Highly diastereoselective reactions of 2-lithiated indoles with chiral N-tert-butanesulfinyl aldimines for the synthesis of chiral (2-indolyl) methanamine derivatives

Article abstract of DOI:10.1016/j.tetasy.2007.07.029

Nucleophilic addition reactions of 2-lithiated N-phenylsulfonylindoles with (R)-N-tert-butanesulfinyl aldimines provided chiral (2-indolyl) methanamine derivatives in moderate to good yields (up to 100%) with excellent diastereoselectivities (>99:1), in which no additional Lewis acids were required.

Full text of DOI:10.1016/j.tetasy.2007.07.029

Tetrahedron: Asymmetry 18 (2007) 1833–1843
Highly diastereoselective reactions of 2-lithiated indoles with chiral
N-tert-butanesulfinyl aldimines for the synthesis
of chiral (2-indolyl) methanamine derivatives
Liang Cheng,a,b Li Liu,a,* Yong Sui,a,b Dong Wanga and Yong-Jun Chena,*
aBeijing National Laboratory for Molecular Sciences (BNLMS), Laboratory for Chemical Biology, Institute of Chemistry,
Chinese Academy of Sciences, Beijing 100080, PR China
bGraduate School of Chinese Academy of Sciences, Beijing 100049, PR China
Received 25 June 2007; accepted 18 July 2007
Abstract—Nucleophilic addition reactions of 2-lithiated N-phenylsulfonylindoles with (R)-N-tert-butanesulfinyl aldimines provided
chiral (2-indolyl) methanamine derivatives in moderate to good yields (up to 100%) with excellent diastereoselectivities (>99:1), in which
no additional Lewis acids were required.
ꢀ 2007 Elsevier Ltd. All rights reserved.
1. Introduction
inhibitors of HIV protease,6 5HT2B receptor antagonists,7
as well as chiral ligands.8 Although the reaction of 2-metal-
lated indole with imines could provide 2-indolyl methan-
amines efficiently,9 the development of such an
asymmetric version was limited.10 Recently, chiral sulfinyl
aldimines were widely used in asymmetric synthesis.11 In
the addition of 5-methylfuryllithium with chiral sulfinyl-
imines, high diastereoselectivity was obtained, however stoi-
chiometric Lewis acid was necessary.12 Herein, we report
highly diastereoselective addition reactions of 2-lithiated
indole with N-tert-butanesulfinyl aldimines without any
additive in application for the synthesis of chiral (2-indoly)-
methanamine derivatives.
Indole moieties occur widely in natural products, func-
tional materials and pharmaceutical compounds.1 As a
matter of fact, the synthesis of indole derivatives has gained
much attention in organic chemistry for many decades.2
Although well-established classical methods have been suc-
cessfully applied to the construction of the indole ring, the
functionalization of existing indole ring systems has not
been extensively developed.
Indoles bearing a substitution at the C-2 position are an
important structural unit of many alkaloids and bioactive
substances.3 The Friedel–Crafts alkylation of indoles gen-
erally provides C-3 substituted products. Among the vari-
ous synthetic methodologies, ortho-metallation of indole
followed by trapping with electrophiles has emerged as
an important route for generating 2-functionalized
indoles.4
2. Results and discussion
Initially, the ortho-metallation reaction of N-Boc-indole 1a
with n-BuLi was carried out in THF at ꢀ78 ꢁC, followed
by the addition with (R)-N-tert-butanesulfinyl aldimine
2a in THF. The reaction provided (2-indolyl)methanamine
3a in low yield (Scheme 1, Table 1, entry 1). Fortunately,
when N-SO2Ph-indole 1b was used in the reaction with
2a, [(1-phenylsulfonyl-1H-indol-2-yl)phenylmethane]-tert-
butane-sulfinamide 3b was obtained in high yield with
excellent diastereoselectivity (dr >99:1) (Table 1, entry 2).
The choice of solvent had great influence on the reaction
yield, but less on the diastereoselectivity (entries 2–4).
Recently the asymmetric addition of indoles with imines
has been successfully developed to provide enantiopure 3-
indolyl methanamine derivatives.5 As important C-3 indole
analogues, (2-indolyl)methanamines could be used as
*
Corresponding authors. Tel.: +86 10 62554614; fax: +86 10 62554449
(L.L.); e-mail addresses: lliu@mail.iccas.ac.cn; yjchen@mail.iccas.ac.cn
0957-4166/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2007.07.029

1834
L. Cheng et al. / Tetrahedron: Asymmetry 18 (2007) 1833–1843
R2
O
S
O
S
NH
R1
n
-BuLi
+
N
R2
solvent, -78oC
N
R
N
R
R1
H
3
1
1
2
3a
, R=Boc, R =
p
-Cl-C6H4, R2=Bu-t
-Cl-C6H4, R2=Bu-t
-Tol
2a
, R1=p-Cl-C6H4, R2=Bu-
1a
1b
t
, R=Boc
3b, R=SO2Ph, R1=
3c, R=SO2Ph, R1=Ph, R2=
p
1
2
2b
, R =Ph, R =p-Tol
, R=SO2Ph
p
Scheme 1.
Table 1. Reaction of 2-lithiated indoles 1 with chiral sulfinyl aldimines 2a
Entry
Indole
Imine
Solvent
Time (h)
Product
Yieldb (%)
drc
1
2
3
4
5e
6
1a
1b
1b
1b
1b
1b
2a
2a
2a
2a
2a
2b
THF
THF
Et2O
Toluene
THF
2
2
2
2
2
0.5
3a
3b
3b
3b
3b
3c
25
84
68
10
70
80
ndd
>99:1
>99:1
>99:1
>99:1
86:14
THF
a Reactants ratio: indole/imine/base 1.0:0.8:1.2.
b Isolated yields.
c Determined by 1H NMR and 13C NMR of the crude reaction mixture.
d Not determined.
e LDA was used as base.
When Et2O and toluene were used, the yields of 3a
decreased to 68% and 10%, respectively, which implied
the lower efficiency of these solvents on disaggregation of
the lithium complex in solution. However, the diastereose-
lectivity remained as high as >99:1. The change of the base
from n-BuLi to LDA resulted in a slight drop of the yield,
without any loss of diastereoselectivity (Table 1, entry 5).
When (R)-N-p-toluenesulfinyl imine 2b was used in the
reaction with 1a, although the reaction was completed in
0.5 h and provided 3c in 80% yield, the diastereoselectivity
decreased to 86:14 (Table 1, entry 6).
The stereochemical assignment for the detectable diastereo-
mer of the addition reaction is based on X-ray single-crys-
tal diffraction. The new stereogenic centre generated, from
the analysis of product 3i (Fig. 1), is (S)-configured. The
observed stereoselectivity is consistent with the prediction
of the Yamamoto model,13 which 2-lithioindole attacks
the C@N bond from Re face, other than through the six-
membered ring transition state, which is proposed in the
case of the addition using Grignard reagent.11 Unlike the
addition of some lithium reagents with chiral N-but-
anesulfinylimines, in which Lewis acids were necessary
for the chelation with both the nitrogen and sulfinyl oxygen
of imine,12,14 the present reaction could achieve high diaste-
reoselectivity without any additive, probably due to the
coordination of lithium with the sulfonyl oxygen of indole,
which might facilitate the steric hindrance effect (Fig. 2).
Subsequently, various chiral N-butanesulfinyl aldimines 2
were reacted with indoles 1 under the optimized reaction
conditions (Scheme 2, Table 2). All imines derived from
the alkyl (entries 1 and 2), aryl (entries 3–12), heteroaryl
(entry 13), as well as a,b-unsaturated (entry 14) aldehydes
provided the desired products in excellent diastereoselectiv-
ities (>99:1) and moderate to good yields. On the other
hand, substituted indoles 1c,d could also afford the respec-
tive products 3r–s in excellent diasteroselectivities and good
yields (entries 16 and 17).
In order to cleave the chiral auxiliary, products 3 were sub-
jected to facile acidic hydrolysis conditions. It was found
that the sulfinyl group was cleaved cleanly under the condi-
tions employed. As to the potential instability of the gener-
ated free amine on silica gel, the hydrolysis product was
subsequently protected with Tos group. All the chiral N-
protected amines 5a–g were obtained in good yields with
excellent enantioselectivities [Scheme 3 (1), Table 3, entries
3–9]. On the other hand, the tert-butyl sulfinyl group could
also be oxidized conveniently into a Bus group 4a,b, which
is often utilized in organic synthesis as a protecting group
[Scheme 3 (2), Table 3, entries 1 and 2]. Finally, the cleav-
age of the N-protecting group (PhSO2–) in the indole ring
was performed [Scheme 3 (3)]. The product was also
required to be protected by a Tos group to give (S)-(2-indol-
yl) methyl (p-chlorophenyl) amine 6 in 45% overall yield
with 97% ee.
O
S
O
S
NH
1
R
n
-BuLi, THF
-78 C
1
R
N
+
N
º
2
N
R
2
SO Ph
2
R
H
SO Ph
2
1
2
3
Scheme 2.

L. Cheng et al. / Tetrahedron: Asymmetry 18 (2007) 1833–1843
Table 2. 1,2-Additions of 2-lithioindole 1b–d to N-sulfinyl aldimines 2a,c–qa
1835
Entry
Indole
Aldimine
Time (h)
Product
Yieldb (%)
66
drc
O
S
N
O
O
1
1b
2c
2d
2e
1.5
3d
3e
3f
>99.1
>99.1
>99.1
S
NH
N
SO2Ph
N
PhO2S
O
S
S
NH
N
2
1b
1
66
N
PhO2S
O
O
S
NH
O
S
N
3
1b
1
53
N
PhO2S
S
NH
O
N
S
N
4
1b
2a
2
3b
84
>99.1
Cl
PhO2S
Cl
O
S
NH
O
N
S
N
5
6
7
1b
1b
1b
2f
2
1
1
3g
3h
3i
68
72
75
>99.1
>99.1
>99.1
O2N
PhO2S
NO2
O
O
O
S
N
N
S
NH
2g
N
Cl
Br
PhO2S
Cl
Br
O
O
S
S
NH
2h
N
PhO2S
S
NH
O
N
S
N
8
1b
2i
1.5
3j
63
>99.1
H3C
PhO2S
CH3
(continued on next page)

1836
L. Cheng et al. / Tetrahedron: Asymmetry 18 (2007) 1833–1843
Table 2 (continued)
Entry
Indole
Aldimine
Time (h)
1
Product
Yieldb (%)
76
drc
O
S
O
N
9
1b
2j
3k
S
NH
>99.1
H3CO
N
PhO2S
OCH3
O
O
O
S
NH
N
S
10
1b
2k
2
3l
79
>99.1
N
N
OCH3
SO2Ph
PhO2S
OCH3
S
NH
O
N
O
S
11
1b
2l
1.5
3m
N
100
>99.1
PhO2S
O
S
NH
N
S
12
13
1b
2m
3
1
3n
88
74
>99.1
>99.1
N
PhO2S
O
O
S
NH
O
N
S
1b
2n
3o
N
O
O
PhO2S
S
NH
O
S
N
14
1b
2o
1
3p
N
91
>99.1
PhO2S
O
S
NH
O
15
1b
2p
1
3q
64
>99.1
N
S
N
PhO2S
O
S
CH3
CH3
NH
N
16
1c
2b
1
3r
85
>99.1
PhO2S
N
SO2Ph
Cl

L. Cheng et al. / Tetrahedron: Asymmetry 18 (2007) 1833–1843
1837
Table 2 (continued)
Entry
Indole
Aldimine
Time (h)
1
Product
Yieldb (%)
77
drc
NO2
NO2
1d
O
17d
2b
3s
>99.1
S
NH
N
N
SO2Ph
PhO2S
Cl
a Reactants ratio: indole/aldimine/base 1.0:0.8:1.2.
b Isolated yields.
c Determined by 1H NMR and 13C NMR of the crude reaction mixture.
d LDA was used instead of n-BuLi.
obtained in CDCl3 with Bruker DMX-300 (300 MHz)
spectrometer. Chemical shifts are given in ppm relative to
tetramethylsilane (TMS). Elemental analyses were per-
formed on a Carlo Flash 1112 Element Analysis instru-
ment. Mass spectra were recorded on a Bruker APEX-2
spectrometer using the FAB technique or a GCT-MS
Micromass spectrometer. HPLC analyses were performed
on Shimadzu CTO_10ASVP equipped with chiral columns.
Melting points were measured using a Beijing-Taike X-4
apparatus and were uncorrected. Optical rotations were
measured on Optical AA-10 digital polarimeter. X-ray
structure was determined on a Bruker Smart-1000 X-ray
diffraction meter. Unless otherwise noted, all reagents were
obtained from commercial suppliers and were used without
further purification. Tetrahedrofuran (THF), toluene and
diethyl ether (Et2O) were distilled from Na/benzophenone.
Dry CH2Cl2 was distilled from CaH2. All reactions were
Figure 1. ORTEP presentation of (RS,S)-3i.
carried out under
glassware.
a N2 atmosphere in oven-dried
Re face
4.2. The synthesis of N-phenylsulfonyl indoles
R
R
H
N
Li
O
:
Starting from indoles and PhSO2Cl, N-phenylsulfonyl
indoles 1a–d were synthesized.15
O
N
S
O
4.2.1. 4-Nitro-1-(phenylsulfonyl)-1H-indole 1d. Yield 91%.
Yellow powder, mp 179–180 ꢁC. FTIR (KBr): 595, 679,
741, 856, 913, 1089, 1128, 1176, 1214, 1308, 1340, 1520,
Figure 2. Yamamoto-type non-chelation addition modle.
1769 cmꢀ1 1H NMR (300 MHz) d 7.40–7.51 (m, 4H),
.
3. Conclusion
7.56–7.61 (m, 1H), 7.81–7.83 (d, 1H, J = 3.9 Hz), 7.88–
7.91 (m, 2H), 8.17–8.20 (d, 1H, J = 8.1 Hz), 8.33–8.36 (d,
1H, J = 8.1 Hz). 13C NMR (75 MHz) d 108.4, 119.7,
120.2, 124.1, 125.3, 126.8, 129.6, 130.1, 134.5, 136.4,
137.7, 140.8. HRMS (EI) m/z: [M]+ calcd for
C14H10N2O4S, 302.0361; found: 302.0363.
In conclusion, we have demonstrated a highly diastereo-
selective nucleophilic addition of 2-lithiated N-phenyl-
sulfonylindoles with (R)-N-tert-butanesulfinyl aldimines.
After the cleavage of the chiral auxiliary, 2-indolyl methan-
amines were obtained in good yields with excellent enantio-
selectivities. Further application of this methodology into
the synthesis of some bioactive substances is currently
under research in our lab.
4.3. Typical experimental procedure for the synthesis of
N-tert-butanesulfinyl aldimines 216
The tert-butanesulfinamide (100 mg, 0.824 mmol) and
benzaldehyde (87 mg, 0.8 mmol) were mixed in dry CH2Cl2
(5 mL) under N2, Ti(OEt)4 (1 mL, 4.1 mmol) was added
into the solution. The reaction mixture was stirred at room
temperature until completion as indicated by TLC,
quenched with H2O and filtered through diatomite. The fil-
ter residue was washed with CH2Cl2 and the aqueous layer
4. Experimental
4.1. General
IR spectra were recorded on a Perkin–Elmer 782 infra-
1
red spectrometer. H NMR and 13C NMR spectra were

1838
L. Cheng et al. / Tetrahedron: Asymmetry 18 (2007) 1833–1843
HN Ts
1) HCl, MeOH, Dioxane, r.t., 1h
R
3b,f-t
(1)
(2)
2) TsCl, Pyridine, r.t., overnight
1
N
R
SO Ph
2
5a-g
HN Bus
O
S
R
MCPBA, CH Cl
2
2
3d-e
NH
1
N
R
R
r.t., 0.5h
SO Ph
1
2
N
R
SO Ph
2
4a-b
3
HN Ts
N
H
1)HCl, MeOH, Dioxane, r.t. 1 h
3b
(3)
2)Mg, MeOH, Ultrasonic, r.t. 0.5 h
3)TsCl, Pyridine, r.t. overnight
Cl
6
overall yield 45%
e.e. 97%
Scheme 3.
Table 3. Cleavage of the chiral auxiliary
Entry
Sulfinamide
Product
Yielda (%)
eeb (%)
R
R1
1
2
3
4
5
6
7
8
9
3d
3e
3b
3g
3i
4a
4b
5a
5b
5c
5d
5e
5f
H
H
H
H
H
H
H
3-Me
4-NO2
i-Pr
t-Bu
4-Cl–C6H4
4-NO2–C6H4
2-Br–C6H4
4-OMe–C6H4
2-Furyl
4-Cl–C6H4
4-Cl–C6H4
99
92
90
96
67
80
92
96
98
99
>99
>99
99
>99
99
98
98
98
3k
3o
3s
3t
5g
a Isolated yields.
b Determined by chiral HPLC.
was extracted with CH2Cl2. The organic phase was
collected and dried over Na2SO4. Most of the solvent was
removed under reduced pressure. The residue was purified
by flash chromatography on silica gel (elute: PE/EtOAc =
4:1) to afford product 2e (147 mg, yield 85%) as a colourless
oil.
(d, 1H, J = 7.2 Hz), 8.98 (s, 1H). 13C NMR (75 MHz) d
22.2, 57.5, 126.7, 128.8, 129.9, 130.9, 132.8, 136.1, 159.3.
HRMS (EI) m/z: [M]+ calcd for C11H14NOSCl, 243.0485;
found, 243.0488.
4.3.3.
(R,E)-N-(2-Bromobenzylidene)-2-methylpropane-2-
20
sulfinamide 2h. Yield 64%. Colourless oil. ½aꢁD ¼ ꢀ207:2
4.3.1. (R,E)-N-(4-Nitrobenzylidene)-2-methylpropane-2-sul-
finamide 2f. Yield 76%. Yellow solid, mp 142–144 ꢁC.
(c 3.1, CHCl3). FTIR (KBr): 448, 583, 662, 760, 1026,
1087, 1179, 1273, 1361, 1463, 1588, 2961 cmꢀ1. H NMR
1
20
½aꢁD ¼ ꢀ58:0 (c 2.5, CHCl3). FTIR (KBr): 493, 661, 688,
(300 MHz) d 1.26 (s, 9H), 7.32–7.38 (m, 2H), 7.61–7.64
(dd, 1H, J = 1.2, 7.5 Hz), 8.01–8.04 (dd, 1H, J = 2.1,
7.5 Hz), 8.96 (s, 1H). 13C NMR (75 MHz) d 22.2, 57.5,
126.0, 127.3, 129.2, 132.5, 132.9, 133.3, 161.8. HRMS
(EI) m/z: [M]+ calcd for C11H14NOSBr, 286.9979; found,
286.9975.
734, 836, 856, 1086, 1175, 1341, 1469, 1518, 1589, 2949,
1
3108 cmꢀ1. H NMR (300 MHz) d 1.27 (s, 9H), 7.99–8.02
(d, 2H, J = 8.7 Hz), 8.29–8.32 (d, 2H, J = 8.7 Hz), 8.65
(s, 1H). 13C NMR (75 MHz) d 22.2, 58.0, 123.8, 129.6,
138.5, 149.4, 160.3. HRMS (EI) m/z: [M]+ calcd for
C11H14N2O3S, 254.0725; found, 254.0729.
4.3.4. (R,E)-N-(2-Methoxybenzylidene)-2-methylpropane-2-
sulfinamide 2k. Yield 84%. White solid, mp 55–56 ꢁC.
4.3.2. (R,E)-N-(2-Chlorobenzylidene)-2-methylpropane-2-
20
20
sulfinamide 2g. Yield 79%. Colourless oil. ½aꢁD ¼ ꢀ195:6
½aꢁD ¼ ꢀ230:4 (c 1.9, CHCl3). FTIR (KBr): 756, 1083,
(c 4.3, CHCl3). FTIR (KBr): 453, 583, 683, 758, 1087,
1163, 1254, 1358, 1466, 1597, 2963 cmꢀ1 1H NMR
.
(300 MHz) d 1.24 (s, 9H), 3.87 (s, 3H), 6.93–7.01 (m,
2H), 7.42–7.45 (m, 1H), 7.95–7.99 (dd, 1H, J = 1.8,
1179, 1274, 1362, 1468, 1590, 2963 cmꢀ1
.
1H NMR
(300 MHz) d 1.21 (s, 9H), 7.28–7.37 (m, 3H), 7.98–8.00

L. Cheng et al. / Tetrahedron: Asymmetry 18 (2007) 1833–1843
1839
7.8 Hz), 9.05 (s, 1H); 13C NMR (75 MHz) d 22.2, 55.1,
57.2, 111.0, 120.3, 122.4, 127.8, 133.5, 158.4, 159.3. HRMS
(EI) m/z: [M]+ calcd for C12H17NO2S, 239.0980; found,
239.0982.
133.3, 136.9, 137.8, 141.2. HRMS (FAB) m/z: [M+Na]+
calcd for C23H30N2O3S2, 469.1590; found, 469.1586.
4.4.4.
(RS,S)-N-[(1-Phenylsulfonyl-1H-indol-2-yl)phenyl-
methane]-2-tert-butanesulfinamide 3f. White solid, mp
20
4.4. Typical experimental procedure for the nucleophilic
addition of 2-lithilated indoles 1 to N-tert-butanesulfinyl
aldimines 2
188–190 ꢁC. ½aꢁD ¼ þ38:0 (c 2.0, CHCl3). FTIR (KBr):
588, 634, 691, 729, 835, 1061, 1176, 1370, 1450, 2960,
1
3074 cmꢀ1. H NMR (300 MHz) d 1.26 (s, 9H), 3.73 (br
s, 1H), 6.56–6.57 (d, 1H, J = 2.4 Hz), 6.93 (s, 1H), 7.22–
7.46 (m, 10H), 7.50–7.58 (m, 3H), 8.13–8.15 (d, 1H,
J = 8.4 Hz). 13C NMR (75 MHz) d 22.2, 55.7, 56.3,
111.7, 114.7, 120.6, 123.5, 124.5, 126.2, 127.9, 128.0,
128.5, 128.7, 128.8, 133.3, 137.2, 137.9, 139.9, 141.4.
HRMS (EI) m/z: [M]+ calcd for C25H26N2O3S2,
466.1385; found, 466.1390.
To a solution of N-phenylsulfonyl indole 1b (52 mg,
0.2 mmol) in THF (2 mL) at ꢀ78 ꢁC was added n-BuLi
(0.13 mL, 0.22 mmol, 1.6 M in hexane) dropwise. After
the reaction was aged for 1 h at ꢀ78 ꢁC, the solution of
(R)-N-(4-chlorobenzylidene)-2-methylpropanesulfinamide
2a (44 mg, 0.18 mmol) in THF (2 mL) was added in one
portion and the mixture stirred at ꢀ78 ꢁC for 2 h. The
reaction mixture was quenched by a saturated aqueous
solution of NH4Cl (5 mL), followed by extraction with
CH2Cl2. The combined organic phase was dried over
Na2SO4. Most of the solvent was removed under reduced
pressure. The residue was purified by flash chromatogra-
phy on silica gel (elute: PE/EtOAc = 2:1 to 1:1) to afford
product 3b (67 mg, yield 84%) as a white solid.
4.4.5. (RS,S)-N-[(1-Phenylsulfonyl-1H-indol-2-yl)(p-nitro-
phenyl)methane]-2-tert-butanesulfinamide 3g. White solid,
20
mp 96–98 ꢁC. ½aꢁD ¼ þ67:7 (c 2.7, CHCl3). FTIR (KBr):
445, 741, 1065, 1265, 1348, 3407 cmꢀ1
.
1H NMR
(300 MHz) d 1.26 (s, 9H), 4.05 (br s, 1H), 6.57 (s, 1H),
6.95 (s, 1H), 7.21–7.30 (m, 4H), 7.41–7.59 (m, 6H), 7.99–
8.04 (m, 2H), 8.09–8.12 (d, 1H, J = 8.1 Hz). 13C NMR
(75 MHz) d 22.2, 56.1, 56.5, 112.6, 114.7, 120.9, 123.4,
123.9, 125.1, 125.8, 128.6, 128.9, 133.6, 137.4, 137.8,
139.8, 147.1. HRMS (FAB) m/z: [M+1]+ calcd for
C25H25N5O3S2, 512.1308; found, 512.1294.
4.4.1. (RS,S)-N-[(1-Phenylsulfonyl-1H-indol-2-yl)(p-chloro-
phenyl)methane]-2-tert-butanesulfinamide 3b. White solid,
20
mp 75–76 ꢁC. ½aꢁD ¼ þ46:7 (c 0.6, CHCl3). FTIR (KBr):
588, 647, 685, 730, 832, 910, 1017, 1062, 1147, 1176,
1370, 1450, 1489, 1589, 2961, 3215 cmꢀ1
.
1H NMR
4.4.6. (RS,S)-N-[(1-Phenylsulfonyl-1H-indol-2-yl)(o-chloro-
phenyl)methane]-2-tert-butanesulfinamide 3h. White solid,
(300 MHz) d 1.26 (s, 9H), 3.71 (br s, 1H), 6.50 (s, 1H),
6.90 (s, 1H), 7.20–7.35 (m, 8H), 7.45–7.58 (m, 4H), 8.14–
8.16 (d, 1H, J = 8.4 Hz). 13C NMR (75 MHz) d 22.2,
55.8, 56.0, 111.8, 114.7, 120.7, 123.6, 124.7, 126.0, 128.5,
128.6, 128.7, 129.3, 133.3, 133.8, 137.4, 138.0, 138.4,
140.8. HRMS (EI) m/z: [M]+ calcd for C25H25N2O3S2Cl,
500.0995; found, 500.1000.
20
mp 188–189 ꢁC. ½aꢁD ¼ þ23:4 (c 1.0, CHCl3). FTIR
(KBr): 587, 771, 1059, 1176, 1219, 1371, 1447, 2960 cmꢀ1
.
1H NMR (300 MHz) d 1.12 (s, 9H), 3.80 (s, 1H), 6.75–
6.76 (d, 1H, J = 4.2 Hz), 6.83 (s, 1H), 6.95–7.00 (m, 2H),
7.09–7.20 (m, 5H), 7.29–7.31 (m, 2H), 7.38–7.40 (d, 1H,
J = 7.5 Hz), 7.55–7.58 (d, 2H, J = 7.7 Hz), 8.02–8.04 (d,
1H, J = 8.2 Hz). 13C NMR (75 MHz) d 22.2, 54.1, 56.0,
113.1, 114.5, 120.8, 123.5, 124.7, 126.1, 126.6, 128.4,
128.8, 129.3, 129.4, 129.7, 133.4, 133.6, 136.7, 137.4,
138.2, 140.1. HRMS (FAB) m/z: [M+1]+ calcd for
C25H25N2O3S2, 501.1068; found, 501.1066.
4.4.2. (RS,S)-N-[(1-Phenylsulfonyl-1H-indol-2-yl)(iso-propan-
yl)methane]-2-tert-butanesulfinamide 3d. White solid, mp
20
134–136 ꢁC. ½aꢁD ¼ þ145:3 (c 1.8, CHCl3). FTIR (KBr):
570, 590, 629, 685, 749, 836, 1050, 1126, 1175, 1368,
1449, 2962 cmꢀ1 1H NMR (300 MHz) d 0.86–0.89 (d,
.
3H, J = 6.7 Hz), 1.12–1.15 (d, 3H, J = 6.9 Hz), 1.22 (s,
9H), 2.42–2.44 (m, 1H), 3.51–3.52 (d, 1H, J = 3.3 Hz),
5.22 (s, 1H), 6.58 (s, 1H), 7.19–7.31 (m, 2H), 7.36–7.51
(m, 4H), 7.78–7.80 (d, 2H, J = 7.5 Hz), 8.19–8.21 (d, 1H,
J = 8.1 Hz), 13C NMR (75 MHz) d 15.9, 19.5, 22.1, 33.3,
55.6, 57.5, 111.1, 115.0, 120.3, 123.6, 124.2, 126.1, 128.8,
129.1, 133.4, 137.2, 137.8, 142.2. HRMS (FAB) m/z:
[M+Na]+ calcd for C22H28N2O3S2, 455.1434; found,
455.1437.
4.4.7. (RS,S)-N-[(1-Phenylsulfonyl-1H-indol-2-yl)(o-bromo-
phenyl)methane]-2-tert-butanesulfinamide 3i. White solid,
20
mp 194–195 ꢁC. ½aꢁD ¼ þ38:3 (c 2.2, CHCl3). FTIR
(KBr): 586, 649, 686, 750, 832, 916, 1061, 1147, 1176,
1
1222, 1270, 1370, 1448, 1568, 2959, 3062 cmꢀ1. H NMR
(300 MHz) d 1.26 (s, 9H), 3.82–3.83 (d, 1H, J = 3.3 Hz),
6.80–6.81 (d, 1H, J = 3.0 Hz), 6.95 (s, 1H), 7.10–7.18 (m,
3H), 7.26–7.37 (m, 5H), 7.45–7.54 (m, 2H), 7.63–7.66 (m,
1H), 7.70–7.73 (m, 2H), 8.13–8.16 (d, 1H, J = 8.1 Hz).
13C NMR (75 MHz) d 22.7, 56.4, 56.7, 113.7, 114.9,
121.2, 123.8, 124.6, 125.1, 126.6, 127.6, 128.8, 129.2,
129.9, 130.2, 133.6, 133.7, 137.7, 138.57, 138.60, 140.4.
HRMS (FAB) m/z: [M+Na]+ calcd for C25H25BrN2O3S2,
567.0382; found, 567.0382. The crystal used for the X-ray
study had the dimensions 0.24 · 0.20 · 0.18 mm. Crystal
data: C25H25BrN2O3S2, M 545.50, monoclinic, space group
4.4.3. (RS,S)-N-[(1-Phenylsulfonyl-1H-indol-2-yl)(tert-butyl)-
methane]-2-tert-butanesulfinamide 3e. White solid, mp
20
209–210 ꢁC. ½aꢁD ¼ þ211:2 (c 2.9, CHCl3). FTIR (KBr):
569, 591, 627, 687, 751, 839, 1065, 1142, 1181, 1219,
1
1368, 1449, 1474, 2963 cmꢀ1. H NMR (300 MHz) d 1.06
(s, 9H), 1.16 (s, 9H), 3.56–3.57 (d, 1H, J = 2.4 Hz), 5.44–
5.45 (d, 1H, J = 2.7 Hz), 6.56 (s, 1H), 7.22–7.46 (m, 6H),
7.88–7.90 (d, 2H, J = 7.8 Hz), 8.24–8.26 (d, 1H,
J = 8.1 Hz). 13C NMR (75 MHz) d 22.1, 26.1, 36.2, 55.4,
58.7, 112.6, 115.4, 120.2, 123.6, 124.1, 126.7, 128.6, 129.1,
˚
˚
˚
P2(1), a = 8.587(2) A, b = 16.232(4) A, c = 9.929(3) A,
3
V = 1288.9(6) A , Z = 2, Dcalcd = 1.406 g cmꢀ3, F0 = 560,
˚
˚
reflections collected: 6365, k=0.71073 A.

1840
L. Cheng et al. / Tetrahedron: Asymmetry 18 (2007) 1833–1843
4.4.8. (RS,S)-N-[(1-Phenylsulfonyl-1H-indol-2-yl)(p-methyl-
phenyl)methane]-2-tert-butanesulfinamide 3j. White solid.
6.86–6.91 (m, 2H), 7.15–7.21 (m, 1H), 7.24–7.38 (m, 7H),
7.56–7.59 (m, 1H), 7.70–7.71 (m, 1H), 7.89 (br, 2H),
8.01–8.04 (m, 1H), 8.30 (s, 1H), 8.56 (br, 2H). 13C NMR
(75 MHz) d 22.3, 52.2, 56.1, 113.2, 114.7, 120.8, 123.5,
124.0, 124.4, 124.5, 126.0, 128.1, 128.4, 128.85, 128.91,
129.8, 130.4, 131.2, 132.4, 138.0, 138.4, 142.7. HRMS
(EI) m/z: [M]+ calcd for C33H30N2O3S2, 566.1698; found,
566.1705.
20
½aꢁD ¼ þ54:9 (c 2.6, CHCl3). Mp 144–145 ꢁC. FTIR
1
(KBr): 589, 751, 1061, 1175, 1369, 1449, 2968 cmꢀ1. H
NMR (300 MHz) d 1.16 (s, 9H), 2.22 (s, 3H), 3.60 (br s,
1H), 6.43 (s, 1H), 6.83 (s, 1H), 6.97–6.99 (d, 2H,
J = 7.8 Hz), 7.12–7.23 (m, 6H), 7.32–7.49 (m, 4H), 8.04–
8.06 (d, 1H, J = 7.8 Hz). 13C NMR (75 MHz) d 20.6,
22.2, 55.7, 56.0, 111.6, 114.7, 120.6, 123.4, 124.4, 126.2,
127.9, 128.6, 128.8, 129.1, 133.1, 137.0, 137.3, 137.7,
138.0, 141.6. HRMS (EI) m/z: [M]+ calcd for
C26H28N2O3S2, 480.1541; found, 480.1547.
4.4.13. (RS,S)-N-[(1-Phenylsulfonyl-1H-indol-2-yl)(fur-2-yl)-
methane]-2-tert-butanesulfinamide 3o. White solid, mp
20
168–170 ꢁC. ½aꢁD ¼ ꢀ16:0 (c 0.9, CHCl3). FTIR (KBr):
1
586, 686, 746, 909, 1062, 1176, 1369, 1450, 2959 cmꢀ1. H
4.4.9. (RS,S)-N-[(1-Phenylsulfonyl-1H-indol-2-yl)(p-meth-
oxyphenyl)methane]-2-tert-butanesulfinamide 3k. White
NMR (300 MHz) d 1.25 (s, 9H), 3.93 (br s, 1H), 6.30 (d,
1H, J = 1.2 Hz), 6.55–6.57 (d, 1H, J = 5.7 Hz), 6.80 (s,
1H), 7.23–7.39 (m, 6H), 7.46–7.49 (d, 2H, J = 7.4 Hz),
7.68–7.71 (d, 2H, J = 7.6 Hz), 8.10–8.13 (d, 1H,
J = 8.3 Hz). 13C NMR (75 MHz) d 22.1, 51.0, 56.1,
108.8, 110.3, 112.2, 114.7, 120.8, 123.6, 124.7, 126.1,
128.7, 128.8, 133.4, 137.0, 137.9, 139.3, 142.3, 152.1.
HRMS (EI) m/z: [M]+ calcd for C23H24N2O4S2,
456.1178; found, 456.1172.
20
solid, mp 168–169 ꢁC. ½aꢁD ¼ þ51:9 (c 1.1, CHCl3). FTIR
(KBr): 589, 752, 832, 1059, 1175, 1252, 1369, 1450, 1512,
1585, 3381 cmꢀ1 1H NMR (300 MHz) d 1.22 (s, 9H),
.
3.70 (s + br s, 4H), 6.53 (s, 1H), 6.73–6.76 (d, 2H,
J = 8.6 Hz), 6.95 (s, 1H), 7.21–7.37 (m, 7H), 7.49–7.57
(m, 3H), 8.11–8.14 (d, 1H, J = 8.1 Hz). 13C NMR
(75 MHz) d 22.7, 55.3, 56.1, 56.2, 111.9, 114.1, 115.1,
121.1, 123.9, 124.8, 126.5, 129.1, 129.2, 129.7, 132.4,
133.6, 127.6, 138.3, 142.2, 159.5. HRMS (FAB) m/z:
[M+1]+ calcd for C26H28N2O4S2, 497.1563; found,
497.1556.
4.4.14.
(RS,S)-N-[(1-Phenylsulfonyl-1H-indol-2-yl)styryl
methane]-2-tert-butanesulfinamide 3p. White solid, mp
20
160–161 ꢁC. ½aꢁD ¼ þ6:5 (c 2.2, CHCl3). FTIR (KBr):
416, 446, 587, 750, 764, 1051, 1260, 1276, 1449, 1585,
4.4.10. (RS,S)-N-[(1-Phenylsulfonyl-1H-indol-2-yl)(o-meth-
2922, 3400 cmꢀ1 1H NMR (300 MHz) d 1.23 (s, 9H),
.
oxyphenyl)methane]-2-tert-butanesulfinamide
3l. Sticky
oil. ½aꢁD ¼ ꢀ20:9 (c 2.8, CHCl3). FTIR (KBr): 589, 752,
1056, 1176, 1246, 1371, 1449, 2958 cmꢀ1 1H NMR
3.90 (s, 1H), 6.08 (s, 1H), 6.42–6.50 (dd, 1H, J = 6.6,
15.9 Hz), 6.60–6.65 (d, 1H, J = 15.9 Hz), 6.81 (s, 1H),
7.19–7.38 (m, 10H), 7.46–7.48 (d, 1H, J = 7.5 Hz), 7.78–
7.80 (d, 2H, J = 7.5 Hz), 8.14–8.16 (d, 1H, J = 8.1 Hz).
13C NMR (75 MHz) d 22.7, 55.0, 56.3, 111.6, 115.2,
121.1, 124.0, 125.0, 126.6, 126.8, 128.2, 128.6, 129.0,
129.26, 129.31, 133.3, 133.8, 136.1, 137.6, 138.5, 141.8.
HRMS (FAB) m/z: calcd for [M+1]+ C27H28N2O3S2,
493.1614; found, 493.1621.
20
.
(300 MHz) d 1.25 (s, 9H), 3.91 (s, 3H), 3.94–3.96 (d, 1H,
J = 5.7 Hz), 6.72 (s, 1H), 6.82–6.85 (m, 2H), 6.93–6.96 (d,
1H, J = 8.1 Hz), 7.01 (d, 1H, J = 7.5 Hz), 7.22–7.36 (m,
5H), 7.44–7.47 (m, 2H), 7.70–7.72 (d, 2H, J = 7.5 Hz),
8.10–8.13 (d, 1H, J = 8.4 Hz). 13C NMR (75 MHz) d
22.2, 52.0, 55.2, 55.9, 110.8, 112.3, 114.6, 120.2, 120.5,
123.3, 124.3, 126.3, 128.2, 128.4, 128.6, 128.7, 129.1,
133.2, 137.2, 138.2, 141.5, 156.4. HRMS (EI) m/z: [M]+
calcd for C26H28N2O4S2, 496.1491; found, 496.1499.
4.4.15.
(RS,S)-N-[(1-Phenylsulfonyl-1H-indol-2-yl)benzyl
methane]-2-tert-butanesulfinamide 3q. Colourless oil.
20
½aꢁD ¼ þ4:4 (c 0.2, CHCl3). FTIR (KBr): 423, 590, 751,
4.4.11. (RS,S)-N-[(1-Phenylsulfonyl-1H-indol-2-yl)naphthyl-
methane]-2-tert-butanesulfinamide 3m. White solid, mp
1
1062, 1177, 1368, 1450, 2960 cmꢀ1. H NMR (300 MHz)
20
d 1.14 (s, 9H), 3.09–3.13 (m, 1H), 3.62–3.68 (dd, 2H,
J = 4.9, 13.8 Hz), 5.59 (s, 1H), 6.59 (s, 1H), 7.23–7.51 (m,
11H), 7.76–7.79 (d, 2H, J = 7.6 Hz), 8.17–8.20 (d, 1H,
J = 8.2 Hz). 13C NMR (75 MHz) d 22.1, 43.3, 52.8, 55.5,
110.9, 114.8, 120.5, 123.5, 124.4, 126.1, 126.7, 128.3,
128.9, 129.0, 129.3, 133.4, 136.1, 137.1, 137.7, 141.7.
HRMS (FAB) m/z: [M+1]+ calcd for C26H28N2O3S2,
481.1614; found, 481.1616.
103–104 ꢁC. ½aꢁD ¼ þ17:1 (c 1.2, CHCl3). FTIR (KBr):
478, 587, 650, 685, 741, 822, 863, 912, 1062, 1147, 1175,
1273, 1306, 1370, 1450, 1508, 1599, 1722, 1807, 1912,
1
2869, 2961, 3060, 3212 cmꢀ1. H NMR (300 MHz) d 1.27
(s, 9H), 3.80 (br s, 1H), 6.71 (s, 1H), 7.01–7.08 (m, 3H),
7.24–7.34 (m, 3H), 7.42–7.48 (m, 4H), 7.52–7.58 (m, 2H),
7.64–7.65 (m, 2H), 7.77–7.81 (m, 2H), 8.16–8.19 (d, 1H,
J = 8.4 Hz). 13C NMR (75 MHz) d 22.2, 55.8, 56.5,
111.7, 114.7, 120.6, 123.4, 124.5, 125.8, 125.9, 126.1,
127.2, 127.9, 128.37, 128.41, 128.7, 132.7, 132.8, 133.0,
137.1, 137.4, 138.0, 141.2. HRMS (EI) m/z: calcd for
[M+Na]+ C29H28N2O3S2, 539.1439; found, 539.1445.
4.4.16. (RS,S)-N-[(1-Phenylsulfonyl-1H-3-methyl-indol-2-
yl)(p-chlorophenyl)methane]-2-tert-butanesulfinamide
3r.
20
White solid, mp 85–87 ꢁC. ½aꢁD ¼ þ93:7 (c 0.8, CHCl3).
FTIR (KBr): 595, 668, 751, 808, 861, 960, 1018, 1091,
1126, 1173, 1219, 1318, 1363, 1450, 1768, 2928,
4.4.12. (RS,S)-N-[(1-Phenylsulfonyl-1H-indol-2-yl)(9-anthryl)-
methane]-2-tert-butanesulfinamide 3n. Pale solid, mp 120–
1
3374 cmꢀ1. H NMR (300 MHz) d 1.20 (s, 9H), 2.34 (s,
20
121 ꢁC. ½aꢁD ¼ ꢀ69:3 (c 1.0, CHCl3). FTIR (KBr): 424,
3H), 6.33 (br, 1H), 7.09–7.45 (m, 12H), 7.53–7.55 (m,
1H), 8.16–8.19 (d, 1H, J = 8.0 Hz). 13C NMR (75 MHz)
d 9.8, 22.6, 56.1, 56.6, 115.1, 119.2, 119.5, 123.8, 125.7,
126.1, 128.3, 128.4, 128.9, 130.2, 133.2, 133.4, 135.9,
583, 649, 684, 741, 789, 837, 911, 1058, 1176, 1220, 1367,
1
1449, 1717, 2959, 3054 cmꢀ1. H NMR (300 MHz) d 1.27
(s, 9H), 4.25–4.26 (d, 1H, J = 3.0 Hz), 6.77–6.81 (m, 2H),

L. Cheng et al. / Tetrahedron: Asymmetry 18 (2007) 1833–1843
1841
136.7, 138.7, 138.9. HRMS (EI) m/z: [M]+ calcd for
C26H27N2O3S2Cl, 514.1152; found, 514.1161.
664, 745, 817, 926, 1018, 1090, 1160, 1334, 1370, 1448,
1
1490, 1596, 3063, 3275 cmꢀ1. H NMR (300 MHz) d 2.27
(s, 3H), 5.81 (br s, 1H), 6.30–6.33 (d, 1H, J = 8.2 Hz),
6.75 (s, 1H), 6.93–6.96 (d, 1H, J = 8.3 Hz), 7.07–7.09 (d,
4H, J = 8.4 Hz), 7.18–7.30 (m, 4H), 7.35–7.47 (m, 4H),
7.58–7.61 (d, 2H, J = 8.2 Hz), 7.99–8.02 (d, 1H,
J = 8.2 Hz). 13C NMR (75 MHz) d 20.3, 54.5, 112.3,
113.8, 120.1, 123.0, 124.2, 125.3, 126.0, 127.0, 127.7,
128.0, 128.4, 128.9, 132.7, 132.9, 136.2, 136.3, 136.5,
137.1, 137.8, 142.6. HRMS (EI) m/z: [M]+ calcd for
C28H23N2O4S2Cl, 550.0788; found, 550.0793. Ee was deter-
mined by HPLC (Daicel Chiralcel OD-H, hexane/i-
4.4.17. (RS,S)-N-[(1-Phenylsulfonyl-1H-4-nitro-indol-2-yl)-
(p-chlorophenyl)methane]-2-tert-butanesulfinamide 3s. Yel-
20
low powder, mp 204–206 ꢁC. ½aꢁD ¼ þ144:6 (c 2.0, CHCl3).
FTIR (KBr): 599, 685, 731, 804, 1065, 1175, 1281, 1337,
1
1519, 2923 cmꢀ1. H NMR (300 MHz) d 1.25 (s, 9H), 4.05
(br s, 1H), 6.57 (s, 1H), 6.95 (s, 1H), 7.21–7.30 (m, 4H),
7.41–7.59 (m, 5H), 7.99–8.04 (m, 2H), 8.09–8.12 (d, 1H,
J = 8.1 Hz). 13C NMR (75 MHz) d 22.6, 56.6, 56.9, 113.0,
115.1, 121.3, 123.8, 124.3, 125.5, 126.2, 129.0, 129.3, 134.0,
137.8, 138.1, 140.2, 147.5, 178.2. HRMS (FAB) m/z:
[M+Na]+ calcd for C25H24N3O5S2Cl, 568.0738; found,
568.0723.
PrOH = 7:3, 0.5 mL minꢀ1): tminor = 13.1 min, tmajor
=
15.1 min.
4.5.4.
(S)-N-[(1-Phenylsulfonyl-1H-indol-2-yl)(p-nitro-
4.5. The synthesis of chiral (2-indolyl)methanamine deriva-
tives through deprotection of chiral tert-butylsulfinyl group
phenyl)methane]-p-toluenesulfonamide 5b. White solid,
20
mp 94–95 ꢁC. ½aꢁD ¼ þ103:2 (c 2.8, CHCl3). FTIR (KBr):
566, 590, 665, 751, 816, 928, 1089, 1160, 1347, 1448,
1523, 1600, 3276 cmꢀ1 1H NMR (300 MHz) d 2.27 (s,
.
According to the reported procedures, cleavage of the chi-
ral tert-butylsulfinyl group was carried out either through
hydrolysis17a or oxidation reaction.17b
3H), 5.85 (br s, 1H), 6.38–6.41 (d, 1H, J = 8.7 Hz), 6.73
(s, 1H), 7.07–7.10 (d, 2H, J = 8.1 Hz), 7.22–7.49 (m,
10H), 7.58–7.61 (d, 2H, J = 8.3 Hz), 7.95–8.00 (m, 3H).
13C NMR (75 MHz) d 20.9, 55.3, 113.7, 114.5, 120.8,
123.2, 123.9, 125.2, 125.7, 126.6, 127.5, 127.7, 128.1,
128.7, 129.1, 133.6, 136.7, 137.3, 137.7, 143.5, 145.4,
147.1. HRMS (EI) m/z: [M]+ calcd for C28H23N3O6S2,
561.1028; found, 561.1033. Ee was determined by HPLC
(Daicel Chiralcel OD-H, hexane/i-PrOH = 7:3, 0.6 mL
minꢀ1): tminor = 23.5 min, tmajor = 39.3 min.
4.5.1. (S)-N-[(1-Phenylsulfonyl-1H-2-yl)(iso-propanyl) meth-
ane]-tert-butanesulfonamide 4a. White powder, mp 143–
20
144 ꢁC. ½aꢁD ¼ þ42:9 (c 0.9, CHCl3). FTIR (KBr): 590,
751, 902, 1126, 1173, 1307, 1448, 1700, 2971 cmꢀ1 1H
.
NMR (300 MHz) d 0.62–0.64 (d, 3H, J = 7.0 Hz), 1.15–
1.17 (d, 3H, J = 6.7 Hz), 1.29 (s, 9H), 2.46–2.47 (m, 1H),
4.49–4.53 (d, 1H, J = 10.3 Hz), 5.28–5.31 (d, 1H,
J = 10.0 Hz), 6.69 (s, 1H), 7.00–7.05 (t, 1H, J = 7.4 Hz),
7.10–7.15 (t, 2H, J = 7.4 Hz), 7.21–7.34 (m, 4H), 7.75–
7.77 (d, 2H, J = 7.6 Hz), 7.95–7.98 (d, 1H, J = 8.2 Hz).
13C NMR (75 MHz) d 14.6, 20.1, 23.8, 33.5, 58.2, 60.0,
110.5, 114.7, 120.5, 123.6, 124.1, 126.5, 128.7, 129.0,
133.4, 137.29, 137.34, 143.3. HRMS (FAB) m/z:
[M+Na]+ calcd for C22H28N2O4S2, 471.1383; found,
471.1379. Ee was determined by HPLC (Daicel Chiralcel
4.5.5.
(S)-N-[(1-Phenylsulfonyl-1H-indol-2-yl)(o-bromo-
phenyl)methyl]-p-toluenesulfonamide 5c. Pale yellow solid,
20
mp 95–97 ꢁC. ½aꢁD ¼ þ52:6 (c 2.3, CHCl3). FTIR (KBr):
405, 568, 589, 666, 724, 750, 814, 924, 1089, 1157, 1335,
1372, 1446, 3273 cmꢀ1 1H NMR (300 MHz) d 2.24 (s,
.
3H), 5.06–5.08 (d, 1H, J = 6.3 Hz), 6.49 (s, 1H), 6.65–
6.67 (d, 1H, J = 6.6 Hz), 6.87–7.03 (m, 5H), 7.13–7.32
(m, 5H), 7.39–7.47 (m, 4H), 7.66–7.69 (d, 2H,
J = 8.1 Hz), 8.01–8.04 (d, 1H, J = 8.1 Hz). 13C NMR
(75 MHz) d 21.0, 55.5, 113.6, 114.5, 120.7, 123.5, 124.0,
124.7, 126.3, 127.09, 127.12, 128.3, 128.8, 128.9, 129.3,
129.5, 133.1, 133.5, 137.2, 137.3, 138.0, 138.4, 143.0.
HRMS (EI) m/z: [M]+ calcd for C28H23N2O4S2Br,
594.0283; found, 594.0286. Ee was determined by HPLC
(Daicel Chiralcel OD-H, hexane/i-PrOH = 7:3, 0.5
mL minꢀ1): tminor = 19.3 min, tmajor = 17.3 min.
AD-H, hexane/i-PrOH = 7:3, 0.6 mL minꢀ1): tminor
10.2 min, tmajor = 8.2 min.
=
4.5.2. (S)-N-[(1-Phenylsulfonyl-1H-indole-2-yl)(tert-butyl)
methane]-tert-butanesulfonamide 4b. White powder, mp
20
126–128 ꢁC. ½aꢁD ¼ þ134:7 (c 1.5, CHCl3). FTIR (KBr):
591, 751, 909, 1125, 1303, 1366, 1448, 1701, 2976,
1
3291 cmꢀ1. H NMR (300 MHz) d 1.10 (s, 9H), 1.43 (s,
9H), 4.60–4.63 (d, 1H, J = 10.2 Hz), 5.66–5.69 (d, 1H,
J = 10.2 Hz), 6.73 (s, 1H), 6.98–7.01 (m, 1H), 7.09–7.19
(m, 2H), 7.34–7.44 (m, 3H), 7.81–7.84 (d, 1H,
J = 8.4 Hz), 8.02–8.05 (d, 2H, J = 7.2 Hz). 13C NMR
(75 MHz) d 23.9, 26.4, 36.6, 59.1, 60.1, 110.0, 114.4,
120.4, 123.1, 123.6, 127.3, 128.5, 128.6, 133.2, 136.1,
138.0, 143.0. HRMS (FAB) m/z: [M+Na]+ calcd for
C23H30N2O4S2, 485.1539; found, 485.1547. Ee was deter-
mined by HPLC (Daicel Chiralcel AD-H, hexane/i-
4.5.6. (S)-N-[(1-Phenylsulfonyl-1H-indol-2-yl)(p-metho-xy-
phenyl)methane]-p-toluenesulfonamide 5d. Pale yellow
20
powder, mp 78–80 ꢁC. ½aꢁD ¼ þ78:6 (c 2.0, CHCl3). FTIR
(KBr): 590, 665, 801, 1091, 1170, 1257, 1369, 1448, 1511,
2962, 3285 cmꢀ1 1H NMR (300 MHz) d 2.30 (s, 3H),
.
3.74 (s, 3H), 5.34 (br s, 1H), 6.29–6.31 (d, 1H,
J = 7.1 Hz), 6.65–6.67 (d, 2H, J = 7.8 Hz), 6.77 (s, 1H),
6.88–6.91 (d, 2H, J = 8.0 Hz), 7.12–7.28 (m, 6H), 7.39–
7.45 (m, 4H), 7.62–7.64 (d, 2H, J = 7.6 Hz), 7.97–8.00 (d,
1H, J = 7.8 Hz). 13C NMR (75 MHz) d 21.4, 55.3, 55.7,
112.8, 114.0, 114.8, 121.0, 123.8, 124.8, 126.5, 127.2,
128.6, 128.9, 129.5, 131.0, 133.5, 137.3, 137.5, 138.2,
143.4, 159.4. HRMS (EI) m/z: [M]+ calcd for
PrOH = 7:3, 0.6 mL minꢀ1): tminor = 11.7 min, tmajor
=
10.8 min.
4.5.3.
(S)-N-[(1-Phenylsulfonyl-1H-indol-2-yl)(p-chloro-
phenyl)methane]-p-toluenesulfonamide 5a. Viscous oil.
20
½aꢁD ¼ þ122:7 (c 1.5, CHCl3). FTIR (KBr): 567, 590,

1842
L. Cheng et al. / Tetrahedron: Asymmetry 18 (2007) 1833–1843
C29H26N2O5S2, 546.1283; found, 546.1281. Ee was deter-
5.88 (t, 1H, J = 0.9 Hz), 6.99–7.07 (m, 5H), 7.11–7.15 (m,
3H), 7.22–7.25 (d, 1H, J = 7.0 Hz), 7.40–7.42 (d, 1H,
J = 7.8 Hz), 7.45–7.48 (d, 2H, J = 8.3 Hz), 8.56 (br s,
1H). 13C NMR (75 MHz) d 21.4, 55.6, 102.7, 111.2,
120.0, 120.6, 122.5, 127.0, 127.7, 128.7, 128.8, 129.5,
134.0, 136.47, 136.51, 136.59, 136.64, 143.9. Anal. Calcd
for C22H19N2O2SCl: C, 64.30; H, 4.66; N, 6.82; Found:
C, 64.07; H, 4.73; N, 6.86. Ee was determined by HPLC
mined by HPLC (Daicel Chiralcel OD-H, 10 ꢁC, hexane/
i-PrOH = 7:3, 0.6 mL minꢀ1): tminor = 18.2 min, tmajor
=
19.7 min.
4.5.7.
(R)-N-[(1-Phenylsulfonyl-1H-indol-2-yl)(2-furyl)-
20
methyane]-p-toluenesulfonamide 5e. Viscous oil. ½aꢁD
¼
þ64:6 (c 1.3, CHCl3). FTIR (KBr): 589, 680, 745, 815,
911, 1089, 1161, 1222, 1334, 1369, 1448, 1718, 2922,
(Daicel
Chiralpak
OD-H,
hexane/i-PrOH = 7:3,
3271 cmꢀ1. H NMR (300 MHz) d 2.28 (s, 3H), 5.75 (br
0.6 mL min): tminor = 20.2 min and tmajor = 16.6 min.
1
s, 1H), 6.09–6.10 (d, 1H, J = 2.7 Hz), 6.20 (d, 1H,
J = 2.4 Hz), 6.51–6.54 (d, 1H, J = 8.4 Hz), 6.74 (s, 1H),
7.08–7.48 (m, 9H), 7.62–7.65 (d, 4H, J = 8.1 Hz), 7.96–
7.99 (d, 1H, J = 8.4 Hz). 13C NMR (75 MHz) d 20.9,
49.8, 108.2, 110.2, 112.6, 114.5, 120.8, 123.5, 124.7, 126.2,
126.7, 128.6, 128.7, 129.0, 133.4, 136.9, 137.4, 137.5,
142.0, 143.0, 150.6. HRMS (EI) m/z: [M]+ calcd for
C26H22N2O5S2, 506.0970; found, 506.0966. Ee was deter-
mined by HPLC (Daicel Chiralcel AD-H, hexane/i-
Acknowledgement
We thank the National Natural Science Foundation of
China and the Chinese Academy of Sciences for financial
support.
PrOH = 7:3, 0.6 mL min ꢀ 1): tminor = 24.7 min, tmajor
=
References
27.6 min.
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4.5.8. (S)-N-[(1-Phenylsulfonyl-1H-3-methyl-indol-2-yl)(p-
chlorophenyl)methane]-p-toluenesulfonamide 5f. White
20
solid, mp 124–125 ꢁC. ½aꢁD ¼ þ117:5 (c 0.6, CHCl3). FTIR
(KBr): 553, 594, 673, 752, 811, 960, 1091, 1123, 1163, 1224,
1340, 1450, 1490, 2915, 3326 cmꢀ1. 1H NMR (300 MHz) d
1.98 (s, 3H), 2.21 (s, 3H), 6.18–6.22 (d, 1H, J = 10.8 Hz),
6.79–6.86 (m, 5H), 7.05–7.10 (m, 6H), 7.25–7.39 (m, 4H),
7.48–7.51 (d, 2H, J = 8.1 Hz), 7.99–8.01 (d, 1H,
J = 7.5 Hz). 13C NMR (75 MHz) d 9.09, 20.7, 51.8,
114.4, 118.9, 121.4, 123.5, 125.4, 125.6, 125.8, 127.0,
128.0, 128.36, 128.39, 129.4, 131.8, 132.8, 133.1, 136.2,
136.3, 136.7, 137.8, 142.6. HRMS (FAB) m/z: [M+Na]+
calcd for C29H25ClN2O4S2, 587.0836; found, 587.0840. Ee
was determined by HPLC (Daicel Chiralcel OD-H,
hexane/i-PrOH = 7:3, 0.6 mL minꢀ1): tminor = 11.3 min,
tmajor = 13.1 min.
4.5.9.
(S)-N-[(1-Phenylsulfonyl-1H-4-nitro-indol-2-yl)(p-
chlorophenyl) methane]-p-toluenesulfonamide 5g. Pale yel-
20
low solid, mp 251–253 ꢁC. ½aꢁD ¼ þ77:8 (c 0.7, CHCl3).
FTIR (KBr): 569, 680, 747, 808, 1090, 1161, 1336, 1519,
1
3294 cmꢀ1. H NMR (300 MHz) d 2.25 (s, 3H), 5.49 (br
s, 1H), 6.45–6.48 (d, 1H, J = 7.5 Hz), 6.99–7.59 (m, 15H),
8.16–8.19 (d, 1H, J = 8.1 Hz), 8.39–8.41 (d, 1H,
J = 8.4 Hz). 13C NMR (75 MHz) d 21.3, 55.4, 120.6,
120.8, 123.4, 124.4, 126.5, 127.1, 128.9, 129.0, 129.4,
129.5, 134.4, 134.5, 136.5, 137.1, 137.6, 138.8, 140.4,
143.8. HRMS (FAB) m/z: [M+Na]+ calcd for
C28H22ClN3O6S2, 618.0531; found, 618.0540. Ee was deter-
mined by HPLC (Daicel Chiralcel OD-H, hexane/i-
PrOH = 7:3, 0.6 mL minꢀ1): tminor = 31.9 min, tmajor
=
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25.5 min.
4.5.10.
(S)-N-[(1H-Indol-2-yl)(p-chlorophenyl)methyl]-p-
toluenesulfonamide 6. Overall yield 45%. Yellow solid,
20
mp 199–200 ꢁC. ½aꢁD ¼ ꢀ24:3 (c 2.8, CH2Cl2). FTIR
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3283 cmꢀ1. H NMR (300 MHz) d 2.31 (s, 3H), 5.65–5.68
1
(d, 1H, J = 8.6 Hz), 5.73–5.76 (d, 1H, J = 8.7 Hz), 5.87–

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