Bronsted acid catalyzed and NIS-promoted cyclization of diynones: Selective synthesis of 4-pyrone, 4-pyridone, and 3-pyrrolone derivatives

Article abstract of DOI:10.1021/jo402055a

Bronsted acid catalyzed tandem cyclization was found to be highly effective for the preparation of a series of polysubstituted 4-pyrones from diynones (yield up to 99%). 4-Pyridone and 3-pyrrolone derivatives were also selectively synthesized by employing NIS and/or Bronsted acid. NIS as an electrophilic reagent could promote these reactions efficiently and rapidly under very mild reaction conditions.

Full text of DOI:10.1021/jo402055a

Article
pubs.acs.org/joc
Brønsted Acid Catalyzed and NIS-Promoted Cyclization of Diynones:
Selective Synthesis of 4‑Pyrone, 4‑Pyridone, and 3‑Pyrrolone
Derivatives
Yi-Feng Qiu,† Fang Yang,† Zi-Hang Qiu,† Mei-Jin Zhong,† Li-Jing Wang,† Yu-Ying Ye,† Bo Song,†
and Yong-Min Liang*,†,‡
†State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, People’s Republic of China
‡State Key Laboratory of Solid Lubrication, Lanzhou Institute of Chemical Physics, Chinese Academy of Science, Lanzhou 730000,
People’s Republic of China
S
* Supporting Information
ABSTRACT: Brønsted acid catalyzed tandem cyclization was
found to be highly effective for the preparation of a series of
polysubstituted 4-pyrones from diynones (yield up to 99%). 4-
Pyridone and 3-pyrrolone derivatives were also selectively
synthesized by employing NIS and/or Brønsted acid. NIS as
an electrophilic reagent could promote these reactions
efficiently and rapidly under very mild reaction conditions.
of these heterocyclic compounds with high efficiency warrants
further investigation.
INTRODUCTION
■
Five- and six-membered oxygen- or nitrogenated heterocycles,
such as 4-pyrone, 4-pyridone, and 3-pyrrolone, are greatly
valuable intermediates1 for the synthesis of pharmacologically
relevant therapeutic agents and biologically active natural
products.2 As the key structural subunit, 4-pyrone occurred
widely in lots of drug molecules, such as phenoxan,3a,b maltol,3c
and kojic acid.3d,e Meanwhile 4-pyridone and 3-pyrrolone
subunits are also found in many representative bioactive
molecules, such as aspernigrin A,4a iodopyridone,4b clopidol,4c
and vermelhotin.5 So far, various conventional methods have
been reported for the development of these skeletons. The well-
known synthetic routes to 4-pyrones are via the condensation
cyclization reaction of the carbonyl compounds,3b,6 while the
traditional methods for preparing 4-pyridones are involved in the
reaction of primary amines with 4-pyrones2l,m,3d,7 or 1,3,5-
triketones6a and the three-component hetero-Diels−Alder
reaction.8 Recently, the synthetic strategy via a N to C 1,3-acyl
migration of N-aryl acetoacetamides has been reported.9 The
oxidation of substituted pyrrolols,10 cyclization of carbonyl
compounds,1m,2n,11 and flash vacuum pyrolysis of N,N-
disubstituted aminomethylene Meldrum’s acid derivatives12 are
considered to be efficient methods for the synthesis of
polysubstituted 3-pyrrolones as well.13 However, there are still
some limitations for the development of these synthetic methods
due to the expensive transition-metal catalysts6d,8,11c,13 and not
readily available substrates.7,8b,10−12 Therefore, a new environ-
mentally friendly (metal free) synthetic strategy for the synthesis
It is known that diynones are symmetric molecules with
multiple reaction sites, which lead to diverse types of interesting
cyclization products. Previously, our group has reported
Brønsted acid catalyzed highly regioselective cycloisomerization
of 5,2-enyn-1-ones to prepare various 4-pyranones,14a as well as
Brønsted acid catalyzed and iodine-promoted tandem cyclization
of the similar substrates to selectively synthesize highly
substituted benzene derivatives.14b (Scheme 1) Thus, we
designed Brønsted acid catalyzed and NIS-promoted C−O and
C−N bond formations for the synthesis of 4-pyrone and 4-
pyridone derivatives by using diynones with an alcohol and an
amine as a nucleophile, respectively. In the process of exploring
the synthesis of 4-pyridone derivatives, an NIS-promoted
cyclization reaction for the synthesis of 3-pyrrolone derivatives
was discovered occasionally. Herein, different reaction systems
with diverse nucleophiles afforded various 4-pyrone, 4-pyridone,
and 3-pyrrolone derivatives are reported.
RESULTS AND DISCUSSION
■
Initially, we attempted to explore the designed reaction for the
synthesis of 4-pyrones by employing 1,5-diphenylpenta-1,4-diyn-
3-one 1a with p-TsOH (20 mol %) in methanol at 65 °C (Table
1, entry 1).14 After 24 h, we got 35% of the corresponding
product 2a and 32% of the substrate 1a was recovered.
Received: September 16, 2013
© XXXX American Chemical Society
A
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Scheme 1. Design of Proposed Cyclization of Ynones
entries 3−7). A variety of Lewis acids, such as FeCl3, HAuCl4·
4H2O, AuCl3, and (PPh3)AuNTf2, were also screened; however,
no superior yields were obtained (Table 1, entries 8−13). To
further optimize the conditions, we adjusted p-TsOH to 15 mol
%, and the yield increased to 93% after 14 h (Table 1, entry 14).
When the temperature was increased to 110 °C, 2a was isolated
in a yield of 99% after 8.5 h (Table 1, entry 17). Finally, with the
series of detailed attempts mentioned above, the use of p-TsOH
(15 mol %) in methanol (1.0 mL) at 110 °C was considered to be
the optimal reaction conditions for producing 2a (conditions A).
At the beginning, we used propylamine (1.1 equiv) as a
nucleophile in acetonitrile to try to perform our envisaged
reaction for the synthesis of 4-pyridones, with FeCl3 (20 mol %)
and HAuCl4·4H2O (20 mol %) as catalysts at room temperature,
respectively (Table 2, entries 1 and 2). However, only an
intermediate (Z)-1,5-diphenyl-1-(propylamino)pent-1-en-4-yn-
3-one 3a was obtained through Michael addition of 1a with
propylamine without further cyclization after 24 h. It even could
be isolated in a high yield of 96% without adding any catalysts
(Table 2, entry 3). After attempting a series of iodine-containing
reagents, we found that a new product (E)-4-iodo-2-(iodo-
(phenyl)methylene)-5-phenyl-1-propyl-1H-pyrrol-3(2H)-one
5a was formed with NIS (2.0 equiv) (Table 2, entries 4−7).
From the above, we believed that ferric chloride as a strong Lewis
acid may activate the carbonyl of the intermediate 3a, which
subsequently went through further cyclization in the presence of
iodine-containing reagents.14b,15 Therefore, ferric chloride (20
mol %) was added first, and then, NIS (2.0 equiv) was added after
1a completely converted to 3a (determined by TLC analysis).
Finally, we got 28% of the expected product 4a; meanwhile, 21%
of 5a and 15% of 1a were isolated (Table 2, entry 9). We
increased the amount of NIS to 3.0 equiv, and ferric chloride to 1
equiv. In this way, the reaction progressed to completion and the
selectivity was improved at the same time (Table 2, entry 11).
Then a series of Lewis acids and Brønsted acids as additives were
screened to improve the selectivity (Table 2, entries 12−17). As a
result, reaction with p-TsOH (1.0 equiv) gave the highest yield of
78% for 4a, and no 5a was detected by TLC analysis (Table 2,
entry 16). The optimal ratio of NIS and p-TsOH was finalized
after a series of adjustments (Table 2, entries 18−20).
Table 1. Optimization of Cascade Cyclization for the
Synthesis of 2a
a
entry
cat. (mol %)
p-TsOH (20)
temp. (°C) time (h) yield (%)
b
1
2
65
90
24
10
9
35
86
70
24
56
trace
72
67
78
84
80
p-TsOH (20)
TfOH (20)
3
90
4
TFA (20)
90
10.5
12
18
9
5
HCl (20)
90
c
6
4-chlorobenzoic acid (20)
90
d
7
MSA (20)
90
8
FeCl3
90
7
9
HAuCl4·4H2O
AuCl3
90
5
10
11
90
9
(PPh3)AuNTf2
I2
90
8
e
12
90
2
e
13
NIS
90
3
14
15
16
17
p-TsOH (15)
p-TsOH (10)
p-TsOH (15)
p-TsOH (15)
p-TsOH (15)
p-TsOH (15)
p-TsOH (15)
90
14
19
12
8.5
9
93
74
94
99
95
91
62
90
100
110
110
110
110
f
18
g
19
9
h
20
9
a
Reaction conditions: 1a (0.1 mmol) and MeOH (1.0 mL) in the
b
presence of Brønsted or Lewis acids. 32% of 1a was recovered, and
20% of intermediate A was isolated. 44% of 1a was recovered, and
c
d
40% of intermediate A was isolated. MSA = methylsulfonic acid.
e
f
g
Products cannot be detected. In ethanol. In MeOH (1.0 mL) with
h
H2O (1.0 equiv). In MeOH (1.0 mL) with H2O (10.0 equiv).
Therefore, we raised the temperature to 90 °C. Encouragingly,
86% of 2a was isolated, and no residual 1a was detected by TLC
analysis (Table 1, entry 2). Followed by this approach, after
attempting a series of different Brønsted acids, we found that p-
TsOH was proved to be the most efficient catalyst (Table 1,
B
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a
unsubstituted phenyl and aryl with weak electron-donating
groups (EDG) gave the satisfying yields (2a−2d, except 2e),
whereas aryl with electron-withdrawing groups (EWG) slightly
decreased the yields (2g−2j). Furthermore, substrates bearing
larger and more branched alkyl groups worked better for this
transformation (2f, 2k−2m). However, when R1 and R2 were
both a p-methoxyphenyl group, only a trace amount of 2t was
detected, whereas 66% of 2o was still obtained when one
substituent was replaced by phenyl. We believed that the strong
EDG increased the electron density and decreased the
electrophilicity of the carbon−carbon triple bond of the
substrate, which made it difficult for oxygen atom to attack.
When R1 was an aryl group, and R2 was a sterically hindered
group (1-naphthyl group; 1r) or a heterocyclic group (2-thienyl;
1s), the reaction still occurred smoothly and the yields of 64%
and 65% for their corresponding products were obtained.
Subsequently, we explored the scope of the NIS-promoted
selective synthesis of 4-pyridone derivatives under standard
conditions B, with the above substrates (shown in Table 3).
Notably, most of the substrates converted into the corresponding
4-pyridone derivatives in moderate yields. The reaction was more
sensitive to substituent electronic effects than the p-TsOH-
catalyzed reaction mentioned above, but with the similar rules.
Substrates with alkyl groups gave lower yields (4f), even trace
yields of the products (4k−4m). For aryl and cyclopropyl
groups, the enamine tautomer with a more nucleophile nitrogen
is more stable due to conjugation of these groups with the alkene.
For alkyl groups, formation of a less nucleophilic imine tautomer
is consistent with the observed results. However, the substrate
contained a sterically hindered group, the 1-naphthyl group, 1r,
which gave the much lower yield than phenyl, indicating that the
steric effect played a major role in this transformation. When R2
was a tert-butyl group, 29% yield of 4p was obtained and a trace of
4q was detected by MS.
Table 2. Optimization of Cyclization for the Synthesis of 4a
and 5a
b
yield (%)
entry
cat. (equiv)
FeCl3 (0.2)
additive (equiv)
4a
5a
1
2
HAuCl4·4H2O (0.2)
c
3
d
4
I2 (2)
d
5
IBr (2)
d
6
ICl (2)
e
7
NIS (2)
I2 (2)
trace
49
e
8
FeCl3 (0.2)
f
9
NIS (2)
NIS (3)
NIS (3)
NIS (3)
NIS (3)
NIS (3)
NIS (3)
NIS (3)
NIS (3)
NIS (3)
NIS (2.8)
NIS (2.5)
NIS (2.5)
NIS (2.8)
NIS (3.0)
FeCl3 (0.2)
28
33
56
trace
45
22
26
78
74
80
81
63
0
21
45
22
53
33
49
51
0
10
11
12
13
14
15
16
17
18
19
20
21
22
23
FeCl3 (0.2)
FeCl3 (1.0)
Sc(OTf)3 (1.0)
AlCl3 (1.0)
BF3·Et2O (1.0)
TfOH (1.0)
p-TsOH (1.0)
TFA (1.0)
trace
0
p-TsOH (1.2)
p-TsOH (1.2)
p-TsOH (1.2)
0
0
Next, we tested the substrate tolerance of NIS-promoted
selective synthesis of 3-pyrrolone derivatives under conditions C.
Various symmetrical diynones proceeded smoothly to afford the
corresponding products in moderate yields. The electronic effect
and steric effect of the substituents were similar to the NIS-
promoted synthesis of 4-pyridone derivatives. The selective
addition of propylamine with asymmetrical diynones would lead
to different 3-pyrrolones. Then we chose substrates 1n and 1p to
study the regioselectivity of the reaction of amines and the alkyne
moiety. We found that nucleophiles tended to attack the
carbon−carbon triple with EWG; the yields of 5na and 5pb were
better than 5nb and 5pa, respectively.
69
82
80
0
0
a
Reaction conditions: 1a (0.1 mmol) and propylamine (1.1 mmol) in
the presence of Brønsted or Lewis acids in MeCN (1.0 mL) at room
temperature; NIS was added after 1a completely converted to 3a.
Reaction conditions: 1a (0.1 mmol) and propylamine (1.1 mmol) in
the presence of NIS in MeCN (1.0 mL) at room temperature. 96% of
intermediate 3a was isolated. Products cannot be detected. 20% of
intermediate 3a was recovered. 15% of intermediate 3a was recovered.
b
c
d
e
f
To explore the scope of NIS promoting the synthesis of 4-
pyridone and 3-pyrrolone derivatives for the amines and
electrophilic reagents, we also investigated different amines and
electrophilic reagents under conditions B and C, respectively
(Scheme 2). Aliphatic amines could react with good yields,
whereas the aromatic amine only gave a trace yield. We believe,
due to that the lone pair electrons of nitrogen atoms in
arylamines made conjugation with aryl groups, the nucleophil-
icity of arylamines was weaker than aliphatic amines. Therefore, a
37% yield of intermediate 3ad from aniline was obtained. The
structure of 4ab was confirmed by X-ray crystal structure analysis
(see the Supporting Information).
An obvious feature of our method is that the iodosubstituted 4-
pyridones and 3-pyrrolones generated by NIS-promoted
cyclization can be the advantageous intermediates for the
synthesis of some natural products by using various palladium-
catalyzed reactions.16 For example, the Suzuki coupling17 of 4a,
Meanwhile, the best conditions to generate 5a were also settled
by modifying the dose of NIS (Table 2, entries 21−23).
Ultimately, the optimal conditions for generating 4a were
identified as propylamine (1.1 equiv) and p-TsOH (1.2 equiv) in
MeCN (1.0 mL); NIS (2.8 equiv) was added after the full
conversion of 1a at room temperature (conditions B). The best
conditions for generating 5a were propylamine (1.1 equiv) in
MeCN with NIS (2.8 equiv) at room temperature (conditions
C).
A series of symmetrical and asymmetrical diynones (1b−1m,
1t, and 1n−1s) were prepared to investigate the scope of the p-
TsOH-catalyzed electrophilic cyclization reaction. The corre-
sponding substituted 4-pyrone derivatives 2a−2s were obtained
in moderate to good yields under conditions A (Table 3). The
structure of 2a was confirmed by X-ray crystal structure analysis
(see the Supporting Information). The influences of substituent
electronic effects on the reaction were shown as the following:
C
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a
Table 3. Synthesis of 4-Pyrone Derivatives 2, 4-Pyridone Derivatives 4, and 3-Pyrrolone Derivatives 5 from Diynones 1
yield (%)
entry
substrate (R1)
substrate (R2)
2
4
5
1
2
Ph
Ph
99 (2a)
99 (2b)
84 (2c)
81 (2d)
55 (2e)
83 (2f)
84 (2g)
60 (2h)
88 (2i)
61 (2j)
99 (2k)
76 (2l)
64 (2m)
93 (2n)
66 (2o)
70 (2p)
78 (2q)
64 (2r)
65 (2s)
trace (2t)
81 (4a)
90 (4b)
85 (4c)
76 (4d)
55 (4e)
45 (4f)
81 (4g)
63 (4h)
90 (4i)
35 (4j)
trace (4k)
82 (5a)
93 (5b)
82 (5c)
79 (5d)
58 (5e)
46 (5f)
79 (5g)
51 (5h)
86 (5i)
42 (5j)
trace (5k)
m-MeC6H4
p-MeC6H4
p-EtC6H4
p-(n-PrC6H4)
cyclopropyl
o-FC6H4
m-FC6H4
p-FC6H4
p-ClC6H4
tert-butyl
n-Pr
m-MeC6H4
p-MeC6H4
p-EtC6H4
p-(n-PrC6H4)
cyclopropyl
o-FC6H4
m-FC6H4
p-FC6H4
p-ClC6H4
tert-butyl
n-Pr
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
c
c
c
c
trace (4l)
trace (5l)
c
c
n-pentyl
m-MeC6H4
Ph
n-pentyl
trace (4m)
67 (4n)
40 (4o)
29 (4p)
trace (5m)
o-FC6H4
p-OMeC6H4
n-Pr
Ph
d
p-MeC6H4
p-MeC6H4
Ph
tert-butyl
1-naphthyl
2-thienyl
p-OMeC6H4
trace (4q)
39 (4r)
46 (4s)
b
b
b
p-OMeC6H4
trace (4t)
trace (5t)
a
Conditions A for 2: the reaction was carried out by using 1 (0.1 mmol) and p-TsOH (15 mol %) in methanol (1.0 mL) at 110 °C. Conditions B for
4: the reaction was carried out by using 1 (0.1 mmol) and propylamine (1.1 equiv) with p-TsOH (1.2 equiv) in acetonitrile (1.0 mL) at room
temperature. NIS (2.8 equiv) was added after 1 converted into 3 completely (detected by TLC analysis). Conditions C for 5: the reaction was
b
carried out by using 1 (0.1 mmol) and propylamine (1.1 equiv) with NIS (2.8 equiv) in acetonitrile (1.0 mL) at room temperature. Decomposed.
c
d
Over 50% of intermediate 3 could be obtained without adding NIS. 52% of (Z)-6,6-dimethyl-1-(propylamino)-1-(p-tolyl)hept-1-en-4-yn-3-one
1
and 43% of (Z)-6,6-dimethyl-5-(propylamino)-1-(p-tolyl)hept-4-en-1-yn-3-one were obtained without adding NIS (distinguished by H NMR and
H−H COSY).
4b, and 5ab afforded the corresponding products 6a, 6b, and 6ab
in good yields, respectively (Scheme 3).
carbon−carbon triple bond of B affords C, which undergoes
demethylation to produce 4-pyrones 2.
On the basis of the above observations and the isolation of
intermediate A,18a,19 a possible reaction mechanism for the
synthesis of 2 is proposed, as depicted in Scheme 4. Brønsted acid
activates the carbonyl, followed by methanol attacks the carbon−
carbon triple bond and via keto−enol tautomerization14
generates intermediate A. Upon heating, A undergoes
subsequent conversion to B by the configuration turning. Once
again, attack of the intramolecular methoxyl group onto the
On the basis of the study about the intermediate 3,18b,c we
propose the following plausible mechanisms for the formation of
4 and 5. Amines as nucleophiles react via Michael addition with 1
to form intermediate 3. The electrophile (iodine cation) attacks
the carbon−carbon triple bond (or double bond) of 3 to afford
iodonium ion D (or H). After an intramolecular nucleophilic
attack and the attack of the second iodine cation on the double
bond (or triple bond), G (or I) formed rapidly. Again, the
D
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intramolecular nitrogen atom onto the carbon−carbon triple
bond of the other side affords F, which undergoes the second
attack by the iodine cation released by NIS to generate 4-
pyridone 4.20
Scheme 2. Influence of Different Amines and Electrophilic
Reagents for the Synthesis of 4 and 5
CONCLUSION
■
In summary, we have reported a Brønsted acid catalyzed direct
and efficient protocol for preparing polysubstituted 4-pyrone
derivatives and NIS-promoted selective synthesis of 4-pyridone
and 3-pyrrolone derivatives from diynones. For different
nucleophiles, different catalysts were employed to facilitate
cyclization. Some of the 4-pyrones can be obtained in very high
yields up to 99%. As an electrophilic reagent, NIS promotes the
cyclization of diynones rapidly with high capacity and selectivity
under considerably gentle reaction conditions (at room
temperature). In addition, these reactions provide a metal-free
and straightforward route for C−O and C−N bond formation,
and the position of cyclization can be selected by adding
Brønsted acid, which is more environmentally friendly and
efficient compared to traditional synthesis methods.
Scheme 3. Palladium-Catalyzed Suzuki Coupling Reaction
EXPERIMENTAL SECTION
General Procedure A: Synthesis of 1a−1m, 1t.
■
For the synthesis of 1a: To a stirred solution of phenylacetylene (A; 1.76
mL, 16.0 mmol) in dry THF (30 mL) under argon was added n-BuLi
(6.72 mL, 16.8 mmol, 2.5 M solution in hexane) via a syringe at 0 °C.
The mixture was allowed to stir for 15 min at 0 °C. Then methyl formate
(0.49 mL, 8 mmol) was added. The mixture was allowed to stir for an
additional 5 min at 0 °C, and then for 2 h at room temperature. The
mixture was poured into an aqueous saturated solution of NH4Cl, and
the product was extracted with ether. The combined organic layers were
washed with a saturated aqueous sodium chloride solution, dried over
Na2SO4, and filtered, and the solvents were removed under reduced
pressure. The residue was purified by flash column chromatography
(silica gel, PE/EA = 10/1) to give 1,5-diphenylpenta-1,4-diyn-3-ol B
(85%).
nitrogen atom attacks the iodonium ion, which generates J,
which subsequently afforded 3-pyrrolone 5 via proton capture.20
The proton from the Brønsted acid activates the carbonyl
oxygen atom of D, which gives complex E. An endo attack of the
Scheme 4. Proposed Mechanisms
E
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MnO2 (75 mmol, 15 equiv) was added to a solution of 1,5-
diphenylpenta-1,4-diyn-3-ol (B; 5 mmol) in CH2Cl2 (15 mL) at room
temperature. The resulting mixture was stirred overnight. Then the solid
was filtered, and the solvents were removed under reduced pressure.
The residue was purified by flash column chromatography (silica gel,
PE/EA = 50/1) to give 1,5-diphenylpenta-1,4-diyn-3-one 1a (82%).
General Procedure B: Synthesis of 1n−1s.
determined by TLC analysis, the reaction mixture was diluted with
ethyl ether (30 mL), washed with 5% of an aqueous solution of
potassium hydroxide and saturated brine, dried over Na2SO4, and
evaporated under reduced pressure. The residue was purified by
chromatography on silica gel to afford the product (E)-4-iodo-2-
(iodo(phenyl)methylene)-5-phenyl-1-propyl-1H-pyrrol-3(2H)-one 5a.
The reaction and after-treatment procedures should be away from light.
General Procedure F: Synthesis of 6. For the synthesis of 6a: To a
solution of 3,5-diiodo-2,6-diphenyl-1-propylpyridin-4(1H)-one 4a
(0.20 mmol) in DMF (1.0 mL) with H2O (0.25 mL) under argon
were sequentially added 2 mol % of Pd(OAc)2, 3.0 equiv of K2CO3, and
PhB(OH)2. Then the reaction mixture was allowed to stir at 40 °C for 12
h. The reaction mixture was diluted with ethyl ether (30 mL), washed
with saturated brine twice, dried over Na2SO4, and evaporated under
reduced pressure. The residue was purified by chromatography on silica
gel to afford the product 2,3,5,6-tetraphenyl-1-propylpyridin-4(1H)-one
6a.
Characterization Data of 2a−2s. 2,6-Diphenyl-4H-pyran-4-one
(2a). Yield 99%; 24.6 mg; white solid; 1H NMR (400 MHz, CDCl3) δ
ppm 7.87−7.85 (m, 4H), 7.54−7.53 (m, 6H), 6.82 (s, 2H); 13C NMR
(100 MHz, CDCl3) δ ppm 180.2, 163.3, 131.5, 131.4, 129.1, 125.9,
111.4; IR (neat, cm−1) 3059, 2924, 1647, 1614, 1604, 1493, 1449, 1390,
945, 772, 685; HRMS (ESI) calcd for C17H12O2 ([M + H]+) =
249.0910; found, 249.0913.
2,6-Di-m-tolyl-4H-pyran-4-one (2b). Yield 99%; 27.3 mg; light
yellow solid; 1H NMR (400 MHz, CDCl3) δ ppm 7.67−7.63 (m, 4H),
7.42 (t, J = 7.6 Hz, 2H), 7.34 (d, J = 7.6 Hz, 2H), 6.78 (s, 2H), 2.46 (s,
6H); 13C NMR (100 MHz, CDCl3) δ ppm 180.2, 163.5, 138.9, 132.1,
131.5, 129.0, 126.5, 123.1, 111.3, 21.5; IR (neat, cm−1) 3062, 2922,
1644, 1611, 1484, 1427, 1384, 1262, 924, 784, 693, 423; HRMS (ESI)
calcd for C19H16O2 ([M + H]+) = 277.1223; found, 277.1228.
2,6-Di-p-tolyl-4H-pyran-4-one (2c). Yield 84%; 23.3 mg; white
solid; 1H NMR (400 MHz, CDCl3) δ ppm 7.74 (d, J = 8.0 Hz, 4H), 7.32
(d, J = 7.6 Hz, 4H), 6.76 (s, 2H), 2.44 (s, 6H); 13C NMR (100 MHz,
CDCl3) δ ppm 180.3, 163.4, 141.9, 129.8, 128.7, 125.8, 110.6, 21.5; IR
(neat, cm−1) 3065, 2920, 1646, 1607, 1569, 1508, 1414, 1384, 942, 818,
716, 637, 528, 482; HRMS (ESI) calcd for C19H16O2 ([M + H]+) =
277.1223; found, 277.1229.
For the synthesis of 1o: To a stirred solution of iodobenzene (C; 2.04 g,
10 mmol) in triethylamine (20 mL) under argon were sequentially
added Pd(PPh3)2Cl2 (105.3 mg, 0.15 mmol) and CuI (57.1 mg, 0.3
mmol) at room temperature. The mixture was allowed to stir for 10 min.
Then prop-2-yn-1-ol (0.62 g, 11 mmol) was added. The mixture was
allowed to stir overnight. The mixture was poured into an aqueous
saturated solution of NH4Cl, and the product was extracted with ether.
The combined organic layers were washed with a saturated aqueous
sodium chloride solution, dried over Na2SO4, and filtered, and the
solvents were removed under reduced pressure. The residue was
purified by flash column chromatography (silica gel, PE/EA = 4/1) to
give the 3-phenylprop-2-yn-1-ol D (99%).
D used the same procedure as general procedure A to give 3-
phenylpropiolaldehyde E (90%) (silica gel, PE/EA = 10/1).
To a stirred solution of 1-ethynyl-4-methoxybenzene (1.06 g, 8
mmol) in dry THF (30 mL) under argon was added n-BuLi (3.36 mL,
8.4 mmol, 2.5 M solution in hexane) via a syringe at 0 °C. The mixture
was allowed to stir for 15 min at 0 °C. Then 3-phenylpropiolaldehyde
(E; 1.04 g, 8 mmol) was added. The mixture was allowed to stir for an
additional 5 min at 0 °C, and then for 2 h at room temperature. It was
then poured into aqueous saturated NH4Cl solution and extracted with
ether. The combined organic layers were washed with a saturated
aqueous sodium chloride solution, dried over Na2SO4, and filtered, and
the solvents were removed under reduced pressure. The residue was
purified by flash column chromatography (silica gel, PE/EA = 5/1) to
give 1-(4-methoxyphenyl)-5-phenylpenta-1,4-diyn-3-ol F (85%).
F used the same procedure as general procedure A to give 1-(4-
methoxyphenyl)-5-phenylpenta-1,4-diyn-3-one 1o (80%) (silica gel,
PE/EA = 50/1).
General Procedure C: Synthesis of 2. For the synthesis of 2a: To a
solution of 1,5-diphenylpenta-1,4-diyn-3-one 1a (0.10 mmol) in MeOH
(1.0 mL) was added 15 mol % of p-TsOH. The resulting mixture was
stirred at 110 °C in a sealed tube. When the reaction was considered
complete, as determined by TLC analysis, the reaction mixture was
diluted with ethyl ether (30 mL), washed with water and saturated brine,
dried over Na2SO4, and evaporated under reduced pressure. The residue
was purified by chromatography on silica gel to afford the product 2,6-
diphenyl-4H-pyran-4-one 2a.
General Procedure D: Synthesis of 4. For the synthesis of 4a: To
a solution of 1,5-diphenylpenta-1,4-diyn-3-one 1a (0.10 mmol) in
acetonitrile (1.0 mL) was sequentially added 1.1 equiv of propylamine
and 1.2 equiv of p-TsOH. The resulting mixture was stirred at room
temperature. NIS (2.8 equiv) was added after 1a converted into 3a
completely, detected by TLC analysis. When the reaction was
considered complete, as determined by TLC analysis, the reaction
mixture was diluted with ethyl ether (30 mL), washed with 5% of an
aqueous solution of potassium hydroxide and saturated brine, dried over
Na2SO4, and evaporated under reduced pressure. The residue was
purified by chromatography on silica gel to afford the product 3,5-
diiodo-2,6-diphenyl-1-propylpyridin-4(1H)-one 4a.
General Procedure E: Synthesis of 5. For the synthesis of 5a: To a
solution of 1,5-diphenylpenta-1,4-diyn-3-one 1a (0.10 mmol) in
acetonitrile (1.0 mL) were sequentially added 1.1 equiv of propylamine
and 2.8 equiv of NIS. The resulting mixture was stirred at room
temperature. When the reaction was considered complete, as
2,6-Bis(4-ethylphenyl)-4H-pyran-4-one (2d). Yield 81%; 24.6 mg;
1
white solid; H NMR (400 MHz, CDCl3) δ ppm 7.78 (d, J = 8.0 Hz,
4H), 7.35 (d, J = 8.4 Hz, 4H), 6.77 (s, 2H), 2.73 (q, J = 7.6 Hz, 4H), 1.29
(t, J = 7.6 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ ppm 180.4, 163.5,
148.2, 129.0, 128.6, 126.0, 110.7, 28.8, 15.2; IR (neat, cm−1) 3070, 2963,
2929, 1649, 1610, 1510, 1457, 1420, 1385, 1187, 1014, 945, 837, 643;
HRMS (ESI) calcd for C21H20O2 ([M + H]+) = 305.1536; found,
305.1536.
2,6-Bis(4-propylphenyl)-4H-pyran-4-one (2e). Yield 55%; 18.3 mg;
light yellow solid; 1H NMR (400 MHz, CDCl3) δ ppm 7.78 (d, J = 8.4
Hz, 4H), 7.33 (d, J = 8.4 Hz, 4H), 6.78 (s, 2H), 2.67 (t, J = 7.6 Hz, 4H),
1.74−1.65 (m, 4H), 0.97 (t, J = 7.6 Hz, 6H); 13C NMR (100 MHz,
CDCl3) δ ppm 180.4, 163.5, 146.6, 129.2, 129.0, 125.9, 110.7, 37.9, 24.3,
13.7; IR (neat, cm−1) 3212, 2957, 2927, 2864, 1651, 1609, 1508, 1460,
1419, 1381, 945, 839, 810, 646, 474; HRMS (ESI) calcd for C23H24O2
([M + H]+) = 333.1849; found, 333.1835.
2,6-Dicyclopropyl-4H-pyran-4-one (2f). Yield 83%; 14.6 mg; white
solid; 1H NMR (400 MHz, CDCl3) δ ppm 6.06 (s, 2H), 1.78−1.71 (m,
2H), 1.02−0.96 (m, 4H), 0.96−0.90 (m, 4H); 13C NMR (100 MHz,
CDCl3) δ ppm 179.4, 168.4, 111.1, 13.7, 7.7; IR (neat, cm−1) 3051,
2925, 2855, 1655, 1601, 1453, 1401, 1096, 1055, 862; HRMS (ESI)
calcd for C11H12O2 ([M + H]+) = 177.0910; found, 177.0904.
2,6-Bis(2-fluorophenyl)-4H-pyran-4-one (2g). Yield 84%; 23.9 mg;
light yellow solid; 1H NMR (400 MHz, CDCl3) δ ppm 7.84−7.80 (m,
2H), 7.54−7.49 (m, 2H), 7.34−7.30 (m, 2H), 7.23 (dd, J = 11.6 Hz 7.6
Hz, 2H), 6.92 (s, 2H); 13C NMR (100 MHz, CDCl3) δ ppm 179.9,
160.4 (d, J = 234 Hz, 1C), 159.1 (d, J = 16 Hz, 1C), 132.8 (d, J = 9 Hz,
1C), 128.7, 124.7 (d, J = 4 Hz, 1C), 119.8 (d, J = 10 Hz, 1C), 117.0 (d, J =
22 Hz, 1C), 115.9 (d, J = 11 Hz, 1C); IR (neat, cm−1) 3071, 2924, 1663,
1613, 1577, 1487, 1453, 1389, 1215, 945, 863, 756, 644; HRMS (ESI)
calcd for C17H10F2O2 ([M + H]+) = 285.0722; found, 285.0728.
F
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2,6-Bis(3-fluorophenyl)-4H-pyran-4-one (2h). Yield 60%; 17.0 mg;
white solid; H NMR (400 MHz, CDCl3) δ ppm 7.64 (d, J = 7.6 Hz,
2-(tert-Butyl)-6-(p-tolyl)-4H-pyran-4-one (2q). Yield 78%; 18.9 mg;
white solid; H NMR (400 MHz, CDCl3) δ ppm 7.66 (d, J = 8.0 Hz,
1
1
2H), 7.56−7.50 (m, 4H), 7.28−7.24 (m, 2H), 6.81 (s, 2H); 13C NMR
(100 MHz, CDCl3) δ ppm 179.7, 163.1 (d, J = 227 Hz, 1C), 161.9 (d, J =
17 Hz, 1C), 133.4 (d, J = 8 Hz, 1C), 130.5 (d, J = 8 Hz, 1C), 121.7 (d, J =
3 Hz, 1C), 118.5 (d, J = 21 Hz, 1C), 113.0 (d, J = 24 Hz, 1C), 112.2; IR
(neat, cm−1) 3084, 1658, 1586, 1490, 1438, 1395, 1276, 929, 870, 782,
689; HRMS (ESI) calcd for C17H10F2O2 ([M + H]+) = 285.0722; found,
285.0718.
2,6-Bis(4-fluorophenyl)-4H-pyran-4-one (2i). Yield 88%; 25.0 mg;
white solid; 1H NMR (400 MHz, CDCl3) δ ppm 7.86−7.83 (m, 4H),
7.26−7.21 (m, 4H), 6.75 (s, 2H); 13C NMR (100 MHz, CDCl3) δ ppm
179.8, 164.6 (d, J = 252 Hz, 1C), 162.3, 128.1 (d, J = 9 Hz, 1C), 127.6 (d,
J = 3 Hz, 1C), 116.4 (d, J = 22 Hz, 1C), 111.2; IR (neat, cm−1) 3068,
2922, 1667, 1601, 1505, 1415, 1379, 1238, 836, 778, 583; HRMS (ESI)
calcd for C17H10F2O2 ([M + H]+) = 285.0722; found, 285.0729.
2,6-Bis(4-chlorophenyl)-4H-pyran-4-one (2j). Yield 61%; 19.3 mg;
yellow solid; 1H NMR (400 MHz, CDCl3) δ ppm 7.77 (d, J = 8.8 Hz,
4H), 7.51 (d, J = 8.8 Hz, 4H), 6.79 (s, 2H); 13C NMR (100 MHz,
CDCl3) δ ppm 179.7, 162.3, 137.8, 129.7, 129.5, 127.2, 111.6; IR (neat,
cm−1) 3204, 3057, 1656, 1596, 1557, 1488, 1410, 1379, 1090, 830, 724,
666; HRMS (ESI) calcd for C17H10Cl2O2 ([M + H]+) = 317.0131;
found, 317.0125.
2,6-Di-tert-butyl-4H-pyran-4-one (2k). Yield 99%; 20.3 mg; white
solid; 1H NMR (400 MHz, CDCl3) δ ppm 6.14 (s, 2H), 1.29 (s, 18H);
13C NMR (100 MHz, CDCl3) δ ppm 181.4, 175.2, 109.4, 36.2, 27.7; IR
(neat, cm−1) 2969, 2873, 1659, 1614, 1491, 1464, 1399, 1371, 1259,
1101, 943, 867; HRMS (ESI) calcd for C13H20O2 ([M + H]+) =
209.1536; found, 209.1539.
2,6-Dipropyl-4H-pyran-4-one (2l). Yield 76%; 13.7 mg; colorless
liquid; 1H NMR (400 MHz, CDCl3) δ ppm 6.07 (s, 2H), 2.47 (t, J = 7.6
Hz, 4H), 1.73−1.63 (m, 4H), 0.99 (t, J = 7.6 Hz, 6H); 13C NMR (100
MHz, CDCl3) δ ppm 180.5, 168.9, 113.1, 35.4, 20.1, 13.4; IR (neat,
cm−1) 3461, 2964, 2875, 1665, 1619, 1461, 1398, 1148, 933, 864; HRMS
(ESI) calcd for C11H16O2 ([M + H]+) = 181.1223; found, 181.1222.
2,6-Dipentyl-4H-pyran-4-one (2m). Yield 64%; 15.1 mg; colorless
liquid; 1H NMR (400 MHz, CDCl3) δ ppm 6.06 (s, 2H), 2.48 (t, J = 7.6
Hz, 4H), 1.68−1.61 (m, 4H), 1.37−1.31 (m, 8H), 0.92−0.89 (m, 6H);
13C NMR (100 MHz, CDCl3) δ ppm 180.4, 169.1, 113.0, 33.4, 30.9,
26.3, 22.2, 13.8; IR (neat, cm−1) 2957, 2930, 2864, 1666, 1625, 1462,
1395, 1146, 928, 866; HRMS (ESI) calcd for C15H24O2 ([M + H]+) =
237.1849; found, 237.1853.
2-(2-Fluorophenyl)-6-(m-tolyl)-4H-pyran-4-one (2n). Yield 93%;
26.0 mg; yellow solid; 1H NMR (400 MHz, CDCl3) δ ppm 7.84−7.81
(m, 1H), 7.64 (d, J = 8.0 Hz, 2H), 7.51 (t, J = 6.4 Hz, 1H), 7.40 (t, J = 7.6
Hz, 1H), 7.33 (t, J = 7.6 Hz, 2H), 7.24−7.21 (m, 1H), 6.89 (d, J = 1.6 Hz,
1H), 6.80 (d, J = 1.2 Hz, 1H), 2.45 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ ppm 180.1, 162.7 (d, J = 236 Hz, 1C), 159.0, 159.0, 138.9,
132.7 (d, J = 9 Hz, 1C), 132.3, 131.3, 129.0, 128.8 (d, J = 1 Hz, 1C),
126.5, 124.7 (d, J = 4 Hz, 1C), 123.2, 120.0 (d, J = 11 Hz, 1C), 117.0 (d, J
= 22 Hz, 1C), 116.0 (d, J = 9 Hz, 1C), 111.3, 21.5; IR (neat, cm−1) 3066,
2923, 1648, 1614, 1489, 1453, 1384, 1215, 868, 764, 696; HRMS (ESI)
calcd for C18H13FO2 ([M + H]+) = 281.0972; found, 281.0983.
2-(4-Methoxyphenyl)-6-phenyl-4H-pyran-4-one (2o). Yield 66%;
18.4 mg; yellow solid; 1H NMR (400 MHz, CDCl3) δ ppm 7.86−7.80
(m, 4H), 7.54−7.52 (m, 3H), 7.03 (d, J = 8.8 Hz, 2H), 6.78 (d, J = 2.0
Hz, 1H), 6.73 (d, J = 2.0 Hz, 1H), 3.89 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ ppm 180.3, 163.4, 163.1, 162.2, 131.5, 131.3, 129.1, 127.6,
125.9, 123.7, 114.5, 111.2, 109.9, 55.5; IR (neat, cm−1) 3435, 3067,
2929, 2843, 1642, 1605, 1511, 1450, 1424, 1392, 1025, 836, 773, 690;
HRMS (ESI) calcd for C18H14O3 ([M + H]+) = 279.1016; found,
279.1012.
2H), 7.30 (d, J = 8.0 Hz, 2H), 6.67 (d, J = 1.6 Hz, 1H), 6.26 (d, J = 2.0
Hz, 1H), 2.42 (s, 3H), 1.36 (s, 9H); 13C NMR (100 MHz, CDCl3) δ
ppm 180.9, 175.2, 163.5, 141.8, 129.7, 128.8, 125.6, 110.3, 109.8, 36.3,
28.0, 21.4; IR (neat, cm−1) 2969, 2927, 1653, 1611, 1510, 1459, 1417,
1384, 1101, 945, 866, 822; HRMS (ESI) calcd for C16H18O2 ([M + H]+)
= 243.1380; found, 243.1388.
2-(Naphthalen-1-yl)-6-(p-tolyl)-4H-pyran-4-one (2r). Yield 64%;
20.0 mg; yellow solid; 1H NMR (400 MHz, CDCl3) δ ppm 8.14−8.12
(m, 1H), 8.03 (d, J = 8.4 Hz, 1H), 7.97−7.95 (m, 1H), 7.76−7.69 (m,
4H), 7.60−7.57 (m, 3H), 7.32 (d, J = 8.0 Hz, 1H), 6.90 (s, 1H), 6.69 (s,
1H), 2.40 (s, 3H); 13C NMR (100 MHz, CDCl3) δ ppm 180.2, 164.9,
164.1, 142.1, 133.8, 131.4, 130.4, 130.1, 129.8, 128.7, 128.4, 127.9, 127.5,
126.6, 125.8, 125.1, 124.7, 116.7, 110.5, 21.5; IR (neat, cm−1) 3059,
2923, 1650, 1610, 1509, 1452, 1413, 1383, 1245, 1187, 945, 866, 820,
776, 733, 645; HRMS (ESI) calcd for C22H16O2 ([M + H]+) =
313.1223; found, 313.1236.
2-Phenyl-6-(thiophen-2-yl)-4H-pyran-4-one (2s). Yield 65%; 16.5
mg; deep yellow solid; 1H NMR (400 MHz, CDCl3) δ ppm 7.83 (dd, J =
5.6 Hz 2.0 Hz, 2H), 7.65 (dd, J = 2.4 Hz 1.6 Hz, 1H), 7.56−7.52 (m,
4H), 7.19−7.17 (m, 1H), 6.76 (d, J = 1.6 Hz, 1H), 6.68 (d, J = 1.6 Hz,
1H); 13C NMR (100 MHz, CDCl3) δ ppm 179.7, 162.7, 158.9, 134.6,
131.4, 131.0, 129.7, 129.1, 128.4, 127.7, 125.8, 111.2, 109.7; IR (neat,
cm−1) 3059, 2928, 1643, 1616, 1496, 1450, 1424, 1397, 1258, 1078,
1048, 1000, 942, 899, 839, 768, 736, 685, 638; HRMS (ESI) calcd for
C15H10O2S ([M + H]+) = 255.0474; found, 255.0470.
Characterization Data of A. (E)-1-Methoxy-1,5-diphenylpent-1-
en-4-yn-3-one (A). Yield 20%; 5.2 mg; light yellow liquid; 201H NMR
(400 MHz, CDCl3) δ ppm 7.58−7.56 (m, 2H), 7.44−7.40 (m, 3H), 7.32
(t, J = 7.6 Hz, 1H), 7.24−7.20 (m, 2H), 7.09−7.07 (m, 2H), 5.82 (s,
1H), 3.88 (s, 3H); 13C NMR (100 MHz, CDCl3) δ ppm 176.5, 173.7,
134.6, 132.8, 130.7, 129.9, 128.1, 128.0, 127.9, 120.4, 105.6, 91.0, 88.7,
56.8; IR (neat, cm−1) 3057, 2930, 2193, 1591, 1561, 1490, 1441, 1364,
1225, 1126, 1089, 760, 692; HRMS (ESI) calcd for C18H14O2 ([M +
H]+) = 263.1067; found, 263.1065.
Characterization Data of 3a, 3ab, 3qa, and 3qb. (Z)-1,5-
Diphenyl-1-(propylamino)pent-1-en-4-yn-3-one (3a). Yield 96%;
1
27.8 mg; light yellow liquid; H NMR (400 MHz, CDCl3) δ ppm
7.52−7.51 (m, 2H), 7.44−7.42 (m, 3H), 7.37−7.29 (m, 5H), 5.39 (s,
1H), 3.16 (q, J = 6.8 Hz, 2H), 1.60−1.51 (m, 2H), 0.90 (t, J = 7.6 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ ppm 172.6, 166.9, 134.5, 132.3,
129.6, 129.2, 128.4, 128.2, 127.5, 121.5, 100.1, 89.9, 86.2, 46.5, 23.8,
11.0; IR (neat, cm−1) 3059, 2965, 2931, 2874, 2204, 1591, 1485, 1328,
1262, 1165, 1123, 1024, 1002, 919, 760, 696, 609, 525; HRMS (ESI)
calcd for C20H19NO ([M + H]+) = 290.1539; found, 290.1543.
(Z)-1-(Benzylamino)-1,5-diphenylpent-1-en-4-yn-3-one (3ab).
1
Yield 91%; 30.7 mg; light yellow solid; H NMR (400 MHz, CDCl3)
δ ppm 11.36 (s, 1H), 7.54−7.52 (m, 2H), 7.44−7.25 (m, 11H), 7.19 (d,
J = 7.2 Hz, 2H), 5.48 (m, 1H), 4.42 (d, J = 6.4 Hz, 2H); 13C NMR (100
MHz, CDCl3) δ ppm 173.3, 166.8, 137.9, 134.3, 132.4, 129.9, 129.4,
128.7, 128.5, 128.3, 127.6, 127.5, 126.7, 121.5, 100.8, 89.9, 86.7, 48.5; IR
(neat, cm−1) 2925, 2858, 2197, 1565, 1537, 1480, 1447, 1368, 1324,
1116, 1070, 919, 763, 693, 671, 476; HRMS (ESI) calcd for C24H19NO
([M + H]+) = 338.1539; found, 338.1551.
(Z)-6,6-Dimethyl-1-phenyl-1-(propylamino)hept-1-en-4-yn-3-one
(3qa). Yield 52%; 14.0 mg; yellow liquid; 1H NMR (400 MHz, CDCl3)
δ ppm 10.99 (s, 1H), 7.23 (s, 4H), 5.22 (s, 1H), 3.15 (q, J = 6.8 Hz, 2H),
2.39 (s, 3H), 1.57−1.48 (m, 2H), 1.25 (s, 9H), 0.89 (t, J = 7.2 Hz, 3H);
13C NMR (100 MHz, CDCl3) δ ppm 173.4, 166.5, 139.5, 131.8, 128.9,
127.4, 99.7, 96.1, 80.7, 46.3, 30.3, 27.4, 23.8, 21.2, 11.0; IR (neat, cm−1)
2967, 2928, 2862, 2206, 1593, 1563, 1496, 1452, 1324, 1254, 1137, 826,
772, 610, 489; HRMS (ESI) calcd for C18H23NO ([M + H]+) =
270.1852; found, 270.1855.
2-Phenyl-6-propyl-4H-pyran-4-one (2p). Yield 70%; 15.0 mg;
1
orange solid; H NMR (400 MHz, CDCl3) δ ppm 7.77−7.75 (m,
2H), 7.50−7.48 (m, 3H), 6.71 (d, J = 2.0 Hz, 1H), 6.19 (d, J = 2.4 Hz,
1H), 2.61 (t, J = 7.6 Hz, 2H), 1.83−1.74 (m, 2H), 1.04 (t, J = 7.6 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ ppm 180.3, 168.7, 163.4, 131.4,
131.2, 129.0, 125.7, 113.7, 110.8, 35.5, 20.2, 13.5; IR (neat, cm−1) 3065,
2963, 1659, 1617, 1493, 1451, 1395, 1160, 937, 866, 772, 691; HRMS
(ESI) calcd for C14H14O2 ([M + H]+) = 215.1067; found, 215.1072.
(Z)-6,6-Dimethyl-1-phenyl-5-(propylamino)hept-4-en-1-yn-3-one
(3qb). Yield 43%; 11.6 mg; yellow liquid; 1H NMR (400 MHz, CDCl3)
δ ppm 11.93 (s, 1H), 7.43 (d, J = 8.0 Hz, 2H), 7.20 (d, J = 8.0 Hz, 2H),
5.42 (s, 1H), 3.52−3.47 (m, 2H), 2.34 (s, 3H), 1.73−1.64 (m, 2H), 1.30
(s, 9H), 1.04 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ ppm
175.4, 172.1, 139.3, 132.2, 129.0, 118.6, 95.2, 89.8, 85.9, 47.4, 35.8, 28.8,
G
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23.6, 21.4, 11.2; IR (neat, cm−1) 2975, 2926, 2870, 2193, 1611, 1561,
1513, 1456, 1324, 1258, 1134, 908, 820, 725; HRMS (ESI) calcd for
C18H23NO ([M + H]+) = 270.1852; found, 270.1859.
249 Hz, 1C), 151.6, 139.5 (d, J = 8 Hz, 1C), 131.1 (d, J = 5 Hz, 1C),
124.7, 117.2 (d, J = 20 Hz, 1C), 116.2 (d, J = 23 Hz, 1C), 93.9, 56.3, 24.5,
10.5; IR (neat, cm−1) 2967, 2930, 1586, 1562, 1518, 1474, 1435, 1259,
1219, 788, 731, 692, 667; HRMS (ESI) calcd for C20H15F2I2NO ([M +
H]+) = 577.9284; found, 577.9284.
2,6-Bis(4-fluorophenyl)-3,5-diiodo-1-propylpyridin-4(1H)-one (4i).
Yield 90%; 51.9 mg; white solid; 1H NMR (400 MHz, acetone) δ ppm
7.59−7.55 (m, 4H), 7.41−7.36 (m, 4H), 3.60−3.56 (m, 2H), 1.53−1.43
(m, 2H), 0.30 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, acetone) δ ppm
171.0, 163.8 (d, J = 247 Hz, 1C), 153.1, 135.6 (d, J = 4 Hz, 1C), 132.2 (d,
J = 9 Hz, 1C), 116.6 (d, J = 22 Hz, 1C), 94.4, 57.0, 24.3, 10.5; IR (neat,
cm−1) 2968, 2932, 1601, 1579, 1506, 1486, 1409, 1225, 1081, 843, 819,
786; HRMS (ESI) calcd for C20H15F2I2NO ([M + H]+) = 577.9284;
found, 577.9283.
Characterization Data of 4a−4j, 4n−4p, 4r, and 4s. 3,5-Diiodo-
2,6-diphenyl-1-propylpyridin-4(1H)-one (4a). Yield 81%; 43.8 mg;
light yellow solid; 1H NMR (400 MHz, CDCl3) δ ppm 7.57−7.49 (m,
6H), 7.34−7.29 (m, 4H), 3.50−3.46 (m, 2H), 1.42−1.32 (m, 2H), 0.25
(t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ ppm 171.1, 152.9,
138.0, 129.7, 128.9, 128.6, 93.8, 56.2, 24.2, 10.4; IR (neat, cm−1) 3055,
2968, 2926, 2866, 1599, 1560, 1515, 1445, 1408, 1199, 1083, 1026, 752,
701, 667; HRMS (ESI) calcd for C20H17I2NO ([M + H]+) = 541.9472;
found, 541.9467.
3,5-Diiodo-1-propyl-2,6-di-m-tolylpyridin-4(1H)-one (4b). Yield
90%; 51.2 mg; light yellow solid; 1H NMR (400 MHz, CDCl3) δ ppm
7.42 (t, J = 8.0 Hz, 2H), 7.31 (d, J = 7.6 Hz, 2H), 7.11 (s, 4H), 3.50−
3.46(m, 2H), 2.43(s, 6H), 1.42−1.30 (m, 2H), 0.28 (t, J = 7.6 Hz, 3H);
13C NMR (100 MHz, CDCl3) δ ppm 171.2, 153.1, 138.8, 138.0, 130.4,
2,6-Bis(4-chlorophenyl)-3,5-diiodo-1-propylpyridin-4(1H)-one
1
(4j). Yield 35%; 21.3 mg; light yellow solid; H NMR (400 MHz,
CDCl3) δ ppm 7.54 (dd, J = 6.8 Hz 2.0 Hz, 4H), 7.27−7.26 (m, 4H),
3.49−3.45 (m, 2H), 1.40−1.30 (m, 2H), 0.34 (t, J = 7.6 Hz, 3H); 13C
NMR (100 MHz, CDCl3) δ ppm 171.2, 151.9, 136.3, 136.2, 130.2,
129.6, 94.3, 56.3, 24.4, 10.6; IR (neat, cm−1) 2925, 2855, 1639, 1593,
1465, 1403, 1090, 1015, 815, 756, 713; HRMS (ESI) calcd for
C20H15Cl2I2NO ([M + H]+) = 609.8693; found, 609.8688.
129.1, 128.8, 125.8, 93.7, 56.2, 24.4, 21.5, 10.5; IR (neat, cm−1) 2967,
2926, 2873, 2234, 1599, 1561, 1515, 1469, 1410, 1217, 1181, 1082, 914,
782, 732; HRMS (ESI) calcd for C22H21I2NO ([M + H]+) = 569.9785;
found, 569.9789.
3,5-Diiodo-1-propyl-2,6-di-p-tolylpyridin-4(1H)-one (4c). Yield
1
2-(2-Fluorophenyl)-3,5-diiodo-1-propyl-6-(m-tolyl)pyridin-4(1H)-
85%; 48.4 mg; white solid; H NMR (400 MHz, CDCl3) δ ppm 7.34
1
one (4n). Yield 67%; 38.4 mg; yellow solid; H NMR (400 MHz,
(d, J = 7.6 Hz, 4H), 7.19 (d, J = 7.6 Hz, 4H), 3.49 (t, J = 8.0 Hz, 2H), 2.45
(s, 6H), 1.40−1.29 (m, 2H), 0.28 (t, J = 7.6 Hz, 3H); 13C NMR (100
MHz, CDCl3) δ ppm 171.3, 153.1, 139.8, 135.3, 129.6, 128.5, 94.1, 56.2,
24.3, 21.5, 10.5; IR (neat, cm−1) 2975, 2922, 1600, 1563, 1490, 1463,
1404, 1198, 1082, 807, 754, 697; HRMS (ESI) calcd for C22H21I2NO
([M + H]+) = 569.9785; found, 569.9778.
2,6-Bis(4-ethylphenyl)-3,5-diiodo-1-propylpyridin-4(1H)-one (4d).
Yield 76%; 45.4 mg; light yellow solid; 1H NMR (400 MHz, CDCl3) δ
ppm 7.35 (d, J = 7.6 Hz, 4H), 7.21 (d, J = 8.0 Hz, 4H), 3.48 (t, J = 8.4 Hz,
2H), 2.50 (q, J = 8.0 Hz, 4H), 1.29 (d, J = 7.6 Hz, 6H), 0.26 (t, J = 7.2 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ ppm 171.4, 153.2, 146.1, 135.6,
128.6, 128.4, 94.1, 56.3, 28.7, 24.3, 15.2, 10.5; IR (neat, cm−1) 2966,
2928, 1597, 1561, 1506, 1458, 1408, 1082, 838, 757, 730, 693, 526;
HRMS (ESI) calcd for C24H25I2NO ([M + H]+) = 598.0098; found,
598.0094.
3,5-Diiodo-1-propyl-2,6-bis(4-propylphenyl)pyridin-4(1H)-one
(4e). Yield 55%; 34.4 mg; yellow solid; 1H NMR (400 MHz, CDCl3) δ
ppm 7.33 (d, J = 8.0 Hz, 4H), 7.20 (d, J = 8.0 Hz, 4H), 3.50−3.46 (m,
2H), 2.70−2.67 (m, 4H), 1.75−1.65 (m, 4H), 1.39−1.30 (m, 2H), 0.95
(t, J = 7.2 Hz, 6H), 0.25 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ ppm 171.4, 153.2, 144.5, 135.6, 129.0, 128.5, 94.1, 56.3, 37.7,
24.3, 24.2, 13.6, 10.5; IR (neat, cm−1) 2959, 2868, 1602, 1564, 1508,
1489, 1461, 1408, 1200, 1084, 1021, 846, 798, 756, 732, 641, 559;
HRMS (ESI) calcd for C26H29I2NO ([M + H]+) = 626.0411; found,
626.0417.
CDCl3) δ ppm 7.58−7.59 (m, 1H), 7.45−7.41 (m, 1H), 7.37−7.31 (m,
3H), 7.24 (d, J = 8.8 Hz, 1H), 7.12 (s, 2H), 3.60−3.51 (m, 1H), 3.48−
3.93 (m, 1H), 2.43 (s, 3H), 1.40−1.35 (m, 2H), 0.30 (t, J = 7.2 Hz, 3H);
13C NMR (100 MHz, CDCl3) δ ppm 171.2, 158.4 (d, J = 239 Hz, 1C),
153.5, 147.7, 138.9 (d, J = 14 Hz, 1C), 137.9, 132.4 (d, J = 8 Hz, 1C),
130.9 (d, J = 19 Hz, 1C), 130.6, 129.0, 128.9 (d, J = 10 Hz, 1C), 125.9 (d,
J = 13 Hz, 1C), 125.7 (d, J = 7 Hz, 1C), 124.8, 116.4 (d, J = 15 Hz, 1C),
94.8, 93.8, 56.4, 23.9, 21.5, 10.5; IR (neat, cm−1) 2967, 2928, 2236, 1605,
1557, 1519, 1483, 1413, 1195, 1080, 911, 761, 732, 672; HRMS (ESI)
calcd for C21H18FI2NO ([M + H]+) = 573.9535; found, 573.9537.
3,5-Diiodo-2-(4-methoxyphenyl)-6-phenyl-1-propylpyridin-
4(1H)-one (4o). Yield 40%; 22.8 mg; light yellow solid; 1H NMR (400
MHz, CDCl3) δ ppm 7.56−7.49 (m, 3H), 7.32−7.30 (m, 2H), 7.22 (d, J
= 8.4 Hz, 2H), 7.04 (d, J = 8.8 Hz, 2H), 3.89 (s, 3H), 3.50 (t, J = 8.4 Hz,
2H), 1.40−1.29 (m, 2H), 0.28 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ ppm 171.4, 160.4, 152.9, 138.3, 130.5, 130.1, 129.8, 129.0,
128.7, 114.3, 94.8, 93.9, 56.3, 55.4, 24.3, 10.5; IR (neat, cm−1) 2964,
2930, 1598, 1557, 1502, 1462, 1251, 1085, 911, 732, 703; HRMS (ESI)
calcd for C21H19I2NO2 ([M + H]+) = 571.9578; found, 571.9590.
3,5-Diiodo-2-phenyl-1,6-dipropylpyridin-4(1H)-one (4p). Yield
1
29%; 14.7 mg; yellow liquid; H NMR (400 MHz, CDCl3) δ ppm
7.53 (d, J = 6.4 Hz, 3H), 7.25−7.23 (m, 2H), 3.72 (t, J = 8.0 Hz, 2H),
3.06 (t, J = 8.0 Hz, 2H), 1.78−1.68 (m, 2H), 1.63−1.53 (m, 2H), 1.11 (t,
J = 7.2 Hz, 3H), 0.66 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ
ppm 171.2, 152.9, 152.4, 138.5, 129.8, 129.1, 128.6, 94.3, 92.9, 54.8, 40.1,
24.6, 21.9, 14.2, 10.7; IR (neat, cm−1) 2962, 2928, 1595, 1565, 1514,
1462, 1415, 1198, 1082, 763, 702; HRMS (ESI) calcd for C17H19I2NO
([M + H]+) = 507.9629; found, 507.9634.
3,5-Diiodo-2-(naphthalen-1-yl)-1-propyl-6-(p-tolyl)pyridin-4(1H)-
one (4r). Yield 39%; 23.6 mg; deep yellow solid; 1H NMR (400 MHz,
CDCl3) δ ppm 8.01 (d, J = 8.4 Hz, 1H), 7.97−7.95 (m, 1H), 7.61−7.55
(m, 2H), 7.50 (d, J = 7.6 Hz, 2H), 7.34 (d, J = 6.0 Hz, 3H), 7.20−7.17
(m, 2H), 3.50−3.45 (m, 2H), 2.45 (s, 3H), 1.39−1.30 (m, 2H), 0.11 (t, J
= 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ ppm 171.5, 153.6, 151.5,
140.0, 135.3, 135.2, 133.5, 130.4, 129.8, 129.7, 129.0, 128.6, 128.2, 127.8,
126.9, 125.2, 123.9, 94.8, 94.5, 56.4, 24.8, 21.5, 10.5; IR (neat, cm−1)
2958, 2923, 1597, 1557, 1498, 1462, 1404, 1084, 802, 780, 729, 649;
HRMS (ESI) calcd for C25H21I2NO ([M + H]+) = 605.9785; found,
605.9804.
2,6-Dicyclopropyl-3,5-diiodo-1-propylpyridin-4(1H)-one (4f).
1
Yield 45%; 21.1 mg; yellow solid; H NMR (400 MHz, CDCl3) δ
ppm 4.72 (t, J = 7.2 Hz, 2H), 1.88−1.81 (m, 2H), 1.63−1.53 (m, 2H),
1.44−1.39 (m, 4H), 0.86 (t, J = 7.6 Hz, 3H), 0.81−0.77 (m, 4H); 13C
NMR (100 MHz, CDCl3) δ ppm 171.3, 154.2, 96.8, 50.8, 24.9, 19.1,
14.0, 11.2; IR (neat, cm−1) 3082, 3001, 2963, 2232, 1594, 1558, 1504,
1459, 1405, 1163, 1076, 910, 730; HRMS (ESI) calcd for C14H17I2NO
([M + H]+) = 469.9472; found, 469.9462.
2,6-Bis(4-ethylphenyl)-3,5-diiodo (4g). Yield 81%; 46.7 mg; light
yellow solid; 1H NMR (400 MHz, CDCl3) δ ppm 7.59−7.53 (m, 2H),
7.37−7.29 (m, 5H), 7.24 (s, 1H), 3.51 (t, J = 8.4 Hz, 2H), 1.42−1.32 (m,
2H), 0.33 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ ppm
171.2, 158.5 (d, J = 248 Hz, 1C), 148.2, 132.5, 130.9 (d, J = 29 Hz, 1C),
125.9 (d, J = 16 Hz, 1C), 124.9 (d, J = 27 Hz, 1C), 116.9, 116.6 (d, J = 12
Hz, 1C), 116.4, 95.0, 56.6, 23.6, 10.7; IR (neat, cm−1) 2926, 1598, 1564,
1487, 1450, 1415, 1197, 1078, 814, 760, 732; HRMS (ESI) calcd for
C20H15F2I2NO ([M + H]+) = 577.9284; found, 577.9279.
3,5-Diiodo-1-propyl-2-(thiophen-2-yl)-6-(p-tolyl)pyridin-4(1H)-
one (4s). Yield 46%; 25.3 mg; deep yellow solid; 1H NMR (400 MHz,
CDCl3) δ ppm 7.58−7.50 (m, 4H), 7.32 (d, J = 7.2 Hz, 2H), 7.18 (t, J =
3.6 Hz, 2H), 3.59 (t, J = 8.4 Hz, 2H), 1.51−1.43 (m, 2H), 0.36 (t, J = 7.6
Hz, 3H); 13C NMR (100 MHz, CDCl3) δ ppm 171.1, 153.4, 146.3,
138.0, 129.9, 129.9, 129.0, 128.7, 128.3, 127.3, 97.5, 94.3, 56.7, 25.0,
10.5; IR (neat, cm−1) 2966, 2930, 1596, 1563, 1463, 1410, 1197, 1083,
2,6-Bis(3-fluorophenyl)-3,5-diiodo-1-propylpyridin-4(1H)-one
(4h). Yield 63%; 36.3 mg; orange solid; 1H NMR (400 MHz, CDCl3) δ
ppm 7.58−7.51 (m, 2H), 7.26−7.22 (m, 2H), 7.13 (d, J = 7.6 Hz, 2H),
7.07−7.05 (m, 2H), 3.52−3.47 (m, 2H), 1.44−1.35 (m, 2H), 0.33 (t, J =
7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ ppm 171.1, 162.6 (d, J =
H
dx.doi.org/10.1021/jo402055a | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
910, 766, 732, 706; HRMS (ESI) calcd for C18H15I2NOS ([M + H]+) =
547.9036; found, 547.9030.
4H), 1.73−1.61 (m, 4H), 1.06−0.99 (m, 2H), 0.95 (q, J = 7.2 Hz, 6H),
0.30 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ ppm 183.0,
168.5, 145.9, 144.6, 140.6, 135.5, 129.3, 129.1, 128.7, 128.5, 127.2, 92.4,
68.5, 49.2, 37.9, 37.7, 24.2, 24.1, 21.0, 13.8, 13.6, 10.6; IR (neat, cm−1)
2964, 2930, 2876, 1671, 1602, 1540, 1493, 1462, 1364, 1067, 840, 765,
730; HRMS (ESI) calcd for C26H29I2NO ([M + H]+) = 626.0411;
found, 626.0418.
(E)-5-Cyclopropyl-2-(cyclopropyliodomethylene)-4-iodo-1-prop-
yl-1H-pyrrol-3(2H)-one (5f). Yield 46%; 21.6 mg; light yellow solid; 1H
NMR (400 MHz, CDCl3) δ ppm 4.15 (t, J = 7.6 Hz, 2H), 1.50−1.43 (m,
2H), 1.09−1.05 (m, 5H), 0.87−0.83 (m, 8H); 13C NMR (100 MHz,
CDCl3) δ ppm 182.3, 171.6, 140.3, 122.9, 68.9, 48.2, 21.6, 12.3, 11.5,
11.2, 8.6, 8.5; IR (neat, cm−1) 2963, 2928, 1601, 1481, 1293, 1100, 908,
732; HRMS (ESI) calcd for C14H17I2NO ([M + H]+) = 469.9472;
found, 469.9483.
(E)-5-(2-Fluorophenyl)-2-((2-fluorophenyl)iodomethylene)-4-
iodo-1-propyl-1H-pyrrol-3(2H)-one (5g). Yield 79%; 45.6 mg; red
solid; 1H NMR (400 MHz, CDCl3) δ ppm 7.55−7.50 (m, 1H), 7.42−
7.31 (m, 4H), 7.30−7.18 (m, 2H), 7.14−7.10 (m, 1H), 2.79 (q, J = 7.6
Hz, 2H), 1.19−1.05 (m, 2H), 0.34−0.30 (m, 3H); 13C NMR (100 MHz,
CDCl3) δ ppm 182.3 (d, J = 7 Hz, 1C), 163.6, 161.8 (d, J = 344 Hz, 1C),
158.5 (d, J = 195 Hz, 1C), 156.9 (d, J = 23 Hz, 1C), 134.9 (d, J = 7 Hz,
1C), 133.0, 131.7, 131.1, 130.8, 130.6 (d, J = 12 Hz, 1C), 124.6 (d, J = 22
Hz, 1C), 124.1, 118.1 (d, J = 14 Hz, 1C), 116.4 (d, J = 39 Hz, 1C), 81.6,
67.4 (d, J = 13 Hz, 1C), 48.8 (d, J = 15 Hz, 1C), 21.4, 10.5 (d, J = 12 Hz,
1C); IR (neat, cm−1) 2963, 2927, 1642, 1614, 1508, 1462, 1229, 1105,
816, 759; HRMS (ESI) calcd for C20H15F2I2NO ([M + H]+) =
577.9284; found, 577.9289.
(E)-5-(3-Fluorophenyl)-2-((3-fluorophenyl)iodomethylene)-4-
iodo-1-propyl-1H-pyrrol-3(2H)-one (5h). Yield 51%; 29.4 mg; red
solid; 1H NMR (400 MHz, CDCl3) δ ppm 7.54−7.39 (m, 2H), 7.29−
7.18 (m, 5H), 7.09−7.04 (m, 1H), 2.80 (t, J = 7.6 Hz, 2H), 1.12−1.03
(m, 2H), 0.37 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ ppm
183.0, 167.1 (d, J = 2 Hz, 1C), 163.5 (d, J = 39 Hz, 1C), 161.0 (d, J = 40
Hz, 1C), 145.1 (d, J = 7 Hz, 1C), 135.7, 131.9 (d, J = 7 Hz, 1C), 130.7 (d,
J = 8 Hz, 1C), 130.2 (d, J = 8 Hz, 1C), 125.0, 124.9 (d, J = 2 Hz, 1C),
118.0 (d, J = 21 Hz, 1C), 116.7 (d, J = 21 Hz, 1C), 116.4 (d, J = 8 Hz,
1C), 116.1 (d, J = 9 Hz, 1C), 89.8 (d, J = 2 Hz, 1C), 69.3, 49.3, 21.1, 10.6;
IR (neat, cm−1) 2965, 2928, 2246, 1672, 1582, 1541, 1478, 1436, 1260,
1062, 955, 783, 734, 707; HRMS (ESI) calcd for C20H15F2I2NO ([M +
H]+) = 577.9284; found, 577.9280.
Characterization Data of 4aa, 4ab, and 4ac. 1-Butyl-3,5-diiodo-
2,6-diphenylpyridin-4(1H)-one (4aa). Yield 81%; 45.0 mg; light yellow
solid; 1H NMR (400 MHz, CDCl3) δ ppm 7.57−7.49 (m, 6H), 7.34−
7.32 (m, 4H), 3.54 (t, J = 8.4 Hz, 2H), 1.37−1.29 (m, 2H), 0.67−0.58
(m, 2H), 0.38 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ ppm
171.2, 152.9, 138.0, 129.8, 128.9, 128.7, 93.8, 54.5, 32.4, 19.0, 12.5; IR
(neat, cm−1) 3059, 2960, 2868, 2237, 1587, 1520, 1461, 1444, 1411,
1200, 1087, 918, 731, 701, 647; HRMS (ESI) calcd for C21H19I2NO ([M
+ H]+) = 555.9629; found, 555.9621.
1-Benzyl-3,5-diiodo-2,6-diphenylpyridin-4(1H)-one (4ab). Yield
75%; 44.2 mg; light yellow solid; 1H NMR (400 MHz, CDCl3) δ ppm
7.41−7.35 (m, 6H), 7.22−7.17 (m, 3H), 7.09 (s, 4H), 6.57−6.55 (m,
2H), 4.81 (d, J = 18.0 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ ppm
171.6, 153.7, 137.8, 136.6, 129.8, 128.8, 128.6, 128.5, 127.7, 125.2, 94.2,
58.1; IR (neat, cm−1) 3059, 3029, 2236, 1713, 1598, 1562, 1486, 1448,
1409, 1215, 1083, 911, 757, 732, 700; HRMS (ESI) calcd for
C24H17I2NO ([M + H]+) = 589.9472; found, 589.9461.
1-Benzyl-3,5-dibromo-2,6-diphenylpyridin-4(1H)-one (4ac). Yield
72%; 35.5 mg; light yellow solid; 1H NMR (400 MHz, CDCl3) δ ppm
7.42−7.31 (m, 7H), 7.22−7.16 (m, 3H), 7.12 (d, J = 6.0 Hz, 4H), 6.55
(d, J = 6.4 Hz, 2H), 4.77 (s, 2H); 13C NMR (100 MHz, CDCl3) δ ppm
168.7, 150.6, 136.3, 134.4, 129.8, 128.8, 128.6, 128.4, 127.7, 125.2, 116.1,
56.8; IR (neat, cm−1) 3060, 3032, 2235, 1705, 1606, 1572, 1530, 1488,
1217, 1103, 912, 846, 757, 732, 698; HRMS (ESI) calcd for
C24H17Br2NO ([M + H]+) = 493.9750; found, 493.9747.
Characterization Data of 5a−5j, 5ab, 5na, 5nb, 5pa, and 5pb.
(E)-4-Iodo-2-(iodo(phenyl)methylene)-5-phenyl-1-propyl-1H-pyrrol-
1
3(2H)-one (5a). Yield 82%; 44.4 mg; red solid; H NMR (400 MHz,
CDCl3) δ ppm 7.51−7.41 (m, 9H), 7.34 (t, J = 7.2 Hz, 1H), 2.76 (t, J =
7.6 Hz, 1H), 1.09−0.99 (m, 2H), 0.31 (t, J = 7.6 Hz, 3H); 13C NMR
(100 MHz, CDCl3) δ ppm 183.1, 168.5, 143.3, 135.6, 130.9, 130.1,
129.6, 129.2, 129.2, 128.7, 128.5, 92.1, 68.7, 49.2, 21.1, 10.6; IR (neat,
cm−1) 2962, 2926, 1670, 1576, 1538, 1483, 1444, 1063, 753, 694; HRMS
(ESI) calcd for C20H17I2NO ([M + H]+) = 541.9472; found, 541.9480.
(E)-4-Iodo-2-(iodo(m-tolyl)methylene)-1-propyl-5-(m-tolyl)-1H-
1
pyrrol-3(2H)-one (5b). Yield 93%; 52.9 mg; red solid; H NMR (400
MHz, CDCl3) δ ppm 7.44−7.37 (m, 1H), 7.34−7.21 (m, 7H), 7.16 (d, J
= 7.6 Hz, 1H), 2.79 (t, J = 7.6 Hz, 2H), 2.44 (s, 3H), 2.40 (s, 3H), 1.11−
1.02 (m, 2H), 0.33 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ
ppm 183.0, 168.6, 143.3, 138.5, 138.3, 135.3, 131.6, 130.3, 129.9, 129.6,
129.4, 128.6, 128.3, 126.2, 126.1, 92.1, 68.3, 49.0, 21.4, 21.3, 21.1, 10.5;
IR (neat, cm−1) 2961, 2925, 2867, 1670, 1582, 1535, 1477, 1066, 764,
734, 706; HRMS (ESI) calcd for C22H21I2NO ([M + H]+) = 569.9785;
found, 569.9780.
(E)-5-(4-Fluorophenyl)-2-((4-fluorophenyl)iodomethylene)-4-
iodo-1-propyl-1H-pyrrol-3(2H)-one (5i). Yield 86%; 49.6 mg; red solid;
1H NMR (400 MHz, CDCl3) δ ppm 7.52−7.47 (m, 4H), 7.21 (t, J = 8.4
Hz, 2H), 7.14 (t, J = 8.8 Hz, 2H), 2.78 (t, J = 7.6 Hz, 2H), 1.90−1.00 (m,
2H), 0.36 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ ppm
182.9, 166.4 (d, J = 224 Hz, 1C), 163.5 (d, J = 151 Hz, 1C), 161.7, 139.2
(d, J = 3 Hz, 1C), 135.8, 131.4 (d, J = 7 Hz, 1C), 131.4 (d, J = 6 Hz, 1C),
125.8 (d, J = 4 Hz, 1C), 116.2 (d, J = 22 Hz, 1C), 115.7 (d, J = 22 Hz,
1C), 90.7, 69.5, 49.3, 20.9, 10.7; IR (neat, cm−1) 2965, 2929, 2246, 1667,
1601, 1543, 1496, 1462, 1407, 1232, 1156, 1064, 844, 763, 733; HRMS
(ESI) calcd for C20H15F2I2NO ([M + H]+) = 577.9284; found,
577.9284.
(E)-4-Iodo-2-(iodo(p-tolyl)methylene)-1-propyl-5-(p-tolyl)-1H-
1
pyrrol-3(2H)-one (5c). Yield 82%; 46.7 mg; red solid; H NMR (400
MHz, CDCl3) δ ppm 7.37 (t, J = 8.4 Hz, 4H), 7.30−7.27 (m, 2H), 7.22
(d, J = 8.0 Hz, 2H), 2.81 (t, J = 7.2 Hz, 2H), 2.50−2.38 (m, 6H), 1.07−
0.98 (m, 2H), 0.32 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ
ppm 183.0, 168.5, 141.3, 140.3, 139.9, 135.5, 129.7, 129.3, 129.3, 129.1,
129.1, 128.9, 126.9, 92.6, 68.5, 49.2, 21.6, 21.3, 10.7; IR (neat, cm−1)
2962, 2924, 1669, 1609, 1542, 1497, 1458, 1363, 1063, 815, 761, 732,
686; HRMS (ESI) calcd for C22H21I2NO ([M + H]+) = 569.9785;
found, 569.9774.
(E)-5-(4-Chlorophenyl)-2-((4-chlorophenyl)iodomethylene)-4-
iodo-1-propyl-1H-pyrrol-3(2H)-one (5j). Yield 42%; 25.6 mg; red solid;
1H NMR (400 MHz, CDCl3) δ ppm 7.55 (t, J = 6.0 Hz, 1H), 7.49 (d, J =
(E)-5-(4-Ethylphenyl)-2-((4-ethylphenyl)iodomethylene)-4-iodo-
1-propyl-1H-pyrrol-3(2H)-one (5d). Yield 79%; 47.2 mg; red solid; 1H
NMR (400 MHz, CDCl3) δ ppm 7.42−7.35 (m, 5H), 7.31 (d, J = 8.0 Hz,
2H), 7.27−7.7.24 (m, 3H), 2.80 (t, J = 7.6 Hz, 2H), 2.73−2.68 (m, 4H),
1.26 (q, J = 8.0 Hz, 6H), 1.07−0.98 (m, 2H), 0.31 (t, J = 7.6 Hz, 3H); 13C
NMR (100 MHz, CDCl3) δ ppm 183.0, 168.5, 147.4, 146.1, 140.5,
135.5, 129.4, 129.2, 128.1, 127.9, 127.1, 92.5, 68.5, 49.2, 28.7, 28.6, 21.0,
15.2, 15.0, 10.6; IR (neat, cm−1) 2965, 2930, 2872, 2244, 1668, 1609,
1540, 1496, 1459, 1364, 1064, 839, 761, 733; HRMS (ESI) calcd for
C24H25I2NO ([M + H]+) = 598.0098; found, 598.0089.
8.8 Hz, 2H), 7.45 (d, J = 2.0 Hz, 1H), 7.42 (s, 4H), 7.34 (d, J = 3.2 Hz,
1H), 2.79 (t, J = 7.6 Hz, 2H), 1.90−1.00 (m, 2H), 0.37 (t, J = 7.6 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ ppm 183.0, 167.3, 141.6, 137.3,
135.8, 130.7, 130.6, 129.3, 128.9, 128.6, 128.3, 90.5, 69.6, 49.4, 21.0,
10.7; IR (neat, cm−1) 2963, 2927, 1670, 1596, 1537, 1481, 1398, 1365,
1179, 1092, 1063, 1012, 817, 733; HRMS (ESI) calcd for C20H15-
Cl2I2NO ([M + H]+) = 609.8693; found, 609.8695.
(E)-1-Butyl-4-iodo-2-(iodo(phenyl)methylene)-5-phenyl-1H-pyr-
1
rol-3(2H)-one (5aa). Yield 77%; 42.7 mg; red solid; H NMR (400
MHz, CDCl3) δ ppm 7.48−7.40 (m, 9H), 7.33 (q, J = 2.4 Hz, 1H),
2.82−2.79 (m, 2H), 0.97 (d, J = 4.8 Hz, 2H), 0.65−0.62 (m, 2H), 0.51−
0.46 (m, 3H); 13C NMR (100 MHz, CDCl3) δ ppm 182.9, 168.3, 143.1,
135.5, 130.8, 129.8, 129.5, 129.2, 129.0, 128.6, 128.4, 92.1, 68.7, 47.4,
29.6, 19.2, 13.3; IR (neat, cm−1) 2964, 2932, 1670, 1578, 1548, 1483,
(E)-4-Iodo-2-(iodo(4-propylphenyl)methylene)-1-propyl-5-(4-pro-
pylphenyl)-1H-pyrrol-3(2H)-one (5e). Yield 58%; 36.3 mg; red solid;
1H NMR (400 MHz, CDCl3) δ ppm 7.40−7.37 (m, 4H), 7.30−7.27 (m,
2H), 7.22 (d, J = 8.0 Hz, 2H), 2.79 (t, J = 7.6 Hz, 2H), 2.64 (q, J = 7.6 Hz,
I
dx.doi.org/10.1021/jo402055a | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
1444, 1063, 757, 699; HRMS (ESI) calcd for C21H19I2NO ([M + H]+) =
555.9629; found, 555.9629.
(d, J = 7.2 Hz, 3H), 6.61 (d, J = 7.2 Hz, 2H), 4.18 (s, 2H); 13C NMR
(100 MHz, CDCl3) δ ppm 183.4, 169.7, 140.6, 139.9, 138.5, 136.5,
136.3, 134.3, 131.7, 131.3, 130.9, 130.9, 130.1, 129.6, 129.3, 128.9, 128.8,
128.5, 128.4, 128.2, 128.1, 127.9, 127.7, 127.1, 126.8, 51.5; IR (neat,
cm−1) 2967, 2930, 1586, 1561, 1514, 1478, 1434, 798, 721; HRMS
(ESI) calcd for C36H27NO ([M + H]+) = 490.2165; found, 490.2168.
(E)-1-Benzyl-4-iodo-2-(iodo(phenyl)methylene)-5-phenyl-1H-pyr-
1
rol-3(2H)-one (5ab). Yield 73%; 43.0 mg; red solid; H NMR (400
MHz, CDCl3) δ ppm 7.46 (t, J = 7.6 Hz, 5H), 7.41−7.32 (m, 5H), 7.15−
7.06 (m, 3H), 6.43 (d, J = 6.8 Hz, 2H), 4.11 (s, 2H); 13C NMR (100
MHz, CDCl3) δ ppm 182.9, 168.1, 143.0, 136.2, 135.8, 131.0, 129.8,
129.7, 129.2, 128.7, 128.3, 128.3, 127.5, 126.4, 93.5, 69.4, 51.2; IR (neat,
cm−1) 2966, 2942, 1670, 1579, 1543, 1481, 1440, 1062, 757, 698; HRMS
(ESI) calcd for C24H17I2NO ([M + H]+) = 589.9472; found, 589.9477.
(E)-5-(2-Fluorophenyl)-4-iodo-2-(iodo(m-tolyl)methylene)-1-
propyl-1H-pyrrol-3(2H)-one (5na). Yield 62%; 35.5 mg; red solid; 1H
NMR (400 MHz, CDCl3) δ ppm 7.59−7.41 (m, 2H), 7.38−7.09 (m,
6H), 2.73 (t, J = 7.6 Hz, 2H), 2.38 (m, 2H), 2.38 (m, 3H), 1.11−1.02 (m,
2H), 0.31 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ ppm
182.6, 163.3, 160.1, 157.6, 143.1, 138.2, 134.6, 132.9, 132.8, 131.2, 130.4,
129.8, 128.3, 126.5, 124.5, 124.5, 118.4, 118.3, 116.6, 116.4, 92.9, 68.2,
49.0, 21.5, 21.3, 10.5; IR (neat, cm−1) 2964, 2878, 1728, 1669, 1615,
1548, 1450, 1458, 1378, 1066, 762; HRMS (ESI) calcd for
C21H18FI2NO ([M + H]+) = 573.9535; found, 573.9531.
ASSOCIATED CONTENT
■
S
* Supporting Information
1
X-ray diffraction data and H NMR/13C NMR spectra. This
material is available free of charge via the Internet at http://pubs.
acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: liangym@lzu.edu.cn.
■
Notes
The authors declare no competing financial interest.
(E)-2-((2-Fluorophenyl)iodomethylene)-4-iodo-1-propyl-5-(m-
1
tolyl)-1H-pyrrol-3(2H)-one (5nb). Yield 19%; 10.9 mg; red solid; H
ACKNOWLEDGMENTS
■
NMR (400 MHz, CDCl3) δ ppm 7.40−7.34 (m, 3H), 7.30 (d, J = 7.6 Hz,
1H), 7.26−7.22 (m, 4H), 2.85−2.79 (m, 2H), 2.42 (s, 3H), 1.44−1.06
(m, 2H), 0.23 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ ppm
182.7, 168.8, 159.4, 156.9, 138.6, 135.8, 131.7, 131.5, 131.4, 130.9, 129.8,
129.4, 128.6, 126.2, 124.4, 124.3, 117.9, 116.3, 116.1, 81.0, 67.4, 48.9,
21.4, 21.0, 10.6; IR (neat, cm−1) 2966, 2927, 1727, 1672, 1536, 1481,
1455, 1361, 1064, 897, 798, 710; HRMS (ESI) calcd for C21H18FI2NO
([M + H]+) = 573.9535; found, 573.9542.
Financial support was received from the National Science
Foundation (NSF 21072080), the National Basic Research
Program of China (973 Program, 2010CB833203), the Program
for Changjiang Scholars and Innovative Research Team in
University (IRT1138), and the Fundamental Research Funds for
the Central Universities (lzujbky-2013-ct02).
(E)-4-Iodo-2-(1-iodobutylidene)-5-phenyl-1-propyl-1H-pyrrol-
3(2H)-one (5pa). Yield 22%; 11.2 mg; red solid; 1H NMR (400 MHz,
CDCl3) δ ppm 7.42−7.31 (m, 5H), 2.88 (t, J = 8.0 Hz, 2H), 2.62 (t, J =
8.0 Hz, 2H), 1.65−1.69 (m, 2H), 1.22−1.42 (m, 2H), 1.05 (t, J = 7.6 Hz,
3H), 0.45 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ ppm
182.2, 169.8, 143.3, 134.7, 129.3, 128.8, 128.3, 89.5, 66.2, 47.2, 30.5,
21.9, 21.1, 13.9, 10.5; IR (neat, cm−1) 2964, 2928, 2872, 1670, 1539,
1390, 1052, 703, 612; HRMS (ESI) calcd for C17H19I2NO ([M + H]+) =
507.9629; found, 507.9633.
(E)-4-Iodo-2-(iodo(phenyl)methylene)-1,5-dipropyl-1H-pyrrol-
3(2H)-one (5pb). Yield 49%; 24.8 mg; red solid; 1H NMR (400 MHz,
CDCl3) δ ppm 7.66−7.60 (m, 2H), 7.50−7.44 (m, 3H), 2.86 (t, J = 7.2
Hz, 2H), 2.44 (t, J = 7.6 Hz, 2H), 1.66−1.61 (m, 2H), 1.19−1.14 (m,
2H), 0.97 (t, J = 7.6 Hz, 3H), 0.53 (t, J = 7.2 Hz, 3H); 13C NMR (100
MHz, CDCl3) δ ppm 184.0, 168.8, 143.2, 135.2, 129.3, 128.7, 128.4,
90.1, 61.4, 47.5, 34.6, 25.8, 25.6, 13.9, 11.5; IR (neat, cm−1) 2964, 2881,
1658, 1483, 1436, 1331, 899, 806, 728; HRMS (ESI) calcd for
C17H19I2NO ([M + H]+) = 507.9629; found, 507.9628.
Characterization Data of 6a, 6b, and 6ab. 2,3,5,6-Tetraphenyl-
1-propylpyridin-4(1H)-one (6a). Yield 86%; 37.9 mg; light yellow solid;
1H NMR (400 MHz, CDCl3) δ ppm 7.26 (s, 10H), 7.10−7.08 (m, 7H),
7.06 (d, J = 4.8 Hz, 1H), 7.04−7.00 (m, 2H), 3.51−3.47 (m, 2H), 1.40−
1.31 (m, 2H), 0.29 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ
ppm 175.3, 149.3, 135.3, 134.4, 131.1, 130.0, 128.5, 128.1, 127.1, 126.1,
52.7, 36.4, 24.0, 10.6; IR (neat, cm−1) 2962, 1675, 1583, 1480, 1443,
1077, 748; HRMS (ESI) calcd for C32H27NO ([M + H]+) = 442.2165;
found, 442.2180.
3,5-Diphenyl-1-propyl-2,6-di-m-tolylpyridin-4(1H)-one (6b). Yield
92%; 43.2 mg; light yellow solid; 1H NMR (400 MHz, CDCl3) δ ppm
7.14−7.05 (m, 14H), 7.03−6.97 (m, 4H), 3.49 (t, J = 8.0 Hz, 2H), 2.28
(s, 3H), 2.26 (s, 3H), 1.40−1.31 (m, 2H), 0.32 (t, J = 7.6 Hz, 3H); 13C
NMR (100 MHz, CDCl3) δ ppm 175.3, 149.4, 137.7, 137.6, 135.5,
134.3, 131.2, 131.1, 130.6, 130.5, 129.1, 128.4, 128.1, 127.9, 127.9, 127.2,
127.1, 127.0, 126.0, 52.6, 24.1, 21.2, 21.2, 10.6; IR (neat, cm−1) 2964,
2862, 1612, 1522, 1425, 1370, 1296, 1082, 792, 759; HRMS (ESI) calcd
for C34H31NO ([M + H]+) = 470.2478; found, 470.2487.
1-Benzyl-2-(diphenylmethylene)-4,5-diphenyl-1H-pyrrol-3(2H)-
one (6ab). Yield 79%; 38.6 mg; red solid; 1H NMR (400 MHz, CDCl3)
δ ppm 7.63 (d, J = 4.4 Hz, 2H), 7.52 (d, J = 5.2 Hz, 4H), 7.46−7.45 (m,
4H), 7.37−7.34 (m, 3H), 7.30−7.24 (m, 3H), 7.18−7.12 (m, 4H), 7.02
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