Gold(I)-Catalyzed Synthesis of Tetrahydrobenzo[b]furan Derivatives .1 Experimental

第三章實驗部分

3.2 Gold(I)-Catalyzed Synthesis of Tetrahydrobenzo[b]furan Derivatives .1 Experimental

Synthesis of 2-(2-Propynyl)-1,3-cyclohexandione (II-163)

To a solution of 1,3-cyclohexanedione (7.849 g, 70 mmol ) in KOH (4.870 g, 87 mmol) and water (16 mL) was added via syringe propargyl bromide (7.8 mL, 70 mmol) at 0 ℃. The reaction was allowed to stir at 0 ℃ for 10 min and warmed to ambient temperature.

T

he reaction mixture was stirred for 15 h at room temperature and then 3 h at 40℃. The mixture was poured into 4 M NaOH

_(aq)

(7.115 g, 45 mL) and extracted with diethyl ether (50 mL × 1). The aqueous solution was acidified with cold HCl solution ( 37 g of 12 M HCl in 37 g of cracked ice). After filtration of the precipitate, the remaining solution was washed with water and dried in vacuo and was further crystallized from dichloromethane/hexanes to give a light-yellow powder (4.415 g, 29 mmol, 42%, R

_f

= 0.13 in 50% ethyl acetate/50% hexanes);

¹

H NMR (400 MHz, CDCl

₃

) δ 3.31 (d, J = 2.6 Hz, 2H), 2.50 (t, J = 6.5 Hz, 4H), 2.23 (t, J = 2.8 Hz, 1H), 1.98 (quin, J = 6.4 Hz, 2H)

68

Synthesis of 3-Methoxy-2-(2-propynyl)-cyclohex-2-en-1-one (II-162)

The 2-(2-propynyl)-1,3-cyclohexandione (3.421 g, 23 mmol) was dissolved in MeOH (163 mL). The solution was added trimethyl orthoformate (22 mL, 205 mmol) followed by slow addition of conc. H

₂

₄

(1.4 mL). The mixture was allowed to stir at room temperature for 10 h. After which time, reaction mixture was neutralized with a saturated NaHCO

_3(aq)

(50 mL) and the resulting solution was concentrated in vacuo. The aqueous solution was then extracted with CH

₂

(100 mL × 3), and the combined extracts were dried over anhydrous MgSO

₄

(40 g), and concentrated under reduced pressure to give a crude powder.

The crude mixture was purified by flash column chromatography over silica gel (ethyl acetate/hexanes 1:2) to afford a yellow powder (2.020 g, 12 mmol, 54%, R

_f

= 0.25 in 50% ethyl acetate/50% hexanes): mp 123‒125 ℃;

¹

H NMR (400 MHz, CDCl

₃

) δ 3.88 (s, 3H), 3.19 (d, J = 2.1 Hz, 2H), 2.60 (t, J = 6.2 Hz, 2H), 2.38 (t, J = 6.7 Hz, 2H), 2.02 (quin, J = 6.5 Hz, 2H), 1.84 (t, J = 2.7 Hz, 1H);

¹³

C NMR (100 MHz, CDCl

₃

) δ 196.6, 173.0, 114.6, 83.2, 65.8, 55.5, 36.0, 24.8, 20.5, 11.5

69

Synthesis of 2-(2-Propynyl)-cyclohex-2-en-1-one (II-161a)

DIBAL (28 mL of a 1.2 M solution in toluene, 34 mmol) was added dropwise over 30 min to a stirring solution of 3-methoxy-2-(2-propynyl)-cyclohex-2-en-1-one (3.727 g, 23 mmol) in anhydrous toluene (76 mL) at 0 ℃ under nitrogen. After stirred at 0 ℃ for 2 h, the reaction mixture was added water (21 mL) dropwise followed by addition of 2 M HCl (13 mL). The mixture was allowed to stir vigorously for 30 min. The reaction mixture was extracted with diethyl ether (50 mL × 4) and combined organic extracts were washed with a saturated NaHCO

_3(aq)

(100 mL) and then dried over MgSO

₄

(30 g). The filtrate was concentrated under reduced pressure, and the resulting crude product was purified by flash column chromatography over silica gel (ethyl acetate/hexanes 1:30) yielding an oil (2.014 g, 15 mmol, 66%, R

_f

= 0.33 in 10% ethyl acetate/hexanes);

¹

H NMR (400 MHz, CDCl

₃

) δ 7.21‒7.15 (m, 1H), 3.16 (t, J = 2.2 Hz, 1H), 3.15 (t, J = 2.1 Hz, 1H), 2.48‒2.40 (m, 4H), 2.17 (t, J = 2.7 Hz, 1H), 2.01 (quin, J = 6.4 Hz, 2H);

¹³

C NMR (100 MHz, CDCl

₃

) δ 197.7, 146.0, 133.7, 80.6, 71.6, 37.9, 25.7, 22.7, 18.7

70

Synthesis of 5,5-Dimethyl-2-(prop-2-yn-1-yl)cyclohex-2-enone (II-161b)

The synthesis of 5,5-dimethyl-2-(prop-2-yn-1-yl)cyclohex-2-enone (II-161b) is similar to that of 2-(2-propynyl)-cyclohex-2-en-1-one (II-161a);

¹

H NMR (400 MHz, CDCl

₃

) δ 7.05‒7.00 (m, 1H), 3.14 (t, J = 2.1 Hz, 2H), 2.34‒2.29 (m, 4H), 2.21 (t, J = 2.6 Hz, 1H), 1.04 (s, 6H)

General Procedure I: Arylation of Terminal Alkynes Employing the Sonogashira Reaction Conditions. Synthesis of

2-(3-Phenylpropargyl)cyclohex-2-en-1-one (II-160a)

To the 2-(2-propynyl)-cyclohex-2-en-1-one (0.567 g, 4.2 mmol) in Et

₃

N (4.2 mL) were added Pd(PPh

₃

)

₄

(9.8 mg, 0.008 mmol), CuI (0.032 g, 0.17 mmol), and iodobenzene (1.035 g, 5.1 mmol) under nitrogen. The reaction mixture was stirred at room temperature for 8 h before quenching with a saturated NH

₄

_(aq)

(20 mL). The resulting solution was extracted with CH

₂

(50 mL × 3). To combine organic solution was washed with water (50 mL × 3) and brine (50 mL × 3) and dried over MgSO

₄

(20 g). The filtrate was concentrated in vacuo to give a crude oil. The crude mixture was purified via flash column chromatography over silica gel (ethyl acetate/hexanes 1:30) to give a tan oil (0.790 g, 3.8 mmol, 89%, R

_f = 0.28 in 10% ethyl acetate/hexanes).

71

General Procedure II: Addition of Organolithium Reagents to 2-(3-Arylpropargyl)cyclohex-2-en-1-ones. Synthesis of

1-Phenyl-2-(3-phenylpropargyl)cyclohex-2-en-1-ol (II-159a)

Phenyllithium (0.5 mL of a 2.0 M solution in dibutyl ether, 0.90 mmol) was added dropwise over 20 min to a stirred solution of 2-(3-phenylpropargyl)cyclohex-2-en-1-one (0.126 g, 0.60 mmol) in dried THF (1.5 mL) at ‒78 ℃ under nitrogen. The mixture was stirred at ‒78 ℃ for 4 h.

After which time, the reaction mixture was quenched with a saturated NH

₄

_(aq)

(20 mL) at ‒78 ℃. The reaction mixture was extracted with ethyl acetate (30 mL × 3) and dried over MgSO

₄

(10 g). The mixture was concentrated, and the residue was purified via flsah chromatography over silica gel (ethyl

acetate/hexanes 1:30) to produce

1-phenyl-2-(3-phenylpropargyl)cyclohex-2-en-1-ol (0.098 g, 0.34 mmol, 57%, R

_f

= 0.28 in 10% in ethyl acetate/hexane). mmol) and 1-phenyl-2-(3-phenylpropargyl)cyclohex-2-en-1-ol (0.057 g, 0.20 mmol) in CH

₂

(1.0 mL) under N

₂

flow. After reactant consumed (monitored

72

by TLC, 1 min), the resulting dark brown solution was filtered through a bed of Celite. The filtrate was concentrated in vacuo to give the crude mixture. The residue was purified by flash column chromatography over silica gel (hexanes) to give 2-benzyl-4-phenyl-4,5,6,7-tetrahydrobenzo[b]furan (0.035 g, 0.12 mmol, 61%, R

_f

= 0.63 in 10% ethyl acetate/hexanes) as a yellow brown oil.

73

3.2.2 Synthesis of 2-(3-Arylprop-2-yn-1-yl)cyclohex-2-enone 2-(3-Phenylprop-2-yn-1-yl)cyclohex-2-enone (II-160a)

In General Procedure I, to a solution of II-161a (0.567 g, 4.2 mmol) in Et

₃

N (4.2 mL) were added sequentially iodobenzene (1.035 g, 5.1 mmol), Pd(PPh

₃

)

₄

(9.8 mg, 0.008 mmol) and CuI (0.032 g, 0.17 mmol) at room temperature under an atmosphere of nitrogen. The reaction mixture was stirred for 8 h and the crude mixture was purified by flash column chromatography over silica gel (ethyl acetate/hexanes 1:30) to give II-160a (0.790 g, 3.8 mmol, 89%, R

_f

= 0.28 in 10% ethyl acetate/hexanes) as a tan oil:

¹

H NMR (400 MHz, CDCl

₃

) δ 7.44 (d, J = 7.3 Hz, 1H), 7.43 (d, J = 5.9 Hz, 1H), 7.34‒7.26 (m, 3H), 7.24 (dt,

J = 3.9, 2.2 Hz, 1H), 3.38 (q, J = 2.1 Hz, 2H), 2.51‒2.41 (m, 4H), 2.03 (quin, J

= 6.4 Hz, 2H);

¹³

C NMR (100 MHz, CDCl

₃

) δ 198.2, 146.2, 134.5, 131.6 (2C), 128.2 (2C), 127.8, 123.5, 86.3, 84.1, 38.2, 26.0, 23.0, 19.9; IR (CH

₂

) 3330, 2950, 2200, 1667, 1599, 1493, 759, 695 cm

^‒1

; MS (ESI) m/e (%) 233.1 ([M + Na]

⁺

, 100), 228.1 (4), 211.1 (2), 158.1 (1); HRMS (ESI) calcd for C

₁₅

₁₄

ONa [M + Na]

⁺

233.0942, found 233.0939.

74

2-(3-(p-Tolyl)prop-2-yn-1-yl)cyclohex-2-enone (II-160b)

In General Procedure I, to a solution of II-161a (0.403 g, 3.0 mmol) in Et

₃

N (3.0 mL) were added sequentially 4-iodotoluene (0.785 g, 3.6 mmol), Pd(PPh

₃

)

₄

(6.9 mg, 0.006 mmol) and CuI (0.023 g, 0.12 mmol) at room temperature under an atmosphere of nitrogen. The reaction mixture was stirred for 8 h and the crude mixture was purified by flash column chromatography over silica gel (ethyl acetate/hexanes 1:30) to give II-160b (0.568g, 2.5 mmol, 84%, R

_f

= 0.25 in 10% ethyl acetate/hexanes) as a pale yellow solid: mp 73‒74

℃;

¹

H NMR (400 MHz, CDCl

₃

) δ 7.32 (d, J = 8.1 Hz, 2H), 7.23 (dt, J = 4.0, 2.1 Hz, 1H), 7.10 (d, J = 8.0 Hz, 2H), 3.37 (q, J = 2.1 Hz, 2H), 2.50‒2.40 (m, 4H), 2.34 (s, 3H), 2.02 (quin, J = 6.4 Hz, 2H);

¹³

C NMR (100 MHz, CDCl

₃

) δ 198.3, 146.2, 137.9, 134.6, 131.4 (2C), 129.0 (2C), 120.4, 85.4, 84.2, 38.2, 26.0, 23.0, 21.4, 19.9; IR (CH

₂

) 2935, 2874, 1670, 1512, 1417, 1383, 816 cm

^‒1

; MS (ESI) m/e (%) 247.1 ([M + Na]

⁺

, 100), 233.1 (6), 190.0 (4), 176.1 (2), 143.1 (3); HRMS (ESI) calcd for C

₁₆

ONa [M + Na]

⁺

247.1099, found 247.1100.

75

2-(3-(m-Tolyl)prop-2-yn-1-yl)cyclohex-2-enone (II-160c)

In General Procedure I, to a solution of II-161a (0.800 g, 6.0 mmol) in Et

₃

N (6.0 mL) were added sequentially 3-iodotoluene (1.560 g, 7.2 mmol), Pd(PPh

₃

)

₄

(13.8 mg, 0.012 mmol) and CuI (0.045 g, 0.24 mmol) at room temperature under an atmosphere of nitrogen. The reaction mixture was stirred for 8 h and the crude mixture was purified by flash column chromatography over silica gel (ethyl acetate/hexanes 1:30) to give II-160c (1.277 g, 5.7 mmol, 95%, R

_f

= 0.28 in 10% ethyl acetate/hexanes) as a tan oil:

¹

H NMR (400 MHz, CDCl

₃

) δ 7.28‒7.21 (m, 3H), 7.18 (t, J = 7.6 Hz, 1H), 7.10 (d, J = 7.5 Hz, 1H), 3.37 (q, J = 2.0 Hz, 2H), 2.50‒2.40 (m, 4H), 2.32 (s, 3H), 2.03 (quin, J = 6.4 Hz, 2H);

¹³

C NMR (100 MHz, CDCl

₃

) δ 198.2, 146.2, 137.9, 134.6, 132.2, 128.7, 128.6, 128.1, 123.3, 85.9, 84.3, 38.2, 26.0, 23.0, 21.2, 19.9; IR (CH

₂

) 3328, 2937, 2184, 1668, 1598, 1579, 1376, 879, 783, 691 cm

^‒1

; MS (ESI) m/e (%) 247.1 ([M + Na]

⁺

, 14), 225.1 (2), 190.0 (1); HRMS (APCI) calcd for C

₁₆

ONa [M + Na]

⁺

247.1099, found 247.1094.

76

2-(3-(Naphthalen-1-yl)prop-2-yn-1-yl)cyclohex-2-enone (II-160d)

In General Procedure I, to a solution of II-161a (0.800 g, 6.0 mmol) in Et

₃

N (6.0 mL) were added sequentially 1-iodonaphthalene (2.272 g, 8.9 mmol), Pd(PPh

₃

)

₄

_f

= 0.23 in 10% ethyl acetate/hexanes) as a tan solid: mp 55‒57 ℃;

¹

H NMR (400 MHz, CDCl

₃

) δ 8.34 (d, J = 8.1 Hz, 1H), 7.82 (dd, J = 15.9, 7.9 Hz, 2H), 7.66 (dd, J = 7.1, 0.9 Hz, 1H), 7.56 (ddd, J = 8.2, 6.8, 1.4 Hz, 1H), 7.51 (ddd, J = 8.0, 6.8, 1.3 Hz, 1H), 7.41 (dd, J = 8.2, 7.2 Hz, 1H), 7.33 (ddt, J = 4.0, 4.0, 1.9 Hz, 1H), 3.54 (q, J = 2.1 Hz, 2H), 2.53‒2.42 (m, 4H), 2.05 (quin, J = 6.4 Hz, 2H);

¹³

C NMR (100 MHz, CDCl

₃

) δ 198.2, 146.3, 134.7, 133.5, 133.2, 130.3, 128.3, 128.2, 126.6, 126.3, 126.2, 125.2, 121.3, 91.3, 82.1, 38.3, 26.1, 23.0, 20.3; IR (CH

₂

) 2942, 2228, 1670, 1587, 1508, 1455, 1391, 800, 774, 736 cm

^‒1

; MS (ESI) m/e (%) 283.1 ([M + Na]

⁺

, 100), 265.1 (4), 247.1 (11), 233.1 (5), 190.0 (4), 176.1 (2), 143.1 (3); HRMS (ESI) calcd for C

₁₉

₁₆

ONa [M + Na]

⁺

283.1099, found 283.1105.

77

2-(3-([1,1'-Biphenyl]-4-yl)prop-2-yn-1-yl)cyclohex-2-enone (II-160e)

In General Procedure I, to a solution of II-161a (0.295 g, 2.2 mmol) in Et

₃

N (7.0 mL) were added sequentially 4-bromobiphenyl (0.664 g, 2.9 mmol), Pd(PPh

₃

)

₄

(5.1 mg, 0.004 mmol) and CuI (0.017 g, 0.09 mmol) at room temperature under an atmosphere of nitrogen. After addition, the reaction mixture was stirred at reflux for 24 h. The crude mixture was purified by flash column chromatography over silica gel (ethyl acetate/hexanes 1:30) to give II- 160e (0.240 g, 0.84 mmol, 38%, R

_f

= 0.20 in 10% ethyl acetate/hexanes) as a tan oil:

¹

H NMR (400 MHz, CDCl

₃

) δ 7.58 (d, J = 7.6 Hz, 2H), 7.52 (q, J = 8.2 Hz, 4H), 7.44 (t, J = 7.6 Hz, 2H), 7.27‒7.23 (m, 1H), 7.35 (t, J = 7.3 Hz, 1H), 3.40 (d, J = 1.6 Hz, 2H), 2.52-2.42 (m ,4H), 2.04 (quin, J = 6.4 Hz, 2H);

13

C NMR (100 MHz, CDCl

₃

) δ 198.3, 146.3, 140.7, 140.4, 134.6, 132.0 (2C), 128.8 (2C), 127.5, 127.0 (2C), 126.9 (2C), 122.5, 87.0, 84.0, 38.3, 26.0, 23.0, 20.0; IR (CH

₂

) 2937, 2339, 1664, 1594, 1513, 1483, 1380, 838, 764, 694 cm

^‒1

; MS (ESI) m/e (%) 285.1 ([M – H]

^–

, 58), 283.3 (9), 255.2 (5), 247.0 (6), 224.8 (12), 200.9 (4), 195.0 (2); HRMS (ESI) calcd for C

₂₁

₁₇

O [M – H]

^–

285.1279, found 285.1276.

78

2-(3-(4-Methoxyphenyl)prop-2-yn-1-yl)cyclohex-2-enone (II-160f)

In General Procedure I , to a solution of II-161a (0.800 g, 6.0 mmol) in Et

₃

N (6.0 mL) were added sequentially 4-iodoanisole (1.674 g, 7.2 mmol), Pd(PPh

₃

)

₄

(13.8 mg, 0.012 mmol) and CuI (0.045 g, 0.24 mmol) at room temperature under an atmosphere of nitrogen. The reaction mixture was stirred for 8 h and the crude mixture was purified by flash column chromatography over silica gel (ethyl acetate/hexanes 1:30) to give II-160f (1.137 g, 4.7 mmol, 79%, R

_f

= 0.18 in 10% ethyl acetate/hexanes) as a tan oil:

¹

H NMR (400 MHz, CDCl

₃

) δ 7.37 (d, J = 8.7 Hz, 2H), 7.23 (t, J = 4.2 Hz, 1H), 6.83 (d, J = 8.7 Hz, 2H), 3.80 (s, 3H), 3.36 (d, J = 1.2 Hz, 2H), 2.51‒2.40 (m, 4H), 2.02 (quin, J = 6.4 Hz, 2H);

13

C NMR (100 MHz, CDCl

₃

) δ 198.3, 159.2, 146.2, 134.6, 132.9 (2C), 115.6, 113.8 (2C), 84.6, 83.9, 55.2, 38.2, 26.0, 23.0, 19.9; IR (CH

₂

) 3329, 2937, 2189. 1668, 1607, 1512, 1173, 833 cm

^‒1

; MS (ESI) m/e (%) 263.1 ([M + Na]

⁺

, 100), 258.1 (4), 199.0 (6), 190.0 (5), 143.1 (12), 135.1 (38), 122.5 (8); HRMS (ESI) calcd for C

₁₆

₂

Na [M + Na]

⁺

263.1048, found 263.1043.

79

5,5-Dimethyl-2-(3-phenylprop-2-yn-1-yl)cyclohex-2-enone (II-160t)

In General Procedure I, to a solution of II-161b (0.600 g, 3.7 mmol) in Et

₃

N (3.7 mL) were added sequentially iodobenzene (0.905 g, 4.4 mmol), Pd(PPh

₃

)

₄

(8.6 mg, 0.007 mmol) and CuI (0.028 g, 0.15 mmol) at room temperature under an atmosphere of nitrogen. The reaction mixture was stirred for 8 h and the crude mixture was purified by flash column chromatography over silica gel (ethyl acetate/hexanes 1:30) to give II-160t (0.733g, 3.1 mmol, 83%, R

_f

= 0.35 in 10% ethyl acetate/hexanes) as a tan oil:

¹

H NMR (400 MHz, CDCl

₃

) δ 7.44 (d, J = 7.2 Hz, 1H), 7.43 (d, J = 6.0 Hz, 1H), 7.34‒7.27 (m, 3H), 7.08 (dt, J = 4.0, 2.1 Hz, 1H), 3.38 (q, J = 2.0 Hz, 2H), 2.35‒2.30 (m, 4H), 1.05 (s, 6H);

¹³

C NMR (100 MHz, CDCl

₃

) δ 198.4, 144.0, 133.5, 131.6 (2C), 128.2 (2C), 127.9, 123.5, 86.3, 84.1, 51.8, 40.1, 34.2, 28.3, 19.6; IR (CH

₂

) 2958, 2869, 2230, 1676, 1645, 1599, 757, 692 cm

^‒1

; MS (APCI) m/e (%) 239.1 ([M + H]

⁺

, 100), 229.2 (1), 202.1 (1), 165.1 (3); HRMS (APCI) calcd for C

₁₇

₁₉

O [M + H]

⁺

239.1436, found 239.1430.

80

3.2.3 Synthesis of 1-Aryl-2-(3-Arylpropargyl)cyclohex-2-en-1-ol 6-(3-Phenylprop-2-yn-1-yl)-1,2,3,4-tetrahydro-[1,1'-biphenyl]-1-ol (II-159a)

In General Procedure II, phenyllithium (2.0 M, 0.5 mL, 0.90 mmol) was added to a solution of the corresponding enone II-160a (0.126 g, 0.60 mmol) in 1.5 mL of anhydrous THF at ‒78 ℃ under nitrogen. The reaction mixture was stirred for 4 h and maintained the temperature at ‒78 ℃. Then the crude mixture was purified by flash column chromatography over silica gel (ethyl acetate/hexanes 1:30) to give II-159a (0.098 g, 0.34 mmol, 57%, R

_f

= 0.28 in 10% in ethyl acetate/hexanes) as a tan oil:

¹

H NMR (400 MHz, CDCl

₃

) δ 7.46 (dt, J = 8.2, 1.6 Hz, 2H), 7.35 (tt, J = 7.9, 2.2 Hz, 4H), 7.29‒7.24 (m, 4H), 6.25 (ddt, J = 4.4, 3.1, 1.8 Hz, 1H), 3.15 (dq, J = 19.5, 2.2 Hz, 1H), 2.87 (dq, J = 19.6, 1.8 Hz, 1H), 2.34 (s, 1H), 2.28‒2.17 (m , 2H), 2.02‒1.90 (m, 2H), 1.80‒

1.70 (m, 1H), 1.66‒1.57 (m, 1H);

¹³

C NMR (100 MHz, CDCl

₃

) δ 146.1, 135.8, 131.5 (2C), 128.3 , 128.2 (2C), 128.1 (2C), 127.7, 126.8, 125.7 (2C), 123.6, 87.6, 83.8, 75.3, 41.6, 25.7, 22.7, 19.0; IR (CH

₂

) 3444, 2935, 2235, 1723, 1599, 1493, 1447, 759, 698 cm

^‒1

; MS (ESI) m/e (%) 311.1 ([M + Na]

⁺

, 100), 288.1 (14), 265.1 (15), 247.1 (27), 224.1 (10), 190.0 (12), 143.1 (11); HRMS (ESI) calcd for C

₂₁

₂₀

ONa [M + Na]

⁺

311.1412, found 311.1405.

81

6-(3-(p-Tolyl)prop-2-yn-1-yl)-1,2,3,4-tetrahydro-[1,1'-biphenyl]-1-ol (II-159b)

In General Procedure II, phenyllithium (2.0 M, 1.1 mL, 2.2 mmol) was added to a solution of the corresponding enone II-160b (0.330 g, 1.5 mmol) in 3.7 mL of anhydrous THF at ‒78 ℃ under nitrogen. The reaction mixture was stirred for 4 h and maintained the temperature at ‒78 ℃. Then the crude mixture was purified by flash column chromatography over silica gel (ethyl acetate/hexanes 1:30) to give II-159b (0.149 g, 0.50 mmol, 33%, R

_f

= 0.28 in 10% ethyl acetate/hexanes) as a yellow oil:

¹

H NMR (400 MHz, CDCl

₃

) δ 7.45 (dt, J = 8.3, 1.6 Hz, 2H), 7.35 (td, J = 6.8, 1.6 Hz, 2H), 7.28‒7.24 (m, 3H), 7.08 (d, J = 8.0 Hz, 2H), 6.24 (ddt, J = 4.4, 3.1, 1.7 Hz, 1H), 3.13 (dq, J = 19.5, 2.1 Hz, 1H), 2.86 (dq, J = 19.5, 1.8 Hz, 1H), 2.39 (s,1H), 2.33 (s, 3H), 2.28‒2.15 (m, 2H), 2.02‒1.89 (m, 2H), 1.80‒1.69 (m, 1H), 1.66‒1.59 (m, 1H);

¹³

C NMR (100 MHz, CDCl

₃

) δ 146.1, 137.8, 135.9, 131.4 (2C), 128.9 (2C), 128.3, 128.1 (2C), 126.8, 125.8 (2C), 120.5, 86.8, 83.9, 75.3, 41.6, 25.7, 22.8, 21.4, 19.0; IR (CH

₂

) 3452, 2927, 2197, 1712, 1606, 1512, 1447, 1175, 816, 759, 702 cm

^‒1

; MS (ESI) m/e (%) 325.2 ([M + Na]

⁺

, 31), 298.2 (4), 288.1 (10), 248.1 (4), 247.1 (21); HRMS (ESI) calcd for C

₂₂

ONa [M + Na]

⁺

325.1568, found 325.1564.

82

6-(3-(m-Tolyl)prop-2-yn-1-yl)-1,2,3,4-tetrahydro-[1,1'-biphenyl]-1-ol (II-159c)

In General Procedure II, phenyllithium (2.0 M, 11 mL, 4.4 mmol) was added to a solution of the corresponding enone II-160c (0.897 g, 4.0 mmol) in 10 mL of anhydrous THF at ‒78 ℃ under nitrogen. The reaction mixture was stirred for 4 h and maintained the temperature at ‒78 ℃. Then the crude mixture was purified by flash column chromatography over silica gel (ethyl acetate/hexanes 1:30) to give II-159c (0.207 g, 0.68 mmol, 17%, R

_f

= 0.26 in 10% ethyl acetate/hexanes) as a yellow oil:

¹

H NMR (400 MHz, CDCl

₃

) δ 7.46 (d, J = 8.2 Hz, 2H), 7.35 (t, J = 7.4 Hz, 2H), 7.25 (t, J = 6.9 Hz, 2H), 7.17 (t, J = 5.1 Hz, 3H), 7.09 (d, J = 4.7 Hz, 1H), 6.24 (s, 1H), 3.13 (d, J = 19.7 Hz, 1H), 2.87 (d, J = 19.5 Hz, 1H), 2.37 (s, 1H), 2.31 (s, 3H), 2.28‒2.17 (m, 2H), 2.02‒1.90 (m, 2H), 1.81‒1.70 (m, 1H), 1.67‒1.57 (m, 1H);

¹³

C NMR (100 MHz, CDCl

₃

)

δ 146.0, 137.8, 135.8, 132.1, 128.6, 128.5, 128.2, 128.1 (3C), 126.7, 125.7 (2C),

123.3, 87.2, 83.9, 75.2, 41.6, 25.6, 22.7, 21.1, 19.0; IR (CH

₂

) 3453, 2929, 2228, 1697, 1598, 1576, 1487, 1443, 779, 757, 698 cm

^‒1

; MS (ESI) m/e (%) 325.2 ([M + Na]

⁺

, 60), 294.1 (8), 288.1 (28), 284.2 (25), 247.1 (10); HRMS (ESI) calcd for C

₂₂

ONa [M + Na]

⁺

325.1568, found 325.1560.

83

6-(3-(Naphthalen-1-yl)prop-2-yn-1-yl)-1,2,3,4-tetrahydro-[1,1'-biphenyl]-1-ol (II-159d)

In General Procedure II, phenyllithium (2.0 M, 8.3 mL, 3.3 mmol) was added to a solution of the corresponding enone II-160d (0.781 g, 3.0 mmol) in 7.5 mL of anhydrous THF at ‒78 ℃ under nitrogen. The reaction mixture was stirred for 4 h and maintained the temperature at ‒78 ℃. Then the crude mixture was purified by flash column chromatography over silica gel (ethyl acetate/hexanes 1:30) to give II-159d (0.146 g, 0.43 mmol, 14%, R

_f

= 0.23 in 10% ethyl acetate/hexanes) as a tan oil:

¹

H NMR (400 MHz, CDCl

₃

) δ 8.27 (d, J = 8.2 Hz, 1H), 7.83 (d, J = 8.1 Hz, 1H), 7.78 (d, J = 8.2 Hz, 1H), 7.60 (d, J = 7.3 Hz, 1H), 7.56‒7.47 (m, 4H), 7.39 (t, J = 7.5 Hz, 1H), 7.38 (t, J = 7.5 Hz, 2H), 7.28 (tt, J = 7.3, 1.6 Hz, 1H), 6.36 (ddt, J = 4.5, 3.1, 1.7 Hz, 1H), 3.32 (dq, J = 19.6, 2.1 Hz, 1H), 3.02 (dq, J = 19.6, 1.8 Hz, 1H), 2.32‒2.18 (m, 2H), 2.05‒1.93 (m, 2H), 1.82‒1.72 (m, 1H), 1.69‒1.59 (m, 1H);

¹³

C NMR (100 MHz, CDCl

₃

) δ 146.0, 136.0, 133.4, 133.2, 130.2, 128.4, 128.2 (3C), 128.1, 126.8, 126.5, 126.3, 126.2, 125.8 (2C), 125.2, 121.3, 92.6, 81.8, 75.3, 41.7, 25.7, 23.0, 19.0; IR (CH

₂

) 3444, 3057, 2935, 2220, 1712, 1583, 1493, 1447, 800, 770, 759, 706 cm

^‒1

; MS (ESI) m/e (%) 361.1 ([M + Na]

⁺

, 25), 236.2 (8), 235.2 (100), 119.1 (4), 118.1 (63); HRMS (ESI) calcd for C

₂₅

₂₂

ONa [M + Na]

⁺

361.1568, found 361.1565.

84

6-(3-([1,1'-Biphenyl]-4-yl)prop-2-yn-1-yl)-1,2,3,4-tetrahydro-[1,1'-biphenyl -]-1-ol (II-159e)

In General Procedure II, phenyllithium (2.0 M, 1.7 mL, 3.3 mmol) was added to a solution of the corresponding enone II-160e (0.859 g, 3.0 mmol) in 7.5 mL of anhydrous THF at ‒78 ℃ under nitrogen. The reaction mixture was stirred for 4 h and maintained the temperature at ‒78 ℃. Then the crude mixture was purified by flash column chromatography over silica gel (ethyl acetate/hexanes 1:30) to give II-159e (0.512 g, 1.4 mmol, 47%, R

_f

= 0.23 in 10% ethyl acetate/hexanes) as a pale yellow solid: mp 100‒102 ℃;

¹

H NMR (400 MHz, CDCl

₃

) δ 7.58 (d, J = 7.5 Hz, 2H), 7.52 (d, J = 8.2 Hz, 2H), 7.47 (dd, J = 9.6, 2.2 Hz, 2H), 7.44 (td, J = 7.7, 2.3 Hz, 4H), 7.36 (t, J = 7.0 Hz, 2H), 7.34 (d, J = 7.2 Hz, 1H), 7.26 (t, J = 7.3 Hz, 1H), 6.27 (t, J = 3.8 Hz, 1H), 3.17 (dq, J = 19.7, 2.1 Hz, 1H), 2.90 (dd, J = 19.6, 1.5 Hz, 1H), 2.35 (s, 1H), 2.31‒2.15 (m, 2H), 2.03‒1.91 (m, 2H), 1.81‒1.70 (m, 1H), 1.67‒1.59 (m, 1H);

¹³

C NMR (100 MHz, CDCl

₃

) δ 146.0, 140.5, 140.4, 135.8, 131.9 (2C), 128.8 (2C), 128.3, 128.1 (2C), 127.5, 127.0 (2C), 126.9 (2C), 126.8, 125.7 (2C), 122.5, 88.3, 83.6, 75.3, 41.6, 25.7, 22.8, 19.0; IR (CH

₂

) 3446, 2935, 2230, 1668, 1601, 1519, 1488, 1447, 840, 762, 700 cm

^‒1

; MS (ESI) m/e (%) 387.2 ([M + Na]

⁺

, 100), 359.2 (22), 342.2 (12), 391.2 (13), 284.2 (7), 235.2 (15), 118.1 (53); HRMS (ESI) calcd for C

₂₇

₂₄

ONa [M + Na]

⁺

387.1725, found 387.1723.

85

6-(3-(4-Methoxyphenyl)prop-2-yn-1-yl)-1,2,3,4-tetrahydro-[1,1'-biphenyl]-1-ol (II-159f)

In General Procedure II, phenyllithium (2.0 M, 2.3 mL, 4.7 mmol) was added to a solution of the corresponding enone II-160f (0.800 g, 3.3 mmol) in 8.3 mL of anhydrous THF at ‒78 ℃ under nitrogen. The reaction mixture was stirred for 4 h and maintained the temperature at ‒78 ℃. Then the crude mixture was purified by flash column chromatography over silica gel (ethyl acetate/hexanes 1:30) to give II-159f (0.920 g, 2.9 mmol, 87%, R

_f

= 0.18 in 10% ethyl acetate/hexanes) as a yellow oil:

¹

H NMR (400 MHz, CDCl

₃

) δ 7.46 (d, J = 8.0 Hz, 2H), 7.35 (t, J = 7.6 Hz, 2H), 7.30 (d, J = 8.6 Hz, 2H), 7.25 (t, J = 7.3 Hz, 1H), 6.80 (d, J = 8.6 Hz, 2H), 6.23 (s, 1H), 3.80 (s, 3H), 3.12 (d, J = 19.3 Hz, 1H), 2.86 (d, J = 19.3 Hz, 1H), 2.40 (s, 1H), 2.29‒2.14 (m, 2H), 2.02‒1.89 (m, 2H), 1.81‒1.69 (m, 1H), 1.67‒1.56 (m, 1H);

¹³

C NMR (100 MHz, CDCl

₃

)

δ 159.2, 146.2, 136.0, 132.9 (2C), 128.3, 128.1 (2C), 126.8, 125.8 (2C), 115.7,

113.8 (2C), 85.9, 83.6, 75.3, 55.3, 41.6, 25.7, 22.8, 19.0; IR (CH

₂

) 3455, 2937, 2360, 1715, 1606, 1510, 1447, 1032, 832, 761, 703 cm

^‒1

; MS (ESI) m/e (%) 341.2 ([M + Na]

⁺

, 100), 294.1 (13), 290.2 (9), 135.1 (15); HRMS (ESI) calcd for C

₂₂

₂

Na [M + Na]

⁺

341.1517, found 341.1515.

86

1-Methyl-2-(3-phenylprop-2-yn-1-yl)cyclohex-2-enol (II-159g)

In General Procedure II, methyllithium (1.6 M, 1.2 mL, 2.0 mmol) was added to a solution of the corresponding enone II-160a (0.376 g, 1.8 mmol) in 4.5 mL of anhydrous THF at ‒78 ℃ under nitrogen. The reaction mixture was stirred for 4 h and maintained the temperature at ‒78 ℃. Then the crude mixture was purified by flash column chromatography over silica gel (ethyl acetate/hexanes 1:30) to give II-159g (0.255 g, 1.1 mmol, 63%, R

_f

= 0.18 in 10% ethyl acetate/hexanes) as a yellow liquid:

¹

H NMR (400 MHz, CDCl

₃

) δ 7.42 (d, J = 7.4 Hz, 1H), 7.42 (d, J = 5.7 Hz, 1H), 7.28 (t, J = 3.3 Hz, 3H), 5.95 (t, J = 3.8 Hz, 1H), 3.40 (dq, J = 19.5, 2.0 Hz, 1H), 3.22 (dd, J = 19.3, 1.8 Hz, 1H), 2.18‒

2.08 (m, 1H), 2.08‒1.99 (m, 1H), 1.82‒1.64 (m, 5H);

¹³

C NMR (100 MHz, CDCl

₃

) δ 137.0, 131.5 (2C), 128.2 (2C), 127.7, 126.0, 123.7, 87.9, 83.6, 70.2, 39.7, 27.1, 25.7, 21.7, 19.5; IR (CH

₂

) 3392, 2936, 2238, 1715, 1598, 1490, 756, 692 cm

^‒1

; MS (ESI) m/e (%) 249.1 ([M + Na]

⁺

, 100), 232.1 (50), 228.2 (12), 226.2 (8), 191.1(4), 118.1 (7); HRMS (ESI) calcd for C

₁₆

₁₈

ONa [M + Na]

⁺

249.1255, found 249.1255.

87

1-Ethyl-2-(3-phenylprop-2-yn-1-yl)cyclohex-2-enol (II-159h)

Ethylmagnesium bromide (9.2 mL of a 0.9 M solution in THF, 8.3 mmol) was added dropwise over 10 min to a stirred solution of 2-(3-phenylpropargyl)cyclohex-2-en-1-one (0.500 g, 2.4 mmol) in anhydrous THF (24 mL) at 0 ℃ under nitrogen. The mixture was stirred for 3 h at 0 ℃ and quenched with water (30 mL) at 0 ℃. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (50 mL × 3). The combined organic layers were dried over MgSO

₄

(20 g) and concentrated under reduced pressure to give a crude product. The mixture was purified by flash column chromatography over silica gel (ethyl acetate/hexanes 1:30) to obtain 1-ethyl-2-(3-phenylpropargyl)cyclohexen-2-en-1-ol (0.210 g, 0.87 mmol, 37%, R

_f

= 0.23 in 10% ethyl acetate/hexanes) as a yellow liquid:

¹

H NMR (400 MHz, CDCl

₃

) δ 7.42 (d, J = 7.5 Hz, 1H), 7.41 (d, J = 5.6 Hz, 1H), 7.29 (dd, J

= 3.4, 1.3 Hz, 1H), 7.28 (t, J = 2.4 Hz, 1H), 7.27 (t, J = 2.2 Hz, 1H), 6.05 (ddt,

J = 4.7, 3.1, 1.4 Hz, 1H), 3.36 (dq, J = 19.3, 2.0 Hz, 1H), 3.15 (ddt, J = 19.4,

2.6, 1.3 Hz, 1H), 2.18‒2.08 (m, 1H), 2.05‒1.95 (m, 1H), 1.81 (s, 1H), 1.81‒

1.73 (m, 1H), 1.71 (td, J = 7.5, 1.8 Hz, 2H), 1.68‒1.62 (m, 3H), 0.89 (t, J = 7.5 Hz, 3H);

¹³

C NMR (100 MHz, CDCl

₃

) δ 136.2, 131.5 (2C), 128.2 (2C), 127.7, 127.5, 123.6, 87.9, 83.6, 72.4, 34.8, 31.5, 25.7, 21.6, 18.8, 8.3; IR (CH

₂

) 3419, 2937, 2230, 1705, 1598, 1490, 1442, 756, 692 cm

^‒1

; MS (EI, 70 eV) m/e

88

(%) 240.1 ([M]

⁺

, 16), 239.1 (23), 223.1 (22), 211.1 (100), 165.1 (6), 155.1 (11), 105.0 (20); HRMS (EI) calcd for C

₁₇

₂₀

O [M]

⁺

240.1514, found 240.1518.

89

Butyl-2-(3-phenylprop-2-yn-1-yl)cyclohex-2-enol (II-159i)

In General Procedure II, n-butyllithium (1.6 M, 1.6 mL, 2.6 mmol) was added to a solution of the corresponding enone II-160a (0.500 g, 2.4 mmol) in 6.0 mL of anhydrous THF at ‒78 ℃ under nitrogen. The reaction mixture was stirred for 4 h and maintained the temperature at ‒78 ℃. Then the crude mixture was purified by flash column chromatography over silica gel (ethyl acetate/hexanes 1:30) to give II-159i (0.203 g, 0.75 mmol, 32%, R

_f

= 0.21 in 10% ethyl acetate/hexanes) as a yellow oil:

¹

H NMR (400 MHz, CDCl

₃

) δ 7.42 (d, J = 7.1 Hz, 1H), 7.42 (d, J = 5.5 Hz, 1H), 7.29 (t, J = 3.4 Hz, 1H), 7.28 (t, J = 2.4 Hz, 2H), 6.03 (t, J = 3.5 Hz, 1H), 3.37 (dd, J = 19.4, 1.3 Hz, 1H), 3.15 (dd, J = 19.4, 1.0 Hz, 1H), 2.18‒2.08 (m, 1H), 2.05‒1.95 (m, 1H), 1.87‒

1.73 (m, 2H), 1.71‒1.62 (m, 5H), 1.38‒1.29 (m, 3H), 1.24‒1.14 (m, 1H), 0.92 (t, J = 7.1 Hz, 3H);

¹³

C NMR (100 MHz, CDCl

₃

) δ 136.5, 131.5 (2C), 128.2 (2C), 127.7, 127.4, 123.7, 87.9, 83.7, 72.2, 38.9, 35.6, 26.2, 25.7, 23.3, 21.7, 18.9, 14.1; IR (CH

₂

) 3419, 2935, 2871, 2360, 1715, 1598, 1490, 1455, 756, 691 cm

^‒1

; MS (EI, 70 eV) m/e (%) 268.2 ([M]

⁺

, 2), 267.2 (3), 211.1 (100), 183.1 (4), 153.1 (10), 105.0 (14); HRMS (EI) calcd for C

₁₉

₂₄

O [M]

⁺

268.1827, found 268.1831.

90

4'-Methoxy-6-(3-phenylprop-2-yn-1-yl)-1,2,3,4-tetrahydro-[1,1'-biphenyl]-1-ol (II-159j)

The n-BuLi (3.1 mL of a 1.6 M solution in hexane, 5.0 mmol) was added dropwise over 20 min to a ‒78 ℃ cooled solution of 4-bromoanisole (0.6 mL, 5.0 mmol) in anhydrous THF (25 mL). The reaction mixture was stirred for 10 min at ‒78 ℃ under nitrogen. Then the resultant (4-methoxyphenyl)lithium solution was cannulated dropwise into a stirred solution of 2-(3-phenylpropargyl)cyclohex-2-en-1-one (0.700 g, 3.3 mmol) in dried THF (17 mL) at ‒78 ℃ under nitrogen. The reaction mixture was maintained this temperature and stirred for 4 h. The mixture was poured into a saturated NH

₄

_(aq)

(40 mL) and extracted with ethyl acetate (60 mL × 4). The combined organic layers were dried over MgSO

₄

(20 g) and removed of solvent under reduced pressure to give a crude product. The residue was purified by flash column chromatography over silica gel (ethyl acetate/hexanes 1:30) to afford 1-(4-methoxyphenyl)-2-(3-phenylpropargyl)cyclohex-2-en-1-ol (0.603 g, 1.9 mmol, 57%, R

_f

= 0.15 in 10% ethyl acetate/hexanes) as a yellow oil:

¹

H NMR (400 MHz, CDCl

₃

) δ 7.37 (d, J = 6.1 Hz, 2H), 7.37 (d, J = 5.4 Hz, 2H), 7.30‒

7.26 (m, 3H), 6.88 (d, J = 8.6 Hz, 2H), 6.23 (s, 1H), 3.81 (s, 3H), 3.16 (d, J = 19.5 Hz, 1H), 2.88 (d, J = 19.6 Hz, 1H), 2.27 (s, 1H), 2.25‒2.12 (m, 2H), 2.00‒

1.88 (m, 2H), 1.79‒1.68 (m, 1H), 1.64‒1.55 (m, 1H);

¹³

C NMR (100 MHz,

91

CDCl

₃

) δ 158.4, 138.1, 135.9, 131.4 (2C), 128.1 (2C), 127.8, 127.6, 126.9 (2C), 123.6, 113.4 (2C), 87.7, 83.7, 74.9, 55.1, 41.6, 25.6, 22.5, 19.0; IR (CH

₂

) 3446, 2937, 2360, 1724, 1609, 1511, 1491, 1249, 1035, 832, 757, 692 cm

^‒1

; MS (ESI) m/e (%) 341.2 ([M + Na]

⁺

, 100), 324.1 (8), 322.2 (4), 301.2 (11), 259.2 (3), 230.2 (2); HRMS (ESI) calcd for C

₂₂

₂

Na [M + Na]

⁺

341.1517, found 341.1511.

92

6-(Prop-2-yn-1-yl)-1,2,3,4-tetrahydro-[1,1'-biphenyl]-1-ol (II-159k)

In General Procedure II, phenyllithium (2.0 M, 16.0 mL, 33 mmol) was added to a solution of the corresponding enone II-161a (2.000 g, 15 mmol) in 37 mL of anhydrous THF at ‒78 ℃ under nitrogen. The reaction mixture was stirred for 4 h and maintained the temperature at ‒78 ℃. Then the crude mixture was purified by flash column chromatography over silica gel (ethyl acetate/hexanes 1:30) to give II-159k (2.588 g, 12 mmol, 82%, R

_f

= 0.23 in 10% ethyl acetate/hexanes) as a colorless oil:

¹

H NMR (400 MHz, CDCl

₃

) δ 7.43‒7.39 (m, 2H), 7.34 (t, J = 7.6 Hz, 1H), 7.33 (t, J = 5.9 Hz, 1H), 7.25 (tt, J

= 7.2, 1.7 Hz, 1H), 6.22 (ddt, J = 4.5, 3.1, 1.6 Hz, 1H), 2.93 (tdd, J = 2.5, 2.3, 2.3 Hz, 1H), 2.64 (tdd, J = 2.6, 2.1, 2.1 Hz, 1H), 2.28‒2.15 (m, 3H), 2.21 (s, 1H), 2.13 (t, J = 2.7 Hz, 1H), 2.00‒1.88 (m, 2H), 1.77‒1.67 (m, 1H), 1.65‒1.57 (m, 1H);

¹³

C NMR (100 MHz, CDCl

₃

) δ 145.8, 135, 128.3, 128.1 (2C), 126.8, 125.7 (2C), 82.2, 75.2, 71.4, 41.6, 25.6, 21.6, 19.0; IR (CH

₂

) 3447, 2939, 2120, 1602, 1491, 1447, 1176, 761, 703 cm

^‒1

; MS (ESI) m/e (%) 211.1 ([M

‒

^–

, 98), 205.2 (13), 191.1 (8), 166.0 (9), 132.9 (10), 125.9 (12), 113.0 (100);

HRMS (ESI) calcd for C

₁₅

O [M

‒

^–

211.1123, found 211.1117.

93

6-(3-(4-Nitrophenyl)prop-2-yn-1-yl)-1,2,3,4-tetrahydro-[1,1'-biphenyl]-1-ol (II-159l)

In General Procedure I, to a solution of II-159k (0.425 g, 2.0 mmol) in Et

₃

N (2.0 mL) were added sequentially 1-iodo-4-nitrobenzene (0.598 g, 2.4 mmol), Pd(PPh

₃

)

₄

(9.2 mg, 0.008 mmol) and CuI (0.030 g, 0.16 mmol) at room temperature under an atmosphere of nitrogen. The reaction mixture was stirred for 8 h and the crude mixture was purified by flash column chromatography over silica gel (ethyl acetate/hexanes 1:20) to give II-159l (0.542 g, 1.6 mmol, 81%, R

_f

= 0.28 in 20% ethyl acetate/hexanes) as a yellow solid: mp 120‒121

℃;

¹

H NMR (400 MHz, CDCl

₃

) δ 8.14 (dt, J = 9.1, 2.1 Hz, 2H), 7.50‒7.44 (m, 4H), 7.36 (t, J = 7.6 Hz, 1H), 7.36 (t, J = 5.9 Hz, 1 H), 7.27 (tt, J = 7.3, 1.2 Hz, 1H), 6.24 (ddt, J = 4.2, 3.1, 1.8 Hz, 1H), 3.21 (dq, J = 19.9, 2.0 Hz, 1H), 2.92 (dq, J = 19.8, 1.8 Hz, 1H), 2.32‒2.19 (m, 2H), 2.16 (d, J = 2.5 Hz, 1H), 2.00 (t,

J = 7.6 Hz, 1H), 1.96 (t, J = 7.5 Hz, 1H), 1.73 (dq, J = 13.2, 6.6 Hz, 1H), 1.67‒

1.56 (m, 1H);

¹³

C NMR (100 MHz, CDCl

₃

) δ 146.7, 145.7, 135.4, 132.2 (2C), 130.7, 128.4, 128.2 (2C), 127.0, 125.7 (2C), 123.5 (2C), 93.9, 82.2, 75.2, 41.6, 25.6, 22.7, 19.0; IR (CH

₂

) 3558, 2938, 2229, 1593, 1518, 1492, 1343, 854 cm

^‒1

; MS (ESI) m/e (%) 332.1 ([M ‒ H]

^–

, 100), 298.0 (4), 252.0 (3), 211.1 (2);

HRMS (ESI) calcd for C

₂₁

₁₈

₃

[M ‒ H]

^–

332.1287, found 322.1279.

94

6-(3-(3-Nitrophenyl)prop-2-yn-1-yl)-1,2,3,4-tetrahydro-[1,1'-biphenyl]-1-ol (II-159m)

In General Procedure I, to a solution of II-159k (0.318 g, 1.5 mmol) in Et

₃

N (1.5 mL) were added sequentially 1-iodo-3-nitrobenzene (0.448 g, 1.8 mmol), Pd(PPh

₃

)

₄

_f

= 0.25 in 20% ethyl acetate/hexanes) as a tan oil:

¹

H NMR (400 MHz, CDCl

₃

) δ 8.18 (t, J = 1.8 Hz, 1H), 8.12 (ddd, J = 8.3, 2.3, 0.9 Hz, 1H), 7.64 (dt,

J = 7.7, 1.1 Hz, 1H), 7.49‒7.42 (m, 3H), 7.36 (t, J = 7.7 Hz, 1H), 7.36 (t, J =

5.9 Hz, 1H), 7.27 (tt, J = 7.1, 1.5 Hz, 1H), 6.24 (ddt, J = 4.2, 3.0, 1.8 Hz, 1H), 3.19 (dq, J = 19.8, 2.0 Hz, 1H), 2.91 (dq, J = 19.7, 1.9 Hz, 1H), 2.33‒2.17 (m, 2H), 2.15 (s, 1H), 2.00 (t, J = 7.8 Hz, 1H), 1.97 (t, J = 7.6 Hz, 1H), 1.73 (dq, J

= 13.1, 6.5 Hz, 1H), 1.63 (dqd, J = 12.4, 6.2, 1.8 Hz, 1H);

¹³

C NMR (100 MHz, CDCl

₃

) δ 148.0, 145.7, 137.2, 135.4, 129.1, 128.3, 128.2 (2C), 126.9, 126.3, 125.7 (2C), 125.5, 122.4, 90.8, 81.5, 75.2, 41.6, 25.6, 22.5, 19.0; IR (CH

₂

) 3560, 2937, 2229, 1530, 1491, 1447, 1350, 937, 806, 761, 736, 703 cm

^‒1

; MS (ESI) m/e (%) 332.1 ([M

‒

^–

, 100), 316.7 (8), 298.0 (2), 252.0 (1), 224.8 (1);

HRMS (ESI) calcd for C

₂₁

₁₈

₃

‒

^–

332.1287, found 332.1280.

95

6-(3-(2-Nitrophenyl)prop-2-yn-1-yl)-1,2,3,4-tetrahydro-[1,1'-biphenyl]-1-ol (II-159n)

In General Procedure I, to a solution of II-159k (0.318 g, 1.5 mmol) in Et

₃

N (1.5 mL) were added sequentially 1-iodo-2-nitrobenzene (0.448 g, 1.8 mmol), Pd(PPh

₃

)

₄

_f

= 0.30 in 20% ethyl acetate/hexanes) as a dark brown oil:

¹

H NMR (400 MHz, CDCl

₃

) δ 8.00 (d, J = 8.2 Hz, 1H), 7.55‒7.49 (m, 2H), 7.47 (d, J = 7.8 Hz, 2H), 7.40 (ddd, J = 8.4, 5.6, 3.0 Hz, 1H), 7.35 (t, J = 7.6 Hz, 2H), 7.25 (t, J = 7.3 Hz, 1H), 6.32 (ddt, J = 4.4, 3.1, 1.7 Hz, 1H), 3.21 (dq, J = 19.6, 2.0 Hz, 1H), 2.95 (dd, J = 19.7, 1.8 Hz, 1H), 2.29 (s, 1H), 2.35‒2.16 (m, 2H), 2.01 (dt, J = 13.6, 3.7 Hz, 1H), 1.96 (dt, J = 13.8, 4.4 Hz, 1H), 1.80‒1.69 (m, 1H), 1.67‒1.58 (m, 1H);

¹³

C NMR (100 MHz, CDCl

₃

) δ 149.7, 145.8, 135.3, 134.9, 132.6, 128.9, 128.2 (2C), 128.0, 126.8, 125.8 (2C), 124.5, 119.1, 96.8, 78.8, 75.2, 41.7, 25.7, 23.1, 19.0; IR (CH

₂

) 3556, 2937, 2229, 1608, 1520, 1447, 1344, 761, 745, 703 cm

^‒1

; MS (ESI) m/e (%) 332.1 ([M ‒ H]

^–

, 100), 314.1 (11), 231.0 (4), 210.1 (22), 195.1 (5), 126.9 (3); HRMS (ESI) calcd for C

₂₁

₁₈

₃

[M ‒ H]

^–

332.1287, found 332.1287.

96

Ethyl-

4-(3-(1-hydroxy-1,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)prop-1-yn-1-yl)ben -zoate (II-159o)

In General Procedure I, to a solution of II-159k (0.477 g, 2.2 mmol) in Et

₃

N (2.2 mL) were added sequentially ethyl 4-iodobenzoate (0.745 g, 2.7 mmol), Pd(PPh

₃

)

₄

(10.4 mg, 0.009 mmol) and CuI (0.034 g, 0.18 mmol) at room temperature under an atmosphere of nitrogen. The reaction mixture was stirred for 8 h and the crude mixture was purified by flash column chromatography over silica gel (ethyl acetate/hexanes 1:20) to give II-159o (0.711 g, 2.0 mmol, 88%, R

_f

= 0.23 in 10% ethyl acetate/hexanes) as a pale yellow solid: mp 73‒74

℃;

¹

H NMR (400 MHz, CDCl

₃

) δ 7.95 (dt, J = 8.5, 1.7 Hz, 2H), 7.49‒7.44 (m, 2H), 7.40 (dt, J = 8.6, 1.9 Hz, 2H), 7.35 (t, J = 7.6 Hz, 1H), 7.35 (t, J = 6.0 Hz, 1H), 7.26 (tt, J = 7.3, 1.1 Hz, 1H), 6.25 (ddt, J = 4.5, 3.1, 1.7 Hz, 1H), 4.37 (q,

J = 7.1 Hz, 2H), 3.18 (dq, J = 19.7, 2.1 Hz, 1H), 2.90 (dq, J = 19.7, 2.0 Hz, 1H),

2.27 (s, 1H), 2.31‒2.15 (m, 2H), 2.03‒1.91 (m, 2H), 1.79‒1.68 (m, 1H), 1.67‒

1.59 (m, 1H), 1.39 (t, J = 7.1 Hz, 3H);

¹³

C NMR (100 MHz, CDCl

₃

) δ 166.1, 145.9, 135.6, 131.4 (2C), 129.4, 129.3 (2C), 128.4, 128.3, 128.2 (2C), 126.9, 125.7 (2C), 91.0, 83.2, 75.2, 61.0, 41.6, 25.6, 22.7, 19.0, 14.3; IR (CH

₂

) 3502, 2937, 2230, 1715, 1606, 1447, 1368, 1273, 1175, 1107, 858, 769, 702 cm

^‒1

; MS (ESI) m/e (%) 359.2 ([M ‒ H]

^–

, 100), 328.1 (4), 298.0 (12), 295.0 (3),

97

252.0 (6), 245.0 (2), 211.1 (5); HRMS (ESI) calcd for C

₂₄

₂₃

₃

[M ‒ H]

^–

359.1647, found 359.1643.

98

Ethyl-

3-(3-(1-hydroxy-1,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)prop-1-yn-1-yl)ben -zoate (II-159p)

In General Procedure I, to a solution of II-159k (0.500 g, 2.4 mmol) in Et

₃

N (2.4 mL) were added sequentially ethyl 3-iodobenzoate (0.780 g, 2.8 mmol), Pd(PPh

₃

)

₄

(10.9 mg, 0.009 mmol) and CuI (0.036 g, 0.19 mmol) at room temperature under an atmosphere of nitrogen. The reaction mixture was stirred for 8 h and the crude mixture was purified by flash column chromatography over silica gel (ethyl acetate/hexanes 1:20) to give II-159p (0.628 g, 1.7 mmol, 74%, R

_f

= 0.33 in 20% ethyl acetate/hexanes) as a tan oil:

¹

H NMR (500 MHz, CDCl

₃

) δ 8.04 (t, J = 1.5 Hz,1H), 7.94 (dt, J = 7.9, 1.4 Hz, 1H), 7.53 (dt, J = 7.7, 1.4 Hz, 1H), 7.48‒7.44 (m, 2H), 7.36 (t, J = 7.7 Hz, 2H), 7.35 (t, J = 7.8 Hz, 1H), 7.26 (tt, J = 7.3, 1.2 Hz, 1H), 6.26 (ddt, J = 4.5, 3.1, 1.7 Hz, 1H), 4.38 (q, J = 7.1 Hz, 2H), 3.16 (dq, J = 19.7, 2.1 Hz, 1H), 2.88 (dq, J = 19.6, 1.9 Hz, 1H), 2.31‒2.16 (m, 2H), 2.24 (s, 1H), 2.02‒1.92 (m, 2H), 1.78‒1.70 (m, 1H), 1.66‒1.58 (m, 1H), 1.40 (t, J = 7.1 Hz, 3H);

¹³

C NMR (125 MHz, CDCl

₃

) δ 166.0, 145.9, 135.7, 135.6, 132.6, 130.7, 128.8, 128.4, 128.3, 128.2 (2C), 126.9, 125.8 (2C), 124.0, 88.7, 82.9, 75.3, 61.1, 41.7, 25.6, 22.6, 19.0, 14.3; IR (CH

₂

) 3501, 2938, 2236, 1716, 1601, 1579, 1447, 1302, 1229, 816, 756,

99

703 cm

^‒1

; MS (ESI) m/e (%) 383.2 ([M + Na]

⁺

, 100), 361.2 (18), 311.2 (13), 261.6 (17), 143.1 (28), 122.5 (16); HRMS (ESI) calcd for C

₂₄

₃

Na [M + Na]

⁺

383.1623, found 383.1624.

100

6-(3-(4-Bromophenyl)prop-2-yn-1-yl)-1,2,3,4-tetrahydro-[1,1'-biphenyl]-1-ol (II-159q)

In General Procedure I, to a solution of II-159k (0.500 g, 2.4 mmol) in Et

₃

N (2.4 mL) were added sequentially 1-bromo-4-iodobenzene (0.800 g, 2.8 mmol), Pd(PPh

₃

)

₄

_f

= 0.20 in 10% ethyl acetate/hexanes) as a pale yellow oil:

¹

H NMR (400 MHz, CDCl

₃

) δ 7.45 (d, J = 7.9 Hz, 2H), 7.40 (dt, J = 8.7, 2.1 Hz, 2H), 7.35 (t, J = 7.6 Hz, 2H), 7.26 (t, J = 7.3 Hz, 1H), 7.21 (dt, J = 8.9, 2.1 Hz, 2H), 6.22 (dt, J = 3.9, 1.9 Hz, 1H), 3.13 (dq, J = 19.7, 2.0 Hz, 1H), 2.86 (dd, J = 19.6, 1.8 Hz, 1H), 2.25 (s, 1H), 2.30‒2.14 (m, 2H), 1.99 (dt, J = 13.3, 3.5 Hz, 2H), 1.79‒1.68 (m, 1H), 1.66‒1.56 (m, 1H);

¹³

C NMR (100 MHz, CDCl

₃

) δ 145.9, 135.6, 133.0 (2C), 131.4 (2C), 128.4, 128.2 (2C), 126.9, 125.7 (2C), 122.6, 121.9, 88.9, 82.8, 75.2, 41.6, 25.6, 22.7, 19.0; IR (CH

₂

) 3452, 2936, 2234, 1601, 1486, 1447, 1070, 824, 760, 702 cm

^‒1

; MS (ESI) m/e (%) 365.1 ([M ‒ H]

^–

, 85), 367.1 (100), 327.3 (9), 281.3 (11), 275.1 (17), 268.9 (16), 229.1 (15), 200.9 (69), 126.9 (6); HRMS (ESI) calcd for C

₂₁

₁₈

OBr [M ‒ H]

^–

365.0541, found 365.0540.

101

6-(3-(3-(Trifluoromethyl)phenyl)prop-2-yn-1-yl)-1,2,3,4-tetrahydro-[1,1'-bi -phenyl]-1-ol (II-159r)

In General Procedure I, to a solution of II-159k (0.500 g, 2.4 mmol) in Et

₃

N (2.4 mL) were added sequentially 3-iodobenzotrifluoride (0.800 g, 2.8 mmol), Pd(PPh

₃

)

₄

_f

= 0.25 in 10% ethyl acetate/hexanes) as a pale yellow oil:

¹

H NMR (400 MHz, CDCl

₃

) δ 7.59 (s, 1H), 7.52 (d, J = 7.7 Hz, 2H), 7.46 (d, J = 7.8 Hz, 2H), 7.40 (d, J = 7.7 Hz, 1H), 7.36 (t, J = 7.5 Hz, 2H), 7.26 (t, J = 7.3 Hz, 1H), 6.24 (t, J = 3.8 Hz, 1H), 3.17 (dd, J = 19.7, 1.9 Hz, 1H), 2.90 (dd, J = 19.7, 1.7 Hz, 1H), 2.33‒2.16 (m, 2H), 2.21 (s, 1H), 2.03‒1.92 (m, 2H), 1.73 (dq, doublet of quintets, J = 13.1, 6.6 Hz, 1H), 1.67‒1.57 (m, 1H);

¹³

C NMR (100 MHz, CDCl

₃

) δ 145.8, 135.5, 134.5, 130.7 (q,

² J _CF = 32 Hz), 128.6, 128.2 (q, J _CF

= 4 Hz), 128.0 (d, J

_CF

= 4 Hz, 3C), 126.8 (d, J

_CF

= 3 Hz), 125.8 (2C), 124.5, 123.7 (q,

¹ J _CF

= 271 Hz, CF

₃

), 124.1 (q, J

_CF

= 4 Hz), 89.6, 82.3, 75.2, 41.5, 25.5, 22.4, 18.9;

¹⁹

F NMR (CDCl

₃

, 376 MHz) δ −63.9 (s, 3F); IR (CH

₂

) 3452, 2939, 2244, 1602, 1488, 1433, 1336, 1237, 1168, 1094, 937, 801 cm

^‒1

; MS (ESI) m/e

102

(%) 355.1 ([M – H]

^–

, 100), 298.0 (3), 275.1 (2), 229.1 (2), 190.0 (1), 189.0 (17);

HRMS (ESI) calcd for C

₂₂

₁₈

₃

[M ‒ H]

^–

355.1310, found 355.1309.

103

6-(Hept-2-yn-1-yl)-1,2,3,4-tetrahydro-[1,1'-biphenyl]-1-ol (II-159s)

The n-BuLi (3.4 mL of a 1.6 M solution in hexane, 5.4 mmol) was added dropwise over 20 min to a stirred solution of 1-phenyl-2-(2-propynyl)cyclohex-2-en-1-ol (0.550 g, 2.6 mmol) in anhydrous THF (13 mL) at ‒78 ℃ under nitrogen. The reaction mixture was stirred for 1 h at this temperature. After that, 1-bromobutane (0.390 g, 2.8 mmol) in HMPA (1.1 mL, 6.5 mmol) was added to the reaction mixture at ‒78 ℃ and the reaction mixture was stirred for 24 h at room temperature. The mixture was quenched with a saturated NaHCO

_3(aq)

(30 mL) and extracted with diethyl ether (50 mL × 4). The combined organic layers were dried over MgSO

₄

(20 g) and concentrated under vacuum. The crude mixture was purified by flash column chromatography over silica gel (ethyl acetate/hexanes 1:30) yielding 1-phenyl-2-(3-butylpropargyl)cyclohex-2-en-1-ol (0.301 g, 1.1 mmol, 43%, R

_f

= 0.35 in 10% ethyl acetate/hexanes) as a tan oil:

¹

H NMR (400 MHz, CDCl

₃

)

δ 7.41 (d, J = 7.7 Hz, 2H), 7.32 (t, J = 7.6 Hz, 2H), 7.23 (t, J = 7.2 Hz, 1H),

6.15‒6.09 (m, 1H), 2.86 (dq, J = 18.9, 2.2 Hz, 1H), 2.67‒2.58 (m, 1H), 2.57 (s, 1H), 2.26‒2.16 (m, 2H), 2.14 (tt, J = 6.9, 2.3 Hz, 2H), 1.95 (ddd, J = 13.1, 7.2, 3.1 Hz, 1H)1.87 (td, J = 11.7, 3.1 Hz, 1H), 1.80‒1.70 (m, 1H), 1.64‒1.56 (m, 1H), 1.49‒1.32 (m, 4H), 0.90 (t, J = 7.2 Hz, 3H);

¹³

C NMR (100 MHz, CDCl

₃

)

δ 146.4, 136.2, 128.0 (3C) 126.6, 125.7 (2C), 83.8, 77.6, 75.3, 41.5, 31.0, 25.6,

104

22.4, 21.9, 19.0, 18.4, 13.6; IR (CH

₂

) 3526, 2933, 2230, 1601, 1491, 1447, 1175, 760, 703 cm

^‒1

; MS (ESI) m/e (%) 291.2 ([M + Na]

⁺

, 100), 288.2 (3), 251.2 (29), 216.1 (5), 215.6 (19), 143.1 (9), 122.5 (4); HRMS (ESI) calcd for C

₁₉

₂₄

ONa [M + Na]

^{+ 2}

291.1725, found 291.1726.

105

3,3-Dimethyl-6-(3-phenylprop-2-yn-1-yl)-1,2,3,4-tetrahydro-[1,1'-biphenyl]

-1-ol (II-159t)

In General Procedure II, phenyllithium (2.0 M, 2.2 mL, 4.5 mmol) was added to a solution of the corresponding enone II-160t (0.713 g, 3.0 mmol) in 7.5 mL of anhydrous THF at ‒78 ℃ under nitrogen. The reaction mixture was stirred for 4 h and maintained the temperature at ‒78 ℃. Then the crude mixture was purified by flash column chromatography over silica gel (ethyl acetate/hexanes 1:30) to give II-159t (0.713 g, 2.3 mmol, 75%, R

_f = 0.35 in 10% ethyl

acetate/hexanes) as a yellow oil:

¹

H NMR (400 MHz, CDCl

₃

) δ 7.43‒7.36 (m, 4H), 7.32 (t, J = 7.7 Hz, 2H), 7.29‒7.24 (m, 3H), 7.22 (t, J = 7.2 Hz, 1H), 6.21‒

6.15 (m, 1H), 3.11 (dd, J = 19.4, 2.0 Hz, 1H), 2.83 (d, J = 19.4 Hz, 1H), 2.49 (s, 1H), 2.09 (dd, J = 17.5, 2.4 Hz, 1H), 2.04 (dd, J = 17.2, 5.2 Hz, 1H), 1.85 (s, 2H), 1.19 (s, 3H), 0.95 (s, 3H);

¹³

C NMR (100 MHz, CDCl

₃

) δ 147.5, 134.8, 131.5 (2C), 128.2 (4C), 127.7, 126.7, 126.5, 125.3 (2C), 123.5, 87.7, 83.7, 75.8, 54.5, 39.8, 31.8, 29.7, 26.6, 22.3; IR (CH

₂

) 3537, 2951, 2237, 1599, 1490, 1445, 1032, 755, 702 cm

^‒1

; MS (EI, 70 eV) m/e (%) 316.3 ([M + Na]

⁺

, 59), 260.2 (100), 239.2 (78), 183.2 (93), 105.2 (68); HRMS (EI) calcd for C

₂₃

₂₄

O [M]

⁺

316.1827, found 316.1835.

106

3.2.4 Synthesis of Tetrahydrobenzo[b]furan Derivatives 2-Benzyl-4-phenyl-4,5,6,7-tetrahydrobenzofuran (II-174a)

In General Procedure III, to a solution of AgOTf (2.5 mg, 0.010 mmol) in 2.0 mL of CH

₂

was added sequentially Ph

₃

PAuCl (4.9 mg, 0.010 mmol) and compound II-159a (0.057 g, 0.20 mmol) at room temperature under an atmosphere of nitrogen. The reaction mixture was stirred for 1 min until all II-159a was disappeared by TLC. The resulting dark brown solution was filtered through a bed of Celite, and the crude mixture was purified by flash column chromatography over silica gel (hexanes) to give II-174a (0.035 g, 0.12 mmol, 61%, R

_f

= 0.63 in 10% ethyl acetate/hexanes) as a yellow brown oil:

1

H NMR (400 MHz, CDCl

₃

) δ 7.31‒7.26 (m, 5H), 7.23 (d, J = 6.8 Hz, 2H), 7.20 (dt, J = 6.0, 1.9 Hz, 1H), 7.17‒7.14 (m, 2H), 5.63 (s, 1H), 3.90 (s, 2H), 3.81 (dd, J = 7.6, 5.6 Hz, 1H), 2.70‒2.55 (m, 2H), 2.07 (dddd, J = 12.9, 7.4, 5.3, 2.3 Hz, 1H), 1.96‒1.87 (m, 1H), 1.82‒1.71 (m, 1H), 1.64 (dddd, J = 17.9, 12.9, 10.2, 2.6 Hz, 1H);

¹³

C NMR (100 MHz, CDCl

₃

) δ 152.4, 150.5, 145.7, 138.5, 128.7 (2C), 128.4 (2C), 128.2 (2C), 128.0 (2C), 126.3, 126.1, 120.1, 106.9, 40.2, 34.7, 33.7, 23.1, 21.4; IR (CH

₂

) 3399, 2927, 2859, 1708, 1599, 1493, 1451, 1266, 755, 736, 698 cm

^‒1

; MS (EI, 70 eV) m/e (%) 288.1 ([M]

⁺

, 23), 284.1 (32), 283.1 (16), 214.1 (12), 181.1 (14), 157.1 (15), 122.0 (31); HRMS (EI) calcd for C

₂₁

₂₀

O [M]

⁺

288.1514, found 288.1507.

107

2-(4-Methylbenzyl)-4-phenyl-4,5,6,7-tetrahydrobenzofuran (II-174b)

In General Procedure III, to a solution of AgOTf (4.5 mg, 0.018 mmol) in 3.5 mL of CH

₂

was added sequentially Ph

₃

PAuCl (8.7 mg, 0.018 mmol) and compound II-159b (0.106 g, 0.35 mmol) at room temperature under an atmosphere of nitrogen. The reaction mixture was stirred for 1 min until all II-159b was disappeared by TLC. The resulting dark brown solution was filtered through a bed of Celite, and the crude mixture was purified by flash column chromatography over silica gel (hexanes) to give II-174b (0.040 g, 0.13 mmol, 38%, R

_f

= 0.60 in 10% ethyl acetate/hexanes) as a pale yellow oil:

1

H NMR (400 MHz, CDCl

₃

) δ 7.27 (t, J = 7.1 Hz, 2H), 7.19 (t, J = 7.3 Hz, 1H), 7.16‒7.13 (m, 2H), 7.12 (d, J = 8.2 Hz, 2H), 7.09 (d, J = 8.1 Hz, 2H), 5.60 (s, 1H), 3.85 (s, 2H), 3.80 (dd, J = 7.5, 5.6 Hz, 1H), 2.69‒2.55 (m, 2H), 2.31 (s, 3H), 2.07 (dddd, J = 12.9, 7.4, 5.3, 2.2 Hz, 1H), 1.96‒1.86 (m, 1H), 1.81‒1.70 (m, 1H), 1.63 (dddd, J = 17.9, 12.9, 10.2, 2.5 Hz, 1H);

¹³

C NMR (100 MHz, CDCl

₃

) δ 152.7, 150.4, 145.8, 135.8, 135.4, 129.1 (2C), 128.6 (2C), 128.2 (2C), 128.0 (2C), 126.1, 120.0, 106.7, 40.2, 34.3, 33.7, 23.1, 21.5, 21.0; IR (CH

₂

) 2935, 2859, 1602, 1572, 1515, 1493, 1224, 804, 755, 698 cm

^‒1

; MS (ESI) m/e (%) 325.2 ([M + Na]

⁺

, 28), 288.1 (49), 265.1 (12), 247.1 (100), 233.1 (18), 190.0 (10), 143.1 (11); HRMS (ESI) calcd for C

₂₂

₂₀

ONa [M + Na]

⁺

325.1568, found 325.1561.

108

2-(3-Methylbenzyl)-4-phenyl-4,5,6,7-tetrahydrobenzofuran (II-)

In General Procedure III, to a solution of AgOTf (3.9 mg, 0.015 mmol) in 3.0 mL of CH

₂

was added sequentially Ph

₃

PAuCl (7.4 mg, 0.015 mmol) and compound II-159c (0.091 g, 0.30 mmol) at room temperature under an atmosphere of nitrogen. The reaction mixture was stirred for 1 min until all II-159c was disappeared by TLC. The resulting dark brown solution was filtered through a bed of Celite, and the crude mixture was purified by flash column chromatography over silica gel (hexanes) to give II-174c (0.046 g, 0.15 mmol, 51%, R

_f

= 0.60 in 10% ethyl acetate/hexanes) as a yellow oil:

¹

H NMR (400 MHz, CDCl

₃

) δ 7.28 (tt, J = 7.1, 1.3 Hz, 2H), 7.22‒7.18 (m, 1H), 7.17 (d,

J = 1.8 Hz, 2H), 7.15 (d, J = 1.8 Hz, 1H), 7.05 (s, 1H), 7.03 (t, J = 7.7 Hz, 2H),

5.62 (s, 1H), 3.85 (s, 2H), 3.81 (dd, J = 7.4, 5.7 Hz, 1H), 2.69‒2.56 (m, 2H), 2.32 (s, 3H), 2.07 (dddd, J = 12.9, 7.5, 5.3, 2.3 Hz, 1H), 1.95‒1.87 (m, 1H), 1.81‒1.70 (m, 1H), 1.64 (dddd, J = 17.8, 12.9, 10.2, 2.5 Hz, 1H);

¹³

C NMR (100 MHz, CDCl

₃

) δ 152.5, 150.5, 145.8, 138.4, 138.0, 129.5, 128.3, 128.2 (2C), 128.0 (2C), 127.1, 126.1, 125.8, 120.0, 106.8, 40.2, 34.7, 33.7, 23.1, 21.4 (2C); IR (CH

₂

) 2922, 2856, 1601, 1564, 1487, 1443, 1155, 753, 698 cm

^‒1

; MS (EI, 70 eV) m/e (%) 302.1 ([M]

⁺

, 11), 298.1 (9), 202.1 (8), 182.1 (63), 181.1 (14), 119.0 (18); HRMS (EI) calcd for C

₂₂

O [M]

⁺

302.1671, found 302.1668.

109

2-(Naphthalen-1-ylmethyl)-4-phenyl-4,5,6,7-tetrahydrobenzofuran (II-174d)

In General Procedure III, to a solution of AgOTf (3.9 mg, 0.015 mmol) in 3.0 mL of CH

₂

was added sequentially Ph

₃

PAuCl (7.4 mg, 0.015 mmol) and compound II-159d (0.102 g, 0.30 mmol) at room temperature under an atmosphere of nitrogen. The reaction mixture was stirred for 1 min until all II-159d was disappeared by TLC. The resulting dark brown solution was filtered through a bed of Celite, and the crude mixture was purified by flash column chromatography over silica gel (hexanes) to give II-174d (0.051g, 0.15 mmol, 50%, R

_f

= 0.58 in 10% ethyl acetate/hexanes) as a yellow oil:

¹

H NMR (400 MHz, CDCl

₃

) δ 8.05 (dd, J = 7.2, 2.1 Hz,1 H), 7.86‒7.81 (m, 1H), 7.74 (d,

J = 8.0 Hz, 1H), 7.51‒7.43 (m, 2H), 7.40 (t, J = 7.5 Hz, 1H), 7.35 (d, J = 6.7

Hz, 1H), 7.26‒7.21 (m, 2H), 7.16 (tt, J = 7.3, 2.2 Hz, 1H), 7.14‒7.09 (m, 2H), 5.57 (s, 1H), 4.35 (d, J = 2.0 Hz, 2H), 3.78 (dd, J = 7.4, 5.7 Hz, 1H), 2.70‒2.56 (m, 2H), 2.06 (dddd, J = 12.9, 7.6, 5.3, 2.3 Hz, 1H), 1.94‒1.85 (m, 1H), 1.80‒

1.70 (m, 1H), 1.67‒1.57 (m, 1H);

¹³

C NMR (100 MHz, CDCl

₃

) δ 151.9, 150.4, 145.7, 134.4, 133.9, 132.0, 128.6, 128.2 (2C), 128.0 (2C), 127.3, 126.9, 126.0, 125.9, 125.6, 125.5, 124.1, 120.1, 107.3, 40.2, 33.8, 32.2, 23.1, 21.4; IR (CH

₂

) 2935, 2859, 1599, 1568, 1512, 1493, 1224, 778, 698 cm

^‒1

110

; MS (EI, 70 eV) m/e (%) 338.1 ([M]

⁺

, 100), 310.1 (14), 309.1 (5), 197.1 (18), 141.1 (24), 115.0 (8); HRMS (EI) calcd for C

₂₅

₂₂

O [M]

⁺

338.1671, found 338.1669.

111

2-([1,1'-Biphenyl]-4-ylmethyl)-4-phenyl-4,5,6,7-tetrahydrobenzofuran (II-174e)

In General Procedure III, to a solution of AgOTf (3.9 mg, 0.015 mmol) in 3.0 mL of CH

₂

was added sequentially Ph

₃

PAuCl (7.4 mg, 0.015 mmol) and compound II-159e (0.109 g, 0.30 mmol) at room temperature under an atmosphere of nitrogen. The reaction mixture was stirred for 4 min until all II-159e was disappeared by TLC. The resulting dark brown solution was filtered through a bed of Celite, and the crude mixture was purified by flash column chromatography over silica gel (hexanes) to give II-174e (0.072 g, 0.20 mmol, 66%, R

_f

= 0.53 in 10% ethyl acetate/hexanes) as a pale yellow solid: mp 105‒106 ℃;

¹

H NMR (400 MHz, CDCl

₃

) δ 7.57 (d, J = 7.2 Hz, 2H), 7.52 (d,

J = 8.2 Hz, 2H), 7.42 (t, J = 7.6 Hz, 2H), 7.35‒7.26 (m, 5H), 7.23‒7.18 (m, 1H),

7.17 (d, J = 7.2 Hz, 2H), 5.68 (s, 1H), 3.94 (s, 2H), 3.83 (dd, J = 7.4, 5.7 Hz, 1H), 2.71‒2.58 (m, 2H), 2.08 (dddd, J = 12.8, 7.4, 5.3, 2.3 Hz, 1H), 1.97‒1.88 (m, 1H), 1.83‒1.72 (m, 1H), 1.65 (dddd, J = 17.8, 12.8, 10.2, 2.5 Hz, 1H);

¹³

C NMR (100 MHz, CDCl

₃

) δ 152.2, 150.6, 145.7, 141.0, 139.4, 137.6, 129.1 (2C), 128.7 (2C), 128.2 (2C), 128.0 (2C), 127.2 (2C), 127.1, 127.0 (2C), 126.1, 120.1, 107.0, 40.2, 34.4, 33.7, 23.1, 21.5; IR (CH

₂

) 2932, 2855, 1680, 1602, 1573, 1488, 1453, 1224, 848, 757, 699 cm

^‒1

; MS (EI, 70 eV) m/e (%) 364.2 ([M]

⁺

, 100), 336.1 (13), 335.1 (6), 214.1 (5), 197.1 (18), 167.1 (29), 152.1 (11), 141.1 (8); HRMS (EI) calcd for C

₂₇

₂₄

O [M]

⁺

364.1827, found 364.1820.

112

2-(4-Methoxybenzyl)-4-phenyl-4,5,6,7-tetrahydrobenzofuran (II-174f)

In General Procedure III, to a solution of AgOTf (3.9 mg, 0.015 mmol) in 3.0 mL of CH

₂

was added sequentially Ph

₃

PAuCl (7.4 mg, 0.015 mmol) and compound II-159f (0.096 g, 0.30 mmol) at room temperature under an atmosphere of nitrogen. The reaction mixture was stirred for 20 min until all II-159f was disappeared by TLC. The resulting dark brown solution was filtered through a bed of Celite, and the crude mixture was purified by flash column chromatography over silica gel (ethyl acetate/hexanes 1:50) to give II-174f (0.026 g, 0.08 mmol, 27%, R

_f

= 0.48 in 10% ethyl acetate/hexanes) as a yellow brown oil:

¹

H NMR (400 MHz, CDCl

₃

) δ 7.28 (t, J = 7.1 Hz, 2H), 7.19 (tt, J = 7.3, 2.0 Hz, 1H), 7.15 (d, J = 8.7 Hz, 2H), 7.15 (d, J = 9.0 Hz, 2H), 6.83 (dt, J = 9.2, 2.4 Hz, 2H), 5.59 (s, 1H), 3.83 (s, 2H), 3.81 (dd, J = 7.7, 5.9 Hz, 1H), 3.78 (s, 3H), 2.69‒2.56 (m, 2H), 2.07 (dddd, J = 12.8, 7.5, 5.3, 2.3 Hz, 1H), 1.96‒1.87 (m, 1H), 1.81‒1.70 (m, 1H), 1.64 (dddd, J = 17.9, 12.9, 10.3, 2.5 Hz 1H);

¹³

C NMR (100 MHz, CDCl

₃

) δ 158.2, 152.9, 150.4, 145.8, 130.6, 129.7 (2C), 128.2 (2C), 128.0 (2C), 126.1, 120.0, 113.9 (2C), 106.7, 55.3, 40.2, 33.9, 33.7, 23.1, 21.5; IR (CH

₂

) 2926, 2855, 1612, 1512, 1455, 1247, 807, 757, 701 cm

^‒1

; MS (EI, 70 eV) m/e (%) 318.1 ([M]

⁺

, 100), 290.1 (13), 287.1 (7), 197.1 (22), 169.1 (9), 121.1 (17); HRMS (EI) calcd for C

₂₂

₂

[M]

⁺

318.1620, found 318.1625.

113

2-Benzyl-4-methyl-4,5,6,7-tetrahydrobenzofuran (II-174g)

In General Procedure III, to a solution of AgOTf (3.9 mg, 0.015 mmol) in 3.0 mL of CH

₂

was added sequentiallyPh

₃

PAuCl (7.4 mg, 0.015 mmol) and compound II-159g (0.068 g, 0.30 mmol) at room temperature under an atmosphere of nitrogen. The reaction mixture was stirred for 60 min until all

In General Procedure III, to a solution of AgOTf (3.9 mg, 0.015 mmol) in 3.0 mL of CH

₂

was added sequentiallyPh

₃

PAuCl (7.4 mg, 0.015 mmol) and compound II-159g (0.068 g, 0.30 mmol) at room temperature under an atmosphere of nitrogen. The reaction mixture was stirred for 60 min until all

在文檔中金（I）催化1-芳香基-2-(3-芳香基丙炔基)環己-2-烯-1-醇的分子內環化反應：四氫苯并[b]呋喃衍生物的合成 (頁 81-148)

Gold(I)-Catalyzed Synthesis of Tetrahydrobenzo[b]furan Derivatives .1 Experimental

第三章 實驗部分

3.2 Gold(I)-Catalyzed Synthesis of Tetrahydrobenzo[b]furan Derivatives .1 Experimental

T

(aq)

f

1

3

68

2

4

3(aq)

2

2

4

f

1

3

13

3

69

3(aq)

4

f

1

3

13

3

70

1

3

3

3

4

4

(aq)

2

2

4

f = 0.28 in 10% ethyl acetate/hexanes).

71

4

(aq)

4

f

2

2

2

72

f

73

3

3

4

f

1

3

J = 3.9, 2.2 Hz, 1H), 3.38 (q, J = 2.1 Hz, 2H), 2.51‒2.41 (m, 4H), 2.03 (quin, J

13

3

2

2

‒1

+

15

14

+

74

3

3

4

f

1

3

13

3

2

2

‒1

+

第三章實驗部分

_(aq)

_f

¹

₃

₂

₄

_3(aq)

₂

₂

₄

_f

¹

₃

¹³

₃

_3(aq)

₄

_f

¹

₃

¹³

₃

¹

₃

₃

₃

₄

₄

_(aq)

₂

₂

₄

_f = 0.28 in 10% ethyl acetate/hexanes).

₄

_(aq)

₄

_f

₂

₂

₂

_f

₃

₃

₄

_f

¹

₃

¹³

₃

₂

₂

^‒1

⁺

₁₅

₁₄

⁺

₃

₃

₄

_f

¹

₃

¹³

₃

₂

₂

^‒1

⁺

₁₆

₁₆

⁺

₃

₃

₄

_f

¹

₃

¹³

₃