Ir-catalyzed regiospecific mono-sulfamidation of arylquinazolinones

Article abstract of DOI:10.1016/j.cclet.2019.05.013

An Ir-catalyzed selective mono-sulfamidation of 2-arylquinazolinones has been achieved with a low catalyst loading under mild conditions. A series of regioselective mono-sulfamided 2-arylquinazolinones were obtained in up to 90% yields. Compared with our

Full text of DOI:10.1016/j.cclet.2019.05.013

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CCLET 4981 No. of Pages 3
Chinese Chemical Letters xxx (2019) xxx–xxx
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Chinese Chemical Letters
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Communication
Ir-catalyzed regiospecific mono-sulfamidation of arylquinazolinones
b
a
a
a
a
Yadong Fenga,b, , Zhenyue Zhang , Qi Fu , Qiuhong Yao , Huabin Huang , Jinhai Shen ,
Xiuling Cui
a
*
b,**
College of Environment and Public Health, Xiamen Huaxia University, Xiamen 361024, China
Engineering Research Center of Molecular Medicine of Ministry of Education, Key Laboratory of Fujian Molecular Medicine, Key Laboratory of Xiamen
b
Marine and Gene Drugs, School of Biomedical Sciences, Huaqiao University, Xiamen 361021, China
A R T I C L E I N F O
A B S T R A C T
Article history:
An Ir-catalyzed selective mono-sulfamidation of 2-arylquinazolinones has been achieved with a low
catalyst loading under mild conditions. A series of regioselective mono-sulfamided 2-arylquinazolinones
were obtained in up to 90% yields. Compared with our previous work of constructing di-sulfamidated 2-
arylquinazolinones, the mono-sulfamided products could be obtained selectively by changing the ratio of
substrates, the loading of catalyst, acid additive, and reaction time.
Received 26 March 2019
Received in revised form 24 April 2019
Accepted 7 May 2019
Available online xxx
© 2019 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.
Published by Elsevier B.V. All rights reserved.
Keywords:
Ir-catalyzed
C-H activation
Mono-sulfamidation
Selectivity
Arylquinazolinones
Quinazolinone is ubiquitous framework in drugs and natural
products because of their various biological activities [1]. As a
result, the construction and modification of quinazolinones have
been attractive for the organic chemists. Our group has developed
alkenylation/tandem hydroamidative cyclization of quinazoli-
nones leading to the selective mono- or di-alkenylation products
[7]. In 2018, Jana group has developed a Ru-catalyzed redox-
neutral CÀÀH bond allylation/hydroamination cascade reaction to
synthesize dihydroisoquinolino[1,2-b]quinazolinones [8]. For this
direction, our group reported a Pd-catalyzed aerobic oxidative
reaction of arylquinazolinones with alkynes to assemble fused-
polycyclic systems containing tetrahydropyridine and dihydro-
furan rings [9]. On the other hand, organic azides have been
extensively explored in C–H amination or amidation reactions for
their ability to act as an internal oxidant and environmentally
benign reagent [10]. For example, Chang group reported the first
intermolecular amidation of arenes with sulfonyl azides via Rh-
catalyzed C–H activation in 2012 [11]. Subsequently, in 2013,
Glorius group reported a Rh/Cu-cocatalyzed synthesis of indazoles
through CÀÀH amidation and NÀÀN bond formation from
arylimidates and organo azides [12]. After that, the groups of
Ackermann, Kanai, Wang, Li, Cui, and Zhu have reported many
other similar strategies for C–N bond construction via C–H
amination or amidation reactions using organic azides [13].
However, controlling site selectivity is still one of the challenges
in these current reactions. Recently, our group has developed an Ir-
catalyzed direct di-sulfamidation of arylquinazolinones using
sulfonyl azides as amino sources (Scheme 1a) [14]. However, it
is not easy to regioselectivity obtain mono-substituted products in
the metal-catalyzed arylation, alkenylation, allylation or sulfami-
dation of quinazolinones, in which additives, such as acid and base,
were necessary for the transformations. In our continuing effort to
a
copper-catalyzed synthesis of quinazolinones from easily
available 2-arylindoles and amines or ammoniums in 2015 [2].
In 2016, Huang group reported a Cu-catalyzed domino reaction for
the synthesis of pyrido-fused quinazolinone derivatives, which
involved CÀÀN/CÀÀC bond cleavage and two CÀÀN bond formations
in a one-pot operation [3]. In 2018, Su group developed an
Au-catalyzed selective cyclization of alkynyl quinazolinone-
tethered pyrroles for the synthesis of fused quinazolinone scaffolds
[4]. Chen group developed a Pd-catalyzed tandem reaction of
quinazolinone-based nitriles with arylboronic acids for the
synthesis of 2-(4-arylquinazolin-2-yl)anilines [5]. Great process
on transition metal-catalyzed functionalization of CÀÀH bond has
been achieved during past decade to obtain various quinazolinone
derivatives. For example, in 2017, Mhaske group reported a Pd-
catalyzed mono-arylation of aromatic rings by CÀÀH bond
activation using quinazolinone as the inherent directing group,
in which Na2CO3 was found to be crucial for this transformation
[6]. Moreover, the same group developed
a Ru-catalyzed
* Corresponding author at: College of Environment and Public Health, Xiamen
Huaxia University, Xiamen 361024, China.
** Corresponding author.
E-mail addresses: fengyd@hxxy.edu.cn (Y. Feng), cuixl@hqu.edu.cn (X. Cui).
https://doi.org/10.1016/j.cclet.2019.05.013
1001-8417/© 2019 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.
Please cite this article in press as: Y. Feng, et al., Ir-catalyzed regiospecific mono-sulfamidation of arylquinazolinones, Chin. Chem. Lett. (2019),
https://doi.org/10.1016/j.cclet.2019.05.013

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Y. Feng et al. / Chinese Chemical Letters xxx (2019) xxx–xxx
be reduced to trace, and the yield of 3a was selectively increased to
71% when 5.0 equiv. of AcOH was introduced into the reaction
(Table 1, entry 1 vs. entries 6–11). Moreover, the yield of 3a could be
increased to 90% when the reaction time was reduced to 1.0 h
(Table 1, entries 12–16). Based on the results, under the optimum
reaction conditions, the target product 3a was obtained selectively
in 90% yield in DCE at 80 ꢀC when [IrCp*Cl2]2 (2 mol%) was used as a
catalyst with AgSbF6 (8.0 mol%), AcOH (5.0 equiv.) under air for
1.0 h (Table 1, entry 15), and the yield of 4a was reduced to trace.
With the optimized reaction conditions in hand, the scope of
the substrates was examined (Table 2). First, toluenesulfonyl azide
(2a) reacted smoothly with 2-phenylquinazolin-4(3H)-one (1a)
and its derivatives (1b-m) to give 3a-m in good to excellent yields
(45%–90%). 6-Cl, 6ÀOCH3, and 5-F substituted arylquinazolinones
could provide the corresponding products 3b–3d in 83%, 68% and
45% yields, respectively. F group at the 2- and 4-position of 2-
phenyl in 2-aryl-quinazolin-4(3H)-one provided the correspond-
ing products 3e and 3f in 84% and 90% yields, which indicated that
steric effect did not significantly affect this transformation. Other
groups, such as Cl, Br, CH3, CF3, OCH3, and NO2 could be well
tolerated and gave the corresponding products in satisfactory
yields (3g-l) (65%–87%). It can be seen that the electron density on
the 2-arylquinazolinones did not significantly affect the efficiency
of the reaction as well. The reaction did not occur when
quinazolinones with both ortho-positions of aryl ring were
substituted, such as 2-(2,6-dimethylphenyl)quinazolin-4(3H)-
one. Meanwhile, 2-phenylquinazolin-4(3H)-one (1a) also reacted
smoothly with benzenesulfonyl azide (2b) to give the desired
product 3 m in 85% yield. Moreover, when other groups, such as
methyl, 4-methoxyphenyl, benzoyl, and 4-nitrophenyl are chosen
as R3 in this reaction, the yields of corresponding products are very
low, and di-sulfamided 2-arylquinazolinones were detected as
main products.
Scheme 1. Ir-catalyzed direct amidation of 2-arylquinazolinones.
develop efficient methods controlling site selectivity in C–H bond
activation [15], herein, we disclose an Ir-catalyzed direct mono-
amidation of 2-arylquinazolinones with sulfonyl azides to produce
ortho-amided quinazolinones (Scheme 1b), in which mono-
sulfamidated products were selectively obtained with high yields
by changing the ratio of substrates, the loading of catalyst, acid
additive and reaction time.
Initially, the amidation of 2-phenylquinazolin-4(3H)-one (1a)
(0.20 mmol) with para-toluenesulfonyl azide (2a) (0.20 mmol) was
chosen as a model reaction to examine the impact of various
parameters on the reaction (Table 1). The results revealed that
monoamidated 2-phenylquinazolin-4(3H)-one (3a) and diami-
dated 2-phenylquinazolin-4(3H)-one (4a) were obtained in 40%
and 23% yield respectively in DCE (1,2-dichloroethane) at 80 ꢀC
when [IrCp*Cl2]2 (1.0 mol%) was used as a catalyst with AgSbF6
(4.0 mol%), TFA (4.0 equiv.) under air (Table 1, entry 1). When the
loading amount of [IrCp*Cl2]2 and AgSbF6 were changed to 2.0 mol
% and 8.0 mol%, the yield of 3a was increased to 55% as well as 19%
yield of 4a (Table 1, entry 1 vs. entries 2–5). Notably, when AcOH
was chosen as the acid additive instead of TFA, the yield of 4a could
Based on the results obtained and literatures [16], the proposed
mechanism was the same with the first catalytic cycle in the
reaction for di-sulfamidated arylquinazolinones and was not
described again here (Scheme 2). However, it was noteworthy
that changing acid additive stopped the reaction in the first
catalytic cycle, because AcOH was too weak to stabilize the metal
intermediate in sequential two C–H bonds activation. At the same
time, increasing the loading of catalyst and reducing the reaction
time could assist the first C–H bond activation to proceed more
thoroughly.
Table 1
Optimization of the reaction conditionsa
In summary, we have demonstrated an Ir-catalyzed selective
mono-sulfamidation of 2-arylquinazolinones with a low catalyst
.
Table 2
Scope of substrates
Entry
[IrCp*Cl2]2 (mol
%)
AgSbF6 (mol
%)
Acid (equiv.) t (h) Yield (%)b
a
.
3a
4a
1
2
3
4
5
6
7
8
1.0
0.5
1.5
2.0
2.5
2.0
2.0
2.0
4.0
2.0
6.0
8.0
10.0
8.0
8.0
8.0
TFA (4.0)
TFA (4.0)
TFA (4.0)
TFA (4.0)
TFA (4.0)
AcOH (4.0)
TfOH (4.0)
PhCOOH
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
40
36
51
55
52
63
nd
nd
23
18
20
19
22
12
nd
nd
Entry
1
R1
R2
R3
3
Yield (%)b
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
1g
1h
1i
H
6-Cl
6-OCH3
5-F
H
H
H
H
H
H
H
H
H
H
H
H
H
2-F
4-F
4-Cl
4-Br
4-CH3
4-CF3
4-OCH3
4-NO2
H
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
H
3a
3b
3c
3d
3e
3f
3g
3h
3i
90
83
68
45
84
90
78
82
77
87
83
65
85
(4.0)
9
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
8.0
8.0
8.0
8.0
8.0
8.0
8.0
8.0
AcOH (3.0)
AcOH (5.0)
AcOH (6.0)
AcOH (5.0)
AcOH (5.0)
AcOH (5.0)
AcOH (5.0)
AcOH (5.0)
2.5
2.5
2.5
3.0
2.0
1.5
1.0
0.5
50
71
70
69
77
83
90
62
8
10
11
12
13
14
15
16
trace
trace
trace
trace
trace
trace
trace
9
10
11
12
13
1j
1k
1l
3j
3k
3l
1a
3 m
a
Reaction conditions: 1 (0.20 mmol), 2 (0.2 mmol), Ir (2.0 mol %), Ag (8.0 mol %),
a
Reaction conditions: 1a (0.20 mmol), 2a (0.20 mmol), 80 ꢀC, DCE (2.0 mL), air.
Isolated yields. nd = not detected.
AcOH (5.0 equiv), DCE (2.0 mL), air.
b
b
Isolated yields.
Please cite this article in press as: Y. Feng, et al., Ir-catalyzed regiospecific mono-sulfamidation of arylquinazolinones, Chin. Chem. Lett. (2019),
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3
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This work was supported by the National Natural Science
Foundation of China (No. 21572072), Xiamen Southern Oceano-
graphic Center (No. 15PYY052SF01), 111 Project (No. BC2018061)
and Y. Feng thanks the Postgraduates Innovative Fund in Scientific
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Appendix A. Supplementary data
Supplementary material related to this article can be
found, in the online version, at doi:https://doi.org/10.1016/j.
cclet.2019.05.013.
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Please cite this article in press as: Y. Feng, et al., Ir-catalyzed regiospecific mono-sulfamidation of arylquinazolinones, Chin. Chem. Lett. (2019),
https://doi.org/10.1016/j.cclet.2019.05.013