1,3-Diiodo-5-methylbenzene

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Copper iodide (332 mg, 1.74 mmol), cesium carbonate (5.6 g, 17.4 mmol), and picolinic acid (429 mg, 3.49 mmol) were added to a dried flask under a nitrogen atmosphere. A solution of 3,5-diiodotoluene (3 g, 8.7 mmol) in dioxane (10 mL) was added, followed by the addition of di-tert-butyl malonate (1.3 mL, 8.7 mmol). The atmosphere inside the flask was removed under vacuum and replaced with nitrogen gas; this process was repeated a total of three times. The reaction mixture was then heated to 80° C. and stirred for 24 hours. The reaction mixture was then cooled to room temperature, quenched with saturated aqueous ammonium chloride solution (50 mL), and extracted twice with diethyl ether (50 mL). The organic layers were combined, dried over MgSO4, and concentrated under reduced pressure. The resulting residue was purified by chromatography on silica gel eluted with ethyl acetate in hexanes to provide the title product as an orange oil (0.62 g). The atmosphere inside the flask was removed under vacuum The reaction mixture was then cooled to room temperature quenched with saturated aqueous ammonium chloride solution (50 mL) extracted twice with diethyl ether (50 mL) dried over MgSO4 concentrated under reduced pressure The resulting residue was purified by chromatography on silica gel eluted with ethyl acetate in hexanes

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Copper iodide (332 mg, 1.74 mmol), cesium carbonate (5.6 g, 17.4 mmol), and picolinic acid (429 mg, 3.49 mmol) were added to a dried flask under a nitrogen atmosphere. A solution of 3,5-diiodotoluene (3 g, 8.7 mmol) in dioxane (10 mL) was added, followed by the addition of di-tert-butyl malonate (1.3 mL, 8.7 mmol). The atmosphere inside the flask was removed under vacuum and replaced with nitrogen gas; this process was repeated a total of three times. The reaction mixture was then heated to 80° C. and stirred for 24 hours. The reaction mixture was then cooled to room temperature, quenched with saturated aqueous ammonium chloride solution (50 mL), and extracted twice with diethyl ether (50 mL). The organic layers were combined, dried over MgSO4, and concentrated under reduced pressure. The resulting residue was purified by chromatography on silica gel eluted with ethyl acetate in hexanes to provide the title product as an orange oil (0.62 g). The atmosphere inside the flask was removed under vacuum The reaction mixture was then cooled to room temperature quenched with saturated aqueous ammonium chloride solution (50 mL) extracted twice with diethyl ether (50 mL) dried over MgSO4 concentrated under reduced pressure The resulting residue was purified by chromatography on silica gel eluted with ethyl acetate in hexanes

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Copper iodide (332 mg, 1.74 mmol), cesium carbonate (5.6 g, 17.4 mmol), and picolinic acid (429 mg, 3.49 mmol) were added to a dried flask under a nitrogen atmosphere. A solution of 3,5-diiodotoluene (3 g, 8.7 mmol) in dioxane (10 mL) was added, followed by the addition of di-tert-butyl malonate (1.3 mL, 8.7 mmol). The atmosphere inside the flask was removed under vacuum and replaced with nitrogen gas; this process was repeated a total of three times. The reaction mixture was then heated to 80° C. and stirred for 24 hours. The reaction mixture was then cooled to room temperature, quenched with saturated aqueous ammonium chloride solution (50 mL), and extracted twice with diethyl ether (50 mL). The organic layers were combined, dried over MgSO4, and concentrated under reduced pressure. The resulting residue was purified by chromatography on silica gel eluted with ethyl acetate in hexanes to provide the title product as an orange oil (0.62 g). The atmosphere inside the flask was removed under vacuum The reaction mixture was then cooled to room temperature quenched with saturated aqueous ammonium chloride solution (50 mL) extracted twice with diethyl ether (50 mL) dried over MgSO4 concentrated under reduced pressure The resulting residue was purified by chromatography on silica gel eluted with ethyl acetate in hexanes

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

Procedure: A mixture of 1,3-diiodo-5-methylbenzene (2.00 g), tris(dibenzylideneacetone)dipalladium (0) (20 mg), bis(diphenylphosphino)ferrocene (22 mg), triethylamine (1.5 ml) and 1-methyl-2-pyrrolidinone (3 ml) were stirred at to 20° under nitrogen for 1 h. Cyclopentanethiol (0.15 ml) was added and the mixture was heated to 60° for 18 h. The mixtue was cooled to 20° and was treated with phosphate buffer solution (pH 6.5) and water. The mixture was extracted with EtOAc and the extract dried (Na2SO4). Solvent evaporation in vacuo gave a residue which was purified by Flashmaster™ chromatography (silica, 70 g). Elution with cyclohexane gave the title compound (444 mg). LCMS RT=4.21 min. the mixture was heated to 60° for 18 h The mixtue was cooled to 20° The mixture was extracted with EtOAc the extract dried (Na2SO4) Solvent evaporation in vacuo gave a residue which was purified by Flashmaster™ chromatography (silica, 70 g) Elution with cyclohexane

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Copper iodide (332 mg, 1.74 mmol), cesium carbonate (5.6 g, 17.4 mmol), and picolinic acid (429 mg, 3.49 mmol) were added to a dried flask under a nitrogen atmosphere. A solution of 3,5-diiodotoluene (3 g, 8.7 mmol) in dioxane (10 mL) was added, followed by the addition of di-tert-butyl malonate (1.3 mL, 8.7 mmol). The atmosphere inside the flask was removed under vacuum and replaced with nitrogen gas; this process was repeated a total of three times. The reaction mixture was then heated to 80° C. and stirred for 24 hours. The reaction mixture was then cooled to room temperature, quenched with saturated aqueous ammonium chloride solution (50 mL), and extracted twice with diethyl ether (50 mL). The organic layers were combined, dried over MgSO4, and concentrated under reduced pressure. The resulting residue was purified by chromatography on silica gel eluted with ethyl acetate in hexanes to provide the title product as an orange oil (0.62 g). The atmosphere inside the flask was removed under vacuum The reaction mixture was then cooled to room temperature quenched with saturated aqueous ammonium chloride solution (50 mL) extracted twice with diethyl ether (50 mL) dried over MgSO4 concentrated under reduced pressure The resulting residue was purified by chromatography on silica gel eluted with ethyl acetate in hexanes