Copper-catalyzed regioselective allylic oxidation of olefins via C–H activation

Article abstract of DOI:10.1016/j.tetlet.2017.09.047

A regioselective oxidation of allylic C–H bond to C–O bond catalyzed by copper (I) was developed with diacyl peroxides as oxidants. The oxidation of allylic C–H bond was accomplished with good yield and regioselectivity under mild reaction conditions. This method has a broad substrate scope including cyclic olefins, terminal and internal acyclic olefins and allyl benzene compounds. The reaction proceeds by a radical mechanism as suggested by spin trapping experiments.

Full text of DOI:10.1016/j.tetlet.2017.09.047

Accepted Manuscript
Copper-Catalyzed Regioselective Allylic Oxidation of Olefins via C-H Activa-
tion
Nengbo Zhu, Bo Qian, Haigen Xiong, Hongli Bao
PII:
S0040-4039(17)31174-7
DOI:
http://dx.doi.org/10.1016/j.tetlet.2017.09.047
TETL 49317
Reference:
Tetrahedron Letters
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Revised Date:
Accepted Date:
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12 September 2017
16 September 2017
Please cite this article as: Zhu, N., Qian, B., Xiong, H., Bao, H., Copper-Catalyzed Regioselective Allylic Oxidation
of Olefins via C-H Activation, Tetrahedron Letters (2017), doi: http://dx.doi.org/10.1016/j.tetlet.2017.09.047
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Copper-Catalyzed Regioselective Allylic
Oxidation of Olefins via C-H Activation
Leave this area blank for abstract info.
Nengbo Zhu, Bo Qian, Haigen Xiong, and Hongli Bao*

1
Tetrahedron Letters
jo u r n a l h o m e p a g e : w w w . e ls e v ie r . c o m
Copper-Catalyzed Regioselective Allylic Oxidation of Olefins via C-H Activation
Nengbo Zhu, Bo Qian, Haigen Xiong, and Hongli Bao*
Key Laboratory of Coal to Ethylene Glycol and Its Related Technology, State Key Laboratory of Structural Chemistry, Fujian Institute of Research on
the Structure of Matter, University of Chinese Academy of Sciences, 155 Yangqiao Road West, Fuzhou, Fujian 350002, People's Republic of China. E-
mail: hlbao@fjirsm.ac.cn
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A regioselective oxidation of allylic C-H bond to C-O bond catalyzed by copper (I) was
developed with diacyl peroxides as oxidants. The oxidation of allylic C-H bond was
accomplished with good yield and regioselectivity under mild reaction conditions. This
method has a broad substrate scope including cyclic olefins, terminal and internal acyclic olefins
and allyl benzene compounds. The reaction proceeds by a radical mechanism as suggested by
spin trapping experiments.
Available online
Keywords:
Allylic oxidation
Olefin
Regioselective
Diacyl peroxides
Copper catalysis
Allylic radical
The direct functionalization of C-H bond is a key task in
modern organic chemistry.1 Allylic oxidation2 of olefins is a
typical C-H bond functionalization reaction which could directly
convert C-H bond into diverse functional groups.3 Allylic esters4
are important intermediates which can be converted into allylic
alcohols5 and provide facile access to a variety of valuable
compounds.6 The first copper-catalyzed allylic oxidation7 of
olefins with perester was published by Kharasch and Sosnovsky
in 1959.8 As a useful tool for direct C-H bond functionalization at
the allylic position of olefins, Kharasch-Sosnovsky reaction has
been further developed by many researchers.9 The results for
cyclic olefins9f are excellent (Scheme 1a).10 However, the yields
for acyclic olefins are unsatisfying.10 The best yield for allylic C-
H oxidation was 54% using 10 equivalents of acyclic olefin
(Scheme 1a).10e In 2005, White and coworkers developed a
palladium-catalyzed allylic oxidation system affording branched
products with morderate yield (Scheme 1b).6d Very recently,
Hartwig and coworkers reported oxidation of hindered alkenes to
form linear allylic esters (Scheme 1b).6e Herein, we report a
copper-catalyzed regioselective allylic oxidation of olefins with
high yield and broad substrate scope including cyclic olefins,
terminal and internal acyclic olefins and allyl benzene
compounds (Scheme 1c).
using CuBr as the catalyst, the ratio of olefin: oxidant: catalyst
was investigated. To our delight, when the ratio of olefin: oxidant:
catalyst was 1: 1.5: 0.1, the reaction gave 71% yield and good
regioselectivity (B/L is 8.2:1) (entry 12).
We initiated our studies by adopting benzoyl peroxide as the
oxidant in the presence of various catalysts for the oxidation of 1-
octene and the results are summarized in Table 1. During
preliminary catalyst screening, CuBr and CuBr2 were found
effective in this system, gave the desired products in 61% and
Scheme 1. Allylic C-H oxidation reactions: (a) Examples of
traditional Kharasch and Sosnovsky reactions. (b) Examples of
Palladium catalyzed allylic C-H oxidation reactions. (c) This
work.
o
58% yield, respectively (entries 5 and 6). It was found that 70 C
was the best reaction temperature when different temperatures
o
were investigated using CuBr as catalyst (entries 6-8). At 70 C

2
Tetrahedron
Under the optimized reaction conditions, the scope of
oxidants was evaluated with 1-octene (Table 2). In general, the
oxidants with the different substituents on the phenyl group can
be transformed into the desired products with moderate yields
and regioselectivities. The oxidants having 3-methyl and 3,5-
dimethyl substituents gave 69% and 62% yields, respectively
(entries 2 and 3). The oxidants with 4-fluoro and 4-chloro groups
delivered the corresponding products in 62% and 72% yields,
respectively (entries 6 and 7). Interestingly, sterically bulky 2-
naphthoic peroxyanhydride (2j) can also be used as an oxidant
for the reaction, although the yield and regioselectivitiy were
lower than those of benzoyl peroxides (entry 9).
5
51
4.2:1
6
7
8
62
72
49
4.6:1
7:1
4.6:1
Table 1. Reaction conditions optimization. [a]
9
32
4.6:1
[a] The reaction was conducted on a 0.5 mmol scale in 4 mL 1,2-
dichlorobenzene under argon atmosphere. [b] Isolated yield. [c] Determined
by 1H NMR.
Entry Catalyst
(mol%)
Temp.
(°C)
70
Olefin/
Oxidant (%)[b]
Yield
3a/
4a[c]
We next examined the scope of olefins (Table 3). A range of
acyclic terminal olefins reacted smoothly and afforded the
corresponding products in moderate to good yields (entries 1-5).
Notably, TBS group is tolerated under the reaction condition.
Moreover, the cyclic olefins, such as cyclohexene and 1,3-
cyclooctadiene delivered allylic oxidation products in 71% and
57% yields, respectively (entries 6 and 7). 1,1-Disubstituted
olefin 5h 1-methylenecyclohexane (entry 8) afforded the
products in 50% yield with moderate regioselectivity
(6h/7h=3.7:1). It is worth noting that the internal olefins worked
well in this system. (E)-3-hexene gave 71% yield and 1:1 mixture
of two phenyl esters was formed (entry 9). The substrate with
two terminal alkenes (1,7-octadiene, entry 10) was studied and
gave mono-fuctionalization products in moderate yield ( 53%,
6j/7j=5:1). Methyl 10-undecenoate (5k) afforded the desired
products in 64% yield with B/L=8.7:1. Finally, (but-3-
enyloxy)benzene (5l) and (hept-6-enyloxy)benzene (5m) were
examined and obtained corresponding products in moderate
yields and regioselectivities.
1
CuTc (10)
CuOTf (10)
NiCl2 (10)
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1.5
1:1.5
7
0.6:1
2
70
70
ND
Trace
13
3
4
Pd(TFA)2 (10) 70
0.6:1
8.0:1
7.3:1
7.2:1
7.1:1
6.5:1
8.4:1
8.2:1
5
CuBr2 (10)
CuBr (10)
CuBr (10)
CuBr (10)
CuBr (5)
CuBr (15)
CuBr (10)
None
70
70
60
80
70
70
70
70
58
6
61
7
38
8
46
9
60
10
12
13
55
71[d]
ND
Table 3. Scope of alkenes[a].
[a] The reaction was conducted on a 0.5 mmol scale in 4 mL 1,2-
diclorobenzene under argon atmosphere. [b] GC yield (1,4-
Dimethoxybenzene as internal standard). [c] Determined by GC. [d] Isolated
yield.
Table 2. Scope of benzoyl peroxides.[a]
Products,
Entry
1
Olefins
yield of 6+7(%)[b]
and ratio of 6/7[c]
Yield of
Entry
1
Benzoyl peroxide
3/4[c]
(3+4)[b](%)
51
5.7:1
2
2
3
69
62
8.3:1
4.6:1
3
4
4
46
1.5:1

3
The previous reports13 and the results of mechanistic
experiments are consistent with a radical pathway for allylic
oxidation and two plausible pathways mechanism are proposed
(Scheme 3). The reaction started with the homolysis of benzoyl
peroxide under heating conditions (with or without the
involvement of the copper catalyst) to afford benzoyloxy
radical14 (I). The Cu(I) species is oxidized by benzoyloxy radical
to offer the copper(II) benzoate15 (intermediate II) and another
molecule of benzoyloxy radical abstracts an allylic hydrogen
atom to give benzoic acid and allylic radical (III). In path a,
Cu(II) benzoate species II transfers benzoyloxy group to the
allylic radical III to form the desired products and regenerate the
Cu(I). An alternative pathway involves copper (III) benzoate
species16 (intermediate IV). The last step is the reductive
elimination of the intermediate IV affording allylic ester products
and regenerating copper (I) catalyst.
5
6
7
8
9
10
11
Scheme 3. Proposed catalytic cycle for oxidation of allylic C-H bond.
12
13
In conclusion, we have developed a practical method for the
allylic C-H oxidation of olefins, including acyclic terminal,
acyclic internal and cyclic olefins. This is an atom efficient
reaction using one equivalent of alkene and commercially
available oxidant (BPO) to deliver the corresponding products in
moderate to good yields. Functional groups like TMS, TBS, ester,
and ether were tolerated.
[a] The reaction was conducted on a 0.5 mmol scale in 4 mL 1,2-
dichlorobenzene under argon atmosphere.[b] Isolated yield. [c] Determined
by 1H NMR. [d] Determined by GC.
Acknowledgments
To explore the reaction mechanism, several experiments were
carried out. Initially, when TEMPO11 was added into the reaction,
no desired products were observed. Next, with NHPI12 (N-
hydroxyphthalimide), the anticipated products 3a ， 4a and a
NHPI adduct 8 were isolated in 41%, 3% and 14% yield,
respectively (scheme 2). Compound 8 presumably arises from the
formation of a nitroxyl radical form NHPI under the reaction
conditions.
We thank NSFC (grant no. 21402200), Strategic Priority
Research Program of the Chinese Academy of Sciences (Grant
No. XDB20000000), The 100 Talents Program, “The 1000
Youth Talents Program” for financial support.
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5
Highlights
(1) It’s a convenient and practical protocol for
the oxidation of allylic C-H bond.
(2) Acyclic terminal and internal olefins,
cyclic olefins work well in this system.
(3) Functional groups like TMS, TBS, ester,
and ether are tolerated.

6
Tetrahedron