Organoselenium-Catalyzed Oxidative C=C Bond Cleavage: A Relatively Green Oxidation of Alkenes into Carbonyl Compounds with Hydrogen Peroxide

Article abstract of DOI:10.1021/acs.joc.7b01245

A relatively green oxidative C=C bond cleavage of alkenes was achieved by organoselenium-catalyzed alkene oxidation reaction in ethanol with hydrogen peroxide, affording carbonyl compounds under relatively mild conditions. It is a new reaction style for the organoselenium-catalyzed oxidation of alkenes and largely contributes to the growing field of organoselenium catalysis.

Full text of DOI:10.1021/acs.joc.7b01245

Subscriber access provided by Eastern Michigan University | Bruce T. Halle Library
Article
Organoselenium-Catalyzed Oxidative C=C Bond Cleavage: A Relatively Green
Oxidation of Alkenes into Carbonyl Compounds with Hydrogen Peroxide
Tingting Wang, Xiaobi Jing, Chao Chen, and Lei Yu
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b01245 • Publication Date (Web): 16 Aug 2017
Downloaded from http://pubs.acs.org on August 16, 2017
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a free service to the research community to expedite the
dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts
appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been
fully peer reviewed, but should not be considered the official version of record. They are accessible to all
readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered
to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published
in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just
Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor
changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers
and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors
or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
The Journal of Organic Chemistry is published by the American Chemical Society.
1155 Sixteenth Street N.W., Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 26
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
OrganoseleniumꢀCatalyzed Oxidative C=C Bond
Cleavage: A Relatively Green Oxidation of Alkenes
into Carbonyl Compounds with Hydrogen Peroxide
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
48
49
50
51
52
53
54
55
56
57
58
59
60
†
†
Tingting Wang, Xiaobi Jing, Chao Chen, and Lei Yu*
School of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou, Jiangsu
225002, China
ABSTRACT: A relatively green oxidative C=C bond cleavage of alkenes was achieved by
organoseleniumꢀcatalyzed alkene oxidation reaction in ethanol with hydrogen peroxide,
affording carbonyl compounds under relatively mild conditions. It is a new reaction style for the
organoseleniumꢀcatalyzed oxidation of alkenes and largely contributes to the growing field of
organoselenium catalysis.
ACS Paragon Plus Environment
1

The Journal of Organic Chemistry
Page 2 of 26
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
1
. INTRODUCTION
1
ꢀ4
Organoselenium catalysis is a unique topic just unfolding in recent years. It has attracted much
3
ꢀ4
attention in both academia and industry owning to its green features since, first of all, selenium
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1a,1c,3c,5
is a metabolizable element that does not accumulate in organisms and is very ecoꢀfriendly.
Secondly, organoseleniumꢀcatalyzed reactions are usually transition metalꢀfree, which can avoid
the heavy metal contaminant in the products. Moreover, organic selenium compounds are much
less toxic than inorganic selenium compounds. Among the frequently used organoselenium
6
catalysts, diselenides exhibit only moderate toxicity. In addition, organoselenium catalysts are
4aꢀe
very stable and can be recycled and reused for many times without deactivation. Regarding
the organoseleniumꢀcatalyzed oxidation reactions, H O is usually employed as the oxidant,
2
2
which is clean and will not generate other waste than the water. During the last three years, we
have achieved a series of organoseleniumꢀcatalyzed green transformations, such as the
4
b,4d,4f
4c
dihydroxylation of cyclohexenes,
BaeyerꢀVilliger oxidation of ketones, dehydration of
4
e
4a
aldoximes, and deoximation.
On the other hand, oxidation of alkenes is an important subject because of the broad
application scopes. It has also attracted much attention from organic chemists for the changeful
reaction selectivities. Generally, there are three paths for alkene oxidation (Scheme 1): The
7
allylic CꢀH oxidations lead to α,βꢀunsaturated ketones, aldehydes or alcohols, or heterocycles
8
for certain wellꢀdesigned substrates [Scheme 1, path (A)]; The oxidations of C=C bond produce
9
epoxides or 1,2ꢀdiols [Scheme 1, path (B)]; The oxidative scissions of alkenes are very
important transformations for the synthesis of carbonyl compounds, deprotection of the
10
functional groups, and degradation of large molecules, such as the derivatives from biomass,
but many of them require transition metal catalysts, strong chemical oxidants or nitroꢀcontained
ACS Paragon Plus Environment
2

Page 3 of 26
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
solvents that generate large amount of wastes and are unfriendly to environments [Scheme 1,
path (C)]. In the field of organoselenium catalysis, the former two conversions have already been
4
b,4d,4f
3cꢀd,11
achieved by us
and other groups,
while the oxidative alkene scission still remains a
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
48
49
50
51
52
53
54
55
56
57
58
59
60
tremendous challenge that has not been conquered yet, probably due to the high C=C bond
energy and the relatively complex reaction paths. Recently, after a series of catalyst screenings as
well as the condition optimizations, we successfully cut off the double bond of alkenes by using
H O as oxidant and diselenides as catalyst to produce carbonyls. The reaction provided a
2
2
relatively green synthetic tool and largely expanded the scope of organoselenium catalysis.
Herein, we wish to report our findings.
Scheme 1. Three Paths for Alkene Oxidation
R4'
R4'
R3
R3
(A)
allylic oxidation
O
HO
or
R1 R2
R3
4
4
R = R 'CH
2
R1 R2
R3
R4 R3
epoxidation or
O] dihydroxylation
R4 OH
R4
R1
[
O
R2
or
(B)
R1
R2
R1 2OH
R
oxidative
C=C cleavage
O
O
+
(C)
R1 R2
R4 R3
2. RESULTS AND DISCUSSION
The oxidation reaction of etheneꢀ1,1ꢀdiyldibenzene (1a) was initially chosen as the template for
catalyst screenings (Table 1). Heating alkene 1a with H O in the presence of (PhSe) catalyst in
2
2
2
o
MeCN at 80 C for 48 h, the desired product benzophenone (3a) was obtained in 48% yield
(Table 1, entry 1). A series of diselenides were then tested and it was found that the product yield
ACS Paragon Plus Environment
3

The Journal of Organic Chemistry
Page 4 of 26
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
decreased with the increase of the electron density of the diselenide catalysts (Table 1, entries, 2ꢀ
4
vs 1). [3,5ꢀ(CF ) C H Se] , the favorite catalyst for alkene epoxidation and dihydroxylation
3 2 6 3 2
3
d,4d
that has been screened out by us and others previously,
was unfortunately unfavorable for the
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
oxidative C=C cleavage and led to 3a in only 48% yield (Table 1, entry 5). Using electronꢀ
deficient (4ꢀFC H Se) , the product yield could be slightly enhanced to 51% (Table 1, entry 6),
6
4
2
but the diselenide catalysts with fluorine at metaꢀ and orthoꢀpositions were obviously less
reactive (Table 1, entries 7ꢀ8). Interestingly, dialkyl diselenides, such as (PhCH Se) , (nꢀ
2
2
C H Se) and (cꢀC H Se) (1,2ꢀdicyclohexyldiselane), which were rarely employed in
4
9
2
6
11
2
organoselenium catalysis, were preferable catalysts and the reactions finished within 12ꢀ15 h to
produce 3a in 55ꢀ66% yields (Table 1, entries 9ꢀ11).
a
Table 1. Catalyst Screenings
b
c
entry
1
R
t (h)
3a/%
d
Ph
48
48
d
2
3
4
5
4ꢀMeC H
48
48
48
15
42
6
4
d
4ꢀMeOC H
39
6
4
d
4ꢀMe NC H
4
23
2
6
3,5ꢀ(CF ) C H
3
48
3 2
6
ACS Paragon Plus Environment
4

Page 5 of 26
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
d
d
d
6
7
8
9
1
4ꢀFC H
48
48
48
15
14
12
51
45
30
57
55
66
6
4
4
4
3ꢀFC H
6
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
48
49
50
51
52
53
54
55
56
57
58
59
60
2ꢀFC H
6
PhCH2
0
1
nꢀC H
4
9
1
cꢀC H
6
11
a
Reaction conditions: 0.5 mmol of 1a, 2.5 mmol of H O (30 w/w %), and 2 mL of MeCN were
2
2
b
c
d
employed. Reactions were monitorred by TLC. Isolated yields based on 1a. Reaction not
completed.
The reaction conditions were then further optimized. Elevated catalyst amount accelerated the
procedure, but depressed the desired product yield (Table 2, entries 1 vs 2), while the reduced
catalyst dosages retarded the reactions (Table 2, entries 3ꢀ5 vs 2). A blank reaction without
organoselenium catalyst was also tested, but afforded the product 3a in only 8% yield, while
most of the starting materials were not converted (Table 2, entry 6). The reaction was hardly
improved with enhanced H O dosage (Table 2, entry 7). It was found that excess H O was
2
2
2
2
crucial for the full conversion of 1a (Table 2, entries 2 vs 8ꢀ10). Extension of the reaction time to
8 h could further improve the product yield (Table 2, entries 11 vs 2). Water or acetone as
4
solvent resulted in very poor 3a yield (Table 2, entries 12ꢀ13). Reactions in alcohol solvent were
also tested and it was found that although the reaction speed was reduced in ethanol, its product
o
yield was increased to 74% (Table 2, entries 14ꢀ16). The reactions were decelerated at 60ꢀ70 C
o
(Table 2, entries 17ꢀ18). Enhanced reaction temperature at 100 C led to a full conversion of 1a
ACS Paragon Plus Environment
5

The Journal of Organic Chemistry
Page 6 of 26
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
within 36 h (Table 2, entry 19), and the product yield decreased with extended reaction time,
possibly due to the generation of a series of overꢀoxidation byꢀproducts such as benzoic acid,
1
2
phenol, benzoyl peroxide and etc., as detected by GCꢀMS analysis (Table 2, entry 20).
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
a,b
Table 2. Condition Optimizations
c
d
entry
1
cat./%
10
2/1a
conditions
3a/%
o
5
MeCN, 80 C, 8 h
57
o
2
5
5
5
5
5
5
6
4
2
1
5
MeCN, 80 C, 12 h
66
o
3
3
MeCN, 80 C, 12 h
60
o
e
4
1
MeCN, 80 C, 36 h
56
o
e
5
0.5
0
MeCN, 80 C, 48 h
38
o
e
6
MeCN, 80 C, 48 h
8
o
7
5
MeCN, 80 C, 12 h
67
o
e
8
5
MeCN, 80 C, 36 h
64
o
e
9
5
MeCN, 80 C, 48 h
36
o
e
10
5
MeCN, 80 C, 48 h
23
o
11
5
MeCN, 80 C, 48 h
70
ACS Paragon Plus Environment
6

Page 7 of 26
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
o
e
e
e
e
e
e
e
1
2
3
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
H O, 80 C, 48 h
48
20
74
59
51
50
30
72
55
2
o
1
acetone, 80 C, 48 h
o
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
48
49
50
51
52
53
54
55
56
57
58
59
60
14
EtOH, 80 C, 48 h
i
t
o
15
PrOH, 80 C, 48 h
o
16
17
18
BuOH, 80 C, 48 h
o
EtOH, 70 C, 48 h
o
EtOH, 60 C, 48 h
o
19
EtOH, 100 C, 36 h
o
20
EtOH, 100 C, 48 h
a
b
Reaction conditions: 0.5 mmol of 1a and 2 mL of solvent were employed. Cat./% = Molar ratio
c
of (cꢀC H Se) vs 1a; 2/1a = Molar ratio of H O vs 1a. Reactions were monitorred by TLC.
6
11
2
2
2
d
e
Iaolated yields of 3a based on 1a. Reaction not completed.
We then tried to expand the application scopes of the reaction to other gemꢀdisubstituted
ethenes (Table 3). Besides 1a, the oxidative C=C bond cleavage of bulky alkene 1b could also
occur, but both high temperature and extended reaction time were required for the transformation
(
Table 3, entries 2 vs 1). Catalyzed by (nꢀC H Se) , the electronꢀdeficient substrate 1c produced
4 9 2
3c in 72% yield (Table 3, entry 3). Similarly, the oxidation of 1d provided 3d in 65% yield,
o
whereas (PhCH Se) as catalyst and high reaction temperature at 120 C were required (Table 3,
2
2
entry 4). Alkene 1e with strong electron donation groups led to the product 3e in 50% yield and
the generation of the complex byꢀproducts were also observed (Table 3, entry 5). Oxidation of 1f
ACS Paragon Plus Environment
7

The Journal of Organic Chemistry
Page 8 of 26
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
generated acetophenone (3f) in 70% GC yield, but due to the product volatility, the isolated yield
decreased to 51% after purification (Table 3, entry 6). (PhCH Se) ꢀcatalyzed oxidation reaction
2
2
o
of 1g at 120 C led to 3g in 62% yield (Table 3, entry 7). It was very interesting that the strained
cyclopropyl ring showed some degree of stability under the highly oxidative and acidic
conditions and the product cyclopropyl(phenyl)methanone (3h) were smoothly synthesized in
moderate yield from 1h (Table 3, entry 8). Reactions of the bulky, electronꢀdeficient and
electronꢀenriched methyl alkenes 1iꢀk produced the corresponding ketones 3iꢀk in moderate
yields respectively (Table 3, entries 9ꢀ11). The protocol was also effective for exocyclic C=C
bond and 2,3ꢀdihydroꢀ1Hꢀindenꢀ1ꢀone (3l) could be prepared through the oxidative deꢀmethylene
reaction of alkene 1l (Table 3, entry 12). Experiments with aliphatic alkenes were also conducted:
Oxidation of methylenecyclohexane 1m afforded cyclohexanone (3m) in 73% GC yield, while
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
3e
oxepanꢀ2ꢀone, the deep oxidation byꢀproduct, was also generated in 8% GC yield (Table 3,
entry 13). In the reaction of chained aliphatic alkene 2ꢀmethylbutene (1n), besides the desired
product butanꢀ2ꢀone (3n), the over oxidized product ethyl acetate was even generated as the
3e, 4c
major product (in 56% GC yield) due to the high activity of 3n in Baeyer Villiger oxidations
under the strong oxidation conditions (Table 3, entry 14).
a
Table 3. Oxidation of the gem-Disubstited Ethenes
1
2
b
entry
1
R , R (1)
(RSe) , conditions
yield/% (3)
2
o
Ph, Ph (1a)
(cꢀC H Se) 80 C, 48 h
74 (3a)
6
11
2,
ACS Paragon Plus Environment
8

Page 9 of 26
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
o
2
3
4
5
6
7
1ꢀC H , Ph (1b)
(cꢀC H Se) 120 C, 96 h
52 (3b)
72 (3c)
1
0
7
6
11
2,
o
4ꢀClC H , Ph (1c)
(nꢀC H Se) 80 C, 96 h
4 9 2,
6
4
o
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
48
49
50
51
52
53
54
55
56
57
58
59
60
4ꢀClC H 4ꢀClC H (1d)
6
4,
6
4
(PhCH Se) , 120 C, 48 h
2
2
65 (3d)
50 (3e)
o
4ꢀMeOC H 4ꢀMeOC H (1e) (cꢀC H Se) , 80 C, 48 h
6
4,
6
4
6
11
2
o
Me, Ph (1f)
(cꢀC H Se) , 80 C, 48 h
51 (70) (3f)
62, (3g)
6
11
2
o
(PhCH Se) , 120 C, 48 h
2
2
(1g)
o
8
(cꢀC H Se) , 80 C, 48 h
50 (58) (3h)
6
11
2
(1h)
o
9
1
1
Me, 1ꢀC H (1i)
(nꢀC H Se) 120 C, 96 h
52 (3i)
1
0
7
4
9
2,
o
0
1
Me, 4ꢀClC H (1j)
(cꢀC H Se) , 80 C, 48 h
40 (52) (3j)
50 (66) (3k)
48 (3l)
6
4
6
11
2
o
Me, 4ꢀMeC H (1k)
(cꢀC H Se) , 120 C, 96 h
6 11 2
6
4
o
12
(cꢀC H Se) , 120 C, 96 h
6 11 2
(1l)
c
c
o
d
1
3
4
(cꢀC H Se) 80 C, 48 h
(73) (3m)
6
11
2,
(1m)
o
e
1
Et, Me (1n)
(cꢀC H Se) 80 C, 48 h
(30) (3n)
6
11
2,
ACS Paragon Plus Environment
9

The Journal of Organic Chemistry
Page 10 of 26
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
a
b
Reaction conditions: 0.5 mmol of 1, 2.5 mmol of H O and 2 mL of EtOH were employed.
2
2
Isolated yields of 3 based on 1 outside the brackets and GC yields of 3 inside the brackets (with
c
d
biphenyl as internal standard). Reaction performed in a sealed tube. Oxepanꢀ2ꢀone was also
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
e
generated in 8% GC yield. Ethyl acetate was also generated in 56% GC yield.
Reactions of the 1,1,2ꢀtrisubstituted and tetrasubstituted ethenes were also tested (Table 4).
Oxidation of 1,1ꢀdiphenylpropene (1o) afforded 3a in 52% yield (Table 4, entry 1). Replacing
methyl with nꢀpropyl or phenyl, the yields of 3a were slightly decreased (Table 4, entries 2ꢀ3).
With (PhCH Se) as catalyst, the oxidation reactions of electronꢀdeficient trisubstituted ethenes
2
2
1
r and 1s provided 3d in 53ꢀ62% yields (Table 4, entries 4ꢀ5). Compared with the reaction of 1e,
oxidations of electronꢀenriched trisubstituted ethenes 1t and 1u even produced 3e in slightly
enhanced yields (Table 4, entries 6ꢀ7 vs Table 3, entry 5). Acetophenone 3f could be smoothly
synthesized through the oxidation of trisubstituted ethenes 1v and 1w as well (Table 4, entries 8ꢀ
9
). Though bearing a bulky naphthalene group, both (E)ꢀ1ꢀ(1ꢀphenylpropꢀ1ꢀenꢀ1ꢀyl)naphthalene
(1x) and (E)ꢀ1ꢀ(1,2ꢀdiphenylvinyl)naphthalene (1y) as substrates could lead to the desired
product 3b in moderate yield at elevated temperature and with extended reaction time (Table 4,
entries 10ꢀ11). The electronꢀenriched trisubstituted ethene 1z as substrate led to elevated 3a yield
over the reaction of 1o (Table 4, entries 12 vs 1), while the reaction of electronꢀdeficient
trisubstituted ethene 1aa was difficult to occur (Table 4, entry 13). Tetrasubstituted ethene, such
as 1ab, was inactive for the reaction (Table 4, entry 14).
a
Table 4. Oxidation of the 1,1,2-Trisubstited and Tetrasubstituted Ethenes
ACS Paragon Plus Environment
10

Page 11 of 26
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
1
2
3
4
b
entry
1
R , R , R , R (1)
(RSe) , conditions
yield/% (3)
2
o
Ph, Ph, Me, H (1o)
(cꢀC H Se) , 80 C
52 (3a)
6
11
2
o
2
3
4
5
6
7
8
9
Ph, Ph, nꢀC H , H (1p)
(cꢀC H Se) , 80 C
50 (3a)
49 (3a)
62 (3d)
53 (3d)
57 (3e)
54 (3e)
3
7
6
11
2
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
48
49
50
51
52
53
54
55
56
57
58
59
60
o
Ph, Ph, Ph, H (1q)
(cꢀC H Se) , 80 C
6 11 2
o
4ꢀClC H 4ꢀClC H , Me, H (1r)
(PhCH Se) , 120 C
2 2
6
4,
6
4
o
4ꢀClC H 4ꢀClC H , Ph, H (1s)
(PhCH Se) , 120 C
2 2
6
4,
6
4
o
4ꢀMeOC H 4ꢀMeOC H , Me, H (1t)
(cꢀC H Se) , 100 C
6 11 2
6
4,
6
4
o
4ꢀMeOC H 4ꢀMeOC H , Ph, H (1u)
(cꢀC H Se) , 100 C
6 11 2
6
4,
6
4
o
Me, Ph, Me, H (1v)
Me, Ph, Ph, H (1w)
(cꢀC H Se) , 80 C
46 (65) (3f)
44 (62) (3f)
6
11
2
o
(cꢀC H Se) , 80 C
6
11
2
o
c
10
11
12
1ꢀC H , Ph, Me, H (1x)
(cꢀC H Se) 120 C
56 (3b)
1
0
7
6
11
2,
o
c
1ꢀC H , Ph, Ph, H (1y)
(cꢀC H Se) 120 C
50 (3b)
1
0
7
6
11
2,
o
Ph, Ph, MeO, H (1z)
(cꢀC H Se) , 80 C
72 (3a)
6
11
2
o
c,d
13
Ph, Ph, CO Et, H (1aa)
(cꢀC H Se) , 80 C
N. R.
2
6
11
2
o
c,e
14
Ph, Ph, Ph, Ph (1ab)
(cꢀC H Se) , 120 C
trace (3a)
6
11
2
a
Reaction conditions: 0.5 mmol of 1, 2.5 mmol of H O and 2 mL of EtOH were employed.
2
2
b
Isolated yields of 3 based on 1 outside the brackets and GC yields of 3 inside the brackets (with
c
biphenyl as internal standard). Reaction time was extended to 96 h.
ACS Paragon Plus Environment
11

The Journal of Organic Chemistry
Page 12 of 26
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
d
e
No reaction detected.
GC yield of 3a < 3%.
Moreover, the oxidative C=C bond cleavage reactions of (E)ꢀ1,2ꢀdiphenylethene (1ac) and
E)ꢀpropꢀ1ꢀenꢀ1ꢀylbenzene (1ad) led to the desired product benzaldehyde (3n) in 21ꢀ22% yield,
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(
while the deep oxidation products benzoic acid (4) and its ester 5 were also obtained in 21ꢀ26%
yields (eq 1). Like ethyl 3,3ꢀdiphenylacrylate (1aa), the electron deficient alkene ethyl cinnamate
(1ae) was stable under the reaction conditions and no reaction was detected (eq 1). Because of
the low steric hindrance in substrate, the oxidation of styrene (1af) led to the addition product 2ꢀ
ethoxyꢀ2ꢀphenylethanꢀ1ꢀol (6) in 42% yield and ethyl 2ꢀphenylacetate (7) was also generated as
the byꢀproduct (eq 2). Cyclic alkenes as substrates were also tested: Instead of C=C cleavage, the
reactions of cyclohexene (1ag) and 1ꢀphenyl cyclohexene (1ah) led to the adducts transꢀ
cyclohexaneꢀ1,2ꢀdiol (8a) and cisꢀ1ꢀphenylcyclohexaneꢀ1,2ꢀdiol (8b) respectively (eq 3).
Introducing a phenyl obviously enhanced the activity of 1ah and a series of unidentified
complexes were also observed in TLC and GCꢀMS.
ACS Paragon Plus Environment
12

Page 13 of 26
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
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
48
49
50
51
52
53
54
55
56
57
58
59
60
The mechanisms of this interesting reaction were our next concern. Since homo cleavage of
SeꢀSe bond could happen to generate selenium free radicals under heating or visible light
13
irradiation conditions, these organoseleniumꢀcatalyzed reactions might proceed through free
radical reaction routes. Control experiments were performed to prove or exclude the possible
mechanism: The addition of AIBN as free radical initiator promoted the reaction and the 3a yield
was elevated to 82% (Table 5, entry 1 vs Table 3, entry 1); The reaction was restrained when free
radical scavenger 2,2,6,6ꢀtetramethylꢀ1ꢀpiperidinyloxy (TEMPO) was added (Table 5, entry 2 vs
Table 3, entry 1). As the homoꢀcleavage of SeꢀSe bond to generate free radicals could be driven
13b
by visible light, the free radical procedures in this reaction were likely initiated by background
visible light irradiation. A parallel experiment in dark was conducted and the yield of 3a was
decreased by 6% (Table 5, entry 3 vs Table 3, entry 1). Addition of TEMPO into the reaction
further reduced the 3a yield to 29% (Table 5, entry 4). Experimental results of these partially
inhibited reactions indicated that the free radical procedures might be incorporated, but were not
the only course in mechanisms, and both the thermalꢀinitiated and visible lightꢀdriven free
radical generations were involved in the reaction.
a
Table 5. Control Experiments
(
c-C H Se) (5 mol %)
O
6
11
2
+
Ph
H O
2 2
o
additives, EtOH, 80 C, 48 h
Ph
Ph
Ph
1a
3a
ACS Paragon Plus Environment
13

The Journal of Organic Chemistry
Page 14 of 26
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
b
Entry
1
Additives
3a/%
AIBN (5 mol %)
82
[c]
2
3
TEMPO (100 mol %)
ꢀ (in dark)
32
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
[
[
c]
c]
68
29
4
TEMPO (100 mol %, in dark)
a
b
Reactions were performed under standard conditions described in Table 3, entry 1. Isolated
c
yields of 3a based on 1a. Reaction not completed.
Experimental results in Table 2, entries 2 and 11 revealed more important clues for
mechanism study: Although the starting materials 1a disappeared in TLC after 12 h (Table 2,
entry 2), the product yield could be further enhanced by extending the reaction time (Table 2,
entry 11). The phenomena indicated that the reaction proceeded through two steps: The
substrates were initially converted into certain reaction intermediates and the prolonged reaction
time facilitated the transformation of the intermediates into final products. According to
3
c,4d,4f
literatures,
it was suggested that in the procedures, dihydroxylation occurred first to
produce the intermediate diols 9 (eq 4), which was then oxidized into degraded ketones.
To support the above hypothesis, a reaction of 1,1ꢀdiphenylethaneꢀ1,2ꢀdiol 9a with H O was
2
2
performed under standard conditions and the product 3a could be obtained in 64% yield as
expected (eq 4). The oxidation of diol 9a was hardly restrained by adding TEMPO (eq 4),
ACS Paragon Plus Environment
14

Page 15 of 26
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
indicating that the free radical reactions in the alkene oxidation processes only occurred in the
starting steps, e.g. the epoxidation or dihydroxylation of the alkenes. Moreover, detection of the
epoxide 10a and the overꢀoxidation byꢀproduct 11a or 12a by GCꢀMS analysis further confirmed
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
48
49
50
51
52
53
54
55
56
57
58
59
60
12
the existence of the intermediate step of the reaction (Scheme 2).
Scheme 2. Reaction Intermediate Capture by GC-MS
3
ꢀ4
On the basis of references as well as the above experimental phenomenon, a plausible
mechanism was supposed (Scheme 3). Organoseleniumꢀcatalyzed epoxidation of alkene 1
occurred initially to produce the epoxide 10 through free radical (as indicated by the results in
1
4
3d
3c,4d,4f
Table 5) or electrophilic mechanisms. Hydration of 10 led to the diol 9,
which was then
oxidized into the degrade carbonyl products through two catalysis cycles: In cycle A, the catalyst
4
cꢀd
(
RSe) was oxidized by H O to furnish the active species RSe(O)OOH,
which then
2
2
2
3
1
2
dehydrated with 9 at the R other than R , R site hydroxyl for the lower steric hindrance reason
4e
to produce 13. Rearrangement in 13 led to the intermediate 14 and RSe(O)OH, which could be
4
cꢀd
oxidized by H O to regenerate RSe(O)OOH.
2
2
ACS Paragon Plus Environment
15

The Journal of Organic Chemistry
Page 16 of 26
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Scheme 3. Possible Mechanisms
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
In cycle B, the nucleophilic addition of RSe(O)OOH with the generated 14 led to the
4
a
organoselenium peroxide 15, in which the rearrangement produced the intermediate 16 and
1
5
RSe(O)OH. Further hydration of 16 generated the final product 3 and carboxylic acids, which
reacted with EtOH solvent and was observed in TLC as the byꢀproduct ethyl benzoate 5 in the
case of the reaction of 1q (Table 4, entry 3). It was difficult to generate the key intermediate 14
from tetrasubstituted ethenes. Thus, tetrasubstituted alkene 1ab was inactive for the reaction
(Table 4, entry 10). Moreover, heating 2ꢀhydroxyꢀ1,2ꢀdiphenylethanꢀ1ꢀone (14a, intermediate for
the reaction of 1ac in eq 1) with H O in the presence of (cꢀC H Se) catalyst afforded the
2
2
6
11
2
desired product 4 in 72% yield (eq 6), further supporting that 14 might be the inevitable
intermediate in the alkene oxidation reaction.
ACS Paragon Plus Environment
16

Page 17 of 26
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
OH
Ph
(c-C6H11Se)2 (5 mol %)
Ph
+ H O
PhCO H (6)
2
2
2
o
EtOH, 80 C, 48 h
O
1
4a
4, 72%
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
48
49
50
51
52
53
54
55
56
57
58
59
60
In the dihydroxylation of alkene, electronꢀdeficient diselenides, such as [3,5ꢀ(CF ) C H Se]
2
3
2
6
3
3d,4d
etc., were favorable catalysts,
while in the BaeyerꢀVilliger oxidation of ketones, electronꢀ
4
c
enriched diselenides were preferable. Thus, the conflict of the requirements on catalyst at
different steps resulted in the difficulties in condition optimizations by adjusting electron density
of the catalysts (Table 1, entries 1ꢀ8). As indicated by our previous investigations, the dialkyl
4c
diselenides were good catalysts for BaeyerꢀVilliger oxidations, which were involved as the key
step of the oxidative C=C bond cleavage (cycle B), and should be better catalysts for this
transformation, but the complex reaction mechanisms that underwent dihydroxylation (eq 4) and
alcohol oxidation (cycle A) resulted in the nonꢀgeneral applicability of the catalyst (Tables 3ꢀ4).
3
. CONCLUSION
In conclusion, we have achieved the organoseleniumꢀcatalyzed oxidative scission of alkenes
into carbonyls. The reactions were performed in ethanol with H O as oxidant and were
2
2
relatively green transformations. Although undergoing multiple steps including the alkene
dihydroxylation, the alcohol oxidation and the BaeyerꢀVilliger oxidation, the protocol still
worked efficiently to produce carbonyls in moderate yields. The reaction also revealed more
comprehensive application scopes of organoselenium catalysis and largely contributed to the
development of this unique research direction.
4
. EXPERIMENTAL SECTION
ACS Paragon Plus Environment
17

The Journal of Organic Chemistry
Page 18 of 26
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
4
.1 General Methods. Reagents were purchased from merchant with their purities more than
9
8% and were directly used as received. Solvents were analytical pure (AR) and directly used
without any special treatment. Diselenides were commercially available or prepared according to
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
4d,16
the literature method.
GC analysis was performed on a JieDao TECH GC1690 instrument.
GC yields of the reactions were determined according to the internal standard curve by using
biphenyl as the internal standard. Melting points were measured by WRSꢀ2A digital instrument.
1
IR spectra were measured on Bruker Tensor 27 Infrared spectrometer. H NMR spectra were
recorded on a Bruker Avance instrument using CDCl as the solvent and Me Si as the internal
3
4
1
standard. Chemical shifts for H NMR were referred to internal Me Si (0 ppm) and Jꢀvalues were
4
shown in Hz. Mass spectra were measured on a Shimadzu GCMSꢀQP2010 Ultra spectrometer
(EI).
4.2 Typical Procedure for the Alkene Oxidations. To a 10 mL reaction tube, 0.5 mmol of
alkene and 0.025 mmol of diselenide were added. 2.5 mmol of H O (30 w/w% aqueous
2
2
solution) in 2 mL solvent was then injected by a syringe. The tube was equipped with condenser
o
and heated (for reactions at the temperature higher than 100 C, the tube was sealed). The
reaction was monitored by TLC. When the reaction terminated, the mixture was quenched by 2
mL of aqueous Na SO (1 mol/L) and extracted by EtOAc (2 mL × 3). The combined organic
2
3
layers were dried by Na SO and the solvent was evaporated by a rotary evaporator. The residue
2
4
was subjected to preparative thin layer chromatography (TLC, eluent: petroleum ether/EtOAc =
: 1) to produce the related products. The GC yields were calculated according to the internal
standard curves using biphenyl as the internal standard.
8
ACS Paragon Plus Environment
18

Page 19 of 26
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
4
.3 Characterization of the Products. Benzophenone 3a. 67.4 mg, 74%; Solid, m. p. 47.9–
o
o
ꢀ1 1
4
8.6 C (lit. 48.5 C); IR (KBr): 3055, 1660, 1590, 1445, 1276, 1158, 1076, 929, 702 cm ; H
NMR (600 MHz, CDCl , TMS): δ 7.79 (d, J = 7.2 Hz, 4H), 7.56 (t, J = 7.8 Hz, 2H), 7.46 (t, J =
3
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
48
49
50
51
52
53
54
55
56
57
58
59
60
13
7
.8 Hz, 4H); C NMR (150 MHz, CDCl ): δ 196.8, 137.6, 132.5, 130.1, 128.3; Known
3
1
7a
compound.
o
Naphthalenꢀ1ꢀyl(phenyl)methanone 3b. 60.3 mg, 52%; Solid, m. p. 75.1–76.0 C (lit. 74.5–
o
ꢀ1 1
7
5.5 C); IR (KBr): 3062, 1654, 1579, 1446, 1288, 1164, 1015, 791 cm ; H NMR (600 MHz,
CDCl , TMS): δ 8.09 (d, J = 8.4 Hz, 1H), 7.96 (d, J = 8.4 Hz, 1H), 7.88 (d, J = 7.8 Hz, 1H), 7.84
3
13
(
d, J = 7.8 Hz, 2H), 7.56–7.54 (m, 2H), 7.50–7.45 (m, 3H), 7.41 (t, J = 7.8 Hz, 2H); C NMR
(
150 MHz, CDCl ): δ 198.1, 138.36, 136.39, 133.8, 133.3, 131.4, 131.0, 130.5, 128.53, 128.50,
3
+
+
1
27.9, 127.3, 126.5, 125.8, 124.4; MS (EI, 70 eV): m/z (%) 233 (6) [M +1], 232 (34) [M ], 127
17b
(
100), 105 (43); Known compound.
o
o
(4ꢀChlorophenyl)(phenyl)methanone 3c. 77.4 mg, 72%; Solid, m. p. 77.8–78.4 C (77–78 C);
1
H NMR (600 MHz, CDCl , TMS): δ 7.77–7.74 (m, 4H), 7.59 (t, J = 7.2 Hz, 1H), 7.49–7.44 (m,
3
1
3
4
H); C NMR (150 MHz, CDCl ): δ 195.5, 138.9, 137.2, 135.9, 132.7, 131.5, 130.0, 128.7,
3
+
+
128.4; MS (EI, 70 eV): m/z (%) 217 (6) [M +1], 216 (42) [M ], 105 (100), 181 (14); Known
17b
compound.
o
Bis(4ꢀchlorophenyl)methanone 3d. 81.6 mg, 65%; Solid, m. p. 147.2–147.9 C (lit. 146–147
o
ꢀ1
1
C); IR (KBr): 1651, 1580, 1478, 1280, 1156, 1086, 842 cm ; H NMR (600 MHz, CDCl ,
3
13
TMS): δ 7.72 (d, J = 7.2 Hz, 4H), 7.47–7.45 (m, 4H); C NMR (150 MHz, CDCl ): δ 194.2,
3
+
1
39.2, 135.5, 131.4, 128.8; MS (EI, 70 eV): m/z (%) 250 (9) [M ], 139 (100), 215 (6); Known
1
7c
compound.
ACS Paragon Plus Environment
19

The Journal of Organic Chemistry
Page 20 of 26
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
o
Bis(4ꢀmethoxyphenyl)methanone 3e. 60.6 mg, 50%; Solid, m. p. 143.7–144.6 C (144–145
o
ꢀ1
1
C); IR (KBr): 3008, 1596, 1454, 1318, 1254, 1157, 925 cm ; H NMR (600 MHz, CDCl ,
3
1
3
TMS): δ 7.90–7.88 (m, 4H), 7.44–7.42 (m, 4H), 2.59 (s, 6H); C NMR (150 MHz, CDCl ): δ
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
17c
1
94.5, 162.9, 132.2, 130.7, 113.5, 55.5; Known compound.
Acetophenone 3f. 30.7 mg, 51% (70% GC yield); Oil; IR (film): 3065, 1687, 1595, 1443,
ꢀ1 1
1
360, 1263, 1171, 956, 762 cm ; H NMR (600 MHz, CDCl , TMS): δ 7.94 (d, J = 7.8 Hz, 2H),
3
13
7
.53 (t, J = 7.2 Hz, 1H), 7.43 (t, J = 7.8 Hz, 2H), 2.57 (s, 3H); C NMR (150 MHz, CDCl ): δ
3
+
+
198.1, 137.1, 133.1, 128.6, 128.3, 26.6; MS (EI, 70 eV): m/z (%) 121 (4) [M +1], 120 (42) [M ],
17a
1
05 (100), 77 (42); Known compound.
o
o
Cyclohexyl(phenyl)methanone 3g. 58.7 mg, 62%; Solid, m. p. 50.8–51.6 C (lit. 52–53 C); IR
ꢀ1 1
(
KBr): 3012, 1670, 1592, 1448, 1387, 1226, 992, 703 cm ; H NMR (600 MHz, CDCl , TMS): δ
3
7
.94 (d, J = 8.4 Hz, 2H), 7.53 (t, J = 7.2 Hz, 1H), 7.45 (t, J = 7.2 Hz, 2H), 3.29–3.24 (m, 1H),
1.90–1.83 (m, 4H), 1.73 (d, J = 12.6 Hz, 1H), 1.53–1.40 (m, 2H), 1.39–1.35 (m, 2H), 1.31–1.23
1
3
(
m, 1H); C NMR (150 MHz, CDCl ): δ 203.9, 136.3, 132.8, 128.6, 128.3, 45.6, 29.5, 26.0,
3
+
+
2
5.9; MS (EI, 70 eV): m/z (%) 189 (3) [M +1], 188 (23) [M ], 105 (100), 83 (2); Known
1
7d
compound.
1
Cyclopropyl(phenyl)methanone 3h. 36.6 mg, 50% (58% GC yield); Oil; H NMR (600 MHz,
CDCl , TMS): δ 7.90 (d, J = 7.8 Hz, 2H), 7.43 (t, J = 7.8 Hz, 1H), 7.34 (t, J = 7.8 Hz, 2H), 2.57–
3
1
3
2.53 (m, 1H), 1.14–1.11 (m, 2H), 0.93–0.90 (m, 2H); C NMR (150 MHz, CDCl ): δ 200.7,
3
+
+
1
38.0, 132.8, 128.5, 128.0, 17.2, 11.7; MS (EI, 70 eV): m/z (%) 147 (3) [M +1], 146 (22) [M ],
1
7d
1
05 (100), 69 (4); Known compound.
ACS Paragon Plus Environment
20

Page 21 of 26
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
o
o
1
ꢀ(Naphthalenꢀ1ꢀyl)ethanꢀ1ꢀone 3i. 44.5 mg, 52%; Solid, m. p. 33.6–34.4 C (lit. 34 C); IR
ꢀ1 1
(
KBr): 3052, 1681, 1508, 1433, 1353, 1189, 1075, 942, 785 cm ; H NMR (600 MHz, CDCl ,
3
TMS): δ 8.76 (d, J = 9.0 Hz, 1H), 7.89 (d, J = 7.8 Hz, 1H), 7.83 (d, J = 7.2 Hz, 1H), 7.79 (d, J =
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
48
49
50
51
52
53
54
55
56
57
58
59
60
13
8
.4 Hz, 1H), 7.56–7.53 (m, 1H), 7.46 (t, J = 7.2 Hz, 1H), 7.40–7.38 (m, 1H), 2.65 (s, 3H); C
NMR (150 MHz, CDCl ): δ 201.8, 135.3, 134.0, 133.1, 130.2, 128.9, 128.5, 128.1, 126.5, 126.1,
3
1
7a
124.4, 30.0; Known compound.
1
ꢀ(4ꢀChlorophenyl)ethanꢀ1ꢀone 3j. 30.9 mg, 40% (52% GC yield); Oil; IR (film): 3006, 1689,
ꢀ1 1
1587, 1402, 1358, 1261, 1096, 959, 830 cm ; H NMR (600 MHz, CDCl , TMS): δ 7.88 (d, J =
3
13
9
1
1
.0 Hz, 2H), 7.42 (d, J = 8.4 Hz, 2H), 2.58 (s, 3H); C NMR (150 MHz, CDCl ): δ 196.8, 139.5,
3
+
+
35.4, 129.7, 128.9, 26.6; MS (EI, 70 eV): m/z (%) 155 (2) [M +1], 154 (27) [M ], 139 (100),
1
7a
11 (53); Known compound.
1
ꢀ(pꢀTolyl)ethanꢀ1ꢀone 3k. 33.6 mg, 50% (66 % GC yield); Oil; IR (film): 2925, 1684, 1608,
ꢀ1 1
1418, 1358, 1265, 1179, 956, 817 cm ; H NMR (600 MHz, CDCl , TMS): δ 7.83 (d, J = 8.4
3
1
3
Hz, 2H), 7.22 (d, J = 7.8 Hz, 2H), 2.54 (s, 3H), 2.38 (s, 3H); C NMR (150 MHz, CDCl ): δ
3
+
1
97.8, 143.9, 134.7, 129.2, 128.4, 26.5, 21.6; MS (EI, 70 eV): m/z (%) 135 (3) [M +1], 134 (28)
+
17a
[M ], 119 (100), 91 (61); Known compound.
o
o
1
2
,3ꢀDihydroꢀ1Hꢀindenꢀ1ꢀone 3l. 31.7 mg, 48%; Solid, m. p. 41.6–42.5 C (lit. 41–42 C); H
NMR (600 MHz, CDCl , TMS): δ 7.74 (d, J = 7.8 Hz, 1H), 7.57 (t, J = 7.2 Hz, 1H), 7.47 (d, J =
3
1
3
7.8 Hz, 1H), 7.35 (t, J = 7.8 Hz, 1H), 3.14–3.12 (m, 2H), 2.68–2.66(m, 2H); C NMR (150
MHz, CDCl ): δ 207.1, 155.2, 137.0, 134.6, 127.3, 126.7, 123.6, 36.2, 25.8; MS (EI, 70 eV): m/z
3
+
+
17a
(%) 133 (7) [M +1], 132 (100) [M ], 76 (9); Known compound.
ACS Paragon Plus Environment
21

The Journal of Organic Chemistry
Page 22 of 26
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
1
Benzaldehyde 3o. 22.3 mg, 21%; Oil; H NMR (600 MHz, CDCl , TMS): δ 10.01 (s, 1H),
3
1
3
7
.87 (d, J = 7.6 Hz, 2H), 7.61 (t, J = 7.0 Hz, 1H), 7.51 (t, J = 7.4 Hz, 2H); C NMR (150 MHz,
1
7e
CDCl ): δ 192.3, 136.4, 134.4, 129.7, 128.9; Known compound.
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
o
o
1
Benzoic acid 4. 31.7 mg, 26%; Solid, m. p. 122.1ꢀ122.2 C (lit. 122.13 C); H NMR (600
MHz, CDCl , TMS): δ 13.02 (s, 1H), 8.13 (d, J = 7.2 Hz, 2H), 7.60 (t, J = 7.4 Hz, 1 H), 7.47 (t, J
3
1
3
=
7.6 Hz, 2 H); C NMR (150 MHz, CDCl ): δ172.7, 133.8, 130.2, 129.3, 128.5; Known
3
1
7e
compound.
1
Ethyl benzoate 5. 34.5 mg, 23%; Oil; H NMR (600 MHz, CDCl , TMS): δ 8.00 (d, J = 7.2 Hz,
3
2
H), 7.47 (t, J = 7.2 Hz, 1 H), 7.35 (d, J = 6.8 Hz, 2 H), 4.33ꢀ4.30 (m, 2 H), 1.33 (t, J = 7.0 Hz);
1
3
C NMR (150 MHz, CDCl ): δ166.4, 132.7, 130.5, 129.4, 128.2, 60.8, 14.2; Known
3
1
7e
compound.
1
2
ꢀEthoxyꢀ2ꢀphenylethanꢀ1ꢀol 6. 34.9 mg, 42%; Oil; H NMR (600 MHz, CDCl , TMS): δ
3
7.35–7.26 (m, 5H), 4.41 (m, 1H), 3.69–3.65 (m, 1H), 3.59 (m, 1H), 3.51–3.46 (m, 1H), 3.43–
1
3
3
.38 (m, 1H), 2.89 (s, 1H), 1.21 (t, J = 6.6 Hz, 3H); C NMR (150 MHz, CDCl ): δ 139.2,
3
1
7f
1
28.5, 128.0, 126.8, 83.0, 67.3, 64.5, 15.3; Known compound.
1
Ethyl 2ꢀphenylacetate 7. 12.3 mg, 15%; Oil; H NMR (600 MHz, CDCl , TMS): δ 7.31–7.23
3
13
(
m, 5H), 4.14–4.11 (m, 2H), 3.59 (s, 2H), 1.23 (t, J = 7.2 Hz, 3H); C NMR (150 MHz, CDCl ):
3
1
7g
δ 171.6, 134.2, 129.3, 128.6, 127.1, 60.9, 41.5, 14.2; Known compound.
o
cisꢀ1ꢀPhenylcyclohexaneꢀ1,2ꢀdiol 8b. 21.2 mg, 22%; Solid, m. p. 91.1–92.3 C (lit. 91.8–92.5
o
1
C); H NMR (400 MHz, CDCl , TMS): δ 7.52–7.26 (m, 5H), 4.08–4.00 (m, 1H), 3.07–3.04 (m,
3
1
3
1H), 1.91–1.39 (m, 8H); C NMR (100 MHz, CDCl ): δ 146.3, 128.5, 127.0, 125.1, 75.7, 74.5,
3
ACS Paragon Plus Environment
22

Page 23 of 26
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
+
3
8.5, 29.2, 24.3, 21.1; MS (EI, 70 eV): m/z (%) 192 (38) [M ], 133 (82), 105 (100); Known
1
7h
compound.
ASSOCIATED CONTENT
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
48
49
50
51
52
53
54
55
56
57
58
59
60
Supporting Information
The Supporting Information is available free of charge on the ACS Publications website at
DOI: 10.1021/.
1
13
Massꢀspectra of the detected byꢀproducts and H and C NMR spectra of the products.
AUTHOR INFORMATION
Corresponding Author
*Eꢀmail: yulei@yzu.edu.cn
Author Contributions
†
These authors contributed equally.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
The work was financially supported by NNSFC (21202141), Priority Academic Program
Development (PAPD) of Jiangsu Higher Education Institutions, the Open Project Program of
Jiangsu Key Laboratory of Zoonosis (R1509) and the High Level Talent Support Project of
Yangzhou University. We thank the testing centre of Yangzhou University for assistances in
analysis. We thank Changzhou Chen for assistances in experiments.
ACS Paragon Plus Environment
23

The Journal of Organic Chemistry
Page 24 of 26
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
REFERENCES
1) For reviews, please see: (a) Freudendahl, D. M.; Santoro, S.; Shahzad, S. A.; Santi, C.;
(
Wirth, T. Angew. Chem. Int. Ed. 2009, 48, 8409. (b) Santi, C.; Santoro, S.; Battistelli, B. Curr.
Org. Chem. 2010, 14, 2442. (c) Santoro, S.; Azeredo, J. B.; Nascimento, V.; Sancineto, L.;
Braga, A. L.; Santi, C. RSC Adv. 2014, 4, 31521. (d) Młochowski, J.; WójtowiczꢀMłochowska,
H. Molecules 2015, 20, 10205. (e) Breder, A.; Ortgies, S. Tetrahedron Lett. 2015, 56, 2843. (f)
Guo, R.; Liao, L.; Zhao, X. Molecules 2017, 22, 835.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(2) (a) Liao, L.; Guo, R. Zhao, X. Angew. Chem. Int. Ed. 2017, 56, 3201. (b) Guo, R.ꢀZ.;
Huang, J.ꢀC.; Huang, H.ꢀY.; Zhao, X.ꢀD. Org. Lett. 2016, 18, 504. (c) Ortgies, S.; Depken, C.;
Breder, A. Org. Lett. 2016, 18, 2856. (d) Cresswell, A. J.; Eey, S. T.ꢀC.; Denmark, S. E. Nat.
Chem. 2015, 7, 146. (e) Deng, Z.ꢀM.; Wei, J.ꢀL.; Liao, L.ꢀH.; Huang, H.ꢀY.; Zhao, X.ꢀD. Org.
Lett. 2015, 17, 1834. (f) Ortgies, S.; Breder, A. Org. Lett. 2015, 17, 2748. (g) Chen, F.; Tan, C.
K.; Yeung, Y.ꢀY. J. Am. Chem. Soc. 2013, 135, 1232. (h) Trenner, J.; Depken, C.; Weber, T.;
Breder, A. Angew. Chem. Int. Ed. 2013, 52, 8952.
(3) (a) Sancineto, L.; Tidei, C.; Bagnoli, L.; Marini, F.; Lenardao, E. J.; Santi, C. Molecules
2015, 20, 10496. (b) Santi, C.; Di Lorenzo, R.; Tidei, C.; Bagnoli, L.; Wirth, T. Tetrahedron
2012, 68, 10530. (c) Santoro, S.; Santi, C.; Sabatini, M.; Testaferri, L.; Tiecco, M. Adv. Synth.
Catal. 2008, 350, 2881. (d) ten Brink, G.ꢀJ.; Fernandes, B. C. M.; van Vliet, M. C. A.; Arends, I.
W. C. E.; Sheldon, R. A. J. Chem. Soc. Perkin Trans. 1 2001, 224. (e) ten Brink, G.ꢀJ.; Vis, J.ꢀM.;
Arends, I. W. C. E.; Sheldon, R. A. J. Org. Chem. 2001, 66, 2429.
(4) (a) Jing, X.ꢀB.; Yuan, D.ꢀD.; Yu, L. Adv. Synth. Catal. 2017, 359, 1194. (b) Wang, Y.ꢀG.;
Yu, L.ꢀH.; Zhu, B.ꢀC.; Yu, L. J. Mater. Chem. A 2016, 4, 10828. (c) Zhang, X.; Ye, J.ꢀQ.; Yu, L.;
ACS Paragon Plus Environment
24

Page 25 of 26
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Shi, X.ꢀK.; Zhang, M.; Xu, Q.; Lautens, M. Adv. Synth.Catal. 2015, 357, 955. (d) Yu, L.; Wang,
J.; Chen, T.; Wang, Y.ꢀG.; Xu, Q. Appl. Organomet. Chem. 2014, 28, 652. (e) Yu, L.; Li, H.ꢀY.;
Zhang, X.; Ye, J.ꢀQ.; Liu, J.ꢀP.; Xu, Q.; Lautens, M. Org. Lett. 2014, 16, 1346. (f) Yu, L.; Wang,
J.; Chen, T.; Ding, K.ꢀH.; Pan, Y. Youji Huaxue 2013, 33, 1096.
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
48
49
50
51
52
53
54
55
56
57
58
59
60
(
5) Rayman,M. P. Lancet 2012, 379, 1256.
(6) Meotti, F.C.; Borges, V.C.; Zeni, G.; Rocha, J.B.T.; Nogueira, C.W. Toxicol. Lett. 2003,
43, 9.
1
(7) (a) Horn, E. J.; Rosen, B. R.; Chen, Y.; Tang, J.; Chen, K.; Eastgate, M. D.; Baran, P. S.
Nature 2016, 533, 77.(b) Waldvogel, S. R.; Selt, M. Angew. Chem. Int. Ed. 2016, 55, 12578.
(8) Wang, P.ꢀS.; Liu, P.; Zhai, Y.ꢀJ.; Lin, H.ꢀC.; Han, Z.ꢀY.; Gong, L.ꢀZ. J. Am. Chem. Soc.
2
015, 137, 12732.
(
9) (a) Mirzaee, M.; Bahramian, B.; Gholizadeh, J.; Feizi, A.; Gholami, R. Chem. Eng. J. 2017,
308, 160. (b) Colomer, I.; Barcelos, R. C.; Christensén, K. E.; Donohoe, T. J. Org. Lett. 2016, 18,
880.
5
(10) (a) GonzalezꢀdeꢀCastro, A.; Xiao, J.ꢀL. J. Am. Chem. Soc. 2015, 137, 8206. (b) Moorthy, J.
N.; Parida, K. N. J. Org. Chem. 2014, 79, 11431. (c) Daw, P.; Petakamsetty, R.; Sarbajna, A.;
Laha, S.; Ramapanicker, R.; Bera, J. K. J. Am. Chem. Soc. 2014, 136, 13987. (d) Hossain, M. M.;
Huang, W.ꢀK.; Chen, H.ꢀJ.; Wang, P.ꢀH.; Shyu, S.ꢀG. Green Chem. 2014, 16, 3013. (e) Wang,
G.ꢀZ.; Li, X.ꢀL.; Dai, J.ꢀJ.; Xu, H.ꢀJ. J. Org. Chem. 2014, 79, 7220. (f) Wang, T.; Jiao, N. J. Am.
Chem. Soc. 2013, 135, 11692. (g) Lin, R.; Chen, F.; Jiao, N. Org. Lett. 2012, 14, 4158.
ACS Paragon Plus Environment
25

The Journal of Organic Chemistry
Page 26 of 26
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
(
11) (a) Niyomura, O.; Cox, M.; Wirth, T. Synlett 2006, 251. (b) Browne, D. M.; Niyomura, O.;
Wirth, T. Org. Lett. 2007, 9, 3169. (c) Singh, F. V.; Wirth, T. Org. Lett. 2011, 13, 6504.
(12) Detailed mass spectra of the reaction byꢀproducts or intermediates were included in
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Supporting information of this article.
(13) (a) Liu, L.ꢀP.; Shi, M. Chem. Commun. 2004, 2878. (b) Yu, L.; Huang, X. Synlett 2006,
2
136. (c) Kawaguchi, S.ꢀI.; Shirai, T.; Ohe, T.; Nomoto, A.; Sonoda, M.; Ogawa, A. J. Org.
Chem. 2009, 74, 1751. (d) Ogawa, A.; Ogawa, I.; Sonoda, N. J. Org. Chem. 2000, 65, 7682. (e)
Ogawa, A.; Doi, M.; Ogawa, I.; Hirao, T. Angew. Chem. Int. Ed. 1999, 38, 2027.
(
14) Panzella, L.; Manini, P.; Napolitano, A.; d'Ischia, M. Chem. Res. Toxicol. 2004, 17, 1716.
15) Syper, L. Tetrahedron 1987, 43, 2853.
(
(16) Sharpless, K. B.; Young, M. W. J. Org. Chem. 1975, 40, 947.
(
17) (a) Bai, C.ꢀH.; Li, A.ꢀQ.; Yao, X.ꢀF.; Liu, H.ꢀL.; Li, Y.ꢀW. Green Chem. 2016, 18, 1061.
b) Li, M.ꢀZ.; Wang, C.; Ge, H.ꢀB. Org. Lett. 2011, 13, 2062. (c) Rao, M. L. N.; Venkatesh, V.;
Dasgupta, P. Tetrahedron. Lett. 2010 51, 4975. (d) Wong, Y.ꢀC.; Parthasarathy, K.; Cheng,
(
,
C.ꢀH. Org. Lett. 2010, 12, 1736. (e) Spectral Database for Organic Compounds, SDBS,
http://sdbs.db.aist.go.jp/sdbs/cgiꢀbin/direct_frame_top.cgi. (f) Robinson, M. W. C.; Davies, A.
M.; Buckle, R.; Mabbett, I.; Taylor, S. H.; Graham, A. E. Org. Biomol. Chem. 2009, 7, 2559. (g)
Zimmermann, B.; Dzik, W. I.; Himmler, T.; Gossen, L. J. J. Org. Chem. 2011, 76, 8107. (h)
Wang, Z.; Cui, Y.ꢀT.; Xu, Z.ꢀB.; Qu, J. J. Org. Chem. 2008, 73, 2270.
ACS Paragon Plus Environment
26