Synthesis of Functionalized Benzofurans by a Double Heck Reaction of 2,3-Dibromofurans and Subsequent 6π-Electrocyclization/Dehydrogenation

Abstract

The twofold Heck reaction of 2,3-dibromofurans afforded 2,3-di(alkenyl)furans which were transformed into functionalized benzofurans by a domino 6π-electrocyclization/dehydrogenation reaction.

Benzofurans are of considerable pharmacological relevance in medicinal chemistry and occur in many natural products. [¹] For example, amiodarone represents a synthetic antiarrhythmic and antianginal drug. [²] The core structures of 7-alkanoylbenzofurans and 7-alkanoyl-2,3-dihydrobenzofurans are present in a number of natural products (e.g., longicaudatin, [³] the sessiliflorols A and B, flemistrictin E, tovophenone C, vismiaguianone C and piperaduncin B). [4]

Polyhalogenated compounds represent interesting substrates in palladium(0)-catalyzed cross-coupling reactions. [5] [6] Bach and Krüger reported Sonogashira and Stille reactions of 2,3-dibromofuran. [7] These reactions proceed with very good site-selectivity in favor of position 2. de Meijere and co-workers reported that the combination of a twofold Heck reaction with 6π-electrocyclization provides a convenient approach to various carbocycles. [8] In recent years, we have studied the application of this methodology to heterocyclic systems. [9] Herein, we report what is, to the best of our knowledge, the first synthesis of functionalized benzofurans by a double Heck reaction of 2,3-dibromofurans and subsequent 6π-electrocyclization and dehydrogenation. This methodology provides a convenient approach to benzofurans containing substituents located at positions 5 and 6 which are not readily accessible by electrophilic substitution reactions.

The Heck reaction of 2,3-dibromofuran (1) with acrylates and styrenes 2a-i (2.5 equiv) afforded the 2,3-di(alkenyl)furans 3a-i in good yields (Scheme  [¹] , Table  [¹] ). The reaction was thoroughly optimized for derivatives 3b and 3f (Table  [²] ). The best yields were obtained when palladium(II) acetate (5 mol%) and the biaryl monophosphine ligands SPhos or XPhos [¹0] (10 mol%) were used. The employment of tetrakis(triphenylphosphine)palladium(0) resulted in considerably lower yields (Table  [²] , entry 1). The reactions were carried out in N,N-dimethylformamide at 120 ˚C. A relatively long reaction time (36 h) was necessary to achieve a complete conversion.

Our next target was to find suitable conditions for a 6π-electrocyclization. In fact, 2,3-di(alkenyl)furans 3 proved to be rather reluctant to undergo the desired transformation. Stirring of a diphenyl ether solution of 3a-d at 200 ˚C for 24 hours was required to induce the desired electrocyclization. To the reaction mixture was added palladium on carbon (10 mol%) and the mixture was stirred for an additional 24 hours at 200 ˚C to give benzofurans 4a-d by dehydrogenation (see Table  [¹] ). Heating of 3f resulted in decomposition of the tert-butyl ester moiety. Heating of the styrene-derived products 3g-i also resulted in decomposition.

The twofold Heck reaction of 2,3-dibromo-5-(ethoxycarbonyl)furan (5) with acrylates and styrenes 2a-f,j,k afforded the 2,3-di(alkenyl)furans 6a-h (Scheme  [²] , Table  [³] ). The reactions proceeded at slightly lower temperature (100 ˚C, 24 h) as compared to the synthesis of 3a-i. The transformation of 2,3-di(alkenyl)furans 6a,b,d-h to benzofurans 7a,b,d-h required less drastic conditions (stirring at 170 ˚C, 2 × 12 h) as compared to the synthesis of 4a-d (200 ˚C, 2 × 24 h). Similar to 3f, heating of tert-butyl ester 6c resulted in decomposition. In contrast to 3g-i, electrocyclization of the styrene-derived 2,3-di(al­kenyl)furan 6h proved to be possible and afforded 7h in good yield.

It was noted above that Sonogashira and Stille reactions of 2,3-dibromofurans are known to proceed with excellent site-selectivity in favor of position 2. The site-selectivity of palladium(0)-catalyzed reactions of polyhalogenated substrates is generally controlled by steric and electronic effects. More electron-deficient carbon atoms are usually more reactive than electron-rich atoms; however, all attempts to carry out site-selective mono-Heck reactions of dibromofuran 1 or 5 failed. All reactions resulted in the isolation of double-Heck products 3 and 6 and of unreacted starting material. This might be explained by a proximity effect. The first attack occurs at carbon atom C-2 of the furan. The palladium catalyst is coordinated by the alkene and the reactivity of the neighbored carbon atom C-3 might thus be increased. In the case of products 3a-f and 6a-g, the increased reactivity of C-3 might alternatively be explained by the electron-withdrawing effect of the acrylate moiety located at carbon C-2.

In conclusion, functionalized benzofurans were prepared by a twofold Heck reaction of 2,3-dibromofurans and a subsequent domino 6π-electrocyclization/dehydrogenation reaction. The products are not readily available by other methods.

All solvents were dried by standard methods and all reactions were carried out under an inert atmosphere. For ^¹H and ^¹³C NMR spectra, the deuterated solvents indicated were used. Mass spectrometric data (MS) were obtained by electron ionization (EI, 70 eV), chemical ionization (CI, isobutane) or electrospray ionization (ESI). For preparative-scale chromatography, silica gel 60 (0.063-0.200 mm, 70-230 mesh) was used. Melting points are uncorrected.

2,3-Di(alkenyl)furans 3a-i and 6a-h; General Procedure

In a pressure tube (glass bomb), a suspension of Pd(OAc)₂ (12 mg, 5 mol%) and XPhos or SPhos (10 mol%) in DMF (5 mL) was purged with argon and stirred at 20 ˚C to give a yellowish or brownish clear solution. To the stirred solution were added dibromofuran 1 (0.12 mL, 1.0 mmol) or 5 (300 mg, 1.0 mmol), Et₃N (1.1 mL, 8.0 mmol) and the acrylate or styrene 2a-i (2.5 mmol). The reaction mixture was stirred at 120 ˚C for 36 h (for 3a-i) or at 100 ˚C for 24 h (for 6a-h). The solution was cooled to 20 ˚C, poured into H₂O (25 mL) and CH₂Cl₂ (25 mL), and the organic layer and the aqueous layer were separated. The latter was extracted with CH₂Cl₂ (3 × 25 mL). The combined organic layers were dried (Na₂SO₄) and concentrated under reduced pressure. The residue was purified by flash silica gel chromatography (heptanes-EtOAc).

Dimethyl (2 E ,2′ E )-3,3′-(Furan-2,3-diyl)diacrylate (3a)

Yield: 172 mg (73%); light yellow oil.

IR (KBr): 3100 (w), 2850 (m), 1711 (s), 1676 (w), 1631 (m), 1510 (w), 1445, 1292 (m), 1275, 1245, 1178 (s), 1035, 970, 872, 749 (m), 861, 756 (w), 721 (m), 530 (m) cm^-¹.

^¹H NMR (300 MHz, CDCl₃): δ = 3.72 (s, 3 H, CH₃O), 3.74 (s, 3 H, CH₃O), 6.16 (d, J = 15.8 Hz, 1 H, CH), 6.34 (d, J = 15.8 Hz, 1 H, CH), 6.57 (d, J = 2.2 Hz, 1 H, ArH), 7.38 (d, J = 1.7 Hz, 1 H, ArH), 7.55 (d, J = 15.8 Hz, 1 H, CH), 7.62 (d, J = 15.8 Hz, 1 H, CH).

^¹³C NMR (75.5 MHz, CDCl₃): δ = 51.79, 51.85 (CH₃O), 109.4, 117.8, 119.8 (CH), 124.8 (C), 127.4, 132.7, 145.2 (CH), 150.5 (C), 166.9, 167.0 (CO).

GC-MS (EI, 70 eV): m/z (%) = 236 (11) [M⁺], 230 (14), 213 (29), 187 (100), 173 (5), 151 (6), 111 (4).

HRMS (EI, 70 eV): m/z calcd for C₁₂H₁₂O₅: 236.06847; found: 236.06801.

Diethyl (2 E ,2′ E )-3,3′-(Furan-2,3-diyl)diacrylate (3b)

Compound 3b was directly transformed into 4b without characteri­zation.

Diisobutyl (2 E ,2′ E )-3,3′-(Furan-2,3-diyl)diacrylate (3c)

Yield: 297 mg (93%); light yellow oil.

IR (KBr): 3119 (w), 2935 (s), 2852 (m), 1711 (s), 1631 (m), 1579, 1509 (w), 1290 (m), 1272, 1257 (s), 1045, 832, 740 (m), 658, 606 (w), 530 (m) cm^-¹.

^¹H NMR (300 MHz, CDCl₃): δ = 0.89 (d, J = 6.8 Hz, 12 H, 4 CH₃), 1.86-1.97 (m, 2 H, 2 CH), 3.90 (d, J = 6.7 Hz, 2 H, CH₂O), 3.91 (d, J = 6.7 Hz, 2 H, CH₂O), 6.17 (d, J = 15.6 Hz, 1 H, CH), 6.35 (d, J = 15.6 Hz, 1 H, CH), 6.58 (d, J = 1.8 Hz, 1 H, ArH), 7.37 (d, J = 2.0 Hz, 1 H, ArH), 7.55 (d, J = 15.6 Hz, 1 H, CH), 7.59 (d, J = 15.6 Hz, 1 H, CH).

^¹³C NMR (62.9 MHz, CDCl₃): δ = 19.1 (4 CH₃), 27.8 (2 CH), 70.7, 70.8 (CH₂O), 109.3, 118.2, 120.3 (CH), 124.7 (C), 127.2, 132.4, 145.1 (CH), 150.5 (C), 166.4, 166.5 (CO).

GC-MS (EI, 70 eV): m/z (%) = 320 (71) [M⁺], 305 (18), 290 (11), 262 (11), 249 (20), 189 (17), 153 (19), 147 (100).

HRMS (EI, 70 eV): m/z calcd for C₁₈H₂₄O₅: 320.16237; found: 320.16360.

Dibutyl (2 E ,2′ E )-3,3′-(Furan-2,3-diyl)diacrylate (3d)

Yield: 249 mg (78%); light yellow oil.

IR (KBr): 3133, 3118 (w), 2925 (s), 2850 (m), 1711 (s), 1676 (w), 1631 (m), 1549, 1500 (w), 1445 (m), 1290 (m), 1275, 1255, 1168 (s), 1035, 969, 862, 749 (m), 746 (w), 720 (m), 648, 606 (w), 539 (m) cm^-¹.

^¹H NMR (300 MHz, CDCl₃): δ = 0.86 (t, J = 7.3 Hz, 6 H, 2 CH₃), 1.28-1.40 (m, 4 H, 2 CH₂), 1.56-1.65 (m, 4 H, 2 CH₂), 4.10-4.15 (m, 4 H, 2 CH₂O), 6.14 (d, J = 15.6 Hz, 1 H, CH), 6.32 (d, J = 15.6 Hz, 1 H, CH), 6.56 (d, J = 1.9 Hz, 1 H, ArH), 7.36 (d, J = 2.0 Hz, 1 H, ArH), 7.52 (d, J = 15.6 Hz, 1 H, CH), 7.57 (d, J = 15.5 Hz, 1 H, CH).

^¹³C NMR (75.5 MHz, CDCl₃): δ = 13.6 (2 CH₃), 19.1 (2 CH₂), 30.7 (2 CH₂), 64.4, 64.5 (CH₂O), 109.3, 118.2, 120.3 (CH), 124.7 (C), 127.2, 132.3, 145.1 (CH), 150.5 (C), 166.5, 166.6 (CO).

GC-MS (EI, 70 eV): m/z (%) = 320 (71) [M⁺], 264 (8), 247 (23), 190 (17), 163 (86), 147 (100), 134 (11), 119 (53).

HRMS (EI, 70 eV): m/z calcd for C₁₈H₂₄O₅: 320.16238; found: 320.16236.

Dihexyl (2 E ,2′ E )-3,3′-(Furan-2,3-diyl)diacrylate (3e)

Yield: 331 mg (88%); light yellow oil.

IR (KBr): 3122, 3108 (w), 2921, 1711 (s), 1631 (m), 1549, 1500 (w), 1445 (m), 1377 (w), 1292 (m), 1275, 1255, 1167 (s), 1069 (w), 1035 (m), 1018 (w), 959 (m), 933 (w), 862 (m), 825 (w), 749 (m), 746 (w), 721 (m), 648, 607 (w), 538 (m) cm^-¹.

^¹H NMR (300 MHz, CDCl₃): δ = 0.83-0.86 (m, 6 H, 2 CH₃), 1.16-1.34 (m, 12 H, 6 CH₂), 1.58-1.68 (m, 4 H, 2 CH₂), 4.13 (t, J = 6.8 Hz, 2 H, CH₂O), 4.14 (t, J = 6.7 Hz, 2 H, CH₂O), 6.16 (d, J = 15.5 Hz, 1 H, CH), 6.35 (d, J = 15.5 Hz, 1 H, CH), 6.57 (d, J = 2.4 Hz, 1 H, ArH), 7.37 (d, J = 1.9 Hz, 1 H, ArH), 7.55 (d, J = 15.5 Hz, 1 H, CH), 7.60 (d, J = 15.6 Hz, 1 H, CH).

^¹³C NMR (75.5 MHz, CDCl₃): δ = 14.0 (2 CH₃), 22.5, 22.6, 28.7, 31.4 (2 CH₂), 64.9, 65.0 (CH₂O), 109.4, 118.3, 120.3 (CH), 124.7 (C), 127.2, 132.4, 145.1 (CH), 150.5 (C), 166.5, 166.6 (CO).

GC-MS (EI, 70 eV): m/z (%) = 376 (1) [M⁺], 345 (8), 291 (3), 206 (10), 189 (100), 162 (8).

HRMS (EI, 70 eV): m/z calcd for C₂₂H₃₂O₅: 376.22497; found: 376.22397.

Di- tert -butyl (2 E ,2′ E )-3,3′-(Furan-2,3-diyl)diacrylate (3f)

Yield: 252 mg (79%); light yellow oil.

IR (KBr): 2976, 2931 (m), 1705 (s), 1636, 1454, 1392, 1367, 1313, 1283, 1253 (m), 1146 (s), 1018, 977, 844, 767 (m), 711, 685, 594, 574 (w) cm^-¹.

^¹H NMR (300 MHz, CDCl₃): δ = 1.46 (s, 18 H, 6 CH₃), 6.03 (d, J = 16.1 Hz, 1 H, CH), 6.27 (d, J = 15.5 Hz, 1 H, CH), 6.54 (d, J = 2.3 Hz, 1 H, ArH), 7.34 (d, J = 2.3 Hz, 1 H, ArH), 7.44 (d, J = 15.5 Hz, 1 H, CH), 7.45 (d, J = 15.7 Hz, 1 H, CH).

^¹³C NMR (75.5 MHz, CDCl₃): δ = 28.2 (6 CH₃), 80.7, 80.8 (C), 109.4, 120.1, 122.1 (CH), 124.4 (C), 126.5, 131.6, 144.8 (CH), 150.5 (C), 165.8, 165.9 (CO).

GC-MS (EI, 70 eV): m/z (%) = 320 (15) [M⁺], 247 (11), 208 (100), 163 (31), 147 (21), 119 (26).

HRMS (EI, 70 eV): m/z calcd for C₁₈H₂₄O₅: 320.16237; found: 320.16232.

2,3-Bis(4-methoxystyryl)furan (3g)

Yield: 299 mg (90%); light yellow oil.

IR (KBr): 3030, 2996, 2992, 2930, 2833 (w), 1599, 1571, 1508, 1497, 1456, 1436, 1417, 1298, 1290, 1267 (m), 1246 (s), 1174, 1145, 1109, 1061, 958, 934, 895, 852, 845 (m), 815 (s), 740, 720 (m), 696, 659, 637, 610, 561, 547 (w) cm^-¹.

^¹H NMR (300 MHz, CDCl₃): δ = 3.74 (s, 6 H, 2 CH₃O), 6.56 (d, J = 2.1 Hz, 1 H, ArH), 6.71 (d, J = 16.2 Hz, 1 H, CH), 6.82 (d, J = 8.8 Hz, 4 H, ArH), 6.87-6.92 (m, 3 H), 7.25 (d, J = 2.0 Hz, 1 H, ArH), 7.34 (d, J = 8.6 Hz, 2 H, ArH), 7.38 (d, J = 8.7 Hz, 2 H, ArH).

^¹³C NMR (62.9 MHz, CDCl₃): δ = 55.3 (CH₃O), 108.7, 112.1, 114.1, 114.2, 116.0 (CH), 121.6 (C), 126.8, 127.4, 127.7, 128.1 (CH), 130.0, 130.3 (C), 142.1 (CH), 150.0, 159.2, 159.4 (C).

GC-MS (EI, 70 eV): m/z (%) = 332 (100) [M⁺], 207 (20), 166 (10), 121 (17).

HRMS (EI, 70 eV): m/z calcd for C₂₂H₂₀O₃: 332.14070; found: 332.14073.

2,3-Bis(4-methylstyryl)furan (3h)

Yield: 270 mg (89%); light yellow oil.

IR (KBr): 3020, 2992, 2963, 2833 (w), 1599, 1571, 1508, 1498, 1456, 1436, 1418, 1298, 1290 (m), 1246, 1174 (s), 1029, 959, 815, 740, 720 (m), 659, 638, 610, 562, 548 (w) cm^-¹.

^¹H NMR (300 MHz, CDCl₃): δ = 2.24 (s, 6 H, 2 CH₃), 6.54 (d, J = 2.0 Hz, 1 H, ArH), 6.68 (d, J = 16.2 Hz, 1 H, CH), 6.97 (m, 3 H), 7.05 (d, J = 7.9 Hz, 4 H, ArH), 7.22 (d, J = 2.0 Hz, 1 H, ArH), 7.28 (d, J = 7.9 Hz, 2 H, ArH), 7.29 (d, J = 8.2 Hz, 2 H, ArH).

^¹³C NMR (62.9 MHz, CDCl₃): δ = 21.3, 21.4 (CH₃), 108.8, 113.1, 117.1 (CH), 122.0 (C), 126.2, 126.5, 127.4, 128.7, 129.4, 129.5 (CH), 134.4, 134.8, 137.3, 137.7 (C), 142.3 (CH), 150.1 (C).

GC-MS (EI, 70 eV): m/z (%) = 300 (100) [M⁺], 281 (33), 245 (8), 216 (10), 204 (8), 198 (10).

HRMS (EI, 70 eV): m/z calcd for C₂₂H₂₀O: 300.15142; found: 300.15133.

2,3-Bis(4- tert -butoxystyryl)furan (3i)

Yield: 361 mg (87%); light yellow oil.

IR (KBr): 3033, 2972, 2929, 2872, 1623 (w), 1503, 1362, 1271 (m), 1159 (s), 1102, 1060, 1029, 968, 959, 947 (w), 891, 864, 832, 743, 690, 677, 591 (m) cm^-¹.

^¹H NMR (300 MHz, CDCl₃): δ = 1.37 (s, 18 H, 6 CH₃), 6.54 (d, J = 2.0 Hz, 1 H, ArH), 6.67 (d, J = 16.1 Hz, 1 H, CH), 6.80-6.94 (m, 7 H), 7.23 (d, J = 2.0 Hz, 1 H, ArH), 7.30 (d, J = 8.5 Hz, 2 H, ArH), 7.31 (d, J = 8.6 Hz, 2 H, ArH).

^¹³C NMR (62.9 MHz, CDCl₃): δ = 28.9 (6 CH₃), 78.7, 78.8 (CO), 108.8, 112.9, 116.9 (CH), 121.8 (C), 124.2, 124.3, 126.7, 126.9, 127.0, 128.3 (CH), 132.4, 132.7 (C), 142.3 (CH), 150.1, 155.0, 155.3 (C).

GC-MS (EI, 70 eV): m/z (%) = 416 (14) [M⁺], 360 (7), 304 (100), 210 (7).

HRMS (EI, 70 eV): m/z calcd for C₂₈H₃₂O₃: 416.23460; found: 416.23516.

Diisobutyl (2 E ,2′ E )-3,3′-[5-(Ethoxycarbonyl)furan-2,3-diyl]di­acrylate (6a)

Yield: 318 mg (81%); light yellow solid; mp 152-154 ˚C.

IR (KBr): 3109, 2958, 2874 (w), 1709 (s), 1633, 1578, 1515, 1469 (m), 1394 (w), 1368 (m), 1343 (w), 1318 (s), 1300, 1270 (w), 1255 (m), 1239 (w), 1220 (m), 1171 (s), 1114 (m), 1080 (w), 1008, 962 (s), 875, 861, 837 (w), 765, 748, 720, 693, 657 (m), 609, 595, 542 (w) cm^-¹.

^¹H NMR (300 MHz, CDCl₃): δ = 0.89 (d, J = 6.7 Hz, 12 H, 4 CH₃), 1.40 (t, J = 7.3 Hz, 3 H, CH₃), 1.96-2.01 (m, 2 H, 2 CH), 4.01 (d, J = 3.6 Hz, 2 H, CH₂O), 4.03 (d, J = 3.5 Hz, 2 H, CH₂O), 4.41 (q, J = 7.1 Hz, 2 H, CH₂O), 6.34 (d, J = 15.8 Hz, 1 H, CH), 6.71 (d, J = 15.8 Hz, 1 H, CH), 7.37 (s, 1 H, ArH), 7.62 (d, J = 8.6 Hz, 1 H, CH), 7.67 (d, J = 8.4 Hz, 1 H, CH).

^¹³C NMR (75.5 MHz, CDCl₃): δ = 14.3 (CH₃), 19.1 (4 CH₃), 27.8 (2 CH), 61.7, 71.0, 71.1 (CH₂O), 115.8, 121.5, 121.6 (CH), 125.2 (C), 126.5, 131.5 (CH), 145.5, 152.4 (C), 158.0, 166.2, 166.5 (CO).

GC-MS (EI, 70 eV): m/z (%) = 393 (22), 392 (80) [M⁺], 347 (22), 336 (18), 320 (10), 319 (49), 280 (53), 263 (16), 235 (72), 219 (100), 206 (44).

HRMS (EI, 70 eV): m/z calcd for C₂₁H₂₈O₇: 392.18295; found: 392.18259.

Dihexyl (2 E ,2′ E )-3,3′-[5-(Ethoxycarbonyl)furan-2,3-diyl]di­acrylate (6b)

Yield: 382 mg (85%); yellow solid; mp 162-164 ˚C.

IR (KBr): 3107, 2953, 2929, 2857 (w), 1715, 1632 (s), 1579, 1518, 1467 (m), 1453, 1392, 1368, 1346 (w), 1321 (s), 1301, 1265, 1252, 1240 (w), 1223 (m), 1175 (s), 1123, 1107, 1052, 1038 (w), 1024, 977, 961 (m), 910 (w), 875, 860 (m), 822, 799 (w), 764, 724, 661, 596 (m) cm^-¹.

^¹H NMR (300 MHz, CDCl₃): δ = 0.81-0.86 (m, 6 H, 2 CH₃), 1.23-1.28 (m, 12 H, 6 CH₂), 1.38 (t, J = 7.3 Hz, 3 H, CH₃), 1.59-1.68 (m, 4 H, 2 CH₂), 4.02 (d, J = 3.7 Hz, 2 H, CH₂O), 4.05 (d, J = 3.6 Hz, 2 H, CH₂O), 4.32 (q, J = 7.1 Hz, 2 H, CH₂O), 6.23 (d, J = 15.7 Hz, 1 H, CH), 6.61 (d, J = 15.8 Hz, 1 H, CH), 7.27 (s, 1 H, ArH), 7.53 (d, J = 8.0 Hz, 1 H, CH), 7.58 (d, J = 8.0 Hz, 1 H, CH).

^¹³C NMR (75.5 MHz, CDCl₃): δ = 14.0 (2 CH₃), 14.3 (CH₃), 22.5, 25.6, 28.6, 31.4 (2 CH₂), 61.7, 65.0, 65.2 (CH₂O), 115.8, 121.6, 121.7 (CH), 125.2 (C), 126.5, 131.5 (CH), 145.8, 152.4 (C), 158.0, 166.2, 166.5 (CO).

GC-MS (EI, 70 eV): m/z (%) = 449 (14), 448 (49) [M⁺], 403 (17), 347 (18), 320 (10), 291 (7), 280 (19), 246 (22), 235 (100).

HRMS (EI, 70 eV): m/z calcd for C₂₅H₃₆O₇: 448.24555; found: 448.24519.

Di- tert -butyl (2 E ,2′ E )-3,3′-[5-(Ethoxycarbonyl)furan-2,3-diyl]diacrylate (6c)

Yield: 326 mg (83%); orange solid; mp 158-160 ˚C.

IR (KBr): 3109, 2979, 2930 (w), 1714, 1699 (s), 1633 (m), 1575, 1509, 1475, 1455, 1391 (w), 1367, 1322, 1280, 1256, 1220 (m), 1141 (s), 1079, 1019 (w), 975, 958 (m), 885, 863, 844 (w), 763, 750, 722, 653 (m), 607, 579 (w) cm^-¹.

^¹H NMR (250 MHz, CDCl₃): δ = 1.32 (t, J = 7.2 Hz, 3 H, CH₃), 1.46 (s, 18 H, 6 CH₃), 4.31 (q, J = 7.2 Hz, 2 H, CH₂O), 6.14 (d, J = 15.4 Hz, 1 H, CH), 6.53 (d, J = 15.7 Hz, 1 H, CH), 7.24 (s, 1 H, ArH), 7.42 (d, J = 4.3 Hz, 1 H, CH), 7.48 (d, J = 4.3 Hz, 1 H, CH).

^¹³C NMR (62.9 MHz, CDCl₃): δ = 14.3 (CH₃), 28.1 (6 CH₃), 61.5 (CH₂), 81.1, 81.2 (C), 115.9, 123.4, 123.5 (CH), 124.9 (C), 125.7, 130.5 (CH), 145.6, 152.3 (C), 158.1, 165.3, 165.4 (CO).

GC-MS (EI, 70 eV): m/z (%) = 392 (11) [M⁺], 336 (9), 280 (100), 235 (23), 219 (17), 206 (34).

HRMS (EI, 70 eV): m/z calcd for C₂₁H₂₈O₇: 392.18295; found: 392.18307.

Bis(6-methylheptyl) (2 E ,2′ E )-3,3′-[5-(Ethoxycarbonyl)furan-2,3-diyl]diacrylate (6d)

Yield: 430 mg (85%); yellow solid; mp 153-155 ˚C.

IR (KBr): 3107, 2956, 2948, 2857 (w), 1717, 1635 (s), 1579, 1517, 1469 (m), 1457, 1392, 1368, 1346 (w), 1323 (s), 1311, 1266, 1253, 1242 (w), 1224 (m), 1178 (s), 1125, 1105, 1053, 1039 (w), 1021, 978, 962 (m), 910 (w), 875, 861 (m), 823, 798 (w), 764, 723, 663, 598 (m) cm^-¹.

^¹H NMR (300 MHz, CDCl₃): δ = 0.72-0.87 (m, 12 H, 4 CH₃), 0.89-0.90 (m, 2 H, 2 CH), 1.10-1.23 (m, 8 H, 4 CH₂), 1.32 (t, J = 7.3 Hz, 3 H, CH₃), 1.36-1.39 (m, 8 H, 4 CH₂), 4.10-4.22 (m, 4 H, 2 CH₂O), 4.32 (q, J = 7.1 Hz, 2 H, CH₂O), 6.23 (dd, J = 2.8, 15.8 Hz, 1 H, CH), 6.61 (dd, J = 2.8, 15.8 Hz, 1 H, CH), 7.27 (s, 1 H, ArH), 7.53 (d, J = 8.2 Hz, 1 H, CH), 7.58 (d, J = 8.2 Hz, 1 H, CH).

^¹³C NMR (62.9 MHz, CDCl₃): δ = 14.3 (CH₃), 19.5 (4 CH₃), 23.4, 25.7, 28.6, 31.4 (2 CH₂), 27.7 (2 CH), 61.6, 65.1, 65.4 (CH₂O), 115.7, 121.4, 121.8 (CH), 125.2 (C), 126.7, 131.8 (CH), 145.7, 152.6 (C), 158.4, 166.2, 166.4 (CO).

GC-MS (EI, 70 eV): m/z (%) = 504 (40) [M⁺], 459 (30), 457 (60), 392 (35), 376 (100), 348 (53), 317 (33), 280 (26), 246 (50), 219 (72).

HRMS (EI, 70 eV): m/z calcd for C₂₉H₄₄O₇: 504.30816; found: 504.30782.

Dibutyl (2 E ,2′ E )-3,3′-[5-(Ethoxycarbonyl)furan-2,3-diyl]di­acrylate (6e)

Yield: 346 mg (88%); light yellow solid; mp 158-160 ˚C.

IR (KBr): 3107, 2953, 2929, 2857 (w), 1715, 1632 (s), 1579, 1518, 1467 (m), 1453, 1392, 1368, 1346 (w), 1321 (s), 1301, 1265, 1252, 1240 (w), 1223 (m), 1175 (s), 1123, 1107, 1052, 1038 (w), 1024, 977, 961 (m), 910 (w), 875, 860 (m), 822, 799 (w), 764, 724, 661, 596 (m) cm^-¹.

^¹H NMR (300 MHz, CDCl₃): δ = 0.89 (t, J = 7.4 Hz, 6 H, 2 CH₃), 1.32 (t, J = 7.1 Hz, 3 H, CH₃), 1.35-1.42 (m, 4 H, 2 CH₂), 1.57-1.67 (m, 4 H, 2 CH₂), 4.12-4.18 (m, 4 H, 2 CH₂O), 4.32 (q, J = 7.1 Hz, 2 H, CH₂O), 6.23 (d, J = 15.8 Hz, 1 H, CH), 6.61 (d, J = 15.5 Hz, 1 H, CH), 7.27 (s, 1 H, ArH), 7.53 (d, J = 8.1 Hz, 1 H, CH), 7.58 (d, J = 8.1 Hz, 1 H, CH).

^¹³C NMR (75.5 MHz, CDCl₃): δ = 13.7 (2 CH₃), 14.3 (CH₃), 19.1 (2 CH₂), 30.7 (2 CH₂), 61.6, 64.8, 64.9 (CH₂O), 115.8, 121.6, 121.7 (CH), 125.2 (C), 126.5, 131.4 (CH), 145.9, 152.3 (C), 158.0, 166.1, 166.2 (CO).

GC-MS (EI, 70 eV): m/z (%) = 392 (43) [M⁺], 347 (9), 336 (11), 319 (23), 291 (16), 263 (15), 235 (60), 219 (49), 191 (100).

HRMS (EI, 70 eV): m/z calcd for C₂₁H₂₈O₇: 392.18295; found: 392.18324.

Dimethyl (2 E ,2′ E )-3,3′-[5-(Ethoxycarbonyl)furan-2,3-diyl]di­acrylate (6f)

Yield: 259 mg (84%); orange solid; mp 150-152 ˚C.

IR (KBr): 3397, 3109, 2985 (w), 1708 (s), 1639 (m), 1580, 1517, 1443, 1395 (w), 1367, 1321 (m), 1267, 1256, 1234, 1223 (w), 1182 (s), 1117, 1083 (w), 1036, 968, 957 (s), 893, 874, 863, 810 (w), 763, 746, 722, 656 (m), 607, 585 (w) cm^-¹.

^¹H NMR (300 MHz, CDCl₃): δ = 1.32 (t, J = 7.1 Hz, 3 H, CH₃), 3.74 (s, 3 H, CH₃O), 3.76 (s, 3 H, CH₃O), 4.32 (q, J = 7.3 Hz, 2 H, CH₂O), 6.23 (d, J = 15.9 Hz, 1 H, CH), 6.59 (d, J = 15.9 Hz, 1 H, CH), 7.27 (s, 1 H, ArH), 7.54 (d, J = 8.7 Hz, 1 H, CH), 7.59 (d, J = 8.7 Hz, 1 H, CH).

^¹³C NMR (75.5 MHz, CDCl₃): δ = 13.2 (CH₃), 50.9, 51.1 (CH₃O), 60.7 (CH₂O), 114.7, 120.1, 120.2 (CH), 124.2 (C), 125.7, 130.7 (CH), 145.0, 151.3 (C), 157.0, 165.4, 165.5 (CO).

GC-MS (EI, 70 eV): m/z (%) = 308 (100) [M⁺], 277 (36), 263 (20), 249 (63), 235 (91), 217 (31), 205 (55), 177 (44), 162 (30), 145 (92).

HRMS (EI, 70 eV): m/z calcd for C₁₅H₁₆O₇: 308.08905; found: 308.08870.

Diethyl (2 E ,2′ E )-3,3′-[5-(Ethoxycarbonyl)furan-2,3-diyl]di­acrylate (6g)

Yield: 317 mg (94%); yellow solid; mp 168-170 ˚C.

IR (KBr): 3399, 3108, 2983 (w), 1705 (s), 1637 (m), 1579, 1515, 1444, 1392 (w), 1366, 1320 (m), 1268, 1255, 1234, 1221 (w), 1180 (s), 1116, 1081 (w), 1037, 969, 958 (s), 893, 874, 863, 810 (w), 763, 746, 722, 656 (m), 607, 585 (w) cm^-¹.

^¹H NMR (300 MHz, CDCl₃): δ = 1.25-1.35 (m, 9 H, 3 CH₃), 4.17-4.25 (m, 4 H, 2 CH₂O), 4.32 (q, J = 7.3 Hz, 2 H, CH₂O), 6.23 (d, J = 15.7 Hz, 1 H, CH), 6.60 (d, J = 15.7 Hz, 1 H, CH), 7.27 (s, 1 H, ArH), 7.54 (d, J = 8.1 Hz, 1 H, CH), 7.59 (d, J = 8.1 Hz, 1 H, CH).

^¹³C NMR (62.9 MHz, CDCl₃): δ = 14.2 (2 CH₃), 14.3 (CH₃), 60.8, 61.0, 61.6 (CH₂O), 115.7, 121.6, 121.7 (CH), 125.2 (C), 126.5, 131.4 (CH), 145.9, 152.3 (C), 158.0, 166.0, 166.1 (CO).

GC-MS (EI, 70 eV): m/z (%) = 336 (100) [M⁺], 291 (53), 263 (89), 235 (45), 219 (46), 217 (35), 191 (70).

HRMS (EI, 70 eV): m/z calcd for C₁₇H₂₀O₇: 336.12035; found: 336.11988.

Ethyl 4,5-Bis(4-chlorostyryl)furan-2-carboxylate (6h)

Compound 6h was directly transformed into 7h without characteri­zation.

Functionalized Benzofurans 4a-d and 7a-h; General Procedure

A diphenyl ether solution (3 mL) of a 2,3-di(alkenyl)furan 3a-d or 6a-h (0.5 mmol) was stirred at 200 ˚C for 24 h (for 3a-d) or at 170 ˚C for 12 h (for 6a-h) in a pressure tube. The solution was allowed to cool to 20 ˚C and Pd/C (10 mol%) was added. The solution was stirred at 200 ˚C for 24 h (for 3a-d) or at 170 ˚C for 12 h (for 6a-h) under argon atmosphere. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. The residue was purified by flash silica gel chromatography (heptanes-EtOAc).

Dimethyl Benzofuran-5,6-dicarboxylate (4a)

Yield: 105 mg (90%); light yellow oil.

IR (KBr): 3010, 2850 (w), 1723, 1716 (s), 1583, 1486, 1435 (w), 1229, 1202, 1165, 1071, 1021, 981, 865, 797, 750, 692, 666 (s) cm^-¹.

^¹H NMR (300 MHz, CDCl₃): δ = 3.81 (s, 3 H, CH₃O), 3.82 (s, 3 H, CH₃O), 6.75 (d, J = 2.1 Hz, 1 H, ArH), 7.63 (d, J = 2.2 Hz, 1 H, ArH), 7.80 (s, 1 H, ArH), 7.90 (s, 1 H, ArH).

^¹³C NMR (75.5 MHz, CDCl₃): δ = 52.6, 52.7 (CH₃O), 107.0, 112.6, 122.6 (CH), 127.4, 128.2, 129.6 (C), 148.3 (CH), 155.2 (C), 167.9, 168.4 (CO).

GC-MS (EI, 70 eV): m/z (%) = 234 (10) [M⁺], 204 (4), 187 (100), 171 (5), 149 (6), 111 (4).

HRMS (EI, 70 eV): m/z calcd for C₁₂H₁₀O₅: 234.05282; found: 234.05277.

Diethyl Benzofuran-5,6-dicarboxylate (4b)

Yield: 122 mg (93%); light yellow oil.

IR (KBr): 3411, 3120, 2931, 2872 (w), 1715 (s), 1619, 1586, 1529 (w), 1488, 1465 (m), 1391 (w), 1367 (m), 1300, 1219, 1149, 1125, 1102, 1039 (s), 896, 859, 772, 691, 588 (m) cm^-¹.

^¹H NMR (300 MHz, CDCl₃): δ = 0.86 (t, J = 7.5 Hz, 6 H, 2 CH₃), 4.30-4.35 (m, 4 H, 2 CH₂O), 6.77 (d, J = 2.2 Hz, 1 H, ArH), 7.69 (d, J = 2.2 Hz, 1 H, ArH), 7.81 (s, 1 H, ArH), 7.91 (s, 1 H, ArH).

^¹³C NMR (75.5 MHz, CDCl₃): δ = 14.1 (2 CH₃), 61.6, 61.7 (CH₂O), 107.3, 112.4, 122.5 (CH), 127.8, 128.8, 129.5 (C), 148.2 (CH), 155.2 (C), 167.6, 168.0 (CO).

GC-MS (EI, 70 eV): m/z (%) = 262 (18) [M⁺], 234 (4), 217 (19), 189 (100), 175 (5), 145 (6), 133 (4), 116 (7).

HRMS (EI, 70 eV): m/z calcd for C₁₄H₁₄O₅: 262.08458; found: 262.08413.

Diisobutyl Benzofuran-5,6-dicarboxylate (4c)

Yield: 146 mg (92%); light yellow oil.

IR (KBr): 3434 (w), 2959, 2874 (m), 1769 (w), 1716 (s), 1614, 1585, 1529 (w), 1468, 1377 (m), 1305, 1218 (s), 1125 (m), 1103, 1035, 938 (s), 893, 773 (m), 691, 632 (w) cm^-¹.

^¹H NMR (300 MHz, CDCl₃): δ = 0.92 (d, J = 6.7 Hz, 6 H, 2 CH₃), 0.93 (d, J = 6.8 Hz, 6 H, 2 CH₃), 1.96-2.01 (m, 2 H, 2 CH), 4.02 (d, J = 6.7 Hz, 2 H, CH₂O), 4.03 (d, J = 6.7 Hz, 2 H, CH₂O), 6.76 (d, J = 2.2 Hz, 1 H, ArH), 7.71 (d, J = 2.1 Hz, 1 H, ArH), 7.81 (s, 1 H, ArH), 7.91 (s, 1 H, ArH).

^¹³C NMR (75.5 MHz, CDCl₃): δ = 19.1 (4 CH₃), 27.5 (2 CH), 71.8, 71.9 (CH₂O), 107.0, 112.6, 122.6 (CH), 127.9, 128.8, 129.5 (C), 148.2 (CH), 155.2 (C), 167.6, 168.0 (CO).

GC-MS (EI, 70 eV): m/z (%) = 318 (1) [M⁺], 263 (3), 189 (100), 162 (9), 144 (4), 133 (2), 116 (6).

HRMS (ESI⁺): m/z calcd for C₁₈H₂₂O₅: 318.14674; found: 318.14664.

Dibutyl Benzofuran-5,6-dicarboxylate (4d)

Yield: 151 mg (95%); light yellow, highly viscous oil.

IR (KBr): 3144, 3117 (w), 2959, 2921, 2852 (m), 1711 (s), 1631, 1462, 1446, 1377, 1292 (w), 1275, 1255, 1223, 1169 (m), 1036, 969, 862, 794, 721, 539 (w) cm^-¹.

^¹H NMR (300 MHz, CDCl₃): δ = 0.86 (t, J = 7.3 Hz, 6 H, 2 CH₃), 1.30-1.43 (m, 4 H, 2 CH₂), 1.60-1.69 (m, 4 H, 2 CH₂), 4.24 (t, J = 6.7 Hz, 2 H, CH₂O), 4.25 (t, J = 6.7 Hz, 2 H, CH₂O), 6.74 (d, J = 2.2 Hz, 1 H, ArH), 6.67 (d, J = 2.2 Hz, 1 H, ArH), 7.78 (s, 1 H, ArH), 7.88 (s, 1 H, ArH).

^¹³C NMR (75.5 MHz, CDCl₃): δ = 13.7 (2 CH₃), 19.2 (2 CH₂), 30.6 (2 CH₂), 65.5, 65.6 (CH₂O), 107.0, 112.5, 122.5 (CH), 127.8, 128.7, 129.4 (C), 148.1 (CH), 155.1 (C), 167.5, 168.0 (CO).

GC-MS (EI, 70 eV): m/z (%) = 318 (5) [M⁺], 245 (5), 189 (100), 116 (10).

HRMS (ESI⁺): m/z calcd for C₁₈H₂₂O₅: 318.14623; found: 318.14626.

2-Ethyl 5,6-Diisobutyl Benzofuran-2,5,6-tricarboxylate (7a)

Yield: 185 mg (95%); light yellow oil.

IR (KBr): 2874 (w), 1719 (s), 1621 (w), 1583, 1467 (m), 1442, 1394 (w), 1369, 1345 (m), 1309 (s), 1259 (m), 1194, 1155, 1100 (s), 1038, 982, 943 (m), 901, 846 (w), 765, 740, 690 (m) cm^-¹.

^¹H NMR (300 MHz, CDCl₃): δ = 0.92 (d, J = 6.5 Hz, 12 H, 4 CH₃), 1.37 (t, J = 7.1 Hz, 3 H, CH₃), 1.96-2.01 (m, 2 H, 2 CH), 4.03 (d, J = 3.4 Hz, 2 H, CH₂O), 4.05 (d, J = 3.3 Hz, 2 H, CH₂O), 4.40 (q, J = 7.1 Hz, 2 H, CH₂O), 7.49 (s, 1 H, ArH), 7.87 (s, 1 H, ArH), 8.01 (s, 1 H, ArH).

^¹³C NMR (75.5 MHz, CDCl₃): δ = 14.3 (CH₃), 19.1, 19.2 (4 CH₃), 27.7 (2 CH), 62.0, 72.0, 72.1 (CH₂O), 113.4, 113.5, 124.3 (CH), 128.6, 128.8, 131.9, 148.7, 155.7 (C), 158.8, 167.1, 167.1 (CO).

GC-MS (EI, 70 eV): m/z (%) = 390 (5) [M⁺], 345 (20), 278 (30), 261 (100), 233 (16).

HRMS (EI, 70 eV): m/z calcd for C₂₁H₂₆O₇: 390.16730; found: 390.16659.

2-Ethyl 5,6-Dihexyl Benzofuran-2,5,6-tricarboxylate (7b)

Yield: 216 mg (97%); light yellow oil.

IR (KBr): 2955, 2928, 2857 (w), 1720 (s), 1621, 1582 (w), 1462 (m), 1369, 1344 (w), 1302 (s), 1258 (m), 1193, 1156, 1101 (s), 1017 (m), 944, 900, 836 (w), 765 (m), 740, 690, 574 (w) cm^-¹.

^¹H NMR (300 MHz, CDCl₃): δ = 0.81-0.85 (m, 6 H, 2 CH₃), 1.24-1.28 (m, 12 H, 6 CH₂), 1.37 (t, J = 7.2 Hz, 3 H, CH₃), 1.63-1.72 (m, 4 H, 2 CH₂), 4.22-4.28 (m, 4 H, 2 CH₂O), 4.40 (q, J = 7.4 Hz, 2 H, CH₂O), 7.50 (s, 1 H, ArH), 7.86 (s, 1 H, ArH), 8.01 (s, 1 H, ArH).

^¹³C NMR (75.5 MHz, CDCl₃): δ = 14.0 (2 CH₃), 14.3 (CH₃), 22.5, 25.6, 28.5, 31.5 (2 CH₂), 62.0, 66.1, 66.2 (CH₂O), 113.4, 113.5, 124.3 (CH), 128.5, 128.7, 131.9, 148.7, 155.7 (C), 158.8, 167.1, 167.3 (CO).

GC-MS (EI, 70 eV): m/z (%) = 446 (20) [M⁺], 401 (20), 363 (20), 345 (10), 278 (14), 261 (100), 233 (12).

HRMS (EI, 70 eV): m/z calcd for C₂₅H₃₄O₇: 446.22990; found: 446.22914.

2-Ethyl 5,6-Bis(6-methylheptyl) Benzofuran-2,5,6-tricarboxylate (7d)

Yield: 221 mg (88%); light yellow oil.

IR (KBr): 3109, 2958, 2874 (w), 1709 (s), 1633, 1578, 1515, 1469 (m), 1394 (w), 1368 (m), 1343 (w), 1318 (s), 1300, 1270 (w), 1255 (m), 1239 (w), 1220 (m), 1171 (s), 1114 (m), 1080 (w), 1008, 962 (s), 875, 861, 837 (w), 765, 748, 720, 693, 657 (m), 609, 595, 542 (w) cm^-¹.

^¹H NMR (300 MHz, CDCl₃): δ = 0.74-0.89 (m, 12 H, 4 CH₃), 0.90-0.91 (m, 2 H, 2 CH), 1.11-1.23 (m, 8 H, 4 CH₂), 1.33 (t, J = 7.3 Hz, 3 H, CH₃), 1.37-1.41 (m, 8 H, 4 CH₂), 4.12-4.24 (m, 4 H, 2 CH₂O), 4.34 (q, J = 7.1 Hz, 2 H, CH₂O), 7.49 (s, 1 H, ArH), 7.85 (s, 1 H, ArH), 8.00 (s, 1 H, ArH).

^¹³C NMR (75.5 MHz, CDCl₃): δ = 14.4 (CH₃), 19.8 (4 CH₃), 23.5, 25.8, 28.7, 31.6 (2 CH₂), 27.3 (2 CH), 61.7, 65.2, 65.5 (CH₂O), 113.6, 113.7, 124.5 (CH), 128.7, 128.9, 131.7, 148.4, 155.8 (C), 158.6, 166.3, 166.5 (CO).

GC-MS (EI, 70 eV): m/z (%) = 502 (20) [M⁺], 457 (30), 391 (28), 279 (21), 261 (100), 233 (15).

HRMS (EI, 70 eV): m/z calcd for C₂₉H₄₂O₇: 502.29251; found: 502.29179.

5,6-Dibutyl 2-Ethyl Benzofuran-2,5,6-tricarboxylate (7e)

Yield: 176 mg (90%); highly viscous, yellow oil.

IR (KBr): 2873 (w), 1719 (s), 1621 (w), 1583 (m), 1563, 1508, 1488 (w), 1462 (m), 1369, 1344 (w), 1302 (s), 1257, 1242 (w), 1193, 1156, 1100 (s), 1060, 1037, 1015, 961 (w), 941 (m), 901, 840 (w), 765, 740, 691 (m), 643, 603, 579 (w) cm^-¹.

^¹H NMR (300 MHz, CDCl₃): δ = 0.89 (t, J = 7.3 Hz, 6 H, 2 CH₃), 1.32 (t, J = 7.2 Hz, 3 H, CH₃), 1.35-1.45 (m, 4 H, 2 CH₂), 1.62-1.71 (m, 4 H, 2 CH₂), 4.12-4.18 (m, 4 H, 2 CH₂O), 4.40 (q, J = 7.2 Hz, 2 H, CH₂O), 7.49 (s, 1 H, ArH), 7.86 (s, 1 H, ArH), 8.00 (s, 1 H, ArH).

^¹³C NMR (75.5 MHz, CDCl₃): δ = 13.7 (2 CH₃), 14.3 (CH₃), 19.2 (2 CH₂), 30.5, 30.6 (CH₂), 62.0, 65.8, 65.9 (CH₂O), 113.4, 113.5, 124.3 (CH), 128.5, 128.7, 131.9, 148.7, 155.7 (C), 158.8, 167.1, 167.3 (CO).

GC-MS (EI, 70 eV): m/z (%) = 390 (43) [M⁺], 345 (30), 335 (11), 317 (40), 278 (18), 261 (100), 233 (17).

HRMS (EI, 70 eV): m/z calcd for C₂₁H₂₆O₇: 390.16730; found: 390.16658.

2-Ethyl 5,6-Dimethyl Benzofuran-2,5,6-tricarboxylate (7f)

Yield: 142 mg (93%); light yellow oil.

IR (KBr): 2951, 2925, 2853 (w), 1721 (s), 1620, 1578 (w), 1564 (m), 1535, 1488, 1475, 1465 (w), 1431, 1372, 1347 (m), 1310 (s), 1265, 1242 (m), 1207, 1156, 1100 (s), 1043, 1019, 966 (m), 934, 919, 876 (w), 854, 825, 785 (m), 765 (s), 742, 690, 667, 641, 568 (m) cm^-¹.

^¹H NMR (300 MHz, CDCl₃): δ = 1.37 (t, J = 7.1 Hz, 3 H, CH₃), 3.86 (s, 3 H, CH₃O), 3.88 (s, 3 H, CH₃O), 4.40 (q, J = 7.3 Hz, 2 H, CH₂O), 7.49 (s, 1 H, ArH), 7.86 (s, 1 H, ArH), 8.03 (s, 1 H, ArH).

^¹³C NMR (75.5 MHz, CDCl₃): δ = 14.3 (CH₃), 52.8, 53.0 (CH₃O), 62.1 (CH₂O), 113.4, 113.5, 124.4 (CH), 128.0, 128.9, 131.5, 148.8, 155.8 (C), 158.8, 167.6, 167.7 (CO).

GC-MS (EI, 70 eV): m/z (%) = 306 (40) [M⁺], 276 (15), 275 (100), 261 (8), 247 (44), 217 (5).

HRMS (EI, 70 eV): m/z calcd for C₁₅H₁₄O₇: 306.07340; found: 306.07314.

Triethyl Benzofuran-2,5,6-tricarboxylate (7g)

Yield: 157 mg (94%); highly viscous, orange oil.

IR (KBr): 3055, 2981, 2929 (w), 1714 (s), 1622 (w), 1581, 1564 (m), 1536, 1504 (w), 1488, 1474, 1445, 1396 (m), 1368 (s), 1345 (w), 1305, 1238, 1198, 1156, 1102 (s), 1043, 1020, 906, 868, 837, 785 (m), 765 (s), 740, 691, 671, 643, 562 (w) cm^-¹.

^¹H NMR (250 MHz, CDCl₃): δ = 1.29-1.40 (m, 9 H, 3 CH₃), 4.18-4.45 (m, 6 H, 3 CH₂O), 7.49 (s, 1 H, ArH), 7.86 (s, 1 H, ArH), 8.03 (s, 1 H, ArH).

^¹³C NMR (62.9 MHz, CDCl₃): δ = 14.0, 14.1, 14.3 (CH₃), 61.8, 61.9, 62.0 (CH₂O), 113.3, 113.4, 124.3 (CH), 128.4, 128.7, 131.8, 148.7, 155.7 (C), 158.8, 167.1, 167.2 (CO).

GC-MS (EI, 70 eV): m/z (%) = 334 (25) [M⁺], 306 (4), 289 (26), 261 (100), 247 (7), 233 (32), 217 (6).

HRMS (EI, 70 eV): m/z calcd for C₁₇H₁₈O₇: 334.10470; found: 334.10407.

Ethyl 5,6-Bis(4-chlorophenyl)benzofuran-2-carboxylate (7h)

Yield: 185 mg (90%); light brown, highly viscous oil.

IR (KBr): 2957, 2922, 2852 (w), 1720 (s), 1657, 1622, 1581, 1566, 1555 (w), 1494, 1455 (m), 1434, 1392 (w), 1368, 1328, 1301, 1285, 1261, 1240, 1228 (m), 1183, 1152, 1089, 1012 (s), 953 (m), 934, 889, 871, 854 (w), 827 (s), 765, 756, 743, 728 (m), 697, 682, 646, 636, 625, 590, 537 (w).

^¹H NMR (250 MHz, CDCl₃): δ = 1.37 (t, J = 7.1 Hz, 3 H, CH₃), 4.39 (q, J = 7.1 Hz, 2 H, CH₂O), 6.96-7.00 (dd, J = 2.3, 8.6 Hz, 4 H, ArH), 7.13-7.17 (dd, J = 2.0, 8.5 Hz, 4 H, ArH), 7.48 (s, 1 H, ArH), 7.51 (s, 1 H, ArH), 7.59 (s, 1 H, ArH).

^¹³C NMR (62.9 MHz, CDCl₃): δ = 13.3 (CH₃), 60.6 (CH₂O), 112.5, 112.7, 123.3 (CH), 125.6 (C), 127.2, 127.3, 130.1, 130.2 (CH), 131.9, 132.2, 135.0, 138.2, 138.3, 138.5, 145.8, 154.2 (C), 158.3 (CO).

GC-MS (EI, 70 eV): m/z (%) = 412 (68), 411 (26), 410 (100) [M⁺], 382 (5), 367 (4), 365 (5), 347 (4), 312 (14), 302 (10).

HRMS (ESI⁺): m/z calcd for C₂₃H₁₆O₃Cl₂: 410.04710; found: 410.04713.

Acknowledgment

Financial support by the DAAD (scholarships for A.A., G.A.S. and R.A.K.), by the State of Pakistan (HEC scholarships for M.H. and R.A.K.) and by the State of Mecklenburg-Vorpommern (scholarship for M.H.) is gratefully acknowledged.

References

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References

• 1a Miyata O. Takeda N. Morikami Y. Naito T. Org. Biomol. Chem.  2003,  1:  254 
  Search in Google Scholar
• 1b Xie X. Chen B. Lu J. Han J. She X. Pan X. Tetrahedron Lett.  2004,  45:  6235 
  Search in Google Scholar
• 1c Zhang H. Ferreira EM. Stoltz BM. Angew. Chem. Int. Ed.  2004,  43:  6144 
  Search in Google Scholar
• 1d Hagiwara H. Sato K. Nishino D. Hoshi T. Suzuki T. Ando M. J. Chem. Soc., Perkin Trans. 1  2001,  2946 
• For a review, see:
• 1e Butin AV. Gutnow AV. Abaev VT. Krapivin GD. Molecules  1999,  4:  52 
  Search in Google Scholar
• 1f Fuerst DE. Stoltz BM. Wood JL. Org. Lett.  2000,  2:  3521 
  Search in Google Scholar
• 1g Schneider B. Phytochemistry  2003,  64:  459 
  Search in Google Scholar
• 1h Katritzky AR. Kirichenkok K. Ji Y. Steel PJ. Karelson M. ARKIVOC  2003,  (vi):  49 
  Search in Google Scholar
• 2a Wendt B. Ha HR. Hesse M. Helv. Chim. Acta  2002,  85:  2990 
  Search in Google Scholar
• 2b Carlsson B. Singh BN. Temciuc M. Nilsson S. Li YL. Mellin C. Malm J. J. Med. Chem.  2002,  45:  623 ; and references cited therein
  Search in Google Scholar
• 2c Kwiecien H. Baumann E. J. Heterocycl. Chem.  1997,  34:  1587 
  Search in Google Scholar
• 2d Larock RC. Harrison LW. J. Am. Chem. Soc.  1984,  106:  4218 
  Search in Google Scholar
• 2e Mátyus P. Varga I. Rettegi T. Simay A. Kállay N. Károlyházy L. Kocsis A. Varró A. Pénzes I. Papp JG. Curr. Med. Chem.  2004,  11:  61 
  Search in Google Scholar
• 2f Wong HNC. Yu P. Yick C.-Y. Pure Appl. Chem.  1999,  71:  1041 
  Search in Google Scholar
• For longicaudatin, see:
• 3a Joshi AS. Li X.-C. Nimrod AC. ElSohly HN. Walker LA. Clark AM. Planta Med.  2001,  67:  186 
  Search in Google Scholar
• For related natural products, see:
• 3b Sigstad E. Catalan CAN. Diaz JG. Herz W. Phytochemistry  1993,  33:  165 
  Search in Google Scholar
• 3c Drewes SE. Hudson NA. Bates RB. J. Chem. Soc., Perkin Trans. 1  1987,  2809 
• For sessiliflorol A, see:
• 4a Chan JA. Shultis EA. Carr SA. DeBrosse CW. Eggleston DS. J. Org. Chem.  1989,  54:  2098 
  Search in Google Scholar
• For sessiliflorol B, see:
• 4b Marston A. Zagorski MG. Hostettmann K. Helv. Chim. Acta  1988,  71:  1210 
  Search in Google Scholar
• 4c Drewes SE. Hudson NA. Bates RB. Linz GS. Tetrahedron Lett.  1984,  25:  105 
  Search in Google Scholar
• For flemistrictin E, see:
• 4d Subrahmanyam K. Rao JM. Vemuri VSS. Babu SS. Roy CP. Rao KVJ. Indian J. Chem., Sect. B  1982,  21:  895 
  Search in Google Scholar
• For tovophenone C, see:
• 4e Seo E.-K. Wall ME. Wani MC. Navarro H. Mukherjee R. Farnsworth NR. Kinghorn AD. Phytochemistry  1999,  52:  669 
  Search in Google Scholar
• For vismiaguianone C, see:
• 4f Seo E.-K. Wani MC. Wall ME. Navarro H. Mukherjee R. Farnsworth NR. Kinghorn AD. Phytochemistry  2000,  55:  35 
  Search in Google Scholar
• 4g For piperaduncin B, see ref. 3a and: Bohlmann F. Zdero C. Chem. Ber.  1976,  109:  1436 
  Search in Google Scholar
• For reviews of cross-coupling reactions of polyhalogenated heterocycles, see:
• 5a Schröter S. Stock C. Bach T. Tetrahedron  2005,  61:  2245 
  Search in Google Scholar
• 5b Schnürch M. Flasik R. Khan AF. Spina M. Mihovilovic MD. Stanetty P. Eur. J. Org. Chem.  2006,  3283 
• 6a Dang TT. Ahmad R. Dang TT. Reinke H. Langer P. Tetrahedron Lett.  2008,  49:  1698 
  Search in Google Scholar
• 6b Dang TT. Villinger A. Langer P. Adv. Synth. Catal.  2008,  350:  2109 
  Search in Google Scholar
• 6c Dang TT. Dang TT. Rasool N. Villinger A. Langer P. Adv. Synth. Catal.  2009,  351:  1595 
  Search in Google Scholar
• 7a Bach T. Krüger L. Tetrahedron Lett.  1998,  39:  1729 
  Search in Google Scholar
• 7b Bach T. Krüger L. Eur. J. Org. Chem.  1999,  2045 
• 7c Bach T. Krüger L. Synlett  1998,  1185 
• 8 de Meijere and co-workers reported twofold Heck reactions of 1,2-dibromocycloalk-1-enes and related substrates and subsequent 6π-electrocyclization; see: Voigt K. von Zezschwitz P. Rosauer K. Lansky A. Adams A. Reiser O. de Meijere A. Eur. J. Org. Chem.  1998,  1521 ; and references cited therein
• 9a Hussain M. Nguyen TH. Langer P. Tetrahedron Lett.  2009,  50:  3929 
  Search in Google Scholar
• 9b Tengho Toguem S.-M. Hussain M. Malik I. Villinger A. Langer P. Tetrahedron Lett.  2009,  50:  4962 
  Search in Google Scholar
• 10 Billingsley K. Buchwald SL. J. Am. Chem. Soc.  2007,  129:  3358 ; and references cited therein
  Search in Google Scholar