Palladium-Catalyzed Carbonylative Synthesis of Amides from Aryltriazenes under Additive-Free Conditions

Article abstract of DOI:10.1002/ejoc.201700784

An interesting palladium-catalyzed carbonylative synthesis of amides from aryltriazenes was developed. By using Pd(MeCN₂)Cl₂ as the catalyst precursor under CO pressure through a N₂ extrusion/CO insertion sequence, a broad range of aryltriazenes were transformed into the corresponding amides in good yields with excellent functional group tolerance. Remarkably, no additives such as acids or phosphine ligands were required.

Full text of DOI:10.1002/ejoc.201700784

A Journal of
Accepted Article
Title: Palladium-Catalyzed Carbonylative Synthesis of Amides from
Aryltriazenes under Additive-free Conditions
Authors: Xiao-Feng Wu, Zhiping Yin, and Zechao Wang
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201700784
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10.1002/ejoc.201700784
European Journal of Organic Chemistry
COMMUNICATION
Palladium-Catalyzed Carbonylative Synthesis of Amides from
Aryltriazenes under Additive-free Conditions
Zhiping Yin,a Zechao Wang,a and Xiao-Feng Wu*a
Abstract: An interesting palladium-catalyzed carbonylative
synthesis of amides from aryltriazenes has been developed.
By using Pd(MeCN2)Cl2 as the catalyst precursor under CO
pressure via N2 extrusion/CO insertion sequence, broad
range of aryltriazenes were transformed into the
corresponding amides in good yields with excellent functional
groups tolerance. Remarkably, no additives such as acid or
phosphine ligand are required here.
acid as the additive to activate the aryltriazenes.[5,6] In 2015,
we reported new palladium-catalyzed carbonylative
a
reaction of aryltriazenes (Scheme 1, eq. a).[7a] Nevertheless,
besides the necessity of MeSO3H addition, only N-alkyl
benzamides can be produced as the terminal products.
Under these backgrounds, we find it would be interesting if
we could develop a new procedure to overcome the
mentioned drawbacks (Scheme 1, eq. b).
Among all the carboxylic acid derivatives, amides are
attractive due to their numerous applications in advanced
materials and pharmaceutical molecules.[1] The traditional
procedure for their construction is based on the combination
of their parent carboxylic acid derivatives with amines.
Although various alternative methodologies have been
established during the past decades, challenges such as
complexed reaction system, limited substrates scope, low
functional group tolerance and/or low reaction efficiency are
still existing.[2] Hence, new synthetic procedures which can
overcome one or some of the mentioned drawbacks will be
still under demand.[3]
Scheme 1. Carbonylation transformation of triazenes.
On the other hand, transition metal-catalyzed
carbonylative transformations have experienced decades of
developments and proven to be a powerful toolbox for the
synthesis of carbonyl-containing molecules. By introducing
one or two molecules of carbon monoxide into the parent
compounds, values added chemicals can be effectively
formed. In the known carbonylation reactions, amides can be
selectively produced via aminocarbonylation of aryl halides
with amines as the coupling partner.[4]
Initially,
the
reaction
was
performed
using
diphenyltriazene 1a as the model substrate with Pd(OAc)2 as
the catalyst in DMF under the pressure of CO (20 bar) at
110°C. To our delight, diphenyltriazene 1a was transformed
into the desired N-phenyl benzamide in 30% yield without
any acid additive or phosphine ligand (Table 1, entry 1). With
this exciting result in hand, we continued to optimize this new
reaction. Then different palladium(II) catalyst precursors
were tested under identical reaction conditions (Table 1,
entries 2-7). As we expected, N-phenyl benzamide can be
detected in all the cases and the best yield can be reached
by using Pd(MeCN)2Cl2 as the catalyst (Table 1, entry 7;
65% yield). The yield can be further improved to 87% by
using 1.4-dioxane as the reaction media (Table 1, entry 10).
Other solvents, such as DCE and MeCN were all inferior to
1.4-dioxane. Then the loading of Pd(MeCN)2Cl2 was
checked as well, up to 82% of the desired amide can be
obtained with even 2 mol% of the palladium catalyst (Table 1,
entry 11). Additionally, no significant reaction efficiency
decreasing was observed with decreased CO pressure or
reaction temperature (Table 1, entry 12-14). Finally, we
found that the combination of 5 mol% Pd(MeCN)2Cl2 in 1.4-
dioxane under CO atmosphere (20 bar) at 110°C for 16
hours can provide the best outcome of the target amide
(88% isolated yield; Table 1, entry 10).
Aryltriazenes are considered as an analogue of
stabilized aryl diazonium salts and have been extensively
explored in organic synthesis.[5] They have advantages
including easy preparation, good stability and readily
conversion to other functional groups. However, in general,
most of these transformations need Lewis acids or Brønsted
[a]
Z. Yin, Z. Wang, Prof. Dr. X.-F. Wu
Leibniz-Institut für Katalyse e.V. an der Universität Rostock,
Albert-Einstein-Straße 29a, 18059 Rostock, Germany; Prof.
Dr. X.-F. Wu, Department of Chemistry, Zhejiang Sci-Tech
University, Xiasha Campus, Hangzhou, 310018, People’s
Republic of China
E-mail: Xiao-Feng.Wu@catalysis.de
https://www.catalysis.de/forschung/hydrierungen-und-
hydroformylierungen/katalyse-zu-heterocyclen/
Supporting information for this article is given via a link at the end
of the document.
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10.1002/ejoc.201700784
European Journal of Organic Chemistry
COMMUNICATION
Table 1. Optimization of the reaction conditions.[a]
Yield[b]
30%
8%
Catal.
Pd(OAc)2
Solvent
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DCE
CO
Entry
20 bar
20 bar
20 bar
20 bar
20 bar
20 bar
20 bar
20 bar
20 bar
1
2
3
4
5
6
7
8
9
Pd(dba)2
57%
62%
40%
61%
65%
32%
69%
Pd(CF3CO2)2
[Pd(cinnamyl)Cl]2
PdCl2(cod)
PdCl2
Pd(MeCN)2Cl2
Pd(MeCN)2Cl2
Pd(MeCN)2Cl2
MeCN
87%
(88%)[c]
Pd(MeCN)2Cl2
1.4-dioxane
20 bar
10
82%[d]
Pd(MeCN)2Cl2
Pd(MeCN)2Cl2
Pd(MeCN)2Cl2
Pd(MeCN)2Cl2
1.4-dioxane
1.4-dioxane
1.4-dioxane
1.4-dioxane
20 bar
10 bar
5 bar
11
12
13
14
85%
74%
76%[e]
20 bar
a: Reaction conditions: 1a (0.20 mmol), [Pd] (0.01 mmol, 5 mol%) , solvent (2
mL), CO, 110 °C, 16 h. b: GC yields were determined by using hexadecane as
the internal standard. c: isolated yield, obtained in separate runs. d:
Pd(MeCN)2Cl2 (2 mol%). e: 100 oC. DCE = 1,2-Dichloroethane; DMF = N,N-
Dimethylmethanamide.
With the optimized reaction conditions in hand, we
examined the substrates scope of this transformation with a
range of aryltriazenes (Tables 2 and 3). As shown in Table 2,
the desired amide products were formed in good yields in
general with the aryltriazenes tested. Both electron-
withdrawing and electron-donating substituted aryltriazene
can provide the desired N-aryl arylamides products in good
to excellent yields. Notably, halogen functional groups can
be well tolerated as well, good yields of the desired amides
were isolated (Table 2, entries 2, 4, 5, 8). These halogen
functional group containing amides products are ready for
further modifications via cross-coupling reactions.
Furthermore, by using dialkylamines as the starting
materials, various dialkyl-aryltriazenes were prepared and
tested under our reaction conditions. As shown in Table 3,
aryltriazenes 1k-1p with different substituents at ortho, meta
and para were smoothly converted into the desired
aryl(piperidin-1-yl)methanonethes in high yields (Table 3,
entries 1-6). Moreover, good yields can also be observed
from the reaction of other alkylamine substrates such as
morpholine, diethyl and 4-methyl-piperidine (Table 3, entries
7-10).
Scheme 2. Control experiments.
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10.1002/ejoc.201700784
European Journal of Organic Chemistry
COMMUNICATION
Scheme 3. Proposed reaction mechanism.
In summary,
a
new palladium(II)-catalyzed N2
extrusion/CO insertion reaction of aryltriazenes has been
developed. With Pd(MeCN)2Cl2 as the only catalyst, a series
of N-aryl and N-alkyl benzamides were synthesized in good
to excellent yields from the corresponding triazenes. Notably,
no additives such as acid or phosphine ligand are required
here.
Experimental Section
General procedure of Pd-catalyzed carbonylative reaction of
aryltriazenes: To each screw-cap vial (4 mL) equipped with a
septum, a small cannula, and a stirring bar was added aryltriazene
substrates (0.20 mmol), Pd(MeCN)2Cl2 (2.6 mg, 0.01 mmol) and 1.4-
dioxane (2 mL). The vials then were purged with argon three times
before 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 20 bar CO
was set and the reaction was performed for 16 hours at 110°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 = 2:1).
Finally, in order to get some insight of the reaction
pathway of this procedure, control experiments were
performed. As shown in scheme 2, the start material 1m was
recovered in 82% yield when the reaction was conducted
under the same reaction condition but in the absence of CO.
However, the start material can be fully converted when
some CO source (TFBen: benzene-1,3,5-triyl triformate) was
introduced but no desired amide product could be
detected.[8] Hence we propose that CO has three roles in this
transformation (Scheme 3): 1) as ligand and coordinates with
palladium to increase its Lewis acidity which then activates
triazenes; 2) as reductant to reduce Pd(II) to Pd(0) which
then starts the catalytic cycle; 3) as carbonyl source to
replace N2 and produce amides.
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 Professors
Matthias Beller and Armin Börner in LIKAT.
Keywords: amides • aryltriazenes • palladium • carbonylation •
cascade process
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COMMUNICATION
Zhiping Yin, Zechao Wang, and Xiao-
Feng Wu*
Page No. – Page No.
Palladium-Catalyzed Carbonylative
Synthesis of Amides from
Aryltriazenes under Additive-free
Conditions
Self-activated: A new palladium-catalyzed carbonylation reaction of aryltriazenes
has been developed. With Pd(MeCN)2Cl2 as the catalyst, a series of N-aryl and N-
alkyl benzamides were synthesized in good to excellent yields from the
corresponding triazenes. Notably, no additives such as acid or phosphine ligand are
required here.
This article is protected by copyright. All rights reserved.