Studies on enantioselective allylic oxidation of olefins using peresters catalyzed by Cu(I)-complexes of chiral pybox ligands

Article abstract of DOI:10.1039/b612423b

Enantioselective allylic oxidation of olefins with various peresters, using a catalytic amount of Cu(i)-pybox complex, can be tuned to achieve high asymmetric induction (up to 98% ee) by choosing a unique combination of a ligand and a perester at room temperature. The asymmetric induction in the reaction strongly depends on the nature of the substituents attached to the aryl ring of peresters. The presence of a gem-diphenyl group at C-5 and secondary or tertiary alkyl substituents at the chiral center (C-4) of the oxazoline rings is crucial for high enantioselectivity. A π-π stacking model has been proposed and discussed to explain the stereochemical outcome of the reaction. The Royal Society of Chemistry 2006.

Full text of DOI:10.1039/b612423b

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www.rsc.org/obc | Organic & Biomolecular Chemistry
Studies on enantioselective allylic oxidation of olefins using peresters
catalyzed by Cu(I)-complexes of chiral pybox ligands†
Sandeep K. Ginotra and Vinod K. Singh*
Received 29th August 2006, Accepted 10th October 2006
First published as an Advance Article on the web 24th October 2006
DOI: 10.1039/b612423b
Enantioselective allylic oxidation of olefins with various peresters, using a catalytic amount of
Cu(I)-pybox complex, can be tuned to achieve high asymmetric induction (up to 98% ee) by choosing a
unique combination of a ligand and a perester at room temperature. The asymmetric induction in the
reaction strongly depends on the nature of the substituents attached to the aryl ring of peresters. The
presence of a gem-diphenyl group at C-5 and secondary or tertiary alkyl substituents at the chiral center
(C-4) of the oxazoline rings is crucial for high enantioselectivity. A p–p stacking model has been
proposed and discussed to explain the stereochemical outcome of the reaction.
pybox ligand. The results described here would provide an insight
into the p–p stacking6 in the transition state model.
Introduction
Enantioselective allylic oxidation of olefins with peresters to chiral
allylic esters catalyzed by chiral copper complexes is an important
Results and discussion
transformation in organic synthesis.1,2 Although a reasonable
progress has been made in this reaction using copper complexes
of a variety of chiral bisoxazoline,3 trisoxazoline,4 and pybox
ligands,5 a balance of high enantioselectivity and shorter reaction
time still remains a major concern. High enantioselectivity (94–
99% ee) has been achieved for this transformation with the use of
tert-butyl p-nitroperbenzoate as an oxidant, but only at the cost
of very poor reactivity of catalysts (reaction time 8–17 days).3f
The reactivity of catalysts prepared from the pybox ligand in
our laboratory was enhanced by employing phenylhydrazine in
acetone, but the enantioselectivity could not be improved beyond
93% under this condition.5c In this paper we demonstrate that by
choosing a unique ligand–substrate–reagent combination, one can
obtain, for the first time, excellent enantioselectivity (up to 98%
ee) without losing the reactivity of the catalysts.
Since the reaction is supposed to proceed via a cleavage of the O–
O bond of the perester, it was logical to start with an electron
withdrawing group such as nitro at the para position of the
phenyl ring of the perester which, besides facilitating the cleavage
reaction, should give high enantiomeric excess (ee) in the allylic
oxidation reaction due to a better p–p stacking. Unfortunately,
it was not the case. The reaction was sluggish and the ee was
slightly inferior (86% ee; Table 1, entry 2). A nitro group at the
ortho and meta positions of the phenyl ring gave similar results
(entries 3 and 4). This led us to examine the influence of other
aryl substituents of peroxyesters on enantioselectivity in the allylic
oxidation reaction (Scheme 1) and the results are summarized in
Table 1. Electron donating groups such as methoxy and alkyl
on the phenyl ring of peresters gave similar results as phenyl
(entries 5–7 and entry 11). Since the pentafluorophenyl group
is known to show strong p–p interactions with phenyl groups,
pentafluoro substituted phenyl peroxyester was also used in the
allylic oxidation reaction. Unfortunately, the reaction was very
sluggish (32 h) and the ee dropped down to 40% (entry 13).
A complex of a chiral ligand, 2,6-pyridine bis(4ꢀ-isopropyl-5ꢀ,5ꢀ-
diphenyloxazoline) 1a (henceforth we will call it ‘ip-pybox-diph’)
with Cu(OTf)2 in conjunction with phenylhydrazine in acetone
is known to give 91% ee in the allylic oxidation of cyclohexene
with tert-butyl perbenzoate.5c The reaction was explained using a
transition state model based on p-stacking between phenyl groups
of the pybox ligand and the perester used in the reaction (vide
infra). It is logical to think that electron donating and electron
withdrawing groups on these phenyl substituents would affect the
electron density on the p-face of the aromatic rings, giving useful
information about the transition state model. It was easier to see
the above effect by having different substituents on the phenyl
ring of the peresters. In this paper, we describe our results in a
systematic study for enantioselective allylic oxidation of olefins
using different substituents on the aryl ring of a perester and the
Scheme 1 Enantioselective allylic oxidation of cyclohexene with different
peresters and pybox ligands.
So far we have studied allylic oxidation of cyclohexene with
the ip-pybox-diph ligand 1a using different peresters by changing
the electronic environment in the phenyl ring and have achieved a
maximum of 93% ee using tert-butyl p-methoxyperbenzoate (entry
5). In order to gain more information about the reaction, a few
more chiral ligands were synthesized where substituents at only
two positions (C-4 and C-5) were varied (Fig. 1). A single ligand
that produces allyl esters in high selectivity with a wide range of
Department of Chemistry Indian Institute of Technology, Kanpur, India –
208 016. E-mail: vinodks@iitk.ac.in; Fax: +91-512-2597436; Tel: +91-512-
2597291
† Electronic supplementary information (ESI) available: 1H, 13C-NMR and
HPLC data for the allylic oxidation products. See DOI: 10.1039/b612423b
4370 | Org. Biomol. Chem., 2006, 4, 4370–4374
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Table 1 Enantioselective allylic oxidation of cyclohexene with different
the C-5 positions, but the variation was made only at the chiral
center, C-4 by having different substituents such as i-Pr (1a), s-Bu
(1b), i-Bu (1c), Bn (1d), Me (1e), Ph (1f), t-Bu (1g). A copper
complex of these ligands was tested for the allylic oxidation
reaction of cyclohexene under the above conditions using selected
peresters. The results are summarized in Table 1. It was observed
that the behavior of the ligands, sb-pybox-diph (1b) and tb-pybox-
diph (1g) was similar to that of ip-pybox-diph (1a). The ligand
1b, that had an s-butyl group at the chiral center, gave excellent
enantioselectivity (98% ee) in the reaction when tert-butyl
o-methoxyperbenzoate was used (entry 19). It was observed that
when a bulkier substituent such as a tert-butyl group at the chiral
center was used as in the ligand 1g, the enantioselectivity dropped
down to 89% (entries 40 and 41). Copper complexes of ligands
1c, 1d, and 1e having other alkyl substituents at the chiral center
gave moderate enantioselectivity (entries 27–35). The ligand 1f
having a phenyl group at the chiral center showed poor catalytic
activity in the allylic oxidation of cyclohexene (entries 36–38).
In order to find out the role of the gem-diphenyl group of the
ligands on enantioselectivity, we studied enantioselective allylic
oxidation with ligands ip-pybox-bn (1h) and ip-pybox (1i) where
the phenyl groups at C-5 of the oxazoline ring were replaced by
benzyl and hydrogen, respectively. From the results in Table 1 (en-
tries 42–47), it was observed that the gem-diphenyl group is crucial
for getting high enantioselectivity in the allylic oxidation reaction.
Based on the results in Table 1, ligands 1a and 1b were chosen for
further study of the above reaction on other olefins and the results
are summarized in Table 2. It was noticed that an optimal combi-
peresters and pybox ligandsa (Scheme 1)
Entry
L* Ar
1a Phenyl
Time/h
Yield (%)
ee (%)b
1
2
3
4
5
6
7
8
9
1
10
16
24
2
5
5
4
5
6
1
1
32
8
15
15
18
5
2
3
2
3
2
5
21
56
5
4
7
11
29
8
72
48
55
11
17
7
2
2
7
4
67
65
43
56
60
50
57
72
61
44
65
63
56
57
49
65
63
61
71
63
69
68
55
61
66
68
77
71
56
70
77
69
74
64
61
40
40
35
59
62
58
74
61
73
85
73
67
91c
86
80
88
93
91
91
87
88
89
91
72d
40d
91
87
83
86
92
98
90
89
87
85
89
79d
52d
65
67
68
66
63
64
56
58
59
19
10
12
87
89
89
66
71
70
65c,e
70
70
p-Nitrophenyl
o-Nitrophenyl
m-Nitrophenyl
p-Methoxyphenyl
o-Methoxyphenyl
m-Methoxyphenyl
p-Chlorophenyl
o-Chlorophenyl
m-Chlorophenyl
4-i-Propylphenyl
2,6-Difluorophenyl
Pentafluorophenyl
Phenyl
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
1b
p-Nitrophenyl
o-Nitrophenyl
m-Nitrophenyl
p-Methoxyphenyl
o-Methoxyphenyl
m-Methoxyphenyl
p-Chlorophenyl
o-Chlorophenyl
m-Chlorophenyl
4-i-Propylphenyl
2,6-Difluorophenyl
Pentafluorophenyl
Phenyl
p-Methoxyphenyl
o-Methoxyphenyl
Phenyl
p-Methoxyphenyl
o-Methoxyphenyl
Phenyl
1c
1d
1e
1f
Table 2 Enantioselective allylic oxidation of cyclic olefins with different
peresters using ligands 1a and 1ba
p-Methoxyphenyl
o-Methoxyphenyl
Phenyl
p-Methoxyphenyl
o-Methoxyphenyl
Phenyl
p-Methoxyphenyl
o-Methoxyphenyl
Phenyl
p-Methoxyphenyl
o-Methoxyphenyl
Phenyl
1g
1h
1i
5
2
18
18
20
p-Methoxyphenyl
o-Methoxyphenyl
Time/h
Yield (%) ee (%)b
1b 1a 1b 1a 1b
20 76 75 70c 65
a 5 mol% of the chiral ligand was used. b Determined by chiral HPLC
columns. c See ref. 5c. d Determined by converting into benzoyl ester.
e Pfaltz et al. have reported 71% ee (ref. 3a) under other conditions (1i-
CuOTf, MeCN, 3 days).
Entry Olefin
Ar
1a
1
2
3
4
5
6
7
8
9
Phenyl
3
13
3
4
6
p-Nitrophenyl
p-Methoxyphenyl
o-Methoxyphenyl
Phenyl
6
3
47 42 62
55 57 77
71 74 80
58
72
80
—
90
94
87
4
—
47
—
86c
p-Nitrophenyl
64
72 36 40 85
18 45 45 91
16 42 39 91
p-Methoxyphenyl 96
o-Methoxyphenyl 13
Phenyl
6
24 34 34 94c 95
10
11
12
13
14
15
16
p-Nitrophenyl
p-Methoxyphenyl 21
o-Methoxyphenyl 33
Phenyl
p-Nitrophenyl
p-Methoxyphenyl 29
o-Methoxyphenyl 10
36
72 28 39 91
19 31 42 96
48 38 43 91
88
90
92
—
65
96
82
Fig. 1 Chiral pybox ligands.
120
48
—
31
—
80c
substrates will most likely never be found. The metal–ligand
combination will continue to be fine-tuned for each substrate
for both reactivity and selectivity.1a This study is important as
small changes in conformational, steric, and electronic properties
of chiral ligands can often lead to dramatic variation in the
enantioselectivity. The ligands 1a–1g had gem-diphenyl groups at
72 42 45 66
15 49 50 95
16 62 52 86
a 5 mol% of the chiral ligand was used. b Determined by HPLC chiral
columns. c See ref. 5c.
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Table 3 Enantioselective allylic oxidation of 1,5-cyclooctadine using
ligands 1a and 1ba
Table 5 Enantioselective allylic oxidation of 1-octene using ligands 1a
and 1ba
ee (%)b
Ratio
ee (%)b
Ratio
Entry
L*
Time/h
4a
4b
Yield (%)
4a
Entry
L*
Time/h
2a
2b
Yield (%)
2a
2b
1
2
1a
1b
39
39
7
6
3
4
39
35
31
28
1
2
1a
1b
12
5
3
1
2
1
68
70
93
93
94
93
a 5 mol% of the chiral ligand was used. b Enantiomeric excess was
determined by HPLC using a Chiralpak AD-H column.
a 5 mol% of the chiral ligand was used. b Enantiomeric excess was
determined by HPLC using a Chiralpak AD-H column.
The above results have been rationalized by a transition state
model shown in Fig. 2.1a,5a The initial attack of copper(II) benzoate
on the allylic radical can produce two diastereomeric allyl adducts.
In a favorable transition state assembly, copper benzoate may
attain an orientation to provide a p-stacking of the two aromatic
nation of chiral ligands and peresters was desired in order to get
high enantioselectivity. In the case of cyclopentene, a combination
of either 1a or 1b and tert-butyl o-methoxyperbenzoate was more
compatible (80% ee; entry 4). For cycloheptene, a combination of
1b and tert-butyl p-methoxyperbenzoate was quite suitable (94%
ee) in the allylic oxidation reaction (entry 7). Cyclooctene gave
the highest enantioselectivity (96% ee) with a combination of 1a
and tert-butyl p-methoxyperbenzoate (entry 11). Similarly, high
enantioselectivity (95–96% ee) was obtained in the allylic oxidation
of 1,3-cyclooctadiene with a combination of the chiral ligand 1a
or 1b and tert-butyl p-methoxyperbenzoate (entry 15).7
The allylic oxidation of 1,5-cyclooctadiene with tert-butyl-p-
methoxyperbenzoate, under the above conditions, using catalyst
1a and 1b gave a mixture of products 2a and 2b. The optical purity
of these products was 93–94% (Table 3).7
The allylic oxidation of cis and trans mixture of Cyclododecene
was also studied with the catalyst 1a and 1b using tert-butyl-p-
methoxyperbenzoate and a mixture of cis (3a) and trans (3b) allylic
oxidation products was obtained. Under the optimal condition,
3b was obtained with maximum of 57% ee using the chiral ligand
1b (Table 4).7
rings. Since the distance between both the rings is approximately
5a
˚
3.5 A, there might be some attractive interaction which would
stabilize the drawn conformation. In this case, the allylic radical
will approach the Cu species from the less hindered side as
shown. The benzoate oxygen attacks the allylic carbon, which is
electrophilic in nature due to coordination of the incipient double
bond with the copper species leading to the (S)-enantiomer as the
major product. If the olefin approaches the Cu(II) benzoate ester in
an alternative way (unfavored), severe non-bonding interactions of
the aryl group and the olefin with substituents at the chiral centers
make it difficult. Some support for our assumption of p-stacking
of the two aromatic rings in the transition state comes from the
results of chiral ligands 1h and 1i, which lacked gem-diphenyl rings.
We observed that either by increasing the distance of phenyl ring
by one carbon or removing it from the C-5 carbon of the oxazoline
ring, p-stacking gets disturbed and hence enantioselectivity drops
down (Table 1, entries 42–47).
Although high enantioselectivities were obtained for most of the
cyclic olefins, the reaction was not effective for acyclic olefins. As
summarized in Table 5, 1-octene under optimal conditions with
tert-butyl-p-methoxyperbenzoate gave an inseparable mixture of
4a and 4b with poor enantioselectivity (31% ee).
Table 4 Enantioselective allylic oxidation of a cis and trans mixture of
cyclododecene using ligands 1a and 1ba
Yield (%)
ee (%)b
Fig. 2 Transition state models.
Entry
L*
Time/h
3a
3b
3a
3b
If the p–p stacking is involved in the reaction, we should have got
better results when X was nitro or halo. But, it was not the case. In
fact, we got better results when X was a methoxy group. It was also
surprising that pentafluoro groups on the phenyl ring gave very
poor results. These anomalies can be rationalized using the same
1
2
1a
1b
12
5
13
14
37
40
17
06
56
57
a 5 mol% of the chiral ligand was used. b Enantiomeric excess was
determined by HPLC using a Chiralpak AD-H column.
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models (Fig. 2). When X is such a group which provides better p–p
stacking, it can also move to some extent towards the left side and
show attractive interaction with the phenyl group on the left hand
side of the ligand. This attractive interaction outweighs the steric
repulsion caused by the alkyl group on the chiral carbon. Under
this arrangement, the ‘O’ of the peroxy group would attack the
other face of the olefin giving rise to the (R)-enantiomer, resulting
in lowering of the ee of the (S)-enantiomer. This is the reason
the pentafluoro substituted phenyl ring is not effective in giving
a high ee in the reaction. Electron donating groups such as alkyl
and methoxy behave like a simple phenyl group that provides
optimum stacking which is not strong enough to outweigh steric
repulsion with the alkyl group at the chiral center. This is the
reason it orients only in the right hand side giving products in
high ee’s. The model also fits well for the effect of substituents on
chiral centers. When R is i-Pr (1a), s-Bu (1b), and t-Bu (1g), we get
high enantioselectivity. However, substituents such as i-Bu (1c), Bn
(1d), and Me (1e), gave poor results because the steric repulsion
shown in Fig. 2 is not enough to outweigh the p-stacking. It is very
surprising that the ligands having R as a phenyl group gave very
poor enantioselectivity (<20% ee). This could be because of the
planarity of the ring, it orients in a manner to provide less steric
repulsion in the transition state.
Evaporations of solvents were performed at reduced pressure.
Tetrahydrofuran (THF) was distilled from sodium benzophenone
ketyl under nitrogen. Dichloromethane was distilled from CaH2
and acetone was distilled from anhydrous potassium carbonate
under nitrogen.
2,6-Bis[5ꢀ,5ꢀ-diphenyl-4ꢀ-(S)-sec-butyloxazolin-2ꢀ-yl]
pyridine
(1b). This was prepared as per the general procedure5c from
pyridine dicarboxylic acid and (S)-isoleucine to afford the product
1b as a white amorphous solid; yield 70%; mp 77–79 ◦C; Rf 0.52
(1 : 2, EtOAc in petroleum ether); [a]2D5 −337.3 (c 1.2, CHCl3);
mmax/cm−1 (solid) 3060, 3028, 2961, 1656, 1454, 1372, 1129, 956
and 755; dH (400 MHz; CDCl3; Me4Si) 0.48 (6H, t, J = 7.3 Hz, 2 ×
CH2CH3), 1.07 (6H, d, J = 6.6 Hz, 2 × CHCH3), 1.23–1.30 (4H,
m, 2 × CH3CH2CH), 1.56–1.64 (2H, m, 2 × CH3CHCH2), 4.94
(2H, d, J = 4.4 Hz, 2 × NCHCH), 7.21–7.38 (16H, m, Ar), 7.60
(4H, d, J = 7.6 Hz, Ar), 7.96 (1H, t, J = 7.8 Hz, Ar), 8.21 (2H,
d, J = 7.8 Hz, Ar); dC (100 MHz; CDCl3; Me4Si) 11.4, 18.0, 23.9,
36.7, 80.4, 93.6, 125.4, 126.2, 126.9, 127.2, 127.6, 127.8, 128.3,
137.5, 140.3, 145.1, 146.9, 160.2. Anal. calcd for C43H43N3O2: C,
81.48; H, 6.84; N, 6.63. Found: C, 81.23; H, 7.02; N, 6.70%.
2,6-Bis[5ꢀ,5ꢀ-diphenyl-4ꢀ-(S)-isobutyloxazolin-2ꢀ-yl] pyridine (1c).
This was prepared as per our general procedure5c from pyridine
dicarboxylic acid and (S)-leucine to afford th◦e product 1c as a
white amorphous solid; yield 72%; mp 80–82 C; Rf 0.61 (1 : 2,
EtOAc in petroleum ether); [a]2D5 −372.7 (c 1.0, CHCl3); mmax/cm−1
(solid) 3060, 3030, 2955, 1658, 1455, 1373, 1131, 966 and 751; dH
(400 MHz; CDCl3; Me4Si) 0.86 (6H, d, J = 5.6 Hz, 2 × CHCH3),
1.01 (6H, d, J = 5.6 Hz, 2 × CHCH3), 1.04–1.16 (4H, m, 2 ×
CHCH2CH), 1.99–2.09 (2H, m, 2 × CH3CHCH3), 5.03 (2H, dd,
J = 11.2 and 3.4 Hz, NCHCH2), 7.18–7.34 (12H, m, Ar), 7.39
(4H, t, J = 7.6 Hz, Ar), 7.57 (4H, d, J = 8.0 Hz, Ar), 7.95 (1H,
t, J = 7.6 Hz, Ar), 8.21 (2H, dd, J = 7.8 and 1.3 Hz, Ar); dC
(100 MHz; CDCl3; Me4Si) 21.6, 23.9, 25.3, 43.1, 73.4, 93.6, 125.6,
126.4, 126.8, 127.4, 127.8, 127.9, 128.4, 137.6, 140.6, 144.2, 147.3,
160.5. Anal. calcd for C43H43N3O2: C, 81.48; H, 6.84; N, 6.63.
Found: C, 81.63; H, 6.99; N, 6.75%.
Conclusions
We have investigated enantioselective allylic oxidation of a variety
of cyclic olefins with copper complexes of different pybox ligands
with various peresters. We have shown that high enantioselectivity
(98% ee for cyclohexene; 96% ee for cyclooctene and 1,3-
cyclooctadiene; 94% ee for cycloheptene and 1,5-cyclooctadiene;
80% ee for cyclopentene) can be achieved in the allylic oxidation of
cyclic olefins to allylic esters by choosing a unique combination of
a chiral ligand and a perester at room temperature. The presence
of a gem-diphenyl group at C-5 and a secondary or tertiary alkyl
substituent at the chiral center at C-4 of the oxazoline rings is
crucial for high enantioselectivity. A stereochemical outcome of
the reaction is also discussed with the help of a transition state
model.
2,6-Bis[5ꢀ,5ꢀ-diphenyl-4ꢀ-(S)-tert-butyloxazolin-2ꢀ-yl]
pyridine
(1g). This was prepared as per our general procedure5c from
pyridine dicarboxylic acid and (S)-tert-leucine to afford the
product 1g as a white amorphous solid; yield 80%; mp 221–
Experimental
◦
223 C; Rf 0.58 (1 : 2, EtOAc in petroleum ether); [a]2D5 −347.2
(c 1.0, CHCl3); mmax/cm−1 (solid) 3057, 3027, 2944, 1656, 1566,
1446, 1226, 1158, 964 and 748; dH (400 MHz; CDCl3; Me4Si) 0.90
(18H, s, 6 × CCH3), 4.90 (2H, s, NCHC), 7.25 (9H, m, Ar), 7.36
(3H, t, J = 7.3 Hz, Ar), 7.40–7.43 (4H, m, Ar), 7.69 (4H, d, J =
7.3 Hz, Ar), 7.95 (1H, t, J = 7.8 Hz, Ar), 8.23 (2H, d, J = 7.8 Hz,
Ar); dC (100 MHz; CDCl3; Me4Si) 28.0, 35.5, 83.1, 93.9, 125.5,
126.5, 127.2, 127.5, 127.8, 128.2, 128.7, 137.5, 140.0, 146.1, 147.0,
160.2; Anal. calcd for C43H43N3O2: C, 81.48; H, 6.84; N, 6.63.
Found: C, 81.55; H, 6.96; N, 6.55%.
General methods
Chemicals were purchased and used without further purification.
1H, 13C and 19F NMR spectra were recorded on a JEOL JNM-
LA 400 spectrometer. All chemical shifts are quoted on the d
scale, with TMS as internal standard, and coupling constants are
reported in Hz. Routine monitoring of reactions was performed
by TLC, using 0.2 mm Kieselgel 60 F254 precoated aluminium
sheets, commercially available from Merck. Visualization was
done by fluorescence quenching at 254 nm, or by exposure to
iodine vapor. All the column chromatographic separations were
done by using silica gel (Acme’s, 60–120 mesh). HPLC was done
on a Daicel chiral column having 0.46 cm internal diameter ×
25 cm length. Petroleum ether used was of boiling range 60–
80 ◦C. Reactions that needed anhydrous conditions were run under
an atmosphere of nitrogen or argon using flame-dried glassware.
The organic extracts were dried over anhydrous sodium sulfate.
2,6-Bis[5ꢀ,5ꢀ-dibenzyl-4ꢀ-(S)-isopropyloxazolin-2ꢀ-yl]
pyridine
(1h). This was prepared as per our general procedure5c from
pyridine dicarboxylic acid and (S)-valine to afford the product
1h as a white amorphous solid; yield 85%; mp 80–82 ◦C; Rf 0.45
(1 : 2, EtOAc in petroleum ether); [a]2D5 +227.9 (c 1.0, CHCl3);
mmax/cm−1 (solid) 3060, 3026, 2922, 1664, 1571, 1490, 1443, 1168,
1138, 979 and 759; dH (400 MHz; CDCl3; Me4Si) 1.19 (6H, d, J =
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6.6 Hz, 2 × CHCH3), 1.26 (6H, d, J = 6.6 Hz, 2 × CHCH3), 2.13
(2H, m, 2 × CH3CHCH3), 2.77 (2H, d, J = 14.6 Hz, CH2Ph),
2.88 (2H, d, J = 14.1 Hz, CH2Ph), 3.32 (4H, m, 2 × CH2Ph), 3.66
(2H, d, J = 10 Hz, NCHCH), 7.10–7.20 (8H, m, Ar), 7.22–7.35
(12H, m, Ar), 7.92–8.02 (3H, m, Ar); dC (100 MHz; CDCl3;
Me4Si) 21.2, 21.8, 28.2, 39.7, 42.2, 76.3, 90.7, 124.9, 126.5, 128.0,
128.2, 131.0, 131.1, 136.2, 136.6, 137.5, 147.2, 159.6; Anal. calcd
for C45H47N3O2: C, 81.66; H, 7.16; N, 6.35. Found: C, 81.79; H,
7.05; N, 6.41%.
0.06 mmol), and the mixture was stirred for 30 min. During this
time, the color of the solution changed to dark brown, giving
an indication for the reduction of Cu(II) to Cu(I) species. Then,
an olefin (10 mmol) was added followed by a dropwise addition
of a perester (1 mmol) under N2 atmosphere. After few minutes,
the color of the solution changed to green. The reaction mixture
was left at room temperature until the reaction was complete
(disappearance of the perester by TLC) during which time the
color of the reaction mixture again changed to dark brown. After
the reaction was over, the solvent was removed in vacuo and the
crude product was purified by column chromatography using silica
gel.
General procedure for the synthesis of peresters
Caution! Peroxy compounds present a serious detonation hazard.
While peresters are not nearly as reactive as peracids, use of a
teflon coated spatula for solid material is recommended.
Ethyl chloroformate (0.4 mL, 5 mmol) was added dropwise
to a solution of an acid (5 mmol) and triethylamine (0.7 mL,
5 mmol) in CH2Cl2 (15 mL) at 0 ◦C under N2 atmosphere. After
stirring the reaction mixture for 30 min, triethylamine (0.7 mL,
5 mmol) was again added. Then, tert-butyl hydroperoxide (5–6 M
in nonane, 1.1 mL, 6 mmol) was added dropwise to the solution
while maintaining the same temperature. The reaction was warmed
to room temperature and then stirred for 12 h. It was diluted
with some CH2Cl2 and washed with aqueous NaHCO3, water,
and brine. The organic layer was dried (Na2SO4) and the solvent
was evaporated on a rotary evaporator to get a crude yellow liquid,
which was purified over silica gel by column chromatography (65–
85% yield).
Acknowledgements
V.K.S. thanks the Department of Science and Technology, India
for a research grant. S.K.G. thanks the Council of Scientific and
Industrial research, New Delhi, for a Senior Research Fellowship.
We thank Dr J. N. Moorthy from our department for useful
discussions on the transition state models.
References
1 For reviews in this area, see: (a) M. B. Andrus and J. C. Lashley,
Tetrahedron, 2002, 58, 845–866, and references cited therein; (b) R. M.
Kamble, G. Sekar, M. Chandrasekhar and V. K. Singh, PINSA–A: Proc.
Indian Nat. Sci. Acad., Part A, 2002, 68, 423–433; (c) J. Eames and
M. Watkinson, Angew. Chem., Int. Ed., 2001, 40, 3567–3571; (d) J.-M.
Brunel, O. Legrand and G. Buono, C. R. Acad. Sci., Ser. IIc: Chim.,
1999, 19–23.
tert-Butyl 2,6-difluoroperbenzoate. This compound was pre-
pared following the general procedure described above using 2,6-
difluorobenzoyl chloride; yield 80%; mmax/cm−1 (film) 3105, 3071,
2984, 1775, 1469, 1242, 1080, 1010, 795; dH (400 MHz; CDCl3;
Me4Si) 1.40 (9H, s, 3 × CCH3), 7.00 (2H, t, J = 8.6 Hz, Ar),
7.46–7.50 (1H, m, Ar); dC (100 MHz; CDCl3; Me4Si) 25.8, 84.4,
111.8, 112.0, 133.6, 159.0, 161.6.
2 (a) J. Bayardon, D. Sinou, M. Guala and G. Desimoni, Tetrahedron:
Asymmetry, 2004, 15, 3195–3200; (b) J. S. Clark, M.-R. Clarke, J. Clough,
A. J. Blake and C. Wilson, Tetrahedron Lett., 2004, 45, 9447–9450.
3 (a) A. S. Gokhale, A. B. E. Minidis and A. Pfaltz, Tetrahedron Lett.,
1995, 36, 1831–1834; (b) M. B. Andrus, A. B. Argade, X. Chen and M. G.
Pamment, Tetrahedron Lett., 1995, 36, 2945–2948; (c) M. B. Andrus and
X. Chen, Tetrahedron, 1997, 53, 16229–16240; (d) M. B. Andrus, D.
Asgari and J. A. Sclafani, J. Org. Chem., 1997, 62, 9365–9368; (e) M. B.
Andrus and D. Asgari, Tetrahedron, 2000, 56, 5775–5780; (f) M. B.
Andrus and Z. Zhou, J. Am. Chem. Soc., 2002, 124, 8806–8807; (g) J. S.
Clark and C. Roche, Chem. Commun., 2005, 5175–5177.
4 (a) K. Kawasaki, S. Tsumura and T. Katsuki, Synlett, 1995, 1245–1246;
(b) K. Kawasaki and T. Katsuki, Tetrahedron, 1997, 53, 6337–6350; (c) Y.
Kohmura and T. Katsuki, Tetrahedron Lett., 2000, 41, 3941–3945.
5 (a) A. DattaGupta and V. K. Singh, Tetrahedron Lett., 1996, 37, 2633–
2636; (b) G. Sekar, A. DattaGupta and V. K. Singh, J. Org. Chem., 1998,
63, 2961–2967; (c) S. K. Ginotra and V. K. Singh, Tetrahedron, 2006, 62,
3573–3581.
6 For a review on p-stacking in asymmetric synthesis see: (a) G. B. Jones
and B. J. Chapman, Synthesis, 1995, 475–497; (b) S. V. Lindeman, D.
Kosynkin and J. K. Kochi, J. Am. Chem. Soc., 1998, 120, 13268–13269;
(c) C. A. Hunter, K. R. Lawson, J. Perkins and C. J. Urch, J. Chem. Soc.,
Perkin Trans. 2, 2001, 651–669; (d) W. B. Jennings, B. M. Farrell and J. E.
Malone, Acc. Chem. Res., 2001, 34, 885–894; (e) S. Tsuzuki, K. Honda,
T. Uchimaru, M. Mikami and K. Tanabe, J. Am. Chem. Soc., 2001, 124,
104–112; (f) E. A. Meyer, R. K. Castellano and F. Diederich, Angew.
Chem., Int. Ed., 2003, 42, 1210–1250.
tert-Butyl pentafluoroperbenzoate. This compound was pre-
pared following the general procedure described above using
2,3,4,5,6-pentafluorobenzoyl chloride; yield 82%; mmax/cm−1 (film)
2987, 1778, 1502, 1323, 1178, 1000, 774; dH (400 MHz; CDCl3;
Me4Si) 1.40 (9H, s, 3 × CCH3); dC (100 MHz; CDCl3; Me4Si) 25.8,
85.1, 156.5; dF (376 MHz; CDCl3; Me4Si) −156.82 to −156.93 (2F,
m), −166.95 to −167.1 (1F, m), −179.79 to −179.45 (2F, m).
General procedure for enantioselective allylic oxidation of olefins
with peresters in the presence of PhNHNH2 using a complex of
chiral ligands and Cu(OTf)2
A solution of a chiral ligand (0.06 mmol) and Cu(OTf)2 (18.1 mg,
0.05 mmol) in acetone (4 mL) was stirred at room temperature
for 1 h. To this colored (green for 1a, 1b, 1d, 1f, 1g and 1h;
blue for 1c, 1e and 1i) solution was added phenylhydrazine (6 lL,
7 The absolute stereochemistry is temporarily assigned based on other
cyclic olefins.
4374 | Org. Biomol. Chem., 2006, 4, 4370–4374
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The Royal Society of Chemistry 2006
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