General information
All reactions were conducted under a nitrogen atmosphere with oven-dried glassware and standard Schlenk or vacuum line techniques. All solutions were handled under nitrogen and transferred via syringe. Anhydrous solvents were purchased and stored over activated 4 Å molecular sieves. Unless otherwise stated, reagents were commercially available and used as purchased without further purification. Chemicals were purchased from Sigma-Aldrich, Acros, Alfa Aesar or TCI. Progress of reactions was monitored by thin-layer chromatography using Merck 60 F254 precoated silica gel plate and visualized by short-wave ultraviolet light as well as by treatment with basic solution of potassium permanganate or acidic solution of ceric molybdate. Flash chromatography was performed with Silica Flash P60 silica gel (230 – 400 mesh). 1H and 13C NMR spectra were obtained using an Agilent 400- MR DD2 Fourier-transform NMR spectrometer. Chemical shifts were reported in units of parts per million (ppm) downfield from tetramethylsilane (TMS), and all coupling constants were reported in hertz. The residual solvent signals were taken as the reference (CDCl3, 7.26 ppm 1H NMR spectra and CDCl3, 77.0 ppm for 13C NMR spectra). The signals observed are described as: s (singlet), d (doublet), t (triplet), q (quartet), m (multiplets). Mass analysis were carried out using Advion Expression CMS mass spectrometer or Agilent 6130 Quadrupole LC/MS. High resolution mass analysis was performed with JOEL AccuTOF 4G+ DART-HRMS and on Bruker, 1200 Series & HCT Basic System.
35
General Procedure (A) for benzothiophene synthesis
The reaction was carried out under N2 atmosphere, in undivided cell. A 5 mL vial was charged with the alkenyl disulfide 1 (0.1 mmol, 1 equiv.), Et4NOTs (0.3 mmol, 0.1 M), 1,2-dichloroethane (3 mL), and a stir bar, and was closed with a cap attached with a graphite anode and a nickel cathode. The solution was stirred at 900 rpm for 1 minute at room temperature before current was turned on. The electrolysis was performed at a constant current of 2.0 mA. Upon full consumption of the disulfide starting material as determined by thin-layer chromatography analysis, electrolysis was terminated. The reaction mixture was transferred into the round bottom flask and the electrodes were washed several times with ethyl acetate which was combined into the same round bottom flask. The combined solution was concentrated under reduced pressure and purified by flash chromatography.
36 Characterization data for the Electrolysis Products Characterization data for benzothiophene
Methyl benzo[b]thiophene-2-carboxylate (2a)
General procedure (A), 8 h, 70% yield; White solid; 1H NMR (400 MHz, CDCl3) δ 8.07 (s, 1H), 7.88 (t, J = 5.2 Hz, 2H), 7.51 – 7.35 (m, 2H), 3.95 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 163.2, 142.1, 138.6, 133.3, 130.6, 126.9, 125.5, 124.8, 122.7, 52.4; HRMS (DART) calcd for C10H9O2S+ 193.0318, observed 193.0316
Ethyl benzo[b]thiophene-2-carboxylate (2b)
General procedure (A), 11 h, 54% yield; Light yellow solid; 1H NMR (400 MHz, CDCl3) δ 8.05 (s, 1H), 7.90 – 7.80 (m, 2H), 7.48 – 7.34 (m, 2H), 4.40 (q, J = 7.1 Hz, 2H), 1.41 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 162.8, 142.2, 138.7, 133.9, 130.3, 126.8, 125.5, 124.8, 122.7, 61.5, 14.3;
HRMS (DART) calcd for C11H11O2S+ 207.0475, observed 207.0479 tert-butyl benzo[b]thiophene-2-carboxylate (2c)
General procedure (A), 8 h, 49% yield; Colorless oil; 1H NMR (400 MHz, CDCl3) δ 7.95 (s, 1H), 7.89 – 7.77 (m, 2H), 7.47 – 7.29 (m, 2H), 1.61 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 162.0, 142.1, 138.8, 135.8, 129.6, 126.6, 125.3, 124.7, 122.6, 82.3, 28.2; HRMS (DART) calcd for C13H15O2S+ 235.0788, observed 235.0788
Benzyl benzo[b]thiophene-2-carboxylate (2d)
General procedure (A), 8 h, 60% yield; White solid; 1H NMR (400 MHz, CDCl3) δ 8.09 (s, 1H), 7.93 – 7.77 (m, 2H), 7.52 – 7.32 (m, 7H), 5.39 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 162.6, 142.3, 138.7, 135.6, 133.4, 130.7, 128.6, 128.4, 128.2, 127.0, 125.5, 124.9, 122.7, 67.1; HRMS (ESI) calcd for C16H12NaO2S+ 291.0451, observed 291.0452
Methyl 5-nitrobenzo[b]thiophene-2-carboxylate (2e)
37
General procedure (A), 8 h, 71% yield; White solid; 1H NMR (400 MHz, CDCl3) δ 8.80 – 8.77 (m, 1H), 8.31 (dd, J = 8.9, 2.0 Hz, 1H), 8.19 (s, 1H), 8.00 (d, J = 8.8 Hz, 1H), 3.99 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 162.2, 147.3, 145.9, 138.3, 137.2, 130.7, 123.6, 121.2, 120.9, 52.9; HRMS (DART) calcd for C10H8NO4S+ 238.0169, observed 238.0171
Methyl 5-methoxybenzo[b]thiophene-2-carboxylate (2f)
General procedure (A), 8 h, 65% yield; White solid; 1H NMR (400 MHz, CDCl3) δ 7.98 (s, 1H), 7.72 (d, J = 8.8 Hz, 1H), 7.29 – 7.27 (m, 1H), 7.12 (dd, J = 8.9, 2.4 Hz, 1H), 3.94 (s, 3H), 3.88 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 166.8, 159.0, 143.2, 135.1, 134.0, 120.7, 117.6, 116.0, 112.6, 55.6, 51.9;
HRMS (DART) calcd for C11H11O3S+ 223.0424, observed 223.0428 Benzo[b]thiophen-2-yl(morpholino)methanone (2g)
General procedure (A), 8 h, 68% yield; White solid; 1H NMR (400 MHz, CDCl3) δ 7.89 – 7.77 (m, 2H), 7.48 (s, 1H), 7.42 – 7.34 (m, 2H), 3.81 – 3.70 (m, 8H); 13C NMR (100 MHz, CDCl3) δ 163.9, 140.1, 138.5, 136.1, 125.8, 125.3, 124.8, 124.6, 122.3, 66.8, 45.1; HRMS (DART) calcd for C13H14NO2S+ 248.0740, observed 248.0738
N-methoxy-N-methylbenzo[b]thiophene-2-carboxamide (2h)
General procedure (A), 6 h, 57% yield; Yellow solid; 1H NMR (400 MHz, CDCl3) δ 8.20 (s, 1H), 7.89 – 7.84 (m, 2H), 7.46 – 7.36 (m, 2H), 3.82 (s, 3H), 3.42 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 162.5, 142.5, 138.1, 133.4, 131.1, 126.5, 125.3, 124.6, 122.3, 61.8, 33.2; HRMS (DART) calcd for
C11H12NO2S+ 222.0584, observed 222.0582 Benzo[b]thiophene-2-carbonitrile (2i)
General procedure (A), 12 h, 62% yield; Colorless oil; 1H NMR (400 MHz, CDCl3) δ 7.92 – 7.83 (m, 3H), 7.53 (t, J = 7.2 Hz, 1H), 7.47 (t, J = 7.5 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 141.3, 137.5,
38
135.0, 127.9, 125.7, 125.3, 122.4, 114.4, 109.7; HRMS (ESI) calcd for C9H5NNaS+ 182.0035, observed 182.0035
Benzo[b]thiophen-2-ylmethyl acetate (2j)
General procedure (A), 10 h, 54% yield; White solid; 1H NMR (400 MHz, CDCl3) δ 7.82 – 7.78 (m, 1H), 7.77 – 7.73 (m, 1H), 7.37 – 7.31 (m, 2H), 7.29 (s, 1H), 5.34 (s, 2H), 2.11 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 170.6, 140.4, 139.2, 138.8, 124.7, 124.4, 124.3, 123.8, 122.4, 61.3, 20.9; HRMS (DART) calcd for C11H11O2S+ 207.0475, observed 207.0478
Benzo[b]thiophen-2-ylmethyl benzoate (2k)
General procedure (A), 10 h, 46% yield; White solid; 1H NMR (400 MHz, CDCl3) δ 8.08 (d, J = 7.2 Hz, 2H), 7.86 – 7.70 (m, 2H), 7.56 (t, J = 7.4 Hz, 1H), 7.44 (t, J = 7.6 Hz, 2H), 7.38 (s, 1H), 7.36 – 7.29 (m, 2H), 5.60 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 166.2, 140.4, 139.2, 138.9, 133.2, 129.8, 128.5, 128.4, 124.7, 124.4, 124.3, 123.8, 122.4, 61.9; HRMS (DART) calcd for C16H13O2S+ 269.0631, observed 269.0632
(benzo[b]thiophen-2-ylmethoxy)(tert-butyl)diphenylsilane (2l)
General procedure (A), 6 h, 22% yield; White solid; 1H NMR (400 MHz, CDCl3) δ 7.85 – 7.64 (m, 6H), 7.52 – 7.21 (m, 8H), 7.05 (s, 1H), 4.97 (s, 2H), 1.11 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 139.1, 137.1, 136.9, 135.6, 132.9, 129.9, 127.8, 124.9, 124.7, 122.6, 121.3, 115.4, 60.3, 26.8, 19.4;
HRMS (DART) calcd for C25H27OSSi+ 403.1547, observed 403.1549 Benzo[b]thiophen-2-ylmethanol (2m)
General procedure (A), 7 h, 33% yield; White solid; 1H NMR (400 MHz, CDCl3) δ 7.80 (d, J = 7.6 Hz, 1H), 7.71 (d, J = 7.9 Hz, 1H), 7.37 – 7.26 (m, 2H), 7.19 (s, 1H), 4.91 (s, 2H), 2.03 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 144.8, 139.9, 139.5, 124.3, 124.3, 123.5, 122.5, 121.5, 60.8; HRMS (DART) calcd for C9H9OS+ 165.0369, observed 165.0372
39 Synthesis of substrates
Preparation and characterization of disulfide derivatives.
General Procedure (B) for alkenyl disulfide synthesis
Substrates were prepared according to the reported procedure.
To a stirred suspension of LiAlH4 (1.00 g, 26 mmol, 1.2 equiv.) in anhydrous THF (24 mL) at 0 ℃ was added a solution of thiosalicylic acid (3.35 g, 21.7 mmol, 1 equiv.) in anhydrous THF (30 mL).
Once the reaction was determined to be completed by TLC, the mixture was cooled to 0 ℃ and was carefully added water (1 mL), 15% aqueous NaOH (1 mL) and then water (3 mL). The resulting aqueous phase was acidified with 1 N HCl solution until pH 2-3 and extracted with ethyl acetate three times. The combined organic layers were dried over Na2SO4, filtered and concentrated. The resulting yellow liquid was used without further purification.
To a mixture of (2-mercaptophenyl)methanol (2.94 g, 21 mmol, 1 equiv.) in dry CH2Cl2 (52.5 mL, 0.4 M) was added PCC (9.24 g, 42 mmol, 2 equiv.). After stirring at room temperature, the mixture was passed through a plug of silica gel, rinsing with CH2Cl2, to yield the dialdehyde as a colorless solid. 54%
yield.
To a solution of dialdehyde (1.56 g, 5.7 mmol, 1 equiv.) in dry CH2Cl2 (14.3 mL, 0.4 M) was added PPh3=CHCO2Me (4.19 g, 12.5 mmol, 2.2 equiv.). After stirring at room temperature, the solution was concentrated under reduced pressure. The crude material was purified through the flash chromatography to yield 1a as a colorless solid.
Dimethyl 3,3'-(disulfanediylbis(2,1-phenylene))(2E,2'E)-diacrylate (1a)
Prepared according to the general procedure (B), 62% yield; White solid; 1H NMR (400 MHz, CDCl3) δ 8.05 (d, J = 15.9 Hz, 2H), 7.63 – 7.27 (m, 8H), 6.31 (d, J = 15.9 Hz, 2H), 3.80 (s, 6H); 13C NMR
40
(100 MHz, CDCl3) δ 166.8, 141.3, 136.7, 136.0, 132.6, 130.5, 128.9, 127.1, 120.3, 51.7; MS (APCI):
m/z 387.3 [M+H]+
Diethyl 3,3'-(disulfanediylbis(2,1-phenylene))(2E,2'E)-diacrylate (1b)
Prepared according to the general procedure (B), PPh3=CHCO2Et was used, 61% yield; Colorless oil;
1H NMR (400 MHz, CDCl3) δ 8.06 (d, J = 15.8 Hz, 2H), 7.63 – 7.44 (m, 4H), 7.35 – 7.23 (m, 4H), 6.31 (d, J = 15.8 Hz, 2H), 4.26 (q, J = 5.8 Hz, 4H), 1.34 (t, J = 5.9 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 166.3, 140.9, 136.7, 136.0, 132.3, 130.4, 128.7, 127.1, 120.8, 60.5, 14.3; MS (APCI): m/z 415.5 [M+H]+
Di-tert-butyl 3,3'-(disulfanediylbis(2,1-phenylene))(2E,2'E)-diacrylate (1c)
Prepared according to the general procedure (B), PPh3=CHCO2tBu was used, 42% yield; Colorless oil; 1H NMR (400 MHz, CDCl3) δ 8.00 (d, J = 15.8 Hz, 2H), 7.67 – 7.56 (m, 2H), 7.55 – 7.45 (m, 2H), 7.30 – 7.23 (m, 4H), 6.25 (d, J = 15.8 Hz, 2H), 1.54 (s, 18H); 13C NMR (100 MHz, CDCl3) δ 165.7, 139.9, 136.6, 135.8, 131.7, 130.3, 128.5, 127.1, 122.6, 80.6, 28.2; MS (APCI): m/z 471.6 [M+H]+
Dibenzyl 3,3'-(disulfanediylbis(2,1-phenylene))(2E,2'E)-diacrylate (1d)
Prepared according to the general procedure (B), PPh3=CHCO2Bn was used, 68% yield; Yellow oil;
1H NMR (400 MHz, CDCl3) δ 8.07 (d, J = 15.9 Hz, 2H), 7.62 – 7.54 (m, 2H), 7.49 – 7.31 (m, 12H),
41
7.25 – 7.21 (m, 4H), 6.31 (d, J = 15.9 Hz, 2H), 5.24 (s, 4H); 13C NMR (100 MHz, CDCl3) δ 166.0, 141.5, 136.6, 136.0, 132.7, 130.5, 128.8, 128.5, 128.5, 128.2, 128.2, 127.0, 120.2, 66.2; MS (APCI):
m/z 539.5 [M+H]+
(2E,2'E)-3,3'-(disulfanediylbis(2,1-phenylene))bis(1-morpholinoprop-2-en-1-one) (1g)
Prepared according to the general procedure (B), 1-Morpholin-4-yl-2-(triphenyl-phosphanylidene)- ethanone was used, 89% yield; Colorless oil; 1H NMR (400 MHz, CDCl3) δ 8.01 (d, J = 15.3 Hz, 2H), 7.62 – 7.55 (m, 2H), 7.54 – 7.41 (m, 2H), 7.30 – 7.16 (m, 4H), 6.75 (d, J = 15.3 Hz, 2H), 3.88 – 3.51 (m, 16H); 13C NMR (100 MHz, CDCl3) δ 165.1, 139.3, 136.3, 136.2, 131.0, 129.7, 128.1, 127.2, 120.1, 66.7, 46.2, 42.3; MS (APCI): m/z 492.3 [M+H]+
(2E,2'E)-3,3'-(disulfanediylbis(2,1-phenylene))bis(N-methoxy-N-methylacrylamide) (1h)
Prepared according to the general procedure (B), N-methoxy-N-methyl-2-
(triphenylphosphoranylidene)acetamide was used, 73% yield; Colorless oil; 1H NMR (400 MHz, CDCl3) δ 8.14 (d, J = 15.6 Hz, 2H), 7.66 – 7.61 (m, 2H), 7.58 – 7.51 (m, 2H), 7.32 – 7.27 (m, 3H), 7.26 – 7.21 (m, 1H), 6.95 (d, J = 15.6 Hz, 2H), 3.76 (s, 6H), 3.31 (s, 6H); 13C NMR (100 MHz, CDCl3) δ 166.3, 139.7, 136.7, 135.8, 130.4, 130.0, 127.9, 127.3, 119.0, 61.9, 32.4; MS (APCI): m/z 445.6 [M+H]+
(2E,2'E)-3,3'-(disulfanediylbis(2,1-phenylene))diacrylonitrile (1i)
42
Prepared according to the general procedure (B), PPh3=CHCN was used, 67% yield; Colorless oil; 1H NMR (400 MHz, CDCl3) δ 7.68 (d, J = 16.6 Hz, 2H), 7.62 – 7.56 (m, 2H), 7.53 – 7.48 (m, 2H), 7.45 – 7.36 (m, 4H), 5.74 (d, J = 16.6 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 147.2, 136.1, 135.8, 134.7, 131.6, 130.1, 126.3, 117.6, 98.3; MS (APCI): m/z 321.4 [M+H]+
Synthesis of (2E,2'E)-3,3'-(disulfanediylbis(2,1-phenylene))bis(prop-2-en-1-ol) (1m)
Substrate was prepared according to the reported procedure.
To a solution of dimethyl 3,3'-(disulfanediylbis(2,1-phenylene))(2E,2'E)-diacrylate (386 mg, 1 mmol, 1 equiv.) in dry toluene (5 ml, 0.2 M) at -35 ℃ was added dropwise DIBAL-H (1.0 M solution in toluene, 6 ml, 6 mmol, 6 equiv.). After stirring at -35 ℃ for 30 min, 0.04 mL of water, 0.04 mL of 15%
aqueous NaOH and 0.1 mL of water was added slowly at -78 ℃. The reaction mixture was allowed to warm to room temperature and stirred for 30 min. The resulting aqueous phase was extracted with ethyl acetate three times. The combined organic layers were dried over Na2SO4, filtered and concentrated.
The crude material was purified by flash chromatography to yield 1m as a colorless oil. 74% yield; 1H NMR (400 MHz, CDCl3) δ 7.56 (d, J = 7.4 Hz, 2H), 7.45 (d, J = 7.3 Hz, 2H), 7.32 – 7.14 (m, 4H), 6.97 (d, J = 15.7 Hz, 2H), 6.25 (dt, J = 15.6, 5.4 Hz, 2H), 4.24 (d, J = 4.7 Hz, 4H); 13C NMR (100 MHz, CDCl3) δ 137.8, 134.6, 131.5, 131.2, 128.2, 128.0, 127.6, 126.3, 63.3; MS (APCI): m/z 331.3 [M+H]+
Synthesis of 1,2-bis(2-((E)-3-((tert-butyldiphenylsilyl)oxy)prop-1-en-1-yl)phenyl)disulfane (1l)
Substrate was prepared according to the reported procedure.
To a solution of (2E,2'E)-3,3'-(disulfanediylbis(2,1-phenylene))bis(prop-2-en-1-ol) (66 mg, 0.2 mmol, 1 equiv.) in dry CH2Cl2 (1 ml, 0.2 M) was added NEt3 (0.11 mL, 0.8 mmol, 4 equiv.), DMAP (5 mg, 0.04 mmol, 0.2 equiv.) and TBDPSCl (0.21 mL, 0.8 mmol, 4 equiv.). After stirring at room temperature, the reaction mixture was quenched by addition of water. The aqueous phase was extracted with ethyl
43
acetate with three times. The combined organic layers were dried over Na2SO4, filtered and concentrated.
The crude material was purified by flash chromatography to yield 1l as a colorless oil. 80% yield; 1H NMR (400 MHz, CDCl3) δ 7.77 – 7.71 (m, 8H), 7.57 – 7.51 (m, 2H), 7.45 – 7.33 (m, 14H), 7.25 – 7.06 (m, 6H), 6.19 (dt, J = 16.1, 4.4 Hz, 2H), 4.60 – 4.19 (m, 4H), 1.11 (s, 18H); 13C NMR (100 MHz, CDCl3) δ 137.5, 135.6, 134.8, 133.6, 131.8, 129.7, 129.7, 127.9, 127.7, 127.6, 126.4, 126.2, 64.4, 26.9, 19.3;
MS (APCI): m/z 807.5 [M+H]+
Synthesis of (2E,2'E)-(disulfanediylbis(2,1-phenylene))bis(prop-2-ene-3,1-diyl) diacetate (1j)
To a solution of (2E,2'E)-3,3'-(disulfanediylbis(2,1-phenylene))bis(prop-2-en-1-ol) (66 mg, 0.2 mmol, 1 equiv.) in dry CH2Cl2 (1.3 ml, 0.15 M) at 0 ℃ was added NEt3 (0.11 mL, 0.8 mmol, 4 equiv.) and acetyl chloride (0.04 ml, 0.6 mmol, 3 equiv.). The reaction mixture was stirred at room temperature.
After completion of the reaction, water was added, and the aqueous phase was extracted with ethyl acetate three times. The combined organic layers were dried over Na2SO4, filtered and concentrated.
The crude material was purified by flash chromatography to yield 1j as a colorless oil. 89% yield; 1H NMR (400 MHz, CDCl3) δ 7.54 (d, J = 7.5 Hz, 2H), 7.46 (d, J = 7.5 Hz, 2H), 7.32 – 7.14 (m, 4H), 7.04 (d, J = 15.8 Hz, 2H), 6.19 (dt, J = 15.6, 6.2 Hz, 2H), 4.67 (d, J = 6.1 Hz, 4H), 2.11 (s, 6H); 13C NMR (100 MHz, CDCl3) δ 170.6, 137.3, 135.0, 131.4, 130.6, 128.5, 128.4, 126.4, 126.0, 64.8, 20.9; MS (APCI): m/z 415.2 [M+H]+
Synthesis of (2E,2'E)-(disulfanediylbis(2,1-phenylene))bis(prop-2-ene-3,1-diyl) dibenzoate (1k)
To a solution of (2E,2'E)-3,3'-(disulfanediylbis(2,1-phenylene))bis(prop-2-en-1-ol) (66 mg, 0.2 mmol, 1 equiv.) and pyridine (0.05 mL, 0.6 mmol, 3equiv.) in dry CH2Cl2 (1 ml, 0.2 M) at 0 ℃ was added benzoyl chloride (0.07 mL, 0.6 mmol, 3 equiv.) via syringe. The reaction mixture was stirred at room temperature and quenched by the addition of water. The aqueous phase was extracted with ethyl acetate with three times. The combined organic layers were dried over Na2SO4, filtered and concentrated. The crude material was purified by flash chromatography to yield 1k as a colorless oil. 92% yield; 1H NMR (400 MHz, CDCl3) δ 8.09 (d, J = 7.5 Hz, 4H), 7.56 (t, J = 6.0 Hz, 4H), 7.46 (dt, J = 15.5, 8.3 Hz, 6H),
44
7.28 – 7.08 (m, 6H), 6.30 (dt, J = 15.6, 6.1 Hz, 2H), 4.90 (d, J = 6.1 Hz, 4H); 13C NMR (100 MHz, CDCl3) δ 166.2, 137.5, 135.1, 133.0, 131.8, 130.8, 130.1, 129.6, 128.5, 128.5, 128.4, 126.5, 126.0, 65.3;
MS (APCI): m/z 539.2 [M+H]+
Synthesis of dimethyl 3,3'-(disulfanediylbis(5-nitro-2,1-phenylene))(2E,2'E)-diacrylate (1e)
Substrates were prepared according to reported procedures.
KNO3 (109 mg, 1.08 mmol, 1.15 equiv.) was added slowly to a stirred solution of 2-
bromobenzaldehyde (174 mg, 0.94 mmol, 1 equiv.) in H2SO4 (0.94 mL, 1 M) at 0 ℃. The reaction mixture was poured over ice water, extracted with ethyl acetate three times. The combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuo. The crude was purified by flash chromatography to yield 2-bromo-5-nitrobenzaldehyde as a yellow solid. 93% yield.
DMSO (0.25 mL, 3.48 mmol, 4 equiv.) and powdered KOH (53.7 mg, 0.96 mmol, 1.1 equiv.) were stirred at room temperature. After 5 min, 2-methyl-2-propanethiol (0.15 mL, 1.3 mmol, 1.5 equiv.) was added, and the mixture was stirred for 20 min. 2-bromo-5-nitrobenzaldehyde (200 mg, 0.87 mmol, 1 equiv.) was added, and the reaction was heated to 110 ℃. After completion of the reaction, it was diluted with water and extracted with ethyl acetate three times. The combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuo. The crude material was purified by flash chromatography to yield 2-(tert-butylthio)-5-nitrobenzaldehyde as a yellow oil. 78% yield.
2-(tert-butylthio)-5-nitrobenzaldehyde (162 mg, 0.68 mmol, 1 equiv.) was dissolved in acetic acid (0.23 mL, 4.08 mmol, 6 equiv.) and HBr (0.34 mL, 2.04 mmol, 3 equiv.) with DMSO (0.05 ml, 0.68 mmol, 1 equiv.) was added. The reaction mixture was stirred at room temperature. Once the reaction was determined to be completed by TLC, the mixture was poured into water and precipitate was collected and washed with water. The crude material was dried and purified by flash chromatography to yield 6,6'-disulfanediylbis(3-nitrobenzaldehyde) as a yellow solid. 63% yield.
To a solution of 6,6'-disulfanediylbis(3-nitrobenzaldehyde) (78 mg, 0.21 mmol, 1 equiv.) in dry CH2Cl2 (0.53 mL) was added PPh3=CHCO2Me (154 mg, 0.46 mmol, 2.2 equiv.). After stirring at room temperature, the solution was concentrated under reduced pressure. The crude material was purified through the flash chromatography to yield 1e as a yellow oil. 58% yield; 1H NMR (400 MHz, CDCl3) δ 8.38 (d, J = 2.0 Hz, 2H), 8.15 (dd, J = 8.7, 2.2 Hz, 2H), 8.03 (d, J = 15.7 Hz, 2H), 7.77 (d, J = 8.7 Hz,
45
2H), 6.53 (d, J = 15.7 Hz, 2H), 3.85 (s, 6H); 13C NMR (100 MHz, CDCl3) δ 165.9, 147.6, 142.9, 138.0, 135.7, 129.8, 124.7, 124.0, 122.3, 52.2; MS (APCI): m/z 477.8 [M+H]+
Synthesis of dimethyl 3,3'-(disulfanediylbis(5-methoxy-2,1-phenylene))(2E,2'E)-diacrylate (1f)
Substrates were prepared according to reported procedures.
To a solution of 3-methoxybenzaldehyde (127 mg, 0.93 mmol, 1 equiv.) in DMF (1.2 mL, 0.8 M) was added NBS (196 mg, 1.1 mmol, 1.2 equiv.) at room temperature under N2. To the reaction mixture was added H2O at 0 ℃. The precipitate was collected by filtration, washed with water, and dried under vacuum to give 2-bromo-5-methoxybenzaldehyde as a colorless solid. 78% yield.
To a stirred suspension of NaH (60% in mineral oil; 32 mg, 0.8 mmol, 1.1 equiv.) in DMF (1.5 mL, 0.5 M) at 0 ℃ was added 2-methyl-2-propanethiol (0.09 ml, 0.8 mmol, 1.1 equiv.) dropwise. After evolution of H2 gas had ceased, 2-bromo-5-methoxybenzaldehyde (156 mg, 0.73 mmol, 1 equiv.) was added dropwise and the mixture was stirred at the room temperature. Saturated aqueous NH4Cl was added, and the mixture was extracted with ethyl acetate three times. The combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuo. The crude material was purified by flash chromatography to yield 2-(tert-butylthio)-5-methoxybenzaldehyde as a yellow oil. 45% yield.
2-(tert-butylthio)-5-methoxybenzaldehyde (74 mg, 0.33 mmol, 1 equiv.) was dissolved in acetic acid (0.11 mL, 1.98 mmol, 6 equiv.) and HBr (0.16 mL, 0.99 mmol, 3 equiv.) with DMSO (23.4 ml, 0.33 mmol, 1 equiv.) was added. The reaction mixture was then vigorously stirred at room temperature.
Once the reaction was determined to be completed by TLC, the mixture was poured into water and precipitate was collected and washed with water. The crude material was dried and purified by flash chromatography to yield 6,6'-disulfanediylbis(3-methoxybenzaldehyde) as a yellow oil. 61% yield.
To a solution of 6,6'-disulfanediylbis(3-methoxybenzaldehyde) (33 mg, 0.1 mmol, 1 equiv.) in dry CH2Cl2 (0.25 mL) was added PPh3=CHCO2Me (73.6 mg, 0.22 mmol, 2.2 equiv.). After stirring at room temperature, the solution was concentrated under reduced pressure. The crude material was purified through the flash chromatography to yield 1f as a colorless oil. 73% yield; 1H NMR (400 MHz, CDCl3) δ 7.83 (d, J = 16.0 Hz, 2H), 7.45 (d, J = 8.6 Hz, 2H), 6.99 (d, J = 2.5 Hz, 2H), 6.84 (dd, J = 8.6, 2.7 Hz, 2H), 6.17 (d, J = 15.9 Hz, 2H), 3.82 (s, 6H), 3.76 (s, 6H); 13C NMR (100 MHz, CDCl3) δ 166.7, 161.0, 142.1, 139.5, 138.1, 128.0, 119.6, 116.8, 111.6, 55.4, 51.6; MS (APCI): m/z 447.7 [M+H]+
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