Hydroxyamination of aryl C-H bonds with N-hydroxycarbamate by synergistic Rh/Cu catalysis at room temperature

Article abstract of DOI:10.1039/c3cc49496a

A novel hydroamination of aryl C-H bonds has been accomplished using N-Boc-hydroxyamine via synergistic combination of rhodium and copper catalysis. The merger of two robust catalytic systems has allowed for the development of a mild and sustainable protocol for the direct formation of benzo[c]isoxazol-3(1H) -ones. This journal is the Partner Organisations 2014.

Full text of DOI:10.1039/c3cc49496a

Showcasing research from Prof. Xianxiu Xu and Qian Zhang’s
Laboratory/ Key Laboratory of Design and Synthesis of
Functional Organic Molecules of Jilin, Northeast Normal
University, Changchun, China.
As featured in:
A novel synergistic rhodium and copper catalyzed C–H
activation/hydroamination reaction for the synthesis of
benzo[c]isoxazol-3(1H)-ones
A novel hydroamination of aryl C–H bonds has been
accomplished using N-Boc-hydroxyamine via synergistic
combination of rhodium and copper catalysis. The merger of two
robust catalytic systems has allowed for the development of a
mild and sustainable protocol for the direct formation of
benzo[c]isoxazol-3(1H)-ones.
See Xianxiu Xu, Qian Zhang et al.,
Chem. Commun., 2014, 50, 4420.
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Hydroxyamination of aryl C–H bonds with
N-hydroxycarbamate by synergistic Rh/Cu
catalysis at room temperature†
Cite this: Chem. Commun., 2014,
50, 4420
Received 15th December 2013,
Accepted 9th January 2014
Wei Yang, Jiaqiong Sun, Xianxiu Xu,* Qian Zhang* and Qun Liu
DOI: 10.1039/c3cc49496a
www.rsc.org/chemcomm
A novel hydroamination of aryl C–H bonds has been accomplished step-economical C–C and C–heteroatom bond formation through
using N-Boc-hydroxyamine via synergistic combination of rhodium C–H functionalization.11 Among the various coupling partners
and copper catalysis. The merger of two robust catalytic systems employed in the Rh(III)-catalyzed C–H bond activation reaction, some
has allowed for the development of a mild and sustainable protocol electrophiles, such as imines,12 aldehydes13 and isocyanates,14 have
for the direct formation of benzo[c]isoxazol-3(1H)-ones.
been successfully explored. Since nitrosocarbonyl compounds are
reactive electrophiles, it is reasonable that they may be good coupling
partners in the Rh-catalyzed C–H activation reactions.15 Thus, as part of
our continuing interest in the development of Rh(III)-catalyzed
C–H activation,16 we envisioned that the nitrosocarbonyl compounds
A could be trapped by the rhodacycle intermediate B if they can be
formed compatibly in situ (eqn (2)). Herein we present the successful
development of a synergistic Rh and Cu catalytic system applicable to
the hydroamination of aryl C–H bonds by commercially available
N-Boc-hydroxylamine using O2 as an oxidant at room temperature. This
synergistic catalysis provides a new sustainable process for the prepara-
tion of benzo[c]isoxazole derivatives, which are the subunits of natural
products, parnafungins A and B17 and other bioactive compounds.18
Synergistic catalysis, a synthetic strategy wherein both the nucleo-
phile and the electrophile are simultaneously activated by two
distinct catalysts, has attracted increasing interest in the design
of new chemical reactions for improving efficiency and selectivity of
a known reaction in organic chemistry.1 During the past few years,
various co-catalyst systems, such as a combination of transition-
metal and organocatalysis,1,2 transition-metal and photoredox
catalysis,1,3 and other bimetal catalysis,1,4 have been extensively
investigated. However, despite their high synthetic potential, the
success of synergistic catalysis is still immature and there is a need
to develop new synergistic catalysis, especially for the sustainable
chemical process.
Nitrosocarbonyl compounds are very unstable and highly reactive
species and have attracted considerable attention in organic
synthesis.5–7 They are generally produced in situ as transient
intermediates and have been studied quite extensively in hetero-
Diels–Alder and ene reactions.7 Recently, Read de Alaniz and
co-workers extended the synthetic utility of nitrosocarbonyl to
a-hydroamination of reactive b-ketoesters by N-hydroxy-
carbamates using synergistic CuCl/Cu(OTf)2 catalysis, during
which nitrosoformate intermediates were generated in situ by
aerobic oxidation (eqn (1)).8 In addition, Maruoka reported an
enantioselective a-hydroxyamination of aldehydes with nitro-
socarbonyl compounds.9 Yamamoto developed a catalytic
enantioselective O-nitrosocarbonyl aldol reaction of b-dicarbonyl
compounds with nitrosocarbonyl compounds.10 On the other hand,
Rh(III) complexes have stood out as efficient catalysts for atom- and
(1)
(2)
Department of Chemistry, Northeast Normal University, Changchun 130024, China.
E-mail: xuxx677@nenu.edu.cn, zhangq651@nenu.edu.cn; Fax: +86-431-85099759;
Tel: +86-431-85099759
Initially, the reaction of N-methoxy benzamides 1a with N-Boc-
hydroxylamine 2a was employed to screen catalysts and reaction
† Electronic supplementary information (ESI) available: Experimental details and
spectral data for 3. See DOI: 10.1039/c3cc49496a
4420 | Chem. Commun., 2014, 50, 4420--4422
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Table 1 Optimization of reaction conditionsa
Table 2 Synthesis of benzo[c]isoxazol-3(1H)-ones 3
Catalyst II
(mol%)
Additive
(100 mol%)
Yieldb
(%)
Entry
Solvent
1
2
3
4
5
6
7
8
MeOH
EtOH
t-AmOH
Acetone
CuCl (10)
CuCl (10)
CuCl (10)
CuCl (10)
CuCl (10)
CuBr (10)
CuI (10)
CuOAc (10)
CuOTf (10)
—
HOAc
HOAc
HOAc
HOAc
HOAc
HOAc
HOAc
HOAc
HOAc
HOAc
HOAc
HCOOH
PivOH
PivOH
11
35
Trace
32
70
42
40
60
0
Acetone–EtOHc
Acetone–EtOH
Acetone–EtOH
Acetone–EtOH
Acetone–EtOH
Acetone–EtOH
Acetone–EtOH
Acetone–EtOH
Acetone–EtOH
Acetone–EtOH
9
10
11
12
13
14
0
CuCl (50)
CuCl (10)
CuCl (10)
CuCl (10)
53
17
72
88d
a
Reaction conditions: 1a (0.2 mmol), 2a (0.24 mmol), additive
b
c
(0.2 mmol), solvent (2 mL). Isolated yields. The ratio of acetone
and EtOH is 1 : 1 (v : v). 2 Equiv. of 2a was used, 1 equiv. was added
d
at the beginning of the reaction, the other 1 equiv. was added after 24 h.
conditions for the hydroamination of aryl C–H bonds (Table 1).
Because copper salt is compatible with (Cp*RhCl2)2,11 Read de
Alaniz’s copper-catalyzed aerobic oxidation conditions8,19 were
employed to produce nitrosocarbonyl compounds. Fortunately,
benzo[c]isoxazol-3(1H)-one 3a was obtained in a 11% isolated yield,
when the reaction was conducted in methanol in the presence of
(Cp*RhCl2)2 (2.5 mol%), CuCl (10 mol%) and 1.0 equivalent of acetic
acid in the open air (Table 1, entry 1). Solvent screening revealed that
ethanol and acetone gave moderate product yields (Table 1, entries 2 highly regioselective manner (3h–m). Reactions with ortho-
and 4) when a mixture of ethanol and acetone (1 : 1) was used as substituted and disubstituted benzamides also proceeded smoothly
solvent, and to our delight, the yield of 3a was improved to 70% to give the corresponding products in good to high yields (3n–q).
(Table 1, entry 5). Among the copper salts tested, CuCl was the most a- and b-naphthamide also produced the corresponding naphtho-
favorable with respect to product yield (Table 1, entries 5–9). Product [2,1-c]isoxazol-1(3H)-one 3r and naphtho[2,3-c]isoxazol-3(1H)-one 3s
3a could not be detected in the absence of CuCl (Table 1, entry 10), regioselectively and in good yields. It is worth mentioning that a wide
whereas 3a was obtained in a low yield upon increasing the amount range of important functional groups on the aryl moieties of benz-
of CuCl to 50 mol% (Table 1, entry 11). Different additives were also amides 1, such as methoxy, chloro, bromo, iodo and trifluoromethyl
screened (Table 1, entries 5, 12 and 13) and it was found that PivOH groups, were well tolerated under the reaction conditions (3f–j).
was as effective as HOAc (Table 1, entry 13). More importantly, the
To shed light on the reaction mechanism of this synergistic
yield of product 3a could be improved to 88% when 2 equivalents of catalysis process, firstly, a routine Diels–Alder trapping for the
2a were employed (1 equivalent was added to the reaction mixture at nitrosocarbonyl compound20 was performed to determine whether
the beginning and the other was added after 24 h; Table 1, entry 14). this unstable and transient intermediate was involved. When
It should be noted that the reaction was performed under very mild cyclohexa-1,3-diene (2.0 equiv.) was added to the reaction mixture
conditions, such as at room temperature and in the open air and of 1a and 2a under the standard conditions, the Diels–Alder product
gave the benzo[c]isoxazole derivatives with exclusively N-selectivity of 4 was obtained in 44% yield along with product 3a only in 10% yield
the nitrosocarbonyl compounds.
(eqn (3)). Then, deuterium-labeling experiments were further carried
With the optimal conditions in hand, we surveyed various out to gain some insights into the catalytic mechanism. When the
substrates to determine the scope of the reaction. Catalyzed by Rh reaction of 1a was conducted in deuterated acetone and methanol in
and Cu system, the reactions proceeded smoothly to afford benzo[c]- the absence of 2a, 94% deuterium incorporation was observed at the
isoxazol-3(1H)-ones in good to excellent yields (Table 2). Substrates two ortho positions (eqn (4)). If the same reaction was conducted in
with both electron-donating and electron-withdrawing groups at the the presence of 2a, 89 and 94% deuterium incorporation into the
para position of aryl groups participated in this reaction (3a–j). meta- product 3a and the recovered starting material 1a were observed
Substituted benzamides reacted smoothly to give the corresponding respectively (eqn (4)). These results indicate that the C–H bond
benzo[c]isoxazol-3(1H)-ones in good to excellent yields and in a metalation step is reversible under the reaction conditions.
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This research is supported by the NNSFC (21172030). Prof.
Xingwei Li (Dalian Institute of Chemical Physics, Chinese
Academy of Sciences) is thanked for insightful discussions.
Notes and references
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Scheme 1 Proposed mechanism for the formation of 3a.
Moreover, a competition reaction between protio and deutero 1a was
conducted at early conversion, and 1H NMR spectroscopic analysis of
the product mixture gave a kinetic isotope effect (KIE) of 1.5 (eqn (5)).
On the basis of the above results, a mechanistic pathway is
proposed (Scheme 1). First, a reversible C–H bond cleavage of 1a
occurs to produce a five-membered rhodacycle intermediate A.
Next, coordination of the nitrosocarbonyl compound (produced
by copper-catalyzed aerobic oxidation of N-Boc-hydroxylamine
2a)8,19,20 affords intermediate B, which undergoes nucleophilic
addition to form seven-membered rhodacycle C. Protonolysis
gives a hydroxyamination intermediate D. Metal or acid catalyzed
nucleophilic substitution reaction occurs to furnish the final
product 3a with the release of a O-methyl hydroxamine (the
propan-2-one O-methyl oxime 5 was detected using GC-MS).
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(5)
In summary, we have developed a novel aryl C–H bond hydro-
amination using N-Boc-hydroxyamine via synergistic combination of
rhodium and copper catalysis for the convenient synthesis of
benzo[c]isoxazol-3(1H)-ones. In this process, the unstable and transient
nitrosocarbonyl compounds were generated in situ by aerobic oxida-
tion and used as coupling partner to form both C–N and C–O bonds.
The reaction features mild reaction conditions (room temperature and
in the open air), broad substrate scope and good functional-group
tolerance. Additional mechanism studies and more transformations
by synergistic catalysis are being carried out in our laboratory.
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4422 | Chem. Commun., 2014, 50, 4420--4422
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