Iridium-catalyzed enantioselective allylation of sodium 2-aminobenzenethiolate: An access to chiral benzo-fused N,S-heterocycles

Article abstract of DOI:10.1016/j.tet.2012.09.010

The use of sodium 2-aminobenzenethiolate in the enantioselective iridium catalyzed allylic substitution with a range of methyl allyl carbonates allows the concise synthesis of the branch-type products with both excellent regio- and enantioselectivities, which are functionalized N,S-containing allylic intermediates for the formation of chiral benzo-fused N,S-heterocycles.

Full text of DOI:10.1016/j.tet.2012.09.010

Tetrahedron 68 (2012) 9413e9418
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Iridium-catalyzed enantioselective allylation of sodium 2-aminobenzenethiolate:
an access to chiral benzo-fused N,S-heterocycles
,
Ning Gao a, Xin-Wen Guo b, Sheng-Cai Zheng a, Wei-Kang Yang a, Xiao-Ming Zhao a
*
a Department of Chemistry, Tongji University, 1239 Siping Road, Shanghai 200092, PR China
b State Key Laboratory of Fine Chemicals, Dalian University of Technology, 158 Zhongshan Road, Dalian 116012, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 28 April 2012
Received in revised form 27 August 2012
Accepted 4 September 2012
Available online 17 September 2012
The use of sodium 2-aminobenzenethiolate in the enantioselective iridium catalyzed allylic substitution
with a range of methyl allyl carbonates allows the concise synthesis of the branch-type products with
both excellent regio- and enantioselectivities, which are functionalized N,S-containing allylic in-
termediates for the formation of chiral benzo-fused N,S-heterocycles.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Allylation
Iridium
Phosphoramidite ligand
Sodium 2-aminobenzenethiolate
Benzo-fused N,S-heterocycle
1. Introduction
chiral carbonesulfur bond formation catalyzed via iridium complex
has been made by the group of Hartwig,6 You,7 and us.8 To date, the
Analogs of both antiarrhythmic KT-3621 and Dazolicine1c (Fig. 1)
are of great importance with regards to benzo-fused N,S-hetero-
cycle with interesting biological activities.2 Construction of the
carbonesulfur bond by means of the asymmetrical transition
metal-catalyzed allylic substitution is less studied,3 however, use of
sulfur nucleophile in the enantioselective palladium-catalyzed al-
lylic alkylation was described.4 Few sulfur nucleophiles, such as 4-
chloro-thiophenol, 2-mercaptopyridine and 2-mercaptopyrimidine
are effective for the palladium catalyst system but more basic sulfur
nucleophiles fail to undergo this reaction.4a,4c Iridium-catalyzed
enantioselective allylation has become one of the powerful
methods for the synthesis of chiral compounds.5 Recent progress in
utilization of sodium 2-aminobenzenethiolate in the iridium-
catalyzed allylation has not been explored, in which an ortho sub-
stituent group may lead to the detrimental ortho substituent effect
on the stereoselectivity. In connect of our efforts aimed at forming
carbonesulfur bond, we have discovered that different types of
sulfur nucleophiles have a strong influence on regio- and enan-
tioselectivity of the iridium-catalyzed allylation.7 We envision that
the
asymmetrical
allylic
substitution
of
sodium
2-
aminobenzenethiolate could provide useful N,S-containing in-
termediates for the preparation of chiral benzo-fused N,S-
heterocycles.
Herein we report the enantioselective iridium-catalyzed allylic
substitution of sodium 2-aminobenzenethiolate with structurally
diverse allylic carbonates. This study presents the first example for
the preparation of N,S-containing allyl branch-type products in
good yields with both excellent regio- and enantioselectivities.
H
S
O
N
OMe
OMe
N
S
N
•
N
CO2H
2. Results and discussion
Cl
HO2C
N
KT-362
Dazolicine
Our first attempt involved a model reaction of (E)-cinnamyl
methyl carbonate (2a) with sodium 2-aminobenzenethiolate (3a),
which has two different nucleophilic positions, N or S. This reaction
was performed under our previous optimized conditions8a and
a mixture of the branched product 4a and linear product 5a in
a ratio of 65/35 was obtained. To our delight, 96% ee of 4a was
Fig. 1. The chemical structures of both KT-365 and Dazolicine.
* Corresponding author. Tel./fax: þ86 21 65981376; e-mail addresses:
xmzhao08@mail.tongji.edu.cn, xmzhao08@tongji.edu.cn (X.-M. Zhao).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.09.010

9414
N. Gao et al. / Tetrahedron 68 (2012) 9413e9418
achieved; a trace amount of the amination product 6a was also
observed (Table 1, entry 1). In contrast, this reaction without the
use of CsF also gave similar results (Table 1, entry 1 vs entry 2).
regioselectivity, albeit with 86% ee (Table 1, entry 13). The iridium
complex derived from ligand L4 resulted in somewhat improved re-
sults compared with L2 (Table 1, entry 13 vs entry 14). The remaining
Table 1
Optimization of the enantioselective Ir-catalyzed allylic substitution of sodium 2-aminobenzenethiolate with (E)-cinnamyl methyl carbonatea
H
H2N
S
Ph
N
Ph
OCO2Me
H2N
S
[Ir(COD)Cl]2 (2 mol %)
2a
L (4 mol %)
+
+
+
Ph
S
NH2
SNa
additive, solvent, t
5a
Ph
Ph
4a
6a
3a
Entry
L
Solvent
Base
2a/3
2.5/1
Temp [ꢀC]
Yieldb [%]
4a/5a/6ac
eed [%]
1
2
3
4
5
6
7
8
L3
L3
L3
L3
L3
L3
L3
L3
L3
L3
L3
L1
L2
L4
L5
L6
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
THF
Toluene
CH3CN
DCM
DCM
DCM
DCM
DCM
CsF
d
25
25
25
25
25
25
0
Reflux
25
25
25
25
25
25
25
25
58
59
39
66
83
30
65/35/Trace
70/30/trace
70/30/-
72/23/5
96/4/trace
58/42/-
d
96
98
95
98
96
96
d
96
d
d
d
d
86
95
d
d
2.5/1
2.5/1
2.5/1
2.5/1
1.5/1
2.5/1
2.5/1
2.5/1
2.5/1
2.5/1
2.5/1
2.5/1
2.5/1
2.5/1
2.5/1
DABCO
Cs2CO3
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
tracee
41
79/21/trace
d
9
Tracee
Tracee
Tracee
Tracee
20
10
11
12
13
14
15
16
d
d
d
31/69/-
75/25/trace
d
54
Tracee
Tracee
d
a
Reaction conditions: 2 mol % of [Ir(COD)Cl]2, 4 mol % of L, and 5.0 equiv of additive.
Isolated yields of 4a.
b
c
Determined by 1H NMR of the crude reaction mixture.
Determined by chiral HPLC analysis.
d
e
Monitored by TLC.
As is commonly seen in the iridium-catalyzed allylic substitution
ligand L1, L5, and L6 are ineffective for this reaction (Table 1, entries
12, 15, and 16).
of sulfur compounds,6e8 the nature of bases has a dramatic influence
on efficiency, regio-, and enantioselectivity. Thus, a range of bases
including DABCO,9 Cs2CO3, and KOAc was probed. Use of DABCO gave
the poorregioselectivities (Table 1, entry 3). WhenCs2CO3 wasused, it
led to the slight improvement of the yield and regioselectivity; the
formation of 6a was observed as well (Table 1, entry 4). Interestingly,
employing KOAc gave rise to the branched product 4a in the highest
yield (83%) with both excellent regio- and enantioselectivity (96/4
and 96% ee, Table 1, entry 5). Probably, KOAc may prevent the co-
ordinationof3atoIr-complexinthecourseof thereaction.10 Variation
of 2a/3a ratio and change of the reaction temperature both have
a drastic effect on the results of this reaction (Table 1, entries 5e8).
Solvent screen revealed that DCM is the optimum solvent for this
allylation, whereasother solvents(e.g., THF, toluene, and CH3CN) gave
poor outcomes (Table 1, entries 5, 9e11). In order to evaluate how the
structural variation of ligands influences efficiency, regio-, and
enantioselectivity, a range of phosphoramidite ligands including L1,11
L2,12 L3,13 L4,11 L5,14 and L615 was screened (Fig. 2). The reaction with
ligand L2 led to the branched product 4a in the poor yield and
Having established the optimized reaction conditions, the gen-
erality and scope of the enantioselective iridium-catalyzed allyla-
tion of sodium 2-aminobenzenethiolate with a range of methyl
allylic carbonates were further examined. All aromatic methyl al-
lylic substrates 2ae2f with either electron-donating group (e.g., 3-
CH3O, 4-CH3O, and 4-CH3) or electron-withdrawing group (e.g., 4-
Cl, 4-Br, and 3-CF3) on the phenyl ring gave the branch-type
products 4ae4g in good to high isolated yields (58e84%) with
both excellent regioselectivities (90/10e94/6) and enantiose-
lectivities (93e97% ee, Table 2, entries 1e7). The detrimental ortho
substituent effect of sodium 2-aminobenzenethiolate on the
regioselectivity is in agreement with results obtained by the tran-
sition metal-catalyzed allylic substitution reaction.16 To our sur-
prise, 8% yield of the diallylation product 6b was also obtained
when methyl allylic carbonate 2b, with a meta-methoxyl group on
the phenyl ring, was used as a substrate (Table 2, entry 2). It should
be noted that the aliphatic allylic substrates 2he2k resulted in the
allylation product 4he4k and 4n in moderate to good yields
(54e76%) with excellent regioselectivities (90/10e98/2) and
enantioselectivities (81e96% ee), except for 2he2k, which led to
4he4k and 4n along with a trace amount of the inseparable 5he5k,
and 5n, respectively (Table 2, entries 8e11). The different nucleo-
phile, such as sodium 2-amino-4-chlorobenzenethiolate 3b was
employed to react with allylic carbonates 2a, 2f, and 2i, respectively
(Table 2, entries 12e14); they gave the corresponding 4l, 4m, and
4n in good yields (52e58%) and good to high regioselectivities (85/
15e90/10) with the high level of regioselectivities (89e94% ee).
The X-ray crystal structure analysis of 4f (Fig. 3, see the
Supplementary data for details) generated from 2f in the enantio-
pure form revealed its absolute configuration as R.
Fig. 2. Chiral ligands L1eL6 evaluated for the titled allylic substitution.

N. Gao et al. / Tetrahedron 68 (2012) 9413e9418
9415
Table 2
3. Conclusions
Ir-catalyzed enantioselective allylic alkylation of sodium 2-aminobenzenethiolate
with a range of methyl allylic carbonatesa
We have developed a highly efficient iridium-catalyzed allyla-
tion of sodium 2-aminobenzenethiolate with a range of methyl
allylic carbonates, which provided N,S-containing branch-type al-
lylic products with both excellent regio- and enantioselectivities.
Using this method, an enantioenriched benzo-fused N,S-heterocy-
cle was synthesized in high yield with excellent ee value.
H2N
S
R2
R1
R2
OCO2Me
H
N
2
R1
R2
[Ir(COD)Cl]2 (2 mol %)
+
+
R1
L3 (4 mol %)
NH2
SNa
4
S
H2N
S
R2
KOAc, DCM, 25 °C, 12h
+
R1
6
3
R1
5
4. Experimental section
Entry
R1
R2
Yieldb of 4 [%]
4/5/6c
eed [%]
4.1. General procedure for the synthesis of sodium 2-
aminobenzenethiolate 3a
1
2
3
4
5
6
7
8
Ph
H
H
H
H
H
H
H
H
H
H
H
Cl
Cl
Cl
4a, 83
4b, 74
4c, 70
4d, 67
4e, 58
4f, 67
4g, 75
4h, 84f
4i, 75f
4j, 76f
4k, 54
4l, 58
96/4/trace
84/8/8
96
96
96
96
97
93
97
94
94
81
94
94
93
89
3-MeOC6H4
4-MeOC6H4
4-MeC6H4
4-ClC6H4
4-BrC6H4
3-CF3C6H4
BnCH2
n-Pr
Et
Me
Ph
4-BrC6H4
n-Pr
90/10/trace
93/7/trace
94/6/trace
94/6/trace
94/6/trace
90/10/tracee
96/4/tracee
97/3tracee
98/2/tracee
86/14/trace
85/15/trace
90/10/trace
NaH (9.6 mmol, 1.2 equiv, 80% in liquid paraffin) was added in
THF (15 mL) at 0 ꢀC, into which 2-aminothiophenol (8.0 mmol,
1.0 equiv) was added dropwise. This reaction was performed about
2 h at 0 ꢀC, and then the solvent was evaporated. The residual was
washed with petroleum ether and ether, respectively. Sodium 2-
aminobenzenethiolate 3a was obtained as pale gray powder.
Sodiun 2-amino-4-chlorobenenethiolate 3b was prepared accord-
ing to this method.
9
10
11
12
13
14
4m, 52
4n, 56f
a
Reaction conditions: 2 mol % of [Ir(COD)Cl]2, 4 mol % of L3, and 5.0 equiv of
4.2. General procedure for iridium-catalyzed allylation of
sodium 2-aminobenzenethiolate
KOAc.
b
c
d
e
f
Isolated yields.
Determined by 1H NMR of the crude reaction mixture.
Determined by chiral HPLC analysis.
Determined by GCeMS.
[Ir(COD)Cl]2 (0.0040 mmol, 2.0 mol %), phosphoramidite ligand
L3
[O,O’-(S)-(1,10-dinaphthyl-2,20-diyl)-N,N’-di-(S,S)[phenyl-
The yield of 4þ5.
ethylphospho-ramidite] (0.0080 mmol, 4.0 mol %) were dissolved
in THF (0.5 mL) and propylamine (0.3 mL) in a dry Schlenk tube
filled with argon. The reaction mixture was heated at 50 ꢀC for
30 min and then the volatile solvents were removed under vacuum
to give a yellow solid. After that, allylic carbonate 2 (0.50 mmol,
2.5 equiv), sodium 2-aminobenzenethiolate 3 (0.20 mmol), potas-
sium acetate (1.0 mmol, 5.0 equiv), and dichloromethylene (2.0 mL)
were added. The reaction mixture was stirred at room temperature
overnight. The crude residue was purified by flash column chro-
matography to give the desired products 4.
4.2.1. (R)-2-(1-Phenylallylthio)aniline (4a). Yield 83% (38.9 mg);
20
a white solid; mp 68e70 ꢀC; [
a]
ꢁ24.8 (c 1.0, CHCl3). The enan-
D
tiomeric excess of the product is determined by HPLC analysis
(214 nm, 25 ꢀC) tR¼7.16 min (minor); 7.82 min (major) [Daicel
CHIRALPAK AD-H (0.46 cmꢂ25 cm); hexane/2-propanol, 90/10,
1.0 mL/min] to be 96%; 1H NMR (400 MHz, CDCl3) 7.35e7.26 (m, 4H,
Ar), 7.24e7.21 (m, 2H, Ar), 7.10 (dd, J¼8.0, 7.2 Hz, 1H, Ar), 6.70 (d,
J¼8.0 Hz, 1H, Ar), 6.61 (dd, J¼7.6, 7.2 Hz, 1H, Ar), 6.13 (ddd, J¼16.8,
9.6, 8.8 Hz, 1H, ]CH), 5.00 (d, J¼10.0 Hz, 1H, ]CH), 4.90 (d,
J¼16.8 Hz, 1H, ]CH), 4.62 (d, J¼8.4 Hz, 1H, CH), 4.55e4.16 (m, 2H,
NH2) ppm; 13C NMR (100 MHz, CDCl3) 149.0, 140.4, 137.6, 137.3,
130.4, 128.5, 127.7, 127.3, 118.2, 116.9, 116.2, 114.8, 55.9 ppm; IR (KBr,
cmꢁ1) 3461, 3359, 3061, 3018, 1747, 1604, 1479, 1449, 1412, 1311,
1265, 1159, 981, 922, 741, 716; HRMS (EI) calcd for C15H15NS
241.0925; found 241.0930.
Fig. 3. X-ray structure of (R)-4f.
As an exemplification of the employment of this methodology,
an enantioenriched eight-membered benzo-fused N,S-heterocycle
was prepared by the following synthetic sequence (Scheme 1). The
enantioenriched 4kb, which was produced by the protection of the
branched product 4k and the alkylation with allylic bromide, was
oxidized with mCPBA, followed via the ring-closing metathesis
(RCM) in the presence of Grubbs’ first-generation catalyst
(2.5 mol %) to furnish the enantioenriched benzo-fused N,S-het-
erocycle 4kd17 in 62% yield of two steps with 92% ee.
Ts
N
a)TsCl, pyridine, DCM
NH2
reflux, Ar
4.2.2. (R)-2-(1-(3-Methoxyphenyl)allylthio)aniline (4b). Yield 74%
20
S
b) Allylic bromide, K2CO3
acetone, rt, Ar
S
(38.8 mg); a pale yellow thick oil; [
a]
ꢁ29.2 (c 0.8, CHCl3); The
D
4kb, 86% yield
4k, 93% ee
enantiomeric excess of the product was determined by HPLC
analysis (214 nm, 25 ꢀC) tR¼9.89 min (minor); 12.46 min (major)
[Daicel CHIRALPAK AD-H (0.46 cmꢂ25 cm); hexane/2-propanol,
90/10, 1.0 mL/min] to be 96%; 1H NMR (400 MHz, CDCl3) 7.26e7.19
(m, 2H), 7.10 (ddd, J¼8.0, 6.4, 1.6 Hz, 1H, Ar), 6.91 (d, J¼7.6 Hz, 1H,
Ar), 6.85e6.82 (m, 1H, Ar), 6.78 (dd, J¼8.4, 2.0 Hz, 1H, Ar), 6.70 (dd,
J¼8.0, 0.8 Hz, 1H, Ar), 6.62 (ddd, J¼7.2, 6.4, 1.2 Hz, 1H, Ar), 6.12 (ddd,
J¼16.8, 10.0, 8.4 Hz, 1H, ]CH), 5.01 (d, J¼10.0 Hz, 1H, ]CH), 4.91 (d,
J¼16.8 Hz, 1H, ]CH), 4.58 (d, J¼8.4 Hz, 1H, CH), 4.55e4.05 (m, 2H,
93% ee
Ts
N
a) mCPBA, DCM
0 oC, Ar
b) GrubbsI (2.5 mol%)
DCM, reflux, Ar
S
O
O
4kd, 69% yield
92% ee
Scheme 1. Synthesis of the enantioenriched benzo-fused N,S-heterocycle 4kd from
the enantioenriched allyl product 4k.

9416
N. Gao et al. / Tetrahedron 68 (2012) 9413e9418
NH2), 3.76 (s, 3H, OMe); 13C NMR (100 MHz, CDCl3) 159.6, 149.0,
141.9, 137.6, 137.2, 130.4, 129.5, 120.0, 118.2, 116.8, 116.1, 114.8, 113.3,
112.9, 55.9, 55.2 ppm; IR (KBr, cmꢁ1) 3456, 3362, 3061, 3004, 2924,
2833, 2360, 1605, 1584, 1477, 1435, 1309, 1263, 1156, 1046, 920, 750,
694; HRMS (EI) calcd for C16H17NOS 271.1031; found 271.1032.
55.0 ppm; IR (KBr, cmꢁ1) 3470, 3366, 1599, 1477, 1448, 1384, 1303,
1162, 922, 826, 750, 509; HRMS (EI): calcd for C15H14BrNS
319.0030; found 319.0028.
4.2.7. (R)-2-(1-(3-(Trifluoromethyl)phenyl)allylthio)aniline
(4g). Yield 75% (50.8 mg); a colorless oil; [
a
]
20 ꢁ130.9 (c 1.2, CHCl3).
D
4.2.3. (R)-2-(1-(4-Methoxyphenyl)allylthio)aniline (4c). Yield 70%
The enantiomeric excess of the product was determined by HPLC
analysis (214 nm, 25 ꢀC) tR¼7.65 min (minor); 7.97 min (major)
[Daicel CHIRALPAK AD-H (0.46 cmꢂ25 cm); hexane/2-propanol,
90/10, 0.7 mL/min] to be 97%; 1H NMR (400 MHz, CDCl3) 7.49e7.45
(m, 3H, Ar), 7.41e7.37 (m, 1H, Ar), 7.15e7.08 (m, 2H, Ar), 6.70 (dd,
J¼8.0, 1.2 Hz, 1H, Ar), 6.59 (ddd, J¼7.6, 6.4, 1.2 Hz, 1H), 6.13 (ddd,
J¼16.8, 10.0, 8.4 Hz, 1H, ]CH), 5.10 (d, J¼10.0 Hz, 1H, ]CH), 5.01 (d,
J¼16.8 Hz, 1H, ]CH), 4.69 (d, J¼8.4 Hz, 1H, ]CH), 4.32 (m, 2H, NH2)
ppm; 13C NMR (100 MHz, CDCl3) 149.1, 141.5, 137.6, 136.4, 131.2 (q,
J¼1.4 Hz), 130.7 (q, J¼32.1 Hz), 130.68, 128.9, 124.6 (q, J¼3.6 Hz),
124.1 (q, J¼3.6 Hz), 124.0 (q, J¼270.5 Hz), 118.3, 117.1, 116.0, 114.9,
20
(37.4 mg); a white solid; mp 86e87 ꢀC; [
a
]
ꢁ39.2 (c 0.5, CHCl3).
D
The enantiomeric excess of the product was determined by HPLC
analysis (214 nm, 25 ꢀC) tR¼9.71 min (minor); 11.59 min (major)
[Daicel CHIRALPAK AD-H (0.46 cmꢂ25 cm); hexane/2-propanol,
90/10, 1.0 mL/min] to be 98%; 1H NMR (400 MHz, CDCl3) 7.25e7.20
(m, 3H, Ar), 7.10 (ddd, J¼7.6, 6.4, 1.2 Hz, 1H, Ar), 6.86e6.82 (m, 2H,
Ar), 6.70 (dd, J¼8.0, 1.2 Hz, 1H, Ar), 6.62 (ddd, J¼7.6, 6.4, 1.2 Hz, 1H,
Ar), 6.11 (ddd, J¼16.8,10.0, 8.4 Hz, 1H, ]CH), 4.99 (d, J¼10.0 Hz, 1H,
]CH), 4.88 (d, J¼16.8 Hz, 1H, ]CH), 4.60 (d, J¼8.4 Hz, 1H, CH),
4.39e4.27 (m, 2H, NH2), 3.79 (s, 3H, OMe) ppm; 13C NMR (100 MHz,
CDCl3) 158.8, 149.0, 137.6, 137.5, 132.4, 130.3, 128.8, 118.2, 117.1,
115.8, 114.8, 113.9, 55.34, 55.26 ppm; IR (KBr, cmꢁ1) 3467, 3365,
3083, 2987, 2954, 2913, 2833, 1600, 1510, 1477, 1447, 1303, 1241,
1178, 1035, 908, 834, 748; HRMS (EI) calcd for C16H17NOS 271.1031;
found 271.1033.
55.0 ppm; 19F NMR (376 MHz, CDCl3) ꢁ62.6 ppm; IR (KBr, cmꢁ1
)
3458, 3357, 3059, 2916, 2846, 1602, 1475, 1446, 1330, 1249, 1163,
1122, 1072, 918, 804, 748, 702; HRMS (EI): calcd for C16H15F3NS
[MþH]þ 310.0877; found 310.0872.
4.2.8. (S)-2-(5-Phenylpent-1-en-3-ylthio)aniline (4h). Yield 84%
(47.8 mg, 4h together with a small amount of the linear product 5h,
which cannot be separated by flash column chromatography); a col-
4.2.4. (R)-2-(1-p-Tolylallylthio)aniline (4d). Yield 67% (28.3 mg);
20
a white solid; mp 81e83 ꢀC; [
a
]
ꢁ27.0 (c 0.9, CHCl3). The enan-
D
tiomeric excess of the product was determined by HPLC analysis
(214 nm, 25 ꢀC) tR¼10.20 min (minor); 12.94 min (major) [Daicel
CHIRALPAK AD-H (0.46 cmꢂ25 cm); hexane/2-propanol, 90/10,
0.7 mL/min] to be 96%; 1H NMR (400 MHz, CDCl3) 7.26e7.19 (m, 3H,
Ar), 7.14e7.07 (m, 3H, Ar), 6.70 (dd, J¼8.0, 1.2 Hz, 1H, Ar), 6.62 (ddd,
J¼7.6, 7.2, 1.2 Hz, 1H, Ar), 6.11 (ddd, J¼16.8, 10.0, 8.4 Hz, 1H, ]CH),
4.97 (d, J¼10.0 Hz, 1H, ]CH), 4.86 (d, J¼16.8 Hz, 1H, ]CH), 4.58 (d,
J¼8.4 Hz, 1H, CH), 4.43e4.24 (m, 2H, NH2), 2.32 (s, 3H, OMe); 13C
NMR (100 MHz, CDCl3) 149.0, 137.6, 137.5, 137.3, 137.0, 130.2, 129.2,
127.6, 118.2, 117.1, 115.8, 114.8, 55.9, 21.1 ppm; IR (KBr, cmꢁ1) 3457,
3357, 2917, 2358, 1602, 1509, 1478, 1447, 1310, 1255, 1019, 923, 822,
740; HRMS (EI) calcd for C16H17NS 255.1082; found 255.1083.
orless oil; [
a
]
20 ꢁ16.8 (c 0.9, CHCl3). The enantiomeric excess of the
D
product was determined by HPLC analysis (214 nm, 25 ꢀC)
tR¼6.88 min (minor); 8.96 min (major) [Daicel CHIRALPAK AD-H
(0.46 cmꢂ25 cm); hexane/2-propanol, 90/10, 1.0 mL/min] to be
93%; 1H NMR (400 MHz, CDCl3) 7.30e7.25 (m, 3H, Ar), 7.20e7.16 (m,
3H, Ar), 7.10 (dd, J¼8.0, 6.4, 1.6 Hz, 1H, Ar), 6.70 (dd, J¼8.0, 1.2 Hz, 1H,
Ar), 6.64 (dd, J¼8.4, 7.2 Hz,1H, Ar), 5.70 (ddd, J¼16.8, 9.6, 7.2 Hz,1H, ]
CH), 4.93 (dd, J¼10.0, 0.4 Hz, 1H, ]CH), 4.77 (d, J¼17.2 Hz, 1H, ]CH),
4.36e4.24 (m, 2H, NH2), 3.44 (dt, J¼8.4, 6.0 Hz,1H, CH), 2.80e2.68 (m,
2H, CH2), 2.07e1.88 (m, 2H, CH2) ppm; 13C NMR (100 MHz, CDCl3)
149.0,141.4,138.4,137.6,130.0,128.40,128.37,125.9,118.2,116.4,116.0,
114.8, 51.4, 35.8, 33.3 ppm; IR (KBr, cmꢁ1) 3467, 3368, 3062, 3026,
2926, 2855,1747,1605,1496,1478,1440,1384,1266, 971, 942,792,748,
699; HRMS (EI) calcd for C17H19NS 269.1238; found 269.1235.
4.2.5. (R)-2-(1-(4-Chlorophenyl)allylthio)aniline (4e). Yield 58%
20
(27.2 mg); a pale gray solid; mp 80e82 ꢀC; [
a
]
ꢁ83.7 (c 0.5,
D
CHCl3). The enantiomeric excess of the product was determined by
HPLC analysis (214 nm, 25 ꢀC) tR¼7.39 min (minor); 7.90 min
(major) [Daicel CHIRALPAK AD-H (0.46 cmꢂ25 cm); hexane/2-
propanol, 90/10, 1.0 mL/min] to be 97%; 1H NMR (400 MHz,
CDCl3) 7.27e7.20 (m, 4H, Ar), 7.17 (dd, J¼7.6, 1.2 Hz, 1H, Ar), 7.11 (dd,
J¼8.0, 7.6 Hz, 1H, Ar), 6.70 (dd, J¼8.0, 1.2 Hz, 1H, Ar), 6.61 (ddd,
J¼7.6, 7.6, 1.2 Hz, 1H, Ar), 6.09 (ddd, J¼17.2, 10.0, 8.8 Hz, 1H, ]CH),
5.05 (d, J¼10.0 Hz, 1H, ]CH), 4.95 (d, J¼16.8 Hz, 1H, ]CH), 4.60 (d,
J¼8.4 Hz, 1H, CH), 4.33 (m, 2H, NH2) ppm; 13C NMR (100 MHz,
CDCl3) 149.0, 139.0, 137.6, 136.82, 133.0, 130.5, 129.1, 128.6, 118.3,
116.6, 116.4, 114.9, 55.0 ppm; IR (KBr, cmꢁ1) 3661, 3469, 3365, 2922,
2851, 1600, 1477, 1447, 1400, 1306, 1254, 1159, 1091, 922, 827, 750,
515; HRMS (EI): calcd for C15H14ClNS 275.0535; found 275.0532.
4.2.9. (S)-2-(Hex-1-en-3-ylthio)aniline (4i). Yield 75% (29.3 mg, 4i
containing a trace amount of the linear product 5i, which cannot be
20
separated by flash column chromatography), a colorless oil; [a]
D
ꢁ28.6 (c 0.5, CHCl3). The enantiomeric excess of the product was
determined by HPLC analysis (214 nm, 25 ꢀC) tR¼19.69 min (major);
27.74 min (minor) [Daicel CHIRALCEL OJ-H (0.46 cmꢂ25 cm); hex-
ane/2-propanol, 98/2, 1.0 mL/min] to be 94%; 1H NMR (400 MHz,
CDCl3) 7.30 (dd, J¼8.0,1.6 Hz,1H, Ar), 7.11 (ddd, J¼7.2, 6.4,1.6 Hz,1H,
Ar), 6.71 (dd, J¼8.0, 1.2 Hz, 1H, Ar), 6.66 (ddd, J¼7.2, 6.0, 1.2 Hz, 1H,
Ar), 5.64 (ddd, J¼16.8, 9.6, 7.2 Hz, 1H, ]CH), 4.87 (dd, J¼10.0, 1.2 Hz,
1H, ]CH), 4.72 (ddd, J¼16.8,1.6,1.2 Hz,1H, ]CH), 4.41e4.28 (m, 2H,
NH2), 3.43 (dt, J¼8.8, 5.6 Hz, 1H, CH), 1.68e1.56 (m, 2H, CH2),
1.49e1.38 (m, 2H, CH2), 0.91 (t, J¼7.2 Hz, 3H, CH3) ppm; 13C NMR
(100 MHz, CDCl3) 149.0, 138.8, 137.6, 130.0, 118.1, 116.8, 115.4, 114.7,
52.0, 36.4, 20.5, 13.8 ppm. IR (KBr, cmꢁ1) 3462, 3364, 3065, 2957,
2929, 2871, 2360, 2342,1605,1559,1477,1384,1157, 913, 747; HRMS
(EI): calcd for C12H17NS 207.1082; found 207.1080.
4.2.6. (R)-2-(1-(4-Bromophenyl)allylthio)aniline (4f). Yield 67%
20
(44.3 mg); a white solid; mp 93e95 ꢀC; [
a
]
ꢁ40.0 (c 0.5, CHCl3).
D
The enantiomeric excess of the product was determined by HPLC
analysis (214 nm, 25 ꢀC) tR¼8.96 min (minor); 9.85 min (major)
[Daicel CHIRALPAK AD-H (0.46 cmꢂ25 cm); hexane/2-propanol,
90/10, 1.0 mL/min] to be 93%; 1H NMR (400 MHz, CDCl3) 7.41 (d,
J¼8.4 Hz, 2H, Ar), 7.19e7.14 (m, 3H, Ar), 7.12 (ddd, J¼8.0, 7.6, 1.2 Hz,
1H, Ar), 6.71 (d, J¼8.0 Hz, 1H, Ar), 6.61 (ddd, J¼7.6, 7.6, 0.8 Hz, 1H,
Ar), 6.08 (ddd, J¼16.8, 10.0, 8.4 Hz, 1H, ]CH), 5.05 (d, J¼10.0 Hz, 1H,
]CH), 4.94 (d, J¼16.8 Hz, 1H, ]CH), 4.59 (d, J¼8.4 Hz, 1H, CH),
4.55e3.83 (m, 2H, NH2) ppm; 13C NMR (100 MHz, CDCl3) 149.0,
139.5, 137.6, 137.7, 131.6, 130.5, 129.5, 121.1, 118.4, 116.7, 116.4, 114.9,
4.2.10. (S)-2-(Pent-1-en-3-ylthio)aniline(4j). Yield 76% (32.8 mg, 4j
along with a trace amount of the linear product 5j, which cannot be
20
separated by flash column chromatography); a colorless oil; [a]
D
ꢁ27.7 (c 0.5, CHCl3). The enantiomeric excess of the product was
determined by HPLC analysis (214 nm, 25 ꢀC) tR¼11.12 min (minor);
12.51 min (major) [Daicel CHIRALCEL OD-H (0.46 cmꢂ25 cm);
hexane/2-propanol, 98/2, 0.7 mL/min] to be 81%; 1H NMR
(400 MHz, CDCl3) 7.31 (d, J¼7.6 Hz, 1H, Ar), 7.11 (ddd, J¼8.0, 6.8,

N. Gao et al. / Tetrahedron 68 (2012) 9413e9418
9417
1.2 Hz, 1H, Ar), 6.72 (d, J¼8.0 Hz, 1H, Ar), 6.66 (dd, J¼7.6, 7.2 Hz, 1H,
Ar), 5.65 (ddd, J¼16.8, 9.6, 7.2 Hz, 1H, ]CH), 4.91 (d, J¼10.0 Hz, 1H,
]CH), 4.77 (d, J¼16.8 Hz, 1H, ]CH), 4.44e4.28 (m, 2H, NH2),
3.39e3.29 (m, 1H, CH), 1.78e1.58 (m, 2H, CH2), 0.99 (t, J¼7.2 Hz, 3H,
CH3) ppm; 13C NMR (100 MHz, CDCl3) 149.0, 138.5, 137.6, 130.0,
118.2, 116.8, 115.7, 114.7, 53.9, 27.5, 11.8 ppm; IR (KBr, cmꢁ1) 3650,
2962, 2361, 2344, 1541, 1508, 1384, 1260, 1093, 1021, 800, 746;
HRMS (ESI) calcd for C11H16NS[MþH]þ 194.1003; found 194.1001.
1H, ]CH), 4.88 (dd, J¼10.0, 1.2 Hz, 1H, ]CH), 4.71 (d, J¼16.8 Hz, 1H, ]
CH), 4.42 (m, 2H, NH2), 3.37 (dt, J¼8.8, 6.0 Hz, 1H, CH), 1.70e1.52 (m,
2H, CH2), 1.48e1.37 (m, 2H, CH2), 0.91 (t, J¼7.2 Hz, 3H, CH3) ppm; 13
C
NMR (100 MHz, CDCl3) 149.9, 138.7, 138.4, 135.6, 118.1, 115.7, 115.2,
114.2, 52.3, 36.3, 20.5, 13.7 ppm; IR (KBr, cmꢁ1) 3462, 3381, 2954,
2922, 2862, 1597, 1471, 1411, 1245, 1085, 902, 840, 792; HRMS (ESI):
calcd for C12H17ClNS [MþH]þ 242.0770; found 242.0772.
4.2.15. N-((S)-1-Phenylallyl)-2-((R)-1-phenylallylthio)aniline (6a). A
colorless oil; 1H NMR (400 MHz, CDCl3) 7.38e7.22 (m, 11H, Ar), 7.09
(dd, J¼8.0, 8.0 Hz, 1H, Ar), 6.55 (dd, J¼8.0, 8.0 Hz, 1H, Ar), 6.50 (d,
J¼8.0 Hz, 1H, Ar), 6.21e5.97 (m, 2H, ]CH), 5.65e5.56 (m, 1H, CH),
5.29e5.16 (m, 2H, ]CH, NH), 5.00 (d, J¼8.0 Hz, 1H, ]CH),
4.95e4.90 (m, 1H, CH), 4.87 (d, J¼16.0 Hz, 1H, ]CH), 4.59 (d,
J¼8.0 Hz, 1H, CH) ppm; 13C NMR (100 MHz, CDCl3) 148.6, 141.6,
140.3, 139.0, 137.6, 137.2, 130.5, 128.7, 128.5, 127.7, 127.44, 127.36,
127.0, 116.8, 116.2, 115.8, 111.4, 60.6, 56.5 ppm. HRMS (ESI) calcd for
C24H24NS [MþH]þ 358.1629; found 358.1630.
4.2.11. (S)-2-(But-3-en-2-ylthio)aniline (4k). Yield 54% (20.8 mg);
a colorless oil; [
a
]
D
20 ꢁ33.8 (c 0.4, CHCl3). The enantiomeric excess of
the product was determined by HPLC analysis (214 nm, 25 ꢀC)
tR¼11.83 min (minor); 12.44 min (major) [Daicel CHIRALCEL OJ-H
(0.46 cmꢂ25 cm); hexane/2-propanol, 90/10, 1.0 mL/min] to be
94%; 1H NMR (400 MHz, CDCl3) 7.33 (d, J¼7.6 Hz, 1H, Ar), 7.12 (dd,
J¼7.6, 7.2 Hz, 1H, Ar), 6.72 (d, J¼8.0 Hz, 1H, Ar), 6.67 (dd, J¼7.6,
7.2 Hz, 1H, Ar), 5.79 (ddd, J¼16.8, 9.6, 9.2 Hz, 1H, ]CH), 4.90 (d,
J¼10.0 Hz, 1H, ]CH), 4.84 (d, J¼17.2 Hz, 1H, ]CH), 4.48e4.24 (m,
2H, NH2), 3.61 (dd, J¼7.2, 6.8 Hz, 1H, CH), 1.35 (d, J¼6.8 Hz, 3H, CH3)
ppm; 13C NMR (100 MHz, CDCl3) 149.0, 139.8, 137.6, 130.1, 118.2,
116.8, 114.8, 114.5, 46.2, 20.1 ppm; IR (KBr, cmꢁ1) 3459, 3362, 3063,
2963, 2933, 1605, 1477, 1446, 1384, 1306, 1023, 916, 748, 711; HRMS
(EI) calcd for C10H13NS 179.0769; found 179.0771.
4.3. General procedure for the synthesis of compound
(4kd)2aed
(S)-2-(But-3-en-2-ylthio)aniline 4k (34.5 mg, 0.2 mmol) was
added to a solution of CH2Cl2 (6.0 mL) containing pyridine (0.2 mL),
and then toluenesulfonyl chloride (88.9 mg, 0.47 mmol) was added
at room temperature. The reaction mixture was then heated at
reflux for 12 h. The solvent was evaporated and the residue was
purified by column chromatography (PE/EA¼15/1) to afford 4ka as
a colorless thick oil (60.6 mg, 94% yield). Allyl bromide (162.0 mg,
1.3 mmol) and K2CO3 (151.0 mg, 1.1 mmol) were added to a solution
of (S)-N-(2-(but-3-en-2-ylthio)phenyl)-4-methyl-benzenesulfona-
mide 4ka (60.0 mg, 0.18 mmol) in acetone (5 mL), and the reaction
mixture was then stirred at room temperature for 24 h. The base
was removed by filtration and the solvent was removed under re-
duced pressure, then the residue was purified by column chroma-
tography (PE/EA¼10/1) to produce 4kb as a colorless thick oil
(60.9 mg, 91% yield). The compound 4kb was oxidized by mCPBA
(2.5 equiv) at room temperature under argon in dry DCM. After
completion, the reaction mixture was then poured into a saturated
solution of Na2CO3 (15 mL) and extracted with additional DCM
(15 mL). The organic extracts were washed with brine (15 mL),
dried over Na2SO4, filtered, and evaporated to give a thick yellow oil
(4kc). After simple workout, dissolving the Grubbs’ first generation
catalyst (G1) (2.3 mg, 0.0028 mmol, 3.3 mol %) in dry DCM (2 mL)
under argon, and a solution of sulfane 4kc in dry DCM (3 mL) was
added in. The reaction mixture was heated at reflux under argon for
12 h. The reaction mixture was evaporated and the residue was
purified by column chromatography (PE/EA¼1/1) to afford 4kd as
a white solid (29.4 mg, two steps 69% yields).
4.2.12. (R)-5-Chloro-2-(1-phenylallylthio)aniline (4l). Yield 58%
(37.6 mg); a white solid; mp 66e67 ꢀC; [
a
]
20 ꢁ131.9 (c 1.8, CHCl3).
D
The enantiomeric excess of the product was determined by HPLC
analysis (214 nm, 25 ꢀC) tR¼8.42 min (major); 9.07 min (minor)
[Daicel CHIRALCEL OD-H (0.46 cmꢂ25 cm); hexane/2-propanol, 90/
10, 0.7 mL/min] to be 94%; 1H NMR (400 MHz, CDCl3) 7.30e7.27 (m,
4H, Ar), 7.26e7.21 (m, 1H, Ar), 7.10 (d, J¼8.4 Hz, 1H, Ar), 6.68 (d,
J¼2.4 Hz, 1H, Ar), 6.57 (dd, J¼8.0, 2.0 Hz, 1H, Ar), 6.10(ddd, J¼17.2,
10.0, 8.4 Hz, 1H, ]CH), 5.02 (d, J¼10.0 Hz, 1H, ]CH), 4.92 (d,
J¼16.8 Hz, 1H, ]CH), 4.56 (d, J¼8.8 Hz, 1H, CH), 4.39 (m, 2H, NH2)
ppm; 13C NMR (100 MHz, CDCl3) 149.9, 140.0, 138.6, 136.9, 136.0,
128.6, 127.7, 127.4, 118.2, 116.5, 115.1, 114.3, 56.1 ppm; IR (KBr, cmꢁ1
)
3460, 3357, 2912, 1593, 1548, 1471, 1411, 1253, 1068, 908, 844, 781,
723, 696; HRMS (ESI): calcd for C15H15ClNS [MþH]þ 276.0614;
found 276.0682.
4.2.13. (R)-2-(1-(4-Bromophenyl)allylthio)-5-chloroaniline
20
(4m). Yield 52% (38.8 mg); a white solid; mp 91e92 ꢀC; [
a]
D
ꢁ141.8 (c 1.5, CHCl3). The enantiomeric excess of the product was
determined by HPLC analysis (214 nm, 25 ꢀC) tR¼10.40 min (mi-
nor); 10.76 min (major) [Daicel CHIRALPAK AD-H (0.46 cmꢂ25 cm);
hexane/2-propanol, 90/10, 0.7 mL/min] to be 93%; 1H NMR
(400 MHz, CDCl3) 7.43e7.40 (m, 2H, Ar), 7.16e7.12 (m, 2H, Ar), 7.06
(d, J¼8.4 Hz, 1H, Ar), 6.69 (d, J¼2.0 Hz, 1H, Ar), 6.57 (dd, J¼8.0,
2.0 Hz, 1H, Ar), 6.05(ddd, J¼17.2, 10.0, 8.0 Hz, 1H, ]CH), 5.06 (d,
J¼10.0 Hz, 1H, ]CH), 4.95 (d, J¼16.8 Hz, 1H, ]CH), 4.53 (d,
J¼8.4 Hz, 1H, CH), 4.39 (m, 2H, NH2) ppm; 13C NMR (100 MHz,
CDCl3) 149.9, 139.2, 138.6, 136.4, 136.2, 131.6, 129.4, 121.3, 118.3,
117.0, 114.6, 114.4, 55.2 ppm; IR (KBr, cmꢁ1) 3471, 3363, 2958, 2918,
2848, 1597, 1548, 1467, 1413, 1398, 1253, 1089, 1070, 1008, 921, 825,
788, 750; HRMS (EI): calcd for C15H13BrClNS 352.9641; found
352.9641.
4.3.1. (S)-N-(2-(But-3-en-2-ylthio)phenyl)-4 methylbenzene-
20
sulfonamide (4ka). Yield 94% (60.0 mg); a colorless thick oil; [a]
D
ꢁ124.5 (c 0.4, CHCl3). The enantiomeric excess of the product was
determined by HPLC analysis (214 nm, 25 ꢀC) tR¼36.32 min (mi-
nor);
38.43
min
(major)
[Daicel
CHIRALPAK
AD-H
(0.46 cmꢂ25 cm); hexane/2-propanol, 98/2, 0.7 mL/min] to be
98%; 1H NMR (400 MHz, CDCl3) 8.01e7.93 (m, 1H, Ar), 7.70 (d,
J¼8.4 Hz, 2H, Ar), 7.64 (dd, J¼8.4, 1.2 Hz, 1H, Ar), 7.35 (dd, J¼8.0,
1.6 Hz, 1H, Ar), 7.29e7.25 (m, 1H, Ar), 7.22 (d, J¼8.0 Hz, 2H, Ar),
6.98(ddd, J¼7.6, 7.6, 1.2 Hz, 1H, Ar), 5.61 (ddd, J¼17.2, 10.0, 8.8 Hz,
1H, ]CH), 4.79 (d, J¼10.0 Hz, 1H, ]CH), 4.59 (d, J¼17.2 Hz, 1H, ]
CH), 3.28e3.17 (m, 1H, NH), 2.36 (s, 3H, CH3), 1.28 (d, J¼6.8 Hz, 3H,
CH3) ppm; 13C NMR (100 MHz, CDCl3) 144.0, 139.5, 138.6, 137.3,
136.3, 130.2, 129.6, 127.2, 124.1, 122.7, 118.8, 115.6, 48.4, 21.5,
19.9 ppm; IR (KBr, cmꢁ1) 3258, 2966, 2923, 1589, 1476, 1448, 1386,
4.2.14. (S)-5-Chloro-2-(hex-1-en-3-ylthio)aniline (4n). Yield 56%
(29.5 mg, 4 n containing a trace amount of the linear product 5n,
which cannot be separated by flash column chromatography); a col-
orless oil; [
a
]
20 ꢁ18.1 (c 1.3, CHCl3). The enantiomeric excess of the
D
product was determined by HPLC analysis (214 nm, 25 ꢀC)
tR¼7.27 min (major); 7.67 min (minor) [Daicel CHIRALPAK AD-H
(0.46 cmꢂ25 cm); hexane/2-propanol, 98/2, 1.0 mL/min] to be 89%;
1H NMR (400 MHz, CDCl3) 7.20 (d, J¼8.0 Hz,1H, Ar), 6.80 (d, J¼2.4 Hz,
1H, Ar), 6.62 (dd, J¼8.0, 2.4 Hz, 1H, Ar), 5.60 (ddd, J¼17.2, 9.6, 7.2 Hz,

9418
N. Gao et al. / Tetrahedron 68 (2012) 9413e9418
1336, 1273, 1164, 1091, 916, 813, 756, 706, 664, 564; HRMS (ESI)
References and notes
calcd for C17H19NO2S2Na [MþNa]þ 356.0755; found 356.0749.
1. (a) Kiyosue, T.; Ito, M.; Cheng, Y.; Saikawa, T.; Arita, M. Cardiovasc. Drug Rev.
1996, 14, 231e245; (b) Ueyama, N.; Wakabayashi, S.; Tomiyama, T. Chem. Pharm.
Bull. 1997, 45, 1761e1766; (c) Blancafort, P.; Serradell, M. N.; Castar, J.; Koch, H.
Drugs Future 1981, 6, 540e542.
4.3.2. (S)-N-Allyl-N-(2-(but-3-en-2-ylthio)phenyl)-4-methylbenzene-
20
sulfon-amide (4kb). Yield 91% (60.9 mg); a colorless thick oil; [a]
D
2. (a) Yadav, D. B.; Morgans, G. L.; Aderibigbe, B. A.; Madeley, L. G.; Fernandes, M.
A.; Michael, J. P.; de Koning, C. B.; Van Otterlo, W. A. L. Tetrahedron 2011, 67,
2991e2997; (b) Wessels, M.; Mahajan, V.; Boßhammer, S.; Raabe, G.; Gais, H. J.
Eur. J. Org. Chem. 2011, 2431e2449; (c) Morgans, G. L.; Ngidi, E. L.; Madeley, L.
G.; Khanye, S. D.; Michael, J. P.; de Koning, C. B.; Van Otterlo, W. A. L. Tetrahedron
2009, 65, 10650e10659; (d) Van Otterlo, W. A. L.; Morgans, G. L.; Khanye, S. D.;
Aderibigbe, B. A. A.; Michael, J. P.; Billing, D. G. Tetrahedron Lett. 2004, 45,
9171e9175.
3. For review, see: Kondo, T.; Mitsudo, T. Chem. Rev. 2000, 100, 3205e3220.
4. (a) Frank, M.; Gais, H. J. Tetrahedron: Asymmetry 1998, 9, 3353e3357; (b) Gais,
H. J.; Spalthoff, N.; Thomas, J.; Frank, M.; Raabe, G. Tetrahedron Lett. 2000, 41,
3809e3812; (c) Gais, H. J.; Thomas, J.; Spalthoff, N.; Gerhards, F.; Frank, M.;
Raabe, G. Chem.dEur. J. 2003, 9, 4202e4221.
5. For reviews, see: (a) Helmchen, G.; Dahnz, A.; Dubon, P.; Schelwies, M.; Wei-
hofen, R. Chem. Commun. 2007, 675e691; (b) Hartwig, J. F.; Stanley, L. M. Acc.
Chem. Res. 2010, 43, 1461e1475; (c) Liu, W.; Xia, J.; You, S. Top. Organomet. Chem.
2012, 38, 155e208.
6. Ueda, M.; Hartwig, J. F. Org. Lett. 2010, 12, 92e94.
7. (a) Xu, Q.; Liu, W.; Dai, L.; You, S. J. Org. Chem. 2010, 75, 4615e4618; (b) Xu, Q.;
ꢁ84.9 (c 0.6, CHCl3). The enantiomeric excess of the product was
determined by HPLC analysis (214 nm, 25 ꢀC) tR¼10.48 min (minor);
11.20 min (major) [Daicel CHIRALPAK AD-H (0.46 cmꢂ25 cm); hex-
ane/2-propanol, 90/10, 1.0 mL/min] to be 93%; 1H NMR (400 MHz,
CDCl3) 7.67 (d, J¼8.0 Hz, 2H, Ar), 7.34 (d, J¼8.0 Hz, 1H, Ar), 7.27 (d,
J¼8.0Hz, 2H, Ar), 7.25e7.20(m,1H, Ar),7.05(dd,J¼8.0, 7.2Hz,1H, Ar),
6.92e6.80 (m,1H, Ar), 5.92e5.64 (m, 2H, ]CH), 5.24e4.87 (m, 4H, ]
CH), 4.24e4.08 (m, 2H, CH2), 3.93e3.83 (m,1H, CH), 2.43 (s, 3H, CH3),
1.45e1.36 (m, 3H, CH3) ppm; 13C NMR (100 MHz, CDCl3) 143.3,136.8,
132.8,130.4,130.2,129.3,128.4,128.1,128.0,125.6,125.4,118.9,115.5,
114.7, 54.0, 44.3, 21.5, 20.0 ppm; IR (KBr, cmꢁ1) 3080, 2970, 2923,
1597,1467,1384,1304,1219,1163,1091,1057, 991, 923, 864, 815, 726,
662, 577, 548; HRMS (ESI) calcd for C20H23NO2S2Na [MþNa]þ
396.1068; found 396.1062.
Dai, L.; You, S. Org. Lett. 2010, 12, 800e803.
4.3.3. 5,6-Dihydro-2H-1,6-benzothiazocine-1,1-dioxide (4kd). Yield
8. (a) Zheng, S.; Gao, N.; Liu, W.; Liu, D.; Zhao, X.; Cohen, T. Org. Lett. 2010, 12,
4454e4457; (b) Gao, N.; Zheng, S.; Yang, W.; Zhao, X. Org. Lett. 2011, 13,
1514e1516; (c) Zheng, S.; Huang, W.; Gao, N.; Cui, R.; Zhang, M.; Zhao, X. Chem.
Commun. 2011, 6969e6971; (d) Huang, W.; Zheng, S.; Tang, J.; Zhao, X. Org.
Biomol. Chem. 2011, 9, 7897e7903.
9. The use of DABCO in the enantioselective iridium-catalyzed allylic amination of
aniline leads to the improvement of both yield and regioselectivity, for details,
see: Shu, C.; Leitner, A.; Hartwig, J. F. Angew. Chem., Int. Ed. 2004, 43,
4797e4800.
10. 2-Aminothiophenol was successfully used as a nucleophile in Cu-catalyzed
Michael reaction and its both the amine and thiol functionalities may co-
ordinate with copper to form a stable copper complex, see: Takanori, O.; Naoya,
K.; Masakatsu, S. Angew. Chem., Int. Ed. 2012, 51, 8551e8554.
11. Hoen, R.; Berg, M.; Bernsmann, H.; Minnaard, A. J.; Vries, G. J.; Fering, L. B. Org.
Lett. 2004, 6, 1433e1436.
20
93% (29.4 mg); a white solid; mp 169e171 ꢀC; [
a]
D
ꢁ65.8 (c 0.7,
CHCl3). The enantiomeric excess of the product was determined by
HPLC analysis (214 nm, 25 ꢀC) tR¼42.46 min (major); 45.19 min (mi-
nor) [Daicel CHIRALPAK AD-H (0.46 cmꢂ25 cm); hexane/2-propanol,
90/10,1.0mL/min]tobe93%;1HNMR(400MHz,CDCl3)8.14e8.08(m,
1H, Ar), 7.89 (d, J¼8.4 Hz, 2H, Ar), 7.60e7.53 (m, 2H, Ar), 7.40 (d,
J¼8.0 Hz, 2H, Ar), 7.14e7.08 (m,1H, Ar), 5.55e5.42 (m, 2H, ]CH), 4.83
(dq, J¼15.6, 6.8 Hz, 1H, CH), 4.62 (d, J¼15.6 Hz, 1H, CH), 3.68 (dd,
J¼15.6, 5.6 Hz, 1H, CH), 2.49 (s, 3H, CH3), 1.59 (d, J¼6.8 Hz, 3H, CH3)
ppm;13CNMR (100MHz,CDCl3)144.9,140.3,135.2,134.8,134.0,130.7,
130.1,130.0,129.7,128.7,128.2,128.0, 59.5, 50.1, 21.6,11.7 ppm; IR (KBr,
cmꢁ1) 3064, 2923,1596,1477,1444,1353,1306,1219,1164,1142,1091,
1062,1010, 963, 872, 818, 802, 769, 730, 713, 679, 660, 637, 548; HRMS
(ESI) calcd for C18H19NO4S2Na [MþNa]þ 400.0653; found 400.0648.
12. Alexakis, A.; Rosset, S.; Allamand, J.; March, S.; Guillen, F.; Benhaim, C. Synlett
2001, 1375e1378.
13. (a) Tissot-Croset, K.; Polet, D.; Gille, S.; Hawner, C.; Alexakis, A. Synthesis 2004,
2586e2590; (b) Arnold, L. A.; Imbos, R.; Mandoli, A.; de Vries, A. H. M.; Naasz,
R.; Feringa, B. L. Tetrahedron 2000, 56, 2865e2878.
14. Cram, D. J.; Helgeson, R. C.; Peacock, S. C.; Kaplan, L. J.; Domeier, L. A.; Moreau,
P.; Koga, K.; Mayer, J. M.; Chao, Y.; Siegel, M. G.; Hoffman, D. H.; Sogah, G. D. Y. J.
Org. Chem. 1978, 43, 1930e1946.
Acknowledgements
15. (a) Matt, P. V.; Pfaltz, A. Angew. Chem., Int. Ed. Engl. 1993, 32, 566e568; (b)
Sprinz, J.; Helmchen, G. Tetrahedron Lett. 1995, 34, 1769e1772.
16. N or O Aromatic nucleophile with an ortho-substituent on the phenyl ring was
employed in transition metal-catalyzed allylic substitution and it gave the
slight decrease of the yield and regioselectivity, for details, see: Ref. 9 and
Gurbuz, N.; Ozdemir, I.; C¸ etickaya, B.; Renaud, J. L.; Demerseman, B.; Bruneau, C.
Tetrahedron Lett. 2006, 47, 535e538.
17. An analogue of 4kd containing a chiral carbonesulfur centre was prepared in
good yield, for details, see: Urbanski, M. J.; Chen, R.; Demarest, K. T.; Gunnet, J.;
Look, R.; Ericson, E.; Murray, W. V.; Rybczynski, P. J.; Zhang, X. Bioorg. Med.
Chem. Lett. 2003, 13, 4031e4034.
We gratefully acknowledge Pu Jiang Program of Shanghai
(2010e2013), the NSFC (21272175), State Key Laboratory of Fine
Chemicals, Dalian University of Technology (KF1006) for generous
financial support.
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Supplementary data
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2012.09.010.