mmc1

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SUPPORTING INFORMATION

Regioselective synthesis of phenanthrenes and evaluation of their anti-oxidant based anti-

inflammatory 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

*[email protected]

* Author for correspondence

Table of Contents

1. General procedure for preparing compounds: S2-S14

2. Selected 1H,

13C, MS and HPLC spectra of compounds: S15-S83

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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; 1H NMR

(400 MHz, CDCl3) δ 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)+.

1.2. 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) νmax 3340, 2925,

1614, 1593, 1466, 1332 cm-1; 1H NMR (400 MHz, CDCl3) δ 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(81Br)]-H)

+, 200.9 ([M(

79Br)]-H)

+; TLC (DCM : Acetone 9.8: 0.2) Rf 0.19; HPLC purity:100%, tR:

10.50 min (column-1, method-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) νmax 2972,

1604,1374, 1318 cm-1; 1H NMR (400 MHz, CDCl3) δ 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(81Br)]+H)

+, 371([M(

79Br)]+H)

+; HPLC purity:98.4%, tR: 34.7

min (column-1, method-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 (Pet-

ether : 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) νmax 3279(OH), 1606, 1586, 1476, 1355 cm-1; 1H NMR (400

MHz, CDCl3) δ 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(81Br)]-H)

+, 214.9 ([M(

79Br)]-H)

+; HPLC purity:

97.1%, tR: 23.8 min (column-1, method-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: 1H NMR

(400 MHz, CDCl3) δ 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(81Br)]+H)

+, 331([M(

79Br)]+H)

+.

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 (Pet-

ether, 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: 1H NMR (400 MHz,

CDCl3) δ 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, Ar-

H); EIMS m/z 412 ([M(81Br)]+H)

+, 410 ([M(

79Br)]+H)

+.

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: 1H NMR (400 MHz, CDCl3) δ 0.19 (s, 6H,

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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) νmax

1752(CO) cm-1; 1H NMR (400 MHz, CDCl3) δ 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(81Br)]+H)

+, 261([M(

79Br)]+H)

+.

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;

1H NMR (400 MHz, CDCl3) δ 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(81Br)]+H)

+, 338 ([M(

79Br)]+H)

+; HPLC purity: 79.0%, tR: 30.6 min (column-1,

method-1).

1.10. 2-[2-(3-hydroxy-5-methoxyphenyl)ethyl]-6-methoxyphenol (24)

mp 148-150 °C; 1H NMR (400 MHz, CDCl3) δ 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; 1H NMR (400 MHz, CDCl3) δ 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(81Br)]+Na)

+, 438.7

([M(79Br)]+Na)

+; HPLC purity: 92.9%, tR: 33.1 min (column-1, method-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; 1H NMR (400 MHz, CDCl3) δ 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); 13C NMR (100 MHz, CDCl3+

CD3SOCD3) δ 56.7 (OMe), 106.2, 106.6, 107.8, 134.8, 157.3, 158.2, 192.6 (CHO); EIMS m/z 230.9

([M(81Br)]-H)

+, 228.9 ([M(

79Br)]-H)

+.

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: 1H NMR (400 MHz, CDCl3) δ 0.23 (s, 6H, Si(Me)2), 1.00 (s, 9H, C(Me)3), 3.91 (s,

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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(81Br)]+H)

+, 345 ([M(

79Br)]+H)

+.

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: 1H NMR (400 MHz, CDCl3) δ 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)+.

1.15. 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; 1H

NMR (400 MHz, CDCl3) δ 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); 13C NMR (100 MHz, CDCl3) δ

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( 81Br)]+H)

+, 321 ([M(

79Br)]+H)

+; HPLC purity: 96.9%, tR: 33.6 min

(column-1, method-1).

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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) νmax 1696 (CO) cm-1; 1H NMR (400 MHz,

CDCl3) δ 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).

1.17. [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) νmax 3363 (OH) cm-1; 1H NMR (400 MHz, CDCl3) δ 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: 1H NMR (400 MHz,

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CDCl3) δ 3.90 (s, 3H, OMe), 4.51 (s, 2H, benzylic CH2), 5.16 (s, 2H, benzylic CH2), 6.90-6.99 (m, 2H, Ar-

H), 7.06 (t, 1H, J=8.0 Hz, Ar-H) 7.34-7.54 (m, 5H, Ar-H); EIMS m/z 309 ([M(81Br)]+H)

+, 307 ([M(

79Br)]+H)

+;

HPLC purity: 86.6%, tR: 34.6 min (column-1, method-1).

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; 1H NMR (400 MHz,

CD3OD) δ 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, Ar-

H), 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).

1.20. 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: 1H NMR (400 MHz, CDCl3) δ

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(81Br)]+Na)

+, 553 ([M(

79Br)]+Na)

+; HPLC tR 6.3 min (a)

and 6.9 min (b).

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; 1H NMR (400 MHz,

CDCl3) δ 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).

1.22. 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; 1H NMR

S11

(400 MHz, CDCl3) δ 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, Ar-

H), 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(

81Br)]+H)

+, 532.9 ([M(

79Br)]+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; 1H NMR (400 MHz, CDCl3) δ 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).

1.24. 1-(2-benzyloxy-3-methoxyphenyl)-2-(3-benzyloxy-5-methoxyphenyl)ethane (39a)

mp 96-98 °C; 1H NMR (400 MHz, CDCl3) δ 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, Ar-

H), 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).

1.25. 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) νmax 1700(CO) cm-1;

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

7.33-7.46 (m, 6H, Ar-H), 10.24 (s, 1H, CHO); EIMS m/z 345 ([M(81Br)]+Na)

+, 343 ([M(

79Br)]+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) νmax 1696(CO) cm-1; 1H NMR

(400 MHz, CDCl3) δ 3.82 (s, 3H, OMe), 5.17(s, 2H, benzylic CH2), 6.76 & 7.06 (d, 2H, AB, J=2.8 Hz, Ar-

H), 7.30-7.50 (m, 5H, Ar-H), 10.43 (s, 1H, CHO); EIMS m/z 323 ([M(81Br)]+H)

+, 321 ([M(

79Br)]+H)

+.

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; 1H NMR (400 MHz,

CDCl3) δ 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)+.

1.28. 6,6’-dibenzyloxy-4,4’-dimethoxybiphenyl-2,2’-dicarbaldehyde (43a)

mp 90-95 °C; 1H NMR (400 MHz, CDCl3) δ 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)+.

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

mp 68-70 °C; 1H NMR (400 MHz, CDCl3) δ 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: 1H NMR (400 MHz,

CDCl3) δ 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), 6.70-

7.50 (m, 13H); EIMS m/z 479 (M+H)+.

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; 1H NMR (400 MHz, CDCl3) δ 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),

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(81Br)]+H)

+, 531([M(

79Br)]+H)

+; HPLC tR: a: 6.79 min, b: 7.34 min (column -2, method-2).

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; 1H NMR (400 MHz, CDCl3) δ 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, Ar-

H), 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).

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 Index S15-S16 Compound 26 1H NMR CDCl3 S33

Compound 7 1H NMR CDCl3 S17 Compound 26 13C NMR CDCl3 S34

Compound 7 13C NMR CDCl3 S18 Compound 27 1H NMR CDCl3 S35

Compound 9 1H NMR CDCl3 S19 Compound 28 1H NMR CDCl3 S36

Compound 9 13C NMR CDCl3 S20 Compound 31 1H NMR CDCl3 S37Compound 9 C NMR CDCl3 S20 Compound 31 H NMR CDCl3 S37







C d 17 1H NMR CDCl S27 C d 35 1H NMR CD OD S44Compound 17 1H NMR CDCl3 S27 Compound 35 1H NMR CD3OD S44

Compound 18 1H NMR CDCl3 S28 Compound 35 13C NMR CD3OD S45

Compound 19 1H NMR CDCl3 S29 Compound 36-mixture-1

1H NMR CDCl3 S46

Compound 24 1H NMR CDCl3 S30 Compound 36-mixture-1 HPLC Column‐2,

method‐2 S47

Compound 24 13C NMR CDCl3 S31 Compound 36-mixture-2

1H NMR CDCl3 S48

Compound 25 1H NMR CDCl3 S32 Compound 36-mixture-2

13C NMR CDCl3 S49

S16

Table of Contents

Compound 36-mixture-2 HPLC Column‐2,

method‐2 S50 Compound 43a 1H NMR CDCl3 S67

Compound 37 1H NMR CDCl3 S51 Compound 43b 1H NMR CDCl3 S68

Compound 37 13C NMR CDCl3 S52 Compound 43c 1H NMR CDCl3 S69



Compound 39 1H NMR CDCl3 S55 Compound 46 HPLC Column‐2, method‐2 S72

Compound 39 13C NMR CDCl3 S56 Compound 45 1H NMR CDCl3 S73Compound 39 C NMR CDCl3 S56 Compound 45 H NMR CDCl3 S73

Compound 39a 1H NMR CDCl3 S57 Compound 45 1H NMR CDCl3 S74

Compound 39a 13C NMR CDCl3 S58 Compound 2 1H NMR CDCl3 S75

Compound 1 1H NMR CD3COCD3 S59 Compound 2 1H NMR CD3COCD3 S76


Compound 1 1H NMR CD3SOCD3 S61 Compound 2 13C NMR CD3COCD3 S78

Compound 1 13C NMR CD3COCD3 S62 Compound 2 HPLC Column‐1, method‐1 S79

Compound 1 MS S63 Compound 2 MS S80

Compound 1 HPLC Column‐1, method 1 S64 Compound 3 1H NMR CDCl3 S81p method‐1

p 3


Compound 42 1H NMR CDCl3 S66 Compound 3 MS S83

S17

CHO

OMeOTBDMS

7

S18

CHO

OMeOTBDMS

7

S19

OH

9

MeBr

OH

S20

OH

9

MeBr

OH

S21

OTs

11

MeBr

MeO

S22

OTs

O

11

MeBr

MeO

S23

OH

12

MeBr

MeO

S24

OH

MeBr

MeO

12

S25

OTBDMS

13

MeMeOBr

S26

OTBDMS

15

MeMeOBr

Br

S27

OTBDMS

17

MeMeO

S28

OAc

18

MeMeOBr

S29

OAc

19

MeOBr

CH2Br

S30

OH

MeO

24

OMeOH

S31

OH

MeO

24

OMeOH

S32

OAc

25

CHBr2MeOBr

S33

OH

26

CHOBr

MeO

S34

OH

26

CHOBr

MeO

S35

OTBDMS

27

CHOMeOBr

S36

CH2OH

28

OMeOTBDMS

2

S37

OBn

31

MeOBr

CHO

S38

OBn

31

MeOBr

CHO

S39

CHO

32

OBnOMe

S40

CHO

32

OBnOMe

S41

CH2OH

33

2

OBnOMe

S42

CH2OH

33

2

OBnOMe

S43

CH2Br

34

2

OBnOMe

S44

CH2PPh3Br

35

2 3

OBnOMe

S45

CH2PPh3Br

35

2 3

OBnOMe

S46

OBn

MeOBr

OMeOBn

36

(mixture-1)

S47

(mixture-1)HPLC chromatogram of 36

S48

OBn

MeOBr

OMeOBn

36

(mixture-2)

S49

OBn

MeOBr

OMeOBn

36

(mixture-2)

S50

HPLC chromatogram of 36(mixture-2)

S51

OBn

MeO

37

OBnOMe

S52

OBn

MeO

37

OBnOMe

S53

MeOBr

OBn

38

OBn

OMe

S54

MeOBr

OBn

38

OBn

OMe

S55

OBn

MeO

39

OBnOMe

S56

OBn

MeO

39

OBnOMe

S57

OBn

MeO

39a

OBnOMe

S58

OBn

MeO

39a

OBnOMe

S59

OH

MeO

1

OHOMe

S60

OH

MeO

1

OHOMe

S61

OH

MeO

1

OHOMe

S62

OH

MeO

1

OHOMe

S63

OH

MeO

1

OHOMe

S64

OH

MeO

OH

1

OHOMe

S65

CHOBr

OBnOMe

41

S66

OMe

42

CHOBnOBr

S67

OMe

CHOCHOBnO

BnO

43a

OMe

S68

OMe

CHOCHO

BnO

OMeOBn

43b

S69

OMe

CHOCHO

OBn

CHO

OMeOBn

43c

S70

OMe

BnO

OBnOMe

44

S71

OMe

BnO

OBn

Br

OBnOMe

46

S72

OMe

BnOBr 46

OBnOMe

S73

OMe

BnO

OBnOMe

45

Synthesized via Suzuki-coupling

S74

OMe

BnO

OBnOM

Synthesized via Wittig

OMe

45

S75

OMe

OH

OHOMe

2

S76

OMe

OH

OHOMe

2

S77

OMe

OH

OHOMe

2

S78

OMe

OH

OHOMe

2

S79

OMe

OH

OHOMe

2

OMe

S80

OMe

OH

OHOMe

2

S81

OMe

MeO

OH

OH

3

S82

OMeOH

MeO

OH

3

S83

OMe

MeO

OH

OH

3

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