Manganese-Catalyzed C?H Amidation of Heteroarenes in Water

Article abstract of DOI:10.1002/adsc.201800544

We have developed an efficient manganese-catalyzed amidation of various heteroarenes via C?H bond activation using readily available sulfonyl azides. The key step is heteroarene directed electrophilic aromatic metalation using MnBr(CO)₅ as catalyst. This method offers excellent chemical yields and regioselectivity with good functional group tolerance. This base metal catalyzed reaction proceeds efficiently using water as the only solvent and nitrogen is the only byproduct. (Figure presented.).

Full text of DOI:10.1002/adsc.201800544

Title: Manganese-Catalyzed C–H Amidation of Heteroarenes in Water
Authors: Xianqiang Kong, Nong Ling, and Bo Xu
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10.1002/adsc.201800544
Advanced Synthesis & Catalysis
COMMUNICATION
DOI: 10.1002/adsc.201
Manganese-Catalyzed C–H Amidation of Heteroarenes in
Water
Xianqiang Kong, Nong Ling, Bo Xu*
College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, 2999 North Renmin Lu, Shanghai
201620, China; e-mail: bo.xu@dhu.edu.cn
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
Abstract: We have developed an efficient manganese-
catalyzed amidation of various heteroarenes via C–H
bond activation using readily available sulfonyl azides.
The key step is heteroarene directed electrophilic
aromatic metalation using MnBr(CO)5 as catalyst. This
method offers excellent chemical yields and
regioselectivity with good functional group tolerance.
This base metal catalyzed reaction proceeds efficiently
using water as the only solvent and nitrogen is the only
byproduct.
Keywords: C-H activations, manganese, directing
group, amidation
C-H activation has evolved as an atom- and step-
economic tool for synthesis of complex organic
molecular. Transition metals such as Rh,[1] Pd,[2] Ir[3]
and Ru[4] based catalysts have played a leading role in
C-H activation. However, from the viewpoint of
green chemistry, it is desirable to develop more
economic alternatives to these precious metals. Also
most C-H activation protocols are conducted in
organic solvents, especially halogenated solvents such
as dichloroethane and dichlorobenzene are commonly
used. It is also highly desirable to replace the
conventional solvents with greener solvent such as
water.
Along this line, first-row transition metals such as
Scheme 1. Selected examples of Mn-catalyzed C–H
activations using organo azide as amidation reagent.
7]
iron,[5] cobalt,[6] copper,[2e,
and manganese[8] are
naturally abundant and inexpensive and could be
promising candidates for catalyst development in C-H
activation. More specifically, manganese is of low
cost and low toxicity. Manganese based catalysts have
Indeed, the groups of Chang, Ackermann and Zhu
have significantly advanced the field of organo azides
based amidation process (Scheme 1). For examples,
Chang and coworkers have reported Ir-catalyzed,[10]
Rh-catalyzed[11] and Ru-catalyzed[12] direct arene
C−H bond amidation using organo azides as amino
sources respectively (Scheme 1, a-c). Ackermann and
coworkers also have reported C–H amidations of
heteroaryl arenes catalyzed by versatile Ru (II)
catalysts.[13] Along this line, Zhu and coworkers have
reported a Cu-catalyzed amidation with azides as
amino sources[7a] and Kanai, Matsunaga and
coworkers reported a cationic cobalt catalyzed C-H
amidation of indoles.[14] However, most of these
protocol were based on the precious transitional metal
catalysts. What is more, all these syntheses used
been
shown
unique
reactivity
for
C–H
functionalization.[8] Aromatic amine is
a
key
component in numerous natural products and
synthetic compounds displaying important chemical
and biological properties.[9] And the direct C-H
amidation of aromatic compounds is one of the most
straightforward method to make them and this method
does not generate hazardous byproducts. In the
context of environmentally benign synthesis, among
many amidation reagents, organo azide is an ideal
amino source which releasing N2 as the single
byproduct without using of external oxidants.
1
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10.1002/adsc.201800544
Advanced Synthesis & Catalysis
chlorinated solvent systems. Herein, we are glad to tolerance of the manganese-catalyzed amidation of
report a highly efficient base metal (Mn) catalyzed C- pyridinyl benzene 1a with different aromatic and
H amidation process using water as the only solvent.
aliphatic sulfonyl azides 2 (Table 2). The substitution
pattern (meta, para) and electronic properties of
substitution (electron deficient or rich) on the
aromatic ring of sulfonyl azides played a small role;
good yields were obtained regardless (Table 2, 3a-3f).
And various functional groups such as amine (Table 2,
3b), nitrile (Table 2, 3e), ether (Table 2, 3h), halides
(Table 2, 3d, 3q, 3r), ester (Table 2, 3s) were well
tolerated. This reaction also worked equally well for
aliphatic sulfonyl azides 2 (Table 2, 3f, 3t, 3m, 3v). It
should be noted that no reaction took place when a
highly bulky sulfonyl azides 2 was used (Table 2, 3x).
Table 1. Optimization of conditions.a
Entry
Additive
（mol%）
Solvent
Temp
（oC）
80
Yieldg
（%）
32
1
2
3
4
5
6
7
8
-
-
-
-
-
-
-
-
DCE
Dioxane
THF
Toulene
DMF
DMSO
DMA
CH3CN
H2O
80
80
80
80
80
80
80
80
80
80
80
19
Trace
Trace
Trace
Trace
Trace
Trace
35
42
75
73
Table 2. Scope for manganese-catalyzed amidation of 1a.a
9
-
TMABb（10）
TPABc（10）
TBABd（10）
10
11
12
H2O
H2O
H2O
TBAIe（10）
TBACf（10）
TPAB（10）
TPAB（10）
TPAB（10）
TPAB（10）
TPAB（10）
TPAB（5）
13
14
15
16
17
18
19
20
21
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
80
80
90
100
110
120
130
120
120
13
19
80
84
87
93
92
83
92
TPAB（15）
Conditions: 1a (0.2 mmol), sulfonyl azide 2a (0.4 mmol), MnBr(CO)5 (10
mol %), additive (10 mol%) and solvent (1 mL), 120 oC for 16 h. bTMAB:
(CH3)4NBr. cTPAB: (n-C3H7)4NBr. dTBAB: (n-C4H9)4NBr. eTBAI: (n-
C4H9)4NI. fTBAC: (n-C4H9)4NCl. gDetermined by GC-MS analysis.
We used the amidation of 1a as our model reaction
(Table 1). Using MnBr(CO)5 as catalyst, first we
investigated the solvent effect (Table 1, entries 1-9).
The solvent has a big influence on the reaction: most
solvents only give trace amount of product 3a, only
DCE, dioxane and water offer moderate conversion
and water appeared to be the best solvent (Table 1,
entry 9). Szostak and coworker have reported a
Ru(II)-catalyzed C−H arylation of indoles with
arylsilanes in water.[4a] Our result indicated that water,
as a sustainable solvent, may also have great potential
in Mn-catalyzed C-H functionalizations. Because both
starting material and product are not very solvable in
water, use of surfactant may enhance the mass
transfer.[15] So we screened several common
surfactants (Table 1, entries 10-14). To our delight,
surfactants such as TBAB ((n-C4H9)4NBr) did
significantly increase the chemical yield of 3a (75%,
Table 1, entry 11). And screening of reaction
temperature (Table 1, entries 15-19) indicated that
a
Conditions: 1 (0.2 mmol), sulfonyl azide 2 (0.4 mmol), MnBr(CO)5
o
(10 mol %), TPAB (10 mol%) and water (1 mL), 120 oC for 16 h. All
120 C was the optimal temperature (Table 1, entry
18). We also investigated the effect of surfactant
loading (Table 1, entries 20-21). Reduction of
surfactant loading from 10% to 5% leaded to poorer
yields. However, increase of surfactant loading from
10% to 15% did not improve the reaction, so we used
10% loading as our optimal conditions.
yields are isolated yields.
We then evaluated reaction of various pyridinyl/
quinolinyl/benzoquinolinyl heteroarenes with tosyl
azide 2a (Table 3). The substitution pattern (meta,
para) and electronic properties of substitution
(electron deficient or rich) on the aromatic rings of
With the optimized conditions in hand, first we
explored the substrate scope and functional group
2
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10.1002/adsc.201800544
Advanced Synthesis & Catalysis
pyridinyl benzene played a small role; good yields
were obtained regardless.
Table 3. Scope for manganese-catalyzed amidation of
heteroarenes with tosyl azide 2a.a
a
Conditions: 1 (0.2 mmol), sulfonyl azide 2 (0.4 mmol), MnBr(CO)5
(10 mol %), TPAB (10 mol%) and water (1 mL), 120 oC for 16 h. All
yields are isolated yields.
a
Conditions: 1 (0.2 mmol), sulfonyl azide 2 (0.4 mmol), MnBr(CO)5
(10 mol %), TPAB (10 mol%) and water (1 mL), 120 oC for 16 h. All
yields are isolated yields.
Our reaction conditions also worked well for the
amidation of indoles using pyrimidine as the directing
group (Table 4). Similarly, this reaction also worked
very well with both aromatic and aliphatic sulfonyl
azides 2. And the structure assignment of our
obtained product was confirmed by the single-crystal
X-ray diffraction of a typical product (see the ORTEP
drawing of 3av[16] in Table 4).
The proposed mechanism is illustrated in Scheme 2
based on precedent reports.[8] The catalytic cycle
starts with the generation of manganese specie A from
1a and catalyst MnBr(CO)5 via an electrophilic
aromatic metalation pathway.
A
reversible
coordination of tosylazide to the cationic Mn center in
A gives Mn-intermediate B, then an amido insertion
gives Mn-intermediate C by releasing a nitrogen
molecule. In the last, the protodemetalation of C of
affords the final amidated product 3a and regenerates
the Mn catalyst. The water solvent may play an
import role in mediating the protodemetalation
process.
Also, our methodology can be used in larger scale
synthesis without complications (eq 1).
Table 4. Scope for manganese-catalyzed amidation of
indoles.a
3
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10.1002/adsc.201800544
Advanced Synthesis & Catalysis
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Scheme 2. Proposed mechanism for C-H activation of 1a.
[3]
In summary, we have developed an efficient
amidation of various heteroarenes via C–H bond
activation using readily available sulfonyl azides
catalyzed by base metal catalyst - MnBr(CO)5. Other
manganese-catalyzed C-H activation systems are
currently being investigated in our laboratories.
Experimental Section
General procedure for admidation of 1
1 (0.2 mmol), sulfonyl azide 2 (0.4 mmol), MnBr(CO)5 (10
mol %), TPAB (10 mol%) and water (1 mL) were added to
an oven-dried 25 mL glass reactor equipped with a stir bar.
The reaction mixture was stirred in a pre-heated oil bath at
o
120 C for 16 h with vigorous stirring. Upon completion,
the mixture was diluted with CH2Cl2. The reaction mixture
was extracted with CH2Cl2 (10 mL × 3). The combined
organic layers were dried over MgSO4. The solvents were
removed under reduced pressure and the crude mixture was
purified by chromatography on silica gel (hexanes/EtOAc)
to give the desired product 3.
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Acknowledgements
We are grateful to the National Science Foundation of China for
financial support (NSFC-21472018) and China Recruitment
Program of Global Experts for financial support.
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5
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10.1002/adsc.201800544
Advanced Synthesis & Catalysis
COMMUNICATION
Manganese-Catalyzed C–H Amidation of
Heteroarenes in Water
Adv. Synth. Catal. Year, Volume, Page – Page
Xianqiang Kong, Nong Ling, Bo Xu*
6
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