1-bromo-4-prop-2-enylbenzene

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under a nitrogen atmosphere, to 1,4-dibromobenzene (1) (15 g, 15.9 mmol), cyclopentyl methyl ether (CPME) (90 ml) was added and cooled to around −10° C. using salt ice, tetrahydrofuran (THF) solution (iPrMgCl solution) of 2M isopropyl magnesium chloride (0.35 equivalents, 11.2 ml) and hexane solution (nBuLi solution) of 1.67M normal-butyl lithium (0.7 equivalents, 26.8 ml) were added dropwise. The mixture was stirred for 2 hours at −10° C. Then allyl bromide (1.1 equivalents, 6.8 ml) was added and stirred at room temperature for 14 hours. To the reacted mixture, diethyl ether was added and neutralized by adding saturated ammonium chloride. The obtained water layer was extracted by diethyl ether. The collected organic layer was washed with saturated saline solution, dried over anhydrous magnesium sulfate, then filtered and concentrated under reduced pressure, obtaining a crude product of 1-allyl-4-bromobenzene (2) (yield: 13.0 g, yield (%): 103%) were added dropwise stirred at room temperature for 14 hours The obtained water layer was extracted by diethyl ether The collected organic layer was washed with saturated saline solution dried over anhydrous magnesium sulfate filtered concentrated under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 1-allyl-4-bromo-benzene (2.0 g, 10.2 mmol) in acetone (60 mL) is treated with OsO4 (52 mg, 0.20 mmol), NMO (1.44 g, 12.2 mmol) and water (approx. 0.3 mL). The clear solution is stirred at rt for 2 h, diluted with DCM (150 mL) and washed twice with 10% aq. citric acid (2×75 mL). The aqueous phase is extracted twice with DCM. The organic extracts are combined, dried over MgSO4 and evaporated. The crude product is purified by CC on silica gel eluting with EA to give 3-(4-bromo-phenyl)-propane-1,2-diol (1.41 g) as an almost colourless oil; LC-MS: tR=0.72 min; 1H NMR (CDCl3): δ 7.46-7.40 (m, 2H), 7.14-7.08 (m, 2H), 3.96-3.87 (m, 1H), 3.73-3.67 (m, 1H), 3.55-3.47 (m, 1H), 2.81-2.67 (m, 2H), 1.90 (s br, 2H). washed twice with 10% aq. citric acid (2×75 mL) The aqueous phase is extracted twice with DCM dried over MgSO4 evaporated The crude product is purified by CC on silica gel eluting with EA

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 1-allyl-4-bromo-benzene (2.0 g, 10.2 mmol) in acetone (60 mL) is treated with OsO4 (52 mg, 0.20 mmol), NMO (1.44 g, 12.2 mmol) and water (approx. 0.3 mL). The clear solution is stirred at rt for 2 h, diluted with DCM (150 mL) and washed twice with 10% aq. citric acid (2×75 mL). The aqueous phase is extracted twice with DCM. The organic extracts are combined, dried over MgSO4 and evaporated. The crude product is purified by CC on silica gel eluting with EA to give 3-(4-bromo-phenyl)-propane-1,2-diol (1.41 g) as an almost colourless oil; LC-MS: tR=0.72 min; 1H NMR (CDCl3): δ 7.46-7.40 (m, 2H), 7.14-7.08 (m, 2H), 3.96-3.87 (m, 1H), 3.73-3.67 (m, 1H), 3.55-3.47 (m, 1H), 2.81-2.67 (m, 2H), 1.90 (s br, 2H). washed twice with 10% aq. citric acid (2×75 mL) The aqueous phase is extracted twice with DCM dried over MgSO4 evaporated The crude product is purified by CC on silica gel eluting with EA

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: At 5° C., a solution of allylbromide (5.64 g, 46.6 mmol) in THF (40 mL) is slowly added to the Grignard reagent freshly prepared from 1,4-dibromobenzene (10.0 g, 42.4 mmol) and Mg-turnings (1.13 g, 46.6 mmol) in THF. The reaction mixture becomes slightly warm and a fine precipitate forms. Upon completion of the addition, the suspension is stirred at rt for 1 h before it is diluted with diethyl ether and washed with two portions of 1 N aq. HCl and one portion of water. The wash solutions are extracted twice with diethyl ether. The organic extracts are combined, dried over MgSO4 and evaporated. The crude product is purified by CC on silica gel eluting with heptane:EA 9:1 to give 1-allyl-4-bromo-benzene (5.50 g) as a colourless oil. The reaction mixture becomes slightly warm Upon completion of the addition washed with two portions of 1 N aq. HCl and one portion of water The wash solutions are extracted twice with diethyl ether dried over MgSO4 evaporated The crude product is purified by CC on silica gel eluting with heptane:EA 9:1

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Tris(dibenzylideneacetone)dipalladium(0) [Pd2(dba)3, 0.2623 g, 2.864×10−4 mol] and tri-tert-butylphosphine (0.11 g, 5.437×10−4 mol) were weighed out in a glove box, transferred to a Schlenk line, and stirred for about 5 min in hexanes before adding sodium tert-butoxide (2.000 g, 2.081×10−2 mol) as a slurry in hexanes, Compound 1 (2.810 g, 1.426×10−2 mol), and 80 mL hexanes. Next, distilled aniline (1.43 mL, 1.57×10−2 mol) was added over a period of about 3 min with stirring. A brown precipitate formed after about 5 min at room temperature, and stirring was halted after 2 h. The mixture was then filtered through Celite, and the hexanes were removed in vacuo at ≦45° C. so as to minimize allyl group isomerization. The resulting oil was then placed in a freezer at −23° C. for 1 h to solidify. The resulting solid was then recrystallized from pentane to yield light tan crystals of Compound 2 (2.43 g, 82% yield) that were collected by filtration and rinsed 3× with cold pentane. GC/MS: single peak; m/z (rel. intensity) 210 (M+ +H, 17), 209 (M+, 100), 208 (M+ −H, 29), 182 (38) 117 (33). 1H NMR (CDCl3): δ7.24 (m, 2H), 7.09 (d, J=8.5 Hz, 2H), 7.04 (d, J=6.5 Hz, 2H), 7.03 (d, J=6.5 Hz, 2H), 6.89 (t, J=7 Hz, 1 H), 5.94 (m, 1H), 5.64 (s, 1H), 5.06 (m, 2H), 3.34 (d, J=6.5 Hz, 2H). 13C NMR (CD2Cl2): δ144.0, 141.4, 138.4, 133.3, 129.7, 129.6, 120.7, 118.7, 117.3, 115.5, 39.8. EA for C15H15N: Calc. %: C, 86.08; H, 7.22; N, 6.69; Found %: C, 85.95; H, 7.11; N, 6.82. transferred to a Schlenk was added over a period of about 3 min A brown precipitate formed after about 5 min at room temperature stirring The mixture was then filtered through Celite the hexanes were removed in vacuo at ≦45° C. so as The resulting oil was then placed in a freezer at −23° C. for 1 h The resulting solid was then recrystallized from pentane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a Stille coupling reaction, 1-bromo-4-iodobenzene and allyltri-n-butyltin were reacted to yield Compound 1. Thus, tetrakistriphenylphosphine palladium(0) (1.976 g, 1.710×10−3 mol) was weighed out in a nitrogen-filled glove box and transferred to a Schlenk line. Allyltri-n-butyltin (10.60 mL, 3.419×10−2 mol) and 1-bromo-4-iodobenzene (9.680 g, 3.422×10−2 mol) were added along with 115 mL distilled, degassed 1,4-dioxane to yield a yellow reaction mixture that darkened to orange as the reaction progressed. The reaction mixture was stirred at 70° C. for 46 h until analysis by TLC (hexanes) and GC/MS showed that reaction was complete. The mixture was next cooled to room temperature, filtered through Celite (rinsing with hexanes), and resulting solution washed with both hexanes and water, to remove PPh3. Then the organic portion was dried over MgSO4. Filtration through Celite and removal of the solvent in a rotary evaporator at <75° C. yielded an orange oil. Column chromatography on silica gel with hexanes as eluant afforded only Compound 1 and tri-n-butyltin iodide. These were separated via vacuum distillation at 160 mTorr, where Compound 1 distills at about 50° C. (never exceed 75° C., which can potentially cause allyl group isomerization) as a clear colorless oil (2.810 g, 42% yield). GC/MS: single peak; m/z (rel. intensity) 198 (M+, 46), 196 (M+, 46), 117 (100), 115 (86). 1H NMR (CDCl3): δ7.41 (d, J=8.5 Hz, 2H), 7.07 (d, J=8.0 Hz, 2H), 5.90 (m, 1H), 5.09 (m, 2H), 3.36 (d, J=7.0 Hz, 2H). filled glove box transferred to a Schlenk distilled degassed 1,4-dioxane to yield a yellow reaction mixture that darkened to orange as the reaction showed that reaction filtered through Celite (rinsing with hexanes) resulting solution washed with both hexanes and water to remove PPh3 Then the organic portion was dried over MgSO4 Filtration through Celite and removal of the solvent in a rotary evaporator at <75° C. yielded an orange oil

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a Stille coupling reaction, 1-bromo-4-iodobenzene and allyltri-n-butyltin were reacted to yield Compound 1. Thus, tetrakistriphenylphosphine palladium(0) (1.976 g, 1.710×10−3 mol) was weighed out in a nitrogen-filled glove box and transferred to a Schlenk line. Allyltri-n-butyltin (10.60 mL, 3.419×10−2 mol) and 1-bromo-4-iodobenzene (9.680 g, 3.422×10−2 mol) were added along with 115 mL distilled, degassed 1,4-dioxane to yield a yellow reaction mixture that darkened to orange as the reaction progressed. The reaction mixture was stirred at 70° C. for 46 h until analysis by TLC (hexanes) and GC/MS showed that reaction was complete. The mixture was next cooled to room temperature, filtered through Celite (rinsing with hexanes), and resulting solution washed with both hexanes and water, to remove PPh3. Then the organic portion was dried over MgSO4. Filtration through Celite and removal of the solvent in a rotary evaporator at <75° C. yielded an orange oil. Column chromatography on silica gel with hexanes as eluant afforded only Compound 1 and tri-n-butyltin iodide. These were separated via vacuum distillation at 160 mTorr, where Compound 1 distills at about 50° C. (never exceed 75° C., which can potentially cause allyl group isomerization) as a clear colorless oil (2.810 g, 42% yield). GC/MS: single peak; m/z (rel. intensity) 198 (M+, 46), 196 (M+, 46), 117 (100), 115 (86). 1H NMR (CDCl3): δ7.41 (d, J=8.5 Hz, 2H), 7.07 (d, J=8.0 Hz, 2H), 5.90 (m, 1H), 5.09 (m, 2H), 3.36 (d, J=7.0 Hz, 2H). were reacted

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: BH3 (1M in THF, 412 mL, 412 mmol) is added to a sol. of 1-allyl-4-bromo-benzene (204 g, 1.03 mmol) in THF (1.00 L) under nitrogen at 0° C. The mixture is stirred overnight while warming up to rt. Aq. NaOH (2.5M, 1.65 L, 4.12 mol) is added, and the mixture is cooled to 0° C. H2O2 (35%, 480 mL, 5.15 mol) is dropped carefully, and the mixture is stirred for 3 h. Et2O is added, and the phases are separated. The org. layer is washed with water (1×), and brine (1×). The org. layer is dried over MgSO4, filtered, and the solvents are removed under reduced pressure. Purification by FC (Et2O/petroleum ether 1:1→Et2O) yields the title compound (97.4 g, 44%). the mixture is cooled to 0° C the mixture is stirred for 3 h the phases are separated layer is washed with water (1×), and brine (1×) layer is dried over MgSO4 filtered the solvents are removed under reduced pressure Purification by FC (Et2O/petroleum ether 1:1→Et2O)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Mg (8.76 g, 360 mmol) is suspended in THF (90 mL) under nitrogen in a three-necked flask equipped with a condenser and a dropping funnel. The dropping funnel is filled with 1,4-dibromobenzene (77.3 g, 327 mmol) in THF (40 mL). About 5% of the 1,4-dibromobenzene sol. is added carefully to the Mg-suspension and the reaction is started with the help of a heat gun. When the reaction starts, the 1,4-dibromobenzene sol. is added to such a speed so that the reaction mixture is refluxing gently (about 20 min). The mixture is stirred for further 30 min, and is cooled to 0° C. THF (100 mL) is added and the dropping funnel is filled with a sol. of allyl bromide (30.5 mL, 360 mmol) in THF (50 mL). The allyl bromide sol. is added slowly, maintaining the reaction temperature below 20° C. When the addition is complete, the mixture is stirred for further 30 min, while being cooled to 0° C. Aq. 1M HCl is added. The mixture is diluted with Et2O, and washed with aq. 1M HCl and brine. The combined aq. extracts are extracted back with Et2O. The combined org. extracts are dried over MgSO4, filtered, and the solvents are removed under reduced pressure. Distillation of the residue (11 mbar, 88-92° C.) yields the title compound (39.3 g, about 61%), together with another, unidentified impurity. equipped with a condenser and a dropping funnel is refluxing gently (about 20 min) maintaining the reaction temperature below 20° C When the addition the mixture is stirred for further 30 min while being cooled to 0° C washed with aq. 1M HCl and brine The combined aq. extracts are extracted back with Et2O extracts are dried over MgSO4 filtered the solvents are removed under reduced pressure Distillation of the residue (11 mbar, 88-92° C.)

Conditions: temp:32.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of t-butylnitrite (535 μl, 4.5 mmol) and allyl bromide (3.9 ml, 45.0 mmol) in CH3CN (3 ml), 4-bromoaniline (516 mg, 3.0 mmol) was added during 20 minutes, while maintaining the temperature of the reaction mixture at 30-35° C. At the end of the addition of the aniline, extra t-butylnitrite (180 μl, 1.5 mmol) was added to the reaction mixture which then was stirred at 30° C. for one hour. The volatile material in the reaction mixture was removed at reduced pressure. Column chromatography (pentane) gave 200 mg (34%) of 4-allylbromobenzene as a clear oil. 1H NMR (CDCl3, 400 MHz) δ 7.43, (m, 2H, J=8.3 Hz), 7.08, (m, 2H, J=8.3 Hz), 6.00-5.89, (m, 1H), 5.12-5.05, (m, 2H), 3.35, (d, 2H, J 6.7 Hz); 13C NMR (CDCl3, 100 MHz) δ 139.4, 137.2, 131.9, 130.8, 120.3, 116.7, 40.0; Anal HRMS Calcd. for C9H9Br (M): 195.9888. Found: 195.9887. was added to the reaction mixture which The volatile material in the reaction mixture was removed at reduced pressure

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Cyclopentyl methyl ether (CPME) (90 ml) was added to 1,4-dibromobenzene (1) (15 g, 15.9 mmol) under a nitrogen atmosphere, the mixture was cooled to around −10° C. with brine ice, a solution of 2 M isopropylmagnesium chloride in tetrahydrofuran (THF) (iPrMgCl solution) (0.35 equivalent amount, 11.2 ml) and a solution of 1.67 M n-butyllithium in hexane (nBuLi solution) (0.7 equivalent amount, 26.8 ml) were respectively added dropwise. The mixture was stirred at around −10° C. for 2 hours, allyl bromide (1.1 equivalent amount, 6.8 ml) was then added, and the mixture was stirred at room temperature for 14 hours. Diethyl ether was added to the reaction mixture, and the mixture was neutralized with a saturated aqueous solution of ammonium chloride. The aqueous layer was extracted with diethyl ether, and the combined organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under a reduced pressure to give a crude product of 1-allyl-4-bromobenzene (2) (yield amount: 13.0 g, tentative yield: 103%), as shown in the following chemical reaction formula. the mixture was stirred at room temperature for 14 hours The aqueous layer was extracted with diethyl ether the combined organic layer was washed with saturated brine dried over anhydrous magnesium sulfate filtered concentrated under a reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture comprising sufficiently dried metal magnesium (120 mmol) and 30 ml of tetrahydrofuran (hereinafter referred to as THF), was gradually added a solution of 120 mmol of the 4-allyl-bromobenzene in 200 ml of THF to prepare a Grignard reagent. To this reagent was added dropwise a solution of trimethyl borate (120 mmol) in 100 ml of THF at a temperature not exceeding -65° C., stirred for a whole day and night. Subsequently, the mixture was kept at 0° C., 200 ml of 10% hydrochloric acid was gradually added thereto at the same temperature, and then the reaction mixture was stirred for 30 min. The mixture thus obtained was extracted twice with 500 ml of diethyl ether, the organic layer was washed with a saturated brine solution, and then the solvent was removed under a reduced pressure. The residue was sufficiently washed with 500 ml of heptane and then dried to obtain 4-allylphenyl boric acid (79 mmol). exceeding -65° C. was kept at 0° C. at the same temperature, and then the reaction mixture was stirred for 30 min The mixture thus obtained was extracted twice with 500 ml of diethyl ether the organic layer was washed with a saturated brine solution the solvent was removed under a reduced pressure The residue was sufficiently washed with 500 ml of heptane dried