Visible-Light-Mediated Decarboxylative Benzylation of Imines with Arylacetic Acids

Article abstract of DOI:10.1021/acs.joc.8b01849

A straightforward method for the visible-light-mediated decarboxylative benzylation of imines is reported. The key feature of this method is the use of simple primary, secondary, and tertiary arylacetic acids as precursors of benzyl radicals, enabling the facile benzylation of a variety of imines under mild conditions. A variety of structurally diverse β-arylethylamines (37 examples) was accessed using this method.

Full text of DOI:10.1021/acs.joc.8b01849

Subscriber access provided by UNIV OF LOUISIANA
Article
Visible-Light-Mediated Decarboxylative
Benzylation of Imines with Arylacetic Acids
Jing Guo, Wu Qiaolei, Ying Xie, Jiang Weng, and Gui Lu
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 21 Sep 2018
Downloaded from http://pubs.acs.org on September 21, 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 19
The Journal of Organic Chemistry
1
2
3
4
Visible-Light-Mediated Decarboxylative Benzylation of Imines
5
6
7
with Arylacetic Acids
8
9
Jing Guo, QiaoꢀLei Wu, Ying Xie, Jiang Weng,* Gui Lu*
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
Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of
Pharmaceutical Sciences, Sun Yatꢀsen University, Guangzhou 510006, P. R. China
ABSTRACT:
A straightforward method for the visibleꢀlightꢀmediated decarboxylative benzylation of
imines is reported. The key feature of this method is the use of simple primary, secondary and
tertiary arylacetic acids as precursors of benzyl radicals, enabling the facile benzylation of a
variety of imines under mild conditions. A variety of structurally diverse βꢀarylethylamines (37
examples) have been accessed using this method.
1
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 19
1
2
3
4
INTRODUCTION
In the past decade, photoredox catalysis is emerging as an important method in modern synthetic
chemistry.1 In this context, it is essential to explore new strategies and reagents for generation of
radicals. Recently, radical decarboxylation is known to be an efficient strategy for
functionalization of carboxylic acids and derivatives through generating radical species. A wide
range of carbonꢀcentered radicals including αꢀamino, αꢀoxy, and simple alkyl radicals can be
accessed using this strategy.2 However, to our surprise, the direct formation of benzylic radical via
visibleꢀlightꢀinduced decarboxylation of arylacetic acids has less been investigated.3
Nishibayashi3a and Tunge3b described the visibleꢀlightꢀmediated decarboxylative radical addition
and allylation of arylacetic acids, respectively. Note that only phenylacetic acids bearing
paraꢀamino groups can undergo the photocatalytic decarboxylation process to generate the
benzylic radical. Ravelli and coworkers recently developed the decarboxylative benzylic radical
addition of simple arylacetic acids to olefins.3c However, the substrate scope was limited to highly
electronꢀdeficient and easily reducible olefins. Alternatively, a series of novel benzylic radical
precursors including benzylic trifluoroborates,4 silanes,5 ethers,6 1,4ꢀdihydropyridines (DHP)7 and
active esters8 have been elegantly developed (Figure 1). Despite these advances, direct conversion
of simple arylacetic acids into benzyl radicals is undoubtedly one of the most straightforward
strategies for benzylic functionalization.
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
Figure 1 Precursors of benzylic radicals
Amines are perhaps the most important class of compounds in a wide variety of natural and
unnatural compounds.9 The highly pronounced biological activities of amineꢀcontaining
compounds have made them attractive synthetic targets in medicinal chemistry.10 Imines are one
of the most important precursors for the synthesis of amine. Classical strategies depend on
organometal reagents or radicalꢀbased methods to realize efficient alkylation of imines (Scheme
1a).11 In recent years, photoredoxꢀcatalyzed radical alkylation of imines has emerged as a
complementary approach for the sustainable synthesis of amines. However, less attention has been
devoted to benzylation of imine (Scheme 1b), albeit the resulting βꢀarylethylamine is a widespread
structural moiety in nature. MacMillan et al. pioneered the photoredoxꢀcatalyzed coupling of
imines with benzylic ethers via αꢀoxy benzyl radicals.6 Molander et al. used benzyl
bis(catecholato)silicates to enable SET processes to form benzyl radical species that can react with
imine radical anions to generate βꢀphenylethylamine.12 Yu et al. reported the radical benzylation of
imines with benzyl 1,4ꢀdihydropyridines (DHP) coꢀcatalyzed by photocatalyst and Brønsted acid
under visible light irradiation.13 Although these photocatalyzed methods could furnish various
benzylated amines, their success relies on the introduction of αꢀheteroatomꢀstabilized radicals, the
use of organosilicon reagents or Hantzsch esters. In this work, we envisioned that simple
2
ACS Paragon Plus Environment

Page 3 of 19
The Journal of Organic Chemistry
1
2
3
arylacetic acids might also facilitate the direct benzylation of imine via the coupling between
4
5
6
7
8
9
imine radical anions A and benzylic radicals B under photoredox catalysis (Scheme 1c).
Classical approaches for alkylation of imines
R3 [M]
nucleophilc addition
PG
R3
PG
R2
HN
R1
N
(a)
R1
R2
R3 LG
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
radical-based methods
-------------------------------------------------------------------------------------------------------------------
Previous work: Photocatalytic benzylation of imines with different Bn radical precursors
Ar2
OMe
photocatalyst, hv
R
PG
PG
H
HN
Ar1
N
Ar2
[Si]
Ar2
(b)
Ar1
photocatalyst, hv
R
R
Ar2
photocatalyst, hv
DHP
-------------------------------------------------------------------------------------------------------------------
This work: Photocatalytic decarboxylative benzylation of imines with arylacetic acids
PG
HN
PG
H
photocatalyst
R
N
Ar2
(c)
Ar1
base
+
Ar2
CO2H
blue LEDs, rt
Ar1
R
Photoredox
Cycle
reduction
oxidation
PG
N
i) radical-radical coupling
ii) + H+
Ar2
R
+
H
A
Ar1
B
Scheme 1 Synthetic strategies for alkylation of imines
RESULTS AND DISCUSSION
Initially, this decarboxylative alkylation reaction was performed with NꢀTs aldimine (1a) and
2ꢀ(4ꢀmethoxyphenyl)acetic acid (2a) as model substrates in the presence of 2 mol% 4CzIPN
red
(1,2,3,5ꢀtetrakis(carbazolyl)ꢀ4,6ꢀdicyanobenzene, E1/2 = +1.35 V vs SCE in MeCN)14 as
photocatalyst and 2 equiv. of Ca(OH)2 as base. As expected, the reaction did proceed under the
irradiation of two 12 W Blue LED bulbs, providing the desired product 3a in modest yield (Table
1 entry 1). Given the successful implementation of Ir(III) and Ru(II) photocatalysts in previous
decarboxylative functionalizations, Ir[dF(CF3)ppy]2(bpy)PF6 (E1/2red = +1.32 V vs SCE in MeCN)2
and [Ru(bpy)3]Cl2 (E1/2red = +0.77 V vs SCE in MeCN)15 were used to promote this single electron
transformation.16 To our delight, when Ir[dF(CF3)ppy]2(bpy)PF6 was employed, a higher yield was
obtained (Table 1 entries 2ꢀ3). Moreover, eosin Y, a catalyst that exhibits a lower oxidizing excited
state than Ir[dF(CF3)ppy]2(bpy)PF6 (E1/2 = +0.83 V vs SCE in 1:1 MeCN/H2O )17 did not
red
promote the desired coupling between aldimine 1a and arylacetic acid 2a. In order to improve the
yield, a variety of inorganic and organic bases, such as K2CO3, Li2CO3, NaOAc, Cs2CO3, KOH,
NaOH, K2HPO4, KH2PO4, DBU, Et3N and pyridine were examined (Table 1 entries 5ꢀ15).
Significant improvement was observed when the reaction was performed with K2HPO4 as base,
3
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 19
1
2
3
4
5
6
7
8
9
while organic bases could not promote the reaction (Table 1 entries 13ꢀ15). Encouraged by this
promising result, we conducted further investigations on the effect of reaction media, including
polar solvent (DMF, THF, DMSO and DCM) and nonpolar solvent (toluene). However, MeCN
remained the best choice and yielded the best result (Table 1 entries 16ꢀ20). Increasing the
reaction time and performing the reaction under 18 W blue LEDs resulted in lower yields (Table 1
entries 21ꢀ22). The control experiments revealed that photocatalyst, base and light irradiation are
essential for the success of this transformation (Table 1 entries 23ꢀ25).
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 the reaction conditionsa
Entry Photocatalyst
Base
Solvent Yield (%)b
1
A
B
C
D
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
Ca(OH)2 MeCN
Ca(OH)2 MeCN
Ca(OH)2 MeCN
Ca(OH)2 MeCN
45
50
2
3c
15
4
0
5
K2CO3
Li2CO3
MeCN
MeCN
62
6
64
7
NaOAc MeCN
Cs2CO3 MeCN
55
8
45
9
KOH
MeCN
MeCN
35
10
11
12
13
14
15
16
17
18
19
20
21d
NaOH
39
K2HPO4 MeCN
KH2PO4 MeCN
80
52
DBU
Et3N
MeCN
MeCN
trace
trace
trace
23
pyridine MeCN
K2HPO4
K2HPO4
DMF
THF
78
K2HPO4 DMSO
K2HPO4 DCM
K2HPO4 toluene
K2HPO4 MeCN
<5
60
55
65
4
ACS Paragon Plus Environment

Page 5 of 19
The Journal of Organic Chemistry
1
2
3
4
5
6
7
22e
23
B
-
K2HPO4 MeCN
K2HPO4 MeCN
40
0
24
25f
B
B
ꢀ
MeCN
20
0
K2HPO4 MeCN
8
9
a Reaction condition: 1a (0.1 mmol), 2a (0.2 mmol), base (0.2 mmol), photocatalyst (0.002 mmol),
b
c
solvent (2 mL) under 12 W blue LEDs for 18 h at 25 °C. Isolated yield. Under 12 W green
LEDs. d Under 18 W blue LEDs. e Reaction time is 24 h. f No light.
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 2 Scope of aldiminesa,b
a
Reaction conditions: 1 (0.1 mmol), 2a (0.2 mmol), Ir[dF(CF3)ppy]2(bpy)PF6 (2 mol%), K2HPO4
b
c
(2 equiv.), MeCN (2 mL), under 12 W blue LEDs for 18 h at 25 °C. Isolated yield. 2 mol%
4CzIPN as photocatalyst.
With the optimal reaction condition in hand (entry 11 in Table 1), we next examined the scope
of this new protocol with different aldimines, and the results were shown in Table 2. In general,
aldimines bearing electronꢀneutral, electronꢀwithdrawing, and electronꢀdonating groups on the
phenyl ring all worked well to afford the corresponding products (3aꢀ3o) in moderate to excellent
yields (38%ꢀ80%). Benzylation of electronꢀneutral group (4ꢀH) and electronꢀwithdrawing groups
(4ꢀF, 4ꢀCl, 4ꢀCN and 4ꢀCOOMe) substituted aldimines gave the products in 60−80% yields.
Electronꢀrich arenes bearing methyl, tertꢀbutyl, and phenyl were also compatible to provide the
desired products (3b, 3e, 3f) in 61ꢀ65% yields. However, aldimines with electronꢀwithdrawing
groups as 4ꢀCF3 on the phenyl ring led to the corresponding product in 38% yield. In addition,
aldimines with ortho-substituent could afford the desired products in moderate yields (3j-3m,
5
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 19
1
2
3
4
5
6
7
8
9
46ꢀ63%). For substrates with meta-substituents on the phenyl ring, both electronꢀdeficient and
electronꢀrich arenes performed well to afford the products in good yields (3nꢀ3o, 77ꢀ79%).
Moreover, aldimine substrates with heteroaromatic pyridine (3p, 55% yield) and naphthalene
(3qꢀ3r, 55ꢀ65% yield) were well tolerated. Changing Nꢀprotective group of aldimines from tosyl
to methylsulfonyl, phenylsulfonyl, phenyl, and carbamates were also appropriate and effective
(70ꢀ81% yields). Unfortunately, this reaction could not be extended to aliphatic aldimines and
ketimines.
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 3 Scope of arylacetic acidsa,b
a
Reaction conditions: 1a (0.1 mmol), 2 (0.2 mmol), Ir[dF(CF3)ppy]2(bpy)PF6 (2 mol%), K2HPO4
b
c
(2 equiv.), MeCN (2 mL), under 12 W blue LEDs for 18 h at 25 °C. Isolated yield. THF as
solvent. d 2 mol% 4CzIPN as photocatalyst. e CsF as base and THF as solvent.
Next, we tried to expand the range of arylacetic acids in this photocatalyzed alkylation (Table 3).
To our delight, we found that phenylacetic acids with either electronꢀdonating or
electronꢀwithdrawing groups on the phenyl ring were tolerated in this reaction, giving the desired
products (3y-3ae) in moderate yields (41ꢀ50%). Naphthylacetic acids were also compatible with
this photocatalyzed condition, and the alkylated products (3afꢀ3ag) were obtained in mild yields
(50%). More importantly, a wide range of heteroaryl acetic acid were well tolerated, affording the
corresponding products (3ahꢀ3aj) in mild to good yields (51ꢀ62%), which might be useful in
medicinal chemistry.
Given the potential for wide applications, it is important to recognize whether a variety of 2°
and 3° phenylacetic acids still perform well in this C–C bond forming reaction. To our delight, not
only 2ꢀmethoxyꢀ2ꢀphenylacetic acid, but also 2ꢀmethylꢀ2ꢀphenylpropanoic acid, can participate in
this reaction to provide the desired products (3akꢀ3al) with moderate yields (45ꢀ56%).
To determine whether the approach developed in this effort displays acceptable levels of
aldimines selectivity, alkylation reaction of substrate 4a, which contains both aldehyde and
aldimines, was evaluated. The exclusive formation of the desired product 3am indicated that the
photocatalyzed alkylation reactions of the substrate occur in a highly selective manner on the aryl
6
ACS Paragon Plus Environment

Page 7 of 19
The Journal of Organic Chemistry
1
2
3
4
5
substituted C=N bond. A similar outcome occurred when a mixture of aldimine 1a and
benzaldehyde 4b was performed in the reaction. In this case, the benzyl radical coupled in a
manner similar to C=N bond rather than to C=O bond (Scheme 2).
6
7
8
Scheme 2 Intraꢀ and intermolecular chemoselectivities
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
To explore the practical utility of this method, a gramꢀscale experiment was performed with 1a
and 2ꢀ(4ꢀmethoxyphenyl)acetic acid 2a (Scheme 3). The desired product 3a can be obtained with
minimal loss of yield (72%, from 5 mmol of 1a) in the presence of 3 mol% photocatalyst, which
demonstrated that this protocol was scalable and practical. However, an increasing amount of
photocatalyst was necessary to perform the gramꢀscale reaction, which indicated that the reaction
equipment might need to be improved.
Scheme 3 Gramꢀscale synthesis of 3a
Based on literatures6,12 and fluorescence quenching studies (see supporting information), a
plausible mechanistic pathway for this photocatalyzed decarboxylative alkylation of imines was
proposed and depicted in Figure 2. Upon visibleꢀlight irradiation, the iridium(III) photocatalyst (A)
will produce the longꢀlived excitedꢀstate *Ir(III) species B. Then B was engaged in singleꢀelectron
transfer with carboxylate anion (C), whose oxidation potentials E(RꢀCOO•/RꢀCOO−) fall in the +1
−1.6 V vs SCE,18,2b,3a,3c to afford hydrogen ion, benzylic radical (D), and carbon dioxide. The
excited *Ir(III) species should be simultaneously favorable to generate the reduced Ir(II) (E),
which in turn can reduce the aldimines (F) under the reaction conditions through a SET process to
7
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 19
1
2
3
4
5
6
7
8
9
afford the αꢀamino radical anion (G). The new CꢀC bond formation should be facilitated by the
benzylic radical (D) combined with αꢀamino radical anion to afford the desired products (H).
Although a radical−radical coupling pathway is proposed, in this case, an addition of benzylic
radical (D) to imine (F) and subsequent reduction of the Nꢀcentered radical is also conceivable.
However, we didn’t observe any imine reduction and imine dimer byproducts in this process, which
ruled out the possible radical−radical coupling pathway.6
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Figure 2 Proposed mechanism of photocatalyzed decarboxylative alkylation of imines
CONCLUSION
In conclusion, we have developed a visibleꢀlightꢀmediated decarboxylative benzylation of imines
with arylacetic acids. This versatile method tolerates a variety of functional groups and shows
broad scope with regard to primary, secondary and tertiary arylacetic acids. In contrast to
previously described methods, this photoredox reaction does not require prefunctionalized or
αꢀheteroatomꢀstabilized substrates. In addition, this method features operational simplicity, mild
reaction conditions and scalability, thus provides an alternative approach for the synthesis of
βꢀarylethylamines and derivatives.
EXPERIMENTAL SECTION
General Information. All the commercial reagents were used as such without further purification.
All solvents were used as commercial anhydrous grade without further purification. The flash
column chromatography was carried out over silica gel (230ꢀ400 mesh). 1H and 13C NMR spectra
were recorded on a Bruker Avanceꢀ400 MHz and Bruker Avanceꢀ500 MHz spectrometer.
Chemical shifts in 1H NMR spectra were reported in parts per million (ppm, δ) downfield from the
internal standard Me4Si (TMS, δ = 0 ppm). Chemical shifts in 13C NMR spectra were reported
relative to the central line of the chloroform signal (δ = 77.0 ppm). Peaks were labeled as singlet
(s), doublet (d), triplet (t), quartet (q), and multiplet (m). High resolution mass spectra were
8
ACS Paragon Plus Environment

Page 9 of 19
The Journal of Organic Chemistry
1
2
3
4
5
obtained with a Shimadzu LCMSꢀITꢀTOF mass spectrometer. Chemical yields refer to pure
isolated substances.
6
7
8
9
General Synthetic Method of Aldimines. All of aldimines was prepared following a known
method,19 the related characterization data for these compounds were consistent with known
compounds.19bꢀc A 25 mL vial equipped with a stirrer was charged with aldehyde (5 mmol),
sulfonamide (6 mmol), dry toluene (10 mL) and Ti(OEt)4 (5 mmol). The vial was closed and
heated at 150 °C for 12 hour. After completion, the mixture was cooled to room temperature and
extracted with EA. The combined organic layer was dried over Na2SO4 and concentrated under
reduced pressure. The crude product was purified by flash column chromatography on silica gel to
afford the title compounds.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
General Procedure and Characterization of Products. To a solution of 1a (25.9 mg, 0.1 mmol)
and 2a (33.2 mg, 0.2 mmol) in acetonitrile (2 mL) was added K2HPO4 (34.8 mg, 0.2 mmol) and
PC (0.002 mmol). The reaction mixture was degassed by bubbling a stream of nitrogen for 15 min
at 0 °C, then stirred and irradiated with 12 W blue LEDs with a fan placed nearby for cooling.
After 18 h, the mixture was extracted with EA, the combined organic layer was dried over Na2SO4
and concentrated under reduced pressure. The crude product was purified by flash column
chromatography on silica gel to afford the title compounds.
N-(2-(4-Methoxyphenyl)-1-phenylethyl)-4-methylbenzenesulfonamide (3a). Yield: 80% (30.5
mg). White solid. M.p.: 113ꢀ115 °C. The crude product was purified by flash column
1
chromatography (petroleum ether/EtOAc 10:1). H NMR (400 MHz, CDCl3) δ: 7.46 (d, J = 7.8
Hz, 2H), 7.19 (m, 3H), 7.14ꢀ6.98 (m, 4H), 6.83 (d, J = 7.9 Hz, 2H), 6.76ꢀ6.60 (m, 2H), 4.97 (d, J =
6.2 Hz, 1H), 4.49 (q, J = 6.8 Hz, 1H), 3.78 (s, 3H), 2.94 (m, 2H), 2.38 (s, 3H). 13C NMR (101
MHz, CDCl3) δ: 158.5, 142.9, 140.5, 137.2, 130.3, 130.3, 129.3, 129.3, 128.3, 128.3, 128.3, 127.4,
127.1, 127.1, 126.7, 126.7, 113.9, 113.9, 59.3, 55.2, 43.2, 21.4. ESIꢀHRMS: m/z [M+Na]+ calcd.
for C22H23NO3SNa: 404.1291; found: 404.1295.
N-(2-(4-Methoxyphenyl)-1-(p-tolyl)ethyl)-4-methylbenzenesulfonamide (3b). Yield: 61% (24.1
mg). White solid. M.p.: 107ꢀ109 °C. The crude product was purified by flash column
1
chromatography (petroleum ether/EtOAc 10:1). H NMR (400 MHz, CDCl3) δ: 7.43 (d, J = 8.0
Hz, 2H), 7.07 (d, J = 8.0 Hz, 2H), 6.95 (m, 4H), 6.74 (m, 4H), 5.04 (d, J = 6.3 Hz, 1H), 4.39 (q, J
= 6.8 Hz, 1H), 3.75 (s, 3H), 2.89 (t, J = 6.7 Hz, 2H), 2.36 (s, 6H). 13C NMR (101 MHz, CDCl3) δ:
158.4, 142.8, 137.6, 137.2, 137.0, 130.3, 130.3, 129.2, 129.2, 129.0, 129.0, 128.5, 127.1, 127.1,
126.7, 126.7, 113.9, 113.9, 59.2, 55.2, 43.2, 21.5, 21.1. ESIꢀHRMS: m/z [M+Na]+ calcd. for
C23H25NO3SNa: 418.1447; found: 418.1441.
N-(1-(4-Fluorophenyl)-2-(4-methoxyphenyl)ethyl)-4-methylbenzenesulfonamide (3c). Yield:
68% (27.1 mg). White solid. M.p.: 100ꢀ102 °C. The crude product was purified by flash column
1
chromatography (petroleum ether/EtOAc 10:1). H NMR (400 MHz, CDCl3) δ: 7.42 (d, J = 7.9
Hz, 2H), 7.18ꢀ6.91 (m, 4H), 6.90ꢀ6.54 (m, 6H), 5.12 (d, J = 6.1 Hz, 1H), 4.44 (q, J = 6.8 Hz, 1H),
3.76 (s, 3H), 2.87 (d, J = 7.2 Hz, 2H), 2.37 (s, 3H). 13C NMR (101 MHz, CDCl3) δ: 163.2, 160.8,
158.5, 143.1, 137.1, 136.3, 130.3, 130.3, 129.3, 129.3, 128.5 (d, J = 32 Hz, 1C), 128.0, 127.0, 127.0,
115.2, 115.0, 114.0, 114.0, 58.7, 55.2, 43.3, 21.5. ESIꢀHRMS: m/z [M+Na]+ calcd. for
C22H22FNO3SNa: 422.1197; found: 422.1202.
9
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 19
1
2
3
N-(1-(4-Chlorophenyl)-2-(4-methoxyphenyl)ethyl)-4-methylbenzenesulfonamide (3d). Yield:
4
5
6
7
8
9
68% (29.1 mg). White solid. M.p.: 123ꢀ125 °C. The crude product was purified by flash column
1
chromatography (petroleum ether/EtOAc 10:1). H NMR (400 MHz, CDCl3) δ: 7.40 (d, J = 8.0
Hz, 2H), 7.18ꢀ7.03 (m, 4H), 6.97 (d, J = 8.1 Hz, 2H), 6.80 (d, J = 8.4 Hz, 2H), 6.69 (d, J = 8.5 Hz,
2H), 5.22ꢀ4.80 (m, 1H), 4.43 (q, J = 6.7 Hz, 1H), 3.77 (s, 3H), 2.86 (t, J = 7.4 Hz, 2H), 2.38 (s,
3H). 13C NMR (101 MHz, CDCl3) δ: 158.6, 143.2, 139.0, 136.9, 133.1, 130.3, 130.3, 129.3, 129.3,
128.4, 128.4, 128.2, 128.2, 127.7, 127.1, 127.1, 114.0, 114.0, 58.6, 55.2, 43.1, 21.5. ESIꢀHRMS:
m/z [M+Na]+ calcd. for C22H22ClNO3SNa 438.0901; found: 438.0905.
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
N-(1-([1,1'-Biphenyl]-4-yl)-2-(4-methoxyphenyl)ethyl)-4-methylbenzenesulfonamide
(3e).
Yield: 68% (28.3 mg). White solid. M.p.: 172ꢀ174 °C. The crude product was purified by flash
column chromatography (petroleum ether/EtOAc 10:1). 1H NMR (400 MHz, CDCl3) δ: 7.58ꢀ7.48
(m, 2H), 7.47ꢀ7.29 (m, 7H), 7.09 (m, 4H), 6.93ꢀ6.79 (m, 2H), 6.76ꢀ6.51 (m, 2H), 4.99 (d, J = 6.0
Hz, 1H), 4.51 (q, J = 6.7 Hz, 1H), 3.76 (s, 3H), 2.94 (m, 2H), 2.32 (s, 3H). 13C NMR (101 MHz,
CDCl3) δ: 158.5, 143.0, 140.7, 140.3, 139.5, 137.1, 130.3, 130.3, 129.3, 129.3, 128.8, 128.8, 128.2,
127.3, 127.3, 127.3, 127.3, 127.1, 127.1, 127.0, 127.0, 127.0, 114.0, 114.0, 59.0, 55.2, 43.1, 21.5.
ESIꢀHRMS: m/z [M+Na]+ calcd. for C28H27NO3SNa 480.1604; found: 480.1604.
N-(1-(4-(tert-Butyl)phenyl)-2-(4-methoxyphenyl)ethyl)-4-methylbenzenesulfonamide
(3f).
Yield: 65% (28.4 mg). White solid. M.p.: 105ꢀ107 °C. The crude product was purified by flash
column chromatography (petroleum ether/EtOAc 10:1). 1H NMR (400 MHz, CDCl3) δ: 7.38 (d, J
= 8.1 Hz, 2H), 7.14 (s, 2H), 7.03 (d, J = 8.0 Hz, 2H), 6.96 (d, J = 8.2 Hz, 2H), 6.90ꢀ6.79 (m, 2H),
6.77ꢀ6.60 (m, 2H), 4.81 (d, J = 5.8 Hz, 1H), 4.46 (m, 1H), 3.78 (s, 3H), 3.06ꢀ2.63 (m, 2H), 2.34 (s,
3H), 1.26 (s, 9H). 13C NMR (101 MHz, CDCl3 ) δ: 158.5, 150.3, 142.7, 137.3, 137.2, 130.3, 130.3,
129.1, 129.1, 128.4, 127.1, 127.1, 126.4, 126.4, 125.1, 125.1, 113.9, 113.9, 58.9, 55.2, 43.1, 34.4,
31.4, 21.5. ESIꢀHRMS: m/z [M+Na]+ calcd. for C26H31NO3SNa 460.1917; found: 460.1917.
N-(1-(4-Cyanophenyl)-2-(4-methoxyphenyl)ethyl)-4-methylbenzenesulfonamide (3g). Yield:
80% (32.5 mg). White solid. M.p.: 142ꢀ144 °C. The crude product was purified by flash column
chromatography (petroleum ether/EtOAc 9:1). 1H NMR (500 MHz, CDCl3) δ: 7.42 (dd, J = 18.9,
7.8 Hz, 4H), 7.14 (dd, J = 46.0, 7.8 Hz, 4H), 6.72 (dd, J = 46.8, 8.2 Hz, 4H), 5.45 (d, J = 5.9 Hz,
1H), 4.48 (m, 1H), 3.76 (s, 3H), 2.85 (t, J = 6.9 Hz, 2H), 2.39 (s, 3H). 13C NMR (126 MHz, CDCl3)
δ: 158.7, 146.2, 143.5, 136.7, 132.1, 132.1, 130.2, 130.2, 129.4, 129.4, 127.6, 127.6, 127.2, 127.0,
127.0, 118.7, 114.1, 114.1, 111.1, 59.0, 55.2, 42.9, 21.5. ESIꢀHRMS: m/z [M+Na]+ calcd. for
C23H22N2O3SNa 429.1243; found: 429.1248.
Methyl 4-(2-(4-methoxyphenyl)-1-(4-methylphenylsulfonamido)ethyl)benzoate (3h). Yield:
60% (26.4 mg). White solid. M.p.: 125ꢀ127 °C. The crude product was purified by flash column
1
chromatography (petroleum ether/EtOAc 10:1). H NMR (500 MHz, CDCl3) δ: 7.80 (d, J = 8.2
Hz, 2H), 7.42 (d, J = 8.1 Hz, 2H), 7.12 (d, J = 8.2 Hz, 2H), 7.05 (d, J = 8.0 Hz, 2H), 6.78 (d, J =
8.5 Hz, 2H), 6.65 (d, J = 8.5 Hz, 2H), 5.57 (d, J = 6.7 Hz, 1H), 4.51 (q, J = 7.0 Hz, 1H), 3.89 (s,
3H), 3.74 (s, 3H), 2.88 (d, J = 7.2 Hz, 2H), 2.34 (s, 3H). 13C NMR (126 MHz, CDCl3) δ: 166.8,
158.5, 145.9, 143.2, 137.0, 130.3, 130.3, 129.6, 129.6, 129.4, 129.1, 127.8, 127.0, 127.0, 126.9,
126.9, 126.9, 114.0, 113.9, 59.2, 55.2, 52.2, 43.0, 21.4. ESIꢀHRMS: m/z [M+Na]+ calcd. for
C24H25NO5SNa 462.1346; found: 462.1353.
N-(2-(4-Methoxyphenyl)-1-(4-(trifluoromethyl)phenyl)ethyl)-4-methylbenzenesulfonamide
10
ACS Paragon Plus Environment

Page 11 of 19
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
(3i). Yield: 38% (17.1 mg). White solid. M.p.: 159ꢀ161 °C. The crude product was purified by
1
flash column chromatography (petroleum ether/EtOAc 8:1). H NMR (500 MHz, CDCl3) δ:
7.50ꢀ7.28 (m, 4H), 7.09 (m, 4H), 6.77 (m, 4H), 5.05 (d, J = 5.8 Hz, 1H), 4.53 (q, J = 6.6 Hz, 1H),
3.77 (s, 3H), 3.00ꢀ2.69 (m, 2H), 2.34 (s, 3H). 13C NMR (126 MHz, CDCl3) δ: 158.7, 144.5, 143.3,
136.8, 130.2, 130.2, 130.2, 129.3, 129.3, 129.3, 127.4, 127.2, 127.2, 127.0, 127.0, 127.0, 125.2,
114.1, 114.1, 58.8, 55.2, 43.0, 21.4. ESIꢀHRMS: m/z [M+Na]+ calcd. for C23H22F3NO3SNa
472.1165; found: 472.1165.
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
N-(2-(4-Methoxyphenyl)-1-(o-tolyl)ethyl)-4-methylbenzenesulfonamide (3j). Yield: 63% (24.9
mg). White solid. M.p.: 100ꢀ102 °C. The crude product was purified by flash column
1
chromatography (petroleum ether/EtOAc 10:1). H NMR (400 MHz, CDCl3) δ: 7.42 (d, J = 8.0
Hz, 2H), 7.18ꢀ6.88 (m, 6H), 6.89ꢀ6.49 (m, 4H), 4.92 (d, J = 5.9 Hz, 1H), 4.69 (q, J = 6.8 Hz, 1H),
3.76 (s, 3H), 2.88 (dd, J = 7.1, 3.9 Hz, 2H), 2.35 (s, 3H), 2.04 (s, 3H). 13C NMR (101 MHz,
CDCl3) δ: 158.5, 143.0, 138.7, 137.0, 134.8, 130.3, 130.3, 130.2, 129.3, 129.3, 128.4, 127.1, 127.0,
127.0, 126.2, 126.1, 113.9, 113.9, 55.2, 55.1, 42.7, 21.5, 19.0. ESIꢀHRMS: m/z [M+Na]+ calcd. for
C23H25NO3SNa: 418.1447; found: 418.1442.
N-(1-(2-Methoxyphenyl)-2-(4-methoxyphenyl)ethyl)-4-methylbenzenesulfonamide (3k). Yield:
63% (25.9 mg). White solid. M.p.: 102ꢀ104 °C. The crude product was purified by flash column
1
chromatography (petroleum ether/EtOAc 10:1). H NMR (400 MHz, CDCl3) δ: 7.44 (d, J = 8.0
Hz, 2H), 7.05 (dd, J = 32.6, 7.5 Hz, 3H), 6.94ꢀ6.52 (m, 7H), 5.70ꢀ5.60 (d, J = 12.0 Hz, 1H)
4.76ꢀ4.35 (m, 1H), 3.75 (s, 6H), 3.00 (m, 2H), 2.32 (s, 3H). 13C NMR (101 MHz, CDCl3) δ: 158.2,
156.3, 142.5, 137.5, 130.3, 130.3, 129.6, 129.2, 128.9, 128.9, 128.4, 127.6, 126.8, 126.8, 120.4,
113.6, 113.6, 110.4, 58.2, 55.2, 55.2, 41.3, 21.4. ESIꢀHRMS: m/z [M+Na]+ calcd. for
C23H25NO4SNa: 434.1397; found: 434.1389.
N-(1-(2-Chlorophenyl)-2-(4-methoxyphenyl)ethyl)-4-methylbenzenesulfonamide (3l). Yield:
63% (21.6 mg). White solid. M.p.: 108ꢀ110 °C. The crude product was purified by flash column
1
chromatography (petroleum ether/EtOAc 10:1). H NMR (500 MHz, CDCl3) δ: 7.40 (d, J = 8.1
Hz, 2H), 7.24 (m, 2H), 7.12 (m, 2H), 7.06 (d, J = 8.0 Hz, 2H), 6.83 (d, J = 8.4 Hz, 2H), 6.67 (d, J
= 8.4 Hz, 2H), 5.08 (d, J = 5.7 Hz, 1H), 4.93ꢀ4.72 (m, 1H), 3.77 (s, 3H), 3.03 (m, 1H), 2.68 (m,
1H), 2.36 (s, 3H). 13C NMR (126 MHz, CDCl3) δ: 158.6, 143.1, 138.3, 136.2, 132.0, 130.1, 130.1,
129.5, 129.5, 129.3, 129.3, 128.6, 128.5, 128.0, 127.1, 127.1, 126.9, 114.0, 114.0, 56.2, 55.2, 41.3.
ESIꢀHRMS: m/z [M+Na]+ calcd. for C22H22NO3SClNa: 438.0901; found: 438.0908.
N-(1-(2-Bromophenyl)-2-(4-methoxyphenyl)ethyl)-4-methylbenzenesulfonamide (3m). Yield:
46% (21.1 mg). White solid. M.p.: 107ꢀ109 °C. The crude product was purified by flash column
chromatography (petroleum ether/EtOAc 10:1). 1H NMR (400 MHz, CDCl3) δ: 7.45 (m, 3H), 7.30
(d, J = 10.8 Hz, 1H), 7.20 (t, J = 7.4 Hz, 1H), 7.09 (d, J = 7.8 Hz, 3H), 6.87 (d, J = 8.3 Hz, 2H),
6.69 (d, J = 8.3 Hz, 2H), 5.08 (s, 1H), 4.85 (m, 1H), 3.81 (s, 3H), 3.06 (dd, J = 14.2, 4.6 Hz, 1H),
2.63 (dd, J = 13.8, 9.2 Hz, 1H), 2.39 (s, 3H). 13C NMR (101 MHz, CDCl3) δ: 158.6, 143.1, 140.0,
136.1, 132.8, 130.1, 130.1, 129.3, 129.3, 128.7, 128.7, 127.9, 127.5, 127.1, 127.1, 122.3, 114.0,
114.0, 58.3, 55.2, 41.5, 21.5. ESIꢀHRMS: m/z [M+Na]+ calcd. for C22H22NO3SBrNa: 482.0396;
found: 482.0382.
N-(1-(3-Bromophenyl)-2-(4-methoxyphenyl)ethyl)-4-methylbenzenesulfonamide (3n). Yield:
79% (36.3 mg). White solid. M.p.: 114ꢀ116 °C. The crude product was purified by flash column
11
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 19
1
2
3
4
5
6
7
8
9
chromatography (petroleum ether/EtOAc 10:1). 1H NMR (500 MHz, CDCl3) δ: 7.39 (dd, J = 8.3,
2.8 Hz, 2H), 7.32ꢀ7.25 (m, 1H), 7.16ꢀ6.95 (m, 5H), 6.82 (d, J = 2.1 Hz, 2H), 6.77ꢀ6.55 (m, 2H),
5.19ꢀ4.77 (m, 1H), 4.43 (m, 1H), 3.77 (s, 3H), 2.97ꢀ2.61 (m, 2H), 2.37 (s, 3H). 13C NMR (101
MHz, CDCl3) δ: 158.7, 143.3, 142.8, 136.8, 130.4, 130.2, 130.2, 129.9, 129.8, 129.3, 129.3, 127.6,
127.0, 127.0, 125.6, 122.4, 114.1, 114.1, 58.7, 55.2, 43.1, 21.5. ESIꢀHRMS: m/z [M+Na]+ calcd.
for C22H22BrNO3SNa: 482.0396; found: 482.0400.
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
N-(1-(3,5-diMethoxyphenyl)-2-(4-methoxyphenyl)ethyl)-4-methylbenzenesulfonamide (3o).
Yield: 77% (33.9 mg). White solid. M.p.: 122ꢀ124 °C. The crude product was purified by flash
column chromatography (petroleum ether/EtOAc 8:1). 1H NMR (400 MHz, CDCl3) δ: 7.45 (d, J =
8.2 Hz, 2H), 7.09 (d, J = 8.0 Hz, 2H), 6.94ꢀ6.76 (m, 2H), 6.76ꢀ6.56 (m, 2H), 6.20 (dd, J = 27.5,
2.2 Hz, 3H), 5.04 (d, J = 6.4 Hz, 1H), 4.39 (q, J = 6.8 Hz, 1H), 3.71 (d, J = 41.9 Hz, 9H), 2.89 (m,
2H), 2.36 (s, 3H). 13C NMR (101 MHz, CDCl3) δ: 160.6, 160.6, 158.5, 143.0, 142.9, 137.2, 130.3,
130.3, 129.2, 129.2, 128.3, 127.1, 127.1, 113.9, 113.9, 104.8, 104.8, 99.4, 59.4, 55.2, 55.2, 55.2,
43.0, 21.5. ESIꢀHRMS: m/z [M+Na]+ calcd. for C24H27NO5SNa: 464.1502; found: 464.1514.
N-(2-(4-Methoxyphenyl)-1-(pyridin-3-yl)ethyl)-4-methylbenzenesulfonamide (3p). Yield: 68%
(19.9 mg). White solid. M.p.: 164ꢀ166 °C. The crude product was purified by flash column
1
chromatography (petroleum ether/EtOAc 10:1). H NMR (400 MHz, CDCl3) δ: 8.37 (d, J = 44.0
Hz, 2H), 7.43 (d, J = 7.6 Hz, 3H), 7.11 (d, J = 7.9 Hz, 3H), 6.97ꢀ6.50 (m, 4H), 5.12 (d, J = 5.8 Hz,
1H), 4.49 (q, J = 6.7 Hz, 1H), 3.77 (s, 3H), 3.18ꢀ2.66 (m, 2H), 2.37 (s, 3H). 13C NMR (101 MHz,
CDCl3) δ: 158.8, 148.7, 148.5, 143.4, 136.7, 134.3, 130.2, 130.2, 129.5, 129.5, 127.3, 127.0, 127.0,
123.2, 114.2, 114.2, 100.0, 57.0, 55.2, 43.0, 21.5. ESIꢀHRMS: m/z [M+H]+ calcd. for
C21H23N2O3S: 383.1424; found: 383.1410.
N-(2-(4-Methoxyphenyl)-1-(naphthalen-1-yl)ethyl)-4-methylbenzenesulfonamide (3q). Yield:
65% (26.7 mg). White solid. M.p.: 164ꢀ166 °C. The crude product was purified by flash column
chromatography (petroleum ether/EtOAc 10:1). 1H NMR (500 MHz, CDCl3) δ: 8.11ꢀ7.58 (m, 3H),
7.57ꢀ7.46 (m, 2H), 7.37ꢀ7.35 (m, 2H), 7.27ꢀ7.23 (m, 2H), 6.96ꢀ6.94 (m, 2H), 6.84ꢀ6.82 (m, 2H),
6.71ꢀ6.68 (m, 2H), 5.30 (t, J = 7.3 Hz, 1H), 4.93 (d, J = 13.4 Hz, 1H), 3.77 (s, 3H), 3.20 (m, 1H),
3.06ꢀ2.79 (m, 1H), 2.29 (s, 3H). 13C NMR (126 MHz, CDCl3) δ: 158.6, 142.9, 136.7, 135.9, 133.8,
130.4, 130.4, 130.2, 129.1, 129.1, 129.0, 128.2, 128.0, 127.0, 127.0, 126.3, 125.5, 125.1, 124.6,
122.3, 114.0, 114.0, 55.2, 55.2, 42.1, 21.4. ESIꢀHRMS: m/z [M+Na]+ calcd. for C26H25NO3SNa:
454.1447; found: 454.1440.
N-(2-(4-Methoxyphenyl)-1-(naphthalen-2-yl)ethyl)-4-methylbenzenesulfonamide (3r). Yield:
55% (23.7 mg). White solid. M.p.: 160ꢀ162 °C. The crude product was purified by flash column
chromatography (petroleum ether/EtOAc 10:1). 1H NMR (400 MHz, CDCl3) δ: 7.83ꢀ7.68 (m, 1H),
7.63 (t, J = 8.1 Hz, 2H), 7.41 (m, 5H), 7.23ꢀ7.11 (m, 1H), 6.88 (m, 4H), 6.68 (d, 2H), 5.07 (d, J =
6.3 Hz, 1H), 4.64 (q, J = 6.8 Hz, 1H), 3.74 (s, 3H), 3.01 (t, J = 7.6 Hz, 2H), 2.20 (s, 3H). 13C NMR
(101 MHz, CDCl3) δ: 158.5, 143.0, 137.6, 137.1, 133.0, 132.7, 130.3, 130.3, 129.1, 129.1, 128.2,
128.2, 127.9, 127.5, 127.0, 127.0, 126.0, 126.0, 125.9, 124.5, 114.0, 114.0, 59.4, 55.2, 43.0, 21.3.
ESIꢀHRMS: m/z [M+Na]+ calcd. for C26H25NO3SNa: 454.1447; found: 454.1446.
N-(2-(4-Methoxyphenyl)-1-phenylethyl)methanesulfonamide (3s). Yield: 70% (21.4 mg).
White solid. M.p.: 102ꢀ104 °C. The crude product was purified by flash column chromatography
1
(petroleum ether/EtOAc 10:1). H NMR (500 MHz, CDCl3) δ: 7.64ꢀ7.16 (m, 5H), 7.01 (m, 2H),
12
ACS Paragon Plus Environment

Page 13 of 19
The Journal of Organic Chemistry
1
2
3
4
5
6
7
6.80 (m, 2H), 4.92ꢀ4.50 (m, 2H), 3.78 (s, 3H), 3.25ꢀ2.82 (m, 2H), 2.43 (s, 3H). 13C NMR (126
MHz, CDCl3) δ: 158.7, 140.9, 130.5, 130.5, 128.8, 128.8, 128.4, 128.0, 126.9, 126.9, 114.1, 114.1,
59.4, 55.3, 43.1, 41.6. ESIꢀHRMS: m/z [M+Na]+ calcd. for C16H19NO3SNa: 328.0978; found:
328.0980.
8
9
N-(2-(4-Methoxyphenyl)-1-phenylethyl)benzenesulfonamide (3t). Yield: 81% (29.7 mg). White
solid. M.p.: 100ꢀ102 °C. The crude product was purified by flash column chromatography
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
(petroleum ether/EtOAc 10:1). H NMR (400 MHz, CDCl3) δ: 7.66ꢀ7.47 (m, 2H), 7.46ꢀ7.33 (m,
1H), 7.33ꢀ7.20 (m, 2H), 7.15 (d, J = 3.5 Hz, 3H), 7.03 (dd, J = 3.1, 1.5 Hz, 2H), 6.88ꢀ6.73 (m, 2H),
6.68 (d, J = 6.6 Hz, 2H), 5.10 (d, J = 6.4 Hz, 1H), 4.49 (q, J = 6.8 Hz, 1H), 3.75 (s, 3H), 3.05ꢀ2.64
(m, 2H). 13C NMR (101 MHz, CDCl3) δ: 158.5, 140.4, 140.1, 132.2, 130.3, 130.3, 128.7, 128.7,
128.3, 128.3, 128.2, 127.5, 127.0, 127.0, 126.7, 126.7, 114.0, 114.0, 59.4, 55.2, 43.3. ESIꢀHRMS:
m/z [M+Na]+ calcd. for C21H21NO3SNa: 390.1134; found: 390.1134.
N-(2-(4-Methoxyphenyl)-1-phenylethyl)aniline (3u). Yield: 71% (20 mg). White solid. M.p.:
125ꢀ127 °C. The crude product was purified by flash column chromatography (petroleum
ether/EtOAc 15:1). 1H NMR (500 MHz, CDCl3) δ: 7.25 (d, J = 42.0 Hz, 5H), 7.18ꢀ6.94 (m, 4H),
6.79 (d, J = 7.9 Hz, 2H), 6.61 (s, 1H), 6.44 (d, J = 7.9 Hz, 2H), 4.70ꢀ4.37 (m, 1H), 4.10 (s, 1H),
3.74 (d, J = 3.3 Hz, 3H), 3.25ꢀ2.73 (m, 2H). 13C NMR (126 MHz, CDCl3) δ: 158.5, 147.4, 143.6,
130.3, 130.3, 129.7, 129.1, 129.1, 128.6, 128.6, 127.1, 126.6, 117.5, 114.0, 114.0, 113.7, 113.7,
59.4, 55.3, 44.4. ESIꢀHRMS: m/z [M+H]+ calcd. for C21H22NO: 304.1696; found: 304.1689.
tert-Butyl (2-(4-methoxyphenyl)-1-phenylethyl)carbamate (3v). Yield: 80% (26.2 mg). White
solid. M.p.: 132ꢀ134 °C. The crude product was purified by flash column chromatography
1
(Petroleum ether/EtOAc 20:1). H NMR (400 MHz, CDCl3) δ: 7.41ꢀ7.08 (m, 5H), 7.05ꢀ6.86 (m,
2H), 6.76 (d, J = 8.6 Hz, 2H), 4.87 (s, 2H), 3.76 (s, 3H), 2.99 (s, 2H), 1.37 (s, 9H). 13C NMR (101
MHz, CDCl3) δ: 158.2, 155.2, 130.4, 130.4, 130.4, 129.4, 128.4, 128.4, 127.2, 127.2, 126.5, 126.5,
113.7, 113.7, 79.5, 55.2, 42.5, 28.3. ESIꢀHRMS: m/z [M+H]+ calcd. for C20H25NO3: 350.1727;
found: 350.1728.
4-Methyl-N-(1-phenyl-2-(p-tolyl)ethyl)benzenesulfonamide (3y). Yield: 45% (16.4 mg). White
solid. M.p.: 98ꢀ100 °C. The crude product was purified by flash column chromatography
1
(petroleum ether/EtOAc 10:1). H NMR (400 MHz, CDCl3) δ: 7.49ꢀ7.32 (m, 2H), 7.18ꢀ7.16 (m,
3H), 7.08ꢀ7.06 (m, 4H), 6.96 (d, J = 7.8 Hz, 2H), 6.79 (d, J = 7.8 Hz, 2H), 4.82 (d, J = 6.0 Hz, 1H),
4.59ꢀ4.29 (m, 1H), 2.93 (dd, J = 16.9, 7.1 Hz, 2H), 2.32 (d, J = 30.1 Hz, 6H). 13C NMR (101 MHz,
CDCl3) δ: 142.9, 140.6, 137.1, 136.4, 133.1, 129.2, 129.2, 129.2, 129.2, 129.2, 128.3, 128.3, 127.4,
127.4, 127.1, 127.1, 126.7, 126.7, 59.1, 43.7, 21.5, 21.1. ESIꢀHRMS: m/z [M+Na]+ calcd. for
C22H23NO2SNa: 388.1342; found: 388.1344.
N-(2-(4-Fluorophenyl)-1-phenylethyl)-4-methylbenzenesulfonamide (3z). Yield: 50% (19.1
mg). White solid. M.p.: 115ꢀ117 °C. The crude product was purified by flash column
1
chromatography (petroleum ether/EtOAc 10:1). H NMR (400 MHz, CDCl3) δ: 7.44 (d, J = 8.0
Hz, 2H), 7.16 (d, J = 3.6 Hz, 3H), 7.12ꢀ6.95 (m, 4H), 6.84 (d, J = 6.3 Hz, 4H), 5.09 (d, J = 6.8 Hz,
1H), 4.46 (q, J = 7.0 Hz, 1H), 2.96 (d, J = 7.1 Hz, 2H), 2.20 (s, 3H). 13C NMR (101 MHz, CDCl3)
δ: 163.0, 160.6, 143.1, 140.2, 137.1, 132.1 (d, J = 16 Hz, 1C), 130.8 (d, J = 32 Hz, 1C), 129.3,
129.3, 128.4, 128.4, 127.6, 127.0, 127.0, 126.6, 126.6, 115.4, 115.1, 59.4, 43.2, 21.5. ESIꢀHRMS:
m/z [M+Na]+ calcd. for C21H20FNO2SNa: 392.1091; found: 392.1098.
13
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 14 of 19
1
2
3
N-(2-(4-Chlorophenyl)-1-phenylethyl)-4-methylbenzenesulfonamide (3aa). Yield: 41% (15.8
4
5
6
7
8
9
mg). White solid. M.p.: 145ꢀ149 °C. The crude product was purified by flash column
1
chromatography (petroleum ether/EtOAc 10:1). H NMR (500 MHz, CDCl3) δ: 7.43 (d, J = 7.9
Hz, 2H), 7.23ꢀ7.14 (m, 3H), 7.08 (dd, J = 8.0, 5.8 Hz, 4H), 7.04 (dd, J = 6.5, 3.0 Hz, 2H), 6.82 (d,
J = 7.9 Hz, 2H), 5.14 (d, J = 6.9 Hz, 1H), 4.46 (q, J = 7.1 Hz, 1H), 2.95 (dd, J = 7.3, 3.2 Hz, 2H),
2.38 (s, 3H). 13C NMR (126 MHz, CDCl3) δ: 143.2, 140.2, 137.0, 135.0, 132.7, 130.6, 130.6,
129.4, 129.4, 128.5, 128.5, 128.5, 128.5, 127.6, 126.9, 126.9, 126.6, 126.6, 59.3, 43.4, 21.5.
ESIꢀHRMS: m/z [M+Na]+ calcd. for C21H20ClNO2SNa: 408.0795; found: 408.0792.
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
N-(2-(4-Bromophenyl)-1-phenylethyl)-4-methylbenzenesulfonamide (3ab). Yield: 42% (18
mg). White solid. M.p.: 100ꢀ102 °C. The crude product was purified by flash column
1
chromatography (petroleum ether/EtOAc 10:1). H NMR (400 MHz, CDCl3) δ: 7.44 (d, J = 7.9
Hz, 2H), 7.26ꢀ7.15 (m, 5H), 7.15ꢀ6.93 (m, 4H), 6.76 (d, J = 8.1 Hz, 2H), 4.80 (d, J = 6.7 Hz, 1H),
4.47 (q, J = 7.0 Hz, 1H), 2.95 (dd, J = 7.1, 4.2 Hz, 2H), 2.38 (s, 3H). 13C NMR (101 MHz, CDCl3)
δ: 143.2, 140.2, 137.0, 135.5, 131.5, 131.5, 131.0, 131.0, 129.4, 129.4, 128.5, 128.5, 127.7, 126.9,
126.9, 126.6, 126.6, 120.8, 59.2, 43.5, 21.5. ESIꢀHRMS: m/z [M+Na]+ calcd. for
C21H20BrNO2SNa: 452.0290; found: 452.0277.
N-(2-([1,1'-Biphenyl]-4-yl)-1-phenylethyl)-4-methylbenzenesulfonamide (3ac). Yield: 42%
(17.9 mg). White solid. M.p.: 125ꢀ127 °C. The crude product was purified by flash column
chromatography (petroleum ether/EtOAc 10:1). 1H NMR (400 MHz, CDCl3) δ: 7.60ꢀ7.51 (m, 2H),
7.43 (dd, J = 8.1, 6.1 Hz, 4H), 7.37 (dd, J = 7.5, 5.6 Hz, 2H), 7.35ꢀ7.29 (m, 1H), 7.19 (dd, J = 5.0,
1.9 Hz, 3H), 7.10 (dd, J = 6.7, 3.0 Hz, 2H), 7.05 (d, J = 8.0 Hz, 2H), 7.01ꢀ6.91 (m, 2H), 5.02 (d, J
= 6.4 Hz, 1H), 4.55 (q, J = 6.8 Hz, 1H), 3.02 (m, 2H), 2.28 (s, 3H). 13C NMR (101 MHz, CDCl3) δ:
143.0, 140.6, 140.6, 139.6, 137.1, 135.4, 129.7, 129.7, 129.3, 129.3, 128.8, 128.8, 128.4, 128.4,
127.5, 127.3, 127.1, 127.1, 127.0, 127.0, 126.9, 126.9, 126.7, 126.7, 59.2, 43.8, 21.4. ESIꢀHRMS:
m/z [M+Na]+ calcd. for C27H25NO2SNa: 450.1498; found: 450.1494.
N-(2-(2-Methoxyphenyl)-1-phenylethyl)-4-methylbenzenesulfonamide (3ad). Yield: 42% (16
mg). White solid. M.p.: 113ꢀ115 °C. The crude product was purified by flash column
chromatography (petroleum ether/EtOAc 10:1). 1H NMR (400 MHz, CDCl3) δ: 7.37ꢀ7.12 (m, 8H),
7.00 (d, J = 8.0 Hz, 2H), 6.85 (dd, J = 7.4, 1.7 Hz, 1H), 6.77 (t, J = 7.7 Hz, 2H), 5.43 (d, J = 4.9
Hz, 1H), 4.45 (m, 1H), 3.78 (s, 3H), 3.12ꢀ2.65 (m, 2H), 2.34 (s, 3H). 13C NMR (101 MHz, CDCl3)
δ: 157.1, 142.5, 141.9, 136.9, 131.1, 129.1, 129.1, 128.3, 128.3, 128.3, 127.2, 126.9, 126.9, 126.5,
126.5, 125.4, 121.0, 110.6, 59.0, 55.4, 39.0, 21.4. ESIꢀHRMS: m/z [M+Na]+ calcd. for
C22H23NO3SNa: 404.1291; found: 404.1292.
N-(2-(3-Methoxyphenyl)-1-phenylethyl)-4-methylbenzenesulfonamide (3ae). Yield: 50% (20.2
mg). White solid. M.p.: 102ꢀ104 °C. The crude product was purified by flash column
1
chromatography (petroleum ether/EtOAc 10:1). H NMR (500 MHz, CDCl3) δ: 7.44 (d, J = 8.4
Hz, 2H), 7.28 (s, 1H), 7.21 (m, 3H), 7.10 (t, J = 2.4 Hz, 4H), 6.74 (m, 1H), 6.65ꢀ6.48 (m, 1H),
6.40 (t, J = 2.0 Hz, 1H), 5.15ꢀ4.88 (m, 1H), 4.49 (q, J = 6.5 Hz, 1H), 3.68 (s, 3H), 3.14ꢀ2.76 (m,
2H), 2.39 (s, 3H). 13C NMR (126 MHz, CDCl3) δ: 159.6, 143.0, 140.6, 137.8, 136.9, 129.6, 129.3,
129.3, 128.4, 128.4, 127.5, 127.0, 127.0, 126.7, 126.7, 121.6, 114.5, 112.7, 59.1, 55.0, 44.2, 21.5.
ESIꢀHRMS: m/z [M+Na]+ calcd. for C22H23NO3SNa: 404.1291; found: 404.1288.
4-Methyl-N-(2-(naphthalen-1-yl)-1-phenylethyl)benzenesulfonamide (3af). Yield: 50% (20.1
14
ACS Paragon Plus Environment

Page 15 of 19
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
mg). White solid. M.p.: 152ꢀ154 °C. The crude product was purified by flash column
chromatography (petroleum ether/EtOAc 10:1). 1H NMR (500 MHz, CDCl3) δ: 7.89ꢀ7.74 (m, 2H),
7.67 (m, 1H), 7.50ꢀ7.38 (m, 2H), 7.22 (m, 8H), 7.02 (d, J = 6.9 Hz, 1H), 6.82 (d, J = 8.0 Hz, 2H),
5.18 (d, J = 5.8 Hz, 1H), 4.55 (m, 1H), 3.57ꢀ3.12 (m, 2H), 2.25 (s, 3H). 13C NMR (126 MHz,
CDCl3) δ: 142.7, 141.4, 136.2, 134.0, 132.5, 131.6, 129.1, 129.1, 128.9, 128.5, 128.5, 127.9, 127.8,
127.6, 126.7, 126.7, 125.5, 126.5, 126.3, 125.6, 125.3, 123.2, 58.2, 41.9, 21.5. ESIꢀHRMS: m/z
[M+Na]+ calcd. for C25H23NO2SNa: 424.1342; found: 424.1344.
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-Methyl-N-(2-(naphthalen-2-yl)-1-phenylethyl)benzenesulfonamide (3ag). Yield: 50% (20.1
mg). White solid. M.p.: 154ꢀ156 °C. The crude product was purified by flash column
chromatography (petroleum ether/EtOAc 10:1). 1H NMR (500 MHz, CDCl3) δ: 7.81ꢀ7.72 (m, 1H),
7.63 (m, 2H), 7.52ꢀ7.41 (m, 2H), 7.38 (s, 1H), 7.36ꢀ7.27 (m, 2H), 7.20 (t, J = 2.5 Hz, 3H), 7.14 (m,
2H), 6.99 (m, 1H), 6.88 (d, J = 8.0 Hz, 2H), 4.97 (d, J = 6.2 Hz, 1H), 4.57 (m, 1H), 3.26ꢀ2.96 (m,
2H), 2.27 (s, 3H). 13C NMR (101 MHz, CDCl3) δ: 142.9, 140.7, 136.8, 133.9, 133.3, 132.4, 129.2,
129.2, 128.5, 128.5, 128.2, 128.0, 127.6, 1127.6, 127.6, 127.2, 126.9, 126.9, 126.7, 126.7, 126.1,
125.8, 59.2, 44.4, 21.5. ESIꢀHRMS: m/z [M+Na]+ calcd. for C25H23NO2SNa: 424.1342; found:
424.1348.
4-Methyl-N-(1-phenyl-2-(thiophen-2-yl)ethyl)benzenesulfonamide (3ah). Yield: 51% (18.2
mg). White solid. M.p.: 82ꢀ84 °C. The crude product was purified by flash column
1
chromatography (petroleum ether/EtOAc 10:1). H NMR (400 MHz, CDCl3) δ: 7.43 (d, J = 8.0
Hz, 2H), 7.15ꢀ6.84 (m, 8H), 6.74 (m, 1H), 6.53 (d, J = 3.4 Hz, 1H), 5.09 (d, J = 6.7 Hz, 1H), 4.44
(q, J = 6.8 Hz, 1H), 3.33ꢀ2.80 (m, 2H), 2.28 (s, 3H). 13C NMR (101 MHz, CDCl3) δ: 142.1, 138.8,
137.2, 136.1, 128.3, 128.3, 127.4, 127.4, 126.6, 126.1, 126.1, 125.8, 125.7, 125.7, 125.7, 123.6,
58.0, 36.8, 20.4. ESIꢀHRMS: m/z [M+Na]+ calcd. for C19H19NO2S2Na: 380.0749; found:
380.0741.
4-Methyl-N-(1-phenyl-2-(thiophen-3-yl)ethyl)benzenesulfonamide (3ai). Yield: 56% (20 mg).
White solid. M.p.: 81ꢀ84 °C. The crude product was purified by flash column chromatography
(petroleum ether/EtOAc 10:1). 1H NMR (400 MHz, CDCl3) δ: 7.48 (d, J = 8.3 Hz, 2H), 7.23ꢀ6.91
(m, 8H), 6.79 (m, 1H), 6.69ꢀ6.45 (m, 1H), 4.91 (d, J = 6.4 Hz, 1H), 4.51 (q, J = 6.6 Hz, 1H),
3.19ꢀ2.81 (m, 2H), 2.37 (s, 3H). 13C NMR (101 MHz, CDCl3) δ: 143.1, 140.4, 137.1, 136.5, 129.4,
129.4, 128.4, 128.4, 128.3, 127.5, 127.1, 127.1, 126.6, 126.6, 125.9, 122.9, 58.3, 38.4, 21.5.
ESIꢀHRMS: m/z [M+Na]+ calcd. for C19H19NO2S2Na: 380.0749; found: 380.0747.
4-Methyl-N-(2-(2-methyl-1H-indol-3-yl)-1-phenylethyl)benzenesulfonamide (3aj). Yield: 62%
(25 mg). White solid. M.p.: 197ꢀ199 °C. The crude product was purified by flash column
1
chromatography (petroleum ether/EtOAc 3:1). H NMR (400 MHz, CDCl3) δ: 7.71 (s, 1H), 7.37
(d, J = 8.3 Hz, 2H), 7.30ꢀ7.17 (m, 5H), 7.12ꢀ7.07 (m, 3H), 7.00ꢀ6.94 (m, 3H), 4.86 (d, J = 5.5 Hz,
1H), 4.66ꢀ4.26 (m, 1H), 3.06 (d, J = 6.7 Hz, 2H), 2.32 (s, 3H), 1.94 (s, 3H). 13C NMR (101 MHz,
CDCl3) δ: 142.9, 141.3, 136.6, 135.2, 132.9, 129.2, 129.2, 128.4, 128.3, 128.3, 127.3, 126.9, 126.9,
126.6, 126.6, 121.3, 119.6, 117.7, 110.2, 106.0, 58.3, 33.6, 21.5, 11.3. ESIꢀHRMS: m/z [M+Na]+
calcd. for C24H24N2O2SNa: 427.1451; found: 427.1455.
N-(2-Methoxy-1,2-diphenylethyl)-4-methylbenzenesulfonamide (3ak). Yield: 45% (17.1 mg).
White solid. M.p.: 152ꢀ154 °C. The crude product was purified by flash column chromatography
(petroleum ether/EtOAc 10:1). 1H NMR (500 MHz, CDCl3) δ: 7.45 (d, J = 8.3 Hz, 2H), 7.23ꢀ7.10
15
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 16 of 19
1
2
3
4
5
6
7
8
(m, 3H), 7.04 (t, J = 7.1 Hz, 3H), 6.95 (t, J = 7.7 Hz, 2H), 6.80 (d, J = 8.3 Hz, 2H), 6.75ꢀ6.63 (m,
2H), 5.55 (d, J = 7.9 Hz, 1H), 4.51 (d, J = 6.4 Hz, 2H), 3.20 (s, 3H), 2.18 (s, 3H). 13C NMR (126
MHz, CDCl3) δ: 142.8, 137.6, 136.8, 135.7, 129.2, 129.2, 128.4, 128.4, 128.0, 128.0, 128.0, 127.4,
127.4, 127.2, 127.1, 127.1, 127.0, 127.0, 86.1, 62.4, 57.3, 21.4. ESIꢀHRMS: m/z [M+Na]+ calcd.
for C22H23NO3SNa: 404.1291; found: 404.1288.
9
4-Methyl-N-(2-methyl-1,2-diphenylpropyl)benzenesulfonamide (3al). Yield: 56% (21.2 mg).
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
White solid. M.p.: 130ꢀ132 °C. The crude product was purified by flash column chromatography
1
(petroleum ether/EtOAc 10:1). H NMR (400 MHz, CDCl3) δ: 7.38ꢀ7.19 (m, 5H), 7.17ꢀ6.86 (m,
7H), 6.63 (d, J = 7.5 Hz, 2H), 4.80 (d, J = 8.0 Hz, 1H), 4.28 (d, J = 8.0 Hz, 1H), 2.28 (s, 3H), 1.36
(s, 3H), 1.27 (s, 3H). 13C NMR (101 MHz, CDCl3) δ: 144.0, 142.7, 137.6, 136.8, 129.0, 129.0,
128.5, 128.5, 128.2, 128.2, 127.2, 127.2, 127.0, 127.0, 127.0, 127.0, 127.0, 126.7, 66.9, 42.2, 27.0,
24.7, 21.4. ESIꢀHRMS: m/z [M+Na]+ calcd. for C23H25NO2SNa: 402.1498; found: 402.1495.
N-(1-(4-Formylphenyl)-2-(4-methoxyphenyl)ethyl)-4-methylbenzenesulfonamide
(3am).
Yield: 50% (20.5 mg). White solid. M.p.: 125ꢀ130 °C. The crude product was purified by flash
1
column chromatography (petroleum ether/EtOAc 10:1). H NMR (400 MHz, CDCl3) δ: 9.94 (s,
1H), 7.69 (d, J = 8.1 Hz, 2H), 7.42 (d, J = 8.2 Hz, 2H), 7.25 (d, J = 8.0 Hz, 2H), 7.07 (d, J = 7.9
Hz, 2H), 6.89ꢀ6.74 (m, 2H), 6.73ꢀ6.53 (m, 2H), 5.24 (m, 1H), 4.52 (q, J = 6.7 Hz, 1H), 3.76 (s,
3H), 2.89 (m, 2H), 2.35 (s, 3H). 13C NMR (101 MHz, CDCl3) δ: 191.8, 158.7, 147.7, 143.3, 136.8,
135.5, 130.2, 130.2, 129.8, 129.8, 129.4, 129.4, 127.5, 127.5, 127.4, 127.0, 127.0, 114.1, 114.1,
59.0, 55.2, 42.9, 21.5. ESIꢀHRMS: m/z [M+Na]+ calcd. for C23H23NO4SNa: 432.1240; found:
432.1249.
ASSOCIATED CONTENT
Supporting Information
Supporting Information available: 1H and 13C NMR spectra of products 3a-3am and the
fluorescence quenching studies (pdf).
AUTHOR INFORMATION
Corresponding Author
* Jiang Weng: wengj2@mail.sysu.edu.cn
* Gui Lu: lugui@mail.sysu.edu.cn
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
This work was financially supported by the National Science and Technology Major Project of
the Ministry of Science and Technology of China (No. 2018ZX09735010), Guangdong Provincial
Key Laboratory of Construction Foundation (No. 2017B030314030), the Guangdong Natural
Science Foundation (No. 2015A030313184) and Science and Technology Program of Guangzhou
(No. 201607010118).
REFERENCES
16
ACS Paragon Plus Environment

Page 17 of 19
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
1. a) 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; b)
Shi, L.; Xia, W. Photoredox functionalization of C–H bonds adjacent to a nitrogen atom.
Chem. Soc. Rev. 2012, 41, 7687; c) Twilton, J.; Le, 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, 52; d) Lee, K. N.; Ngai, M.ꢀY. Recent developments in transitionꢀmetal
photoredoxꢀcatalysed reactions of carbonyl derivatives. Chem. Commun. 2017, 53, 13093.
2. a) Zhou, Q.ꢀQ.; Guo, W.; Ding, W.; Wu, X.; Chen, X.; Lu, L.ꢀQ.; Xiao, W.ꢀJ. Decarboxylative
alkynylation and carbonylative alkynylation of carboxylic acids enabled by visibleꢀlight
photoredox catalysis. Angew. Chem., Int. Ed. 2015, 54, 11196; b) Huang, H.; Zhang, G.; Chen,
Y. Dual hypervalent iodine(III) reagents and photoredox catalysis enable decarboxylative
ynonylation under mild conditions. Angew. Chem., Int. Ed. 2015, 54, 7872; c) Zuo, D.ꢀT.;
Ahneman, L.; Chu, J.ꢀA.; Terrett, A.; Doyle, G.; MacMillan, D. W. C. Merging photoredox
with nickel catalysis: Coupling of αꢀcarboxyl sp3ꢀcarbons with aryl halides. Science, 2014,
345, 437; d) Ventre, S.; Petronijevic, F. R.; MacMillan, D. W. C. Decarboxylative fluorination
of aliphatic carboxylic acids via photoredox catalysis. J. Am. Chem. Soc. 2015, 137, 5654; e)
Wu, X.; Meng, C.; Yuan, X.; Jia, X.; Qian, X.; Ye, J. Transitionꢀmetalꢀfree visibleꢀlight
photoredox catalysis at roomꢀtemperature for decarboxylative fluorination of aliphatic
carboxylic acids by organic dyes. Chem. Commun. 2015, 51, 11864; f) Xu, G.ꢀQ.; Xu, J.ꢀT.;
Feng, Z.ꢀT.; Liao, H.; Wang, Z.ꢀY.; Qin, Y.; Xu, P.ꢀF. Dual C(sp3)−H bond functionalization of
Nꢀheterocycles through sequential visibleꢀlight photocatalyzed dehydrogenation/[2+2]
cycloaddition reactions. Angew. Chem., Int. Ed. 2018, 57, 5110; g) An, X.ꢀD.; Jiao, Y.ꢀY.;
Zhang, H.; Gao, Y.; Yu, S. Photoredoxꢀinduced radical relay toward functionalized βꢀamino
alcohol derivatives. Org. Lett. 2018, 20, 401.
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. a) Miyake, Y.; Nakajima, K.; Nishibayashi, Y. Visible lightꢀmediated oxidative
decarboxylation of arylacetic acids into benzyl radicals: addition to electronꢀdeficient alkenes
by using photoredox catalysts. Chem. Commun. 2013, 49, 7854; b) Lang, S. B.; O’Nele, K. M.;
Tunge, J. A. Decarboxylative allylation of amino alkanoic acids and esters via dual catalysis. J.
Am. Chem. Soc. 2014, 136, 13606; c) Capaldo, L.; Buzzetti, L.; Merli, D.; Fagnoni, M.;
Ravelli, D. Smooth. Photocatalyzed benzylation of electrophilic olefins via decarboxylation of
arylacetic acids. J. Org. Chem. 2016, 81, 7102.
4. Matsui, J. K.; Primer, D. N.; Molander, G. A. Metalꢀfree C–H alkylation of heteroarenes with
alkyltrifluoroborates: A general protocol for 1°, 2° and 3° alkylation. Chem. Sci. 2017, 8,
3512.
5. a) Montanaro, S.; Ravelli, D.; Merli, D.; Fagnoni, M.; Albini, A. Decatungstate as photoredox
catalyst: Benzylation of electronꢀpoor olefins. Org. Lett. 2012, 14, 4218; b) Maruyama, T.;
Mizuno, Y.; Shimizu, I.; Suga, S.; Yoshida, J. Reactions of a Nꢀacyliminium ion pool with
benzylsilanes. Implication of a radical/cation/radical cation chain mechanism involving
oxidative C−Si bond cleavage. J. Am. Chem. Soc. 2007, 129, 1902.
6. Hager, D.; MacMillan, D. W. C. Activation of C–H bonds via the merger of photoredox and
organocatalysis: A coupling of benzylic ethers with Schiff bases. J. Am. Chem. Soc. 2014, 136,
16986.
7. a) Chen, W. X.; Liu, Z.; Tian, J. Q.; Li, J.; Ma, J.; Cheng, X.; Li, G. Building congested
ketone: Substituted Hantzsch ester and nitrile as alkylation reagents in photoredox catalysis. J.
17
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 18 of 19
1
2
3
4
5
6
7
8
9
Am. Chem. Soc. 2016, 138, 12312; b) GutierrezꢀBonet, Á.; Tellis, J. C.; Matsui, J. K.; Vara, B.
A.; Molander, G. A. 1,4ꢀDihydropyridines as alkyl radical precursors: Introducing the
aldehyde feedstock to nickel/photoredox dual catalysis. ACS Catal. 2016, 6, 8004; c) Buzzetti,
L.; Prieto, A.; Roy, S. R.; Melchiorre, P. Radicalꢀbased CꢀC bondꢀforming processes enabled
by the photoexcitation of 4ꢀalkylꢀ1,4ꢀdihydropyridines. Angew. Chem. Int. Ed. 2017, 56,
15039.
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
8. Qin, T.; Malins, L. R.; Edwards, J. T.; Merchant, R. R.; Novak, A. J. E.; Zhong, J. Z.; Mills, R.
B.; Yan, M.; Yuan, C.; Eastgate, M. D.; Baran, P. S. Nickelꢀcatalyzed Barton decarboxylation
and Giese reactions: A practical take on classic transforms. Angew. Chem., Int. Ed. 2017, 56,
260.
9. a) Ferraris, D. Catalytic, asymmetric alkylation of imines. Tetrahedron 2007, 63, 9581; b)
Liddell, J. R. Pyrrolizidine alkaloids. Nat. Prod. Rep. 2002, 19, 773; c) Taylor, R. D.;
MacCoss, M.; Lawson, A. D. G. Rings in drugs. J. Med. Chem. 2014, 57, 5845; d) O’Hagan,
D. Pyrrole, pyrrolidine, pyridine, piperidine and tropane alkaloids. Nat. Prod. Rep. 2000, 17,
435; e) Ruggeri, P.; Fumagalli, L.; Binda, M.; Mucchietto, V.; Sciaccaluga, M.; Budriesi, R.;
Fucile, S.; Pallavicini, M. Chemistry and pharmacology of a series of unichiral analogues of
2ꢀ(2ꢀpyrrolidinyl)ꢀ1,4ꢀbenzodioxane, prolinol phenyl ether, and prolinol 3ꢀpyridyl ether
designed as α4β2ꢀnicotinic acetylcholine receptor agonists. J. Med. Chem. 2015, 58, 6665.
10. a) Das, D.; Seidel, D. Redoxꢀneutral αꢀC–H bond functionalization of secondary amines with
concurrent C–P bond formation/Nꢀalkylation. Org. Lett. 2013, 15, 4358; b) Sagara, Y.;
Kimura, T.; Fujikawa, T.; Noguchi, K.; Ohtake, N. Identification of novel muscarinic M3
selective antagonists with a conformationally restricted HypꢀPro spacer. Bioorg. Med. Chem.
Lett. 2003, 13, 57; c) Smith, B.; Chang, H.ꢀH.; Medda, F.; Gokhale, V.; Dietrich, J.; Davis, A.;
Meuillet, E.; Hulme, C. Synthesis and biological activity of 2ꢀaminothiazoles as novel
inhibitors of PGE2 production in cells. Bioorg. Med. Chem. Lett. 2012, 22, 3567.
11. a) Kobayashi, S.; Ishitani, H. Catalytic enantioselective addition to imines. Chem. Rev. 1999,
99, 1069; b) Kobayashi, S.; Mori, Y.; Fossey, J. S.; Salter, M. M. Catalytic enantioselective
formation of C−C bonds by addition to imines and hydrazones: A tenꢀyear update. Chem. Rev.
2011, 111, 2626; c) Zhang, H.; Yang, B.; Yang, Z.; Lu, H.; Li, G. Asymmetric synthesis of
chiral αꢀmethylꢀα,βꢀdiamino acid derivatives via groupꢀassisted purification chemistry using
Nꢀphosphonyl imines and a Ni(II)ꢀcomplexed alanine Schiff base. J. Org. Chem. 2016, 81,
7654; d) Li, G.; Chen, R.; Wu, L.; Fu, Q.; Zhang, X.; Tang, Z. Alkyl transfer from CꢀC
cleavage. Angew. Chem., Int. Ed. 2013, 52, 8432.
12. Patel, N. R.; Kelly, C. B.; Siegenfeld, A. P.; Molander, G. A. Mild, redoxꢀneutral alkylation of
imines enabled by an organic photocatalyst. ACS Catal. 2017, 7, 1766.
13. Zhang, H.ꢀH.; Yu, S. Radical alkylation of imines with 4ꢀalkylꢀ1,4ꢀdihydropyridines enabled
by photoredox/Brønsted acid cocatalysis. J. Org. Chem. 2017, 82, 9995.
14. a) Meng, Q.ꢀY.; Wang, S.; Huff, G. S.; König, B. Ligandꢀcontrolled regioselective
hydrocarboxylation of styrenes with CO2 by combining visible light and nickel catalysis. J.
Am. Chem. Soc. 2018, 140, 3198; b) Zhou, R. Goh, Y. Y.; Liu, H.ꢀW.; Tao, H.ꢀR.; Li, L.ꢀH.;
Wu, J. Visibleꢀlightꢀmediated metalꢀfree hydrosilylation of alkenes through selective
hydrogen atom transfer for Si−H activation. Angew. Chem., Int. Ed. 2017, 56, 16621; c) Zhao,
B; Shang, R; Cheng, W.ꢀM.; Fu, Y. Decarboxylative formylation of aryl halides with glyoxylic
acid by merging organophotoredox with palladium catalysis. Org. Chem. Front. 2018, 5, 1782.
18
ACS Paragon Plus Environment

Page 19 of 19
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
15. Creutz, C.; Sutin, N. Electronꢀtransfer reactions of excited states. Reductive quenching of the
tris(2,2'ꢀbipyridine)ruthenium(II) luminescence. Inorg. Chem. 1976, 15, 496.
16. a) Sahoo, B.; Hopkinson, M. N.; Glorius, F. Combining gold and photoredox catalysis: Visible
lightꢀmediated oxyꢀ and aminoarylation of alkenes. J. Am. Chem. Soc. 2013, 135, 5505; b)
Zhang, Q.; Zhang, Z.ꢀQ.; Fu, Y.; Yu, H. Mechanism of the visible lightꢀmediated
goldꢀcatalyzed oxyarylation reaction of alkenes. ACS Catal. 2016, 6, 798; c) Ghosh, I.; Marzo,
L.; Das, A.; Shaikh, R.; König, B. Visible light mediated photoredox catalytic arylation
reactions. Acc. Chem. Res. 2016, 49, 1566; d) Fabry, D. C.; Rueping, M. Merging visible light
photoredox catalysis with metal catalyzed C–H activations: On the role of oxygen and
superoxide ions as oxidants. Acc. Chem. Res. 2016, 49, 1969.
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
17. Hari, D. P.; König, B. Synthetic applications of eosin Y in photoredox catalysis. Chem.
Commun. 2014, 50, 6688.
18. Perkins, R. J.; Xu, H.ꢀC.; Campbell, J. M.; Moeller, K. D. Anodic coupling of carboxylic acids
to electronꢀrich double bonds: A surprising nonꢀKolbe pathway to lactones. Beilstein J. Org.
Chem. 2013, 9, 1630.
19. a) Ortiz, P.; Collados, J. F.; Harutyunyan. S. R. Direct synthesis of enolizable Nꢀsulfonyl
ketimines under microwave irradiation. Eur. J. Org. Chem. 2016, 2016, 1247; b) Sisko, J.;
Weinre, S. M. A convenient in situ procedure for effecting interꢀ and intramolecular
DielsꢀAlder reactions of Nꢀsulfonyl imines. Tetrahedron Lett, 1989, 30, 3037; c) Dong, D.ꢀJ.;
Li, H.ꢀH.; Tian, S.ꢀK. A highly tunable stereoselective olefination of semistabilized
triphenylphosphonium ylides with Nꢀsulfonyl imines. J. Am. Chem. Soc. 2010, 132, 5018.
19
ACS Paragon Plus Environment