17 : 合成吡咯化合物 II-48 的反應機構

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2.4 結論

本論文利用鈴木耦合反應與薗頭耦合反應成功合成出具芳香環或芳香乙炔基團之合環前起始物，並使用三氯化金催化劑進行分子內合環反應，

反應時間由數分鐘至一個小時內，即可生成吡咯化合物。為實驗室成功合成吡咯骨架化合物之官能基容忍度測試，提供更完整的官能基多樣性，其為合成吡咯架構化合物一項有效的方法，並且此吡咯衍生物帶有順式共軛烯酮取代，具有進行衍生反應的潛在能力。

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第三章實驗部分

3.1 分析儀器及基本實驗操作

1. 核磁共振光譜儀（Nuclear Magnetic Resonance Spectroscopy，簡稱 NMR）：使用 BRUKER AVANCE 500 NMR（500 MHz）、BRUKER AVANCE 400 NMR（400 MHz）和 BRUKER AVANCE III HD 400 NMR（400 MHz）三

台核磁共振儀進行測定。樣品以氘化氯仿（chloroform-d，CDCl₃）作為溶

劑，化學位移（chemical shift）單位為 ppm；¹H NMR 光譜以四甲基矽烷

（tetramethylsilane，簡稱為 TMS）作為內標準品，定義其化學位移為 0.00 ppm。分裂形式（splitting pattern）定義如下： s，單峰（singlet）；d，雙重峰（doublet）；t，三重峰（triplet）；q，四重峰（quartet）；quin，五重峰

（quintet）；m，多重峰（multiplet）。偶合常數（coupling constant）以 J 表 示，單位為 Hz。光譜數據的記錄順序是：化學位移（分裂形式，偶合常數，

氫核數）。¹³C NMR 光譜也以上述三台儀器進行操作，化學位移是以氘化

氯仿（CDCl₃）中間線作為內標準，定義其化學位移為 77.0 ppm。

2. 紅外線光譜儀（Infrared Spectroscopy，簡稱 IR）：使用 JASCOF/IR-5300 型光譜儀作為測定儀器。內標準品是以聚乙烯（polystyrene，PS）之 1601 cm^-1吸收峰進行校正，紅外線光譜單位為波數（cm^-1）。

3. 質譜儀（Mass Spectrometry，簡稱 MS）：使用 ThermoFinnigan LCQ Advantage 型質譜儀作為測定儀器。係委託黃岫妮老師於國立臺灣師範大學貴重儀器使用中心代測；高解析質譜（High Resolution Mass Spectroscopy，

簡稱 HRMS）則是使用 Waters XeV HMS G2-S TOF 型質譜儀作為測定儀器。委託黃岫妮老師於國立臺灣師範大學貴重儀器使用中心代測。

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4. 薄層色層分析（ Thin Layer Chromatography，簡稱為 TLC ）：使用 MACHEREY-NAGEL Pre-coated TLC sheets ALUGRAM Xtra SIL G/UV₂₅₄ 0.2 mm silica gel 60 的鋁箔薄片展開後，再以紫外燈來檢視薄層色層分析片。

5. 管柱色層分析（Column Chromatography）：使用友和 Silicycle Silica gel 60，

230-240 mesh ATSM 作為填充物，用加壓快速層析（ flash column chromatography）依 Still 的操作方式來分離。沖提液（eluent）若是兩種溶劑系統，是依體積比值而配製，記錄的方法為兩種溶劑之體積比值。

6. 熔點（metling point，簡稱 mp）：係由 Mel-Temp 熔點測定儀所測定。此儀器並未校正。

7. 所有反應物試劑和溶劑皆為試藥級或分析級，若藥品需進一步純化或乾燥，則依標準處理手續。乙醚（ether）、四氫呋喃（THF）、二氯甲烷（CH₂Cl₂）、乙腈（CAN）及甲苯（toluene）皆經過溶劑純化系統乾燥（active alumina column）。

8. 除水反應皆在氮氣下進行，並以磁石攪拌，在反應進行前須經過真空加

熱並填充氮氣（至少重複三次）。低溫反應（如：0 ^oC）主要以冰水與氯化

鈉控制冷卻溫度，如需更低溫（如：‒78 ^oC）則以乾冰加工業級丙酮控制

冷卻溫度。另外，反應時間的控制是以薄層色層分析（TLC）或核磁共振光譜儀（NMR）來測定。

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3.2 Gold(III) Chloride-Catalyzed Synthesis of Pyrrole Derivatives.

3.2.1 Experiments

Synthesis of N-((5-Bromofuran-2-yl)methyl)-4-methylbenzenesulfonamide (II-37 ).

Scheme S8

To an ice cooled solution of 5-bromofuran-2-carbaldehyde (II-40) (3.500 g, 20.00 mmol) in MeOH (100.0 mL) was added NaBH₄ (0.756 g, 20.00 mmol) in small portions. The reaction mixture was warmed to room temperature and stirred for 1 h. The solvent was removed under reduced pressure. The residue was dissolved in DCM (100 mL) and washed subsequently with water (50 mL), brine (50 mL), and dried over MgSO₄, and concentrated under reduced pressure to give (5-bromofuran-2-yl)methanol (II-39) (3.522 g, 19.9 mmol, 99%) as a colorless oil.

To a flame-dried two-neck-flask were added triphenylphosphine (PPh₃, 6.295 g, 24.00 mmol), diisopropyl azodicarboxylate (DIAD, 4.8 mL, 24.00 mmol), NHTs(Boc) (5.426 g, 20.00 mmol), and anhydrous THF (60 mL). The mixture was warmed to room temperature and stirred for 0.5 h. The solution of

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(5-bromofuran-2-yl)methanol (II-39) (3.522 g, 19.9 mmol) in 40 mL THF was added to the flask. The reaction was stirred for an additional 1 h. The solvent was removed under reduced pressure. The residue was purified via flash column chromatography (silica gel, EtOAc/hexanes 1:15) to afford tert-butyl ((5-bromofuran-2-yl)methyl)(tosyl)carbamate (II-38) as a brown oil ( 7.573 g, 17.60 mmol, 88%).

The tert-butyl ((5-bromofuran-2-yl)methyl)(tosyl)carbamate (II-38) (7.573 g, 17.60 mmol) was dissolved in MeOH (176.0 mL). The solution was added K₂CO₃ (17.026 g, 123.2 mmol). The reaction mixture was stirred at 50 ^oC for 8 hours. The solvent was removed under reduced pressure and the reaction was quenched with HCl(aq) and diluted with CH₂Cl₂. The residue was extracted with CH₂Cl₂ (3 × 60 mL), dried over MgSO₄, and concentrated under reduced pressure to give the residue. The residue was purified via flash column chromatography over silica gel (EtOAc/hexanes 1:2) to give

N-((5-bromofuran-2-yl)methyl)-4-methylbenzenesulfonamide (II-37) as a

white solid (3.169 g, 9.60 mmol, 55%) (Scheme S1).

GP 2-1: Synthesis of 4-Methyl-N-((5-arylfuran-2-yl)methyl)benzene sulfonamide II-36 .

Scheme S2

Example for the Synthesis of II-36 . The appropriate arylboronic acid

(0.6078 g, 4.00 mmol) and Pd(PPh₃)₄ (0.116 g, 0.10 mmol) were added to a

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solution of

N-((5-Bromofuran-2-yl)methyl)-4-methylbenzenesulfonamide (II-37) (0.660 g, 2.00 mmol) in a 1:1 mixture of THF (6.0 mL) and 1 M

KOH_(aq) (6.0 mL). The reaction mixture was stirred under nitrogen atmosphere for 20 h at 65 ^oC, poured into water (40.0 mL), extracted with EtOAc (3 × 60 mL). The combined organic layer was washed with brine and dried over MgSO₄, and concentrated to give the residue. The residue was purified via flash column chromatography over silica gel (EtOAc/hexanes 1:2) to give

N-((5-(3-methoxyphenyl)furan-2-yl)methyl)-4-methylbenzenesulfonamide (II-36) as a white solid (0.686 g, 1.92 mmol, 96%) (Scheme S2).

GP 2-2: Synthesis of tert-Butyl ((5-(arylethynyl)furan-2-yl)methyl)(tosyl) carbamate II-43 .

Scheme S3

Example for the Synthesis of II-43. To a dry and nitrogen-flushed two-neck-flask, equipped with a magnetic stirring bar and a septum, were charged with Pd(PPh₃)₄ (0.116 g, 0.1 mmol), CuI (0.048 g, 0.25 mmol), Cs₂CO₃ (1.157 g, 6 mmol), tert-butyl ((5-bromofuran-2-yl)methyl)(tosyl) carbamate (II-38) (2.152 g, 5.00 mmol), acetonitrile (25.0 mL). The reaction mixture was kept in dark, stirred at room temperature for 30 min and then were added ethynylbenzene (II-45) (0.664 g, 6.50 mmol). The reaction stirred at 60

oC until starting material was used up which can be detected on TLC. Upon

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back to room temperature, the reaction mixture was filtered and concentrated.

The residue was purified by flash column chromatography (silica gel, EtOAc/hexanes 1:30) yielding II-43 (0.902 g, 2.00 mmol, 40%) (Scheme S3).

GP 2-3: Synthesis of N-((5-(Arylethynyl)furan-2-yl)methyl)-4-methyl benzenesulfonamide II-42.

Scheme S4

tert-Butyl ((5-(phenylethynyl)furan-2-yl)methyl)(tosyl)carbamate (II-43)

(0.902 g, 2.00 mmol) was dissolved in MeOH (20.0 mL). The solution was added K₂CO₃ (1.935 g, 14.0 mmol). The reaction mixture was stirred at 50 ^oC for 8 hours. The solvent was removed under reduced pressure and the reaction was quenched with HCl_(aq) and diluted with CH₂Cl₂. The residue was extracted with CH₂Cl₂ (3 × 60 mL), dried over MgSO₄, and concentrated under reduced pressure to give the residue. The residue was purified via flash column chromatography over silica gel (EtOAc/hexanes 1:1) to give 4-methyl-N-((5-(phenylethynyl)furan-2-yl)methyl)benzenesulfonamide (II-42) as a white solid (0.210 g, 1.2 mmol, 60%) (Scheme S4).

GP 2-4: Synthesis of Methyl 3-((5-(((4-methylphenyl)sulfonamido)methyl) furan-2-yl)ethynyl)benzoate II-42i.

Scheme S5

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To an ice cooled solution of methyl 3-((5-(((N-(tert-butoxycarbonyl) -4-methylphenyl)sulfonamido)methyl)furan-2-yl)ethynyl)benzoate (II-43i) (1.554 g, 3.05 mmol) in DCM (30.5 mL) was added trifluoroacetic acid (TFA, 4.7 mL, 61.0 mmol). The mixture was warmed to room temperature and stirred for 2.0 h. Saturated NaHCO_3(aq) was added to the reaction mixture stirring vigorously. The aqueous layer was extracted with DCM (30.0 mL × 3). The organic portion was washed with brine (30.0 mL × 3), dried over anhydrous MgSO₄, and finally evaporated under reduced pressure to give the crude product. The crude mixture was purified via flash column chromatography over silica gel (EtOAc/hexanes 1:4) to give methyl 3-((5-(((4-methylphenyl) sulfonamido)methyl)furan-2-yl)ethynyl)benzoate (II-42i) as a white solid (0.573 g, 1.40 mmol, 46%) (Scheme S4).

GP 2-5: General Experimental Procedure for the Preparation of Ynamide-Tethered Furan II-47.

Scheme S6

- 46 -

Example for the Synthesis of II-47. To a dry and nitrogen-flushed

two-neck-flask, equipped with a magnetic stirring bar and a septum, were charged with (bromoethynyl)benzene II-36 (0.272 g, 1.50 mmol), toluene (6.0 mL), N-((5-(3-methox yphen yl)furan -2-yl)meth yl)-4-methylbenzene sulfonamide (II-46a) (0.3574 g, 1.00 mmol), and Cs₂CO₃ (0.652 g, 2.00 mmol).

The reaction mixture was stirred at room temperature for 5 min and then were added CuI (0.040 g, 0.21 mmol) and DMEDA (0.084 g, 0.95 mmol). The reaction was stirred at 50 ^oC until no trace of starting material can be detected on TLC. Upon cooling to room temperature, the reaction mixture was filtered and concentrated. The residue was purified by flash column chromatography (silica gel, EtOAc/hexanes 1:25) yielding II-47 (0.366 g, 0.8 mmol, 80%) (Scheme S6).

GP 2-6: General Experimental Procedure for the AuCl

₃

-Catalyzed Synthesis of (Z)-1-Aryl-3-(1H-pyrrol-3-yl)prop-2-en-1-one II-48 .

Scheme S7

Example for the Synthesis of II-48. A solution of AuCl

₃ (0.0038 g, 0.0125 mmol) in toluene (1.0 mL) in a dry and nitrogen-flushed two-neck-flask equipped with a stirring bar and capped with a rubber septum at room temperature was evacuated (oil pump) and filled with nitrogen three times. The

- 47 -

solution were added to a solution of N-((5-(3-methoxyphenyl)furan-2-yl) methyl)-4-methyl-N-(phenylethynyl)benzenesulfonamide (II-47) (0.1144 g, 0.25 mmol) in toluene (1.5 mL). After starting material had been consumed (monitored by TLC), the reaction mixture was filtered through a pad of Celite/silica gel and concentrated under reduced pressure. The residue was purified by flash column chromatography (silica gel, EtOAc/hexanes 1:27) yielding II-48 (0.080 g, 0.16 mmol, 70%) as a yellow oil (Scheme S7).

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3.3 Synthesis of N-((5-(Aryl)furan-2-yl)methyl)-4-methylbenzene sulfonamide II-36.

4-Methyl-N-((5-(p-tolyl)furan-2-yl)methyl)benzenesulfonamide (II-36a)

According to GP 2-1, II-37 (0.660 g, 2.00 mmol), THF (6.0 mL), KOH_(aq) (6.0 mL), p-tolylboronic acid (0.5443 g, 4.00 mmol), Pd(PPh₃)₄ (0.1156 g, 0.10 mmol) were employed. The mixture was stirred at 65 ℃ for 19 h. The crude mixture was purified via flash column chromatography over silica gel (ethyl acetate/hexanes = 1:3) to give II-36a as a white solid (0.423 g, 1.24 mmol, 62%) : R_f 0.18 (ethyl acetate /hexanes = 1:3), m.p. 161－162 ^oC.

H NMR (400 MHz, CDCl

₃): δ 7.73 – 7.68 (m, 2H), 7.39 – 7.34 (m, 2H), 7.21 (d, J = 8.1 Hz, 2H), 7.14 (d, J = 8.0 Hz, 2H), 6.37 (d, J = 3.3 Hz, 1H), 6.14 (d,

J = 3.2 Hz, 1H), 4.91 (s, 1H), 4.24 (s, 2H), 2.35 (s, 3H), 2.31 (s, 3H) ppm.

C NMR (100 MHz, CDCl

₃): δ 154.2, 148.5, 143.4, 137.4, 137.0, 129.6, 129.2, 127.6, 127.0, 123.6, 110.3, 104.7, 40.3, 21.4, 21.2 ppm.

IR (CH

₂Cl₂): ν 3301, 2363, 1620, 1436, 1316, 1159, 1064, 795, 658, 560 cm^-1.

MS (ESI) m/e (%) 364.3 ([M+Na]

⁺, 100).

HRMS (ESI) m/e calcd for C

₁₉H₁₉NO₃NaS [M+Na]⁺ 364.0983, found 364.0984.

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N-((5-(3-Methoxyphenyl)furan-2-yl)methyl)-4-methylbenzenesulfonamide (II-36b)

According to GP 2-1, II-37 (0.660 g, 2.00 mmol), THF (6.0 mL), KOH_(aq) (6.0 mL), (3-methoxyphenyl)boronic acid (0.6078 g, 4.00 mmol), Pd(PPh₃)₄ (0.1156 g, 0.10 mmol) were employed. The mixture was stirred at 65 ℃ for 20 h. The crude mixture was purified via flash column chromatography over silica gel (ethyl acetate/hexanes = 1:2) to give II-36b as a white solid (0.684 g, 1.91 mmol, 96%) : R_f 0.23 (ethyl acetate /hexanes = 1:3), m.p. 98－99 ^oC.

H NMR (400 MHz, CDCl

₃): δ 7.69 (d, J = 8.1 Hz, 2H), 7.26 (t, J = 8.0 Hz, 1H), 7.16 (d, J = 7.8 Hz, 2H), 7.06 (d, J = 7.8 Hz, 1H), 7.02 – 7.00 (m, 1H), 6.78 (dd, J = 8.2, 2.4 Hz, 1H), 6.40 (d, J = 3.3 Hz, 1H), 6.15 (d, J = 3.2 Hz, 1H), 5.32 – 5.20 (m, 1H), 4.22 (d, J = 6.1 Hz, 2H) ppm.

C NMR (100 MHz, CDCl

₃): δ 159.7, 153.6, 149.1, 143.3, 136.8, 131.5, 129.5, 129.4, 126.9, 116.2, 113.0, 110.3, 109.1, 105.8, 77.3, 77.0, 76.7, 55.2, 41.2, 21.2 ppm.

IR (CH

₂Cl₂): ν 3286, 2364, 1605, 1430, 1317, 1219, 1155, 1048, 810, 663, 545 cm^-1.

MS (ESI) m/e (%) 380.2 ([M+Na]

⁺, 100).

HRMS (ESI) m/e calcd for C

₁₉H₁₉NO₄NaS [M+Na]⁺ 380.0932, found 380.0934.

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N-((5-(4-Methoxyphenyl)furan-2-yl)methyl)-4-methylbenzenesulfonamide (II-36c)

According to GP 2-1, II-37 (0.660 g, 2.00 mmol), THF (6.0 mL), KOH_(aq) (6.0 mL), (4-methoxyphenyl)boronic acid (0.6078 g, 4.00 mmol), Pd(PPh₃)₄ (0.1156 g, 0.10 mmol) were employed. The mixture was stirred at 65 ℃ for 24 h. The crude mixture was purified via flash column chromatography over silica gel (ethyl acetate/hexanes = 1:2) to give II-36c as a white solid (0.608 g, 1.70 mmol, 85%) : R_f 0.18 (ethyl acetate /hexanes = 1:3), m.p. 140－141 ^oC.

H NMR (400 MHz, CDCl

₃): δ 7.73 – 7.69 (m, 2H), 7.43 – 7.38 (m, 2H), 7.22 (d, J = 8.1 Hz, 2H), 6.91 – 6.85 (m, 2H), 6.30 (d, J = 3.4 Hz, 1H), 6.14 (d, J = 3.4 Hz, 1H), 4.80 (s, 1H), 4.24 (d, J = 5.4 Hz, 2H), 3.83 (s, 3H), 2.33 (s, 3H) ppm.

C NMR (100 MHz, CDCl

₃): δ 159.2, 154.1, 148.2, 143.4, 137.0, 130.0, 127.1, 125.1, 123.4, 114.0, 110.4, 103.9, 55.3, 40.4, 21.4 ppm.

IR (CH

₂Cl₂): ν 3297, 2363, 1601, 1318, 1255, 1157, 1032, 787, 659, 546 cm^-1.

MS (ESI) m/e (%) 380.4 ([M+Na]

⁺, 100).

HRMS (ESI) m/e calcd for C

₁₉H₁₉NO₄NaS [M+Na]⁺ 380.0932, found 380.0929.

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4-Methyl-N-((5-(4-nitrophenyl)furan-2-yl)methyl)benzenesulfonamide (II-36d)

According to GP 2-1, II-37 (0.660 g, 2.00 mmol), THF (6.0 mL), KOH_(aq) (6.0 mL), (4-nitrophenyl)boronic acid (0.6660 g, 4.00 mmol), Pd(PPh₃)₄ (0.1156 g, 0.10 mmol) were employed. The mixture was stirred at 65 ℃ for 11 h. The crude mixture was purified via flash column chromatography over silica gel (ethyl acetate/hexanes = 1:1) to give II-36d as a orange solid (0.383 g, 1.02 mmol, 51%) : R_f 0.10 (ethyl acetate /hexanes = 1:3), m.p. 186－187 ^oC.

H NMR (400 MHz, CDCl

₃): δ 8.24 – 8.18 (m, 2H), 7.73 (d, J = 8.2 Hz, 2H), 7.64 – 7.58 (m, 2H), 7.24 (d, J = 8.1 Hz, 2H), 6.70 (d, J = 3.4 Hz, 1H), 6.29 (d,

J = 3.4 Hz, 1H), 4.94 (m, 1H), 4.29 (d, J = 6.2 Hz, 2H), 2.33 (s, 3H) ppm.

C NMR (100 MHz, CDCl

₃): δ 151.6, 151.5, 146.5, 143.6, 136.9, 135.8, 129.7, 127.1, 124.2, 123.8, 111.1, 109.6, 40.2, 21.4 ppm.

IR (CH

₂Cl₂): ν 3301, 2363, 1620, 1436, 1316, 1159, 1064, 795, 658, 560 cm^-1.

MS (ESI) m/e (%) 371.3 ([M－H]

^－, 100).

HRMS (ESI) m/e calcd for C

₁₈H₁₅N₂O₅S [M－H]^－ 371.0702, found 371.0703.

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N-((5-(4-Cyanophenyl)furan-2-yl)methyl)-4-methylbenzenesulfonamide (II-36e)

According to GP 2-1, II-37 (0.660 g, 2.00 mmol), THF (6.0 mL), KOH_(aq) (6.0 mL), (4-cyanophenyl)boronic acid (0.5878 g, 4.00 mmol), Pd(PPh₃)₄ (0.1156 g, 0.10 mmol) were employed. The mixture was stirred at 65 ℃ for 20 h. The crude mixture was purified via flash column chromatography over silica gel (ethyl acetate/hexanes = 1:2) to give II-36e as a yellow solid (0.486 g, 1.38 mmol, 69%) : R_f 0.10 (ethyl acetate /hexanes = 1:3), m.p. 182－183 ^oC.

H NMR (400 MHz, CDCl

₃): δ 7.72 (d, J = 8.3 Hz, 2H), 7.65 – 7.59 (m, 2H), 7.59 – 7.53 (m, 2H), 7.22 (d, J = 8.1 Hz, 2H), 6.62 (d, J = 3.4 Hz, 1H), 6.26 (d,

J = 3.3 Hz, 1H), 5.03 – 4.96 (m, 1H), 4.27 (d, J = 6.2 Hz, 2H), 2.32 (s, 3H)

ppm.

C NMR (100 MHz, CDCl

₃): δ 151.9, 151.0, 143.6, 136.4, 134.0, 132.5, 129.6, 127.0, 123.8, 118.8, 110.9, 110.5, 108.7, 40.2, 21.4 ppm.

IR (CH

₂Cl₂): ν 3301, 2363, 1620, 1436, 1316, 1159, 1064, 795, 658, 560 cm^-1.

MS (ESI) m/e (%) 351.3 ([M－H]

^－, 100).

HRMS (ESI) m/e calcd for C

₁₉H₁₅N₂O₃S [M－H]^－ 351.0803, found 351.0805.

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3.4 Synthesis of tert-Butyl ((5-(arylethynyl)furan-2-yl)methyl)(tosyl) carbamate II-43.

tert-Butyl ((5-(phenylethynyl)furan-2-yl)methyl)(tosyl)carbamate (II-43a)

According to GP 2-2, Pd(PPh₃)₄ (0.116 g, 0.1 mmol), CuI (0.048 g, 0.25 mmol),Cs₂CO₃ (1.157 g, 6 mmol), tert-butyl ((5-bromofuran-2-yl)methyl) (tosyl)carbamate (II-38) (2.152 g, 5.00 mmol) were dissolved in acetonitrile (25.0 mL). The mixture was stirred at room temperature for 30 min and then were added ethynylbenzene (II-45a) (0.664 g, 6.50 mmol). The reaction stirred at 60 ^oC for 3d. The crude mixture was purified via flash column chromatography over silica gel (ethyl acetate/hexanes = 1:40) to give II-43a as a brown oil (0.902 g, 2.00 mmol, 40%) : R_f 0.18 (ethyl acetate /hexanes = 1:10).

H NMR (400 MHz, CDCl

₃): δ 7.74 – 7.69 (m, 2H), 7.38 – 7.33 (m, 3H) , 7.26 (s, 1H), 7.24 (s, 1H), 6.60 (d, J = 3.3 Hz, 1H), 6.37 (d, J = 3.3 Hz, 1H), 5.03 (s, 2H), 2.39 (s, 3H),1.38 (s, 9H) ppm.

C NMR (100 MHz, CDCl

₃): δ 151.8, 150.5, 144.2, 136.8, 136.7, 131.3, 129.1, 128.7, 128.4, 128.3, 122.3, 116.1, 110.3, 93.3, 84.7, 79.4, 42.6, 27.9, 21.56 ppm.

IR (CH

₂Cl₂): ν 2981, 1732, 1598, 1359, 1309, 1257, 1152, 1089, 803, 567 cm^-1.

MS (ESI) m/e (%) 474.0 ([M+Na]

⁺, 100).

HRMS (ESI) m/e calcd for C

₂₅H₂₅NO₅NaS [M+Na]⁺ 474.1351, found 474.1353.

- 54 -

tert-Butyl ((5-(o-tolylethynyl)furan-2-yl)methyl)(tosyl)carbamate (II-43b)

According to GP 2-2, Pd(PPh₃)₄ (0.116 g, 0.1 mmol), CuI (0.048 g, 0.25 mmol), Cs₂CO₃ (1.157 g, 6 mmol), tert-butyl ((5-bromofuran-2-yl)methyl) (tosyl)carbamate (II-38) (2.152 g, 5.00 mmol) were dissolved in acetonitrile (25.0 mL). The mixture was stirred at room temperature for 30 min and then were added 1-ethynyl-2-methylbenzene (II-45b) (0.755 g, 6.50 mmol). The reaction stirred at 60 ^oC for 4d. The crude mixture was purified via flash column chromatography over silica gel (ethyl acetate/hexanes = 1:40) to give

II-43b as a yellow oil (0.791 g, 1.70 mmol, 34%) : R

_f 0.18 (ethyl acetate /hexanes = 1:10).

H NMR (400 MHz, CDCl

₃): δ 7.71 (d, J = 8.3 Hz, 2H), 7.47 (d, J = 7.5 Hz, 1H), 7.28 – 7.21 (m, 4H), 7.17 (td, J = 7.2, 2.0 Hz, 1H), 6.60 (d, J = 3.3 Hz, 1H), 6.38 (d, J = 3.4 Hz, 1H), 5.04 (s, 2H), 2.47 (s, 3H), 2.38 (s, 3H), 1.38 (s, 9H) ppm.

C NMR (100 MHz, CDCl

₃): δ 151.7, 150.5, 144.2, 140.0, 136.7, 136.6, 131.6, 129.5, 129.1, 128.7, 128.2, 125.6, 122.0, 115.8, 110.3, 92.2, 84.7, 83.1, 42.5, 27.8, 21.5, 20.6 ppm.

IR (CH

₂Cl₂): ν 2981, 1731, 1359, 1310, 1152, 1089,758, 565 cm^-1.

MS (ESI) m/e (%) 488.0 ([M+Na]

⁺, 100).

HRMS (ESI) m/e calcd for C

₂₆H₂₇NO₅NaS [M+Na]⁺ 488.1580, found 488.1507.

- 55 -

tert-Butyl ((5-(m-tolylethynyl)furan-2-yl)methyl)(tosyl)carbamate (II-43c)

According to GP 2-2, Pd(PPh₃)₄ (0.116 g, 0.1 mmol), CuI (0.048 g, 0.25 mmol), Cs₂CO₃ (1.157 g, 6 mmol), tert-butyl ((5-bromofuran-2-yl)methyl) (tosyl) carbamate (II-38) (2.152 g, 5.00 mmol) were dissolved in acetonitrile (25.0 mL). The mixture was stirred at room temperature for 30 min and then were added 1-ethynyl-3-methylbenzene (II-45c) (0.754 g, 6.50 mmol). The reaction stirred at 60 ^oC for 3.5d. The crude mixture was purified via flash column chromatography over silica gel (ethyl acetate/hexanes = 1:30) to give

II-43c as a yellow oil (1.023 g, 2.20 mmol, 44%) : R

_f 0.22 (ethyl acetate /hexanes = 1:10).

H NMR (400 MHz, CDCl

₃): δ 7.72 (d, J = 8.3 Hz, 2H), 7.35 – 7.29 (m, 2H), 7.28 – 7.21 (m, 3H), 7.19 – 7.14 (m, 1H), 6.58 (d, J = 3.3 Hz, 1H), 6.37 (d, J = 3.3 Hz, 1H), 5.03 (s, 2H), 2.39 (s, 3H), 2.35 (s, 3H), 1.38 (s, 9H) ppm.

C NMR (100 MHz, CDCl

₃): δ 151.7, 150.5, 144.2, 138.1, 136.8, 136.7, 131.8, 129.6, 129.1, 128.4, 128.3, 128.2, 122.0, 115.9, 110.3, 93.5, 84.7, 79.0, 42.5, 27.8, 21.5, 21.2 ppm.

IR (CH

₂Cl₂): ν 2982, 1731, 1599, 1360, 1309,1152, 1089, 1018, 847, 787, 715, 568 cm^-1.

MS (ESI) m/e (%) 488.0 ([M+Na]

⁺, 100).

HRMS (ESI) m/e calcd for C²⁶H₂₇NO₅NaS [M+Na]⁺ 488.1580, found 488.1508.

- 56 -

tert-Butyl ((5-(p-tolylethynyl)furan-2-yl)methyl)(tosyl)carbamate (II-43d)

According to GP 2-2, Pd(PPh₃)₄ (0.116 g, 0.1 mmol), CuI (0.048 g, 0.25 mmol), Cs₂CO₃ (1.157 g, 6 mmol), tert-butyl ((5-bromofuran-2-yl)methyl) (tosyl) carbamate (II-38) (2.152 g, 5.00 mmol) were dissolved in acetonitrile (25.0 mL). The mixture was stirred at room temperature for 30 min and then were added 1-ethynyl-4-methylbenzene (II-45d) (0.754 g, 6.50 mmol). The reaction stirred at 60 ^oC for 2.5d. The crude mixture was purified via flash column chromatography over silica gel (ethyl acetate/hexanes = 1:25) to give

II-43d as a yellow solid (1.581 g, 3.40 mmol, 68%) : R

_f 0.35 (ethyl acetate /hexanes = 1:10), m.p. 134－135 ^oC.

H NMR (400 MHz, CDCl

₃): δ 7.72 (d, J = 8.2 Hz, 2H), 7.40 (d, J = 8.0 Hz, 2H), 7.25 (d, J = 7.9 Hz, 2H), 7.16 (d, J = 8.0 Hz, 2H), 6.57 (d, J = 3.3 Hz, 1H), 6.36 (d, J = 3.3 Hz, 1H), 5.03 (s, 2H), 2.39 (s, 3H), 2.37 (s, 3H), 1.38 (s, 9H) ppm.

C NMR (100 MHz, CDCl

₃): δ 151.6, 150.5, 144.2, 139.0, 136.8, 136.7, 131.3, 129.2, 129.1, 128.2, 119.4, 115.8, 110.3, 93.4, 84.7, 78.7, 42.5, 27.8, 21.5, 21.5 ppm.

IR (CH

₂Cl₂): ν 2981, 1732, 1359, 1311, 1249, 1153, 1089, 813, 713, 571 cm^-1.

MS (ESI) m/e (%) 488.1 ([M+Na]

⁺, 100).

HRMS (ESI) m/e calcd for C

₂₆H₂₇NO₅NaS [M+Na]⁺ 488.1508, found 488.1509.

- 57 -

tert-Butyl ((5-((4-methoxyphenyl)ethynyl)furan-2-yl)methyl)(tosyl)

carbamate (II-43e)

According to GP 2-2, Pd(PPh₃)₄ (0.116 g, 0.1 mmol), CuI (0.048 g, 0.25 mmol), Cs₂CO₃ (1.157 g, 6 mmol), tert-butyl ((5-bromofuran-2-yl)methyl) (tosyl) carbamate (II-38) (2.152 g, 5.00 mmol) were dissolved in acetonitrile (25.0 mL). The mixture was stirred at room temperature for 30 min and then were added 1-ethynyl-4-methoxybenzene (II-45e) (0.859 g, 6.50 mmol). The reaction stirred at 60 ^oC for 2.5d. The crude mixture was purified via flash column chromatography over silica gel (ethyl acetate/hexanes = 1:20) to give

II-43e as a yellow solid (1.276 g, 2.65 mmol, 53%) : R

_f 0.12 (ethyl acetate /hexanes = 1:10), m.p. 106－108 ^oC.

H NMR (400 MHz, CDCl

₃): δ 7.72 (d, J = 8.3 Hz, 2H), 7.43 (d, J = 8.7 Hz, 2H), 7.24 (d, J = 8.2 Hz, 2H), 6.87 (d, J = 8.8 Hz, 2H), 6.55 (d, J = 3.3 Hz, 1H), 6.36 (d, J = 3.4 Hz, 1H), 5.03 (s, 2H), 3.79 (s, 3H), 2.37 (s, 3H), 1.37 (s, 9H) ppm.

C NMR (100 MHz, CDCl

₃): δ 159.9, 151.3, 150.4, 144.1, 136.8, 136.5, 132.8, 129.0, 128.1, 115.4, 114.1, 114.0, 110.2, 93.1, 84.5, 78.0, 55.1, 42.4, 27.7, 21.45ppm.

IR (CH

₂Cl₂): ν 2976, 1731, 1358, 1286, 1250, 1152, 804, 566 cm^-1.

MS (ESI) m/e (%) 504.1 ([M+Na]

⁺, 100).

- 58 -

tert-Butyl ((5-([1,1'-biphenyl]-4-ylethynyl)furan-2-yl)methyl)(tosyl)

carbamate (II-43f)

According to GP 2-2, Pd(PPh₃)₄ (0.116 g, 0.1 mmol), CuI (0.048 g, 0.25 mmol), Cs₂CO₃ (1.157 g, 6 mmol), tert-butyl ((5-bromofuran-2-yl)methyl) (tosyl) carbamate (II-38) (2.152 g, 5.00 mmol) were dissolved in acetonitrile (25.0 mL). The mixture was stirred at room temperature for 30 min and then were added 4-ethynyl-1,1'-biphenyl (II-45f) (1.159 g, 6.50 mmol). The reaction stirred at 60 ^oC for 3.5d. The crude mixture was purified via flash column chromatography over silica gel (ethyl acetate/hexanes = 1:20) to give II-43f as a white solid (1.557 g, 2.95 mmol, 59%) : R_f 0.18 (ethyl acetate /hexanes = 1:10), m.p. 143－144 ^oC.

H NMR (400 MHz, CDCl

₃): δ 7.72 (d, J = 8.4 Hz, 2H), 7.63 – 7.55 (m, 6H), 7.49 – 7.43 (m, 2H), 7.40 – 7.34 (m, 1H), 7.26 (d, J = 8.0 Hz, 2H), 6.62 (d, J = 3.3 Hz, 1H), 6.38 (d, J = 3.2 Hz, 1H), 5.04 (s, 2H), 2.40 (s, 3H), 1.38 (s, 9H) ppm.

C NMR (100 MHz, CDCl

₃): δ 151.8, 150.5, 144.2, 141.4, 140.1, 136.7, 136.6, 131.7, 129.1, 128.8, 128.2, 127.7, 127.0, 126.9, 121.1, 116.1, 110.4, 93.2, 84.7, 80.0, 42.5, 27.8, 21.5 ppm.

IR (CH

₂Cl₂): ν 2981, 1735, 1357, 1278, 1150, 1089, 804, 764, 712, 566 cm^-1.

MS (ESI) m/e (%) 550.1 ([M+Na]

⁺, 100).

HRMS (ESI) m/e calcd for C31H29NO5NaS [M+Na]+ 550.1664, found

550.1661.

- 59 -

tert-Butyl ((5-((3-nitrophenyl)ethynyl)furan-2-yl)methyl)(tosyl)carbamate (II-43g)

According to GP 2-2, Pd(PPh₃)₄ (0.116 g, 0.1 mmol), CuI (0.048 g, 0.25 mmol), Cs₂CO₃ (1.157 g, 6 mmol), tert-butyl ((5-bromofuran-2-yl)methyl) (tosyl) carbamate (II-38) (2.152 g, 5.00 mmol) were dissolved in acetonitrile (25.0 mL). The mixture was stirred at room temperature for 30 min and then were added 1-ethynyl-3-nitrobenzene (II-45) (0.956 g, 6.50 mmol). The reaction stirred at 60 ^oC for 0.5d. The crude mixture was purified via flash column chromatography over silica gel (ethyl acetate/hexanes = 1:12) to give

II-43g as a yellow oil (0.695 g, 1.40 mmol, 28%) : R

_f 0.20 (ethyl acetate /hexanes = 1:5).

H NMR (400 MHz, CDCl

₃): δ 8.37 – 8.33 (m, 1H), 8.23 – 8.17 (m, 1H), 7.80 (d, J = 7.7 Hz, 1H), 7.71 (d, J = 8.3 Hz, 2H), 7.56 (t, J = 8.0 Hz, 1H), 7.28 (d, J

= 7.8 Hz, 2H), 6.70 (d, J = 3.4 Hz, 1H), 6.42 (d, J = 3.4 Hz, 1H), 5.05 (s, 2H), 2.42 (s, 3H), 1.38 (s, 9H) ppm.

C NMR (100 MHz, CDCl

₃): δ 152.8, 150.5, 148.1, 144.4, 136.7, 135.7, 129.5, 129.2, 128.2, 126.0, 124.1, 123.2, 117.6, 110.5, 91.0, 84.9, 81.9, 42.5, 27.8, 21.6 ppm.

IR (CH

₂Cl₂): ν 2978, 1731, 1528, 1351, 1307, 1154, 806, 674 cm^-1.

MS (ESI) m/e (%) 519.3 ([M+Na]

⁺, 100).

HRMS (ESI) m/e calcd for C

₂₅H₂₄N₂O₇NaS [M+Na]⁺ 519.1202, found 519.1201.

- 60 -

tert-Butyl ((5-(thiophen-3-ylethynyl)furan-2-yl)methyl)(tosyl)carbamate (II-43h)

According to GP 2-2, Pd(PPh₃)₄ (0.116 g, 0.1 mmol), CuI (0.048 g, 0.25 mmol), Cs₂CO₃ (1.157 g, 6 mmol), tert-butyl ((5-bromofuran-2-yl)methyl) (tosyl) carbamate (II-38) (2.152 g, 5.00 mmol) were dissolved in acetonitrile (25.0 mL). The mixture was stirred at room temperature for 30 min and then were added 3-ethynylthiophene (II-45h) (0.703 g, 6.50 mmol). The reaction stirred at 60 ^oC for 2.75d. The crude mixture was purified via flash column chromatography over silica gel (ethyl acetate/hexanes = 1:15) to give II-43h as a yellow solid (1.052 g, 2.30 mmol, 46%) : R_f 0.18 (ethyl acetate /hexanes = 1:10), m.p. 121－122 ^oC.

H NMR (400 MHz, CDCl

₃): δ 7.71 (d, J = 8.3 Hz, 2H), 7.55 – 7.51 (m, 1H), 7.32 – 7.28 (m, 1H), 7.26 (d, J = 8.2 Hz, 2H), 7.17 (dd, J = 4.9, 0.7 Hz, 1H), 6.58(d, J = 3.4 Hz, 1H), 6.37 (d, J = 3.3 Hz, 1H), 5.03 (s, 2H), 2.38 (s, 3H), 1.37 (s, 9H) ppm.

C NMR (100 MHz, CDCl

₃): δ 151.6, 150.4, 144.2, 136.6, 136.4, 129.4, 129.1, 129.0, 128.1, 125.6, 121.1, 115.9, 110.2, 88.4, 84.6, 78.8, 42.4, 27.7, 21.4 ppm.

IR (CH

₂Cl₂): ν 2980, 1730, 1638, 1357, 1310, 1153, 1089, 778, 566 cm^-1.

MS (ESI) m/e (%) 480.3 ([M+Na]

⁺, 100).

HRMS (ESI) m/e calcd for C

₂₃H₂₃NO₅NaS₂ [M+Na]⁺480.0915, found 480.0919.

- 61 -

Methyl 3-((5-(((N-(tert-butoxycarbonyl)-4-methylphenyl)sulfonamido) methyl)furan-2-yl)ethynyl)benzoate (II-43i)

According to GP 2-2, Pd(PPh₃)₄ (0.116 g, 0.1 mmol), CuI (0.048 g, 0.25 mmol), Cs₂CO₃ (1.157 g, 6 mmol), tert-butyl ((5-bromofuran-2-yl)methyl) (tosyl)arbamate (II-38) (2.152 g, 5.00 mmol) were dissolved in acetonitrile (25.0 mL). The mixture was stirred at room temperature for 30 min and then were added methyl 3-ethynylbenzoate (II-45i) (1.040 g, 6.50 mmol). The reaction stirred at 60 ^oC for 4.5d. The crude mixture was purified via flash column chromatography over silica gel (ethyl acetate/hexanes = 1:15) to give

II-43i as a yellow solid (1.554 g, 3.05 mmol, 61%) : R

_f 0.15 (ethyl acetate /hexanes = 1:10), m.p. 96－97 ^oC.

H NMR (400 MHz, CDCl

₃): δ 8.18 (s, 1H), 8.01 (d, J = 7.8 Hz, 1H), 7.72 (d,

J = 8.2 Hz, 2H), 7.67 (d, J = 7.8 Hz, 1H), 7.44 (t, J = 7.8 Hz, 1H), 7.26 (d, J =

8.2 Hz, 2H), 6.64 (d, J = 3.3 Hz, 1H), 6.39 (d, J = 3.3 Hz, 1H), 5.04 (s, 2H), 3.93 (s, 3H), 2.40 (s, 3H), 1.38 (s, 9H) ppm.

C NMR (100 MHz, CDCl

₃): δ 166.1, 152.1, 150.5, 144.2, 136.7, 136.2, 135.2, 132.6, 130.5, 129.5, 129.1, 128.5, 128.2, 122.8, 116.6, 110.3, 92.2, 84.7, 80.2, 52.2, 42.5, 27.8, 21.5 ppm.

IR (CH

₂Cl₂): ν 2983, 1731, 1598, 1439, 1359, 1258, 1155, 1089, 1018, 804, 676, 569 cm^-1.

MS (ESI) m/e (%) 532.0 ([M+Na]

⁺, 100).

HRMS (ESI) m/e calcd for C

₂₇H₂₇NO₇NaS [M+Na]⁺ 532.1406, found 532.1403.

- 62 -

3.5 Synthesis of 4-Methyl-N-(arylethynyl)furan-2-yl)methyl)benzene sulfonamide II-42.

4-Methyl-N-((5-(phenylethynyl)furan-2-yl)methyl)benzenesulfonamide (II-42a)

According to GP 2-3, tert-butyl ((5-(phenylethynyl)furan-2-yl)methyl) (tosyl)carbamate (II-43a) (0.902 g, 2.00 mmol) was dissolved in MeOH (20.0 mL). The solution was added K₂CO₃ (1.935 g, 14.0 mmol). The reaction mixture was stirred at 50 ^oC for 8 hours. The crude mixture was purified via flash column chromatography over silica gel (ethyl acetate/hexanes = 1:1) to give II-42a as a yellow solid (0.421 g, 1.20 mmol, 60%) : R_f 0.22 (ethyl acetate /hexanes = 1: 3), m.p. 171－172 ^oC.

H NMR (400 MHz, CDCl

₃): δ 7.73 – 7.69 (m, 2H), 7.53 – 7.46 (m, 2H), 7.39 – 7.33 (m, 3H), 7.28 (d, J = 8.2 Hz, 2H), 6.46 (d, J = 3.3 Hz, 1H), 6.13 (d, J = 3.2 Hz, 1H), 4.80 (s, 1H), 4.20 (s, 2H), 2.40 (s, 3H) ppm.

C NMR (100 MHz, CDCl

₃): δ 150.6, 143.6, 137.0, 136.8, 131.4, 129.7, 128.9, 128.4, 127.1, 122.0, 115.9, 109.6, 93.6, 78.9, 40.3, 21.5 ppm.

IR (CH

₂Cl₂): ν 3251, 1595, 1438, 1317, 1157, 1052, 812, 685, 542 cm^-1.

MS (ESI) m/e (%) 374.2 ([M+Na]

⁺, 100).

HRMS (ESI) m/e calcd for C

₂₀H₁₇NO₃NaS [M+Na]⁺ 374.0827, found 374.0826.

- 63 -

4-Methyl-N-((5-(o-tolylethynyl)furan-2-yl)methyl)benzenesulfonamide (II-42b)

According to GP 2-3, tert-butyl ((5-(o-tolylethynyl)furan-2-yl)methyl) (tosyl)carbamate (II-43b) (0.931 g, 2.00 mmol) was dissolved in MeOH (20.0 mL). The solution was added K₂CO₃ (1.935 g, 14.0 mmol). The reaction mixture was stirred at 50 ^oC for 8 hours. The crude product was purified by recrystallization from ethyl acetate and hexane. Obtained II-42b as a white solid (0.607 g, 1.66 mmol, 83%) : R_f 0.22 (ethyl acetate /hexanes = 1: 3), m.p.

153－154 ^oC.

H NMR (400 MHz, CDCl

₃): δ 7.74 – 7.69 (m, 2H), 7.45 (d, J = 7.5 Hz, 1H), 7.30 – 7.20 (m, 4H), 7.16 (td, J = 7.4, 1.6 Hz, 1H), 6.44 (d, J = 3.4 Hz, 1H), 6.13 (d, J = 3.2 Hz, 1H), 5.01 – 4.93 (m, 1H), 4.19 (d, J = 6.2 Hz, 2H), 2.46 (s, 3H), 2.38 (s, 3H) ppm.

C NMR (100 MHz, CDCl

₃): δ 150.6, 143.6, 140.1, 137.1, 136.7, 131.7, 129.6, 129.5, 128.8, 127.1, 125.6, 121.8, 115.7, 109.6, 92.5, 82.7, 40.2, 21.5, 20.6 ppm.

IR (CH

₂Cl₂): ν 3252, 2364, 1598, 1437, 1320, 1157, 1053, 954, 890, 813, 720, 543 cm^-1.

MS (ESI) m/e (%) 388.4 ([M+Na]

⁺, 100).

HRMS (ESI) m/e calcd for C

₂₁H₁₉NO₃NaS [M+Na]⁺ 388.0983, found 388.0984.

- 64 -

4-Methyl-N-((5-(m-tolylethynyl)furan-2-yl)methyl)benzenesulfonamide (II-42c)

According to GP 2-3, tert-butyl ((5-(m-tolylethynyl)furan-2-yl)methyl) (tosyl)carbamate (II-43c) (0.931 g, 2.00 mmol) was dissolved in MeOH (20.0 mL). The solution was added K₂CO₃ (1.935 g, 14.0 mmol). The reaction mixture was stirred at 50 ^oC for 8 hours. The crude mixture was purified via flash column chromatography over silica gel (ethyl acetate/hexanes = 1:2) to give II-42c as a yellow solid (0.373 g, 1.02 mmol, 51%) : R_f 0.25 (ethyl acetate /hexanes = 1: 3), m.p. 166－167 ^oC.

H NMR (400 MHz, CDCl

₃): δ 7.71 (d, J = 8.2 Hz, 2H), 7.33 – 7.27 (m, 3H), 7.27 – 7.21 (m, 2H), 7.19 – 7.14 (m, 1H), 6.43 (d, J = 3.3 Hz, 1H), 6.12 (d, J = 3.4 Hz, 1H), 4.96 – 4.89 (m, 1H), 4.19 (d, J = 6.2 Hz, 2H), 2.39 (s, 3H), 2.35 (s, 3H) ppm.

C NMR (100 MHz, CDCl

₃): δ 150.6, 143.6, 138.1, 137.0, 136.7, 131.9, 129.7, 129.6, 128.4, 128.3, 127.1, 121.8, 125.8, 109.5, 93.8, 78.6, 40.2, 21.5, 21.2 ppm.

IR (CH

₂Cl₂): ν 3250, 2365, 1621, 1432, 1321, 1159, 1041, 814, 725, 544 cm^-1.

MS (ESI) m/e (%) 388.2 ([M+Na]

⁺, 100).

HRMS (ESI) m/e calcd for C

₂₁H₁₉NO₃NaS [M+Na]⁺ 388.0983, found 388.0985.

- 65 -

4-Methyl-N-((5-(p-tolylethynyl)furan-2-yl)methyl)benzenesulfonamide (II-42d)

According to GP 2-3, tert-butyl ((5-(p-tolylethynyl)furan-2-yl)methyl) (tosyl)carbamate (II-43d) (0.930 g, 2.00 mmol) was dissolved in MeOH (20.0 mL). The solution was added K₂CO₃ (1.935 g, 14.0 mmol). The reaction mixture was stirred at 50 ^oC for 8 hours. The crude mixture was purified via flash column chromatography over silica gel (ethyl acetate/hexanes = 1:2) to give II-42d as a white solid (0.614 g, 1.68 mmol, 84%) : R_f 0.13 (ethyl acetate /hexanes = 1: 5), m.p. 190－192 ^oC.

H NMR (400 MHz, CDCl

₃): δ 7.71 (d, J = 8.2 Hz, 2H), 7.39 (d, J = 8.0 Hz, 2H), 7.27 (d, J = 9.4 Hz, 2H), 7.16 (d, J = 8.0 Hz, 2H), 6.43 (d, J = 3.3 Hz, 1H), 6.11 (d, J = 3.3 Hz, 1H), 4.86 – 4.78 (m, 1H), 4.19 (d, J = 6.2 Hz, 2H), 2.39 (s, 3H), 2.37 (s, 3H) ppm.

C NMR (100 MHz, CDCl

₃): δ 150.5, 143.6, 139.1, 137.2, 136.8, 131.3, 129.6, 129.2, 127.1, 118.9, 115.6, 109.5, 93.8, 78.3, 40.2, 21.6, 21.5 ppm.

IR (CH

₂Cl₂): ν 3255, 2363, 1594, 1438, 1320, 1159, 1052, 811, 719, 545 cm^-1.

MS (ESI) m/e (%) 388.2 ([M+Na]

⁺, 100).

HRMS (ESI) m/e calcd for C

₂₁H₁₉NO₃NaS [M+Na]⁺ 388.0983, found 388.0984.

- 66 -

N-((5-((4-Methoxyphenyl)ethynyl)furan-2-yl)methyl)-4-methylbenzene

sulfonamide (II-42e)

According to GP 2-3, tert-butyl ((5-((4-methoxyphenyl)ethynyl) furan-2-yl)methyl)(tosyl)carbamate (II-43e) (0.963 g, 2.00 mmol) was dissolved in MeOH (20.0 mL). The solution was added K₂CO₃ (1.935 g, 14.0 mmol). The reaction mixture was stirred at 50 ^oC for 8 hours. The crude product was purified by recrystallization from ethyl acetate and hexane.

Obtained II-42e as a white solid (0.664 g, 1.74 mmol, 87%) : R_f 0.10 (ethyl acetate /hexanes = 1: 3), m.p. 187－188 ^oC.

H NMR (400 MHz, CDCl

₃): δ 7.73 – 7.68 (m, 2H), 7.46 – 7.40 (m, 2H), 7.27 (d, J = 8.2 Hz, 2H), 6.91 – 6.85 (m, 2H), 6.41 (d, J = 3.3 Hz, 1H), 6.11 (d, J = 3.4 Hz, 1H), 4.99 – 4.92 (m, 1H), 4.18 (d, J = 6.2 Hz, 2H), 3.83 (s, 3H), 2.39 (s, 3H) ppm.

C NMR (100 MHz, CDCl

₃): δ 160.1, 150.3, 143.6, 137.3, 136.7, 133.0, 129.6, 127.1, 115.3, 114.1, 114.0, 109.5, 93.6, 77.7, 55.3, 40.3, 21.5 ppm.

IR (CH

₂Cl₂): ν 3253, 2366, 1598, 1501, 1320, 1253, 1160, 1048, 813, 739, 540 cm^-1.

MS (ESI) m/e (%) 404.2 ([M+Na]

⁺, 100).

HRMS (ESI) m/e calcd for C

₂₁H₁₉NO₄NaS [M+Na]⁺ 404.0932, found 404.0932.

- 67 -

N-((5-([1,1'-Biphenyl]-4-ylethynyl)furan-2-yl)methyl)-4-methylbenzene

sulfonamide (II-42f)

According to GP 2-3, tert-butyl ((5-([1,1'-biphenyl]-4-ylethynyl) furan-2-yl)methyl)(tosyl)carbamate (II-43f) (1.055 g, 2.00 mmol) was dissolved in MeOH (20.0 mL). The solution was added K₂CO₃ (1.935 g, 14.0 mmol). The reaction mixture was stirred at 50 ^oC for 8 hours. The crude mixture was purified via flash column chromatography over silica gel (ethyl acetate/hexanes = 1:2) to give II-42f as a yellow solid (0.598 g, 1.40 mmol, 70%) : R_f 0.12 (ethyl acetate /hexanes = 1: 5), m.p. 221－222 ^oC.

H NMR (400 MHz, CDCl

₃): δ 7.74 – 7.69 (m, 2H), 7.63 – 7.58 (m, 4H), 7.58 – 7.54 (m, 2H), 7.49 – 7.43 (m, 2H), 7.41 – 7.34 (m, 1H), 7.29 (d, J = 8.0 Hz, 2H), 6.48 (d, J = 3.4 Hz, 1H), 6.14 (d, J = 3.4 Hz, 1H), 4.84 – 4.77 (m, 1H), 4.21 (d, J = 6.2 Hz, 2H), 2.41 (s, 3H) ppm.

C NMR (100 MHz, CDCl

₃): δ 150.7, 143.7, 141.6, 140.1, 137.1, 136.8, 131.8, 129.7, 128.9, 127.8, 127.1, 127.0, 120.9, 116.0, 109.6, 93.6, 79.6, 40.3, 21.5 ppm.

IR (CH

₂Cl₂): ν 3258, 2378, 1625, 1434, 1320, 1159, 1050, 808, 724, 544 cm^-1.

MS (ESI) m/e (%) 450.3 ([M+Na]

⁺, 100).

HRMS (ESI) m/e calcd for C

₂₆H₂₁NO₃NaS [M+Na]⁺ 450.1140, found 450.1140.

- 68 -

4-Methyl-N-((5-((3-nitrophenyl)ethynyl)furan-2-yl)methyl)benzene sulfonamide (II-42g)

According to GP 2-3, tert-butyl ((5-((3-nitrophenyl)ethynyl)furan-2-yl) methyl)(tosyl)carbamate (II-43g) (0.993 g, 2.00 mmol) was dissolved in MeOH (20.0 mL). The solution was added K₂CO₃ (1.935 g, 14.0 mmol). The reaction mixture was stirred at 50 ^oC for 8 hours. The crude mixture was purified via flash column chromatography over silica gel (ethyl acetate/hexanes

= 1: 2) to give II-42g as a yellow solid (0.658 g, 1.66 mmol, 83%) : R_f 0.25 (ethyl acetate /hexanes = 1: 3), m.p. 160－162 ^oC.

H NMR (400 MHz, CDCl

₃): δ 8.36 – 8.32 (m, 1H), 8.23 – 8.18 (m, 1H), 7.81 – 7.76 (m, 1H), 7.72 (d, J = 8.2 Hz, 2H), 7.56 (t, J = 8.0 Hz, 1H), 7.29 (d, J = 8.2 Hz, 2H), 6.56 (d, J = 3.4 Hz, 1H), 6.18 (d, J = 3.4 Hz, 1H), 4.89 – 4.82 (m, 1H), 4.21 (d, J = 6.2 Hz, 2H), 2.41 (s, 3H) ppm.

C NMR (100 MHz, CDCl

₃): δ 151.7, 148.2, 143.7, 136.7, 136.1, 129.7, 129.6, 127.1, 126.0, 124.0, 123.4, 117.3, 109.7, 91.2, 81.4, 40.2, 21.5 ppm.

IR (CH

₂Cl₂): ν 3255, 2361, 1618, 1529, 1350, 1151, 1050, 807, 681, 544 cm^-1.

MS (ESI) m/e (%) 395.3 ([M－H]

^－, 100).

HRMS (ESI) m/e calcd for C

₂₀H₁₅N₂O₅S [M－H]^－ 395.0702, found 395.0702.

- 69 -

4-Methyl-N-((5-(thiophen-3-ylethynyl)furan-2-yl)methyl)benzene sulfonamide (II-42h)

According to GP 2-3, tert-butyl ((5-(thiophen-3-ylethynyl)furan-2-yl) methyl)(tosyl)carbamate (II-43h) (0.915 g, 2.00 mmol) was dissolved in MeOH (20.0 mL). The solution was added K₂CO₃ (1.935 g, 14.0 mmol). The reaction mixture was stirred at 50 ^oC for 8 hours. The crude mixture was purified via flash column chromatography over silica gel (ethyl acetate/hexanes

= 1: 1) to give II-42h as a yellow solid (0.643 g, 1.80 mmol, 90%) : R_f 0.25 (ethyl acetate /hexanes = 1: 3), m.p. 180－181 ^oC.

H NMR (400 MHz, CDCl

₃): δ 7.71 (d, J = 8.3 Hz, 2H), 7.53 (dd, J = 2.9, 0.9 Hz, 1H), 7.31 (dd, J = 5.1, 3.0 Hz, 1H), 7.28 (d, J = 8.2 Hz, 2H), 7.17 (dd, J = 4.8, 0.7 Hz, 1H), 6.44 (d, J = 3.4 Hz, 1H), 6.12 (d, J = 3.3 Hz, 1H), 4.88 – 4.81 (m, 1H), 4.19 (d, J = 6.2 Hz, 2H), 2.40 (s, 3H) ppm.

C NMR (100 MHz, CDCl

₃): δ 150.6, 143.6, 136.9, 136.7, 129.7, 129.5, 129.4, 127.1, 125.7, 121.0, 115.8, 109.5, 88.8, 78.4, 40.2, 21.5 ppm.

IR (CH

₂Cl₂): ν 3253, 2364, 1627, 1441, 1320, 1159, 1053, 774, 720, 544 cm^-1.

MS (ESI) m/e (%) 380.5 ([M+Na]

⁺, 100).

HRMS (ESI) m/e calcd for C

₁₈H₁₅NO₃NaS₂ [M+Na]⁺ 380.0391, found 380.0393.

- 70 -

Methyl 3-((5-(((4-methylphenyl)sulfonamido)methyl)furan-2-yl)ethynyl) benzoate (II-42i)

According to GP 2-4, methyl 3-((5-(((N-(tert-butoxycarbonyl)-4- methylphenyl)sulfonamido)methyl)furan-2-yl)ethynyl)benzoate (II-43i) (1.554 g, 3.05 mmol) was dissolved in DCM (30.5 mL). The solution was added trifluoroacetic acid (TFA, 4.7 mL, 61.0 mmol). The reaction mixture was stirred at r.t. for 2 hours. The crude mixture was purified via flash column chromatography over silica gel (ethyl acetate/hexanes = 1: 4) to give II-42i as a orange solid (0.573 g, 1.40 mmol, 46%) : R_f 0.20 (ethyl acetate /hexanes = 1: 3), m.p. 162－164 ^oC.

H NMR (400 MHz, CDCl

₃): δ 8.19 – 8.15 (m, 1H), 8.05 – 7.98 (m, 1H), 7.71 (d, J = 8.3 Hz, 2H), 7.68 – 7.63 (m, 1H), 7.43 (t, J = 7.8 Hz, 1H), 7.28 (d, J = 8.4 Hz, 2H), 6.49 (d, J = 3.3 Hz, 1H), 6.14 (d, J = 3.3 Hz, 1H), 4.20 (s, 2H), 3.94 (s, 3H), 2.39 (s, 3H) ppm.

C NMR (100 MHz, CDCl

₃): δ 166.2, 151.1, 143.6, 136.8, 136.6, 135.3, 132.4, 130.6, 129.7, 129.6, 128.6, 127.1, 122.5, 116.4, 109.6, 92.5, 79.8, 52.3, 40.2, 21.5 ppm.

IR (CH

₂Cl₂): ν 3246, 2210, 1726, 1614, 1438, 1361, 1158, 1101, 812, 753, 544 cm^-1.

MS (ESI) m/e (%) 432.3 ([M+Na]

⁺, 100).

HRMS (ESI) m/e calcd for C

₂₂H₁₉NO₅NaS [M+Na]⁺ 432.0882, found 432.0883.

- 71 -

3.6 Synthesis of Ynamide-Tethered Furan II-47.

4-Methyl-N-(phenylethynyl)-N-((5-(p-tolyl)furan-2-yl)methyl)benzene sulfonamide (II-47a)

According to GP 2-5, (bromoethynyl)benzene (0.272 g, 1.50 mmol), toluene (6.0 mL),4-methyl-N-((5-(p-tolyl)furan-2-yl)methyl)benzenesulfon amide(II-36a) (0.341 g, 1.00 mmol), Cs₂CO₃(0.652 g, 2.00 mmol), CuI (0.040 g, 0.21 mmol), and DMEDA (0.084 g, 0.95 mmol). The mixture was stirred at 50 ^oC for 2 h. The crude mixture was purified via flash column chromatography over silica gel (EtOAc/hexanes 1:35) to give II-47a as a yellow solid (0.397 g, 0.90 mmol, 90%) : R_f 0.35 (EtOAc/hexanes 1:5), m.p. 90

－91 ^oC.

H NMR (400 MHz, CDCl

₃): δ 7.81 – 7.75 (m, 2H), 7.42 – 7.36 (m, 2H), 7.35 – 7.29 (m, 2H), 7.28 – 7.23 (m, 3H), 7.20 (d, J = 8.1 Hz, 2H), 7.13 (d, J = 8.0 Hz, 2H), 6.44 (d, J = 3.4 Hz, 1H), 6.36 (d, J = 3.4 Hz, 1H), 4.72 (s, 2H), 2.35 (s, 3H), 2.28 (s, 3H) ppm.

C NMR (100 MHz, CDCl

₃): δ 154.6, 146.9, 144.5, 137.4, 134.6, 131.3, 129.5, 129.2, 128.2, 127.7, 127.6, 127.5, 123.8, 122.8, 112.5, 104.8, 82.4, 71.3, 48.6, 21.5, 21.2 ppm.

IR (CH

₂Cl₂): ν 3034, 2922, 2237, 1597, 1496, 1364, 1167, 1090, 1019, 791,

- 72 -

690, 572 cm^-1.

MS (ESI) m/e (%) 464.0 ([M+Na]

⁺, 100).

HRMS (ESI) m/e calcd for C

₂₇H₂₃NO₃NaS [M+Na]⁺ 464.1296, found 464.1295.

- 73 -

N-((5-(3-Methoxyphenyl)furan-2-yl)methyl)-4-methyl-N-(phenylethynyl) benzenesulfonamide (II-47b)

According to GP 2-5, (bromoethynyl)benzene (0.272 g, 1.50 mmol), toluene (6.0 mL), N-((5-(3-methoxyphenyl)furan-2-yl)methyl)-4-methyl benzenesulfonamide (II-36b) (0.357 g, 1.00 mmol), Cs₂CO₃(0.652 g, 2.00 mmol), CuI (0.040 g, 0.21 mmol), and DMEDA (0.084 g, 0.95 mmol). The mixture was stirred at 50 ^oC for 1.5 h. The crude mixture was purified via flash column chromatography over silica gel (EtOAc/hexanes 1:25) to give II-47b as a beige solid (0.366 g, 0.80 mmol, 80%) : R_f 0.25 (EtOAc/hexanes 1:5), m.p.

116－117 ^oC.

H NMR (400 MHz, CDCl

₃): δ 7.77 (d, J = 8.3 Hz, 2H), 7.35 – 7.29 (m, 2H), 7.28 – 7.23 (m, 4H), 7.22 – 7.17 (m, 2H), 7.12 – 7.07 (m, 1H), 7.02 (t, J = 1.8 Hz, 1H), 6.79 (dd, J = 8.1, 2.4 Hz, 1H), 6.50 (d, J = 3.4 Hz, 1H), 6.37 (d, J = 3.3 Hz, 1H), 4.72 (s, 2H), 3.76 (s, 3H), 2.27 (s, 3H) ppm.

C NMR (100 MHz, CDCl

₃): δ 159.8, 154.2, 147.4, 144.6, 134.5, 131.5, 131.3, 129.6, 129.5, 128.2, 127.7, 127.6, 122.8, 116.4, 113.3, 112.5, 109.2, 105.9, 82.5, 71.3, 55.2, 48.6, 21.4 ppm.

IR (CH

₂Cl₂): ν 3057, 2941, 2239, 1598, 1455, 1366, 1293, 1169, 1090, 1020, 781, 690, 574 cm^-1.

MS (ESI) m/e (%) 480.1 ([M+Na]

⁺, 100).

HRMS (ESI) m/e calcd for C

₂₇H₂₃NO₄NaS [M+H]⁺ 480.1245, found 480.1246.

- 74 -

N-((5-(4-Methoxyphenyl)furan-2-yl)methyl)-4-methyl-N-(phenylethynyl) benzenesulfonamide (II-47c)

According to GP 2-5, (bromoethynyl)benzene (0.272 g, 1.50 mmol), toluene (6.0 mL), N-((5-(4-methoxyphenyl)furan-2-yl)methyl)-4-methyl benzenesulfonamide (II-36c) (0.357 g, 1.00 mmol), Cs₂CO₃(0.652 g, 2.00 mmol), CuI (0.040 g, 0.21 mmol), and DMEDA (0.084 g, 0.95 mmol). The mixture was stirred at 50 ^oC for 2 h. The crude mixture was purified via flash column chromatography over silica gel (EtOAc/hexanes 1:25) to give II-47c as a yellow solid (0.421 g, 0.92 mmol, 92%) : R_f 0.25 (EtOAc/hexanes 1:5), m.p.

107－108 ^oC.

H NMR (400 MHz, CDCl

₃): δ 7.78 (d, J = 8.3 Hz, 2H), 7.46 – 7.40 (m, 2H), 7.35 – 7.28 (m, 2H), 7.28 – 7.23 (m, 3H), 7.21 (d, J = 8.2 Hz, 2H), 6.89 – 6.83 (m, 2H), 6.35 (q, J = 3.4 Hz, 2H), 4.71 (s, 2H), 3.83 (s, 3H), 2.30 (s, 3H) ppm.

C NMR (100 MHz, CDCl

₃): δ 159.2, 154.5, 146.6, 144.5, 134.6, 131.4, 129.6, 128.2, 127.8, 127.7, 125.3, 123.5, 122.9, 114.0, 112.6, 104.0, 82.5, 71.3, 55.4, 48.7, 21.6 ppm.

IR (CH

₂Cl₂): ν 3053, 2943, 2237, 1598, 1497, 1365, 1251, 1169, 1026, 787, 691, 573 cm^-1.

MS (ESI) m/e (%) 480.4 ([M+Na]

⁺, 100), 482.4 ([M+2+ Na]⁺, 40).

HRMS (ESI) m/e calcd for C

₂₇H₂₄NO₄NaS [M+H]⁺ 458.1426, found 458.1419.

- 75 -

4-Methyl-N-((5-(4-nitrophenyl)furan-2-yl)methyl)-N-(phenylethynyl) benzenesulfonamide (II-47e)

According to GP 2-5, (bromoethynyl)benzene (0.272 g, 1.50 mmol), toluene (6.0 mL), 4-methyl-N-((5-(4-nitrophenyl)furan-2-yl)methyl) benzene sulfonamide (II-36e) (0.372 g, 1.00 mmol), Cs₂CO₃(0.652 g, 2.00 mmol), CuI (0.040 g, 0.21 mmol), and DMEDA (0.084 g, 0.95 mmol). The mixture was stirred at 50 ^oC for 3 h. The crude mixture was purified via flash column chromatography over silica gel (EtOAc/hexanes 1:20) to give II-47e as a yellow solid (0.076 g, 0.16 mmol, 16%) : R_f 0.20 (EtOAc/hexanes 1:5), m.p.

159－161 ^oC.

H NMR (400 MHz, CDCl

₃): δ 8.22 – 8.17 (m, 2H), 7.80 (d, J = 8.3 Hz, 2H), 7.66 – 7.61 (m, 2H), 7.35 – 7.28 (m, 4H), 7.28 – 7.26 (m, 2H), 7.24 (s, 1H), 6.76 (d, J = 3.4 Hz, 1H), 6.48 (d, J = 3.4 Hz, 1H), 4.75 (s, 2H), 2.33 (s, 3H) ppm.

C NMR (100 MHz, CDCl

₃): δ 152.0, 149.8, 146.5, 144.8, 135.8, 134.5, 131.3, 129.6, 128.3, 128.0, 127.7, 124.2, 124.0, 122.5, 113.0, 109.5, 82.1, 71.5, 48.4, 21.6 ppm.

IR (CH

₂Cl₂): ν 2923, 2236, 1601, 1515, 1353, 1333, 1169, 1020, 798, 691, 573 cm^-1.

- 76 -

MS (EI) m/e (%) 472.2 (20), 316.2 (100), 271.2 (10), 202.1 (57), 155.1 (11),

91.1(10).

HRMS (EI) m/e calcd for C

₂₆H₂₀N₂O₅S [M+H]⁺ 472.1093, found 472.1092.

- 77 -

N-((5-(4-Cyanophenyl)furan-2-yl)methyl)-4-methyl-N-(phenylethynyl) benzenesulfonamide (II-47f)

According to GP 2-5, (bromoethynyl)benzene (0.272 g, 1.50 mmol), t o l u e n e ( 6 . 0 m L ) , N - ( ( 5 - ( 4 - c ya n o p h e n yl ) f u r a n - 2 - yl ) m e t h yl ) - 4 - methylbenzenesulfonamide (II-36f) (0.352 g, 1.00 mmol), Cs₂CO₃(0.652 g, 2.00 mmol), CuI (0.040 g, 0.21 mmol), and DMEDA (0.084 g, 0.95 mmol).

The mixture was stirred at 50 ^oC for 3 h. The crude mixture was purified via flash column chromatography over silica gel (EtOAc/hexanes 1:30) to give

II-47f as a beige solid (0.036 g, 0.08 mmol, 8%) : R

_f 0.25 (EtOAc/hexanes 1:5), m.p. 158－160 ^oC.

H NMR (400 MHz, CDCl

₃): δ 7.81 – 7.77 (m, 2H), 7.63 – 7.56 (m, 4H), 7.33 – 7.26 (m, 5H), 7.26 – 7.22 (m, 2H), 6.69 (d, J = 3.4 Hz, 1H), 6.45 (d, J = 3.4 Hz, 1H), 4.73 (s, 2H), 2.32 (s, 3H) ppm.

C NMR (100 MHz, CDCl

₃): δ 152.3, 149.3, 144.7, 134.5, 134.0, 132.5, 131.3, 129.6, 128.3, 128.0, 127.7, 124.0, 122.6, 118.8, 112.8, 110.5, 108.7, 82.2, 71.4, 48.5, 21.4 ppm.

IR (CH

₂Cl₂): ν 2924, 2226, 1610, 1489, 1365, 1169, 1020, 756, 574 cm^-1.

MS (EI) m/e (%) 452.2 (23), 296.2 (100), 279.2 (12), 182.1 (76), 155.1 (12),

139.1 (12), 130.1(24), 91.1 (21).

HRMS (EI) m/e calcd for C

₂₇H₂₀N₂O₃S [M+H]⁺ 452.1194, found 452.1195.

- 78 -

4-Methyl-N-(phenylethynyl)-N-((5-(phenylethynyl)furan-2-yl)methyl) benzenesulfonamide (II-47g)

According to GP 2-5, (bromoethynyl)benzene (0.272 g, 1.50 mmol), toluene (6.0 mL), 4-methyl-N-((5-(phenylethynyl)furan-2-yl)methyl) benzenesulfonamide (II-42a) (0.351 g, 1.00 mmol), Cs₂CO₃(0.652 g, 2.00 mmol), CuI (0.040 g, 0.21 mmol), and DMEDA (0.084 g, 0.95 mmol). The mixture was stirred at 50 ^oC for 2 h. The crude mixture was purified via flash column chromatography over silica gel (EtOAc/hexanes 1:25) to give II-47g as a white solid (0.420 g, 0.93 mmol, 93%) : R_f 0.20 (EtOAc/hexanes 1:5), m.p.

104－105 ^oC.

H NMR (400 MHz, CDCl

₃): δ 7.85 – 7.80 (m, 2H), 7.54 – 7.48 (m, 2H), 7.38 – 7.30 (m, 7H), 7.29 – 7.25 (m, 3H), 6.51 (d, J = 3.4 Hz, 1H), 6.32 (d, J = 3.4 Hz, 1H), 4.66 (s, 2H), 2.39 (s, 3H) ppm.

C NMR (100 MHz, CDCl

₃): δ 149.0, 144.8, 137.4, 134.4, 131.4, 131.3, 129.6, 128.8, 128.4, 128.2, 127.9, 127.8, 122.7, 122.1, 116.0, 111.7, 93.6, 82.0, 79.1, 71.5, 48.3, 21.6 ppm.

IR (CH

₂Cl₂): ν 3058, 2924, 2239, 1597, 1366, 1169, 1090, 1012, 798, 756, 690, 573 cm^-1.

MS (ESI) m/e (%) 474.1 ([M+Na]

⁺, 100), 472.1 ([M+2+Na]⁺, 30).

HRMS (ESI) m/e calcd for C

₂₈H₂₁NO₃NaS [M+Na]⁺ 474.1140, found 474.1145.

- 79 -

4-Methyl-N-(phenylethynyl)-N-((5-(o-tolylethynyl)furan-2-yl)methyl) benzenesulfonamide (II-47h)

According to GP 2-5, (bromoethynyl)benzene (0.272 g, 1.50 mmol),

在文檔中三氯化金輔佐C-2炔醯胺呋喃化合物的分子內環化反應：吡咯衍生物的合成 (頁 49-200)

- 38 -

- 39 -

第三章 實驗部分

- 40 -

- 41 -

3.2.1 Experiments

Synthesis of N-((5-Bromofuran-2-yl)methyl)-4-methylbenzenesulfonamide (II-37 ).

Scheme S8

- 42 -

N-((5-bromofuran-2-yl)methyl)-4-methylbenzenesulfonamide (II-37) as a

GP 2-1: Synthesis of 4-Methyl-N-((5-arylfuran-2-yl)methyl)benzene sulfonamide II-36 .

Scheme S2

Example for the Synthesis of II-36 . The appropriate arylboronic acid

- 43 -

N-((5-Bromofuran-2-yl)methyl)-4-methylbenzenesulfonamide (II-37) (0.660 g, 2.00 mmol) in a 1:1 mixture of THF (6.0 mL) and 1 M

N-((5-(3-methoxyphenyl)furan-2-yl)methyl)-4-methylbenzenesulfonamide (II-36) as a white solid (0.686 g, 1.92 mmol, 96%) (Scheme S2).

GP 2-2: Synthesis of tert-Butyl ((5-(arylethynyl)furan-2-yl)methyl)(tosyl) carbamate II-43 .

Scheme S3

- 44 -

GP 2-3: Synthesis of N-((5-(Arylethynyl)furan-2-yl)methyl)-4-methyl benzenesulfonamide II-42.

Scheme S4

tert-Butyl ((5-(phenylethynyl)furan-2-yl)methyl)(tosyl)carbamate (II-43)

GP 2-4: Synthesis of Methyl 3-((5-(((4-methylphenyl)sulfonamido)methyl) furan-2-yl)ethynyl)benzoate II-42i.

Scheme S5

- 45 -

GP 2-5: General Experimental Procedure for the Preparation of Ynamide-Tethered Furan II-47.

Scheme S6

- 46 -

Example for the Synthesis of II-47. To a dry and nitrogen-flushed

GP 2-6: General Experimental Procedure for the AuCl

-Catalyzed Synthesis of (Z)-1-Aryl-3-(1H-pyrrol-3-yl)prop-2-en-1-one II-48 .

Scheme S7

Example for the Synthesis of II-48. A solution of AuCl

- 47 -

- 48 -

4-Methyl-N-((5-(p-tolyl)furan-2-yl)methyl)benzenesulfonamide (II-36a)

H NMR (400 MHz, CDCl

J = 3.2 Hz, 1H), 4.91 (s, 1H), 4.24 (s, 2H), 2.35 (s, 3H), 2.31 (s, 3H) ppm.

C NMR (100 MHz, CDCl

IR (CH

MS (ESI) m/e (%) 364.3 ([M+Na]

HRMS (ESI) m/e calcd for C

- 49 -

N-((5-(3-Methoxyphenyl)furan-2-yl)methyl)-4-methylbenzenesulfonamide (II-36b)

H NMR (400 MHz, CDCl

C NMR (100 MHz, CDCl

IR (CH

MS (ESI) m/e (%) 380.2 ([M+Na]

HRMS (ESI) m/e calcd for C

- 50 -

N-((5-(4-Methoxyphenyl)furan-2-yl)methyl)-4-methylbenzenesulfonamide (II-36c)

H NMR (400 MHz, CDCl

C NMR (100 MHz, CDCl

IR (CH

MS (ESI) m/e (%) 380.4 ([M+Na]

HRMS (ESI) m/e calcd for C

- 51 -

4-Methyl-N-((5-(4-nitrophenyl)furan-2-yl)methyl)benzenesulfonamide (II-36d)

H NMR (400 MHz, CDCl

J = 3.4 Hz, 1H), 4.94 (m, 1H), 4.29 (d, J = 6.2 Hz, 2H), 2.33 (s, 3H) ppm.

C NMR (100 MHz, CDCl

IR (CH

MS (ESI) m/e (%) 371.3 ([M－H]

HRMS (ESI) m/e calcd for C

- 52 -

N-((5-(4-Cyanophenyl)furan-2-yl)methyl)-4-methylbenzenesulfonamide (II-36e)

H NMR (400 MHz, CDCl

J = 3.3 Hz, 1H), 5.03 – 4.96 (m, 1H), 4.27 (d, J = 6.2 Hz, 2H), 2.32 (s, 3H)

C NMR (100 MHz, CDCl

IR (CH

MS (ESI) m/e (%) 351.3 ([M－H]

HRMS (ESI) m/e calcd for C

- 53 -

tert-Butyl ((5-(phenylethynyl)furan-2-yl)methyl)(tosyl)carbamate (II-43a)

H NMR (400 MHz, CDCl

C NMR (100 MHz, CDCl

IR (CH

MS (ESI) m/e (%) 474.0 ([M+Na]

HRMS (ESI) m/e calcd for C

第三章實驗部分