Selective Metalations of 1,4-Dithiins and Condensed Analogs using TMP-Magnesium and -Zinc Bases
|
|
- Jasmin Bryan
- 6 years ago
- Views:
Transcription
1 Selective Metalations of,4-dithiins and Condensed Analogs using TMP-Magnesium and -Zinc Bases Alicia Castelló-Micó, a Julia Nafe, a Kosuke Higashida, a Konstantin Karaghiosoff, a Marc Gingras, b Paul Knochel a * a Department Chemie, Ludwig-Maximilians-Universita t, Butenandtstrasse 5-3, 8377 München, Germany b CNRS, Aix-Marseille Université, CINAM UMR 7325, 63 Avenue de Luminy, 3288 Marseille, France *Paul.Knochel@cup.uni-muenchen.de Supporting Information S
2 Table of contents A) General Information S3 B) Starting Material Synthesis S3-S6 C) General Procedures S6-S7 D) Compounds Synthesized According to the General Procedures S7-S3 E) NMR Spectra S32-S70 F) Single Crystal X-Ray Diffraction Studies S7-S8 S2
3 A) General Information All air and moisture sensitive reactions were carried out under argon atmosphere in flame-dried glassware. Syringes which were used to transfer anhydrous solvents or reagents were purged with argon prior to use. THF was continuously refluxed and freshly distilled from sodium benzophenone ketyl under nitrogen and stored over molecular sieves. Reactions were monitored by gas chromatography (GC and GC-MS) or thin layer chromatography (TLC). TLC was performed with aluminium plates covered with SiO 2 (Merck 60, F-254) and visualized by UV detection. Yields refer to isolated yields of compounds estimated to be > 95% pure as determined by H-NMR (25 C) and capillary GC. NMR spectra were recorded in solutions in CDCl 3 with residual solvent reference (δ = 7.26 ppm for H-NMR and δ = 77. ppm for 3 C-NMR). Abbreviations for signal coupling are as follows: s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet; br, broad. Purification by column chromatography was performed using SiO 2 ( mm, mesh ASTM) from Merck or using preparative high performance liquid chromatography (HPLC). All reagents were obtained from commercial sources. TMPH was distilled prior to use. CuCN, ZnCl 2 and LiCl were obtained from Merck. B) Starting material synthesis. Preparation of Organometallic reagents: i-prmgcl LiCl was purchased as a solution in THF from Rockrood Lithium and titrated against iodine prior to use. Preparation of CuCN 2LiCl solution: CuCN 2LiCl solution ( M in THF) was prepared by drying CuCN (7.7 g, 80 mmol) and LiCl (6.77 g, 60 mmol) in a Schlenk-flask under vacuum at 40 C for 5 h. After cooling, dry THF (80 ml) was added and stirring was continued until all salts were dissolved (24 h). Preparation of ZnCl 2 solution: ZnCl 2 solution ( M in THF) was prepared by drying ZnCl 2 (36.3 g, 00 mmol) in a Schlenk-flask under vacuum at 40 C for 5 h. After cooling, dry THF (00 ml) was added and stirring was continued until all salts were dissolved (2 h). Preparation of TMPMgCl LiCl (6): 2 In a dry and argon flushed Schlenk-flask TMPH (2,2,6,6-tetramethylpiperidine, 4.8 g, 05 mmol) was added to iprmgcl LiCl (7.4 ml, 00 mmol,.40 M in THF) at 25 C and the mixture was stirred for 3 days at 25 C. The freshly prepared TMPMgCl LiCl was titrated prior to use at 0 C with benzoic acid using 4-(phenylazo)diphenylamine as indicator. Preparation of TMPZn LiCl (3): Krasovskiy, A.; Knochel, P. Synthesis 2006, 2006, Krasovskiy, A.; Krasovskaya, V.; Knochel, P. Angew. Chem. 2006, 8, 3024; Angew. Chem., Int. Ed. 2006, 45, S3
4 A flame-dried and argon flushed Schlenk-flask, equipped with a magnetic stirring bar and rubber septum, was charged with TMPH (2,2,6,6-tetramethylpiperidine, ml, 60 mmol) dissolved in THF (60 ml). The solution was cooled to -40 C and nbuli (25 ml, 60 mmol, 2.4 M in hexane) was added dropwise and the mixture was allowed to warm up to -0 C for h. ZnCl 2 solution (66 ml, 66 mmol, M in THF) was added dropwise and the resulting solution was stirred for 30 min at -0 C and then 30 min at 25 C. The solvents were removed under vacuum affording a yellowish solid. Freshly distilled THF was then slowly added and the solution was stirred until all salts were completely dissolved. The freshly prepared TMPZnCl LiCl was titrated prior to use at 0 C with benzoic acid using 4-(phenylazo)-diphenylamine as indicator. 2. Preparation of,4-dithiine () 3 According to the literature, 3 thionyl chloride (8.5 g,.3 ml, 56 mmol) was added to a solution of,4-dithiane-2,5-diol (6.77 g, 44.4 mmol) in dry DMF (250 ml) at 0 C. After the addition, the reaction mixture was stirred at 25 C for 2 h. The product which codistills with DMF, was distilled under reduced pressure (00 C, 270 mbar). After reducing half of the volume, another dry DMF (00 ml) was added to the reaction flask and the distillation was continued until a black residue was left. The distilled DMF was extracted with water (50 ml) and Et 2O (400 ml). The organic phase was washed with water (3 x 50 ml), sat. aq. NaHCO 3 solution (2 x 00 ml) and sat. aq. NaCl solution (00 ml). The organic phase was dried over anhydrous MgSO 4 and, after filtration, the solvent was evaporated in vacuo.,4-dithiine () was obtained as yellow liquid (4.8 g, 8%) and was used without further purification. H NMR (400 MHz, CDCl 3) δ/ppm: 6.8 (s, 4H). 3. Preparation of bis(phenylsulfonyl)sulfide (20) 4 According to the literature, 4 sodium benzenesulfinate (4 g, 250 mmol) was suspended in dry Et 2O (300 ml) and a solution of sulfur dichloride (3 g, 25 mmol) in dry Et 2O (50 ml) was added dropwise. The mixture was stirred for 2 h at 40 C. Afterwards water was added and the insoluble product was filtered off. After recrystallization from acetone, bis(phenylsulfonyl)sulfide was obtained as white crystals (24 g, 60%). H NMR (400 MHz, CDCl 3) δ/ppm: 8.02 (d, J=7.6 Hz, 4 H), 7.7 (t, J=7.3 Hz, 2 H), 7.59 (t, J=7.8 Hz, 4 H). 3 Grant, A. S.; Faraji-Dana, S.; Graham, E. J. Sulfur Chem. 2009, 30, (a) Allared, F.; Hellberg, J.; Remonen, T. Tetrahedron Lett. 2002, 43, 553. (b) Dostert, C.; Wanstrath, C.; Frank, W.; Müller, T. J. J. Chem. Commun. 202, 48, 727. S4
5 4. Preparation of,4,5,8-tetrathianaphthalene (4) 4.. Synthesis of tetraethylammonium bis(,3-dithiole-2-thione-4,5-dithiol) zincate (2) According to the literature, 5 an oven-dried L round-bottomed flask, equipped with a mechanical stirrer, a 250-mL pressure-equalizing dropping funnel, and a gas inlet tube, was connected to nitrogen. The flask was charged with sodium (4.6 g, 200 mmol) and placed in an ice-water bath. Carbon disulfide (36 ml, 600 mmol) was introduced into the flask through the dropping funnel, after which 60 ml of DMF were added dropwise over 45 min. After the addition, the reaction mixture was allowed to warm to 25 C and stir overnight. Methanol (20 ml) was added slowly through the dropping funnel to the reaction mixture in an ice bath. Afterwards, a mixture of methanol (80 ml) and deionized water (00 ml), was then added rapidly through the dropping funnel. A solution of ZnCl 2 (4. g, 30 mmol) in concentrated aqueous ammonium hydroxide (50 ml) and methanol (00 ml) was then added through the dropping funnel. A solution of tetraethylammonium bromide ( g, 50 mmol) in water (50 ml) was added dropwise via the dropping funnel with vigorous stirring over at least 45 min, and the solution was stirred 2 h. The precipitated was collected by suction on a Büchner funnel and washed with water (00 ml), isopropanol (80 ml) and diethyl ether (40 ml). The product was then dried in a desiccator under vacuum affording 2 as a red powder (5 g, 84%). 3 C NMR (0 MHz, CDCl 3) δ/ppm: 209.4, 35., 52.0, Synthesis of 4,5-dibenzoylthio-,3-dithiole--thione (22). According to the literature, 5 tetraethylammonium bis(,3-dithiole-2-thione-4,5-dithio) zincate (2, 6 g, 223 mmol) was dissolved in acetone (400 ml) of benzoyl chloride (48.4 g, 345 mmol) was added dropwise. The reaction mixture was stirred for 2 h and the resulting yellow-light brown precipitate was collected by suction and washed with water (500 ml) and acetone (300 ml). This crude material was dissolved in chloroform (350 ml), Norit ( g) was added and the mixture was heated under reflux for 0 min. The mixture was filtered while still hot, and washed with chloroform. The combined chloroform solutions were concentrated to 50 ml and the resulting mixture was warmed and methanol (50 ml) was added portionwise with stirring. The solution was then left overnight in the refrigerator. The resulting crystalline precipitate was collected by suction and air-dried, affording 22 (8.5 g, 43%). 3 C NMR (0 MHz, CDCl 3) δ/ppm: 22.5, 85.6, 35.0, 34.9, 33.8, 29.3, Hansen, T. K.; Becher, J.; Joergensen, T.; Varma, K. S.; Khedekar, R.; Cava, M. P.Organic Syntheses, 996, 73, 270. S5
6 4.3. Synthesis of,4,5,8-tetrathianaphthalene (4). According to the literature, 6 sodium (3.0 g, 30 mmol) was dissolved in ethanol (50 ml) under N 2 in a 3-necked L round bottom flask equiped with a stir bar and two 250 ml addition funnels. Then, THF (65 ml) was added and the solution was refluxed. At that moment, 4,5-bis(benzoylthio)-,3-dithiole--thione (23, 5.3 g, 3 mmol in 80 ml of THF) and cis-,2-dichloroethylene (2.6 g, 27mmol in 80 ml of THF) were added simultaneously dropwise over h to the sodium ethoxide solution. The reaction mixture was refluxed for 2 h. Water (30 ml) was added to dissolve the precipitate and then, the THF was removed under reduced pressure. The solid was collected and washed with water. The solid was purified by flash column chromatography on silica gel (ihexane) yielding 4 as yellow solid (.6 g, 60%). H NMR (400 MHz, CDCl 3) δ/ppm: 6.46 (s, 4 H). C) General procedures Typical Procedure for the magnesiation of,4-dithiine () with TMPMgCl LiCl (6) (TP): A dry and argon flushed Schlenk-flask was charged with a solution of,4-dithiine (; equiv) in dry THF ( M). TMPMgCl LiCl (6;. equiv) was added dropwise at -40 C and the reaction mixture was stirred for h. The completion of the reaction was checked by GC analysis of reaction aliquots quenched with iodine in dry THF. Typical Procedure 2 for the magnesiation or zincation of monofunctionalized,4- dithiine derivatives (9) withtmpmgcl LiCl (6) or TMPZnCl LiCl (7) (TP2): A dry and argon flushed Schlenk-flask was charged with a solution of the corresponding monofunctionalized,4-dithiine derivative (9; equiv) in dry THF ( M). TMPMgCl LiCl (6; 5 -. equiv) or TMPZnCl LiCl (7;. equiv) was added dropwise at the indicated temperature and the reaction mixture was stirred for h. The completion of the reaction was checked by TLC analysis of reaction aliquots quenched with iodine in dry THF. Typical Procedure 3 for the magnesiation of,4,5,8-tetrathianaphthalene (4) with TMPMgCl LiCl (6) (TP3): A dry and argon flushed Schlenk-flask was charged with a solution of,4,5,8- tetrathianaphthalene (4; equiv) in dry THF (3 M). TMPMgCl LiCl (6;.2 equiv) was added dropwise at -78 C and the reaction mixture was stirred for 0 min. The completion of the reaction was checked by GC analysis of reaction aliquots quenched with iodine in dry THF. 6 Meline, R. L.; Elsenbaumer, R. L. Synthetic Metals, 997, 86, 845. S6
7 Typical Procedure 4 for the zincation of monofunctionalized,4,5,8- tetrathianaphthalene derivatives (4) with TMPZnCl LiCl (7) (TP4): A dry and argon flushed Schlenk-flask was charged with a solution of the corresponding monofunctionalized,4,5,8-tetrathianaphthalene derivative (4; equiv) in dry THF (3 M). TMPZnCl LiCl (7;. equiv) was added dropwise at -40 C and the reaction mixture was stirred for h. The completion of the reaction was checked by TLC analysis of reaction aliquots quenched with iodine in dry THF. Typical Procedure 5 for the zincation of,4,5,6,9,0-hexathiaanthracene (5) with TMPZnCl LiCl (7) (TP5): A dry and argon flushed Schlenk-flask was charged with a solution of,4,5,6,9,0- hexathiaanthracene (5; equiv) in dry THF (0.03 M). TMPZnCl LiCl (7;. equiv) was added dropwise at -40 C and the reaction mixture was stirred for 2 h. The completion of the reaction was checked by GC analysis of reaction aliquots quenched with iodine in dry THF. D) Compounds synthesized according to the general procedures. Preparation of monofunctionalized,4-dithiine derivatives.. Synthesis of 2-iodo-,4-dithiine (9a) According to TP,,4-dithiine (; 6 mg, mmol) was dissolved in dry THF (2 ml). TMPMgCl LiCl (9 ml,. mmol) was added dropwise at -40 C and the reaction mixture was stirred for h. The freshly prepared magnesium reagent was added to a solution of iodine (77 mg, mmol) in dry THF ( ml) at -78 C. The resulting solution was stirred at this temperature for h and was then quenched with sat. aq. Na 2S 2O 3 solution (5 ml), extracted with Et 2O (3 x 0 ml) and dried over anhydrous Na 2SO 4. After filtration, the solvents were evaporated in vacuo. The crude product was purified by flash column chromatography on silica gel (ihexane) yielding 9a as yellow liquid (27 mg, 75%). H NMR (400 MHz, CDCl 3) δ/ppm: (m, 2H), 6.24 (d, J = 6.6, H). 3 C NMR (0 MHz, CDCl 3) δ/ppm: 25.9, 22.7, 2.7, IR (Diamond-ATR, neat) ~ /cm - : 3025, 292, 678, 598, 554, 534, 53, 469, 273, 27, 34, 885, 839, 794, 768, 732, 668, 566. MS (70 ev, EI) m/z (%): 242 (69), 5 (00), 89 (2), 7 (78), 57 (30), 45 (56). HRMS (EI): m/z (M + ) for C 4H 3IS 2: calcd ; found Synthesis of 2-bromo-,4-dithiine (9b) S7
8 According to TP,,4-dithiine (; 6 mg, 5.0 mmol) was dissolved in dry THF (0 ml). TMPMgCl LiCl (4.95 ml, 5.5 mmol) was added dropwise at -40 C and the reaction mixture was stirred for h. The freshly prepared magnesium reagent was added to a solution of,2-dibromotetrachloroethane (.4 g, 3.5 mmol) in dry THF (5 ml) at -78 C. The resulting solution was stirred at this temperature for 2 h and was then quenched with sat. aq. NH 4Cl solution (0 ml), extracted with Et 2O (3 x 80 ml) and dried over anhydrous Na 2SO 4. After filtration, the solvents were evaporated in vacuo. The crude product was purified by flash column chromatography on silica gel (ihexane) yielding 9b as yellow liquid (529 mg, 78%). H NMR (400 MHz, CDCl 3) δ/ppm: 6.40 (d, J=6.4 Hz, H), (m, 2 H). 3 C NMR (0 MHz, CDCl 3) δ/ppm: 26.0, 22.8, 2.9, IR (Diamond-ATR, neat) ~ /cm - : 303, 563, 555, 524, 503, 493, 468, 446, 43, 322, 275, 28, 88, 35, 09, 070, 03, 0, 99, 886, 860, 827, 799, 773, 752, 70, 668. MS (70 ev, EI) m/z (%): 96 (53), 94 (47), 5 (00), 7 (4), 57 (0), 45 (6). HRMS (EI): m/z (M + ) for C 4H 3BrS 2: calcd ; found Synthesis of 2-chloro-,4-dithiine (9c) According to TP,,4-dithiine (; 83 mg, 7.0 mmol) was dissolved in dry THF (4 ml). TMPMgCl LiCl (6.94 ml, 7.7 mmol) was added dropwise at -40 C and the reaction mixture was stirred for h. The freshly prepared magnesium reagent was added to a solution of benzenesulfonyl chloride (865 mg, 4.9 mmol) in dry THF (5 ml) at -78 C. The resulting solution was stirred at this temperature for 2 h and was then quenched with sat. aq. NH 4Cl solution (0 ml), extracted with Et 2O (3 x 80 ml) and dried over anhydrous Na 2SO 4. After filtration, the solvents were evaporated in vacuo. The crude product was purified by flash column chromatography on silica gel (ihexane) yielding 9c as yellow liquid (43 mg, 56%). H NMR (400 MHz, CDCl 3) δ/ppm: 6.37 (d, J=6.6 Hz, H), 6.33 (d, J=6.6 Hz, H), 6.6 (s, H). 3 C NMR (0 MHz, CDCl 3) δ/ppm: 23.0, 22.6, 22.3, 7.3. IR (Diamond-ATR, neat) ~ /cm - : 3035, 2922, 279, 60, 579, 548, 528, 455, 402, 278, 206, 36, 065, 97, 928, 896, 88, 770, 668. MS (70 ev, EI) m/z (%): 52 (2), 50 (52), 5 (87), 05 (3), 89 (4), 88 (7), 79 (2), 7 (45), 58 (23), 57 (52), 45 (00). S8
9 HRMS (EI): m/z (M + ) for C 4H 3ClS 2: calcd ; found Synthesis of,4-dithiine-2-carbonitrile (9d) According to TP,,4-dithiine (; 6 mg, mmol) was dissolved in dry THF (2 ml). TMPMgCl LiCl (9 ml,. mmol) was added dropwise at -40 C and the reaction mixture was stirred for h. The freshly prepared magnesium reagent was added to a solution of p-toluenesulfonyl cyanide (27 mg, mmol) in dry THF (2 ml) at -60 C. The resulting solution was stirred at this temperature for 2 h and was then quenched with sat. aq. NH 4Cl solution (5 ml), extracted with Et 2O (3 x 0 ml) and dried over anhydrous Na 2SO 4. After filtration, the solvents were evaporated in vacuo. The crude product was purified by flash column chromatography on silica gel (ihexane/et 2O, 95:5) yielding 9d as orange oil (59 mg, 60%). H NMR (400 MHz, CDCl 3) δ/ppm: 7.3 (s, H), 6.32 (d, J=6.6 Hz, H), 6.28 (d, J=6.6 Hz, H). 3 C NMR (0 MHz, CDCl 3) δ/ppm: 4, 22.0, 2., 4.5, IR (Diamond-ATR, neat) ~ /cm - : 3034, 2924, 227, 654, 594, 558, 525, 447, 33, 28, 240, 76, 40, 084, 054, 999, 958, 932, 892, 85, 805, 785, 674, 66. MS (70 ev, EI) m/z (%): 4 (00), 4 (9), 96 (3), 7 (27), 45 (33). HRMS (EI): m/z (M + ) for C 5H 3NS 2: calcd. 4707; found Synthesis of -(,4-dithiin-2-yl)-N,N-dimethylmethanamine (9e) A dry and argon-flushed Schlenk-flask was charged with N,N,N,N - tetramethylmethanediamine (2 mg,. mmol) and anydrous CH 2Cl 2 (. ml). Trifluoroacetic anhydride (23 mg,. mmol) was added dropwise and the solution was stirred for 5 min at 0 C. 7 In a second dry and argon-flushed Schlenk flask, according to TP,,4-dithiine (; 6 mg, mmol) was dissolved in dry THF (2 ml). TMPMgCl LiCl (4 ml,. mmol) was added dropwise at -40 C and the reaction mixture was stirred for h. Then, the previously prepared methylene(dimethyl)iminium trifluoroacetate was added at -78 C to the magnesiated,4-dithiin solution. The reaction mixture was stirred for 3 h warming to 25 ºC. The crude mixture was quenched with sat. aq. NaHCO 3 and extracted with EtOAc (3 x 20 ml). The combined organic layers were washed with sat. aq. NaCl and dried over anhydrous Na 2SO 4. After filtration, the solvents were evaporated in vacuo. The crude product was purified by flash column 7 V. Werner, M. Ellwart, A. J. Wagner, P. Knochel, Org. Lett. 205, 7, S9
10 chromatography on silica gel (ihexane/etoac, 8:2) yielding 9e as orange oil (00 mg, 58%). H NMR (400 MHz, CDCl 3) δ/ppm: 6.26 (d, J=7.0 Hz, H), 6.24 (d, J=7.0 Hz, H), 6.02 (s, H), 3.0 (s, 2 H), 2.24 (s, 6 H). 3 C NMR (0 MHz, CDCl 3) δ/ppm: 35.5, 22.3, 2.9, 7.3, 64.5, IR (Diamond-ATR, neat) ~ /cm - : 3025, 2973, 2942, 2853, 287, 277, 538, 464, 450, 35, 262, 225, 74, 47, 09, 042, 023, 982, 890, 859, 834, 809, 782, 73, 668. MS (70 ev, EI) m/z (%): 73 (23), 30 (6), 97 (8), 58 (00), 45 (), 44 (6), 43 (8), 42 (), 4 (7). HRMS (EI): m/z (M + ) for C 7H NS 2: calcd ; found Synthesis of (,4-dithiin-2-yl)(phenyl)methanol (9f) According to TP,,4-dithiine (; 58 mg, mmol) was dissolved in dry THF ( ml). TMPMgCl LiCl (0 ml, 5 mmol) was added dropwise at -40 C and the reaction mixture was stirred for h. The freshly prepared magnesium reagent was added to a solution of benzaldehyde (37 mg, 5 mmol) in dry THF ( ml) at -78 C. The resulting solution was stirred at this temperature for 2 h and was then quenched with sat. aq. NH 4Cl solution (5 ml), extracted with Et 2O (3 x 0 ml) and dried over anhydrous Na 2SO 4. After filtration, the solvents were evaporated in vacuo. The crude product was purified by flash column chromatography on silica gel (ihexane/etoac, 7:) yielding 9f as yellowish solid (75 mg, 97%). m.p.: C. H NMR (400 MHz, CDCl 3) δ/ppm: (m, 6 H), 6.34 (d, J=6.8 Hz, H), 6.28 (s, H), 6.20 (d, J=6.8 Hz, H), 5.36 (s, H), 2.6 (br. s., H). 3 C NMR (0 MHz, CDCl 3) δ/ppm: 4, 39.6, 28.5, 28.3, 26.6, 23.7, 2.9, 8.3, IR (Diamond-ATR, neat) ~ /cm - : 379, 327, 3029, 306, 2894, 2666, 957, 887, 728, 7, 598, 587, 573, 564, 537, 492, 46, 446, 392, 372, 322, 30, 267, 28, 87, 77, 57, 42, 092, 070, 03, 0, 99, 892, 859, 827, 794, 777, 748, 699, 687, 672. MS (70 ev, EI) m/z (%): 223 (5), 222 (00), 6 (60), 07 (23), 05 (36), 03 (3), 79 (54), 77 (64), 7 (36), 58 (), 45 (23). HRMS (EI): m/z (M + ) for C H 0OS 2: calcd ; found S0
11 .7. Synthesis of ethyl,4-dithiine-2-carboxylate (9g) According to TP,,4-dithiine (; 697 mg, 6.0 mmol) was dissolved in dry THF (2 ml). TMPMgCl LiCl (5.95 ml, 6.6 mmol) was added dropwise at -40 C and the reaction mixture was stirred for h. The freshly prepared magnesium reagent was added to a solution of ethyl cyanoformate (47 mg, 4.2 mmol) in dry THF (6 ml) at -60 C. The resulting solution was stirred at this temperature for 2 h and was then quenched with sat. aq. NH 4Cl solution (0 ml), extracted with Et 2O (3 x 70 ml) and dried over anhydrous Na 2SO 4. After filtration, the solvents were evaporated in vacuo. The crude product was purified by flash column chromatography on silica gel (ihexane/et 2O, 95:5) yielding 9g as red liquid (704 mg, 89%). H NMR (300 MHz, CDCl 3) δ/ppm: 7.29 (s, H), 6.9 (d, J=7. Hz, H), 6.03 (d, J=7. Hz, H), 4.26 (q, J=7. Hz, 2 H),.32 (t, J=7. Hz, 4 H). 3 C NMR (0 MHz, CDCl 3) δ/ppm: 6., 33.8, 25.6, 22.0, 9.6, 62.0, 4.. IR (Diamond-ATR, neat) ~ /cm - : 3037, 2980, 2932, 2904, 702, 573, 533, 464, 444, 39, 366, 292, 243, 28, 7,, 094, 040, 994, 973, 889, 850, 830, 790, 73, 666. MS (70 ev, EI) m/z (%): 90 (2), 89 (2), 88 (00), 62 (0), 60 (9), 43 (6), 42 (26), 5 (22), 4 (8), (9). HRMS (EI): m/z (M + ) for C 7H 8O 2S 2: calcd ; found Synthesis of (,4-dithiin-2-yl)(phenyl)methanone (9h) According to TP,,4-dithiine (;.6 g, 0.0 mmol) was dissolved in dry THF (20 ml). TMPMgCl LiCl (9.9 ml, mmol) was added dropwise at -40 C and the reaction mixture was stirred for h. ZnCl 2 solution (2.0 ml, 2.0 mmol, M in THF) was added and the reaction mixture was allowed to stir for 5 min. CuCN.2LiCl solution (2.0 ml, 2.0 mmol, M in THF) was added and the reaction mixture was allowed to stir for 5 min, before benzoyl chloride (984 mg, 7.0 mmol) was added. The reaction mixture was stirred at 25 C for 2 h and was then quenched with sat. aq. NH 4Cl/NH 3 solution (8:, 50 ml), extracted with Et 2O (3 x 00 ml) and dried over anhydrous Na 2SO 4. After filtration, the solvents were evaporated in vacuo. The crude product was purified by flash column chromatography on silica gel (ihexane/et 2O, 94:6) yielding 9h as red liquid (.20 g, 78%). H NMR (400 MHz, CDCl 3) δ/ppm: 7.69 (d, J=7.6 Hz, 2 H), 7.56 (t, J=7.6 Hz, H), 7.45 (t, J=7.6 Hz, 2 H), 6.96 (s, H), 6.28 (d, J=7.6 Hz, H), 6.0 (d, J=7.6 Hz, H). S
12 3 C NMR (0 MHz, CDCl 3) δ/ppm: 88.6, 37.0, 36.8, 34.2, 32.5, 29., 28.4, 22.6, 9.7. IR (Diamond-ATR, neat) ~ /cm - : 3092, 3035, 2973, 2955, 2928, 2868, 2360, 748, 693, 638, 563, 528, 468, 396, 366, 26, 26, 020, 938, 900, 872, 858, 770, 737, 666. MS (70 ev, EI) m/z (%): 220 (40), 05 (00), 77 (63). HRMS (EI): m/z (M + ) for C H 8OS 2: calcd ; found Synthesis of cyclopropyl(,4-dithiin-2-yl)methanone (9i) According to TP,,4-dithiine (; 232 mg, 2.0 mmol) was dissolved in dry THF (4 ml). TMPMgCl LiCl (.98 ml, 2.2 mmol) was added dropwise at -40 C and the reaction mixture was stirred for h. ZnCl 2 solution (2.4 ml, 2.4 mmol, M in THF) was added and the reaction mixture was allowed to stir for 5 min. CuCN.2LiCl solution (2.4 ml, 2.4 mmol, M in THF) was added and the reaction mixture was allowed to stir for 5 min, before cyclopropanecarbonyl chloride (46 mg,.4 mmol) was added. The reaction mixture was stirred at 25 C for 20 h and was then quenched with sat. aq. NH 4Cl/NH 3 solution (8:, 5 ml), extracted with Et 2O (3 x 0 ml) and dried over anhydrous Na 2SO 4. After filtration, the solvents were evaporated in vacuo. The crude product was purified by flash column chromatography on silica gel (ihexane/et 2O, 9:) yielding 9i as red oil (68 mg, 65%). H NMR (400 MHz, CDCl 3) δ/ppm: 7.3 (s, H), 6.20 (d, J=7.4 Hz, H), 6.06 (d, J=7.4 Hz, H), (m, H), (m, 2 H), 2-0 (m, 2 H). 3 C NMR (0 MHz, CDCl 3) δ/ppm: 92.6, 35.2, 33.2, 22.3, 9.7, 7.3,.8. IR (Diamond-ATR, neat) ~ /cm - : 3033, 2360, 2086, 645, 56, 528, 438, 48, 385, 292, 98, 6, 28, 090, 06, 029, 984, 925, 878, 792, 78. MS (70 ev, EI) m/z (%): 203 (98), 86 (2), 85 (3), 84 (00), 6 (5), 5 (20), (0), 05 (2), 85 (), 7 (30), 69 (88), 45 (32), 44 (3), 4 (6). HRMS (EI): m/z (M + ) for C 8H 8OS 2: calcd ; found Synthesis of 2-(cyclohex-2-en--yl)-,4-dithiine (9j) S2
13 According to TP,,4-dithiine (; 58 mg, mmol) was dissolved in dry THF ( ml). TMPMgCl LiCl (0 ml, 5 mmol) was added dropwise at -40 C and the reaction mixture was stirred for h. ZnCl 2 solution ( ml, mmol, M in THF) was added and the reaction mixture was allowed to stir for 5 min. CuCN.2LiCl solution ( ml, mmol, M in THF) was added and the reaction mixture was allowed to stir for 5 min, and afterwards, 3-bromocyclohexene (56 mg, 5 mmol) was added. The reaction mixture was stirred at 25 C for 2 h and was then quenched with sat. aq. NH 4Cl/NH 3 solution (8:, 5 ml), extracted with Et 2O (3 x 0 ml) and dried over anhydrous Na 2SO 4. After filtration, the solvents were evaporated in vacuo. The crude product was purified by flash column chromatography on silica gel (ihexane) yielding 9j as yellow oil (50 mg, 73%). H NMR (300 MHz, CDCl 3) δ/ppm: 6.35 (d, J=6.8 Hz, H), 6.30 (d, J=6.8 Hz, H), 5.92 (s, H), (m, H), (m, H), (m, H), (m, 2 H), (m, H), (m, 2 H), (m, H). 3 C NMR (0 MHz, CDCl 3) δ/ppm: 42.4, 29.8, 27.7, 23.4, 22.6, 5.6, 42.4, 28.6, 24.9, 2. IR (Diamond-ATR, neat) ~ /cm - : 309, 2926, 2856, 283, 720, 647, 584, 535, 444, 429, 343, 22, 59, 34, 086, 045, 09, 978, 964, 898, 887, 869, 805, 793, 784, 772, 734, 723, 708, 669, 652, 624, 62, 596, 587, 576, 57, 568, 564, 555. MS (70 ev, EI) m/z (%): 96 (20), 79 (23), 77 (2), 53 (34), 52 (22), 45 (00). HRMS (EI): m/z (M + ) for C 0H 2S 2: calcd ; found Synthesis of 2-(,4-dithiin-2-yl)aniline (9k) According to TP,,4-dithiine (;.6 g, 0.0 mmol) was dissolved in dry THF (20 ml). TMPMgCl LiCl (9.9 ml, mmol) was added dropwise at -40 C and the reaction mixture was stirred for h. ZnCl 2 solution (2.0 ml, 2.0 mmol, M in THF) was added and the reaction mixture was allowed to stir for 5 min. The freshly prepared zinc reagent was added over h to a solution of 2-iodoaniline (.75 g, 8.0 mmol), Pd(dba) 2 (73 mg, mmol) and P(2-furyl) 3 (39 mg, mmol) in dry THF (7 ml) at 25 C. The reaction mixture was stirred at 25 C for 6 h and was then quenched with sat. aq. NH 4Cl solution (50 ml), extracted with Et 2O (3 x 00 ml) and dried over anhydrous Na 2SO 4. After filtration, the solvents were evaporated in vacuo. The crude product was purified by flash column chromatography on silica gel (ihexane/etoac, 4:) yielding 9k as yellow oil (.56 g, 94%). H NMR (400 MHz, CDCl 3) δ/ppm: (m, 2 H), (m, 2 H), 6.46 (d, J=6.8 Hz, H), 6.39 (d, J=6.8 Hz, H), 6.20 (s, H), 3.93 (br. s., 2 H). S3
14 3 C NMR (0 MHz, CDCl 3) δ/ppm: 43.9, 35.0, 3, 29.7, 23.0, 22.8, 22.8, 9., 8.5, 6.0. IR (Diamond-ATR, neat) ~ /cm - : 3435, 3352, 3204, 3024, 2923, 2853, 2620, 936, 669, 6, 575, 533, 486, 450, 365, 302, 28, 256, 2, 57, 38, 054, 032, 007, 939, 90, 855, 792, 777, 746, 673, 655, 634, 577, 558. MS (70 ev, EI) m/z (%): 207 (90), 90 (37), 74 (94), 73 (5), 30 (55), 7 (00), 90 (6), 89 (47), 77 (6), 63 (7), 58 (), 57 (), 45 (40), 43 (). HRMS (EI): m/z (M + ) for C 0H 9NS 2: calcd ; found Synthesis of di(,4-dithiin-2-yl)sulfane (9l) According to TP,,4-dithiine (; 348 mg, 2.0 mmol) was dissolved in dry THF (4 ml). TMPMgCl LiCl (2.0 ml, 2.2 mmol) was added dropwise at -40 C and the reaction mixture was stirred for h. Bis(phenylsulfonyl)sulfide (20, 34 mg, mmol) in dry THF (2 ml) was added at -78 C and stirred for 2 h allowing to reach 23 C. The resulting solution was then quenched with sat. aq. NH 4Cl solution (0 ml), extracted with EtOAc (3 x 20 ml) and dried over anhydrous Na 2SO 4. After filtration, the solvents were evaporated in vacuo. The crude product was purified by flash column chromatography on silica gel (ihexane/ch 2Cl 2, 9:) yielding 9l as brown solid (96 mg, 75%). m.p.: C. H NMR (400 MHz, CDCl 3) δ/ppm: 6.4 (s, 2 H), (m, 4 H). 3 C NMR (0 MHz, CDCl 3) δ/ppm: 26.9, 24.2, 22.8, IR (Diamond-ATR, neat) ~ /cm - : 3026, 292, 2850, 680, 573, 52, 276, 26, 25, 34, 090, 020, 883, 82, 769. MS (70 ev, EI) m/z (%): 262 (32), 47 (4), 03 (00), 7 (30), 45 (34), 44 (53). HRMS (EI): m/z (M + ) for C 8H 6S 5: calcd ; found Preparation of difunctionalized,4-dithiine derivatives 2.. Synthesis of,'-(,4-dithiine-2,3-diyl)bis(n,n-dimethylmethanamine) (a) A dry and argon-flushed Schlenk-flask was charged with N,N,N,N - tetramethylmethanediamine (45 mg, 4 mmol) and anydrous CH 2Cl 2 (4 ml). Trifluoroacetic anhydride (92 mg, 4 mmol) was added dropwise and the solution was S4
15 stirred for 5 min at 0 C. 7 In a second dry and argon-flushed Schlenk flask, according to TP2, -(,4-dithiin-2-yl)-N,N-dimethylmethanamine (9e; 69 mg, mmol) was dissolved in dry THF ( ml). TMPMgCl LiCl ( ml, mmol) was added dropwise at -78 C and the reaction mixture was stirred for h. Then, the previously prepared methylene(dimethyl)iminium trifluoroacetate was added at -78 C to the magnesiated - (,4-dithiin-2-yl)-N,N-dimethylmethanamine solution. The reaction mixture was stirred for h at -78 C. The crude mixture was quenched with sat. aq. NaHCO 3 and extracted with EtOAc (3 x 20 ml). The combined organic layers were washed with sat. aq. NaCl and dried over anhydrous Na 2SO 4. After filtration, the solvents were evaporated in vacuo. The crude product was purified by flash column chromatography on silica gel (ihexane/etoac, 8:2) yielding a as orange oil (59 mg, 64%). H NMR (400 MHz, CDCl 3) δ/ppm: 6.43 (s, 2 H), 3.7 (s, 4 H), 2.27 (s, 2 H). 3 C NMR (0 MHz, CDCl 3) δ/ppm: 3.7, 24.3, 6.7, IR (Diamond-ATR, neat) ~ /cm - : 3388, 2973, 294, 2853, 287, 2767, 609, 536, 453, 344, 260, 75, 35, 096, 04, 029, 007, 947, 9, 84, 804, 770, 73, 67. MS (70 ev, EI) m/z (%): 230 (), 85 (00), 4 (2), 40 (47), 29 (), 94 (2), 58 (79), 42 (2). HRMS (EI): m/z (M + ) for C 0H 8N 2S 2: calcd ; found Synthesis of -(3-chloro-,4-dithiin-2-yl)-N,N-dimethylmethanamine (b) According to TP2, -(,4-dithiin-2-yl)-N,N-dimethylmethanamine (9e; 74 mg, 3 mmol) was dissolved in dry THF ( ml). TMPMgCl LiCl (2 ml, 5 mmol) was added dropwise at -78 C and the reaction mixture was stirred for h. hexachloroethane (53 mg, 5 mmol) was added and the resulting solution was stirred for 2 h. Then, the reaction mixture was quenched with sat. aq. NH 4Cl solution (5 ml), extracted with EtOAc (3 x 0 ml) and dried over anhydrous Na 2SO 4. After filtration, the solvents were evaporated in vacuo. The crude product was purified by flash column chromatography on silica gel (ihexane/etoac, 8:2) yielding b as orange oil (38 mg, 43%). H NMR (400 MHz, CDCl 3) δ/ppm: 6.46 (d, J=6.4 Hz, H), 6.40 (d, J=6.4 Hz, H), 3.26 (s, 2 H), 2.28 (s, 6 H). 3 C NMR (0 MHz, CDCl 3) δ/ppm: 29.9, 24.4, 22.7, 9.2, 62.0, 45.. IR (Diamond-ATR, neat) ~ /cm - : 2974, 2943, 2856, 2820, 2772, 587, 562, 535, 453, 348, 262, 74, 56, 095, 042, 027, 983, 888, 842, 80, 746, 673. MS (70 ev, EI) m/z (%): 209 (9), 207 (23), 7 (4), 58 (00), 55 (5), 45 (5), 44 (7), 4 (5). HRMS (EI): m/z (M + ) for C 7H 0ClNS 2: calcd ; found S5
16 2.3. Synthesis of ethyl 3-iodo-,4-dithiine-2-carboxylate (c) According to TP2, ethyl,4-dithiine-2-carboxylate (9g; 9 g, 5.8 mmol) was dissolved in dry THF (20 ml). TMPMgCl LiCl (5.76 ml, 6.39 mmol) was added dropwise at -78 C and the reaction mixture was stirred for h. The freshly prepared magnesium reagent was added to a solution of iodine (3 g, 4.07 mmol) in dry THF (6 ml) at -78 C. The resulting solution was stirred at this temperature for h and was then quenched with sat. aq. Na 2S 2O 3 solution (50 ml), extracted with Et 2O (3 x 00 ml) and dried over anhydrous Na 2SO 4. After filtration, the solvents were evaporated in vacuo. The crude product was purified by flash column chromatography on silica gel (ihexane/ch 2Cl 2, 2:) yielding c as orange liquid (793 mg, 62%). H NMR (400 MHz, CDCl 3) δ/ppm: 6.6 (d, J = 6.2 Hz, H), 6.25 (d, J = 6.2 Hz, H), 4.3 (q, J = 7.2 Hz, 2H),.37 (t, J = 7. Hz, 3H). 3 C NMR (0 MHz, CDCl 3) δ/ppm: 62.2, 26.6, 24.4, 23.5, 83.2, 62.5, 4.0. IR (Diamond-ATR, neat) ~ /cm - : 3033, 2979, 2934, 70, 60, 558, 50, 463, 443, 388, 365, 22, 3, 093, 030, 889, 85, 795, 76, 676. MS (70 ev, EI) m/z (%): 34 (00), 59 (69), 44 (0), 5 (6), 4 (20), 88 (2), 7 (3), 58 (0), 45 (4). HRMS (EI): m/z (M + ) for C 7H 7O 2IS 2: calcd ; found Synthesis of diethyl,4-dithiine-2,3-dicarboxylate (d) According to TP2, ethyl,4-dithiine-2-carboxylate (9g; 88 mg, mmol) was dissolved in dry THF (2 ml). TMPMgCl LiCl (5 ml, 5 mmol) was added dropwise at -78 C and the reaction mixture was stirred for h. Ethyl cyanoformate (49 mg,.5 mmol) was added and the resulting solution was stirred at this temperature for 3 h. Then, the reaction mixture was quenched with sat. aq. NH 4Cl solution (5 ml), extracted with EtOAc (3 x 0 ml) and dried over anhydrous Na 2SO 4. After filtration, the solvents were evaporated in vacuo. The crude product was purified by flash column chromatography on silica gel (ihexane/etoac, 8:2) yielding d as orange oil (234 mg, 90%). H NMR (400 MHz, CDCl 3) δ/ppm: 6.4 (s, 2 H), 4.28 (q, J=7.2 Hz, 4 H),.33 (t, J=7. Hz, 6 H). 3 C NMR (0 MHz, CDCl 3) δ/ppm: 62.3, 33.3, 23.8, 62.6, 3.9. IR (Diamond-ATR, neat) ~ /cm - : 3040, 2982, 2938, 2904, 74, 580, 537, 464, 444, 390, 366, 230, 3, 094, 069, 022, 965, 906, 853, 795, 765, 743, 680. S6
17 MS (70 ev, EI) m/z (%): 260 (00), 60 (36), 59 (25), 42 (34), 7 (9), 43 (35). HRMS (EI): m/z (M + ) for C 0H 2O 4S 2: calcd ; found Synthesis of 2,3-diiodo-,4-dithiine (e) According to TP2, 2-iodo-,4-dithiine (a; 242 mg, mmol) was dissolved in dry THF (2 ml). TMPZnCl LiCl (3 ml,. mmol) was added dropwise at -40 C and the reaction mixture was stirred for h. The freshly prepared zinc reagent was added to a solution of iodine (77 mg, mmol) in dry THF ( ml) at -78 C. The resulting solution was stirred at this temperature for h and was then quenched with sat. aq. Na 2S 2O 3 solution (5 ml), extracted with Et 2O (3 x 0 ml) and dried over anhydrous Na 2SO 4. After filtration, the solvents were evaporated in vacuo. The crude product was purified by flash column chromatography on silica gel (ihexane) yielding e as yellow solid (75 mg, 68%). m.p.: C. H NMR (400 MHz, CDCl 3) δ/ppm: 6.43 (s, 2H). 3 C NMR (0 MHz, CDCl 3) δ/ppm: 23.4, IR (Diamond-ATR, neat) ~ /cm - : 3024, 2962, 592, 544, 485, 260, 092, 020, 885, 872, 790, 757, 67. MS (70 ev, EI) m/z (%): 368 (58), 24 (95), 27 (2), 4 (00), 88 (49), 6 (3), 45 (3), 43 (7). HRMS (EI): m/z (M + ) for C 4H 2I 2S 2: calcd : found Synthesis of 2,3-dibromo-,4-dithiine (f) According to TP2, 2-bromo-,4-dithiine (9b; 969 mg, 5.0 mmol) was dissolved in dry THF (0 ml). TMPZnCl LiCl (6.4 ml, 5.5 mmol) was added dropwise at -40 C and the mixture was stirred for h.,2-dibromotetrachloroethane (2.4 g, 7.5 mmol) in dry THF (4mL) was added and the resulting solution was stirred for 2 h and allowed to reach 23 C. Then, the reaction mixture was quenched with sat. aq. NH 4Cl solution (20 ml), extracted with EtOAc (3 x 50 ml) and dried over anhydrous Na 2SO 4. After filtration, the solvents were evaporated in vacuo. The crude product was purified by HPLC yielding f as light brown oil (680 mg, 50%). H NMR (400 MHz, CDCl 3) δ/ppm: 6.47 (s, 2 H). 3 C NMR (0 MHz, CDCl 3) δ/ppm: 23.6, S7
18 IR (Diamond-ATR, neat) ~ /cm - : 3032, 594, 548, 523, 275, 258, 28, 920, 883, 86, 803, 775, 754, 79, 669. MS (70 ev, EI) m/z (%): 276 (23), 274 (33), 95 (78), 93 (64), 4 (38), (29), 97 (33), 95 (63), 9 (58), 85 (39), 83 (47), 82 (29), 8 (27), 7 (67), 69 (57), 67 (28), 57 (00), 56 (27), 55 (64), 44 (55), 43 (62), 4 (5). HRMS (EI): m/z (M + ) for C 4H 2 8 Br 2S 2: calcd ; found Synthesis of 2-allyl-3-bromo-,4-dithiine (g) According to TP2, 2-bromo-,4-dithiine (9b; 36 mg,.6 mmol) was dissolved in dry THF (3 ml). TMPZnCl LiCl (.34 ml,.78 mmol) was added dropwise at -40 C and the reaction mixture was stirred for h. CuCN.2LiCl solution (.94 ml,.94 mmol, M in THF) was added and the reaction mixture was allowed to stir for 5 min, before allyl bromide (37 mg,. mmol) was added. The reaction mixture was stirred at -40 C for h and was then quenched with sat. aq. NH 4Cl/NH 3 solution (8:, 5 ml), extracted with Et 2O (3 x 0 ml) and dried over anhydrous Na 2SO 4. After filtration, the solvents were evaporated in vacuo. The crude product was purified by flash column chromatography on silica gel (ihexane) yielding g as yellow liquid (9 mg, 74%). H NMR (400 MHz, CDCl 3) δ/ppm: 6.47 (d, J=6.6 Hz, H), 6.38 (d, J=6.6 Hz, H), 5.77 (ddt, J=6.7,, 6.3, 6.0 Hz, H), (m, 2 H), 3.23 (d, J=6.0 Hz, 2 H). 3 C NMR (0 MHz, CDCl 3) δ/ppm: 32.0, 32.0, 23.7, 23.4, 7.7, 03.2, 4.5. IR (Diamond-ATR, neat) ~ /cm - : 3032, 308, 2925, 2853, 2832, 78, 648, 585, 563, 556, 520, 500, 492, 466, 433, 43, 34, 275, 24, 80, 62, 33, 090, 053, 029, 02, 979, 966, 95, 899, 885, 865, 822, 798, 780, 778, 74, 730, 705, 668, 654. MS (70 ev, EI) m/z (%): 236 (78), 234 (75), 95 (6), 93 (6), 55 (28), 53 (), 40 (4), 27 (3), 25 (0), 23 (9), 22 (00), 2 (38), (23), 97 (20), 95 (), 85 (4), 83 (4), 8 (0), 7 (22), 69 (32), 57 (28), 55 (6), 45 (27), 44 (4), 43 (28), 4 (2). HRMS (EI): m/z (M + ) for C 7H 7BrS 2: calcd ; found Synthesis of 3-iodo-,4-dithiine-2-carbonitrile (h) According to TP2,,4-dithiine-2-carbonitrile (9d; 93 mg, 6 mmol) was dissolved in dry THF (3 ml). TMPZnCl LiCl (5 ml, 3 mmol) was added dropwise at 0 C and the reaction mixture was stirred for h. The freshly prepared zinc reagent was added to a solution of iodine (7 mg, 6 mmol) in dry THF ( ml) at -78 C. The resulting solution was stirred at this temperature for h and was then quenched with sat. aq. Na 2S 2O 3 S8
19 solution (5 ml), extracted with Et 2O (3 x 0 ml) and dried over anhydrous Na 2SO 4. After filtration, the solvents were evaporated in vacuo. The crude product was purified by flash column chromatography on silica gel (ihexane/ch 2Cl 2, 2:) yielding h as orange liquid (06 mg, 86%). H NMR (400 MHz, CDCl 3) δ/ppm: 6.62 (d, J=6.2 Hz, H), 6.3 (d, J=6.2 Hz, H). 3 C NMR (0 MHz, CDCl 3) δ/ppm: 24.3, 22., 6.0, 09.0, IR (Diamond-ATR, neat) ~ /cm - : 3039, 3028, 2954, 2920, 285, 222, 594, 573, 553, 522, 502, 463, 373, 28, 262, 30, 072, 054, 022, 892, 874, 84, 802, 79, 730, 679, 60, 557. MS (70 ev, EI) m/z (%): 267 (84), 42 (0), 4 (4), 40 (00), 27 (3), 4 (0), 96 (6), 82 (0), 45 (5). HRMS (EI): m/z (M + ) for C 5H 2NIS 2: calcd ; found Synthesis of (3-iodo-,4-dithiin-2-yl)(phenyl)methanone (i) According to TP2, (,4-dithiin-2-yl)(phenyl)methanone (9h; 220 mg, mmol) was dissolved in dry THF (2 ml). TMPZnCl LiCl (3 ml,. mmol) was added dropwise at 0 C and the reaction mixture was stirred for h. The freshly prepared zinc reagent was added to a solution of iodine (78 mg, mmol) in dry THF ( ml) at -78 C. The resulting solution was stirred at this temperature for h and was then quenched with sat. aq. Na 2S 2O 3 solution (5 ml), extracted with Et 2O (3 x 0 ml) and dried over anhydrous Na 2SO 4. After filtration, the solvents were evaporated in vacuo. The crude product was purified by flash column chromatography on silica gel (ihexane/ch 2Cl 2, 2:) yielding i as orange oil (89 mg, 78%). H NMR (400 MHz, CDCl 3) δ/ppm: 7.88 (d, J=7.8 Hz, 2 H), 7.65 (t, J=7.3 Hz, H), 7.5 (t, J=7.6 Hz, 2 H), 6.66 (d, J=6.4 Hz, H), 6.55 (d, J=6.4 Hz, H). 3 C NMR (0 MHz, CDCl 3) δ/ppm: 9.2, 34.4, 33.4, 33.0, 30.0, 28.9, 25.9, 22.4, IR (Diamond-ATR, neat) ~ /cm - : 303, 2923, 963, 656, 594, 578, 528, 447, 3, 234, 75, 60, 30, 055, 022, 999, 974, 935, 894, 806, 782, 727, 677. MS (70 ev, EI) m/z (%): 348 (), 347 (3), 346 (98), 220 (3), 29 (4), 9 (6), 90 (25), 47 (2), 05 (00), 77 (72), 5 (26), 43 (45). HRMS (EI): m/z (M + ) for C H 7OIS 2: calcd ; found Preparation of 2,3,5-tribromo-,4-dithiine (2) S9
20 2,3-dibromo-,4-dithiine (g; 23 mg, 8 mmol) was dissolved in dry CH 2Cl 2 (2 ml). Bromine (3 mg, 3 mmol) in dry CH 2Cl 2 (2 ml) and Et 3N (9 ml,.33 mmol) were added dropwise at 0 C. The reaction was stirred for 24 h and allowed to reach 23 C. Then, the reaction mixture was quenched with aq. HCl solution (5.0 ml, 2.0 M) and extracted with CH 2Cl 2 (3 x 0 ml) The combined organic phases were washed with water and brine and dried over anhydrous Na 2SO 4. After filtration, the solvents were evaporated in vacuo. The crude product was purified by flash column chromatography on silica gel (ihexane) yielding 2 as white solid (230 mg, 84%). m.p.: C H NMR (400 MHz, CDCl 3) δ/ppm: 6.52 (s, H). 3 C NMR (0 MHz, CDCl 3) δ/ppm: 22.0,,, IR (Diamond-ATR, neat) ~ /cm - : 3035, 2358, 553, 532, 59, 222, 206, 94, 97, 860, 809, 776, 757, 720, 72. MS (70 ev, EI) m/z (%): 356 (2), 354 (7), 352 (6), 350 (2), 275 (0), 273 (9), 27 (9), 94 (), 92 (), 6 (6), 45 (5), 44 (2), 43 (00), 4 (5). HRMS (EI): m/z (M + ) for C 4H 79 Br 3S 2: calcd ; found Preparation of perbromo-,4-dithiine (3) 2,3,5-Tribromo-,4-dithiine (2; 57 mg,.5 mmol) was dissolved in dry THF (9 ml). TMPZnCl LiCl (.8 ml,.6 mmol) was added dropwise at -78 C and the mixture was stirred for 5 min.,2-dibromotetrachloroethane (723 mg, 2.2 mmol) in dry THF ( ml) was added and the resulting solution was allowed to reach 23 C for 24 h, after which time it was warmed to 50 C and stirred for further 2 h.. Then, the reaction mixture was quenched with sat. aq. NH 4Cl solution (5 ml), extracted with EtOAc (3 x 0 ml) and dried over anhydrous Na 2SO 4. After filtration, the solvents were evaporated in vacuo. The crude product was purified by flash column chromatography on silica gel (ihexane) yielding 3 as white solid (357 mg, 56%). m.p.: C NMR (0 MHz, CDCl 3) δ/ppm:. IR (Diamond-ATR, neat) ~ /cm - : 3078, 3028, 292, 285, 64, 593, 556, 530, 54, 423, 407, 265, 08, 047, 985, 937, 94, 884, 848, 830, 798, 769, 676. S20
21 MS (70 ev, EI) m/z (%): 434 (8), 432 (25), 430 (8), 355 (35), 353 (00), 35 (94), 349 (29), 274 (36), 272 (69), 270 (32), 49 (24), 47 (23), 37 (3), 35 (29), 88 (39), 68 (30). HRMS (EI): m/z (M + ) for C 4 79 Br 4S 2: calcd ; found Preparation of monosubstituted,4,5,8-tetrathianaphthalene 5.. Synthesis of 2-iodo-[,4]dithiino[2,3-b][,4]dithiine (4a) According to TP3,,4,5,8-tetrathianaphthalene (4; 02 mg, mmol) was dissolved in dry THF (4 ml). TMPMgCl LiCl ( ml, mmol) was added dropwise at -78 C and the mixture was stirred for 0 min. Iodine (9 mg, 5 mmol) in dry THF ( ml) was added and the resulting solution was stirred at this temperature for 2 h. Then, the reaction mixture was quenched with sat. aq. Na 2S 2O 3 solution (5 ml), extracted with EtOAc (3 x 0 ml) and dried over anhydrous Na 2SO 4. After filtration, the solvents were evaporated in vacuo. The crude product was purified by flash column chromatography on silica gel (ihexane) yielding 4a as yellow solid (47 mg, 89%). m.p.: C. H NMR (400 MHz, CDCl 3) δ/ppm: 6.70 (s, H), 6.47 (d, J=6.6 Hz, H), 6.44 (d, J=6.6 Hz, H). 3 C NMR (0 MHz, CDCl 3) δ/ppm: 29.4, 25.7, 25.6, 2, 2, IR (Diamond-ATR, neat) ~ /cm - : 3025, 2926, 607, 568, 533, 50, 470, 366, 260, 23, 28, 965, 906, 887, 864, 834, 80, 778, 759, 733. MS (70 ev, EI) m/z (%): 330 (86), 285 (4), 203 (78), 59 (00), 46 (46), 27 (32), 88 (69), 69 (48), 57 (36), 45 (55). HRMS (EI): m/z (M + ) for C 6H 3IS 4: calcd ; found Synthesis of 2-bromo-[,4]dithiino[2,3-b][,4]dithiine (4b) According to TP3,,4,5,8-tetrathianaphthalene (4; 02 mg, mmol) was dissolved in dry THF (4 ml). TMPMgCl LiCl ( ml, mmol) was added dropwise at -78 C and the mixture was stirred for 0 min.,2-dibromotetrachloroethane (244 mg, 5 mmol) in dry THF ( ml) was added and the resulting solution was stirred at this temperature for 2 h. Then, the reaction mixture was quenched with sat. aq. NH 4Cl solution (5 ml), extracted with EtOAc (3 x 0 ml) and dried over anhydrous Na 2SO 4. After filtration, the solvents were evaporated in vacuo. The crude product was purified by flash column chromatography on silica gel (ihexane) yielding 4b as yellow solid (26 mg, 89%). S2
22 m.p.: C. H NMR (400 MHz, CDCl 3) δ/ppm: 6.53 (s, H), (m, 2 H). 3 C NMR (0 MHz, CDCl 3) δ/ppm: 25.9, 25.6, 23.8, 2.8, 9.6, 2.8. IR (Diamond-ATR, neat) ~ /cm - : 3032, 2923, 55, 538, 57, 280, 263, 208, 35, 966, 904, 870, 850, 804, 782, 759, 70, 673. MS (70 ev, EI) m/z (%): 284 (67), 282 (60), 239 (47), 237 (44), 203 (86), 59 (00), 27 (54), 88 (79), 69 (40), 45 (5). HRMS (EI): m/z (M + ) for C 6H 3 8 BrS 4: calcd ; found Synthesis of [,4]dithiino[2,3-b][,4]dithiine-2-carbonitrile (4c) According to TP3,,4,5,8-tetrathianaphthalene (4; 02 mg, mmol) was dissolved in dry THF (4 ml). TMPMgCl LiCl ( ml, mmol) was added dropwise at -78 C and the mixture was stirred for 0 min. 4-Tolylsulfonyl cyanide (36 mg, 5 mmol) in dry THF ( ml) was added and the resulting solution was stirred for 2 h allowing to reach 23 C. Then, the reaction mixture was quenched with sat. aq. NH 4Cl solution (5 ml), extracted with EtOAc (3 x 0 ml) and dried over anhydrous Na 2SO 4. After filtration, the solvents were evaporated in vacuo. The crude product was purified by flash column chromatography on silica gel (ihexane/etoac, 96:4) yielding 4c as orange solid (84 mg, 73%). m.p.: C. H NMR (400 MHz, CDCl 3) δ/ppm: 7.3 (s, H), 6.49 (d, J=6.4 Hz, H), 6.46 (d, J=6.4 Hz, H). 3 C NMR (0 MHz, CDCl 3) δ/ppm: 43.3, 25.7, 25.2, 20.0, 8.6, 3.7, IR (Diamond-ATR, neat) ~ /cm - : 3027, 2222, 578, 559, 543, 506, 28, 263, 23, 9, 099, 062, 966, 885, 862, 852, 803, 767, 678. MS (70 ev, EI) m/z (%): 23 (4), 229 (20), 96 (4), 86 (4), 84 (29), 65 (8), 59 (8), 53 (6), 02 (6), 88 (0), 76 (7), 73 (4), 70 (8), 6 (4), 45 (3), 43 (00), 42 (5). HRMS (EI): m/z (M + ) for C 7H 3NS 4: calcd ; found Synthesis of 2-(methylthio)-[,4]dithiino[2,3-b][,4]dithiine (4d) According to TP3,,4,5,8-tetrathianaphthalene (4; 4 mg, mmol) was dissolved in dry THF (.6 ml). TMPMgCl LiCl ( ml, 4 mmol) was added dropwise at -78 C S22
23 and the mixture was stirred for 0 min. S-Methyl thiomethanesulfonate (38 mg, mmol) was added and the resulting solution was stirred for 2 h allowing to reach 23 C. Then, the reaction mixture was quenched with sat. aq. NH 4Cl solution (5 ml), extracted with EtOAc (3 x 0 ml) and dried over anhydrous Na 2SO 4. After filtration, the solvents were evaporated in vacuo. The crude product was purified by flash column chromatography on silica gel (ihexane) yielding 4d as light yellow solid (39 mg, 78%). m.p.: C. H NMR (400 MHz, CDCl 3) δ/ppm: (m, 2 H), 6.08 (s, H), 2.40 (s, 3 H). 3 C NMR (0 MHz, CDCl 3) δ/ppm: 39.0, 25.6, 25.6, 23.4, 9.9, 6.2, 8.. IR (Diamond-ATR, neat) ~ /cm - : 309, 2977, 290, 2850, 575, 556, 539, 5, 47, 429, 4, 30, 264, 229, 34, 968, 95, 904, 888, 857, 798, 766, 735. MS (70 ev, EI) m/z (%): 250 (2), 59 (0), 70 (3), 6 (7), 45 (5), 43 (00). HRMS (EI): m/z (M + ) for C 7H 6S 5: calcd ; found Synthesis of ethyl [,4]dithiino[2,3-b][,4]dithiine-2-carboxylate (4e) According to TP3,,4,5,8-tetrathianaphthalene (4; 62 mg, 3.0 mmol) was dissolved in dry THF (24 ml). TMPMgCl LiCl (3.3 ml, 3.6 mmol) was added dropwise at -78 C and the mixture was stirred for 0 min. Ethyl cyanoformate (446 mg, 4.5 mmol) was added and the resulting solution was stirred for 2 h allowing to reach 23 C. Then, the reaction mixture was quenched with sat. aq. NH 4Cl solution (5 ml), extracted with EtOAc (3 x 0 ml) and dried over anhydrous Na 2SO 4. After filtration, the solvents were evaporated in vacuo. The crude product was purified by flash column chromatography on silica gel (ihexane/ch 2Cl 2, 8:2 to 7:3) yielding 4e as orange solid (600 mg, 72%). m.p.: C. H NMR (400 MHz, CDCl 3) δ/ppm: 7.45 (s, H), 6.49 (d, J=6.6 Hz, H), 6.44 (d, J=6.6 Hz, H), 4.25 (q, J=7. Hz, 2 H),.32 (t, J=7. Hz, 3 H). 3 C NMR (0 MHz, CDCl 3) δ/ppm: 6, 36.7, 3, 25.8, 25.0, 2, 6.8, 62.3, 4.. IR (Diamond-ATR, neat) ~ /cm - : 3033, 2979, 704, 572, 552, 463, 443, 39, 366, 263, 244, 28, 094, 040, 997, 886, 856, 828, 805, 770, 73, 677. MS (70 ev, EI) m/z (%): 295 (20), 276 (00), 23 (76), 22 (43), 207 (25), 203 (88), 59 (80), 47 (22), 46 (35), 03 (2), 9 (25), 88 (46), 85 (24), 8 (20), 76 (3), 7 (3), 70 (22), 69 (4), 69 (27), 57 (55), 55 (27), 44 (60), 43 (32), 40 (26). HRMS (EI): m/z (M + ) for C 9H 8O 2S 4: calcd ; found S23
24 5.6. Synthesis of [,4]dithiino[2,3-b][,4]dithiin-2- yl(cyclopropyl)methanone (4f) According to TP3,,4,5,8-tetrathianaphthalene (4; 02 mg, mmol) was dissolved in dry THF (4 ml). TMPMgCl LiCl ( ml, mmol) was added dropwise at -78 C and the mixture was stirred for 0 min. CuCN 2LiCl ( ml, mmol, M in THF) was then introduced followed by cyclopropanecarbonyl chloride (78 mg, 5 mmol) and the reaction warmed to 40 ºC and stirring was continued for a further 8 h. Then, the reaction mixture was quenched with sat. aq. NH 4Cl/NH 3 solution (8:, 5 ml), extracted with EtOAc (3 x 0 ml) and dried over anhydrous Na 2SO 4. After filtration, the solvents were evaporated in vacuo. The crude product was purified by flash column chromatography on silica gel (ihexane/etoac, 96:4) yielding 4f as dark red solid (89 mg, 65%). m.p.: C. H NMR (400 MHz, CDCl 3) δ/ppm: 7.48 (s, H), 6.50 (d, J=6.4 Hz, H), 6.44 (d, J=6.6 Hz, H), (m, H),. -.2 (m, 2 H), 5-6 (m, 2 H). 3 C NMR (0 MHz, CDCl 3) δ/ppm: 92.5, 39.7, 35.6, 25.9, 24.8, 2, 6.8, 7.6, 2.3. IR (Diamond-ATR, neat) ~ /cm - : 307, 3042, 303, 3004, 2954, 2923, 2853, 627, 574, 558, 542, 523, 463, 435, 47, 397, 322, 276, 262, 222, 204, 73, 27, 095, 087, 057, 030, 959, 923, 890, 878, 847, 838, 827, 8, 800, 783, 769, 732, 79, 69, 674. MS (70 ev, EI) m/z (%): 272 (00), 227 (63), 59 (59), 46 (9), 88 (2). HRMS (EI): m/z (M + ) for C 0H 8OS 4: calcd ; found Preparation of disubstituted,4,5,8-tetrathianaphthalene 6.. Synthesis of 2-iodo-3-allyl-[,4]dithiino[2,3-b][,4]dithiine (5a) According to TP4, 2-iodo-[,4]dithiino[2,3-b][,4]dithiine (4a; 99 mg, mmol) was dissolved in dry THF (2.4 ml). TMPZnCl LiCl ( ml, 3 mmol) was added dropwise at -40 C and the mixture was stirred for h. CuCN 2LiCl (0.06 ml, 0.06 mmol, M in THF) was then introduced followed by allyl bromide (54 mg, 5 mmol) and the reaction was stirred for 2 h allowing to reach 23 C. Then, the reaction mixture was quenched with sat. aq. NH 4Cl/NH 3 solution (8:, 5 ml), extracted with EtOAc (3 x 5 ml) and dried over anhydrous Na 2SO 4. After filtration, the solvents were evaporated in vacuo. S24
Efficient Mono- and Bis-Functionalization of 3,6-Dichloropyridazine using (tmp) 2 Zn 2MgCl 2 2LiCl ** Stefan H. Wunderlich and Paul Knochel*
Efficient Mono- and Bis-Functionalization of 3,6-Dichloropyridazine using (tmp) 2 Zn 2Mg 2 2Li ** Stefan H. Wunderlich and Paul Knochel* Ludwig Maximilians-Universität München, Department Chemie & Biochemie
More informationPreparation of the reagent TMPMgCl LiCl [1] (1):
Regio- and Chemoselective Magnesiation of Protected Uracils and Thiouracils using TMPMgCl LiCl and TMP 2 Mg 2LiCl upporting nformation Marc Mosrin, adège Boudet and Paul Knochel Ludwig-Maximilians-Universität
More informationDirected Zincation of Sensitive Aromatics and
1 TMPZn Li: A ew Active Selective Base for the Directed Zincation of Sensitive Aromatics and Heteroaromatics Marc Mosrin and Paul Knochel* Department Chemie & Biochemie, Ludwig-Maximilians-Universität,
More informationSupporting Information
Supporting Information Wiley-VCH 2007 69451 Weinheim, Germany (TMP) 2 Zn 2MgCl 2 2LiCl: A ew Highly Chemoselective Base for the Directed Zincation of Sensitive Aromatics and Heteroaromatics** Stefan H.
More informationCoupling with Aryl and Heteroaryl Iodides
Regioselective Zincation of Indazoles using TMP 2 Zn 2LiCl and egishi Cross- Coupling with Aryl and Heteroaryl Iodides Andreas Unsinn and Paul Knochel* Ludwig Maximilians-Universität München, Department
More informationRegioselective Metalation and Functionalization of the. Pyrazolo[1,5-a]pyridine Scaffold using Mg- and Zn-TMP Bases
Regioselective Metalation and Functionalization of the Pyrazolo[1,5-a]pyridine Scaffold using Mg- and Zn-TMP Bases Moritz Balkenhohl, Bruno Salgues, Takahiro Hirai, Konstantin Karaghiosoff, and Paul Knochel
More informationTetrahydrofuran (THF) was distilled from benzophenone ketyl radical under an argon
SUPPLEMENTARY METHODS Solvents, reagents and synthetic procedures All reactions were carried out under an argon atmosphere unless otherwise specified. Tetrahydrofuran (THF) was distilled from benzophenone
More informationSupporting Information. for. Angew. Chem. Int. Ed. Z Wiley-VCH 2004
Supporting Information for Angew. Chem. Int. Ed. Z54084 Wiley-VCH 2004 69451 Weinheim, Germany A LiCl-Mediated Br/Mg-Exchange Reaction for the Preparation of Functionalized Aryl and Heteroaryl Magnesium
More informationContent. General considerations..2 Typical procedures (TP)...4. Preparation of products.. 6. NMR-spectra...28
Electronic Supplementary Material (ESI) for Chemical Science. This journal is The Royal Society of Chemistry 2015 Content General considerations..2 Typical procedures (TP)....4 Preparation of products..
More informationSupplementary Note 1 : Chemical synthesis of (E/Z)-4,8-dimethylnona-2,7-dien-4-ol (4)
Supplementary Note 1 : Chemical synthesis of (E/Z)-4,8-dimethylnona-2,7-dien-4-ol (4) A solution of propenyl magnesium bromide in THF (17.5 mmol) under nitrogen atmosphere was cooled in an ice bath and
More informationSynthetic Studies on Norissolide; Enantioselective Synthesis of the Norrisane Side Chain
rganic Lett. (Supporting Information) 1 Synthetic Studies on Norissolide; Enantioselective Synthesis of the Norrisane Side Chain Charles Kim, Richard Hoang and Emmanuel A. Theodorakis* Department of Chemistry
More informationSupporting Information
Supporting Information Wiley-VCH 2008 69451 Weinheim, Germany Supporting Information Unmasking Representative Structures of TMP-Active Hauser and Turbo Hauser Bases Pablo García-Álvarez, David V. Graham,
More informationhydroxyanthraquinones related to proisocrinins
Supporting Information for Regiodefined synthesis of brominated hydroxyanthraquinones related to proisocrinins Joyeeta Roy, Tanushree Mal, Supriti Jana and Dipakranjan Mal* Address: Department of Chemistry,
More informationSupporting Material. 2-Oxo-tetrahydro-1,8-naphthyridine-Based Protein Farnesyltransferase Inhibitors as Antimalarials
Supporting Material 2-Oxo-tetrahydro-1,8-naphthyridine-Based Protein Farnesyltransferase Inhibitors as Antimalarials Srinivas Olepu a, Praveen Kumar Suryadevara a, Kasey Rivas b, Christophe L. M. J. Verlinde
More informationSupporting Information
Supporting Information Precision Synthesis of Poly(-hexylpyrrole) and its Diblock Copolymer with Poly(p-phenylene) via Catalyst-Transfer Polycondensation Akihiro Yokoyama, Akira Kato, Ryo Miyakoshi, and
More informationHow to build and race a fast nanocar Synthesis Information
How to build and race a fast nanocar Synthesis Information Grant Simpson, Victor Garcia-Lopez, Phillip Petemeier, Leonhard Grill*, and James M. Tour*, Department of Physical Chemistry, University of Graz,
More informationSupporting Information. Table of Contents. 1. General Notes Experimental Details 3-12
Supporting Information Table of Contents page 1. General Notes 2 2. Experimental Details 3-12 3. NMR Support for Timing of Claisen/Diels-Alder/Claisen 13 4. 1 H and 13 C NMR 14-37 General Notes All reagents
More informationSupplementary Material
10.1071/CH13324_AC CSIRO 2013 Australian Journal of Chemistry 2013, 66(12), 1570-1575 Supplementary Material A Mild and Convenient Synthesis of 1,2,3-Triiodoarenes via Consecutive Iodination/Diazotization/Iodination
More informationAn Efficient Total Synthesis and Absolute Configuration. Determination of Varitriol
An Efficient Total Synthesis and Absolute Configuration Determination of Varitriol Ryan T. Clemens and Michael P. Jennings * Department of Chemistry, University of Alabama, 500 Campus Dr. Tuscaloosa, AL
More informationSupporting Information
Supporting Information Copyright Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, 2012 Subcellular Localization and Activity of Gambogic Acid Gianni Guizzunti,* [b] Ayse Batova, [a] Oraphin Chantarasriwong,
More informationSUPPORTING INFORMATION
Y. Yamane, K. Sunahara, K. Okano, and A. Mori SUPPORTING INFORMATION Magnesium Bisamide-Mediated Halogen Dance of omothiophenes Yoshiki Yamane, Kazuhiro Sunahara, Kentaro Okano,* and Atsunori Mori Department
More informationSupplementary Material for: Unexpected Decarbonylation during an Acid- Mediated Cyclization to Access the Carbocyclic Core of Zoanthenol.
Tetrahedron Letters 1 Pergamon TETRAHEDRN LETTERS Supplementary Material for: Unexpected Decarbonylation during an Acid- Mediated Cyclization to Access the Carbocyclic Core of Zoanthenol. Jennifer L. Stockdill,
More informationSupporting Information
Supporting Information (Tetrahedron. Lett.) Cavitands with Inwardly and Outwardly Directed Functional Groups Mao Kanaura a, Kouhei Ito a, Michael P. Schramm b, Dariush Ajami c, and Tetsuo Iwasawa a * a
More informationThe First Asymmetric Total Syntheses and. Determination of Absolute Configurations of. Xestodecalactones B and C
Supporting Information The First Asymmetric Total Syntheses and Determination of Absolute Configurations of Xestodecalactones B and C Qiren Liang, Jiyong Zhang, Weiguo Quan, Yongquan Sun, Xuegong She*,,
More informationNon-Deprotonative Primary and Secondary Amination of (Hetero)Arylmetals
Supporting Information Non-Deprotonative Primary and Secondary Amination of (Hetero)Arylmetals Zhe Zhou, Zhiwei Ma, Nicole Erin Behnke, Hongyin Gao and László Kürti* Department of Chemistry, Rice University,
More informationSYNTHESIS OF A 3-THIOMANNOSIDE
Supporting Information SYNTHESIS OF A 3-THIOMANNOSIDE María B Comba, Alejandra G Suárez, Ariel M Sarotti, María I Mangione* and Rolando A Spanevello and Enrique D V Giordano Instituto de Química Rosario,
More informationSupporting Information. (1S,8aS)-octahydroindolizidin-1-ol.
SI-1 Supporting Information Non-Racemic Bicyclic Lactam Lactones Via Regio- and cis-diastereocontrolled C H insertion. Asymmetric Synthesis of (8S,8aS)-octahydroindolizidin-8-ol and (1S,8aS)-octahydroindolizidin-1-ol.
More informationSupporting Information for Synthesis of C(3) Benzofuran Derived Bis-Aryl Quaternary Centers: Approaches to Diazonamide A
Fuerst et al. Synthesis of C(3) Benzofuran Derived Bis-Aryl Quaternary Centers: Approaches to Diazonamide A S1 Supporting Information for Synthesis of C(3) Benzofuran Derived Bis-Aryl Quaternary Centers:
More informationSupporting Information for:
Supporting Information for: Photoenolization of 2-(2-Methyl Benzoyl) Benzoic Acid, Methyl Ester: The Effect of The Lifetime of the E Photoenol on the Photochemistry Armands Konosonoks, P. John Wright,
More informationSynthesis of Trifluoromethylated Naphthoquinones via Copper-Catalyzed. Cascade Trifluoromethylation/Cyclization of. 2-(3-Arylpropioloyl)benzaldehydes
Supporting Information to Synthesis of Trifluoromethylated Naphthoquinones via Copper-Catalyzed Cascade Trifluoromethylation/Cyclization of 2-(3-Arylpropioloyl)benzaldehydes Yan Zhang*, Dongmei Guo, Shangyi
More informationA Mild, Catalytic and Highly Selective Method for the Oxidation of α,β- Enones to 1,4-Enediones. Jin-Quan Yu, a and E. J.
A Mild, Catalytic and Highly Selective Method for the Oxidation of α,β- Enones to 1,4-Enediones Jin-Quan Yu, a and E. J. Corey b * a Department of Chemistry, Cambridge University, Cambridge CB2 1EW, United
More informationStraightforward Synthesis of Enantiopure (R)- and (S)-trifluoroalaninol
S1 Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010 Straightforward Synthesis of Enantiopure (R)- and (S)-trifluoroalaninol Julien
More informationAn unusual dianion equivalent from acylsilanes for the synthesis of substituted β-keto esters
S1 An unusual dianion equivalent from acylsilanes for the synthesis of substituted β-keto esters Chris V. Galliford and Karl A. Scheidt* Department of Chemistry, Northwestern University, 2145 Sheridan
More informationSupporting Information
Supporting Information for Cu-Mediated trifluoromethylation of benzyl, allyl and propargyl methanesulfonates with TMSCF 3 Xueliang Jiang 1 and Feng-Ling Qing* 1,2 Address: 1 Key Laboratory of Organofluorine
More informationElectronic Supplementary Information
Electronic Supplementary Material (ESI) for Journal of Materials Chemistry A. This journal is The Royal Society of Chemistry 2014 Electronic Supplementary Information Micro- and mesoporous poly(schiff-base)s
More informationSUPPORTING INFORMATION. Fathi Elwrfalli, Yannick J. Esvan, Craig M. Robertson and Christophe Aïssa
Electronic Supplementary Material (ESI) for ChemComm. This journal is The Royal Society of Chemistry 2018 SUPPORTING INFORMATION S1 Fathi Elwrfalli, Yannick J. Esvan, Craig M. Robertson and Christophe
More informationSupporting Information for
Page of 0 0 0 0 Submitted to The Journal of Organic Chemistry S Supporting Information for Syntheses and Spectral Properties of Functionalized, Water-soluble BODIPY Derivatives Lingling Li, Junyan Han,
More informationSupporting Information
Supporting Information Divergent Reactivity of gem-difluoro-enolates towards Nitrogen Electrophiles: Unorthodox Nitroso Aldol Reaction for Rapid Synthesis of -Ketoamides Mallu Kesava Reddy, Isai Ramakrishna,
More informationTable of Contents for Supporting Information
Table of Contents for Supporting Information General... S2 General Pd/Cu Coupling Reaction Procedures... S2 General Procedure for the Deprotection of Trimethylsilyl-Protected Alkynes.... S3 2,5-Dibromo-1,4-diiodobenzene
More informationSynthesis of Glaucogenin D, a Structurally Unique. Disecopregnane Steroid with Potential Antiviral Activity
Supporting Information for Synthesis of Glaucogenin D, a Structurally Unique Disecopregnane Steroid with Potential Antiviral Activity Jinghan Gui,* Hailong Tian, and Weisheng Tian* Key Laboratory of Synthetic
More informationSupporting Information
Supporting Information Total Synthesis of (±)-Grandilodine B Chunyu Wang, Zhonglei Wang, Xiaoni Xie, Xiaotong Yao, Guang Li, and Liansuo Zu* School of Pharmaceutical Sciences, Tsinghua University, Beijing,
More informationSupporting Information for
Electronic Supplementary Material (ESI) for New Journal of Chemistry. This journal is The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2017 Supporting Information for
More informationReactions. James C. Anderson,* Rachel H. Munday. School of Chemistry, University of Nottingham, Nottingham, NG7 2RD, UK
Vinyl-dimethylphenylsilanes as Safety Catch Silanols in Fluoride free Palladium Catalysed Cross Coupling Reactions. James C. Anderson,* Rachel H. Munday School of Chemistry, University of Nottingham, Nottingham,
More informationAccessory Information
Accessory Information Synthesis of 5-phenyl 2-Functionalized Pyrroles by amino Heck and tandem amino Heck Carbonylation reactions Shazia Zaman, *A,B Mitsuru Kitamura B, C and Andrew D. Abell A *A Department
More informationSupplementary Information (Manuscript C005066K)
Supplementary Information (Manuscript C005066K) 1) Experimental procedures and spectroscopic data for compounds 6-12, 16-19 and 21-29 described in the paper are given in the supporting information. 2)
More informationSynthesis of borinic acids and borinate adducts using diisopropylaminoborane
Synthesis of borinic acids and borinate adducts using diisopropylaminoborane Ludovic Marciasini, Bastien Cacciuttolo, Michel Vaultier and Mathieu Pucheault* Institut des Sciences Moléculaires, UMR 5255,
More informationSupporting Text Synthesis of (2 S ,3 S )-2,3-bis(3-bromophenoxy)butane (3). Synthesis of (2 S ,3 S
Supporting Text Synthesis of (2S,3S)-2,3-bis(3-bromophenoxy)butane (3). Under N 2 atmosphere and at room temperature, a mixture of 3-bromophenol (0.746 g, 4.3 mmol) and Cs 2 C 3 (2.81 g, 8.6 mmol) in DMS
More informationSupporting Information
Supporting Information Wiley-VCH 2012 69451 Weinheim, Germany Concise Syntheses of Insect Pheromones Using Z-Selective Cross Metathesis** Myles B. Herbert, Vanessa M. Marx, Richard L. Pederson, and Robert
More informationFast and Flexible Synthesis of Pantothenic Acid and CJ-15,801.
Fast and Flexible Synthesis of Pantothenic Acid and CJ-15,801. Alan L. Sewell a, Mathew V. J. Villa a, Mhairi Matheson a, William G. Whittingham b, Rodolfo Marquez a*. a) WestCHEM, School of Chemistry,
More informationSUPPORTING INFORMATION
SUPPORTING INFORMATION For Synthesis of Fluorenone Derivatives through Palladium-Catalyzed Dehydrogenative Cyclization Hu Li, Ru-Yi Zhu, Wen-Juan Shi, Ke-Han He, and Zhang-Jie Shi* Beijing National Laboratory
More informationElectronic Supplementary Information
Electronic Supplementary Information Effect of polymer chain conformation on field-effect transistor performance: synthesis and properties of two arylene imide based D-A copolymers Dugang Chen, a Yan Zhao,
More informationBlock: Synthesis, Aggregation-Induced Emission, Two-Photon. Absorption, Light Refraction, and Explosive Detection
Electronic Supplementary Information (ESI) Luminogenic Materials Constructed from Tetraphenylethene Building Block: Synthesis, Aggregation-Induced Emission, Two-Photon Absorption, Light Refraction, and
More informationSupporting Information For:
Supporting Information For: Peptidic α-ketocarboxylic Acids and Sulfonamides as Inhibitors of Protein Tyrosine Phosphatases Yen Ting Chen, Jian Xie, and Christopher T. Seto* Department of Chemistry, Brown
More informationSupporting Information
Supporting Information Organocatalytic Enantioselective Formal Synthesis of Bromopyrrole Alkaloids via Aza-Michael Addition Su-Jeong Lee, Seok-Ho Youn and Chang-Woo Cho* Department of Chemistry, Kyungpook
More informationSupplemental material for: Concise Total Syntheses of (±)-Mesembrane and (±)-Crinane. Table of Contents
Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry. This journal is The Royal Society of Chemistry 2015 Das, De, Shubhashish and Bisai Supporting Information 1 Supplemental material
More informationSupporting Information. Application of the Curtius rearrangement to the synthesis of 1'- aminoferrocene-1-carboxylic acid derivatives
Electronic Supplementary Material (ESI) for New Journal of Chemistry. This journal is The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2018 Supporting Information Application
More informationSupporting Information
An Improved ynthesis of the Pyridine-Thiazole Cores of Thiopeptide Antibiotics Virender. Aulakh, Marco A. Ciufolini* Department of Chemistry, University of British Columbia 2036 Main Mall, Vancouver, BC
More informationHighly stereocontrolled synthesis of trans-enediynes via
Supporting Information for Highly stereocontrolled synthesis of trans-enediynes via carbocupration of fluoroalkylated diynes Tsutomu Konno*, Misato Kishi, and Takashi Ishihara Address: Department of Chemistry
More informationHalogen halogen interactions in diiodo-xylenes
Electronic Supplementary Material (ESI) for CrystEngComm. This journal is The Royal Society of Chemistry 2016 Electronic Supplementary Information (ESI) for CrystEngComm. This journal is The Royal Society
More informationSynthesis of hydrophilic monomer, 1,4-dibromo-2,5-di[4-(2,2- dimethylpropoxysulfonyl)phenyl]butoxybenzene (Scheme 1).
Supporting Information Materials. Hydroquinone, potassium carbonate, pyridine, tetrahydrofuran (THF for organic synthesis) were purchased from Wako Pure Chemical Industries Ltd and used as received. Chlorosulfuric
More informationExperimental details
Supporting Information for A scalable synthesis of the (S)-4-(tert-butyl)-2-(pyridin-2-yl)-4,5-dihydrooxazole ((S)-t-BuPyx) ligand Hideki Shimizu 1,2, Jeffrey C. Holder 1 and Brian M. Stoltz* 1 Address:
More informationSupplementary Material. Ionic liquid iodinating reagent for mild and efficient iodination of. aromatic and heteroaromatic amines and terminal alkynes
Supplementary Material onic liquid iodinating reagent for mild and efficient iodination of aromatic and heteroaromatic amines and terminal alkynes Mahboobe Nouzarian 1, Rahman Hosseinzadeh 1,*, and Hamid
More informationSUPPLEMENTARY INFORMATION
Supplementary Method Synthesis of 2-alkyl-MPT(R) General information (R) enantiomer of 2-alkyl (18:1) MPT (hereafter designated as 2-alkyl- MPT(R)), was synthesized as previously described 1, with some
More informationSupporting Information for: Direct Conversion of Haloarenes to Phenols under Mild, Transition-Metal-Free Conditions
Supporting Information for: Direct Conversion of Haloarenes to Phenols under Mild, Transition-Metal-Free Conditions Patrick S. Fier* and Kevin M. Maloney* S1 General experimental details All reactions
More informationSupporting Information. for. Angew. Chem. Int. Ed. Z Wiley-VCH 2003
Supporting Information for Angew. Chem. Int. Ed. Z53001 Wiley-VCH 2003 69451 Weinheim, Germany 1 Ordered Self-Assembly and Electronic Behavior of C 60 -Anthrylphenylacetylene Hybrid ** Seok Ho Kang 1,
More informationStereoselective Synthesis of a Topologically Chiral Molecule: The Trefoil Knot
Stereoselective Synthesis of a Topologically Chiral Molecule: The Trefoil Knot Laure-Emmanuelle Perret-Aebi, Alexander von Zelewsky 1, Christiane Dietrich- Buchecker and Jean-Pierre Sauvage Bis-5,6-pinene
More informationPoly(4-vinylimidazolium)s: A Highly Recyclable Organocatalyst Precursor for. Benzoin Condensation Reaction
Electronic Supplementary Material (ESI) for RSC Advances. This journal is The Royal Society of Chemistry 24 Supporting Information Poly(4-vinylimidazolium)s: A Highly Recyclable rganocatalyst Precursor
More informationSynthesis of Simple Diynals, Diynones, Their Hydrazones, and Diazo Compounds: Precursors to a Family of Dialkynyl Carbenes (R 1 C C C C C R 2 )
Supporting Information Synthesis of Simple Diynals, Diynones, Their Hydrazones, and Diazo Compounds: Precursors to a Family of Dialkynyl Carbenes (R 1 C C C C C R 2 ) Nathan P. Bowling, Nicola J. Burrmann,
More informationSupporting Information
Electronic upplementary Material (EI) for rganic Chemistry rontiers. This journal is the Partner rganisations 0 upporting Information Convenient ynthesis of Pentafluoroethyl Thioethers via Catalytic andmeyer
More informationFormal Total Synthesis of Optically Active Ingenol via Ring-Closing Olefin Metathesis
Formal Total Synthesis of Optically Active Ingenol via Ring-Closing Olefin Metathesis Kazushi Watanabe, Yuto Suzuki, Kenta Aoki, Akira Sakakura, Kiyotake Suenaga, and Hideo Kigoshi* Department of Chemistry,
More informationBulletin of the Chemical Society of Japan
Supporting Information Bulletin of the Chemical Society of Japan Enantioselective Copper-Catalyzed 1,4-Addition of Dialkylzincs to Enones Followed by Trapping with Allyl Iodide Derivatives Kenjiro Kawamura,
More informationSupporting Information
1 A regiodivergent synthesis of ring A C-prenyl flavones Alberto Minassi, Anna Giana, Abdellah Ech-Chahad and Giovanni Appendino* Dipartimento di Scienze Chimiche, Alimentari, Farmaceutiche e Farmacologiche
More information2017 Reaction of cinnamic acid chloride with ammonia to cinnamic acid amide
217 Reaction of cinnamic acid chloride with ammonia to cinnamic acid amide O O Cl NH 3 NH 2 C 9 H 7 ClO (166.6) (17.) C 9 H 9 NO (147.2) Classification Reaction types and substance classes reaction of
More informationSupporting Information
Supporting Information ACA: A Family of Fluorescent Probes that Bind and Stain Amyloid Plaques in Human Tissue Willy M. Chang, a Marianna Dakanali, a Christina C. Capule, a Christina J. Sigurdson, b Jerry
More informationSUPPLEMENTARY INFORMATION
Synthetic chemistry ML5 and ML4 were identified as K P.(TREK-) activators using a combination of fluorescence-based thallium flux and automated patch-clamp assays. ML5, ML4, and ML5a were synthesized using
More informationBrønsted Base-Catalyzed Reductive Cyclization of Alkynyl. α-iminoesters through Auto-Tandem Catalysis
Supporting Information Brønsted Base-Catalyzed Reductive Cyclization of Alkynyl α-iminoesters through Auto-Tandem Catalysis Azusa Kondoh, b and Masahiro Terada* a a Department of Chemistry, Graduate School
More informationSupporting Information
Supporting Information Silver-Mediated Oxidative Trifluoromethylation of Alcohols to Alkyl Trifluoromethyl Ethers Jian-Bo Liu, Xiu-Hua Xu, and Feng-Ling Qing Table of Contents 1. General Information --------------------------------------------------------------------------2
More informationSupporting Information
Supporting Information Synthesis of H-Indazoles from Imidates and Nitrosobenzenes via Synergistic Rhodium/Copper Catalysis Qiang Wang and Xingwei Li* Dalian Institute of Chemical Physics, Chinese Academy
More informationSynthesis of fluorophosphonylated acyclic nucleotide analogues via Copper (I)- catalyzed Huisgen 1-3 dipolar cycloaddition
Synthesis of fluorophosphonylated acyclic nucleotide analogues via Copper (I)- catalyzed Huisgen 1-3 dipolar cycloaddition Sonia Amel Diab, Antje Hienzch, Cyril Lebargy, Stéphante Guillarme, Emmanuel fund
More informationPhotooxidations of 2-(γ,ε-dihydroxyalkyl) furans in Water: Synthesis of DE-Bicycles of the Pectenotoxins
S1 Photooxidations of 2-(γ,ε-dihydroxyalkyl) furans in Water: Synthesis of DE-Bicycles of the Pectenotoxins Antonia Kouridaki, Tamsyn Montagnon, Maria Tofi and Georgios Vassilikogiannakis* Department of
More informationElectronic Supplementary Material (ESI) for Medicinal Chemistry Communications This journal is The Royal Society of Chemistry 2012
Supporting Information. Experimental Section: Summary scheme H 8 H H H 9 a H C 3 1 C 3 A H H b c C 3 2 3 C 3 H H d e C 3 4 5 C 3 H f g C 2 6 7 C 2 H a C 3 B H c C 3 General experimental details: All solvents
More information5.37 Introduction to Organic Synthesis Laboratory
MIT pencourseware http://ocw.mit.edu 5.37 Introduction to rganic Synthesis Laboratory Spring 2009 For information about citing these materials or our Terms of Use, visit: http://ocw.mit.edu/terms. URIECA
More informationSupporting Information
Electronic Supplementary Material (ESI) for RSC Advances. This journal is The Royal Society of Chemistry 2016 Supporting Information TEMPO-catalyzed Synthesis of 5-Substituted Isoxazoles from Propargylic
More informationFacile Multistep Synthesis of Isotruxene and Isotruxenone
Facile Multistep Synthesis of Isotruxene and Isotruxenone Jye-Shane Yang*, Hsin-Hau Huang, and Shih-Hsun Lin Department of Chemistry, National Taiwan University, Taipei, Taiwan 10617 jsyang@ntu.edu.tw
More informationAsymmetric Synthesis of Hydrobenzofuranones via Desymmetrization of Cyclohexadienones using the Intramolecular Stetter Reaction
Asymmetric Synthesis of Hydrobenzofuranones via Desymmetrization of Cyclohexadienones using the Intramolecular Stetter Reaction Qin Liu and Tomislav Rovis* Department of Chemistry, Colorado State University
More informationKinetics experiments were carried out at ambient temperature (24 o -26 o C) on a 250 MHz Bruker
Experimental Materials and Methods. All 31 P NMR and 1 H NMR spectra were recorded on 250 MHz Bruker or DRX 500 MHz instruments. All 31 P NMR spectra were acquired using broadband gated decoupling. 31
More informationSupplementary Information. Low volume shrinkage polymers by photo Polymerization of 1,1- Bis(ethoxycarbonyl)-2-vinylcyclopropanes
Electronic Supplementary Material (ESI) for Polymer Chemistry. This journal is The Royal Society of Chemistry 2015 Supplementary Information Low volume shrinkage polymers by photo Polymerization of 1,1-
More informationSUPPORTING INFORMATION
Dynamic covalent templated-synthesis of [c2]daisy chains. Altan Bozdemir, a Gokhan Barin, a Matthew E. Belowich, a Ashish. Basuray, a Florian Beuerle, a and J. Fraser Stoddart* ab a b Department of Chemistry,
More informationSUPPLEMENTARY INFORMATION
DOI: 10.1038/NCHEM.1989 Cooperative activation of cyclobutanones and olefins leads to bridged ring systems by a catalytic [4+2] coupling Haye Min Ko and Guangbin Dong* Department of chemistry and biochemistry,
More informationSupplementary Materials
Supplementary Materials ORTHOGOALLY POSITIOED DIAMIO PYRROLE- AD IMIDAZOLE- COTAIIG POLYAMIDES: SYTHESIS OF 1-(3-SUBSTITUTED-PROPYL)-4- ITROPYRROLE-2-CARBOXYLIC ACID AD 1-(3-CHLOROPROPYL)-4- ITROIMIDAZOLE-2-CARBOXYLIC
More informationIron Catalyzed Cross Couplings of Azetidines: Application to an Improved Formal Synthesis of a Pharmacologically Active Molecule
Electronic Supplementary Material (ESI) for ChemComm. This journal is The Royal Society of Chemistry 2014 Iron Catalyzed Cross Couplings of Azetidines: Application to an Improved Formal Synthesis of a
More informationSupporting Information
Supporting Information for Engineering of indole-based tethered biheterocyclic alkaloid meridianin into -carboline-derived tetracyclic polyheterocycles via amino functionalization/6-endo cationic π-cyclization
More informationSupplementary Table S1: Response evaluation of FDA- approved drugs
SUPPLEMENTARY DATA, FIGURES AND TABLE BIOLOGICAL DATA Spheroids MARY-X size distribution, morphology and drug screening data Supplementary Figure S1: Spheroids MARY-X size distribution. Spheroid size was
More informationSupporting Information. Total Synthesis of Solandelactone I
Supporting Information Total Synthesis of Solandelactone I Nils C. Eichenauer,, Roxanne Tschersich,, Jörg Pietruszka*, Institut für Bioorganische Chemie, Heinrich-Heine-Universität Düsseldorf im Forschungszentrum
More informationElectronic Supplementary Information. An Ultrafast Surface-Bound Photo-active Molecular. Motor
This journal is The Royal Society of Chemistry and wner Societies 2013 Electronic Supplementary Information An Ultrafast Surface-Bound Photo-active Molecular Motor Jérôme Vachon, [a] Gregory T. Carroll,
More informationCurtius-Like Rearrangement of Iron-Nitrenoid Complex and. Application in Biomimetic Synthesis of Bisindolylmethanes
Supporting Information Curtius-Like Rearrangement of Iron-itrenoid Complex and Application in Biomimetic Synthesis of Bisindolylmethanes Dashan Li,, Ting Wu,, Kangjiang Liang,, and Chengfeng Xia*,, State
More informationDivergent Synthesis of CF 3 -Substituted Polycyclic Skeletons Based on Control of Activation Site of Acid Catalysts
Electronic Supplementary Material (ESI) for ChemComm. This journal is The Royal Society of Chemistry 2018 Divergent Synthesis of CF 3 -Substituted Polycyclic Skeletons Based on Control of Activation Site
More informationSupporting Information
Supporting Information SmI 2 -Mediated Carbon-Carbon Bond Fragmentation in α-aminomethyl Malonates Qiongfeng Xu,, Bin Cheng, $, Xinshan Ye,*, and Hongbin Zhai*,,,$ The State Key Laboratory of Natural and
More informationScalable Synthesis of Fmoc-Protected GalNAc-Threonine Amino Acid and T N Antigen via Nickel Catalysis
Scalable Synthesis of Fmoc-Protected GalNAc-Threonine Amino Acid and T N Antigen via Nickel Catalysis Fei Yu, Matthew S. McConnell, and Hien M. Nguyen* Department of Chemistry, University of Iowa, Iowa
More informationSUPPORTING INFORMATION
SUPPRTING INFRMATIN A Direct, ne-step Synthesis of Condensed Heterocycles: A Palladium-Catalyzed Coupling Approach Farnaz Jafarpour and Mark Lautens* Davenport Chemical Research Laboratories, Chemistry
More information