Photocatalytic Hydroacylation of Alkenes by Directly Using Acyl Oximes

Article abstract of DOI:10.1021/acs.joc.0c01818

Acyl oximes are directly used as the acyl radical precursors in the hydroacylation reactions for the first time. In this work, acyl radicals can be effectively generated via β-scission of a phosphoranyl radical under photocatalytic conditions. As a result, the hydroacylation of alkenes triggered by the resulting acyl radicals leads to facile syntheses of a range of valuable ketones.

Full text of DOI:10.1021/acs.joc.0c01818

Subscriber access provided by University of Wollongong Library
Note
Photocatalytic Hydroacylation of Alkenes by Directly Using Acyl Oximes
Lan Zheng, Peng-Ju Xia, Qing-Lan Zhao, Yu-En Qian, Wen-Nian Jiang, Hao-Yue Xiang, and Hua Yang
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 14 Aug 2020
Downloaded from pubs.acs.org on August 14, 2020
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 20
The Journal of Organic Chemistry
1
2
3
4
5
6
7
Photocatalytic Hydroacylation of Alkenes by Directly
Using Acyl Oximes
8
Lan Zheng,† Peng-Ju Xia,† Qing-Lan Zhao,† Yu-En Qian,† Wen-Nian,
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
Jiang, Hao-Yue Xiang,*,† and Hua Yang*,†,§
†College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, P.
R. China
§Key Laboratory of Hunan Province for Water Environment and Agriculture Product Safety, Central
South University, Changsha 410083, P. R. China
e-mail: hyangchem@csu.edu.cn, xianghaoyue@csu.edu.cn
ABSTRACT: Acyl oximes are directly used as the acyl radical precursors in the
hydroacylation reactions for the first time. In this work, acyl radicals can be effectively
generated via β-scission of a phosphoranyl radical under photocatalytic conditions. As
a result, the hydroacylation of alkenes triggered by the resulting acyl radicals leads to
facile syntheses of a range of valuable ketones.
Ketones are versatile building blocks and ubiquitous functionalities in
pharmaceuticals, fine chemicals and agrochemicals.1 As such, there is a growing
demand for developing convenient synthetic methods in the construction of valuable
ketones. Despite the impressive advances in this field, hydroacylation of alkenes, 2 as a
straightforward synthetic pathway to access structurally varied ketones, has persistently
received particular attention. In this context, transition-metal-catalyzed strategy is
frequently employed,3 which often involves the use of carbon monoxide under high
pressure or the preinstallation of coordinating functional groups. Alternatively, acyl
radical-mediated approaches,4 offering a large portfolio of methods for the functional
group interconversion, provide intrinsic complementarity to two-electron strategies in
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 20
1
2
3
4
5
6
7
8
9
the hydroacylation of alkenes respect to both selectivity and reactivity. It is worth
mentioning that most of the traditional strategies for generating acyl radicals involve
harsh conditions and/or use of highly reactive acid derivatives.5 As a consequence, the
generation of acyl radicals under mild conditions would be highly desirable to
overcome the hurdle of this attractive methodology.
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
Scheme 1. Photoredox-Catalyzed Generation of Acyl Radicals from Acyl
Oximes and Its Derivatives.
Over the past decades, the blossom of photocatalysis has been providing fresh
opportunities for the synthetic chemistry, thus expanding the potentials of acyl radical
chemistry.6 To date, a wide range of precursors including aldehydes,7 α-ketocarboxylic
acids,8 anhydrides,9 and acyl chlorides/thioesters/silanes10 have been widely utilized in
a set of acyl radical-involved transformations, offering new synthetic routes to valuable
ketones under visible-light photoredox-catalyzed conditions. It is worth mentioning that
only limited efforts have been made to exploit aliphatic acyl radicals while most of the
reported examples focused on aroyl radicals. In 2017, Fagnoni’s group10c reported that
aliphatic acyl radicals could be obtained from acylsilanes under photoredox-catalyzed
conditions and a series of unsymmetrical ketones were thus prepared. In 2019, oxime
esters were first utilized as aliphatic acyl radical precursors by Wu and co-authors to
ACS Paragon Plus Environment

Page 3 of 20
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
react with various Michael acceptors,11 delivering diverse cyclic and linear ketones
(Scheme 1a). In this case, the reaction of acyl oximes with 1,1-diphenylene or styrenes
only gave 4,4-diphenylbut-3-en-2-one or β-carbonyl imides respectively, but no direct
hydroacylation product was isolated. While these elegant methodologies enable the
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
Table 1. Optimization of Reaction Conditionsa
entry solvent
photocatalyst
base
phosphine
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
yield (%)b
68
1
2
CH3CN [Ir(dFCF3ppy)2dtbpy][PF6]
CH3OH [Ir(dFCF3ppy)2dtbpy][PF6]
Na2CO3
Na2CO3
trace
86 (n. d.)c
trace
46
3
CH2Cl2 [Ir(dFCF3ppy)2dtbpy][PF6] Na2CO3
4
THF
[Ir(dFCF3ppy)2dtbpy][PF6]
[Ir(dFCF3ppy)2dtbpy][PF6]
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
NaOAc
Cs2CO3
K2HPO4
K2CO3
NEt3
5
CHCl3
6
Toluene [Ir(dFCF3ppy)2dtbpy][PF6]
trace
37
7
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
Ru(bpy)3PF6
Eosin Y
Ir(ppy)3
-
8
n. d.
51
9
10
11
12
13
14
15
16
17
18
19
20
21
n. d.
67
[Ir(dFCF3ppy)2dtbpy][PF6]
[Ir(dFCF3ppy)2dtbpy][PF6]
[Ir(dFCF3ppy)2dtbpy][PF6]
[Ir(dFCF3ppy)2dtbpy][PF6]
[Ir(dFCF3ppy)2dtbpy][PF6]
[Ir(dFCF3ppy)2dtbpy][PF6]
[Ir(dFCF3ppy)2dtbpy][PF6]
[Ir(dFCF3ppy)2dtbpy][PF6]
[Ir(dFCF3ppy)2dtbpy][PF6]
[Ir(dFCF3ppy)2dtbpy][PF6]
[Ir(dFCF3ppy)2dtbpy][PF6]
trace
39
trace
n.d.
DBU
n.d.
PPh3
n-Bu3P
45
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
MePPh2
Me2PPh
PPh3
42
29
82d
-
n. d.
aReaction conditions: Oxime 1a (0.4 mmol, 2 equiv.), 3-(1-phenylethenyl)pyridine 2a (0.2 mmol,
1 equiv.), phosphine (0.3 mmol, 1.5 equiv.), base (0.3 mmol, 1.5 equiv.), photocatalyst(2 mol %),
solvent (1 mL), 30 W blue LEDs, argon atmosphere, room temperature, 72 h. bYield of isolated
product; n. d. not detected. cIn the dark or added 3 equiv. of TEMPO. dPPh3 (0.4 mmol, 2.0 equiv.).
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 20
1
2
3
4
5
6
7
8
9
success on the preparation of aliphatic ketones, the introduction of electrophores is
usually necessitated to manipulate the redox potentials of the acyl radical precursors.
Rather surprisingly, the photoredox generation of acyl radicals from acyl oximes has
never been succeeded to date. On the other hand, the elegant works from Xie, Zhu,
Doyle and Rovis documented the generation of aryl radicals direct from carboxylic
acids via β-scission of a phosphoranyl radical under visible-light photoredox
conditions.12 Specifically, most recently, carboxylic acids have been directly employed
in the photocatalytic hydroacylation of styrenes to generate dialkyl ketones by Doyle
and coworkers.12b Inspired by these pioneering works, we speculated that the direct
activation of N-O bond of acyl oximes might be realized through a photocatalytic,
phosphoranyl radical-mediated process. As part of our continued interest in the
photoredox catalysis,13 we herein report the photocatalytic hydroacylation of alkenes
with readily available acyl oximes, thus enriching the arsenal of acyl radicals precursors
and providing a unique access to ketones under mild conditions (Scheme 1b).
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
We commenced our investigations by monitoring the reaction of acyl oxime 1a
with 3-(1-phenylethenyl)pyridine 2a in the presence of phosphine and photocatalyst
under irradiation of 30 W blue LEDs at room temperature (Table 1). To our delight,
through optimizing the reaction solvents, ketone 3a was furnished in an excellent yield
in CH2Cl2 (Table 1, entries 1-6). Among the screened catalysts,
[Ir(dFCF3ppy)2dtbpy][PF6] was proven to be the best choice, whereas organic dye
Esoin Y was ineffective in the reaction (Table 1, entries 7-10). A series of inorganic and
organic bases were then evaluated. Stronger bases (K2CO3 or Cs2CO3) caused severe
decomposition for the acyl oximes and significant amount of unidentified by-products
were observed. The tested organic bases were incompatible in this transformation and
Na2CO3 was finally identified to be the optimum base (Table 1, entries 11-16). The use
of other phosphines, including n-Bu3P, MePPh2 and PhPMe2, resulted in less efficient
reactions (Table 1, entries 17-19). Further increasing the amount of PPh3 to 2 equiv.
was unable to improve the product yield (Table 1, entry 20). Control experiments
showed that photocatalyst, light, and phosphine were essential for this process (Table
1, entry 21). A quantum yield  = 0.38 is in agreement with the observed requirement
ACS Paragon Plus Environment

Page 5 of 20
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
of continuous light irradiation. Noticeably, only phosphine was able to quench the
excited photocatalyst (see supporting information for details). By adding 3 equiv. of
2,2,6,6-tetramethyl-1-piperdinyloxy (TEMPO), the reaction was significantly inhibited,
indicating that a free-radical pathway might be involved (Table 1, entry 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
Scheme 2. Scope for Hydroacylation a
aReaction conditions: Oxime 1a (0.4 mmol, 2 equiv.), alkenes 2a (0.2 mmol, 1 equiv.), PPh3 (0.3
mmol, 1.5 equiv.), Na2CO3 (0.3 mmol, 1.5 equiv.), [Ir(dFCF3ppy)2dtbpy][PF6] (2 mol %), CH2Cl2
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 20
1
2
3
4
5
6
7
8
(1 mL), 30 W blue LEDs, argon atmosphere, room temperature, 72 h; Yield of isolated product.
bPerformed at 5 mmol, and 0.82 g of 3h was isolated. cReactivity ratio (rr) of the corresponding
1,1-difluoro- and CF3- products were detected by 19F NMR.
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
With these optimized reaction conditions, the generality and limitation of the
methodology were next investigated (Scheme 2). A set of structurally varied acyl
oximes were successfully converted to the corresponding ketones 3a-3e. Unfortunately,
aroyl oximes including phenyl acyl oximes and methyl 2-hydroxyimino propanoate
were unable to deliver the corresponding product under the reaction conditions. We
subsequently investigated the scope of a variety of 1,1-disubstituted alkenes. Alkenes
bearing both electron-donating and electron-withdrawing groups were able to be
converted to the desired ketones 3f-3u, Comparable reactivity was also observed for
the halogenated substrates, which could provide a handle for further functionalization
of the resulting products. Notably, seven- or six-membered cyclic diphenyl methane
derivatives were suitable substrates, delivering the corresponding ketones 3s-3u
respectively. As such fused tricyclic scaffolds are ubiquitous in antidepressants, further
derivatization of the as-prepared products could greatly broaden the versatility for this
protocol in drug discovery. The scalability of this protocol was successfully
demonstrated by performing the reaction on a gram scale for 3h under standard reaction
conditions to give a slightly reduced yield (63% vs 55%). α-Trifluoromethyl alkenes
are also amenable to this developed platform, but mainly giving γ,γ-difluoroallylic
ketone 3v-3z, 3aa with good reactivity ratio (rr) via a E1cB-type fluoride elimination
pathway rather than the hydroacylation process. Interestingly, this protocol also
provides access to direct acylation of quinoxalin-2(1H)-ones (3ab and 3ac), broadly
expanding the substrate scope for this photocatalytic strategy. However, other simple
alkenes including 2-vinylnaphthalene and 2-vinylpyridine, or functional alkenes
bearing benzenesulfonyl- or keto- groups only rendered fairly complex reactions, and
the corresponding products were unable to be isolated.
On the basis of the literature reports, a plausible mechanism for this process is
ACS Paragon Plus Environment

Page 7 of 20
The Journal of Organic Chemistry
1
2
3
4
proposed in Scheme 3. Under the irradiation of blue light, the excited *IrIII [E1/2
red
5
6
7
8
(*IrIII/IrII) = +1.21 V vs SCE] was reductively quenched by Ph3P (E1/2red = + 0.98 V vs
SCE)14 to form the corresponding IrII and triphenylphosphine radical cation.12
Subsequently, nucleophilic trapping of the triphenylphosphine radical cation with the
deprotonated acyl oximes delevered a phosphoranyl radical A. The N-O bond of acyl
oximes dissociated sequentially to give the iminyl radical B via β-scission of radical
species A. A facile radical transposition through a rapid C-C single bond cleavage
yielded an acyl radical C along with the generation of MeCN.11 This highly reactive
acyl radical was immediately captured by the alkenes to generate radical species D,
which was then reduced by IrII to form carbanion intermediate E with the concurrent
regeneration of potocatalyst. Direct protonation of intermediate E furnished the
corresponding ketones 3.
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
Scheme 3. Proposed Mechanism
In summary, we have developed a photocatalytic, phosphoranyl radical-mediated
hydroacylation for a range of alkenes. This protocol allows facile and efficient
preparation of functionalized ketones from readily available acyl oximes under mild
conditions. Importantly, acyl oximes were employed to serve as effective aliphatic acyl
radical precursors for the first time. The versatility and scalability of this transformation
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 20
1
2
3
4
5
6
would greatly broaden synthetic utilizations of acyl oximes in the domain of
photochemistry.
7
8
9
EXPERIMENTAL SECTION
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 Experimental Methods. Unless otherwise noted, all the reagents were purchased
from commercial suppliers and used without further purification. And the light source used for
illuminating the reaction vessel (commercial supplier: Synthware) consisted of blue LEDs (λmax
=
460 nm) purchased from Taobao (https://gpiled.taobao.com). A clip fan was placed over the reaction
1
vials to cool down the reaction system during the whole process of the reaction. H NMR spectra
were recorded at 400 MHz. The chemical shifts were recorded in ppm relative to tetramethylsilane
and with the solvent resonance as the internal standard. Data were reported as follows: chemical
shift, multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, br = broad), coupling
constants (Hz), integration. 13C NMR data were collected at 100 MHz with complete proton
decoupling. Chemical shifts were reported in ppm from the tetramethylsilane with the solvent
resonance as internal standard. 19F NMR data were collected at 376 MHz with complete proton
decoupling. UV–Vis spectra were recorded using a Shimadzu UV-2600. Infrared spectra (IR) were
measured by FT-IR apparatus. High resolution mass spectroscopy (HRMS) was recorded on TOF
MS ES+ mass spectrometer and acetonitrile was used to dissolve the sample. Column
chromatography was carried out on silica gel (200-300 mesh). Oximes11 1 and alkenes 215 were
prepared according to the reported procedures, respectively.
General procedure for the preparation of 3a-3z, 3aa-3ac. To an oven-dried 15 mL Schleck
flask equipped with a magnetic stir bar, oximes 1 (0.40 mmol, 2 equiv.), alkenes or quinoxalin-
2(1H)-ones or α-Trifluoromethyl alkenes 2 (0.20 mmol, 1.0 equiv.), PPh3 (0.3 mmol, 1.5 equiv.),
[Ir(dFCF3ppy)2dtbpy][PF6] (2.00 mol%), Na2CO3 (0.30 mmol, 1.5 equiv.) and CH2Cl2 (1 mL) were
added. The vessel was evacuated and backfilled with Ar. The tube was screw-capped and stirred at
room temperature under irradiation of 30 W blue LEDs (distance app. 5 cm) for 3 days. The residue
was purified by flash column chromatography (PE-PE/EtOAc = 9/1) to afford the desired products
3. The data of known compounds 3 are consistent with the previously reports16 and the copies of
their 1HNMR spectra are included in the Supporting Information.
Scale-up Reaction. To an oven-dried 100 mL Schleck flask equipped with a magnetic stir bar,
ACS Paragon Plus Environment

Page 9 of 20
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
acyl oxime 1a (10 mmol, 1.01 g, 2 equiv.), 4-(1-phenylvinyl)-1,1'-biphenyl 2d (5 mmol, 1.28 g, 1.0
equiv.), [Ir(dFCF3ppy)2dtbpy][PF6] (2.00 mol%), PPh3 (7.5 mmol, 1.97g, 1.5 equiv.), Na2CO3 (7.5
mmol, 0.79 g, 1.5 equiv.)and CH2Cl2 (25 mL) were added. The vessel was evacuated and backfilled
with Ar. The tube was screw-capped and stirred at room temperature under irradiation of 30 W blue
LEDs (distance app. 5 cm) for 4 days. The solvent was removed under reduced pressure, and then
the residue was purified by flash column chromatography (PE/EtOAc = 19/1) to afford the desired
product 3h (0.82 g, 55% 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
Characterization Data of Compound 3a-3z, 3aa-3ac.
4-Phenyl-4-(pyridin-3-yl)butan-2-one (3a). Following the general procedure, 38.7 mg of 3a
was isolated by FC on silica (PE/EtOAc 9/1) in 86% yield as yellow oil; IR (neat) ν 3357, 2919,
1684, 1372, 1169 cm-1; 1H NMR (400 MHz, Chloroform-d) δ 8.51 (d, J = 4.8 Hz, 1H), 7.50 (t, J =
7.7 Hz, 1H), 7.31 – 7.21 (m, 4H), 7.22 – 7.14 (m, 1H), 7.13 (d, J = 7.9 Hz, 1H), 7.06 (t, J = 7.4 Hz,
1H), 4.69 (dd, J = 9.0, 5.7 Hz, 1H), 3.72 (dd, J = 17.2, 9.0 Hz, 1H), 2.97 (dd, J = 17.2, 5.6 Hz, 1H),
2.15 (s, 3H); 13C{1H} NMR (100 MHz, Chloroform-d) δ 207.5, 162.1, 148.8, 143.4, 136.4, 128.7,
128.0, 126.7, 123.8, 121.4, 48.5, 48.0, 30.6.; HRMS (ESI): C15H16NO+ [M+H]+ Calcd 226.1226,
Found 226.1230.
1-Phenyl-1-(pyridin-3-yl)pentan-3-one (3b). Following the general procedure, 30.2 mg of 3b
was isolated by FC on silica (PE/EtOAc 9/1) in 63% yield as yellow oil; IR (neat) ν 3382, 2928,
1682, 1383, 1167 cm-1; 1H NMR (400 MHz, Chloroform-d) δ 8.53 (d, J = 2.4 Hz, 1H), 8.42 (d, J =
4.8 Hz, 1H), 7.51 (d, J = 7.9 Hz, 1H), 7.35 – 7.23 (m, 2H), 7.24 – 7.08 (m, 4H), 4.64 (t, J = 7.4 Hz,
1H), 3.18 (d, J = 7.6 Hz, 2H), 2.36 (q, J = 7.3 Hz, 2H), 0.97 (t, J = 7.3 Hz, 3H); 13C{1H} NMR (100
MHz, Chloroform-d) δ 208.7, 149.2, 147.8, 142.8, 139.4, 135.3, 128.8, 127.7, 126.8, 123.4, 47.9,
43.6, 36.7, 7.6; HRMS (ESI): C16H18NO+ [M+H]+ Calcd 240.1383, Found 240.1383.
1-Phenyl-1-(pyridin-3-yl)hexan-3-one (3c). Following the general procedure, 32.8 mg of 3c
was isolated by FC on silica (PE/EtOAc 9/1) in 65% yield as yellow oil; IR (neat) ν 3364, 2925,
1688, 1376, 1162 cm-1; 1H NMR (400 MHz, Chloroform-d) δ 8.54 (s, 1H), 8.43 (s, 1H), 7.51 (d, J
= 7.9 Hz, 1H), 7.33 – 7.24 (m, 2H), 7.24 – 7.13 (m, 4H), 4.64 (t, J = 7.5 Hz, 1H), 3.18 (d, J = 7.5
Hz, 2H), 2.32 (t, J = 7.3 Hz, 2H), 1.56 – 1.47 (m, 2H), 0.81 (t, J = 7.4 Hz, 3H); 13C{1H} NMR (100
MHz, Chloroform-d) δ 208.2, 149.2, 147.8, 142.8, 139.5, 135.4, 128.8, 127.7, 126.8, 123.5, 48.3,
45.5, 43.5, 17.0, 13.6; HRMS (ESI): C17H20NO+ [M+H]+ Calcd 254.1539, Found 254.1538.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 20
1
2
3
4
5
6
7
8
9
1-Phenyl-1-(pyridin-3-yl)heptan-3-one (3d). Following the general procedure, 22.4 mg of 3d
was isolated by FC on silica (PE/EtOAc 9/1) in 42% yield as yellow oil; IR (neat) ν 3366, 3186,
2920, 1682, 1374 cm-1; 1H NMR (400 MHz, Chloroform-d) δ 8.53 (s, 1H), 8.43 (s, 1H), 7.51 (d, J
= 8.0 Hz, 1H), 7.33 – 7.25 (m, 3H), 7.24 – 7.15 (m, 3H), 4.63 (t, J = 7.5 Hz, 1H), 3.18 (d, J = 7.4
Hz, 2H), 2.34 (t, J = 7.4 Hz, 2H), 1.56 – 1.40 (m, 2H), 1.27 – 1.11 (m, 2H), 0.83 (t, J = 7.3 Hz, 3H);
13C{1H} NMR (100 MHz, Chloroform-d) δ 208.3, 149.3, 147.8, 142.8, 139.5, 135.4, 128.8, 127.7,
126.8, 123.4, 48.3, 43.5, 43.3, 25.6, 22.2, 13.8.; HRMS (ESI): C18H22NO+ [M+H]+ Calcd 298.1696,
Found 268.1697.
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-methyl-1-phenyl-1-(pyridin-3-yl)hexan-3-one (3e). Following the general procedure, 22.3
mg of 3e was isolated by FC on silica (PE/EtOAc 9/1) in 42% yield as yellow oil; IR (neat) ν 3620,
2945, 2594, 1687, 631 cm-1; 1H NMR (400 MHz, Chloroform-d) δ 8.53 (s, 1H), 8.43 (d, J = 3.6 Hz,
1H), 7.52 (d, J = 8.0 Hz, 1H), 7.32 – 7.27 (m, 2H), 7.22 – 7.17 (m, 4H), 4.64 (t, J = 7.6 Hz, 1H),
3.16 (d, J = 7.2 Hz, 2H), 2.23 (d, J = 6.8 Hz, 2H), 2.11 – 2.01 (m, 1H), 0.81 (d, J = 6.6 Hz, 6H);
13C{1H} NMR (100 MHz, Chloroform-d) δ 207.9, 149.3, 147.8, 142.8, 139.5, 135.4, 128.8, 127.7,
126.8, 123.4, 52.6, 48.7, 43.5, 24.4, 22.4, 22.3. HRMS (ESI): C18H21NNaO+ [M+Na]+ Calcd
290.1515, Found 290.1540.
4,4-Diphenylbutan-2-one (3f).16a Following the general procedure, 37.2 mg of 3f was isolated
by FC on silica (PE/EtOAc 19/1) in 83% yield as yellow oil; 1H NMR (400 MHz, Chloroform-d) δ
7.29 – 7.14 (m, 10H), 4.58 (t, J = 7.6 Hz, 1H), 3.17 (d, J = 7.6 Hz, 2H), 2.07 (s, 3H); 13C{1H} NMR
(100 MHz, Chloroform-d) δ 206.8, 143.9, 128.6, 127.7, 126.5, 49.7, 46.1, 30.7.
4-Phenyl-4-(p-tolyl)butan-2-one (3g).16a Following the general procedure, 27.4 mg of 3g was
1
isolated by FC on silica (PE/EtOAc 19/1) in 58% yield as yellow oil; H NMR (400 MHz,
Chloroform-d) δ 7.20 – 7.10 (m, 5H), 7.04 – 6.98 (m, 4H), 4.47 (t, J = 7.5 Hz, 1H), 3.08 (d, J = 7.6
Hz, 2H), 2.20 (s, 3H), 1.99 (s, 3H); 13C{1H} NMR (100 MHz, Chloroform-d) δ 206.0, 143.1, 139.8,
134.9, 128.2, 127.5, 126.6, 126.5, 125.3, 48.7, 44.7, 29.6, 19.9.
4-([1,1'-Biphenyl]-4-yl)-4-phenylbutan-2-one (3h).17 Following the general procedure, 37.5mg
1
of 3h was isolated by FC on silica (PE/EtOAc 19/1) in 63% yield as yellow solid; H NMR (400
MHz, Chloroform-d) δ 7.53 (d, J = 7.4 Hz,, 2H), 7.49 (d, J = 8.0 Hz, 2H), 7.39 (t, J = 7.6 Hz, 2H),
7.34 – 7.21 (m, 7H), 7.21 – 7.14 (m, 1H), 4.63 (t, J = 7.6 Hz, 1H), 3.20 (d, J = 7.6 Hz, 2H), 2.09 (s,
3H); 13C{1H} NMR (100 MHz, Chloroform-d) δ 206.8, 143.8, 143.0, 140.8, 139.4, 128.7, 128.6,
ACS Paragon Plus Environment

Page 11 of 20
The Journal of Organic Chemistry
1
2
3
4
128.1, 127.8, 127.3, 127.2, 127.0, 126.6, 49.7, 45.8, 30.7.
5
6
4-Phenyl-4-(m-tolyl)butan-2-one (3i). 16a Following the general procedure, 35.7 mg of 3i was
7
8
1
isolated by FC on silica (PE/EtOAc 19/1) in 75% yield as yellow oil; H NMR (400 MHz,
9
Chloroform-d) δ 7.26 – 7.19 (m, 4H), 7.18 – 7.12 (m, 2H), 7.03 – 6.95 (m, 3H), 4.54 (t, J = 7.5 Hz,
1H), 3.15 (d, J = 7.5 Hz, 2H), 2.28 (s, 3H), 2.05 (s, 3H); 13C{1H} NMR (100 MHz, Chloroform-d)
δ 206.9, 144.0, 143.8, 138.2, 128.6, 128.5, 127.7, 127.3, 126.4, 124.7, 49.8, 46.1, 30.7, 21.5.
4-Phenyl-4-(o-tolyl)butan-2-one (3j). 16a Following the general procedure, 33.6 mg of 3j was
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
isolated by FC on silica (PE/EtOAc 19/1) in 71% yield as yellow oil; H NMR (400 MHz,
Chloroform-d, as an inseparable mixture of atropisomers) δ 7.35 – 7.30 (m, 1H), δ 7.26 – 7.10 (m,
8H), 4.80 – 4.75 (m, 1H), 3.14 – 3.12 (m, 2H), 2.29 – 2.28 (m, 3H), 2.07 – 2.05 (m, 3H); 13C{1H}
NMR (100 MHz, Chloroform-d) δ 207.0, 143.5, 141.5, 136.4, 130.8, 128.5, 128.0, 126.5, 126.3,
126.1, 50.0, 41.9, 30.7, 19.8.
4-(4-Chlorophenyl)-4-phenylbutan-2-one (3k).16a Following the general procedure, 34.2 mg of
3k was isolated by FC on silica (PE/EtOAc 19/1) in 65% yield as yellow oil; 1H NMR (400 MHz,
Chloroform-d) δ 7.30 – 7.22 (m, 4H), 7.21 – 7.13 (m, 5H), 4.56 (t, J = 7.5 Hz, 1H), 3.15 (d, J = 7.5
Hz, 2H), 2.08 (s, 3H); 13C{1H} NMR (100 MHz, Chloroform-d) δ 206.5, 143.4, 142.4, 132.2, 129.1,
128.7, 127.6, 126.7, 49.5, 45.3, 30.7.
4-(3-Chlorophenyl)-4-phenylbutan-2-one (3l).18 Following the general procedure, 29.9 mg of
3l was isolated by FC on silica (PE/EtOAc 19/1) in 58% yield as yellow oil; 1H NMR (400 MHz,
Chloroform-d) δ 7.30 – 7.25 (m, 2H), 7.23 – 7.08 (m, 7H), 4.56 (t, J = 7.5 Hz, 1H), 3.16 (d, J = 7.5
Hz, 2H), 2.09 (s, 3H); 13C{1H} NMR (100 MHz, Chloroform-d) δ 206.2, 146.1, 143.1, 134.4, 129.9,
128.8, 127.9, 127.7, 126.8, 126.7, 126.0, 49.4, 45.6, 30.6.
4-(2-Chlorophenyl)-4-phenylbutan-2-one (3m).19 Following the general procedure, 27.5 mg of
3m was isolated by FC on silica (PE/EtOAc 19/1) in 53% yield as yellow oil; 1H NMR (400 MHz,
Chloroform-d) δ 7.35 – 7.31 (m, 1H), 7.29 – 7.15 (m, 7H), 7.11 (m, 1H), 5.09 (t, J = 7.5 Hz, 1H),
3.21 – 3.07 (m, 2H), 2.09 (s, 3H); 13C{1H} NMR (100 MHz, Chloroform-d) δ 206.2, 142.2, 141.2,
134.0, 130.0, 128.6, 128.5, 128.1, 127.8, 127.0, 126.7, 49.1, 42.4, 30.2.
4,4-Bis(4-chlorophenyl)butan-2-one (3n). 20 Following the general procedure, 26.3 mg of 3n
1
was isolated by FC on silica (PE/EtOAc 19/1) in 45% yield as yellow oil; H NMR (400 MHz,
Chloroform-d) δ 7.24 (d, J = 8.5 Hz, 4H), 7.11 (d, J = 8.4 Hz, 4H), 4.54 (t, J = 7.5 Hz, 1H), 3.13 (d,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 20
1
2
3
4
5
6
J = 7.5 Hz, 2H), 2.09 (s, 3H); 13C{1H} NMR (100 MHz, Chloroform-d) δ 206.0, 141.9, 132.5, 129.0,
128.8, 49.3, 44.6, 30.7.
7
8
9
4-(4-Fluorophenyl)-4-phenylbutan-2-one (3o).16a Following the general procedure, 27.3 mg of
3o was isolated by FC on silica (PE/EtOAc 19/1) in 57% yield as yellow oil; 1H NMR (400 MHz,
Chloroform-d) δ 7.29 – 7.25 (m, 2H), 7.20 – 7.16 (m, 5H), 6.95 (t, J = 8.7 Hz, 2H), 4.57 (t, J = 7.5
Hz, 1H), 3.15 (d, J = 7.5 Hz, 2H), 2.08 (s, 3H);13C{1H} NMR (100 MHz, Chloroform-d) δ 206.7,
161.5 (d, JC-F = 244.8 Hz), 143.7, 139.6 (d, JC-F = 3.2 Hz), 129.2 (d, JC-F = 7.9 Hz), 128.7, 127.6,
126.6, 115.4 (d, JC-F = 21.2 Hz), 49.8, 45.2, 30.7.
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-(2-Fluorophenyl)-4-phenylbutan-2-one (3p).19 Following the general procedure, 30.4 mg of
3p was isolated by FC on silica (PE/EtOAc 19/1) in 63% yield as yellow oil; 1H NMR (400 MHz,
Chloroform-d) δ 7.20 – 7.14 (m, 4H), 7.14 – 7.05 (m, 3H), 6.98 (t, J = 7.4 Hz, 1H), 6.91 (t, J = 8.1
Hz, 1H), 4.78 (t, J = 7.6 Hz, 1H), 3.13 (d, J = 7.6 Hz, 2H), 2.02 (s, 3H); 13C{1H} NMR (100 MHz,
Chloroform-d) δ 206.5, 160.6 (d, JC-F = 244.8 Hz), 142.6, 130.7 (d, JC-F = 14.1 Hz), 128.8 (d, JC-F
= 4.5 Hz), 128.6, 128.2 (d, JC-F = 8.4 Hz), 127.7, 126.7, 124.2 (d, JC-F = 3.5 Hz), 115.8 (d, JC-F
22.5 Hz), 48.5, 39.7 (d, JC-F = 2.0 Hz), 30.3.
=
4,4-Bis(4-fluorophenyl)butan-2-one (3q).21 Following the general procedure, 20.0 mg of 3q
1
was isolated by FC on silica (PE/EtOAc 19/1) in 39% yield as yellow oil; H NMR (400 MHz,
Chloroform-d) δ 7.19 – 7.10 (m, 4H), 6.96 (t, J = 8.7 Hz, 4H), 4.57 (t, J = 7.5 Hz, 1H), 3.13 (d, J =
7.2 Hz, 2H), 2.09 (s, 3H); 13C{1H} NMR (100 MHz, Chloroform-d) δ 206.4, 161.5 (d, JC-F = 245.1
Hz), 139.5 (d, JC-F = 3.1 Hz), 129.1 (d, JC-F = 7.9 Hz), 115.5 (d, JC-F = 21.3 Hz), 49.8, 44.4, 30.7.
4-(2-Fluorophenyl)-4-(4-fluorophenyl)butan-2-one (3r). Following the general procedure,
27.3 mg of 3r was isolated by FC on silica (PE/EtOAc 19/1) in 52% yield as brown oil; IR (neat) ν
3387, 3185, 2917, 1715, 1366 cm-1; 1H NMR (400 MHz, Chloroform-d) δ 7.24 – 7.15 (m, 4H), 7.10
– 7.04 (m, 1H), 7.03 – 6.92 (m, 3H), 4.84 (t, J = 7.5 Hz, 1H), 3.19 (d, J = 7.5 Hz, 2H), 2.11 (s, 3H).
13C{1H} NMR (100 MHz, Chloroform-d) δ 206.2, 161.5 (d, JC-F = 245.0 Hz), 1610.5 (d, JC-F
=
246.0 Hz), 138.3 (d, JC-F = 3.3 Hz), 130.6 (d, JC-F = 14.1 Hz), 129.2 (d, JC-F = 7.8 Hz), 128.6 (d, JC-
F = 4.4 Hz), 128.3 (d, JC-F = 8.4 Hz), 124.3 (d, JC-F = 3.6 Hz), 115.9 (d, JC-F = 22.5 Hz), 115.4 (d,
JC-F = 21.3 Hz), 48.5, 39.0 (d, JC-F = 2.2 Hz), 30.4; HRMS (ESI): C16H14F2NaO+ [M+Na]+ Calcd
283.0905, Found 283.0897.
1-(5H-Dibenzo[a,d][7]annulen-5-yl)propan-2-one (3s). Following the general procedure, 29.6
ACS Paragon Plus Environment

Page 13 of 20
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
mg of 3s was isolated by FC on silica (PE/EtOAc 19/1) in 60% yield as yellow oil; 1H NMR (400
MHz, Chloroform-d) δ 7.39 – 7.36 (m, 2H), 7.33 – 7.28 (m, 4H), 7.23 – 7.21 (m, 2H), 6.95 (s, 2H),
4.61 (t, J = 7.5 Hz, 1H), 2.87 (d, J = 7.5 Hz, 2H), 1.81 (s, 3H); 13C{1H} NMR (100 MHz,
Chloroform-d) δ 207.4, 140.1, 134.0, 131.1, 129.8, 129.7, 128.9, 126.6, 49.1, 44.2, 30.6; HRMS
(ESI): C18H16NaO+ [M+Na]+ Calcd 271.1093, Found 271.1102.
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-(10,11-Dihydro-5H-dibenzo[a,d][7]annulen-5-yl)propan-2-one (3t).16d Following the
general procedure, 29.0 mg of 3t was isolated by FC on silica (PE/EtOAc 19/1) in 58% yield as
yellow oil; 1H NMR (400 MHz, Chloroform-d) δ 7.24 – 7.20 (m, 2H), 7.14 – 7.06 (m, 6H), 4.79 (t,
J = 7.5 Hz, 1H), 3.36 – 3.26 (m, 2H), 3.21 (d, J = 8.0 Hz, 2H), 3.13 – 3.02 (m, 2H), 2.01 (s, 3H);
13C{1H} NMR (100 MHz, Chloroform-d) δ 206.7, 141.1, 139.3, 130.4, 129.3, 126.9, 126.3, 51.5,
46.4, 33.2, 30.7.
1-(9H-Thioxanthen-9-yl)propan-2-one (3u).16d Following the general procedure, 29.0 mg of
3u was isolated by FC on silica (PE/EtOAc 19/1) in 57% yield as yellow oil; 1H NMR (400 MHz,
Chloroform-d) δ 7.44 – 7.34 (m, 4H), 7.22 – 7.16 (m, 4H), 4.68 (t, J = 7.5 Hz, 1H), 2.88 (d, J = 7.5
Hz, 2H), 1.88 (s, 3H) ;13C{1H} NMR (100 MHz, Chloroform-d) δ 207.0, 137.5, 132.5, 129.1, 127.0,
126.8, 126.7, 45.3, 44.2, 30.9.
4-([1,1'-Biphenyl]-4-yl)-5,5-difluoropent-4-en-2-one (3v). Following the general procedure,
27.7 mg of 3v was isolated by FC on silica (PE/EtOAc 19/1) in 51% yield as light yellow oil; IR
(neat) ν 2951, 1739, 1238, 1069, 899, 721 cm-1; 1H NMR (400 MHz, Chloroform-d) δ 7.59 – 7.55
(m, 4H), 7.44 (t, J = 7.5 Hz, 2H), 7.39 – 7.34 (m, 3H), 3.50 (t, J = 2.3 Hz, 2H), 2.19 (s, 3H).; 19F{1H}
NMR (376 MHz, Chloroform-d) δ -87.23 (d, J = 35.0 Hz, 1F), -88.47 (d, J = 35.0 Hz, 1F); 13C{1H}
NMR (100 MHz, Chloroform-d) δ 204.5, 154.9 (dd, JC-F = 294.0, 288.7 Hz), 140.4, 140.3, 132.0 (t,
JC-F = 4.0 Hz), 128.8, 128.1 (t, JC-F = 3.8 Hz), 127.5, 127.3, 127.0, 87.0 (dd, JC-F = 22.0, 16.4 Hz),
42.9 (d, JC-F = 2.1 Hz), 29.3; HRMS (ESI): C17H14F2NaO+ [M+Na]+ Calcd 295.0905, Found
295.0925.
5,5-difluoro-4-(p-tolyl)pent-4-en-2-one (3w)Following the general procedure, 23.9 mg of 3w
was isolated by FC on silica (PE/EtOAc 19/1) in 57% yield as brown oil; IR (neat) ν 2926, 1707,
1242, 1106, 906, 722 cm-1; 1H NMR (400 MHz, Chloroform-d) δ 7.20 – 7.14 (m, 4H), 3.44 (t, J =
2.2 Hz, 2H), 2.33 (s, 3H), 2.16 (s, 3H).; 19F{1H} NMR (376 MHz, Chloroform-d) δ-88.35 (d, J =
37.0 Hz, 1F), -89.44 (d, J = 37.2 Hz, 1F); 13C{1H} NMR (100 MHz, Chloroform-d) δ 204.6, 154.7
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 14 of 20
1
2
3
4
5
6
7
8
(dd, JC-F = 292.9, 288.0 Hz), 137.5, 130.0 (t, JC-F = 3.9 Hz),, 129.3, 127.7 (t, JC-F = 3.6 Hz), 87.1
(dd, JC-F = 21.7, 16.6 Hz), 43.0 (d, JC-F = 2.2 Hz), 29.2, 21.1; HRMS (ESI): C12H12F2NaO+ [M+Na]+
Calcd 233.0748, Found 233.0743.
9
5,5-difluoro-4-(4-methoxyphenyl)pent-4-en-2-one (3x).22 Following the general procedure,
19.8 mg of 3x was isolated by FC on silica (PE/EtOAc 19/1) in 44% yield as yellow oil; 1H NMR
(400 MHz, Chloroform-d) 7.22 (d, J = 8.4 Hz, 2H), 6.88 (d, J = 8.4 Hz, 2H), 3.80 (s, 3H), 3.43 (s,
2H), 2.16 (s, 3H); 19F{1H} NMR (376 MHz, Chloroform-d) δ -89.02 (d, J = 38.6 Hz, 1F), -90.08 (d,
J = 38.5 Hz, 1F); 13C{1H} NMR (100 MHz, Chloroform-d) δ 204.8, 158.9, 154.5 (dd, JC-F = 292.2,
287.6 Hz), 129.0 (t, JC-F = 3.6 Hz), 114.1, 86.8 (dd, JC-F = 22.0, 16.8 Hz), 55.3, 43.1 (d, JC-F = 2.1
Hz), 29.2.
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
4-(4-tert-butylphenyl)-5,5-difluoropent-4-en-2-one (3y). Following the general procedure, 26.2
mg of 3y was isolated by FC on silica (PE/EtOAc 19/1) in 52% yield as brown oil; IR (neat) ν 2937,
1741, 1374, 1238, 1067, 906 cm-1; 1H NMR (400 MHz, Chloroform-d) δ 7.36 (d, J = 8.3 Hz, 2H),
7.23 (d, J = 8.0 Hz, 2H), 3.45 (s, 2H), 2.17 (s, 3H), 1.31 (s, 9H); 19F{1H} NMR (376 MHz,
Chloroform-d) δ-88.00 (d, J = 37.0 Hz, 1F), -89.21 (d, J = 36.0 Hz, 1F); 13C{1H} NMR (100 MHz,
Chloroform-d) δ 204.8, 154.8 (dd, JC-F = 293.4, 288.0 Hz), 150.6, 129.9 (t, JC-F = 4.0 Hz), 127.4 (t,
JC-F = 3.7 Hz), 125.6, 87.0 (dd, JC-F = 21.7, 16.4 Hz), 43.0, 34.5, 31.2, 29.2; HRMS (ESI):
C15H18F2NaO+ [M+Na]+ Calcd 275.1218, Found 275.1216.
4-(4-chlorophenyl)-5,5-difluoropent-4-en-2-one (3z).22 Following the general procedure, 12.2
mg of 3z was isolated by FC on silica (PE/EtOAc 19/1) in 26% yield as yellow oil; 1H NMR (400
MHz, Chloroform-d) δ 7.32 (d, J = 8.7 Hz, 2H), 7.23 (d, J = 7.5 Hz, 2H), 3.45 (t, J = 2.2 Hz, 2H),
2.18 (s, 3H); 19F{1H} NMR (376 MHz, Chloroform-d) -87.11 (d, J = 34.6 Hz, 1F), -88.31 (d, J =
34.6 Hz, 1F); 13C{1H} NMR (100 MHz, Chloroform-d) δ 204.0, 154.8 (dd, JC-F = 293.7, 288.9 Hz),
133.5, 131.6 (t, JC-F = 4.1 Hz), 129.2 (t, JC-F = 3.7 Hz), 128.8, 86.5 (dd, JC-F = 22.6, 16.6 Hz), 42.8
(d, JC-F = 2.0 Hz), 29.3; HRMS (ESI): C11H10ClF2O+ [M+H]+ Calcd 231.0383, Found 231.0378.
5,5-difluoro-4-(naphthalen-2-yl)pent-4-en-2-one (3aa). Following the general procedure, 22.1
mg of 3aa was isolated by FC on silica (PE/EtOAc 19/1) in 45% yield as light yellow oil; IR (neat)
ν 2944, 1714, 1243, 1084, 897, 719 cm-1; 1H NMR (400 MHz, Chloroform-d) δ 7.84 – 7.78 (m, 4H),
7.73 (s, 1H), 7.50 – 7.42 (m, 3H), 3.56 (t, J = 2.3 Hz, 2H), 2.19 (s, 3H); 19F{1H} NMR (376 MHz,
Chloroform-d) δ -87.25 (d, J = 35.0 Hz, 1F), -88.71 (d, J = 35.0 Hz, 1F); 13C{1H} NMR (100 MHz,
ACS Paragon Plus Environment

Page 15 of 20
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Chloroform-d) δ 204.4 (t, JC-F = 2.9 Hz), 155.0 (dd, JC-F = 293.7, 288.5 Hz), 133.2, 132.5, 130.5 (t,
JC-F = 4.0 Hz), 128.3, 128.0, 127.6, 127.0 (t, JC-F = 3.7 Hz), 126.4, 126.4, 125.5 (dd, JC-F = 4.7, 2.6
Hz), 87.4 (dd, JC-F = 22.0, 16.6 Hz), 43.1 (d, JC-F = 2.0 Hz), 29.3; HRMS (ESI): C15H12F2NaO+
[M+Na]+ Calcd 269.0748, Found 269.0740.
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
3-Acetyl-1-methylquinoxalin-2(1H)-one (3ab).23 Following the general procedure, 21.6 mg of
3y was isolated by FC on silica (PE/EtOAc 3/1) in 53% yield as a white solid; 1H NMR (400 MHz,
Chloroform-d) δ 7.96 (d, J = 8.0 Hz, 1H), 7.69 (t, J = 8.1 Hz, 1H), 7.41 (t, J = 7.7 Hz, 1H), 7.36 (d,
J = 8.5 Hz, 1H), 3.74 (s, 3H), 2.72 (s, 3H);13C{1H} NMR (100 MHz, Chloroform-d) δ 198.1, 152.9,
151.9, 134.5, 132.8, 131.9, 131.5, 124.2, 113.9, 29.0, 28.5.
3-Acetyl-1-ethylquinoxalin-2(1H)-one (3ac).24 Following the general procedure, 23.1 mg of 3z
was isolated by FC on silica (PE/EtOAc 3/1) in 53% yield as a yellow solid; 1H NMR (400 MHz,
Chloroform-d) δ 7.97 (d, J = 8.0 Hz, 1H), 7.68 (t, J = 8.0 Hz, 1H), 7.43 – 7.36 (m, 2H), 4.35 (q, J =
7.2 Hz, 2H), 2.72 (s, 3H), 1.40 (t, J = 7.2 Hz, 3H);13C{1H} NMR (100 MHz, Chloroform-d) δ 198.2,
152.4, 151.8, 133.5, 132.7, 132.2, 131.8, 124.0, 113.7, 37.4, 28.6, 12.4.
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the ACS Publications website at DOI:
10.1021/acs.joc.xxxxxxx
Mechanistic studies.
1H NMR and 13C NMR spectra spectra for compounds 3, and 19F NMR spectra for compound 3v-
3z, 3aa.
AUTHOR INFORMATION
Corresponding Author
* Email: hyangchem@csu.edu.cn (H. Yang)
* Email: xianghaoyue@csu.edu.cn (H. Y. Xiang)
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 16 of 20
1
2
3
4
5
6
7
8
We gratefully acknowledge the financial support from the National Natural Science Foundation of
China (21576296, 21776318, 21676302 and 81703365), the Fundamental Research Funds for
Central South University (2019zzts222 and 2020zzts401) and Central South University.
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) Shibasaki, M.; Kanai, M. Asymmetric Synthesis of Tertiary Alcohols and α-
Tertiary Amines via Cu-Catalyzed C−C Bond Formation to Ketones and Ketimines.
Chem. Rev. 2008, 108, 2853-2873. (b) Wong, O. A.; Shi, Y. Organocatalytic Oxidation.
Asymmetric Epoxidation of Olefins Catalyzed by Chiral Ketones and Iminium Salts.
Chem. Rev. 2008, 108, 3958-3987. (c) Prasad, P. K.; Reddi, R. N.; Arumugam, S.
Recent Methods for the Synthesis of Alpha-Acyloxy Ketones. Org. Biomol. Chem.
2018, 16, 9334-9348.
2. (a) Ghosh, A.; Johnson, K. F.; Vickerman, K. L.; Walker, J. A.; Stanley, L. M.,
Recent Advances in Transition Metal-Catalysed Hydroacylation of Alkenes and
Alkynes. Org. Chem. Front. 2016, 3, 639-644. (b) Kim, J.; Yi, C. S. Intermolecular
Markovnikov-Selective Hydroacylation of Olefins Catalyzed by a Cationic Ruthenium-
Hydride Complex. ACS Catal. 2016, 6, 3336-3339. (c) Willis, M. C., Transition Metal
Catalyzed Alkene and Alkyne Hydroacylation. Chem.Rev. 2010, 110, 725-748.
3. (a) Park, Y. J.; Park, J.-W.; Jun, C.-H., Metal−Organic Cooperative Catalysis in
C−H and C−C Bond Activation and Its Concurrent Recovery. Acc. Chem. Res. 2008,
41, 222-234. (b) Murphy, S. K.; Bruch, A.; Dong, V. M. Mechanistic Insights into
Hydroacylation with Non-Chelating Aldehydes. Chem. Sci. 2015, 6, 174-180.
4. (a) Banerjee, A.; Lei, Z.; Ngai, M. Y. Acyl Radical Chemistry via Visible-Light
Photoredox Catalysis. Synthesis 2019, 51, 303-333. (b) Ge, L.; Li, Y.; Bao, H. Iron-
Catalyzed Radical Acyl-Azidation of Alkenes with Aldehydes: Synthesis of
Unsymmetrical beta-Azido Ketones. Org. Lett. 2019, 21, 256-260. (c) Jiao, Y.; Chiou,
M.-F.; Li, Y.; Bao, H., Copper-Catalyzed Radical Acyl-Cyanation of Alkenes with
Mechanistic Studies on the tert-Butoxy Radical. ACS Catal. 2019, 9, 5191-5197. (d)
Guo, Y. Q.; Wang, R.; Song, H.; Liu, Y.; Wang, Q. Visible-Light-Induced
Deoxygenation/Defluorination Protocol for Synthesis of gamma,gamma-
ACS Paragon Plus Environment

Page 17 of 20
The Journal of Organic Chemistry
1
2
3
4
Difluoroallylic Ketones. Org. Lett. 2020, 22, 709-713.
5
6
7
8
5. Chatgilialoglu, C.; Crich, D.; Komatsu, M.; Ryu, I. Chemistry of Acyl Radicals.
Chem. Rev. 1999, 99, 1991-2070.
9
6. (a) Prier, C. K.; Rankic, D. A.; MacMillan, D. W. Visible Light Photoredox
Catalysis with Transition Metal Complexes: Applications in Organic Synthesis. Chem.
Rev. 2013, 113, 5322-5363. (b) Narayanam, J. M.; Stephenson, C. R. Visible Light
Photoredox Catalysis: Applications in Organic Synthesis. Chem. Soc. Rev. 2011, 40,
102-113. (c) Romero, N. A.; Nicewicz, D. A. Organic Photoredox Catalysis. Chem. Rev.
2016, 116, 10075-10166. (d) Wang, C.-S.; Dixneuf, P. H.; Soulé, J.-F., Photoredox
Catalysis for Building C–C Bonds from C(sp2)–H Bonds. Chem. Rev. 2018, 118, 7532-
7585.
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
7. (a) de Souza, G. F. P.; Bonacin, J. A.; Salles, A. G., Jr. Visible-Light-Driven
Epoxyacylation and Hydroacylation of Olefins Using Methylene Blue/Persulfate
System in Water. J. Org. Chem. 2018, 83, 8331-8340. (b) Fan, P.; Zhang, C.; Lan, Y.;
Lin, Z.; Zhang, L.; Wang, C. Photocatalytic hydroacylation of trifluoromethyl alkenes.
Chem. Commun. 2019, 55, 12691-12694.
8. (a) Penteado, F.; Lopes, E. F.; Alves, D.; Perin, G.; Jacob, R. G.; Lenardao, E. J.
alpha-Keto Acids: Acylating Agents in Organic Synthesis. Chem. Rev. 2019, 119, 7113-
7279. (b) Zhao, J. J.; Zhang, H. H.; Shen, X.; Yu, S. Enantioselective Radical
Hydroacylation of Enals with alpha-Keto acids Enabled by Photoredox/Amine
Cocatalysis. Org. Lett. 2019, 21, 913-916. (c) Chen, Z.; Lu, F.; Yuan, F.; Sun, J.; Du, L.;
Li, Z.; Gao, M.; Shi, R.; Lei, A., Photocatalytic Decarboxylative Coupling Between α-
Oxocarboxylicacids and alkenes. Sci. China Chem. 2019, 62, 1497-1500.
9. Dong, S.; Wu, G.; Yuan, X.; Zou, C.; Ye, J. Visible-Light Photoredox Catalyzed
Hydroacylation of Electron-Deficient Alkenes: Carboxylic Anhydride as an Acyl
Radical Source. Org. Chem. Front. 2017, 4, 2230-2234.
10. (a) Wang, C.-M.; Song, D.; Xia, P.-J.; Wang, J.; Xiang, H.-Y.; Yang, H. Visible-
Light-Promoted Synthesis of 1,4-Dicarbonyl Compounds via Conjugate Addition of
Aroyl Chlorides. Chem. Asian J. 2018, 13, 271-274. (b) Norman, A. R.; Yousif, M. N.;
McErlean, C. S. P. Photoredox-Catalyzed Indirect Acyl Radical Generation from
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 18 of 20
1
2
3
4
5
6
7
8
9
Thioesters. Org. Chem. Front. 2018, 5, 3267-3298. (c) Capaldo, L.; Riccardi, R.;
Ravelli, D.; Fagnoni, M. Acyl Radicals from Acylsilanes: Photoredox-Catalyzed
Synthesis of Unsymmetrical Ketones. ACS Catal. 2017, 8, 304-309. (d) Liu Y.; Wang
Q. L.; Zhou C. S.; Xiong B. Q.; Zhang, P. L.; Yang, C. A.; Tang, K. W., Visible-Light-
Mediated Ipso-Carboacylation of Alkynes: Synthesis of 3-Acylspiro[4,5]trienones
from N-(p-Methoxyaryl)propiolamides and Acyl Chlorides. J. Org. Chem. 2018, 83,
2210–2218. (e) Sarkar S.; Banerjee A.; Yao W.; Patterson, E. V.; Ngai M. Y.,
Photocatalytic Radical Aroylation of Unactivated Alkenes: Pathway to β-
Functionalized 1,4-, 1,6-, and 1,7-Diketones. ACS Catal. 2019, 9, 10358–10364. (f) Lei
Z.; Banerjee A.; Kusevska E.; Rizzo E.; Liu P.; Ngai M. Y., β‐Selective Aroylation of
Activated Alkenes by Photoredox Catalysis. Angew. Chem. Int. Ed. 2019, 58, 7318-
7323. (g) Zhao Q. S.; Xu G. Q.; Liang H.; Wang Z. Y.; Xu P. F., Aroylchlorination of
1,6-Dienes via a Photoredox Catalytic Atom-Transfer Radical Cyclization Process. Org.
Lett. 2019, 21, 8615–8619.
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) Cheng, Y. Y.; Lei, T.; Su, L.; Fan, X.; Chen, B.; Tung, C. H.; Wu, L. Z. Visible
Light Irradiation of Acyl Oxime Esters and Styrenes Efficiently Constructs beta-
Carbonyl Imides by a Scission and Four-Component Reassembly Process. Org. Lett.
2019, 21, 8789-8794. (b) Fan, X.; Lei, T.; Chen, B.; Tung, C. H.; Wu, L. Z.
Photocatalytic C-C Bond Activation of Oxime Ester for Acyl Radical Generation and
Application. Org. Lett. 2019, 21, 4153-4158.
12. (a) Zhang, M.; Xie, J.; Zhu, C., A General Deoxygenation Approach for Synthesis
of Ketones from Aromatic Carboxylic Acids and Alkenes. Nat. Commun. 2018, 9, 3517.
(b) Martinez Alvarado, J. I.; Ertel, A. B.; Stegner, A.; Stache, E. E.; Doyle, A. G. Direct
Use of Carboxylic Acids in the Photocatalytic Hydroacylation of Styrenes To Generate
Dialkyl Ketones. Org. Lett. 2019, 21, 9940-9944. (c) Stache, E. E.; Ertel, A. B.; Rovis,
T.; Doyle, A. G., Generation of Phosphoranyl Radicals via Photoredox Catalysis
Enables Voltage–Independent Activation of Strong C–O Bonds. ACS Catal. 2018, 8,
11134-11139.
13. (a) Song, D.; Wang, C.-M.; Ye, Z.-P.; Xia, P.-J.; Deng, Z.-X.; Xiao, J.-A.; Xiang,
H.-Y.; Yang, H. Visible-Light-Driven, Photoredox-Catalyzed Cascade of ortho-
ACS Paragon Plus Environment

Page 19 of 20
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Hydroxycinnamic Esters To Access 3-Fluoroalkylated Coumarins. J. Org. Chem. 2019,
84, 7480-7487. (b) Xiang, H.; Zhao, Q.-L.; Xia, P.-J.; Xiao, J.-A.; Ye, Z.-P.; Xie, X.;
Sheng, H.; Chen, X.-Q.; Yang, H. Visible-Light-Induced External Radical-Triggered
Annulation To Access CF2-Containing Benzoxepine Derivatives. Org. Lett. 2018, 20,
1363-1366. (c) Xia, P.-J.; Ye, Z.-P.; Hu, Y.-Z.; Song, D.; Xiang, H.-Y.; Chen, X.-Q.;
Yang, H., Photocatalytic, Phosphoranyl Radical-Mediated N–O Cleavage of Strained
Cycloketone Oximes. Org. Lett. 2019, 21, 2658-2662.
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. Pandey, G.; Pooranchand, D.; Bhalerao, U. T.; Photoinduced Single Electron
Transfer Activation of Organophosphines: Nucleophilic Trapping of Phosphine Radical
Cation. Tetrahedron 1991, 47, 1745-1752.
15. Onuigbo, L.; Raviola, C.; Di Fonzo, A.; Protti, S.; Fagnoni, M., Sunlight-Driven
Synthesis of Triarylethylenes (TAEs) via Metal-Free Mizoroki-Heck-Type Coupling.
Eur. J. Org. Chem. 2018, 2018, 5297-5303.
16. (a) Mannathan, S.; Raoufmoghaddam, S.; Reek, J. N. H.; de Vries, J. G.; Minnaard,
A. J.. Palladium(II) Acetate Catalyzed Reductive Heck Reaction of Enones; A Practical
Approach. ChemCatChem 2015, 7, 3923-3927. (b) Aoyama, T.; Hayakawa, M.; Kubota,
S.; Ogawa, S.; Nakajima, E.; Mitsuyama, E.; Iwabuchi, T.; Kaneko, H.; Obara, R.;
Takido, T.; Kodomari, M.; Ouchi, A. Simple Method for sp2–sp3 and sp3–sp3 Carbon–
Carbon Bond Activation in 2-Substituted 1,3-Diketones. Synthesis 2015, 47, 2945-2956.
(c) Chen, W.; Chen, H.; Xiao, F.; Deng, G. J. Palladium-catalyzed conjugate addition
of arylsulfonyl hydrazides to alpha,beta-unsaturated ketones. Org. Biomol. Chem. 2013,
11, 4295-4298. (d) Yang, C.; Shen, C.; Li, H.; Tian, S., Ferric Chloride-Catalyzed
Decarboxylative Alkylation of β-Keto Acids with Benzylic Alcohols. Chin. Sci. Bull.
2012, 57, 2377-2381.
17. Zhang W.; Wu L.; Chen P.; Liu G. Enantioselective Arylation of Benzylic C−H
Bonds by Copper-Catalyzed Radical Relay. Angew. Chem. Int. Ed. 2019, 58, 6425-6429.
18. Nishikata, T.; Yamamoto, Y.; Miyaura, N. Palladium(II)-Catalyzed 1,4-Addition of
Arylboronic Acids to β-Arylenones for Enantioselective Synthesis of 4-Aryl-4H-
chromenes. Adv. Synth. Catal. 2007, 349, 1759-1764.
19. Chen, W.; Chen, H.; Xiao, F.; Deng, G.-J. Palladium-Catalyzed Conjugate Addition
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 20 of 20
1
2
3
4
5
6
of Arylsulfonyl Hydrazides to α, β-Unsaturated Ketones. Org. Biomol. Chem. 2013, 11,
4295-4298.
7
8
9
20. Mane, R. B.; Desai, U. V.; Hebbalkar, G. D. Synthesis of Juvabione Analogs.
Collect. Czech. Chem. Commun. 1988, 53, 646-657.
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
21. Buschauer, A.; Friese-Kimmel, A.; Baumann, G.; Schunack, W. Synthesis and
Histamine H2 Agonistic Activity of Arpromidine Analogs: Replacement of the
Pheniramine-like Moiety by Non-heterocyclic Groups. Eur. J. Med. Chem. 1992, 27,
321-330.
22. Cao, C.; Ou, S.; Jiang, M.; Liu J. -T. An Efficient Method for the Synthesis of gem-
Difluoroolefins. Tetrahedron Lett. 2017, 58, 482-485.
23. Zeng, X.; Liu, C.; Wang, X.; Zhang, J.; Wang, X.; Hu, Y. Silver-Catalyzed
Decarboxylative Acylation of Quinoxalin-2(1H)-ones with α-Oxo-carboxylic Acids.
Org. Biomol. Chem. 2017, 15, 8929-8935.
24. Mamedov, V. A.; Kalinin, A. A.; Gubaidullin, A. T.; Isaikina, O. G.; Litvinov, I. A.
Synthesis and Functionalization of 3-Ethylquinoxalin-2(1H)-one. Russ. J. Org. Chem.
2005, 41, 599-606.
ACS Paragon Plus Environment