Copper-Catalyzed Unstrained C-C Single Bond Cleavage of Acyclic Oxime Acetates Using Air: An Internal Oxidant-Triggered Strategy toward Nitriles and Ketones

Article abstract of DOI:10.1021/acs.joc.8b02103

A copper-catalyzed aerobic oxidative C-C single bond cleavage of acyclic unstrained oxime acetates is reported, providing various aryl nitriles and ketones in good yields. Mechanistic studies indicate a radical procedure is involved in this transformation, and the oxygen atom in the ketone products is originated from O₂ in the air. Oxime acetates as an internal oxidant have been proved to be an initiator, which may promote the discovery of novel protocol for C-C bond cleavage and dioxygen activation.

Full text of DOI:10.1021/acs.joc.8b02103

Subscriber access provided by UNIV OF CAMBRIDGE
Note
Copper-Catalyzed Unstrained C-C Single Bond Cleavage
of Acyclic Oxime Acetates Using Air: An Internal
Oxidants Triggered Strategy toward Nitriles and Ketones
Chuanle Zhu, Fulin Chen, Chi Liu, Hao Zeng, Zhiyi Yang, Wanqing Wu, and Huanfeng Jiang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b02103 • Publication Date (Web): 10 Oct 2018
Downloaded from http://pubs.acs.org on October 10, 2018
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 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 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.
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 31
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
CopperꢀCatalyzed Unstrained CꢀC Single Bond Cleavage of
Acyclic Oxime Acetates Using Air: An Internal Oxidants
Triggered Strategy toward Nitriles and Ketones
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
Chuanle Zhu, Fulin Chen, Chi Liu, Hao Zeng, Zhiyi Yang, Wanqing Wu, and
Huanfeng Jiang*
Key Laboratory of Functional Molecular Engineering of Guangdong Province, School
of Chemistry and Chemical Engineering, South China University of Technology,
Guangzhou 510640, P. R. China
Fax: (+86) 20ꢀ8711ꢀ2906; Eꢀmail: jianghf@scut.edu.cn
NOAc
R2
N
[Cu]/air
[Cu]
O
R2
CN
+
Ar
Ar
Ar
R1 R2
R1
R1
Unstrained C-C bond cleavage of acyclic oxime acetates
Internal oxidants triggered strategy toward aryl nitirles and ketones
Catalytic copper/air system
Abstract: A copperꢀcatalyzed aerobic oxidative CꢀC single bond cleavage of acyclic
unstrained oxime acetates is reported, providing various aryl nitriles and ketones in
good yields. Mechanistic studies indicate a radical procedure is involved in this
transformation, and the oxygen atom in the ketone products is originated from O2 in
the air. Oxime acetates as an internal oxidant have been proved to be an initiator,
which may promote the discovery of novel protocol for CꢀC bond cleavage and
dioxygen activation.
Carbonꢀcarbon bond cleavage is an attractive research area in organic chemistry and
petroleum industry.1 Due to their thermodynamic stability, the selective cleavage of
relative inertness CꢀC single bonds is one of the most challenging and on the cutting
edge research topics.2 The most common strategies to promote CꢀC single bond
cleavage focused on strain relief of strained skeletons (three and four membered
rings),3 the use of chelation assistance,4 and CꢀCN bond cleavage.5 However, to
cleave unstrained inert CꢀC bonds, harsh conditions with stoichiometric oxidants such
as toxic metal salts and peroxides have been required traditionally. Thus, the
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 31
1
2
3
4
5
6
development of environmentally sustainable and efficient methods to cleave
unstrained inert CꢀC bonds is highly desired but still underdeveloped.6
In recent years, aerobic oxidative cleavage of CꢀC multiple bonds with dioxygen
has attracted significant research interest,7 because molecular oxygen has been
recognized as an ideal oxidant in organic synthesis due to its environmentally benign
character.8 The elegant early works for the challenging aerobic oxidative cleavage of
unstrained CꢀC single bond with dioxygen were focused on the cleavage of
C(CO)ꢀC(alkyl) single bonds, and these reactions were usually performed under
dioxygen atmosphere (Scheme 1, a).9 Given the issues of relative safety, sustainable
abundance, extremely low cost, and ease of manipulation, the development of novel
aerobic oxidative unstrained CꢀC single bond cleavage reactions employing air is
highly preferred. However, owing to the high activation energy and reduced reactivity
at lower concentration of dioxygen,10 it is often challenging to use air instead of
dioxygen in aerobic oxidative CꢀC single bond cleavage.9
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
Oxime esters as an internal oxidant, which serves as both a substrate and an oxidant
in reactions, have attracted considerable attention.11ꢀ14 Recently, the groups of
Uemura,12a Selander12b, Shi12c and Guo12dꢀf independently reported Pd, Fe, Cu, and
Niꢀcatalyzed CꢀC single bond cleavage of strained or less strained cyclic oxime esters
to give aliphatic nitriles, driving by internal oxidant triggered strain relief of strained
or less strained four or five membered rings (Scheme 1, b). In sharp contrast,
transitionꢀmetal catalyzed CꢀC single bond cleavage of unstrained acyclic oxime
esters remains an unsolved challenge, because this internal oxidant triggered strategy
for acyclic oxime esters prefers to the αꢀCsp3ꢀH bond activation process, especially
under copper catalysis.11, 13ꢀ14 As our continuous effort toward aerobic CꢀC bond
cleavage reactions under air,7a, 11b as well as our interest in exploiting the potential
abilities of oxime acetates,11, 14 we herein report a copperꢀcatalyzed unstrained CꢀC
bond cleavage of oxime acetates that gives rise to valuable aryl nitriles and ketones
avoiding the use of toxic cyanide sources (Scheme 1, c). Remarkably, this process is a
novel aerobic oxidative cleavage of unstrained CꢀC bond under air triggered by an
internal oxidant.
ACS Paragon Plus Environment

Page 3 of 31
The Journal of Organic Chemistry
1
2
3
4
Scheme 1. CꢀC Single Bond Cleavage by Aerobic or/and Internal Oxidation
5
6
a) Aerobic oxidation: under O2 atmosphere
O
[TM]/O2/[FG]
-H2
O
C
C
FG
C
O
7
8
9
b) Internal oxidation: strained or less strained C-C single bond
OR
N
N
R1
R2
TM
R3
R3
n
R3
NC
n
n
-ROH
R1 R2
R1 R2
n = 1, 2
n = 1, 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
c) This work: unstrained C-C single bond using air
NOAc
R2
N
[Cu]/air
[Cu]
O
R2
+
Ar CN
Ar
Ar
R1 R2
R1
R1
After tremendous attempts, acyclic oxime acetate 1aa was selected as the model
substrate to establish the optimized reaction conditions (Table 1). First, different types
of copper catalysts, such as CuCl, CuBr, CuI, CuCl2, Cu(OAc)2, Cu(OTf)2,
Cu(MeCN)4BF4, and Cu(MeCN)4PF6 were investigated, a catalyst of CuI gave the
aryl nitrile product 2a in 88% isolated yield, and the corresponding ketone product 3a
was not determined (entries 1ꢀ8). Next, other well documented metal catalysts such as
Pd2(dba)3, FeCl2, and NiCl2 for CꢀC single bond cleavage of strained or less strained
cyclic oxime esters were examined, they were almost uneffective in this
transformation (entries 9ꢀ11). No product was detected without copper catalyst (entry
12). Furthermore, we evaluated other reaction solvents, DMF, 1,4ꢀdioxane, MeCN,
DCE (1,2ꢀdichloroethane), toluene, and EtOH, but we found DMSO was optimum for
this unstrained CꢀC single bond cleavage reaction (entries 13ꢀ18). Additionally, either
reducing or increasing the reaction temperature eroded the yield of 3a slightly (entries
19ꢀ20).
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 31
1
2
3
4
Table 1. Optimization of the Reaction Conditionsa
5
6
7
8
9
entry
1
catalyst
CuCl
solvent
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMF
temperature (oC)
yield (%)b
90
90
90
90
90
90
90
90
90
90
90
90
90
90
90
90
90
90
80
100
32
50
91 (88)
53
23
51
20
15
3
2
CuBr
3
CuI
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
4
CuCl2
Cu(OAc)2
Cu(OTf)2
Cu(MeCN)4BF4
Cu(MeCN)4PF6
Pd2(dba)3
FeCl2
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
5
NiCl2
3
ꢀ
0
CuI
80
79
33
11
6
CuI
1.4ꢀdioxane
MeCN
DCE
CuI
CuI
CuI
toluene
EtOH
CuI
21
84
89
CuI
DMSO
CuI
DMSO
aUnless otherwise noted, all reactions were carried out with 1aa (0.2 mmol), catalyst (10 mol%), and solvent (2
mL) in a 25 mL test tube at 90 oC for 12 h under air. bThe yields were determined by 1H NMR spectroscopy of the
crude product with CH2Br2 as an internal standard. The number in the parentheses was isolated yield. n.d. = not
determined.
Under the optimized reaction conditions, we turned our attention to the generality
of acyclic oxime acetates in this internal oxidantsꢀtriggered unstrained CꢀC single
bond cleavage reaction under air. The results were outlined in Scheme 2. In general,
substituted oxime acetates with electronꢀdonating groups such as alkoxyl and alkyl
groups, electronꢀneutral group, and electronꢀwithdrawing groups such as fluoro,
chloro, bromo, iodo, and trifluoromethyl groups on the paraꢀ, metaꢀ, and
orthoꢀposition of the phenyl ring all could give the desired aryl nitriles in high yields
(2aꢀ2p). Oxime acetates derived from 1ꢀ(naphthalenꢀ2ꢀyl)ethanꢀ1ꢀone was applicable
to this internal oxidantsꢀtriggered system, providing the desired product 2q in 74%
yield. Furthermore, different hetereo aromatic groups such as thienyl, and
indolylꢀbearing oxime acetates were also found to be good substrates, delivering the
corresponding products with high yields (2rꢀ2s). Acyclic aliphatic nitrile 2t was also
obtained in 13% GC yield
.
Additionally, although fiveꢀmembered cyclic oxime acetate
ACS Paragon Plus Environment

Page 5 of 31
The Journal of Organic Chemistry
1
2
3
4
5
6
1ua did not give the desired ketonitrile 2u in isolatable yield (< 10%) under the
standard reaction conditions, sixꢀmembered cyclic oxime acetate 1va afforded
ketonitrile 2v in 23% yield.
7
8
9
Scheme 2. Substrate Scope of Oxime Acetatesa
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
NOAc
CuI, DMSO
O
+
R
CN
R
Air, 90 oC, 12 h
1
2
3a: n.d.
MeO
Me
MeO
CN
CN
MeO
CN
Me
CN
CN
CN
MeO
2a: 88%b
CN
2b: 77%
2c: 71%
2d: 73%
F
2e: 71%
F
F
Cl
CN
CN
CN
2i: 65%
2f: 56% (71%c)
2g: 63%
2h: 64%
2j: 71%
Cl
Cl
Br
Br
CN
I
CN
Cl
CN
CN
CN
2k: 73%
2p: 73%
2l: 61%
2m: 75%
2n: 63%
CN
2o: 61%
S
CN
F3C
CN
CN
8
CN
CN
N
Bn
2s: 64%
2t: 13%[b]
CN
2q: 74%
2r: 64%
NOAc
NOAc
F
O
F
O
1ua
2u: < 10%
1va
2v: 23%
aUnless otherwise noted, the reaction was run at 0.2 mmol scale under the standard reaction conditions. bThe
average isolated yield of two parallel runs. cGCꢀMS yield. n.d. = not determined.
To further define the limitation of our protocol, as well as figuring out the
other products from this CꢀC bond cleavage reaction, diverse αꢀsubstituted
oxime acetates were investigated under the standard reaction conditions
(Scheme 3). Interestingly, oxime acetates with only one αꢀH were more suitable
in this internal oxidantsꢀtriggered unstrained CꢀC single bond cleavage
transformation (1faꢀ1ff). We assumed that the αꢀtertiary carbon might be very
important for the stability of the reaction intermediates. Besides the benzonitrile
product, it is worth to mentioning that ketone products such as aryl ketone 3e
and 4ꢀalphatic ketone 3f were isolated in 53% and 35% yields from the
corresponding oxime acetates (3fe
types of oxime acetates with αꢀtertiary carbon were investigated (1fg
better results were obtained compared to that of 1fa
ꢀ
3ff), respectively. Additionally, different
ꢀ
1fj), no
.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 31
1
2
3
4
5
Scheme 3. αꢀSubstituted Oxime Acetatesa
6
7
8
9
NOAc
R2
CuI, DMSO
O
CN
+
Ph
90 oC, 12 h, air
R1 R2
R1
1
2f
3
2f
3
2f
3
NOAc
NOAc
O
O
71%b
45%
Ph
Ph
Ph
Ph
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
1fa
NOAc
3a: n.d.
1ff
3f: 35%c
NOAc
O
O
6%
27%
7%
Ph
Ph
Ph
Ph
H
H
1fb
3b: n.d.
1fg
3g: n.d.
NOAc
O
NOAc
O
11%
H
1fc
3c: n.d.
1fh
3h: n.d.
NOAc
O
NOAc
O
34%
67%
20%
50%
Ph
Ph
Ph
Ph
Ph
H
1fd
3d: 6%
1fi
NOAc
3i: n.d.
NOAc
O
Ph
O
Ph
Ph
3e: 50%c
1fe
1fj
3j: 20%
aUnless otherwise noted, the reaction was run at 0.2 mmol scale under the standard reaction conditions.
bGCꢀMS yield. cIsolated yield. n.d. = not determined.
To cast some light on the mechanism details of this internal
oxidantsꢀtriggered unstrained CꢀC single bond cleavage reaction, a series of
control experiments were performed. First, different types of oxime esters
(
1faꢀ1fc) and unprotected oxime 1fd were examined under the standard
reaction conditions. The product benzonitrile 2f was obtained in 0% to 71% GC
yields, indicating that the oxidative property of oxime esters is very important
to this transformation (Scheme 4, eq 1). Next, the CꢀC single bond cleavage
reaction of oxime acetate 1fa was independently performed under N2, O2, and
air. Owing to only 5% of benzonitrile 2f was detected under N2, which is a
dramatically lower yield compared to that under O2 (71%), or air (71%). We
believed that O2 is necessary to promote this unstrained CꢀC single bond
cleavage reaction (Scheme 4, eq 2). Interestingly, oxidizing radical scavenger
TEMPO enhanced the yield of product 2f to 76% GC yield, probably related to
the excellent dioxygen activation property of CuI/TEMPO system (Scheme 4,
eq 3).15 While non oxidizing radical scavenger tertꢀbutylhydroxytoluene (BHT)
completely inhibited this unstrained CꢀC single bond cleavage reaction, and the
radical trapping product
4 was isolated in 38% yield, indicating that a radical
process was involved in this reaction (Scheme 4, eq 4). Furthermore,
ACS Paragon Plus Environment

Page 7 of 31
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
αꢀhydroxyl oxime 5a and αꢀhydroxyl oxime acetate 5b were synthesized and
independently performed this unstrained CꢀC single bond cleavage
transformation under standard reaction conditions (Scheme 4, eq 5). No
benzonitrile 2f was detected from αꢀhydroxyl oxime 5a, while αꢀhydroxyl
oxime acetate 5b gave product 2f quantitatively. These results showed that this
reaction was initially triggered by copperꢀcatalyzed NꢀO bond cleavage of
oxime acetates, and a hydroxyl group was introduced into one of the reaction
intermediates, which further converted to the ketone product. Finally, to figure
out the original source of the oxygen atom in the ketone products, the
unstrained CꢀC single bond cleavage reaction of 1fe to give acetophenone
product was selected as the model reaction. Treated 1fe with 2 equivalent of
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
18
H2 O under the standard reaction conditions, GCꢀMS analysis showed the ratio
of 18Oꢀlabeled acetophenone 3e is less than 5%, indicating that the oxygen atom
in acetophenone 3e is not originated from H2O (Scheme 4, eq 6). No
16
18Oꢀlabeled acetophenone 3e was obtained under O2 atmosphere (Scheme 4,
eq 7), while the ratio of 18Oꢀlabeled acetophenone 3e is 85% when the reaction
18
was performed under O2 atmosphere (Scheme 4, eq 8). Thus, we confirmed
that dioxygen is the original source of the oxygen atom in the ketone products.
Additionally, CH3SO2CH3 as the byproduct was detected by GCꢀMS (Scheme 4,
eqs 7ꢀ8), which indicates that DMSO can be a reductant in this transformation.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 31
1
2
3
4
Scheme 4. Control Experiments
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
aUnless otherwise noted, the yields were GCꢀMS yields. bIsolated yields.
On the basis of these experimental results as well as previous works,11ꢀ14 we
tentatively proposed the reaction mechanism as illustrated in Scheme 5. Firstly,
reduction of 1fa by CuI affords CuII salts and iminyl radical
quickly isomerize to αꢀcarbon radical . And then the carbon radical
priority over the iminyl radical to be trapped by O2 providing peroxide
radical intermediate . A subsequent intramolecular 1,5ꢀhydrogen atom transfer
(1,5ꢀHAT) procedure leads to the peroxide iminyl radical D,16 which could be
reduced by DMSO17 to generate αꢀhydroxyl iminyl radical
. Finally, oxidative
A
, which may
has
B
B
A
C
E
CꢀC bond cleavage by CuII salts regenerated the CuI catalyst and gave
benzonitrile 2f and acetone 3a as the products.
ACS Paragon Plus Environment

Page 9 of 31
The Journal of Organic Chemistry
1
2
3
4
Scheme 5. Proposed Mechanism
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
In summary, we have reported the first copperꢀcatalyzed aerobic oxidative unstrained
CꢀC single bond cleavage reaction that is triggered by an internal oxidant. This
unstrained CꢀC single bond cleavage reaction of oxime acetates provides various aryl
nitriles and ketones in good yields using air. Mechanistic studies indicated that this
reaction involved a radical procedure. Oxime acetates as an internal oxidant have
been proved to be an initiator, which may promote the discovery of novel protocol for
CꢀC bond cleavage and dioxygen activation. Application of this internal oxidants
triggered strategy in other challenging CꢀC bond cleavage and dioxygen activation
reactions is currently under investigation in our laboratory.
EXPERIMENTAL SECTION
General Information. Toluene were distilled from sodium/benzophenone;
1,2ꢀdichloroethane (DCE) was distilled from calcium hydride; acetonitrile (MeCN)
was distilled from phosphorus pentoxide. Other commercially available reagents were
purchased and used without further purification. Analytical thinꢀlayer chromatography
was performed on 0.20 mm silica gel plates (GF254) using UV light as a visualizing
agent. Flash column chromatography was carried out using silica gel (200–300 mesh)
with the indicated solvent system. All reactions were conducted in ovenꢀdried test
tubes. All the reaction temperatures reported are oil bath temperatures. Melting points
were measured using a melting point instrument and are uncorrected. Chemical shifts
were reported in ppm from the solvent resonance as the internal standard (CDCl3 δH =
7.26 ppm, δC = 77.16 ppm). Multiplicity was indicated as follows: s (singlet), d
(doublet), t (triplet), q (quartet), m (multiplet). Coupling constants were reported in
Hertz (Hz). IR spectra were obtained with an infrared spectrometer on either
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 31
1
2
3
4
5
6
7
8
9
potassium bromide pellets or liquid films between two potassium bromide pellets.
GC−MS data were obtained using electron ionization. HRMS was carried out on a
highꢀresolution mass spectrometer (LCMSꢀITꢀTOF). TLC was performed using
commercially available 100−400 mesh silica gel plates (GF254).
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
General Procedure for the Synthesis of Oxime esters: To a roundꢀbottome flask
equipped with a reflux condenser and a magnetic bar was added ketones (5 mmol),
NH2OH·HCl (7.5 mmol), NaOAc (7.5 mmol), H2O (5 mL), and EtOH (5 mL). The
resulting mixture was stirred at 80 oC for 2 h, then cooled to room temperature, added
water (15 mL), extracted with EtOAc (15 mL × 3). The combined organic phases
were dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The resulted
oxime was further purified by flash column chromatography on silica gel or directly
treated with CH2Cl2 (10 mL), acid anhydride (10 mmol), and stirred at room
temperature overnight. The resulting mixture was added water (15 mL), extracted
with CH2Cl2 (15 mL × 3). The combined organic phases were wished with brine (15
mL × 3), dried over anhydrous Na2SO4, filtered and concentrated in vacuo. Further
purification by flash column chromatography on silica gel (eluting with petroleum
ether/ethyl acetate = 30/1) provided the oxime esters 1.
1ꢀ(4ꢀMethoxyphenyl)ꢀ2ꢀMethylpropanꢀ1ꢀOne OꢀAcetyl Oxime (1aa): colorless oil;
1
73% yield (857.7 mg); E/Z isomer mixtures (E/Z = 63/37); H NMR (400 MHz,
CDCl3) δ 7.44 (d, J = 8.4 Hz, 0.76H), 7.17 (d, J = 8.4 Hz, 1.23H), 7.53−7.58 (m,
2.00H), 3.86 (s, 1.85H), 3.81 (s, 1.12H), 3.50 (hept, J = 7.2 Hz, 0.37H), 2.98 (hept, J
= 6.8 Hz, 0.63H), 2.23 (s, 1.17H), 2.00 (s, 1.81H), 1.25 (d, J = 6.8 Hz, 2.33H), 1.18 (d,
13
J = 6.8 Hz, 3.67H); C {1H} NMR (100 MHz, CDCl3) δ 171.2, 171.0, 169.0, 168.9,
160.7, 160.0, 129.5, 128.6, 126.4, 125.0, 113.7, 113.5, 55.2, 55.2, 32.0, 30.1, 20.0,
19.8, 19.6, 19.5; IR (KBr): 2962, 1764, 1609, 1508, 1205 cm−1; HRMS (ESIꢀTOF)
m/z: [M+H]+ Calcd. for C13H18NO3, 236.1281; found, 236.1282
1ꢀ(3,4ꢀDimethoxyphenyl)ꢀ2ꢀMethylpropanꢀ1ꢀOne OꢀAcetyl Oxime (1ba): colorless
1
oil; 65% yield (861.3 mg); E/Z isomer mixtures (E/Z = 56/44); H NMR (400 MHz,
CDCl3) δ 6.72−7.06 (m, 3.00H), 3.87−3.91 (m, 6.00H), 3.49 (hept, J = 6.8 Hz, 0.44H),
ACS Paragon Plus Environment

Page 11 of 31
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
2.98 (hept, J = 6.8 Hz, 0.56H), 2.23 (s, 1.25H), 2.00 (s, 1.60H), 1.26 (d, J = 7.5 Hz,
2.81H), 1.18 (d, J = 6.8 Hz, 3.20H); 13C {1H} NMR (100 MHz, CDCl3) δ 171.4,
171.1, 169.0, 168.8, 150.4, 149.5, 148.7, 148.5, 126.7, 125.3, 121.0, 119.9, 111.3,
110.7, 110.6, 56.0, 55.9, 55.9, 55.8, 35.1, 30.2, 20.0, 19.8, 19.7, 19.6; IR (KBr): 2961,
1763, 1597, 1515, 1457, 1210 cm−1; HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd. for
C14H20NO4, 266.1387; found, 266.1388
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
1ꢀ(3ꢀMethoxyphenyl)ꢀ2ꢀMethylpropanꢀ1ꢀOne OꢀAcetyl Oxime (1ca): colorless oil;
1
77% yield (904.7 mg); E/Z isomer mixtures (E/Z = 67/33); H NMR (400 MHz,
CDCl3) δ 6.70−7.34 (m, 4.00H), 3.82 (s, 3.00H), 3.53 (hept, J = 6.8 Hz, 0.33H), 2.98
(hept, J = 6.8 Hz, 0.67H), 2.24 (s, 0.93H), 1.98 (s, 1.97H), 1.23 (d, J = 6.8 Hz, 1.98H),
1.18 (d, J = 6.8 Hz, 3.91H); 13C {1H} NMR (100 MHz, CDCl3) δ 171.8, 171.5, 168.8,
168.8, 159.4, 159.3, 135.3, 134.2, 129.3, 129.3, 120.4, 19.1, 115.1, 114.0, 113.8, 112.7,
55.3, 55.3, 35.0, 30.0, 19.9, 19.8, 19.6, 19.6; IR (KBr): 2961, 1765, 1589, 1464, 1204
cm−1; HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd. for C13H18NO3, 236.1281; found,
236.1283
2ꢀMethylꢀ1ꢀ(pꢀTolyl)propanꢀ1ꢀOne OꢀAcetyl Oxime (1da): colorless oil; 78% yield
1
(854.1 mg); E/Z isomer mixtures (E/Z = 54/46); H NMR (400 MHz, CDCl3) δ 7.37
(d, J = 8.0 Hz, 0.83H), 7.08−7.24 (m, 3.33H), 3.53 (hept, J = 7.2 Hz, 0.46H), 3.00
(hept, J = 7.2 Hz, 0.54H), 2.39−2.40 (m, 3.00H), 2.25 (s, 1.27H), 1.99 (s, 1.64H), 1.25
(d, J = 7.2 Hz, 2.70H), 1.19 (d, J = 7.2 Hz, 3.28H); 13C {1H} NMR (100 MHz, CDCl3)
δ 171.8, 171.7, 169.0, 139.6, 138.8, 131.2, 130.0, 128.9, 128.8, 128.0, 126.9, 35.0,
30.0, 26.1, 21.3, 20.0, 19.9, 19.6, 19.6; IR (KBr): 2928, 1764, 1619, 1454, 1368, 1202
cm−1; HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd. for C13H18NO2, 220.1332; found,
220.1333
2ꢀMethylꢀ1ꢀ(oꢀTolyl)propanꢀ1ꢀOne OꢀAcetyl Oxime (1ea): colorless oil; 75% yield
1
(821.3 mg); E/Z isomer mixtures (E/Z = 60/40); H NMR (400 MHz, CDCl3) δ
7.18−7.30 (m, 2.86H), 6.95−7.07 (m, 1.29H), 3.52 (hept, J = 6.8 Hz, 0.40H), 2.97
(hept, J = 6.8 Hz, 0.60H), 2.36−2.37 (m, 3.00H), 2.23 (d, J = 1.2 Hz, 1.16H), 1.96 (d,
J = 1.2 Hz, 1.79H), 1.23 (d, J = 7.2 Hz, 2.41H), 1.18 (d, J = 7.2 Hz, 3.57H); 13C {1H}
NMR (100 MHz, CDCl3) δ 172.1, 171.8, 168.9, 168.8, 138.0, 137.8, 134.0, 133.0,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 31
1
2
3
4
5
6
130.2, 129.6, 128.7, 128.1, 128.0, 127.2, 125.1, 124.0, 35.0, 30.1, 26.0, 21.4, 19.9,
19.8, 19.6, 19.6; IR (KBr): 2966, 1767, 1602, 1459, 1368, 1206 cm−1; HRMS
(ESIꢀTOF) m/z: [M+H]+ Calcd. for C13H18NO2, 220.1332; found, 220.1334
7
8
9
2ꢀMethylꢀ1ꢀPhenylpropanꢀ1ꢀOne OꢀAcetyl Oxime (1fa): colorless oil; 83% yield
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
1
(850.7 mg); E/Z isomer mixtures (E/Z = 63/37); H NMR (400 MHz, CDCl3) δ
7.16−7.45 (m, 5.00H), 3.54 (hept, J = 6.8 Hz, 0.37H), 3.00 (hept, J = 6.8 Hz, 0.63H),
2.24 (s, 1.08H), 1.95 (s, 1.88H), 1.17−1.24 (m, 6.00H); 13C {1H} NMR (100 MHz,
CDCl3) δ 171.9, 171.7, 168.8, 134.0, 133.0, 129.5, 128.8, 128.2, 128.1, 128.1, 126.8,
35.0, 30.0, 19.9, 19.8, 19.6; IR (KBr): 2970, 1766, 1620, 1454, 1369, 1205 cm−1;
HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd. for C12H16NO2, 206.1176; found, 206.1177
1ꢀ(4ꢀFluorophenyl)ꢀ2ꢀMethylpropanꢀ1ꢀOne OꢀAcetyl Oxime (1ga): colorless oil;
1
80% yield (892.0 mg); E/Z isomer mixtures (E/Z = 62/38); H NMR (400 MHz,
CDCl3) δ 7.43−7.45 (m, 0.73H), 7.05−7.18 (m, 3.21H), 3.47−3.55 (m, 0.38H),
2.93−3.00 (m, 0.62H), 2.22 (d, J = 4.4 Hz, 1.19H), 1.97 (d, J = 4.4 Hz, 1.85H),
1.14−1.23 (m, 6.00H); 13C {1H} NMR (100 MHz, CDCl3) δ 171.0, 170.6, 168.8,
1
1
168.6, 163.5 (d, JCꢀF = 248.5 Hz), 162.8 (d, JCꢀF = 247.2 Hz), 130.1, 130.0, 129.0,
128.9, 115.4, 115.2, 35.0, 29.9, 19.8, 19.7, 19.5, 19.5; IR (KBr): 2970, 1768, 1606,
1507, 1370, 1210 cm−1; HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd. for C12H15FNO2,
224.1081; found, 224.1083
1ꢀ(3ꢀFluorophenyl)ꢀ2ꢀMethylpropanꢀ1ꢀOne OꢀAcetyl Oxime (1ha): colorless oil;
1
76% yield (847.4 mg); E/Z isomer mixtures (E/Z = 57/43); H NMR (400 MHz,
CDCl3) δ 6.90−7.43 (m, 4.00H), 3.50−3.57 (m, 0.43H), 2.95−3.02 (m, 0.57H), 2.25 (s,
1.30H), 1.99 (s, 1.68H), 1.18−1.25 (m, 6.00H); 13C {1H} NMR (100 MHz, CDCl3) δ
1
1
170.7, 170.2, 168.6, 168.5, 162.4 (d, JCꢀF = 245.5 Hz), 162.3 (d, JCꢀF = 245.8 Hz),
136.1 (d, 3JCꢀF = 7.8 Hz), 134.9 (d, 3JCꢀF = 7.5 Hz), 130.0 (d, 4JCꢀF = 2.1 Hz), 129.9 (d,
3
3
2
4JCꢀF = 2.1 Hz), 123.8 (d, JCꢀF = 3.1 Hz), 122.6 (d, JCꢀF = 3.2 Hz), 116.5 (d, JCꢀF
=
20.9 Hz), 115.8 (d, JCꢀF = 20.9 Hz), 115.3 (d, 2JCꢀF = 22.6 Hz), 114.1 (d, JCꢀF = 22.6
Hz), 34.9, 29.9, 19.8, 19.7, 19.5, 19.5; IR (KBr): 2973, 1768, 1584, 1443, 1368, 1204
cm−1; HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd. for C12H15FNO2, 224.1081; found,
224.1082
2
2
ACS Paragon Plus Environment

Page 13 of 31
The Journal of Organic Chemistry
1
2
3
4
5
6
1ꢀ(2ꢀFluorophenyl)ꢀ2ꢀMethylpropanꢀ1ꢀOne OꢀAcetyl Oxime (1ia): colorless oil;
1
53% yield (591.0 mg); E/Z isomer mixtures (E/Z = 68/32); H NMR (400 MHz,
CDCl3) δ 7.38−7.41 (m, 1.01H), 7.11−7.21 (m, 3.01H), 3.51−3.56 (m, 0.32H),
2.97−3.03 (m, 0.68H), 2.23−2.25 (m, 0.91H), 1.97−1.98 (m, 2.09H), 1.15−1.22 (m,
6.00H); 13C {1H} NMR (100 MHz, CDCl3) δ 169.6, 168.5, 168.4, 166.7, 160.0 (d,
1JCꢀF = 256.1 Hz), 158.1 (d, 1JCꢀF = 246.8 Hz), 131.1 (d, 3JCꢀF = 8.1 Hz), 130.8 (d, 3JCꢀF
= 7.9 Hz), 128.0 (d, 4JCꢀF = 3.7 Hz), 124.0 (d, 4JCꢀF = 4.0 Hz), 123.9 (d, 3JCꢀF = 3.4 Hz),
121.8 (d, 3JCꢀF = 16.7 Hz), 120.9 (d, 2JCꢀF = 18.0 Hz), 115.8 (d, 2JCꢀF = 21.6 Hz), 115.6
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
2
(d, JCꢀF = 21.4 Hz), 34.8, 30.2, 19.6, 19.5, 19.4, 18.9; IR (KBr): 2926, 1769, 1628,
1463, 1203 cm−1; HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd. for C12H15FNO2, 224.1081;
found, 224.1084
1ꢀ(4ꢀChlorophenyl)ꢀ2ꢀMethylpropanꢀ1ꢀOne OꢀAcetyl Oxime (1ja): colorless oil;
1
74% yield (884.3 mg); E/Z isomer mixtures (E/Z = 55/45); H NMR (400 MHz,
CDCl3) δ 7.34−7.43 (m, 3.00H), 7.12−7.14 (m, 1.07H), 3.53 (hept, J = 6.8 Hz, 0.45H),
2.98 (hept, J = 6.8 Hz, 0.55H), 2.24 (s, 1.26H), 1.98 (s, 1.64H), 1.16−1.24 (m, 6.00H);
13C {1H} NMR (100 MHz, CDCl3) δ 170.8, 170.4, 168.6, 168.5, 135.7, 134.9, 132.5,
131.3, 129.5, 128.5, 128.3, 34.9, 30.0, 19.8, 19.7, 19.5, 19.5; IR (KBr): 2971, 1766,
1603, 1480, 1369, 1201 cm−1; HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd. for
C12H15ClNO2, 240.0786; found, 240.0788
1ꢀ(3,4ꢀDichlorophenyl)ꢀ2ꢀMethylpropanꢀ1ꢀOne OꢀAcetyl Oxime (1ka): colorless
oil; 77% yield (1051.5 mg); E/Z isomer mixtures (E/Z = 57/43); 1H NMR (400 MHz,
CDCl3) δ 7.28−7.57 (m, 2.52H), 7.02−7.04 (m, 0.56H), 3.48−3.55 (m, 0.43H),
2.93−2.98 (m, 0.57H), 2.23−2.25 (m, 1.16H), 1.99−2.01 (m, 1.73H), 1.15−1.25 (m,
6.00H); 13C {1H} NMR (100 MHz, CDCl3) δ 169.7, 169.0, 168.5, 168.3, 134.0, 133.3,
132.7, 130.4, 130.3, 130.1, 128.8, 127.4, 126.4, 34.9, 29.9, 19.8, 19.7, 19.5, 19.5; IR
(KBr): 2970, 1770, 1623, 1464, 1371, 1199 cm−1; HRMS (ESIꢀTOF) m/z: [M+H]+
Calcd. for C12H14Cl2NO2, 274.0396; found, 274.0399
1ꢀ(3ꢀChlorophenyl)ꢀ2ꢀMethylpropanꢀ1ꢀOne OꢀAcetyl Oxime (1la): colorless oil;
1
77% yield (932.8 mg); E/Z isomer mixtures (E/Z = 64/36); H NMR (400 MHz,
CDCl3) δ 7.05−7.45 (m, 4.00H), 3.53 (hept, J = 6.8 Hz, 0.36H), 2.98 (hept, J = 6.8 Hz,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 14 of 31
1
2
3
4
5
6
7
8
9
0.64H), 2.25 (s, 1.07H), 2.00 (s, 1.96H), 1.18−1.25 (m, 6.00H); 13C {1H} NMR (100
MHz, CDCl3) δ 170.7, 170.1, 168.6, 168.5, 135.8, 134.7, 134.3, 134.3, 129.6, 129.6,
129.0, 128.3, 126.8, 126.3, 125.1, 34.9, 29.9, 19.8, 19.7, 19.6, 19.5; IR (KBr): 2969,
1766, 1604, 1462, 1371, 1199 cm−1; HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd. for
C12H15ClNO2, 240.0786; found, 240.0789
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
1ꢀ(4ꢀBromophenyl)ꢀ2ꢀMethylpropanꢀ1ꢀOne OꢀAcetyl Oxime (1ma): colorless oil;
1
85% yield (1207.0 mg); E/Z isomer mixtures (E/Z = 67/33); H NMR (400 MHz,
CDCl3) δ 7.51−7.57 (m, 1.94H), 7.35 (d, J = 8.0 Hz, 0.69H), 7.07 (d, J = 8.0 Hz,
1.26H), 3.53 (hept, J = 6.8 Hz, 0.33H), 2.97 (hept, J = 6.8 Hz, 0.67H), 2.24 (s, 1.00H),
1.99 (s, 2.01H), 1.18−1.24 (m, 6.00H); 13C {1H} NMR (100 MHz, CDCl3) δ 170.8,
170.4, 168.6, 168.5, 133.0, 131.8, 131.5, 131.4, 129.7, 128.6, 124.0, 123.1, 34.9, 29.8,
19.8, 19.7, 19.5, 19.5; IR (KBr): 2969, 1767, 1597, 1474, 1370, 1201 cm−1; HRMS
(ESIꢀTOF) m/z: [M+H]+ Calcd. for C12H15BrNO2, 284.0281; found, 284.0283
1ꢀ(3ꢀBromophenyl)ꢀ2ꢀMethylpropanꢀ1ꢀOne OꢀAcetyl Oxime (1na): colorless oil;
1
81% yield (1150.2 mg); E/Z isomer mixtures (E/Z = 64/36); H NMR (400 MHz,
CDCl3) δ 7.11−7.61 (m, 4.00H), 3.48−3.54 (m, 0.36H), 2.93−3.00 (m, 0.64H), 2.24 (s,
1.34H), 1.99 (s, 1.67H), 1.17−1.24 (m, 6.00H); 13C {1H} NMR (100 MHz, CDCl3) δ
170.6, 169.9, 168.6, 168.5, 136.0, 134.9, 132.6, 132.0, 131.0, 129.8, 129.6, 126.7,
125.6, 122.4, 122.3, 34.9, 29.9, 19.8, 19.7, 19.5, 19.5; IR (KBr): 2968, 1766, 1560,
1462, 1366, 1199 cm−1; HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd. for C12H15BrNO2,
284.0281; found, 284.0284
1ꢀ(4ꢀIodophenyl)ꢀ2ꢀMethylpropanꢀ1ꢀOne OꢀAcetyl Oxime (1oa): colorless oil;
1
53% yield (877.2 mg); E/Z isomer mixtures (E/Z = 55/45); H NMR (400 MHz,
CDCl3) δ 7.71−7.76 (m, 2.00H), 6.90−7.02 (m, 2.00H), 3.50 (hept, J = 6.8 Hz, 0.45H),
2.95 (hept, J = 6.8 Hz, 0.55H), 2.23 (s, 1.30H), 1.98 (s, 1.65H), 1.15−1.22 (m, 6.00H);
13C {1H} NMR (100 MHz, CDCl3) δ 171.0, 170.6, 168.7, 168.6, 137.5, 137.4, 133.6,
132.4, 129.8, 128.6, 95.9, 95.0, 34.9, 29.8, 19.8, 19.8, 19.6, 19.5; IR (KBr): 2968,
1765, 1587, 1470, 1369, 1199 cm−1; HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd. for
C12H15INO2, 332.0142; found, 332.0143
2ꢀMethylꢀ1ꢀ(4ꢀ(Trifluoromethyl)phenyl)propanꢀ1ꢀOne OꢀAcetyl Oxime (1pa):
ACS Paragon Plus Environment

Page 15 of 31
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
1
colorless oil; 61% yield (832.7 mg); E/Z isomer mixtures (E/Z = 54/46); H NMR
(400 MHz, CDCl3) δ 7.58−7.71 (m, 2.89H), 7.30−7.32 (m, 1.11H), 3.56 (hept, J = 6.8
Hz, 0.46H), 3.02 (hept, J = 6.8 Hz, 0.54H), 2.26 (s, 1.24H), 1.98 (s, 1.66H),
1.18−1.25 (m, 6.00H); 13C {1H} NMR (100 MHz, CDCl3) δ 170.8, 170.3, 168.6,
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
2
2
168.5, 137.6, 136.7, 131.5 (q, JCꢀF = 32.6 Hz), 131.0 (q, JCꢀF = 32.7 Hz), 128.6,
127.3, 125.2 (q, 3JCꢀF = 3.5 Hz), 125.2 (q, 3JCꢀF = 3.8 Hz), 123.8 (q, 1JCꢀF = 260.5 Hz),
1
123.8 (q, JCꢀF = 260.5 Hz), 34.9, 29.8, 19.7, 19.6, 19.4, 19.2; IR (KBr): 2973, 1772,
1615, 1463, 1324, 1196, 1127 cm−1; HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd. for
C13H15F3NO2, 274.1049; found, 274.1051
2ꢀMethylꢀ1ꢀ(Naphthalenꢀ2ꢀyl)propanꢀ1ꢀOne OꢀAcetyl Oxime (1qa): colorless oil;
1
80% yield (1020.0 mg); E/Z isomer mixtures (E/Z = 55/45); H NMR (400 MHz,
CDCl3) δ 7.82−7.96 (m, 3.36H), 7.50−7.65 (m, 3.11H), 7.25−7.28 (m, 0.66H), 3.61
(hept, J = 6.0 Hz, 0.45H), 3.10 (hept, J = 6.8 Hz, 0.55H), 2.26 (s, 0.96H), 1.92 (s,
2.05H), 1.21−1.31 (m, 6.00H); 13C {1H} NMR (100 MHz, CDCl3) δ 171.8, 171.7,
168.9, 168.9, 133.6, 133.2, 132.8, 132.7, 131.6, 130.6, 128.5, 128.3, 128.0, 127.8,
127.7, 127.0, 126.9, 126.6, 126.5, 126.0, 125.1, 124.8, 35.3, 30.3, 26.1, 20.0, 19.7,
19.6; IR (KBr): 2969, 1764, 1606, 1457, 1367, 1201 cm−1; HRMS (ESIꢀTOF) m/z:
[M+H]+ Calcd. for C16H18NO2, 256.1332; found, 256.1334
2ꢀMethylꢀ1ꢀ(Thiophenꢀ2ꢀyl)propanꢀ1ꢀOne OꢀAcetyl Oxime (1ra): colorless oil;
1
50% yield (527.5 mg); E/Z isomer mixtures (E/Z = 80/20); H NMR (400 MHz,
CDCl3) δ 7.37−7.62 (m, 2.00H), 7.04−7.15 (m, 1.00H), 3.49−3.56 (m, 0.20H),
3.25−3.33 (m, 0.80H), 2.24−2.30 (m, 3.00H), 1.32−1.38 (m, 6.00H); 13C {1H} NMR
(100 MHz, CDCl3) δ 168.6, 168.2, 165.5, 160.6, 136.4, 131.8, 131.2, 128.9, 128.8,
127.3, 126.3, 33.8, 30.4, 27.2, 21.3, 20.1, 19.5; IR (KBr): 2974, 1771, 1594, 1427,
1367, 1193 cm−1; HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd. for C10H14SNO2, 212.0740;
found, 212.0742
1ꢀ(1ꢀBenzylꢀ1HꢀIndolꢀ3ꢀyl)ꢀ2ꢀMethylpropanꢀ1ꢀOne OꢀAcetyl Oxime (1sa):
colorless oil; 53% yield (885.1 mg); E/Z isomer mixtures (E/Z = 94/6); 1H NMR (400
MHz, CDCl3) δ 7.62 (d, J = 8.0 Hz, 0.92H), 7.43 (s, 0.98H), 7.17−7.37 (m, 8.39H),
5.38 (s, 1.99H), 3.44 (hept, J = 6.8 Hz, 0.06H), 3.23 (hept, J = 6.8 Hz, 0.94H), 2.34 (s,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 16 of 31
1
2
3
4
5
6
7
8
9
0.16H), 2.03 (s, 2.81H), 1.30−1.34 (m, 6.00H); 13C {1H} NMR (100 MHz, CDCl3) δ
169.3, 165.5, 136.5, 136.2, 129.5, 129.0, 128.0, 126.9, 126.8, 122.6, 121.6, 120.8,
110.2, 108.0, 50.4, 35.2, 20.7, 20.0; IR (KBr): 2923, 1755, 1626, 1457, 1365, 1202
cm−1; HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd. for C21H23N2O2, 335.1754; found,
335.1757
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
2ꢀMethyltetradecanꢀ3ꢀOne OꢀAcetyl Oxime (1ta): colorless oil; 67% yield (948.1
mg); E/Z isomer mixtures (E/Z = 89/11); 1H NMR (400 MHz, CDCl3) δ 3.22−3.30 (m,
0.11H), 2.66−2.72 (m, 0.89H), 2.28−2.32 (m, 2.00H), 2.16−2.16 (m, 3.00H),
1.51−1.54 (m, 2.00H), 1.27−1.32 (m, 16.00H), 1.11−1.17 (m, 6.00H), 0.87−0.90 (m,
3.00H); 13C {1H} NMR (100 MHz, CDCl3) δ 173.4, 169.1, 34.0, 31.9, 30.0, 29.6, 29.4,
29.3, 29.1, 27.7, 26.6, 22.6, 19.8, 19.8, 14.1; IR (KBr): 2930, 2862, 1767, 1457, 1366,
1205 cm−1; HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd. for C17H34NO2, 284.2584; found,
284.2587
5ꢀFluoroꢀ2ꢀMethylꢀ2,3ꢀDihydroꢀ1HꢀIndenꢀ1ꢀOne OꢀAcetyl Oxime (1ua): colorless
1
oil; 63% yield (696.2 mg); E/Z isomer mixtures (E/Z = 64/36); H NMR (400 MHz,
CDCl3) δ 8.23−8.27 (m, 0.36H), 7.82−7.86 (m, 0.64H), 6.98−7.04 (m, 2.00H),
3.28−3.60 (m, 2.00H), 2.61−2.72 (m, 1.00H), 2.24−2.30 (m, 3.00H), 1.32−1.39 (m,
3.00H); 13C {1H} NMR (100 MHz, CDCl3) δ 171.9, 168.8, 168.6, 168.5, 165.5 (d,
1JCꢀF = 250.6 Hz), 165.2 (d, 1JCꢀF = 252.9 Hz), 152.1 (d, 3JCꢀF = 9.3 Hz), 150.7 (d, 3JCꢀF
= 9.1 Hz), 131.8 (d, 3JCꢀF = 9.6 Hz), 129.5 (d, 4JCꢀF = 2.3 Hz), 128.4 (d, 4JCꢀF = 2.5 Hz),
2
2
125.2 (d, 3JCꢀF = 9.7 Hz), 115.3 (d, JCꢀF = 23.5 Hz), 114.9 (d, JCꢀF = 22.7 Hz), 112.7
(d, 2JCꢀF = 23.3 Hz), 112.5 (d, 2JCꢀF = 22.4 Hz), 38.0, 37.8, 37.2, 36.0, 20.1, 19.6, 19.5,
18.7; IR (KBr): 2942, 1765, 1603, 1472, 1356, 1207 cm−1; HRMS (ESIꢀTOF) m/z:
[M+Na]+ Calcd. for C12H12FNO2Na, 244.0744; found, 244.0747
(E)ꢀ2ꢀMethylꢀ3,4ꢀDihydronaphthalenꢀ1(2H)ꢀOne OꢀAcetyl Oxime (1va): white
solid, mp: 96−97 oC; 67% yield (727.0 mg); 1H NMR (400 MHz, CDCl3) δ 8.14 (d, J
= 8.0 Hz, 1.00H), 7.30 (t, J = 7.6 Hz, 1.00H), 7.18 (t, J = 7.6 Hz, 1.00H), 7.13 (d, J =
7.6 Hz, 1.00H), 3.55−3.63 (m, 1.00H), 2.91−2.99 (m, 1.00H), 2.64−2.70 (m, 1.00H),
2.24 (s, 3.00H), 1.92−2.01 (m, 1.00H), 1.71−1.77 (m, 1.00H), 1.19 (d, J = 7.2 Hz,
3.00H); 13C {1H} NMR (100 MHz, CDCl3) δ 169.1, 164.7, 139.9, 130.7, 128.8, 128.1,
ACS Paragon Plus Environment

Page 17 of 31
The Journal of Organic Chemistry
1
2
3
4
5
6
126.4, 126.0, 28.5, 28.2, 24.7, 19.9, 15.6; IR (KBr): 2933, 1762, 1452, 1357, 1205
cm−1; HRMS (ESIꢀTOF) m/z: [M+Na]+ Calcd. for C13H15NO2Na, 240.0995; found,
240.0998
7
8
9
o
(E)ꢀ1ꢀPhenylethanꢀ1ꢀOne OꢀAcetyl Oxime (1fb): white solid, mp: 54−55 C; 96%
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
yield (849.6 mg); 1H NMR (400 MHz, CDCl3) δ 7.72−7.73 (m, 2.00H), 7.37−7.40 (m,
3.00H), 2.35−2.37 (m, 3.00H), 2.23−2.25 (m, 3.00H); 13C {1H} NMR (100 MHz,
CDCl3) δ 168.9, 162.4, 134.9, 130.6, 128.6, 127.0, 19.8, 14.3; IR (KBr): 2928, 1761,
1615, 1306, 1196 cm−1; HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd. for C10H12NO2,
178.0863; found, 178.0864
1ꢀPhenylpropanꢀ1ꢀOne OꢀAcetyl Oxime (1fc): colorless oil; 88% yield (840.4 mg);
1
E/Z isomer mixtures (E/Z = 87/13); H NMR (400 MHz, CDCl3) δ 7.30−7.72 (m,
5.00H), 2.85 (q, J = 7.6 Hz, 1.75H), 2.70 (q, J = 7.6 Hz, 0.25H), 1.99−2.25 (m,
3.00H), 1.08−1.19 (m, 3.00H); 13C {1H} NMR (100 MHz, CDCl3) δ 169.1, 167.3,
133.8, 130.5, 128.6, 127.2, 21.7, 19.8, 11.3; IR (KBr): 2964, 1765, 1616, 1450, 1361,
1201 cm−1; HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd. for C11H14NO2, 192.1019; found,
192.1021
(E)ꢀ1,2ꢀDiphenylethanꢀ1ꢀOne OꢀAcetyl Oxime (1fd): colorless oil; 88% yield
(1113.2 mg); 1H NMR (400 MHz, CDCl3) δ 7.73 (d, J = 7.6 Hz, 2.00H), 7.32−7.39 (m,
3.00H), 7.26−7.27 (m, 2.00H), 7.17−7.19 (m, 3.00H), 4.22 (s, 2.00H), 2.20 (s, 3.00H);
13C {1H} NMR (100 MHz, CDCl3) δ 168.7, 163.8, 135.4, 134.1, 130.7, 128.9, 128.7,
128.4, 127.6, 126.8, 34.3, 19.8; IR (KBr): 2938, 1766, 1595, 1444, 1364, 1199 cm−1;
HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd. for C16H16NO2, 254.1176; found, 254.1177
1,2ꢀDiphenylpropanꢀ1ꢀOne OꢀAcetyl Oxime (1fe): colorless oil; 94% yield (1254.9
mg); E/Z isomer mixtures (E/Z = 60/40); 1H NMR (400 MHz, CDCl3) δ 7.22−7.34 (m,
9.00H), 6.84 (d, J = 7.6 Hz, 1.00H), 4.93 (q, J = 7.2 Hz, 0.40H), 4.18 (q, J = 7.2 Hz,
0.60H), 2.14 (s, 1.27H), 1.96 (s, 1.81H), 1.53−1.57 (m, 3.00H); 13C {1H} NMR (100
MHz, CDCl3) δ 169.4, 169.3, 168.8, 168.5, 140.3, 140.0, 133.7, 132.8, 129.8, 128.8,
128.7, 128.6, 128.5, 128.2, 128.0, 127.9, 127.2, 127.2, 127.0, 126.9, 45.9, 38.8, 19.7,
19.6, 18.2, 16.3; IR (KBr): 2926, 1762, 1609, 1444, 1364, 1194 cm−1; HRMS
(ESIꢀTOF) m/z: [M+H]+ Calcd. for C17H18NO2, 268.1332; found, 268.1334
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 18 of 31
1
2
3
4
5
6
2ꢀMethylꢀ1,4ꢀDiphenylbutanꢀ1ꢀOne OꢀAcetyl Oxime (1ff): colorless oil; 75% yield
1
(1106.3 mg); E/Z isomer mixtures (E/Z = 53/47); H NMR (400 MHz, CDCl3) δ
7.35−7.49 (m, 4.00H), 7.08−7.26 (m, 6.00H), 3.42 (sextet, J = 7.2 Hz, 0.47H), 2.91
(sextet, J = 6.8 Hz, 0.53H), 2.55−2.76 (m, 2.00H), 1.95−2.16 (m, 4.00H), 1.65−1.91
(m, 1.00H), 1.21−1.29 (m, 3.00H); 13C {1H} NMR (100 MHz, CDCl3) δ 170.7, 170.7,
141.8, 141.4, 134.4, 133.0, 129.7, 129.0, 128.5, 128.4, 128.4, 128.2, 128.1, 126.9,
126.1, 126.0, 39.8, 35.8, 35.5, 35.1, 34.0, 33.4, 19.8, 19.6, 18.0, 17.7; IR (KBr): 2933,
1766, 1609, 1449, 1368, 1203 cm−1; HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd. for
C19H22NO2, 296.1645; found, 296.1648
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
Cyclopropyl(phenyl)methanone OꢀAcetyl Oxime (1fg): colorless oil; 71% yield
1
(720.6 mg); E/Z isomer mixtures (E/Z = 72/28); H NMR (400 MHz, CDCl3) δ
7.24−7.40 (m, 5.00H), 2.34−2.39 (m, 0.72H), 2.34 (s, 1.95H), 1.91−1.94 (m, 1.30H),
0.67−1.02 (m, 4.00H); 13C {1H} NMR (100 MHz, CDCl3) δ 169.2, 169.0, 169.0,
168.6, 132.4, 132.0, 129.5, 129.2, 128.8, 128.1, 128.1, 127.2, 19.8, 19.5, 15.7, 10.8,
6.6, 6.3; IR (KBr): 3020, 1765, 1602, 1366, 1207 cm−1; HRMS (ESIꢀTOF) m/z:
[M+H]+ Calcd. for C12H14NO2, 204.1019; found, 204.1021
o
Cyclobutyl(phenyl)methanone OꢀAcetyl Oxime (1fh): white solid, mp: 92−93 C;
1
77% yield (835.5 mg); E/Z isomer mixtures (E/Z = 58/42); H NMR (400 MHz,
CDCl3) δ 7.23−7.39 (m, 5.00H), 3.87 (quint, J = 9.2 Hz, 0.42H), 3.54 (quint, J = 8.4
Hz, 0.58H), 1.72−2.38 (m, 9.00H); 13C {1H} NMR (100 MHz, CDCl3) δ 170.1, 168.8,
168.6, 168.6, 133.7, 132.9, 129.6, 129.1, 128.3, 128.2, 128.0, 126.9, 40.1, 36.6, 28.6,
26.3, 19.8, 19.6, 19.3, 18.3; IR (KBr): 2961, 1757, 1436, 1364, 1203 cm−1; HRMS
(ESIꢀTOF) m/z: [M+H]+ Calcd. for C13H16NO2, 218.1176; found, 218.1177
Cyclopentyl(phenyl)methanone OꢀAcetyl Oxime (1fi): colorless oil; 76% yield
1
(877.8 mg); E/Z isomer mixtures (E/Z = 57/43); H NMR (400 MHz, CDCl3) δ
7.18−7.43 (m, 5.00H), 3.51 (quint, J = 8.4 Hz, 0.43H), 3.09 (quint, J = 8.0 Hz, 0.57H),
2.21−2.24 (m, 2.00H), 1.96−2.06 (m, 3.00H), 1.87−1.91 (m, 1.00H), 1.60−1.74 (m,
5.00H); 13C {1H} NMR (100 MHz, CDCl3) δ 171.1, 170.1, 169.0, 168.9, 134.5, 133.7,
129.4, 128.8, 128.2, 128.1, 128.1, 126.8, 45.9, 40.5, 30.4, 30.1, 25.8, 24.9, 19.9, 19.6;
IR (KBr): 2955, 1766, 1615, 1367, 1204 cm−1; HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd.
ACS Paragon Plus Environment

Page 19 of 31
The Journal of Organic Chemistry
1
2
3
4
for C14H18NO2, 232.1332; found, 232.1333
5
6
7
Cyclohexyl(phenyl)methanone OꢀAcetyl Oxime (1fj): colorless oil; 75% yield
1
(918.8 mg); E/Z isomer mixtures (E/Z = 56/44); H NMR (400 MHz, CDCl3) δ
8
9
7.14−7.39 (m, 5.00H), 3.21−3.27 (m, 0.44H), 2.63−2.69 (m, 0.56H), 2.02−2.25 (m,
2.00H), 1.62−2.03 (m, 6.00H), 1.15−1.53 (m, 5.00H); 13C {1H} NMR (100 MHz,
CDCl3) δ 171.2, 171.0, 169.0, 168.8, 134.4, 133.3, 129.3, 128.7, 128.1, 128.1, 126.7,
44.7, 40.5, 30.2, 29.4, 26.1, 25.9, 25.8, 19.8, 19.5; IR (KBr): 2929, 2855, 1765, 1444,
1365, 1202 cm−1; HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd. for C15H20NO2, 246.1489;
found, 246.1491
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
2ꢀMethylꢀ1ꢀPhenylpropanꢀ1ꢀOne OꢀPivaloyl Oxime (1fk): colorless oil; 70% yield
1
(864.5 mg); E/Z isomer mixtures (E/Z = 66/34); H NMR (400 MHz, CDCl3) δ
7.13−7.47 (m, 5.00H), 3.50 (hept, J = 7.2 Hz, 0.34H), 3.01 (hept, J = 7.2 Hz, 0.66H),
1.34 (s, 3.00H), 1.19−1.26 (m, 6.00H), 0.99 (s, 6.00H); 13C {1H} NMR (100 MHz,
CDCl3) δ 175.2, 175.0, 173.1, 172.3, 134.2, 133.2, 129.4, 128.6, 128.2, 128.1, 128.0,
126.6, 38.7, 38.3, 34.9, 30.1, 27.3, 27.1, 26.8, 19.8, 19.5; IR (KBr): 2970, 1754, 1619,
1468, 1271, 1113 cm−1; HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd. for C15H22NO2,
248.1645; found, 248.1647
2ꢀMethylꢀ1ꢀPhenylpropanꢀ1ꢀOne OꢀBenzoyl Oxime (1fl): white solid, mp: 51−52
1
oC; 47% yield (627.5 mg); E/Z isomer mixtures (E/Z = 70/30); H NMR (400 MHz,
CDCl3) δ 8.13 (d, J = 7.2 Hz, 1.00H), 7.60−7.69 (m, 2.00H), 7.41−7.52 (m, 5.00H),
7.24−7.32 (m, 2.00H), 3.67 (hept, J = 6.8 Hz, 0.30H), 3.10 (hept, J = 6.8 Hz, 0.70H),
1.24−1.33 (m, 6.00H); 13C {1H} NMR (100 MHz, CDCl3) δ 173.1, 172.7, 171.4,
163.9, 134.0, 133.7, 133.3, 133.2, 133.0, 130.2, 129.7, 129.6, 129.5, 129.0, 128.9,
128.6, 128.5, 128.3, 128.2, 126.9, 35.0, 30.4, 19.9, 19.7; IR (KBr): 2970, 1742, 1605,
1454, 1249 cm−1; HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd. for C17H18NO2, 268.1332;
found, 268.1334
o
2ꢀMethylꢀ1ꢀPhenylpropanꢀ1ꢀOne Oxime (1fm): white solid, mp: 59−60 C; 95%
1
yield (774.3 mg); E/Z isomer mixtures (E/Z = 63/37); H NMR (400 MHz, CDCl3) δ
8.78 (brs, 1.00H), 7.24−7.43 (m, 5.00H), 3.60 (hept, J = 6.8 Hz, 0.37H), 2.83 (hept, J
13
= 6.8 Hz, 0.63H), 1.12−1.23 (m, 6.00H); C {1H} NMR (100 MHz, CDCl3) δ 163.4,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 20 of 31
1
2
3
4
5
6
135.7, 133.7, 128.6, 128.5, 128.2, 128.2, 127.7, 127.6, 34.5, 27.7, 20.1, 19.4; IR
(KBr): 3283, 2964, 1761, 1451, 1202 cm−1; HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd.
for C10H14NO, 164.1070; found, 164.1072
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
General Procedure for the Internal OxidantsꢀTriggered CopperꢀCatalyzed
Unstrained CꢀC Bond Cleavage of Oxime acetates 1: A 25 mL ovenꢀdried test tube
equipped with a magnetic stirring bar, CuI (10 mol %), oxime acetate 1 (0.2 mmol),
o
and DMSO (2 mL) was vigorously stirred at 90 C for 12 h under air. Then the
mixture was cooled to room temperature, added water (15 mL), extracted with EtOAc
(15 mL × 3). The combined organic phases were dried over anhydrous Na2SO4,
filtered and concentrated in vacuo. Further purification by flash column
chromatography on silica gel or silica gel preparative plate (eluting with petroleum
ether/ethyl acetate = 100/1) provided the product 2 and 3.
o
1
4ꢀMethoxybenzonitrile (2a)18a: white solid, mp: 58−59 C; 88% yield (23.4 mg); H
NMR (400 MHz, CDCl3) δ 7.57 (d, J = 8.8 Hz, 2.00H), 6.95 (d, J = 8.8 Hz, 2.00H),
3.86 (s, 3.00H); 13C {1H} NMR (100 MHz, CDCl3) δ 162.9, 133.9, 119.3, 114.8,
103.8, 55.6
3,4ꢀDimethoxybenzonitrile (2b)18b: white solid, mp: 65−66 oC; 77% yield (25.1 mg);
1H NMR (400 MHz, CDCl3) δ 7.29 (dd, J = 2.0 Hz, 2.0 Hz, 1.00H), 7.08 (d, J = 2.0
Hz, 1.00H), 6.91 (d, J = 8.4 Hz, 1.00H), 3.94 (s, 3.00H), 3.91 (s, 3.00H); 13C {1H}
NMR (100 MHz, CDCl3) δ 152.9, 149.2, 126.5, 119.2, 113.9, 111.2, 103.9, 56.1, 56.1
1
3ꢀMethoxybenzonitrile (2c)18c: colorless oil; 71% yield (18.9 mg); H NMR (400
MHz, CDCl3) δ 7.36 (t, J = 8.4 Hz, 1.00H), 7.21 (d, J = 7.6 Hz, 1.00H), 7.11 (d, J =
6.8 Hz, 2.00H), 3.81 (s, 3.00H); 13C {1H} NMR (100 MHz, CDCl3) δ 159.6, 130.4,
124.4, 119.3, 118.8, 116.9, 113.1, 55.5
1
4ꢀMethylbenzonitrile (2d)18a: colorless oil; 73% yield (17.1 mg); H NMR (400
MHz, CDCl3) δ 7.53 (d, J = 8.0 Hz, 2.00H), 7.27 (d, J = 8.0 Hz, 2.00H), 2.42 (s,
3.00H); 13C {1H} NMR (100 MHz, CDCl3) δ 143.7, 132.1, 129.9, 119.2, 109.3, 21.9
3ꢀMethylbenzonitrile (2e)18c: colorless oil; 71% yield (16.6 mg); 1H NMR (400 MHz,
CDCl3) δ 7.39−7.44 (m, 3.00H), 7.35 (q, J = 7.6 Hz, 1.00H), 2.38 (s, 3.00H); 13C {1H}
ACS Paragon Plus Environment

Page 21 of 31
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
NMR (100 MHz, CDCl3) δ 139.3, 133.7, 132.4, 129.2, 129.0, 119.0, 112.2, 21.1
Benzonitrile (2f)18a: colorless oil; 56% yield (11.5 mg); 1H NMR (400 MHz, CDCl3)
δ 7.64 (d, J = 8.0 Hz, 2.00H), 7.61 (t, J = 7.2 Hz, 1.00H), 7.47 (t, J = 7.6 Hz, 2.00H);
13C {1H} NMR (100 MHz, CDCl3) δ 132.8, 132.1, 129.2, 118.9, 112.4
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
4ꢀFluorobenzonitrile (2g)18c: colorless oil; 63% yield (15.2 mg);1H NMR (400 MHz,
CDCl3) δ 7.68−7.72 (m, 2.00H), 7.20 (t, J = 8.4 Hz, 2.00H); 13C {1H} NMR (100
MHz, CDCl3) δ 165.0 (d, 1JFꢀC = 254.8 Hz), 134.7 (d, 3JFꢀC = 9.3 Hz), 118.1, 116.8 (d,
2JFꢀC = 22.6 Hz), 108.5 (d, 4JFꢀC = 3.6 Hz)
3ꢀFluorobenzonitrile (2h)18d: colorless oil; 64% yield (15.5 mg); 1H NMR (400 MHz,
CDCl3) δ 7.47−7.52 (m, 2.00H), 7.30 (t, J = 7.6 Hz, 1.00H), 7.24 (t, J = 8.8 Hz,
1
1.00H); 13C {1H} NMR (100 MHz, CDCl3) δ 163.1 (d, JFꢀC = 257.2 Hz), 135.2 (d,
4
2
3JFꢀC = 8.2 Hz), 133.6, 124.9 (d, JFꢀC = 3.7 Hz), 116.5 (d, JFꢀC = 19.2 Hz), 114.0,
101.5 (d, 2JFꢀC = 15.2 Hz)
2ꢀFluorobenzonitrile (2i)18e: colorless oil; 65% yield (15.8 mg); 1H NMR (400 MHz,
CDCl3) δ 7.63−7.67 (m, 2.00H), 7.32−7.37 (m, 2.00H); 13C {1H} NMR (100 MHz,
1
3
4
CDCl3) δ 162.2 (d, JFꢀC = 248.7 Hz), 131.2 (d, JFꢀC = 8.2 Hz), 128.2 (d, JFꢀC = 3.6
2
2
4
Hz), 120.5 (d, JFꢀC = 20.9 Hz), 119.1 (d, JFꢀC = 24.4 Hz), 117.5 (d, JFꢀC = 3.1 Hz),
113.9 (d, 3JFꢀC = 9.3 Hz)
o
1
4ꢀChlorobenzonitrile (2j)18a: white solid, mp: 91−92 C; 71% yield (19.5 mg); H
NMR (400 MHz, CDCl3) δ 7.60 (d, J = 8.4 Hz, 2.00H), 7.46 (d, J = 8.4 Hz, 2.00H);
13C {1H} NMR (100 MHz, CDCl3) δ 139.5, 133.4, 129.7, 118.0, 110.8
o
3,4ꢀDichlorobenzonitrile (2k)18f: white solid, mp: 72−73 C; 73% yield (25.1 mg);
1H NMR (400 MHz, CDCl3) δ 7.75 (s, 1.00H), 7.59 (d, J = 8.4 Hz, 1.00H), 7.52−7.54
(m, 1.00H); 13C {1H} NMR (100 MHz, CDCl3) δ 138.1, 133.9, 133.7, 131.5, 131.2,
116.8, 112.0
o
1
3ꢀChlorobenzonitrile (2l)18g: white solid, mp: 39−40 C; 61% yield (16.7 mg); H
NMR (400 MHz, CDCl3) δ 7.53−7.58 (m, 3.00H), 7.42 (t, J = 8.0 Hz, 1.00H); 13C {1H}
NMR (100 MHz, CDCl3) δ 135.1, 133.3, 131.8, 130.6, 130.3, 117.4, 113.9
4ꢀBromobenzonitrile (2m)18a: white solid, mp: 111−112 oC; 75% yield (27.2 mg); 1H
NMR (400 MHz, CDCl3) δ 7.63 (d, J = 8.4 Hz, 2.00H), 7.53 (d, J = 8.4 Hz, 2.00H);
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 22 of 31
1
2
3
4
5
6
7
8
9
13C {1H} NMR (100 MHz, CDCl3) δ 133.5, 132.6, 128.0, 118.1, 111.2
o
1
3ꢀBromobenzonitrile (2n)19a: white solid, mp: 38−39 C; 63% yield (22.8 mg); H
NMR (400 MHz, CDCl3) δ 7.77 (s, 1.00H), 7.74 (d, J = 8.4 Hz, 1.00H), 7.61 (d, J =
7.6 Hz, 1.00H), 7.38 (t, J = 8.0 Hz, 1.00H); 13C {1H} NMR (100 MHz, CDCl3) δ
136.2, 134.7, 130.8, 130.7, 122.9, 117.3, 114.2
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
1
4ꢀIodobenzonitrile (2o)19b: white solid, mp: 120−121 C; 61% yield (27.9 mg); H
NMR (400 MHz, CDCl3) δ 7.84 (d, J = 8.4 Hz, 2.00H), 7.37 (d, J = 8.4 Hz, 2.00H);
13C {1H} NMR (100 MHz, CDCl3) δ 138.5, 133.2, 118.3, 111.7, 100.4
4ꢀ(Trifluoromethyl)benzonitrile (2p)18c: colorless oil; 73% yield (25.0 mg); H
1
NMR (400 MHz, CDCl3) δ 7.84 (d, J = 8.4 Hz, 2.00H), 7.78 (d, J = 8.0 Hz, 2.00H);
13C {1H} NMR (100 MHz, CDCl3) δ 134.4 (q, 2JFꢀC = 33.0 Hz), 132.7, 126.1 (q, 3JFꢀC
= 3.7 Hz), 123.0 (1, 1JFꢀC = 271.2 Hz), 117.4, 116.0
2ꢀNaphthonitrile (2q)19c: white solid, mp: 64−65 oC; 74% yield (22.6 mg); H NMR
1
(400 MHz, CDCl3) 8.17 (s, 1.00H), 7.84−7.88 (m, 3.00H), 7.55−7.64 (m, 3.00H); 13C
{1H} NMR (100 MHz, CDCl3) δ 134.6, 134.2, 132.2, 129.2, 129.1, 128.4, 128.1,
127.7, 126.3, 119.3, 109.3
Thiopheneꢀ2ꢀCarbonitrile (2r)18d: colorless oil; 64% yield (14.0 mg); 1H NMR (400
MHz, CDCl3) δ 7.63 (d, J = 4.4 Hz, 2.00H), 7.14 (t, J = 4.4 Hz, 1.00H); 13C {1H}
NMR (100 MHz, CDCl3) δ 137.5, 132.8, 127.8, 114.3, 109.7
1ꢀBenzylꢀ1HꢀIndoleꢀ3ꢀCarbonitrile (2s)19d: light yellow solid, mp: 74−75 C; 64%
o
1
yield (29.7 mg); H NMR (400 MHz, CDCl3) 7.81 (t, J = 4.1 Hz, 1.00H), 7.62 (s,
1.00H), 7.32−7.41 (m, 6.00H), 7.17−7.19 (m, 2.00H), 5.36 (s, 2.00H); 13C {1H} NMR
(100 MHz, CDCl3) δ 135.7, 135.3, 135.1, 129.2, 128.0, 127.2, 124.1, 122.3, 120.0,
115.9, 110.9, 86.2, 50.9
1
2ꢀ(3ꢀOxobutyl)benzonitrile (2v): oil; 23% yield (8.0 mg); H NMR (400 MHz,
CDCl3) 7.62 (d, J = 7.6 Hz, 1.00H), 7.51 (t, J = 7.6 Hz, 1.00H), 7.36 (d, J = 7.6 Hz,
1.00H), 7.31 (t, J = 7.6 Hz, 1.00H), 3.12 (t, J = 7.6 Hz, 2.00H), 2.85 (t, J = 7.6 Hz,
2.00H), 2.17 (s, 3.00H); 13C {1H} NMR (100 MHz, CDCl3) δ 206.7, 145.1, 133.0,
130.0, 126.9, 117.9, 112.3, 43.9, 30.0, 28.4; IR (KBr): 3036, 2928, 1711, 1356, 1161
cm−1; HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd. for C11H12NO, 174.0913; found,
ACS Paragon Plus Environment

Page 23 of 31
The Journal of Organic Chemistry
1
2
3
4
174.0915
1
Acetophenone (3e)19e: colorless oil; 50% yield (12.0 mg); H NMR (400 MHz,
CDCl3) 7.95 (d, J = 8.8 Hz, 2.00H), 7.55 (t, J = 7.2 Hz, 1.00H), 7.45 (t, J = 8.0 Hz,
2.00H), 2.59 (s, 3.00H); 13C {1H} NMR (100 MHz, CDCl3) δ 198.1, 137.1, 133.1,
128.6, 128.3, 26.6
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
4ꢀPhenylbutanꢀ2ꢀone (3f)19f: colorless oil; 35% yield (10.4 mg); 13C {1H} NMR (400
MHz, CDCl3) 7.27 (t, J = 8.0 Hz, 2.00H), 7.18 (t, J = 7.2 Hz, 3.00H), 2.89 (t, J = 7.6
Hz, 2.00H), 2.74 (t, J = 7.6 Hz, 2.00H), 2.12 (s, 3.00H); 13C NMR (100 MHz, CDCl3)
δ 207.9, 141.0, 128.5, 128.3, 126.1, 45.2, 30.1, 29.8
Procedure for the Radical Trapping Experiment: A 25 mL ovenꢀdried test tube
equipped with a magnetic stirring bar, CuI (10 mol %), oxime acetate 1fa (0.2 mmol),
BHT (0.4 mmol) and DMSO (2 mL) was vigorously stirred at 90 oC for 12 h under air.
Then the mixture was cooled to room temperature, added water (15 mL), extracted
with EtOAc (15 mL × 3). The combined organic phases were dried over anhydrous
Na2SO4, filtered and concentrated in vacuo. Further purification by flash column
chromatography on silica gel (eluting with petroleum ether/ethyl acetate = 100/1)
provided the product 4.
3ꢀ(3,5ꢀDiꢀtertꢀButylꢀ4ꢀHydroxyphenyl)ꢀ2,2ꢀDimethylꢀ1ꢀPhenylpropanꢀ1ꢀone (4):
white solid, mp: 107−108 oC; 38% yield (27.8 mg); 1H NMR (400 MHz, CDCl3) 7.43
(d, J = 8.0 Hz, 2.00H), 7.39 (d, J = 6.8 Hz, 1.00H), 7.33 (t, J = 7.6 Hz, 2.00H), 6.84 (s,
2.00H), 5.05 (s, 1.00H), 3.00 (s, 2.00H), 1.36 (s, 18.00H), 1.30 (s, 6.00H); 13C {1H}
NMR (100 MHz, CDCl3) δ 209.8, 152.4, 139.6, 135.4, 130.6, 128.5, 128.0, 127.6,
126.9, 49.1, 46.8, 34.2, 30.3, 26.4; IR (KBr): 3584, 2961, 1664, 1442, 1223, 1123
cm−1; HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd. for C25H35O2, 367.2632; found,
367.2635
Procedure for the synthesis of 5a: A 25 mL roundꢀbottom flask equipped with a
magnetic stirring bar, 2ꢀhydroxyꢀ2ꢀmethylꢀ1ꢀphenylpropanꢀ1ꢀone (5 mmol),
NH2OH·HCl (7.5 mmol), NaOAc (10 mmol), EtOH (5 mL), and H2O (5 mL) was
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 24 of 31
1
2
3
4
5
6
7
8
9
vigorously stirred at room temperature for 12 h. Then the mixture was added water
(15 mL), extracted with EtOAc (30 mL × 3). The combined organic phases were dried
over anhydrous Na2SO4, filtered and concentrated in vacuo. Further purification by
flash column chromatography on silica gel (eluting with petroleum ether/ethyl acetate
= 4/1) provided the product 5a.
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
(E)ꢀ2ꢀHydroxyꢀ2ꢀMethylꢀ1ꢀPhenylpropanꢀ1ꢀOne Oxime (5a): white solid, mp:
o
1
109−110 C; 97% yield (868.2 mg); H NMR (400 MHz, CDCl3) 7.40−7.49 (m,
3.00H), 7.25 (d, J = 6.8 Hz, 2.00H), 1.44 (s, 6.00H); 13C {1H} NMR (100 MHz,
CDCl3) δ 163.7, 132.2, 128.6, 128.3, 127.9, 73.2, 28.3; IR (KBr): 3269, 3126, 2928,
1476, 1366, 1177, 990 cm−1; HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd. for C10H14NO2,
180.1019; found, 180.1022
Procedure for the synthesis of 5b: A 25 mL roundꢀbottom flask equipped with a
magnetic stirring bar, 5a (3 mmol), Ac2O (6 mmol), and CH2Cl2 (5 mL) was
vigorously stirred at room temperature for 12 h under N2. Then the mixture was added
water (15 mL), extracted with CH2Cl2 (20 mL × 3). The combined organic phases
were dried over anhydrous Na2SO4, filtered and concentrated in vacuo. Further
purification by flash column chromatography on silica gel (eluting with petroleum
ether/ethyl acetate = 10/1) provided the product 5b.
(E)ꢀ2ꢀHydroxyꢀ2ꢀMethylꢀ1ꢀPhenylpropanꢀ1ꢀOne OꢀAcetyl Oxime (5b): white
o
1
solid, mp: 113−114 C; 95% yield (629.9 mg); H NMR (400 MHz, CDCl3)
7.36−7.38 (m, 3.00H), 7.13−7.15 (m, 2.00H), 4.45 (brs, 1.00H), 1.88 (s, 3.00H), 1.43
(s, 6.00H); 13C {1H} NMR (100 MHz, CDCl3) δ 172.0, 169.0, 131.8, 128.8, 128.1,
127.0, 73.4, 28.1, 19.4; IR (KBr): 3275, 2980, 1752, 1450, 1370, 1188 cm−1; HRMS
(ESIꢀTOF) m/z: [M+H]+ Calcd. for C12H16NO3, 222.1125; found, 222.1127
Supporting Information
1
GCꢀMS analysis data for control experiments, Copies of H and 13C NMR spectra
data for all the reactants 1 and products. This material is available free of charge via
the Internet at http://pubs.acs.org.
ACS Paragon Plus Environment

Page 25 of 31
The Journal of Organic Chemistry
1
2
3
4
5
6
Acknowledgments
The authors thank the National Program on Key Research Project
(2016YFA0602900), the National Natural Science Foundation of China
(21420102003, 21702064), the Pearl River S&T Nova Program of Guangzhou
(201806010138), the Guangdong Natural Science Foundation (2016A030310460),
and National Undergraduate Innovative and Entrepreneurial Training Program
(201810561085) for financial support.
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
References
(1) (a) Murakami, M.; Ito, Y. Cleavage of CarbonꢀCarbon Single Bonds by Transition
Metals. Top. Organomet. Chem. 1999, 3, 97. (b) Jun, C.ꢀH. Transition
MetalꢀCatalyzed CarbonꢀCarbon Bond Activation. Chem. Soc. Rev. 2004, 33, 610. (c)
Park, Y. J.; Park, J.ꢀW.; Jun, C.ꢀH. MetalꢀOrganic Cooperative Catalysis in CꢀH and
CꢀC Bond Activation and Its Concurrent Recovery. Acc. Chem. Res. 2008, 41, 222. (d)
Souillart, L.; Cramer, N. Catalytic CꢀC Bond Activations via Oxidative Addition to
Transition Metals. Chem. Rev. 2015, 115, 9410. (e) Kim, D.ꢀS.; Park, W.ꢀJ.; Jun, C.ꢀH.
MetalꢀOrganic Cooperative Catalysis in CꢀH and CꢀC Bond Activation. Chem. Rev.
2017, 117, 8977.
(2) (a) Cleavage of CarbonꢀCarbon Single Bonds by Transition Metal; Murakami, M.,
Chatani, N., Ed.; WileyꢀVCH: Weinheim, 2015. (b) Murakami, M.; Ishida, N.
Potential of MetalꢀCatalyzed CꢀC Single Bond Cleavage for Organic Synthesis. J. Am.
Chem. Soc. 2016, 138, 13759.
(3) (a) Kulinkovich, O. G. The Chemistry of Cyclopropanols. Chem. Rev. 2003, 103,
2597. (b) Rubin, M.; Rubina, M.; Gevorgyan, V. Transition Metal Chemistry of
Cyclopropenes and Cyclopropanes. Chem. Rev. 2007, 107, 3117. (c) Seiser, T.;
Cramer, N. Enantioselective MetalꢀCatalyzed Activation of Strained Rings. Org.
Biomol. Chem. 2009, 7, 2835. (d) Carson, C. A.; Kerr, M. A. Heterocycles From
Cyclopropanes: Applications in Natural Product Synthesis. Chem. Soc. Rev. 2009, 38,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 26 of 31
1
2
3
4
5
6
7
8
9
3051. (e) Seiser, T.; Saget, T.; Tran, D. N.; Cramer, N. Cyclobutanes in Catalysis.
Angew. Chem. Int. Ed. 2011, 50, 7740. (f) Gao, Y.; Fu, X.ꢀF.; Yu, Z.ꢀX. In CꢀC Bond
Activation; Dong, G., ed.; Springer: Berlin, 2014, Vol. 346, PP. 195ꢀ232. (g) Xu, T.;
Dermenci, A.; Dong, G. In CꢀC Bond Activation; Dong, G., ed.; Springer: Berlin, 2014,
Vol. 346, PP. 133ꢀ258. (h) Chen, P.; Dong, G. Cyclobutenones and
Benzocyclobutenones: Versatile Synthons in Organic Synthesis. Chem. Eur. J. 2016,
22, 18290. (i) Fumagalli, G.; Stanton, S.; Bower, J. F. Recent Methodologies That
Exploit CꢀC SingleꢀBond Cleavage of Strained Ring Systems by Transition Metal
Complexes. Chem. Rev. 2017, 117, 9404.
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
(4) (a) Jun, C.ꢀH.; Park, J.ꢀW. In CꢀC Bond Activation; Dong, G., ed.; Springer: Berlin,
2014, Vol. 346, 59ꢀ83. (b) Dreis, A.; Douglas, C. In CꢀC Bond Activation; Dong, G.,
ed.; Springer: Berlin, 2014, Vol. 346, 85ꢀ110.
(5) (a) Tobisu, M.; Chatani, N. Catalytic Reactions Involving The Cleavage of
CarbonꢀCyano and Carbonꢀcarbon Triple Bonds. Chem. Soc. Rev. 2008, 37, 300. (b)
Nakao, Y.; Hiyama, T. NickelꢀCatalyzed Carbocyanation of Alkynes. Pure Appl.
Chem. 2008, 80, 1097. (c) Nakao, Y. In CꢀC Bond Activation; Dong, G., ed.; Springer:
Berlin, 2014, Vol. 346, 33ꢀ58.
(6) (a) Chen, F.; Wang, T.; Jiao, N. Recent Advances in TransitionꢀMetalꢀCatalyzed
Functionalization of Unstrained CarbonꢀCarbon Bonds. Chem. Rev. 2014, 114, 8613.
(b) Liu, H.; Feng, M.; Jiang, X. Unstrained CarbonꢀCarbon Bond Cleavage. Chem.
Asian J. 2014, 9, 3360. (c) Xia, Y.; Lu, G.; Liu, P.; Dong, G. Catalytic Activation of
CarbonꢀCarbon Bonds in Cyclopentanones. Nature 2016, 539, 546. (d) Xia, Y.; Wang,
J.; Dong, G. DistalꢀBondꢀSelective CꢀC Activation of RingꢀFused Cyclopentanones:
An Efficient Access to Spiroindanones. Angew. Chem. Int. Ed. 2017, 56, 2376. (e) Xia,
Y.; Wang, J.; Dong, G. SuzukiꢀMiyaura Coupling of Simple Ketones via Activation of
Unstrained CarbonꢀCarbon Bonds. J. Am. Chem. Soc. 2018, 140, 5347.
(7) (a) Wu, W.; Jiang, H. PalladiumꢀCatalyzed Oxidation of Unsaturated
Hydrocarbons Using Molecular Oxygen. Acc. Chem. Res. 2012, 45, 1736. (b) Wang,
T.; Jiao, N. Direct Approaches to Nitriles via Highly Efficient Nitrogenation Strategy
through CꢀH or CꢀC Bond Cleavage. Acc. Chem. Res. 2014, 47, 1137. (c) Liang, Y.ꢀF.;
ACS Paragon Plus Environment

Page 27 of 31
The Journal of Organic Chemistry
1
2
3
4
5
6
Jiao, N. Oxygenation via CꢀH/CꢀC Bond Activation with Molecular Oxygen. Acc.
Chem. Res. 2017, 50, 1640.
(8) (a) Stahl, S. S. Palladium Oxidase Catalysis: Selective Oxidation of Organic
Chemicals by Direct DioxygenꢀCoupled Turnover. Angew. Chem. Int. Ed. 2004, 43,
3400. (b) Punniyamurthy, T.; Velusamy, S.; Iqbal, J. Recent Advances in Transition
Metal Catalyzed Oxidation of Organic Substrates with Molecular Oxygen. Chem. Rev.
2005, 105, 2329. (c) Shi, Z.; Zhang, C.; Tang, C.; Jiao, N. Recent Advances in
TransitionꢀMetal Catalyzed Reactions Using Molecular Oxygen as the Oxidant. Chem.
Soc. Rev. 2012, 41, 3381. (d) Campbell, A. N.; Stahl, S. S. Overcoming the “Oxidant
Problem”: Strategies to Use O2 as the Oxidant in Organometallic CꢀH Oxidation
Reactions Catalyzed by Pd (and Cu). Acc. Chem. Res. 2012, 45, 851. (e) Allen, S. E.;
Walvoord, R. R.; PadillaꢀSalinas, R.; Kozlowski, M. C. Aerobic CopperꢀCatalyzed
Organic Reactions. Chem. Rev. 2013, 113, 6234. (f) Wang, D.; Weinstein, A. B.;
White, P. B.; Stahl, S. S. LigandꢀPromoted PalladiumꢀCatalyzed Aerobic Oxidation
Reactions. Chem. Rev. 2018, 118, 2636.
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
(9) (a) Liu, H.; Dong, C.; Zhang, Z.; Wu, P.; Jiang, X. TransitionꢀMetalꢀFree Aerobic
Oxidative Cleavage of CꢀC Bonds in αꢀHydroxy Ketones and Mechanistic Insight to
the Reaction Pathway. Angew. Chem. Int. Ed. 2012, 51, 12570. (b) Zhang, L.; Bi, X.;
Guan, X.; Li, X.; Liu, Q.; Barry, B.ꢀD.; Liao, P. Chemoselective Oxidative C(CO)
ꢀC(methyl) Bond Cleavage of Methyl Ketones to Aldehydes Catalyzed by CuI with
Molecular Oxygen. Angew. Chem. Int. Ed. 2013, 52, 11303. (c) Zhang, C.; Feng, P.;
Jiao, N. CuꢀCatalyzed Esterification Reaction via Aerobic Oxygenation and CꢀC Bond
Cleavage: An Approach to αꢀKetoesters. J. Am. Chem. Soc. 2013, 135, 15257. (d)
Tang, C.; Jiao, N. CopperꢀCatalyzed Aerobic Oxidative CꢀC Bond Cleavage for CꢀN
Bond Formation: From Ketones to Amides. Angew. Chem. Int. Ed. 2014, 53, 6528. (e)
Huang, X.; Li, X.; Zou, M.; Song, S.; Tang, C.; Yuan, Y.; Jiao, N. From Ketones to
Esters by a CuꢀCatalyzed Highly Selective C(CO)ꢀC(alkyl) Bond Cleavage: Aerobic
Oxidation and Oxygenation with Air. J. Am. Chem. Soc. 2014, 136, 14858. (f) Tsang,
A. S.ꢀK.; Kapat, A.; Schoenebeck, F. Factors That Control CꢀC Cleavage Versus CꢀH
Bond Hydroxylation in CopperꢀCatalyzed Oxidations of Ketones with O2. J. Am.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 28 of 31
1
2
3
4
Chem. Soc. 2016, 138, 518.
5
6
7
8
(10) (a) GarciaꢀBosch, I.; Company, A.; Frisch, J. R.; TorrentꢀSucarrat, M.; Cardellach,
M.; Gamba, I.; Güell, M.; Casella, L.; Que Jr., L.; Ribas, X.; Luis, J. M.; Costas, M.
O2 Activation and Selective Phenolate Ortho Hydroxylation by An Unsymmetric
Dicopper ꢁꢀη1：ηꢀPeroxido Complex. Angew. Chem. Int. Ed. 2010, 49, 2406. (b) Long,
R.; Mao, K.; Ye, X.; Yan, W.; Huang, Y.; Wang, J.; Fu, Y.; Wang, X.; Wu, X.; Xie, Y.;
Xiong, Y. Surface Facet of Palladium Nanocrystals: A Key Parameter to the
Activation of Molecular Oxygen for Organic Catalysis and Cancer Treatment. J. Am.
Chem. Soc. 2013, 135, 3200. (c) Long, R.; Mao, K.; Gong, M.; Zhou, S.; Hu, J.; Zhi,
M.; You, Y.; Bai, S.; Jiang, J.; Zhang, Q.; Wu, X.; Xiong, Y. Tunable Oxygen
Activation for Catalytic Organic Oxidation: Schottky Junction versus Plasmonic
Effects. Angew. Chem. Int. Ed. 2014, 53, 3205.
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
(11) (a) Huang, H.; Ji, X.; Wu, W.; Jiang, H. Transition MetalꢀCatalyzed CꢀH
Functionalization of Nꢀoxyenamine Internal Oxidants. Chem. Soc. Rev. 2015, 44, 1155.
(b) Tang, X.; Wu, W.; Zeng, W.; Jiang, H. CopperꢀCatalyzed Oxidative
CarbonꢀCarbon and/or CarbonꢀHeteroatom Bond Formation with O2 or Internal
Oxidants. Acc. Chem. Res. 2018, 51, 1092. (c) Huang, H.; Cai, J.; Deng, G. OꢀAcyl
Oximes: Versatile Building Blocks for NꢀHeterocycle Formation in Recent Transition
Metal Catalysis. Org. Biomol. Chem. 2016, 14, 1519. (d) Huang, H.; Cai, J.; Tang, L.;
Wang, Z.; Li, F.; Deng, GꢀJ. MetalꢀFree Assembly of Polysubstituted Pyridines from
Oximes and Acroleins. J. Org. Chem. 2016, 81, 1499. (e) Huang, H.; Xu, Z.; Ji, X.; Li,
B.; Deng, GꢀJ. ThiopheneꢀFused Heteroaromatic Systems Enabled by Internal
OxidantꢀInduced Cascade BisꢀHeteroannulation. Org. Lett. 2018, 20, 4197. (f) Zhao,
B.; Chen, C.; Lv, J.; Li, Z.; Yuan, Y.; Shi, Z. Photoinduced
FragmentationꢀRearrangement Sequence of Cycloketoxime Esters. Org. Chem. Front.
2018, 5, 2719. (g) Zhao, B.; Tan, H.; Chen, C.; Jiao, N.; Shi, Z. Photoinduced CꢀC
Bond Cleavage and Oxidation of Cycloketoxime Esters. Chin. J. Chem. 2018, 36,
995.
(12) (a) Nishimura, T.; Uemura, S. Palladium(0)ꢀCatalyzed Ring Cleavage of
Cyclobutanone Oximes Leading to Nitriles via βꢀCarbon Elimination. J. Am. Chem.
ACS Paragon Plus Environment

Page 29 of 31
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Soc. 2000, 122, 12049. (b) Yang, H.ꢀB.; Selander, N. Divergent IronꢀCatalyzed
Coupling of OꢀAcyloximes with Silyl Enol Ethers. Chem. Eur. J. 2017, 23, 1779. (c)
Zhao, B.; Shi, Z. CopperꢀCatalyzed Intermolecular HeckꢀLike Coupling of
Cyclobutanone Oximes Initiated by Selective CꢀC Bond Cleavage. Angew. Chem. Int.
Ed. 2017, 56, 12727. (d) Gu, Y.ꢀR.; Duan, X.ꢀH.; Yang, L.; Guo, L.ꢀN. Direct CꢀH
Cyanoalkylation of Heteroaromatic NꢀOxides and Quinones via CꢀC Bond Cleavage
of Cyclobutanone Oximes. Org. Lett. 2017, 19, 5908. (e) Yang, L.; Gao, P.; Duan,
X.ꢀH.; Gu, Y.ꢀR.; Guo, L.ꢀN. Direct CꢀH Cyanoalkylation of Quinoxalinꢀ2(1H)ꢀones
via Radical CꢀC Bond Cleavage. Org. Lett. 2018, 20, 1034. (f) Zhao, J.ꢀF.; Gao, P.;
Duan, X.ꢀH.; Guo, L.ꢀN. IronꢀCatalyzed RingꢀOpening/Allylation of Cyclobutanone
Oxime Esters with Allylic Sulfones. Adv. Synth. Catal. 2018, 360, 1775.
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) For selected examples: (a) Ren, Z.ꢀH.; Zhang, Z.ꢀY.; Yang, B.ꢀQ.; Wang, Y.ꢀY.;
Guan, Z.ꢀH. CopperꢀCatalyzed Coupling of Oxime Acetates with Aldehydes: A New
Strategy for Synthesis of Pyridines. Org. Lett. 2011, 13, 5394. (b) Wei, Y.; Yoshikai,
N. Modular Pyridine Synthesis from Oximes and Enals through Synergistic
Copper/Iminium Catalysis. J. Am. Chem. Soc. 2013, 135, 3756. (c) Ke, J.; Tang, Y.;
Yi, H.; Li, Y.; Cheng, Y.; Liu, C.; Lei, A. CopperꢀCatalyzed Radical/Radical
Csp3ꢀH/PꢀH CrossꢀCoupling: αꢀPhosphorylation of Aryl Ketone OꢀAcetyloximes.
Angew. Chem. Int. Ed. 2015, 54, 6604. (d) Huang, H.; Cai, J.; Ji, X.; Xiao, F.; Chen,
Y.; Deng, G.ꢀJ. Internal OxidantꢀTriggered Aerobic Oxygenation and Cyclization of
Indoles under Copper Catalysis. Angew. Chem. Int. Ed. 2016, 55, 307.
(14) (a) Huang, H.; Ji, X.; Tang, X.; Zhang, M.; Li, X.; Jiang, H. Conversion of
Pyridine to Imidazo[1,2‑a]pyridines by CopperꢀCatalyzed Aerobic Dehydrogenative
Cyclization with Oxime Esters. Org. Lett. 2013, 15, 6254. (b) Zhu, C.; Zhu, R.; Zeng,
H.; Chen, F.; Liu, C.; Wu, W.; Jiang, H. CopperꢀCatalyzed C(sp3)ꢀH/C(sp3)ꢀH
CrossꢀDehydrogenative Coupling with Internal Oxidants: Synthesis of
2ꢀTrifluoromethylꢀSubstituted Dihydropyrrolꢀ2ꢀols. Angew. Chem. Int. Ed. 2017, 56,
13324. (c) Zhu, C.; Zeng, H.; Chen, F.; Liu, C.; Zhu, R.; Wu, W.; Jiang, H.
CopperꢀCatalyzed Coupling of Oxime Acetates and Aryldiazonium Salts: An
ACS Paragon Plus Environment