Peri -Selective Direct Acylmethylation and Amidation of Naphthalene Derivatives Using Iridium and Rhodium Catalysts

Article abstract of DOI:10.1055/a-1472-1059

An iridium-catalyzed acylmethylation and a rhodium-catalyzed amidation of naphthalene derivatives are reported, adopting sulfoxonium ylides and dioxazolones as carbene and nitrene transfer agents, respectively. The use of SMe group as a directing group was key to ensure the peri -selective functionalization, and it can be easily removed or diversely transformed to other synthetically useful functionalities after the catalysis.

Full text of DOI:10.1055/a-1472-1059

SYNTHESIS
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart
2021, 53, A–K
special topic
A
Bond Activation – in Honor of Prof. Shinji
C. N. Kona et al.
Special Topic
Synthesis
Peri-Selective Direct Acylmethylation and Amidation of Naphtha-
lene Derivatives Using Iridium and Rhodium Catalysts
Chandrababu Naidu Kona
Rikuto Oku
O
O
O
O
O
S
Me
R
SMe
H
SMe
R
NH SMe
O
O
Me
Yuji Nishii*
R
N
R
Masahiro Miura*
0
0
0
0
-
0
0
0
1
-
8
2
8
8
-
6
4
3
9
cat. Cp*Ir
cat. Cp*Rh
R
R
R
C–H acylmethylation
C–H amidation
Department of Applied Chemistry, Graduate School of Engineering,
Osaka University, Suita, Osaka 565-0871, Japan
miura@chem.eng.osaka-u.ac.jp
21 examples
up to 97% yield
11 examples
up to 88% yield
y_nishii@chem.eng.osaka-u.ac.jp
Dedicated to Professor Shinji Murai for his great contribution to the
chemistry of catalytic C–H bond activation.
Published as part of the Special Topic
Bond Activation – in Honor of Prof. Shinji Murai
Corresponding Authors
Received: 17.03.2021
Accepted after revision: 31.03.2021
Published online: 31.03.2021
onium ylides have been established as alternative carbene
sources for the chelation-assisted C–H activation strategy
using group 9 metal complexes.5,6 As demonstrated in pio-
neering works by Aïssa5a and Li5b in 2017, the ylide reagents
have successfully been applied to the direct acylmethyla-
tion under mild reaction conditions, releasing DMSO as the
sole by-product. Meanwhile, transition metal nitrenoids
have also been key active species for direct C–H amination
(amidation) reactions.7 Azides and iminoiodinanes have
been used as nitrene precursors in an early stage of this
strategy. Because of the intrinsic instability and the han-
dling difficulty of these reagents, new nitrene precursors
have become increasingly popular as user-friendly alterna-
tives for the amination over the last several years. In partic-
ular, dioxazolone and anthranil derivatives are now recog-
nized as practically valuable nitrene transfer agents in vir-
tue of elegant works by Chang8 and Li.9
Recently, our group have been interested in the use of
thioether directing groups for the catalytic C–H activation
strategy.10,11 This reaction system exhibited unique site-se-
lectivity as compared to common carbonyl-based and sp2-
nitrogen directing groups, thereby achieving peri-selective
direct functionalization12 over the ortho-positions of naph-
thalene derivatives.13 Furthermore, C4- and C7-selective C–
H functionalization of indoles have also been established
based on this concept. Another notable feature of the sulfur
directing group is its ease of removal and transformation
into other functionalities after the catalysis. Upon our con-
tinuous interest in this research area, we herein report an
Ir-catalyzed acylmethylation and a Rh-catalyzed amida-
tion14 of naphthalenes derivatives (Scheme 1).
DOI: 10.1055/a-1472-1059; Art ID: ss-2021-f0150-st
Abstract An iridium-catalyzed acylmethylation and a rhodium-cata-
lyzed amidation of naphthalene derivatives are reported, adopting sulf-
oxonium ylides and dioxazolones as carbene and nitrene transfer
agents, respectively. The use of SMe group as a directing group was key
to ensure the peri-selective functionalization, and it can be easily re-
moved or diversely transformed to other synthetically useful functional-
ities after the catalysis.
Key words C–H Activation, iridium, rhodium, alkylation, amidation
Polycyclic aromatic hydrocarbons as well as het-
eroarenes have attracted significant attention from the syn-
thetic community during the past decades because of their
unique optical and electrochemical properties.1 In particu-
lar, naphthalene derivatives have been of key motifs in vari-
ous binaphthyl-based chiral functional molecules and in
numerous bioactive compounds.2 Owing to their potential
applications, strategic synthesis of functionalized naphtha-
lenes has attracted significant attention among the syn-
thetic community. In order to achieve site-selective func-
tionalization of the aromatic core, transition-metal-cata-
lyzed direct C–H bond functionalization has emerged as an
effective tool and, particularly, chelation-assisted reactions
are among the most powerful methods to introduce func-
tionalities at specific positions.3
Insertion reactions of metal-carbenoid species have
widely been utilized for the construction of C–C and C–het-
eroatom bonds.4 -Diazo carbonyl compounds, hydrazones,
and triazole derivatives have functioned as carbene precur-
sors in this transformation; however, the use of these di-
azo-based reagents suffers from a potential safety risk of
the vigorous release of nitrogen gas under the reaction con-
ditions as well as upon storage. To address this issue, sulfox-
At the outset, we conducted an optimization study for
the model reaction of 1-(methylthio)naphthalene (1a) (0.2
mmol) with 2.0 equivalents of a sulfoxonium ylide 2a (Table 1).
Under the standard reaction conditions adopting [Cp*IrCl2]2
(2.5 mol%) as catalyst and AcOH (2.0 equiv) in HFIP (hexa-
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–K
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
C. N. Kona et al.
Special Topic
Synthesis
Table 1 Optimization Study for the Acylmethylation of 1a with 2a
(a) Iridium-catalyzed direct acylmethylation
SMe
O
O
H
R
R
SMe
O
O
O
cat. Cp*Ir
+
S
Me
Me
H
SMe
[Cp*IrCl2]2 (2.5 mol%)
AcOH (2.0 equiv.)
R
Ph
SMe
O
O
S
Me
Me
+
Ph
(b) Rhodium-catalyzed direct amidation
SMe
HFIP, 100 °C, 36 h
H
O
NH SMe
1a (0.2 mmol)
2a (0.4 mmol)
3aa
cat. Cp*Rh
O
+
O
N
Deviation from standard conditionsa
Yield (%)b of 3aa
R
Entry
Scheme 1 Schematic representation of the sulfur-directed peri-selec-
tive C–H functionalization of naphthalenes
1
2
–
85
without [Cp*IrCl2]2
[Cp*RhCl2]2 as catalyst
without AcOH
n.d.
trace
n.d.
trace
n.d.
10
3
fluoro-2-propanol) solvent, the target peri-functionalized
naphthalene 3aa was isolated in 85% yield (Table 1, entry 1).
The product was not detected in the absence of the catalyst,
and an analogous rhodium complex [Cp*RhCl2]2 was not ef-
fective (entries 2 and 3). AcOH was found to be essential to
the reaction (entry 4), whereas the use of PivOH in place of
AcOH resulted in the recovery of 1a (entry 5). The product
was not obtained in the presence of NaOAc (entry 6).10e The
addition of AgSbF6 (10 mol%) significantly decreased the
product yield (entry 7). Slightly lower yield was obtained
when the amount of 2a was reduced to 1.5 equivalents (en-
try 8). Other solvents such as DCE, THF, and TFE (trifluo-
roethanol) were totally ineffective (entries 9–11). This reac-
tion could be conducted in 1.0 mmol scale to give 3aa in
84% yield (entry 12).
4
5
PivOH instead of AcOH
with AcOH and NaOAc (3.0 equiv. each)
with AgSbF6 (10 mol%)
1.5 equiv. of 2a
6
7
8
72
9
DCE as solvent
n.d.
n.d.
n.d.
84
10
11
12
THF as solvent
TFE as solvent
1.0 mmol scalec
a Standard conditions: 1a (0.2 mmol), 2a (0.4 mmol), [Cp*IrCl2]2 (2.5
mol%), AcOH (0.4 mmol), HFIP (1.0 mL), 100 °C, 36 h.
b Isolated yield. n.d.: Not detected.
c 1a (1.0 mmol), 2a (2.0 mmol), [Cp*IrCl2]2 (2.5 mol%), AcOH (2.0 mmol),
HFIP (5.0 mL), 100 °C, 36 h.
With the optimized conditions in hand, we examined
the direct acylmethylation for a series of aromatic com-
pounds 1 adopting 2a as a representative carbene precursor
(Scheme 2). Bromo substituent of 1b was tolerated to pro-
vide a 1,4,8-trisubstituted naphthalene 3ba in 84% yield.
The present reaction system was also applicable to anthra-
cene 1c, phenanthrene 1d, and pyrene 1e analogues, giving
the corresponding coupling products 3ca (49%), 3da (82%),
and 3ea (73%), respectively. The connectivity of 3ea was un-
ambiguously determined by the X-ray crystallographic
analysis. Interestingly, this protocol tends to trigger mono
C–H functionalization even in the presence of two SMe di-
recting groups within the substrate. No double C–H activa-
tion was observed for the reaction of 1f and 1g, producing
3fa and 3ga in moderate yields.
Next, we evaluated the scope of sulfoxonium ylides
(Scheme 3). Various ylides bearing aromatic 2b–j, aliphatic
2k–n, and alkenyl 2o groups were synthesized to test the
reaction with 1a under the optimal conditions. Functional
groups such as chloro 2b,d,f, bromo 2c,e,g, ester 2h, and
alkoxy 2i groups were all compatible to deliver the corre-
sponding coupling products in high to excellent yields. The
substitution position at the benzene ring did not exert
much effect on the reactivity. 2-Naphthyl ylide 2j was also
highly productive. Although acetyl ylide 2k somewhat de-
O
H
SMe
[Cp*IrCl2]2 (2.5 mol%)
AcOH (2.0 equiv.)
Ph
SMe
O
O
S
Me
Me
+
Ph
HFIP, 100 °C, 36 h
1 (0.2 mmol)
2a (0.4 mmol)
3
O
O
O
Ph
SMe
Ph
SMe
Ph
SMe
3ba, 84%
3ca, 49%
3da, 82%
Br
O
O
O
Ph
SMe
Ph
SMe
SMe
Ph
SMe
3ea, 73%
3ga, 32%
SMe
3fa, 46%
Scheme 2 Scope of aromatic compounds
creases the yield, sulfoxonium ylides with secondary alkyl
2l,m and tertiary alkyl 2n groups reacted smoothly. An
enone moiety could be installed directly onto the aromatic
core adopting the alkenyl ylide 2o.
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–K

C
C. N. Kona et al.
Special Topic
Synthesis
pyrene 3ea variants into the polycyclic chromene deriva-
tives (Scheme 5). The structure of 3ea-1 was confirmed by
the X-ray crystallography. These compounds were consid-
erably emissive to exhibit yellow-green fluorescence under
UV irradiation with quantum efficiency of 0.22 for 3da-1
and 0.24 for 3ea-1, respectively (for details, see the Sup-
porting Information).
O
H
SMe
[Cp*IrCl2]2 (2.5 mol%)
AcOH (2.0 equiv.)
R
SMe
O
O
S
Me
Me
+
R
HFIP, 100 °C, 36 h
1a (0.2 mmol)
2 (0.4 mmol)
3
R
O
O
R = Cl
(3ab) 72%
R = Cl
SMe (3ad) 76%
R
SMe
O
Ph
R = Br
R = Br
(3ac) 70%
(3ae) 74%
Ph
SMe
O
1. MeOTf, DCE
60 °C, 12 h
O
O
O
R = Cl (3af) 97%
2. Cs2CO3, DMF
rt, 12 h
SMe
SMe
SMe
R = Br (3ag) 91%
R = CO2Me (3ah) 90%
R = OMe (3ai) 79%
3da
R
3da-1, 88%
3aj, 82%
O
Ph
O
O
O
Ph
SMe
Me
1. MeOTf, DCE
60 °C, 12 h
Me
SMe
SMe
Me
2. Cs2CO3, DMF
rt, 12 h
3ak, 32%
3al, 94%
3am, 86%
O
O
3ea
3ea-1, 90%
Me
Me
SMe
Ph
SMe
Scheme 5 Synthesis of polycyclic chromene derivatives
Me
3an, 70%
3ao, 31%
Some additional examples of derivatization are show-
cased in Scheme 6. The directing group was oxidized to the
sulfoxide 3aa-4 in 95% yield by utilizing H2O2/Tf2O system.
Addition of a Grignard reagent to the installed carbonyl
moiety proceeded smoothly to give the tertiary alcohol
3aa-5 in 91% yield. Such an orthogonal reactivity would be
potentially beneficial to the synthesis of unsymmetrically
substituted naphthalene derivatives. The palladium-cata-
lyzed coupling of 3ba with 1-naphthylboronic acid gave a
Scheme 3 Scope of sulfoxonium ylides
Recently, ease of removal and conversion into other
functional groups of the directing group has been utmost
important in transition metal catalysis (Scheme 4).15 It is
thus notable that the SMe directing group of 3aa was clean-
ly removed upon treatment with Raney Ni to afford 3aa-1
in 95% yield. Alternatively, a one-pot methylation and Pd-
catalyzed borylation16 was utilized to synthesize the corre-
sponding boronic ester 3aa-2. During the study, we found
that the sulfonium intermediate underwent intramolecular
O
Me
HO
Ph
O
Me
Ph
S
SMe
H2O2, Tf2O
MeMgBr
cyclization under basic conditions to form
a ben-
3aa
zo[de]chromene 3aa-3 in 92% yield, unexpectedly.17
EtOH
THF, rt, 4 h
0 °C to rt, 2 h
This base-mediated cyclization was considerably gener-
3aa-4, 95%
3aa-5, 91%
al and successfully converted the phenanthrene 3da and
O
O
Ph
SMe
Ph
SMe
B(OH)2
O
Pd(OAc)2, PPh3
K2CO3
Ph
Ph
H
+
Raney Ni
3aa-1
95%
1,4-dioxane
80 °C, 12 h
EtOH
reflux, 5 h
Br
3ba
O
O
3ba-1, 84%
Ph
SMe
1. MeOTf, DCE
60 °C, 12 h
Bpin
O
O
3aa-2
41%
2. Pd(OAc)2, XPhos
B2pin2, K3PO4
60 °C, 5 h
Ph
SMe
Ph
SMe
SMe
[Cp*Rh(MeCN)3][SbF6]2
Cu(OAc)2·H2O
3aa
+
CO2nBu
tAmOH, 80 °C, 6 h
Ph
1. MeOTf, DCE
60 °C, 12 h
SMe
O
3aa-3
92%
3fa
CO2nBu
3fa-1, 76%
2. Cs2CO3, DMF
rt, 12 h
Scheme 4 Removal and transformation of the sulfur directing group
Scheme 6 Derivatization of the coupling products
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–K

D
C. N. Kona et al.
Special Topic
Synthesis
binaphthyl compound 3ba-1. Since the reaction of 2f pref-
erentially produced the mono-functionalized product 3fa,
the subsequent C–H alkenylation with butyl acrylate under
rhodium catalysis was feasible to afford the doubly func-
tionalized product 3fa-1 in 76% yield.
O
O
Ph
NH SMe
Ph
NH
H
Raney Ni
5aa-1
53%
EtOH, reflux, 8 h
5aa
To our delight, the sulfur-directed peri-selective C–H ac-
tivation strategy was also applicable to a C–N bond forming
reaction through nitrene insertion. According to the semi-
nal work by Chang et al., dioxazolone derivatives 4 were ad-
opted as the nitrene source herein (Scheme 7). Under the
optimized reaction conditions using 4a (2.0 equiv) and
[Cp*Rh(MeCN)3][SbF6]2 (5.0 mol%) catalyst in HFIP solvent,
1a was converted to the target compound 5aa in 72% isolat-
ed yield. In a similar manner, phenanthrene 1d, pyrene 1e,
and 2-methylnaphthalene 1h analogues afforded the corre-
sponding products. We then examined a series of amidating
reagents. 3-Aryldioxazolones with bromo 4b, chloro 4c, and
methoxy 4d groups as well as aliphatic dioxazolones 4e–g
were successfully utilized to the catalysis, giving 5ab–ag in
moderate to high yields. In addition, a cinnamyl amide 5ah
was obtained in 34% yield as a single isomer. As similar to
the acylmethylation, the sulfur directing group of 5aa was
readily removed upon treatment with Raney Ni (Scheme 8).
Scheme 8 Directing group removal of 5aa
group. The use of -carbonyl sulfoxonium ylides and oxazo-
lones was a key factor in achieving the direct functionaliza-
tion of naphthalene derivatives as well as related higher ar-
omatic hydrocarbons. An interesting feature is that the sul-
fur directing group can be easily removed or transformed
after the catalysis. Additionally, the carbene insertion reac-
tion was utilized to the construction of densely fused
chromene derivatives via the base-mediated cyclization.
All manipulations were performed under N2 using standard Schlenk
techniques, unless otherwise noted. DMF and 1,4-dioxane were dried
and deoxygenated by a Glass Counter Solvent Dispending System
(Nikko Hansen & Co., Ltd.). Dichloroethane (DCE) and tert-AmOH
were distilled from CaH2. THF and EtOH were purchased as dehydrat-
ed solvent and used as received. Aryl sulfides 1,10a,c sulfoxonium
ylides5,18 and amidating reagents 4 were prepared according to the lit-
erature procedure.8,19
O
H
SMe
[Cp*Rh(MeCN)3][SbF6]2
(5.0 mol%)
R
NH SMe
NMR spectra were recorded on Bruker Avance III 400 spectrometer
operating at 400 MHz (1H NMR) and at 100 MHz (13C NMR) in 5 mm
NMR tubes. 1H NMR chemical shifts were reported in ppm relative to
the resonance of TMS ( = 0.00) or the residual solvent signals at  =
7.26 for CDCl3. 13C NMR chemical shifts were reported in ppm relative
to the residual solvent signals at  = 77.2 for CDCl3. High-resolution
mass spectra (HRMS) were recorded by APCI-TOF. Preparative gel per-
meation chromatography (GPC) was conducted with Showa Denko H-
2001/H-2002 column. Absorption and fluorescence spectra were re-
corded on JASCO V-750 and JASCO FP-8500 spectrometers. Quantum
efficiency was determined using an integration sphere system. Single
crystals of 3ea and 3ea-1 suitable for the analysis were obtained by
slow evaporation from CHCl3 solutions.20 The structures were refined
by full-matrix least-squares method using SHELXL-2016/6.21 Hydro-
gen atoms were included in the refinement on calculated positions
riding on their carrier atoms.
O
O
N
O
+
HFIP, 100 °C, 16 h
R
1 (0.2 mmol)
4 (0.4 mmol)
5
O
O
O
Ph
NH SMe
Ph
NH SMe
Ph
NH SMe
5aa, 72%
5ea, 23%
5da, 65% (40 h)
O
O
O
O
Ph
NH SMe
Cl
NH SMe
Me
NH SMe
Br
5ha, 59%
5ab, 55%
5ac, 88%
O
O
Iridium-Catalyzed Direct Acylmethylation of Naphthalene Deriva-
tives; General Procedure (Schemes 2 and 3)
MeO
Ph
NH SMe
Me
NH SMe
NH SMe
MeO
5ad, 60%
To an oven-dried screw-top tube were added aryl sulfide 1 (0.2 mmol,
1.0 equiv.), sulfoxonium ylide 2 (0.4 mmol, 2.0 equiv.), [Cp*IrCl2]2 (4.0
mg, 2.5 mol%), AcOH (23 L, 0.4 mmol, 2.0 equiv.), and HFIP (1.0 mL).
The mixture was heated for 36 h at 100 °C under N2 in an oil bath.
After cooling to rt, the resulting mixture was filtered through a pad of
silica gel eluting with CHCl3. Volatiles were removed under reduced
pressure, and the crude material was purified by silica gel column
chromatography.
5ae, 53%
5af, 79%
O
O
NH SMe
Ph
NH SMe
5ag, 83%
5ah, 34%
Scheme 7 Scope of direct amidation
2-[8-(Methylthio)naphthalen-1-yl]-1-phenylethan-1-one (3aa)
In summary, we have developed peri-selective Ir-cata-
lyzed C–H carbene insertion and Rh-catalyzed C–H nitrene
insertion reactions with the aid of thioether directing
White solid; yield: 50 mg (85%); Rf = 0.4 (hexane/EtOAc 4:1); mp 127–
129 °C.
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–K

E
C. N. Kona et al.
Special Topic
Synthesis
1H NMR (400 MHz, CDCl3):  = 8.11–8.13 (m, 2 H), 7.81 (dd, J = 8.2, 1.3
Hz, 1 H), 7.75 (dd, J = 8.1, 1.2 Hz, 1 H), 7.56–7.62 (m, 1 H), 7.49–7.54
(m, 3 H), 7.43 (dd, J = 8.1, 7.1 Hz, 1 H), 7.38 (dd, J = 8.0, 7.4 Hz, 1 H),
7.30 (dd, J = 7.0, 1.3 Hz, 1 H), 5.23 (s, 2 H), 2.30 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 196.3, 137.4, 135.9, 135.0, 132.7,
132.3, 132.3, 131.9, 129.9, 129.5, 128.6, 128.6, 128.2, 125.5, 125.2,
48.5, 20.9.
HRMS (APCI): m/z [M + H]+ calcd for C25H19OS: 367.1151; found:
367.1155.
2-[5,8-Bis(methylthio)naphthalen-1-yl]-1-phenylethan-1-one
(3fa)
Orange solid; yield: 31 mg (46%); Rf = 0.4 (hexane/EtOAc 4:1); mp
121–123 °C.
HRMS (APCI): m/z [M + H]+ calcd for C19H17OS: 293.0995; found:
293.0961.
1H NMR (400 MHz, CDCl3):  = 8.38 (dd, J = 8.6, 1.2 Hz, 1 H), 8.10–8.12
(m, 2 H), 7.57–7.62 (m, 1 H), 7.48–7.53 (m, 4 H), 7.32–7.35 (m, 2 H),
5.22 (s, 2 H), 2.56 (s, 3 H), 2.26 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 16.5, 21.4, 48.6, 123.5, 125.3, 125.7,
128.1, 128.5, 130.5, 132.4, 132.4, 132.6, 132.7, 133.6, 136.3, 137.3,
196.0.
2-[5-Bromo-8-(methylthio)naphthalen-1-yl]-1-phenylethan-1-
one (3ba)
Pale yellow solid; yield: 63 mg (84%); Rf = 0.5 (hexane/EtOAc 4:1); mp
134–136 °C.
HRMS (APCI): m/z [M + H]+ calcd for C20H19OS2: 339.0872; found:
1H NMR (400 MHz, CDCl3):  = 8.36 (dd, J = 8.6, 1.3 Hz, 1 H), 8.01–8.12
(m, 2 H), 7.71 (d, J = 8.0 Hz, 1 H), 7.59–7.63 (m, 1 H), 7.50–7.57 (m, 3
H), 7.35 (dd, J = 7.1, 1.1 Hz, 1 H), 7.31 (d, J = 8.1 Hz, 1 H), 5.22 (s, 2 H),
2.29 (s, 3 H).
339.0874.
2-[4,8-Bis(methylthio)naphthalen-1-yl]-1-phenylethan-1-one
(3ga)
13C NMR (100 MHz, CDCl3):  = 195.9, 137.1, 135.6, 133.6, 133.4,
133.3, 132.8, 132.4, 129.5, 129.2, 128.6, 128.6, 128.1, 126.8, 122.8,
48.2. 20.7.
HRMS (APCI): m/z [M + H]+ calcd for C19H16BrOS: 371.0100; found:
371.0101.
Yellow solid; yield: 22 mg (32%); Rf = 0.4 (hexane/EtOAc 4:1); mp
128–130 °C.
1H NMR (400 MHz, CDCl3):  = 8.31 (dd, J = 8.5, 1.3 Hz, 1 H), 8.10–8.12
(m, 2 H), 7.55–7.62 (m, 2 H), 7.49–7.53 (m, 2 H), 7.44 (dd, J = 8.4, 7.4
Hz, 1 H), 7.37 (d, J = 7.6 Hz, 1 H), 7.24 (d, J = 7.6 Hz, 1 H), 5.18 (s, 2 H),
2.57 (s, 3 H), 2.29 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 196.2, 137.4, 136.6, 135.7, 133.7,
132.7, 132.6, 132.0, 130.4, 129.5, 128.6, 128.1, 125.4, 124.4, 123.6,
48.5, 21.0, 16.5.
HRMS (APCI): m/z [M + H]+ calcd for C20H19OS2: 339.0872; found:
339.0874.
2-[9-(Methylthio)anthracen-1-yl]-1-phenylethan-1-one (3ca)
Green gummy oil; yield: 34 mg (49%); Rf = 0.4 (hexane/EtOAc 4:1).
1H NMR (400 MHz, CDCl3):  = 8.89–8.91 (m, 1 H), 8.51 (s, 1 H), 8.17–
8.19 (m, 2 H), 7.98–8.01 (m, 2 H), 7.48–7.64 (m, 5 H), 7.43 (dd, J = 8.2,
6.8 Hz, 1 H), 7.37–7.39 (m, 1 H), 5.27 (s, 2 H), 2.00 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 195.4, 137.8, 135.0, 133.7, 133.6,
133.4, 132.6, 132.2, 131.5, 130.8, 130.2, 130.1, 128.8, 128.6, 128.0,
127.2, 127.1, 125.4, 124.5, 49.8, 22.8.
1-(2-Chlorophenyl)-2-[8-(methylthio)naphthalen-1-yl]ethan-1-
one (3ab)
HRMS (APCI): m/z [M + H]+ calcd for C23H19OS: 343.1151; found:
343.1155.
Pale yellow solid; yield: 47 mg ((72%): Rf = 0.4 (hexane/EtOAc 4:1); mp
132–134 °C.
1H NMR (400 MHz, CDCl3):  = 7.80–7.83 (m, 2 H), 7.74 (dd, J = 8.1, 1.8
Hz, 1 H), 7.51 (dd, J = 7.4, 1.3 Hz, 1 H), 7.43–7.49 (m, 2 H), 7.34–7.43
(m, 4 H), 5.25 (s, 2 H), 2.42 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 198.5, 138.7, 135.8, 134.9, 132.5,
132.0, 131.6, 131.5, 131.1, 130.8, 129.9, 129.6, 129.1, 128.4, 126.7,
125.5, 125.2, 52.2, 20.3.
2-[10-(Methylthio)phenanthren-1-yl]-1-phenylethan-1-one (3da)
Yellow solid; yield: 56 mg (82%); Rf = 0.4 (hexane/EtOAc 4:1); mp
150–152 °C.
1H NMR (400 MHz, CDCl3):  = 8.76–8.78 (m, 1 H), 8.64–8.66 (m, 1 H),
8.12–8.14 (m, 2 H), 7.76–7.78 (m, 1 H), 7.73 (s, 1 H), 7.57–7.65 (m, 4
H), 7.50–7.55 (m, 2 H), 7.42 (dd, J = 7.1, 1.1 Hz, 1 H), 5.26 (s, 2 H), 2.38
(s, 3 H).
HRMS (APCI): m/z [M + H]+ calcd for C19H16ClOS: 327.0605; found:
327.0611.
13C NMR (100 MHz, CDCl3):  = 196.3, 137.3, 133.6, 133.0, 132.7,
132.4, 131.3, 130.8, 129.9, 129.4, 128.6, 128.2, 127.3, 126.9, 126.6,
126.2, 123.1, 123.0, 48.6, 20.4.
1-(2-Bromophenyl)-2-[8-(methylthio)naphthalen-1-yl]ethan-1-
one (3ac)
HRMS (APCI): m/z [M + H]+ calcd for C23H19OS: 343.1151; found:
343.1160.
Yellow solid; yield: 52 mg (70%); Rf = 0.4 (hexane/EtOAc 4:1); mp
117–119 °C.
1H NMR (400 MHz, CDCl3):  = 7.81 (dd, J = 8.1, 1.4 Hz, 1 H), 7.73–7.78
(m, 2 H), 7.67 (dd, J = 8.0, 1.0 Hz, 1 H), 7.51 (dd, J = 7.4, 1.3 Hz, 1 H),
7.45 (dd, J = 8.0, 7.0 Hz, 1 H), 7.36–7.43 (m, 3 H), 7.29–7.33 (m, 1 H),
5.24 (s, 2 H), 2.49 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 199.3, 140.8, 135.8, 135.0, 134.0,
132.4, 132.1, 131.5, 130.9, 129.6, 129.4, 129.0, 128.4, 127.2, 125.5,
125.2, 119.6, 51.7, 20.4.
2-[3-(Methylthio)pyren-4-yl]-1-phenylethan-1-one (3ea)
Pale yellow solid; yield: 54 mg (73%); Rf = 0.5 (hexane/EtOAc 4:1); mp
181–183 °C.
1H NMR (400 MHz, CDCl3):  = 8.14–8.17 (m, 3 H), 8.03–8.09 (m, 4 H),
7.95–8.00 (m, 2 H), 7.87 (s, 1 H), 7.60–7.64 (m, 1 H), 7.52–7.56 (m, 2
H), 5.31 (s, 2 H), 2.36 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 195.7, 137.5, 133.7, 132.6, 132.5,
131.3, 131.0, 130.8, 130.7, 130.5, 128.6, 128.1, 127.6, 127.1, 126.9,
126.1, 125.6, 125.1, 124.5, 49.3, 21.9.
HRMS (APCI): m/z [M + H]+ calcd for C19H16BrOS: 371.0100; found:
371.0078.
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C. N. Kona et al.
Special Topic
Synthesis
1-(3-Chlorophenyl)-2-[8-(methylthio)naphthalen-1-yl]ethan-1-
one (3ad)
Methyl 4-{2-[8-(Methylthio)naphthalen-1-yl]acetyl}benzoate
(3ah)
Pale yellow solid; yield: 50 mg (76%); Rf = 0.4 (hexane/EtOAc 4:1); mp
Yellow solid; yield: 63 mg (90%); Rf = 0.3 (hexane/EtOAc 4:1); mp
146–148 °C.
123–125 °C.
1H NMR (400 MHz, CDCl3):  = 8.10 (d, J = 1.8 Hz, 1 H), 7.98–8.00 (m, 1
H), 7.83 (dd, J = 8.2, 1.3 Hz, 1 H), 7.76 (dd, J = 8.2, 1.2 Hz, 1 H), 7.56–
7.59 (m, 1 H), 7.53 (dd, J = 7.4, 1.3 Hz, 1 H), 7.37–7.47 (m, 3 H), 7.28
(dd, J = 7.0, 1.3 Hz, 1 H), 5.16 (s, 2 H), 2.30 (s, 3 H).
1H NMR (400 MHz, CDCl3):  = 8.14–8.19 (m, 4 H), 7.83 (dd, J = 8.2, 1.2
Hz, 1 H), 7.76 (dd, J = 8.1, 1.2 Hz, 1 H), 7.51 (dd, J = 7.4, 1.3 Hz, 1 H),
7.37–7.46 (m, 2 H), 7.30 (dd, J = 7.0, 1.3 Hz, 1 H), 5.20 (s, 2 H), 3.97 (s,
3 H), 2.27 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 194.7, 139.0, 135.8, 134.8, 134.7,
132.6, 132.4, 132.1, 131.2, 130.2, 129.9, 129.6, 128.7, 128.2, 126.2,
125.5, 125.2, 48.5, 21.0.
13C NMR (100 MHz, CDCl3):  = 195.4, 166.3, 140.7, 135.8, 134.6,
133.5, 132.4, 132.1, 131.3, 130.2, 129.8, 129.6, 128.7, 128.0, 125.5,
125.2, 52.4, 48.7, 20.9.
HRMS (APCI): m/z [M + H]+ calcd for C19H16ClOS: 327.0605; found:
HRMS (APCI): m/z [M + H]+ calcd for C21H19O3S: 351.1049; found:
327.0618.
351.1030.
1-(3-Bromophenyl)-2-[8-(methylthio)naphthalen-1-yl]ethan-1-
one (3ae)
1-(4-Methoxyphenyl)-2-[8-(methylthio)naphthalen-1-yl]ethan-1-
one (3ai)
Yellow solid; yield: 55 mg (74%); Rf = 0.4 (hexane/EtOAc 4:1); mp
White solid; yield: 51 mg (79%); Rf = 0.4 (hexane/EtOAc 4:1); mp 123–
148–150 °C.
125 °C.
1H NMR (400 MHz, CDCl3):  = 8.24 (t, J = 1.8 Hz, 1 H), 8.02–8.05 (m, 1
H), 7.83 (dd, J = 8.2, 1.3 Hz, 1 H), 7.76 (dd, J = 8.1, 1.2 Hz, 1 H), 7.71–
7.73 (m, 1 H), 7.52 (dd, J = 7.4, 1.3 Hz, 1 H), 7.37–7.46 (m, 3 H), 7.28
(dd, J = 7.0, 1.3 Hz, 1 H), 5.16 (s, 2 H), 2.30 (s, 3 H).
1H NMR (400 MHz, CDCl3):  = 8.08–8.11 (m, 2 H), 7.80 (d, J = 8.1 Hz, 1
H), 7.74 (d, J = 8.0 Hz, 1 H), 7.49 (d, J = 7.2 Hz, 1 H), 7.35–7.44 (m, 2 H),
7.28 (d, J = 7.0 Hz, 1 H), 6.96–7.00 (m, 2 H), 5.19 (s, 2 H), 3.89 (s, 3 H),
2.32 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 194.6, 139.2, 135.8, 135.5, 134.7,
132.4, 132.1, 131.2, 131.1, 130.2, 129.7, 128.8, 126.7, 125.5, 125.3,
122.9, 48.5, 21.0.
13C NMR (100 MHz, CDCl3):  = 195.1, 163.1, 135.8, 135.1, 132.3,
132.2, 132.1, 130.4, 130.3, 129.5, 129.3, 128.4, 125.4, 125.1, 113.7,
55.4, 48.1, 20.7.
HRMS (APCI): m/z [M + H]+ calcd for C19H16BrOS: 371.0100; found:
HRMS (APCI): m/z [M + H]+ calcd for C20H19O2S: 323.1100; found:
371.0083.
323.1111.
1-(4-Chlorophenyl)-2-[8-(methylthio)naphthalen-1-yl]ethan-1-
one (3af)
2-[8-(Methylthio)naphthalen-1-yl]-1-(naphthalen-2-yl)ethan-1-
one (3aj)
Yellow solid; yield: 64 mg (97%); Rf = 0.4 (hexane/EtOAc 4:1); mp
Yellow solid; yield: 56 mg (82%); Rf = 0.4 (hexane/EtOAc 5:1); mp
164–166 °C.
134–136 °C.
1H NMR (400 MHz, CDCl3):  = 8.04–8.07 (m, 2 H), 7.83 (dd, J = 8.2, 1.2
Hz, 1 H), 7.76 (dd, J = 8.1, 1.2 Hz, 1 H), 7.47–7.53 (m, 3 H), 7.37–7.46
(m, 2 H), 7.28 (dd, J = 7.0, 1.2 Hz, 1 H), 5.16 (s, 2 H), 2.30 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 194.9, 139.0, 135.8, 135.7, 134.7,
132.3, 132.1, 131.4, 129.9, 129.6, 129.5, 128.8, 128.7, 125.4, 125.2,
48.3, 20.8.
1H NMR (400 MHz, CDCl3):  = 8.69 (br s, 1 H), 8.20 (dd, J = 8.6, 1.8 Hz,
1 H), 8.04 (d, J = 8.0 Hz, 1 H), 7.92–7.97 (m, 2 H), 7.85 (dd, J = 8.2, 1.3
Hz, 1 H), 7.78 (dd, J = 8.1, 1.2 Hz, 1 H), 7.57–7.65 (m, 2 H), 7.52 (dd, J =
7.4, 1.3 Hz, 1 H), 7.47 (dd, J = 8.1, 7.0 Hz, 1 H), 7.38–7.42 (m, 1 H), 7.35
(dd, J = 7.0, 1.3 Hz, 1 H), 5.37 (s, 2 H), 2.30 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 196.1, 135.8, 135.4, 135.0, 134.7,
132.6, 132.4, 132.2, 131.9, 129.7, 129.5, 129.4, 128.5, 128.3, 128.1,
127.7, 126.6, 125.5, 125.2, 124.2, 48.5, 20.7.
HRMS (APCI): m/z [M + H]+ calcd for C19H16ClOS: 327.0605; found:
327.0627.
HRMS (APCI): m/z [M + H]+ calcd for C23H19OS: 343.1151; found:
343.1170.
1-(4-Bromophenyl)-2-[8-(methylthio)naphthalen-1-yl]ethan-1-
one (3ag)
1-[8-(Methylthio)naphthalen-1-yl]propan-2-one (3ak)
Yellow solid; yield: 68 mg (91%); Rf = 0.4 (hexane/EtOAc 4:1); mp
167–169 °C.
White semi-solid; yield: 15 mg (32%); Rf = 0.4 (20% hexane/EtOAc
4:1).
1H NMR (400 MHz, CDCl3):  = 7.96–7.99 (m, 2 H), 7.82 (dd, J = 8.2, 1.2
Hz, 1 H), 7.76 (dd, J = 8.1, 1.2 Hz, 1 H), 7.63–7.67 (m, 2 H), 7.51 (dd, J =
7.3, 1.3 Hz, 1 H), 7.37–7.46 (m, 2 H), 7.28 (dd, J = 7.0, 1.2 Hz, 1 H), 5.15
(s, 2 H), 2.29 (s, 3 H).
1H NMR (400 MHz, CDCl3):  = 7.78 (dd, J = 8.2, 1.3 Hz, 1 H), 7.72 (dd,
J = 8.1, 1.2 Hz, 1 H), 7.50 (dd, J = 7.4, 1.3 Hz, 1 H), 7.36–7.43 (m, 2 H),
7.22 (dd, J = 7.0, 1.3 Hz, 1 H), 4.61 (s, 2 H), 2.45 (s, 3 H), 2.31 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 195.0, 136.1, 135.8, 134.7, 132.3,
132.1, 131.8, 131.4, 130.0, 129.7, 129.6, 128.7, 127.7, 125.4, 125.2,
48.3, 20.8.
13C NMR (100 MHz, CDCl3):  = 205.6, 135.8, 134.9, 132.2, 131.9,
131.7, 129.5, 129.1, 128.4, 125.5, 125.2, 53.2, 29.7, 20.4.
HRMS (APCI): m/z [M + H]+ calcd for C14H15OS: 231.0838; found:
231.0831.
HRMS (APCI): m/z [M + H]+ calcd for C19H16BrOS: 371.0100; found:
371.0128.
3-Methyl-1-[8-(methylthio)naphthalen-1-yl]butan-2-one (3al)
Colorless semi-solid; yield: 49 mg (94%); Rf = 0.4 (hexane/EtOAc 4:1).
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–K

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C. N. Kona et al.
Special Topic
Synthesis
1H NMR (400 MHz, CDCl3):  = 7.77 (dd, J = 8.2, 1.3 Hz, 1 H), 7.71 (dd,
J = 8.1, 1.2 Hz, 1 H), 7.48 (dd, J = 7.4, 1.3 Hz, 1 H), 7.35–7.42 (m, 2 H),
7.21 (dd, J = 7.0, 1.3 Hz, 1 H), 4.71 (s, 2 H), 2.86–2.97 (m, 1 H), 2.46 (s,
3 H), 1.23 (s, 3 H), 1.21 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 211.3, 135.8, 135.0, 132.1, 132.1,
131.9, 129.3, 128.8, 128.3, 125.4, 125.1, 50.4, 40.3, 20.3, 18.7.
1H NMR (400 MHz, CDCl3):  = 8.08–8.10 (m, 2 H), 7.85–7.89 (m, 2 H),
7.80 (d, J = 8.2 Hz, 1 H), 7.57–7.61 (m, 1 H), 7.47–7.52 (m, 4 H), 7.43
(dd, J = 8.2, 7.0 Hz, 1 H), 7.35–7.37 (m, 1 H), 4.75 (s, 2 H).
13C NMR (100 MHz, CDCl3):  = 197.6, 136.7, 133.9, 133.3, 132.2,
131.3, 128.8, 128.7, 128.5, 128.0, 127.9, 126.3, 125.7, 125.5, 123.8,
43.1.
HRMS (APCI): m/z [M + H]+ calcd for C16H19OS: 259.1151; found:
HRMS (APCI): m/z [M + H]+ calcd for C18H15O: 247.1117; found:
259.1134.
247.1117.
1-Cyclohexyl-2-[8-(methylthio)naphthalen-1-yl]ethan-1-one
(3am)
Palladium-Catalyzed Borylation; 1-Phenyl-2-[8-(4,4,5,5-tetra-
methyl-1,3,2-dioxaborolan-2-yl)naphthalen-1-yl]ethan-1-one
(3aa-2) (Scheme 4)
Pale yellow solid; yield: 51 mg (86%); Rf = 0.4 (hexane/EtOAc 4:1); mp
53–55 °C.
To a Schlenk tube were added 3aa (30 mg, 0.10 mmol), 1,2-dichlo-
roethane (2.0 mL), and MeOTf (16 L, 0.14 mmol). The mixture was
stirred for 12 h at 60 °C. After the completion of the reaction as indi-
cated by TLC, all volatiles were removed under reduced pressure.
Then, bis(pinacolato)diboron (51 mg, 0.20 mmol), Pd(OAc)2 (1.1 mg,
0.005 mmol), XPhos (2.4 mg, 0.005 mmol), K3PO4 (26 mg, 0.12 mmol),
and THF (2.0 mL) were introduced into the tube and stirred for 5 h at
60 °C. Upon completion of the reaction, the mixture was cooled to rt
and filtered through a pad of silica gel. The filtrate was concentrated
and the residue was purified by silica gel chromatography to afford
3aa-2; pale yellow oil; yield: 12 mg (41%); Rf = 0.4 (hexane/EtOAc
1:1).
1H NMR (400 MHz, CDCl3):  = 7.77 (dd, J = 8.2, 1.2 Hz, 1 H), 7.71 (dd,
J = 8.1, 1.1 Hz, 1 H), 7.48 (dd, J = 7.4, 1.3 Hz, 1 H), 7.34–7.41 (m, 2 H),
7.19 (dd, J = 7.0, 1.3 Hz, 1 H), 4.70 (s, 2 H), 2.62–2.69 (m, 1 H), 2.45 (s,
3 H), 1.98–2.05 (m, 2 H), 1.80–1.86 (m, 2 H), 1.67–1.72 (m, 1 H), 1.43–
1.53 (m, 2 H), 1.22–1.37 (m, 3 H).
13C NMR (100 MHz, CDCl3):  = 210.5, 135.7, 135.0, 132.1, 132.0,
131.9, 129.2, 128.9, 128.3, 125.4, 125.1, 50.5, 50.3, 28.9, 25.9, 25.8,
20.3.
HRMS (APCI): m/z [M + H]+ calcd for C19H23OS: 299.1464; found:
299.1473.
1H NMR (400 MHz, CDCl3):  = 7.90–7.95 (m, 3 H), 7.85 (dd, J = 6.9, 1.4
Hz, 1 H), 7.74 (dd, J = 8.1, 0.7 Hz, 1 H), 7.46–7.52 (m, 2 H), 7.31–7.39
(m, 3 H), 7.21–7.23 (m, 1 H), 4.88 (s, 2 H), 1.31 (s, 12 H).
3,3-Dimethyl-1-[8-(methylthio)naphthalen-1-yl]butan-2-one
(3an)
Colorless semi-solid; yield: 39 mg (70%); Rf = 0.4 (hexane/EtOAc 4:1).
13C NMR (100 MHz, CDCl3):  = 198.3, 136.5, 134.4, 134.0, 133.1,
132.5, 131.6, 128.8, 128.6, 127.9, 125.3, 124.7, 84.3, 45.1, 24.7.
HRMS (APCI): m/z [M + H]+ calcd for C24H26BO3: 373.1970; found:
373.1975.
1H NMR (400 MHz, CDCl3):  = 7.76 (dd, J = 8.2, 1.3 Hz, 1 H), 7.71 (dd,
J = 8.1, 1.2 Hz, 1 H), 7.49 (dd, J = 7.4, 1.3 Hz, 1 H), 7.34–7.41 (m, 2 H),
7.15 (dd, J = 7.0, 1.3 Hz, 1 H), 4.84 (s, 2 H), 2.45 (s, 3 H), 1.33 (s, 9 H).
13C NMR (100 MHz, CDCl3):  = 212.8, 135.8, 135.0, 132.5, 132.4,
131.6, 129.2, 129.1, 128.4, 125.3, 125.0, 46.9, 44.0, 27.3, 20.3.
HRMS (APCI): m/z [M + H]+ calcd for C17H21OS: 273.1308; found:
Chromane Synthesis through Base-Mediated Cyclization; General
Procedure (Schemes 4 and 5)
273.1306.
To a Schlenk tube were added 3 (0.10 mmol), 1,2-dichloroethane (2.0
mL), and MeOTf (16 L, 0.14 mmol) and the mixture was stirred for
12 h at 60 °C. After the completion of the reaction as indicated by TLC,
all volatiles were removed under reduced pressure. The sulfonium
salt was dissolved in DMF (0.5 mL), and this solution was added to an-
other Schlenk tube charged with Cs2CO3 (49 mg, 0.15 mmol) and DMF
(1.0 mL). The mixture was stirred at rt for 12 h. The resulting mixture
was extracted with EtOAc, and the combined organic layers were
dried (Na2SO4), concentrated under reduced pressure. The residue
was purified by silica gel column chromatography.
(E)-1-[8-(Methylthio)naphthalen-1-yl]-4-phenylbut-3-en-2-one
(3ao)
Yellow solid; yield: 20 mg (31%); Rf = 0.3 (hexane/EtOAc 4:1); mp
144–146 °C.
1H NMR (400 MHz, CDCl3):  = 7.81 (dd, J = 8.2, 1.3 Hz, 1 H), 7.74 (dd,
J = 8.1, 1.2 Hz, 1 H), 7.69 (d, J = 16.1 Hz, 1 H), 7.55–7.60 (m, 2 H), 7.52
(dd, J = 7.4, 1.3 Hz, 1 H), 7.37–7.45 (m, 5 H), 7.29 (dd, J = 7.0, 1.3 Hz, 1
H), 6.95 (d, J = 16.1 Hz, 1 H), 4.88 (s, 2 H), 2.41 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 196.2, 141.8, 135.8, 135.0, 134.8,
132.3, 132.1, 131.7, 130.2, 129.5, 128.9, 128.5, 128.3, 126.1, 125.5,
125.2, 51.0, 20.7.
HRMS (APCI): m/z [M + H]+ calcd for C21H19OS: 319.1151; found:
319.1168.
2-Phenylbenzo[de]chromene (3aa-3)
Yellow solid; yield: 23 mg (92%); Rf = 0.4 (hexane/EtOAc 5:1); mp 81–
83 °C.
1H NMR (400 MHz, CDCl3):  = 7.76–7.79 (m, 2 H), 7.36–7.45 (m, 3 H),
7.33 (dd, J = 8.4, 0.8 Hz, 1 H), 7.26–7.30 (m, 1 H), 7.19–7.23 (m, 2 H),
6.85 (dd, J = 7.5, 1.1 Hz, 1 H), 6.77 (dd, J = 7.0, 0.7 Hz, 1 H), 6.50 (s, 1 H).
13C NMR (100 MHz, CDCl3):  = 153.0, 152.1, 134.8, 133.1, 130.0,
129.1, 128.5, 127.9, 127.5, 124.6, 123.5, 123.2, 119.4, 115.9, 107.1,
103.1.
Directing Group Removal under Reductive Conditions; 2-(Naph-
thalen-1-yl)-1-phenylethan-1-one (3aa-1)22 (Scheme 4)
To a solution of 3aa (30 mg, 0.10 mmol) in EtOH (5.0 mL) in a round-
bottomed flask was added Raney Ni [slurry in water (TCI), ca. 100 mg]
and refluxed for 5 h. Upon completion of the reaction, the mixture
was cooled to rt and filtered through a small pad of silica gel. The fil-
trate was concentrated in vacuo, and the residue was purified by silica
gel chromatography to afford 3aa-1; white solid; yield: 24 mg (95%);
Rf = 0.4 (hexane/EtOAc 4:1); mp 104–106 °C.
HRMS (APCI): m/z [M + H]+ calcd for C18H13O: 245.0961; found:
245.0945.
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C. N. Kona et al.
Special Topic
Synthesis
5-Phenyldibenzo[de,g]chromene (3da-1)
4.45 (d, J = 14.6 Hz, 1 H), 3.93 (d, J = 14.6 Hz, 1 H), 2.55 (s, 3 H), 3.13 (s,
1 H), 1.49 (s, 3 H).
Pale yellow solid; yield: 26 mg (88%); Rf = 0.6 (hexane/EtOAc 5:1); mp
13C NMR (100 MHz, CDCl3):  = 148.6, 135.8, 134.8, 134.0, 132.6,
132.4, 129.1, 128.1, 127.9, 126.6, 126.3, 125.0, 124.9, 124.6, 75.2, 49.1,
29.4, 18.6.
136–138 °C.
1H NMR (400 MHz, CDCl3):  = 8.42–8.44 (m, 1 H), 8.23 (d, J = 8.4 Hz, 1
H), 7.82–7.85 (m, 2 H), 7.71–7.74 (m, 1 H), 7.39–7.54 (m, 6 H), 7.13 (s,
1 H), 7.07 (d, J = 7.3 Hz, 1 H), 6.54 (s, 1 H).
HRMS (APCI): m/z [M – H2O + H]+ calcd for C20H19S: 291.1202; found:
13C NMR (100 MHz, CDCl3):  = 151.8, 150.8, 133.6, 133.0, 131.4,
130.2, 129.2, 128.5, 128.4, 127.3, 127.2, 126.0, 124.7, 124.1, 122.7,
122.3, 120.1, 119.4, 104.5, 102.0.
291.1202.
Suzuki–Miyaura Coupling Reaction of 3ba; 2-[4-(Methylthio)-
[1,1′-binaphthalen]-5-yl]-1-phenylethan-1-one (3ba-1) (Scheme
6)
HRMS (APCI): m/z [M + H]+ calcd for C22H15O: 295.1117; found:
295.1108.
To a Schlenk tube were added 3ba (37 mg, 0.10 mmol), 1-naphthylbo-
ronic acid (34 mg, 0.20 mmol), Pd(OAc)2 (1.1 mg, 0.005 mmol), PPh3
(2.6 mg, 0.005 mmol), K2CO3 (27 mg, 0.2 mmol), and 1,4-dioxane (2.0
mL), and the mixture was stirred for 8 h at 80 °C. After cooling to rt,
the mixture was filtered through a pad of silica gel. The filtrate was
concentrated and the residue was purified by silica gel chromatogra-
phy to give 3ba-1; white solid; yield: 37 mg (84%); Rf = 0.4 (hex-
ane/EtOAc 4:1); mp 145–147 °C.
1H NMR (400 MHz, CDCl3):  = 8.17–8.19 (m, 2 H), 7.94–7.97 (m, 2 H),
7.58–7.65 (m, 3 H), 7.53–7.57 (m, 2 H), 7.47–7.51 (m, 2 H), 7.39–7.44
(m, 3 H), 7.28–7.34 (m, 2 H), 7.23 (dd, J = 8.3, 7.0 Hz, 1 H), 5.35 (d, J =
18.4 Hz, 1 H), 5.26 (d, J = 18.4 Hz, 1 H), 2.41 (s, 3 H).
4-Phenylphenaleno[2,1,9-def]chromene (3ea-1)
Greenish yellow solid; yield: 27 mg (90%); Rf = 0.6 (hexane/EtOAc
5:1); mp 176–178 °C.
1H NMR (400 MHz, CDCl3):  = 7.94 (d, J = 8.5 Hz, 1 H), 7.84–7.87 (m, 2
H), 7.72–7.81 (m, 5 H), 7.41–7.51 (m, 4 H), 7.15 (s, 1 H), 6.66 (s, 1 H).
13C NMR (100 MHz, CDCl3):  = 152.4, 150.3, 133.8, 133.2, 132.3,
129.2, 128.6, 126.8, 126.5, 126.0, 125.9, 125.6, 125.1, 124.7, 122.2,
122.0, 118.4, 114.6, 112.3, 104.0.
HRMS (APCI): m/z [M + H]+ calcd for C24H15O: 319.1117; found:
319.1130.
13C NMR (100 MHz, CDCl3):  = 196.3, 138.8, 138.2, 137.4, 135.1,
134.8, 133.4, 132.8, 132.7, 132.4, 132.3, 131.9, 128.7, 128.6, 128.2,
128.1, 127.9, 127.8, 127.4, 126.6, 126.0, 125.8, 125.5, 125.4, 48.8, 20.7.
Oxidation of the SMe Group of 3aa; 2-[8-(Methylsulfinyl)naphtha-
len-1-yl]-1-phenylethan-1-one (3aa-4) (Scheme 6)
HRMS (APCI): m/z [M + H]+ calcd for C29H23OS: 419.1464; found:
419.1463.
To a round-bottomed flask were added 3aa (30 mg, 0.1 mmol) and
EtOH (5.0 mL). After cooling to 0 °C, Tf2O (9.0 L, 0.05 mmol) and 30%
H2O2 (23 mg, 0.2 mmol) were subsequently added to the vessel and
the mixture was stirred for 5 min at this temperature. Then the mix-
ture was allowed to warm to rt and stirred for another 2 h. The reac-
tion was quenched by adding H2O (5.0 mL) and extracted with EtOAc.
The combined organic layers were dried (Na2SO4), concentrated in
vacuo, and the residue was subjected to silica gel column chromatog-
raphy to give 3aa-4; white solid; yield: 30 mg (95%); Rf = 0.4 (hex-
ane/EtOAc 1:1); mp 188–190 °C.
1H NMR (400 MHz, CDCl3):  = 8.48 (dd, J = 7.4, 1.4 Hz, 1 H), 8.07–8.10
(m, 2 H), 8.04 (dd, J = 8.2, 1.4 Hz, 1 H), 7.91 (dd, J = 8.2, 1.1 Hz, 1 H),
7.66–7.70 (m, 1 H), 7.61–7.66 (m, 1 H), 7.49–7.55 (m, 3 H), 7.35–7.37
(m, 1 H), 5.19 (d, J = 18.6 Hz, 1 H), 4.70 (d, J = 18.6 Hz, 1 H), 2.52 (s, 3
H).
Rhodium-Catalyzed Direct Alkenylation of 3fa; Butyl (E)-3-[5,8-
Bis(methylthio)-4-(2-oxo-2-phenylethyl)naphthalen-1-yl]acry-
late (3fa-1) (Scheme 6)
To an oven dried screw-top tube were added 3fa (34 mg, 0.1 mmol,
1.0 equiv), butyl acrylate (29 L, 0.4 mmol, 2.0 equiv),
[Cp*Rh(MeCN)3][SbF6]2 (3.4 mg, 4.0 mol%), Cu(OAc)2·H2O (40 mg, 0.4
mmol, 2.0 equiv), and tert-AmOH (1.0 mL). The mixture was heated
for 6 h at 100 °C under N2 in an oil bath. After cooling to rt, the result-
ing mixture was filtered through a pad of silica gel eluting with CHCl3.
The filtrate was concentrated and the residue was subjected to silica
gel column chromatography; deep yellow solid; yield: 35 mg (76%);
Rf = 0.6 (hexane/EtOAc 5:1); mp 96–98 °C.
13C NMR (100 MHz, CDCl3):  = 197.1, 144.0, 136.3, 135.2, 133.5,
133.2, 132.9, 129.4, 129.3, 129.0, 128.9, 128.1, 126.0, 125.4, 123.7,
47.9, 45.5.
HRMS (APCI): m/z [M + H]+ calcd for C19H17O2S: 309.0944; found:
309.0929.
1H NMR (400 MHz, CDCl3):  = 8.80 (d, J = 15.4 Hz, 1 H), 8.08–8.10 (m,
2 H), 7.58–7.62 (m, 1 H), 7.49–7.53 (m, 3 H), 7.44–7.46 (m, 2 H), 7.26–
7.28 (m, 1 H), 6.21 (d, J = 15.4 Hz, 1 H), 5.17 (s, 2 H), 4.24 (t, J = 6.6 Hz,
2 H), 2.39 (s, 3 H), 2.26 (s, 3 H), 1.68–1.75 (m, 2 H), 1.42–1.51 (m, 2 H),
0.98 (t, J = 7.4 Hz, 3 H).
13C NMR (100 MHz, CDCl3):  = 195.6, 167.3, 148.2, 137.2, 135.9,
134.9, 134.1, 134.0, 132.8, 132.1, 129.9, 128.6, 128.3, 128.1, 128.0,
116.2, 64.3, 48.8, 30.8, 21.1, 20.2, 19.2, 13.8.
Grignard Reaction of 3aa; 1-[8-(Methylthio)naphthalen-1-yl]-2-
phenylpropan-2-ol (3aa-5) (Scheme 6)
HRMS (APCI): m/z [M + H]+ calcd for C27H29O3S2: 465.1553; found:
465.1543.
To an ice-cold solution of solution of 3aa (30 mg, 0.1 mmol) in THF
(5.0 mL) was added 3.0 mol/L MeMgBr in THF (45 L, 0.13 mmol), and
the mixture was stirred at rt for 4 h. The reaction was quenched by
adding aq NH4Cl and extracted with EtOAc. The combined organic
layers were dried (Na2SO4), concentrated in vacuo, and the residue
was subjected to silica gel column chromatography to give 3aa-5; yel-
low semi-solid; yield: 29 mg (91%); Rf = 0.4 (hexane/EtOAc 4:1).
1H NMR (400 MHz, CDCl3):  = 7.73 (dd, J = 8.1, 1.3 Hz, 1 H), 7.68 (dd,
J = 8.0, 1.3 Hz, 1 H), 7.44–7.47 (m, 2 H), 7.42 (dd, J = 7.4, 1.4 Hz, 1 H),
7.27–7.37 (m, 4 H), 7.21–7.26 (m, 1 H), 7.06 (dd, J = 7.2, 1.4 Hz, 1 H),
Rhodium-Catalyzed Direct Amidation of Naphthalene Derivatives;
General Procedure (Scheme 7)
To an oven dried screw-top tube were added aryl sulfide 1 (0.2 mmol,
1.0 equiv), amidating reagent
4
(0.4 mmol, 2.0 equiv),
[Cp*Rh(MeCN)3][SbF6]2 (8.4 mg, 5.0 mol%), and HFIP (1.0 mL). The
mixture was heated for 16 h at 100 °C under N2 in an oil bath. After
cooling to rt, the resulting mixture was filtered through a pad of silica
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–K

I
C. N. Kona et al.
Special Topic
Synthesis
gel eluting with CHCl3. Volatiles were removed under reduced pres-
sure, and the crude material was purified by silica gel column chro-
matography.
1H NMR (400 MHz, CDCl3 + CS2):  = 11.81 (s, 1 H), 8.55 (d, J = 7.6 Hz, 1
H), 7.96 (d, J = 8.6 Hz, 2 H), 7.82–7.85 (m, 1 H), 7.65–7.73 (m, 4 H),
7.55 (t, J = 8.0 Hz, 1 H), 7.39 (t, J = 7.7 Hz, 1 H), 2.36 (s, 3 H).
13C NMR (100 MHz, CDCl3 and CS2):  = 164.7, 136.2, 135.1, 134.3,
134.2, 132.0, 130.7, 129.6, 129.0, 126.6, 126.3, 126.3, 125.4, 125.2,
121.4, 21.5.
N-[8-(Methylthio)naphthalen-1-yl]benzamide (5aa)14
Yellow solid; yield: 42 mg (72%); Rf = 0.3 (hexane/EtOAc 5:1); mp
HRMS (APCI): m/z [M + H]+ calcd for C18H15BrNOS: 372.0052; found:
121–123 °C.
1H NMR (400 MHz, CDCl3):  = 11.77 (s, 1 H), 8.58 (d, J = 7.7 Hz, 1 H),
8.09–8.11 (m, 2 H), 7.83 (d, J = 8.2 Hz, 1 H), 7.71 (t, J = 7.3 Hz, 2 H),
7.51–7.60 (m, 4 H), 7.38 (t, J = 8.0 Hz, 1 H), 2.36 (s, 3 H).
372.0037.
3-Chloro-N-[8-(methylthio)naphthalen-1-yl]benzamide (5ac)
13C NMR (100 MHz, CDCl3):  = 165.7, 136.2, 135.4, 134.9, 134.4,
131.8, 130.6, 129.8, 128.8, 127.4, 126.3, 126.2, 125.3, 121.5, 21.5 (1
peak overlapped).
HRMS (APCI): m/z [M + H]+ calcd for C18H16NOS: 294.0947; found:
294.0952.
White solid; yield: 58 mg (88%); Rf = 0.4 (hexane/EtOAc 5:1); mp 138–
140 °C.
1H NMR (400 MHz, CDCl3):  = 11.8 (s, 1 H), 8.54 (d, J = 7.6 Hz, 1 H),
8.09 (t, J = 1.8 Hz, 1 H), 7.95 (d, J = 7.8 Hz, 1 H), 7.83 (dd, J = 8.2, 1.1 Hz,
1 H), 7.68–7.72 (m, 2 H), 7.52–7.56 (m, 2 H), 7.46 (t, J = 7.8 Hz, 1 H),
7.38 (t, J = 7.7 Hz, 1 H), 2.37 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 164.4, 137.3, 136.1, 135.0, 134.9,
134.1, 131.8, 130.6, 130.0, 129.7, 127.9, 126.4, 126.3, 125.4, 125.3,
125.2, 121.5, 21.5.
N-[10-(Methylthio)phenanthren-1-yl]benzamide (5da)
White solid; yield: 45 mg (65%); Rf = 0.2 (hexane/EtOAc 5:1); mp 168–
170 °C.
HRMS (APCI): m/z [M + H]+ calcd for C18H15ClNOS: 328.0557; found:
328.0556.
1H NMR (400 MHz, CDCl3):  = 11.28 (s, 1 H), 8.61 (t, J = 8.0 Hz, 2 H),
8.48 (d, J = 7.8 Hz, 1 H), 8.11 (d, J = 6.8 Hz, 2 H), 7.91 (s, 1 H), 7.78 (dd,
J = 7.8, 1.5 Hz, 1 H), 7.51–7.73 (m, 6 H), 2.37 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 165.8, 135.3, 135.0, 134.1, 133.0,
131.8, 131.0, 130.3, 128.8, 127.8, 127.6, 127.5, 127.3, 127.0, 123.4,
123.2, 123.1, 120.5, 20.5 (1 peak overlapped).
3,4-Dimethoxy-N-[8-(methylthio)naphthalen-1-yl]benzamide
(5ad)
White solid; yield: 42 mg (60%); Rf = 0.4 (hexane/EtOAc 1:1); mp 161–
163 °C.
HRMS (APCI): m/z [M + H]+ calcd for C22H18NOS: 344.1104; found:
344.1094.
1H NMR (400 MHz, CDCl3):  = 11.71 (s, 1 H), 8.57 (d, J = 7.7 Hz, 1 H),
7.83 (d, J = 8.2 Hz, 1 H), 7.67–7.72 (m, 4 H), 7.53–7.57 (m, 1 H), 7.35–
7.39 (m, 1 H), 6.97 (dd, J = 9.0, 1.4 Hz, 1 H), 3.99 (d, J = 0.9 Hz, 3 H),
3.97 (d, J = 1.2 Hz, 3 H), 2.34 (d, J = 1.3 Hz, 3 H).
13C NMR (100 MHz, CDCl3):  = 165.2, 152.0, 149.0, 136.2, 134.9,
134.5, 130.6, 129.7, 128.0, 126.3, 125.9, 125.2, 125.2, 121.3, 120.2,
110.7, 110.5, 56.1, 21.5 (1 peak overlapped).
N-[3-(Methylthio)pyren-4-yl]benzamide (5ea)14
Yellow solid; yield: 17 mg (23%); Rf = 0.3 (hexane/EtOAc 5:1); mp
157–159 °C.
1H NMR (400 MHz, CDCl3):  = 12.16 (s, 1 H), 9.30 (s, 1 H), 8.13–8.24
(m, 5 H), 8.07–8.09 (m, 2 H), 7.99–8.03 (m, 2 H), 7.55–7.61 (m, 3 H),
2.46 (s, 3 H).
HRMS (APCI): m/z [M + H]+ calcd for C20H20NO3S: 354.1158; found:
354.1166.
13C NMR (100 MHz, CDCl3):  = 166.1, 135.6, 134.4, 132.8, 132.1,
131.8, 131.0, 130.8, 128.8, 128.4, 127.5, 127.2, 127.1, 127.1, 126.7,
125.7, 125.6, 125.1, 122.3, 121.2, 22.0 (1 peak overlapped).
N-[8-(Methylthio)naphthalen-1-yl]acetamide (5ae)
White solid; yield: 24 mg (53%); Rf = 0.3 (hexane/EtOAc 1:1); mp 134–
136 °C.
1H NMR (400 MHz, CDCl3):  = 10.77 (s, 1 H), 8.29 (d, J = 7.6 Hz, 1 H),
7.76 (d, J = 8.1 Hz, 1 H), 7.63 (t, J = 8.0 Hz, 2 H), 7.48 (t, J = 7.8 Hz, 1 H),
7.35 (t, J = 7.6 Hz, 1 H), 2.50 (s, 3 H), 2.30 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 168.4, 136.0, 134.0, 133.1, 130.6,
129.9, 126.2, 126.1, 125.3, 125.0, 121.6, 25.2, 20.9.
HRMS (APCI): m/z [M + H]+ calcd for C13H14NOS: 232.0791; found:
HRMS (APCI): m/z [M + H]+ calcd for C24H18NOS: 368.1104; found:
368.1100.
N-[7-Methyl-8-(methylthio)naphthalen-1-yl]benzamide (5ha)
Brown oil; yield: 36 mg (59%); Rf = 0.2 (hexane/EtOAc 10:1).
1H NMR (400 MHz, CDCl3):  = 12.78 (s, 1 H), 8.70 (dd, J = 7.7, 1.4 Hz, 1
H), 8.09–8.11 (m, 2 H), 7.76 (d, J = 8.4 Hz, 1 H), 7.49–7.63 (m, 5 H),
7.38 (d, J = 8.3 Hz, 1 H), 2.76 (s, 3 H), 2.17 (s, 3 H).
232.0800.
13C NMR (100 MHz, CDCl3):  = 165.6, 143.9, 135.8, 135.0, 134.4,
131.7, 131.0, 128.7, 128.6, 127.3, 126.5, 125.8, 125.7, 125.5, 121.1,
22.8, 20.4.
N-[8-(Methylthio)naphthalen-1-yl]-3-phenylpropanamide (5af)14
White solid; yield: 51 mg (79%); Rf = 0.3 (hexane/EtOAc 3:1); mp 117–
119 °C.
HRMS (APCI): m/z [M + H]+ calcd for C19H18NOS: 308.1104; found:
308.1105.
1H NMR (400 MHz, CDCl3):  = 10.95 (s, 1 H), 8.39 (d, J = 7.5 Hz, 1 H),
7.77 (d, J = 8.1 Hz, 1 H), 7.62–7.64 (m, 2 H), 7.49 (t, J = 7.9 Hz, 1 H),
7.29–7.37 (m, 5 H), 7.19–7.22 (m, 1 H), 3.15 (t, J = 7.6 Hz, 2 H), 2.81 (t,
J = 7.9 Hz, 2 H), 2.35 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 170.4, 141.1, 136.0, 134.1, 133.6,
130.4, 130.1, 128.6, 128.5, 126.3, 125.9, 125.3, 124.8, 121.1, 40.3, 31.6,
21.0 (1 peak overlapped).
4-Bromo-N-[8-(methylthio)naphthalen-1-yl]benzamide (5ab)14
After column chromatography, the crude material was dissolved in
EtOAc. Hexane was added to this solution, and the precipitate was
collected, washed with hexane, and dried in vacuo to give the pure
product; white solid; yield: 41 mg (55%); Rf = 0.3 (hexane/EtOAc 5:1);
mp 194–196 °C.
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–K

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C. N. Kona et al.
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HRMS (APCI): m/z [M + H]+ calcd for C20H20NOS: 322.1260; found:
322.1273.
References
(1) For reviews, see: (a) Anthony, J. E. Angew. Chem. Int. Ed. 2008,
47, 452. (b) Weil, T.; Vosch, T.; Hofkens, J.; Peneva, K.; Müllen, K.
Angew. Chem. Int. Ed. 2010, 49, 9068. (c) Duarte, T. M. F.; Müllen,
K. Chem. Rev. 2011, 111, 7260. (d) Takimiya, K.; Shinamura, S.;
Osaka, I.; Miyazaki, E. Adv. Mater. 2011, 23, 4347.
(2) For reviews, see: (a) de Koning, C. B.; Rousseau, A. L.; van
Otterlo, W. A. L. Tetrahedron 2003, 59, 7. (b) Makar, S.; Saha, T.;
Singh, S. K. Eur. J. Med. Chem. 2019, 161, 252. (c) Vargas, J. A. M.;
Day, D. P.; Burtoloso, A. C. B. Eur. J. Org. Chem. 2021, 741.
(3) For a recent comprehensive review on the C–H bond functional-
ization, see: Sambiagio, C.; Schönbauer, D.; Blieck, R.; Dao-Huy,
T.; Pototschnig, G.; Schaaf, P.; Wiesinger, T.; Zia, M. F.; Wencel-
Delord, J.; Besset, T.; Maes, B. U. W.; Schnürch, M. Chem. Soc. Rev.
2018, 47, 6603.
(4) For selected recent reviews, see: (a) Jia, M.; Ma, S. Angew. Chem.
Int. Ed. 2016, 55, 9134. (b) Xia, Y.; Qiu, D.; Wang, J. Chem. Rev.
2017, 117, 13810. (c) Zhu, D.; Chen, L.; Fan, H.; Yao, Q.; Zhu, S.
Chem. Soc. Rev. 2020, 49, 908. (d) Nunewar, S.; Kumar, S.;
Talakola, S.; Nanduri, S.; Kanchupalli, V. Chem. Asian J. 2021, 16,
443.
(5) (a) Barday, M.; Janot, C.; Halcovitch, N. R.; Muir, J.; Aïssa, C.
Angew. Chem. Int. Ed. 2017, 56, 13117. (b) Xu, Y.; Zhou, X.;
Zheng, G.; Li, X. Org. Lett. 2017, 19, 5256. (c) Wu, X.; Sun, S.; Yu,
J.-T.; Cheng, J. Synlett 2019, 30, 21.
(6) For selected recent examples of direct acylmethylation, see:
(a) Ji, S.; Yan, K.; Li, B.; Wang, B. Org. Lett. 2018, 20, 5981.
(b) You, C.; Pi, C.; Wu, Y.; Cui, X. Adv. Synth. Catal. 2018, 360,
4068. (c) Xu, G.-D.; Huang, K. L.; Huang, Z.-Z. Adv. Synth. Catal.
2019, 361, 3318. (d) Nie, R.; Lai, R.; Lv, S.; Xu, Y.; Guo, L.; Wang,
Q.; Wu, Y. Chem. Commun. 2019, 55, 11418. (e) Li, H.; Wu, C.;
Liu, H.; Wang, J. J. Org. Chem. 2019, 84, 13262. (f) Li, C.; Li, M.;
Zhong, W.; Jin, Y.; Li, J.; Wu, W.; Jiang, H. Org. Lett. 2019, 21, 872.
(g) Yu, J.; Wen, S.; Ba, D.; Lv, W.; Chen, Y.; Cheng, G. Org. Lett.
2019, 21, 6366. (h) Lyu, X.-L.; Huang, S.-S.; Huang, Y.-Q.; Song,
H.-J.; Liu, Y.-X.; Li, Y.-Q.; Yang, S.-X.; Wang, Q.-M. Asian J. Org.
Chem. 2021, 10, 176. (i) Liu, X.; Shao, Y.; Sun, J. Org. Lett. 2021,
23, 1038.
(7) For reviews, see: (a) Ramirez, T. A.; Zhao, B.; Shi, Y. Chem. Soc.
Rev. 2012, 41, 931. (b) Dequirez, G.; Pons, V.; Dauban, P. Angew.
Chem. Int. Ed. 2012, 51, 7384. (c) Jeffrey, J. L.; Sarpong, R. Chem.
Sci. 2013, 4, 4092. (d) Park, Y.; Kim, Y.; Chang, S. Chem. Rev.
2017, 117, 9247. (e) van Vliet, K. M.; de Bruin, B. ACS Catal.
2020, 10, 4751.
N-[8-(Methylthio)naphthalen-1-yl]cyclohexanecarboxamide (5ag)
White solid; yield: 50 mg (83%); Rf = 0.4 (hexane/EtOAc 3:1); mp 163–
165 °C.
1H NMR (400 MHz, CDCl3):  = 10.89 (s, 1 H), 8.43 (d, J = 7.4 Hz, 1 H),
7.77 (d, J = 8.1 Hz, 1 H), 7.63 (t, J = 9.7 Hz, 2 H), 7.47 (t, J = 7.9 Hz, 1 H),
7.35 (t, J = 7.6 Hz, 1 H), 2.48 (s, 3 H), 2.34–2.40 (m, 1 H), 2.03–2.07 (m,
2 H), 1.84–1.89 (m, 2 H), 1.62–1.71 (m, 3 H), 1.27–1.39 (m, 3 H).
13C NMR (100 MHz, CDCl3):  = 174.6, 136.0, 134.4, 133.7, 130.3,
130.2, 126.25, 125.7, 125.2, 124.8, 121.0, 47.6, 29.7, 25.8, 21.3 (1 peak
overlapped).
HRMS (APCI): m/z [M + H]+ calcd for C18H22NOS: 300.1417; found:
300.1412.
N-[8-(Methylthio)naphthalen-1-yl]cinnamamide (5ah)
Yellow solid; yield: 22 mg (34%); Rf = 0.3 (hexane/EtOAc 5:1); mp
153–155 °C.
1H NMR (400 MHz, CDCl3):  = 11.56 (s, 1 H), 8.62 (s, 1 H), 7.80–7.86
(m, 2 H), 7.51–7.71 (m, 5 H), 7.36–7.41 (m, 4 H), 6.67 (d, J = 15.5 Hz, 1
H), 2.49 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 164.1, 142.0, 136.1, 134.9, 134.4,
130.6, 129.9, 128.9, 128.0, 126.3, 126.0, 125.4, 124.7, 121.9, 120.9,
21.6 (2 peaks overlapped).
HRMS (APCI): m/z [M + H]+ calcd for C20H18NOS: 320.1104; found:
320.1088.
Directing Group Removal of 5aa; N-(Naphthalen-1-yl)benzamide
(5aa-1)23 (Scheme 8)
To a solution of 5aa (29 mg, 0.10 mmol) in EtOH (5.0 mL) in a round-
bottomed flask was added Raney Ni [slurry in water (TCI), ca. 100 mg]
and refluxed for 8 h. Upon completion of the reaction, the mixture
was cooled to rt and filtered through a small pad of silica gel. The fil-
trate was concentrated in vacuo, and the residue was purified by silica
gel chromatography to afford 5aa-1; white solid; yield: 13 mg (53%);
Rf = 0.4 (hexane/EtOAc 4:1).
1H NMR (400 MHz, CDCl3):  = 8.25 (br s, 1 H), 7.97–8.02 (m, 3 H),
7.89–7.92 (m, 2 H), 7.75 (d, J = 8.3 Hz, 1 H), 7.57–7.62 (m, 1 H), 7.49–
7.56 (m, 5 H).
13C NMR (100 MHz, CDCl3):  = 166.2, 134.8, 134.1, 132.3, 131.9,
128.9, 128.8, 127.4, 127.2, 126.4, 126.1, 126.0, 125.8, 121.2, 120.7.
(8) Park, Y.; Park, K. T.; Kim, J. G.; Chang, S. J. Am. Chem. Soc. 2015,
137, 4534.
(9) Yu, S.; Tang, G.; Li, Y.; Zhou, X.; Lan, Y.; Li, X. Angew. Chem. Int.
Ed. 2016, 55, 8696.
Conflict of Interest
(10) (a) Shigeno, M.; Nishii, Y.; Satoh, T.; Miura, M. Asian J. Org.
Chem. 2018, 7, 1334. (b) Kona, C. N.; Nishii, Y.; Miura, M. Org.
Lett. 2018, 20, 4898. (c) Moon, S.; Nishii, Y.; Miura, M. Org. Lett.
2019, 21, 233. (d) Kona, C. N.; Nishii, Y.; Miura, M. Angew. Chem.
Int. Ed. 2019, 58, 9856. (e) Kona, C. N.; Nishii, Y.; Miura, M. Org.
Lett. 2020, 22, 4806.
(11) Tang, K.-X.; Wang, C.-M.; Gao, T.-H.; Chen, L.; Fan, L.; Sun, L.-P.
Adv. Synth. Catal. 2019, 361, 26.
(12) For recent reviews, see: (a) Large, B.; Prim, D. Synthesis 2020, 52,
2600. (b) Prévost, S. ChemPlusChem 2020, 85, 476.
The authors declare no conflict of interest.
Funding Information
This work was supported by JSPS KAKENHI Grant No. JP 19K15586
(Grant-in-Aid for Young Scientists) to Y.N. and JP 17H06092 (Grant-
in-Aid for Specially Promoted Research) to M.M.Japa
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(13) (a) Yang, S.; Cheng, R.; Zhang, M.; Bin, Z.; You, J. ACS Catal. 2019,
9, 6188. (b) Saito, H.; Yamamoto, K.; Sumiya, Y.; Liu, L.-J.; Nogi,
K.; Maeda, S.; Yorimitsu, H. Chem. Asian J. 2020, 15, 2442.
(c) Sato, T.; Nogi, K.; Yorimitsu, H. ChemCatChem 2020, 12, 3467.
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/a-1472-1059.
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C. N. Kona et al.
Special Topic
Synthesis
(14) During the course of our investigation, a similar Ir- and Rh-cata-
lyzed amidation was reported: Xie, H.; Zhong, M.; Wang, X.-T.;
Wu, J.-Q.; Cai, Y.-Q.; Liu, J.; Shu, B.; Che, T.; Zhang, S.-S. Org.
Chem. Front. 2021, 8, 635.
(15) For a review, see: Rousseau, G.; Breit, B. Angew. Chem. Int. Ed.
2011, 50, 2450.
(19) (a) Wang, F.; Wang, H.; Wang, Q.; Yu, S.; Li, X. Org. Lett. 2016, 18,
1306. (b) Van Vliet, K. M.; Polak, L. H.; Siegler, M. A.; Van Der
Vlugt, J. I.; Guerra, C. F.; De Bruin, B. J. Am. Chem. Soc. 2019, 141,
15240. (c) Lei, H.; Rovis, T. J. Am. Chem. Soc. 2019, 141, 2268.
(d) Shi, X.; Xu, W.; Wang, R.; Zeng, X.; Qiu, H.; Wang, M. J. Org.
Chem. 2020, 85, 3911.
(16) Minami, H.; Otsuka, S.; Nogi, K.; Yorimitsu, H. ACS Catal. 2018, 8,
579.
(17) Zhao, J.-N.; Kayumov, M.; Wang, D.-Y.; Zhang, A. Org. Lett. 2019,
21, 7303.
(18) (a) Vaitla, J.; Bayer, A.; Hopmann, K. H. Angew. Chem. Int. Ed.
2017, 56, 4277. (b) Talero, A. G.; Martins, B. S.; Burtoloso, A. C. B.
Org. Lett. 2018, 20, 7206. (c) Zhang, L.; Chen, J.; Chen, J.; Jin, L.;
Zheng, X.; Jiang, X.; Yu, C. Tetrahedron Lett. 2019, 60, 1053.
(d) Zhou, B.; Dong, J.; Xu, J. Adv. Synth. Catal. 2019, 361, 4540.
(e) Zhu, S.; Shi, K.; Zhu, H.; Jia, Z.-K.; Xia, X.-F.; Wang, D.; Zou, L.-
H. Org. Lett. 2020, 22, 1504.
(20) CCDC 2027648 (3ea) and CCDC 2027649 (3ea-1) contain the
supplementary crystallographic data for this paper. The data
can be obtained free of charge from The Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/structures
(21) Sheldrick, G. M. Acta Crystallogr., Sect. A 2008, 64, 112.
(22) Malapit, C. A.; Ichiishi, N.; Sanford, M. S. Org. Lett. 2017, 19,
4142.
(23) Yuan, Y.-C.; Kamaraj, R.; Bruneau, C.; Labasque, T.; Roisnel, T.;
Gramage-Doria, R. Org. Lett. 2017, 19, 6404.
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–K