Rhodium-Catalyzed ortho-Bromination of O-Phenyl Carbamates Accelerated by a Secondary Amide-Pendant Cyclopentadienyl Ligand

Article abstract of DOI:10.1002/chem.202000253

It has been established that a newly developed cyclopentadienyl rhodium(III) [Cp^ARh^III] complex, bearing an acidic secondary amide moiety on the Cp ring, is able to catalyze the ortho-bromination of O-phenyl carbamates with N-bromosuccinimide (NBS) at room temperature. The presence of the acidic secondary amide moiety on the Cp^A ligand accelerates the bromination by the hydrogen bond between the acidic NH group of the Cp^A ligand and the carbonyl group of NBS.

Full text of DOI:10.1002/chem.202000253

A Journal of
Accepted Article
Title: Rhodium-Catalyzed Ortho-Bromination of O-Phenyl Carbamates
Accelerated by a Secondary Amide-Pendant Cyclopentadienyl
Ligand
Authors: Jin Tanaka, Yu Shibata, Anton Joseph, Juntaro Nogami,
Jyunichi Terasawa, Ryo Yoshimura, and Ken Tanaka
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To be cited as: Chem. Eur. J. 10.1002/chem.202000253
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10.1002/chem.202000253
Chemistry - A European Journal
COMMUNICATION
Rhodium-Catalyzed Ortho-Bromination of O-Phenyl Carbamates
Accelerated by a Secondary Amide-Pendant Cyclopentadienyl
Ligand
Jin Tanaka, Yu Shibata, Anton Joseph, Juntaro Nogami, Jyunichi Terasawa, Ryo Yoshimura, and Ken
Tanaka*
Abstract: It has been established that
a
newly developed
palladium-catalyzed reaction, but a strong Brønsted acid (TsOH)
and elevated temperatures (80–120 °C) were necessary.[14a]
Rao succeeded in the room temperature reaction, but a more
strong Brønsted acid (TfOH) was necessary.[14b] These strong
Brønsted acid additives deter the use of acid-sensitive
substrates. Glorius reported the Cp*RhIII complex-catalyzed
reaction, which avoids the use of Brønsted acid additives.[14c]
However, this reaction suffered from concurrent dibromination,
cyclopentadienyl rhodium(III) [CpARhIII] complex, bearing an acidic
secondary amide moiety on the Cp ring, is able to catalyze the ortho-
bromination of O-phenyl carbamates with N-bromosuccinimide
(NBS) at room temperature. The presence of the acidic secondary
amide moiety on the CpA ligand accelerates the bromination by the
hydrogen bond between the acidic NH group of the CpA ligand and
the carbonyl group of NBS.
and required an elevated temperature (120 °C) and
stoichiometric amount of Cu(OAc)2.
a
Aryl halides are important compounds in biological and
material science, and useful intermediates in organic
synthesis.[1] Particularly in organic synthesis, aryl bromides have
been widely used as substrates in the transition-metal-catalyzed
cross-coupling reactions due to their high reactivity and stability
comparing with aryl chlorides and iodides, respectively.[2] The
most frequently employed method for the synthesis of aryl
bromides is the electrophilic aromatic substitution reaction with
electrophilic bromination reagents.[3] However, this method
affords a mixture of ortho- and para-bromination products
accompanied by dibromination products (Scheme 1a). For the
regioselective bromination of arenes, the Sandmeyer reaction[4]
and the bromination through directed ortho-lithiation[5] have also
been employed, while these methods suffer from multiple
reaction steps and inconvenient operations.
a) Electrophilic bromination
OR
OR
OR
OR
OR
Br
Br
Br
Br+
Br
Br
Br
b) Transition-metal-catalyzed ortho-bromination
O
O
O
NBS
catalyst, additive
O
NMe2
O
NMe2
O
R
NMe2
Br
Br
Br
(CH2Cl)2
R
1
R
2
3
Nicholas (2012, R = H): 89% yield (2)
Pd(OAc)2 catalyst, TsOH (0.5 equiv), 60–120 °C
Rao (2014, R = Me): 71% yield (2)
Pd(OAc)2 catalyst, TfOH (0.7–3.0 equiv), RT
Glorius (2012, R = H): 35% yield (2) + 49% yield (3)
[Cp*RhCl2]2/AgSbF6 catalyst, Cu(OAc)2 (2.2 equiv), 120 °C
In recent years, the transition-metal-catalyzed C-H bond
functionalization has attracted attention due to its highly atom
economical and environmentally friendly nature.[6] The transition-
metal-catalyzed C-H bond bromination is a good alternative to
the conventional electrophilic bromination because the directing-
group-assisted ortho-C-H bond cleavage realizes the
regioselective bromination.[7] To date, Pd,[8] Rh,[9] Ir,[10] Co,[11]
Ru,[12] and Cu[13] catalysts have been employed for this ortho-C-
H bond bromination of arenes. However, the bromination of
phenol derivatives (O-phenyl carbamates) with readily available
N-bromosuccinimide (NBS) has been reported in a limited
number of examples, and there is room for improvement in
these reactions (Scheme 1b).[14] Nicholas reported the
This work (R = H): 82% yield (2)
[CpARhCl2]2/AgSbF6 catalyst, Cu(OAc)2 (0.2 equiv), RT
Scheme 1. Electrophilic and transition-metal-catalyzed bromination of
protected phenols. TsOH p-toluenesulfonic acid. TfOH
trifluoromethanesulfonic acid.
=
=
On the other hand, our research group developed various
modified cyclopentadienyl (Cp)-rhodium(III) complexes by
reductive complexation of pentasubstituted fulvenes with
RhCl3.[15] These rhodium(III) complexes showed high catalytic
activity in various C-H bond functionalization reactions.[16] In this
paper, we have established that
a
newly developed
cyclopentadienyl rhodium(III) [CpARhIII] complex, bearing an
acidic secondary amide moiety on the Cp ring, is able to
catalyze the ortho-bromination of O-phenyl carbamates with
NBS at room temperature in the presence of a catalytic amount
of Cu(OAc)2. The presence of the acidic secondary amide
moiety on the CpA ligand accelerates the bromination by the
hydrogen bond[17] between the acidic NH group of the CpA ligand
and the carbonyl group of NBS.
[*]
J. Tanaka, Dr. Y. Shibata, A. Joseph, J. Nogami, J. Terasawa, R.
Yoshimura, Prof. Dr. K. Tanaka
Department of Chemical Science and Engineering, Tokyo Institute
of Technology
O-okayama, Meguro-ku, Tokyo 152-8550 (Japan)
E-mail: ktanaka@apc.titech.ac.jp
http://www.apc.titech.ac.jp/~ktanaka/
In our previous reports, electron-deficient CpERhIII and
amide-pendant CpARhIII complexes showed high catalytic activity
toward the ortho-C–H bond functionalization of electron-rich
Supporting information for this article is given via a link at the end
of the document.
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10.1002/chem.202000253
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COMMUNICATION
anilides.[15a,16a,c,f,g,j,m,o] We anticipated that these RhIII complexes
would show high catalytic activity towards the ortho-C-H bond
bromination of O-phenyl carbamates due to their electron-rich
nature. Thus, the reaction of N,N-dimethyl-O-phenyl carbamate
(1a) with NBS (2 equiv) was tested using the CpERhIII complex
(5 mol % Rh), AgSbF6 (10 mol %), and Cu(OAc)2 (220 mol %).
Pleasingly, the desired monobromination product 2a was
obtained in good yield, and only a trace amount of dibromination
product 3a was generated (Table 1, entry 1). The reactions
using previously reported amide-pendant CpA1RhIII and CpA2RhIII
complexes were also examined, which revealed that the use of
tertiary amide-pendant CpA1RhIII complex decreased the yield of
2a (entry 2), on the contrary, the use of secondary amide-
pendant CpA2RhIII complex increased the yield of 2a (entry 3).
complex bearing the most acidic NH group afforded 2a and 3a in
the highest yields (entry 6). Under this condition, the use of
conventional Cp*RhIII complex afforded 2a in only 4% yield
(entry 7). Importantly, the use of CpA5RhIII complex enabled the
reduction of the amount of Cu(OAc)2 to 20 mol % with slight
erosion of the product yield (entry 8). Decreasing the amount of
NBS to 1.1 equiv decreased the yield of dibromination product
3a (entry 9). Finally, by using 12.5 mol % of AgSbF6 (2.5 equiv
to Rh), the yield of 2a improved slightly (entry 10), and the
reaction results were reproducible.
Ph
O
10 mol % [Rh(cod)2]BF4
10 mol % Segphos
Ph
Ph
R
O
N
H
+
O
H
R
(CH2Cl)2, 40 °C, 16 h
N
O
Ph
5
6a (R = 4-MeOC6H4))
6b (R = 4-F3COC6H4))
6c [R = 3,5-(F3C)2C6H3]
7a / 76%
7b / 46%
7c / 43%
Table 1. Optimization of reaction conditions.[a]
(1.1 equiv)
NBS (1.1–2 equiv)
RhCl3•nH2O EtOH
2.5 mol % [CpXRhCl2]2
O
(1 equiv)
60 °C, 16 h
10 mol % AgSbF6
O
NMe2
20–220 mol % Cu(OAc)2
(CH2Cl)2, RT, 18 h
O
H
Ph
N
R
O
Ph
O
O
O
[CpA3RhCl2]2 / 73% from 7a
Rh
1a
Cl
[CpA4RhCl2]2 / 57% from 7b
[CpA5RhCl2]2 / 69% from 7c
O
NMe2
O
NMe2
O
NMe2
Cl
Br
Br
Br
2
Scheme 2. Synthesis of CpA3–5RhIII complexes.
2a
3a
Br 4a
Me
Rh
Ph
Rh
R1
N
Me
The scope of this bromination reaction is shown in Scheme
3a. Unsubstituted O-phenyl carbamates 1a and 1b smoothly
reacted with NBS to give brominated products 2a and 2b in high
yields. Para- and meta-substituted O-phenyl carbamates 1c–i
also reacted with NBS to give brominated products 2a–i in good
yields. Although these products were obtained in acceptable
yields, increasing the amount of Cu(OAc)2 to 220 mol %
improved the product yields, as demonstrated in 2h and 2i. In
the reactions of ortho-substituted O-phenyl carbamates 1j–l, the
corresponding brominated products 2j and 2k were obtained in
good yields, but the yield of 2l derived from sterically demanding
O-(2-methylphenyl) carbamate 1l was low. Fortunately, the use
of 220 mol % Cu(OAc)2 significantly improved the yield of 2l,
although the yield of 2k derived from O-(2-chlorophenyl)
carbamate 1k was improved only slightly. The bromination of
sterically demanding O-(2-biphenyl) carbamate 1m also
proceeded in good yield by increasing the catalyst loading. O-(1-
Naphthyl) carbamate 1n smoothly reacted with NBS to give 2-
bromonaphthalene derivative 2n in high yield. Importantly, the
use of CpA5RhIII complex not only allowed the room temperature
bromination but also improved the product yields (2a and 2h),
which are significantly higher than the previously reported
Cp*RhIII complex-catalyzed reactions at 120 °C.[14c] As
mentioned in the introduction, the palladium-catalyzed
bromination can be conducted at room temperature, but acid-
sensitive substrates can not be employed due to the use of a
strong Brønsted acid (TfOH).[14b] On the contrary, acid-sensitive
O-phenyl carbamates 1o and 1p bearing the silyl and trityl ether
moieties could be used for this process.
CO2Et
Me
Me
EtO2C
Me
Me
R2
O
Me
Me
Ph
O
Rh
Cl
Cl
Cl
Cl
Cl
Cl
2
2
2
[CpERhCl2]2
[CpARhCl2]2
[Cp*RhCl2]2
CpA1 (R1 = R2 = Me)
CpA2 (R1 = H, R2 = Ph)
CpA3 (R1 = H, R2 = 4-MeOC6H4)
CpA4 (R1 = H, R2 = 4-F3CC6H4)
CpA5 (R1 = H, R2 = 3,5-(F3C)2C6H3)
Entry
CpX
Cu(OAc)2
NBS
[equiv]
2.0
Yield [%][b]
[mol %]
220
220
220
220
220
220
220
20
2a
67
43
75
21
76
86
4
3a
3
4a
0
0
0
1
0
0
0
0
0
0
1
2
CpE
CpA1
CpA2
CpA3
CpA4
CpA5
Cp*
CpA5
CpA5
CpA5
2.0
1
3
2.0
2
4
2.0
0
5
2.0
4
6
2.0
10
0
7
2.0
8
2.0
78
79
82[d]
7
9
20
1.1
3
10[c]
20
1.1
5
[a] [CpXRhCl2]2 (0.0025 mmol), AgSbF6 (0.010 mmol), Cu(OAc)2 (0.040–0.220
mmol), 1a (0.100 mmol), NBS (0.110–0.200 mmol), and (CH2Cl)2 (1.0 mL)
were used. [b] Determined by 1H NMR. [c] [CpA5RhCl2]2 (0.0050 mmol),
AgSbF6 (0.025 mmol), Cu(OAc)2 (0.040 mmol), 1a (0.200 mmol), NBS (0.220
mmol), and (CH2Cl)2 (2.0 mL) were used. [d] Isolated yield.
We anticipated that the hydrogen bond between the acidic
NH group of the CpA2 ligand and the carbonyl group of NBS
might accelerate the reaction. Thus, we synthesized CpA3–5RhIII
complexes bearing various pendant secondary amide moieties
with varied acidity of the NH groups. These complexes were
synthesized by reductive complexation of RhCl3 with fulvenes
7a–c, which were prepared by the rhodium(I)-catalyzed [2+2+1]
cycloaddition of 1,6-diyne 5 with cyclopropenylideneacetamides
6a–c (Scheme 2). The acidity of the NH group correlated with
the yields of 2a and 3a (entries 3–6). The use of CpA5RhIII
This bromination reaction was scaleable, and the 1 mmol
scale reaction proceeded with almost the same yield as the
small-scale reaction (Scheme 3b). Finally, the regioselectivity of
the bromination was examined in protected 4-aminophenol
derivative
8
(Scheme 3c). The bromination proceeded
regioselectively at the ortho position relative to the nitrogen to
give bromoarene 9 in high yield without the formation of
bromoarene 10.[18] This result suggests that the amide is a
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10.1002/chem.202000253
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stronger directing group than the carbamate in the CpA5RhIII
to give 12a in high yields. However, the use of CpA5RhIII complex
improved the yields of brominated acetanilides 12e–h,
particularly, the yields of 12f and 12h derived from electron-
deficient acetanilide 11f and sterically demanding 2-
methylacetanilide (11h), respectively, were significantly
improved.
complex-catalyzed ortho-C-H bond bromination.
a) Substrate scope
NBS (1.1 equiv)
2.5 mol % [CpA5RhCl2]2
O
O
12.5 mol % AgSbF6
20 mol % Cu(OAc)2
O
NR1
O
NR1
2
2
Br
(CH2Cl)2, RT, 18–72 h
R2
R2
NBS (1.1 equiv)
2.5 mol % [CpA5RhCl2]2
O
O
1
2
12.5 mol % AgSbF6
20 mol % Cu(OAc)2
HN
Me
HN
Me
Br
O
O
(CH2Cl)2, RT, 18–72 h
O
O
R
R
O
F
NMe2
O
NMe2
O
NMe2
Br
O
N
Br
Br
11
12
Br
O
O
O
O
OMe
HN
Me
HN
Me
HN
Me
HN
Me
2a / 82% (40 h)
(35%, ref 14c)
2b / 81% (18 h)
2c / 66% (18 h)
2d / 70% (64 h)
Br
Br
Br
Br
O
O
O
O
I
F
OMe
O
NMe2
Br
O
NMe2
O
NMe2
O
NMe2
12a / 90% (18 h)
(89%, ref 14c)
(89%, ref 10b)
12b / 89% (18 h)
(87%, ref 10b)
12c / 63% (18 h)
(64%, ref 10b)
12d / 77% (18 h)
Br
Br
Br
MeO
I
F
Cl
O
O
O
O
2e / 74% (72 h)
2f / 71% (72 h)
2g / 49% (72 h)
2h / 70% (72 h)
82% (72 h)[a]
HN
Me
HN
Me
HN
Me
HN
Me
Br
Br
Br
Me
Br
O
O
O
O
O
NMe2
O
NMe2
O
NMe2
O
NMe2
Me
F3C
Cl
Cl
Br
F
Br
Cl
Br
Me
Br
12e / 84%[a] (18 h)
12f / 86% (68 h)
12h / 70% (18 h)
12g / 64% (72 h)[b]
(46%, ref 10b)
(9%, ref 10b)
(2%, ref 10b)
(59%, ref 10b)
Me
2i / 74% (72 h)
95% (72 h)[a]
(76%, ref 14c)
2j / 52% (72 h)
2k / 52% (72 h)
2l / 18% (72 h)
58% (72 h)[a]
76% (72 h)[a]
Scheme 4. CpA5RhIII complex-catalyzed ortho-bromination of acetanilides.
[CpA5RhCl2]2 (0.0050 mmol), AgSbF6 (0.025 mmol), Cu(OAc)2 (0.040 mmol),
11 (0.200 mmol), NBS (0.220 mmol), and (CH2Cl)2 (2.0 mL) were used. The
cited yields were of isolated products. Conditions of ref 14c: [Cp*RhCl2]2 (1
mol %), AgSbF6 (4 mol %), PivOH (110 mol %), NBS (1.1 equiv), 60 °C.
Conditions of ref 10b: [Cp*IrCl2]2 (0.5 mol %), AgNTf2 (5 mol %), Boc-L-Phe-
OH (10 mol %), RT. [a] Isolated as a mixture of 12e (84%) and 4-bromo
isomer (11%). [b] [CpA5RhCl2]2 (0.010 mmol), AgSbF6 (0.050 mmol), Cu(OAc)2
(0.080 mmol), 11 (0.200 mmol), NBS (0.220 mmol), and (CH2Cl)2 (2.0 mL)
were used.
O
O
O
O
O
NMe2
O
NMe2
O
NMe2
Br
O
NMe2
Br
Br
Br
Ph
OSiMe2tBu
OCPh3
2m / 65% (72 h)[b]
2n / 80% (18 h)
2o / 56% (72 h)
2p / 84% (72 h)
67% (72 h)[a]
b) Preparative scale reaction
NBS (1.1 equiv)
To explore the effect of the Cp ligand on the catalytic cycle,
deuterium kinetic isotope effects (DKIEs) of the bromination of
1a with NBS were measured by the two parallel reactions
(Scheme 5a) using the Cp*, CpE, and CpA5RhIII complexes as
catalysts. We found that DKIE values of the reactions using the
Cp* and CpERhIII complexes were small (1.0 and 1.3,
respectively), but that using the CpA5Rh(III) complex was large
(5.4). These results suggest that not the C-H bond cleavage
step but the other rate-limiting steps might be accelerated by the
CpA5RhIII catalyst. Interestingly, in the reactions of 1a and NBS
using Cp* or CpA1RhIII complex as a catalyst, the addition of 3,5-
bis(trifluoromethyl)acetanilide (13) decreased the yield of 2a
(Scheme 5b). Therefore, the acidic amide moiety of the CpA5
ligand might accelerate the reaction intramolecularly. Based on
these experimental results, a possible reaction mechanism for
the formation of 2a from 1a is proposed in Scheme 5c. Cleavage
of the C-H bond of 1a with the acetoxy ligand in intermediate A
affords arylrhodium B. The coordination of NBS gives
intermediate C. Concerted bromine transfer through transition-
state TS-CD, in which there is the hydrogen bond between the
acidic NH group of the CpA ligand and the carbonyl group of
NBS,[19] forms intermediate D. The subsequent Rh-N bond
formation gives rhodiumamide E. Coordination of 1a releases 2a
and generates rhodiumamide F. The ligand exchange
regenerates intermediate A, but cleavage of C-H bond of 1a with
the succinimidyl ligand in F giving arylrhodium C via G might
also exist in the catalytic cycle.
2.5 mol % [CpA5RhCl2]2
12.5 mol % AgSbF6
20 mol % Cu(OAc)2
O
O
O
NMe2
O
NMe2
Br
(CH2Cl)2, RT, 72 h
1a (1 mmol, 165 mg)
2a / 86% (210 mg)
c) Regioselective bromination of protected 4-aminophenols
NBS (1.1 equiv)
O
O
O
2.5 mol % [CpA5RhCl2]2
12.5 mol % AgSbF6
20 mol % Cu(OAc)2
O
N
NMe2
O
N
NMe2
O
N
NMe2
Br
(CH2Cl)2, RT, 18 h
Br
Me
Me
Me
H
H
H
O
O
O
8
9 / 93%
10 / 0%
Scheme 3. CpA5Rh(III) complex-catalyzed ortho-bromination of O-phenyl
carbamates. [CpA5RhCl2]2 (0.0050 mmol), AgSbF6 (0.025 mmol), Cu(OAc)2
(0.040 mmol), 1 (0.200 mmol), NBS (0.220 mmol), and (CH2Cl)2 (2.0 mL) were
used. The cited yields were of isolated products. Conditions of ref 14c:
[Cp*RhCl2]2 (2.5 mol %), AgSbF6 (10 mol %), Cu(OAc)2 (220 mol %), NBS
(1.5–2.0 equiv), 120 °C. [a] Cu(OAc)2 (0.44 mmol) was used. [b] [CpA5RhCl2]2
(0.010 mmol), AgSbF6 (0.050 mmol), Cu(OAc)2 (0.080 mmol) were used.
Thus, the present optimized reaction conditions used for O-
phenyl carbamates 1 was also applied to the ortho-bromination
of acetanilides 11, as shown in Scheme 4. Non-substituted (11a)
and substituted (11b–h) acetanilides reacted with NBS at room
temperature to give the corresponding ortho-bromination
products 12a–h in high yields. The bromination of non-
substituted anilide 11a also proceeded under the previously
reported reaction conditions [Cp*RhIII, 60 °C[14c]; Cp*IrIII, RT[10b]
]
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10.1002/chem.202000253
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COMMUNICATION
a) DKIE experiments
Scheme 5. Mechanistic experiments and proposal.
NBS (1.1 equiv)
2.5 mol % [CpXRhCl2]2
12.5 mol % AgSbF6
20 mol % Cu(OAc)2
O
O
To confirm the pathway from A to E, DFT calculations were
carried out using 1a, NBS, and Cp*RhIII or CpA6RhIII as a model
complex (Scheme 6). In the Cp*RhIII complex-catalyzed reaction,
required energies of 6.9 and 15.3 (4.9+10.4) kcal/mol were
computed for the C－H activation (from A to TS-AB) and bromine
transfer (from B to TS-CD), respectively. The bromine transfer
transition state TS-CD is the highest in energy, and thus the
bromine transfer is in the rate-limiting step. This observation is
consistent with the small DKIE value of 1.0 (Scheme 5a). On the
contrary, in the CpA6RhIII complex-catalyzed reaction, required
energies of 9.7 and 8.3 kcal/mol were computed for the C-H
activation and bromine transfer, respectively. The C-H activation
transition state TS-AB is the highest in energy, and thus the C-H
activation is in the rate-limiting step. This observation is
consistent with the large DKIE value of 5.4 (Scheme 5a).
Importantly, the hydrogen bond between the acidic NH group of
the CpA ligand and the carbonyl group of NBS was clearly
observed in TS-CD.
O
NMe2
O
NMe2
Br
(CH2Cl)2, 2 h
H5/D5
1a or 1a-d5
H4/D4
2a / 2a-d4
Yield [%]
CpX
Temp.
DKIE
2a
2a-d4
Cp*
Cp*
CpE
CpA5
<1
<1
6.3
–
RT
80 °C
RT
6.5
24.9
28.3
1.0
1.3
5.4
18.7
5.3
RT
b) Reactions in the presence of acidic NH-anilide
NBS (2 equiv)
2.5 mol % [CpXRhCl2]2
10 mol % AgSbF6
20 mol % Cu(OAc)2
X mol % 13
O
O
O
NMe2
O
NMe2
Br
(CH2Cl)2, RT, 18 h
O
1a
2a
Me
NH
Cp* / 0% (X = 5), 4% (X = 0)
CpA1 / 19% (X = 5), 43% (X = 0)
F3C
CF3
13
In conclusion, we have established that a newly developed
cyclopentadienyl rhodium(III) [CpARhIII] complex, bearing an
acidic secondary amide moiety on the Cp ring, is able to
catalyze the ortho-bromination of O-phenyl carbamates with
NBS at room temperature. The presence of the acidic secondary
amide moiety on the CpA ligand accelerates the bromination by
the hydrogen bond between the acidic NH group of the CpA
ligand and the carbonyl group of NBS. Future works will include
the further application of the CpARhIII complex with the acidic
secondary amide moiety to the C-H bond functionalization
reactions.
c) Possible reaction mechanism
NMe2
NMe2
C–H cleavage
O
O
O
O
[Rh]
[Rh]
O
O
H
O
O
H
O
Br
N
N
HO
Me
Me
A
B
O
O
O
H
AcOH
AcOH
N
NMe2
O
NBS
NMe2
O
O
C–H cleavage
NMe2
[Rh]
O
O
O
O
O
O
N
[Rh]
[Rh]
H
H
N
O
Br
N
G
O
C
O
O
F
Acknowledgements
2a
1a
This research was supported partly by Grants-in-Aid for
Scientific Research (No. JP26102004) and Young Scientists (No.
17K14481) from JSPS (Japan). We thank Umicore for generous
support in supplying RhCl3·nH2O. The partial calculations were
carried out on the TSUBAME 3.0 super-computer in the Tokyo
Institute of Technology.
‡
NMe2
Me2N
Ph
O
O
O
O
O
O
N
Ph
[Rh]
O
[Rh]
Br
O
Ar
Br
Rh
H
O
N
Me2N
O
Br
N
O
N
O
D
E
O
O
TS-CD
concerted bromine transfer
Free Energy
(kcal/mol)
highest energy
Me
Me
Me
Me
Cp*
CpA6
Me
Rh
10.4
8.0
TS-CD
6.9
9.7
TS-AB
[Rh] = Cp*Rh (black)
4.4
4.7
C
5.9
2.8
D
Me
Rh
H
N
Me2N
0.0
0.0
A
NMe2
Me
Me
Me2N
O
O
Me
Me2N
O
O
–4.9
O
Me
NMe2
O
O
O
[Rh]
Br
O
O
[Rh]
–0.3
B
O
Br
[Rh] O
[Rh] = CpA6Rh (red)
O
O
[Rh]
Br
O
NMe2
N
N
O
O
H
O
[Rh]
NMe2
O
O
N
O
O
Br
N
[Rh]
O
O
O
[Rh]
–26.9
–30.0
E
H
O
O
O
Me
HO
Me
Me
O
Me
N
Me
O
Me
Me
Rh
H
O
Me2N
Br
O
N
O
TS-CD (CpA6Rh)
Scheme 6. DFT calculations. The Gibbs-free energies (in kcal mol–1) were obtained at PW6B95-D3/def2-TZVP//M06/6-31G(d,p) level, using PCM [(CH2Cl)2].
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10.1002/chem.202000253
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COMMUNICATION
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Keywords: cyclopentadienyl ligand • hydrogen bond • ortho-
bromination • phenyl carbamates • rhodium
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[19] Upon
the
formation
of
hydrogen
bonds,
1,1,1,3,3,3-
hexafluoroisopropanol can lower the activation energy of the reductive
elimination step in the IrIII-catalyzed ortho-iodination of benzoic acids
with N-iodosuccinimide. See: ref 10c.
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COMMUNICATION
Entry for the Table of Contents (Please choose one layout)
COMMUNICATION
Ph
O
Jin Tanaka, Yu Shibata, Anton Joseph,
Juntaro Nogami, Jyunichi Terasawa,
Ryo Yoshimura, and Ken Tanaka*
NBS (1.1 equiv)
CF3
2.5 mol % [CpARhCl2]2
12.5 mol % AgSbF6
20 mol % Cu(OAc)2
O
O
O
N
Ph
Br
Rh
H
N
O
NMe2
O
NMe2
O
O
Me2N
Br
CF3
(CH2Cl)2
room temperature
(non-acidic conditions)
O
R
R
Page No. – Page No.
O
up to 84% yield
activation of NBS by CpA ligand
Rhodium-Catalyzed Ortho-
Bromination of O-Phenyl Carbamates
Accelerated by a Secondary Amide-
Pendant Cyclopentadienyl Ligand
It has been established that a newly developed cyclopentadienyl rhodium(III)
[CpARhIII] complex, bearing an acidic secondary amide moiety on the Cp ring, is
able to catalyze the ortho-bromination of O-phenyl carbamates with NBS at room
temperature. The hydrogen bond between the acidic NH group of the CpA ligand
and the carbonyl group of NBS accelerates the bromination.
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