S1

SUPPORTING INFORMATION

Regioselective synthesis of phenanthrenes and evaluation of their anti-oxidant based antiinflammatory potential Yogesh Kanekar, Khalander Basha, Sharad Duche, Rajan Gupte and Arnab Kapat* Reliance Life Sciences Pvt. Ltd., Dhirubhai Ambani Life Sciences Center, Thane Belapur Road, Rabale, Navi Mumbai 400 701, India

*Arnab.Kapat@ril.com
* Author for correspondence

Table of Contents 1. General procedure for preparing compounds: S2-S14 2. Selected H, C, MS and HPLC spectra of compounds: S15-S83
1 13

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1. General procedure for preparing compounds 1.1. 2-[(tert-Butyldimethylsilyl)oxy]-3-methoxybenzaldehyde (7) Diisopropylethyl amine (18.54 mL, 108.44 mmol) was added to a solution of o-Vanillin (6) (11 g, 72.30 mmol) in THF (100 mL) and stirred for 15 min under nitrogen. tert-butyldimethylsilyl chloride (11.47 g, 108.44 mmol) was added to this solution and stirred for 16 h (overnight) at RT. After monitoring the reaction mixture on TLC (Pet-ether : EtOAc 9:1), reaction was quenched by ice cold water (100 mL) and extracted with EtOAc (3 50 mL). Pooled organic layer was washed with water (2 50 mL), brine (25 mL), dried (Na2SO4) and evaporated under reduced pressure. The crude residue was chromatographed over silica gel (Pet-ether: EtOAc 95:5) to give 7 (20 g, 87.9%) as a yellow solid: mp 40-41 C; H NMR (400 MHz, CDCl3) 0.22 (s, 6H, Si(Me)2), 1.01 (s, 9H, C(Me)3), 3.84 (s, 3H, OMe), 6.96 (t, 1H, J = 8.0 Hz, Ar-H), 7.06 (d, 1H, J = 8.0 Hz, Ar-H), 7.39 (d, 1H, J = 8.0 Hz, Ar-H), 10.52 (s, 1H, CHO); EIMS m/z 267 (M+H) .
+ 1

1.2. 4-bromo-5-methylbenzene-1,3-diol (9) method b1: A solution of tetrabutylammonium tribromide (TBABr3) (34.94 g, 72.06 mmol) in dichloromethane : methanol (30 mL:20 mL) was added to a solution of orcinol monohydrate (8) (10 g, 70.35 mmol ) in dichloromethane : methanol (30 mL :20 mL) at 15-20 C over a period of 1.5 h. Reaction was monitored on TLC (DCM : acetone 9.8: 0.2), On completion (~2 h), water (100 mL) was added and layers were separated. The collected organic layer was repeatedly washed with 2.5% NaHCO3 (till aqueous layer neutral to litmus, 3 25 mL), water (25 mL), dried (Na2SO4) and evaporated under reduced pressure. The crude solid was chromatographed over silica gel (Pet-ether-DCM gradient) to give 9 (10 g, 70.1%) as an off white solid. The compound 9 was also prepared by using dioxane dibromide (147.32 g, 703.48 mmol) in diethyl ether (180 mL) instead of TBABr3 as the brominating reagent on 100 g scale (method b2: yield=102 g, 71.4%): mp 134-135 C (reported [20] mp 135 C); IR (KBr) max 3340, 2925, 1614, 1593, 1466, 1332 cm ; H NMR (400 MHz, CDCl3) 2.34 (s, 3H, Me), 4.76 (s, 1H, D2O-exch., OH), 5.60 (s, 1H, D2O-exch., OH), 6.36 (d, 1H, J = 2.4 Hz, Ar-H), 6.40 (d, 1H, J = 2.4 Hz, Ar-H); EIMS m/z 202.9 ([M( Br)]-H) , 200.9 ([M( Br)]-H) ; TLC (DCM : Acetone 9.8: 0.2) Rf 0.19; HPLC purity:100%, tR: 10.50 min (column-1, method-1).
81 + 79 + -1 1

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1.3. 4-bromo-3-methoxy-5-methylphenyl 4-methylbenzenesulfonate (11) p-Tosyl chloride (32.89 g, 172.50 mmol) was added to a mixture of dihydroxybenzene 9 (35.0 g, 172.50 mmol) and K2CO3 (71.52 g, 517.50 mmol) in acetone (2800 mL) and refluxed in a water bath for 24 h. After monitoring the reaction mixture on TLC (Pet-ether : EtOAc 8 : 2), cooled the reaction mixture to RT (25-30 C), Iodomethane (21.5 mL, 345 mmol) was added and continued to stir for next 24 h. After TLC monitoring, filtered off the precipitate and filtrate was concentrated under reduced pressure. Crude material was chromatographed over silica gel (Pet-ether : EtOAc 95 : 5) to give the title compound 11 (43.5 g, 68.0%) as a white solid: mp 73-75 C (reported [22] mp 72.9-74.6 C); IR (KBr) max 2972, 1604,1374, 1318 cm ; H NMR (400 MHz, CDCl3) 2.33 (s, 3H, Me), 2.46 (s, 3H, Me), 3.74 (s, 3H, OMe), 6.38 (d, 1H, J = 2.8 Hz, Ar-H), 6.52 (d, 1H, J = 2.8 Hz, Ar-H), 7.34 (d, 2H, J = 8.0 Hz, Ar-H), 7.74 (d, 2H, J = 8.0 Hz, Ar-H); EIMS m/z 373 ([M( Br)]+H) , 371([M( Br)]+H) ; HPLC purity:98.4%, tR: 34.7 min (column-1, method-1).
81 + 79 + -1 1

1.4. 4-bromo-3-methoxy-5-methylphenol (12) Ethanol (500 mL) was added to the above tosylate 11 (43.0 g, 115.9 mmol) and tosylate was dissolved by heating at 70 C to get a clear solution. Water (500 mL) was added to the solution, followed by KOH (9.73 g, 173.9 mmol) and refluxed the resulting solution for 3 h. Reaction mixture was monitored on TLC (Petether : EtOAc 8:2) and cooled the reaction mixture to RT. Evaporated the ethanol under reduced pressure, neutralized the aqueous layer using acetic acid and extracted with EtOAc (3 100 mL). Pooled EtOAc layer was washed with 1M NaHCO3 (2 50 mL), followed by water (2 50 mL), then brine (50 mL), dried (Na2SO4) and concentrated under reduced pressure. The title compound 12 was purified by silica gel column chromatography (Pet-ether : EtOAc 90 : 10) as white crystals (21 g, 83.5%): mp 120-121 C (reported [22] mp 119-121 C); IR (KBr) max 3279(OH), 1606, 1586, 1476, 1355 cm ; H NMR (400 MHz, CDCl3) 2.34 (s, 3H, Me), 3.85 (s, 3H, OMe), 4.73 (s, 1H, D2O-exch., OH), 6.31 (d, 1H, J = 2.8 Hz, Ar-H), 6.36 (d, 1H, J = 2.8 Hz, Ar-H); EIMS m/z 216.9 ([M( Br)]-H) , 214.9 ([M( Br)]-H) ; HPLC purity: 97.1%, tR: 23.8 min (column-1, method-1).
81 + 79 + -1 1

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1.5. 1-[(tert-butyldimethylsilyl)oxy]-4-bromo-3-methoxy-5-methylbenzene (13) Immidazole (0.345 g, 5.07 mmol) and tert-butyl dimethylsilyl chloride (TBDMSCl, 0.76 g, 5.07 mmol) were added to a solution of phenol 12 (1.0 g, 4.61 mmol) in DCM (10 mL) at 0-5 C and stirred for 2 h at RT. After TLC monitoring (TLC -1 Pet-ether) (TLC-2 Pet-ether : DCM 40 : 60), quenched the reaction by adding ice cold water (20 mL), organic layer was washed with water (2 10 mL), brine (10 mL), dried (Na2SO4), and concentrated under reduced pressure to get 13 (1.48 g, 96.7%) as colorless oil: H NMR (400 MHz, CDCl3) 0.19 (s, 6H, Si(Me)2), 0.99 (s, 9H, C(Me)3), 2.34 (s, 3H, Me), 3.83 (s, 3H, OMe), 6.26 (d, 1H, J = 2.8 Hz, Ar-H), 6.37 (d, 1H, J = 2.8 Hz, Ar-H); EIMS m/z 333 ([M( Br)]+H) , 331([M( Br)]+H) .
81 + 79 + 1

1.6. 1,5-dibromo-2-[(tert-butyldimethylsilyl)oxy]-4-methoxy-6-methylbenzene (15) Benzoyl peroxide (0.0732 g, 0.302 mmol) and N-bromosuccinamide (0.537 g, 3.02 mmol) were added to a solution of ether 13 (1.0 g, 3.02 mmol) in CCl4 (20 mL) and refluxed for 5 h. After TLC monitoring (Petether, re-developed 5 times), filtered off solid, filtrate was concentrated to crude mixture which was purified by si-gel column chromatography (Pet-ether) to get 15 (0.5 g) as an oil: H NMR (400 MHz, CDCl3) 0.26 (s, 6H, Si(Me)2), 1.05 (s, 9H, C(Me)3), 2.61 (s, 3H, Me), 3.82 (s, 3H, OMe), 6.38 (s, 1H, ArH); EIMS m/z 412 ([M( Br)]+H) , 410 ([M( Br)]+H) .
81 + 79 + 1

1.7. 1-(tert-butyldimethylsilyl)oxy-3-methoxy-5-methylbenzene (17) Immidazole (1.44g, 21.10 mmol) and TBDMSCl (2.33 g, 15.48 mmol) were added to a solution of orcinol monohydrate (8) (2.0 g, 14.07 mmol) in DCM (15 mL) at 0-5 C, and stirred for 3 h at RT. After TLC monitoring (Pet-ether : EtOAc 9 : 1), quenched the reaction by adding ice cold water (20 mL), worked up similar to 13 yielded syrup which was purified by si-gel column chromatography (Pet-ether) to get a clear oil (0.8 g) (disilyl ether), further elution yielded a colorless oil (16) (1.4 g) (monosilyl ether). The compound 16 (EIMS m/z 239 (M+H) ) was used for next reaction as described below. K2CO3 (1.62 g, 11.74 mmol), and Iodomethane (1.67 g, 11.74 mmol) were added to a solution of ether 16 (1.4 g, 5.87 mmol) in acetone (10 mL) and stirred at RT overnight. After TLC monitoring (Pet-ether : EtOAc 9 : 1), the solvent was evaporated under reduced pressure and the mixture was purified by si-gel column chromatography (Pet-ether) to give 17 as a colorless oil: H NMR (400 MHz, CDCl3) 0.19 (s, 6H,
1 +

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Si(Me)2), 1.02 (s, 9H, C(Me)3), 2.26 (s, 3H, Me), 3.74 (s, 3H, OMe), 6.20-6.40 (m, 3H, Ar-H); EIMS m/z 253 (M+H) .
+

1.8. 4-bromo-3-methoxy-5-methylphenyl acetate (18) Acetic anhydride (15 mL) and pyridine (12 mL) were added to the solution of bromo phenol 12 (20 g, 92.21 mmol) in DCM (50 mL) and stirred for 2 h at RT. After TLC monitoring (Pet-ether : EtOAc 8:2), reaction was quenched by adding ice-cold water (50 mL), organic layer was separated, washed with chilled 10% aq HCl (3 25 mL), followed by 10% NaHCO3 (25 mL), brine (25 mL), dried (Na2SO4) and concentrated under reduced pressure to yield 18 (23 g, 96.3%) as white solid: mp 84-85 C; IR (KBr) max 1752(CO) cm ; H NMR (400 MHz, CDCl3) 2.29 (s, 3H, OAc), 2.40 (s, 3H, Me), 3.87 (s, 3H, OMe), 6.52 (d, 1H, J = 2.8 Hz, Ar-H), 6.64 (d, 1H, J = 2.8 Hz, Ar-H); EIMS m/z 259 ([M( Br)]+H) , 261([M( Br)]+H) .
81 + 79 + -1 1

1.9. 4-bromo-3-(bromomethyl)-5-methoxyphenyl acetate (19) Benzoyl peroxide (0.11 g, 0.461 mmol) and NBS (0.82 g, 4.61 mmol) were added to a stirred solution of acetate 18 (1.0 g, 4.61 mmol) in CCl4 (20 mL) and refluxed for 4 h. After TLC monitoring (Pet-ether: DCM 7.5: 2.5), the reaction mixture was cooled to RT and filtered off the solid. Filtrate was concentrated under reduced pressure and the crude solid was purified by silica gel column chromatography (Pet-ether: EtOAc 98:2) to give 19 (0.8 g, 61.5%) as white flakes: mp 84-86 C; H NMR (400 MHz, CDCl3) 2.31 (s, 3H, OAc), 3.89 (s, 3H, OMe), 4.60 (s, 2H, benzylic CH2), 6.63 (d, 1H, J = 2.8 Hz, Ar-H), 6.89 (d, 1H, J = 2.8 Hz, Ar-H); EIMS m/z 340 ([M( Br)]+H) , 338 ([M( Br)]+H) ; HPLC purity: 79.0%, tR: 30.6 min (column-1, method-1).
81 + 79 + 1

1.10. 2-[2-(3-hydroxy-5-methoxyphenyl)ethyl]-6-methoxyphenol (24) mp 148-150 C; H NMR (400 MHz, CDCl3) 2.84 (m, 2H, CH2), 2.92 (m, 2H, CH2), 3.76 (s, 3H, OMe), 3.89 (s, 3H, OMe), 4.73 (br s, 1H, D2O exch., OH), 5.71 (br s, 1H, D2O exch., OH), 6.25 (m, 1H, Ar-H), 6.32 (m, 1H, Ar-H), 6.38 (m, 1H, Ar-H), 6.70-6.80 (m, 3H, Ar-H); EIMS m/z 275 (M+H) ; HPLC tR : 27.0 min (column-1, method-1).
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1.11. 4-bromo-3-(dibromomethyl)-5-methoxyphenyl acetate (25) Benzoyl peroxide (1.48 g, 6.126 mmol) and NBS (21.80 g, 122.52 mmol) were added to a stirred solution of acetate 18 (15.86 g, 61.26 mmol) in CCl4 (317 mL) and refluxed for 72 h. NBS was added (0.1 eq) after 24 h, and 48 h. After TLC monitoring (Pet-ether: DCM 7.5: 2.5), the reaction mixture was cooled to RT and filtered off the solid. Filtrate was concentrated under reduced pressure and crude solid was purified by silica gel column chromatography (Pet-ether : EtOAc 98:2) to get 25 (12.14 g, 62.1%) as white flakes: mp 96-98 C; H NMR (400 MHz, CDCl3) 2.33 (s, 3H, OAc), 3.89 (s, 3H, OMe), 6.66 (d, 1H, J = 2.4 Hz, Ar-H), 7.14 (s, 1H, CHBr2), 7.41 (d, 1H, J = 2.4 Hz, Ar-H); EIMS m/z 440.7 ([M( Br)]+Na) , 438.7 ([M( Br)]+Na) ; HPLC purity: 92.9%, tR: 33.1 min (column-1, method-1).
79 + 81 + 1

1.12. 2-bromo-5-hydroxy-3-methoxybenzaldehyde (26) The above acetate 25 (11.8 g, 28.32 mmol) in ethanol (60 mL) was heated to get a clear solution, to which was added ammonium formate (4.46 g, 70.79 mmol) followed by EtOH : Water (18 mL : 18 mL) and refluxed for 24 h. After TLC monitoring (Pet-ether : EtOAc 8:2), reaction mixture was cooled to RT, conc. HCl (1.0 mL) was added, and EtOH was evaporated under reduced pressure. The aqueous layer left was diluted with water (60 mL) and extracted with EtOAc (3 25 mL). Pooled EtOAc layer was washed with water (25 mL), dried (Na2SO4), concentrated under reduced pressure and the product was purified by silica gel column chromatography (Pet-ether: EtOAc 90:10) to get 26 (3.9 g, 59.6%) as white solid: mp 161-162 C; H NMR (400 MHz, CDCl3) 3.93 (s, 3H, OMe), 5.46 (s, 1H, D2O-exch., OH), 6.72 (d, 1H, J = 2.8 Hz, Ar-H), 7.02 (d, 1H, J = 2.8 Hz, Ar-H), 10.39 (s, 1H, CHO);
13 1

C NMR (100 MHz, CDCl3+

CD3SOCD3) 56.7 (OMe), 106.2, 106.6, 107.8, 134.8, 157.3, 158.2, 192.6 (CHO); EIMS m/z 230.9 ([M( Br)]-H) , 228.9 ([M( Br)]-H) .
81 + 79 +

1.13. 2-Bromo-5-[(tert-Butyldimethylsilyl)oxy]-3-methoxybenzaldehyde (27) Immidazole (0.44 g, 6.50 mmol), and TBDMSCl (0.98 g, 6.50 mmol) were added to a clear solution of phenol 26 (1.0 g, 4.33 mmol) in DCM (20 mL)-DMF (1.0 mL) at 0-5 C and stirred for 2 h at RT. After TLC monitoring (Pet-ether: EtOAc 8:2), followed by worked up similar to compound 13 yielded 27 (1.43 g, 95.8%) as colorless oil: H NMR (400 MHz, CDCl3) 0.23 (s, 6H, Si(Me)2), 1.00 (s, 9H, C(Me)3), 3.91 (s,
1

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3H, OMe), 6.64 (d, 1H, J = 2.8 Hz, Ar-H), 6.99 (d, 1H, J = 2.8 Hz, Ar-H), 10.39 (s, 1H, CHO); EIMS m/z 347 ([M( Br)]+H) , 345 ([M( Br)]+H) .
81 + 79 +

1.14. (2-[(tert-Butyldimethylsilyl)oxy]-3-methoxyphenyl)methanol (28) NaBH4 (0.41 g, 10.90 mmol) was added to a solution of aldehyde 7 (5.8 g, 21.80 mmol) in Isopropanol (IPA) (70 mL) and refluxed for 2 h. After TLC monitoring (Pet-ether: EtOAc 9:1), cooled reaction mixture was carefully quenched by adding 10% aq HCl and extracted with EtOAc (3 50 mL). Combined EtOAc layer was washed with 2% aq. NaHCO3 (25 mL), water (25 mL), dried (Na2SO4), concentrated under reduced pressure to crude syrup which was purified by si-gel column chromatography (Pet-ether : EtOAc 95:5) to get 28 (2.83 g, 48.4%) as an oil: H NMR (400 MHz, CDCl3) 0.14 (s, 6H, Si(Me)2), 0.95 (s, 9H, C(Me)3), 3.89 (s, 3H, OMe), 4.86 (s, 2H, benzyl CH2), 6.80-6.85 (m, 3H, Ar-H), 6.91 (s, 1H, D2O-exch., OH); EIMS m/z 291 (M+Na) .
+ 1

1.15. 5-(benzyloxy)-2-bromo-3-methoxybenzaldehyde (31) K2CO3 (16.59 g, 120.05 mmol), and benzyl bromide (8.8 mL, 72.03 mmol) were added to the solution of hydroxybenzaldehyde 26 (13.86 g, 60 mmol) in DMF (70 mL) and stirred at RT overnight. After TLC monitoring (Pet-ether : EtOAc 9:1), toluene (50 mL) was added to the reaction mixture, followed by water (210 mL) and stirred for 10 min. Aqueous layer was extracted with toluene (2 50 mL), combined toluene layer was washed with water (50 mL), dried (Na2SO4), and concentrated under reduced pressure. The product was dissolved in DCM (50 mL), to this clear solution was added n-Hexane (450 mL) and stirred for 4 h. White solid (31) (17.3 g, 89.8%) obtained was collected by filtration and dried: mp 93-94 C; H NMR (400 MHz, CDCl3) 3.90 (s, 3H, OMe), 5.09 (s, 2H, benzylic CH2), 6.80 (d, 1H, J = 2.8 Hz, Ar-H), 7.14 (d, 1H, J = 2.8 Hz, Ar-H), 7.30-7.50 (m, 5H, Ar-H), 10.42 (s, 1H, CHO);
13 1

C NMR (100 MHz, CDCl3)

56.7 (OMe), 70.8 (CH2), 104.6, 104.7, 106.7, 109.6, 127.9, 128.0, 128.6, 128.9, 134.9, 136.2, 157.4, 159.3, 192.3 (CHO); EIMS m/z 323 ([M( (column-1, method-1).
81

Br)]+H) , 321 ([M(

79

Br)]+H) ; HPLC purity: 96.9%, tR: 33.6 min

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1.16. 2-(benzyloxy)-3-methoxybenzaldehyde (32) K2CO3 (90.84 g, 657.25 mmol) and benzyl bromide (48.2 mL, 394.35 mmol) were added to a solution of o-Vanillin (6) (50 g, 328.62 mmol) in DMF (250 mL) and stirred at RT overnight. After TLC monitoring (Pet-ether : EtOAc 9:1), toluene (100 mL) was added to the reaction mixture, followed by water (750 mL) and stirred for 10 min. Aqueous layer was re-extracted with toluene (2 100 mL), combined toluene layer was washed with water (100 mL), dried (Na2SO4) and concentrated under reduced pressure. The product was purified by silica gel column chromatography (Pet-ether : EtOAc 90:10) to get 32 (79.0 g, 99.2%) as white solid: mp 45-46 C (reported [1] mp 45-46 C); IR (KBr) max 1696 (CO) cm ; H NMR (400 MHz, CDCl3) 3.96 (s, 3H, OMe), 5.19 (s, 2H, benzylic CH2), 7.10-7.20 (m, 2H, Ar-H), 7.30-7.41 (m, 6H, Ar-H), 10.24 (s, 1H, CHO); EIMS m/z 243 (M+H) ; HPLC purity: 100%, tR: 31.0 min (column-1, method-1).
+ -1 1

1.17. [2-(benzyloxy)-3-methoxyphenyl]methanol (33) NaBH4 (6.22 g, 164.47 mmol) was added to a solution of benzaldehyde 32 (79 g, 326.45 mmol) in isopropanol (500 mL) and refluxed for 2 h. After TLC monitoring (Pet-ether: EtOAc 9:1), cooled the reaction mixture to RT and carefully added 10% aq. HCl till pH became 4-5. The solution was extracted with EtOAc (3 100 mL), combined organic layer was washed with 2% NaHCO3 (2 100 mL), then water (100 mL), dried (Na2SO4) and concentrated to give the benzyl alcohol (33) (74.6 g, 93.7%) as white solid: mp 51-53 C; IR (KBr) max 3363 (OH) cm ; H NMR (400 MHz, CDCl3) 1.97 (br s, 1H, D2O-exch., OH), 3.92 (s, 3H, OMe), 4.55 (s, 2H, benzylic CH2), 5.10 (s, 2H, benzylic CH2), 6.90-6.94 (m, 2H, Ar-H), 7.07 (t, 1H, J = 8.4 Hz, Ar-H), 7.30-7.50 (m, 5H, Ar-H); EIMS m/z 245 (M+H) ; HPLC purity: 100%, tR: 26.4 min (column-1, method-1). 1.18. 2-(benzyloxy)-1-(bromomethyl)-3-methoxybenzene (34) A solution of PBr3 (5.78 mL, 61.48 mmol) in DCM (80 mL) was added drop wise to the chilled solution of benzyl alcohol 33 (30 g, 122.96 mmol) in DCM (300 mL) over a period of an hour. After TLC monitoring (Pet-ether: EtOAc 9:1), slowly quenched the reaction by adding ice cold water (100 mL). The organic layer was then washed with 2% NaHCO3 (till aq. layer neutral to litmus), water (100 mL), dried (Na2SO4) and concentrated under reduced pressure. Crude solid was purified by silica gel column chromatography (Pet-ether: EtOAc 90:10) to get benzyl bromide (34) (35.91 g, 95.2%) as colorless oil: H NMR (400 MHz,
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CDCl3) 3.90 (s, 3H, OMe), 4.51 (s, 2H, benzylic CH2), 5.16 (s, 2H, benzylic CH2), 6.90-6.99 (m, 2H, ArH), 7.06 (t, 1H, J=8.0 Hz, Ar-H) 7.34-7.54 (m, 5H, Ar-H); EIMS m/z 309 ([M( Br)]+H) , 307 ([M( Br)]+H) ; HPLC purity: 86.6%, tR: 34.6 min (column-1, method-1).
81 + 79 +

1.19. (2-benzyloxy-3-methoxybenzyl) triphenyl phosphonium bromide (35) Triphenyl phosphine (36.83 g, 140.41 mmol) was added to the solution of benzyl bromide (34) (35.0 g, 114 mmol) in toluene (350 mL) and refluxed for 4 h. After TLC monitoring (DCM : MeOH 9.5 : 0.5), cooled the mixture to RT, precipitated solid was collected by filtration, washed with n-Hexane (500 mL), and dried in vacuum to get the compound (35) (58.77 g, 90.54%): mp 221-222 C; H NMR (400 MHz, CD3OD) 3.84 (s, 3H, OMe), 4.54 (d, 2H,J = 14.4 Hz, benzylic CH2), 4.87 (s, 2H, benzylic CH2), 6.56 (dd, 1H, J = 7.6 Hz, J = 2.4 Hz, Ar-H), 6.94 (t, 1H, J = 7.6 Hz, Ar-H), 7.07 (dd, 1H, J = 7.6 Hz, J = 2.4 Hz, ArH), 7.22-7.28 (m, 2H, Ar-H), 7.36-7.46 (m, 9H, Ar-H), 7.58-7.66 (m, 6H, Ar-H), 7.80-7.88 (m, 3H, Ar-H).
1

1.20. 1-benzyloxy-4-bromo-3-[(Z)-2-(2-benzyloxy-3-methoxyphenyl)-ethenyl]-5-methoxybenzene (36) A solution of bromoaldehyde 31 (8.4 g, 26.17 mmol) in DMF (30 mL) was added to a suspension of phosponium salt 35 (14.89 g, 26.17 mmol) in DMF (120 mL) under nitrogen at RT. The reaction mixture was then heated to 100-110 C and to the resulting clear solution was added freshly prepared lithium methoxide (1.99 g, 52.32 mmol) in methanol (60 mL) dropwise over 30 min. Continued heating and stirring for additional 30 min, after TLC monitoring (Pet-ether: EtOAc 9 : 1), cooled the reaction mixture to RT, poured into water (500 mL) and extracted with DCM (3 50 mL). Pooled organic layer was washed with water (50 mL), dried (Na2SO4) and concentrated under reduced pressure. Crude product was purified by silica gel column chromatography (Pet-ether : EtOAc 90 : 10) to get 36 (a mixture of atropisomers, a and b) (8.5 g, mixture-1+ mixture-2, 61.7%) as white solid: H NMR (400 MHz, CDCl3) 3.87 (s, 3H, OMe-a), 3.88 (s, 3H, OMe-b), 3.89 (s, 3H, OMe-a), 3.92 (s, 3H, OMe-b), 4.65 (s, 2H, benzylic CH2-a), 5.00 (s, 2H, benzylic CH2-b), 5.03 (s, 2H, benzylic CH2-a), 5.04 (s, 2H, benzylic CH2-b), 6.33 (d, 1H, J = 2.8 Hz, Ar-H, a), 6.43 (d, 1H, J = 2.8 Hz, Ar-H, a), 6.49 (d, 1H, J = 2.8 Hz, Ar-H, b) 6.60-7.60 (m, 31H, Ar-H, a (15H) + b (16H)); EIMS m/z 555 ([M( Br)]+Na) , 553 ([M( Br)]+Na) ; HPLC tR 6.3 min (a) and 6.9 min (b).
81 + 79 + 1

S10
1.21. 1,7-dibenzyloxy-2,5-dimethoxy-phenanthrene (37) A solution of AIBN (0.5 g, 3.01 mmol) and Bu3SnH (4.86 mL, 18.08 mmol) in toluene (50 mL) was added dropwise to the solution of stilbene 36 (4.0 g, 7.53 mmol) in toluene (100 mL) at RT and the resulting mixture was refluxed for 2 h. After HPLC monitoring (both mixture-1 and mixture-2 yielded 37 as evident by disappearance of tR 6.3 and 6.9 min peaks and appearance of product peak at tR 6.35 min), cooled reaction mixture was poured into water (100 mL) and extracted with DCM (3 200 mL). The combined organic layer was washed with saturated aqueous KF solution (100 mL), water (100 mL), dried (Na2SO4) and concentrated under reduced pressure. NaOAc (1.24 g, 15.07 mmol) and 4-

methylbenzenesulfonohydrazide (7.01 g, 37.67 mmol) were added to a solution of crude reaction mixture (3.5 g) in EtOH (50 mL) under nitrogen and refluxed for 2 h. After HPLC monitoring of the reaction mixture, water (50 mL) was added to the cooled reaction mixture, EtOH was evaporated under reduced pressure and the suspension left was extracted with DCM (3 25 mL). Pooled organic layer was washed with saturated aqueous NaHCO3 (25 mL), water (25 mL), dried (Na2SO4) and concentrated under reduced pressure. Crude product was purified by silica gel column chromatography (Pet-ether : EtOAc 90:10), to get phenanthrene (37) (2.25 g, 66.6%) as white solid: mp 116-118 C; H NMR (400 MHz, CDCl3) 4.03 (s, 3H, OMe), 4.09 (s, 3H, OMe), 5.17 (s, 2H, benzylic CH2), 5.21 (s, 2H, benzylic CH2), 6.85 (d, 1H, J = 2.4 Hz, Ar-H), 6.97 (d, 1H, J = 2.4 Hz, Ar-H), 7.30-7.60 (m, 12H, Ar-H), 8.11 (d, 1H, J = 9.2 Hz, Ar-H), 9.32 (d, 1H, J = 9.2 Hz, Ar-H); EIMS m/z 451 (M+H) ; HPLC tR: 6.35 min (column -2, method-2).
+ 1

1.22. 1-(2-benzyloxy-3-methoxyphenyl)-2-(2-bromo-5-benzyloxy-3-methoxyphenyl)ethane (38) NaOAc (0.618 g, 7.53 mmol) and 4-methylbenzenesulfonohydrazide (0.56 g, 3.01 mmol) were added to the solution of stilbene 36 (0.8 g, 1.51 mmol) in EtOH (20 mL) under nitrogen and refluxed for 2 h. After TLC (Pet-ether : EtOAc 9:1) and HPLC monitoring, water (10 mL) was added to the cooled reaction mixture, EtOH was evaporated under reduced pressure and extracted the suspension with EtOAc (3 25 mL). Pooled organic layer was washed with saturated aqueous NaHCO3 (25 mL), water (25 mL), dried (Na2SO4) and concentrated under reduced pressure. Crude product was purified by silica gel column chromatography (Pet-ether : EtOAc 90:10), to get 38 (0.5 g, 62.3%) as white solid: mp 95-96 C; H NMR
1

S11
(400 MHz, CDCl3) 2.88 (m, 2H, CH2), 2.96 (m, 2H, CH2), 3.83 (s, 3H, OMe), 3.89 (s, 3H, OMe), 4.86 (s, 2H, benzylic CH2), 5.01 (s, 2H, benzylic CH2), 6.33 (d, 1H, J = 1.2 Hz, Ar-H), 6.41 (d, 1H, J = 1.2 Hz, ArH), 6.83 (m, 2H, Ar-H), 7.01 (t, 1H, J = 8.0 Hz, Ar-H), 7.24 - 7.52 (m, 10H, Ar-H); EIMS m/z 534.9 ([M(
81

Br)]+H) , 532.9 ([M(

79

Br)]+H) ; HPLC tR: 7.2 min (column -2, method-2).

1.23. 9,10-Dihydro-1,7-dibenzyloxy-2,5-dimethoxy-phenanthrene (39) mp 116-118 C; H NMR (400 MHz, CDCl3) 2.60 (m, 2H, CH2), 2.74 (m, 2H, CH2), 3.86 (s, 3H, OMe), 3.91 (s, 3H, OMe), 4.98 (s, 2H, benzylic CH2), 5.08 (s, 2H, benzylic CH2), 6.48 (d, 1H, J = 2.4 Hz, Ar-H), 6.53 (d, 1H, J = 2.4 Hz, Ar-H), 6.85 (d, 1H, J = 8.8 Hz, Ar-H), 7.28 - 7.50 (m, 10H, Ar-H), 7.99 (d, 1H, J = 8.8 Hz, Ar-H); EIMS m/z 453 (M+H) ; HPLC tR: 6.08 min (column-2, method-2).
+ 1

1.24. 1-(2-benzyloxy-3-methoxyphenyl)-2-(3-benzyloxy-5-methoxyphenyl)ethane (39a) mp 96-98 C; H NMR (400 MHz, CDCl3) 2.78 (m, 2H, CH2), 2.86 (m, 2H, CH2), 3.71 (s, 3H, OMe), 3.89 (s, 3H, OMe), 4.94 (s, 2H, benzylic CH2), 4.98 (s, 2H, benzylic CH2), 6.30 (s, 1H, Ar-H), 6.37 (m, 2H, ArH), 6.78 (dd, 1H, J=8.0 Hz, J=1.2 Hz, Ar-H), 6.87 (dd, 1H, J=8.0 Hz, J=1.2 Hz, Ar-H), 7.00 (t, 1H, J=8.0 Hz, Ar-H), 7.26-7.52 (m, 10H, Ar-H); EIMS m/z 455 (M+H) ; HPLC tR : 6.15 min (column-2, method-2).
+ 1

1.25. 2-Benzyloxy-6-bromo-3-methoxybenzaldehyde (41) Yellow solid; Yield = 54.9% from 6; mp 49-50 C (reported [45] mp 49 C); IR (KBr) max 1700(CO) cm ;
1 -1

H NMR (400 MHz, CDCl3) 3.91 (s, 3H, OMe), 5.11 (s, 2H, benzylic CH2), 6.98 (d, 1H, J=8.8 Hz, Ar-H),
81 + 79 +

7.33-7.46 (m, 6H, Ar-H), 10.24 (s, 1H, CHO); EIMS m/z 345 ([M( Br)]+Na) , 343 ([M( Br)]+Na) .

1.26. 3-(benzyloxy)-2-bromo-5-methoxybenzaldehyde (42) White solid; Yield = 35%; mp 93-94 C (reported [47] mp 93-94 C); IR (KBr) max 1696(CO) cm ; H NMR (400 MHz, CDCl3) 3.82 (s, 3H, OMe), 5.17(s, 2H, benzylic CH2), 6.76 & 7.06 (d, 2H, AB, J=2.8 Hz, ArH), 7.30-7.50 (m, 5H, Ar-H), 10.43 (s, 1H, CHO); EIMS m/z 323 ([M( Br)]+H) , 321 ([M( Br)]+H) .
81 + 79 + -1 1

S12
1.27. 3,6-dibenzyloxy-4,4-dimethoxybiphenyl-2,2-dicarbaldehyde (43b) A three necked flask previously flushed with argon was charged with bis(pinacolato diboron) (3.61 g, 14.21 mmol), Potassium acetate (3.60 g, 36.71 mmol), PdCl2 (dppf)CH2Cl2 (0.29 g, 0.35 mmol), dimethyl sulphoxide (35 mL) and stirred for 5-10 min. To this was slowly added a solution of 42 (3.8 g, 11.84 mmol) in dimethyl sulphoxide (15 mL) over a period of 10-15 min. The resulting mixture was heated gently for two hours at 80 C. The mixture was then cooled to room temperature and Potassium carbonate (5.24 g, 37.9 mmol), PdCl2(dppf)CH2Cl2 (1.16 g,1.42 mmol) and a solution of 41 (4.55 g, 14.17 mmol) in 100 mL dimethyl sulphoxide (90 mL + 10 mL rinse) were added to it. The resulting suspension was heated gently for 2 h at 80 C. The reaction was quenched by adding water (200 mL), and the solution was extracted with EtOAc (3 50 mL). The pooled organic layer was washed with brine (50 mL), dried (Na2SO4) and concentrated under reduced pressure to a syrup which was subjected to silica gel column chromatography (pet ether-EtOAc gradient) to afford 43a (0.32 g). Further elution afforded 43b (cross coupled) (2.0 g), followed by 43c (0.05 g) as semi solid materials which solidified on standing for 24 h at room temperature. 3,6-dibenzyloxy-4,4-dimethoxybiphenyl-2,2-dicarbaldehyde (43b): mp 78-85 C; H NMR (400 MHz, CDCl3) 3.79 (s, 3H, OMe), 3.90 (s, 3H, OMe), 4.86 (s, 2H, CH2), 5.1 (m, 2H, CH2), 6.62-7.40 (m, 14H, Ar-H), 9.55 (s, 1H, CHO), 10.10 (s, 1H, CHO); EIMS m/z 483 (M+H) .
+ 1

1.28. 6,6-dibenzyloxy-4,4-dimethoxybiphenyl-2,2-dicarbaldehyde (43a) mp 90-95 C; H NMR (400 MHz, CDCl3) 3.81 (s, 6H, two OMe), 4.91 (m, 4H, two CH2), 6.73 (d, 2H, J = 2.4 Hz, Ar-H), 7.01 (m, 4H, Ar-H), 7.11(d, 2H, J = 2.4 Hz, Ar-H), 7.15-7.20 (m, 6H, Ar-H), 9.64 (s, 2H, two CHO); EIMS m/z 483 (M+H) .
+ 1

1.29. 3,3-dibenzyloxy-4,4-dimethoxybiphenyl-2,2-dicarbaldehyde (43c)

mp 68-70 C; 1H NMR (400 MHz, CDCl3) 3.87(s, 6H, two OMe), 5.10 (m, 4H, two CH2), 6.75 (d, 2H, J =
8.4 Hz, Ar-H), 7.04 (d, 2H, J = 8.4 Hz, Ar-H), 7.20-7.40 (m, 10H, ArH), 10.03 (s, 2H, two CHO); EIMS m/z 483 (M+H) .
+

S13
1.30. 3,6-dibenzyloxy-4,4-dimethoxy-2,2-divinyl-biphenyl (44) n-Butyl Lithium (0.74 mL, 1.6 M in hexanes, 1.18 mmol) was dropwise added to a suspension of methyltriphenylphosphonium bromide (0.37 g, 1.037 mmol) in anhydrous THF (11.6 mL) at 0 C. The solution was warmed to room temperature, stirred for 3 h, then cooled to 78 C and a solution of 43b (0.1g, 0.207 mmol) in anhydrous THF (10.4 mL) was added dropwise to this solution over a period of 10 min. The resultant mixture was stirred for 10 min, then warmed to room temperature and stirred overnight. The reaction was quenched by the addition of 1N hydrochloric acid (pH changed to 4-5), then diluted with brine (20 mL) and the mixture was extracted with EtOAc (3 20 mL). The pooled organic layer was dried (Na2SO4), concentrated under reduced pressure and the product was purified by silica gel column chromatography (pet-ether-EtOAc gradient) to afford 44 (0.058 g) as colorless oil: H NMR (400 MHz, CDCl3) 3.77 (s, 3H, OMe), 3.83 (s, 3H, OMe), 4.89 (s, 4H, two benzylic CH2), 4.93 (m, 1H, J = 11.2 Hz), 5.03 (m, 1H, J = 11.2 Hz), 5.37 (d, 1H, J = 18.0 Hz), 5.52 (d, 1H, J = 18.0 Hz), 6.20-6.50 (m, 3H), 6.707.50 (m, 13H); EIMS m/z 479 (M+H) .
+ 1

1.31.1-Benzyloxy-2-bromo-3-[(Z)-2-(2-benzyloxy-3-methoxyphenyl)-vinyl]-5-methoxy-benzene (46) Bromoaldehyde 42 (4.9 g, 15.28 mmol) was added to a suspension of phosphonium salt 35 (8.7 g, 15.28 mmol) in DMF (80 mL) under nitrogen at room temperature. The reaction mixture was heated to 100-110 C and to the resulting clear solution was added freshly prepared lithium methoxide (1.16 g, 30.56 mmol) in methanol (35 mL) drop wise over 30 min. Continued heating and stirring for additional 30 min, and after TLC monitoring (Pet-ether : EtOAc 9:1), cooled the reaction mixture to room temperature, then poured into water (500 mL) and extracted with DCM (3 50 mL). Pooled organic layer was washed with water (50 mL), dried (Na2SO4) and concentrated under reduced pressure. Crude product was purified by silica gel column chromatography (Pet-ether : EtOAc 90:10) to get 46 (4.7 g, 58%) as a syrup (a mixture of atropisomers, a and b) (10:3): mp 108-110 C; H NMR (400 MHz, CDCl3) 3.43 (s, 3H, OMe-a), 3.74 (s, 3H, OMe-b), 3.86 (s, 3H, OMe-a), 3.91 (s, 3H, OMe-b), 5.03 (s, 2H, benzylic CH2-b), 5.06 (s, 2H, benzylic CH2-a), 5.12 (s, 2H, benzylic CH2-a), 5.13 (s, 2H, benzylic CH2-b), 6.26 (d, 1H, J = 2.8 Hz, Ar-H-a), 6.38 (d, 1H, J = 2.8 Hz, Ar-H-a), 6.46 (d, 1H, J = 2.8 Hz, Ar-H-b), 6.63 (m, 1H, H-a), 6.69 (d, 1H, J = 12 Hz, olefin H-a), 6.70 (d, 1H, J = 2.8 Hz, Ar-H-b), 6.77-6.79 (m, 2H, Ar-H-a), 6.85 (d, 1H, J =12 Hz, olefin H-a),
1

S14
6.90 (m, 1H, Ar-H-b), 7.10 (m, 1H, Ar-H-b), 7.28-7.54 (m, 23H, Ar-H-a (10H) and Ar-H-b (13H)); EIMS m/z 533 ([M( Br)]+H) , 531([M( Br)]+H) ; HPLC tR: a: 6.79 min, b: 7.34 min (column -2, method-2).
81 + 79 +

1.32. 1,5-Dibenzyloxy-2,7-dimethoxy-phenanthrene (45) A solution of AIBN (0.5 g, 3.01 mmol) and Bu3SnH (4.86 mL, 18.08 mmol) in toluene (50 mL) was added dropwise to a solution of stilbene 46 (4.7 g, 8.85 mmol) in toluene (100 mL) and refluxed for 2 h. After HPLC monitoring, the reaction mixture was cooled, poured into water (100 mL) and extracted with DCM (3 20 mL). The pooled organic layer was washed with saturated aqueous KF solution (50 mL), water (50 mL), dried (Na2SO4) and concentrated under reduced pressure to syrup. NaOAc (1.24 g, 15.07 mmol) and p-TsNHNH2 (7.01 g, 37.67 mmol) were added to a solution of this syrup (3.5 g) in EtOH (50 mL) under nitrogen and refluxed for 2 h. After TLC and HPLC monitoring, water (50 mL) was added to the cooled reaction mixture, EtOH was then evaporated under reduced pressure and the suspension was extracted with DCM (3 25 mL). Pooled organic layer was washed with saturated aqueous NaHCO3 (25 mL), water (25 mL), dried (Na2SO4) and concentrated under reduced pressure. Crude product obtained was purified by silica gel column chromatography (Pet-ether : EtOAc 90:10), to get 45 (2.64 g, 66.3%) as white solid: mp 148-150 C; H NMR (400 MHz, CDCl3) 3.91 (s, 3H, OMe), 3.98 (s, 3H, OMe), 5.15 (s, 2H, benzylic CH2), 5.32 (s, 2H, benzylic CH2), 6.83 (d, 1H, J = 2.8 Hz, Ar-H), 6.88 (d, 1H, J = 2.8 Hz, ArH), 7.20-7.60 (m, 12H, Ar-H), 8.11 (d, 1H, J = 9.2 Hz, Ar-H), 9.36 (d, 1H, J = 9.2 Hz, Ar-H); EIMS m/z 451 (M+H) ; HPLC purity: 87%, tR: 5.96 min (column -2, method-2).
+ 1

References

[1] A. S. Cotterill, P. Hartopp, G. B. Jones, C. J. Moody, C. L. Norton, N. O'Sullivan, E. Swann, Tetrahedron, 50 (1994) 7857-7874.

S15 Table of Contents

Compound Compound 7 Compound 7 Compound 9 Compound 9 Compound 11 Compound 11 Compound 12 Compound 12 Compound 13 Compound 15 C Compound d 17 Compound 18 Compound 19 Index
1H 13C 1H 13C 1H 13C 1H 13C 1H 1H 1H 1H

S15-S16 CDCl3 CDCl3 CDCl3 CDCl3 CDCl3 CDCl3 CDCl3 CDCl3 CDCl3 CDCl3 CDCl3 CDCl3 CDCl3 S17 S18 S19 S20 S21 S22 S23 S24 S25 S26 S27 S28 S29

Compound 26 Compound 26 Compound 27 Compound 28 Compound 31 Compound 31 Compound 32 Compound 32 Compound 33 Compound 33 Compound 34 C Compound d 35 Compound 35 Compound 36mixture-1 Compound 36mixture-1 Compound 36mixture-2 Compound 36mixture-2

1H 13C 1H 1H 1H 13C 1H 13C 1H 13C 1H 1H 13C

NMR NMR NMR NMR NMR NMR NMR NMR NMR NMR NMR NMR NMR NMR

CDCl3 CDCl3 CDCl3 CDCl3 CDCl3 CDCl3 CDCl3 CDCl3 CDCl3 CDCl3 CDCl3 CD3OD CD3OD CDCl3 Column2, method2

S33 S34 S35 S36 S37 S38 S39 S40 S41 S42 S43 S44 S45 S46

NMR NMR NMR NMR NMR NMR NMR NMR NMR NMR NMR NMR NMR

1H

1H

Compound 24

1H

NMR

CDCl3

S30

HPLC

S47

Compound 24

13C

NMR

CDCl3

S31

1H

NMR

CDCl3

S48

Compound 25

1H

NMR

CDCl3

S32

13C

NMR

CDCl3

S49

S16 Table of Contents

Compound 36mixture-2 Compound 37 Compound 37 Compound 38 Compound 38 HPLC
1H

Column2, method2 CDCl3 CDCl3 CDCl3 CDCl3 CDCl3 CDCl3 CDCl3 CDCl3 CD3COCD3 CDCl3 CD3SOCD3

S50 S51 S52 S53 S54

Compound 43a Compound 43b Compound 43c Compound 44 Compound 46

1H

NMR NMR NMR NMR NMR

CDCl3 CDCl3 CDCl3 CDCl3 CDCl3 Column2, method2 CDCl3 CDCl3 CDCl3 CD3COCD3 CDCl3 CD3COCD3

S67 S68 S69 S70 S71

NMR NMR NMR NMR

1H

13C

1H

1H 13C

1H 1H

Compound 39

1H

NMR

S55

Compound 46

HPLC

S72

Compound 39 Compound 39a Compound 39a Compound 1 Compound 1 Compound 1

13C

NMR NMR NMR NMR NMR NMR

S56 S57 S58 S59 S60 S61

Compound 45 Compound 45 Compound 2 Compound 2 Compound 2 Compound 2

1H

NMR NMR NMR NMR NMR NMR

S73 S74 S75 S76 S77 S78

1H

1H

13C

1H

1H

1H

1H

13C

1H

13C

Compound 1

13C

NMR

CD3COCD3

S62

Compound 2

HPLC

Column1, method1

S79

Compound 1 Compound p 1 Compound 41 Compound 42

MS HPLC
1H 1H

S63 Column1, method1 CDCl3 CDCl3 S64 S65 S66

Compound 2 p 3 Compound Compound 3 Compound 3

MS
1H

S80 CDCl3 CDCl3 S81 S82 S83

NMR NMR

NMR NMR

13C

MS

S17

CHO OTBDMS OMe

7

S18

CHO OTBDMS OMe

7

S19

OH

HO Br
9

Me

S20

OH

HO Br
9

Me

S21

OTs

MeO Br
11

Me

S22

OTs

O MeO Br
11

Me

S23

OH

MeO Br
12

Me

S24

OH

MeO Br
12

Me

S25

OTBDMS

MeO Br
13

Me

S26

OTBDMS Br MeO Br Me

15

S27

OTBDMS

MeO
17

Me

S28

OAc

MeO Br
18

Me

S29

OAc

MeO Br
19

CH2Br

S30

OH

MeO

OH OMe
24

S31

OH

MeO

OH OMe
24

S32

OAc

MeO Br
25

CHBr2

S33

OH

MeO Br
26

CHO

S34

OH

MeO Br
26

CHO

S35

OTBDMS

MeO Br
27

CHO

S36

CH2OH OTBDMS OMe

28

S37

OBn

MeO Br
31

CHO

S38

OBn

MeO Br
31

CHO

S39

CHO OBn OMe

32

S40

CHO OBn OMe

32

S41

CH2OH OBn OMe

33

S42

CH2OH OBn OMe

33

S43

CH2Br OBn OMe

34

S44

CH2PPh3Br OBn OMe

35

S45

CH2PPh3Br OBn OMe

35

S46

OBn

MeO Br

OBn OMe
36 (mixture-1)

S47

HPLC chromatogram of 36 (mixture-1)

S48

OBn

MeO Br

OBn OMe
36 (mixture-2)

S49

OBn

MeO Br

OBn OMe
36 (mixture-2)

S50

HPLC chromatogram of 36 (mixture-2)

S51

OBn

MeO

OBn OMe
37

S52

OBn

MeO

OBn OMe
37

S53

OBn

MeO Br OBn OMe

38

S54

OBn

MeO Br OBn OMe

38

S55

OBn

MeO

OBn OMe
39

S56

OBn

MeO

OBn OMe
39

S57

OBn

MeO

OBn OMe
39a

S58

OBn

MeO

OBn OMe
39a

S59

OH

MeO

OH OMe
1

S60

OH

MeO

OH OMe
1

S61

OH

MeO

OH OMe
1

S62

OH

MeO

OH OMe
1

S63

OH

MeO

OH OMe
1

S64

OH

MeO

OH OMe

S65

Br CHO OBn OMe

41

S66

OMe

BnO Br
42

CHO

S67

OMe

BnO BnO

CHO CHO

OMe
43a

S68

OMe

BnO

CHO CHO OBn OMe

43b

S69

OMe OBn CHO CHO OBn OMe

43c

S70

OMe

BnO

OBn OMe
44

S71

OMe

BnO

Br OBn OMe
46

S72

OMe

BnO

Br OBn OMe

46

S73

OMe

BnO

OBn OMe
45 Synthesized via Suzuki-coupling

S74

OMe

BnO

Synthesized via Wittig

OBn OM OMe
45

S75

OMe

HO

OH OMe
2

S76

OMe

HO

OH OMe
2

S77

OMe

HO

OH OMe
2

S78

OMe

HO

OH OMe
2

S79

OMe

HO

OH OMe

S80

OMe

HO

OH OMe
2

S81

OMe HO MeO

OH
3

S82

OMe HO MeO

OH
3

S83

OMe HO MeO

OH
3