Silver and Palladium Cocatalyzed Carbonylative Activation of Benzotriazoles to Benzoxazinones under Neutral Conditions

Article abstract of DOI:10.1021/acs.orglett.7b03184

A novel and efficient method for the carbonylative activation of benzotriazoles to benzoxazinones has been developed. By using a silver and palladium bimetallic catalyst system, a broad range of benzotriazoles were transformed into the corresponding benzoxazinones in moderate to good yields with excellent functional group tolerance. Notably, this procedure proceeds under neutral conditions.

Full text of DOI:10.1021/acs.orglett.7b03184

Letter
Cite This: Org. Lett. XXXX, XXX, XXX-XXX
pubs.acs.org/OrgLett
Silver and Palladium Cocatalyzed Carbonylative Activation of
Benzotriazoles to Benzoxazinones under Neutral Conditions
Zhiping Yin, Zechao Wang, and Xiao-Feng Wu*
̈
̈
Leibniz-Institut fur Katalyse e.V. an der Universitat Rostock, Albert-Einstein-Straße 29a, 18059 Rostock, Germany
*
S Supporting Information
ABSTRACT: A novel and efficient method for the carbonylative
activation of benzotriazoles to benzoxazinones has been developed.
By using a silver and palladium bimetallic catalyst system, a broad
range of benzotriazoles were transformed into the corresponding
benzoxazinones in moderate to good yields with excellent
functional group tolerance. Notably, this procedure proceeds under neutral conditions.
enzoxazinones are one of the most important heterocyclic
chemistry and medicinal chemistry for the synthesis of a
biological active quinazolin-4(3H)-one derivative. Despite
5
B
compounds endowed with a broad spectrum of biological
1
activities. For example, Cetilistat is an inhibitor of pancreatic
lipase, which can potentially be used for the treatment of
their obvious importance, currently the most commonly
applied methods to construct these heterocyclic compounds
2
6
obesity with or without diabetes (Scheme 1). TEI-5624 and
are based on anthranilic acids. Alternative methodologies have
7
TEI6344 were found to be the inhibitors of human leukocyte
elastase (HLE) and may exert potent therapeutic effects on
pulmnoary emphysema, an adult respiratory distress syn-
been reported as well, such as oxidation of 2-arylindoles and
8
palladium-catalyzed carbonylation of ortho-haloanilines. How-
ever, the reactions are usually carried out under basic or acidic
conditions, which surely limit certain classes of functional
groups.
3
drome. In addition, benzoxazinones are also used as inhibitors
4
of HSV-1 protease and chymotrypsin. Furthermore, benzox-
On the other hand, 1,2,3-benzotriazoles are significan9t
azinones also serve as crucial synthetic scaffolds in organic
heterocyclic units and broadly used in medicinal chemistry,
1
0
11
biochemistry, and material science. One of their particular
properties is that they can go through a ring-opening process to
Scheme 1. Selected Bioactive Benzoxazinones and Known
Synthesis Procedures
12
form the corresponding diazonium species. This aforemen-
tioned reactive intermediate can undergo various trans-
formations, including annulations and cross-coupling reac-
13
14
tions. Due to our continuing interest in palladium-catalyzed
15
carbonylative transformations, we become interested in
exploring the application of 1,2,3-benzotriazoles as substrates
in carbonylative transformations. With such a procedure, readily
available benzotriazoles can be further transformed; properties
of the related materials and drugs can be modified. In addition,
products such as benzoxazinone compounds can be effectively
produced.
Additionally, bimetallic catalysis for new C−C and C−X (X
=
O, N, S, etc.) bond formation is a promising topic and
16
increasing in importance in the synthetic toolbox. New
reactivity can be discovered with a bimetallic system which
cannot be realized with any of the single catalysts. In this letter,
we report a novel silver and palladium cocatalyzed carbon-
ylative transformation of benzotriazoles to benzoxazinones.
Notably, this procedure proceeds under neutral conditions.
Initially, the reaction was performed using 1a as the model
substrate to optimize the reaction conditions. The initial
reaction trial was performed with Pd(OAc) and Xantphos as
2
Received: October 12, 2017
©
XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.7b03184
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
the catalytic system in MeCN under pressure of CO (20 bar) at
Scheme 2. Scope of Acyl 1,2,3-Benzotriazoles
1
20 °C. To our delight, a 60% yield of the desired product was
formed (Table 1, entry 1). The yield of the reaction decreased
a
Table 1. Optimization of the Reaction Conditions
b
entry
variations from the standard conditions
Pd(OAc) instead of PdCl
yield (%)
1
2
3
4
5
6
7
8
9
60
35
40
2
2
Pd(TFA) instead of PdCl
2
2
Pd (dba) ·CHCl instead of PdCl
2
2
3
3
c
−
87, 81
toluene instead of CH CN
79
3
1,4-dioxane instead of CH CN
19
3
tBu P·HBF (10 mol %) instead of Xantphos
75
3
4
BuPAd (10 mol %) instead of Xantphos
73
2
DPPP (5 mol %) instead of Xantphos
80
10
11
12
13
14
15
16
17
AgBF (20 mol %) instead of AgOTf
50
4
Ag CO (10 mol %) instead of AgOTf
trace
30
2
3
AgF (20 mol %) instead of AgOTf
no ligand
63
no AgOTf
trace
50
CO 10 bar instead of 20 bar
100 °C instead of 120 °C
2% PdCl instead of 5% PdCl
70
65
2
2
a
b
Reaction scale: 0.2 mmol, solvent (2 mL). GC yields were
c
determined by using hexadecane as the internal standard. Isolated
yield. DPPP = 1,3-bis(diphenylphosphino)propane.
when using Pd(TFA) as the palladium precursor (Table 1,
2
entry 2). Pd (dba) ·CHCl as the Pd(0) precursor has been
2
3
3
tested as well; 40% of the target molecule was produced (Table
1, entry 3). Delightfully, 81% of 2-phenyl-4H-benzo[d][1,3]-
oxazin-4-one can be isolated with PdCl as the catalyst (Table
2
1, entry 4). The reaction efficiency slightly dropped with
toluene as the reaction solvent, and only a 19% yield could be
obtained if the reaction was performed in 1,4-dioxane (Table 1,
entries 5 and 6). Then, though various other ligands were
tested, the yield of the desired product still cannot be further
improved (Table 1, entries 7−9). Afterward, we turned our
attention to the effect of cocatalysts. Various silver salts were
tested, but reaction efficiency could not be further improved
a
1
a−1r (0.2 mmol), PdCl (5 mol %), Xantphos (5 mol %), AgOTf
2
(
20 mol %), CO (20 bar), dry CH CN (2 mL), 120 °C, 16 h, isolated
3
b
yields. CO (40 bar).
prepared from the corresponding substrates as well (Scheme 2,
entries 3i, 3l, 3o). Those substituents were ready for further
transformations via cross-coupling reactions. Notably, substrate
1d (1H-benzo[d][1,2,3]triazol-1-yl)(p-tolyl)methanone can
give the corresponding benzoxazinone product 3d in 91%
yield. Interestingly, 2-heterocyclic and 2-alkyl substituted
benzoxazinones can also be produced from the corresponding
1,2,3-triazoles (Scheme 2, entries 3q, 3r). Furthermore, various
1,2,3-benzotriazoles with substitutions on the other aromatic
rings were prepared and tested as well. As shown in Table 2,
moderate to good yields of the desired products were achieved
under the standard conditions. Since the two isomers of the
1,2,3-benzotriazoles (Table 2, entries 1 and 2) are impossible to
separate, the products were obtained as a mixture of two
isomers, and the product ratios of the two isomers are 2.2:1 and
(Table 1, entries 10−12). In the absence of ligand, the yield
decreased to 63% (Table 1, entry 13). No reaction occurred in
the absence of silver triflate (Table 1, entry 14). Additionally,
the yield of the target product decreased with lower loading of
the palladium catalyst, lower CO pressure, or lower reaction
temperature (Table 1, entries 15−17). Finally, we found that
the use of 5 mol % of PdCl , 5 mol % of Xantphos, and 20 mol
2
%
of AgOTf under CO pressure (20 bar) in MeCN at 120 °C
gave the desired product 3a in 81% isolated yield (Table 1,
entry 4).
Having determined the best conditions, we then examined
the scope of the reaction with a range of 1,2,3-triazoles. As
shown in Scheme 2, the desired benzoxazinone products were
formed in good yields with different electron-donating or
1
3:1, respectively, determined by H NMR. Halogen substituents
-
withdrawing groups in the ortho or para position of the
on the aromatic ring were well tolerated in our reaction and
gave the desired products in 68% and 63% yields (Table 2,
substrates. Chloro and bromo substituted products can be
B
DOI: 10.1021/acs.orglett.7b03184
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
Table 2. Scope of Benzoyl 1,2,3-Benzotriazoles
Scheme 3. Proposed Reaction Mechanism
various benzoxazinones were produced in moderate to good
yields with excellent functional group tolerance. Notably, the
reactions were performed under neutral conditions.
ASSOCIATED CONTENT
Supporting Information
■
*
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.7b03184.
General comments, general procedure, analytic data, and
NMR spectra (PDF)
AUTHOR INFORMATION
Corresponding Author
■
*
E-mail: xiao-feng.wu@catalysis.de.
ORCID
Xiao-Feng Wu: 0000-0001-6622-3328
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
a
We thank the Chinese Scholarship Council for financial
support. We thank the analytical department of Leibniz-
Institute for Catalysis at the University of Rostock for their
excellent analytical service here. We appreciate the general
Substrate (0.2 mmol), PdCl (5 mol %), Xantphos (5 mol %), AgOTf
2
(
20 mol %), CO (20 bar), dry CH CN (2 mL), 120 °C, 16 h, isolated
3
b
c
yields. Yield of two isomers. CO (40 bar).
̈
support from Professor Armin Borner and Professor Matthias
entries 3−5). A good yield of two methyl substituted 1,2,3-
benzotriazoles can be successfully transformed as well and gave
the desired product in 75% yield (Table 2, entry 6).
Beller in LIKAT.
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