Chiral bisoxazoline ligands with a biphenyl backbone: Development and application in catalytic asymmetric allylic oxidation of cycloolefins

Article abstract of DOI:10.1016/j.tetasy.2013.01.013

A simple and efficient method for the synthesis of chiral biphenylbisoxazoline ligands was developed. The bishydroxylamide precursors of ligands showed a dynamic atropselective resolution effect in the crystallization process. When biphenylbisoxazoline ligands were coordinated to tetrakis(acetonitrile)copper(I) hexafluorophosphate, it resulted in the formation of only a single diastereomer complex (S,aS,S), which behaved as a catalyst for the enantioselective allylic oxidation of cycloolefins. The enantioselectivity, yield, and rate of this reaction were optimized under different conditions, such as a change of solvents, temperature, and additives and also using various copper salts. The use of SBA-15 mesoporous silica as an additive played a crucial role in increasing the efficiency of the reaction.

Full text of DOI:10.1016/j.tetasy.2013.01.013

Tetrahedron: Asymmetry 24 (2013) 269–277
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Tetrahedron: Asymmetry
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Chiral bisoxazoline ligands with a biphenyl backbone: development and
application in catalytic asymmetric allylic oxidation of cycloolefins
⇑
Saadi Samadi, Khosrow Jadidi , Behrouz Notash
Department of Chemistry, Shahid Beheshti University, G.C. Tehran 1983963113, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
A simple and efficient method for the synthesis of chiral biphenylbisoxazoline ligands was developed.
The bishydroxylamide precursors of ligands showed a dynamic atropselective resolution effect in the
crystallization process. When biphenylbisoxazoline ligands were coordinated to tetrakis(acetoni-
trile)copper(I) hexafluorophosphate, it resulted in the formation of only a single diastereomer complex
(S,aS,S), which behaved as a catalyst for the enantioselective allylic oxidation of cycloolefins. The enanti-
oselectivity, yield, and rate of this reaction were optimized under different conditions, such as a change of
solvents, temperature, and additives and also using various copper salts. The use of SBA-15 mesoporous
silica as an additive played a crucial role in increasing the efficiency of the reaction.
Received 7 December 2012
Accepted 17 January 2013
Available online 27 February 2013
Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction
tion of cycloolefins was examined. It is noteworthy to mention that
in the presence of SBA-15 mesoporous silica, as the additive, only
The enantioselective allylic oxidation of olefins using chiral cop-
per complexes has been the subject of great interest over the last
decade. This reaction provides access to chiral allylic alcohols,
which are key intermediates in natural product synthesis.1
A literature survey shows that chiral C2-symmetric bisoxazo-
lines (box’s) are one of the most effective and popular classes of
chiral ligands studied for copper-catalyzed allylic oxidations, and
their application has made a major breakthrough with drastic
improvements in enantioselectivity and yield.2 However, all of
the reported allylic oxidations suffer from at least one disadvan-
tage in terms of long reaction times, unsatisfactory yields, or
enantioselectivities.1f–n Ikeda et al. in 2000 reported on a new class
of atropisomeric chiral biphenylbisoxazoline ligands for the cata-
lytic asymmetric cyclopropanation.3 These ligands exist as a mix-
ture of two diastereomers in equilibrium in solution. However,
when these ligands were coordinated to a copper(I) ion, only one
of the two possible complexes was formed. This feature of the
biphenylbisoxazolines encouraged us to develop a new method
for the synthesis of a series of them through an efficient, high
yielding, and inexpensive procedure, and for the first time apply
them to the catalytic enantioselective allylic oxidation of
cycloolefins.
one enantiomer of the allylic benzoates was obtained with up to
95% ee and up to 99% yield in a reasonably short period of time.
Although two rotatory diastereomers of ligand 1 exist in equi-
librium in solution, the dynamic atropselective resolution effect
in biphenylbisoxazolines 1 was not confirmed. However, the bishy-
droxylamide precursor of ligands 5 showed this effect in the crys-
tallization process.4
2. Results and discussion
The synthesis of chiral biphenyl bisoxazoline ligands 1 was
accomplished in excellent yields and enantiomeric excess from
the inexpensive starting material anthranilic acid 2 (Scheme 1).
Diazotization of anthranilic acid 2 followed by homo-coupling of
aryldiazonium salts in the presence of Cu(I) as the reducing agent
led to symmetrical biphenyl diacid 3 with high yields.5 Diacid 3
was exposed to oxalyl chloride in the presence of a catalytic
amount of DMF and converted into the diacid chloride.1l,m,2 Treat-
ment of the diacid chloride with four individual (S)-amino alcohols
4a–d resulted in the formation of (S,aS,S) and (S,aR,S)-bishy-
droxylamides 5a–d.
In order to achieve the most efficient procedure for the synthe-
sis of the desired ligand 1, we were required to find a useful meth-
od for cyclization of the bishydroxylamide precursor 5. To fulfill
this requirement, three different activating agents were employed
to promote this process (Scheme 1). The first method (a) consists of
transforming bishydroxylamide 5 into its corresponding dichloride
and further cyclization to the box under basic conditions.2e,g,6
Treatment of bishydroxylamide precursor 5 with Ph3P/CCl4/Et3N
It is well known that additives are useful for achieving opti-
mized conditions in allylic oxidation reactions.1f,h,k In this context,
the effect of numerous additives in conjunction with the copper–
biphenylbisoxazoline complexes on the asymmetric allylic oxida-
⇑
Corresponding author. Tel.: +98 2122431661.
E-mail address: k-jadidi@sbu.ac.ir (K. Jadidi).
0957-4166/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetasy.2013.01.013

270
S. Samadi et al. / Tetrahedron: Asymmetry 24 (2013) 269–277
R
R
HN (S)
O
(S)
HN
1. (COCl)2,CH2Cl2,
CO2H
CO2H
DMF (3 drops), 0 °C
O
O
HO
HO
HO
HO
1.NaNO2, HCl, 0 °C
2. CuSO4, NH4OH
NH2
O
CO2H
2. CH2Cl2, NEt3, 0 °C
R
OH
(S)
HN
(S)
HN
R
R
2
H2N
3 (95%)
(S,R,S)
(S,S,S)
4
(Not seperated)
(Method a)
5 (90%)
(Method b)
(45-75%)
(One-pot)
(Method c)
(85-95%)
(85-96%)
(75-90%)
O
O
(S)
(S)
R
N
R
R
N
N
(S)
N
(S)
R
O
O
(S,S,S)
(S,R,S)
1 (R= a: Ph, b: Bn, c: i-Pr, d: i-Bu)
Scheme 1. Synthesis of chiral biphenyl bisoxazoline ligands 1a–d.
afforded the desired ligands in only 45–60% yields (Method b).1t,2e,g
In the third method (c), biphenyl bisoxazoline ligand 1 was pre-
pared by stirring overnight the mixture of bishydroxylamide 5 in
the presence of p-TsCl, DMAP, and Et3N at room temperature.
The convenience of this procedure and the high yield obtained
(>85%) were important features of this cyclization method. By
using activated agents for the cyclization in method c, we managed
to prepare ligand 1 in a one-pot synthesis through the modification
and combination of two final steps of the reaction (Scheme 1). In
general, the reaction via this easy-to-handle method occurred
slightly faster and gave products in higher yields than the other
methods.7
bonding of the molecules of the (S,aS,S)-isomer. Despite an inten-
sive effort, the growth of suitable crystals of ligands 1 for single-
crystal analysis was not successful to confirm the transformation
effect in the ligands.
The copper complexation behavior of these ligands with CuPF6
in chloroform-d was then examined. The 1H NMR spectrum
showed the formation of only one diastereomeric complex. For
example, the 1H NMR spectrum of 1b consisted of two doublet of
doublets at d = 2.95–3.02 (J = 5.2 and 13.6 Hz) with an intensity ra-
tio of 70:30 in the absence of the copper salt; but when this ligand
was coordinated with copper(I) hexafluorophosphate only one of
the diastereomeric complexes was formed with a doublet of dou-
blets at d = 2.76–2.83 (J = 13.6, 5.4 Hz).
As expected, the 1H NMR spectrum of precursor 5 and ligand 1
clearly showed the presence of two rotatory diastereomers and the
ratio of two sets of signals for each pair changed at different tem-
peratures. However, the two atropisomers were not chromato-
graphically separable but the interconversion of the two rotatory
diastereomers was slow enough to be detected by NMR.3,8
The conformational equilibrium between atropisomers 5 and 1
was used to perform a dynamic atropselective resolution in order
to obtain them as pure single crystalline compounds. It is notewor-
thy that crystallization of the precursor mixture 5 led to only one
rotameric diastereoisomer without co-precipitation of the other
diastereomer from the mother liquor. In order to confirm the dy-
namic atropselective resolution effect and to represent the confor-
mational equilibrium between these atropisomers, the single-
crystal X-ray analysis of various samples of 5d was investigated.
We observed that the absolute configuration of this precursor
was (S,aS,S) in all cases and that all of the molecules in the unit cell
have the same sense of chirality at the stereogenic aryl–aryl bond
(Fig. 1). Since the crystallization was accomplished with higher
than 95% yield, the process can be considered to be a crystalliza-
tion-induced asymmetric transportation.4 The shift of the equilib-
rium is most probably controlled by the (more) efficient hydrogen
The configuration of the complex generated was assigned as
(S,aS,S), utilizing a Nuclear Overhauser Effect (NOE) similar to Ike-
da’s analysis procedure.3
Encouraged by this efficient protocol for the synthesis and cop-
per complexation of ligands 1a–d and in order to demonstrate the
new potential of these ligands, their application was investigated
in the copper-catalyzed allylic oxidations of cycloolefins
(Scheme 2). In a typical experimental procedure, the reactions
were carried out by using cyclohexene as the substrate in the pres-
ence of various ligands 1a–d (10 mol %) and [Cu(CH3CN)4]PF6
(10 mol %) as the catalyst at different temperatures in acetonitrile.
The reactions were monitored by TLC for consumption of the
perester and stopped at the given time. Our results are summa-
rized in Table 1. The yields and enantiomeric ratios of the products
showed the temperature dependence of this process. A decrease in
the reaction temperature from ꢀ10 to ꢀ20 °C did not give a favor-
able ee% and greatly decreased the reaction yield; the enantiose-
lectivity also dropped dramatically when the temperature was
increased from ꢀ10 to 40 °C (entries 1–6).
It can also be seen in Table 1 and Figure 2 that the type of
R group on the oxazoline substituent has a great effect on the

S. Samadi et al. / Tetrahedron: Asymmetry 24 (2013) 269–277
271
Figure 1. Two views of the ORTEP diagram of bishydroxylamide precursor 5d. Thermal ellipsoids are at 30% probability level.
O
O
O
(S)
(S)
R
R
R
R
N
N
N
O
O
Ar
(S)
N
Cu
CuPF6(CH3CN)4
N
(S)
O
N
t
(S)
p-NO2-PhCO3 Bu
R
R
(S)
(S)
O
O
(p-NO2-Ph= Ar)
(S,S,S)-Cu(I)
(S,S,S)
(S,R,S)
Yield = 100%
a
b
c
d
R: = Ph, = Bn, = i-Pr, = i-Bu
Scheme 2. Asymmetric allylic oxidation of cyclohexene with chiral ligands 1.
Table 1
and molecular sieves (MS) in order to achieve the best reaction
conditions for the asymmetric allylic oxidation of cyclohexene. A
series of results are presented in Table 2. It was observed that
the reaction rate, yield, and ee of the products were generally im-
proved when molecular sieves were used as an additive (entry 2
versus entry1). When using phenyl hydrazine as an additive, the
enantioselectivity and yield only slightly increased but the reaction
rate improved remarkably (entry 3 versus entry 1). Encouraged by
these results, we performed the reaction in the presence of phenyl
hydrazine and MS simultaneously, and the reaction rate, yield, and
ee values of the products 6 were markedly improved (entry 4). In
order to determine the influence of other peresters on the effi-
ciency of this reaction, phenyl tert-butyl and p-methoxyphenyl
tert-butyl peresters were also used. However, the isolated yield
and ee% in comparison to p-nitrophenyl tert-butyl perester de-
creased (entry 4 vs 5–6).
Effect of catalyst on the reaction at different temperatures
O2CPhNO2-p
t
p-NO2-PhCO3 Bu
1a-d, CuPF6 (10mol%)
(S)
CH3CN (4ml), t (°C)
PhNHNH2 (6µL), MS (10mg)
6
Entry
Catalyst
Temperature (°C)
Time (h)
Yield (%)
ee (%)
1
2
3
4
5
6
7
8
9
1a
1a
1a
1a
1a
1a
1b
1c
1d
40
25
10
1.5
3.5
24
85
90
88
76
77
70
77
65
70
35
45
51
55
62
64
75
23
23
0
82
ꢀ10
ꢀ20
ꢀ10
ꢀ10
ꢀ10
195
292
185
195
186
The effect of Cu salts was also investigated. In all cases, CuPF6
proved to be the best copper source while other Cu salts such as
Cu(OTf)2, Cu(OAc)2, CuCl, and CuI led to a decrease in the ee by
12–38% and longer reaction times (entry 4 vs 7–11).
The application of phenylhydrazine was necessary when
Cu(OTf)2 was used in the reaction because in this case, the Cu(I)
complex that formed in situ, accelerates the oxidation reaction
(compare entry 5 and entry 10). It should be noted that when
CuOTf was used as the Cu(I) source, it resulted in better values in
isolated yield, reactivity, and ee% than the combination of Cu(OTf)2
and phenylhydrazine under similar conditions (compare entry 7
and entry 13).
enantioselectivity of the process. The phenyl or benzyl substituted
oxazolines 1a and 1b resulted in considerably higher enantioselec-
tivities in comparison with the other two ligands 1c and 1d carry-
ing alkyl substitutions (entries
6
and 10). The highest
enantioselectivities and yields were achieved by employing ligand
1b at ꢀ10 °C (entry 7).
There is a gap of efficiency between these two types of ligands
with regard to the ee% of this reaction as illustrated in Figure 2.
Considering ligand 1b as the best ligand, we next focused our
attention on the effects of solvent, copper salts, phenylhydrazine,1j
Three different solvents were examined under various condi-
tions and the best results were obtained in MeCN (entry 4 vs en-
tries 14–15).

272
S. Samadi et al. / Tetrahedron: Asymmetry 24 (2013) 269–277
Figure 2. Dependency of ee values on ligand structure at different temperatures.
Table 2
Table 3
Effect of solvents, additives, and counter anions on the reaction
Effects of catalyst loading on the reaction
O2CPhNO2-p
O2CPhNO2-p
t
t
p-NO2-PhCO3 Bu
p-NO2-PhCO3 Bu
1b, CuPF6
1b, CuX (10mol%)
(S)
(S)
CH3CN (4ml) ,-10 °C
CH3CN (4ml), -10°C
PhNHNH2 (6µL), MS (10mg)
PhNHNH2 (6µL), MS (10mg)
6
6
Entry
Cu salt (10 mol %)
Solvent
Time (h)
Yield (%)
ee (%)
Entry
Catalyst (mol %)
Time (h)
Yield (%)
ee (%)
1a
2b
3c
CuPF6
CuPF6
CuPF6
CuPF6
CuPF6
CuPF6
Cu(OTf)2
CuOTf
Cu(OAc)2
CuCl
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
Acetone
CH2Cl2
370
340
210
185
172
165
390
215
370
440
215
425
350
240
450
60
74
65
77
52
45
60
85
65
48
54
45
69
80
52
40
55
45
75
59
56
38
62
28
19
21
24
48
61
33
1
2
3
4
5
6
1
2.5
5
10
15
20
500
335
295
185
250
210
25
36
50
77
54
45
20
24
38
75
62
56
4
5d
6e
7
8
9
10
11
12b
13b
14
15
Table 4
CuI
Effects of additive on the reaction
Cu(OTf)2
CuOTf
CuPF6
CuPF6
O2CPhNO2-p
t
p-NO2-PhCO3 Bu
1b, CuPF6 (10mol%)
(S)
a
b
c
In the absence of any additives.
In the presence of MS only.
In the presence of PhNHNH2 only.
With phenyl tert-butyl perester.
With p-methoxyphenyl tert-butyl perester.
CH3CN (4ml), -10 °C
PhNHNH2 (6µL), additive
d
e
6
Entry
Additive
Time (h)
Yield (%)
ee (%)
The effects of catalyst loading were also investigated. The re-
1
2
3
4
5
6
7
8
9
MS (10 mg)
185
225
70
89
92
115
82
85
77
60
99
95
90
85
85
80
90
75
55
81
79
60
60
65
71
71
sults which described in Table 3 indicated that the enantioselectiv-
ity, the reactivity, and the yield were influenced by the amount of
catalyst. The best results were obtained when 10% catalyst loading
was used. Lowering the catalyst loading to less than 10 mol % or
increasing it to 20 mol % led to a sharp decrease in the results
(Table 3).
Activated silica gel (10 mg)
SBA-15 (10 mg)
SBA-15 (5 mg)
SBA-15 (2.5 mg)
MCM-41(10 mg)
MgO (10 mg)
TiO2 (10 mg)
CuO (10 mg)
68
Although the use of molecular sieves gave cyclohex-2-enyl ben-
zoate 6 in good yield and enantioselectivity, a longer reaction time
was required (entry 1, Table 4). Therefore, further optimization of
the reaction conditions could be achieved by exploring the effect of
numerous additives on this reaction. For this purpose, we prepared
and examined the activated silica gel,9 mesoporous MCM-4110 and
(entries 3–9). When we performed the reaction in the presence
of SBA-15 as an additive (10 mg/mmol), the enantioselectivity of
the reaction improved up to 81% and the reaction was complete
in only 70 h and provided chiral allylic ester 6 in quantitative yield
(entry 3). Lowering the amount of this mesoporous to 2.5 mg/
mmol slightly reduced the yield and reactivity but greatly de-
creased the ee to 60% (compare entry 5 with entry 3). However,
a further increase in the amount of SBA-15 did not lead to any ob-
servable changes in the results of the reaction.
SBA-1511 silica, nanocrystalline MgO,12 CuO,13 and TiO2 as addi-
14
tives in the asymmetric allylic oxidation of cycloolefins in which
some of them (MgO and CuO) have been successfully used in other
asymmetric transformations.15 The results are shown in Table 4
and it can be seen that the reaction in the presence of these nano-
particles is generally faster than in the case of molecular sieves

S. Samadi et al. / Tetrahedron: Asymmetry 24 (2013) 269–277
273
Table 5
Additive effect on other cycloolefins
O2CPhNO2-p
(S)
O2CPhNO2-p
t
p-NO2-PhCO3 Bu
1b, CuPF6 (10mol%)
n
(S)
n
CH3CN (4ml), -10 °C
PhNHNH2 (6µL), additive
n=1
7: n=1
8: n=3
n=3
n=4
9: n=4
10
1,5-COD
Entry
Additive (mg)
7
8
9
10
Time (h)
Yield (%)
ee (%)
Time (h)
Yield (%)
ee (%)
Time (h)
Yield (%)
ee (%)
Time (h)
Yield (%)
ee (%)
1
2
3
4
5
6
SBA-15 (10)
Activated silica gel (10)
MCM-41 (10)
MgO (2.5)
TiO2 (10)
CuO (10)
80
200
115
90
90
79
99
64
80
85
80
80
75
52
63
70
71
64
92
221
123
86
97
76
87
67
87
82
76
75
70
52
60
67
68
63
109
265
140
103
123
84
85
54
60
55
45
74
72
44
68
54
60
64
70
194
95
76
82
99
62
95
99
99
99
95
58
85
78
71
78
66
Mesoporous MCM-41 silica exhibited higher yields and reactiv-
ity, yet the enantioselectivity dropped considerably in contrast to
MS (compare entry 6 with entry 1). It was also found that utilizing
metal oxides as additives, resulted in comparable enantioselectiv-
ity with higher rates and better yields in comparison with MS (en-
tries 7–9).
The effect of these additives on the allylic oxidation of cyclohex-
ene encouraged us to examine this effect on other substrates. We
extended the reaction to several cycloolefins and in all cases, allylic
esters 7–10 were also obtained in high yields and ees; the best re-
sults were achieved in the presence of SBA-15 (10 mg) (Table 5).
In the case of 1,5-cyclooctadiene in the presence of this meso-
porous silica, the reaction proceeded at a much higher rate in
quantitative yield and highest enantiomeric excess (95%) com-
pared with other cycloolefins.
The SBA-15 was reused in all cases at least three times without
a significant loss of efficiency. The XRD, SEM, and IR results clearly
demonstrated that the mesoporous structure of SBA-15 was pre-
served after reuse for the three times. In order to evaluate the
importance of the nanoparticle systems, we carried out the reac-
tion with activated silica gel (amorphous system) under the similar
conditions. As the results show in Tables 4 and 5, a drastic decrease
in values was observed in terms of yields and enantioselectivities
and reactivities.
These results showed that nanoparticles most probably have a
participatory role in the reaction; it is most likely that the hydroxyl
groups on the surface of the nanoparticles coordinate to the metal
center of the copper(I)-biphenyl bisoxazoline catalyst in general
and SBA-15 in particular. These experimental results demonstrate
the important aspect of nanoparticles in asymmetric chemistry.
However, further experimental study is required in order to exam-
ine the effect of particle size and type of additive on the results of
the reaction, and also computational calculations for proposing a
proper mechanism for the reaction is needed. These investigations
are currently in progress in our laboratory.
the allylic benzoates was obtained with up to 95% ee and up to
99% yield. A new and very important aspect of SBA-15 mesoporous
silica with regard to improving the yields, ees, and rates of the
reaction was discovered. Further efforts to extend the utility of
the nanoparticles in conjunction with the chiral bisoxazoline li-
gands in other enantioselective reactions are currently underway
in our laboratory.
4. Experimental
4.1. General
Melting points were measured on an Electrothermal 9100 appa-
ratus and are uncorrected. Optical rotations were measured with a
Perkin–Elmer 341 polarimeter at 589 nm. 1H and 13C NMR spectra
were recorded on a BRUKER DRX-300 AVANCE spectrometer at
300.13 and 75.47 MHz, 100 MHz in CDCl3, and DMSO-d6 using
TMS (d = 0.0 ppm) as internal standard. IR spectra were recorded
on a Bomen FT-IR-MB-series instrument. Enantiomeric excess
(ee) of the allylic esters 6–10 were determined by HPLC analysis
using an EC 250/4.6 Nucleocel Alpha S column. All reactions were
performed under an atmosphere of dry, oxygen-free nitrogen. All
reagents and starting materials were purchased from Aldrich,
Merck, and Fluka. Olefins were distilled from calcium hydride be-
fore use. All solvents were of reagent grade and were dried and dis-
tilled immediately before use as follows: acetonitrile and acetone
from P2O5, methylene chloride from calcium hydride. Column
chromatography was performed using silica gel 60 (230–400
mesh) eluting with ethyl acetate/n-hexane. TLC was performed
using silica gel 60 F256 plates with visualization by UV.
4.1.1. [1,10-Biphenyl]-2,20-dicarboxylic acid 35
Light yellow powder; (95%); mp 220–224 °C; 1H NMR
(300 MHz, DMSO-d6) dH(ppm) = 7.13–7.15 (m, 2H), 7.42–7.44 (m,
2H), 7.51–7.53 (m, 2H), 7.86–7.89 (m, 2H), 12.21–12.43 (br s OH,
2H). 13C NMR (75 MHz, DMSO-d6): dC(ppm) = 127.2, 127.8, 130.9,
133.3, 136.5, 141.1, 168.7; IR (KBr, cmꢀ1): 1688, 3071.
3. Conclusion
In conclusion, we have developed an efficient and simple meth-
od for the preparation of chiral biphenyl bisoxazoline ligands 1a–d
from an inexpensive starting material, anthranilic acid 2. The cata-
lytic potential of these ligands for the copper-catalyzed allylic oxi-
dations of cycloolefins was investigated utilizing numerous nano-
sized additives. With the optimization of the reaction conditions
in the presence of SBA-15 and with ligand 1b, the reaction took
place in a reasonably short period of time and one enantiomer of
4.1.2. Typical procedure for the synthesis of bishydroxylamide
5a–d
To a solution of diacid 3 (0.73 g, 3.0 mmol) in dichloromethane
(10 mL) were added oxalyl chloride (1.25 mL, 12 mmol) and a
catalytic amount of DMF (3 drops) at 0 °C. After stirring for 4 h at
room temperature under nitrogen, the solvent was removed under
reduced pressure to afford the acid chloride as a light yellow
solid (0.84 g, 99%). This solid residue was then dissolved in

274
S. Samadi et al. / Tetrahedron: Asymmetry 24 (2013) 269–277
dichloromethane (10 mL) and slowly added to a stirred solution of
(S)-phenyl glycinol 4a (0.9 g, 6.5 mmol) and Et3N, (1 mL) in dichlo-
romethane (10 mL) at 0 °C over 30 min. The reaction mixture was
allowed to warm to room temperature slowly and stirred over-
night under nitrogen. The formation of two new compounds
(S,aS,S)- and (S,aR,S)-5a and consumption of acid chloride was con-
firmed by TLC (90:10 EtOAc/n-hexane). After completion of the
reaction, brine (10 ml) was added and the aqueous layer was ex-
tracted with ethyl acetate (3 ꢁ 15 ml) and dried over magnesium
sulfate, filtered and concentrated. The residue was purified by sil-
ica gel column chromatography (eluent: EtOAc/n-hexane; 80–100:
20–0); to afford a white solid in 95%. The total yield for other com-
pounds 5b, 5c, and 5d were 90%, 99%, and 99%, respectively.
3.28–3.40 (m, 2H), 3.83 (m, 2H), 6.92–6.96. (m, 2H), 7.27–7.66
(m, 8H); 13C NMR (75 MHz, CDCl3): dC(ppm) = 22.0, 23.1, 24.6,
39.5, 50.1, 65.2, 129.6–126.7(4C), 136.5, 138.5, 170.4; IR (KBr,
cmꢀ1): 1553, 1640, 3264.
4.2. Typical procedure for the synthesis of ligands 1a–d
Method a: Cyclization procedures of bishydroxylamides 5a–d
were performed according to the Andrus procedure.1m
Method b:
0.5 mmol), triphenylphosphine (0.14, 5.2 mmol), triethylamine
(69 L, 0.44 mmol), and tetrachloromethane (50 L, 0.44 mmol)
A solution of bishydroxylamide 5a (234 mg,
l
l
in dry acetonitrile (3 ml) was stirred overnight. After being concen-
trated in vacuo, the residue was dissolved with CH2Cl2, washed
with water, dried over anhydrous magnesium sulfate, and then
concentrated in vacuo. The residue was purified by silica gel col-
umn chromatography (eluent: n-hexane/EtOAc; 90:10); to afford
a pure light yellow 1a in 89% yield. Compounds 1b, 1c, and 1d were
obtained in a similar manner as light yellow products in 45%, 60%,
and 50% total yield, respectively.1t
Method c: A flame-dried 25 mL Schlenk flask equipped with a
stirrer bar was charged with bishydroxylamide 5a (1 mmol,
0.48 g, 1 equiv), 4-(dimethylamino) pyridine (0.01 g, 0.1 mmol,
0.1 equiv), and dichloromethane (10 mL) under nitrogen. The flask
was placed in ice and triethylamine (0.6, 4.4 mmol, 4.4 equiv) and a
solution of p-toluenesulfonyl chloride (0.38 g, 2 mmol, 2 equiv) in
dichloromethane (4 mL) were added to the reaction mixture. After
stirring at room temperature for 18 h, the mixture was washed
with saturated aqueous NH4Cl (10 mL) and the aqueous layer
was extracted again with dichloromethane (3 ꢁ 10 ml). The ex-
tracted organic layers were combined and washed with saturated
aqueous NaHCO3 (10 mL), dried over Na2SO4 and concentrated.
The light yellow oil 1a obtained was purified by column chroma-
tography (n-hexane/EtOAc; 90:10); to afford pure light yellow 1a
in 95% yield. Other ligands 1b, 1c, and 1d were synthesized via a
similar method in 85%, 96%, and 90% total yield, respectively.
2
2
0
4.1.3. N ,N -Bis((S)-2-hydroxy-1-phenylethyl)-[1,10-biphenyl]-
2,20-dicarboxamide (S,S,S)- and (S,R,S)-5a
The 1H NMR and 13C NMR of 5a showed two sets of signals, ma-
jor/minor (52:48). Mp: 85–92 °C; Rf = 0.38, 0.47 (100% EtOAc); Ma-
jor (S,S,S): 1H NMR (300 MHz, CDCl3): dH(ppm) = 3.57–3.79 (m, 4H),
4.99–5.02 (m, 2H), 6.91–7.60 (m, 20H); 13C NMR (75 MHz, CDCl3):
dC(ppm) = 59.9, 65.2, 126.7–134.4 (8C), 137.9, 138.4, 139.2, 139.4,
170.4. Minor (S,R,S): 1H NMR (300 MHz, CDCl3): dH (ppm) = 3.57–
3.79 (m, 4H), 4.91–4.92 (m, 2H), 6.91–7.60 (m, 20 H); 13C NMR
(75 MHz, CDCl3): dC (ppm) = 59.1, 65.6, 126.6–134.6 (8C), 137.6,
138.9, 140.1, 170.1; IR (KBr, cmꢀ1): 1540, 1640, 3078.
2
2
0
4.1.4. N ,N -Bis((S)-1-hydroxy-3-phenylpropan-2-yl)-[1,10-
biphenyl]-2,20-dicarboxamide (S,S,S)- and (S,R,S)-5b
The 1H NMR and 13C NMR of 5b also showed two sets of signals,
major/minor (73:27). Mp: 70–78 °C; Rf = 0.43, 0.57 (100% EtOAc);
Major (S,S,S): 1H NMR (300 MHz, CDCl3): dH(ppm) = 2.50–2.54 (m,
2H), 2.75–2.78 (m, 2H), 3.55 (m, 4H), 4.07(m, 2H) 7.08–7.57 (m,
20H); 13C NMR (62.5 MHz, CDCl3): dC(ppm) = 37.3, 57.9, 63.5,
125.9–131.2 (8 C), 138.1, 138.7, 169.6;) Minor (S,R,S): 1H NMR
(300 MHz, CDCl3): dH(ppm) = 2.50–2.54 (m, 2H), 2.75–2.78 (m,
2H), 3.59 (m, 4H), 4.07(m, 2H) 7.08–7.57 (m, 20H); 13C NMR
(62.5 MHz MHz, CDCl3): dC(ppm) = 38.6, 57.3, 64.8, 125.9–131.2
(8 C), 138.4, 138.5, 168.9; IR (KBr, cmꢀ1): 1547, 1640, 3270.
The one-pot procedure: To
a solution of diacid 3 (0.73 g,
3.0 mmol) in dichloromethane (10 mL) were slowly added oxalyl
chloride (1.25 mL, 12 mmol) and then three drops of DMF at 0 °C.
The reaction mixture was stirred for 4 h at room temperature un-
der nitrogen. The solvent was evaporated under reduced pressure
to afford the acid chloride as a light yellow solid (0.84 g, 99%). This
solid material was then dissolved in dichloromethane (10 mL) and
a solution of (S)-phenyl glycinol 4a (0.9 g, 6.5 mmol) and Et3N
(1 mL) in dichloromethane (10 mL) was added to the reaction flask
at 0 °C over 30 min. The resulting solution was allowed to warm
slowly to room temperature with stirring overnight. The formation
of bishydroxylamide 5a was monitored by TLC; Rf = 0.38, 0.47
(100% EtOAc). Next, methanesulfonyl chloride (0.51 mL, 6.6 mmol)
was added at 0 °C, and the mixture was stirred at room tempera-
ture for 6 h. After completion, the reaction mixture was diluted
with dichloromethane (10 ml) and washed with saturated aqueous
NH4Cl (10 ml). The aqueous layer was extracted again with dichlo-
romethane (2 ꢁ 10 ml) and the combined organic layers were
washed with saturated aqueous NaHCO3 (10 ml) and dried over
Na2SO4. The solvent was removed under reduced pressure to afford
a light yellow oil, which was chromatographed (n-hexane/EtOAc;
90:10) over silica gel to provide pure light yellow products 1a in
90% total yield. Compounds 1b, 1c, and 1d were synthesized in a
similar manner in 85%, 85%, and 95% total yield, respectively.7
2
2
0
4.1.5. N ,N -Bis((S)-1-hydroxy-3-methylbutan-2-yl)-[1,10-
biphenyl]-2,20-dicarboxamide (S,S,S)- and (S,R,S)-5c
The 1H NMR and 13C NMR of 5c showed two sets of signals, ma-
jor/minor (54:46). Mp: 93–99 °C; Rf = 0.24, 0.30 (100% EtOAc); Ma-
jor (S,S,S): 1H NMR (300 MHz, CDCl3): dH (ppm) = 0.63–0.69 (m,
6H), 0.77–0.83 (m, 6H),1.69–1.78 (m, 2H), 3.27–3.29 (m, 2H),
3.33–3.43 (m, 2H), 3.57 (m, 2H), 7.04–7.10 (m, 2H), 7.32–7.60
(m, 8H); 13C NMR (75 MHz, CDCl3): dC(ppm) = 18.9, 19.3, 28.7,
57.6, 63.2, 126.9–129.9 (4C), 136.5, 138.6, 170.7; Minor (S,R,S):
1H NMR (300 MHz, CDCl3): dH (ppm) = 0.63–0.69 (m, 6H),0.77–
0.83 (m, 6H),1.58–1.69 (m, 2H), 3.27–3.29 (m, 2H), 3.33–3.43 (m,
2H), 3.57 (m, 2H), 7.04–7.10 (m, 2H), 7.32–7.60 (m, 8H); 13C
NMR (75 MHz, CDCl3): dC(ppm) = 18.5, 19.2, 28.8, 57.4, 63.0,
126.9–129.9(4C), 136.0, 138.8, 170.4; IR (KBr, cmꢀ1): 1547, 1633,
1732, 3280.
2
2
0
4.1.6. N ,N -Bis((S)-1-hydroxy-4-methylpentan-2-yl)-[1,10-
biphenyl]-2,20-dicarboxamide (S,S,S)- and (S,R,S)-5d
The 1H NMR and 13C NMR of 5d showed two sets of signals, ma-
jor/minor (77:33), Mp:135–144 °C; Rf = 0.27, 0.34 (100% EtOAc);
Major (S,S,S): 1H NMR (300 MHz, CDCl3): dH (ppm) = 0.71–0.75
(m, 12H), 1.04–1.07 (m, 4H), 1.18–1.25 (m, 2H), 3.14–3.22 (m,
2H), 3.28–3.40 (m, 2H), 3.83 (m, 2H), 6.92–6.96. (m, 2H), 7.27–
7.66 (m, 8H); 13C NMR (75 MHz, CDCl3): dC(ppm) = 21.9, 23.2,
24.4, 39.6, 50.3, 65.5, 129.6–126.7(4C), 135.9, 138.8, 170.5; Minor
(S,R,S): 1H NMR (300 MHz, CDCl3): dH (ppm) = 0.78–0.80 (m,
12H), 1.04–1.07 (m, 4H), 1.18–1.25 (m, 2H), 3.14–3.22 (m, 2H),
4.2.1. 2,20-Bis((S)-4-phenyl-4,5-dihydrooxazol-2-yl)-1,10-
biphenyl (S,S,S)- and (S,R,S)-1a
The 1H NMR of 1a showed two sets of signals, major/minor
(61:39). Rf = 0.35, 0.55 (n-hexane/EtOAc; 40:60); Major (S,S,S): 1H
NMR (300 MHz, CDCl3): dH (ppm) = 3.83–3.93 (m, 2H), 4.39–4.55

S. Samadi et al. / Tetrahedron: Asymmetry 24 (2013) 269–277
275
(m, 2H), 5.12–5.27 (m, 2H), 7.16–7.59 (m, 16H) 7.97–8.03 (m 2H);
13C NMR (75 MHz, CDCl3): dC (ppm) = 69.9, 75.2, 126.7–130.4 (8C),
141.4, 142.4, 166.1; Minor (S,R,S): 1H NMR (300 MHz, CDCl3): dH
(ppm) = 3.99–4.03 (m, 2H), 4.39–4.55 (m, 2H), 5.12–5.27 (m, 2H),
7.16–7.59 (m, 16H) 7.97–8.03(m. 2H); 13C NMR (75 MHz, CDCl3):
dC (ppm) = 69.7, 74.6, 126.7–130.4 (8C), 141.9, 142.5, 165.4; IR
stirred at room temperature for 3 h. After completion of the reac-
tion as indicated by TLC, only a single new spot (Rf = 0.0 in 50%
EtOAc/n-hexane) was observed.
4.3.1. (S)-2,20-Bis((S)-4-phenyl-4,5-dihydrooxazol-2-yl)-1,10-
biphenyl copper(I) hexafluoro phosphate complex (S,aS,S)-1a-
CuPF6
(KBr, cmꢀ1): 1447, 1646, 2886, 3018, 3065; ½a 2D6
¼ ꢀ179:9 (c
ꢂ
0.50, CHCl3); MS m/z (%): 444 (8, M+), 367(12), 298 (100), 226
(31), 77(42).
1H NMR (300 MHz, CDCl3): dH (ppm) = 3.75–3.80 (t, J = 8.4, 2H),
4.40–4.45 (t, J = 10.0, 2H), 5.13–5.19 (t, J = 9.9, 2H), 6.91–7.77 (m,
18H); 13C NMR (75 MHz, CDCl3): dC (ppm) = 69.8, 74.6, 125.9–
128.4 (6C), 132.2, 136.9, 140.0, 142.7, 169.6; IR (KBr, cmꢀ1): 561,
841, 1086, 1514, 1642, 1688, 2302, 2919, 3740;MS m/z (%): 507
(1, [MꢀPF6]+), 444 (18, M+), 326 (22), 298 (100), 206 (73),
4.2.2. 2,20-Bis((S)-4-benzyl-4,5-dihydrooxazol-2-yl)-1,10-
biphenyl (S,S,S)- and (S,R,S)-1b
The 1H NMR of 1b showed two sets of signals: major/minor
(70:30). Rf = 0.15, 0.33 (n-hexane/EtOAc; 40:60); Major (S,S,S): 1H
NMR (300 MHz, CDCl3): dH(ppm) = 2.54–2.68 (m, 2H), 2.95–3.02
(dd, 2H, J 5.2, 13.6 Hz), 3.80–3.90 (m, 2H), 3.97–3.4.03 (t, 2H, J
8.8 Hz), 4.36–4,41 (m, 2H), 7.11–7.53 (m, 16H), 7.81–7.84(d, 2H, J
77(31); ½a 2D6
¼ þ23:4 (c 1, CHCl3).
ꢂ
4.3.2. (S)-2,20-Bis((S)-4-benzyl-4,5-dihydrooxazol-2-yl)-1,10-
biphenyl copper(I) hexafluoro phosphate complex (S,aS,S)-1b-
CuPF6
7.4 Hz);13
C NMR (75 MHz, CDCl3): dC(ppm) = 41.3, 67.9, 71.9,
126.3–130.2 (8C), 138.2, 141.4, 164.6; Minor (S,R,S): 1H NMR
(300 MHz, CDCl3): dH (ppm) = 2.54–2.68 (m, 2H), 2.06–3.12 (dd,
2H, J 4.34, 13.6 Hz), 3.80–3.90 (m, 2H), 4.10–4.15 (t, 2H, J 8.8 Hz),
1H NMR (300 MHz, CDCl3): dH(ppm) = 2.30–2.37 (dd, J = 13.6,
8.8, 2H), 2.76–2.83 (dd, 2H, J = 13.6, 5.4 Hz), 3.69–3.74 (t, J = 7.3,
2H), 3.93–3.99 (t, J = 8.8, 2H), 4.26–4.31 (m, 2H), 7.07–7.65 (m,
18H); 13C NMR (75 MHz, CDCl3): dC (ppm) = 35.9, 65.6, 73.8,
124.6, 125.8, 126.8, 127.9, 128.7, 129.2, 130.1, 132.1, 136.4,
137.0, 170.0; IR (KBr, cmꢀ1): 552, 837, 1082, 1546, 1653, 1692,
2316, 2912, 3748;MS m/z (%): 535 (0.7, [MꢀPF6]+), 472 (20, M+),
4.36–4,41 (m, 2H), 7.11–7.53 (m, 16H), 7.88–7.90 (d, 2H,
J
7.3 Hz);13C NMR (75 MHz, CDCl3): dC (ppm) = 41.5, 67.9, 72.0,
126.3–130.2 (8 C), 138.2, 141.6, 164.5; IR (KBr, cmꢀ1): 1501,
1653, 1726, 2913, 3065; MS m/z (%): 472 (11, M+), 382(19), 313
(100), 238 (27), 93(54); ½a D26
ꢂ
¼ ꢀ193:6 (c 0.50, CHCl3).
381(69), 312 (100), 247 (53), 91(62); ½a D26
¼ þ70:8 (c 1, CHCl3).
ꢂ
4.2.3. 2,20-Bis((S)-4-isopropyl-4,5-dihydrooxazol-2-yl)-1,10-
biphenyl (S,S,S)- and (S,R,S)-1c
4.3.3. (S)-2,20-Bis((S)-4-isopropyl-4,5-dihydrooxazol-2-yl)-1,10-
biphenyl copper(I) hexafluoro phosphate complex (S,aS,S)-1c-
CuPF6
The 1H NMR of 1c showed two sets of signals, major/minor
(80:20); Rf = 0.18, 0.5 (n-hexane/EtOAc; 40: 60); Major (S,S,S): 1H
NMR (300 MHz, CDCl3): dH(ppm) = 0.80–0.82 (m, 12H), 1.65–1.74
(m, 2H), 3.74 (t, 2H, J 7.9 Hz), 3.82–3.90 (m, 2H), 4.14 (t, 2H, J
8.7 Hz), 7.22–7.50 (m, 6H), 7.81 (d, 2H, J 7.6 Hz); 13C NMR
(62.5 MHz, CDCl3): dC(ppm) = 18.7, 19.4, 33.3, 69.4, 72.5, 125.8,
127.1, 128.2, 132.3, 136.1, 140.5, 165.4; Minor (S,R,S): 1H NMR
(300 MHz, CDCl3): dH (ppm) = 0.86–0.88(d, 12H, J 6.7 Hz), 1.65–
1.74 (m, 2H), 3.74 (t, 2H, J 7.9 Hz), 3.82–3.90 (m, 2H), 4.14 (t, 2H,
J 8.7 Hz), 7.22–7.50 (m, 6H), 7.86 (d, 2H, J 7.3 Hz); 13C NMR
(62.5 MHz, CDCl3): dC (ppm) = 18.5, 19.0, 33.0, 70.2, 72.7, 126.2,
127.7, 128.1, 132.1, 136.9, 140.2, 165.1; IR (KBr, cmꢀ1): 1467,
1646, 2873, 2959; MS m/z (%): 376 (10, M+), 334(21), 265 (100),
1H NMR (300 MHz, CDCl3): dH(ppm) = 0.66–0.84 (m, 12H), 1.60–
1.90 (m, 2H), 4.31 (br s, 4H), 4.36–4.58 (m, 2H), 7.15–7.42 (m, 6H),
7.61 (br s, 2H); 13C NMR (100 MHz, CDCl3): dC(ppm) = 18.1, 18.6,
32.6, 70.0, 72.4, 126.6, 126.8, 129.9, 131.4, 137.3, 139.7, 167.1; IR
(KBr, cmꢀ1): 552, 771, 843, 1089, 1381,1474, 1638, 1725, 2269,
2965, 3423; MS m/z (%): 439 (0.5, [MꢀPF6]+), 376 (41, M+), 403
(35), 292 (71), 264 (100), 206 (54), 91(34); ½a D26
¼ þ9:2 (c 1, CHCl3).
ꢂ
4.3.4. (S)-2,20-Bis((S)-4-isobutyl-4,5-dihydrooxazol-2-yl)-1,10-
biphenyl copper(I) hexafluoro phosphate complex (S,aS,S)-1d-
CuPF6
1H NMR (300 MHz, CDCl3): 0.95–1.12 (m, 12H), 1.32–1.55 (m,
4H), 1.70–1.71 (m, 2H), 4.23–4.48 (br s, 4H), 4.96 (m, 2H), 7.56
(m, 6H), 7.80–7.83 (d, J = 8.2, 2H).; 13C NMR (75 MHz, CDCl3):
dC(ppm) = 20.8, 22.6, 25.6, 45.8, 65.3, 73.2, 126.8, 127.6, 128.5,
131.7, 137.5, 141.0, 168; IR (KBr, cmꢀ1): 559, 842, 1089,
1381,1467, 1637, 1719, 2276, 2959, 3409; MS m/z (%): 467 (0.5,
[MꢀPF6]+), 403(11, M+), 347(23), 278 (100), 206 (45), 91(37),
191 (26), 43(46); ½a D26
¼ ꢀ157:5 (c 0.50, CHCl3).
ꢂ
4.2.4. 2,20-Bis((S)-4-isobutyl-4,5-dihydrooxazol-2-yl)-1,10-
biphenyl ((S,S,S)- and (S,R,S)-1d
The 1H NMR of 1d showed two sets of signals: major/minor
(63:38). Rf = 0.4, 0.53 (n-hexane/EtOAc; 50:50); Major (S,S,S): 1H
NMR (300 MHz, CDCl3): dH(ppm) = 0.85–0.90 (m, 12H), 1.11–
1.30(m, 2H), 1.42–1.64 (m, 4H), 3.59–3.65 (m, 2H), 4.05–4.23 (m,
55(56); ½a 2D6
¼ þ62:9 (c 1, CHCl3).
ꢂ
4H), 7.23–7.48 (m, 6H), 7.75–7.77 (d,
J
7.9, 2H); 13C NMR
4.4. Synthesis of tert-butyl 4-nitrobenzoperoxoate1n
(62.5 MHz, CDCl3): dC(ppm) = 19.9, 20.3, 33.7, 43.5, 68.1, 76.1,
126.6, 127.1, 128.1, 131.9, 136.5, 139.7, 164.1; Minor (S,R,S): 1H
NMR (300 MHz, CDCl3): dH(ppm) = 0.85–.90 (m, 12H), 1.11–1.30
(m, 2H), 1.42–1.64 (m, 4H), 3.59–3.65 (m, 2H), 4.05–4.23 (m,
p-Nitrobenzoyl chloride (3.2 g, 17.2 mmol) was dissolved in a
100 mL round bottom flask containing CH2Cl2 (35 mL). The solu-
tion was cooled to ꢀ20 °C and stirred under nitrogen for 15 min.
Pyridine (1.7 mL, 20.0 mmol) was then added and the reaction
mixture was stirred for 10 min. Next, tert-butyl hydroperoxide
(3.5 mL, 20.0 mmol) was added dropwise to the reaction at
ꢀ20 °C, and stirred for 4 h. Then the reaction solution was then
diluted with CH2Cl2 (20 mL), and washed with water. The organic
layer was separated, dried over MgSO4, and evaporated to obtain
4H), 7.23–7.48 (m, 6H), 7.82–7.85 (d,
J
7.4, 2H); 13C NMR
(62.5 MHz, CDCl3): dC(ppm) = 20.1, 20.5, 33.2, 43.6, 67.8, 76.2,
126.1, 126.9, 127.7, 131.6, 136.6, 140.2, 163.5; IR (KBr, cmꢀ1):
1461, 1666, 1726, 2926, 2952. MS m/z (%): 404 (4, M+), 347(9),
278 (100), 206 (24), 91(47), 55(37); ½a D26
¼ ꢀ121:4 (c 0.50, CHCl3).
ꢂ
4.3. General procedure for the synthesis of the 1-Cu complex
a
crude yellow solid product. Purification using flash
chromatography (n-hexane/EtOAc; 90:10) afforded a light yellow
solid product. (3.9 g, 98% yield); Mp 75–78 °C. 1H NMR
(300 MHz, CDCl3): dH(ppm) = 1.45 (9H, s, Me), 8.14–8.35 (4H, m,
Ar).
To a solution of ligand 1 (0.02 mmol) in chloroform-d was
added 1 equiv of Cu(I)PF6(CH3CN)4 (0.018 mmol, 6.6 mg,) under
nitrogen atmosphere. The resulting light yellow solution was

276
S. Samadi et al. / Tetrahedron: Asymmetry 24 (2013) 269–277
4.5. General procedure for the enantioselective allylic oxidation
of cycloolefins using tert-butyl 4-nitrobenzoperoxoate
4.5.5. (S)-Cycloocta-2,6-dien-1-yl 4-nitrobenzoate 101n
Mp: 74–76 °C; Rf = 0.62 (n-Hexane/EtOAc; 90:10); 1H NMR
(300 MHz, CDCl3): dH(ppm) = 5.57–5.84 (m, 4H), 2.21–2.41 (m,
2H), 2.54–2.68 (m, 2H), 2.85–2.95 (m, 2H), 5.57–5.84 (m, 4H),
6.17–6.26 (m, 1H), 8.23(d, 2H, J 8.5 Hz),)8.30 (d, 2H, J 8.4 Hz); IR
To a flame-dried round bottom flask (25 mL), a light yellow
solution of the bisoxazoline ligand 1 (0.065 mmol) and copper
salt (0.55 mmol) were stirred in CH3CN (4 mL) and stirred for
3 h at ambient temperature. In this case, TLC analysis indicated
the formation of a single spot (Rf = 0.0 in 50% EtOAc/ hexanes).
(KBr, cmꢀ1): 1106, 1281, 1523, 1719, 2906; ½a 2D0
¼ ꢀ26:5 (c 1.0,
ꢂ
CHCl3). The enantiomeric excess was determined by chiral HPLC
(EC 250/4.6 Nucleocel Alpha S column, iso-propyl alcohol/hexanes,
99.5:0.5; flow rate 0.4 ml/min; tR = 38.2 min (R), 40.5 min (S))
(maximum ee = 95% (S)).
After the addition of phenyl hydrazine (6 ll, 0.06 mmol), the col-
or of the solution changed from blue green to red. Next, 10 mg
of 4 Å molecular sieves and MCM-41 or SBA-15 (or other nano-
particles) were added. After a few min, cycloolefin (5 mmol) was
added. The reaction mixture was cooled to ꢀ10 °C and then tert-
butyl 4-nitrobenzoperoxoate (0.203 g, 0.85 mmol) was added
dropwise to the reaction solution under a nitrogen atmosphere.
The mixture was kept at ꢀ10 °C until TLC showed the complete
disappearance of perester. The reaction mixture was dissolved in
10% NH4OH, extracted with EtOAc and dried over MgSO4. Re-
moval of solvent in vacuo afforded a yellow residue that was
chromatographed over silica gel to provide the pure white solid
product (yield up to 99%), and recovered bisoxazoline ligand in
80–95%yield.
4.6. Crystal structure determination and refinement of 5d
The X-ray diffraction measurement was made on a STOE IPDS-II
diffractometer with graphite monochromated Mo-K
a radiation.
For 5d, a block colorless crystal was chosen using a polarizing
microscope and was mounted on a glass fiber which was used
for data collection. Cell constants and orientation matrices for data
collection were obtained by least-squares refinement of diffraction
data from 3677 unique reflections. Data were collected to a maxi-
mum 2h value of 58.38° in a series of
x scans in 1° oscillations and
integrated using the Stoe X-AREA16 software package. The data
were corrected for Lorentz and Polarizing effects. The structure
was solved by direct methods17 and subsequent difference Fourier
maps and then refined on F2 by a full-matrix least-squares proce-
dure using anisotropic displacement parameters.18 All hydrogen
atoms attached to the carbon were added in idealized positions.
Hydrogen atoms of N–H and O–H were found in difference Fourier
maps. The atomic factors were taken from the International Tables
for X-ray crystallography.19 All refinements were performed using
the X-STEP32 crystallographic software package.20 CCDC No.
895781 contains crystallographic data for this paper. These data
can be obtained free of charge from the Cambridge Crystallo-
graphic Data Center via http://www.ccdc.cam.ac.uk/data_request/
cif.
4.5.1. (S)-Cyclopent-2-en-1-yl 4-nitrobenzoate 71n
Mp: 77–79 °C; Rf = 0.57 (90: 10, n-hexane/EtOAc); 1H NMR
(300 MHz, CDCl3): dH(ppm) = 1.97–2.04 (1H m), 2.38–2.50 (2H,
m), 2.59–2.63 (1H, m), 5.98 (2H, m), 6.22 (1H, m), 8.20 (d, 2H, J
8.5 Hz), 8.28 (d, 2H, J 8.5 Hz); IR (KBr, cmꢀ1) 1109, 1268, 1520,
1706, 2846; ½a 2D0
¼ ꢀ159:3 (c 1.0, CHCl3); The enantiomeric excess
ꢂ
was determined by chiral HPLC (EC 250/4.6 Nucleocel Alpha S col-
umn, iso-propyl alcohol/hexanes; 99.5:0.5; flow rate 0.4 ml/min;
tR = 35.1 min (R), 36.7 min (S)) (maximum ee = 80% (S)).
4.5.2. (S)-Cyclohex-2-en-1-yl 4-nitrobenzoate 61n
Mp: 68–71 °C; Rf = 0.64 (n-hexane/EtOAc; 90:10, 1H NMR
(300 MHz, CDCl3): dH(ppm) = 1.76–2.14 (6H m), 5.54 (1H m), 5.84
(1H d, J 9.8 Hz), 6.04 (1H d, J 9.8 Hz), 8.21–8.31(4H m); 13C NMR
(300 MHz, CDCl3): dC(ppm) = 18.8, 25.0, 28.2, 69.8, 123.4, 125.0,
130.7, 133.6, 136.2; IR (KBr, cmꢀ1): 1107, 1278, 1525, 1713,
Crystal data for 5d; C26H36N2O4, M = 440.57, colorless block,
crystal dimensions: 0.4 ꢁ 0.32 ꢁ 0.20 mm3; tetragonal, space
group P41212; a = 13.0262(18), b = 13.0262(18), c = 16.027(3) Å;
V = 2719.5(9) Å3; T = 120(2) K; Z = 4; Dcalc = 1.076 g cmꢀ3
;
l
= 0.072 mmꢀ1 (for Mo K
tions collected = 31313;
a
, k = 0.71073 Å); F(000) = 952; reflec-
reflections independent = 3677
2928. ½a 2D0
¼ ꢀ125:2 (c 1.0, CHCl3). The enantiomeric excess was
ꢂ
determined by chiral HPLC (EC 250/4.6 Nucleocel Alpha S column,
iso-propyl alcohol/hexanes; 99.5:0.5; flow rate 0.5 ml/min;
tR = 34.8 min (R), 37.1 min (S)) (maximum ee = 81% (S)).
[Rint = 0.1783]; h range 2.21 to 29.19; h, k, l range: ꢀ17 6 h 6 15,
ꢀ17 6 k 6 17, ꢀ21 6 l 6 21; full-matrix least-squares on F2;
parameters = 154; restraints = 0; R1 = 0.0932; wR2 = 0.1338
[I > 2sigma(I)]; GooF = S = 1.200; largest difference in peak and
4.5.3. (S)-Cyclohept-2-en-1-yl 4-nitrobenzoate 81n
hole,
D
qmax and
D
q
min = 0.198 and ꢀ0.189 e Å3.
Mp: 72–75 °C; Rf = 0.57 (n-Hexane/EtOAc; 90:10); 1H NMR
(300 MHz, CDCl3): dH(ppm) = 1.66–1.72 (m, 4H), 2.02–2.12(m,
2H), 2.07–2.40 (m, 2H), 5.58–5.64 (m, 1H), 5.75–5.82 (m, 1H),
5.92–5.98 (m, 1H), 8.22–8.28 (m, 4H); IR (KBr, cmꢀ1): 1106,
Acknowledgments
We are indebted to the Research Council of Shahid Beheshti
University and Iranian National Science Foundation (Proposal No:
90003165) for financial support. The authors also gratefully thank
Professor J. Michael Chong for his helpful suggestions, consulta-
tions, and all his kindness and hospitality during Dr. Jadidi’s sab-
batical leave in Waterloo University and Professor M. M.
Pouramini for their helpful discussion.
1273, 1528, 1709, 28930; ½a D20
¼ ꢀ68:7 (c 1.0, CHCl3). The enantio-
ꢂ
meric excess was determined by chiral HPLC (EC 250/4.6 Nucleocel
Alpha S column, iso-propyl alcohol/hexanes; 99.5:0.5; flow rate
0.4 ml/min; tR = 26.6 min (R), 28.5 min (S)) (maximum ee = 78%
(S)).
4.5.4. (S)-Cyclooct-2-en-1-yl 4-nitrobenzoate 91n
Mp: 71–74 °C; Rf = 0.67 (n-Hexane/EtOAc; 90:10); 1H NMR
(300 MHz, CDCl3): dH(ppm) = 1.46–1.72 (m, 7H), 2.07–2.40 (m,
3H), 5.60–5.66 (m, 1H), 5.73–5.82 (m, 1H), 5.92–5.96 (m,
1H), 8.22–8.32 (m, 4H); IR (KBr, cmꢀ1): 1108, 1281, 1527,
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