Iron-Promoted Reductive Ring-Opening and Isomerization Reactions of C4-Alkynylisoxazoles Leading to 2-Alkynylenaminones and Polysubstituted Furans

Article abstract of DOI:10.1002/adsc.201901176

A new iron(III)-promoted reductive ring-opening and isomerization reactions of C4-alkynylisoxazoles in the oxidized N-methylpyrrolidone (NMP*) was reported. By changing the substituents at the C3 and C5 position of the isoxazole ring, the reaction selecti

Full text of DOI:10.1002/adsc.201901176

Title: Iron-Promoted Reductive Ring-Opening and Isomerization
Reactions of C4-Alkynylisoxazoles Leading to 2-
Alkynylenaminones and Polysubstituted Furans
Authors: Wen Yang, Yu Chen, Yongqi Yao, Qifu Lin, and Dingqiao
Yang
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201901176
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10.1002/adsc.201901176
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Iron-Promoted Reductive Ring-Opening and Isomerization
Reactions of C4-Alkynylisoxazoles Leading to 2-
Alkynylenaminones and Polysubstituted Furans
Wen Yang,a Yu Chen,b Yongqi Yao,a Qifu Lin,a and Dingqiao Yang*a
aKey Laboratory of Theoretical Chemistry of Environment, Ministry of Education, College of Chemistry, South China
Normal University, Guangzhou 510006, People’s Republic of China
E-mail: yangdq@scnu.edu.cn
bDepartment of Chemistry and Biochemistry, Queens College of the City University of New York, 65-30 Kissena Blvd.,
Queens, New York 11367, United States
E-mail: yu.chen1@qc.cuny.edu
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
Abstract. A new iron(III)-promoted reductive ring-opening ring-opening rather than isomerization reaction in the
and isomerization reactions of C4-alkynylisoxazoles in the presence of FeCl3. It was noteworthy that the NMP* as a
oxidized N-methylpyrrolidone (NMP*) was reported. By solvent and a hydrogen donor was essential for both
changing the substituents at the C3 and C5 position of the reactions. A plausible mechanism for the reductive ring-
isoxazole ring, the reaction selectively produced 2- opening and isomerization was also proposed.
alkynylenaminones and polysubstituted furans in good to
excellent yields. It was very interesting that large group at
the C3 or C5 position of the isoxazole ring was a steric
hindrance tertiary butyl group (t-Bu), the reaction proceeded
Keywords: iron(III) salt, reductive ring-opening,
isomerization, C4-alkynylisoxazoles, 2-alkynylenaminones,
furans
The application of iron salts as catalysts in organic
synthesis has attracted much attention[12] owing to
their environmentally benign, low cost, and the
Introduction
During the past two decades, isoxazoles have been abundance of element iron.[13] However, it is still a
emerging as versatile precursors for the synthesis of challenge to form other heterocycles from isoxazoles
other valuable scaffolds.[1] One of the key structural catalyzed by iron salts. To the best of our knowledge,
elements of isoxazoles depends on the fact that they only a few examples using iron salts as catalysts have
possess a relatively labile N–O bond, which is easy to been
investigated,
of
including:
isoxazoles
(a)
Domino
2,4-
be cleaved into heterocyclic compounds.[1,2] Therefore, transformation
to
many examples employing isoxazoles as the starting dicarbonylpyrroles under Fe(II)/Ni(II) relay catalysis
materials have been developed, including (a) reducing (Scheme 1a);[14] (b) Fe(II)/Au(I) co-catalyzed
isoxazoles into enaminones in the presence of H2 and isomerization of 4-propargylisoxazoles into pyridines
metal catalyst,[3] (b) converting isoxazoles into β-keto (Scheme 1b);[15a] (c) Fe(II)-catalyzed isomerization of
nitriles under basic conditions,[4] (c) transforming 4-vinylisoxazoles into pyrroles (Scheme 1c).[15b] All
isoxazoles into oxazole[5] or imidazole[1h] under of the above reactions depend on the directing groups
photochemical conditions, and (d) halogen-substituted (either an alkoxy or an amino group) at the C5
isoxazole reacting with vinyl ketone to synthesize 2- position of the isoxazole ring. At the same time, a
azafluorenone in the presence of palladium bimetallic co-catalyst system is needed for (a) and (b)
catalyst.[1a] Recently, many research groups used reactions.
isoxazoles as substrates to react with alkynes in the
Furans are the most widely used and important
presence of gold,[6] platinum,[7] Zn(OTf)2,[8] and heterocyclic compounds, which exist in many natural
Tf2NH as catalysts,[9] affording various nitrogen- products and drug molecules.[16] Enaminones have
containing heterocycles. The isoxazoles also could recently been recognized as versatile and valuable
react with salicylaldehyde[10] or 1,2,3-triazole[11] to intermediates because of the enamine ambident
produce secondary enamide or polysubstituted 3- nucleophilic and enone electrophilic characters, which
aminopyrrole in the presence of a rhodium catalyst.
has been used by many researchers for accessing
1
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10.1002/adsc.201901176
Advanced Synthesis & Catalysis
biologically important heterocycles.[17] Herein, we optimized reaction conditions were: FeCl3 (2.0 equiv.),
o
report a new iron(III)-promoted reductive ring- and Li2CO3 (2.0 equiv.) in the NMP* at 150 C for 8
opening and isomerization reactions of C4- h. Unfortunately, this reaction was not catalyzed by
alkynylisoxazoles, which yields 2-alkynylenaminone FeCl2·4H2O and could not occur under the literature
and polysubstituted furan products.
conditions[15b] (Table 1, entry 12).
Table 1. Optimization for isomerization reaction of
substrate 1a.[a]
Entry
1
Fe salt (equiv.)
FeCl3 (0.5)
Yield (%)[b]
46
28
12
40
42
57
79
35
60
n. r
n. r
n. r
2
Fe2O3 (0.5)
3
Fe(acac)2 (0.5)
FeCl2·4H2O (0.5)
FeCl3 (0.2)
4
5
6
FeCl3 (1.0)
7
FeCl3 (2.0)
8
FeCl3 (3.0)
9[c]
10[d]
11[e]
12[f]
FeCl3 (2.0)
FeCl3 (2.0)
FeCl3 (2.0)
Scheme 1. Iron-catalyzed or promoted isoxazoles to form
FeCl2·4H2O (0.1)
other heterocycles.
[a]
Reaction conditions: 1a (0.2 mmol, 1 equiv.), Fe salt,
o
Li2CO3 (2.0 equiv.), and NMP* (2.5 mL) at 150 C for 8 h
in a 10 mL round-bottomed flask sealed with a pressure
Results and Discussion
release cap.[b] Isolated yields.[c] 130 C.[d] 110 C.[e] Newly
purchased NMP.[f] Reaction condition: 1a (0.2 mmol, 1
equiv.), FeCl2·4H2O (0.1 equiv.), and MeCN (2.5 mL) at
65 oC for 12 h in a 10 mL round-bottomed flask sealed with
a pressure release cap.
o
o
A series of substrate C4-alkynylisoxazoles 1 were
synthesized according to our reported method.[18] We
initially
chose
3,5-diphenyl-4-(p-
tolylethynyl)isoxazole 1a as the model substrate to
start our investigation. The reaction was carried out in
the presence of FeCl3 (0.5 equiv.) and Li2CO3 (2.0
equiv.) at 150 oC in the oxidized N-methylpyrrolidone
(NMP*)[19] for 8 h. To our delight, phenyl-(2-phenyl-
5-(p-tolyl)furan-3-yl)methanone 2a was obtained in
46 % yield (Table 1, entry 1). Other iron salts were
screened, and FeCl3 was the best one (Table 1, entries
1–4). The effect of FeCl3 loading on the reaction was
then investigated (Table 1, entries 1, 5–8), and the
results showed that it had a great influence on the
yield of 2a. When FeCl3 loading increased to 2.0
equivalent, the yield of 2a increased to 79% (Table 1,
entry 7). However, further increasing FeCl3 loading
could greatly reduce the yield of 2a (Table 1, entry 8).
The reaction conditions were further optimized by
changing temperature (Table 1, entries 6, 9–10). The
results indicated that the optimum reaction
With the optimized reaction conditions in hand
(Table 1, entry 7), we investigated the generality of
the protocol with various substrates 1a–1q (Scheme
2). Firstly, we investigated the effect of different R3
groups on the yield, while R1=R2=Ph was maintained.
When R3 was phenyl group bearing electron-donating
or electron-withdrawing group, the corresponding
products 2a–2h were obtained in moderate to good
yields (61–79%). The reaction proceeded smoothly
when R3 was cyclohex-1-enyl group, affording the
corresponding product 2i in 90% yield. When R3 was
alkyl group including cyclohexyl, tert-butyl and
cyclopropyl groups, the corresponding targeted
products 2j–2l were obtained in moderate yields (50,
43 and 56%, respectively). The above result of yields
(Scheme 2, see 2a–2l) indicated that phenyl and
cyclohex-1-enyl groups were more compatible for this
reaction than alkyl groups. Furthermore, the
corresponding targeted products 2m–2n were
obtained in moderate yields (50 and 52%, respectively)
when substrates 1m–1n contained different
o
temperature was 150 C, and the reaction couldn’t
proceed when temperature dropped to 110 oC (Table 1,
entry 10). In addition, it was noteworthy that the
reaction couldn’t take place using the newly
purchased NMP (Table 1, entry 11). Therefore, the
2
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10.1002/adsc.201901176
Advanced Synthesis & Catalysis
substituents (R3 were methoxymethyl and thiophen-3- obtained in 50% yield. At the same time, the yield of
yl groups). Subsequently, the effect of R1 and R2 3r could be increased to 70% when the FeCl3 loading
groups on the isomerization reaction were studied was decreased to 0.5 equiv. Subsequently, we chose
when R3 was a 4-CH3Ph group. All the targeted 1s bearing a tert-butyl group at C5 position of
products 2o–2q were obtained in moderate to good isoxazole ring as the substrate, the ring-opening
yields (43, 76 and 43%, respectively). The structure product 3s was obtained in 78% yield. Finally, we
of 2g was undoubtedly confirmed by X-ray studied the electronic effect of the substituents on the
crystallographic analysis (see Supporting Information C3 position of isoxazole 1 on the ring-opening
for details).[20]
reaction. We chose 1t containing strong electron-
donating group (OCH3) and 1u containing strong
Scheme 2. Fe(III)-promoted isomerization of C4- electron-withdrawing group (CF3) as substrates to test
alkynylisoxazoles 1a–1q.[a]
the electronic effects on the ring-opening reaction.
The corresponding ring-opening products 3t and 3u
were obtained in moderate yields (60 and 42%,
respectively). Therefore, the results of electronic
effect indicated that strong electron-donating group
was more advantageous to the yield of ring-opening
product than strong electron-withdrawing group.
Scheme 3. Fe(III)-promoted reductive ring-opening of C4-
alkynylisoxazoles 1r–1u.
[a]
Reaction conditions: 1r–1u (0.2 mmol, 1 equiv.), FeCl3
(0.5 equiv.), Li2CO3 (2.0 equiv.), and NMP* (2.5 mL) at
150 oC for 8 h in a 10 mL round-bottomed flask sealed with
a pressure release cap. The mentioned yields are isolated
yields. [b] FeCl3 (2.0 equiv.).
[a]
Reaction conditions: 1a–1q (0.2 mmol, 1 equiv.), FeCl3
(2.0 equiv.), Li2CO3 (2.0 equiv.), and NMP* (2.5 mL) at
150 oC for 8 h in a 10 mL round-bottomed flask sealed with
a pressure release cap. The mentioned yields are isolated
yields.
To further evaluate the reaction effect on the scale
of preparation, scaled-up reactions were then
conducted under the current standard conditions. The
desired products 2i and 3s were obtained in 84%
(0.551 g) and 71% (0.450 g) yields, respectively,
which indicated the applications of this method in
synthetic chemistry (Scheme 4).
Under the optimized reaction conditions, substrates
1r–1u containing tert-butyl group at C3 or C5
position of isoxazole ring proceeded ring-opening not
isomerization reaction, and the ring-opening products
3r–3u were obtained (Scheme 3). Firstly, substrate 1r
bearing a tert-butyl group at C3 position of isoxazole
ring was employed, the ring-opening product 3r was
3
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10.1002/adsc.201901176
Advanced Synthesis & Catalysis
Conclusion
In summary, we have developed a new synthetic
approach to selectively synthesize 2-
alkynylenaminones and polysubstituted furans by
iron(III)-promoted reductive ring-opening and
isomerization reactions of C4-alkynylisoxazoles in
the NMP*. This is a simple and atom-economical
method for the synthesis of 2-alkynylenaminones and
polysubstituted furans. The different substituents at
the C3 and C5 position of isoxazole ring play the
crucial role in the control of chemical selectivity.
When the steric hindrance group at the C3 or C5
position of isoxazole ring is a tert-butyl group, ring-
opening product 2-alkynylenaminone is obtained. In
addition to a tert-butyl group, the smaller steric
hindrance group at the C3 or C5 position of isoxazole
ring, isomerization product polysubstituted furan is
produced in the presence of FeCl3. The detailed
mechanism and application of 2-alkynylenaminones
and furans in heterocyclic synthesis are underway in
our laboratory.
Scheme 4. Scaled-up experiment of 2i and 3s.
Based on the above results and related
literatures,[19,21] a plausible mechanism for both
reactions is proposed, as shown in Scheme 5. We
initially propose that Fe(III) complex 5 is generated
from 5-hydroxy-N-methyl-2-pyrrolidone 4 in the
presence of Fe(III) salt and Li2CO3. C4-
Alkynylisoxazole 1 then coordinates the Fe(III)
complex 5. A hydride is transferred from 5-hydroxy-
N-methyl-2-pyrrolidone 4 to the nitrogen atom of C4-
alkynylisoxazole 1 through the six-membered ring
transition state 6. The N–O bond breaks, and an
equivalent of 1-methylpyrrolidine-2,5-dione 7 is
released to form intermediate 8. Then intermediate 8
is protonated to afford β-iminoketone 9. Compound 9
tautomerizes to 2-alkynylenaminone 3. When R1 or
R2 is a tert-butyl group, the reaction could proceed
ring-opening, not isomerization. Subsequently,
coordination of Fe(III) salt to 2-alkynylenaminone 3
would form the π-alkyne Fe(III) complex 10 and
improve the electrophilicity of alkynes. The
intramolecular hydroxyl group nucleophilic attacking
alkynes occurs, resulting in intermediate 11.
Protonolysis of 11 would form intermediate 12, which
then undergo hydrolysis to give product 2.
Experimental Section
Procedure for the preparation of the NMP*
The NMP* was prepared according to a literature.[19]
A
total of 100 mL of newly purchased NMP and 5 mL of
deionized water were placed in a 250 mL two-necked flask.
The mixture was purged with nitrogen atmosphere for 10
o
min and then refluxed for 2 h at 160 C while purging with
oxygen gas to yield a yellowish transparent solution. While
cooling to room temperature, the solution was again purged
with nitrogen atmosphere. The solution (NMP*) was kept
in a sealed 150 mL round-bottomed flask.
General procedure (I) for the synthesis of C4-
alkynylisoxazoles (1k–1l, 1r, and 1t).
The C4-alkynylisoxazole 1 was synthesized according to a
[18]
literature. A 10 mL two-necked round-bottomed flask
with a reflux condenser was flame-dried under a stream of
nitrogen and cooled to room temperature. 3,5-disubstituted-
4-iodoisoxazole (0.3 mmol, 1.0 equiv.), Pd(acac)2 (4.7 mg,
5 mol %), PPh3 (7.9 mg, 10 mol %), CuI (5.8 mg, 10
mol %), and Et2NH (43.9 mg, 2 equiv.) were added,
followed by the addition of anhydrous DMF (2.5 mL). The
flask was flushed with nitrogen atmosphere and terminal
acetylene (1.0 M in DMF, 2.0 equiv.) was added gradually
by a syringe. The resulting solution was allowed to stir at
60 oC until completion as monitored by thin layer
chromatography (TLC). After cooling to room temperature,
the reaction mixture was poured into 10 mL ethyl acetate
and washed with water. Organic layer was separated, it was
dried over anhydrous MgSO4, and then filtered. The filtrate
was concentrated under vacuum, and the resulting residue
was purified by column chromatography on silica gel (200–
300 mesh) using ethyl acetate/petroleum ether as eluent to
afford the desired C4-alkynylisoxazole products 1k–1l, 1r,
and 1t.
R2
O
FeLn
N
H3C
O
N
O
H
H3C
R1
N
CH3
R2
O
N
O
R3
O
1
N
Fe(III), Li2CO3
H
R1
O
O
FeLn
6
4
-
5
-HCO3
R3
R2
NH2
O
FeLn
NH
O
R1
tautomerization
R1
R2
ring-opening
CH3
O
HN
R2
R1
R3
O
FeLn
R3
N
-
HCO3
R1 or R2 = t-Bu
O
R3
3
8
9
7
NH R2
R1
R1
NH
R2
R1
LnFe
OH
intramolecular
cyclization
NH
R2
LnFe
R3
protonolysis
Fe(III)
H
O
R3
O
R3
H
R1 and R2 are not t-Bu
R1
FeLn
O
11
12
10
hydrolysis
R2
O
2
-NH3
R3
4-(3,3-Dimethylbut-1-yn-1-yl)-3,5-diphenylisoxazole
(1k). Following general procedure (I), the product 1k was
obtained as a white solid (67.8 mg, 75% yield). Melting
point: 90−92 oC. 1H NMR (600 MHz, CDCl3) δ 8.24 (dd, J
= 8.2, 1.4 Hz, 2H), 8.15–8.11 (m, 2H), 7.51 (ddd, J = 12.9,
4.9, 1.7 Hz, 6H), 1.38 (s, 9H); 13C{1H} NMR (150 MHz,
CDCl3) δ 169.4, 162.6, 130.6, 130.2, 129.2, 128.8, 128.6,
127.9, 127.7, 126.3, 106.1, 97.9, 69.9, 30.7, 28.7; IR (film,
Scheme 5. Proposed mechanism for ring-opening and
isomerization reactions of substrate 1.
4
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10.1002/adsc.201901176
Advanced Synthesis & Catalysis
cm-1) v: 2964, 2213, 1564, 1442, 1406, 1253, 763, 694; (600 MHz, CDCl3) δ 7.90 (dd, J = 8.2, 1.1 Hz, 2H), 7.79
HRMS (ESI-ion trap): m/z [M+H]+ calcd for C21H20NO: (ddd, J = 12.1, 6.0, 4.4 Hz, 4H), 7.54 (dd, J = 10.6, 4.2 Hz,
302.1545. Found: 302.1541.
1H), 7.46–7.40 (m, 4H), 7.37–7.31 (m, 4H), 6.94 (s, 1H);
13C{1H} NMR (150 MHz, CDCl3) δ 192.0, 155.1, 152.6,
138.1, 133.1, 130.0, 129.9, 129.8, 129.2, 129.0, 128.6,
128.5, 128.3, 127.6, 124.2, 122.9, 108.8; IR (film, cm-1) v:
2925, 1650, 1482, 1447, 1236, 889, 767, 728, 691; HRMS
(ESI-ion trap): m/z [M+H]+ calcd for C23H17O2: 325.1229.
Found: 325.1223.
4-(Cyclopropylethynyl)-3,5-diphenylisoxazole
(1l).
Following general procedure (I), the product 1l was
obtained as a white solid (66.8 mg, 78% yield). Melting
o
1
point: 106−108 C. H NMR (600 MHz, CDCl3) δ 8.28–
8.17 (m, 2H), 8.08 (dd, J = 6.5, 3.2 Hz, 2H), 7.51 (dt, J =
5.6, 5.1 Hz, 6H), 1.56 (ddd, J = 10.1, 6.6, 4.1 Hz, 1H),
0.98–0.91 (m, 2H), 0.89–0.83 (m, 2H); 13C{1H} NMR (150 Phenyl(2-phenyl-5-(m-tolyl)furan-3-yl)methanone (2c).
MHz, CDCl3) δ 169.8, 162.9, 130.6, 130.2, 128.9, 128.8, Following general procedure (II), the product 2c was
1
128.7, 127.9, 127.7, 126.2, 101.2, 97.9, 65.9, 8.8, 0.8; IR obtained as a yellow oil (50.8 mg, 75% yield). H NMR
(film, cm-1) v: 2925, 2236, 1565, 1445, 1026, 779, 715, 691; (600 MHz, CDCl3) δ 7.94–7.88 (m, 2H), 7.83–7.79 (m, 2H),
HRMS (ESI-ion trap): m/z [M+H]+ calcd for C20H16NO: 7.60–7.56 (m, 2H), 7.54 (t, J = 7.4 Hz, 1H), 7.43– 7.40 (m,
286.1232. Found: 286.1225.
2H), 7.37–7.31 (m, 4H), 7.16 (d, J = 7.6 Hz, 1H), 6.93 (s,
1H), 2.43 (s, 3H); 13C{1H} NMR (150 MHz, CDCl3) δ
192.0, 155.0, 152.8, 138.7, 138.2, 133.0, 129.9, 129.8,
129.2, 129.1, 128.9, 128.6, 128.5, 127.6, 124.8, 122.9,
121.4, 108.7, 21.6; IR (film, cm-1) v: 2925, 1651, 1485,
1447, 1241, 889, 784, 691; HRMS (ESI-ion trap): m/z
[M+H]+ calcd for C24H19O2: 339.1385. Found: 339.1380.
3-(tert-Butyl)-4-(4-methoxyphenyl)ethynyl-5-
phenylisoxazole (1r). Following general procedure (I), the
product 1r was obtained as a white solid (64.6 mg, 65%
yield). Melting point: 88−90 oC. H NMR (500 MHz,
1
CDCl3) δ 8.21 (dd, J = 8.2, 1.3 Hz, 2H), 7.51–7.44 (m, 5H),
6.97–6.88 (m, 2H), 3.84 (s, 3H), 1.55 (s, 9H);13C{1H}
NMR (125 MHz, CDCl3) δ 171.5, 169.2, 160.1, 132.8, (5-(4-Methoxyphenyl)-2-phenylfuran-3-
130.5, 128.9, 127.8, 126.4, 115.2, 114.4, 97.4, 97.1, 79.1, yl)(phenyl)methanone (2d). Following general procedure
55.5, 33.6, 28.3; IR (film, cm-1) v: 2959, 2215, 1606, 1511, (II), the product 2d was obtained as a yellow oil (55.3 mg,
1250, 829, 688; HRMS (ESI-ion trap): m/z [M+H]+ calcd 78% yield). H NMR (600 MHz, CDCl3) δ 7.88 (d, J = 7.5
1
for C22H22NO2: 332.1651. Found:332.1646.
Hz, 2H), 7.76 (d, J = 7.5 Hz, 2H), 7.68 (d, J = 7.4 Hz, 2H),
7.51 (t, J = 7.3 Hz, 1H), 7.39 (t, J = 7.4 Hz, 2H), 7.33– 7.26
(m, 3H), 6.95 (d, J = 7.4 Hz, 2H), 6.79 (s, 1H), 3.83 (s, 3H);
13C{1H} NMR (150 MHz, CDCl3) δ 192.0, 159.8, 154.5,
152.7, 138.2, 133.0, 130.0, 129.9, 129.0, 128.6, 128.5,
127.5, 125.7, 123.0, 122.8, 114.5, 107.3, 55.5; IR (film,
cm-1) v: 2925, 1650, 1502, 1250, 1174, 889, 837, 691;
HRMS (ESI-ion trap): m/z [M+H]+ calcd for C24H19O3:
355.1324. Found: 355.1326.
5-(tert-Butyl)-3-(4-methoxyphenyl)-4-((4-
methoxyphenyl)ethynyl)isoxazole (1t). Following general
procedure (I), the product 1t was obtained as a white solid
(86.7 mg, 80% yield). Melting point: 81−83 C. H NMR
(600 MHz, CDCl3) δ 8.05 (d, J = 8.7 Hz, 2H), 7.42 (d, J =
8.6 Hz, 2H), 7.00 (d, J = 8.8 Hz, 2H), 6.89 (d, J = 8.7 Hz,
2H), 3.85 (s, 3H), 3.82 (s, 3H), 1.55 (s, 9H); 13C{1H} NMR
(150 MHz, CDCl3) δ 181.6, 161.8, 161.0, 159.9, 132.6,
o
1
129.3, 121.4, 115.3, 114.2, 114.0, 96.7, 95.7, 78.4, 55.5, Phenyl(2-phenyl-5-(4-propylphenyl)furan-3-
55.4, 34.7, 28.4; IR (film, cm-1) v: 2964, 2217, 1609, 1507, yl)methanone (2e). Following general procedure (II), the
1250, 1174, 1029, 832; HRMS (ESI-ion trap): m/z [M+H]+ product 2e was obtained as a yellow oil (55.7 mg, 76%
calcd for C23H24NO: 362.1756. Found: 362.1750.
yield). 1H NMR (600 MHz, CDCl3) δ 7.88 (dd, J = 8.2, 1.2
Hz, 2H), 7.80–7.75 (m, 2H), 7.66 (d, J = 8.2 Hz, 2H), 7.52
–7.49 (m, 1H), 7.38 (dd, J = 10.8, 4.8 Hz, 2H), 7.33–7.27
(m, 3H), 7.24–7.22 (m, 2H), 6.86 (s, 1H), 2.62–2.59 (m,
2H), 1.69–1.62 (m, 2H), 0.95 (t, J = 7.3 Hz, 3H); 13C{1H}
NMR (150 MHz, CDCl3) δ 192.0, 154.8, 152.9, 143.1,
138.2, 133.0, 130.0, 129.9, 129.1, 129.0, 128.6, 128.5,
127.5, 127.4, 124.2, 122.9, 108.2, 38.0, 24.6, 13.9; IR (film,
cm-1) v: 2927, 1647, 1484, 1259, 1011, 798, 762; HRMS
(ESI-ion trap): m/z [M+H]+ calcd for C26H23O2: 367.1698.
Found: 367.1690.
General procedure (II) for the synthesis of
polysubstituted furans (2a–2q).
The substrates 1a–1q (0.2 mmol, 1 equiv.), Li2CO3 (29.6
mg, 2.0 equiv.), FeCl3 (64.3 mg, 2.0 equiv.), and NMP*
(2.5 mL) were added into a 10 mL round-bottomed sealed
with a pressure release cap. The mixed solution was stirred
at 150 oC for 8 h. The reaction mixture was cooled to room
temperature and diluted with 10 mL ethyl acetate. The
mixture was washed with 10 mL of saturated NaCl aqueous
solution. The aqueous phase was extracted with ethyl
acetate (10 mL×3). The combined organic layers were
washed with water (5 mL×2), dried over anhydrous MgSO4
and concentrated under vacuum to yield the crude product,
which was purified by preparative thin layer
(5-(4-(tert-Butyl)phenyl)-2-phenylfuran-3-
yl)(phenyl)methanone (2f). Following general procedure
(II), the product 2f was obtained as a yellow oil (47.2 mg,
1
62% yield). H NMR (600 MHz, CDCl3) δ 7.91 (d, J = 7.2
Hz, 2H), 7.82–7.79 (m, 2H), 7.71 (d, J = 8.4 Hz, 2H), 7.54
(t, J = 7.4 Hz, 1H), 7.48 (d, J = 8.4 Hz, 2H), 7.42 (t, J = 7.7
Hz, 2H), 7.37–7.31 (m, 3H), 6.90 (s, 1H), 1.37 (s, 9H);
13C{1H} NMR (150 MHz, CDCl3) δ 192.0, 154.8, 152.8,
151.5, 138.2, 133.0, 129.9, 129.1, 128.6, 128.5, 127.5,
127.1, 125.9, 124.1, 122.9, 108.3, 34.9, 31.4; IR (film, cm-1)
v: 2959, 1651, 1487, 1451, 1268, 887, 727, 691; HRMS
(ESI-ion trap): m/z [M+H]+ calcd for C27H25O2: 381.1855.
Found: 381.1849.
chromatography
silica
gel
plates
using
ethyl
acetate/petroleum ether as the developing solvents to afford
the desired products 2a–2q.
Phenyl(2-phenyl-5-(p-tolyl)furan-3-yl)methanone (2a).
Following general procedure (II), the product 2a was
obtained as a green oil (53.4 mg, 79% yield). 1H NMR (600
MHz, CDCl3) δ 7.88 (d, J = 7.7 Hz, 2H), 7.79–7.74 (m,
2H), 7.64 (d, J = 8.1 Hz, 2H), 7.51 (t, J = 7.4 Hz, 1H), 7.39
(t, J = 7.7 Hz, 2H), 7.34–7.28 (m, 3H), 7.23 (t, J = 5.4 Hz,
2H), 6.86 (s, 1H), 2.37 (s, 3H); 13C{1H} NMR (150 MHz,
CDCl3) δ 192.0, 154.8, 152.9, 138.3, 138.2, 133.0, 130.0,
129.9, 129.7, 129.1, 128.6, 128.5, 127.5, 127.2, 124.2,
122.9, 108.1, 21.5; IR (film, cm-1) v: 2923, 1651, 1499,
1483, 1236, 889, 815, 731, 691; HRMS (ESI-ion trap): m/z
[M+H]+ calcd for C24H19O2: 339.1385. Found: 339.1383.
(5-(4-Fluorophenyl)-2-phenylfuran-3-
yl)(phenyl)methanone (2g). Following general procedure
(II), the product 2g was obtained as a yellow solid (50.0
o
mg, 73% yield). Melting point: Melting point: 85−87 C.
1H NMR (600 MHz, CDCl3) δ 7.90 (dd, J = 8.2, 1.1 Hz,
2H), 7.77 (dd, J = 8.0, 1.5 Hz, 2H), 7.75–7.69 (m, 2H),
7.56–7.51 (m, 1H), 7.41 (t, J = 7.8 Hz, 2H), 7.36–7.29 (m,
3H), 7.16–7.10 (m, 2H), 6.88 (s, 1H); 13C{1H} NMR (150
MHz, CDCl3) δ 191.8, 163.6, 161.9, 155.1, 151.8, 138.1,
133.1, 129.9, 129.7, 129.2, 128.6 (d, J = 4.5 Hz), 127.6,
126.3 (d, J = 3 Hz), 126.1 (d, J = 9 Hz), 122.9, 116.1 (d, J
= 22.5 Hz), 108.5; IR (film, cm-1) v: 2925, 1651, 1499,
(2,5-Diphenylfuran-3-yl)(phenyl)methanone
(2b).
Following general procedure (II), the product 2b was
1
obtained as a yellow oil (39.6 mg, 61% yield). H NMR
5
This article is protected by copyright. All rights reserved.

10.1002/adsc.201901176
Advanced Synthesis & Catalysis
1234, 1159, 997, 808; HRMS (ESI-ion trap): m/z [M+H]+ (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 191.8, 156.3,
calcd for C23H16O2: 343.1134. Found: 343.1130.
150.6, 138.1, 133.0, 132.4, 132.3, 129.8, 129.3, 128.7,
128.6, 128.5, 128.4, 127.8, 121.5, 113.3, 66.3, 58.4; IR
(film, cm-1) v: 2925, 1651, 1476, 1443, 1093, 885, 725,
691; HRMS (ESI-ion trap): m/z [M+H]+ calcd for
C19H17O3: 293.1178. Found: 293.1172.
Phenyl(5-phenyl-2-(4-(trifluoromethyl)phenyl)furan-3-
yl)methanone (2h). Following general procedure (II), the
product 2h was obtained as a yellow oil (50.0 mg, 73%
yield). 1H NMR (600 MHz, CDCl3) δ 7.89 (dd, J = 8.3, 1.2
Hz, 2H), 7.85 (d, J = 8.1 Hz, 2H), 7.80–7.74 (m, 2H), 7.69 Phenyl(2-phenyl-5-(thiophen-3-yl)furan-3-yl)methanone
(d, J = 8.3 Hz, 2H), 7.56–7.53 (m, 1H), 7.44–7.40 (m, 2H), (2n). Following general procedure (II), the product 2n was
7.37–7.32 (m, 3H), 7.06 (s, 1H); 13C{1H} NMR (150 MHz, obtained as a yellow oil (34.4 mg, 52% yield). H NMR
1
CDCl3) δ 191.6, 156.1, 151.1, 137.9, 133.3, 133.1, 130.1, (600 MHz, CDCl3) δ 7.88 (dd, J = 8.3, 1.2 Hz, 2H), 7.79–
130.0, 129.8, 129.6, 129.5, 128.7 (d, J = 1.5 Hz), 127.8, 7.73 (m, 2H), 7.62 (dd, J = 2.8, 1.3 Hz, 1H), 7.54–7.51 (m,
126.1 (q, J = 3 Hz), 124.3, 124.2 (q, J = 270 Hz), 123.2, 1H), 7.42–7.37 (m, 4H), 7.35–7.30 (m, 3H), 6.76 (s, 1H);
110.7; IR (film, cm-1) v: 2923, 1650, 1485, 1325, 1124, 13C{1H} NMR (150 MHz, CDCl3) δ 191.9, 154.6, 149.7,
1069, 887, 767, 691; HRMS (ESI-ion trap): m/z [M+H]+ 138.1, 133.1, 131.5, 129.9, 129.8, 129.1, 128.6, 128.5,
calcd for C24H16F3O2: 393.1102. Found: 393.1096.
127.6, 126.8, 124.8, 122.6, 120.4, 108.5; IR (film, cm-1) v:
2958, 1651, 1485, 1443, 1263, 1237, 887, 779, 691; HRMS
(ESI-ion trap): m/z [M+H]+ calcd for C21H15O2S: 331.0793.
Found: 331.0786.
(5-(Cyclohex-1-en-1-yl)-2-phenylfuran-3-
yl)(phenyl)methanone (2i). Following general procedure
(II), the product 2i was obtained as a yellow oil (59.1 mg,
90% yield). 1H NMR (600 MHz, CDCl3) δ 7.85 (dd, J = 8.2, 2-Methyl-1-(2-phenyl-5-(p-tolyl)furan-3-yl)propan-1-
1.2 Hz, 2H), 7.72–7.69 (m, 2H), 7.50 (dd, J = 10.5, 4.3 Hz, one (2o). Following general procedure (II), the product 2o
1H), 7.37 (dd, J = 10.8, 4.8 Hz, 2H), 7.31–7.26 (m, 3H), was obtained as a white solid (26.3 mg, 43% yield).
o
1
6.52–6.48 (m, 1H), 6.44 (s, 1H), 2.32 (td, J = 6.1, 2.0 Hz, Melting point: 81−83 C. H NMR (600 MHz, CDCl3) δ
2H), 2.28–2.24 (m, 2H), 1.76 (dt, J = 8.5, 4.7 Hz, 2H), 1.69 7.96 (dt, J = 3.1, 1.8 Hz, 2H), 7.62 (d, J = 8.2 Hz, 2H),
(dt, J = 5.6, 4.6 Hz, 2H); 13C{1H} NMR (150 MHz, CDCl3) 7.47–7.43 (m, 2H), 7.42–7.38 (m, 1H), 7.23–7.21 (m, 2H),
δ 192.2, 154.3, 154.1, 138.3, 132.9, 130.1, 129.9, 128.9, 6.94 (s, 1H), 3.20 (hept, J = 6.8 Hz, 1H), 2.37 (s, 3H), 1.19
128.5, 128.4, 127.5, 126.6, 124.7, 122.4, 107.4, 25.4, 24.9, (d, J = 6.9 Hz, 6H); 13C{1H} NMR (150 MHz, CDCl3) δ
22.4, 22.2; IR (film, cm-1) v: 2933, 1651, 1482, 1444, 1262, 201.3, 155.5, 153.0, 138.3, 130.3, 129.7, 129.5, 128.5,
892, 728, 685; HRMS (ESI-ion trap): m/z [M+H]+ calcd for 128.4, 127.2, 124.1, 123.0, 106.3, 38.9, 21.5, 19.0; IR (film,
C23H21O2: 329.1542. Found: 329.1538.
cm-1) v: 2925, 1668, 1500, 1478, 1045, 935, 808, 745, 682;
HRMS (ESI-ion trap): m/z [M+H]+ calcd for C21H21O2:
305.1542. Found: 305.1535.
(5-Cyclohexyl-2-phenylfuran-3-yl)(phenyl)methanone
(2j). Following general procedure (II), the product 2j was
1
obtained as a yellow oil (33.1 mg, 50% yield). H NMR (2-Pentyl-5-(p-tolyl)furan-3-yl)(phenyl)methanone (2p).
(600 MHz, CDCl3) δ 7.83 (d, J = 7.4 Hz, 2H), 7.67–7.64 Following general procedure (II), the product 2p was
1
(m, 2H), 7.49 (t, J = 7.4 Hz, 1H), 7.36 (t, J = 7.7 Hz, 2H), obtained as a yellow oil (50.5 mg, 76% yield). H NMR
7.29–7.24 (m, 3H), 6.27 (s, 1H), 2.76–2.67 (m, 1H), 2.10 (d, (600 MHz, CDCl3) δ 7.86 (d, J = 7.9 Hz, 2H), 7.57 (dd, J =
J = 12.6 Hz, 2H), 1.85–1.79 (m, 2H), 1.73 (d, J = 12.9 Hz, 14.2, 7.6 Hz, 3H), 7.50 (t, J = 7.6 Hz, 2H), 7.21 (d, J = 8.0
1H), 1.49–1.36 (m, 4H), 1.31–1.25 (m, 1H); 13C{1H} NMR Hz, 2H), 6.74 (s, 1H), 2.98 (t, J = 7.6 Hz, 2H), 2.37 (s, 3H),
(150 MHz, CDCl3) δ 192.4, 160.0, 154.3, 138.4, 132.8, 1.86 – 1.73 (m, 2H), 1.35 (t, J = 8.1 Hz, 4H), 0.91 (t, J =
130.3, 129.9, 128.7, 128.4, 128.3, 127.5, 121.6, 107.2, 37.2, 6.5 Hz, 3H); 13C{1H} NMR (150 MHz, CDCl3) δ 191.5,
31.5, 26.1, 26.0; IR (film, cm-1) v: 2925, 1651, 1446, 1262, 162.8, 151.8, 139.4, 137.8, 132.3, 129.6, 129.1, 128.5,
1171, 886, 725, 693; HRMS (ESI-ion trap): m/z [M+H]+ 127.5, 123.8, 122.0, 105.9, 31.6, 28.1, 28.0, 22.5, 21.4,
calcd for C23H23O2: 331.1698. Found: 331.1693.
14.1; IR (film, cm-1) v: 2927, 1651, 1502, 1257, 898, 810,
693; HRMS (ESI-ion trap): m/z [M+H]+ calcd for
C23H25O2: 333.1855. Found: 333.1849.
(5-(tert-Butyl)-2-phenylfuran-3-yl)(phenyl)methanone
(2k). Following general procedure (II), the product 2k was
1
obtained as a yellow oil (26.2 mg, 43% yield). H NMR (2-Cyclopropyl-5-(p-tolyl)furan-3-yl)(phenyl)methanone
(600 MHz, CDCl3) δ 7.83 (dd, J = 8.2, 1.1 Hz, 2H), 7.68– (2q). Following general procedure (II), the product 2q was
1
7.61 (m, 2H), 7.51–7.47 (m, 1H), 7.36 (t, J = 7.8 Hz, 2H), obtained as a yellow oil (26.1 mg, 43% yield). H NMR
7.29–7.25 (m, 3H), 6.28 (s, 1H), 1.36 (s, 9H); 13C{1H} (600 MHz, CDCl3) δ 7.89 (d, J = 7.4 Hz, 2H), 7.57 (t, J =
NMR (150 MHz, CDCl3) δ 192.4, 163.3, 154.4, 138.4, 7.4 Hz, 1H), 7.52–7.46 (m, 4H), 7.18 (d, J = 8.0 Hz, 2H),
132.8, 130.3, 129.9, 128.7, 128.4, 128.3, 127.5, 121.5, 6.76 (s, 1H), 2.61–2.66 (m, 1H), 2.36 (s, 3H), 1.24–1.21 (m,
106.3, 32.9, 29.1; IR (film, cm-1) v: 2968, 1651, 1485, 1360, 2H), 1.12–1.07 (m, 2H); 13C{1H} NMR (150 MHz, CDCl3)
1260, 886, 726, 688; HRMS (ESI-ion trap): m/z [M+H]+ δ 191.5, 163.1, 150.6, 139.6, 137.7, 132.2, 129.5, 129.2,
calcd for C21H21O2: 305.1542. Found: 305.1536.
128.5, 127.3, 123.7, 122.2, 106.3, 21.4, 10.2, 9.6; IR (film,
cm-1) v: 2918, 1639, 1560, 1394, 1241, 901, 813, 700;
HRMS (ESI-ion trap): m/z [M+H]+ calcd for C21H19O2:
303.1385. Found:303.1388.
(5-Cyclopropyl-2-phenylfuran-3-yl)(phenyl)methanone
(2l). Following general procedure (II), the product 2l was
1
obtained as a yellow oil (32.3 mg, 56% yield). H NMR
(400 MHz, CDCl3) δ 7.85–7.80 (m, 2H), 7.63 (dd, J = 7.8, General procedure (III) for the synthesis of 2-
1.7 Hz, 2H), 7.49 (t, J = 7.4 Hz, 1H), 7.36 (t, J = 7.7 Hz, alkynylenaminones (3r–3u).
2H), 7.28–7.23 (m, 3H), 6.26 (s, 1H), 2.00–1.92 (m, 1H),
0.97 (ddd, J = 8.3, 5.5, 3.5 Hz, 2H), 0.91–0.86 (m, 2H);
Substrates 1r–1u (0.2 mmol, 1 equiv.), Li2CO3 (29.6 mg,
13C{1H} NMR (100 MHz, CDCl3) δ 192.1, 156.5, 154.0,
2.0 equiv.), FeCl3 (16.1 mg, 0.5 equiv.), and NMP* (2.5
138.3, 132.8, 130.1, 129.8, 128.7, 128.4, 128.3, 127.3,
mL) were added into a 10 mL round-bottomed flask sealed
121.8, 107.7, 8.8, 7.2; IR (film, cm-1) v: 2926, 1651, 1484,
with a pressure release cap. The mixed solution was stirred
o
1447, 1260, 1069, 885, 727, 693; HRMS (ESI-ion trap):
at 150 C for 8 h, then cooled to room temperature and
m/z [M+H]+ calcd for C20H17O2: 289.1229. Found:
diluted with 10 mL ethyl acetate. The reaction mixture was
289.1225.
washed with 10 mL of saturated NaCl aqueous solution.
The aqueous phase was extracted with ethyl acetate (10
(5-(Methoxymethyl)-2-phenylfuran-3-
mL×3). The combined organic layers were washed with
yl)(phenyl)methanone (2m). Following general procedure water (5 mL×2), dried over anhydrous MgSO4 and
(II), the product 2m was obtained as a yellow oil (29.3 mg, concentrated under vacuum to yield the crude product,
1
50% yield). H NMR (400 MHz, CDCl3) δ 7.88–7.80 (m, which was purified by preparative thin layer
2H), 7.71–7.68 (m, 2H), 7.52–7.48 (m, 1H), 7.37 (t, J = 7.7 chromatography
Hz, 2H), 7.33–7.27 (m, 3H), 6.64 (s, 1H), 4.48 (s, 2H), 3.45
silica
gel
plates
using
ethyl
6
This article is protected by copyright. All rights reserved.

10.1002/adsc.201901176
Advanced Synthesis & Catalysis
acetate/petroleum ether as the developing solvents to afford Experimental procedure for the scaled-up synthesis of
the desired products 3r–3u.
product 3s.
(Z)-3-Amino-2-((4-methoxyphenyl)ethynyl)-4,4-
Substrate 1s (2 mmol, 1 equiv.), Li2CO3 (295.6 mg, 2.0
dimethyl-1-phenylpent-2-en-1-one
(3r).
Following equiv.), FeCl3 (160.8 mg, 0.5 equiv.), and NMP* (25 mL)
general procedure (III), the product 3r was obtained as a were added into a 100 mL round-bottomed flask sealed
yellow solid (46.4 mg, 70% yield). Melting point: 140–142 with a pressure release cap. The mixed solution was stirred
oC. 1H NMR (600 MHz, CDCl3) δ 12.18 (s, 1H), 7.76 (d, J at 150 C for 8 h, then cooled to room temperature and
o
= 6.9 Hz, 2H), 7.42–7.35 (m, 3H), 6.99 (d, J = 8.4 Hz, 2H), diluted with 40 mL ethyl acetate. The reaction mixture was
6.75 (d, J = 8.5 Hz, 2H), 6.11 (s, 1H), 3.76 (s, 3H), 1.56 (s, washed with 40 mL of saturated NaCl aqueous solution.
9H); 13C{1H} NMR (150 MHz, CDCl3) δ 196.6, 179.5, The aqueous phase was extracted with ethyl acetate (40
158.5, 142.1, 130.7, 129.6, 128.3, 127.3, 117.6, 114.0, 96.4, mL×3). The combined organic layers were washed with
89.9, 89.4, 55.4, 38.4, 27.4; IR (film, cm-1) v: 3404, 2961, water (20 mL×2), dried over anhydrous MgSO4 and
2200, 1607, 1509, 1277, 1248, 1026, 828, 698; HRMS concentrated under vacuum to yield the crude product,
(ESI-ion trap): m/z [M+H]+ calcd for C22H24NO2: 334.1807. which was purified by column chromatography on silica
Found:334.1800.
gel (eluent: acetate/petroleum ether 8/1, v/v) to afford
product 3s as a yellow oil (0.450 g, 71% yield).
(Z)-4-(Amino(phenyl)methylene)-2,2-dimethyl-6-(p-
tolyl)hex-5-yn-3-one (3s). Following general procedure
(III), the product 3s was obtained as a yellow oil (49.8 mg,
Acknowledgements
1
78% yield). H NMR (600 MHz, CDCl3) δ 10.79 (s, 1H),
7.63 (d, J = 6.5 Hz, 2H), 7.49–7.43 (m, 3H), 7.01 (d, J =
7.9 Hz, 2H), 6.93 (d, J = 8.0 Hz, 2H), 5.58 (s, 1H), 2.30 (s,
3H), 1.50 (s, 9H); 13C{1H} NMR (150 MHz, CDCl3) δ
206.9, 168.5, 137.9, 136.5, 129.9, 129.3, 129.0, 128.5,
128.2, 122.1, 94.1, 90.1, 89.6, 44.6, 27.2, 21.5; IR (film,
cm-1) v: 3358, 2925, 2203, 1587, 1563, 1454, 1183, 1116,
816, 696; HRMS (ESI-ion trap): m/z [M+H]+ calcd for
C22H24NO: 318.1858. Found: 318.1852.
We gratefully thank the National Natural Science Foundation of
China (21172081, 21372090), the Natural Science Foundation of
Guangdong Province (S2013020013091) and the City of
Guangzhou
Science
and
Technology
Plan
Projects
(201510010054) for financial support. The authors gratefully
acknowledge the assistance of Huanyong Li from the
characterization center of Jinan University for the single crystal
characterizations.
(Z)-4-(Amino(4-methoxyphenyl)methylene)-6-(4-
methoxyphenyl)-2,2-dimethylhex-5-yn-3-one
(3t).
Following general procedure (III), the product 3t was
obtained as a yellow solid (43.6 mg, 60% yield). Melting
point: 128–130 oC. 1H NMR (600 MHz, CDCl3) δ 10.79 (s,
1H), 7.61 (d, J = 8.8 Hz, 2H), 7.03 (d, J = 8.8 Hz, 2H), 6.94
(d, J = 8.8 Hz, 2H), 6.76 (d, J = 8.8 Hz, 2H), 5.50 (s, 1H),
3.85 (s, 3H), 3.76 (s, 3H), 1.47 (s, 9H); 13C{1H} NMR (150
MHz, CDCl3) δ 206.8, 167.9, 161.0, 158.5, 130.9, 130.3,
130.2, 117.6, 114.0, 113.4, 93.6, 89.6, 89.5, 55.5, 55.4,
44.5, 27.3; IR (film, cm-1) v: 3383, 2927, 2201, 1607, 1507,
1248, 1172, 1033, 832, 681; HRMS (ESI-ion trap): m/z
[M+H]+ calcd for C22H26NO3: 364.1913. Found: 364.1907.
References
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2065.
(Z)-4-(Amino(4-(trifluoromethyl)phenyl)methylene)-
2,2-dimethyl-6-(p-tolyl)hex-5-yn-3-one (3u). Following
general procedure (III), the product 3u was obtained as a
yellow solid (32.4 mg, 42% yield). Melting point: 122−124
oC. 1H NMR (600 MHz, CDCl3) δ 10.70 (s, 1H), 7.75–7.71
(m, 4H), 7.01 (d, J = 7.9 Hz, 2H), 6.85 (d, J = 8.0 Hz, 2H),
5.41 (s, 1H), 2.29 (s, 3H), 1.47 (s, 9H); 13C{1H} NMR (150
MHz, CDCl3) δ 207.2, 166.5, 141.5, 137.1, 131.8 (q, J =
31.5 Hz), 129.5, 129.2, 125.3 (q, J = 3 Hz), 124.0 (q, J =
270 Hz), 121.7, 94.6, 90.3, 89.3, 44.8, 27.2, 21.5; IR (film,
cm-1) v: 3368, 2928, 2202, 1590, 1562, 1318, 1132, 1065,
849, 737; HRMS (ESI-ion trap): m/z [M+H]+ calcd for
C23H23F3NO: 386.1732. Found: 386.1730.
[2] F. Hu, M. Szostak, Adv. Synth. Catal. 2015, 357, 2583–
Experimental procedure for the scaled–up synthesis of
product 2i.
2614.
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10.1002/adsc.201901176
Advanced Synthesis & Catalysis
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8
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10.1002/adsc.201901176
Advanced Synthesis & Catalysis
FULL PAPER
Iron-Promoted Reductive Ring-Opening and
Isomerization Reactions of C4-Alkynylisoxazoles
Leading to 2-Alkynylenaminones and
Polysubstituted Furans
Adv. Synth. Catal. 2019, Volume, Page – Page
Wen Yang,a Yu Chen,b Yongqi Yao,a Qifu Lin,a
and Dingqiao Yang a*
9
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