Copper-catalyzed enantioselective allylic oxidation of acyclic olefins

Article abstract of DOI:10.1016/j.tetlet.2013.03.046

A copper-catalyzed asymmetric allylic oxidation of acyclic olefins has been developed. By using the complexes of copper and chiral spiro bisoxazoline ligands as catalysts, the oxidation of various acyclic olefins was accomplished with excellent regioselec

Full text of DOI:10.1016/j.tetlet.2013.03.046

Tetrahedron Letters 54 (2013) 2665–2668
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Copper-catalyzed enantioselective allylic oxidation of acyclic olefins
⇑
⇑
Bo Zhang, Shou-Fei Zhu , Qi-Lin Zhou
State Key Laboratory and Institute of Elemento-Orgainc Chemistry, Nankai University, Tianjin 300071, China
a r t i c l e i n f o
a b s t r a c t
Article history:
A copper-catalyzed asymmetric allylic oxidation of acyclic olefins has been developed. By using the com-
plexes of copper and chiral spiro bisoxazoline ligands as catalysts, the oxidation of various acyclic olefins
was accomplished with excellent regioselectivity (>20:1 in most cases) and up to 67% ee under mild reac-
tion conditions, which represents one of the best results for the enantioselective allylic oxidation of acy-
clic olefins.
Received 9 January 2013
Revised 25 February 2013
Accepted 8 March 2013
Available online 19 March 2013
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Asymmetric allylic oxidation
Acyclic olefin
Copper catalysis
Chiral spiro ligands
Introduction
Recently we developed a copper-catalyzed asymmetric allylic
oxidation, Kharasch–Sosnovsky reaction, of cyclic olefins with high
The direct functionalization of C–H bonds is one of the most
valuable and challenging tasks in organic synthesis.1 Allylic oxida-
tion of olefins is a typical C–H bond functionalization reaction.
Such reaction can convert simple olefins, the industrial feedstocks,
into allylic alcohols, which are very useful building blocks for the
synthesis of complex molecules and key intermediates in the pro-
ductions of many fine chemicals. The copper-catalyzed allylic oxi-
dation of olefins with peresters, known as Kharasch–Sosnovsky
reaction, represents a powerful tool for direct C–H bond function-
alization at the allylic position of olefins.2 Although the asymmet-
ric Kharasch–Sosnovsky reaction of cyclic olefins has been
developed with high enantioselectivities,3 the results for acyclic
olefins are unsatisfied. Not only the enantioselectivity, but also
the regioselectivity (the ratio of branched product 3 and linear
product 30, b/l, Scheme 1) of the Kharasch–Sosnovsky reaction of
acyclic olefins is a difficult issue.4 To date, the highest enantiose-
lectivity for the Kharasch–Sosnovsky reaction of acyclic olefins is
40% ee with very low regioselectivity (R = Ph, b/l = 47:53).4c In
addition to Kharasch–Sosnovsky reaction, other allylic oxidation
reactions of acyclic olefins also lack efficient catalysts. For example,
in the palladium-catalyzed asymmetric allylic oxidation of acyclic
olefins the enantioselectivity (63% ee) and the regioselectivity (b/
l = 4.4:1) are only moderate.5 Therefore, the development of effi-
cient allylic oxidation reaction of acyclic olefins with high selectiv-
ity is highly desired.
reactivity and good enantioselectivity.6 Herein, we report an enan-
tioselective Kharasch–Sosnovsky reaction of acyclic olefins cata-
lyzed by the copper complexes of chiral spiro bisoxazoline
ligands. The reaction exhibited as high as 20:1 of b/l regioselectiv-
ity and up to 67% ee of enantioselectivity, which represents one of
the best results for the catalytic enantioselective allylic oxidation
of acyclic olefins.
Results and discussion
The asymmetric allylic oxidation of n-decene (1a) was first
studied with tert-butyl perbenzoate (TBPB, 2a) as oxidant in the
presence of copper(I) catalyst generated in situ from Cu(MeCN)4PF6
and chiral spiro bisoxazoline ligand (Ra,S,S)-4a (Table 1). To our de-
light, the reaction ran smoothly in acetone at 30 °C to afford the
branched allylic ester product 3a as almost the only oxidation
product. However, the enantioselectivity was only 22% ee (entry
1). Various chiral spiro bisoxazoline ligands having different sub-
stituents at 4-position of oxazoline rings were then examined in
the reaction (entries 2–8).7 Most of the ligands with aliphatic sub-
stituents at 4-position of oxazoline rings gave excellent regioselec-
tivities (3a/3a0 > 20:1) and higher enantioselectivities than the
ligand with phenyl groups ((Ra,S,S)-4a), with (Ra,S,S)-4f being the
best ligand (52% yield and 54% ee, entry 6). The ligand (Ra,S,S)-4e
bearing bulky isopropyl groups on oxazoline rings gave much low-
er yield and enantioselectivity (entry 5). The ligand (Sa,S,S)-4f gave
very low enantioselectivity comparing with its diastereoisomer
(Ra,S,S)-4f, implying that the configurations in the ligand (Sa,S,S)-
4f are mismatched for controlling the enantioselectivity of the
reaction (entry 9).
⇑
Corresponding author. Tel.: +86 22 2350 0011; fax: +86 22 2350 6177.
E-mail addresses: sfzhu@nankai.edu.cn (S.-F. Zhu), qlzhou@nankai.edu.cn (Q.-L.
Zhou).
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.03.046

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B. Zhang et al. / Tetrahedron Letters 54 (2013) 2665–2668
O
O
O
O
*
Ar
[Cu]/Ligand 4
O
+
+
Ar
O
tBu
R
O
Ar
R
R
2
3
3'
1
4a
R = Ph
R = Me
R = Et
O
4b
4c
4d
4e
4f
R
R
i
N
N
R = Bu
i
R = Pr
R = Bn
4g
4h
O
R = 1-naphthylmethyl
R = 2-naphthylmethyl
Scheme 1. Copper-catalyzed allylic oxidation of acyclic olefins with peresters.
Table 1
Table 2
Copper-catalyzed asymmetric allylic oxidation of n-decene: ligands evaluationa
Copper-catalyzed asymmetric allylic oxidation of n-decene: reaction conditions
investigationa
O
O
5 mol% Cu(MeCN)4PF6
O
Ph
O
6 mol % ligand 4
5 mol% [Cu]
O
Ph
O
O
+
C7H15
C7H15
Ph
O
tBu
*
6 mol% (Ra,S,S)-4f
acetone, 30 oC
O
+
Ph
O
tBu
C7H15
C7H15
1a
2a
3a
Solvent, Temp
1a
2a
3a
Entry
Ligand 4
Yieldb (%)
eec (%)
Entry [Cu]
Solvent Temp. (°C) 1a/2a Yieldb (%) ee (%)
1
2
3
4
5d
6
7
8
9
(Ra,S,S)-4a
(Ra,S,S)-4b
(Ra,S,S)-4c
(Ra,S,S)-4d
(Ra,S,S)-4e
(Ra,S,S)-4f
(Ra,S,S)-4g
(Ra,S,S)-4h
(Sa,S,S)-4f
51
47
43
40
21
52
50
46
30
22 (S)
47 (R)
30 (R)
47 (R)
13 (R)
54 (R)
46 (R)
33 (R)
9 (S)
1
2
3
4
5
6
7
8
Cu(MeCN)4PF6
Cu(MeCN)4PF6
Cu(MeCN)4PF6
Cu(MeCN)4PF6
Cu(MeCN)4PF6
Cu(MeCN)4PF6
Cu(MeCN)4PF6
Cu(MeCN)4PF6
Acetone 30
Acetone 30
Acetone 30
Acetone 10
Acetone 60
10:1
5:1
52
38
51
40
25
49
36
39
52
52
54
37
54 (R)
52 (R)
52 (R)
38 (R)
11 (R)
45 (R)
33 (R)
30 (R)
48 (R)
47 (R)
43 (R)
24 (R)
20:1
10:1
10:1
10:1
10:1
10:1
10:1
10:1
10:1
10:1
MeCN
DCE
DCM
30
30
30
9
Cu(MeCN)4ClO4
(CuOTf)2ꢁtoluene Acetone 30
Acetone 30
a
Reaction conditions: Cu(MeCN)4PF6/ligand/1a/2a = 0.01:0.012:2:0.2 mmol, in
2 ml acetone at 30 °C for 3 days.
10
11c
12d
CuCl
Acetone 30
Acetone 30
b
Isolated yields based on the oxidant 2a. In all cases, 3a/3a0 are >20:1 according
Cu(OTf)2
to 1H NMR analysis.
c
a
b
c
Determined by chiral HPLC using a Chiralcel OD-H column. The absolute con-
The reaction conditions and analysis are the same as those of Table 1, entry 6.
In all cases, 3a/3a0 are >20:1 according to 1H NMR analysis.
6 mol % NaBArfꢁ3H2O was added.
figuration of the product was assigned through the comparison of the specific
rotation with literature data.
d
d
The oxidant 2a cannot be fully consumed at 30 °C in 3 days.
6 mol % PhNHNH2 was added.
By using (Ra,S,S)-4f as ligand, other parameters of the reaction
were investigated. When the ratio of olefin to oxidant was reduced
to 5:1, the yield of the reaction decreased (Table 2, entries 1–3).
The reaction is also sensitive to temperature. Both the yield and
the enantioselectivity of the reaction dropped when the reaction
was carried out at 10 °C and 60 °C (entries 4 and 5 vs entry 1).
The solvent remarkably affected the reactivity and enantioselectiv-
ity of the reaction (entries 6–8). The reaction can be performed in
acetone, acetonitrile (MeCN), 1,2-dichloroethane (DCE), and
dichloromethane (DCM), with acetone being the solvent of choice.
However, other solvents such as benzene, toluene, dimethylsulfox-
ide (DMSO), and tetrahydrofuran (THF) impeded the reaction (data
not shown). Various copper salts were also evaluated as catalyst
precursors. The ionic copper(I) salts Cu(MeCN)4ClO4 and CuOTf
gave almost the same level of yield and enantioselectivity as
Cu(MeCN)4PF6 (entries 9 and 10). The covalent copper(I) salt CuCl
was inert to the reaction, but became active after exchanging the
anion to BArꢀf (tetrakis(3,5-bis(trifluoromethyl)-phenyl)borate)
(entry 11). The copper(II) salt Cu(OTf)2 can be a catalyst precursor
only in the presence of reductant such as PhNHNH2 (entry 12).
Different peresters were tested in the copper-catalyzed asym-
metric allylic oxidation of n-decene. The substituents on the phe-
nyl group of the oxidant tert-butyl perbenzoates 2 remarkably
affected the reactivity and enantioselectivity of the reaction. The
oxidants having an electron-donating group at the para-position
such as tert-butyl 4-methylbenzoperoxoate (2b) and tert-butyl 4-
methoxybenzoperoxoate (2c) exhibited almost the same level of
reactivity and enantioselectivity as those of oxidant 2a (Table 3,
entries 1–3). However, the oxidant with a strong electron-with-
drawing group (2d) and the bulky oxidant, tert-butyl 2,6-dim-
ethylbenzoperoxoate (2h) showed very low reactivity and
enantioselectivity, and the reaction could not complete at 30 °C
in 3 days (entries 4 and 8). The peresters bearing substituents at
ortho-position, regardless electron-donating or electron-withdraw-
ing, gave lower yield and lower enantioselectivity (entries 5–7). In
addition to the perbenzoates, the benzoyl peroxide (BPO, 2i) can
also be used as an oxidant for the reaction albeit the yield and
enantioselectivity were lower than those of 2a (entry 9).
A variety of acyclic olefins were investigated in copper-cata-
lyzed asymmetric allylic oxidation under the optimal reaction con-
ditions. All the tested olefins afforded allylic oxidation products
with excellent regioselectivities except for allylcyclohexane (1c),
which gave a very low ratio of 3/30 (3:1, Table 4, entry 3). The elec-
tronic properties of the substituents of 1-allylarenes markedly af-
fect the reactivity and selectivity of the reaction (entries 4–6).
The electron-donating substituent (4-MeO, 1e) decreased both

B. Zhang et al. / Tetrahedron Letters 54 (2013) 2665–2668
2667
Table 3
Copper-catalyzed asymmetric allylic oxidation of n-decene: oxidants evaluationa
O
5 mol% Cu(MeCN)4PF6
6 mol% (Ra,S,S)-4f
O
Ar
O
oxidant
+
+
C7H15
C7H15
O
Ar
C7H15
acetone, 30 oC
2
1a
3
3'
Entry
Oxidant
3/30
Yield (%)
ee of 3 (%)
1
2
TBPB (2a)
>20:1
>20:1
>20:1
18:1
>20:1
>20:1
17:1
52
52
40
18
38
33
31
12
35
54 (R)
50 (R)
46 (R)
8 (R)
37 (R)
31 (R)
23 (R)
35 (R)
40 (R)
p-CH3-TBPB (2b)
p-OCH3-TBPB (2c)
p-NO2-TBPB (2d)
o-OCH3-TBPB (2e)
o-Cl-TBPB (2f)
o-NO2-TBPB (2g)
2,6-(CH3)2-TBPB (2h)
BPO (2i)
3
4b
5
6
7b
8b
9
17:1
>20:1
a
The reaction conditions and analysis are the same as those of Table 1, entry 6.
The oxidant 2 cannot be fully consumed at 30 °C in 3 days.
b
Table 4
Copper-catalyzed asymmetric allylic oxidation of acyclic olefinsa
O
5 mol% Cu(MeCN)4PF6
6 mol% (Ra,S,S)-4f
Ph
O
O
O
O
+
R
Ph
O
tBu
+
R
*
R
O
Ph
acetone, 30 o
C
1
3
3'
2a
Entry
R
3/30
Yield (%)
ee of 3 (%)
1
2
3
4
C7H15 (1a)
C3H7 (1b)
Cy (1c)
>20:1
13:1
3:1
>20:1
7:1
>20:1
>20:1
20:1
19:1
18:1
>20:1
>20:1
>20:1
52
50
33
64
55
37
57
55
35
43
36
23
55
54 (R)
34 (R)
24 (S)
40 (S)
17
67 (S)
46 (R)
48
40
45
27
10
C6H5 (1d)
5
4-MeOC6H4 (1e)
4-CF3C6H4 (1f)
TBSOC3H6 (1g)
BzOC3H6 (1h)
TBSOCH2 (1i)
BzOCH2 (1j)
CH3COCH2 (1k)
AcO (1l)
6b
7
8
9
10
11
12
13
TMS (1m)
13
a
The reaction conditions and analysis are the same as those of Table 1, entry 6.
The oxidant 2a cannot be fully consumed at 30 °C in 3 days.
b
regioselectivity and enantioselectivity (entry 5). On the contrary,
the electron-withdrawing group (4-CF3, 1f) gave the best
enantioselectivity (67% ee) albeit with lower conversion and yield
(entry 6). The ester groups, silylether groups, or acyl group in the
substrates can be tolerated in the reaction (entries 7–11). The
olefin substrates having an ester or silyl group directly conjunct
to the allylic position provided the desired product in low
enantioselectivities, but still in good regioselectivities (entries 12
and 13).
and understanding the detailed mechanism are undergoing in the
laboratory.
Experimental section
General information and materials
All reactions and manipulations were performed in a nitrogen
atmosphere using standard Schlenk techniques. The reactions
and manipulations for copper-catalyzed asymmetric allylic oxida-
tion could be performed in air, which gave the same level of reac-
tivity and selectivity. All solvents were purified and dried
according to standard procedures before use. CuCl, Cu(MeCN)4PF6,
and Cu(MeCN)4ClO4 were prepared according to the literatures.8
(CuOTf)2ꢁtoluene and Cu(OTf)2 were purchased from Aldrich Co.
and used directly. Peresters were prepared according to the litera-
ture.4b Benzoyl peroxide (2i) was purchased from Acros Co. and
used directly. The allylic substrates 1f–1i were prepared according
Conclusion
In conclusion, a copper-catalyzed enantioselective allylic oxida-
tion reaction of acyclic olefins was developed by using chiral spiro
bisoxazoline ligands. The reaction provides a direct approach to al-
lyl esters from acyclic olefins with excellent regioselectivity and
moderate enantioselectivity at mild reaction conditions. Further
efforts for achieving higher reactivity as well as enantioselectivity

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B. Zhang et al. / Tetrahedron Letters 54 (2013) 2665–2668
to the literature.9 Other olefins were commercial available and
were distilled before use.
References and notes
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Acknowledgments
We thank the National Natural Science Foundation of China, the
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Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2013.03.
046.