Z. Khaddour et al. / Tetrahedron Letters 54 (2013) 5201–5203
5203
Table 3
Synthesis of 7a–c
8. General procedure
A for the synthesis of 5a–g: A solution of 3 (50 mg,
4
7
Ar1
Ar2
% (7)a
0.122 mmol), K2CO3 (2 M, 2 mL), Pd(PPh3)4 (6 mol %), and arylboronic acid 3
(2.4 equiv) in 1,4-dioxane (3 mL) was stirred at 120 °C for 6 h under argon
atmosphere. To the reaction mixture H2O (20 mL) and CH2Cl2 (25 mL) were
added. The organic and the aqueous layers were separated and the latter was
extracted with CH2Cl2 (2 Â 20 mL). The combined organic layers were dried
(Na2SO4), filtered, and the filtrate was concentrated in vacuo. The residue was
purified by column chromatography (silica gel, heptane/EtOAc).
d,g
e,b
h,c
a
b
c
4-MeC6H4
3-MeC6H4
4-ClC6H4
4-(F3C)C6H4
4-(MeO)C6H4
4-EtC6H4
79
86
71
a
Yield of isolated products.
9. Methyl 3,4-bis(4-methoxyphenyl)-2-naphthoate (5b): Starting with 3 (50 mg,
0.122 mmol), 4b (44 mg, 29 mmol), Pd(PPh3)4 (8 mg, 6 mol %), K2CO3
(2 M, 2 mL) and 1,4-dioxane (3 mL), 5b was isolated as a white solid (43 mg,
86%), mp 113–115 °C. 1H NMR (250 MHz, CDCl3): d = 3.56 (s, 3H, OCH3), 3.68 (s,
3H, OCH3), 3.73 (s, 3H, OCH3), 6.62 (d, 2H, J = 8.8 Hz, ArH), 6.73 (d, 2H,
J = 8.8 Hz, ArH), 6.87 (d, 2H, J = 8.7 Hz, ArH), 6.92 (d, 2H, J = 8.8 Hz, ArH), 7.35–
7.51 (m, 3H, ArH), 7.87–7.90 (m, 1H, ArH), 8.25 (br s,1H, ArH). 13C NMR
(62.9 MHz, CDCl3): d = 52.1, 55.0, 55.1 (OCH3), 112.7, 113.2, 126.3, 127.0, 127.8,
128.7, 129.3 (CH), 130.7 (C), 130.9 (CH), 131.7 (C), 132.1 (CH), 132.5, 134.2,
136.8, 157.8, 158.2 (C), 169.4 (CO). IR (KBr): v = 3063, 3034, 3011, 2995, 2917,
2941, 2837 (w), 1708, 1609 (s), 1587,1574 (w), 1515 (s), 1489, 1462, 1440 (m),
1407, 1373, 1440, 1407, 1373, 1333 (w), 1299, 1285, 1260 (m), 1234, 1209,
1175 (s), 1129, 1105 (m), 1026 (s), 968, 921, 892, 865, 850, 828 (w), 813, 802,
786, 764 (m),741, 732, 707, 685, 633, 622, 595, 569, 549, 535 (w) cmÀ1. GC-MS
(EI, 70 eV): m/z (%) = 398 ([M]+, 100), 367 (13), 351 (06), 323 (05), 295 (04), 263
(08). HRMS (EI, 70 eV): calcd for C26H22O4 [M]+: 398.15126; found: 398.15102.
10. General procedure B for the synthesis of 6a–g: A 1,4-dioxane solution of 3
(50 mg, 0.122 mmol), K2CO3 (2 M, 2 mL), Pd(PPh3)4 (3 mol %) and of
O
OTf O
OMe
OTf
Br
Br
1
1
3
8
Scheme 5. Chemoselectivity of Suzuki–Miyaura reactions of 3 and 5.
chemoselectivity of the Suzuki–Miyaura reactions of 3 might be
explained by additive electronic ortho effects, while the selectivity
in case of 8 is a result of steric effects.
arylboronic acid
4 (1.0 equiv) was stirred at 60 °C for 9 h under argon
Acknowledgments
atmosphere. To the reaction mixture were added H2O (20 mL) and CH2Cl2
(25 mL). The organic and the aqueous layers were separated and the latter was
extracted with CH2Cl2 (2 Â 20 mL). The combined organic layers were dried
(Na2SO4), filtered, and the filtrate was concentrated in vacuo. The residue was
purified by column chromatography (silica gel, heptan/EtOAc = 100:5).
Financial support by the DAAD (scholarships for A.M.H., O.A.A.,
and N.E.) and by the Ministry of Higher Education and Scientific
Research Iraq is gratefully acknowledged. The project was also
funded by the EFRE program of the EU.
11. Methyl 4-bromo-3-(4-methoxyphenyl)-2-naphthoate (6b): Starting with
3
(50 mg, 0.122 mmol), 4b (19 mg, 0.122 mmol), Pd(PPh3)4 (4 mg, 3 mol %),
K2CO3 (2 M, 2 mL), and 1,4-dioxane (3 mL), 6b was isolated as a white solid
(41 mg, 92%), mp: 107–110 °C. 1H NMR (300 MHz, CDCl3): d = 3.56 (s, 3H,
OCH3), 3.81(s, 3H, OCH3), 6.91 (d, 2H, J = 8.7 Hz, ArH), 7.14 (d, 2H, J = 8.9 Hz,
ArH), 7.50–7.56 (1H, m, ArH), 7.64 (ddd, 1H, J = 8.5, 6.9, 1.4, Hz, ArH), 7.86 (br d,
1H, J = 8.5 Hz, ArH), 8.25 (s, 1H, ArH), 8.33 (br d, 1H, J = 8.7 Hz, ArH). 13C NMR
(62.9 MHz, CDCl3): d = 52.3, 55.2 (OCH3), 113.2 (CH), 125.9 (C), 127.3, 128.3,
129.0, 129.5, 129.8, 130.4 (CH), 130.9, 132.4, 133.5, 133.6, 138.9, 158.9 (C),
167.9 (C@O). IR (KBr, cmÀ1): v = 3027, 3013, 2959, 2921, 2855 (w), 1722 (s),
1634 (w), 1592 (m), 1461 (w), 1366, 1280, 1203, 1155(m), 980. 922(s), 877,
821 (w), 789, 720, 645 (m), 604, 595, 568, 555 (w). GC-MS (EI, 70 eV): m/z
(%) = 372 ([M, 81Br]+, 99), 370 ([M, 79Br]+, 100), 341 (11), 339 (12), 276 (8), 261
(17), 245 (22), 217 (10), 189 (50), 187 (21). HRMS (EI, 70 eV) calcd for
References and notes
C
19H15BrO3 [M, 81Br]+: 372.01786; found: 372.01693; calcd for C19H15BrO3 [M,
79Br]+: 370.01991; found: 370.01940.
12. CCDC-949185 contain all crystallographic details of this publication and is
ordered from the following address: Cambridge Crystallographic Data Centre,
12 Union Road, GB-Cambridge CB21EZ; fax: +44 1223 336 033; or
13. General procedure for the synthesis of 7a–c: A 1,4-dioxane solution of 2 (50 mg,
0.122 mmol), Ar1B(OH)2 (1.0 equiv), K2CO3 2 M (2 mL) and Pd(PPh3)4 (3 mol %)
was heated at 60 °C for 9 h under argon atmosphere. After cooling to 20 °C,
Ar2B(OH)2 (1.2 equiv) and Pd(PPh3)4 (6 mol %) were added and the reaction
mixture was heated at 120 °C for further 6 h. The reaction mixture was cooled
again to 20 °C, H2O was added and the reaction mixture was extracted with
CH2Cl2 (3 Â 25 mL).The combined organic layers were dried (Na2SO4), filtered,
and the filtrate was concentrated in vacuo. The residue was purified by column
chromatography (EtOAc/heptanes).
14. Methyl 4-(4-methoxyphenyl)-3-(p-tolyl)-2-naphthoate (7b): Starting with
2
(50 mg, 0.122 mmol), 4e (17 mg, 0122 mmol), K2CO3 2 M(2 mL), Pd(PPh3)4
(4 mg, 3 mol %) and 4b (22 mg, 0.146 mmol), 7b was isolated as a white solid
(49 mg, 86%), mp 87–88 °C .1HNMR (300 MHz, CDCl3): d = 2.21 (s, 3H, CH3),
3.54 (s, 3H, OCH3), 3.73 (s, 3H, OCH3), 6.73 (d, 2H, J = 8.9 Hz, ArH), 6.82–6.90
(m, 4H, ArH), 6.93 (d, 2H, J = 8.7 Hz, ArH), 7.35–7.45 (m, 2H, ArH), 7.47–7.50
(m, 1H, ArH), 7.88 (br d, 1H, J = 7.7 Hz, ArH), 8.3 (s, 1H, ArH). 13CNMR
(75.5 MHz, CDCl3): d = 29.9 (CH3), 51.0, 54.2 (OCH3), 112.1 (CH), 117.8, 119.5
(C), 125.3, 125.9, 126.8, 126.9, 127.7, 128.4 (CH), 129.6, 129.7, 130.7 (C),
131.1 (CH), 175.4 (C@O). FT-IR (KBr, cmÀ1):
1727 (s), 1634, 1598, 1507, 1489 (m), 1346, 1277, 1209, 1144(w), 976, 961,
855, 845, 764 (m), 686, 656 (s), 651, 603, 593, 585, 579, 569 (w). GC–MS
(EI,70 eV): m/z (%) = 382 ([M+], 88), 370 (78), 311 (100), 298 (21), 245 (33),
198 (18). HRMS (EI, 70 eV) calcd for
382.01693.
m = 3003, 2956, 2928, 2849 (w),
C
26H22O3 [M]+: 382.01653; found: