NIS-mediated oxidative arene C(sp2)-H amidation toward 3,4-dihydro-2(1H)-quinolinone, phenanthridone, and N-fused spirolactam derivatives

Article abstract of DOI:10.1039/c9ob01277j

A new radical-mediated intramolecular arene C(sp²)-H amidation of 3-phenylpropanamides or [1,1′-biphenyl]-2-carboxamides was developed to prepare a series of 3,4-dihydro-2(1H)-quinolinone and phenanthridone derivatives in moderate to excellent yields (33-94%). Spirolactams could also be obtained using this protocol.

Full text of DOI:10.1039/c9ob01277j

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Takeharu Haino et al.
Solvent-induced emission of organogels based on tris(phenylisoxazolyl)
benzene
rsc.li/obc

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DOI: 10.1039/C9OB01277J
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NIS-mediated oxidative arene C(sp2)–H amidation toward 3,4-
dihydro-2(1H)-quinolinone, phenanthridone, and N-fused
spirolactam derivatives
Received 00th January 20xx,
Accepted 00th January 20xx
Lingang Wu, Yanan Hao, Yuxiu Liu and Qingmin Wang *
DOI: 10.1039/x0xx00000x
A new radical-mediated intramolecular arene C(sp2)–H amidation of 3-phenylpropanamides or [1,1'-
biphenyl]-2-carboxamides was developed to prepare a series of 3,4-dihydro-2(1H)-quinolinone and
phenanthridone derivatives in moderate to excellent yields (33–94%). Spirolactams could also be obtained
using this protocol.
the nitrogen atom. The transition-metal-catalyzed arene amidation
Introduction
of aryl halides has provided a convenient method for the synthesis
of 3,4-dihydro-2(1H)-quinolinones. Furthermore, remarkable
advances have been achieved in the palladium,3a–d copper,3e and
iron catalysis3f of this type of transformation (Scheme 1d).
Nevertheless, exploring direct intramolecular arene C(sp2)–H
amidation, which avoids prefunctionalization, for the synthesis of
these derivatives with high step efficiency and wide substrate scope
Benzo-fused and spiro-fused lactam skeletons are important
motifs in many pharmacologically active compounds. The 3,4-
dihydro-2(1H)-quinolinone and phenanthridone scaffolds are
important members of these classes, and their derivatives are
found in many natural products and medicinally active
compounds (Figure 1).1
remains
a necessary and challenging task. Compared with
OMe
established methods, the construction of lactams using N-centered
amidyl radicals might be a straightforward approach. Recently,
some elegant modifications of the Hofmann–Löffler–Freytag (HLF)4
reaction for the C(sp3)–H functionalization of amides5 have been
developed. However, the cyclic amination of aromatics using a HLF-
type reaction has seen little exploration.6 Herein, we report a novel
synthetic route for the construction benzolactams and spiro-fused
lactams through intramolecular arene C(sp2)–H amidation using an
amidyl radical.
MeO
HO
Cl
NHtBu
O
Cl
N
O
N
N
O
N
O
O
N
H
O
H
O
Arpiprazole
Cartelol
Oxynitidine
O
N
O
NH
N
O(CH2
OPC-21268
)3NHCOCH3
O
HN
Me2
N
O
A) Friedel-Crafts reaction
B) Beckmann rearrangement
O
acid
PJ34
Cl
NOH
H
Figure 1 Examples of natural products and medicinally active
compounds containing 3,4-dihydro-2(1H)-quinolinone and
phenanthridone scaffolds.
N
Lewis acid
O
N
H
C) Cyclization of nitrenium ion
[O]
O
X
N
R
or
R
Generally, the synthesis of 3,4-dihydro-2(1H)-quinolinones relies
on electrophilic aromatic substitution reactions, including the
N
O
N
O
HN
X
O
X
O
X
X = OMe or N-phthalimide
Friedel–Crafts reaction
(Scheme 1a),2a the Beckmann
D) Transition metal catalysis
rearrangement of indanone oxime (Scheme 1b),2b and the
electrophilic cyclization of nitrenium ions (Scheme 1c).2c,d However,
these methods require a stoichiometric amount of metal salt.
Furthermore, these reactions are limited to primary or secondary
amide substrates with methoxy or N-phthalimide substituents on
O
[Pd], [Cu] or [Fe]
NHR
N
R
O
X
X = Cl, Br, or I
This work: radical mediated arene C(sp2)-H amidation
O
O
R
R
N
N
R2
NIS (3 equiv)
R2
NIS (3 equiv)
110 oC, 10h, Ar
or
110 oC, 10h, Ar
N
R1
O
O
HN
R1
O
O
a. State Key Laboratory of Elemento-Organic Chemistry, Research Institute of
Elemento-Organic Chemistry, College of Chemistry, Collaborative Innovation
Center of Chemical Science and Engineering (Tianjin)
4 examples
79-87% yield
25 examples
33-94% yield
Nankai University, Tianjin 300071 (P.R. China)
E-mail: wangqm@nankai.edu.cn.
Scheme 1 General methods for the synthesis of 3,4-dihydro-2(1H)-
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
quinolinones.
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Table 1 Optimization of reaction conditions.a
method, phenanthridinone derivatives 2r–2v bearing different
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substituents on the nitrogen atom were synthesized in moderate to
DOI: 10.1039/C9OB01277J
excellent yields. Furthermore, the removal of the Bn group of 2n
and 2v proceeded under acidic conditions to give N–H 3,4-dihydro-
2(1H)-quinolinone 2l and phenanthridone 3 according to previously
described procedures11. Next, substituents on the phenyl ring
attached to the alkyl moiety were investigated. N-Phenyl-3-(o-
tolyl)propanamide and 3-(3-bromophenyl)-N-phenylpropanamide
afforded amidation products 2w and 2x in moderate yields. Product
2w was unambiguously confirmed by X-ray crystallography.10 For
meta-Me substituted substrate 1y, para-amidation product 2y was
obtained in moderate yield, accompanied by a small amount of
radical initiator
HN
Ph
O
solvent, 110 oC
Ar, 10h
N
O
Ph
2a
1a
Radical
initiator
NIS
NBS
NCS
Amount
(equiv.)
2.0
2.0
2.0
1.5 + 1.5
2.5
Yield
(%)b
65
trace
0
Entry
Solvent
1
2
3
4
5
DCE
DCE
DCE
DCE
DCE
ortho-amidation
product
2y’.
However,
3-(4-
PhI(OAc)2 + I2
NIS
trace
78
methoxyphenyl)propanamide failed to afford desired product 2z.
6
7
8
NIS
NIS
NIS
NIS
3.0
3.0
3.0
3.0
DCE
86
61
54
23
Table 2 Substrate scope for intramolecular C−H amidation.a,b
toluene
CH3CN
DMF
DCE
9
R3
R2
R3
10c
NIS
3.0
79
R2
NIS (3 equiv)
a Reaction was conducted on 0.25-mmol scale. b Isolated yield.
c Reaction was conducted in air.
N
O
DCE, 10 h,110 o
C
NH
O
R1
R1
2
1
Results and discussion
2a
(R = H), 86%;
2b
2c
2d
2e
2f
2g
2h
2i
(R = 4-Me), 87%;
(R = 4-Br), 83%;
(R = 4-F), 86%;
(R = 4-Ph), 84%;
(R = 4-tBu), 83%;
(R = 4-OMe), 51%;
(R = 3-Me), 77%;
(R = 3-NO2), 68%;
(R = 2-Me), 70%
Our initial efforts to trigger the metal-free C−H amidation
reaction were guided by conditions used for the radical C−H
N
O
N
H
O
N
O
amination
of
sulfonamides5b
and
amides5e.
N,3-
2l
, 33%
Cl
Cl
R
Diphenylpropanamide (1a) was selected as a model substrate and
stirred in 1,2-dichloroethane (DCE) at 110 C under an Ar
atmosphere to investigate reaction optimization. Oxidants N-
iodosuccinimide (NIS), N-bromosuccinimide (NBS), and N-
chlorosuccinimide (NCS) were tested initially, with only NIS
affording amidation product 2a in 65% yield (Table 1, entries 1–3).
The combination of PhI(OAc)2 and I2 did not facilitate the desired
reaction (entry 4). When the amount of NIS was increased to 3
equiv., an improved 86% yield was obtained (Table 1, entry 6). The
solvent was also crucial to this transformation. Using toluene, N,N-
dimethylformamide (DMF), and CH3CN as solvent did not further
improve the reaction yield (entries 7–9). The yield of 2a was slightly
lower when the reaction was conducted under air (entry 10).
2k
, 70%
2j
Ph
N
O
N
O
N
O
N
O
Bn
Ph
N
2n
2p
, 89%
, 78%
2o
, 69%
2m
, 51%
Boc
Ph
O
2r
2s
2t
(R = H), 92%;
(R = Cl), 94%;
(R = Me), 80%
Ph
Ph
N
N
R
O
N
O
Ph
Ph
2q
, 43%
2q
, 45%
Me
With optimal conditions in hand (Table 1, entry 6), we next
examined the extent and generality of this transformation (Table 2).
The influence of substituents on the phenyl group attached to the N
atom was examined first. Para-substituents with different
electronic properties were well tolerated in the reaction, affording
3,4-dihydro-2(1H)-quinolinones 2a–2g in good to excellent yields.
Meta- and ortho-substituents afforded desired products 2h, 2i and
2j, respectively, in good yields. Polysubstituted arene (1K) was also
compatible with this protocol. Under the optimized conditions, the
primary amide was also tolerated, but afforded a lower yield (2l,
33%). With Me- (2m), Bn- (2n), or N-protected piperidyl (2o)
substituents on the nitrogen atom, the reactions proceeded
smoothly with moderate yields. Notably, 2o could be further
converted into OPC-21268, an orally bioavailable arginine
vasopressin (AVP) V1 antagonist with high V1 specificity.1g A phenyl
group on the carbonyl -position did not significantly influence the
reaction, affording product 2p. However, when two phenyl groups
were attached at the carbonyl -position, the anticipated
cyclization product 2q was obtained in moderate yield, while
unexpected product 2q’, resulting from aryl migration from carbon
to the nitrogen center, was also produced.7 Using this established
N
O
N
O
N
O
Ph
Bn
OMe
2w
, 52%
CCDC: 1906915
2v
, 85%
2u
, 47%
Br
Me
MeO
N
O
N
Me Ph
O
N
O
N
O
Ph
Ph
, 49%
Ph
, 63%
2x
2z
, trace
2y
2y'
, 18%
a Reaction conditions: 1 (0.25 mmol, 1.0 equiv.) and NIS (0.75 mmol,
3.0 equiv.) in DCE (2 mL) at 110 C under Ar. Isolated product
b
yields.
When the substrates were changed to TBS-protected phenol
derivatives, spirolactams were produced, which are also synthetic
and medicinal intermediates (Scheme 2).8 Pleasingly, the
dearomative spirocyclization of Ph- and Bn-protected amides (2aa
and 2ab) proceeded in an efficient manner, in contrast to most
classical approaches, which require specific N-protecting groups,
such as MeO or N-phthalimide,9 or proceed through the oxidation
2 | J. Name., 2012, 00, 1-3
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yield
additive
of phenolic oxazolines.8 To our knowledge, this represents the first
synthetic approach to spirolactams using an amidyl radical process.
Similarly, ortho-substituted phenol derivatives 1ac and 1ad
underwent cyclization smoothly to afford spirolactams. This
protocol not only provides a concise method for the construction of
novel spirolactams, but also complements previous work.
additive (2 equiv)
NIS (3 equiv)
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trace
TEMPO
DOI: 10.1039/C9OB01277J
DCE, 110 o
Ar, 10 h
C
N
O
HN
Ph
1a
O
Ph
trace
BHT
2a
O
I
Ph
N
I
NIS
Scheme 2 Synthesis of spirolactams through ipso-amidation.a,b
R
HN
Ph
1a 1q
O
R
N
Ph
Ⅱ
O
R
Ⅰ
or
O
R
R=H
R=H
NIS (3 equiv)
2aa (
2ab
R=Ph), 87%
(R=Bn), 83%
N
TBSO
HN
R
O
O
DCE, 10 h, 110 o
C
O
HI
I
N
OTBS
Ph
R
N
O
N
O
NIS (3 equiv)
2ac (
2ad
R=Ph), 80%
(R=Bn), 79%
N
Ph
2a
Ph
R
O
DCE, 10 h, 110 o
C
Ⅲ
HN
O
O
Ⅳ
R
I
R=OTBS
O
aReaction conditions: 1 (0.25 mmol, 1.0 equiv.) and NIS (0.75 mmol,
3.0 equiv.) in DCE (2 mL) at 110 C under Ar. b Isolated product
yields.
TBSI
Ph
N
O
2aa
As shown in Scheme 3, control experiments showed that the
oxidative arene C(sp2)–H amidation of amide 1a was impeded in the
presence of radical inhibitors (2,2,6,6-tetramethylpiperidin-1-yl)oxyl
(TEMPO) and butylated hydroxytoluene (BHT). Similarly, When 2
equivalents of TEMPO were added to the solution of 1aa and NIS in
DCE, the reactions were suppressed. In order to further understand
this transformation, mass spectrom-etryexperiments of 1a had
been done by adding 2.0 equiv of BHT under the model reaction.
The product of the radical captured by BHT were observed via
HRMS detection (for details, see the Supporting Information). These
results indicated that this arene C(sp2)–H amidation might proceed
via a radical pathway. Based on the above results and literature
reports,5,6 a mechanism was proposed for this transformation
(Scheme 3). Amides 1a or 1aa first react with NIS to give N-
iodinated compound I, which undergoes N–I homolytic cleavage to
afford amide N radical II under thermal conditions. Radical II then
undergoes a 5-exo cyclization onto the aromatic ring to give spiro
intermediate III or a 6-endo cyclization to give benzolactam
intermediate IV, which might also be obtained from intermediate III
through ring-expansion via C–N bond migration. Product 2a is then
produced by the rearomatization of radical IV. When the R
substituent is OTBS, intermediate III affords spirolactam 2aa.
Scheme 3 Control experiments and possible reaction mechanism.
Conclusions
In conclusion, a novel and efficient NIS-mediated radical
oxidative arene C(sp2)–H amidation has been developed to
synthesize 3,4-dihydro-2(1H)-quinolinone and phenanthridone
derivatives in moderate to excellent yields. Differently substituted
3-phenylpropanamides or [1,1'-biphenyl]-2-carboxamides were
tolerated. Furthermore, spirolactams bearing Ph or Bn as N-
substituents were readily obtained using this protocol.
EXPERIMENTAL SECTION
General Method and Materials. All reagents were used as
received. Acetonitrile was distilled on phosphorus pentoxide. H
1
and 13C Nuclear Magnetic Resonance (NMR) spectra were recorded
on Bruker Avance 400 Ultrashield NMR spectrometers. Chemical
shifts (δ) were given in parts per million (ppm) and were measured
downfield from internal tetramethylsilane. High-resolution mass
spectrometry (HRMS) data were obtained on an FTICR-MS
instrument (Ionspec 7.0 T). The melting points were determined on
an X-4 microscope melting point apparatus and are uncorrected.
Conversion was monitored by thin layer chromatography (TLC).
Flash column chromatography was performed over silica gel (100-
200 mesh). NH free 3,4-dihydro-2(1H)-quinolinone 2l and
phenanthridone 3 can obtained from the N-benzyl derivatives with
a previously described procedure.11
General procedure A for the preparation of compounds 1a-o.
To a solution of amine (5.0 mmol, 1.0 equiv) in dichloromethane
(20 mL) was added triethylamine (1.0 mL,7.5 mmol, 1.5 equiv) at 0
ºC. After stirring for 10 min at 0 ºC, 3-phenylpropanoyl chloride
(0.47 mL,5.0 mmol, 1.0 equiv) was added dropwise and then the
mixture was stirred at room temperature. After completing reaction,
the mixture was added 30 mL H2O. The organic layer was separated
and the aqueous layer was extracted with dichloromethane (20mL ×
3). The combined organic phase was washed with brine (20 mL),
and then dried over Na2SO4. After filtration, the solvent was
concentrated in vacuo. The products were purified by column
chromatography with petroleum ether and ethyl acetate as an
eluent.
General procedure B for the preparation of compounds 1p-z.
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J. Name., 2013, 00, 1-3 | 3
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A
mixture of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (m, 3H), 7.06 (s, 1H), 6.89 – 6.66 (m, 2H), 3.77 (s, 3H),V3ie.0w4Ar(ttic,leJ O=n7lin.6e
hydrochloride (1.04g, 6.5 mmol, 1.3 equiv), DMAP (0.92g, 7.5 mmol, Hz, 2H), 2.62 (t, J = 7.6 Hz, 2H). 13C NMR (101 MHz, CDCl ) δ 170.2,
DOI: 10.1039/C9OB01277J
3
1.5 equiv), acid (5 mmol, 1.0 equiv), and amine (5 mmol, 1.0 equiv) 156.4, 140.7, 130.8, 128.6, 128.4, 126.3, 121.9, 114.1, 99.9, 55.4,
in CH2Cl2 (20 mL) was stirred at room temperature for 4 h. After 39.3, 31.6.HRMS (ESI): calcd. for C16H18NO2 [M + H]+ 256.1332;
completing reaction, the mixture was added 30 mL H2O. The found 256.1334. Rf 0.2 (Petroleum ether/EtOAc, 5/1).
organic layer was separated and the aqueous layer was extracted
3-phenyl-N-(m-tolyl)propanamide (1h). According to the general
with dichloromethane (20mL × 3). The combined organic phase was procedure A. White solid (1.0 g, 85%). M.p. = 73-75 °C. 1H NMR (400
washed with brine (20 mL), and then dried over Na2SO4. After MHz, CDCl3) δ 7.36 – 7.25 (m, 3H), 7.24 – 7.05 (m, 6H), 6.90 (d, J =
filtration, the solvent was concentrated in vacuo. The products 6.5 Hz, 1H), 3.04 (t, J = 7.6 Hz, 2H), 2.63 (t, J = 7.6 Hz, 2H), 2.30 (s,
were purified by column chromatography with petroleum ether and 3H). 13C NMR (100 MHz, CDCl3) δ 170.4, 140.7, 138.9, 137.7, 128.8,
ethyl acetate as an eluent.
128.7, 128.4, 126.4, 125.1, 120.6, 117.0, 39.5, 31.6, 21.5. HRMS
N,3-diphenylpropanamide (1a). According to the general (ESI): calcd. for C16H18NO [M + H]+ 240.1383; found 240.1388. Rf
1
procedure A. White solid (0.98 g, 87%). M.p. = 95-96 °C. H NMR 0.33 (Petroleum ether/EtOAc, 5/1).
(400 MHz, CDCl3) δ 7.43 (d, J = 7.9 Hz, 2H), 7.35 – 7.14 (m, 8H), 7.08
N-(3-nitrophenyl)-3-phenylpropanamide (1i). According to the
general procedure A. Yellow solid (1.1 g, 82%). M.p. = 109-111 °C.
(t, J = 7.4 Hz, 1H), 3.04 (t, J = 7.6 Hz, 2H), 2.64 (t, J = 7.6 Hz, 2H). 13
C
NMR (100 MHz, CDCl3) δ 170.5, 140.7, 137.8, 129.0, 128.7, 128.4, 1H NMR (400 MHz, CDCl3) δ 8.30 (s, 1H), 7.98 – 7.83 (m, 2H), 7.55 –
126.4, 124.3, 120.0, 39.5, 31.6. HRMS (ESI): calcd. for C15H16NO [M + 7.43 (m, 2H), 7.37 – 7.29 (m, 2H), 7.28 – 7.18 (m, 3H), 3.09 (t, J = 7.5
H]+ 226.1226; found 226.1230. Rf 0.3 (Petroleum ether/EtOAc, 5/1). Hz, 2H), 2.75 (t, J = 7.5 Hz, 2H). 13C NMR (101 MHz, CDCl3) δ 170.8,
3-phenyl-N-(p-tolyl)propanamide (1b). According to the general 148.4, 140.2, 138.7, 129.8, 128.7, 128.7, 128.3, 128.3, 126.6, 125.5,
procedure A. White solid (1.0 g, 87%). M.p. =128-130 °C. 1H NMR 118.9, 114.5, 39.3, 31.3. HRMS (ESI): calcd. for C15H15N2O3 [M + H]+
(400 MHz, CDCl3) δ 7.40 – 7.23 (m, 5H), 7.23 – 7.16 (m, 3H), 7.07 (d, 271.1077; found 271.1077. Rf 0.3 (Petroleum ether/EtOAc, 5/1).
J = 8.1 Hz, 2H), 3.02 (t, J = 7.6 Hz, 2H), 2.61 (t, J = 7.7 Hz, 2H), 2.29 (s,
3-phenyl-N-(o-tolyl)propanamide (1j). According to the general
3H).13C NMR (100 MHz, CDCl3) δ 170.4, 140.7, 135.2, 134.0, 129.5, procedure A. White solid (1.1 g, 90%). M.p. = 118-120 °C.1H NMR
128.6, 128.4, 126.4, 120.2, 39.4, 31.6 , 20.9. HRMS (ESI): calcd. for (400 MHz, CDCl3) δ 7.75 (d, J = 7.3 Hz, 1H), 7.36 – 7.16 (m, 7H), 7.09
C16H18NO [M + H]+ 240.1383; found 240.1387. Rf 0.3 (Petroleum (t, J = 7.2 Hz, 1H), 6.92 (s, 1H), 3.10 (t, J = 7.3 Hz, 2H), 2.74 (t, J = 7.3
ether/EtOAc, 5/1).
Hz, 2H), 2.09 (s, 3H).13C NMR (100 MHz, CDCl3) δ 170.4, 140.6,
N-(4-bromophenyl)-3-phenylpropanamide (1c). According to the 135.5, 130.4, 128.7, 128.5, 126.7, 126.5, 125.3, 123.4, 39.3, 31.8,
general procedure A. White solid (1.28 g, 84%). M.p. = 149-151 °C. 17.6. HRMS (ESI): calcd. for C16H18NO [M + H]+ 240.1383; found
1H NMR (400 MHz, CDCl3) δ 7.41 – 7.34 (m, 2H), 7.33 – 7.27 (m, 4H), 240.1386. Rf 0.4 (Petroleum ether/EtOAc, 5/1).
7.25 – 7.15 (m, 3H), 3.01 (t, J = 7.6 Hz, 2H), 2.63 (t, J = 7.6 Hz, 2H).
N-(3,5-dichlorophenyl)-3-phenylpropanamide (1k). According to
13C NMR (100 MHz, CDCl3) δ 170.6, 140.4, 136.8, 131.9, 128.7, the general procedure A. Grey solid (1.29 g, 89%). M.p. = 97-99 °C.
128.4, 126.5, 121.6, 116.9, 39.4, 31.5. HRMS (ESI): calcd. for 1H NMR (400 MHz, CDCl3) δ 7.45 – 7.27 (m, 5H), 7.25 – 7.17 (m, 3H),
C15H15BrNO [M + H]+ 304.0332; found 304.0327. Rf 0.3 (Petroleum 7.06 (s, 1H), 3.02 (t, J = 7.5 Hz, 2H), 2.65 (t, J = 7.5 Hz, 2H). 13C NMR
ether/EtOAc, 5/1).
(101 MHz, CDCl3) δ 170.7, 140.2, 139.4, 135.1, 128.7, 128.3, 126.5,
N-(4-fluorophenyl)-3-phenylpropanamide (1d). According to the 124.2, 118.1, 39.3, 31.3. HRMS (ESI): calcd. for C15H14Cl2NO [M + H]+
general procedure A. White solid (1.0 g, 82%). M.p. = 116-118 °C. 1H 294.0447; found 294.0443. Rf 0.3 (Petroleum ether/EtOAc, 5/1).
NMR (400 MHz, CDCl3) δ 7.42 – 7.27 (m, 4H), 7.25-7.19(m, 3H), 6.94
3-phenylpropanamide (1l). According to the general procedure
(t, J = 8.5 Hz, 2H), 3.02 (t, J = 7.5 Hz, 2H), 2.63 (t, J = 7.6 Hz, 2H). 13
C
A. White solid (0.57 g, 76%). M.p. = 99-101 °C.1H NMR (400 MHz,
NMR (100 MHz, CDCl3) δ 170.6, 159.4 (d, J = 243.6 Hz), 140.6, 133.7, CDCl3) δ 7.34 – 7.25 (m, 2H), 7.24 – 7.16 (m, 3H), 5.76 (s, 1H), 5.46
128.7, 128.4, 126.5, 122.0 (d, J = 7.3 Hz), 115.6 (d, J = 22.5 Hz), 39.3, (s, 1H), 2.96 (t, J = 7.8 Hz, 2H), 2.52 (t, J = 7.8 Hz, 2H). 13C NMR (100
31.6. HRMS (ESI): calcd. for C15H15FNO [M + H]+ 224.1132; found MHz, CDCl3) δ 174.7, 140.7, 128.6, 128.3, 126.3, 37.5, 31.4. HRMS
224.1131. Rf 0.3 (Petroleum ether/EtOAc, 5/1).
N-([1,1'-biphenyl]-4-yl)-3-phenylpropanamide (1e). According to (Petroleum ether/EtOAc, 1/1).
(ESI): calcd. for C9H12NO [M + H]+ 150.0913; found 150.0913. Rf 0.2
the general procedure A. White solid (1.3 g, 84%). M.p. = 176-
N-methyl-3-phenylpropanamide (1m). According to the general
1
178 °C. H NMR (400 MHz, CDCl3) δ 7.63 – 7.46 (m, 6H), 7.41 (t, J = procedure A. Colorless solid (0.73 g, 90%). M.p. = 58-60 °C. 1H NMR
7.6 Hz, 2H), 7.30 (dd, J = 13.7, 7.2 Hz, 3H), 7.23 (dd, J = 7.5, 3.4 Hz, (400 MHz, CDCl3) δ 7.27 (dd, J = 10.0, 5.1 Hz, 2H), 7.19 (t, J = 6.3 Hz,
3H), 7.19 (s, 1H), 3.06 (t, J = 7.6 Hz, 2H), 2.67 (t, J = 7.6 Hz, 2H).13C 3H), 5.60 (s, 1H), 2.96 (t, J = 7.8 Hz, 2H), 2.75 (s, 3H), 2.51 – 2.38 (m,
NMR (100 MHz, CDCl3) δ 170.4, 140.6, 140.5, 137.2, 137.0, 128.8, 2H).13C NMR (100 MHz, CDCl3) δ 172.8, 141.0, 128.5, 128.3, 126.2,
128.7, 128.4, 127.6, 127.1, 126.9, 126.5, 120.3, 39.52, 31.6. HRMS 38.4, 31.8, 26.3. HRMS (ESI): calcd. for C10H14NO [M + H]+ 164.1070;
(ESI): calcd. for C21H20NO [M + H]+ 302.1539; found 302.1542. Rf 0.3 found 164.1073. Rf 0.2 (Petroleum ether/EtOAc, 2/1).
(Petroleum ether/EtOAc, 5/1).
N-benzyl-3-phenylpropanamide (1n). According to the general
1
N-(4-(tert-butyl)phenyl)-3-phenylpropanamide (1f). According to procedure A. White solid (0.98 g, 87%). M.p. = 83-84 °C. H NMR
the general procedure A. White solid (1.2 g, 87%). M.p. = 136- (400 MHz, CDCl3) δ 7.33 – 7.23 (m, 5H), 7.23 – 7.15 (m, 3H), 7.15 –
1
138 °C. H NMR (400 MHz, CDCl3) δ 7.40 - 7.26 (m, 6H), 7.24 - 7.05 7.08 (m, 2H), 5.82 (s, 1H), 4.36 (d, J = 5.5 Hz, 2H), 2.97 (t, J = 7.6 Hz,
(m, 4H), 3.04 (t, J = 7.6 Hz, 1H), 2.64 (t, J = 7.6 Hz, 1H), 1.29 (s, 9H). 2H), 2.49 (t, J = 7.6 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ 172.0,
13C NMR (101 MHz, CDCl3) δ 170.3, 147.3, 140.7, 135.1, 128.6, 140.8, 138.2, 128.7, 128.6, 128.4, 127.7, 127.5, 126.3, 43.6, 38.5,
128.4, 126.3, 125.7, 119.8, 39.4, 34.3, 31.6, 31.3. HRMS (ESI): calcd. 31.7. HRMS (ESI): calcd. for C16H18NO [M + H]+ 240.1383; found
for C19H24NO [M + H]+ 282.1852; found 282.1852. Rf 0.2 (Petroleum 240.1384. Rf 0.3 (Petroleum ether/EtOAc, 2/1).
ether/EtOAc, 5/1).
tert-butyl
4-(3-phenylpropanamido)piperidine-1-carboxylate
N-(4-methoxyphenyl)-3-phenylpropanamide (1g). According to (1o). According to the general procedure A. White solid (1.2 g, 73%).
the general procedure A. White solid (1.1 g, 86%). M.p. = 128- M.p. = 141-143 °C. 1H NMR (400 MHz, CDCl3) δ 7.35 – 7.14 (m, 5H),
130 °C. 1H NMR (400 MHz, CDCl3) δ 7.35 – 7.27 (m, 4H), 7.25 – 7.19 4.15 – 3.72 (m, 3H), 2.95 (t, J = 7.5 Hz, 2H), 2.80 (s, 2H), 2.45 (t, J =
4 | J. Name., 2012, 00, 1-3
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7.6 Hz, 2H), 1.79 (d, J = 11.9 Hz, 2H), 1.44 (s, 9H), 1.25 – 1.08 (m, 2H). (400 MHz, CDCl3) δ 7.63 – 7.40 (m, 3H), 7.38 – 7.29 (m, 2H), 7.23 –
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13C NMR (100 MHz, CDCl3) δ 171.4, 154.7, 140.8, 128.5, 128.4, 126.3, 7.07 (m, 5H), 3.07 (t, J = 7.8 Hz, 2H), 2.65 (t,DJO=I:71.08.1H03z9, /2CH9)O, B20.31627(7sJ,
79.6, 46.5, 38.6, 32.0, 31.8, 28.4. HRMS (ESI): calcd. for C19H29N2O3 3H). 13C NMR (100 MHz, CDCl3) δ170.8, 138.8, 137.9, 136.1, 130.5,
[M + H]+ 355.1992; found 355.1988 . Rf 0.3 (Petroleum ether/EtOAc, 129.0, 128.7, 126.5, 126.3, 124.3, 120.1, 38.1, 28.8, 19.4. HRMS
3/1).
N,2,3-triphenylpropanamide (1p). According to the general (Petroleum ether/EtOAc, 5/1).
(ESI): calcd. for C16H18NO [M + H]+ 240.1383; found 240.1386. Rf 0.3
1
procedure B. White solid (1.3 g, 84%). M.p. = 167-168 °C. H NMR
3-(3-bromophenyl)-N-phenylpropanamide (1x). According to the
1
(400 MHz, CDCl3) δ 7.34 – 7.26 (m, 6H), 7.24 – 7.09 (m, 8H), 7.03 (t, general procedure B. White solid (1.3 g, 83%). M.p. = 91-93 °C. H
J = 7.3 Hz, 1H), 3.74 (t, J = 7.4 Hz, 1H), 3.60 (dd, J = 13.5, 7.8 Hz, 1H), NMR (400 MHz, CDCl3) δ 7.69 (s, 1H), 7.48 (d, J = 7.9 Hz, 2H), 7.43 –
3.04 (dd, J = 13.5, 7.0 Hz, 1H).13C NMR (100 MHz, CDCl3) δ 171.0, 7.24 (m, 4H), 7.24 – 7.05 (m, 3H), 3.00 (t, J = 7.7 Hz, 2H), 2.63 (t, J =
139.5, 139.2, 137.7, 129.1, 129.0, 128.9, 128.4, 128.1, 127.6, 126.4, 7.7 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ169.9, 143.0, 137.8, 130.2,
124.4, 120.0, 56.5, 39. HRMS (ESI): calcd. for C21H20NO [M + H]+ 129.2, 128.9, 128.6, 125.8, 124.5, 120.6, 119.9, 31.9, 25.2. HRMS
302.1539; found 302.1541. Rf 0.3 (Petroleum ether/EtOAc, 5/1).
(ESI): calcd. for C15H16BrNO [M + H]+ 304.0332; found 304.0331. Rf
N,3,3-triphenylpropanamide (1q). According to the general 0.3 (Petroleum ether/EtOAc, 5/1).
1
procedure B. White solid (1.4 g, 90%). M.p. = 175-177 °C. H NMR
N-phenyl-3-(m-tolyl)propanamide (1y). According to the general
(400 MHz, CDCl3) δ 7.28 (t, J = 8.4 Hz, 11H), 7.25 – 7.20 (m, 3H), 7.06 procedure B. White solid (1.0 g, 87%). M.p. = 70-72 °C. 1H NMR (400
(d, J = 6.6 Hz, 1H), 6.94 (s, 1H), 4.64 (t, J = 7.7 Hz, 1H), 3.08 (d, J = 7.7 MHz, CDCl3) δ 7.50 (d, J = 7.6 Hz, 3H), 7.31 (dd, J = 13.6, 5.6 Hz, 2H),
Hz, 2H).13C NMR (100 MHz, CDCl3) δ 169.4, 143.5, 137.5, 128.9, 7.25 – 7.09 (m, 5H), 3.07 (t, J = 7.8 Hz, 2H), 2.65 (t, J = 7.8 Hz, 2H),
128.8, 127.8, 126.7, 124.4, 120.1, 47.5, 44.4. HRMS (ESI): calcd. for 2.36 (s, 3H).13C NMR (100 MHz, CDCl3) δ 170.8, 138.8, 137.9, 136.1,
C21H20NO [M + H]+ 302.1539; found 302.1536. Rf 0.3 (Petroleum 130.5, 129.0, 128.7, 126.5, 126.3, 124.3, 120.1, 38.1, 28.84, 19.4.
ether/EtOAc, 5/1).
HRMS (ESI): calcd. for C16H18NO [M + H]+ 240.1383; found 240.1383.
N-phenyl-[1,1'-biphenyl]-2-carboxamide (1r). According to the Rf 0.3 (Petroleum ether/EtOAc, 5/1).
general procedure B. White solid (1.1 g, 83%). M.p. = 104-106 °C. 1H
3-(4-methoxyphenyl)-N-phenylpropanamide (1z). According to
NMR (400 MHz, CDCl3) δ 7.86 (d, J = 7.4 Hz, 1H), 7.60 – 7.33 (m, 8H), the general procedure B. White solid (0.97 g, 76%). M.p. = 127-
7.22 (dd, J = 14.5, 6.7 Hz, 2H), 7.10 (d, J = 7.8 Hz, 2H), 7.04 (t, J = 7.3 129 °C. 1H NMR (400 MHz, CDCl3) δ 7.50 – 7.18 (m, 5H), 7.13 – 7.05
Hz, 1H), 6.98 (s, 1H). 13C NMR (100 MHz, CDCl3) δ 167.2, 140.0, (m, 3H), 6.89 -6.70 (m, 2H), 3.76 (s, 3H), 2.96 (t, J = 7.2 Hz, 2H), 2.60
139.6, 137.6, 135.3, 130.7, 130.4, 129.6, 129.0, 128.9, 128.1, 127.9, (t, J = 7.2 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ 170.7, 158.1, 137.8,
124.4, 120.0. HRMS (ESI): calcd. for C19H16NO [M + H]+ 274.1226; 132.7, 129.4, 128.9, 124.3, 120.0, 114.0, 55.3, 39.7, 30.7. HRMS
found 274.1232. Rf 0.4 (Petroleum ether/EtOAc, 5/1).
N-(4-chlorophenyl)-[1,1'-biphenyl]-2-carboxamide
(ESI): calcd. for C16H18NO2 [M + H]+ 256.1332; found 256.1335. Rf
(1s). 0.4 (Petroleum ether/EtOAc, 5/1).
According to the general procedure B. White solid (1.3 g, 86%). M.p.
3-(4-((tert-butyldimethylsilyl)oxy)phenyl)-N-
= 160-162 °C.1H NMR (400 MHz, CDCl3) δ 7.67 (dd, J = 7.6, 1.1 Hz, phenylpropanamide (1aa). According to the general procedure B.
1
1H), 7.35 (td, J = 7.5, 1.4 Hz, 1H), 7.31 – 7.16 (m, 7H), 7.02 – 6.89 (m, White solid (1.6 g, 89%). M.p. = 117-119 °C. H NMR (400 MHz,
2H), 6.90 – 6.80 (m, 2H), 6.71 (s, 1H). 13C NMR (101 MHz, CDCl3) δ CDCl3) δ 7.41 (d, J = 7.8 Hz, 2H), 7.28 (dd, J = 13.1, 5.1 Hz, 2H), 7.08
167.1, 139.8, 139.5, 136.1, 134.9, 130.9, 130.3, 129.6, 129.3, 129.0, (d, J = 7.4 Hz, 4H), 6.76 (d, J = 8.2 Hz, 2H), 2.97 (t, J = 7.5 Hz, 2H),
128.8, 128.2, 128.0, 121.0. HRMS (ESI): calcd. for C19H15ClNO [M + 2.61 (t, J = 7.5 Hz, 2H), 0.97 (s, 9H), 0.18 (s, 6H). 13C NMR (100 MHz,
H]+ 308.0837; found 308.0835. Rf 0.2 (Petroleum ether/EtOAc, 5/1). CDCl3) δ 154.9, 138.4, 133.9, 130.0, 129.7, 125.0, 120.9, 120.6, 40.5,
N-(p-tolyl)-[1,1'-biphenyl]-2-carboxamide (1t). According to the 31.6, 26.4, 18.9, 3.7. HRMS (ESI): calcd. for C21H30NO2Si [M + H]+
general procedure B. White solid (1.25 g, 87%). M.p. = 136- 256.2040; found 256.2042. Rf 0.4 (Petroleum ether/EtOAc, 5/1).
138 °C.1H NMR (400 MHz, CDCl3) δ 8.12 (d, J = 7.6 Hz, 1H), 7.82 –
N-benzyl-3-(4-((tert-butyldimethylsilyl)oxy)phenyl)propanamide
7.60 (m, 8H), 7.25 (q, J = 8.4 Hz, 4H), 7.10 (s, 1H), 2.51 (s, 3H). 13C (1ab). According to the general procedure B. White solid (1.6 g,
1
NMR (101 MHz, CDCl3) δ 167.0, 140.0, 139.5, 135.4, 134.9, 134.0, 85%). M.p. = 80-82 °C. H NMR (400 MHz, CDCl3) δ 7.36 – 7.28 (m,
130.6, 130.3, 129.5, 129.3, 128.9, 128.8, 128.0, 127.9, 120.0, 20.8. 3H), 7.19 (d, J = 7.1 Hz, 2H), 7.07 (d, J = 8.3 Hz, 2H), 6.77 (d, J = 8.3
HRMS (ESI): calcd. for C20H18NO [M + H]+ 288.1383; found 288.1382. Hz, 2H), 5.63 (s, 1H), 4.42 (d, J = 5.6 Hz, 2H), 2.95 (t, J = 7.5 Hz, 2H),
Rf 0.2 (Petroleum ether/EtOAc, 5/1).
2.50 (t, J = 7.6 Hz, 2H), 1.01 (s, 9H), 0.21 (s, 6H). 13C NMR (100 MHz,
N-methoxy-[1,1'-biphenyl]-2-carboxamide (1u). According to the CDCl3) δ 172.1, 154.1, 138.2, 133.4, 129.3, 128.7, 127.8, 127.5,
1
general procedure B. White solid (1.1 g, 83%). M.p. = 99-101 °C. H 120.1, 43.6, 38.8, 31.0, 25.7, 18.2, 4.4. HRMS (ESI): calcd. for
NMR (400 MHz, CDCl3) δ 8.08 – 7.85 (m, 1H), 7.63 (s, 1H), 7.51 (t, J = C22H32NO2Si [M + H]+ 370.2197; found .370.2200. Rf 0.2 (Petroleum
7.5 Hz, 1H), 7.45 – 7.36 (m, 7H), 3.51 (s, 3H).13C NMR (100 MHz, ether/EtOAc, 5/1).
CDCl3) δ 167.5, 140.0, 139.7, 132.3, 130.8, 130.1, 129.2, 128.8,
128.7 ,128.1, 127.7, 63.9. HRMS (ESI): calcd. for C14H14NO2 [M + H]+ phenylpropanamide (1ac). According to the general procedure B.
228.1019; found 228.1021. Rf 0.3 (Petroleum ether/EtOAc, 3/1).
Yellow oil (1.4 g, 80%). 1H NMR (400 MHz, CDCl3) δ 7.42 (d, J = 8.0
3-(2-((tert-butyldimethylsilyl)oxy)phenyl)-N-
N-benzyl-[1,1'-biphenyl]-2-carboxamide (1v). According to the Hz, 2H), 7.32 – 7.21 (m, 3H), 7.11 (ddd, J = 24.7, 16.2, 7.4 Hz, 3H),
1
general procedure B. White solid (1.2 g, 83%). M.p. = 96-98 °C. H 6.87 (t, J = 7.1 Hz, 1H), 6.81 (d, J = 8.0 Hz, 1H), 3.00 (t, J = 7.6 Hz, 2H),
NMR (400 MHz, CDCl3) δ 7.76 (d, J = 7.5 Hz, 1H), 7.59 – 7.30 (m, 8H), 2.63 (t, J = 7.6 Hz, 2H), 1.02 (s, 9H), 0.24 (s, 6H). 13C NMR (100 MHz,
7.25 (dd, J = 14.1, 11.9 Hz, 3H), 7.01 – 6.77 (m, 2H),5.51 (s, 1H), 4.36 CDCl3) δ 170.8, 153.6, 137.9, 131.1, 130.5, 128.9, 127.6, 124.2,
(d, J = 5.5 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ 169.4, 140.3, 139.5, 121.5, 120.0, 118.7, 37.8, 26.7, 25.9, 18.3, 4.1. HRMS (ESI): calcd.
137.5, 135.6, 130.20, 130.1, 128.9, 128.8 128.7, 128.6, 127.8, 127.7, for C21H30NO2Si [M + H]+ 356.2040; found 356.2044. Rf 0.3
127.4, 44.2. HRMS (ESI): calcd. for C20H18NO [M + H]+ 288.1383; (Petroleum ether/EtOAc, 5/1).
found 288.1388. Rf 0.42 (Petroleum ether/EtOAc, 5/1).
N-benzyl-3-(2-((tert-butyldimethylsilyl)oxy)phenyl)propanamide
N-phenyl-3-(o-tolyl)propanamide (1w). According to the general (1ad). According to the general procedure B. Yellow oil (1.3 g, 72%).
1
procedure B. White solid (1.0 g, 84%). M.p. = 96-98 °C.1H H NMR 1H NMR (400 MHz, CDCl3) δ 7.31 – 7.21 (m, 3H), 7.12 (dt, J = 15.5,
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Journal Name
6.6 Hz, 4H), 6.87 (t, J = 7.3 Hz, 1H), 6.77 (d, J = 8.0 Hz, 1H), 5.69 (s, 3.21 – 2.99 (m, 2H), 2.89 – 2.73 (m, 2H), 1.36 (s, 9H).V1i3eCw ANrtMiclRe O(n1l0in1e
1H), 4.39 (d, J = 5.6 Hz, 2H), 2.96 (t, J = 7.6 Hz, 2H), 2.51 (t, J = 7.6 Hz, MHz, CDCl ) δ 170.2, 150.9, 141.8, 135.6, 128.3, 127.7, 127.1, 126.8,
DOI: 10.1039/C9OB01277J
3
2H), 0.99 (s, 9H), 0.22 (s, 6H). 13C NMR (100 MHz, CDCl3) δ 172.2, 125.6, 122.8, 117.1, 34.7, 32.3, 31.4, 25.6. HRMS (ESI): calcd. for
153.5, 138.3, 131.2, 130.5, 128.6, 127.7, 127.4, 121.4, 118.6, 43.5, C19H22NO [M + H]+ 280.1696; found 280.1698. Rf 0.2 (Petroleum
36.8, 26.8, 25.8, 18.2, 4.1. HRMS (ESI): calcd. for C21H32NO2Si [M + ether/EtOAc, 5/1).
H]+ 370.2197; found 370.2201. Rf 0.22 (Petroleum ether/EtOAc,
5/1).
General experimental procedure for 2.
1-(4-methoxyphenyl)-3,4-dihydroquinolin-2(1H)-one (2g). White
solid (29.4 mg 46%). M.p. = 160-162 °C. 1H NMR (400 MHz, CDCl3) δ
7.26 - 7.22 (m, 1H), 7.18 - 7.14 (m, 2H), 7.10 – 6.95 (m, 4H), 6.42 (d,
A mixture of amide 1 (0.25 mmol, 1.0 equiv), NIS (169 mg, 0.75 J = 8.0 Hz, 1H), 3.88 (s, 3H), 3.13 – 3.04 (m, 2H), 2.89 – 2.80 (m, 2H).
mmol, 3 equiv) in 1,2-dichloroethane (2 mL) in pressure tube 13C NMR (101 MHz, CDCl3) δ 170.5, 159.1, 141.9, 130.9, 129.9, 127.7,
(purged with Ar) was heated at 110 oC for 10 hours. Upon 127.1, 125.5, 122.8, 116.9, 115.1, 55.4, 32.2, 25.6. HRMS (ESI): calcd.
completion, the reaction mixture was cooled to room temperature. for C16H16NO2 [M + H]+ 254.1176; found 254.1177. Rf 0.2
The reaction mixture was diluted with 30 mL dichloromethane and (Petroleum ether/EtOAc, 5/1).
then treated with saturated aqueous Na2S2O3 solution. Aqueous
1-(m-tolyl)-3,4-dihydroquinolin-2(1H)-one (2h). White solid (45.6
1
phase was extracted with dichloromethane twice. Combined mg, 77%). M.p. = 62-63 °C. H NMR (400 MHz, CDCl3) δ 7.39 (t, J =
organic phases were dried with Na2SO4. The solvents were removed 7.6 Hz, 1H), 7.24 – 7.18 (m, 2H), 7.03 (d, J = 8.5 Hz, 3H), 6.98 (t, J =
under reduced pressure and the resulting mixture was purified by 7.2 Hz, 1H), 6.37 (d, J = 7.9 Hz, 1H), 3.11 – 3.01 (m, 2H), 2.87 – 2.77
flash column chromatography (silica gel, hexane/EtOAc 5/1).
(m, 2H), 2.39 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 170.2, 141.7,
1-phenyl-3,4-dihydroquinolin-2(1H)-one (2a). White solid (47.9 139.9, 138.3, 129.6, 129.6, 129.5, 127.7, 127.1, 125.9, 125.6, 122.9,
mg, 86%). M.p. = 227-229 °C. 1H NMR (400 MHz, CDCl3) δ 7.50 (t, J = 117.0, 32.2, 25.7, 21.4. HRMS (ESI): calcd. for C16H16NO [M + H]+
7.6 Hz, 2H), 7.42 (t, J = 7.4 Hz, 1H), 7.29-7.15 (m, 3H), 7.05 – 6.95 (m, 238.1226; found 238.1231.
2H), 6.35 (d, J = 7.9 Hz, 1H), 3.19 – 3.00 (m, 2H), 2.82 (m, 2H). 13C
1-(3-nitrophenyl)-3,4-dihydroquinolin-2(1H)-one (2i). Yellow oil
NMR (100 MHz, CDCl3) δ 170.2, 141.7, 138.5, 129.9, 129.1, 128.2, (46.2 mg, 68%). 1H NMR (400 MHz, CDCl3) δ 8.32 (d, J = 7.3 Hz, 1H),
127.8, 127.2, 125.7, 123.0, 117.1, 32.3, 25.7. HRMS (ESI): calcd. for 8.19 (d, J = 1.9 Hz, 1H), 7.85 – 7.55(m, 2H), 7.31 – 7.26 (m, 1H), 7.09
C15H14NO [M + H]+ 224.1070; found 224.1077.
(p, J = 7.3 Hz, 1H), 6.35 (d, J = 7.5 Hz, 1H), 3.13 (t, J = 7.1 Hz, 2H),
1-(p-tolyl)-3,4-dihydroquinolin-2(1H)-one (2b). White solid (51.5 2.88 (t, J = 7.1 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ 170.2, 149.2,
1
mg, 87%). M.p. = 144-146 °C. H NMR (400 MHz, CDCl3) δ 7.31 (d, J 140.8, 139.7, 135.6, 130.6, 128.2, 127.4, 126.1, 124.6, 123.7, 123.0,
= 8.0 Hz, 2H), 7.21 (d, J = 7.1 Hz, 1H), 7.12 (d, J = 8.2 Hz, 2H), 7.01 – 116.8, 32.1, 25.5. HRMS (ESI): calcd. for C15H13N2O3 [M + H]+
6.99 (m, 1H), 6.96 (td, J = 7.4, 1.0 Hz, 1H), 6.39 (d, J = 8.0 Hz, 1H), 269.0921; found 269.0919. Rf 0.2 (Petroleum ether/EtOAc, 5/1).
3.07 – 2.97 (m, 2H), 2.89-2.77 (m, 2H), 2.42 (s, 3H). 13C NMR (100
1-(o-tolyl)-3,4-dihydroquinolin-2(1H)-one (2j). White solid (41.5
1
MHz, CDCl3) δ 170.3, 141.8, 138.1, 135.7, 130.6, 128.7, 127.8, 127.1, mg, 70%). M.p. = 84-86 °C. H NMR (400 MHz, CDCl3) δ 7.39 – 7.29
125.6, 122.9, 117.0, 32.3, 25.7, 21.3. HRMS (ESI): calcd. for (m, 3H), 7.25 – 7.20 (m, 1H), 7.14 (d, J = 6.6 Hz, 1H), 7.01 (dd, J =
C16H16NO [M + H]+ 238.1226; found 238.1230.
13.2, 7.5 Hz, 2H), 6.24 (d, J = 7.9 Hz, 1H), 3.08 (t, J = 7.4 Hz, 2H), 2.84
1-(4-bromophenyl)-3,4-dihydroquinolin-2(1H)-one (2c). White (t, J = 7.2 Hz, 2H), 2.08 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 169.8,
solid (62.7 mg, 83%). M.p. = 194-196 °C. 1H NMR (400 MHz, CDCl3) δ 140.8, 137.1, 136.5, 131.4, 129.2, 128.7, 127.8, 127.5, 127.3, 125.4,
7.66 – 7.55 (m, 2H), 7.21 (d, J = 7.2 Hz, 1H), 7.15 – 7.10 (m, 2H), 7.08 122.9, 116.2, 32.0, 25.7, 17.4. HRMS (ESI): calcd. for C16H16NO [M +
– 7.04 (m, 1H), 7.02 – 6.98 (m, 1H), 6.37 (d, J = 8.0 Hz, 1H), 3.13 – H]+ 238.1226; found 238.1229.
2.97 (m, 2H), 2.86 – 2.78 (m, 2H). 13C NMR (100 MHz, CDCl3) δ 170.2,
1-(3,5-dichlorophenyl)-3,4-dihydroquinolin-2(1H)-one
(1k).
141.3, 137.5, 133.1, 130.8, 128.0, 127.3, 125.8, 123.3, 122.1, 116.9, Colorless oil (61.4 mg 83%). 1H NMR (400 MHz, CDCl3) δ 7.42 (s, 1H),
32.2, 25.6. HRMS (ESI): calcd. for C15H13BrNO [M + H]+ 302.0175; 7.24 – 7.15 (m, 3H), 7.10 (t, J = 7.6 Hz, 1H), 7.03 (t, J = 7.3 Hz, 1H),
found 302.0176.
6.38 (d, J = 8.0 Hz, 1H), 3.06 (t, J = 7.2 Hz, 2H), 2.86 – 2.68 (m, 2H).
1-(4-fluorophenyl)-3,4-dihydroquinolin-2(1H)-one (2d). White 13C NMR (101 MHz, CDCl3) δ 170.0, 140.8, 140.3, 135.8, 128.6, 128.0,
solid (51.8 mg, 86%). M.p. = 124-126 °C. 1H NMR (400 MHz, CDCl3) δ 128.0, 127.4, 125.8, 123.6, 116.9, 32.1, 25.5. HRMS (ESI): calcd. for
7.26 – 7.13 (m, 5H), 7.09 – 7.03 (m, 1H), 7.02 – 6.95 (m, 1H), 6.35 (d, C19H13ClNO [M + H]+ 292.0290; found 292.0287. Rf 0.2 (Petroleum
J = 8.0 Hz, 1H), 3.11 – 3.01 (m, 2H), 2.87 – 2.77 (m, 2H); 13C NMR ether/EtOAc, 5/1).
(100 MHz, CDCl3) δ170.3, 162.08 (d, J = 247.6 Hz), 141.5, 134.2 (d, J
3,4-dihydroquinolin-2(1H)-one (2l). White solid (10.5 mg, 33%).
= 3.1 Hz), 130.7 (d, J = 8.6 Hz), 127.9, 127.2, 125.7, 123.1, 116.90 (d, M.p. = 165-166 °C. 1H NMR (400 MHz, CDCl3) δ 9.35 (s, 1H), 7.17 (t, J
J = 11.2 Hz), 116.7, 32.2, 25.6. HRMS (ESI): calcd. for C15H13FNO [M + = 8.9 Hz, 2H), 6.98 (t, J = 7.4 Hz, 1H), 6.86 (d, J = 7.8 Hz, 1H), 2.97 (t,
H]+ 242.0976; found 242.0975.
J = 7.6 Hz, 2H), 2.65 (t, J = 7.6 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ
(2e). 172.4, 137.3, 127.9, 127.5, 123.6, 123.1, 115.6, 30.7, 25.3. HRMS
1-([1,1'-biphenyl]-4-yl)-3,4-dihydroquinolin-2(1H)-one
White solid (62.9 mg, 84%). M.p. = 174-176 °C. 1H NMR (400 MHz, (ESI): calcd. for C9H10NO [M + H]+ 148.0757; found 148.0757.
CDCl3) δ 7.74 – 7.69 (m, 2H), 7.65 – 7.59 (m, 2H), 7.46 (t, J = 7.6 Hz,
1-methyl-3,4-dihydroquinolin-2(1H)-one (2m). Yellow oil (20.6
2H), 7.37 (t, J = 7.3 Hz, 1H), 7.31 (d, J = 8.3 Hz, 2H), 7.22 (d, J = 7.3 mg, 51%). 1H NMR (400 MHz, CDCl3) δ 7.26 (ddd, J = 9.0, 7.2, 1.5 Hz,
Hz, 1H), 7.11 – 7.03 (m, 1H), 7.00 (dd, J = 7.3, 6.4 Hz, 1H), 6.46 (d, J = 1H), 7.17 (d, J = 6.7 Hz, 1H), 7.08 – 6.90 (m, 2H), 3.36 (s, 3H), 2.94 –
8.0 Hz, 1H), 3.12 – 3.06 (m, 2H), 2.89 – 2.82 (m, 2H); 13C NMR (100 2.87 (m, 2H), 2.69 – 2.62 (m, 2H).;13C NMR (100 MHz, CDCl3) δ 170.5,
MHz, CDCl3) δ 170.3, 141.6, 141.1, 140.3, 137.6, 129.3, 128.8, 128.6, 140.6, 127.7, 127.4, 126.2, 122.8, 114.7, 31.7, 29.5, 25.4. HRMS
127.8, 127.6, 127.3, 127.2, 125.8, 123.1, 117.1, 32.3, 25.7. HRMS (ESI): calcd. for C10H12NO [M + H]+ 162.0913; found 162.0915.
(ESI): calcd. for C21H18NO [M + H]+ 300.1383; found 300.1388.
1-(4-(tert-butyl)phenyl)-3,4-dihydroquinolin-2(1H)-one
1-benzyl-3,4-dihydroquinolin-2(1H)-one (2n). White solid (46.2
(2f). mg, 78%). M.p. = 56-57 °C. 1H NMR (400 MHz, CDCl3) δ 7.29 (dd, J =
Colorless oil (58.4 mg 83%). 1H NMR (400 MHz, CDCl3) δ 7.53 – 7.47 9.9, 5.0 Hz, 2H), 7.22 (dd, J = 12.3, 6.4 Hz, 3H), 7.16 (d, J = 7.3 Hz,
(m, 2H), 7.20 (d, J = 7.3 Hz, 1H), 7.17 – 7.11 (m, 2H), 7.04 (td, J = 7.9, 1H), 7.10 (dd, J = 11.2, 4.4 Hz, 1H), 6.99 – 6.93 (m, 1H), 6.86 (d, J =
1.6 Hz, 1H), 6.97 (td, J = 7.4, 1.2 Hz, 1H), 6.38 (dd, J = 8.0, 0.8 Hz, 1H), 8.1 Hz, 1H), 5.18 (s, 2H), 3.03 – 2.90 (m, 2H), 2.80-2.77 (m, 2H); 13C
6 | J. Name., 2012, 00, 1-3
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Organic & Biomolecular Chemistry
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NMR (100 MHz, CDCl3) δ 170.6, 139.9, 137.0, 128.8, 127.8, 127.4, NMR (100 MHz, CDCl3) δ 157.3, 135.8, 133.0, 132.7, 130.0, 128.5,
127.1, 126.4, 122.9, 115.6, 46.2, 31.9, 25.6. HRMS (ESI): calcd. for 128.1, 126.3, 123.2, 122.0, 118.6, 112.6, 62.7. HRMS (VEiSewI):ArctaicllecdO.nflioner
DOI: 10.1039/C9OB01277J
C16H16NO [M + H]+ 238.1226; found 238.1228.
tert-butyl 4-(2-oxo-3,4-dihydroquinolin-1(2H)-yl)piperidine-1-
C14H12NO [M + H]+ 226.0863; found 226.0859.
5-benzylphenanthridin-6(5H)-one (2v). White solid (61 mg, 85%).
1
1
carboxylate (2o). yellow oil (57.0 mg, 69%). H NMR (400 MHz, M.p. = 128-129 °C. H NMR (400 MHz, CDCl3) δ 8.62 (d, J = 7.8 Hz,
CDCl3) δ 7.24 – 7.14 (m, 2H), 7.12-7.10 (m, 1H), 7.03-6.99 (m, 1H), 1H), 8.27 (t, J = 7.6 Hz, 2H), 7.77 (t, J = 7.5 Hz, 1H), 7.61 (t, J = 7.4 Hz,
4.38-4.26 (m, 3H), 2.88 – 2.73 (m, 4H), 2.59-2.51 (m, 4H), 1.73-1.70 1H), 7.42 – 7.34 (m, 1H), 7.30-7.22 (m, 7H), 5.66 (s, 2H). 13C NMR
(m, 1H), 1.49 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 171.6, 154.7, (100 MHz, CDCl3) δ 161.9, 137.4, 136.6, 133.9, 132.7, 129.6, 129.2,
140.3, 128.7, 127.8, 127.1, 123.2, 116.5, 79.7, 55.8, 33.6, 28.9, 28.5, 128.8, 128.1, 127.2, 126.6, 125.5, 123.3, 122.6, 121.7, 119.5, 116.1,
25.8. HRMS (ESI): calcd. for C19H27N2O3 [M + Na]+ 353.1836; found 46.5. HRMS (ESI): calcd. for C20H16NO [M + H]+ 286.1226; found
353.1835.
286.1224.
1,3-diphenyl-3,4-dihydroquinolin-2(1H)-one (2p). White solid
5-methyl-1-phenyl-3,4-dihydroquinolin-2(1H)-one (2w). White
1
1
(66.6 mg, 89%). M.p. = 86-87 °C. H NMR (400 MHz, CDCl3) δ 7.48 solid (30.8 mg, 52%). M.p. = 97-99 °C. H NMR (400 MHz, CDCl3) δ
(dd, J = 11.5, 4.2 Hz, 2H), 7.39 (t, J = 7.4 Hz, 1H), 7.31 – 7.18 (m, 8H), 7.39 – 7.31 (m, 2H), 7.25-7.22 (m, 3H), 7.10 (d, J = 7.2 Hz, 1H), 7.00
7.04 (td, J = 7.6, 1.1 Hz, 1H), 6.98 (dd, J = 10.5, 4.2 Hz, 1H), 6.38 (d, J (t, J = 7.4 Hz, 1H), 6.94 (d, J = 7.3 Hz, 1H), 3.02 – 2.93 (m, 2H), 2.78 –
= 8.0 Hz, 1H), 4.10 – 4.00 (m, 1H), 3.42 – 3.33 (m, 2H); 13C NMR (100 2.69 (m, 2H), 1.59 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 171.9, 141.2,
MHz, CDCl3) δ 170.6, 141.4, 138.7, 138.1, 129.8, 129.0, 128.6, 128.1, 140.4, 131.5, 131.1, 129.5, 128.6, 127.2, 126.2, 125.1, 124.5, 33.9,
128.1, 127.3, 127.2, 124.8, 123.2, 117.0, 47.2, 33.1. HRMS (ESI): 26.6, 20.5. HRMS (ESI): calcd. for C16H16NO [M + H]+ 238.1226;
calcd. for C21H18NO [M + H]+ 300.1383; found 300.1383.
found 238.1226.
1,4-diphenyl-3,4-dihydroquinolin-2(1H)-one (2q). White solid
6-bromo-1-phenyl-3,4-dihydroquinolin-2(1H)-one (2x). White
(33.7 mg, 45%). M.p. = 145-146 °C. 1H NMR (400 MHz, CDCl3) δ 7.50 solid (37 mg, 49%). M.p. = 90-92 °C. H NMR (400 MHz, CDCl3) δ
(m, 2H), 7.44 – 7.34 (m, 3H), 7.31 – 7.17 (m, 5H), 7.11 – 7.05 (m, 1H), 7.53 (t, J = 7.6 Hz, 2H), 7.45 (t, J = 7.4 Hz, 1H), 7.21 (d, J = 7.4 Hz, 2H),
7.04 – 6.88 (m, 2H), 6.45 (m, 1H), 4.40 (t, J = 6.9 Hz, 1H), 3.24 – 3.06 7.11 (dd, J = 8.0, 1.6 Hz, 1H), 7.07 (d, J = 8.0 Hz, 1H). 6.48 (d, J = 1.4
(m, 2H); 13C NMR (100 MHz, CDCl3) δ 169.0, 141.5, 141.2, 138.4, Hz, 1H), 3.05 – 2.99 (m, 2H), 2.85 – 2.79 (m, 2H). 13C NMR (100 MHz,
129.9, 129.0, 128.9, 128.6, 128.3, 128.2, 127.8, 127.6, 127.3, 123.3, CDCl3) δ 169.9, 143.0, 137.8, 130.1, 129.1, 128.9, 128.6, 125.8,
117.4, 41.8, 39.4. HRMS (ESI): calcd. for C21H18NO [M + H]+ 300.1383; 124.5, 120.6, 119.9, 32.0, 25.3. HRMS (ESI): calcd. for C15H13BrNO
1
found 300.1386.
[M + H]+ 302.0175; found 302.0175.
N,N-diphenylcinnamamide (2q’). White solid (33.2 mg, 43%).
6-methyl-1-phenyl-3,4-dihydroquinolin-2(1H)-one (2y). White
1
1
M.p. = 152-154 °C. H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 15.5 Hz, solid (38 mg, 63%). M.p. = 107-109 °C. H NMR (400 MHz, CDCl3) δ
1H), 7.42 – 7.23 (m, 15H), 6.48 (d, J = 15.5 Hz, 1H); 13C NMR (100 7.53-7.49 (m, 2H), 7.44-7.41 (m, 1H), 7.28 – 7.20 (m, 2H), 7.10-7.08
MHz, CDCl3) δ 166.2, 142.8, 142.6, 135.1, 129.7, 129.3, 128.8, 128.0, (d, J = 7.5 Hz, 1H), 6.80 (d, J = 7.4 Hz, 1H), 6.16 (s, 1H), 3.02 (t, J = 7.2
119.8. HRMS (ESI): calcd. for C21H18NO [M + H]+ 300.1383; found Hz, 2H), 2.80 (t, J = 7.2 Hz, 2H), 2.15 (s, 3H). 13C NMR (100 MHz,
300.1388.
CDCl3) δ 170.4, 141.6, 138.5, 137.0, 129.8, 129.1, 128.2, 127.6,
5-phenylphenanthridin-6(5H)-one (2r). White solid (62.3 mg, 123.6, 122.7, 117.7, 32.5, 25.3, 21.3.HRMS (ESI): calcd. for C16H16NO
92%). M.p. = 227-229 °C. 1H NMR (400 MHz, CDCl3) δ 8.57 (d, J = 7.9 [M + H]+ 238.1226; found 238.1231.
Hz, 1H), 8.48 – 8.16 (m, 2H), 7.84-7.80 (m, 1H), 7.62 (t, J = 7.6 Hz,
8-methyl-1-phenyl-3,4-dihydroquinolin-2(1H)-one
(2y’).
1
3H), 7.54 (t, J = 7.4 Hz, 1H), 7.39 – 7.19 (m, 4H), 6.70 (dd, J = 6.6, 2.9 Colourless oil (11 mg, 18%). H NMR (400 MHz, CDCl3) δ 7.50 (t, J =
Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 161.7, 139.2, 138.3, 134.1, 7.5 Hz, 2H), 7.41 (t, J = 7.1 Hz, 1H), 7.22 (d, J = 7.6 Hz, 2H), 6.93 (t, J
132.8, 130.2, 129.1, 129.0, 128.8, 128.1, 125.9, 123.0, 122.7, 121.8, = 7.8 Hz, 1H), 6.87 (d, J = 7.4 Hz, 1H), 6.21 (d, J = 7.9 Hz, 1H), 3.02 (t,
119.0, 117.1. HRMS (ESI): calcd. for C19H14NO [M + H]+ 272.1070; J = 7.3 Hz, 2H), 2.81 (t, J = 7.3 Hz, 2H), 2.35 (s, 3H). 13C NMR (100
found 272.1076.
MHz, CDCl3) δ 170.1, 141.8, 138.8, 135.6, 129.8, 129.1, 128.1, 126.6,
5-(4-chlorophenyl)phenanthridin-6(5H)-one (1s). Colorless oil 124.9, 124.3, 115.3, 31.8, 21.9, 19.6. HRMS (ESI): calcd. for
(65.7 mg 86%). 1H NMR (400 MHz, CDCl3) δ 8.54 (dd, J = 8.0, 1.1 Hz, C16H16NO [M + H]+ 238.1226; found 238.1227.
1H), 8.43 – 8.16 (m, 2H), 7.94 – 7.76 (m, 1H), 7.67 – 7.52 (m, 3H),
1-phenyl-1-azaspiro[4.5]deca-6,9-diene-2,8-dione (2aa). White
7.42 – 7.11 (m, 4H), 6.82 – 6.54 (m, 1H). 13C NMR (101 MHz, CDCl3) solid (52 mg, 87%). M.p. = 148-150 °C. H NMR (400 MHz, CDCl3) δ
δ 161.7, 138.9, 136.7, 134.7, 134.0, 133.0, 130.6, 130.5, 129.2, 7.37 – 7.22 (m, 3H), 7.17 (d, J = 7.4 Hz, 2H), 6.99 (d, J = 10.1 Hz, 2H),
129.0, 128.2, 125.6, 123.1, 122.9, 121.8, 119.1, 116.8. HRMS (ESI): 6.26 (d, J = 10.0 Hz, 2H), 2.78 (t, J = 8.0 Hz, 2H), 2.33 (t, J = 8.0 Hz,
calcd. for C19H13ClNO [M + H]+ 306.0680; found 306.0680. Rf 0.2 2H). 13C NMR (100 MHz, CDCl3) δ 184.3, 174.0, 149.8, 136.3, 129.8,
1
(Petroleum ether/EtOAc, 5/1).
5-(p-tolyl)phenanthridin-6(5H)-one (1t). Colorless oil (57.6 mg C15H14NO2 [M + H]+ 240.1019; found 240.1021.
80%). 1H NMR (400 MHz, CDCl3) δ 8.60 (dd, J = 8.0, 1.0 Hz, 1H), 8.43
1-benzyl-1-azaspiro[4.5]deca-6,9-diene-2,8-dione (2ab). Yellow
129.2, 127.8, 126.1, 63.9, 31.7, 29.8. HRMS (ESI): calcd. for
1
– 8.27 (m, 2H), 7.84 (ddd, J = 8.3, 7.2, 1.4 Hz, 1H), 7.70 – 7.56 (m, oil (52.6 mg, 83%). H NMR (400 MHz, CDCl3) δ 7.25 (d, J = 4.0 Hz,
1H), 7.44 (d, J = 7.9 Hz, 2H), 7.37 – 7.29 (m, 2H), 7.24 (d, J = 8.2 Hz, 3H), 7.20 – 7.12 (m, 2H), 6.56 (d, J = 9.9 Hz, 2H), 6.16 (d, J = 9.9 Hz,
2H), 6.81 – 6.71 (m, 1H), 2.51 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 2H), 4.32 (s, 2H), 2.66 (t, J = 8.1 Hz, 2H), 2.15 (t, J = 8.0 Hz, 2H); 13C
161.8, 139.3, 138.7, 135.5, 134.0, 132.8, 130.9, 129.0, 128.7, 128.1, NMR (100 MHz, CDCl3) δ 184.5, 174.6, 149.2, 137.5, 129.7, 128.7,
125.9, 122.9, 122.6, 121.7, 119.0, 117.1, 21.3. HRMS (ESI): calcd. for 128.5, 127.8, 62.3, 44.8, 30.3, 29.2. HRMS (ESI): calcd. for C16H16NO2
C20H16NO [M + H]+ 286.1226; found 286.1226. Rf 0.2 (Petroleum [M + H]+ 254.1176; found 254.1179.
ether/EtOAc, 5/1).
1-phenyl-1-azaspiro[4.5]deca-7,9-diene-2,6-dione (2ac). White
1
5-methoxyphenanthridin-6(5H)-one (2u). White solid (26 mg, solid (42.9 mg, 80%). M.p. = 123-124 °C. H NMR (400 MHz, CDCl3)
47%). M.p. = 95-97 °C. 1H NMR (400 MHz, CDCl3) δ 8.56 (dd, J = 8.0, δ 7.32 – 7.25 (m, 2H), 7.20 – 7.02 (m, 4H), 6.38 (dd, J = 9.5, 1.0 Hz,
1.1 Hz, 1H), 8.31 – 8.23 (m, 2H), 7.81 – 7.74 (m, 1H), 7.68 (dd, J = 8.3, 1H), 6.31 – 6.27 (m, 1H), 6.21 (d, J = 9.8 Hz, 1H), 2.91 – 2.82 (m, 1H),
1.0 Hz, 1H), 7.63 – 7.55 (m, 2H), 7.39 – 7.32 (m, 1H), 4.14 (s, 3H). 13
C
2.62 – 2.55 (m, 1H), 2.33 – 2.27 (m, 1H), 2.14 – 2.05 (m, 1H); 13C
This journal is © The Royal Society of Chemistry 20xx
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Organic & Biomolecular Chemistry
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Journal Name
NMR (100 MHz, CDCl3) δ 199.9, 174.9, 143.7, 141.7, 137.2, 128.9,
126.2, 125.3, 123.6, 123.2, 72.2, 29.3, 28.4. HRMS (ESI): calcd. for
C15H14NO2 [M + H]+ 240.1019; found 240.1022.
M. Guan, Y. Pang, J. Zhang and Y. Zhao, Chem. Commun., 2016,
View Article Online
52, 7043-7046. (e) N. He, Y. Huo, J. Liu, YD. HOuI:a1n0g.1,0S3.9Z/Ch9aOngB0a1n2d77QJ.
Cai, Org. Lett., 2015, 17, 374–377. (f) A. Correa, S. Elmore and C.
Bolm, Chem. Eur. J., 2008, 14, 3527–3529.
1-benzyl-1-azaspiro[4.5]deca-7,9-diene-2,6-dione (2ad). Yellow
oil (50.0 mg, 79%). 1H NMR (400 MHz, CDCl3) δ 7.23 – 7.16 (m, 3H),
6.95 – 6.90 (m, 1H), 6.10 – 5.95 (m, 2H), 4.65 (d, J = 14.8 Hz, 1H),
3.96 (d, J = 14.8 Hz, 1H), 2.77 – 2.67 (m, 1H), 2.53 – 2.45 (m, 1H),
2.19 – 2.11 (m, 1H), 1.94 – 1.85 (m, 1H). 13C NMR (100 MHz, CDCl3)
δ 200.8, 176.2, 143.1, 141.0, 136.8, 129.1, 128.3, 127.7, 125.2,
122.5, 70.7, 45.9, 29.4, 28.0. HRMS (ESI): calcd. for C16H16NO2 [M +
H]+ 254.1176; found 254.1181.
4
5
(a) M. E. Wolff, Chem. Rev., 1963, 63, 55–64. (b) R. S. Neale,
Synthesis, 1971, 1–15. (c) P. Mackiewicz and R. Furstoss,
Tetrahedron, 1978, 34, 3241–3260. (d) S. C. Cosgrove, J. M. C.
Plane and S. P. Marsden, Chem. Sci., 2018, 9, 6647–6652. (e) A.
Moroda, S. Furuyama and H. Togo, Synlett, 2009, 1336-1340.
(a) L. R. Reddy, B. V. S. Reddy and E. J. Corey, Org. Lett., 2006, 8,
2819–2821. (b) R. Fan, D. Pu, F. Wen and J. Wu, J. Org. Chem.,
2007, 72, 8994–8997. (c) K. Chen, J. M. Richter and P. S. Baran,
J. Am. Chem. Soc., 2008, 130, 7247–7249. (d) K. Chen and P. S.
Baran, Nature, 2009, 459, 824–828. (e) T. Liu, T. Mei and J.-Q.
Yu, J. Am. Chem. Soc., 2015, 137, 5871–5874. (e) X. Mou, X.
Chen, G. Chen and G. He, Chem. Commun., 2018, 54, 515–518.
(a) H. Togo, Y. Hoshina and M. Yokoyama, Tetrahedron Lett.,
1996, 37, 6129–6132. (b) H. Togo, Y. Hoshina, T. Muraki, H.
Nakayama and M. Yokoyama, J. Org. Chem., 1998, 63, 5193–
5200. (c) Y. Ma, M. Cheng and S.-D. Yang, Org. Lett., 2017, 19,
600–603.
(a) T. Zhou, F. Luo, M. Yang and Z.-J. Shi, J. Am. Chem. Soc.,
2015, 137, 14586–14589. (b) W. Shu, A. Genoux, Z. Li and C.
Nevado, Angew. Chem. Int. Ed., 2017, 56, 10521–10524. (c) N.
Wang, Q. S. Gu, Z. Li, Z. Li, Y. Guo, Z. Guo and X.-Y. Liu, Angew.
Chem. Int. Ed., 2018, 57, 14225–14229.
(a) N. A. Braun, M. A. Ciufolini, K. Peters and E.-M. Peters,
Tetrahedron Lett., 1998, 39, 4667–4670. (b) N. A. Braun, M.
Ousmer, J. D. Bray, D. Bouchu, K. Peters, E.-M. Peters and M. A.
Ciufolini, J. Org. Chem., 2000, 65, 4397–4408. (c) D. J. Wardrop
and A. Basak, Org. Lett., 2001, 3, 1053–1056. (d) M. Ousmer, N.
A. Braun, C. Bavoux, M. Perrin and M. A. Ciufolini, J. Am. Chem.
Soc., 2001, 123, 7534–7538. (e) M. Ousmer, N. A. Braun and M.
A. Ciufolini, Org. Lett., 2001, 3, 765–767.
phenanthridin-6(5H)-one (3)11b. White solid (42.8 mg, 87%).
White solid,1H NMR (300 MHz; DMSO) δ 11.70 (s, 1H), 8.51 (d, J =
8.1 Hz, 1H), 8.45−8.25 (m, 2H), 7.91−7.82 (m, 1H), 7.78−7.65 (m,
1H), 7.53-7.46 (m, 1H), 7.43-7.36 (m, 1H), 7.32-7.18 (m, 1H); 13C
NMR (75 MHz; DMSO) δ 161.3, 137.0, 134.7, 133.3, 130.0, 128.4,
127.9, 126.2, 123.7, 123.0, 122.7, 118.0, 116.6.
6
7
8
Conflicts of interest
There are no conflicts to declare.
Acknowledgements
We are grateful to the National Key Research and Development
Program of China (2018YFD0200100) and the National Natural
Science Foundation of China (21732002, 21672117) for generous
financial support for our programs.
Notes and references
1
(a) M.-H. Chen, P. Fitzgerald, S. B. Singh, E. A. O’Neill, C. D.
Schwartz, C. M. Thompson, S. J. O’Keefe, D. M. Zaller and J. B.
Doherty, Bioorg. Med. Chem. Lett., 2008, 18, 2222–2226. (b) J.
M. Singer, B. M. Barr, L. L. Coughenour, T. F. Gregory and M. A.
Walters, Bioorg. Med. Chem. Lett., 2005, 15, 4560–4563. (c) Y.
Oshiro, Y. Sakurai, S. Sato, N. Kurahashi, T. Tanaka, T. Kikuchi, K.
Tottori, Y. Uwahodo, T. Miwa and T. Nishi, J. Med. Chem. 2000,
43, 177–189. (d) H. Zhao, A. Thurkauf, J. Braun, R. Brodbeck and
A. Kieltyka, Bioorg. Med. Chem. Lett., 2000, 10, 2119–2122. (e)
Y. S. Tamura, A. E. Goldman, W. P. Bergum and E. J. Semple,
Bioorg. Med. Chem. Let., 1999, 9, 2573–2578. (f) R. L. Dow, T. T.
Chou, B. M. Bechle, C. Goddard and E. R. Larson, J. Med. Chem.,
1994, 37, 2224–2231. (g) H. Ogawa, Y. Yamamura, H. Miyamoto,
K. Hondo, H. Yamashita, K. Nakaya, T. Chibara, T. Mori, M.
Tominaga and Y. Yabuuchi, J. Med. Chem., 1993, 36, 2011–2017.
(h) M. E. Wall, M. C. Wani and H. Taylor, J. Nat. Prod., 1987, 50,
1095-1099. (i) K. Nakagawa, N. Murakami, S. Yoshizaki, M.
Tominaga, H. Mori, Y. Yabuuchi and S. Shintani, J. Med. Chem.,
1974, 17, 529–533.
9
(a) D. J. Wardrop, M. S. Burge, W. Zhang and J. A. Ortı́z,
Tetrahedron Lett., 2003, 44, 2587–2591. (b) Y. Amano and S.
Nishiyama, Tetrahedron Lett., 2006, 47, 6505–6507. (c) T. Dohi,
A. Maruyama, Y. Minamitsuji, N. Takenagaa and Y. Kita, Chem.
Commun., 2007, 1224–1226. (d) T. Dohi, N. Takenaga, K.
Fukushima, T. Uchiyama, D. Kato, S. Motoo, H. Fujiokab and Y.
Kita, Chem. Commun., 2010, 7697–7699. (e) A. Maity, S. Hyun
and D. C. Powers, Nat. Chem., 2018, 10, 200–204.
10 CCDC 1906915 (2w) contains supplementary crystallographic
data for this paper. These data can be obtained free of charge
from the Cambridge Crystallographic Data Centre.
11 (a) F. Rombouts, D. Franken, C. Martínez-Lamenca, M. Braeken,
C. Zavattaro, J. Chen and A. A. Trabanco, Tetrahedron Lett.,
2010, 51, 4815-4818. (b) R. Bernini, S. Cacchi, G. Fabrizi and A.
Sferrazza, Synthesis, 2008, 5, 729-738.
2
3
(a) J. R. Beck, R. Kwok, R. N. Booher, A. C. Brown, L. E. Patterson,
P. Pranc, B. Rockey and A. Pohland, J. Am. Chem. Soc., 1968, 90,
4706–4710. (b) Y. Torisawa, T. Nishi and J. Minamikawa, Bioorg.
Med. Chem. Lett., 2007, 17, 448–452. (c) Y. Kikugawa, A.
Nagashima, T. Sakamoto, E. Miyazawa and M. Shiiya, J. Org.
Chem., 2003, 68, 6739–6744. (d) M. Cherest and X. Lusinchi,
Tetrahedron Lett., 1989, 30, 715–718.
(a) B. H. Yang and S. L. Buchwald, Org. Lett., 1999, 1, 35–38. (b)
T. Tsuritani, Y. Yamamoto, M. Kawasaki and T. Mase, Org. Lett.,
2009, 11, 1043–1045. (c) H. Xiao, W. Wang, Y. Sun, H. Luo, B. Li,
X. Wang, W. Lin and F. Luo, Org. Lett., 2019, 21, 1668–1671. (d)
8 | J. Name., 2012, 00, 1-3
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