Synthesis of novel C3 symmetric tris(thiazoline) ligands and their application in the allylic oxidation reaction

Article abstract of DOI:10.1016/j.tetasy.2008.08.028

A series of novel C₃ symmetric tris(thiazoline) ligands were synthesized from trimethyl nitrilotriacetate and an enantiomerically pure amino alcohol via an efficient route. Compound 7a showed moderate to good catalytic enantioselectivity for th

Full text of DOI:10.1016/j.tetasy.2008.08.028

Tetrahedron: Asymmetry 19 (2008) 2159–2163
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Synthesis of novel C3 symmetric tris(thiazoline) ligands and their application
in the allylic oxidation reaction
*
Xue-Ming Cheng, Zhong-Bo Zheng, Nan Li, Zhao-Hai Qin, Bin Fu , Neng-Dong Wang
Department of Applied Chemistry, China Agricultural University, Beijing 100094, PR China
College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
A series of novel C3 symmetric tris(thiazoline) ligands were synthesized from trimethyl nitrilotriacetate
and an enantiomerically pure amino alcohol via an efficient route. Compound 7a showed moderate to
good catalytic enantioselectivity for the asymmetric allylic oxidation of cycloalkenes.
Ó 2008 Elsevier Ltd. All rights reserved.
Received 21 July 2008
Accepted 27 August 2008
Available online 1 October 2008
1. Introduction
Considering that a series of C3 symmetric chiral ligands have
been developed and showed interesting properties,7 we designed
Over the past two decades, a plethora of mono- and bis(oxazo-
line) ligands have been synthesized and applied in a large variety
of catalytic asymmetric reactions.1 In order to find better chiral li-
gands for asymmetric transformations, researchers have also de-
signed and prepared some tris(oxazoline) ligands such as 1,2 23
and 3.4 These ligands showed interesting catalytic reactivity and
selectivity comparable or even better than their bidentate ana-
logues in some reactions. Ligands such as 3 can also be used as host
molecules in the area of molecular recognition.
tris(thiazolines) 7a–d derived from a trimethyl nitrilotriacetate
scaffold. To the best of our knowledge, the preparation and cata-
lytic activity of C3 symmetric tris(thiazoline) ligand have not been
reported. Although several mono(thiazoline) and bis(thiazoline) li-
gands have been prepared and some methods for the construction
of the thiazoline ring have been developed, the already existing
methods may not be efficient in the synthesis of tris(thiazoline) li-
gands. Herein, we report the development of an efficient route for
the synthesis of tris(thiazoline) ligands and an investigation of
O
X
R
R
(CH2)m
(CH2)m
O
O
Ph
O
N
N
N
O
Ph
A
N
N
N
X
N
O
O
N
X
R
R
m(H2C)
m(H2C)
O
O
R
N
Ph
1 A = N or CH
R
3 X= H, Me
m = 0 or 1
2 m = 0 or 1
For further tuning of the coordination ability and the catalytic
activity, some chiral thiazoline ligands have been synthesized in
recent years. However, the application of chiral thiazoline ligands
in asymmetric catalysis is still limited. The investigations on the
comparison between thiazolines and oxazolines in asymmetric
catalysis were reported by Masson5 and Du.6 Thiazoline ligands
gave better results in some cases, while the corresponding oxazo-
line ligands were superior in others. These results prompt us to ex-
plore the synthesis of novel thiazoline ligands and their application
in asymmetric catalytic transformations.
their catalytic activity in the asymmetric allylic oxidation of
cycloalkenes.
2. Results and discussion
Trimethyl nitrilotriacetate 4, which was easily prepared from
commercially available nitrilotriacitic acid,2c was condensed with
chiral aminoalcohol at 80 °C for 72 h to furnish the corresponding
tris(b-hydroxyamide) 5a–d in good yields. With these intermedi-
ates in hand, we turned to the simultaneous thio-substitution
and dehydrative cyclization step. However, when 5a was treated
with phosphorus pentasulfide (P2S5) or Lawesson reagent (LR)
under various conditions, as described by Du
* Corresponding author. Tel.: +86 10 62732873; fax: +86 10 62732948.
E-mail address: fubinchem@cau.edu.cn (B. Fu).
6
and Molina,8
0957-4166/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2008.08.028

2160
X.-M. Cheng et al. / Tetrahedron: Asymmetry 19 (2008) 2159–2163
H
N
Cl
N
3
R
b
O
6
R
c
S
N
COOMe
COOMe
a. R = Ph
b. R = Bn
c. R = i-Pr
H
N
b
a
N
N
MeOOC
N
R
OH
N
S
d
S
. R = i-Bu
3
R
O
4
5
N
7
R
d
f
H
N
H
N
e
OTBDMS
OTBS
N
N
3
S
O
3
R
R
9
8
Scheme 1. Reagents and conditions: (a)
L-aminoalcohol, 80 °C; (b) P2S5, or LR, toluene, reflux; (c) SOCl2; (d) TBDMSCl, imidazole; (e) LR, benzene, (f) (i) TBAF, THF; (ii) MsCl,
TEA.
O
respectively, no desired product was formed. We also tried to
prepare 6a by treatment of 5a with SOCl2 and then cyclize with
P2S5 or Lawesson reagent following Nishio’s9 procedure, which
was successfully used in the cyclization of mono b-halogen substi-
tuted amides, but the tris(thiazoline) was not obtained.
O
Ph
( )n
oxidant
n( )
n = 1, 2
Cu(II)-Ligand
In view of these negative results, some modification must be
made for the route (Scheme 1). Since that the three hydroxyl
groups can interact with each other and make the reaction com-
plex, 5a was protected by use of TBDMSCl (3.50 equiv) under the
catalysis of imidazole, the hydroxyl-protected compound 8a was
obtained in 98% yield. When compound 8a was treated with
Lawesson’s reagent (1.6 equiv) in benzene, the tris(b-siloxythioa-
mide) 9a was afforded in 81% yield.10 After removing the TBDMS-
group by TBAF, the tris(b-hydroxythioamide) intermediate was di-
rectly cyclized by treating with MsCl/Et3N in CH2Cl2 at room tem-
perature. The desired tris(thiazoline) 7a was obtained in good yield
(88% for two steps). Other dehydrating reagents, such as Burgess
reagent11 and DAST,12 were also screened in this step; however
lower yields (41% and 64%, respectively) were obtained. Ligands
7b, 7c and 7d could also be synthesized following the same route
with comparable yields as listed in Table 1. In this synthetic route,
every step proceeded smoothly under mild conditions and gave
good to high yields.
With these new ligands in hand, we evaluated their catalytic
activity in the Cu(II) catalyzed allylic oxidation of cycloalkene
according to Katsuki’s procedure2 (Scheme 2). The asymmetric
allylic oxidation of olefins with peresters represents an efficient
methodology to prepare chiral allylic alcohols and their derivates,
which are useful building blocks in organic syntheses. The oxida-
tion reaction was performed in acetone by employing t-butyl perb-
enzoate as the oxidant and Cu(OTf)2-tris(thiazoline) complexes
Scheme 2.
7a–d (5 mol %) as the catalyst in the presence of 4 Å MS at room
temperature. The experimental results are outlined in Table 2.
Compound 7a showed the best enantioselectivity (77% ee) among
the four Cu(II)–ligand complexes, while 7b had no catalytic activity
(entry 2). Compounds 7c and 7d showed low catalytic activity (en-
tries 3 and 4). When other solvents were used in this catalytic reac-
tion, catalytic activity or enantioselectivity become lower (entries
5–8). Reducing the reaction temperature to 0 °C enhanced the
enantioselectivity, while the yield decreased dramatically even
after prolonged reaction time (entry 9, 81% ee and 17% yield).
These results were in accordance with Katsuki’s report.2 Next, un-
der the optimized conditions, we performed the allylic oxidation of
cyclohexene (entries 10–14), at room temperature four ligand–
Cu(II) complexes showed better catalytic activity (51–87% yield)
than that for cyclopentene; however the enantioselectivities were
very low (11–35% ee); when lowering the temperature to 0 °C the
ee’s value rose to a moderate level (44%), while the chemical yield
also dropped (68%).
In order to get a direct insight of the structure of new tris(thiaz-
oline) ligands, we obtained the single crystal of 7c from its solution
in hexane-ethyl acetate (v/v 7:3) and conducted X-ray crystal
diffraction analysis. The perspective view showed the typical
C3-symmetrical structure as illustrated in Figure 1.13 Due to the
presence of the three –CH2– units between the thiazoline cycle
and the central nitrogen atom, the molecular structure is flexible
to some extent. Although the distance between the three sulfur
atoms is smaller than that between the three nitrogen atoms on
the thiazoline ring, we believe it is more plausible that the three
nitrogen atoms coordinate to the Cu(II) in the catalyst structure.
We also attempted to prepare a single crystal of the Cu(OTf)2–
tris(thiazoline) 7c complex in order to understand the real
Table 1
The yields for the intermediates and tris(thiazoline) ligands
Entry
R
5 (%)
8 (%)
9 (%)
7 (%)
1
2
3
4
Ph
Bn
i-Pr
i-Bu
62
74
68
71
98
92
95
90
81
84
75
78
88
91
85
83

X.-M. Cheng et al. / Tetrahedron: Asymmetry 19 (2008) 2159–2163
2161
Table 2
Asymmetric catalytic allylic oxidation of cyclopentene or cyclohexenea
Entry
(CH2)n
Catalyst
Solvent
Temperature (°C)
Time (h)
Yieldb (%)
eec (%)
Config.d
1
2
3
4
5
6
7
8
9
10
11
12
13
14
1
1
1
1
1
1
1
1
1
2
2
2
2
2
7a
7b
7c
7d
7a
7a
7a
7a
7a
7a
7b
7c
7d
7a
Acetone
Acetone
Acetone
Acetone
(CH2Cl)2
CH2Cl2
25
25
25
25
25
25
25
25
0
25
25
25
25
0
72
72
72
72
72
72
96
72
96
72
72
72
72
72
43
0
77
—
(R)
—
10
12
28
20
0
25
17
87
51
71
66
68
23
17
55
32
—
17
81
35
22
14
11
44
(R)
(R)
(R)
(R)
—
(R)
(R)
(R)
(R)
(R)
(R)
(R)
AcOEt
CH3CN
Acetone
Acetone
Acetone
Acetone
Acetone
Acetone
a
All reactions were conducted with t-butyl perbenzoate as oxidant and ligand–Cu(OTf)2 (5 mol %) as catalyst in the presence of MS-4 Å.
Isolated yield by column chromatography.
b
c
Determined by HPLC (DAICEL CHIRACEL OD-H, n-hexane–i-PrOH = 99.9:0.1).
d
By comparison with the literature rotation.2
Figure 1. The molecular structure of compound (S)-7c from different side view.
structure of the active catalytic species. Unfortunately, no satisfac-
tory crystals were obtained under a variety of conditions.
(S)-cycloalkene ester were determined by HPLC analysis over a chi-
ral column (Daicel Chiralcel OD-H; eluted with hexane–isopropyl
alcohol; UV detector, 254 nm). The absolute configuration of the
major enantiomer was assigned according to the sign of the spe-
cific rotation. Solvents were purified and dried by standard
procedures.
3. Conclusion
In conclusion, novel C3-symmetric tris(thiazoline) ligands were
synthesized from trimethyl nitrilotriacetate and chiral amino alco-
hols in good yields, this route may act as a general method for the
preparation of complex thiazoline compounds. Their application in
the catalytic allylic oxidation of cycloalkene was examined. Com-
plex 7a–Cu(II) showed moderate to good asymmetric catalytic
activity and enantioselectivity. Further applications to extend the
scope of these catalysts are currently in progress in our laboratory.
4.1. N,N0,N00-Tris[(1S)-(2-hydroxy-1-phenylethyl-)]-
nitrilotriacetamide 5a
The procedure was performed according to Katsuki’s report.2c A
mixture of (S)-phenylglycinol and trimethyl nitrilotriacetate was
heated at 80 °C for 72 h. The mixture was purified by silica gel col-
umn chromatography (CH3OH/AcOEt = 4:6) to give 5a (62% yield).
In a similar procedure, 5b, 5c, and 5d were prepared from tri-
4. Experimental
methyl nitrilotriacetate and the corresponding L-amino alcohols.
Melting points were measured on an XT-4 melting point appa-
ratus and are uncorrected. NMR spectra were recorded with a Bru-
ker Avance DPX300 spectrometer with tetramethylsilane as the
internal standard. Infrared spectra were obtained on a Nicolet
AVATAR 330 FT-IR spectrometer.
Mass spectra were obtained on Bruker APEX II FT-ICRMS mass
spectrometer. Optical rotations were measured on a Perkin–Elmer
341 LC polarimeter. Elemental analyses were carried out on an Ele-
mentar Vario EL instrument. The enantiomeric excesses of (R)- and
4.1.1. N,N0,N00-Tris[(1S)-(2-TBDMSO-1-phenylethyl-)]-
nitrilotriacetamide 8a
To a solution of trihydroxy triamide 5a (1.37 g, 2.50 mmol) in
CH2Cl2 (15.0 mL) was added imidazole (0.61 g, 9.0 mmol) at 0 °C,
followed by TBDMSCl (1.20 g, 8.0 mmol). The mixture was stirred
at room temperature for 12 h, then filtered through sintered glass
to remove the salts after which brine was added. The organic
phase was separated and dried over anhydrous Na2SO4, filtered

2162
X.-M. Cheng et al. / Tetrahedron: Asymmetry 19 (2008) 2159–2163
and evaporated in vacuo. Purification by silica gel column chroma-
5.67–5.61 (m, 3H, CHNH), 3.90 (dd, J = 5.10, 10.20 Hz, 3H, CH2O),
3.83 (dd, J = 5.40, 10.50 Hz, 3H, CH2O) 3.65 (s, 6H, NCH2), 0.79 (s,
27H, C(CH3)3), 0.08 (s, 9H), 0.06 (s, 9H). 13C NMR (75 MHz): d
198.4, 137.9, 128.4, 127.7, 127.4, 65.0, 64.8, 60.6, 25.8, 18.1,
ꢁ5.5, ꢁ5.6. HRMS (ESI): m/z calcd for C48H79N4O3S3Si3 (M+H+):
939.46166; found: 939.46315.
tography (petroleum ether/AcOEt, 6:4) gave 8a (2.20 g, 98%) as a
colourless oil. ½a D25
¼ þ30:0 (c 0.50, CH2Cl2).
ꢀ
IR (cmꢁ1): 2929, 2953, 2856, 1653, 1541, 1471, 1254, 1122, 836,
777, 698. 1H NMR (CDCl3): d 7.53 (d, J = 8.1 Hz, 3H, NH), 7.37–7.29
(m, 15H, ArH), 5.17–5.10 (m, 3H, CHNH), 3.91–3.79 (m, 6H, CH2O),
3.47 (s, 6H, CH2N), 0.91 (s, 27H, C(CH3)3), 0.01 (s, 18H, Si(CH3)2).
13C NMR (75 MHz): d 169.8, 139.7, 128.2, 127.2, 126.9, 66.1, 58.9,
54.9, 25.7, 18.1, ꢁ5.65, ꢁ5.70. HRMS (ESI): m/z calcd for
C48H79N4O6Si3 (M+H+): 891.53019; found: 891.53093.
4.1.6. N,N0,N00-Tris[(1S)-(2-TBDMSO-1-benzylethyl-)]-
nitrilotri(thio-acetamide) 9b
Prepared according to the procedure mentioned in Section 4.1.5
starting from 8b (1.12 g, 1.20 mmol) and Lawesson’s reagent
(0.81 g, 2.0 mmol) in toluene (15.0 mL); pale oil, 0.98 g (84.0%).
4.1.2. N,N0,N00-Tris[(1S)-(2-TBDMSO-1-benzylethyl-)]-
nitrilotriacetamide 8b
Prepared according to the procedure mentioned in Section 4.1.1
starting from trihydroxy triamide 5b (1.48 g, 2.50 mmol), imidaz-
ole (0.61 g, 9.0 mmol) and TBDMSCl (1.20 g, 8.0 mmol); colourless
½
a 2D5
ꢀ
¼ þ103:0 (c 0.63, CH2Cl2). IR (cmꢁ1): 2953, 2927, 2856,
1524, 1470, 1113, 836, 813, 777, 699. 1H NMR (300 MHz, CDCl3):
d 8.80 (d, J = 8.40 Hz, 3H, NH), 7.28–7.17 (m, 15H, ArH), 4.89–
4.86 (m, 3H, CHNH), 3.66 (d, J = 3.90 Hz, 6H, CH2O) 3.40 (d,
J = 3.30 Hz, 6H, NCH2), 3.02 (d, J = 7.20 Hz, 6H, CH2Ph), 0.92 (s,
27H, C(CH3)3), 0.06 (s, 9H), 0.05 (s, 9H). 13C NMR (75 MHz): d
198.2, 137.4, 128.1, 128.3, 126.5, 64.6, 61.8, 57.7, 35.7, 25.9, 18.2,
ꢁ5.4. HRMS (ESI): m/z calcd for C51H85N4O3S3Si3 (M+H+):
981.50861; found: 981.51054.
oil, 2.14 g (92%). ½a D25
ꢀ
¼ þ74:4 (c 0.67, CH2Cl2). IR (cmꢁ1): 2953,
2928, 2857, 1654, 1537, 1253, 1116, 836, 776, 745, 699. 1H NMR
(300 MHz, CDCl3): d 7.28–7.14 (m, 15H, ArH), 6.82 (d, J = 9.0 Hz,
3H, NH), 4.27–4.19 (m, 3H, CHNH), 3.58 (dd, J = 3.6, 9.9 Hz, 3H,
CH2O), 3.53 (dd, J = 4.8, 9.9 Hz, 3H, CH2O), 3.00 (s, CH2, 6H,
NCH2), 2.95 (dd, J = 7.2, 13.5 Hz, 3H, one of CH2Ph), 2.77(dd,
J = 7.2, 13.5 Hz, 3H, one of CH2Ph), 0.92 (s, 27H), 0.06 (s, 27H),
0.05 (s, 18H). 13C NMR (75MHz): d 169.4, 138.0, 129.1, 128.1,
126.1, 63.3, 58.1, 51.7, 36.8, 25.7, 18.0, ꢁ5.6 HRMS (ESI): m/z calcd
for C51H85N4O6Si3 (M+H+): 933.57714; found: 933.57811.
4.1.7. N,N0,N00-Tris[(1S)-(2-TBDMSO-1-i-propylethyl-)]-
nitrilotri(thio-acetamide) 9c
Prepared according to the procedure mentioned in Section 4.1.5
starting from 8c (0.95 g, 1.20 mmol) and Lawesson’s reagent
(0.81 g, 2.0 mmol) in toluene (15.0 mL); pale oil, 0.75 g (75.3%).
4.1.3. N,N0,N00-Tris[(1S)-(2-TBDMSO-1-iso-propylethyl-)]-
nitrilotriacetamide 8c
Prepared according to the procedure mentioned in Section 4.1.1
starting from trihydroxy triamide 5c (1.12 g, 2.50 mmol), imidaz-
ole (9.0 mmol), TBDMSCl (1.20 g, 8.0 mmol); colourless oil, 1.87 g
½
a 2D5
ꢀ
¼ ꢁ105:0 (c 0.50, CH2Cl2). IR (cmꢁ1): 2957, 2928, 2856,
1525, 1463, 1411, 1389, 1256, 1103, 837, 802, 776. 1H NMR
(300 MHz, CDCl3): d 8.68 (d, J = 9.60 Hz, 3H, NH), 4.58–4.51 (m,
3H, CHNH), 3.67 (dd, J = 4.20, 10.20 Hz, 3H, CH2O), 3.69 (dd,
J = 5.10, 10.50 Hz, 3H, CH2O), 3.56 (s, 6H, NCH2), 2.17–2.08 (m,
3H, CHMe3), 1.01 (d, J = 6.60 Hz, 9H), 0.93 (d, J = 6.30 Hz, 9H),
0.88 (s, 27H, C(CH3)3), 0.06 (s, 9H), 0.05 (s, 9H). 13C NMR
(75 MHz): d 198.6, 65.2, 61.6, 60.3, 28.6, 25.9, 19.3, 19.0, 18.2,
ꢁ5.38, ꢁ5.43. HRMS (ESI): m/z calcd for C39H85N4O3S3Si3 (M+H+):
837.50861; found: 837.51043.
(95%). ½a 2D5
ꢀ
¼ ꢁ38:1 (c 1.50, CH2Cl2). IR (cmꢁ1): 2957, 2929, 2857,
1655, 1540, 1471, 1255, 1109, 937, 775. 1H NMR (300 MHz, CDCl3):
d 6.84–6.81 (d, J = 9.30 Hz, 3H, NH), 3.80–3.73 (m, 3H, CHNH), 3.62
(dd, J = 4.50, 9.90 Hz, 3H, CH2O), 3.25 (s, 6H, NCH2), 1.92–1.86 (m,
3H, CHMe2), 0.89 (d, J = 6.60 Hz, 9H), 0.84 (d, J = 6.60 Hz, 9H), 0.02
(s, 18H, SiMe2). 13C NMR (75 MHz): d 169.6, 62.7, 58.8, 55.5, 28.2,
25.7, 19.5, 18.1, 18.0, ꢁ5.6. HRMS (ESI): m/z calcd for C39H85N4O6-
Si3 (M+H+): 789.57714; found: 789.57875.
4.1.8. N,N0,N00-Tris[(1S)-(2-TBDMSO-1-i-butylethyl-)]-
nitrilotri(thio-acetamide) 9d
Prepared according to the procedure mentioned in Section 4.1.5
starting from 8d (1.05 g, 1.20 mmol) and Lawesson’s reagent
(0.81 g, 2.0 mmol) in toluene (15.0 mL); pale oil, 0.82 g (78.0%).
4.1.4. N,N0,N00-Tris[(1S)-(2-TBDMSO-1-iso-butylethyl-)]-
nitrilotriacetamide 8d
Prepared according to the procedure mentioned in Section 4.1.1
starting from trihydroxy triamide 5d (1.22 g, 2.50 mmol), imidaz-
ole (9.0 mmol), TBDMSCl (1.20 g, 8.0 mmol); colourless oil, 1.96 g
½
a 2D5
ꢀ
¼ ꢁ62:8 (c 1.0, CH2Cl2). IR (cmꢁ1): 2955, 2929, 2857, 1528,
1470, 1254, 1102, 836, 776. 1H NMR (300 MHz, CDCl3): d 8.78–
8.75 (d, J = 8.40 Hz, 3H, NH), 4.74–4.69 (m, 3H, CHNH), 3.74 (dd,
J = 3.90, 10.20 Hz, 3H, CH2O), 3.62 (dd, J = 5.10, 10.20 Hz, 3H,
CH2O), 3.54 (s, 6H, NCH2), 1.59–1.51 (m, 9H, CH2CH), 0.95 (d,
J = 3.30 Hz, 9H, CH3), 0.92 (d, J = 3.0 Hz, 9H, CH3), 0.89 (s, 27H,
C(CH3)3), 0.07 (s, 9H), 0.06 (s, 9H). 13C NMR (75 MHz): d 197.7,
64.9, 63.2, 54.9, 39.4, 25.8, 24.9, 22.8, 22.3, 18.0, ꢁ5.43, ꢁ5.46.
HRMS (ESI): m/z calcd for C42H91N4O3S3Si3 (M+H+): 879.55556;
found: 879.55738.
(90%). ½a 2D5
ꢀ
¼ ꢁ38:8 (c 1.0, CH2Cl2). IR (cmꢁ1): 2956, 2918, 2850,
1653, 1538, 1253, 1096, 837, 776. 1H NMR (300 MHz, CDCl3): d
6.77 (d, J = 8.7 Hz, 3H, NH), 4.10–4.00 (m, 3H, CHNH), 3.59 (dd,
J = 3.90, 9.90 Hz, 3H, CH2O), 3.52 (dd, J = 5.10, 10.20 Hz, 3H,
CH2O), 3.28 (s, 6H, NCH2), 1.57–1.25 (m, 9H, CH2CH), 0.91(t,
J = 3.90 Hz, 18H), 0.88 (s, 27H), 0.05 (s, 9H), 0.04 (s, 9H). 13C NMR
(75 MHz): d 169.4, 64.9, 58.9, 48.9, 40.4, 25.8, 24.8, 23.1, 22.2,
18.2, ꢁ5.5, ꢁ5.4. HRMS (ESI): m/z calcd for C45H97N4O6Si3
(M+H+): 873.67104; found: 873.67227.
4.1.9. Tri{[2-(4S)-(4-phenyl-1,3-thiazolinyl)] methyl} amine 7a
To a solution of 9a (0.938 g, 1.0 mmol) in THF (10 mL) was
added TBAF (1.0 M solution in THF; 3.5 mL, 3.5 mmol) at 0 °C,
The mixture was allowed to stir at room temperature overnight,
after which a saturated solution of ammonium chloride (20 mL)
was added. The aqueous layer was extracted CH2Cl2 (3 ꢂ 5 mL),
the combined organic extracts were washed twice with brine,
dried (MgSO4) and concentrated in vacuo. The residue obtained
was not further purified, and directly dissolved in a solution of
CH2Cl2 (15 mL) and Et3N (1 mL, 7.5 mmol), and cooled to 0 °C, MsCl
(0.35 g, 3.10 mmol) was added slowly. The mixture was allowed to
warm to room temperature and then stirred for 1.5 h. The mixture
4.1.5. N,N0,N00-Tris[(1S)-(2-TBDMSO-1-phenylethyl-)]-
nitrilotri(thio-acetamide) 9a
To a solution of 8a (1.07 g, 1.20 mmol) in benzene (15.0 mL)
was added Lawesson’s reagent (0.81 g, 2.0 mmol). The mixture
was refluxed for 4 h under N2, then the solvent was removed in va-
cuo. The residue was purified by silica gel column chromatography
(petroleum ether/EtOAc, 9:1) to afford 0.91 g (81%) 9a as a pale oil.
½
a 2D5
ꢀ
¼ þ35:6 (c 0.50, CH2Cl2). IR (cmꢁ1): 2954, 2928, 2856, 1521,
1463, 1408, 1255, 1113, 1006, 836, 777, 697. 1H NMR (300 MHz,
CDCl3): d 9.23 (d, J = 8.10 Hz, 3H, NH), 7.33–7.23 (m, 15H, ArH),

X.-M. Cheng et al. / Tetrahedron: Asymmetry 19 (2008) 2159–2163
2163
was washed with water (2 ꢂ 5 mL). The organic layer was dried
over anhydrous Na2SO4 and concentrated in vacuo to give the
crude product as yellow oil. Purification by silica gel column chro-
matography (petroleum ether/AcOEt, 1:1) afforded 7a (0.48 g, 88%)
was cooled to 0 °C, tert-butyl peroxybenzoate (42 mg, 0.22 mmol)
was added dropwise and the reaction mixture was stirred at
25 °C for 3 days. The mixture was passed through a short silica
gel column (petroleum ether/AcOEt = 9:1) to remove molecular
sieves and copper catalyst. The filtrate was concentrated and puri-
fied by column chromatography (petroleum/AcOEt = 99:1) to give
2-cyclopentenyl benzoate as an oil (17.7 mg, 43% yield). The enan-
tiomeric excess was determined by HPLC with a chiral column
(Daicel Chiralcel OD-H; eluent, hexane–iso-propyl alcohol 99.9:
0.1; flow rate 0.5 mL/min). In a similar procedure, 2-cyclohexenyl
benzoate was obtained.
as a colourless oil, ½a D25
ꢀ
¼ þ126:0 (c 0.25, CH2Cl2). IR (cmꢁ1): 3025,
2926, 2360, 1622, 1492, 1453, 1161, 1027, 825, 772. 1H NMR
(300 MHz, CDCl3): d 7.38–7.25 (m, 15H, ArH), 5.55 (t, J = 9.30 Hz,
3H, CHN@), 3.83 (dd, J = 15.30, 24.0 Hz, 6H, NCH2), 3.70 (dd,
J = 9.0, 12.0 Hz, 3H, one of CH2), 3.22 (t, J = 10.20, 10.50 Hz, 3H,
one of CH2). 13C NMR (75 MHz, CDCl3): d 171.3, 141.6, 128.5,
127.5, 126.4, 80.2, 56.3, 40.1. HRMS (ESI): calcd for C30H30N4S3H
(MH+): 543.1705; found: 543.1693.
Acknowledgements
4.1.10. Tri{[2-(4S)-(4-benzyl-1,3-thiazolinyl)] methyl} amine 7b
Prepared according to the procedure mentioned in Section 4.1.9
starting from 9b; white solid, 0.53 g (91.0%). Compound 7b: Mp
We are grateful to the National Natural Science Foundation
(Grant No. 20772151) and China Agricultural University for finan-
cial support. We thank Professor Da-ming Du for his valuable dis-
cussion and modifications of the manuscript, Tongling Liang is
gratefully acknowledged for her careful determination of the X-
ray crystal diffraction analysis.
82–84 °C, ½a 2D5
ꢀ
¼ þ120:0 (c 0.30, CH2Cl2). IR (cmꢁ1): 3025, 2921,
1622, 1495, 1453, 1166, 1030, 742. 1H NMR (300 MHz, CDCl3): d
7.32–7.19 (m, 15H, ArH), 4.81–4.71 (m, 3H, CHN@), 3.58 (dd,
J = 15.60, 18.10 Hz, 6H, CH2N), 3.22–3.13 (m, 6H, one of CH2S and
one of CH2Ph), 3.00 (dd, J = 7.20, 10.80 Hz, 3H, one of CH2S), 2.75
(dd, J = 9.00, 10.50 Hz, one of CH2Ph). 13C NMR (75 MHz, CDCl3):
d 170.1, 138.2, 129.2, 128.4, 126.4, 78.0, 56.0, 40.3, 36.3. Elemental
Anal. Calcd for C33H36N4S3: C, 67.77; H, 6.20; N, 9.58. Found: C,
67.81; H, 6.36; N 9.51.
References
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Kohmura, Y.; Katsuki, T. Synlett 1999, 1231–1234; (c) Kawasaki, K.; Katsuki,
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41, 3473–3475.
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(c) Kim, H. J.; Moon, D.; Lah, M. S.; Hong, J. I. Angew. Chem., Int. Ed. 2002, 41,
3174–3177; (d) Kim, H. J.; Kim, Y. H.; Hong, J. I. Tetrahedron Lett. 2001, 42,
5049–5052; (e) Kim, S.-G.; Kim, K.-H.; Jung, J.; Shin, S. K.; Ann, K. H. J. Am. Chem.
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H. J. Am. Chem. Soc. 2003, 125, 13819–13824.
5. (a) LeMaux, P.; Abrunhosa, I.; Berchel, M.; Simonneaux, G.; Gulea, M.; Masson,
S. Tetrahedron: Asymmetry 2004, 15, 2569–2573; (b) Abrunhosa, I.; Gulea, M.;
Delain-Bioton, L.; Gaumont, A.-C.; Masson, S. Tetrahedron: Asymmetry 2004, 60,
9263–9272; (c) Abrunhosa, I.; Gulea, M.; Levillain, J.; Masson, S. Tetrahedron:
Asymmetry 2001, 12, 2851–2859.
4.1.11. Tri{[2-(4S)-(4-iso-propyl-1,3-thiazolinyl)] methyl}
amine 7c
Prepared according to the procedure mentioned in Section 4.1.9
starting from 9c; white solid, 0.37 g (85.1%).
Compound 7c: Mp 94–95.5 °C, ½a D25
¼ ꢁ65:0 (c 0.30, CH2Cl2). IR
ꢀ
(cmꢁ1): 2956, 2872, 1526, 1466, 1436, 1364, 1257, 1164, 967, 952.
1H NMR (CDCl3): d 4.28–4.25 (m, 3H, CHN@), 3.56 (dd, J = 1.50,
3.60 Hz, 6H, CH2N), 3.25 (dd, J = 4.50, 10.20 Hz, 3H, one of CH2S),
2.98 (dd, J = 9.60, 10.80 Hz, 3H, one of CH2S), 2.00 (m, 3H, CHMe2),
1.03 (d, J = 6.60 Hz, 9H, CH3), 0.95 (d, J = 4.50 Hz, 9H, CH3). 13C NMR
(75 MHz, CDCl3): d 169.3, 83.5, 56.2, 34.3, 32.9, 19.6, 18.8. Elemen-
tal Anal. Calcd for C21H36N4S3: C, 57.23; H, 8.23; N, 12.71. Found: C,
57.35; H, 8.41; N, 12.74.
6. (a) Liu, H.; Xu, J. X.; Du, D. M. Org. Lett. 2007, 9, 4725–4728; (b) Lu, Sh.-F.; Du,
D.-M.; Xu, J.-X.; Zhang, Sh. W. J. Am. Chem. Soc. 2006, 128, 7418–7419.
7. (a) Gibson, S. E.; Castaldi, M. P. Angew. Chem., Int. Ed. 2006, 45, 4718–4720; (b)
Mosberg, C. Angew. Chem., Int. Ed. 2006, 45, 4721–4723; (c) Zhou, J.; Tang, Y.
Chem. Soc. Rev. 2005, 34, 664.
4.1.12. Tri{[2-(4S)-(4-i-butyl-1,3-thiazolinyl)] methyl} amine 7d
Prepared according to the procedure mentioned in Section 4.1.9
starting from 9c; white solid, 0.40 g (83.0%). Compound 7d: Mp.
84–85.5 °C, ½a 2D5
ꢀ
¼ ꢁ95:0 (c 0.20, CH2Cl2). IR (cmꢁ1): 2954, 2925,
8. Tarrage, A.; Molina, P.; Curiel, D.; Bautista, D. Tetrahedron: Asymmetry 2002, 13,
1621–1628.
2868, 1625, 1467, 1436, 1366, 1169, 832. 1H NMR (CDCl3): d
4.51–4.46 (m, 3H, CHN@), 3.53 (s, 6H, CH2N), 3.34 (dd, J = 8.10,
10.50 Hz, 3H, one of CH2S), 2.88 (dd, J = 8.40, 10.80 Hz, 3H, one of
CH2S), 1.81–1.65 (m, 6H, CH2), 1.43–1.33 (m, 3H, CHMe2), 0.98
(d, J = 3.00 Hz, 9H, CH3), 0.93 (d, J = 3.60 Hz, 9H, CH3). 13C NMR
(75MHz, CDCl3): d 169.1, 75.5, 56.2, 44.2, 37.1, 25.7, 22.8, 22.5. Ele-
mental Anal. Calcd for C24H42N4S3: C, 59.70; H, 8.77; N, 11.60.
Found: C, 59.92; H, 8.90; N, 11.51.
9. Kodama, Y.; Ori, M.; Nishio, T. Helv. Chim. Acta 2005, 88, 187–193.
10. (a) Markovic, R.; Baranac, M.; Jovetic, S. Tetrahedron Lett. 2003, 44, 7087–7090;
(b) Soukara, S.; Wunschh, B. Tetrahedron Lett. 2001, 57, 4359–4363.
11. (a) Wagner, S.; Schumann, D.; Linne, U.; Koert, U.; Marahiel, M. A. J. Am. Chem.
Soc. 2006, 128, 10513; (b) Nicolaou, K. C.; Kim, D. W.; Schlawe, D.; Lizos, D. E.;
de Noronha, R. G.; Longbottom, D. A. Angew. Chem., Int. Ed. 2005, 44, 4925–
4929; (c) McKeever, B.; Pattenden, G. Tetrahedron 2003, 59, 2701–2712.
12. (a) McKeever, B.; Pattenden, G. Tetrahedron 2003, 59, 2713–2727; (b)
Zarantonello, P.; Leslie, C. P.; Ferritto, R.; Kazmierski, W. M. Bioorg. Med.
Chem. Lett. 2002, 12, 561–565.
13. Crystal data for (S)-7c: C21H36N4S3–H2O, M = 458.73, Hexagonal, space group
P6(3)c, a = 15.568(2) Å, b = 15.568(2) Å, c = 6.3100(13) Å,
a = b = 90°, c = 120°,
4.2. Typical procedure for the asymmetric allylic oxidation of
cyclopentene and cyclohexene
V = 1324.4(4) Å3, Z = 2, D = 1.150 mg/m3, Mo K
a (k = 0.71073 Å), T = 173(2) K,
l
= 0.298 mmꢁ1, crystal size (mm) 0.38 ꢂ 0.38 ꢂ 0.31 mm. Area detector data
collected on a Rigaka axis rapid IP diffractometer. A total of 1999 reflections
were collected (2.62 < h < 27.46). Structure solution by direct method (SHELXS
-
A mixture of Cu(OTf)2 (4.0 mg, 11
lmol) was stirred in dry CH2Cl2 (0.5 mL) under nitrogen for 1 h.
The above solution was added to another flask containing acetone
(0.40 mL) and cyclopentene (60 mg, 0.88 mmol) and molecular
sieves 4 Å (85 mg). After being stirred for 30 min, the mixture
lmol) and ligand 5a (8.2 mg,
97), refinement by full-matrix least-squares using all reflections, R1 = 0.0638,
wR2 = 0.1057, GOF = 1.002. Crystallographic Data Centre as supplementary
publication number CCDC 683616. Copies of the data can be obtained, free of
charge, on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK. Fax:
+44 1223 336033 or e-mail: deposit@ccdc.cam.ac.uk.
17