Copper-Catalyzed Carbonylative Cross-Coupling of Arylboronic Acids with N-Chloroamines for the Synthesis of Aryl Amides

Article abstract of DOI:10.1002/ejoc.201700352

A novel copper-catalyzed carbonylative cross-coupling between N-chloroamines and arylboronics acids has been developed. With copper(I) oxide as the catalyst, various desired amide compounds were produced in moderate to good yields. Functional groups such as iodide and alkene are tolerated. Notably, this is the first example of a copper-catalyzed aminocarbonylation with N-chloroamines.

Full text of DOI:10.1002/ejoc.201700352

A Journal of
Accepted Article
Title: Copper-Catalyzed Carbonylative Cross-Coupling of Arylboronic
Acids with N-Chloroamines to Synthesis Aryl Amides
Authors: Xiao-Feng Wu, Zhiping Yin, Zechao Wang, and Wanfang Li
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10.1002/ejoc.201700352
European Journal of Organic Chemistry
COMMUNICATION
Copper-Catalyzed Carbonylative Cross-Coupling of Arylboronic
Acids with N-Chloroamines to Synthesis Aryl Amides
Zhiping Yin,a Zechao Wang,a Wanfang Lia and Xiao-Feng Wu*a,b
Abstract: A novel copper-catalyzed carbonylative cross-coupling
Table 1. Optimization of the reaction conditions.a
between N-chloroamines and arylboronics acids has been
developed. With copper(I) oxide as the catalyst, various the desired
amide compounds were produced in moderate to good yields.
Functional groups such as iodide and alkene can be tolerated.
Notably, this is the first example on copper-catalyzed
aminocarbonylation of N-chloroamines.
Amide is one of the most important function groups in chemistry,
it presents in proteins and also found wildly in numerous natural
products and pharmaceutical molecules.1 Although their obvious
importance, the most commonly applied method for their
construction is based on the combination of activated carboxylic
acids derivatives and amines. Although a vast amount of efforts
have been devoted to develop more efficient methodologies for
amides synthesis, drawbacks including the usage of expensive
reagents, low functional group tolerance and low reaction
efficiency are remaining.2 Therefore, the developments of new
and more efficient methods for amides synthesis are still under
current request.3,4
On the other hand, transition metal-catalyzed carbonylative
coupling reactions have already become a powerful toolbox in
modern organic synthesis. Various carbonyl-containing
molecules can be effectively produced by introducing carbon
monoxide into the parent compounds. Depending on the
nucleophiles applied, aminocarbonylation, with amines as the
coupling partner, provides a promising pathway for amides
preparation.5 However, most of the developed procedures are
facing two challenges: using aryl halides as the electrophiles
and using palladium as the catalysts.6 Under these backgrounds
and also from the academic point of view, we feel it will be
attractive to apply N-chloroamine as reagent in the carbonylative
synthesis of amides which have reported in cross-coupling
reactions.7 Additionally, due to the advantages of copper salts
compared with noble metal catalysts, we decided to explore the
possibility of applying copper catalysts in carbonylative coupling
transformations.8
Initially, the reaction was performed using copper oxide,
NaHCO3, PhB(OH)2 in MTBE under pressure of CO (50 bar) at
40°C. To our delight, the desired product was obtained with 50%
isolated yield (Table 1, entry 1). And the yield can be further
improved to 63% BY rising the reaction temperature to 50 °C
[a]
[b]
Z. Yin, Z. Wang, Dr. W. Li, Prof. Dr. X.-F. Wu
Leibniz-Institut für Katalyse e.V. an der Universität Rostock, Albert-
Einstein-Straße 29a, 18059 Rostock (Germany)
E-mail: Xiao-Feng.Wu@catalysis.de
Prof. Dr. X.-F. Wu
(Table 1, entry 2)
condition and a series of copper catalysts were evaluated,
including CuBr(Me2S), Cu(acac)2, Cu(OSO2CF3),
. Then we continued to optimize the reaction
Department of Chemistry, Zhejiang Sci-Tech University, Xiasha
Campus, Hangzhou 310018, People’s Republic of China
www.catalysis.de
Cu(MeCN)4·BF4, CuBr(ligand 1)PPh3 and CuCl(iPr) (Table 1,
entries 4-9). But all this copper catalysts were inferior to Cu2O.
Supporting information for this article is given via a link at the end of
the document.
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10.1002/ejoc.201700352
European Journal of Organic Chemistry
COMMUNICATION
and 17) and only 6% yield was obtained with tBuOK as base
(Table 1, entry 15). Furthermore, the reaction efficiency dropped
dramatically when using DCE or Benzene as the reaction media
(Table 1, entries 18 and 19). The loading of Cu2O was checked
as well (Table 1, entries 20-21). The amount of catalyst can be
decreased to 5 mol% without losing reaction efficiency. Finally,
we found that the combination of 5 mol% Cu2O and NaHCO3
(1.5 equiv.) under CO atmosphere (50 bar) at 50°C for 16 h
provide the best outcome of target product (66%; Table 1, entry
20).
Table 2. Cu-catalyzed aminocarbonylation of N-chloroamines: Scope of
arylboronic acids.a
With the optimized reaction conditions in hand, we examined
the substrates scope of this transformation with a range of
boronic acids. As shown in Table 2, the desired amide products
were formed in good yields in general with the arylboronic acids
tested with 1-chloropiperidine. Halogen functional groups can be
well tolerated, moderate to good yields of the desired amides
were isolated (Table 2, entries 2-5). Notably, 69% of (4-
iodophenyl)(piperidin-1-yl)methanone
was
produced
successfully under our conditions (Table 2, entry 4). The other
alkyl and aryl substituted arylboronic acids can be applied as
well and provide the desired amides in good yields (Table 2,
entries 6-9). However, when using (4-vinylphenyl)boronic acid or
2-(4-methoxyphenyl)-5,5-dimethyl-1,3,2-dioxaborinane as the
starting materials, the yield of the desired products drops
dramatically (Table 2, entries 10 and 11). And no desired
product could be detected with alkylboronic acid (Table 2, entry
12). Additionally, no reaction occurred with PhBF3K and 4-
methoxyphenylboronic acid, but the decomposition of the
substrates.
Table 3. Cu-catalyzed aminocarbonylation of N-chloroamines: Scope of
chloroamines.a
Subsequently, nitrogen ligands were tested with Cu2O (Table
1, entries 10-14). However, no positive effect could be observed
with the tested ligands. Successively, different bases and
solvents were studied. When tBuOLi or PhONa tested as the
base, no desired product could be detected (Table 1, entries 16
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10.1002/ejoc.201700352
European Journal of Organic Chemistry
COMMUNICATION
mmol) and tBuOMe (2 mL) were added to the reaction mixture by springe.
The vials were then placed on an alloy plate and transferred into a 300
ml autoclave of the 4560 series from Parr instruments under air. After
flushing the autoclave three times with CO, a pressure of 50 bar CO was
settled and the reaction was performed for 16 hours at 50°C. Afterwards,
the autoclave was cooled to room temperature and the pressure was
released carefully. The solvent was removed under reduced pressure
and the crude products were purified by column chromatography on silica
gel (eluent: pentane/ethyl acetate = 3:1)
Furthermore, various N-chloroamines were prepared and
tested under our reaction conditions.9 As shown in Table 3,
moderate yields can be observed from the reaction of 4-
chloromorpholine, 1-chloro-4-methylpiperidine and N-chloro-1-
(4-fluorophenyl)-N-methylmethanamine with phenylboronic acid
under identical conditions. Notably, the attempting in using of
primary amines and aromatic amines analogues of chloroamines
as substrates were all failed, either substrates decomposition or
the corresponding ureas were detected.
Based on our results and literature, a possible reaction
mechanism is proposed (Scheme 1).[7j] Firstly, dialkylaminyl
radical A is generated by SET process from the N-choro
dialkylamine and the Cu(I) is been oxidized to Cu(II). Under CO
pressure, CO coordinated with Cu(II) to give the intermediate B.
Acknowledgements
The analytic supports of Dr. W. Baumann, Dr. C. Fisher, S.
Buchholz, and S. Schareina are gratefully acknowledged. We
also appreciate the general supports from Professor Matthias
Beller and Professor Armin Börner in LIKAT.
Then intermediate
C was formed from the reaction of
dialkylaminyl radical and Cu(II) B. The carbmoyl-metal
intermediate C undergoes transmetalation with boronic acid to
form the intermediate D, which then affords the final amide
product after reductive elimination while the active Cu (I) species
is regenerated for the next catalytic cycle.
Keywords: copper catalyst • carbonylation • amide • radical • N-
chloroamines
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Scheme 1. Proposed reaction mechanism.
In summary,
a
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reaction of N-chorolamines with boronic acids has been
developed. With Cu2O as the catalyst, a series of aromatic
amides were synthesized in moderate to good yields from the
corresponding substrates. Notably, this is the first example on
copper-catalyzed aminocarbonylation of N-chloroamines.
Experimental Section
To each screw-cap vial (4 ml) equipped with a septum, a small cannula,
and a stirring bar was added with boronic acid (0.25 mmol), NaHCO3 (63
mg, 0.75 mmol) and Cu2O (1.8 mg, 0.013 mmol). The vials then were
then purged with argon three times before the N-chloroamines (0.5
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European Journal of Organic Chemistry
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Zhiping Yin, Zechao Wang, Wanfang Li
and Xiao-Feng Wu*
Page No. – Page No.
Copper-Catalyzed Carbonylative
Cross-Coupling of Arylboronic Acids
with N-Chloroamines to Synthesis
Aryl Amides
Corp(Copper) CO! A novel copper-catalyzed carbonylative cross-coupling between
N-chloroamines and arylboronics acids has been developed. With copper(I) oxide
as the catalyst, various the desired amide compounds were produced in moderate
to good yields.
This article is protected by copyright. All rights reserved.