Rhodium(III)-catalyzed C–H amination of 2-arylquinazolin-4(3H)-one with N-alkyl-O-benzoyl-hydroxylamines

Article abstract of DOI:10.1016/j.tet.2018.03.051

N-benzoate alkylamines were used as the aminating agents, a efficient Rh-catalyzed ortho C–H amination of 2-arylquinazolin-4(3H)-one has been reported. The reactions exhibit high efficient and good functional group tolerance. Exclusive 2,6-bis-aminated pr

Full text of DOI:10.1016/j.tet.2018.03.051

Tetrahedron xxx (2018) 1e8
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Rhodium(III)-catalyzed CeH amination of 2-arylquinazolin-4(3H)-one
with N-alkyl-O-benzoyl-hydroxylamines
*
Yuanguang Zhang, Jiang Huang, Zhihong Deng, Xunchun Mao, Yiyuan Peng
Key Laboratory of Functional Small Organic Molecules, Ministry of Education, Jiangxi Province's Key Laboratory of Green Chemistry, Jiangxi Normal
University, Nanchang 330022, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 6 February 2018
Received in revised form
N-benzoate alkylamines were used as the aminating agents, a efficient Rh-catalyzed ortho CeH ami-
nation of 2-arylquinazolin-4(3H)-one has been reported. The reactions exhibit high efficient and good
functional group tolerance. Exclusive 2,6-bis-aminated product and good to excellent yields were ob-
tained under mild reaction conditions.
20 March 2018
Accepted 23 March 2018
Available online xxx
©
2018 Elsevier Ltd. All rights reserved.
Keywords:
CeH activation
Amination
Rh-catalyzed
2-arylquinazolin-4(3H)-one
1
. Introduction
reported amination of electron deficient polyfluoroarenes and
azole compounds catalyzed by Cu(OAc) using O-benzoyl hydrox-
ylamines as nitrogen sources. In 2013, using the same amination
2
Transition-metal-catalyzed CeH activation/amination has
3
i
3j
attracted tremendous interesting in the past decades in the syn-
thesis of arylamines due to its atom/step-economy. Several tran-
reagent, Yu and Zhang independently developed Rue and Rh-
1
catalyzed electrophilic amination of aryl and heteroaryl ortho
3
k
sition metals, such as Ir, Ru, Rh, Pd, Fe, Co, and Cu have been used
for this purpose to afford amines and amides directly from CeH
bonds.1 A large number of amine sources such as O-benzoylhy-
droxylamines, N-chloroamines, sulfonamides, amides, unactivated
free amines, N-fluorobenzenesulfonimide, nitrosobenzenes, and
CeH bonds assisted by a chelating group. Recently, Nakamura
demonstrated Fe(III)- catalyzed amination of aromatic carbox-
amides CeH bond with O-benzoyl hydroxylamines directed by 8-
quinolinylamide. Dong reported site-selective Pd and
norbornene-catalyzed arene CeH amination of aryl halides with O-
3
l
azides have been successfully rendered as effective coupling part-
benzoyl hydroxyllamines.
ners for this protocol.1
b,1d
Among them, O-benzoylhydroxylamines
On the other hand, quinazoline and quinazolinone core struc-
tures are known to exhibit a wide range of important potential
þ
were most widely employed as electronphilic R
ces in transition-metal-catalyzed CeN bond formation, due to
2
N
nitrogen sour-
2
,3
4,5
biological activities. Many quinazoline core with amino building
3
a-c
their easily prepared, fairly stable. For examples, Johnson,
blocks, such as Erlotinib and Gefitinib, are anticancer drugs that
have been approved by the FDA (Fig. 1). As a consequence,
tremendous efforts have been devoted to the development of new
synthetic methods for the construction of diverse quinazoline ar-
Miura,3d and Liebeskind
3e
have respectively reported Cu-
catalyzed amination of arylzinc, arylsilane, arylstannane, and
arylboron with hydroxylamine derivatives. Wang
transition-metal-free amination between arylboron and hydroxyl-
amine derivatives in 2012. In addition to the amination of aryl-
metallic reagents, significant advances have been made in
3
f
realized
6
chitectures and assess their bioactivity.
Additionally, in recent years, a particular emphasis was put on
rhodium catalysis due to its excellent performance on CeH bond
3
g
3h
7
electrophilic amination of aromatic CeH bond. Moreover, Miura
insertion. Thus, many research groups geared their attention to the
8
rhodium catalyzed for CeH bond activation functionalization and
1
a-d,1i,3g,3j,9
amination.
Very recently, We reported rhodium-
catalyzed regioselective direct CeH amidation of 2,4-
diarylquinazoline with sulfonyl azides for the selectively
*
Corresponding author.
E-mail addresses: yiyuanpeng@yahoo.com, yypeng@jxnu.edu.cn (Y. Peng).
https://doi.org/10.1016/j.tet.2018.03.051
040-4020/© 2018 Elsevier Ltd. All rights reserved.
0
Please cite this article in press as: Zhang Y, et al., Rhodium(III)-catalyzed CeH amination of 2-arylquinazolin-4(3H)-one with N-alkyl-O-benzoyl-
hydroxylamines, Tetrahedron (2018), https://doi.org/10.1016/j.tet.2018.03.051

2
Y. Zhang et al. / Tetrahedron xxx (2018) 1e8
Table 1
a
Optimization of the reaction conditions .
Fig. 1. The structure of Erlotinib and Gefitinib.
Entry
Catalyst
Base
Solvent
Yield (%)b
synthesis of mono- and diamidation quinazoline derivatives regu-
lated by steric hindrance. However, this strategy requires a longer
reaction time.
As continuation of our interest in structural elaboration of qui-
nazoline heterocycles and their application,11 we envision to
applicate quinazolinone motif as the intrinsic directing group for
Rh-catalyzed CeH functionalization to enrich the molecular di-
versity and structural complexity. Here, we demonstrated a
rhodium-catalyzed direct CeH amidation of 2-arylquinazolin-
1
2
3
4
5
6
7
8
9
[RhCp*Cl
[RhCp*Cl2]2
2
]
2
CsOAc
DBU
DABCO
t-BuONa
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
Isopropanol
DCE
MeCN
DMF
THF
Toluene
H O
2
Toluene
Toluene
MeOH
MeOH
MeOH
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
32
21
30
49
49
37
52
28
36
89
83
90
92
92
96
NR
87
87
9
16
NR
NR
NR
NR
NR
NR
30
85
88
10
[RhCp*Cl
[RhCp*Cl
[RhCp*Cl
[RhCp*Cl
[RhCp*Cl
[RhCp*Cl
[RhCp*Cl
[RhCp*Cl
2
]
2
]
2
]
2
]
2
]
2
]
2
]
2
]
2
2
2
2
2
2
2
2
Cu(OAc)
Na CO
PO
2
2
3
K
3
4
KF
CsF
1
11
12
0
3
K PO
4
[RhCp*Cl2]2
K3PO4
4
(3H)-one using N-benzoate alkylamines as the amine source.
[RhCp*Cl
[RhCp*Cl
[RhCp*Cl
2
]
2
]
2
]
2
2
2
K
K
K
3
PO
3
PO
3
PO
4
4
4
1
1
3
4
2
. Results and discussion
15
[RhCp*Cl
2
]
2
K
3
PO
4
16
17
18
19
[RhCp*Cl
[RhCp*Cl
[RhCp*Cl
[RhCp*Cl
[RhCp*Cl
e
2
]
]
]
]
]
2
2
2
2
2
K
K
K
3
PO
3
PO
3
PO
4
c
2
2
2
2
4
In the initial study, [RhCp*Cl
2
]
2
was used as the catalyst. 2-(o-
d
4
tolyl)quinazolin-4(3H)-one (1a, 1.0 equiv) and O-benzoyl-N-cyclo-
pentylhydroxylamine (2a, 1.5 equiv) were chosen as the model
substrates, and PivOH as a additive to optimize the reaction con-
ditions. Several parameters such as the base, solvent, and temper-
ature were systematically investigated. The results are summarized
e
e
20
K
K
K
K
K
3
PO
PO
PO
PO
PO
4
4
4
4
4
2
2
2
2
1
2
3
4
3
3
3
3
[RuCl
Pd(OAc)
Cu(OAc)
Fe(acac)3
Co(acac)
[Cp*IrCl
Cp*Rh(OAc)
[Cp*Rh(MeCN)
2
(p-cymene)]
2
2
2
in Table 1. Among the bases screened, K
3
PO
4
was found to be most
25
26
K3PO4
efficient for the transformation (Table 1, entries 1e9), which
delivering 3aa in 52% yield (Table 1, entry 7). Then, different kinds
of solvents were examined, good yields were obtained when the
reaction proceeded in solvents such as isopropanol, DCE (Table 1,
entries10ꢀ11). Excellent yields were reached in MeCN, THF and
DMF (entries 12e14). In toluene, the reaction gave the highest yield
of 96% (entry 15). No evidence of the desired product was observed
2
K
K
K
K
3
PO
3
PO
3
PO
3
PO
4
4
4
4
2
2
2
7
8
9
2 2
]
2
3
6 2
][(SbF ) ]
a
Reaction conditions: 2-(o-tolyl)quinazolin-4(3H)-one 1a (0.1 mmol), O-benzoyl-
*
2 2
N-cyclopentylhydroxylamine 2a (1.5 equiv). [RhCp Cl ] (2.5 mol %), base (2.0
ꢁ
equiv), and PivOH (50 mol %) in solvent (2.0 mL) at 50 C for 12 h.
b
Isolated yield.
Reaction was performed at 40 C.
Reaction was performed at 60 C.
PivOH without added.
c
d
e
ꢁ
ꢁ
in H
perature results lightly diminished the yields (Table 1, entries
7e18). Control experiments showed that lower yields were ob-
2
O (Table 1, entry 16). Raising or lowering the reaction tem-
1
tained in the absence of base (9%, Table 1, entry 19) or PivOH (16%;
Table 1, entry 20), and the reaction could not take place in the
absence of the rhodium catalyst (Table 1, entry 21).
For a better understanding of the relationship between catalyst
and the intrinsic directing group, other transition metal catalysts
such as Pd(II), Cu(II), Fe(III), Co(II), Ru(II) and Ir(III) were examined
under the optimized conditions, and found to show less reactivity
compared to the Rh(III) catalyst (Table 1, entries 22e27). The ami-
nation also occurred when the catalyst was switched to
one gave 3fa only in 64% yield. 2-Heteroarylquinazolin-4(3H)-one,
such as 2-(pyridin-4-yl)quinazolin-4(3H)-one 1g reacted smoothly
giving the corresponding product 3ga in 80% yield. In addition, a
variety of substituents on quinazolinone core were probed. The
reaction of 5-fluoro-2-phenylquinazolin-4(3H)-one 1h gave the
corresponding product 3ha in excellent yield of 93%. Nevertheless,
some problems were found in the study of 6- substituent on qui-
nazolinone substrate. Under the optimized conditions, the yield of
the target products 3iae3la is not satisfactory, only 4e10% of yields
were obtained. By re-screening conditions we found that when the
solvent change from toluene to acetonitrile, the yields were
significantly improvement to 88e99% (Table 2).
We then tried to block the ortho position of the substrate to
improve the selectivity to achieve monoamidation product. Thus, a
variety of substituents at the ortho position of 2-aryl quinazolinone
were investigated (Table 3). Indeed, moderate to good yields of the
corresponding monoaminated product 3mae3oa were obtained by
the reaction of ortho-substituted 2-arylquinazolin-4(3H)-ones. The
Cp*Rh(OAc)
entry 28). Finally, [Cp*Rh(MeCN)
to be a highly active catalyst for this reaction, and affording 3aa in
2
, delivering the desired product in 85% yield. (Table 1,
3
][(SbF ] complex was found also
6 2
)
8
8% yield (Table 1, entry 29).
Under the optimized conditions, we then investigated the sub-
strate scope of the reaction. Initially, the reactions of 2a with
various 2-arylquinazolin-4(3H)-ones were investigated. The results
are depicted in Table 2. The reaction of 2-phenylquinazolin-4(3H)-
one 1b gave exclusive the 2,6-bis-aminated product 3ba, the mono-
aminated product was not isolated. When 1b:2a is 1:2.5, 3ba was
2
obtained in 95% yield. The p-substitute group R effect on 2-aryl of
reaction of 6-substituted-2-(o-tolyl)quinazolin-4(3H)-one 1p-q
quinazoline-4-one were then investigated. No matter the substit-
1
(
R ¼ OMe, Cl) were found to be excellent for this transformation to
uent group is electron-donating or electron-withdrawing group
provide the desired products 3pae3qa in almost quantitative
yields. However, ortho-methoxyl substituted substrate 1r did no
reaction. We suspect that the formation of intramolecular hydrogen
2
(
R ¼ H, Me, OMe and CF
3
), the reactions proceed smoothly to
afford the 2,6-bis-aminated products 3ba¡3ea in excellent yields.
However, the reaction of 2-(p-brominephenyl)quinazolin-4(3H)-
Please cite this article in press as: Zhang Y, et al., Rhodium(III)-catalyzed CeH amination of 2-arylquinazolin-4(3H)-one with N-alkyl-O-benzoyl-
hydroxylamines, Tetrahedron (2018), https://doi.org/10.1016/j.tet.2018.03.051

Y. Zhang et al. / Tetrahedron xxx (2018) 1e8
3
Table 2
Substrate scopea,b.3
Table 3
Substrate scope explorationa,b.4
Please cite this article in press as: Zhang Y, et al., Rhodium(III)-catalyzed CeH amination of 2-arylquinazolin-4(3H)-one with N-alkyl-O-benzoyl-
hydroxylamines, Tetrahedron (2018), https://doi.org/10.1016/j.tet.2018.03.051

4
Y. Zhang et al. / Tetrahedron xxx (2018) 1e8
bonds
inhibits
the
progress
of
such
the
as
reaction.
2-furan-sub-
2-
directing group, the reaction possess high functional group toler-
ance excellent yields of up to 99%.
Heteroarylquinazolin-4(3H)-one,
stitutedquinazolin-4(3H)-one, delivered the desired product 3sa in
7% yield under optimal reaction conditions. It is noteworthy that
in the case of 1t, which has a methyl moiety at the meta position,
the ratio of bis-amidation product 3ta and mono-amidation
product 3ta is almost 3:1 (Table 3).
6
4. Experimental section
1
4.1. General
2
Next, with 1a as the substrate, we explored the reactions of a
variety of O-benzoyl-hydroxylamines as the nitrogen source under
the catalytic reaction conditions (Table 4). In addition to O-benzoyl-
N-cyclopentylhydroxylamine 2a, N-cyclohexyl-O-benzoyl-hydrox-
yl-amine 2b reacted with 1a very well gave 3 ab in a yield of 93%. O-
benzoyl-N-(tert-butyl)hydroxylamine (2c), reacted smoothly to
give products 3ac in 93% yield. The reactions of second-alkyl hy-
droxylamines, such as 2d and 2e finished the corresponding
products 3ad and 3ae in excellent yields. It is noteworthy that in the
case of 2f and 2g, the O-benzoyl-N-primaryalkylhydroxylamine
with 1a gave the corresponding compounds 3afe3ag only in the
yields of 50% and 18% (Table 4).
Unless otherwise noted, commercial reagents were purchased
from Aldrich, Alfa, or other commercial suppliers. All solvents were
dried and distilled according to standard procedures before use.
Reactions were conducted in standard techniques on vacuum line.
Analytical thin-layer chromatography (TLC) was performed using
glass plates pre-coated with 0.25 mm 230e400 mesh silica gel
impregnated with a fluorescent indicator (254 nm). Flash column
chromatography was performed using silica gel (60 Å pore size,
32e63
m
m, standard grade). Organic solutions were concentrated
ꢁ
on rotary evaporators at~20 Torr (house vacuum) at 25e35 C.
Nuclear magnetic resonance (NMR) spectra are recorded in parts
per million (ppm) from internal standard tetramethylsilane (TMS)
It must be mentioned that all the aminating agents used were O-
benzoyl-hydroxylamines bearing only one N-alkyl substituent.
Attempted reactions with reagents bearing N,N-dialkyl sub-
stituents, including O-benzoyl-N,N-diisopropylhydroxylamine and
morpholino benzoate were unsuccessful. By re-screening the re-
action conditions, we found that when the solvent change from
on the d scale.
4.2. General procedure for the preparation of substrate 2 according
to Ganem's procedure (A. J. Biloski, B. Ganem, synthesis, 1983, 537)
toluene to MeOH and the base from K
3 4
PO to CsOAc, the reaction of
1
c and 2h gave exclusive the mono-aminated product 3ch in 85%.
Unfortunately, compounds 3cie3cj were obtained only in the yield
of 30% and 11% (Table 5).
3
. Conclusions
In summary, we have developed a Rh -catalyzed CeH activa-
A 50 mL one-necked round-bottomed flask equipped with a
Teflon-coated magnetic stir bar was charged with benzoyl peroxide
III
2 4 2
2b (1.211 g, 5 mmol), K HPO $3H O (1.71 g, 7.5 mmol), and DMF
tion/amination of ortho 2-arylquinazolin-4(3H)-ones under mild
reaction conditions using N-alkyl-O-benzoyl-hydroxylami-nes as
aminating agents. The quinazolin-4(3H)-one moiety served as the
(12.5 mL) under N atmosphere. The suspension was stirred at
room temperature and the amine 2a (6e12.5 mmol) was added via
syringe in one portion. The suspension was stirred at ambient
2
Table 4
O-benzoyl-hydroxylamine scope explorationa,b.5
Please cite this article in press as: Zhang Y, et al., Rhodium(III)-catalyzed CeH amination of 2-arylquinazolin-4(3H)-one with N-alkyl-O-benzoyl-
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Y. Zhang et al. / Tetrahedron xxx (2018) 1e8
5
Table 5
The reaction of O-benzoyl- N,N-dialkylhydroxylaminea,b.6
temperature for the indicated reaction time according to TLC.
Deionized water (25 mL) was added and the contents were stirred
vigorously for several minutes until all solids dissolved. The reac-
tion mixture was transferred to a 100 mL separator funnel and
extracted with ethyl acetate (25 mL). The organic phase was
z [M þ H]þ calcd. for C20
21 3
H N OS: 320.1763; found: 320.1765.
4.4.2. 2-(2,6-bis(cyclopentylamino)phenyl)quinazolin-4(3H)-one
(3ba)
Yellow solid (95% yield), mp: 122e124 C; 1H NMR (400 MHz,
ꢁ
collected and washed with 25 mL of saturated NaHCO
3
(aq.) solu-
CDCl3)
d
12.07 (s, br, 1H), 8.26 (d, J ¼ 8.0 Hz, 1H), 7.71 (t, J ¼ 7.6 Hz,
tion twice. All of the aqueous fractions were combined and
extracted with ethyl acetate (25 mL x 3). All of the organic fractions
were combined and washed with deionized water (50 mL x 2),
1H), 7.61 (d, J ¼ 8.4 Hz, 1H), 7.41 (t, J ¼ 7.6 Hz, 1H), 7.11 (t, J ¼ 8.2 Hz,
1H), 6.28 (d, J ¼ 8.0 Hz, 2H), 6.09 (br s, 2H), 3.69e3.67 (m, 2H),
13
1.95e1.93 (m, 4H), 1.73e1.72 (m, 4H), 1.61e1.54 (m, 8H). C NMR
brine (25 mL), dried over Na
2
SO
4
, and concentrated on rotary
(100 MHz, CDCl3) d 161.5, 153.0, 148.6, 148.4, 134.2, 132.1, 126.5,
evaporator. The resulting crude product was purified by flash col-
umn chromatography, eluting with EA/petroleum ether, to afford
the desired product 2 as a white solid and stored in fridge for
further usage.
126.4, 126.1, 121.1, 106.8, 103.0, 56.6, 33.1, 23.7. HRMS (ESI): m/z
[M þ H]þ calcd for C24H28N OS: 389.2341; found: 389.2335.
4
4
4
.4.3. 2-(2,6-bis(cyclopentylamino)-4-methyl)phenylquinazolin-
(3H)-one (3ca)
4.3. General procedure for preparation of 3 (3aa as an example)
Yellow solid (83% yield), mp: 202e203 C; 1H NMR (400 MHz,
ꢁ
CDCl
3
)
d
12.43 (s, 1H), 8.27 (dd, J ¼ 8.0, 0.8 Hz, 1H), 7.72 (ddd, J ¼ 8.8,
To a 25 mL of schlenk tube equipped with a Teflon-coated
8.0, 1.6 Hz, 1H), 7.60 (d, J ¼ 8.0 Hz, 1H), 7.42 (ddd, J ¼ 8.0, 7.2, 0.8 Hz,
magnetic stir bar was charged with 2-(o-tolyl)quinazolin-4(3H)-
one 1a (0.2 mmol), substrate 2a (0.3 mmol), [Cp*RhCl (3 mg,
1H), 6.19 (br s, 2H), 6.13 (s, 2H), 3.67 (s, 2H), 2.27 (s, 3H), 1.98e1.92
13
2
]
2
(m, 4H), 1.75e1.72 (m, 4H), 1.62e1.56 (m, 8H). C NMR (100 MHz,
0
.005 mmol), PivOH (10 mg, 0.1 mmol), K
3
PO
4
(85 mg, 0.4 mmol),
CDCl
3
)
d
161.6, 153.3, 148.8, 148.6, 142.7, 134.3, 126.5, 125.9, 121.1,
ꢁ
þ
and Toluene (2.0 mL). The brown suspension was stirred at 50 C for
108.3, 100.7, 57.0, 33.2, 23.8, 22.1. HRMS (ESI): m/z [M þ Na] calcd
1
2 h. The reaction was monitored by TLC. After being cooled to
room temperature, the reaction mixture was diluted with EA
5 mL), transferred to a 50 mL of separatory funnel and washed
30 4
for C25H N OS: 425.2317; found: 425.2299.
(
4.4.4. 2-(2,6-bis(cyclopentylamino)-4-methoxy)phenylquinazolin-
with water (15 mL), extracted with ethyl acetate (10 mL x 3). The
organic phase was collected and washed with brine, dried over
4(3H)-one (3da)
Yellow solid (98% yield), mp: 165e167 C; 1H NMR (400 MHz,
ꢁ
Na
2
SO
4
, and concentrated. The crude residue was purified by a flash
CDCl3)
d
12.16 (s, 1H), 8.21 (dd, J ¼ 8.0, 1.2 Hz, 1H), 7.68 (ddd, J ¼ 8.4,
column chromatography on silica gel using petroleum ether/ethyl
acetate as eluent to give the corresponding pure product 3aa.
6.8, 1.6 Hz, 1H), 7.55 (d, J ¼ 8.0 Hz, 1H), 7.36 (ddd, J ¼ 7.4, 6.8, 0.8 Hz,
1H), 6.37 (br s, 2H), 5.84 (s, 2H), 3.80 (s, 3H), 3.69e3.66 (m, 2H),
13
1
.98e1.94 (m, 4H), 1.75e1.71 (m, 4H), 1.62e1.57 (m, 8H). C NMR
(100 MHz, CDCl 162.6,161.6,153.1,150.4,148.6,134.1,126.3126.2,
25.6, 120.7, 96.8, 92.7, 56.6, 54.9, 33.1, 23.8. HRMS (ESI): m/z [M þ
4
4
.4. Characterization data
3
) d
1
þ
30 4 2
H] calcd for C25H N O S: 419.2447; found: 419.2435.
.4.1. 2-(2-(cyclopentylamino)-6-methylphenyl)quinazolin-4(3H)-
one (3aa)
Yellow solid (96% yield), mp: 191e193 C; 1H NMR (400 MHz,
CDCl
9.55 (s, 1H), 8.31 (d, J ¼ 8.0 Hz, 1H), 7.82e7.75 (m, 2H), 7.53
ꢁ
4.4.5. 2-(2,6-bis(cyclopentylamino)-4-(trifluoromethyl)phenyl)-
quinazolin-4(3H)-one (3ea)
3
) d
Yellow solid (99% yield), mp: 73e74 C; 1H NMR (400 MHz,
ꢁ
(
ddd, J ¼ 8.0, 7.2, 0.8 Hz,1H), 7.19 (t, J ¼ 7.6 Hz, 1H), 6.63e6.59 (m,
2
H), 5.01e4.91 (m, 1H), 3.79e3.74 (m, 1H), 2.28 (s, 3H), 1.97e1.94
CDCl
3
)
d
11.36 (s, 1H), 8.25 (dd, J ¼ 8.0, 1.2 Hz, 1H), 7.74 (ddd, J ¼ 8.0,
13
(
m, 2H), 1.65e1.57 (m, 4H), 1.43e1.40 (m, 2H). C NMR (100 MHz,
CDCl 162.4, 152.4, 148.9, 146.6, 136.6, 134.8, 131.1, 127.5, 127.2,
26.6, 121.0, 119.0, 118.6, 110.2, 54.5, 33.5, 24.0, 20.3. HRMS (ESI): m/
6.8,1.6 Hz, 1H), 7.62 (d, J ¼ 8.0 Hz, 1H), 7.46 (ddd, J ¼ 7.4, 7.2, 0.8 Hz,
1H), 6.46 (s, 2H), 6.03 (br s, 2H), 3.75e3.72 (m, 2H), 2.01e1.97 (m,
3
) d
13
1
4H), 1.74e1.73 (m, 4H), 1.64e1.51 (m, 8H). C NMR (100 MHz,
Please cite this article in press as: Zhang Y, et al., Rhodium(III)-catalyzed CeH amination of 2-arylquinazolin-4(3H)-one with N-alkyl-O-benzoyl-
hydroxylamines, Tetrahedron (2018), https://doi.org/10.1016/j.tet.2018.03.051

6
Y. Zhang et al. / Tetrahedron xxx (2018) 1e8
CDCl
3
)
d
161.4, 151.7, 148.6, 148.2, 134.6, 133.7 (q, 2JC-F ¼ 31.6 Hz),
3.72e3.59 (m, 2H), 2.02e1.91 (m, 4H), 1.79e1.69 (m, 4H), 1.60e1.55
(m, 8H). C NMR (100 MHz, CDCl ) d 162.8,160.6,153.4,150.6, 147.1,
3
1
13
1
26.8, 126.7, 126.6, 123.9 (q,
J
C-F ¼ 271.4 Hz), 121.3, 104.7, 101.6
3
þ
(
q, JC-F ¼ 3.8 Hz), 56.12, 33.27, 23.84. HRMS (ESI): m/z [M þ H]
134.5, 131.2, 130.8, 128.8, 127.7, 125.8, 121.6, 93.1, 56.8, 54.9, 33.1,
þ
calcd for C25
H F
27 3
N
4
OS: 457.2215; found:457.2205.
23.8. HRMS (ESI): m/z [M þ H] calcd for C25
4 2
H29ClN O S: 453.2053;
found:453.2055.
4
4
.4.6. 2-(4-bromo-2,6-bis(cyclopentylamino)phenyl)quinazolin-
(3H)-one (3fa)
Yellow solid (64% yield), mp: 220e222 C; 1H NMR (400 MHz,
4.4.12. 2-(2,6-bis(cyclopentylamino)-4-(trifluoromethyl)phenyl)-6-
methoxyquinazolin-4(3H)-one (3la)
ꢁ
Yellow solid (99% yield), mp: 157e159 C; 1H NMR (400 MHz,
ꢁ
CDCl
6
2
3
)
d
11.51 (s, 1H), 8.24 (dd, J ¼ 7.6, 1.2 Hz, 1H), 7.72 (ddd, J ¼ 8.4,
.8, 1.2 Hz, 1H), 7.59 (d, J ¼ 8.2 Hz, 1H), 7.44 (t, J ¼ 7.6 Hz, 1H), 6.41 (s,
CDCl
3
)
d
11.40 (s, 1H), 7.55 (d, J ¼ 2.8 Hz, 1H), 7.50 (d, J ¼ 8.8 Hz, 1H),
H), 6.08 (br s, 2H), 3.68e3.66 (m, 2H),2.00e1.95 (m, 4H), 1.74e1.71
7.30 (dd, J ¼ 8.8, 2.8 Hz, 1H), 6.43 (s, 2H), 6.00 (br s, 2H), 3.87 (s, 3H),
3.77e3.66 (m, 2H), 2.04e1.90 (m, 4H), 1.78e1.67 (m, 4H), 1.66e1.47
(m, 8H). C NMR (100 MHz, CDCl ) d 161.4,158.5,149.3,148.3,142.7,
3
13
(
3
m, 4H),1.63e1.52 (m, 8H). C NMR (100 MHz, CDCl ) d 161.4,152.3,
13
149.2, 148.3, 134.5, 127.0, 126.6, 126.5, 121.1, 108.7, 101.5, 56.3, 33.2,
3.8. HRMS (ESI): m/z [M þ H]þ calcd for C24
H27BrN
OS: 467.1446;
133.3 (q,
2
J
C-F ¼ 31.5 Hz), 128.2, 123.9 (q,
1
J
C-F ¼ 271.3 Hz), 124.7,
2
4
3
found: 467.1435.
121.9, 105.9, 104.8, 101.2 (q, JC-F ¼ 3.8 Hz), 55.9, 55.7, 33.2, 23.8.
þ
HRMS (ESI): m/z [M þ H] calcd for C26
29 3 4 2
H F N O S: 487.2321;
4
.4.7. 2-(3,5-bis(cyclopentylamino)pyridin-4-yl)quinazolin-4(3H)-
one (3ga)
Yellow solid (80% yield), mp: 134e136 C; 1H NMR (400 MHz,
CDCl
8.28 (dd, J ¼ 8.0, 1.2 Hz, 1H), 7.79e7.71 (m, 3H), 7.63 (d,
J ¼ 8.0 Hz, 1H), 7.48 (ddd, J ¼ 8.0, 6.8, 1.2 Hz, 1H), 6.19 (s, 1H),
.77e3.68 (m, 2H), 2.01e1.95 (m, 4H), 1.80e1.68 (m, 4H), 1.68e1.52
m, 8H). 13C NMR (100 MHz, CDCl
161.3, 151.5, 148.0, 142.2,134.6,
found: 487.2331.
ꢁ
4.4.13. 2-(2-(cyclopentylamino)-6-fluorophenyl)quinazolin-4(3H)
-one (3ma)
3
) d
Yellow solid (85% yield), mp: 198e199 C; 1H NMR (400 MHz,
ꢁ
3
(
CDCl
3
)
d
9.81 (s, 1H), 9.38 (d, J ¼ 5.4 Hz, 1H), 8.29 (d, J ¼ 6.8 Hz, 1H),
3
)
d
7.76 (ddd, J ¼ 7.6, 6.8, 1.6 Hz, 1H), 7.62 (d, J ¼ 8.0 Hz, 1H), 7.47 (ddd,
J ¼ 7.6, 7.2, 0.8 Hz, 1H), 7.24e7.20 (m, 1H), 6.58 (d, J ¼ 8.4 Hz, 1H),
6.38 (ddd, J ¼ 14.0, 8.0, 0.4 Hz, 1H), 3.93e3.89 (m, 1H), 2.09e2.04
1
[
29.7,127.1127.0,126.6,121.6,108.1, 57.0, 33.3, 23.8. HRMS (ESI): m/z
M þ H]þ calcd for C23
27 5
H N OS: 390.2294; found:390.2294.
13
(m, 2H), 1.82e1.79 (m, 2H), 1.72e1.64 (m, 4H). C NMR (100 MHz,
1
3
4
4
.4.8. 2-(2,6-bis(cyclopentylamino)phenyl)-5-fluoroquinazolin-
(3H)-one (3ha)
CDCl
3
)
d
162.7 (d,
J
C-F ¼ 243.5 Hz), 161.4, 150.6 (d,
J
C-F ¼ 5.2 Hz),
3
150.2, 147.8, 134.7, 132.8132.9, 126.8, 126.6, 120.9, 108.7 (d,
J
C-
Yellow solid (93% yield); mp: 145e147 C. 1H NMR (400 MHz,
ꢁ
¼ 2.3 Hz), 101.6 (d, JC-F ¼ 25.6 Hz), 100.4 (d, JC-F ¼ 10.6 Hz), 54.3,
2
2
F
þ
CDCl
1
3
)
d
12.49 (s, 1H), 7.64 (dt, J ¼ 8.0, 5.6 Hz, 1H), 7.39 (d, J ¼ 8.0 Hz,
33.4, 24.1. HRMS (ESI): m/z [M þ H] calcd for C19
3
H18FN OS:
H), 7.14 (t, J ¼ 8.0 Hz, 1H), 7.06 (dd, J ¼ 9.6, 8.4 Hz, 1H), 6.30 (d,
324.1512; found: 324.1515.
J ¼ 8.0 Hz, 2H), 6.19 (br s, 2H), 3.74e3.61 (m, 2H), 2.02e1.90 (m, 4H),
1
3
1.81e1.68 (m, 4H), 1.66e1.51 (m, 8H). C NMR (100 MHz, CDCl
3
)
J
C-
4.4.14. 2-(2-chloro-6-(cyclopentylamino)phenyl)quinazolin-4(3H)
-one (3na)
1
2
d
161.4 (d, JC-F ¼ 263.5 Hz), 158.8, 154.1, 150.5, 148.9, 134.4 (d,
3
2
Yellow solid (65% yield), mp: 175e177 C; 1H NMR (400 MHz,
ꢁ
F
¼ 10.4 Hz), 132.4, 122.3 (d, JC-F ¼ 3.9 Hz), 112.5 (d, JC-F ¼ 20.6 Hz)
3
1
[
10.7 (d, JC-F ¼ 6.8 Hz), 107.3,102.5, 56.9, 33.1, 23.7. HRMS (ESI): m/z
CDCl
6.4, 1.6 Hz, 1H), 7.74 (dd, J ¼ 8.0, 0.4 Hz, 1H), 7.53 (ddd, J ¼ 7.6, 7.2,
.2 Hz, 1H), 7.19 (t, J ¼ 8.2 Hz, 1H), 6.73 (dd, J ¼ 7.6, 0.4 Hz, 1H), 6.67
(d, J ¼ 8.4 Hz, 1H), 5.82 (br s, 1H), 3.80e3.74 (m, 1H), 2.00e1.95 (m,
3
)
d
10.14 (s, 1H), 8.28 (dd, J ¼ 8.0, 1.2 Hz, 1H), 7.80 (ddd, J ¼ 7.6,
M þ H]þ calcd for C24
4
H27FN OS: 406.2169; found: 406.2169.
1
4
4
.4.9. 2-(2,6-bis(cyclopentylamino)phenyl)-6-chloroquinazolin-
(3H)-one (3ia)
Yellow solid (91% yield), mp: 172e174 C; 1H NMR (400 MHz,
13
2H), 1.68e1.58 (m, 4H), 1.47e1.42 (m, 2H)$ C NMR (100 MHz,
CDCl 162.3, 150.4, 148.4, 148.3, 134.7, 132.9, 131.9, 127.3, 127.2,
ꢁ
3
) d
CDCl
3
)
d
12.57 (s,1H), 8.18 (d, J ¼ 2.4 Hz,1H), 7.62 (dd, J ¼ 8.8, 2.4 Hz,
126.6, 121.2, 117.3, 116.0, 110.8, 54.4, 33.3, 23.9. HRMS (ESI): m/z
[M þ Na]þ calcd for C19
H18ClN
OS :362.1036; found: 362.1023.
þ
1
2
4
H), 7.51 (d, J ¼ 8.8 Hz, 1H), 7.12 (t, J ¼ 8.2 Hz, 1H), 6.29 (d, J ¼ 8.0 Hz,
3
H), 6.18 (s, 2H), 3.67 (br s, 2H), 1.96e1.92 (m, 4H), 1.73e1.71 (m,
H), 1.59e1.54 (m, 8H). 13C NMR (100 MHz, CDCl
)
d
160.4, 153.4,
4.4.15. 2-(4-chloro-2-(cyclopentylamino)-6-methylphenyl)quinaz-
olin-4(3H)-one (3oa)
3
148.7, 146.9, 134.6, 132.3, 131.8, 128.0, 125.8, 122.1, 107.3, 102.8, 56.9,
þ
White solid (88% yield), mp: 224e226 C; 1H NMR (400 MHz,
ꢁ
3
4
3.1, 23.8. HRMS (ESI): m/z [M þ Na] calcd for C24
4
H27ClN OS:
45.1771; found: 445.1762.
DMSO)
.64 (d, J ¼ 8.0 Hz,1H), 7.52 (t, J ¼ 7.6 Hz,1H), 6.56 (d, J ¼ 3.2 Hz, 2H),
5.35 (d, J ¼ 6.8 Hz, 1H), 3.75e3.70 (m, 1H), 2.06 (s, 3H), 1.88e1.84
d
12.23 (s, 1H), 8.15 (d, J ¼ 7.6 Hz, 1H), 7.80 (t, J ¼ 7.6 Hz, 1H),
7
4.4.10. 2-(2,6-bis(cyclopentylamino)phenyl)-6-methoxyquinazo-
13
lin-4(3H)-one (3ja)
Yellow solid (98% yield), mp: 112e114 C; 1H NMR (400 MHz,
CDCl
12.07 (s, 1H), 7.66 (d, J ¼ 2.8 Hz, 1H), 7.57 (d, J ¼ 8.8 Hz, 1H),
.34 (dd, J ¼ 8.8, 3.2 Hz, 1H), 7.12 (t, J ¼ 8.0 Hz, 1H), 6.29 (d,
J ¼ 8.0 Hz, 2H), 5.98 (br s, 2H), 3.92 (s, 3H), 3.69e3.66 (m, 2H),
(m, 2H), 1.61e1.44 (m, 4H), 1.40e1.35 (m, 2H). C NMR (100 MHz,
DMSO) 162.4, 152.2, 149.1, 147.5, 138.8, 134.9, 134.3, 127.3, 126.7,
ꢁ
d
3
)
d
125.9, 121.8, 118.6, 116.8, 108.7, 54.0, 32.3, 23.7, 19.6. HRMS (ESI): m/
7
z [M þ H]þ calcd for C20
3
H20ClN OS: 354.1373; found: 354.1373.
13
1.96e1.93 (m, 4H), 1.74e1.71 (m, 4H), 1.61e1.52 (m, 8H). C NMR
4.4.16. 6-Chloro-2-(2-(cyclopentylamino)-6-methylphenyl)quina-
(
1
100 MHz, CDCl 161.5, 158.2, 150.8, 148.4, 143.1, 131.9, 128.2,
3
)
d
zolin-4(3H)-one (3pa)
24.7,121.8,106.8,106.0,103.4, 56.7, 55.8, 33.3, 23.8. HRMS (ESI): m/
Yellow solid (94% yield), mp: 194e196 C; 1H NMR (400 MHz,
ꢁ
þ
z [M þ H] calcd for C25
30
H N
4
O
2
S:419.2447; found:419.2447.
CDCl
H), 6.60 (d, J ¼ 1.8 Hz, 1H), 6.58 (s, 1H), 4.82 (br s, 1H), 3.77e3.71
(m,1H), 2.24 (s, 3H),1.97e1.92 (m, 2H), 1.61e1.56 (m, 4H),1.42e1.39
3
)
d
8.16 (d, J ¼ 2.4 Hz, 1H), 7.70e7.69 (m, 2H), 7.16 (t, J ¼ 8.0 Hz,
1
4
.4.11. 2-(2,6-bis(cyclopentylamino)-4-methoxyphenyl)-6-chloro-
quinazolin-4(3H)-one (3ka)
Yellow solid (88% yield), mp: 202e204 C; 1H NMR (400 MHz,
CDCl
12.50 (s,1H), 8.15 (d, J ¼ 2.4 Hz,1H), 7.59 (dd, J ¼ 8.4, 2.4 Hz,
H), 7.45 (d, J ¼ 8.8 Hz, 1H), 6.40 (br s, 2H), 5.84 (s, 2H), 3.81 (s, 3H),
13
3
(m, 2H). C NMR (100 MHz, CDCl ) d 161.8,152.9,147.3,146.4,136.6,
ꢁ
135.2, 132.9, 131.2, 128.9, 125.8, 121.9, 119.0, 118.5, 110.2, 54.5, 33.4,
þ
3
)
d
23.9, 20.3. HRMS (ESI): m/z [M þ Na] calcd for C20
3
H20ClN OS:
1
376.1373; found: 354.1369.
Please cite this article in press as: Zhang Y, et al., Rhodium(III)-catalyzed CeH amination of 2-arylquinazolin-4(3H)-one with N-alkyl-O-benzoyl-
hydroxylamines, Tetrahedron (2018), https://doi.org/10.1016/j.tet.2018.03.051

Y. Zhang et al. / Tetrahedron xxx (2018) 1e8
7
4
.4.17. 2-(2-(cyclopentylamino)-6-methylphenyl)-6-methoxyquin-
azolin-4(3H)-one (3qa)
Yellow solid (99% yield), mp: 137e139 C; 1H NMR (400 MHz,
CDCl
9.97 (br s, 1H), 7.67 (d, J ¼ 9.2 Hz, 1H), 7.63 (d, J ¼ 3.2 Hz,
H), 7.36 (dd, J ¼ 8.8, 2.8 Hz, 1H), 7.11 (t, J ¼ 8.0 Hz, 1H), 6.56 (d,
7.20 (d, J ¼ 7.2 Hz, 1H), 7.00 (t, J ¼ 8.0 Hz, 1H), 6.57 (d, J ¼ 7.6 Hz, 1H),
6.37 (d, J ¼ 8.0 Hz, 1H), 5.40 (br s, 1H), 4.50e4.48 (m, 1H), 2.29 (s,
ꢁ
13
3H), 1.43 (d, J ¼ 6.8 Hz, 3H). C NMR (100 MHz, CDCl
3
) d 162.8,
3
)
d
152.5, 148.9, 145.8, 144.8, 136.5, 134.8, 130.9, 128.6, 127.4, 127.1,
1
126.8, 126.6, 125.7, 121.0, 119.3, 118.8, 110.6, 53.4, 25.1, 20.3. HRMS
þ
J ¼ 1.6 Hz, 1H), 6.54 (s, 1H), 4.76 (br s, 1H), 3.91 (s, 3H), 3.74e3.68
(ESI): m/z [M þ Na] calcd for C23
21 3
H N OS: 378.1582; found:
(
(
1
3
3
m,1H), 2.21 (s, 3H),1.94e1.90 (m, 2H),1.62e1.54 (m, 4H),1.40e1.37
m, 2H). 13C NMR (100 MHz, CDCl
162.5,158.6,150.1,146.4,143.4,
36.7, 130.8, 128.9, 124.8, 121.7, 119.0, 118.8, 110.0, 106.0, 55.8, 54.48,
378.1592.
3
) d
4
.4.23. 2-(2-(tert-butylamino)-6-methylphenyl)quinazolin-4(3H)-
one (3ad)
Yellow solid (93% yield), mp: 163e165 C; 1H NMR (400 MHz,
þ
3.38, 23.98, 20.1. HRMS (ESI): m/z [M þ H] calcd for C21
23 3 2
H N O S:
50.1869; found: 350.1864.
ꢁ
CDCl 10.25 (s,1H), 8.25 (d, J ¼ 7.6 Hz,1H), 7.79e7.78 (m, 2H), 7.50
ddd, J ¼ 8.4, 6.4, 2.4 Hz, 1H), 7.15 (t, J ¼ 8.0 Hz, 1H), 6.88 (d,
J ¼ 8.4 Hz, 1H), 6.64 (d, J ¼ 7.6 Hz, 1H), 4.92 (br, 1H), 2.25 (s, 3H), 1.27
3
) d
4
.4.18. 2-(3-(cyclopentylamino)furan-2-yl)quinazolin-4(3H)-one
(
(
3sa)
Yellow solid (67% yield), mp: 174e175 C; 1H NMR (400 MHz,
CDCl
9.55 (s, 1H), 8.20 (d, J ¼ 7.6 Hz, 1H), 7.64 (t, J ¼ 8.0 Hz, 1H),
ꢁ
13
(
3
s, 9H). C NMR (100 MHz, CDCl ) d 162.7, 152.7, 148.8, 145.4, 136.9,
3
) d
1
2
34.5, 130.3, 127.4, 127.1, 126.5, 121.2, 120.8, 119.6, 113.8, 51.3, 29.9,
7
6
2
.48 (d, J ¼ 8.0 Hz, 1H), 7.33 (d, J ¼ 0.8 Hz, 1H), 7.27 (t, J ¼ 7.6 Hz, 1H),
0.4. HRMS (ESI): m/z [M þ Na]þ calcd for C19
21 3
H N OS: 330.1582;
.64 (d, J ¼ 5.6 Hz, 1H), 6.31 (d, J ¼ 0.8 Hz, 1H), 3.81e3.80 (m, 1H),
found: 330.1549.
13
.04e2.00 (m, 2H), 1.82e1.80 (m, 2H), 1.69e1.62 (m, 4H). C NMR
161.7, 150.1, 145.7, 145.2, 143.1, 134.4, 126.6,
26.1, 124.9, 124.4, 119.5, 103.9, 56.3, 33.8, 23.7. HRMS (ESI): m/z
(
3
100 MHz, CDCl ) d
4.4.24. 2-(2-(sec-butylamino)-6-methylphenyl)quinazolin-4(3H)-
1
one (3ae)
þ
:
[M þ Na] calcd for C17
H
17
N
3
O
2
S 318.1218; found: 318.1209.
Yellow solid (97% yield), mp: 136e138 C; 1H NMR (400 MHz,
CDCl
10.37 (br s, 1H), 8.25 (d, J ¼ 8.0 Hz, 1H), 7.79e7.75 (m, 2H),
.51 (t, J ¼ 7.2 Hz,1H), 7.15 (t, J ¼ 8.0 Hz,1H), 6.59e6.52 (m, 2H), 4.89
br s, 1H), 3.40e3.30 (m, 1H), 2.26 (s, 3H), 1.54e1.49 (m, 1H),
ꢁ
3
) d
4
4
.4.19. 2-(2,6-bis(cyclopentylamino)-3-methylphenyl)quinazolin-
7
(
(3H)-one (3ta1)
Yellow solid (60% yield), mp: 145e146 C; 1H NMR (400 MHz,
ꢁ
13
1
.44e1.37 (m, 2H), 1.11 (d, J ¼ 6.4 Hz, 3H), 0.89 (t, J ¼ 7.4 Hz, 3H).
C
CDCl
3
)
d
12.74 (br s, 1H), 9.07 (s, 1H), 8.29 (dd, J ¼ 8.0, 1.6 Hz, 1H),
NMR (100 MHz, CDCl 162.9, 152.5, 148.8, 146.1, 136.9, 134.7,
3
) d
7
.73 (ddd, J ¼ 8.4, 6.8, 1.6 Hz, 1H), 7.64 (d, J ¼ 8.0 Hz, 1H), 7.44 (t,
1
31.0, 127.4, 127.0, 126.5, 120.9, 118.9, 118.4, 109.5, 49.7, 29.3, 20.3,
J ¼ 7.6 Hz, 1H), 7.07 (d, J ¼ 8.8 Hz, 1H), 6.43 (d, J ¼ 8.2 Hz, 1H), 3.85
þ
2
3
0.0, 10.2. HRMS (ESI): m/z [M þ Na] calcd for C19
21 3
H N OS:
(
(
br s, 1H), 3.34 (br s, 1H), 3.34e3.30 (m, 1H), 2.18 (s, 3H), 2.03e2.00
m, 2H),1.80e1.76 (m, 4H),1.66e1.63 (m, 6H),1.47e1.46 (m, 4H).
30.1582; found: 330.1583.
13
C
3
NMR (10 MHz, CDCl ) d
1
1
161.7, 153.7, 148.9, 148.6, 145.9, 134.2, 134.1,
4
.4.25. 2-(2-(isobutylamino)-6-methylphenyl)quinazolin-4(3H)-
26.5,126.1,121.3,115.1,107.4,104.3, 63.0, 54.3, 33.6, 32.9, 24.1, 23.4,
7.4. HRMS (ESI): m/z [M þ H]þ calcd for C25
one (3af)
Yellow solid (50% yield), mp: 115e116 C; 1H NMR (400 MHz,
CDCl
10.05 (s,1H), 8.28 (d, J ¼ 8.0 Hz,1H), 7.80e7.74 (m, 2H), 7.52
t, J ¼ 7.2 Hz, 1H), 7.18 (t, J ¼ 8.0 Hz, 1H), 6.60 (d, J ¼ 7.6 Hz, 1H), 6.55
d, J ¼ 8.4 Hz,1H), 5.12 (br s, 1H), 2.88 (d, J ¼ 6.8 Hz, 2H), 2.29 (s, 3H),
30 4
H N OS: 403.2498;
ꢁ
found: 403.2498.
3
) d
(
(
4
.4.20. 2-(2-(cyclopentylamino)-5-methylphenyl)quinazolin-4(3H)
-
one(3ta2)
13
ꢁ
Yellow solid (22% yield), mp: 243e245 C; 1H NMR (400 MHz,
CDCl
10.58 (s, 1H), 8.89 (s, 1H), 8.30 (d, J ¼ 7.6 Hz, 1H), 7.76 (t,
1.85e1.82 (m, 1H), 0.92 (d, J ¼ 6.6 Hz, 6H). C NMR (100 MHz,
CDCl 162.7, 152.5, 148.8, 147.0, 136.6, 134.9, 131.2, 127.4, 127.1,
26.6, 120.9, 118.9, 118.4, 109.1, 51.4, 27.6, 20.4, 20.3. HRMS (ESI): m/
3
) d
3
) d
1
J ¼ 7.6 Hz, 1H), 7.64 (d, J ¼ 8.4 Hz, 1H), 7.56 (s, 1H), 7.45 (t, J ¼ 7.2 Hz,
þ
z [M þ Na] calcd for C19
21 3
H N OS: 330.1582; found: 330.1560.
1
2
4
H), 7.19 (d, J ¼ 8.4 Hz, 1H), 6.76 (d, J ¼ 8.4 Hz, 1H), 3.92 (br s, 1H),
.36 (s, 3H), 2.13e1.98 (m, 2H), 1.88e1.75 (m, 2H), 1.74e1.63 (m,
13
4.4.26. 2-(2-(butylamino)-6-methylphenyl)quinazolin-4(3H)-one
3 ag)
Yellow solid (18% yield), mp: 113e115
CDCl3)
9.85 (br s, 1H), 8.30 (d, J ¼ 7.6 Hz, 1H), 7.81e7.75 (m, 2H),
.53 (ddd, J ¼ 8.0, 6,8, 1.2 Hz, 1H), 7.20 (t, J ¼ 8.0 Hz, 1H), 6.61 (d,
J ¼ 7.6 Hz, 1H), 6.58 (d, J ¼ 8.4 Hz, 1H), 5.30 (s, 1H), 4.14e4.09 (m,
H), 3.06 (t, J ¼ 7.2 Hz, 2H), 2.27 (s, 3H),1.57e1.50 (m, 2H),1.33e1.33
3
H). C NMR (100 MHz, CDCl ) d 162.9, 152.7, 148.6, 147.3, 134.7,
(
1
33.8, 127.5, 126.8, 126.4, 126.3, 123.9, 120.5, 113.2, 111.6, 54.2, 33.5,
ꢁ
C; 1H NMR (400 MHz,
þ
2
C
4.1, 20.4. HRMS (ESI): m/z [M
þ
H]
calcd for
þ
d
20 21
H N
3
OS :320.1763; found:320.1763.
7
4
.4.21. 2-(2-(cyclohexylamino)-6-methylphenyl)quinazolin-4(3H)-
one (3 ab)
Yellow solid (93% yield), mp: 210e212 C; 1H NMR (400 MHz,
CDCl
10.18 (s,1H), 8.26 (d, J ¼ 8.0 Hz,1H), 7.79e7.75 (m, 2H), 7.50
1
13
ꢁ
(m, 2H), 0.90 (t, J ¼ 7.4 Hz, 3H). C NMR (100 MHz, CDCl )
d
162.6,
3
152.4,148.9, 146.9,136.6,134.9,131.2, 127.5, 127.2,126.6,121.0, 119.1,
3
) d
þ
1
18.6, 109.2, 43.4, 31.3, 27.0, 20.2, 13.8. HRMS (ESI): m/z [M þ Na]
(
2
2
1
ddd, J ¼ 7.2, 6.4, 1.6 Hz, 1H), 7.14 (t, J ¼ 8.0 Hz, 1H), 6.59e6.56 (m,
calcd for C19 OS: 330.1582; found: 330.1558.
21 3
H N
H), 4.78 (br s, 1H), 3.24e3.22 (m, 1H), 2.26 (s, 3H), 1.97e1.94 (m,
H), 1.68e1.65 (m, 2H), 1.59e1.55 (m, 1H), 1.33e1.30 (m, 2H),
.16e1.10 (m, 3H). 13C NMR (100 MHz, CDCl
)
d
162.7, 152.5, 148.8,
4.4.27. 2-(4-methyl-2-morpholinophenyl)quinazolin-4(3H)-one
3
1
3
C
45.8, 136.9, 134.7, 131.0, 127.4, 127.0, 126.5, 120.9, 118.7, 109.7, 51.3,
(3ch)
þ
White solid (85% yield), mp: 186e187 C; 1H NMR (400 MHz,
ꢁ
2.9, 25.7, 24.6, 20.3. HRMS (ESI): m/z [M þ Na] calcd for
21
23
H N
3
OS: 356.1739; found: 356.1711.
CDCl
3
)
d
13.22 (s, 1H), 8.33 (dd, J ¼ 8.0, 2.0 Hz, 1H), 8.26 (d,
J ¼ 8.0 Hz, 1H), 7.78e7.67 (m, 2H), 7.42 (dt, J ¼ 8.0, 6.4 Hz, 1H), 7.09
4
4
.4.22. 2-(2-methyl-6-((1-phenylethyl)amino)phenyl)quinazolin-
(3H)-one (3ac)
(d, J ¼ 8.0 Hz, 1H), 7.05 (s, 1H), 4.01e3.87 (m, 4H), 3.01e2.99 m, 4H),
13
3
2.39 (s, 3H). C NMR (100 MHz, CDCl ) d 161.7, 151.9, 150.6, 149.6,
Yellow solid (98% yield), mp: 187e189 C; 1H NMR (400 MHz,
ꢁ
143.2, 134.2, 131.3, 127.7, 126.3, 122.1, 121.5, 121.2, 66.8, 53.4, 21.5.
þ
CDCl
3
)
d
10.35 (s, 1H), 8.27 (d, J ¼ 8.0 Hz, 1H), 7.82 (d, J ¼ 3.6 Hz, 2H),
HRMS (ESI): m/z [M þ H] calcd for C19
19 3 2
H N O S: 322.1556;
7.53e7.50 (m, 1H), 7.34 (d, J ¼ 7.4 Hz, 2H), 7.27 (t, J ¼ 7.6 Hz, 2H),
found:322.1553.
Please cite this article in press as: Zhang Y, et al., Rhodium(III)-catalyzed CeH amination of 2-arylquinazolin-4(3H)-one with N-alkyl-O-benzoyl-
hydroxylamines, Tetrahedron (2018), https://doi.org/10.1016/j.tet.2018.03.051

8
Y. Zhang et al. / Tetrahedron xxx (2018) 1e8
.4.28. 2-(4-methyl-2-(piperidin-1-yl)phenyl)quinazolin-4(3H)-
4. For recent review, see: Shang XF, Morris-Natschke SLL, Liu YQ, et al Med Res
4
Rev. 2017:1e54.
one (3ci)
5. For selected examples, see: (a) Li SG, Wang KB, Gong C, et al. Bioorg Med Chem
White solid (30% yield), mp: 113e115 C; 1H NMR (400 MHz,
ꢁ
Lett. 2018;28:103e106;
CDCl
.2 Hz, 1H), 7.81e7.71 (m, 2H), 7.44 (ddd, J ¼ 8.0, 6.8, 1.2 Hz, 1H),
.09e7.08 (m, 2H), 2.97 (t, J ¼ 4.8 Hz, 4H), 2.39 (s, 3H), 1.96e1.80 (m,
H), 1.71e1.57 (m, 2H). 13C NMR (100 MHz, CDCl
162.1, 152.6,
52.4, 149.7, 143.0, 134.2, 130.9, 128.2, 127.6, 126.4, 126.1, 125.9,
3
)
d
13.91 (br s, 1H), 8.40 (d, J ¼ 8.4 Hz, 1H), 8.31 (dd, J ¼ 8.0,
(b) Haghighijoo Z, Firuzi Q, Hemmateenejad B, Emami S, Edraki N, Miri R. Bioorg
Chem. 2017;74:126e133;
1
7
4
1
(
(
c) Wilson LJ. Org Lett. 2001;3:585e588;
d) Szczepankiewicz W, Wagner P, Danicki M, Suwi nꢀ ski J. Tetrahedron Lett.
3
)
d
2003;44:2015e2017;
e) Yoon DS, Han Y, Stark TM, Haber JC, Gregg BT, Stankovich SB. Org Lett.
004;6:4775e4778;
f) Yan YZ, Zhang YH, Feng CT, Zha ZG, Wang ZY. Angew Chem Int Ed. 2012;51:
8077e8081;
(
2
(
þ
1
22.0, 121.7, 54.8, 26.1, 23.7, 21.5. HRMS (ESI): m/z [M þ H] calcd
for C20 OS: 320.1763; found: 320.1762.
21 3
H N
(
(
g) Fan XS, Li B, Guo SH, Wang YY, Zhang XY. Chem Asian J. 2014;9:739e743;
h) Zhao D, Wang T, Li JX. Chem Commun. 2014;50:6471e6474.
4.4.29. 2-(4-methyl-2-(4-(pyrimidin-2-yl)piperazin-1-yl)phenyl)q-
6
. (a) Garad DN, Viveki AB, Mhaske SB. J Org Chem. 2017;82:6366e6372;
(b) Milite C, Barresi E, Pozzo E, et al. J Med Chem. 2017;60:7897e7909;
(c) Hrast M, Rozman K, Jukic M, Patin D, Gobec S, Sova M. Bioorg Med Chem Lett.
uinazolin-4(3H)-one (3cj)
White solid (11% yield), mp: 192e194 C; 1H NMR (400 MHz,
CDCl
ꢁ
2007;27:3529e3533;
3
)
d
13.42 (s, 1H), 8.41 (d, J ¼ 8.8 Hz, 1H), 8.33 (d, J ¼ 4.8 Hz, 2H),
(d) Ward A, Dong LL, Harris JM, et al. Bioorg Med Chem Lett. 2007;27:
8
1
4
.31e8.27 (m, 1H), 7.83e7.72 (m, 2H), 7.45 (ddd, J ¼ 8.4, 6.8, 1.6 Hz,
3096e3100;
H), 7.14 (dd, J ¼ 8.0, 0.8 Hz, 1H), 7.09 (s, 1H), 6.54 (t, J ¼ 4.8 Hz, 1H),
(e) Abuelizz HA, Dib RE, Marzouk M, et al. Molecules. 2017;22:1094e1107;
(f) Smith GF, Altman MD. Bioorg Med Chem Lett. 2007;27:2721e2726;
13
.21e4.06 (m, 4H), 3.17e3.05 (m, 4H), 2.41 (s, 3H). C NMR
(
(
g) Peng YY, Qiu GYS, Yang Q, Yuan JJ, Deng ZH. Synthesis. 2012;44:1237e1246;
h) Zhao X, Zhou YR, Yang Q, et al. Synthesis. 2013;45:3245e3250;
(
3
100 MHz, CDCl ) d 161.7,157.7,152.1,151.0,149.8,143.3,134.3,131.3,
1
27.8, 126.4, 126.3, 122.3, 121.7, 121.5, 110.4, 53.2, 43.9, 21.6. HRMS
(i) Lu H, Yang Q, Zhou YR, et al. Org Biomol Chem. 2014;12:758e764;
(j) Wei M k, Chai WM, Wang R, Yang Q, Deng ZH, Peng YY. Biorg Med Chem.
þ
(
3
ESI): m/z [M þ H] calcd for C23
22 6
H N OS: 399.1933; found:
2
017;25:1303e1308;
k) Zhao Y, Liu WS, Li Q, et al. Bull Environ Contam Toxicol. 2015;94:376e381.
. (a) Gong B, Shi J, Wang X, et al. Adv Synth Catal. 2014;356:137e143;
b) Umeda N, Hirano K, Satoh T, Miura M. J Org Chem. 2009;74:7094e7099.
99.1935.
(
7
8
(
Acknowledgments
. For selected reviews on rhodium(III)-catalyzed C-H functionalization, see: (a)
Dong Z, Ren Z, Thompson SJ, Xu Y, Dong GB. Chem Rev. 2017;117:9333e9403;
(b) Mishra NK, Sharma S, Park J, Han S, Kim IS. ACS Catal. 2017;7:2821e2847;
Financial support from National Natural Science Foundation of
China (no. 21362014 and 21762020), Jiangxi Provincial Department
of Science and Technology (no. 20171BAB203006), and key labo-
ratory of Functional Small Organic Molecule, Ministry of Education,
Jiangxi Normal University (no. KLFS-KF-201702) is gratefully
acknowledged.
(
1
(
c) Zhu RY, Farmer ME, Chen YQ, Yu JQ. Angew Chem Int Ed. 2016;55:
0578e10599;
d) Colby D, Tsai AS, Bergman RG, Ellman JA. Acc Chem Res. 2012;45:814e825;
(e) Arockiam PB, Bruneau C, Dixneuf PH. Chem Rev. 2012;112:5879e5918.
. (a) Lu XB, Shi YF, Zhong FR. Green Chem. 2018;20:113e117;
9
(b) Mishra NK, Jeon M, Oh Y. Org Chem Front. 2017;4:241e249;
(c) Li HY, Jie JY, Wu SX, Yang XB, Xu H. Org Chem Front. 2017;4:250e254;
(d) Wang HW, Lu Y, Zhang B. Angew Chem Int Ed. 2017;56:7449e7453;
Appendix A. Supplementary data
(e) Ali MA, Yao XY, Li GG, Lu HJ. Org Lett. 2016;18:1386e1389;
(
(
(
f) Wang XY, Jiao N. Org Lett. 2016;18:2150e2153;
g) Shi LL, Wang BT. Org Lett. 2016;18:2820e2823;
h) Zou MC, Liu J,Z, Tang CH, Jiao N. Org Lett. 2016;18:3030e3033;
Supplementary data related to this article can be found at
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(
(
(
(
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Please cite this article in press as: Zhang Y, et al., Rhodium(III)-catalyzed CeH amination of 2-arylquinazolin-4(3H)-one with N-alkyl-O-benzoyl-
hydroxylamines, Tetrahedron (2018), https://doi.org/10.1016/j.tet.2018.03.051