Dirhodium-Catalyzed Chemo-and Site-Selective C-H Amidation of N, N-Dialkylanilines

Article abstract of DOI:10.1055/a-1334-6450

A method for dirhodium-catalyzed C(sp ³)-H amidation of N, N-dimethylanilines was developed. Chemoselective C(sp ³)-H amidation of N-methyl group proceeded exclusively in the presence of C(sp ²)-H bonds of the electron-rich aromatic ring. Site-selective C(sp ³)-H amidation proceeded exclusively at the N-methyl group of N-methyl-N-Alkylaniline derivatives with secondary, tertiary, and benzylic C(sp ³)-H bonds α to a nitrogen atom.

Full text of DOI:10.1055/a-1334-6450

SYNLETT
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart
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020, 31, 728–732
letter
728
en
Synlett
G. Chen et al.
Letter
Dirhodium-Catalyzed Chemo- and Site-Selective C–H Amidation
of N,N-Dialkylanilines
Gong Chen
3
chemoselective for C(sp )–H
site-selective for N–Me group
Kenta Arai
H
N
R’
R
R’
R
H
Kazuhiro Morisaki
Takeo Kawabata
Yoshihiro Ueda*
Rh2 catalyst
TrocNHOTs
H
H
H
N
NHTroc
base
0
0
0
0
-
0
0
0
2
-
5
4
8
5
-2
7
2
2
2
1 examples
3
6–80% yield
Institute for Chemical Research, Kyoto University, Gokasho, Uji,
Kyoto 611-0011, Japan
ueda@fos.kuicr.kyoto-u.ac.jp
YIe nMo s stahi itCiluhoutirer rodef oasU pr@eoCfdonhasde . imkn ugi iccAar lu. kRt yhe oos teroa - ruc .ha ,c K. j py oto University, Gokasho, Uji, Kyoto 611-0011, Japan
Received: 16.11.2020
Accepted after revision: 10.12.2020
Published online: 10.12.2020
3
(
a) Precedents for C(sp )–H amidation via iminium intermediates or the equivalents
oxidative conditions
N source
N
H
(amide or imide)
N
N
X
DOI: 10.1055/a-1334-6450; Art ID: st-2020-u0599-l
N
H
Cu, Fe catalyst
or
3
Abstract A method for dirhodium-catalyzed C(sp )–H amidation of
N,N-dimethylanilines was developed. Chemoselective C(sp )–H amida-
tion of N-methyl group proceeded exclusively in the presence of C(sp )–
H bonds of the electron-rich aromatic ring. Site-selective C(sp )–H ami-
dation proceeded exclusively at the N-methyl group of N-methyl-N-al-
kylaniline derivatives with secondary, tertiary, and benzylic C(sp )–H
bonds  to a nitrogen atom.
transition-metal-free
conditions
N
3
N = amide or imide
2
3
3
(b) This work 1 : Chemoselective C(sp )–H amidation
by direct C–H insertion with dirhodium nitrenes
3
H
Rh2 catalyst
TrocNHOTs
Ph
N
H
H
N
H
N
NHTroc
H
base
Rh Rh
NTroc
Key words C–H amidation, dirhodium complex, aniline, nitrene, site
selectivity
3
(
c) This work 2 : Site-selective C(sp )–H amidation at N-methyl groups
H
H
R’
R
R’
R
Rh2 catalyst
TrocNHOTs
Development of methods for the construction of C–N
bonds is still of great synthetic importance in current syn-
thetic organic chemistry because C–N bonds are ubiqui-
N
H
N
NHTroc
base
1
3
Scheme 1 C(sp )–H amidation of N,N-dialkylanilines. (a) Reported
tously involved in functional materials and bioactive mole-
3
C(sp )–H amidation of N,N-dimethylanilines under oxidative conditions.
2
cules. Especially, direct C–N bond formation through C–H
3
(
b) Dirhodium-catalyzed chemoselective C(sp )–H amidation of N,N-di-
bond cleavage represents an attractive and efficient access
methylanilines. (c) Dirhodium-catalyzed site-selective (N-methyl-group
selective) C(sp )–H amidation of N-alkyl-N-methylanilines (alkyl ≠ methyl).
3
3
to such functional molecules. During the past two decades,
considerable achievements have been made for C–H amida-
tion of N,N-dimethylaniline derivatives via cross-dehydro-
3
amidation via a direct C–H insertion process.3,9 Although
significant progress has been made in dirhodium-catalyzed
genative coupling between amides and C(sp )–H bonds  to
a nitrogen atom (Scheme 1a).4 Under these oxidative con-
ditions, C–H amidation proceeds via an iminium intermedi-
ate or the equivalent. For example, Fu and co-workers de-
–6
3
C–H amidation of electron-rich C(sp )–H bonds such as ter-
3
3
tiary C(sp )–H and C(sp )–H bonds  to a C–C multiple bond
3
veloped Cu-catalyzed C(sp )–H amidation of N,N-dimeth-
and an oxygen atom, only few examples of amidation of
3
ylanilines with amides and imides in the presence of tert-
C(sp )–H bonds  to a nitrogen atom have been reported.
4
a
butyl hydroperoxide as an oxidant. Fe-catalyzed oxidative
Ito, Sugiyama, and co-workers reported dirhodium-cata-
5
3
2
protocols as well as transition-metal-free C(sp )–H amida-
lyzed C(sp )–H amidation of N,N-dialkylaniline derivatives
6
,7
3
tion have also been developed.
ortho to aniline nitrogen, in which C(sp )–H amidation was
3
On the other hand, metal-mediated C(sp )–H amidation
also observed as a side reaction. (The amidated product was
not isolated due to the instability of the aminal structure.)1
In contrast to the report, we found that the C–H amidation
0

to a nitrogen atom via nitrene intermediates has been rel-
8
atively unexplored. Dirhodium nitrene complexes have
been known to be representative active species for C–H
3
took place chemoselectively at the C(sp )–H bond in dirho-
©
2020. Thieme. All rights reserved. Synlett 2021, 32, 728–732
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

729
Synlett
G. Chen et al.
Letter
dium-catalyzed reactions of N,N-dialkylaniline derivatives.
Table 1 Optimization of the Conditions for C–H Amidation of N,N-Di-
methylaniline (1a)
Here, we report a general method for dirhodium-catalyzed
3
C(sp )–H amidation of N,N-dimethylanilines using O-tosyl-
11
Rh2 cat. (5 mol%)
ROCONHOTs (1.0 equiv)
base (1.5 equiv)
H
N
N-trichloroethoxycarbonylhydroxylamine(TrocNHOTs) as
N
H
N
OR
3
a nitrene source (Scheme 1b). The C(sp )–H amidation takes
O
solvent, r.t., 12 h
places chemoselectively in the presence of potentially reac-
1
a (1.5 equiv)
2
aa (R = CH2CCl3)
2ab (R = CH2CF3)
ac (R = CH2CBr3)
2
tive C(sp )–H bonds of the electron-rich aromatic ring. The
2
chemoselectivity shown in Scheme 1b is also in contrast to
our previous report that dirhodium-catalyzed C–H amida-
Entry Catalyst
R
Solvent
Base
K2CO3
Yield of 2a (%)a
2
tion of anisole derivatives took place at the aromatic C(sp )–
1
2
H bond. Another salient feature of the present process is
1
2
3
4
5
6
7
8
9
Rh (tpa)
CH CCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
EtOAc
0
2
4
2
3
3
3
3
3
3
3
site selectivity of the C(sp )–H amidation. Control of the site
Rh
Rh
Rh
Rh
Rh
2
2
2
2
2
(esp)
(OAc)
(tfa)
(piv)
(oct)
2
CH
CH
CH
CH
CH
2
2
2
2
2
CCl
CCl
CCl
CCl
CCl
K
K
K
K
K
2
2
2
2
2
CO
CO
CO
CO
CO
3
3
3
3
3
39
42
36
40
46
39
43
40
60
49
51
52
48
60
44
30
41
54
40
79
3
selectivity is still of challenge in C(sp )–H amidation of N,N-
4
dialkylanilines with two different alkyl groups. For exam-
3
4
ple, nonselective C(sp )–H amindation of methyl and ben-
3
4
zylic C(sp )–H bonds  to nitrogen was reported to take
place in copper-catalyzed C–H amindation of N-benzyl-N-
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
a,d
methylaniline.
On the other hand, under the present
Rh (oct)
CH CF
3
K2CO3
2
2
3
conditions, C(sp )–H amidation of the N-methyl group of
various N-alkyl-N-methylanilines (alkyl ≠ methyl) was ob-
served exclusively even in the presence of potentially reac-
tive benzylic and tertiary C–H bonds  to the nitrogen atom
Rh
Rh
Rh
Rh
Rh
2
2
2
2
2
(oct)
(oct)
(oct)
(oct)
(oct)
CH
CH
CH
CH
CH
2
2
2
2
2
CBr
3
K
K
K
K
K
2
2
2
2
2
CO
CO
CO
CO
CO
3
3
3
3
3
CCl
CCl
CCl
CCl
3
3
3
3
3
3
3
3
3
3
3
3
3
10
2 2
CH Cl
11
CHCl
PhH
PhF
3
(
Scheme 1c).
We commenced our studies on C–H amidation with
12
13
N,N-dimethylaniline (1a) as a substrate in the presence of
various dirhodium catalysts, O-tosyl-N-trihaloethoxycar-
bonylhydroxylamines as nitrene sources, and bases (Table
Rh (oct)
CH CCl
K2CO3
2
2
1
4
5
Rh
Rh
Rh
Rh
Rh
Rh
Rh
Rh
2
2
2
2
2
2
2
2
(oct)
(oct)
(oct)
(oct)
(oct)
(oct)
(oct)
(oct)
CH
CH
CH
CH
CH
CH
CH
CH
2
2
2
2
2
2
2
2
CCl
CCl
CCl
CCl
CCl
CCl
CCl
CCl
PhCF
3
K
K
2
CO
CO
3
1
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
2
3
1
). According to the previously optimized conditions for C–
1
2
13
16
Li
2
CO
3
H amination of anisole derivatives and organosilanes, 1a
1.5 equiv) was treated with TrocNHOTs in the presence of
Rh (tpa) and K CO in chlorobenzene at room temperature
17
Na
2
CO
3
(
18
Cs
2
CO
3
2
4
2
3
to give no C–H-amidated products (entry 1). Use of
1
2
2
9
Rb
2
CO
3
9e
3
Rh (esp) in place of Rh (tpa) gave the desired C(sp )–H-
2
2
2
4
0
KOAc
amidated product 2aa in 39% yield (entry 2). Further cata-
1b
K
CO
3
3
2
lyst screening revealed that Rh (oct) promoted the C(sp )–
2
4
H amidation most effectively to give 2aa in 46% yield (entry
vs 1–5). We assume that lack of the catalytic activity of
Rh (tpa) in the C–H amidation seems to be due to inactiva-
Ph
Me
Me
Me
CF
3
7 15
n-C H
6
Ph
Ph
Me
Me
O
O
O
O
O
O
O
O
2
4
O
O
O
Me
Me
Rh Rh
Rh Rh
tion by stronger and irreversible coordination of 1a to Rh of
Rh (tpa) , while coordination of 1a to Rh of Rh (oct) ap-
Rh
Rh Rh
O
Rh Rh
Rh
2
4
2
4
Rh (tpa)
2
4
Rh
2
(esp)
2
Rh
2
(tfa)
4
2
Rh (piv)
4
2 4
Rh (oct)
pears to be weaker and reversible (for association energies
of 1a with Rh (tpa) and Rh (OAc) , see Scheme S1 in the
a
Determined by crude
nal standard.
Run with 10 equiv of 1a.
1
H NMR analysis, using 1,3-dinitrobenzene as inter-
2
4
2
4
Supporting Information). This behavior could also be ob-
served by the color change of the reaction solution. While
the color of the solution of coordination-free dirhodium
complexes is usually green, it changes to pink by coordina-
tion of 1a to Rh. The color of the solution of 1a and
Rh (tpa) was light pink, indicative of formation of inactive
b
suitable for the purpose (entries 9–15). It is worthy to note
3
that benzylic methyl C(sp )–H bonds of toluene were totally
inactive for amidation, even when toluene was used as a
solvent (entry 15). Use of bases such as Li CO , Na CO , Cs -
2
4
Rh complexes. On the other hand, the color of the solutions
2
3
2
3
2
of 1a and Rh (OAc)4 or Rh (oct) was purple, which may
CO , or Rb CO did not improve the yield of the amidation
2
2
4
3 2 3
suggest weak and reversible coordination of 1a to Rh. Use of
reaction (entry 15 vs 16–20). Finally, the yield of amidation
was improved by use of 10 equivalents of the substrate to
afford the desired 2aa in 79% yield (entry 21).
other nitrene sources with trifluoroethyl and tribromoethyl
3
groups provided C(sp )–H amidated product 2ab and 2ac,
respectively, in the comparable yields (entries 7 and 8). By
solvent screening, CH Cl2 and toluene were found most
2
©
2020. Thieme. All rights reserved. Synlett 2021, 32, 728–732

730
Synlett
G. Chen et al.
Letter
Substrate scope was then investigated with various N,N-
dimethylarylamines under the optimized conditions for the
C–H amidation (Table 1, entry 21; Scheme 2). Substrates 1b,
sumed and the formation of TrocNH was observed, which
2
indicated partial decomposition of the aminating agent un-
1
1b,15,16c
der the reaction conditions.
1
c, and 1d with chloro, bromo, and iodo groups, respective-
H
Rh2(oct)4 (5 mol%)
TrocNHOTs (1.0 equiv)
K CO (1.5 equiv)
NHTroc
ly, at C(4) successfully gave the amidated products 2b, 2c,
and 2d, respectively, in good yields. On the same treatment,
4
with the benzylic methyl C(sp )–H bonds remained intact.
Either an electron-withdrawing or electron-donating group
at C(4) did not affect the efficiency of the C(sp )–H amida-
N
R1
R2
N
R1
2
3
Ar
Ar
R2
,N,N-trimethylaniline (1e) gave 2e as a single regioisomer
H
p–u
toluene, r.t., 12 h
H
1
2p–u
3
method A: 10 equiv
method B: 1.5 equiv
3
NHTroc
NHTroc
NHTroc
N
n-C7H15
3
tion reaction (2f–h). The present procedure for C(sp )–H
N
Me
N
n-C3H7
amidation was found applicable to aniline derivatives 1i–m
with various substituents at the C(2). Compound 1o with a
H
H
H
2
p, A: 40% (33%)
B: 40%
2q, A: 50% (43%)
2r, A: 51% (40%)
1
4
dansyl group, a widely used fluorescent group, also un-
B: 40%
B: 36%
3
derwent selective amidation of the C(sp )–H bond  to the
NHTroc
TrocHN
NHTroc
nitrogen atom. With all the 15 N-methylaniline derivatives
N
N
Me
Me
N
3
Me
H
examined, chemoselective C(sp )–H amidation was ob-
H
H
2
served exclusively in the presence of aromatic C(sp )–H
2
s, A: 52% (42%)
B: 40%
2t, A: 44% (37%)
2u, A: 36% (33%)
bonds. In all cases, TrocNHOTs was almost completely con-
B: 30%
B: 18%
3
Scheme 3 Site selectivity of C(sp )–H amidation of N-alkyl-N-meth-
ylaniline derivatives. The yields were determined by crude H NMR anal-
ysis, using 1,3-dinitrobenzene as internal standard; isolated yields are
given in parentheses.
1
H
Rh2(oct)4 (5 mol%)
TrocNHOTs (1.0 equiv)
K CO (1.5 equiv)
NHTroc
N
N
2
3
Ar
Ar
1
b–o
2b–o
toluene, r.t., 12 h
method A: 10 equiv
method B: 1.5 equiv
Site selectivity of the C–H amidation was investigated
using several aniline derivatives with N-alkyl-N-methyl
groups (alkyl ≠ methyl, Scheme 3). Treatment of N-ethyl-N-
methylaniline (1p) by the present protocol provided the N-
methyl-amidated product 2p as a single regioisomer. Poten-
tial reactivity of the N-ethyl group toward the C–H amida-
tion might be missed because of the instability of the C–H
amidation product generated at the N-ethyl group if
NHTroc
NHTroc
NHTroc
N
N
N
Cl
Br
I
2
2
b, A: 77% (75%)
2c, A: 79% (71%)
2d, A: 74% (69%)
B: 47%
B: 36%
B: 46%
NHTroc
NHTroc
NHTroc
N
N
N
8
b,10
Me
MeO2C
EtO2C
any.
However, this concern seems not to be the case be-
e, A: 53% (41%)
2f, A: 80% (73%)
2g, A: 71% (63%)
cause N-methylaniline, a dealkylated product supposed to
be obtained by decomposition of the aminal generated at
the N-ethyl group, was not obtained. Thus, amidation of 1p
B: 20%
B: 45%
B: 49%
NHTroc
NHTroc
NHTroc
Cl
Br
N
N
N
3
took place site-selectively at the primary C(sp )–H bond ad-
3
MeO
jacent to the nitrogen atom. Similarly, C(sp )–H amidation
2
h, A: 62% (53%)
2i, A: 56% (44%)
2j, A: 71% (59%)
B: 32%
of substrate 1q and 1r with an n-butyl and an n-octyl group
provided N-methyl-amidated products 2q and 2r, respec-
tively, as the single regioisomers. Notably, substrates 2s and
B: 26%
B: 32%
NHTroc
NHTroc
NHTroc
I
Me
OMe
N
N
N
3
2
t with tertiary and benzylic C(sp )–H bonds  to the nitro-
3
gen atom underwent amidation at the primary C(sp )–H
bond selectively, to give 2s and 2t, respectively. The present
method was also applicable to N-methyl-selective C–H ami-
dation of indoline derivative 1u with an electronically reac-
2
k, A: 56% (52%)
2l, A: 53% (43%)
2m, A: 61% (54%)
B: 36%
B: 20%
B: 36%
NHTroc
NHTroc
N
N
PhO3S
3
tive tertiary C(sp )–H bond adjacent to a nitrogen atom.
When slight excess amounts (1.5 equivalents) of the sub-
strates were employed, decrease in the yields of the desired
products was observed in most cases, while products 2p,
2
n, A: 55% (48%)
B: 40%
2o, A: 67% (59%)
B: 40%
3
Scheme 2 Chemoselective C(sp )–H amidation of N,N-dimethylaryl-
amines. The yields were determined by crude H NMR analysis, using
,3-dinitrobenzene as internal standard; isolated yields are given in pa-
2
q, and 2s were obtained in comparable yields with those
1
obtained by the original procedure using 10 equivalents of
substrates (Scheme 2 and 3).
1
rentheses.
©
2020. Thieme. All rights reserved. Synlett 2021, 32, 728–732

731
Synlett
G. Chen et al.
Letter
2
3
NHTroc
provide C(sp )–H-amidated product 4. In the C(sp )–H ami-
dation of N-benzyl-N-methylaniline (1t), steric effect would
be dominant to control the site selectivity. The dirhodium
nitrene species are expected to be selectively inserted into
N
Rh2(oct)4 (5 mol%)
TrocNHOTs (1.0 equiv)
K2CO3 (1.5 equiv)
Ph
N
N
Ph
1
a (1.5 equiv)
2aa
+
+
toluene, r.t., 10 min
1
6–19% conversion
D
D
NDTroc
3
CD3
N
the sterically more accessible primary C(sp )–H bond adja-
cent to the nitrogen atom rather than the electronically
more favorable secondary benzylic C(sp )–H bonds. Similar
Ph
CD3
kH/kD = 3.7
Ph
CD3
3
1
a-d6 (1.5 equiv)
2aa-d6
site selectivity was also observed in -silicon-effect-pro-
Scheme 4 Determination of a kinetic isotope effect (KIE) by competi-
tive reaction between 1a and 1a-d6
3
moted C(sp )–H amidation of organosilicon compounds
1
3
with dirhodium nitrene species.
An application to two-step demethylation of the N-
methyl aniline derivative 1r was demonstrated (Scheme 6).
Treatment of 2r obtained by C(sp )–H amidation of 1r with
Rh Rh
O
O
3
TrocNH-OTs
K2CO3
TrocHN
O
4
Cs CO in toluene under reflux conditions afforded the de-
2
3
Rh Rh
N
KOTs
Troc
3
sired N-demethylated product of 1r, phenyloctylamine (5),
in 58% yield. While N-demethylation reaction seems to be
one of the valuable structural modifications of natural
KHCO3
ref. 12
NHTroc
Rh Rh
N
=
N
H
Troc
1a
1
7
2a
products and drug candidates, the methods for N-de-
methylation have been quite limited. The present method is
assumed to be potentially useful for the application to late-
stage functionalization of bioactive molecules containing
N
Ph
1t
NHTroc
H
N
Ph
Rh Rh
NTroc
Rh2(O2CR)4
Rh Rh
2t
1
8
aromatic N-methyl group.
Scheme 5 Possible reaction paths depending on the substrates
Cs2CO3
(1.5 equiv)
H
conditions
in Scheme 3
NHTroc
H
To get insights into the reaction mechanism, the kinetic
isotope effect (KIE) of the reaction was measured (Scheme
N
N
N
toluene, reflux Ph
n-C8H17
Ph
n-C8H17
Ph
n-C8H17
6
h, 58%
1
r
2r
5
4
). The KIE value was determined by the competitive reac-
Scheme 6 Two-step demethylation of N-methyl-N-octylaniline (1r)
tion of a 1:1 mixture of 1a and 1a-d to be k /k = 3.7. This
6
H
D
result indicated that the C–H bond cleavage is involved in
the product-determining step. Possible reaction paths and
our hypothetical understanding for chemo- and site selec-
tivity of dirhodium-catalyzed C–H amidation depending on
the substrates are described in Scheme 5. A dirhodium ni-
trene complex is assumed to be generated from the dirhodi-
um tetracarboxylate complex, TrocNHOTs, and K CO ac-
In summary, we have developed a general method for
3
the C(sp )–H amidation of various N-methyl-N-alkylaniline
1
9
derivatives catalyzed by dirhodium complexes. A primary
3
C(sp )–H bond of the N-methyl group was selectively con-
verted into the C–N bond in the presence of the secondary,
3
tertiary, and benzylic C(sp )–H bonds  to a nitrogen atom.
2
3
cording to the previous reports.1
1,16
The nitrene species was
The protocol was successfully applied to a two-step de-
methylation process of a N-methylaniline derivative. Fur-
ther studies on mechanistic analysis and late-stage func-
tionalization of complex molecules of biological interests
are currently underway.
3
expected to be inserted into the C(sp )–H bond  to the ni-
trogen atom of 1a in a concerted asynchronous manner, in-
cluding a hydride-transfer process assisted by effective do-
nation of the lone-pair electron of the neighboring nitrogen
atom. On the other hand, dirhodium-catalyzed C–H amida-
2
tion of anisole (3) took place at the aromatic para-C(sp )–H
Funding Information
3
bond even in the presence of C(sp )–H bonds  to the oxy-
12
gen atom. The difference in chemoselectivity could be as-
cribed to the difference in the electronegativity between ni-
trogen and oxygen. The partial positive charge developed in
This research was financially supported by Grants-in-Aids for Scien-
tific Research S (JP26221301) and Scientific Research C (JP20K06964)
from the Japan Society for the Promotion of Science. Y.U. acknowledg-
es the financial support from the Uehara Memorial Foundation. G.C.
acknowledges the China Scholarship Council for the financial support.
3
the transition state of C(sp )–H amidation of the N-methyl
group in 1a would be stabilized by the adjacent nitrogen
lone pair. On the other hand, such stabilization may not to
be effectively operative in the reaction of anisole because of
the stronger negative inductive effect of oxygen than nitro-
gen. As the result, electrophilic aromatic substitution of the
electron-rich aromatic ring of 3 would take place at the
para position distal from the oxygen atom to selectively
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Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/a-1334-6450. Su
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©
2020. Thieme. All rights reserved. Synlett 2021, 32, 728–732

732
Synlett
G. Chen et al.
Letter
References and Notes
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19) General Procedure for Dirhodium-Catalyzed C(sp )–H Ami-
dation of N,N-Dialkylanilines
(
c) Satheesh, V.; Sengoden, M.; Punniyamurthy, T. J. Org. Chem.
2
016, 81, 9792.
To a suspension of N,N-dialkylanilines (0.5 mmol, 10 equiv),
TrocNHOTs (18.1 mg, 0.05 mmol, 1.0 equiv), and K CO (10.4
3
(
7) C(sp )–H amidation with hypervalent iodine reagents or N-
haloimide reagents: (a) Kiyokawa, K.; Kosaka, T.; Kojima, T.;
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2
3
mg, 0.075 mmol, 1.5 equiv) in toluene (0.25 mL) were added
Rh (oct) (1.9 mg, 0.05 equiv) at room temperature. After being
2
4
stirred for 12 h, the reaction was quenched by addition of water
and extracted with EtOAc. The organic layer was washed with
brine and dried over Na SO , filtered, and concentrated. The
3
(
8) Cu-nitrene-mediated C(sp )–H amidation of N-methylaniline
derivatives has been reported, see: (a) Liu, X. W.; Zhang, Y. M.;
Wang, L.; Fu, H.; Jiang, Y. Y.; Zhao, Y. F. J. Org. Chem. 2008, 73,
2
4
1
yields of the aminated product 2 were determined by H NMR
analysis using 1,3-dinitrobenzene as internal standard. The
residue was purified by preparative TLC purification to afford
the aminated product 2.
6207. (b) Bagchi, V.; Paraskevopoulou, P.; Das, P.; Chi, L.; Wang,
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Chem. Soc. 2014, 136, 11362.
Trichloroethyl{[methyl(phenyl)amino]methyl}carbamate
(
9) For selected pioneering examples, see: (a) Breslow, R.; Gellman,
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Bernardinelli, G.; Jacquire, Y.; Moran, M.; Müller, P. Helv. Chim.
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Int. Ed. 2001, 40, 598. (d) Yamawaki, M.; Tsutsui, H.; Kitagaki, S.;
Anada, M.; Hashimoto, S. Tetrahedron Lett. 2002, 43, 9561.
(
2aa)
1
Colorless oil. H NMR (400 MHz, CDCl , 323 K):  = 7.29–7.25
3
(m, 2 H), 6.84–6.81 (m, 3 H), 5.41 (br s, 1 H), 4.91 (d, J = 6.0 Hz, 2
13
H), 4.73 (s, 2 H), 3.01 (s, 3 H). C NMR (100 MHz, CDCl ):  =
1
3
cm
3
54.9, 147.7 129.6, 118.7, 113.6, 95.5, 74.6, 59.6, 37.8. IR (neat):
326, 2952, 1722, 1598, 1499, 1367, 1220, 1132, 1041, 817, 750
(e) Espino, C. G.; Fiori, K. W.; Kim, M.; Du Bois, J. J. Am. Chem.
–1
+
+
. HRMS-ESI : m/z calcd for C11H13Cl N O [M + H] :
3 2 2
311.0115; found: 311.0115.
©
2020. Thieme. All rights reserved. Synlett 2021, 32, 728–732