1-chloro-3-ethenylbenzene

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A round-bottom flask equipped with a overhead stirrer was charged with 3-chlorostyrene (1.00 g, 7.22×10−3 mol), CH2Cl2 (78 mL), (R,R)-4 (0.349 g, 3.61×10−4 mol), and NMO (4.22 g, 3.62×10−2 mol). The solution was cooled to −78° C. before solid m-CPBA (2.51 g, 1.46×10−2 mol) was added in portions over 1.5 minutes. The reaction was monitored by GC. Upon completion (3 h), the reaction was quenched by the addition of a solution of dimethyl sulfide (6 mL) in CH2Cl2 (25 mL) precooled to −78° C. The solution was stirred for an additional 10 minutes at −78° C. before removal of the cold bath and addition of 2N NaOH (20 mL) and CH2Cl2 (20 mL). The phases were separated and the aqueous layer was washed with CH2Cl2 (2×50 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo. Removal of the catalyst was effected by elution through a pad of SiO2 (10 g) using pentane and CH2Cl2 (1:1). The eluent was concentrated in vacuo, and subsequent bulb-to-bulb distillation from CaH2 afforded (R)-3-chlorostyrene oxide (0.963 g, 86%) as a colorless liquid in 81% ee. A round-bottom flask equipped with a overhead stirrer was added in portions over 1.5 minutes Upon completion (3 h), the reaction was quenched by the addition of a solution of dimethyl sulfide (6 mL) in CH2Cl2 (25 mL) precooled to −78° C The phases were separated the aqueous layer was washed with CH2Cl2 (2×50 mL) The combined organic layers were dried over Na2SO4 filtered concentrated in vacuo Removal of the catalyst was effected by elution through a pad of SiO2 (10 g) The eluent was concentrated in vacuo, and subsequent bulb-to-bulb distillation from CaH2

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

Procedure: A 2-necked round-bottom flask equipped with a water-cooled overhead stirrer was charged with 3-chlorostyrene (5.01 g, 3.61×10−2 mol), CH2Cl2 (45 mL), (R,R)-3 (0.578 g, 9.10×10−4 mol), and 4-PPNO (0.924 g, 5.40×10−3 mol). The solution was cooled to 0° C., and precooled buffered bleach (0.6 M, 75 mL, 4.50×10−2 mol, Clorox®, buffered to pH=11.3 with 0.05 M Na2HPO4 and 1M NaOH) was added. The two phase system was stirred vigorously, and the course of the reaction was monitored by GC. Upon complete consumption of starting olefin (<6 h), the reaction mixture was filtered through a plug of Celite on a coarse glass frit and washed with CH2Cl2 (75 mL). The organic layer of the filtrate was washed with distilled water (2×25 mL), and the aqueous layers were extracted with CH2Cl2 (2×25 mL). The combined organic layers were dried over Na2SO4 and concentrated in vacuo. Removal of the catalyst was effected by elution through a pad of SiO2 (30 g) using pentane and CH2Cl2 (1:1). The eluent was concentrated in vacuo, and subsequent bulb-to-bulb distillation (70° C., 0.6 mm Hg) from CaH2 afforded (R)-3-chlorostyrene oxide (5.15 g, 92%) as a pale yellow liquid in 32% ee. cooled overhead stirrer was added Upon complete consumption of starting olefin (<6 h) the reaction mixture was filtered through a plug of Celite on a coarse glass frit washed with CH2Cl2 (75 mL) The organic layer of the filtrate was washed with distilled water (2×25 mL) the aqueous layers were extracted with CH2Cl2 (2×25 mL) The combined organic layers were dried over Na2SO4 concentrated in vacuo Removal of the catalyst was effected by elution through a pad of SiO2 (30 g) The eluent was concentrated in vacuo, and subsequent bulb-to-bulb distillation (70° C., 0.6 mm Hg) from CaH2

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

Procedure: AD mix alpha (86.0 g) was added to a stirred mixture of tert-BuOH (300 mL) and H2O (300 mL), mixture was stirred for 15 min at RT, than cooled to 0° C. 3-Chlorostyrene (8.51 g, 0.061 mol) was added over 15 min and the mixture was stirred at 0° C. for 48 h. The reaction mixture was quenched by adding 10% aq. sodium sulfite (120 mL) followed by addition of EtOAc (200 mL). The layers were separated and the aqueous layer was extracted with EtOAc (200 mL). The combined organic layers were washed with 0.4 M H2SO4 in saturated Na2SO4 (100 mL), followed by drying over Na2SO4. The solvent was evaporated and the residue was separated on SiO2 (70 g) (CHCl3-MeOH 0 to 10%). Colorless oil, 9.83 g (0.057 mol, 93%). AD mix alpha (86.0 g) than cooled to 0° C the mixture was stirred at 0° C. for 48 h The reaction mixture was quenched by adding 10% aq. sodium sulfite (120 mL) followed by addition of EtOAc (200 mL) The layers were separated the aqueous layer was extracted with EtOAc (200 mL) The combined organic layers were washed with 0.4 M H2SO4 in saturated Na2SO4 (100 mL) by drying over Na2SO4 The solvent was evaporated the residue was separated on SiO2 (70 g) (CHCl3-MeOH 0 to 10%)

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

Procedure: To a 25° C. solution of 3-chlorostyrene in anhydrous CH2Cl2 ( 10.0 g, 72.15 mmol) was added a well-stirred solution of Pb(OAc)4 (35.2 g, 79.4 mmol) in trifluoroacetic acid (150 mL), dropwise. Reaction was completed within 30 minutes of the addition and after being stirred for a further 30 minutes, the mixture was poured into water, extracted with ether (3×), the combined organic layers were washed with saturated NaHCO3 solution, water, dried (MgSO4), and concentrated to a volume of about 15 mL and immediately used for the following reaction described below. Reaction was completed within 30 minutes of the addition extracted with ether (3×) the combined organic layers were washed with saturated NaHCO3 solution, water dried (MgSO4) concentrated to a volume of about 15 mL immediately used for the following reaction

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

Procedure: To a solution of m-chlorostyrene (5.70 g, 41.0 mmol) and acetic acid (2.33 mL, 40.9 mmol) in dioxane (33 ml) and H2O (78 ml) at 0° C. was added N-bromosuccinimide (8.02 g, 45.0 mmol) in three portions. The reaction was allowed to warm to R.T. After 4 hours, 2N NaOH (60 ml) was added and the reaction was allowed to stir at RT overnight. The reaction mixture was partitioned between water and EtOAc, and the aqueous phase was extracted with EtOAc. The combined organic phases were washed with brine, dried (Na2SO4), filtered and evaporated in vacuo to give 6.20 g of a slightly tinted oil which was used without further purification. The reaction mixture was partitioned between water and EtOAc the aqueous phase was extracted with EtOAc The combined organic phases were washed with brine dried (Na2SO4) filtered evaporated in vacuo to give 6.20 g of a slightly tinted oil which was used without further purification

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

Procedure: To a solution of m-chlorostyrene (5.70 g, 41.0 mmol) and acetic acid (2.33 mL, 40.9 mmol) in dioxane (33 ml) and H2O (78 ml) at 0° C. was added N-bromosuccinimide (8.02 g, 45.0 mmol) in three portions. The reaction was allowed to warm to R.T. After 4 hours, 2N NaOH (60 ml) was added and the reaction was allowed to stir at RT overnight. The reaction mixture was partitioned between water and EtOAc, and the aqueous phase was extracted with EtOAc. The combined organic phases were washed with brine, dried (Na2SO4), filtered and evaporated in vacuo to give 6.20 g of a slightly tinted oil which was used without further purification. The reaction mixture was partitioned between water and EtOAc the aqueous phase was extracted with EtOAc The combined organic phases were washed with brine dried (Na2SO4) filtered evaporated in vacuo to give 6.20 g of a slightly tinted oil which was used without further purification

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

Procedure: AD mix alpha (86.0 g) was added to a stirred mixture of tert-BuOH (300 mL) and H2O (300 mL), mixture was stirred for 15 min at RT, than cooled to 0° C. 3-Chlorostyrene (8.51 g, 0.061 mol) was added over 15 min and the mixture was stirred at 0° C. for 48 h. The reaction mixture was quenched by adding 10% aq. sodium sulfite (120 mL) followed by addition of EtOAc (200 mL). The layers were separated and the aqueous layer was extracted with EtOAc (200 mL). The combined organic layers were washed with 0.4 M H2SO4 in saturated Na2SO4 (100 mL), followed by drying over Na2SO4. The solvent was evaporated and the residue was separated on SiO2 (70 g) (CHCl3-MeOH 0 to 10%). Colorless oil, 9.83 g (0.057 mol, 93%). AD mix alpha (86.0 g) than cooled to 0° C the mixture was stirred at 0° C. for 48 h The reaction mixture was quenched by adding 10% aq. sodium sulfite (120 mL) followed by addition of EtOAc (200 mL) The layers were separated the aqueous layer was extracted with EtOAc (200 mL) The combined organic layers were washed with 0.4 M H2SO4 in saturated Na2SO4 (100 mL) by drying over Na2SO4 The solvent was evaporated the residue was separated on SiO2 (70 g) (CHCl3-MeOH 0 to 10%)

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

Procedure: Microwave irradiation of styrene 5 in either 1,2-dichloroethane (DCE) at 180° C. for 30 min or 1,1,1-trifluorotoluene at 180° C. for 180 minutes afforded the cyclopenta-naphthalene derivative 6 in nearly quantitative yield with no additional purification required of the final product (entries 1 and 2, Table 1). With conditions for an efficient and high yielding IMDA reaction utilizing a lower boiling solvent in hand, scope and limitations investigations were initiated. First, substitution on the aryl group was examined; exchanging a hydrogen atom for a chlorine atom was deemed valuable, enabling access to a wide-range of naphthalene derivatives via palladium-catalyzed cross coupling reactions. Moreover, a chlorine atom is more stable and accessible than other halides or groups used for coupling, such as triflates. Styrenyl derivatives 5b, 5c, and 5d were prepared and subjected to microwave irradiation. The para-chlorostyrene 5b gave 7-chloronaphthalene 6b in quantitative yield after 200 min (entry 3). The ortho-chlorostyrene 5c also produced only one product, the 5-chloronaphthalene 6c in 86% yield, even though two products are possible (entry 4). The meta-chlorostyrene 5d gave an inseparable 1.4:1 mixture of the 6-chloro- and 8-chloronaphthalenes, 6d and 6d′ in 79% yield (entry 5).

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

Procedure: Microwave irradiation of styrene 5 in either 1,2-dichloroethane (DCE) at 180° C. for 30 min or 1,1,1-trifluorotoluene at 180° C. for 180 minutes afforded the cyclopenta-naphthalene derivative 6 in nearly quantitative yield with no additional purification required of the final product (entries 1 and 2, Table 1). With conditions for an efficient and high yielding IMDA reaction utilizing a lower boiling solvent in hand, scope and limitations investigations were initiated. First, substitution on the aryl group was examined; exchanging a hydrogen atom for a chlorine atom was deemed valuable, enabling access to a wide-range of naphthalene derivatives via palladium-catalyzed cross coupling reactions. Moreover, a chlorine atom is more stable and accessible than other halides or groups used for coupling, such as triflates. Styrenyl derivatives 5b, 5c, and 5d were prepared and subjected to microwave irradiation. The para-chlorostyrene 5b gave 7-chloronaphthalene 6b in quantitative yield after 200 min (entry 3). The ortho-chlorostyrene 5c also produced only one product, the 5-chloronaphthalene 6c in 86% yield, even though two products are possible (entry 4). The meta-chlorostyrene 5d gave an inseparable 1.4:1 mixture of the 6-chloro- and 8-chloronaphthalenes, 6d and 6d′ in 79% yield (entry 5).

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

Procedure: Microwave irradiation of styrene 5 in either 1,2-dichloroethane (DCE) at 180° C. for 30 min or 1,1,1-trifluorotoluene at 180° C. for 180 minutes afforded the cyclopenta-naphthalene derivative 6 in nearly quantitative yield with no additional purification required of the final product (entries 1 and 2, Table 1). With conditions for an efficient and high yielding IMDA reaction utilizing a lower boiling solvent in hand, scope and limitations investigations were initiated. First, substitution on the aryl group was examined; exchanging a hydrogen atom for a chlorine atom was deemed valuable, enabling access to a wide-range of naphthalene derivatives via palladium-catalyzed cross coupling reactions. Moreover, a chlorine atom is more stable and accessible than other halides or groups used for coupling, such as triflates. Styrenyl derivatives 5b, 5c, and 5d were prepared and subjected to microwave irradiation. The para-chlorostyrene 5b gave 7-chloronaphthalene 6b in quantitative yield after 200 min (entry 3). The ortho-chlorostyrene 5c also produced only one product, the 5-chloronaphthalene 6c in 86% yield, even though two products are possible (entry 4). The meta-chlorostyrene 5d gave an inseparable 1.4:1 mixture of the 6-chloro- and 8-chloronaphthalenes, 6d and 6d′ in 79% yield (entry 5). with no additional purification With conditions for an efficient and high yielding were prepared irradiation