Oxidative Coupling of N-Methoxyamides and Related Compounds toward Aromatic Hydrocarbons by Designer μ-Oxo Hypervalent Iodine Catalyst

Article abstract of DOI:10.1055/s-0037-1611661

Oxidative coupling strategies that can directly convert the C-H group for chemical transformations are, in theory, ideal synthetic methods to reduce the number of synthetic steps and byproduct generation. Hypervalent iodine reagents have now become one of the most promising tools in developing oxidative couplings due to their unique reactivities that are replacing metal oxidants. As part of our continuous development of oxidative coupling reactions, we describe in this report highly efficient μ-oxo hypervalent iodine catalysts for the direct oxidative coupling of N -methoxyamides and related compounds with aromatic hydrocarbons. The excellent TONs, up to over 100 times, with a best catalyst loading of 0.5 mol% were determined for the oxidative C-H/N-H coupling method, which can provide the most straightforward route to obtaining these unique arylamide compounds.

Full text of DOI:10.1055/s-0037-1611661

SYNTHESIS
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
Georg Thieme Verlag Stuttgart · New York
2019, 51, A–K
feature
A
en
T. Dohi et al.
Feature
Synthesis
Oxidative Coupling of N-Methoxyamides and Related Compounds
toward Aromatic Hydrocarbons by Designer -Oxo Hypervalent
Iodine Catalyst
Toshifumi Dohi*a
Hirotaka Sasaa
Mio Dochia
Chihiro Yasuia
Yasuyuki Kita*b
0
0
0
0-0
0
0
2-2
8
1
2-9
5
8
1
m-oxo catalyst
R'
R1 FG
N
R1 FG
N
m-oxo hypervalent iodine catalyst
the best 0.5 mol%
H
+
R'
R'
I
I
R2
0
0
0
0-0
0
0
2-2
4
8
2-
0
5
5
1
green co-oxidant
room temperature
R2
(excess)
aryl amides
(up to 99%)
a College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1
Nojihigashi, Kusatsu, Shiga, 525-8577, Japan
td1203@ph.ritsumei.ac.jp
b Research Organization of Science and Technology, Ritsumeikan Uni-
versity, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577, Japan
kita@ph.ritsumei.ac.jp
– 2 H+
R'
catalyst TON over 100
Published as part of the 50 Years SYNTHESIS – Golden Anniversary Issue
Received: 02.12.2018
Accepted: 30.12.2018
Published online: 05.02.2019
DOI: 10.1055/s-0037-1611661; Art ID: ss-2018-z0808-fa
cal C–H coupling route avoiding the preparation of organic
halides and/or organometallic compounds has emerged in
the past few decades.4 In theory, the coupling reaction be-
tween two X–H bonds (X = carbon or heteroatom) present
in organic molecules is ideal,5 which is an important goal of
the modern coupling challenge that requires the nonpro-
duction of metal waste and byproducts during the reaction
and preparation of the substrates. In this regard, the oxida-
tive coupling between nucleophile–H bonds would princi-
pally match with the concept (Scheme 1), but early studies
usually suffered from over-oxidation of the products and
low reaction selectivities, such as uncontrolled homodimer
formations.6
License terms:
Abstract Oxidative coupling strategies that can directly convert the
C–H group for chemical transformations are, in theory, ideal synthetic
methods to reduce the number of synthetic steps and byproduct gener-
ation. Hypervalent iodine reagents have now become one of the most
promising tools in developing oxidative couplings due to their unique
reactivities that are replacing metal oxidants. As part of our continuous
development of oxidative coupling reactions, we describe in this report
highly efficient -oxo hypervalent iodine catalysts for the direct oxida-
tive coupling of N-methoxyamides and related compounds with aro-
matic hydrocarbons. The excellent TONs, up to over 100 times, with a
best catalyst loading of 0.5 mol% were determined for the oxidative
C–H/N–H coupling method, which can provide the most straightfor-
ward route to obtaining these unique arylamide compounds.
oxidative coupling
[O]: oxidant
+ H
Nu1
H
Nu2
Nu1
Nu2
– 2 H+
Key words hypervalent compound, iodine, oxidative coupling, amida-
tion, electrophilic substitution
Scheme 1 Direct oxidative coupling between nucleophilic molecules
without prefunctionalization
The transition-metal-catalyzed cross-coupling strate-
gies established in the 20th century for the reactions of un-
reactive organic halides with nucleophilic organic mole-
cules, such as organometallic compounds (e.g., metal = [Zn]
Negishi, [B] Suzuki, etc.)1 and amines (Buchwald–Hartwig),2
as the coupling partner are powerful tools in organic syn-
thesis due to the high reliability of the reactions to con-
struct the target structures found in pharmaceuticals and
other fine chemicals. Due to their high importance in scien-
tific fields as well as in industrial production processes,3
much effort has been devoted to some improvement of the
original coupling strategies; considering the recent demand
for green and sustainable chemistry, a more step-economi-
Recently, the catalysis of oxidative C–H couplings with-
out a prefunctionalized substrate has been quite progres-
sive for transformations of aromatics, particularly by using
transition-metal chemistry,5 while the catalyst loadings in
these reported cases are somewhat unsatisfactory when
compared to first-generation cross-coupling methodology.
Therefore, developing a new metal-catalyst-free method
should be indispensable, especially in this oxidative cou-
pling area, for further advancement of the green strategy.7
Hypervalent iodine reagents have received significant at-
tention in modern synthesis as a safe tool for oxidation re-
actions8 and they have become promising in realizing met-
Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–K

B
T. Dohi et al.
Feature
Synthesis
Biographical Sketches
Toshifumi Dohi received his
2019, respectively. He received
the IUPAC-ICOS 15 Poster
Award for most excellent pre-
sentation, the PSJ Award for
Young Scientists (2009), Banyu
Chemist Award (2013), Thieme
(2014), and GSC Encourage-
ment Award (2015). His current
research interest is focused on
reagent/catalyst design and
asymmetric oxidation in hyper-
valent iodine chemistry.
Ph.D. in 2005 (Y. Kita), subse-
quently became Assistant Pro-
fessor at Osaka University and
Ritsumeikan University, and was
promoted to Associate Profes-
sor and Professor in 2014 and
Chemistry
Journal
Award
Hirotaka Sasa was born and
grew up in Shiga, Japan. He ob-
tained his B.Sc. degree under
the supervision of Prof. Toshifu-
mi Dohi in 2018. Now he re-
ceives the support of the Nagai
Memorial Research Encourage-
ment from The Pharmaceutical
Society of Japan (PSJ) and works
as a Ph.D. course student in the
same group at the Graduate
School of Pharmaceutical Sci-
ences, Ritsumeikan University.
His current interest is synthetic
studies using hypervalent iodine
catalysts.
Mio Dochi was born in Fukuo-
ka, Japan. She is an undergradu-
ate student and studies organic
chemistry at the Fine Synthetic
Chemistry Laboratory, the Col-
lege of Pharmaceutical Scienc-
es, Ritsumeikan University.
Chihiro Yasui is an undergrad-
uate student and lives in Shiga,
Japan. She studies organic
chemistry at the Fine Synthetic
Chemistry Laboratory, the Col-
lege of Pharmaceutical Scienc-
es, Ritsumeikan University.
Yasuyuki Kita was born in
1945 in Osaka, Japan. He re-
ceived his Ph.D. (1972) from
Osaka University and subse-
quently was a member of the
faculty of Pharmaceutical Sci-
ences of the university. After
two years (1975–1977) of post-
doctoral work with Professor
George Büchi at MIT, he moved
back to Osaka University. He
was promoted to Associate Pro-
fessor in 1983 and to Full Profes-
sor of Osaka University in 1992.
In 2008, he retired from Osaka
University and joined Ritsu-
meikan University as the Dean
of the Faculty of Pharmaceutical
Sciences. From 2011 to 2015,
he held Vice-President of the
Research Organization of Sci-
ence and Technology, Ritsu-
meikan University. Since April
2015, he has been Invited Re-
search Professor and Director of
Research Center for Drug Dis-
covery and Pharmaceutical De-
velopment Science of the same
University. He has a wide range
of research interest in synthetic
chemistry including the devel-
opment of new asymmetric
synthesis, new reagents, and
the total synthesis of biological-
ly active natural products. His
current research interest is in
hypervalent iodine chemistry.
He has published more than
500 original papers. His awards
include the Pharmaceutical So-
ciety of Japan (PSJ) Award for
Young Scientists (1986), the PSJ
Award for Divisional Scientific
Contribution (1997), the PSJ
Award (2002), the Japanese So-
ciety for Process Chemistry
(JSPC) Award for Excellence
(2005), the Society of Iodine
Science (SIS) Award (2007), and
the E.C. Taylor Senior Award
(2017).
Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–K

C
T. Dohi et al.
Feature
Synthesis
al-free oxidative coupling reactions based on our pioneer-
ing studies.9 As a part of our continuous development, we
now report the efficient oxidative C–H couplings of aromat-
ic hydrocarbons toward N–H amides to easily produce func-
tionalized arylamides using our unique -oxo hypervalent
iodine catalyst even at less than 1 mol% catalyst loadings at
room temperature in the presence of dilute peracetic acid10
(Scheme 2).
iodine coupling chemistry, leading to the recent break-
through and elucidations of the metal-free aromatic C–H
functionalization strategy.
PhI(OCOCF3)2
(PIFA)
– CF3CO2TMS
TMSN3
N3
Ph
I
OMe
R1
L
OMe
R1
μ-oxo catalyst precursor
H
N3
(L = N3 or OCOCF3)
R2
R2
R'
HFIP
rt
the best 0.5 mol%
(R1 = H)
R1
FG
R'
R'
I
I
up to 85%
N
H
1
R1
FG
Scheme 3 Hypervalent iodine(III) induced oxidative C–H azidation of
electron-rich aromatics, e.g., anisoles
Ia' (R' = H)
Ib' (R' = Me)
N
amides
R'
+
R2
9% peracetic acid
R2
2 (excess)
3
TFA
solvent
rt
Complimentary to the Buchwald–Hartwig aryl amina-
tion procedures, substantial advances in the oxidative C–H
aminations aiming at a greener goal, which can directly in-
stall amines into non-preactivated aromatic substrates to
give valuable N-arylated molecules, have been extensively
found in recent years under transition-metal catalysis and
even other metal-free conditions.16 The amide alternative
of the hypervalent iodine induced C–H azidation involving
in situ formed electrophilic amido-3-iodane species bear-
ing a methoxy or phthalimide-substituted nitrogen group
was reported in 1990 by the Kikugawa group for a few nuc-
leophilic arenes (Scheme 4).17 Later, this C–H amidation
was successfully improved by using PIFA and/or by the aid
of fluoroalcohols (see Scheme 3) in order to use many dif-
ferent substrates in an intramolecular manner.18,19 For ex-
ample, the optimized C–H amidative cyclization protocols
have been applied to the construction of interesting com-
pounds in the field of medicinal chemistry19a,b as well as the
dearomative spirocyclizations to provide facile access to the
unique spirolactam structures known as useful precursors
of some biologically active alkaloids and natural prod-
ucts.19c,d On the other hand, the intermolecular coupling for
unreactive aromatic hydrocarbons remains relatively diffi-
cult, particularly with the catalytic use of a conventional
hypervalent iodine reagent.20
Indeed, the catalytic generation of PIFA (see Figure 1)
under the re-oxidizing conditions for the oxidative C–N
coupling of arenes is not as effective as other hypervalent
iodine mediated reactions,21 and their typical turnover
number (TON) for intermolecular C–H amidations is esti-
mated to be less than only 10 times. Therefore, based on the
structures of -oxo PIDA and PIFA,22,23 we have previously
introduced the -oxo catalysts I as more efficient tools to
realize practical and greener oxidative C–N couplings.24–26
These catalysts are rationally designed to steadily keep their
activated forms and thus reproduce the high electrophilici-
ty of the iodine(III) atoms caused by the strong trans-influ-
ence of the -oxo oxygen27,28 during the catalytic cycle.
aryl amides
Scheme 2 Oxidative coupling of N-protected amides 1 (FG = OMe,
N-phthalimide) with aromatic hydrocarbons (R2 = alkyl, halogen) or
ethers (R2 = alkoxy) by -oxo hypervalent iodine organocatalyst
The oxidative coupling chemistry of the hypervalent io-
dine reagent for the conversion of aromatics has a long his-
tory since the appearances of the reactive reagents, activa-
tors, and solvents that can increase the oxidation abilities of
the iodanyl groups. We first proposed the use of phenylio-
dine(III) bis(trifluoroacetate) (PIFA) in fluoroalcohols, i.e.,
hexafluoroisopropanol (HFIP) and trifluoroethanol (TFE), as
an efficient oxidative coupling system for the dearomatiza-
tion of phenolic substrates introducing nucleophiles (Nu–
H) in the mid 1980s.11 With this significant improvement as
a turning point, the hypervalent iodine reagent now plays a
crucial role in reproducing the biosynthetic oxidative phe-
nolic coupling processes and syntheses of natural prod-
ucts.9c,h A further important contribution in the metal-free
oxidative C–H coupling area is the direct activation of aro-
matic rings triggered by single-electron-transfer (SET) pro-
cesses discovered in the early 1990s.12 Phenyl ether (and al-
kylarene) rings, not causing oxidation unlike phenols, are
smoothly SET activated by treatment with PIFA, and the in-
troduction of an azide by ligand transfer from in situ gener-
ated PhI(N3)X (X = N3 or OCOCF3) leads to the formation of
aromatic C–H azidation products. Again, the highly polar,
non-nucleophilic fluoroalcohol13 was determined to dra-
matically affect the aromatic azidation process and the
product yield reached 85% when employing this specific ac-
tivator as a solvent (Scheme 3).12a Based on this strategy, a
series of metal-free oxidative couplings of aromatic rings
with nucleophiles (NuH) and that having a TMS group
(Nu–TMS) has become possible;14,15 we believe that these
early discoveries by us were the beginning of hypervalent
Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–K

D
T. Dohi et al.
Feature
Synthesis
Table 1 Optimization: Hypervalent Iodine Induced C–H Amidation of
Toluene by -Oxo Catalysts Ia′ and Ib′a
PhIL2
(L = OAc, OCOCF3)
O
O
Ar
H
FG
μ-oxo catalyst precursor
FG
R'
N
R'
N
H
(in situ generate I)
R'
arene C–H amidation
Ar
(FG = OMe, NPhth)
R'
R'
I
I
– PhI
– HL
Troc
OMe
PhIL2
O
Ar
H
N
H
R'
Ia' (R' = H)
Troc
OMe
Me
N
Ib' (R' = Me)
N
FG
1a
– HL
R'
Ph
I
+
(L = OAc or OCOCF3)
L
9% peracetic acid
3aa
(regio-mixture)
TFA
solvent
rt
Scheme 4 Intermolecular oxidative coupling of N-functionalized am-
ides with aromatic hydrocarbons by using hypervalent iodine reagent
(NPhth = phthalimido)
2a
(15 equiv)
Entry -Oxo catalyst Solvent
Time (h) Yield of 3ab,c
However, the suggested conditions for the intermolecular
direct C–H coupling of toluene (2a) toward the N-methoxy-
amide N–H bond using peracetic acid as a stoichiometric
oxidant in an ordinary solvent29 failed and produced very
low TONs for our -oxo catalysts I (see Table 1). Thus, the
reaction of N-methoxyamide 1a with toluene (2a; 15 equiv)
performed using 4 mol% of the pre-catalysts Ia′ (R′ = H)
with 1.5 equiv of peracetic acid (9% solution in acetic acid)
and trifluoroacetic acid (5 equiv) in 1,2-dichloroethane
(DCE, 0.3 M of amide 1a) resulted in the formation of the
corresponding C–N coupling product 3aa in only 13% yield
as a mixture of regioisomers, with a TON of ca. 3 after 2
hours at room temperature; and a large amount of amide
1a remained unreacted in this case (Table 1, entry 1).
1
Ia′ (4 mol%)
Ia′ (4 mol%)
Ia′ (4 mol%)
Ib′ (4 mol%)
Ib′ (4 mol%)
Ib′ (4 mol%)
Ib′ (2 mol%)
Ib′ (1 mol%)
Ib′ (0.5 mol%)
none
DCE
2d
2
13% (2.6:1:2.8)
2
HFIP/DCE (10:1)
HFIP/DCE (10:1)
HFIP/DCE (10:1)
HFIP/DCE (10:1)f
HFIP/DCE (10:1)
HFIP/DCE (10:1)
HFIP/DCE (10:1)
HFIP/DCE (10:1)
HFIP/DCE (10:1)
76% (2.6:1:2.6)
66% (3.7:1:3.4)
78% (2.1:1:2.2)
67% (2.2:1:2.3)
61% (2.7:1:1.8)
81% (2.3:1:2.4)
80% (2.3:1:2.4)
68% (2.3:1:2.7)
3e
4
2
2
5
2
6g
7
2
2
8
6
9
12
16
h
10
–
a Reaction conditions: amide 1a, toluene (2a; 15 equiv), catalyst, peracetic
acid (9% solution in AcOH, 1.5 equiv), TFA (5 equiv), solvent (0.3 M of
amide 1a), rt; unless otherwise stated.
R'
b The product yields after purification were calculated basis on the amide
1a used.
OCOR
OCOR
I
OCOR
c The regioisomeric ratio (ortho/meta/para) is indicated in parentheses
(calculated value by 1H NMR measurement).
d Large amount of amide 1a was recovered.
e Using TFA (1 equiv).
I
R'
R'
I
O
O
I
OCOR
I
OCOR
OCOR
PIDA (R = Me)
PIFA (R = CF3)
f Higher concentration (0.6 M of amide 1a).
g Using toluene (2a; 5 equiv).
μ-oxo PIDA (R = Me)
μ-oxo PIFA (R = CF3)
R'
h Not determined.
μ-oxo catalyst I
(R = Me, CF3)
Figure 1 Hypervalent iodine reagents, PIDA, PIFA, and their -oxo
dimers and designer -oxo reagent I
also appears that the slight modification of the concentra-
tion affects the TON value (entry 5). In this reaction, the
molar balance of the substrates is rather important, and the
yield of the products 3aa decreased by using 5 equiv of tolu-
ene (2a) relative to the amide 1a (entry 6). Subsequently,
we then examined the reaction to further lower the catalyst
loading. To our delight, a comparable result was obtained in
regard to the yield of the product when using a 2 mol%
amount of the catalyst Ib′ with a higher catalyst TON (entry
7). The coupling reactions proceeded at room temperature,
and the robustness of our catalyst Ib′ under the reaction
conditions maintained the original activity for prolonged
times (entry 8). Thus, the TON giving the product 3aa in an
acceptable yield reached 136 times for the 0.5 mol% catalyst
loading after a 12 h reaction (entry 9). To the best of our
knowledge, this observed TON score for the catalyst Ib′ is
the highest among all the intermolecular C–H/N–H aromat-
ic amidations.16 Of course, the coupling product 3aa was
On the other hand, our reported catalytic conditions of a
mixed fluoroalcohol solvent system (HFIP/DCE 10:1)24 were
found to dramatically improve the TON of the catalyst Ia′ as
well as its turnover frequency (TOF) (Table 1, entry 2); this
is probably because the fluoroalcohol not only accelerates
the generation of the active -oxo species I by enhancing
the re-oxidation ability of peracetic acid30 by powerful hy-
drogen bondings,13 but also facilitates the smooth genera-
tion of the cationic nitrenium (or pseudo-nitrenium) spe-
cies.18 In a short reaction time, the target products 3aa were
thus obtained in 76% yield by simply changing the solvent
in which the addition of trifluoroacetic acid takes place to
produce active -oxo species Ia (R = CF3 in Figure 1) and this
was essential for this catalytic coupling (entry 3). Regarding
the catalyst, the derivative Ib′ (R′ = Me) showed similar cat-
alytic efficiencies for the coupling of amide 1a (entry 4). It
Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–K

E
T. Dohi et al.
Feature
Synthesis
not produced in the absence of the -oxo catalysts (entry
10). In 2016, Muñiz and co-workers also reported a new io-
dine catalyst, 1,2-diiodobenzene, for this type of coupling
reaction.31
TOFs for the reactions. The bulky N-phthalimido group
(NPhth) of the amide 1e strongly directed the regioselectiv-
ities at the aromatic rings to para over the ortho positions.
Ac
NPhth
Ac
NPhth
Ac
NPhth
Ac
NPhth
N
N
N
We then evaluated the optimized catalytic system for
the -oxo catalyst Ib′ using the same-type couplings of a
further series of simple non-activated aromatics 2b–f
(Scheme 5). The reactions of ethylbenzene (2b) and p-xy-
lene (2c) both smoothly produced the corresponding C–N
coupling products 3ab and 3ac within 2 hours using 2 mol%
of the catalyst. Although bromobenzene (2d) is less reactive
during the coupling (see product 3ad), the method can pro-
vide an aryl-deuterated amine with an aromatic halogen
functionality in a single step from the isotopic aromatic
substrate (i.e., bromobenzene-d5), which is beneficial for
further elaboration of the structure and scalable synthesis.
Other aliphatic and aromatic amides 1b and 1c and sulfon-
amide 1d were applicable for the couplings with benzene
2e and other aromatic hydrocarbons. The N-methoxy
groups found in anilides are known to show unique reactiv-
ities, and new reactions utilizing cleavage between the het-
eroatom bond as a driving force have been reported by sev-
eral research groups.32
N
Me
3ea
3ee
Br
Cl
3ed
3eg
Catalyst
Time
Product
3ea 3ed
3eg
3ee
μ-oxo Ib'
(2 mol%)
2 h
50%
(1/1.9)a
55%
70%
91%
(1/2.5)a
99%b
92%b
quant
12 h
μ-oxo Ia'
(3 mol%)
2 h
88%
94%
96%
(1/2.4)a (1/4.7)c (1/3.1)c
Scheme 6 Steric influence of -oxo catalysts Ia′ (R′ = H) and Ib′
(R′ = Me) in the coupling of N-phthalimide 1e. Reagents and conditions:
amide 1e, arene 2a,e,d,g (15 equiv), peracetic acid (9% solution in
AcOH, 1.5 equiv), TFA (5 equiv), catalyst (2–3 mol%), HFIP/DCE (10:1),
rt, unless otherwise stated.
a The ortho and para products are separable. b Exclusively para. c ortho/
para ratio of the mixture, calculated by 1H NMR.
Troc
OMe
Troc
OMe
Troc
OMe
N
N
N
The reaction of anisole (2h) with N-methoxybenzamide
(1c) unexpectedly did not occur using either of the -oxo
iodine catalysts Ia′ and Ib′ under the conditions in a fluoro
alcohol (see the note for Scheme 7). Obviously, a competi-
tive diaryliodonium salt forming path for condensation
with anisole 2h to prevent the catalytic cycle was dominant
in this electron-rich aromatic case in a fluoroalcohol33,34
compared to the rate of the generation of the amide-3-io-
dane intermediate for the C–N coupling. Therefore, the use
of DCE only as a solvent was plausible for this coupling
combination. Interestingly, the formation of an ortho-cou-
pling product of anisole 2h over the para isomer was pre-
ferred by specific control of the methoxy group.35
Et
D/H
Bro/p
3ad
3ac
3ab
40%a,b
(1.7/1)c
99%
(2.1/1/2.5)
73%
Bz
OMe
Cbz
OMe
Bz
OMe
N
N
N
Me
3ce
3cc
3ba
74%a
60%
81%
(2.6/1/2.2)
Bz OMe
Bz
OMe
Ts
OMe
N
N
N
Meo/p
3ca
tBuo/p
3de
3cf
82%a
76%
(1/1.3)c
75%
(1/2.8)c
μ-oxo catalyst precursor
Ib' (R' = Me)
Scheme 5 Catalytic C–H amidation of arenes 2a–f using -oxo catalyst
Ib′. Reagents and conditions: amide 1a–d, arene 2a–f (15 equiv), per-
acetic acid (9% solution in AcOH, 1.5 equiv), TFA (5 equiv), catalyst (2
mol%), HFIP/DCE (10:1), rt, 2 h, unless otherwise stated. The ortho/me-
ta/para ratio calculated by 1H NMR is indicated in parentheses.
a Catalyst: 3 mol%. b Overnight. c ortho/para ratio.
(5 mol%)
Bz
OMe
9% peracetic acid
(1.5 equiv)
N
1c
+
OMe
TFA (5 equiv)
DCE
(0.3 M of 1a)
anisole (2h)
3ch
70%*
(ortho/para = 1.7/1)a
(10 equiv)
rt, 10 h
For N-(acetylamino)phthalimide (1e), the catalyst Ib′
(R′ = Me) and the steric nitrogen group are quite mis-
matched;26c the rates of the product formation were quite
slow in comparison to that for the N-methoxyamides 1a–d,
and the amide 1e was not completely consumed within 2
hours (Scheme 6). As a result, the longer reaction time of 12
hours was required in order to achieve the full conversion
of the substrate. Interestingly, the more flexible -oxo cata-
lyst Ia′ (R′ = H) was somewhat preferred in terms of the
Scheme 7 Alternative solvent for the oxidative C–H amidation of elec-
tron-rich aromatic substrate. Product yield when using catalyst Ib′ (2
mol%) in HFIP/DCE (10:1) for 2 hours was less than 5%. a The regioiso-
meric ratio is calculated by 1H NMR.
As a complement to the transition-metal-catalyzed am-
ination of halogenated aryls, Hartwig and co-workers pro-
posed in 2013 the intermolecular direct coupling of simple
Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–K

F
T. Dohi et al.
Feature
Synthesis
arenes with phthalimide by employing the hypervalent io-
dine reagent as the oxidant for the palladium catalyst.36a
Similarly, the metal-catalyzed intermolecular amidations
by converting the C–H group of aromatic hydrocarbons not
having a directing group typically required the hypervalent
iodine reagent as a stoichiometric activator.36b–d In addition,
enhancing the TON was difficult in these catalyses.36e,f Thus,
the fact that the direct couplings between the amide N–H
group and aromatic C–H bond can proceed by using such a
small amount of hypervalent iodine catalyst without add-
ing any transition-metal element in our case is particularly
noteworthy. The differences in the chemoselectivity during
the C–H amidations were also found during the couplings of
the anilides 4a and 4b (see Scheme 8). It was reported by
the Buchwald group that ortho C–C bond-forming aryla-
tions leading to the formation of biaryl compounds 6ai and
6bi would exclusively occur for these anilide substrates un-
der their conditions using a palladium catalyst,37 rather
than the coupling at the nitrogen group. In clear contrast,
our organocatalytic conditions based on the use of the -
oxo catalyst I′ instead afforded the C–N coupling products
5ai and 5bi in moderate to good yields (see experimental
section).38
addition, the use of related chiral hypervalent iodine cata-
lysts based on the -oxo structures42 has a significant po-
tential for the asymmetric oxidative C–N coupling reactions
under metal-free conditions.43
In general, melting points were measured using a Büchi B 545 appara-
tus and are uncorrected. 1H and 13C NMR spectra were recorded with
a Jeol JMN-300 spectrometer operating at 400 MHz and 100 MHz in
CDCl3 at 25 °C with TMS ( = 0) as the internal standard. Infrared
spectra were recorded by using a Hitachi 270-50 spectrometer. Flash
column chromatography and analytical TLC were carried out on Mer-
ck silica gel 60 (230–400 mesh) and Merck silica gel F254 plates (0.25
mm), respectively. The spots and bands were detected by UV irradia-
tion (254, 365 nm) or by staining with 5% phosphomolybdic acid fol-
lowed by heating.
All arenes 2 employed for the coupling reactions are commercially
available and used without further purification. The amides 1a–
d,31,44a–c 1e,44d 4a, and 4b were prepared from O-methylhydroxyam-
ine, acetohydrazide, and corresponding anilines according to the liter-
ature. Solvents were purchased from commercial suppliers and used
as received for the reactions, extraction, and eluent for column chro-
matography and TLC.
Regarding the -oxo hypervalent iodine catalysts Ia′ and Ib′, 2,2′-
diiodobiphenyl (Ia′) is commercially available, while 2,2′-diiodo-
4,4′,6,6′-tetramethylbiphenyl (Ib′) was prepared from 1-iodo-3,5-di-
methylbenzene in one step by our method.45
R3
μ-oxo catalyst precursor
Ia' (R' = H)
4a (R3 = t-Bu)
4b (R3 = Et)
Ac
N
2,2′-Diiodo-4,4′,6,6′-tetramethylbiphenyl (Ib′)
(10 mol%)
+
Under N2 atmosphere at –78 °C, to a stirred solution of 1-iodo-3,5-di-
methylbenzene (1.62 g, 7.0 mmol) in CH2Cl2 (8.75 mL) was added
dropwise a mixture of PIFA (1.51 g, 3.5 mmol) and BF3·OEt2 (0.88 mL,
7 mmol) in CH2Cl2 (8.75 mL) over a few minutes. The mixture was
stirred at this temperature for 5 h. When the reaction was complete,
the mixture was quenched with sat. aq NaHCO3 and the aqueous layer
was extracted with CH2Cl2. The combined organic layers were washed
with brine and dried (anhyd Na2SO4). After removal of the solvent, the
residue was purified by column chromatography (silica gel, hex-
ane/EtOAc) to give Ib′45b (1.02 g, 2.21 mmol, 63%) as a white powder;
mp 111–113 °C.
optimized conditions
o-xylene
2i
(10 equiv)
C–N coupling
over
C–C coupling
75%: 5ai (R3 = t-Bu)
52%: 5bi (R3 = Et)
R3
R3
R3
Ac
N
Ac
Ac
N
N
H
H
4a (R3 = t-Bu)
4b (R3 = Et)
5ai (R3 = t-Bu)
5bi (R3 = Et)
not observed
6ai (R3 = t-Bu)
6bi (R3 = Et)
IR (KBr): 3014, 1599, 1541, 1035 cm–1
.
1H NMR (400 MHz, CDCl3):  = 1.95 (s, 6 H), 2.31 (s, 6 H), 7.06 (s, 2 H),
7.62 (s, 2 H).
Scheme 8 Oxidative amidation over ortho C–C coupling in the hyper-
valent iodine-catalyzed reaction of anilides 4a and 4b
13C NMR (100 MHz, CDCl3):  = 20.4, 21.2, 100.7, 130.7, 136.9, 137.0,
139.0, 144.3.
2,2,2-Trichloroethyl Methoxy(tolyl)carbamate 3aa; Typical Proce-
dure for Oxidative Coupling Using a Combination of Diiodobiphe-
nyl Catalyst Ib′ with Stoichiometric Peracetic Acid (Schemes 5 and
6)
In this study, we have clarified the extremely high cata-
lytic efficiencies of our designer -oxo hypervalent iodine
catalysts I for the intermolecular direct oxidative coupling
of suitable amides with aromatic hydrocarbons. The C–H
and N–H coupling methods can provide the most straight-
forward route to these arylamide compounds with excel-
lent TONs of over 100 times with a 0.5 mol% catalyst load-
ing. This allows many new direct amination strategies to
extend the scopes recently developed on the basis of the
stoichiometric hypervalent iodine chemistry,39–41 and our
idea for the catalyst design might contribute to the develop-
ments of practical catalysts for these transformations. In
2,2,2-Trichloroethyl carbamate (1a; 111.2 mg, 0.50 mmol, 1 equiv),
toluene (691 mg, 7.5 mmol, 15 equiv), and catalyst Ib′ (4.6 mg, 0.010
mmol, 0.02 equiv) were dissolved in HFIP/DCE (10:1, 1.6 mL) in a
round-bottomed flask at rt. Peracetic acid (9% solution in AcOH, 0.6
mL, 0.75 mmol, 1.5 equiv), and TFA (285 mg, 2.5 mmol, 5 equiv) were
added sequentially. The mixture was then stirred at rt for 2 h. When
the reaction was complete, the resulting solution was washed with
water and extracted with CH2Cl2, and the combined organic extracts
were dried (anhyd Na2SO4). After removal of the solvents by a rotary
Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–K

G
T. Dohi et al.
Feature
Synthesis
evaporator, the residue was subjected to flash column chromatogra-
phy (silica gel (hexane/EtOAc) to give pure 3aa31 (127.5 mg, 0.408
mmol, 81%) as a pale yellow oil; ratio ortho/meta/para 2.3:1:2.4 (1H
NMR).
1H NMR (400 MHz, CDCl3):  = 2.30 (s, 3 H, ortho), 2.31 (s, 3 H, para),
2.33 (s, 3 H, meta), 3.74 (s, 3 H, ortho), 3.76 (s, 3 H, para), 3.77 (s, 3 H,
meta), 4.78 (s, 2 H, ortho), 4.81 (s, 2 H, para), 4.83 (s, 2 H, meta), 6.99–
7.03 (m, 1 H, meta), 7.12–7.35 (m, 11 H, ortho, meta, para).
13C NMR (100 MHz, CDCl3):  = 18.0, 21.1, 21.6, 62.1, 62.4, 62.6, 75.2,
75.3, 75.4, 95.2, 95.3 (2 ×), 119.7, 123.1, 123.3, 126.6, 127.5, 128.2,
128.9, 129.4, 129.6, 131.2, 136.2, 136.7, 136.9, 137.2, 138.6, 139.0,
152.6, 152.7, 153.5.
13C NMR (100 MHz, CDCl3):  = 17.7, 61.9, 67.7, 126.4, 127.9, 128.1,
128.5, 128.9, 131.0, 136.0, 136.5, 138.0, 155.2.
Benzyl Methoxy(3-tolyl)carbamate (meta-3ba) and Benzyl Me-
thoxy(4-tolyl)carbamate (para-3ba)
Yellowish oil; yield: 61.5 mg (41%).
1H NMR (400 MHz, CDCl3):  = 2.32 (s, 3 H, para), 2.34 (s, 3 H, meta),
3.72 (s, 3 H, para), 3.73 (s, 3 H, meta), 5.24 (s, 2 H, para), 5.25 (s, 2 H,
meta), 6.95–7.07 (m, 1 H, meta), 7.12–7.42 (m, 17 H).
13C NMR (100 MHz, CDCl3):  = 21.0, 21.5, 62.2, 62.4, 67.9 (2 ×), 119.3,
122.7, 122.9, 126.9, 128.2 (2 ×), 128.3 (2 ×), 128.6 (2 ×), 129.4, 136.1
(2 ×), 136.2, 137.0, 138.7, 139.4, 154.2, 154.5, 155.4.
The analytical data of all the products 3 are listed below. The physical
and spectral data of all these compounds well matched those previ-
ously reported.29,31,32d,38
N-(2,5-Dimethylphenyl)-N-methoxybenzamide (3cc)
Colorless oil; yield: 103.7 mg (81%).
1H NMR (400 MHz, CDCl3):  = 2.22 (s, 6 H), 3.50–3.85 (br s, 3 H),
6.93–7.71 (m, 8 H).
13C NMR (100 MHz, CDCl3):  = 17.7, 20.9, 61.0, 128.0, 128.4, 128.5,
130.2 (2 ×), 130.8, 131.2, 133.5, 133.6, 136.5.
3,3,3-Trichloro-N-(ethylphenyl)-N-methoxypropanamide 3ab
Yellowish oil; yield: 164.5 mg (99%); ratio ortho/meta/para 2.1:1:2.5
(1H NMR).
1H NMR (400 MHz, CDCl3):  = 1.20–1.30 (m, 9 H), 2.61–2.76 (m, 6 H),
3.80 (s, 3 H), 3.82 (s, 3 H), 3.83 (s, 3 H), 4.81–4.90 (m, 6 H), 7.05–7.11
(m, 1 H, meta), 7.19–7.44 (m, 11 H).
13C NMR (100 MHz, CDCl3):  = 15.5, 15.6, 28.5, 28.9, 62.4, 62.5, 75.3,
95.2, 95.3, 119.9, 122.2, 123.0, 126.3, 128.4, 128.8, 136.3, 138.7, 143.1,
145.3, 152.6, 152.7.
N-Methoxy-N-phenylbenzamide (3ce)
Light yellow oil; yield: 69.5 mg (60%).
1H NMR (400 MHz, CDCl3):  = 3.69 (s, 3 H), 7.20–7.52 (m, 8 H), 7.56–
7.64 (m, 2 H).
13C NMR (100 MHz, CDCl3):  = 61.8, 124.5, 127.2, 128.1, 128.6, 129.1,
130.8, 134.7, 139.4, 168.3.
3,3,3-Trichloro-N-(2,5-dimethylphenyl)-N-methoxypropanamide
(3ac)
N-Methoxy-N-tolylbenzamide (3ca)
Pale yellow oil; yield: 119.2 mg (73%); mixture of rotamers.
Light yellow oil; yield: 91.1 mg (76%); ratio ortho/para 1:1.3 (1H
NMR).
1H NMR (400 MHz, CDCl3):  = 2.25 (s, 3 H, para), 2.28 (s, 3 H, ortho),
1H NMR (400 MHz, CDCl3):  = 2.29 (s, 3 H), 2.30 (s, 3 H), 2.33 (s, 3 H),
2.34 (s, 3 H), 3.77 (s, 3 H), 3.79 (s, 3 H), 4.83 (m, 2 H), 7.03–7.05 (m, 1
H), 7.09–7.13 (m, 3 H), 7.15–7.19 (m, 2 H).
13C NMR (100 MHz, CDCl3):  = 17.4, 17.7, 20.8, 21.2, 61.8, 62.0, 75.1,
95.3, 127.2, 128.0, 128.5, 130.1, 130.8, 131.8, 133.3, 134.5, 136.3,
136.8, 139.4, 153.4, 153.5.
3.62 (s, 6 H), 7.03–7.62 (m, 18 H).
13C NMR (100 MHz, CDCl3):  = 18.2, 21.2, 61.0, 61.5, 125.1, 126.6,
128.1 (2 ×), 128.5, 128.6, 129.3, 130.0, 130.7, 130.8, 131.4, 134.5,
134.8, 136.8, 136.9, 137.5, 168.1.
N-(Bromophenyl)-3,3,3-trichloro-N-methoxypropanamide 3ad
N-(tert-Butylphenyl)-N-methoxybenzamide (3cf)
Light yellow oil; yield: 107.6 mg (75%); ratio ortho/para 1:2.8 (1H
NMR).
Following the typical procedure for 3aa using Ib′ (3 mol%), reaction
time: overnight; pale yellow oil; yield: 81.0 mg (40%); ratio ortho/para
1.7:1 (1H NMR).
1H NMR (400 MHz, CDCl3):  = 3.81 (s, 3 H, para), 3.83 (s, 3 H, ortho),
4.82–4.88 (m, 4 H), 7.22–7.29 (m, 1 H), 7.36–7.43 (m, 4 H, ortho and
para), 7.46–7.53 (m, 2 H, para), 7.68 (dd, J = 8.1, 1.4 Hz, 1 H).
13C NMR (100 MHz, CDCl3):  = 62.8, 63.0, 75.5 (2 ×), 95.0 (2 ×), 119.6,
123.4, 123.6, 128.4, 129.2, 130.1, 133.7, 138.0, 138.1, 152.3, 153.2.
1H NMR (400 MHz, CDCl3):  = 1.27 (s, 9 H, ortho), 1.35 (s, 9 H, para),
3.72 (s, 3 H, para), 3.78 (s, 3 H, ortho), 7.10–7.65 (m, 18 H).
13C NMR (100 MHz, CDCl3):  = 31.0, 31.2, 34.5, 34.6, 61.4, 121.5,
122.2, 124.0, 125.8, 127.9, 128.3, 128.5, 129.6, 130.4, 130.5, 134.6,
134.7, 136.4, 138.9, 150.2, 152.0, 167.8, 168.0.
Benzyl Methoxy(tolyl)carbamate 3ba
N-Methoxy-4-methyl-N-phenylbenzenesulfonamide (3de)
Following the typical procedure for 3aa using Ib′ (3 mol%) gave 3ba
which was separated by column chromatography to give ortho-3ba
and a mixture of meta-3ba and para-3ba; ratio ortho/meta/para
2.6:1:2.2 (1H NMR).
Following the typical procedure for 3aa using Ib′ (3 mol%) gave 3de;
yellowish oil; yield: 113.0 mg (82%).
1H NMR (400 MHz, CDCl3):  = 2.39 (s, 3 H), 3.86 (s, 3 H), 7.05–7.13
(m, 2 H), 7.15–7.45 (m, 7 H).
13C NMR (100 MHz, CDCl3):  = 21.8, 64.4, 123.7, 127.6, 128.4, 129.1,
129.8, 130.2, 141.0, 144.8.
Benzyl Methoxy(2-tolyl)carbamate (ortho-3ba)
Colorless oil; yield: 38.3 mg (33%).
1H NMR (400 MHz, CDCl3):  = 2.23 (s, 3 H), 3.71 (s, 3 H), 5.20 (s, 2 H),
7.16–7.38 (m, 9 H).
N-(1,3-Dioxoisoindolin-2-yl)-N-phenylacetamide (3ee)
Following the typical procedure for 3aa using catalyst Ib′ for 12 h gave
3ee; yellowish solid; yield: 56.8 mg (quant.); mixture of rotamers.
Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–K

H
T. Dohi et al.
Feature
Synthesis
1H NMR (400 MHz, CDCl3):  = 2.09 (s, 3 H), 7.38–7.49 (m, 3 H), 7.64–
N-(4-tert-Butylphenyl)-N-(3,4-dimethylphenyl)acetamide (5ai)
7.91 (m, 6 H).
Following to the typical procedure for 3aa, but using the -oxo cata-
lyst Ia′ (10 mol%) in TFE/CH2Cl2 (2:1, 0.067 M) (Scheme 8) and wet
MCPBA (69% purity, 1.5 equiv) instead of 9% peracetic acid solution
for 3 h gave 5ai; yellowish oil; yield: 44.4 mg (75%).
13C NMR (100 MHz, CDCl3):  = 21.8, 124.1, 129.0, 129.7, 130.0, 130.2,
134.8, 140.8, 165.0, 168.5.
N-(1,3-Dioxoisoindolin-2-yl)-N-(tolyl)acetamide (3ea)
IR (KBr): 2966, 2869, 1675, 1608, 1509, 1369, 1308, 1024 cm–1
.
1H NMR (400 MHz, CDCl3, 50 °C):  = 1.28 (s, 9 H), 2.01 (s, 3 H), 2.22
(s, 6 H), 6.97 (dd, J = 7.8, 2.0 Hz, 1 H), 7.03 (d, J = 1.9 Hz, 1 H), 7.09 (d,
J = 7.8 Hz, 1 H), 7.16 (d, J = 8.3 Hz, 2 H), 7.32 (d, J = 8.8 Hz, 2 H).
Following the typical procedure for 3aa using catalyst Ib′ for 12 h gave
a mixture of para/ortho isomers 2.5:1 that were separated by column
chromatography.
HRMS (DART): m/z [M + H]+ calcd for C20H26ON: 296.2009; found:
296.2009.
N-(1,3-Dioxoisoindolin-2-yl)-N-(4-tolyl)acetamide (para-3ea)
White amorphous; yield: 85.9 mg (65%).
1H NMR (400 MHz, CDCl3):  = 2.08 (s, 3 H), 2.36 (s, 3 H), 7.19–7.29
(m, 2 H), 7.54 (d, J = 8.3 Hz, 2 H), 7.74 (dd, J = 5.9, 2.9 Hz, 2 H), 7.86
(dd, J = 5.4, 3.0 Hz, 2 H).
13C NMR (100 MHz, CDCl3):  = 21.4, 21.8, 124.1, 128.8, 130.3, 130.6,
134.7, 138.3, 139.6, 165.0, 168.7.
N-(4-Ethylphenyl)-N-(3,4-dimethylphenyl)acetamide (5bi)
Following to the typical procedure for 3aa, but using the -oxo cata-
lyst Ia′ (10 mol%) in TFE/CH2Cl2 (2:1, 0.067 M) (Scheme 8) and wet
MCPBA (69% purity, 1.5 equiv) instead of 9% peracetic acid solution
for 3 h gave 5bi; yellowish oil; yield: 27.6 mg (52%).
IR (KBr): 3025, 2964, 2928, 2873, 1671, 1608, 1509, 1454, 1369, 1305,
1121, 1024 cm–1
.
N-(1,3-Dioxoisoindolin-2-yl)-N-(2-tolyl)acetamide (ortho-3ea)
White amorphous; yield: 34.4 mg (26%).
1H NMR (400 MHz, CDCl3):  = 2.02 (s, 3 H), 2.63 (s, 3 H), 7.23–7.35
(m, 3 H), 7.71–7.95 (m, 5 H).
13C NMR (100 MHz, CDCl3):  = 18.2, 21.0, 124.1, 124.4, 127.6, 129.8,
1H NMR (400 MHz, CDCl3, 50 °C):  = 1.21 (t, J = 7.8 Hz, 3 H), 2.02 (s, 3
H), 2.22 (s, 6 H), 2.61 (q, J = 7.8 Hz, 2 H), 6.97 (dd, J = 8.3, 2.0 Hz, 1 H),
7.03 (d, J = 2.0 Hz, 1 H), 7.10–7.28 (m, 5 H).
HRMS (DART): m/z [M + H]+ calcd for C18H22ON: 268.1696; found:
268.1696.
129.9, 131.9, 134.7, 134.9, 135.3, 137.6, 139.6, 165.8, 166.1, 168.9.
5,7-Diacetoxy-5,7-dihydro-1,3,9,11-tetramethyldiben-
zo[d,f][1,3,2]diiodoxepin (Ib) (Figure 1)
N-(4-Bromophenyl)-N-(1,3-dioxoisoindolin-2-yl)acetamide (para-
3ed)
To a stirred solution of peracetic acid (9% solution in AcOH, 6.1 mL,
7.6 mmol) in MeCN (47.5 mL) was successively added AcOH (17.1 mL)
and 2,2′-diiodo-4,4′,6,6′-tetramethylbiphenyl (Ib′; 0.88 g, 1.9 mmol),
and the mixture was stirred overnight at rt. After removal of MeCN
under reduced pressure, the resulting residue was extracted with
CH2Cl2, and then the organic solution was dried (anhyd Na2SO4). After
evaporation of the solvent, the crude solid, that is, Ib, was dissolved in
minimal amount of CH2Cl2, which was then added dropwise to stirred
hexane. The resulting suspension was filtered and dried to give pure
-oxo-bridged hypervalent iodine(III) diacetate Ib24 as a white pow-
der; yield: quant (1.13 g); mp 157 °C.
Following the typical procedure for 3aa using catalyst Ib′ for 12 h gave
para-3ed; brownish solid; yield: 169.0 mg (99%); mp 169–171 °C.
1H NMR (400 MHz, CDCl3):  = 2.09 (s, 3 H), 7.43–7.95 (m, 8 H).
13C NMR (100 MHz, CDCl3):  = 21.8, 123.9, 124.2, 130.1, 130.7, 133.3,
134.9, 139.8, 165.0, 168.1.
N-(4-Chlorophenyl)-N-(1,3-dioxoisoindolin-2-yl)acetamide (para-
3eg)
Following the typical procedure for 3aa using catalyst Ib′ gave para-
3eg; yellowish solid; yield: 57.9 mg (92%); mp 138–140 °C.
1H NMR (400 MHz, CDCl3):  = 2.09 (s, 3 H), 7.30–7.49 (m, 2 H), 7.55–
IR (KBr): 1649, 1559, 1018, 750 cm–1
.
7.66 (m, 2 H), 7.69–7.95 (m, 4 H).
1H NMR (400 MHz, CDCl3):  = 1.85 (s, 6 H), 2.16 (s, 6 H), 2.46 (s, 6 H),
7.38 (s, 2 H), 7.86 (s, 2 H).
13C NMR (100 MHz, CDCl3):  = 21.2 (2 ×), 21.4, 127.0, 133.4, 135.2,
13C NMR (100 MHz, CDCl3):  = 21.8, 124.2, 130.1, 130.3, 130.4, 134.9,
135.8, 139.3, 165.0, 168.2.
137.7, 139.2, 142.8, 177.6.
N-Methoxy-N-(methoxyphenyl)benzamide (3ch)
A pure sample compatible for the X-ray crystallographic analysis was
obtained by recrystallization from MeCN/hexane solution. For crys-
tallographic data of Ib in CIF format, see CCDC 779814.
Following the typical procedure for 3aa, but using DCE instead of the
mixed fluoroalcohol solvent (Scheme 7) and -oxo catalyst Ib′ (5
mol%) gave 3ch; light yellow oil; yield: 91.3 mg (70%); ratio ortho/para
1.7:1.
1H NMR (400 MHz, CDCl3):  = 3.71 (s, 3 H, ortho), 3.72 (s, 3 H, para),
3.81 (s, 3 H, para), 3.85 (s, 3 H, ortho), 6.74–6.89 (m, 4 H), 7.07–7.64
(m, 14 H).
13C NMR (100 MHz, CDCl3):  = 55.6, 55.7, 61.3, 61.6, 112.3, 114.4,
121.0, 127.5, 127.7, 128.1, 128.4, 128.7, 129.3, 130.2, 130.5, 130.7,
130.9, 132.3, 134. 7, 134.8, 155.2, 159.0, 168.1, 169.7.
Acknowledgement
This work was partially supported by a Grant-in-Aid for Scientific Re-
search (C) from JSPS. T.D. acknowledges support from the Ritsu-
meikan Global Innovation Research Organization (R-GIRO) project,
and thanks Central Glass Co., Ltd. for generous gift of fluoroalcohol.
H.S. thanks The Pharmaceutical Society of Japan (PSJ) for support of
the Nagai Memorial Research Encouragement.
Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–K

I
T. Dohi et al.
Feature
Synthesis
References
11957. (d) Mousseau, J. J.; Charette, A. B. Acc. Chem. Res. 2013,
46, 412. (e) Narayan, R.; Manna, S.; Antonchick, A. P. Synlett
2015, 26, 1785. (f) Narayan, R.; Matcha, K.; Antonchick, A. P.
Chem. Eur. J. 2015, 21, 14678. (g) Rossi, R.; Lessi, M.; Manzini, C.;
Marianetti, G.; Bellina, F. Adv. Synth. Catal. 2015, 357, 3777.
(h) Qin, Y.; Zhu, L.; Luo, S. Chem. Rev. 2017, 117, 9433.
(1) For selected reviews, accounts, and publications, see:
(a) Anastasia, L.; Negishi, E. Handbook of Organopalladium
Chemistry for Organic Synthesis; Wiley: New York, 2002, 311–
334. (b) Metal-Catalyzed Cross-Coupling Reactions; Diederich, F.;
Stang, P. J., Ed.; Wiley-VCH: Weinheim, 2004. (c) Negishi, E.
Angew. Chem. Int. Ed. 2011, 50, 6738, Nobel Lecture. (d) Suzuki,
A. Angew. Chem. Int. Ed. 2011, 50, 6722; Nobel Lecture.
(e) Science of Synthesis: Cross Coupling and Heck-Type Reactions 1 ;
Molander, G. A.; Wolfe, J. P.; Larhed, M., Eds.; Thieme: Stuttgart,
2013.
(2) For reviews, see: (a) Yang, B. H.; Buchwald, S. L. J. Organomet.
Chem. 1999, 576, 125. (b) Hartwig, J. F. Handbook of Organopal-
ladium Chemistry for Organic Synthesis; Negishi, E.-i., Ed.; Wiley:
New York, 2002, 1051. (c) Janey, J. M. Name Reactions for Func-
tional Group Transformations; Li, J. J.; Corey, E. J., Ed.; John Wiley
(8) For recent comprehensive reviews and publications, see:
(a) Zhdankin, V. V.; Stang, P. J. Chem. Rev. 2016, 116, 3328.
(b) Zhdankin, V. V.; Stang, P. J. Chem. Rev. 2008, 108, 5299.
(c) Zhdankin, V. V. J. Org. Chem. 2011, 76, 1185. (d) Silva, L. F. Jr.;
Olofsson, B. Nat. Prod. Rep. 2011, 28, 1722. (e) The Chemistry of
Hypervalent Halogen Compounds; Marek, I.; Olofsson, B.;
Rappoport, Z., Ed.; John Wiley & Sons: Chichester, 2018.
(f) Hypervalent Iodine Chemistry, In Topics in Current Chemistry,
Vol. 373; Wirth, T., Ed.; Springer: Switzerland, 2016.
(g) Hypervalent Iodine Chemistry: Modern Developments in
Organic Synthesis, In Topics in Current Chemistry, Vol. 224;
Wirth, T., Ed.; Springer: Berlin, 2003.
&
Sons: Hoboken, 2007, 564–609. (d) Ruiz-Castillo, P.;
Buchwald, S. L. Chem. Rev. 2016, 116, 12564. (e) Heravi, M. M.;
Kheilkordi, Z.; Zadsirjan, V.; Heydari, M.; Malmir, M.
J. Organomet. Chem. 2018, 861, 17.
(9) For our reviews and accounts, see: (a) Kita, Y.; Tohma, H.;
Yakura, T. Trends Org. Chem. 1992, 3, 113. (b) Kita, Y.; Takada, T.;
Tohma, H. Pure Appl. Chem. 1996, 68, 627. (c) Tohma, H.; Kita, Y.
Top. Curr. Chem. 2003, 224, 209. (d) Dohi, T.; Ito, M.; Yamaoka,
N.; Morimoto, K.; Fujioka, H.; Kita, Y. Tetrahedron 2009, 65,
10797. (e) Kita, Y.; Dohi, T.; Morimoto, K. J. Synth. Org. Chem.
Jpn. 2011, 69, 1241. (f) Kita, Y.; Dohi, T. Chem. Rec. 2015, 15, 886.
(g) Dohi, T.; Kita, Y. Curr. Org. Chem. 2016, 20, 580. (h) Dohi, T.;
Kita, Y. Top. Curr. Chem. 2016, 373, 1. (i) Morimoto, K.; Dohi, T.;
Kita, Y. Synlett 2017, 28, 1680.
(10) Dilute peracetic acid is known as a safe and environmentally
friendly oxidant that releases nontoxic acetic acid as the co-
product. It is commercially available and frequently employed
in industrial-scale oxidations, such as epoxidation. Further-
more, its aqueous 0.2–0.3% solution is widely used as a disinfec-
tant in medical situations.
(11) For early studies, see: (a) Tamura, Y.; Yakura, T.; Haruta, J.; Kita,
Y. J. Org. Chem. 1987, 52, 3927. (b) Tamura, Y.; Yakura, T.;
Tohma, H.; Kikuchi, K.; Kita, Y. Synthesis 1989, 126. (c) Kita, Y.;
Yakura, T.; Tohma, H.; Kikuchi, K.; Tamura, Y. Tetrahedron Lett.
1989, 30, 1119. (d) Kita, Y.; Tohma, H.; Kikuchi, K.; Inagaki, M.;
Yakura, T. J. Org. Chem. 1991, 56, 435. (e) Kita, Y.; Tohma, H.;
Inagaki, M.; Hatanaka, K.; Kikuchi, K.; Yakura, T. Tetrahedron
Lett. 1991, 32, 2035. (f) Kita, Y.; Tohma, H.; Inagaki, M.;
Hatanaka, K.; Yakura, T. J. Am. Chem. Soc. 1992, 114, 2175.
(12) (a) Kita, Y.; Tohma, H.; Inagaki, M.; Hatanaka, K.; Yakura, T. Tet-
rahedron Lett. 1991, 32, 4321. (b) Kita, Y.; Tohma, H.; Hatanaka,
K.; Takada, T.; Fujita, S.; Mitoh, S.; Sakurai, H.; Oka, S. J. Am.
Chem. Soc. 1994, 116, 3684.
(13) For the utility of fluoroalcohol solvents, see ref. 9b and the fol-
lowing reviews and accounts: (a) Eberson, L.; Hartshorn, M. P.;
Persson, O.; Radner, F. Chem. Commun. 1996, 2105. (b) Bégué, J.
P.; Bonnet-Delpon, D.; Crousse, B. Synlett 2004, 18. (c) Shuklov,
I. A.; Dubrovina, N. V.; Boerner, A. Synthesis 2007, 2925.
(d) Khaksar, S. J. Fluorine Chem. 2015, 172, 51.
(3) For selected summarizations, see: (a) Torborg, C.; Beller, M. Adv.
Synth. Catal. 2009, 351, 3027. (b) Biffis, A.; Centomo, P.; Del
Zotto, A.; Zecca, M. Chem. Rev. 2018, 118, 2249. (c) Palladium-
Catalyzed Coupling Reactions: Practical Aspects and Future
Developments; Molnár, A., Ed.; Wiley–VCH: Weinheim, 2013.
(d) Cooper, T.; Campbell, I.; Macdonald, S. Angew. Chem. Int. Ed.
2010, 49, 8082. (e) Brown, D. G.; Bostrom, J. J. Med. Chem. 2016,
59, 4443. (f) Cernak, T.; Dykstra, K. D.; Tyagarajan, S.; Vachalb,
P.; Krska, S. W. Chem. Soc. Rev. 2016, 45, 546. (g) Devendar, P.;
Qu, R.; Kang, W.-M.; He, B.; Yang, G.-F. J. Agric. Food Chem. 2018,
66, 8914.
(4) Heck reaction is an early pioneer for the C–H coupling toward
organic halides. See: (a) Heck, R. F. Org. React. 1982, 27, 345. For
the trials reported in 2000s for other types of C–H coupling
reactions, see: (b) Alberico, D.; Scott, M. E.; Lautens, M. Chem.
Rev. 2007, 107, 174. (c) Seregin, I. Y.; Gevorgyan, V. Chem. Soc.
Rev. 2007, 36, 1173. (d) Chen, X.; Engle, K. M.; Wang, D.-H.; Yu,
J.-Q. Angew. Chem. Int. Ed. 2009, 48, 5094. (e) Lyons, T. W.;
Sanford, M. S. Chem. Rev. 2010, 110, 1147. (f) Zhang, Y.-F.; Shi,
Z.-J. Acc. Chem. Res. 2019, 52, 161.
(5) For recent summaries, see: (a) From C–H to C–C Bonds: Cross-
Dehydrogenative-Coupling; Li, C.-J., Ed.; RSC Green Chemistry
Series: Cambridge, 2015. (b) Tang, S.; Zeng, L.; Lei, A. J. Am.
Chem. Soc. 2018, 140, 13128. (c) Yang, Y.; Lan, J.; You, J. Chem.
Rev. 2017, 117, 8787. (d) Varun, B. V.; Dhineshkumar, J.;
Bettadapur, K. R.; Siddaraju, Y.; Alagiri, K.; Prabhu, K. R. Tetrahe-
dron Lett. 2017, 58, 803. (e) He, K.-H.; Li, Y. ChemSusChem 2014,
7, 2788.
(6) For early discussions, see: (a) Dhingra, O. P. Oxidation in Organic
Chemistry, In Organic Chemistry, Part D, Vol. 5; Trahanovsky, W.
S., Ed.; Academic Press: New York, 1982, 207. (b) Brunow, G.;
Kilpeläinen, I.; Sipilä, J.; Syrjänen, K.; Karhunen, P.; Setälä, H.;
Rummakko, P. Lignin and Lignan Biosynthesis; Lewis, N. G.;
Sarkanen, S., Ed.; ACS Symposium Series 687; American Chemi-
cal Society: Washington, 1998, 131. (c) Lessene, G.; Feldman, K.
S. Modern Arene Chemistry; Astruc, D., Ed.; Wiley-VCH: Wein-
heim, 2002, 479–538.
(14) Intramolecular cyclizations of azides: (a) Kita, Y.; Egi, M.;
Okajima, A.; Ohtsubo, M.; Takada, T.; Tohma, H. Chem. Commun.
1996, 1491. (b) Kita, Y.; Watanabe, H.; Egi, M.; Saiki, T.;
Fukuoka, Y.; Tohma, H. J. Chem. Soc., Perkin Trans. 1 1998, 635.
(c) Kita, Y.; Egi, M.; Tohma, H. Chem. Commun. 1999, 143.
(d) Kita, Y.; Egi, M.; Ohtsubo, M.; Saiki, T.; Okajima, A.; Takada,
T.; Tohma, H. Chem. Pharm. Bull. 1999, 47, 241. (e) Kita, Y.; Egi,
M.; Takada, T.; Tohma, H. Synthesis 1999, 885.
(7) For recent interest of metal-free couplings and the use of hyper-
valent iodine reagent, see the following reviews: (a) Sun, C.-L.;
Shi, Z.-J. Chem. Rev. 2014, 114, 9219; and references therein.
(b) Chan, T. L.; Wu, Y.; Choy, P. Y.; Kwong, F. Y. Chem. Eur. J.
2013, 19, 15802. (c) Mehta, V. P.; Punji, B. RSC Adv. 2013, 3,
Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–K

J
T. Dohi et al.
Feature
Synthesis
(15) See ref. 9b and selected examples for introducing heteroatoms:
(a) Kita, Y.; Takada, T.; Mihara, S.; Tohma, H. Synlett 1995, 211.
(b) Kita, Y.; Takada, T.; Mihara, S.; Whelan, B. A.; Tohma, H.
J. Org. Chem. 1995, 60, 7144. (c) Kita, Y.; Egi, M.; Ohtsubo, M.;
Saiki, T.; Takada, T.; Tohma, H. Chem. Commun. 1996, 2225.
(d) Hamamoto, H.; Hata, K.; Nambu, H.; Shiozaki, Y.; Tohma, H.;
Kita, Y. Tetrahedron Lett. 2004, 45, 2293. (e) Hata, K.;
Hamamoto, H.; Shiozaki, Y.; Cämmerer, S. B.; Kita, Y. Tetrahe-
dron 2007, 63, 4052; and references cited therein.
(16) Recent reviews on dehydrogenative aromatic C–H aminations:
(a) Louillat, M.-L.; Patureau, F. W. Chem. Soc. Rev. 2014, 43, 901.
(b) Subramanian, P.; Rudolf, G. C.; Kaliappan, K. P. Chem. Asian J.
2016, 11, 168. (c) Jiao, J.; Murakami, K.; Itami, K. ACS Catal.
2016, 6, 610. (d) Kim, H.; Chang, S. ACS Catal. 2016, 6, 2341.
(e) Henry, M. C.; Mostafa, M. A. B.; Sutherland, A. Synthesis
2017, 49, 4586. (f) Park, Y.; Kim, Y.; Chang, S. Chem. Rev. 2017,
117, 9247. (g) Timsina, Y. N.; Gupton, B. F.; Ellis, K. C. ACS Catal.
2018, 8, 5732. Metal-free hypervalent iodine strategy:
(h) Samanta, R.; Matcha, K.; Antonchick, A. P. Eur. J. Org. Chem.
2013, 5769. (i) Samanta, R.; Antonchick, A. P. Synlett 2012, 23,
809.
(26) (a) Dohi, T.; Nakae, T.; Ishikado, Y.; Kato, D.; Kita, Y. Org. Biomol.
Chem. 2011, 9, 6899. (b) Dohi, T.; Kato, D.; Hyodo, R.; Yamashita,
D.; Shiro, M.; Kita, Y. Angew. Chem. Int. Ed. 2011, 50, 3784.
(c) Dohi, T.; Mochizuki, E.; Yamashita, D.; Miyazaki, K.; Kita, Y.
Heterocycles 2014, 88, 245.
(27) X-ray crystal structure data of PIFA: (a) Stergioudis, G. A.;
Kokkou, S. C.; Bozopoulos, A. P.; Rentzeperis, P. J. Acta Crystal-
logr., Sect. C 1984, 40, 877. PIDA: (b) Lee, C.-K.; Mak, T. C. W.; Li,
W.-K. Acta Crystallogr., Sect. B 1977, 33, 1620. (c) The reported
bond lengths of iodine(III) ligands in the hypervalent iodine
reagents, PIDA and PIFA as well as -oxo-bridged PIFA dimer
and our biaryl alternative Ib (see Figure 1 for the structures),
are summarized in Table 2 below.
Table 2 Bond Lengthsa
Reagent
I-X [Å]
I-O* [Å]
–
PhI(OAc)2
2.16
(X = OAc)
PhI(OCOCF3)2
2.16
(X = OCOCF3)
–
(17) Kikugawa, Y.; Kawase, M. Chem. Lett. 1990, 581.
-oxo-bridged PIFA dimer
(R = CF3)
2.27
(X = OCOCF3)
2.02
2.06
(18) (a) Kikugawa, Y.; Nagashima, A.; Sakamoto, T.; Miyazawa, E.;
Shiiya, M. J. Org. Chem. 2003, 68, 6739. (b) Miyazawa, E.;
Sakamoto, T.; Kikugawa, Y. Heterocycles 2003, 59, 149. (c) Serna,
S.; Tellitu, I.; Dominguez, E.; Moreno, I.; SanMartin, R. Tetrahe-
dron 2004, 60, 6533.
(19) For other early applications, see: (a) Romero, A. G.; Darlington,
W. H.; McMillan, M. W. J. Org. Chem. 1997, 62, 6582. (b) Correa,
A.; Tellitu, I.; Dominguez, E.; Moreno, I.; SanMartin, R. J. Org.
Chem. 2005, 70, 2256. (c) Wardrop, D. J.; Basak, A. Org. Lett.
2001, 3, 1053. (d) Wardrop, D. C.; Zhang, W. Org. Lett. 2001, 3,
2353.
(20) For reviews on catalytic utilizations of hypervalent iodine
reagents, see: (a) Richardson, R. D.; Wirth, T. Angew. Chem. Int.
Ed. 2006, 45, 4402. (b) Ochiai, M.; Miyamoto, K. Eur. J. Org.
Chem. 2008, 4429. (c) Dohi, T.; Kita, Y. Chem. Commun. 2009,
2073. (d) Yusubov, M. S.; Zhdankin, V. V. Mendeleev Commun.
2010, 20, 2073. (e) Singh, F. V.; Wirth, T. Chem. Asian J. 2014, 9,
950.
(21) For the first report of C–N bond-forming reaction using a cata-
lytic amount of hypervalent iodine, see: (a) Dohi, T.; Maruyama,
A.; Minamitsuji, Y.; Takenaga, N.; Kita, Y. Chem. Commun. 2007,
1224. (b) Moroda, A.; Togo, H. Synthesis 2008, 1257.
our -oxo catalyst Ibb
(R = R′ = Me)
2.23
(X = OAc)
a Averaged bond length for the reagents; O*: bridged oxygen.
b For the crystallographic data in CIF, see CCDC 779814.
(28) The existence of strong secondary bondings between the iodine
atoms and the ligand’s carbonyl oxygens appears in the struc-
ture, which was confirmed by the lower shift of carbonyl fre-
quencies for the -oxo PIFA in the infrared resonance spectra
compared to that of PIFA. These observations clearly account for
the enhanced cationic character of the iodine center, see:
(a) Alcock, N. W.; Countryman, R. M.; Esperas, S.; Sawyer, J. F.
J. Chem. Soc., Dalton Trans. 1979, 854. (b) Alcock, N. W.;
Harrison, W. D. J. Chem. Soc., Dalton Trans. 1984, 1709. (c) Bell,
R.; Morgan, K. J. J. Chem. Soc. 1960, 1209.
(29) Samanta, R.; Bauer, J. O.; Strohmann, C.; Antonchick, A. P. Org.
Lett. 2012, 14, 5518.
(30) (a) Minamitsuji, Y.; Kato, D.; Fujioka, H.; Dohi, T.; Kita, Y. Aust. J.
Chem. 2009, 62, 648. (b) Dohi, T.; Yamaoka, N.; Itani, I.; Kita, Y.
Aust. J. Chem. 2011, 64, 529.
(31) The TON of a catalyst, 1,2-diiodobenzene, at the 4 mol% loading
reached 18 times for the reaction between the same substrates
(toluene 2a, 15 equiv) in HFIP/DCE (1:1), see: Lucchetti, N.;
Scalone, M.; Fantasia, S.; Muñiz, K. Adv. Synth. Catal. 2016, 358,
2093.
(32) For utilities of N-methoxy anilides for unique transformations,
see: (a) Kikugawa, Y.; Shimada, M. J. Chem. Soc., Chem. Commun.
1989, 1450. (b) Matsumoto, K.; Kato, M.; Sakamoto, T.;
Kikugawa, Y. J. Chem. Res., Synop. 1995, 34. (c) Nakamura, I.; Jo,
T.; Ishida, Y.; Tashiro, H.; Terada, M. Org. Lett. 2017, 19, 3059.
(d) Ishida, Y.; Nakamura, I.; Terada, M. J. Am. Chem. Soc. 2018,
140, 8629; and references cited therein.
(33) See ref 9d and: (a) Dohi, T.; Ito, M.; Morimoto, K.; Minamitsuji,
Y.; Takenaga, N.; Kita, Y. Chem. Commun. 2007, 4152. (b) Ito, M.;
Ogawa, C.; Yamaoka, N.; Fujioka, H.; Dohi, T.; Kita, Y. Molecules
2010, 15, 1918. (c) Ito, M.; Itani, I.; Toyoda, Y.; Morimoto, K.;
Dohi, T.; Kita, Y. Angew. Chem. Int. Ed. 2012, 51, 12555.
(22) For early studies, see: (a) Alcock, N. W.; Waddington, T. C.
J. Chem. Soc. 1963, 4103. (b) Gallos, J.; Varvoglis, A.; Alcock, N.
W. J. Chem. Soc., Perkin Trans. 1 1985, 757.
(23) We have recently met the notably high reactivity of -oxo-
bridged PIFA dimer in organic solvents as well as in water, see:
(a) Dohi, T.; Uchiyama, T.; Yamashita, D.; Washimi, N.; Kita, Y.
Tetrahedron Lett. 2011, 52, 2212. (b) Takenaga, N.; Uchiyama, T.;
Kato, D.; Fujioka, H.; Dohi, T.; Kita, Y. Heterocycles 2011, 82,
1327. (c) Dohi, T.; Nakae, T.; Takenaga, N.; Uchiyama, T.;
Fukushima, K.; Fujioka, H.; Kita, Y. Synthesis 2012, 44, 1183.
(24) Dohi, T.; Takenaga, N.; Fukushima, K.; Uchiyama, T.; Kato, D.;
Shiro, M.; Fujioka, H.; Kita, Y. Chem. Commun. 2010, 46, 7697.
(25) For utilizations of our -oxo catalysts in other reactions, see:
Ito, M.; Kubo, H.; Itani, I.; Morimoto, K.; Dohi, T.; Kita, Y. J. Am.
Chem. Soc. 2013, 135, 14078; see also ref. 26.
Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–K

K
T. Dohi et al.
Feature
Synthesis
(34) For the reactivities of diaryliodonium(III) salt, see: (a) Merritt,
E. A.; Olofsson, B. Angew. Chem. Int. Ed. 2009, 48, 9052.
(b) Yusubov, M. S.; Maskaev, A. V.; Zhdankin, V. V. ARKIVOC
2011, (i), 370. (c) Olofsson, B. Top. Curr. Chem. 2016, 373, 135.
(d) Stuart, D. R. Chem. Eur. J. 2017, 23, 15852. (e) Yoshimura, A.;
Saito, A.; Zhdankin, V. V. Chem. Eur. J. 2018, 24, 15156. (f) Stang,
P. J.; Zhdankin, V. V. Chem. Rev. 1996, 96, 1123. (g) Müller, U.
Trends Photochem. Photobiol. 1999, 5, 117.
(40) For diaryliodonium(III) salt mediated C–N coupling strategies,
see: (a) Carroll, M. A.; Wood, R. A. Tetrahedron 2007, 63, 11349.
(b) Riedmueller, S.; Nachtsheim, B. J. Synlett 2015, 26, 651.
(c) Yang, Y.; Wu, X.; Han, J.; Mao, S.; Quian, X.; Wang, L. Eur. J.
Org. Chem. 2014, 6854. (d) Tinnis, F.; Stridfeldt, E.; Lundberg, H.;
Adolfsson, H.; Olofsson, B. Org. Lett. 2015, 17, 2688.
(e) Lucchetti, N.; Scalone, M.; Fantasia, S.; Muñiz, K. Angew.
Chem. Int. Ed. 2016, 55, 13335. (f) Sandtorv, A. H.; Stuart, D. R.
Angew. Chem. Int. Ed. 2016, 55, 15812. (g) Basu, S.; Sandtorv, A.
H.; Stuart, D. R. Beilstein J. Org. Chem. 2018, 14, 1034. (h) Purkait,
N.; Kervefors, G.; Linde, E.; Olofsson, B. Angew. Chem. Int. Ed.
2018, 57, 11427.
(35) For ortho-directing effect of amide-containing reagent involving
pseudo-cyclic intermediate in electrophilic aromatic substitu-
tions, see: Shen, H.; Vollhardt, K. P. C. Synlett 2012, 23, 208.
(36) Transition-metal-catalyzed oxidative amidations for aromatic
hydrocarbons with stoichiometric hypervalent iodine reagent,
see: (a) Shrestha, R.; Mukherjee, P.; Tan, Y.; Litman, Z. C.;
Harwig, J. F. J. Am. Chem. Soc. 2013, 135, 8480. (b) Marchetti, L.;
Kantak, A.; Davis, R.; DeBoef, B. Org. Lett. 2015, 17, 358.
(c) Berzina, B.; Sokolovs, I.; Suna, E. ACS Catal. 2015, 5, 7008.
(d) Ito, E.; Fukushima, T.; Kawakami, T.; Murakami, K.; Itami, K.
Chem 2017, 2, 383. The combination of transition metal ([Co])
with photocatalyst: (e) Niu, L.; Yi, H.; Wang, S.; Liu, T.; Liu, J.;
Lei, A. Nat. Commun. 2017, 8, 14226. The use of 0.5 mol%
amount of iridium-based photocatalyst was reported, while the
product yields was up to 52% in this case: (f) Kim, H.; Kim, T.;
Lee, D. G.; Roh, S. W.; Lee, C. Chem. Commun. 2014, 50, 9273.
(37) (a) Brasche, G.; García-Fortanet, J.; Buchwald, S. L. Org. Lett.
2008, 10, 2207. For a recent review of transition-metal-cata-
lyzed ortho C–H functionalizations of aniline derivatives, see:
(b) Leitch, J. A.; Frost, C. G. Synthesis 2018, 50, 2693.
(41) (a) Morimoto, K.; Ohnishi, Y.; Nakamura, A.; Sakamoto, K.;
Dohi, T.; Kita, Y. Asian J. Org. Chem. 2014, 3, 382. (b) Morimoto,
K.; Ogawa, R.; Koseki, D.; Takahashi, Y.; Dohi, T.; Kita, Y. Chem.
Pharm. Bull. 2015, 63, 819.
(42) Related -oxo-bridged chiral hypervalent iodine catalysts:
(a) Dohi, T.; Maruyama, A.; Takenage, N.; Senami, K.;
Minamitsuji, Y.; Fujioka, H.; Cämmerer, S.; Kita, Y. Angew. Chem.
Int. Ed. 2008, 47, 3787. (b) Dohi, T.; Takenaga, N.; Nakae, T.;
Toyoda, Y.; Yamasaki, M.; Shiro, M.; Fujioka, H.; Maruyama, A.;
Kita, Y. J. Am. Chem. Soc. 2013, 135, 4558. (c) Suzuki, S.; Kamo,
T.; Fukushi, K.; Hiramatsu, T.; Tokunaga, E.; Dohi, T.; Kita, Y.;
Shibata, N. Chem. Sci. 2014, 5, 2754. (d) Ogasawara, M.; Sasa, H.;
Hu, H.; Amano, Y.; Nakajima, H.; Takenaga, N.; Nakajima, K.;
Kita, Y.; Takahashi, T.; Dohi, T. Org. Lett. 2017, 19, 4102. (e) Dohi,
T.; Sasa, H.; Miyazaki, K.; Fujitake, M.; Takenaga, N.; Kita, Y.
J. Org. Chem. 2017, 82, 11954.
(38) Antonchick reported this type of coupling reaction using PIDA
as a stoichiometric amount: Antonchick, A. P.; Samanta, R.;
Kulikov, K.; Lategahn, J. Angew. Chem. Int. Ed. 2011, 50, 8605.
(39) Representative examples: (a) Kim, H. J.; Kim, J.; Cho, S. H.;
Chang, S. J. Am. Chem. Soc. 2011, 133, 16382. (b) Kantak, A. A.;
Potavathri, S.; Barham, R. A.; Romano, K. M.; DeBoef, B. J. Am.
Chem. Soc. 2011, 133, 19960. (c) Samanta, R.; Lategahn, I.;
Antonchick, A. P. Chem. Commun. 2012, 48, 3194. (d) Manna, S.;
Serebrennikova, P. O.; Utepova, I. A.; Antonchick, A. P.;
Chupakhin, O. N. Org. Lett. 2015, 17, 4588. (e) Pialat, A.; Bergès,
J.; Sabourin, A.; Vinck, R.; Liégault, B.; Taillefer, M. Chem. Eur. J.
2015, 21, 10014. (f) Mondal, S.; Samanta, S.; Jana, S.; Hajra, A.
J. Org. Chem. 2017, 82, 4504. (g) Zhao, F.; Sun, T.; Sun, H.; Xi, G.;
Sun, K. Tetrahedron Lett. 2017, 58, 3132. (h) Maiti, S.; Mal, P.
J. Org. Chem. 2018, 83, 1340.
(43) Utilizing our spirobiindane catalysts (see refs 42a and 42b), Cai
and co-workers recently developed intramolecular oxidative C–
N cyclizations accompanying asymmetric desymmetrization of
the substrates, see: Ding, Q.; He, H.; Cai, Q. Org. Lett. 2018, 20,
4554.
(44) (a) Kawase, M.; Kitamura, T.; Kikugawa, Y. J. Org. Chem. 1989,
54, 3394. (b) Miyata, O.; Koizumi, T.; Asai, H.; Iba, R.; Naito, T.
Tetrahedron 2004, 60, 3893. (c) Xie, W.; Yang, J.; Wang, B.; Li, B.
J. Org. Chem. 2014, 79, 8278. (d) Brosse, N.; Pinto, M.; Jamart-
Gregoire, B. Eur. J. Org. Chem. 2003, 4757.
(45) (a) Tohma, H.; Morioka, H.; Takizawa, S.; Arisawa, M.; Kita, Y.
Tetrahedron 2001, 57, 345. (b) Tohma, H.; Iwata, M.; Maegawa,
T.; Kita, Y. Tetrahedron Lett. 2002, 43, 9241.
Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–K