)10
Yield >99%; 40% ee [Daicel Chiralcel OD column, n-hexane/i-
PrOH¼70:30, 1.0 mL/min, 254 nm; t1¼12.45 min, t2¼48.66 min
(major)]; 1H NMR (300 MHz, CDCl3)
d
8.05 (s, 1H), 7.49 (d, J¼7.5 Hz,
1H), 7.32 (d, J¼7.8 Hz, 1H), 7.17 (d, J¼8.1 Hz, 1H), 7.10–6.89 (m, 6H),
5.61 (t, J¼8.1 Hz, 1H), 4.87–4.75 (m, 2H); 13C NMR (75 MHz, CDCl3)
(major)]; 1H NMR (300 MHz, CDCl3)
d
7.73 (s, 1H), 7.34 (d, J¼7.8 Hz,
d
138.3, 136.6, 133.5, 129.2, 128.0, 126.3, 124.6, 122.8, 122.1, 120.1,
1H), 7.27–7.12 (m, 6H), 7.08–6.96 (m, 2H), 5.18–4.99 (m, 3H), 2.22 (s,
119.0, 113.3, 111.5, 77.9, 40.7.
3H); 13C NMR (75 MHz, CDCl3)
d
139.7, 135.5, 133.0, 128.8, 127.4,
127.1, 126.9, 121.3, 119.8, 118.6, 110.8, 108.8, 78.7, 40.6, 11.9.
4.3.11. 3-[1-(1-Naphthyl)-2-nitroethyl]-1H-indole (16ak)10
Yield >99%; 53% ee [Daicel Chiralcel OD column, n-hexane/i-
PrOH¼70:30, 1.0 mL/min, 254 nm; t1¼17.72 min, t2¼21.23 min
4.3.18. 5-Bromo-3-(2-nitro-1-phenylethyl)-1H-indole (16da)10
Yield >99%; 60% ee [Daicel Chiralcel OD column, n-hexane/i-
PrOH¼70:30, 1.0 mL/min, 254 nm; t1¼9.90 min, t2¼11.12 min (ma-
(major)]; 1H NMR (300 MHz, CDCl3)
d
8.23 (d, J¼7.2 Hz, 1H), 7.95 (s,
1H), 7.83 (dd, J¼6.9, 2.7 Hz, 1H), 7.72 (t, J¼4.8 Hz, 1H), 7.49–6.97 (m,
jor)]; 1H NMR (300 MHz, CDCl3)
d 8.12 (s, 1H), 7.52 (s, 1H), 7.30–7.19
8H), 6.81 (d, J¼2.4 Hz, 1H), 6.02 (t, J¼7.8 Hz, 1H), 5.02–4.94 (m, 2H);
(m, 6H), 7.12 (d, J¼9.6 Hz, 1H), 6.93 (d, J¼2.4 Hz, 1H), 5.06 (t,
13C NMR (75 MHz, CDCl3)
d 136.7, 134.9, 134.3, 131.3, 129.2, 128.4,
J¼8.1 Hz, 1H), 4.94 (dd, J¼12.6, 8.1 Hz, 1H), 4.84 (dd, J¼12.1, 8.1 Hz,
126.9, 126.2, 126.0, 125.4, 124.7, 122.8, 120.0, 119.3, 118.8, 114.3,
111.6, 78.7, 37.1.
1H); 13C NMR (75 MHz, CDCl3)
d 138.9, 135.2, 129.1, 128.0, 127.8,
127.7, 125.7, 123.0, 121.5, 114.0, 113.3, 113.0, 79.5, 41.4.
4.3.12. 3-[1-Furan-2-yl-2-nitroethyl]-1H-indole (16al)10
4.3.19. 5-Methoxy-3-(2-nitro-1-phenylethyl)-1H-indole (16ea)10
Yield >99%; 56% ee [Daicel Chiralcel OD column, n-hexane/i-
PrOH¼70:30, 1.0 mL/min, 254 nm; t1¼10.05 min, t2¼10.89 min
Yield >99%; 41% ee [Daicel Chiralcel OD column, n-hexane/i-
PrOH¼70:30, 1.0 mL/min, 254 nm; t1¼11.36 min, t2¼15.02 min
(major)]; 1H NMR (300 MHz, CDCl3)
d
8.20 (s, 1H), 7.52 (d, J¼7.8 Hz,
(major)]; 1H NMR (300 MHz, CDCl3)
d 7.99 (s, 1H), 7.27–7.18 (m, 5H),
1H), 7.32 (d, J¼1.5 Hz, 1H), 7.27 (d, J¼8.1 Hz, 1H), 7.17 (t, J¼7.2 Hz,
1H), 7.09 (t, J¼7.5 Hz, 1H), 6.98 (d, J¼2.4 Hz, 1H), 6.26–6.27 (m, 1H),
6.11 (d, J¼3.3 Hz, 1H), 5.20 (t, J¼7.8 Hz, 1H), 5.00 (dd, J¼12.6, 8.1 Hz,
7.12 (dd, J¼6.9, 3.0 Hz, 1H), 6.86–6.79 (m, 3H), 5.08 (t, J¼8.1 Hz, 1H),
4.96 (dd, J¼12.6, 7.5 Hz, 1H), 4.85 (dd, J¼12.6, 8.4 Hz, 1H), 3.72 (s,
3H); 13C NMR (75 MHz, CDCl3)
d 154.3, 139.4, 131.8, 129.0, 127.8,
1H), 4.85 (dd, J¼12.6, 5.1 Hz, 1H); 13C NMR (75 MHz, CDCl3)
d
152.4,
127.6, 126.7, 122.5, 114.0, 112.7, 112.2, 101.1, 79.6, 55.9, 41.6.

1016
S.-z. Lin, T.-pa You / Tetrahedron 65 (2009) 1010–1016
9. The major diastereomers are supposed to be S-axial configurational according
References and notes
to Meyers’ reasoning in their synthesis of binaphthyl bis(oxazoline)s, see
Ref. 8.
10. (a) Liu, H.; Lu, S.-F.; Xu, J.-X.; Du, D.-M. Chem. Asian J. 2008, 3, 1111–1121; (b) Jia,
Y.-X.; Zhu, S.-F.; Yang, Y.; Zhou, Q.-L. J. Org. Chem. 2006, 71, 75–80; (c) Lu, S.-F.;
Du, D.-M.; Xu, J.-X. Org. Lett. 2006, 8, 2115–2118; (d) Singh, P. K.; Bisai, A.; Singh,
V. K. Tetrahedron Lett. 2007, 48, 1127–1129.
11. Herrera, R. P.; Sgarzani, V.; Bernardi, L.; Ricci, A. Angew. Chem., Int. Ed. 2005, 44,
6576–6579.
12. Corey, E. J.; Suggs, J. W. Tetrahedron Lett. 1975, 16, 2647–2650.
13. McKennon, M. J.; Meyers, A. I.; Drauz, K.; Schwarm, M. J. Org. Chem. 1993, 58,
3568–3571.
14. (a) Worrall, D. E. Org. Synth. Coll. 1941, Vol. 1, 413–414; Org. Synth. Coll. 1929, Vol.
9, 66–69; (b) Lucet, D.; Sabelle, S.; Kostelitz, O.; Le Gall, T.; Mioskowski, C. Eur. J.
Org. Chem. 1999, 2583–2591.
15. (a) Hedwig, G. R.; Parker, A. J. J. Am. Chem. Soc. 1974, 96, 6589–6593;
(b) Woodhouse, M. E.; Lewis, F. D.; Marks, T. J. J. Am. Chem. Soc. 1982, 104,
5586–5594.
16. Kyriakides, L. P. J. Am. Chem. Soc. 1914, 36, 987–1005.
17. Cerfontain, H.; Koeberg-Telder, A.; Laali, K.; Lambrechts, H. J. A. J. Org. Chem.
1982, 47, 4069–4075.
1. (a) Akiyama, T. Chem. Rev. 2007, 107, 5744–5758; (b) Hashimoto, T.; Maruoka, K.
J. Am. Chem. Soc. 2007, 129, 10054–10055; (c) Maruoka, K.; Ooi, T.; Kano, T.
Chem. Commun. 2007, 1487–1495.
2. (a) Escher, I. H.; Pfaltz, A. Tetrahedron 2000, 56, 2879–2888; (b) Mu¨ller, P.; Nury,
P. Helv. Chim. Acta 2001, 84, 662–677.
3. (a) Rowland, G. B.; Zhang, H.-L.; Rowland, E. B.; Chennamadhavuni, S.; Wang, Y.;
Antilla, J. C. J. Am. Chem. Soc. 2005, 127, 15696–15697; (b) Li, G.-L.; Liang, Y.-X.;
Antilla, J. C. J. Am. Chem. Soc. 2007, 129, 5830–5831; (c) Zhang, Y.; Desai, A.; Lu,
Z.-J.; Hu, G.; Ding, Z.-S.; Wulff, W. D. Chem.dEur. J. 2008, 14, 3785–3803.
4. (a) Uozumi, Y.; Kato, K.; Hayashi, T. J. Am. Chem. Soc. 1997, 119, 5063–5064; (b)
Uozumi, Y.; Kato, K.; Hayashi, T. J. Org. Chem. 1998, 63, 5071–5075; (c) Uozumi,
Y.; Kyota, H.; Kato, K.; Ogasawara, M.; Hayashi, T. J. Org. Chem. 1999, 64, 1620–
1625; (d) Imai, Y.; Matsuo, S.; Zhang, W.-B.; Nakatsuji, Y.; Ikeda, I. Synlett 2000,
239–241; (e) Uozumi, Y.; Kyota, H.; Kishi, E.; Kitayama, K.; Hayashi, T. Tetra-
hedron: Asymmetry 1996, 7, 1603–1606.
5. (a) Desimoni, G.; Faita, G.; Jørgensen, K. A. Chem. Rev. 2006, 106, 3561–3651; (b)
Meyers, A. I. J. Org. Chem. 2005, 70, 6137–6151.
6. Andrus, M. B.; Asgari, D.; Sclafani, J. A. J. Org. Chem. 1997, 62, 9365–9368.
7. (a) Yamamoto, K.; Kitsuki, T.; Okamoto, Y. Bull. Chem. Soc. Jpn. 1986, 59, 1269–
1270; (b) Kim, J.-I.; Schuster, G. B. J. Am. Chem. Soc. 1992, 114, 9309–9317.
8. Nelson, T. D.; Meyers, A. I. J. Org. Chem. 1994, 59, 2655–2658.
18. Fuson, R. C.; Cleveland, E. A. Org. Synth. Coll. 1955, Vol. 3, 339–340; 1940, Vol. 20,
45–46.