A convenient access to furo[3,2-c]pyridin-6(5H)-ones by the reaction of 5-iodo-4-methoxy-2-pyridones with terminal alkynes under microwave-enhanced Sonogashira conditions

Article abstract of DOI:10.1016/j.tetlet.2009.02.073

N-Alkyl-3-aryl-5-iodo-4-methoxypyridin-2(1H)-ones readily undergo sequential acetylide cross-coupling, demethylation, and furan annulation under classical Sonogashira reaction conditions to furnish 7-arylfuro[3,2-c]pyridin-4(5H)-ones, a class of hitherto

Full text of DOI:10.1016/j.tetlet.2009.02.073

Tetrahedron Letters 50 (2009) 3299–3301
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Tetrahedron Letters
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A convenient access to furo[3,2-c]pyridin-6(5H)-ones by the reaction
of 5-iodo-4-methoxy-2-pyridones with terminal alkynes under
microwave-enhanced Sonogashira conditions
a,
David Conreaux a, Thierry Delaunay a, Philippe Desbordes b, Nuno Monteiro a, , Geneviève Balme
*
*
a ICBMS, Institut de Chimie et de Biochimie Moléculaire et Supramoléculaire (UMR 5246 du CNRS) - Université Lyon 1 - ESCPE Lyon. 43 Bd du 11 novembre 1918,
69622 Villeurbanne, France
b Bayer CropScience, 14/20 rue Baizet, BP 9163, 69623 Lyon Cedex 09, France
a r t i c l e i n f o
a b s t r a c t
Article history:
N-Alkyl-3-aryl-5-iodo-4-methoxypyridin-2(1H)-ones readily undergo sequential acetylide cross-cou-
pling, demethylation, and furan annulation under classical Sonogashira reaction conditions to furnish
7-arylfuro[3,2-c]pyridin-4(5H)-ones, a class of hitherto unknown compounds, in a one-pot operation.
Microwave irradiation was found to significantly reduce reaction times and to allow lower catalysts
and reagent loadings.
Received 15 January 2009
Revised 5 February 2009
Accepted 10 February 2009
Available online 14 February 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Sonogashira cross-coupling
Alkynes
Annulation
Furopyridinones
Microwave-assisted synthesis
The phenyl(dihydro)furopyridinone system is present in several
structurally and biologically interesting fungal metabolites, which
have been recently reported as antibacterial or antifungal antibiot-
ics.1 Two differently fused ring systems are found in these natural
products, namely the phenylfuro[2,3-b]pyridin-4-one I and the
regioisomeric phenylfuro[3,2-c]pyridin-4-one II systems. Synthetic
efforts toward this class of compounds have already been reported
in the literature.2 In the present work, we examined the possibility
of synthesizing arylfuropyridones of type III prompted by the fact
that, to the best of our knowledge, the furo[3,2-c]pyridin-6-one
ring system has never been reported in the literature (Fig. 1).
Recently, we have shown that 5-aryl-3-iodopyridin-2-ones 1
can give easy access to 2-substituted furan derivatives 2 through
in situ sequential Sonogashira-acetylide coupling, demethylation,
and furan annulation reactions. In this one-pot process, Et3N-pro-
moted SN2 demethylation of the intermediate 3-alkynyl-4-meth-
oxypyridin-2-ones was found to induce metal-free anionic
heteroannulation (Scheme 1, Eq. 1).3 We envisioned this methodol-
ogy to be applicable to the synthesis of the regioisomeric arylfuro-
pyridones 4 (Scheme 1, Eq. 2).
from readily available 3-iodo-2-pyridones 54 through Suzuki–
Miyaura cross-coupling reactions5, followed by C-5 iodination of
O
O
O
O
N
N
H
N
O
O
H
H
III
I
II
Figure 1. Regioisomeric phenylfuropyridinone ring systems.
R'
O
OMe
N
I
Ar
Ar
R'
(1)
Pd / Cu
N
O
O
Et3N
R
R
2
1
R'
OMe
O
First, we prepared a series of 3-aryl-5-iodo-4-methoxy-2-pyri-
dones 3a–e, which proved to be easily accessible in high yields
Ar
I
Ar
?
(2)
as above
N
R
O
N
R
O
3
4
* Corresponding authors. Tel.: +33 472 431416; fax: +33 472 431214.
E-mail addresses: monteiro@univ-lyon1.fr (N. Monteiro), balme@univ-lyon1.fr
(G. Balme).
Scheme 1.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.02.073

3300
D. Conreaux et al. / Tetrahedron Letters 50 (2009) 3299–3301
the resulting arylpyridone by N-iodosuccinimide in the presence of
TFA6 (Table 1).
O
O
O
Me
Me
Me
O
O
OEt
O
OEt
OEt
The first assays to determine the viability of 5-iodo-2-pyridones
participating in the coupling–demethylation–annulation process
were carried out by using our previously reported reaction condi-
tions. A series of model substrates including electron-rich and elec-
tron-poor arylpyridones (3a, b, e) were selected to evaluate
possible electronic effects on the rate of reactions. The latter were
heated at 80 °C in Et3N/DMF (2:1) in the presence of 3 equiv of a
terminal alkyne, 10 mol % PdCl2(PPh3)2, and 20 mol % CuI for
5 days. The results are summarized in Table 2. As can be seen,
the desired compounds 4 were obtained in isolated yields ranging
from 20% to 78% depending essentially on the nature of the pyri-
done-substituted arene.7 As illustrated with the reactions of 3a
(Table 2, entries 1–3), the presence of an electron-donating group
on the arylpyridone had a negative effect on the rate of the dealky-
lation process, which left substantial amounts of alkynylpyridone
intermediates 7 unreacted. Conversely, best results were obtained
with an electron-poor arylic group (Table 2, entries 5–7). Indeed, it
is expected that the presence of an electron-withdrawing group,
such as an ester group, on the arylic moiety of the starting pyri-
done would favor cleavage of the methyl ether by triethylamine,
as this generates a highly stabilized triethylmethyl ammonium
enolate 8 (Scheme 2). On the other hand, the nature of the arylacet-
ylene partner did not exert significant influence on the rate of the
reaction.
N
R
O
N
R
O
N
R
O
Et3N
O
Et3N Me
O
OEt
N
R
8
O
Scheme 2.
Table 3
Synthesis of arylfuropyridones 4a–c and 4h–j under micro-wave irradiationa
R1
R1
OMe
O
(1.1 equiv)
I
Ar
O
Ar
O
5 mol % PdCl2(PPh3)2
5 mol% CuI
Et3N/MeCN, µw 160 ºC
60-150 min
N
N
Me
4
Me
3
Despite this success, we were concerned that the present pro-
cess had two considerable drawbacks: (1) reaction times are very
long which render the production of the desired furopyridones
Entry
Starting iodopyridone
Ar=
Alkyne R1=
Time (min) Product 4; yield (%)
1
2
3
4
5
6
p-MeOPh
p-MeOPh
p-MeOPh
p-CO2EtPh
m-CF3Ph
m-CF3Ph
(3a)
(3a)
(3a)
(3c)
(3d)
(3d)
Ph
p-MeOPh
p-CO2MePh 150
p-MeOPh
Ph
150
150
4a; 80
4b; 73
4c; 93
4h; 78
4i; 94
4j; 66b
60
60
Table 1
Synthesis of 3-aryl-5-iodo-2-pyridones 3a–ea
n-Bu
120
OMe
ArB(OH)2
cat Pd(OAc)2
TPPTS
OMe
OMe
N
R
3
a
Isolated yields (single runs).
3 equiv of 1-hexyne was used.
I
b
Ar
O
I
Ar
O
NIS/TFA
N
R
5
O
MeCN, rt.
N
R
6
i-Pr2NH
MeCN/H2O
60 ºC
by this method particularly inconvenient, and (2) high catalyst
loadings as well as large excesses of the alkyne partner are re-
quired. We therefore envisaged the possibility of accelerating this
process by using microwave catalysis. After some experimentation,
we established a successful microwave protocol8 using MeCN as
solvent that allowed low catalysts and alkyne loading coupling
reactions as well as rapid and complete furan formation. The re-
sults are summarized in Table 3. As in the conventional protocol,
it was found that pyridones bearing an electron-rich arylic group
reacted more slowly, but still gave good yields of the desired furo-
pyridones within reasonable reaction times under microwave irra-
diation (compare entries 1–3 in Tables 2 and 3). As illustrated with
the reaction of 1-hexyne (Table 3, entries 6), alkyl-substituted
acetylenes participated less efficiently in the process.
In summary, we have shown that microwave-assisted reaction
of 3-aryl-5-iodo-4-methoxy-2-pyridones with terminal alkynes
under Sonogashira conditions provides an easy and efficient access
to hitherto unknown arylfuro[3,2-c]pyridin-6-one derivatives9
through sequential acetylide cross-coupling, O-dealkylation, and
anionic annulation reactions. Further investigation into the scope
and limitations of this process is underway.
Entry
Pyridone 5 R=
Boronic acid Ar=
6; yield (%)
3; yield (%)
1
2
3
4
5
Me
Me
Me
Me
Bn
p-MeOPh
Ph
p-CO2EtPh
m-CF3Ph
p-CO2EtPh
6a; 89
6b; 82
6c; 90
6d; 87
6e; 88
3a; 95
3b; 74
3c; 52
3d; 92
3e; 98
a
TPPTS: tris(3-sulfonatophenyl)phosphane trisodium salt.
Table 2
Synthesis of arylfuropyridones 4a–g under conventional heatinga
Ar2
Ar2
OMe
Ar2
(3 equiv)
OMe
O
Ar1
O
Ar1
O
I
Ar1
O
+
10 mol % PdCl2(PPh3)2
20 mol% CuI
Et3N/DMF, 80 ºC
5 days
N
R
7
N
R
3
N
R
4
Entry
Starting iodopyridone
Alkyne Ar2=
Products yield (%) 4 (7)
R=
Ar1=
1
2
3
4
5
6
7
3a Me
3a Me
3a Me
3b Me
3e Bn
3e Bn
3e Bn
p-MeOPh
p-MeOPh
p-MeOPh
Ph
p-CO2EtPh
p-CO2EtPh
p-CO2EtPh
Ph
4a; 20 (7a; 74)
4b; 27 (7b; 70)
4c; 33 (7c; 43)
4d; 60 (7d; 38)
4e; 78 (7e; 18)
4f; 61 (7f; 28)
4g; 77 (7g; 19)
p-MeOPh
p-CO2MePh
Ph
Acknowledgments
Ph
Financial support from Bayer CropScience, the CNRS, and the
French Ministry of Higher Education and Research (MESR) is grate-
fully acknowledged. We thank Dr. D. Bouchu for mass spectro-
scopic analysis.
p-MeOPh
p-CO2MePh
a
Isolated yields (single runs).

D. Conreaux et al. / Tetrahedron Letters 50 (2009) 3299–3301
3301
subsequent cooling, the mixture was concentrated in vacuo, and the residue was
purified by column chromatography (silica gel, acetone/CH2Cl2) to give the
corresponding furopyridone.
References and notes
1. (a) Fukuda, T.; Tomoda, H.; Omura, S. J. Antibiot. 2005, 58, 315; (b) Fukuda, T.;
Yamaguchi, Y.; Masuma, R.; Tomoda, H.; Omura, S. J. Antibiot. 2005, 58, 309; (c)
Sakemi, S.; Bordner, J.; DeCosta, D. L.; Dekker, K. A.; Hirai, H.; Inagaki, T.; Kim, Y.-
J.; Kojima, N.; Sims, J. C.; Sugie, Y.; Sugiura, A.; Sutcliffe, J. A.; Tachikawa, K.;
Truesdell, S. J.; Wong, J. W.; Yoshikawa, N.; Kojima, Y. J. Antibiot. 2002, 55, 6.
2. (a) Snider, B. B.; Che, G. Org. Lett. 2004, 6, 2877; (b) Clive, D. L. J.; Huang, X. J. Org.
Chem. 2004, 69, 1872.
9. Analytical data: Compound 4a: Solid; Mp: 160–164 °C. 1H NMR (300 MHz,
CDCl3): d 3.71 (s, NMe); 3.86 (s, OMe), 6.72 (s, 1H), 7.01 (d, J = 8.5 Hz, 2H), 7.34–
7.40 (m, 3H), 7.58 (s, 1H), 7.71 (d, J = 7.5 Hz, 2H), 7.92 (d, J = 8.5 Hz, 2H). 13C NMR
(75 MHz, CDCl3): d 39.2; 55.3; 98.2; 109.1; 113.5; 115.3; 124.4; 124.9; 127.7;
128.8; 129.1; 129.2; 131.2; 156.8; 158.9; 160.1; 161.4. HRMS (ESI): MH+,
332.1288; Calcd for C21H17NO3: 332.1287. Compound 4b: Solid; Mp >205 °C. 1
H
NMR (300 MHz, CDCl3): d 3.71 (s, NMe); 3.84 (s, OMe), 3.87 (s, OMe), 6.57 (s,
1H), 6.94 (dd, J = 6.9 and 2.0 Hz, 2H), 7.02 (d, J = 8.8 Hz, 2H), 7.52 (s, 1H), 7.65
(dd, J = 6.9 and 2.0 Hz, 2H), 7.93 (d, J = 8.8 Hz, 2H). 13C NMR (75 MHz, CDCl3): d
39.2; 55.4; 55.5; 96.3; 113.3; 113.5; 114.3; 115.7; 122.0; 124.5; 126.5; 127.1;
131.2; 157.0; 158.9; 160.1; 160.5. HRMS (ESI): MH+, 362.1392; Calcd for
C22H20NO4: 362.1385. Compound 4c: Solid; Mp >205 °C. 1H NMR (300 MHz,
CDCl3): d 3.72 (s, NMe); 3.88 (s, OMe), 3.93 (s, OMe), 6.85 (s, 1H), 7.02 (d,
J = 8.8 Hz, 2H), 7.64 (s, 1H), 7.76 (d, J = 8.5 Hz, 2H), 7.92 (d, J = 8.8 Hz, 2H), 8.07
(d, J = 8.5 Hz, 2H). 13C NMR (75 MHz, CDCl3): d 39.4; 52.4; 55.4; 100.6; 109.4;
113.6; 115.0; 124.7; 128.5; 130.2; 130.3; 131.2; 132.0; 133.2; 155.7; 159.1;
166.6. HRMS (ESI): MH+, 390.1337; Calcd for C23H19NO5: 390.1341. Compound
4d: Solid; Mp >205 °C. 1H NMR (300 MHz, CDCl3): d 3.71 (s, NMe), 6.72 (s, 1H),
7.35–7.51 (m, 6H), 7.60 (s, 1H), 7.70–7.73 (m, 2H), 7.95–7.98 (m, 2H). 13C NMR
(75 MHz, CDCl3): d 39.6; 98.5; 109.8; 115.6; 125.3; 127.9; 128.4; 128.7; 128.8;
129.0; 129.2; 129.5; 129.6; 130.3; 132.4; 132.4; 132.6; 157.3; 160.8; 161.7.
HRMS (ESI): MH+, 302.1181; Calcd for C20H15NO2: 302.1181. Compound 4e: Oil.
1H NMR (300 MHz, CDCl3): d 1.42 (t, J = 7.1 Hz, 3H), 4.41 (q, J = 7.1 Hz, 2H), 5.33
(s, 2H), 6.68 (s, 1H), 7.30–7.43 (m, 8H), 7.62 (s, 1H), 7.68 (dd, J = 8.1 and 1.5 Hz,
2H), 8.09 (d, J = 8.8 Hz, 2H), 8.16 (d, J = 8.8 Hz, 2H). 13C NMR (75 MHz, CDCl3): d
14.8; 53.7; 61.3; 98.6; 109.0; 116.0; 116.3; 125.3; 128.6; 128.7; 129.2; 129.3;
129.4; 129.5; 129.6; 129.8; 130.2; 136.9; 137.4; 157.6; 161.0; 162.7; 167.1.
HRMS (ESI): MH+, 450.1705; Calcd for C29H23NO4: 450.1713. Compound 4f:
Solid; Mp: 194–196 °C. 1H NMR (300 MHz, CDCl3): d 1.42 (t, J = 7.1 Hz, 3H), 3.84
(s, OMe), 4.41 (q, J = 7.1 Hz, 2H), 5.33 (s, 2H), 6.54 (s, 1H), 6.93 (d, J = 8.5 Hz, 2H),
7.32–7.37 (m, 5H), 7.57 (s, 1H), 7.63 (d, J = 8.5 Hz, 2H), 8.09 (d, J = 8.8 Hz, 2H),
8.16 (d, J = 8.8 Hz, 2H). 13C NMR (75 MHz, CDCl3): d 14.8; 53.7; 55.8; 61.3; 96.6;
114.8; 116.3; 122.0; 126.9; 128.0; 128.5; 128.7; 129.4; 129.5; 129.5; 130.2;
137.0; 137.4; 157.8; 161.0; 162.7; 167.1. HRMS (ESI): MH+, 480.1815; Calcd for
C30H26NO5: 480.1811. Compound 4 g: Solid; Mp: 203–205 °C. 1H NMR
(300 MHz, CDCl3): d 1.42 (t, J = 7.1 Hz, 3H), 3.93 (s, OMe), 4.41 (q, J = 7.1 Hz,
2H), 5.35 (s, 2H), 6.84 (s, 1H), 7.32–7.38 (m, 5H), 7.69 (s, 1H), 7.74 (d, J = 8.4 Hz,
2H), 8.07 (d, J = 8.4 Hz, 4H), 8.16 (d, J = 8.4 Hz, 2H). 13C NMR (75 MHz, CDCl3): d
14.8; 52.7; 53.8; 61.4; 101.0; 109.2; 115.6; 125.0; 128.7; 128.8; 129.4; 129.5;
129.6; 130.2; 130.6; 130.8; 133.1; 136.7; 137.1; 150.4; 156.4; 160.9; 166.8;
167.0. HRMS (ESI): MH+, 508.1761; Calcd for C31H26NO6: 508.1760. Compound
4 h: Solid; Mp >205 °C. 1H NMR (300 MHz, CDCl3): d 1.41 (t, J = 7.1 Hz, 3H), 3.69
(s, NMe), 3.82 (s, OMe), 4.39 (q, J = 7.1 Hz, 2H), 6.55 (s, 1H), 6.93 (d, J = 8.7 Hz,
2H), 7.57 (s, 1H), 7.61 (d, J = 8.7 Hz, 2H), 8.08 (d, J = 8.5 Hz, 2H), 8.14 (d,
J = 8.5 Hz, 2H). 13C NMR (75 MHz, CDCl3): d 14.5; 39.2; 55.5; 61.0; 96.2; 114.4;
115.6; 121.7; 126.5; 128.7; 129.0; 129.2; 129.8; 137.1; 157.2; 160.6; 160.8;
162.4; 166.7. HRMS (ESI): MH+, 404.1499; Calcd for C24H22NO5: 404.1498.
Compound 4i: Solid; Mp: 183–185 °C. 1H NMR (300 MHz, CDCl3): d 3.70 (s,
NMe), 6.71 (s, 1H), 7.35–7.43 (m, 3H), 7.58–7.62 (m, 3H), 7.66–7.69 (m, 2H), 8.24
(dd, J = 4.0 and 1.8 Hz, 1H), 8.34 (s, 1H). 13C NMR (75 MHz, CDCl3): d 39.6; 98.5;
108.0; 115.6; 124.9 (q, J = 271 Hz); 124.4 (q, J = 3.8 Hz); 127.1 (q, J = 3.8 Hz);
129.2; 130.6 (d, J = 32 Hz); 125.2; 128.8; 129.3; 129.6; 129.7; 133.3; 133.4;
157.4; 161.0; 161.4. HRMS (ESI): MH+, 370.1049; Calcd for C21H14F3NO2:
370.1055. Compound 4j: Solid; Mp: 130 °C 1H NMR (300 MHz, CDCl3): d 0.94 (t,
J = 7.1 Hz, 3H), 1.41 (m, 2H), 1.66 (m, 2H), 2.63 (t, J = 7.1 Hz, 2H), 3.68 (s, NMe),
6.10 (s, 1H), 7.50–7.55 (m, 3H), 8.12 (m, 1H), 8.22 (s, 1H). 13C NMR (75 MHz,
CDCl3): d 13.8; 22.3; 27.9; 29.2; 39.1; 98.9; 107.6; 115.1; 122.7; 124.0 (q,
J = 3.8 Hz); 126.8 (q, J = 3.8 Hz); 128.1; 128.3; 128.7; 130.0; 130.5; 133.1 (d,
J = 32 Hz); 161.0; 161.4. HRMS (ESI): MH+, 350.1367; Calcd for C19H19F3NO2:
350.1367.
3. Conreaux, D.; Belot, S.; Desbordes, P.; Monteiro, N.; Balme, G. J. Org. Chem. 2008,
8619.
4. Bossharth, E.; Desbordes, P.; Monteiro, N.; Balme, G. Org. Lett. 2003, 5, 2441.
5. Representative experimental procedure:
A solution of the selected 3-iodo-2-
pyridone (0.2 mmol), the boronic acid (0.3 mmol), Pd(OAc)2 (0.01 mmol), TPPTS
(21 mg, 0.03 mmol), and diisopropylamine (0.6 mmol) in a mixture of MeCN
(3 mL) and water (1 mL) was left to stir at 80 °C for 16 h under Ar, and then
concentrated in vacuo. The residue was purified by column chromatography
(silica gel, acetone/CH2Cl2) to give the corresponding 3-aryl-2-pyridone.
Selected data: Compound 6a: Mp: 108–110 °C. 1H NMR (300 MHz, CDCl3): d
3.54 (s, NMe), 3.78 (s, OMe), 3.83 (s, OMe), 6.15 (d, J = 7.7 Hz, 1H), 6.96 (d,
J = 8.8 Hz, 2H), 7.31 (d, J = 7.7 Hz, 1H), 7.43 (d, J = 8.8 Hz, 2H). Compound 6b:
Mp: 90–92 °C. 1H NMR (300 MHz, CDCl3): d 3.55 (s, NMe), 3.78 (s, OMe), 6.17 (d,
J = 7.7 Hz, 1H), 7.32 (d, J = 7.7 Hz, 1H), 7.35–7.52 (m, 5H). Compound 6c: Mp:
117–120 °C. 1H NMR (300 MHz, CDCl3): d 0.93 (t, J = 7.3 Hz, 3H), 3.48 (s, NMe),
3.72 (s, OMe), 4.31 (q, J = 7.3 Hz, 2H), 6.11 (d, J = 7.7 Hz, 1H), 7.33 (d, J = 7.7 Hz,
1H), 7.48 (d, J = 8.3 Hz, 2H), 7.99 (d, J = 8.3 Hz, 2H). Compound 6d: Mp: 124–
126 °C. 1H NMR (300 MHz, CDCl3): d 3.52 (s, NMe), 3.77 (s, OMe), 6.15 (d,
J = 7.7 Hz, 1H), 7.34 (d, J = 7.7 Hz, 1H), 7.43–7.52 (m, 2H), 7.64 (d, J = 7.1 Hz, 1H),
7.72 (s, 1H). Compound 6e: Mp: 130–132 °C. 1H NMR (300 MHz, CDCl3): d 1.37
(t, J = 7.2 Hz, 3H), 3.76 (s, OMe), 4.36 (q, J = 7.2 Hz, 2H), 5.15 (s, 2H), 6.14 (d,
J = 7.7 Hz, 1H), 7.30–7.35 (m, 5H), 7.39 (d, J = 7.7 Hz, 1H), 7.55 (d, J = 8.5 Hz, 2H),
8.09 (d, J = 8.5 Hz, 2H).
6. Representative experimental procedure:
A solution of the selected 3-aryl-2-
pyridone (0.7 mmol) and NIS (0.77 mmol) in 2 mL MeCN was treated with TFA
(0.7 mmol), and the reaction mixture was left to stir at room temperature for
16 h, and then concentrated in vacuo. The residue was diluted with CH2Cl2
(10 mL) and washed with aqueous Na2S2O3 (10 mL) and 1 N NaOH (10 mL). The
organic layer was dried (MgSO4) and concentrated in vacuo to give the
corresponding 3-aryl-5-iodo-2-pyridone. Selected data: Compound 3a: Mp:
200–205 °C. 1H NMR (300 MHz, CDCl3): d 3.37 (s, NMe), 3.51 (s, OMe), 3.82 (s,
OMe), 6.93 (d, J = 8.7 Hz, 2H), 7.38 (d, J = 8.7 Hz, 2H), 7.62 (s, 1H). Compound 3b:
Mp: 165–166 °C. 1H NMR (300 MHz, CDCl3): d 3.38 (s, NMe), 3.49 (s, OMe), 7.32–
7.47 (m, 5H), 7.69 (s, 1H). Compound 3c: Mp: 150–151 °C. 1H NMR (300 MHz,
CDCl3): d 1.39 (t, J = 7.1 Hz, 3H), 3.35 (s, NMe), 3.53 (s, OMe), 4.37 (q, J = 7.1 Hz,
2H), 7.53 (d, J = 8.3 Hz, 2H), 7.69 (s, 1H), 8.06 (d, J = 8.3 Hz, 2H). Compound 3d:
Mp: 118–120 °C. 1H NMR (300 MHz, CDCl3): d 3.36 (s, NMe), 3.51 (s, OMe), 7.48–
7.59 (m, 2H), 7.65–7.69 (m, 2H), 7.74 (s, 1H). Compound 3e: Mp: 138–141 °C. 1H
NMR (300 MHz, CDCl3): d 1.39 (t, J = 7.1 Hz, 3H), 3.35 (s, OMe), 4.37 (q, J = 7.1 Hz,
2H), 5.09 (s, 2H), 7.30–7.35 (m, 5H); 7.55 (d, J = 6.7 Hz, 2H), 7.69 (s, 1H), 8.07 (d,
J = 6.7 Hz, 2H).
7. Representative experimental procedure using conventional heating: A mixture of
the 3-aryl-5-iodo-2-pyridone (0.2 mmol), the alkyne (0.6 mmol), PdCl2(PPh3)2
(0.02 mmol), and CuI (0.04 mmol) was dissolved in DMF (1 mL) and TEA (2 mL)
in a glass tube fitted with a Teflon screw seal. The reactor was flushed with
argon, and the reaction mixture was left to stir at 80 °C for 5 days, and then
concentrated in vacuo. The residue was purified by column chromatography
(silica gel, acetone/CH2Cl2) to give the corresponding furopyridone.
8. Representative experimental procedure using microwave irradiation: The 3-aryl-5-
iodo-2-pyridone (0.2 mmol), PdCl2(PPh3)2 (0.01 mmol), and CuI (0.01 mmol)
were filled into an appropriate small microwave process vial, and were admixed
with degassed MeCN (1 mL) and TEA (2 mL). The alkyne (0.22 mmol) was then
added, and the vial was sealed with a Teflon septum and placed into a Biotage
InitiatorTM microwave cavity. After irradiation at 160 °C for 60–150 min and