10872
A. Chartoire et al. / Tetrahedron 64 (2008) 10867–10873
([Mþ29]þ, 22), 197 ([Mþ1]þ, 100); ESI-HRMS calcd for C12H8N2O
(MþH)þ: 197.0709, found: 197.0725.
the combined organic layers were washed with a Na2SO3 saturated
aqueous solution (30 mL) and dried (MgSO4). After solvent evapo-
ration, column chromatography purification on silica gel was per-
formed with hexane/AcOEt: 7:3 to 5:5 as eluent and led to the
expected furo[3,2-b]pyridinyl derivative 11 (1.03 g, 91%) as a yellow
powder; mp 112–114 ꢁC; 1H NMR dH 7.23 (s, 1H, H3), 7.30 (dd,
J¼8.6 Hz, J0¼5.0 Hz, 1H, H6), 7.56–7.65 (m, 1H, HAr), 7.69–7.77 (m,
1H, HAr), 7.81–7.89 (m, 2H, HAr), 8.08 (dd, J¼7.8 Hz, J0¼1.3 Hz, 1H,
H7), 8.62 (dd, J¼4.8 Hz, J0¼1.3 Hz,1H, H5),10.5 (s,1H, CHO); 13C NMR
dC 108.8 (C3),118.5 (C6),119.8 (C7),128.6 (CAr),129.7 (CAr),130.1 (CAr),
132.4 (CAr), 133.9 (CAr), 134.2 (CAr), 146.8 (C5), 148.3 (C3a), 148.8 (C7a),
4.6.3. 2-Pyridin-2-ylfuro[3,2-b]pyridine (8)
2-Pyridin-2-ylfuro[3,2-b]pyridine 8 was prepared according to
the method described herein for derivative 6, using 2-bromopyr-
idine (54 mg, 0.34 mmol, 1.0 equiv). Purification on silica gel was
performed with hexane/AcOEt: 7:3 to 5:5 as eluent to afford the
expected furo[3,2-b]pyridinyl derivative 8 (41 mg, 62%) as a white
1
powder; mp 111–113 ꢁC; H NMR dH 7.23–7.35 (m, 2H, H6,H5 ), 7.62
0
0
0
(s, 1H, H3), 7.780–7.87 (m, 2H, H7, H3 ), 7.95 (d, J¼7.9 Hz, 1H, H4 ), 8.58
(dd, J¼4.7 Hz, J ¼1.2 Hz, 1H, H5), 8.73 (d, J¼4.8 Hz, H6 ); 13C NMR dC
157.0 (C2), 191.6 (C]O); IR (KBr) n 1691, 1414, 1268, 1193; MS (CI) m/z
0
105.9 (C3), 118.5 (C6), 119.8 (C7), 120.4 (C5 ), 123.9 (C3 ), 137.0 (C4 ),
252 ([Mþ29]þ, 15), 224 ([Mþ1]þ, 100), 195 (8); ESI-HRMS calcd for
0
0
0
146.7 (C5), 147.1 (C3a), 148.6 (C7a), 148.6 (C2 ), 150.3 (C6 ), 158.5 (C2);
C14H9NO2 (MþH)þ: 224.0706, found: 224.0731.
0
0
IR (KBr)
n
1610,1414,1260,1167; MS (CI) m/z 225 ([Mþ29]þ, 22),197
([Mþ1]þ, 100); ESI-HRMS calcd for C12H8N2O (MþH)þ: 197.0709,
4.7. 2-Thiophen-2-ylfuro[3,2-b]pyridine (13)
found: 197.0739.
To
a solution of furo[3,2-b]pyridine 1 (143 mg, 1.2 mmol,
4.6.4. 2-Trimethylsilanylethynylfuro[3,2-b]pyridine (9)
1.0 equiv) in THF (15 mL), at ꢀ78 ꢁC, was added dropwise n-BuLi
(1.5 mL, 2.4 mmol, 2.0 equiv) under argon atmosphere. After stir-
ring for 1 h at ꢀ78 ꢁC, 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-
dioxaborolane (446 mg, 2.4 mmol, 2.0 equiv) was added in THF
(5 mL) at ꢀ78 ꢁC. After stirring for 1 h at ꢀ78 ꢁC, hydrolysis was
performed using only few drops of water, the solvents were then
evaporated. After flushing the medium with argon, a mixture of
Pd(PPh3)4 (70.0 mg, 0.06 mmol, 5 mol %), 2-bromothiophene
(215 mg, 1.32 mmol, 1.1 equiv) and a 2 M Na2CO3 aqueous solution
(3.0 mL, 6.00 mmol, 2.0 equiv) in THF/toluene (1:1) (5 mL) was
added. After stirring at reflux for 18 h, the reaction mixture was
washed with H2O (2ꢂ20 mL) and extracted with AcOEt (3ꢂ20 mL).
The combined organic layers were washed with a Na2SO3 saturated
aqueous solution (30 mL) and dried (MgSO4). After solvent evapo-
ration, a column chromatography purification on silica gel was
performed with hexane/AcOEt: 9:1 to 5:5 as eluent and led to the
expected furo[3,2-b]pyridinyl derivative 13 (89.0 mg, 37%) as
a yellow powder; mp 74–76 ꢁC; 1H NMR dH 7.07 (s, 1H, H3), 7.13–
7.24 (m, 2H, H6, HAr), 7.44 (dd, J¼5.0 Hz, J0¼1.1 Hz, 1H, HAr), 7.59 (dd,
J¼3.7 Hz, J0¼1.1 Hz, 1H, HAr), 7.75 (d, J¼8.2 Hz, 1H, H7), 8.52 (dd,
J¼4.8 Hz, 1H, H5); 13C NMR dC 102.1 (C3), 117.8 (C6), 118.9 (C7), 126.0
(CAr), 128.3 (CAr), 132.6 (CAr), 146.3 (C5), 147.8 (C3a), 149.1 (C7a), 155.1
Under argon atmosphere, to a suspension PdCl2(PPh3)2 (18 mg,
0.025 mmol, 5 mol %) and CuI (10 mg, 0.05 mmol, 10 mol %) in THF
(2 mL), in the presence of Et3N (1.5 mL, 7.5 mmol, 15.0 equiv) were
added in one portion 2-bromofuro[3,2-b]pyridine 5a (99.0 mg,
0.5 mmol, 1.0 equiv) and trimethylsilylacetylene (64 mg,
0.65 mmol, 1.3 equiv) in THF (2 mL). After stirring at room tem-
perature for 12 h, the reaction mixture was diluted in AcOEt
(20 mL) and washed with an aqueous saturated Na2SO3 solution
(10 mL). After drying (MgSO4) and solvent evaporation, the crude
product was purified by column chromatography on silica gel
(eluent: hexane/AcOEt 9:1 to 7:3) to afford the expected furo[3,2-
b]pyridinyl derivative 9 (93.0 mg, 87%) as a brown powder; mp 44–
46 ꢁC; 1H NMR dH 0.31 (s, 9H, SiCH3), 7.15 (s, 1H, H3), 7.26 (dd,
J¼8.4 Hz, J0¼4.7 Hz, 1H, H6), 7.70 (d, J¼8.4 Hz, 1H, H7), 8.57 (dd,
J¼4.7 Hz, 1H, H5); 13C NMR dC ꢀ0.4 (CH3Si), 93.6 (C), 104.3 (C), 112.8
(C3), 118.2 (C6), 120.2 (C7), 142.2 (C2), 146.9 (C5), 147.3 (C3a), 148.1
(C7a); IR (KBr)
n
2156, 1406, 1250, 1167; MS (CI) m/z 244 ([Mþ29]þ,
22), 216 ([Mþ1]þ, 100), 200 (22); ESI-HRMS calcd for C12H13NOSi
(MþH)þ: 216.0839, found: 216.0858.
4.6.5. 2-Vinylfuro[3,2-b]pyridine (10)
Under argon atmosphere, to a suspension of PdCl2(PPh3)2
(88 mg, 0.125 mmol, 5 mol %) in DMF (10 mL) were added 2-bro-
mofuro[3,2-b]pyridine 5a (495.0 mg, 2.5 mmol, 1.0 equiv) and
vinyltributyltin (872 mg, 2.75 mmol, 1.1 equiv). After stirring at
110 ꢁC for 2 h, the reaction mixture was diluted in CH2Cl2 (20 mL),
washed with an aqueous saturated Na2SO3 solution (10 mL) and
dried (MgSO4). After solvent evaporation, column chromatography
purification on silica gel was performed with hexane/AcOEt: 9:1 to
7:3 as eluent to afford the expected furo[3,2-b]pyridinyl derivative
10 (300.0 mg, 83%) as a brown oil; 1H NMR dH 5.49 (dd, J¼11.5 Hz,
J0¼0.8 Hz, 1H, CH2), 6.06 (dd, J¼17.7 Hz, J0¼0.8 Hz, 1H, CH2), 6.69
(dd, J¼17.7 Hz, J0¼11.5 Hz, 1H, CH), 6.81 (s, 1H, H3), 7.18 (dd,
J¼8.3 Hz, J0¼4.8 Hz, 1H, H6), 7.69 (d, J¼8.3 Hz, 1H, H7), 8.48 (dd,
J¼4.8 Hz, J0¼1.2 Hz, 1H, H5); 13C NMR dC 105.7 (C3), 117.8 (CH2), 117.9
(C6), 119.2 (C7), 125.2 (CH), 146.0 (C5), 148.0 (C3a), 148.7 (C7a), 158.3
(C2); IR (KBr) n
1610, 1403, 1250, 1156; MS (EI) m/z 201 ([M]þ, 100),
172 (9), 108 (9); ESI-HRMS calcd for C11H7NOS (MþH)þ: 202.0321,
found: 202.0336.
4.8. 6,7,8,9-Tetrahydrobenzo[4,5]furo[3,2-b]pyridine-8,9-
dicarboxylic acid diethyl ester (15)
To
a solution of 2-vinylfuro[3,2-b]pyridine 10 (100.0 mg,
0.69 mmol, 1.0 equiv) in xylene (3 mL) was added fumarate diethyl
ester (237.0 mg, 1.38 mmol, 2.0 equiv). The mixture was then
refluxed for 48 h in a sealed tube. After a quick filtration and
evaporation of solvents, a column chromatography purification on
silica gel was performed with hexane/AcOEt: 7:3 to 5:5 as eluent
and led to the expected derivative 15 (109 mg, 50%) as a yellow oil;
1H NMR dH 1.19–1.34 (m, 6H, CH3), 2.29–2.35 and 2.48–2.52 (2m,
2H, CH2), 2.84–2.96 (m, 2H, CH2), 3.30–3.35 (m, 1H, CHCH2), 4.11–
4.19 (m, 2H, CH2CH3), 4.20–4.28 (m, 2H, CH2CH3), 4.43 and 4.55 (2d,
J¼5.1 Hz, 1H, CH), 7.11–7.18 (m, 1H, H3), 7.63–7.67 (m, 1H, H4), 8.48
and 8.52 (2dd, J¼4.7 Hz, J0¼0.7 Hz,1H, H2); 13C NMR dC 14.1 and 14.2
(CH3), 21.0 and 21.8 (CH2), 23.1 and 23.2 (CH2), 38.6 and 40.0 (CH),
42.1 and 42.2 (CH), 61.0 and 61.2 (CH2CH3), 61.3 and 61.5 (CH2CH3),
117.6 and 117.7 (C3), 118.2 and 118.3 (C4), 145.4 and 145.5 (C2), 147.1
(C9b), 147.7 (C4a), 158.6 (C9a), 159.5 (C5a), 172.5 (C]O), 172.7 (C]O);
(C2); IR (NaCl)
n
1414, 1263, 1159; MS (CI) m/z 174 ([Mþ29]þ, 22),
146 ([Mþ1]þ, 100).
4.6.6. 2-Furo[3,2-b]pyridin-2-yl-benzaldehyde (11)
Under argon atmosphere, to
a suspension of Pd(PPh3)4
(289.0 mg, 0.25 mmol, 5 mol %) in THF (20 mL) were added 2-bro-
mofuro[3,2-b]pyridine 5a (1.0 g, 5.05 mmol, 1.0 equiv), 2-for-
mylbenzeneboronic acid (984.0 mg, 6.56 mmol, 1.3 equiv) and
a 2 M Na2CO3 aqueous solution (5.05 mL, 10.10 mmol, 2.0 equiv).
After stirring at reflux for 3 h, the reaction mixture was washed
with H2O (2ꢂ20 mL) and extracted with AcOEt (3ꢂ20 mL). Then,
IR (NaCl)
n
1731, 1250; MS (EI) m/z 317 ([M]þ, 19), 244 (100), 198
(28), 170 (63); ESI-HRMS calcd for C17H19NO5 (MþH)þ: 318.1336,
found: 318.1321.