Visible-Light-Driven Epoxyacylation and Hydroacylation of Olefins Using Methylene Blue/Persulfate System in Water

Article abstract of DOI:10.1021/acs.joc.8b01026

A visible-light-driven strategy for hydroacylation and epoxyacylation of olefins in water using methylene blue as photoredox catalyst and persulfate as oxidant is reported. In this unprecedented unified approach, two different transformations are accomplished using only one set of reagents. The method has a broad scope spanning a range of aromatic and aliphatic aldehydes as well as conjugated and nonconjugated olefins to deliver ketones and epoxyketones from abundant and inexpensive chemical feedstocks.

Full text of DOI:10.1021/acs.joc.8b01026

Subscriber access provided by NEW MEXICO STATE UNIV
Article
Visible light-driven epoxyacylation and hydroacylation of
olefins using methylene blue/persulfate system in water
Gabriela Freitas Pereira de Souza, Juliano A. Bonacin, and Airton Gonçalves Salles
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 06 Jul 2018
Downloaded from http://pubs.acs.org on July 6, 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 35
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Visible lightꢀdriven epoxyacylation and
hydroacylation of olefins using methylene
blue/persulfate system in water
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
Gabriela F. P. de Souza a, Juliano A. Bonacin b and Airton G. Salles, Jr *a
a Department of Organic Chemistry, Institute of Chemistry, University of Campinas, P.O. Box
6154, Campinas, São Paulo, 13084ꢀ862, Brazil.
b Department of Inorganic Chemistry, Institute of Chemistry, University of Campinas, P.O. Box
6154, Campinas, São Paulo, 13084ꢀ862, Brazil.
Email: asalles@iqm.unicamp.br
KEYWORDS: photoredox catalysis, C−H functionalization, epoxyacylation, hydroacylation,
methylene blue
ACS Paragon Plus Environment
1

The Journal of Organic Chemistry
Page 2 of 35
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
ABSTRACT A visible lightꢀdriven strategy for hydroacylation and epoxyacylation of olefins in
water using methylene blue as photoredox catalyst and persulfate as oxidant is reported. In this
unprecedented unified approach, two different transformations are accomplished using only one
set of reagents. The method has a broad scope spanning a range of aromatic and aliphatic
aldehydes as well as conjugated and nonꢀconjugated olefins to deliver ketones and epoxyketones
from abundant and inexpensive chemical feedstocks.
INTRODUCTION
Photoredox catalysis has come to light in the past few years as a powerful tool to the
development of a broad range of new bondꢀforming reactions.1 In spite of substantial advances in
the field of photocatalytic activation of Csp3−H bonds,2 the visible lightꢀmediated selective
activation of Csp2−H bonds has remained somewhat underexplored.3 In this context, cheap and
commercially available aldehydes would be representatives for the mild generation of acyl
radicals. The resulting radical intermediates can promptly engage into several transformations
expanding molecular complexity in an atomꢀeconomical fashion. As a prominent example, the
ACS Paragon Plus Environment
2

Page 3 of 35
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
addition of acyl radicals to olefins converts abundant chemical feedstocks into ketones and α,βꢀ
epoxy ketones, which are relevant precursors for chemical transformations.4 However,
previously reported methods suffer from limited substrate scope (usually the combination of
electronꢀpoor olefins and aromatic aldehydes), harsh reaction conditions and the use of
expensive transition metals as catalysts.5 Regarding the photocatalytic alternative, to date few
reports can be found.6 Furthermore, these methods are somewhat hampered by the use of UVA
irradiation, transition metals, and once again, narrow substrate scope (Scheme 1).
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
ACS Paragon Plus Environment
3

The Journal of Organic Chemistry
Page 4 of 35
1
2
3
4
Scheme 1. Previous Work and Our Approach for Epoxyacylation/Hydroacylation
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
A practical guiding principle of Green Chemistry is the capability to conceive benign
chemical transformations from the very beginning. As Sheldon stated, “Green Chemistry is
primary pollution prevention rather than waste remediation”.7 A lot of effort has been devoted in
the design of environmentally suitable protocols encompassing issues such as atom efficiency,
energy consumption and sustainability of chemical procedures.8 Despite the inherent green
features of photocatalysis, the development of methods employing alternatives to organic
ACS Paragon Plus Environment
4

Page 5 of 35
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
solvents and transition metalꢀbased photocatalysts, so ubiquitous in the wellꢀestablished
approaches, is still highly desirable. Ticking all the boxes of sustainable chemistry, waterꢀsoluble
organic dyes are increasingly attracting the attention of synthetic community as photocatalysts
because of their advantages of being less toxic, lowꢀcost and easily accessible.9 Motivated by 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
desire to develop
a
more sustainable photochemical protocol to perform
hydroacylation/epoxyacylation of olefins, we focused our attention on the use of methylene blue
as a waterꢀsoluble organic photocatalyst.
Herein, we describe a visible lightꢀdriven hydroacylation and epoxyacylation of nonꢀ
conjugated and conjugated olefins, with aliphatic and aromatic aldehydes using potassium
persulfate and methylene blue as an organophotoredox catalyst. The reaction was carried out in
pure water and depending on the nature of the olefin, two different reaction pathways operate
leading to ketones or α,βꢀepoxyketones in moderate to high yields. Isolation of compounds was
performed employing a plug of silica; therefore, preventing a large waste generation.
RESULTS AND DISCUSSION
As an initial design, we chose the reaction between styrene and benzaldehyde as a
representative transformation (Table 1, entry 1). By using 2.5 mol% of methylene blue as
photocatalyst along with potassium persulfate (2 equiv) as oxidant in basic aqueous solution
under 100 W irradiation, 35% of the epoxyketone 3a was formed. Increasing the concentration of
base and decreasing the oxidant loading to 1.0 equivalent led to inferior yield (Table 1, entry 2).
ACS Paragon Plus Environment
5

The Journal of Organic Chemistry
Page 6 of 35
1
2
3
4
5
6
7
Table 1. Optimization of the Visible Lightꢀdriven Epoxyacylation
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
entry
methylene
blue (mol%)
base
K2S2O8
(equiv)
solvent
yield
(mol Lꢀ1)
1
2
3
2.5
2.5
2.5
K2CO3 (1.0)
K2CO3 (1.5)
K2CO3 (0.5)
2.0
1.0
1.0
water
water
water
35%
26%
47%
4
5
2.5
5.0
2.5
ꢀ
K2CO3 (0.5)
K2CO3 (0.5)
NaOH (0.5)
K2CO3 (0.5)
ꢀ
2.0
2.0
2.0
2.0
2.0
ꢀ
water
water
92%
72%
25%
10%
traces
0%
6
water
7
water
8
2.5
2.5
2.5
2.5
2.5
water
9
K2CO3 (0.5)
K2CO3 (0.5)
K2CO3 (0.5)
K2CO3 (0.5)
water
10a
11b
12
2.0
2.0
2.0
water
14%
65%
38%
water
acetonitrile
General conditions: 7 ml of water, 1 (1 mmol), 2 (2 mmol), visible light (100 W
household bulb), 25 oC, 12 h. Yield of isolated product . a No light. N2 atmosphere.
b
To our delight, decreasing the concentration of base to 0.5 M and using 2 equivalents of
potassium persulfate gave access to the targeted product in 92% yield with an excellent
ACS Paragon Plus Environment
6

Page 7 of 35
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
diastereomeric ratio (trans/cis > 95:5, determined by 1H NMR). Interestingly, under the
optimized conditions, we did not observe the corresponding hydroacylation product. In spite of
the photosensitizing ability of methylene blue, we also did not observe any identifiable product
coming from singlet oxygen reactions. As the reaction medium is airꢀequilibrated, we believe the
oxygen concentration in water is not enough to allow substantial singlet oxygen generation.
Control experiments demonstrated that all the reagents and light were essential to obtain
considerable conversion to 3a (Table 1, entries 7˗10). To probe the engagement of O2 in the
process, we performed the reaction in degassed water and kept the aqueous medium under N2
atmosphere, which led to a lower yield (Table 1, entry 11) suggesting an important role of
oxygen in this transformation. We also investigated the use of acetonitrile as solvent and, under
this condition, yield was very low (Table 1, entry 12). In our protocol, an organic suspension in
water is formed and a fast stirring speed (1150 rpm) is of paramount importance to guarantee
acceptable yields.
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
After establishing the optimized conditions for our protocol, we then explored the
substrate scope employing a range of aldehydes and olefins (Scheme 2). Electronꢀdonating and
electronꢀwithdrawing substituents on the phenyl ring of both aldehyde and olefin were found to
be competent substrates in this transformation, furnishing the corresponding epoxyketones in
good to excellent isolated yields (Scheme 2, 3a˗3i, 3k, 3l, 3n). Notably, the reaction between an
aliphatic aldehyde (cyclohexanecarbaldehyde) and styrene was successfully performed in good
yield (Scheme 2, 3j). 2ꢀVinylpyridine with benzaldehyde smoothly underwent the reaction
leading to the corresponding epoxyketone in high yield (Scheme 2, 3m). This outcome indicates
that our process is robust in the presence of a nitrogenꢀbased compound.
ACS Paragon Plus Environment
7

The Journal of Organic Chemistry
Page 8 of 35
1
2
3
4
Scheme 2. Scope of the Visible Lightꢀdriven Epoxyacylation
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
3b, 82%
3e, 89%
3c, 88%
3f, 90%
3a, 92%
3d, 85%
3g, 84%
3j, 79%
3i, 82%
3h, 87%
3l, 75%
3k, 90%
3n, 91%
3m, 83%
General conditions: 7 ml of water, 1 (1 mmol), 2 (2 mmol), visible light (100 W household
bulb), 25 C, 12 h. Yields of isolated products. Diastereomeric ratios were found greater than
o
95:5 (trans/cis) in each case as determined by 1H NMR.
Next, we extended our method to nonꢀconjugated olefins and benzaldehydes.
Interestingly, the reaction between 1ꢀdecene and benzaldehyde gave ketone 5a in 35% yield
(Table 2, entry 1). Longꢀchain ketones represent a class of compounds that might play a useful
role in energy science as fuels10 and in medicinal chemistry as hypocholesterolemic agents11;
ACS Paragon Plus Environment
8

Page 9 of 35
The Journal of Organic Chemistry
1
2
3
4
5
6
hence, we decided to reꢀoptimize the reaction conditions to provide a range of these products in
acceptable yields.
7
8
9
Table 2. Optimization of the Visible Lightꢀdriven Hydroacylation
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
entry
methylene
blue (mol%)
base
K2S2O8
(equiv)
solvent
yield
(mol Lꢀ1)
1
2
3
2.5
2.5
1.2
K2CO3 (0.5)
K2CO3 (1.0)
K2CO3 (1.0)
2.0
2.0
2.0
water
water
water
35%
47%
40%
4
5
1.2
1.2
1.2
1.2
0.5
ꢀ
K2CO3 (2.0)
K2CO3 (2.0)
K2CO3 (2.0)
K2CO3 (2.5)
K2CO3 (2.5)
K2CO3 (2.5)
ꢀ
2.0
3.0
1.0
2.0
1.0
1.0
1.0
ꢀ
water
water
55%
23%
61%
50%
89%
8%
6
water
7
water
8
water
water
9
10
11
12a
13b
14
0.5
0.5
0.5
0.5
0.5
water
traces
0%
K2CO3 (2.5)
K2CO3 (2.5)
K2CO3 (2.5)
K2CO3 (2.5)
water
1.0
1.0
1.0
water
traces
50%
0%
water
acetonitrile
General conditions: 7 ml of water, 4 (1 mmol), 2 (2 mmol), visible light (100 W
household bulb), 25 oC, 12 h. Yield of isolated product . a No light. N2 atmosphere.
b
ACS Paragon Plus Environment
9

The Journal of Organic Chemistry
Page 10 of 35
1
2
3
4
5
6
7
8
9
We tested different reagent stoichiometries and observed that decreasing the amount of
potassium persulfate, increasing the concentration of base and decreasing the photocatalyst
loading afforded 5a in 61% yield (Table 2, entries 2˗7). Gratifyingly, using 1 equivalent of
potassium persulfate, 2.5 M as base concentration and 0.5 mol% of methylene blue under 100 W
irradiation provided 5a in 89% yield. Again, we performed the reaction in degassed water and
kept the aqueous medium under N2 atmosphere. This condition led to a lower yield (Table 2,
entry 13) and advocates the important role of oxygen also in this transformation.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
The scope of the transformation was then evaluated. Electronꢀdonating and electronꢀ
withdrawing substituents on the benzaldehyde aryl moiety together with different size longꢀchain
olefins were all wellꢀtolerated affording the corresponding ketones in moderate to excellent
yields (Scheme 3, 5a˗5i). Unfortunately, aliphatic aldehydes led to inconsistent results, and as
such we concluded that these substrates are not suitable for this transformation. Submitting
styrenes (Styrene, 1ꢀChloroꢀ4ꢀvinylbenzene and 1ꢀMethoxyꢀ4ꢀvinylbenzene) to the optimized
hydroacylation conditions led to the corresponding epoxyketones in traces and recovery of
starting materials unreacted. These results show that only nonꢀconjugated, longꢀchain olefins are
likely to participate in the hydroacylation reaction.
ACS Paragon Plus Environment
10

Page 11 of 35
The Journal of Organic Chemistry
1
2
3
4
Scheme 3. Scope of the Visible Lightꢀdriven Hydroacylation
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
5a, 89%
5b, 80%
5c, 87%
O
Me
5
5d, 82%
5e, 75%
5f, 84%
5g, 71%
5h, 67%
5i, 69%
General conditions: 7 ml of water, 4 (1 mmol), 2 (2 mmol), visible light (100 W household bulb), 25 oC,
12 h. Yields of isolated products.
We also evaluated green chemistry credentials for our protocol using green metrics
calculations. The values were superior in Carbon Efficiency and EꢀFactor when compared to
other procedures reported in the literature for the same transformations and starting materials,
thus demonstrating the improved sustainability of the method (See the Supporting Information
for metrics definitions and calculations).
To show the scalability of this transformation, we carried out a gramꢀscale reaction under
sunlight irradiation (Scheme 4, see the Supporting Information for details). Gratifyingly, we
obtained epoxyketone 3a in 84% yield after 6 h irradiation at room temperature.
ACS Paragon Plus Environment
11

The Journal of Organic Chemistry
Page 12 of 35
1
2
3
4
5
6
Scheme 4. Gramꢀscale preparation of 3a under sunlight
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
Once the basic features of our methodology were explored, a series of experiments were
conducted to gain mechanistic insight into the above transformation. First, we performed the
reaction employing styrene and benzaldehyde under the optimized conditions and TEMPO
((2,2,6,6ꢀtetramethylpiperidinꢀ1ꢀyl)oxyl) was used as a radical scavenger. The presence of
TEMPO (2.0 equiv) completely inhibited the formation of the epoxyketone 3a. Instead, we
observed the corresponding products of radical trapping, (A) and (B), by mass spectrometry
(Scheme 5, item 1, see the Supporting Information for further details) clearly denoting a radical
pathway. Interestingly, the presence of (A) suggests a faster reaction with an oxygenated species
other than TEMPO and then the subsequent formation of TEMPO adduct. At this stage, we
hypothesized whether epoxidation of styrene could provide styrene oxide followed by acyl
radical ringꢀopening reaction to giving access to (C) (Scheme 5, item 2). Trapping of (C) with
TEMPO would furnish the adduct (A) we observed in mass spectrometry. In order to confirm or
exclude this hypothesis, we performed a test where styrene was replaced by commercial styrene
oxide under the optimized conditions to check if epoxyketone 3a could be obtained (Scheme 5,
item 2). After 12 h, 3a was not observed and only the diol coming from styrene oxide ringꢀ
ACS Paragon Plus Environment
12

Page 13 of 35
The Journal of Organic Chemistry
1
2
3
4
5
6
opening reaction along with several unidentifiable byꢀproducts were formed, thus excluding this
hypothesis.
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
ACS Paragon Plus Environment
13

The Journal of Organic Chemistry
Page 14 of 35
1
2
3
4
Scheme 5. Studies on the 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
Next, we hypothesized that hydroperoxyl radical generated in the reaction medium would
combine with (D) (which comes from acyl radical addition to the olefin) leading to the
ACS Paragon Plus Environment
14

Page 15 of 35
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
corresponding peroxide (E) (Scheme 5, item 3, see the Supporting Information for further
discussion). Homolytic cleavage of (E) occurs and subsequent trapping with TEMPO accounts
for the observed product (A). Indeed, Watts et al.12 demonstrated that persulfate rapidly
decomposes to hydroperoxide anion and sulfate at basic pH (Scheme 5, item 3). Hydroperoxyl
radical could then be produced by electron transfer from hydroperoxide anion to methylene blue
triplet (MB*) according to reports in the literature.13,14 Therefore, we believe there is stronger
evidence corroborating this pathway.
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 also performed the reaction employing 1ꢀdecene and benzaldehyde under the
optimized conditions in the presence of TEMPO. Complete inhibition of the transformation was
observed with only the adduct (B) being detected by mass spectrometry (Scheme 6, item 1, see
the Supporting Information for further details).
To assess the influence of the electronics on the reactivity, we conducted experiments
employing benzaldehydes bearing different substituents (Scheme 6, item 2, see the Supporting
Information for details). The results showed that this transformation is more favourable for
electronꢀrich benzaldehydes. It suggests that acyl radical addition to the olefin has an important
role in the overall reaction rate, possibly because of polar effects.15
ACS Paragon Plus Environment
15

The Journal of Organic Chemistry
Page 16 of 35
1
2
3
4
Scheme 6. More studies on the 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
On the basis of the above experiments and literature precedence, we propose a plausible
reaction mechanism for the transformation (Scheme 7, using styrene and benzaldehyde as
representative substrates). Photoexcitation of methylene blue with a household light bulb (100
W) produces MB* as the triplet state electron acceptor. Because of MB* reduction potential
(E1/2 = ˗0.062 V vs SHE)13, it engages in singleꢀelectron transfer (SET) with the hydroperoxide
anion (E1/2 = ˗0.88 V vs SHE)14 generated from persulfate alkaline hydrolysis to afford
ACS Paragon Plus Environment
16

Page 17 of 35
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
hydroperoxyl radical and methylene blue neutral radical (Scheme 7, step I, see the Supporting
Information for control experiments and references 12 and 13(a)). Acyl radical is then generated
through hydrogenꢀatom transfer (HAT) between benzaldehyde and hydroperoxyl radical (Scheme
7, step II). Indeed, hydrogen abstraction from aldehydes by oxygenꢀcentered radicals is one of
the most efficient methods of acyl radicals generation.15 The corresponding acyl radical then
adds to the styrene to provide radical (D) which, followed by combination with hydroperoxyl
radical (from step I, SET), gives access to the peroxide (E) (Scheme 7, steps III and IV). Finally,
elimination of OH˗ from peroxide (E) under alkaline conditions leads to the targeted
epoxyketone. Regeneration of methylene blue may occur through oxidation by oxygen in the
air16 or even persulfate (it would explain why the transformation is still operating even under
oxygenꢀfree conditions, see Table 1, entry 11 and Table 2, entry 13). For the acylation reaction, a
similar mechanism is proposed considering the lower amount of oxidant and photocatalyst
employed in the optimized conditions (See the Supporting Information for further discussion).
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
ACS Paragon Plus Environment
17

The Journal of Organic Chemistry
Page 18 of 35
1
2
3
4
Scheme 7. Proposed reaction 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
CONCLUSION
In summary, we have developed a visible lightꢀdriven hydroacylation and epoxyacylation
of nonꢀconjugated and conjugated olefins with a variety of aldehydes using methylene blue as an
organophotoredox catalyst and potassium persulfate as an oxidant. Pure water is the suitable
solvent for this transformation. Electronꢀrich and electronꢀpoor styrenes and benzaldehydes are
all competent substrates for the epoxyacylation. Regarding the hydroacylation, longꢀchain nonꢀ
conjugated olefins and several benzaldehydes are well tolerated in this transformation. The
protocol can be carried out in gramꢀscale under sunlight with no detrimental effect on yield. We
ACS Paragon Plus Environment
18

Page 19 of 35
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
believe this work will be of substantial interest to the synthetic community because of the
unification feature represented by the range of substrates employed in two different
transformations using only one protocol.
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
EXPERIMENTAL SECTION
General Information
All reagents were purchased from commercial suppliers (SigmaꢀAldrich, Oakwood and Combiꢀ
Blocks) and used without further purification, all solvents were analytical grade. Thin layer
chromatography (TLC) was performed using silica gel GF254, 0.25 mm thickness, visualization
was accomplished with short wave UV light or KMnO4 staining solution followed by heating.
Melting points were measured on Buchi Mꢀ560 melting point apparatus and are uncorrected.
Hydrogen nuclear magnetic resonance spectra (1H NMR) were obtained at 400 MHz and 500
MHz in CDCl3 solutions, at ambient temperature. Carbonꢀ13 nuclear magnetic resonance spectra
(13C NMR) were obtained at 100 MHZ and 125 MHz in CDCl3 solutions, at ambient
temperature. Chemicals shifts (δ) are given in ppm and the residual solvent signals were used as
1
references for H and 13C NMR spectra (CDCl3: δH = 7.27 ppm, δC = 77.00 ppm). High
resolution mass spectra were recorded on Thermo Scientific LTQ FT Ultra and Q Exactive
Orbitrap spectrometers working with an electronspray ionization (ESI).
ACS Paragon Plus Environment
19

The Journal of Organic Chemistry
Page 20 of 35
1
2
3
4
General procedure and characterization of products
5
6
(A) General Procedure for epoxyacylation
7
8
9
Conjugated olefin (1 mmol, 1.0 equiv), aldehyde (2 mmol, 2.0 equiv), K2S2O8 (2.0 mmol, 2.0
equiv) and methylene blue (0.025 mmol, 0.025 equiv) were added to 7 ml of an aqueous solution
of K2CO3 (0.5 M, 3.5 mmol). The resulting airꢀequilibrated suspension was capped with a rubber
septum and irradiated at room temperature for 12 h using a household bulb (100 W) placed 8 cm
from the flask. The stirring speed of the reaction mixture was kept at 1150 rpm to ensure
diffusion of reaction components. After completion of the reaction, ethyl acetate (3 mL) was
added for quenching. The aqueous layer was extracted with ethyl acetate (3 mL), the combined
organic layers were dried over anhydrous Na2SO4 and concentrated. The crude mixture was
filtered through a plug of silica (approximately 5 cm) using a mixture of ethyl acetate / nꢀhexane
(5:95) and followed by TLC to afford the desired pure product.
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
(B) General Procedure for hydroacylation
Nonꢀconjugated olefin (1 mmol, 1.0 equiv), benzaldehyde (2 mmol, 2.0 equiv), K2S2O8 (1.0
mmol, 1.0 equiv) and methylene blue (0.005 mmol, 0.005 equiv) were added to 7 ml of an
aqueous solution of K2CO3 (2.5 M, 17.5 mmol). The resulting airꢀequilibrated suspension is
capped with a rubber septum and irradiated at room temperature for 12 h using a household bulb
(100 W) placed 8 cm from the flask. The stirring speed of the reaction mixture was kept at 1150
rpm to ensure diffusion of reaction components. After completion of the reaction, ethyl acetate (3
mL) was added for quenching. The aqueous layer was extracted with ethyl acetate (3 mL), the
combined organic layers were dried over anhydrous Na2SO4 and concentrated. The crude
mixture was filtered through a plug of silica (approximately 5 cm) using a mixture of ethyl
acetate / nꢀhexane (3:97) and followed by TLC to afford the desired pure product.
ACS Paragon Plus Environment
20

Page 21 of 35
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Phenyl(3ꢀphenyloxiranꢀ2ꢀyl)methanone (3a). Prepared from styrene and benzaldehyde
following the general procedure A to give the product as a colourless oil (92% yield, 206.3 mg).
All data was consistent with that previously reported.5d 1H NMR (500MHz, Chloroformꢀd): δ
4.09 (d, 1H, J = 1.89 Hz), 4.31 (d, 1H, J = 1.89 Hz), 7.37–7.45 (m, 5H),7.48–7.52 (m, 2H), 7.61–
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
13
7.66 (m, 1H), 8.02 (dd, 2H, J = 8.18, 1.26 Hz). C NMR (125MHz, Chloroformꢀd): δ 59.3,
60.9, 125.7, 128.3, 128.7, 128.80, 128.85, 129.0, 133.9, 135.4, 193.1.
(2ꢀchlorophenyl)(3ꢀphenyloxiranꢀ2ꢀyl)methanone (3b). Prepared from styrene and 3ꢀ
chlorobenzaldehyde following the general procedure A to give the product as a colourless oil
(82% yield, 212.1 mg). All data was consistent with that previously reported.17 1H NMR
(400MHz, Chloroformꢀd): δ 4.11 (d, 1H, J = 1.96 Hz), 4.16 (d, 1H, J = 1.96 Hz), 7.35–7.44 (m,
13
8H), 7.64 (dd, 1H, J = 7.83, 1.47 Hz). C NMR (100MHz, Chloroformꢀd): δ 60.4, 62.9, 125.8,
127.1, 128.66, 128.99, 130.1, 130.4, 132.9, 135.2, 136.5, 196.3.
(3ꢀchlorophenyl)(3ꢀphenyloxiranꢀ2ꢀyl)methanone (3c). Prepared from styrene and 3ꢀ
chlorobenzaldehyde following the general procedure A to give the product as a white solid (88%
yield, 227.7 mg, m.p. = 85−87 C). All data was consistent with that previously reported.17 1
H
o
NMR (500MHz, Chloroformꢀd): δ 4.09 (d, 1H, J = 1.89 Hz), 4.24 (d, 1H, J = 1.89 Hz), 7.37–
13
7.46 (m, 6H), 7.60 (d, 1H, J = 7.55 Hz), 7.90 (d, 1H, J = 7.55 Hz), 8.01 (s, 1H). C NMR
(125MHz, Chloroformꢀd): δ 59.5, 61.0, 125.8, 126.5, 128.4, 128.8, 129.2, 130.2, 133.9, 135.1,
135.3, 136.8, 192.1.
(4ꢀchlorophenyl)(3ꢀphenyloxiranꢀ2ꢀyl)methanone (3d). Prepared from styrene and 4ꢀ
chlorobenzaldehyde following the general procedure A to give the product as a white solid (85%
yield, 219.9 mg, m.p. = 123−125 oC). All data was consistent with that previously reported.5d 1
H
NMR (400MHz, Chloroformꢀd): δ 4.09 (d, 1H, J = 1.00 Hz), 4.24 (d, 1H, J = 1.00 Hz), 7.36–
ACS Paragon Plus Environment
21

The Journal of Organic Chemistry
Page 22 of 35
1
2
3
4
5
7.43 (m, 5H), 7.47 (d, 2H, J = 8.30 Hz), 7.97 (d, 2H, J = 8.30 Hz). 13C NMR (100MHz,
Chloroformꢀd): δ 59.4, 61.1, 125.8, 128.8, 129.16, 129.24, 129.80, 133.7, 135.2, 140.6, 192.1.
6
7
8
3ꢀphenyloxiranꢀ2ꢀyl)(pꢀtolyl)methanone
(3e).
Prepared
from
styrene
and
4ꢀ
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
methylbenzaldehyde following the general procedure A to give the product as a pale yellow oil
(89% yield, 212.1 mg). All data was consistent with that previously reported.18 1H NMR
(500MHz, Chloroformꢀd): δ 2.44 (s, 3H), 4.08 (d, 1H, J = 1.89 Hz), 4.29 (d, 1H, J = 1.89 Hz),
13
7.29 (d, 2H, J = 7.55 Hz),7.37–7.45 (m, 5H), 7.93 (d, 2H, J = 8.18 Hz). C NMR (125MHz,
Chloroformꢀd): δ 21.8, 59.3, 60.9, 125.8, 128.5, 128.7, 128.9, 129.5, 133.0, 135.6, 145.1, 192.6.
(4ꢀmethoxyphenyl)(3ꢀphenyloxiranꢀ2ꢀyl)methanone (3f). Prepared from styrene and 4ꢀ
methoxybenzaldehyde following the general procedure A to give the product as a white solid
(90% yield, 228.9 mg, m.p. = 77−79 oC). All data was consistent with that previously reported.5d
1H NMR (400MHz, Chloroformꢀd): δ 3.89 (s, 3H), 4.08 (d, 1H, J = 1.47 Hz), 4.26 (d, 1H, J =
13
1.47 Hz), 6.95 (d, 2H, J = 8.80 Hz), 7.36−7.43 (m, 5H), 8.01 (d, 2H, J = 8.80 Hz). C NMR
(100MHz, Chloroformꢀd): δ 55.5, 59.1, 60.8, 114.1, 125.8, 128.7, 128.9, 130.7, 135.7, 164.2,
191.3.
Naphthalenꢀ1ꢀyl(3ꢀphenyloxiranꢀ2ꢀyl)methanone (3g). Prepared from styrene and 1ꢀ
naphthaldehyde following the general procedure A to give the product as a white solid (84%
yield, 230.4 mg, m.p. = 109−111 oC). All data was consistent with that previously reported.19 1
H
NMR (500MHz, Chloroformꢀd): δ 4.17 (d, 1H, J = 1.26 Hz), 4.27 (d, 1H, J = 1.26 Hz), 7.41 (m,
13
5H), 7.50–7.66 (m, 3H), 7.91−8.07 (m, 3H), 8.68 (d, 1H, J = 8.80 Hz). C NMR (125MHz,
Chloroformꢀd): δ 59.7, 62.6, 124.3, 125.46, 125.83, 126.8, 128.54, 128.75, 128.88, 129.1, 130.2,
133.0, 133.8, 135.5, 196.2.
ACS Paragon Plus Environment
22

Page 23 of 35
The Journal of Organic Chemistry
1
2
3
4
(4ꢀfluorophenyl)(3ꢀphenyloxiranꢀ2ꢀyl)methanone (3h). Prepared from styrene and 4ꢀ
5
6
fluorobenzaldehyde following the general procedure A to give the product as a white solid (87%
7
8
9
o
yield, 210.8 mg, m.p. = 82−84 C). All data was consistent with that previously reported.20 1
H
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
NMR (400MHz, Chloroformꢀd): δ 4.09 (d, 1H, J = 1.96 Hz), 4.31 (d, 1H, J = 1.96 Hz), 7.14–
7.21 (m, 2H),7.36–7.45 (m, 5H), 8.05–8.11 (m, 2H). 13C NMR (100MHz, Chloroformꢀd): δ
59.3, 61.1, 116.1 (d, JC,F = 22.0 Hz), 125.8, 128.8, 129.1, 131.2 (d, JC,F = 10.3 Hz), 131.8 (d, JC,F
= 2.9 Hz), 135.3, 166.2 (d, JC,F = 256 Hz), 191.6.
(3ꢀphenyloxiranꢀ2ꢀyl)(2ꢀ(trifluoromethyl)phenyl)methanone (3i). Prepared from styrene and
2ꢀ(trifluoromethyl)benzaldehyde following the general procedure A to give the product as a pale
1
yellow oil (82% yield, 239.6 mg). H NMR (500MHz, Chloroformꢀd): δ 3.94 (d, 1H, J = 1.26
Hz), 4.01 (d, 1H, J = 1.26 Hz), 7.30–7.44 (m, 5H),7.56–7.79 (m, 4H). 13C NMR (125MHz,
Chloroformꢀd): δ 59.4, 62.7, 125.7, 125.9 (q, JC,F = 32.1 Hz), 126.8 (q, JC,F = 4.02 Hz), 131.8 (d,
JC,F = 2.9 Hz), 128.1, 128.7, 129.1, 130.9, 131.7, 132.4, 134.7, 135.9, 198.1. HRMS (ESIꢀTOF)
m/z: [M + H]+ Calcd for C16H12F3O2 293.0789; Found 293.0793.
Cyclohexyl(3ꢀphenyloxiranꢀ2ꢀyl)methanone
(3j).
Prepared
from
styrene
and
cyclohexanecarbaldehyde following the general procedure A to give the product as a pale yellow
oil (79% yield, 181.9 mg). All data was consistent with that previously reported.21 1H NMR
(400MHz, Chloroformꢀd): δ 1.22−1.35 (m, 6H), 1.45−1.65 (m, 4H), 2.58 (m, 1H), 3.60 (d, 1H, J
= 1.47 Hz), 3.92 (d, 1H, J = 1.47 Hz), 7.28–7.39 (m, 5H). 13C NMR (100MHz, Chloroformꢀd): δ
25.3, 25.85, 25.69, 27.5, 28.4, 46.8, 58.4, 62.0, 125.7, 128.7, 128.9, 135.4, 207.9.
Phenyl(3ꢀ(pꢀtolyl)oxiranꢀ2ꢀyl)methanone (3k). Prepared from 1ꢀmethylꢀ4ꢀvinylbenzene and
benzaldehyde following the general procedure A to give the product as pale yellow oil (90%
yield, 214.4 mg). All data was consistent with that previously reported.6f 1H NMR (400MHz,
ACS Paragon Plus Environment
23

The Journal of Organic Chemistry
Page 24 of 35
1
2
3
4
5
6
Chloroformꢀd): δ 2.39 (s, 3H), 4.05 (d, 1H, J = 1.96 Hz), 4.30 (d, 1H, J = 1.96 Hz), 7.22 (d, 2H,
J = 7.83 Hz), 7.27 (d, 2H, J = 7.83 Hz), 7.50 (t, 2H, J = 7.83 Hz), 7.63 (t, 1H, J = 7.34 Hz), 8.01
7
8
9
13
(d, 2H, J = 7.34 Hz). C NMR (100MHz, Chloroformꢀd): δ 21.2, 59.4, 61.0, 125.7, 128.3,
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
128.8, 129.4, 132.4, 133.9, 135.5, 139.0, 193.2.
(3ꢀ(4ꢀmethoxyphenyl)oxiranꢀ2ꢀyl)(phenyl)methanone (3l). Prepared from 1ꢀmethoxyꢀ4ꢀ
vinylbenzene and benzaldehyde following the general procedure A to give the product as pale
yellow oil (75% yield, 190.7 mg). All data was consistent with that previously reported.6f 1
H
NMR (400MHz, Chloroformꢀd): δ 3.82 (s, 3H), 4.01 (d, 1H, J = 1.90 Hz), 4.26 (d, 1H, J = 1.90
Hz), 6.95 (d, 2H, J = 8.75 Hz), 7.29 (d, 2H, J = 8.75 Hz), 7.49 (t, 2H, J = 7.34 Hz), 7.61 (t, 1H, J
13
= 7.15 Hz), 8.02 (d, 2H, J = 7.34 Hz). C NMR (100MHz, Chloroformꢀd): δ 55.7, 59.4, 61.0,
114.3, 127.07, 127.13, 128.29, 128.74, 133.9, 135.5, 160.3, 193.2.
Phenyl(3ꢀ(pyridinꢀ2ꢀyl)oxiranꢀ2ꢀyl)methanone (3m). Prepared from 2ꢀvinylpyridine and
benzaldehyde following the general procedure A to give the product as colourless oil (83% yield,
186.9 mg). All data was consistent with that previously reported.22 1H NMR (400MHz,
Chloroformꢀd): δ 4.23 (d, 1H, J = 1.80 Hz), 4.57 (d, 1H, J = 1.65 Hz), 7.31 (ddd, 1H, J = 7.50,
4.70, 1.25 Hz), 7.41 (d, 1H, J = 7.80 Hz), 7.48−7.54 (m, 2H), 7.58−7.62 (m, 1H), 7.75 (td, 1H, J
= 7.65, 1.50 Hz), 8.00−8.07 (m, 2H), 8.60 (d, 1H, J = 4.60 Hz). 13C NMR (100MHz,
Chloroformꢀd): δ 59.3, 121.2, 123.8, 128.4, 128.8, 134.0, 135.4, 137.0, 149.8, 154.5, 193.0.
3ꢀ(4ꢀchlorophenyl)oxiranꢀ2ꢀyl)(phenyl)methanone (3n). Prepared from 1ꢀchloroꢀ4ꢀ
vinylbenzene and benzaldehyde following the general procedure A to give the product as pale
yellow oil (91% yield, 235.4 mg). All data was consistent with that previously reported.6f 1
H
NMR (400MHz, Chloroformꢀd): δ 4.09 (d, 1H, J = 1.60 Hz), 4.24 (d, 1H, J = 1.65 Hz), 7.30 (d,
2H, J = 8.80 Hz), 7.38 (d, 2H, J = 8.80 Hz), 7.49 (t, 2H, J = 7.89 Hz), 7.63 (t, 1H, J = 7.35 Hz),
ACS Paragon Plus Environment
24

Page 25 of 35
The Journal of Organic Chemistry
1
2
3
4
13
7.97 (d, 2H, J = 8.31 Hz). C NMR (100MHz, Chloroformꢀd): δ 58.6, 60.8, 127.1, 128.02,
5
6
128.80, 128.93, 133.9, 134.1, 134.8, 135.2, 192.6.
7
8
9
1ꢀphenylundecanꢀ1ꢀone (5a). Prepared from 1ꢀdecene and benzaldehyde following the general
procedure B to give the product as a pale yellow oil (89% yield, 219.3 mg). All data was
consistent with that previously reported.23 1H NMR (500MHz, Chloroformꢀd): δ 0.89 (t, 3H, J =
6.92 Hz), 1.22−1.33 (m, 14H), 1.74 (quint, 2H, J = 6.92 Hz), 2.97 (t, 2H, J = 7.55 Hz), 7.47 (t,
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
2H, J = 8.17 Hz), 7.56 (t, 1H, J = 7.55 Hz), 7.96 (d, 2H, J = 6.92 Hz). C NMR (125MHz,
Chloroformꢀd): δ 14.1, 22.7, 24.4, 29.30, 29.37, 29.46, 29.50, 29.56, 31.9, 38.6, 128.04, 128.53,
132.8, 137.1, 200.6.
1ꢀ(4ꢀchlorophenyl)undecanꢀ1ꢀone (5b). Prepared from 1ꢀdecene and 4ꢀchlorobenzaldehyde
following the general procedure B to give the product as a pale yellow oil (80% yield, 224.7 mg).
All data was consistent with that previously reported.24 1H NMR (500MHz, Chloroformꢀd): δ
0.89 (t, 3H, J = 6.29 Hz), 1.23−1.40 (m, 14H), 1.73 (quint, 2H, J = 7.55 Hz), 2.93 (t, 2H, J =
7.55 Hz), 7.43 (d, 2H, J = 8.17 Hz), 7.90 (d, 2H, J = 8.17 Hz). 13C NMR (125MHz, Chloroformꢀ
d): δ 14.1, 22.7, 24.3, 29.29, 29.45, 29.48, 29.55, 31.9, 38.6, 128.8, 129.5, 135.4, 139.3, 199.3.
1ꢀ(pꢀtolyl)undecanꢀ1ꢀone (5c). Prepared from 1ꢀdecene and 4ꢀmethylbenzaldehyde following
the general procedure B to give the product as a pale yellow oil (87% yield, 226.6 mg). 1H NMR
(500MHz, Chloroformꢀd): δ 0.89 (t, 3H, J = 6.92 Hz), 1.22−1.33 (m, 14H), 1.73 (quint, 2H, J =
7.55 Hz), 2.42 (s, 3H), 2.93 (t, 2H, J = 7.55 Hz), 7.25 (d, 2H, J = 8.17 Hz), 7.86 (d, 2H, J = 8.17
13
Hz). C NMR (125MHz, Chloroformꢀd): δ 14.1, 21.6, 22.7, 24.5, 29.31, 29.40, 29.48, 29.56,
31.9, 38.5, 128.2, 129.2, 134.6, 143.5, 200.3. HRMS (ESIꢀTOF) m/z: [M + H]+ Calcd for
C18H30O 261.2218; Found 261.2225.
ACS Paragon Plus Environment
25

The Journal of Organic Chemistry
Page 26 of 35
1
2
3
4
5
6
7
8
9
1ꢀphenyltridecanꢀ1ꢀone (5d). Prepared from 1ꢀdodecene and benzaldehyde following the
general procedure B to give the product as colourless oil (82% yield, 225.0 mg). All data was
consistent with that previously reported.25 1H NMR (500MHz, Chloroformꢀd): δ 0.89 (t, 3H, J =
6.85 Hz), 1.23−1.42 (m, 18H), 1.74 (quint, 2H, J = 7.34 Hz), 2.97 (t, 2H, J = 7.34 Hz), 7.47 (t,
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
2H, J = 7.34 Hz), 7.56 (t, 1H, J = 7.34 Hz), 7.96 (d, 2H, J = 7.35 Hz). C NMR (125MHz,
Chloroformꢀd): δ 14.1, 22.7, 24.4, 29.34, 29.38, 29.48, 29.51, 29.56, 29.59, 29.63, 29.66, 31.9,
38.6, 128.05, 128.53, 132.8, 137.1, 200.6.
1ꢀ(4ꢀchlorophenyl)tridecanꢀ1ꢀone (5e). Prepared from 1ꢀdodecene and 4ꢀchlorobenzaldehyde
following the general procedure B to give the product as a white solid (75% yield, 231.7 mg,
m.p. = 81−84 C). All data was consistent with that previously reported.25 1H NMR (400MHz,
o
Chloroformꢀd): δ 0.89 (t, 3H, J = 7.34 Hz), 1.23−1.38 (m, 18H), 1.73 (quint, 2H, J = 7.34 Hz),
13
2.93 (t, 2H, J = 7.34 Hz), 7.43 (d, 2H, J = 8.80 Hz), 7.89 (d, 2H, J = 8.50 Hz). C NMR
(100MHz, Chloroformꢀd): δ 14.1, 22.7, 24.3, 29.34, 29.45, 29.48, 29.55, 29.60, 29.64, 31.9,
38.6, 128.8, 129.5, 135.4, 139.3, 199.3.
1ꢀ(4ꢀmethoxyphenyl)tridecanꢀ1ꢀone
(5f).
Prepared
from
1ꢀdodecene
and
4ꢀ
methoxybenzaldehyde following the general procedure B to give the product as colourless oil
(84% yield, 255.8 mg). All data was consistent with that previously reported.25 1H NMR
(500MHz, Chloroformꢀd): δ 0.89 (t, 3H, J = 7.34 Hz), 1.21−1.38 (m, 18H), 1.72 (quint, 2H, J =
7.21 Hz), 2.91 (t, 2H, J = 7.80 Hz), 3.88 (s, 3H), 6.93 (d, 2H, J = 8.75 Hz), 7.94 (d, 2H, J = 8.65
13
Hz). C NMR (125MHz, Chloroformꢀd): δ 14.1, 22.7, 24.7, 29.32, 29.45, 29.50, 29.56, 29.59,
29.63, 29.66, 31.9, 38.3, 55.4, 113.6, 130.25, 130.31, 163.2, 199.2.
1ꢀphenylpentadecanꢀ1ꢀone (5g). Prepared from 1ꢀtetradecene and benzaldehyde following the
general procedure B to give the product as colourless oil (71% yield, 214.8 mg). All data was
ACS Paragon Plus Environment
26

Page 27 of 35
The Journal of Organic Chemistry
1
2
3
4
5
consistent with that previously reported.26 1H NMR (500MHz, Chloroformꢀd): δ 0.89 (t, 3H, J =
6.85 Hz), 1.23−1.38 (m, 22H), 1.74 (quint, 2H, J = 7.00 Hz), 2.97 (t, 2H, J = 7.34 Hz), 7.46 (t,
6
7
8
9
13
2H, J = 7.83 Hz), 7.56 (t, 1H, J = 7.34 Hz), 7.96 (d, 2H, J = 7.34 Hz). C NMR (125MHz,
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
Chloroformꢀd): δ 14.1, 22.7, 24.4, 29.35, 29.45, 29.48, 29.51, 29.56, 29.63, 29.66, 31.9, 38.6,
128.05, 128.53, 132.8, 137.1, 200.6.
1ꢀ(4ꢀchlorophenyl)pentadecanꢀ1ꢀone (5h). Prepared from 1ꢀtetradecene and 4ꢀ
chlorobenzaldehyde following the general procedure B to give the product as colourless oil (67%
1
yield, 225.7 mg). H NMR (500MHz, Chloroformꢀd): δ 0.89 (t, 3H, J = 7.55 Hz),
1.23−1.37 (m, 22H), 1.73 (quint, 2H, J = 6.92 Hz), 2.93 (t, 2H, J = 7.55 Hz), 7.43 (d, 2H, J =
13
8.80 Hz), 7.89 (d, 2H, J = 8.20 Hz). C NMR (125MHz, Chloroformꢀd): δ 14.1, 22.7, 24.3,
29.34, 29.45, 29.48, 29.55, 29.59, 29.64, 31.9, 38.6, 128.8, 129.5, 135.4, 139.3, 199.3. HRMS
(ESIꢀTOF) m/z: [M + H]+ Calcd for C21H35ClO 337.2298; Found 337.2271.
1ꢀ(4ꢀmethoxyphenyl)pentadecanꢀ1ꢀone (5i). Prepared from 1ꢀtetradecene and 4ꢀ
methoxybenzaldehyde following the general procedure B to give the product as colourless oil
1
(69% yield, 229.4 mg). H NMR (500MHz, Chloroformꢀd): δ 0.89 (t, 3H, J = 7.55 Hz),
1.23−1.39 (m, 22H), 1.73 (quint, 2H, J = 6.92 Hz), 2.93 (t, 2H, J = 7.00 Hz), 3.78 (s, 3H), 6.94
13
(d, 2H, J = 8.70 Hz), 7.94 (d, 2H, J = 8.70 Hz). C NMR (125MHz, Chloroformꢀd): δ 14.1,
22.7, 24.3, 29.34, 29.45, 29.48, 29.54, 29.59, 29.64, 29.67, 31.9, 38.6, 55.8, 114.1, 129.5, 135.4,
165.0, 199.1. HRMS (ESIꢀTOF) m/z: [M + H]+ Calcd for C22H38O2 333.2794; Found 333.2788.
ASSOCIATED CONTENT
The Supporting Information is available free of charge on the ACS Publications website at DOI:
ACS Paragon Plus Environment
27

The Journal of Organic Chemistry
Page 28 of 35
1
2
3
4
5
6
Additional experiments probing the mechanism, other mechanistic hypotheses, sunlight gramꢀ
scale experiment, 1H and 13C NMR data (PDF).
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
AUTHOR INFORMATION
Corresponding Author
* Phone: +55 19 35218794. Fax: +55 19 35213023. Eꢀmail: asalles@iqm.unicamp.br.
ORCID
Airton G. Salles Jr.: 0000ꢀ0002ꢀ9423ꢀ2552
Author Contributions
The manuscript was written through contributions of all authors. All authors have given approval
to the final version of the manuscript.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We thank Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, São Paulo,
Brazil) and FaepexꢀUNICAMP for financial support (Grant FAPESP 2017/18400ꢀ6).
ACS Paragon Plus Environment
28

Page 29 of 35
The Journal of Organic Chemistry
1
2
3
4
REFERENCES
5
6
7
8
(1) Selected reviews on visible light photoredox catalysis: (a) Twilton, J.; Le, C. C.; Zhang, P.;
Shaw, M. H.; Evans, R. W.; MacMillan, D. W. C. The Merger of Transition Metal and
Photocatalysis. Nat. Rev. Chem. 2017, 1, 1˗18. (b) Yoon, T. P.; Ischay M. A.; Du, J. Visible
Light Photocatalysis as a Greener Approach to Photochemical Synthesis. Nat. Chem. 2010, 2,
527˗532. (c) Narayanam, J. M. R.; Stephenson, C. R. J. Visible Light Photoredox Catalysis:
Applications in Organic Synthesis. Chem. Soc. Rev. 2011, 40, 102˗113. (d) Prier, C. K.; Rankic,
D. A.; MacMillan, D. W. C. Visible Light Photoredox Catalysis with Transition Metal
Complexes: Applications in Organic Synthesis. Chem. Rev. 2013, 113, 5322˗5363.
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) (a) Zhang, J.; Li, Y.; Zhang, F.; Hu, C.; Chen, Y. Generation of Alkoxyl Radicals by
Photoredox Catalysis Enables Selective C(sp3)−H Functionalization under Mild Reaction
Conditions. Angew. Chem. Int. Ed. 2016, 55, 1872˗1875. (b) Yayla, H. G.; Wang, H.; Tarantino,
K. T.; Orbe, H. S.; Knowles, R. R. Catalytic RingꢀOpening of Cyclic Alcohols Enabled by PCET
Activation of Strong O–H Bonds. J. Am. Chem. Soc. 2016, 138,10794˗10797. (c) Hu, X. Q.;
Chen, J. R.; Xiao, W. J. Controllable Remote C−H Bond Functionalization by VisibleꢀLight
Photocatalysis. Angew.Chem. Int. Ed. 2017, 56, 1960˗1962.
(3) (a) Oelgemöller, M.; Schiel, C.; Fröhlich, R.; Mattay, J. The “PhotoꢀFriedelꢀCrafts
Acylation” of 1,4ꢀNaphthoquinones. Eur. J. Org. Chem. 2002, 15, 2465˗2474. (b) Chudasama,
V.; Fitzmaurice, R. J.; Caddick, S. Hydroacylation of α,βꢀunsaturated Esters via Aerobic C−H
Activation. Nat. Chem. 2010, 2, 592˗596. (c) Chudasama, V.; Fitzmaurice, R. J.; Ahern, J. M.;
Caddick, S. Dioxygen Mediated Hydroacylation of Vinyl Sulfonates and Sulfones on Water
Chem. Commun. 2010, 46, 133˗135. (d) Fitzmaurice, R. J., Ahern, J. M.; Caddick, S. Synthesis
of Unsymmetrical Ketones via Simple C–H Activation of Aldehydes and Concomitant
ACS Paragon Plus Environment
29