methylidenecyclohexane

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

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

Procedure: A mixture of methylene cyclohexane (0.96 g, 10 mmoles), p-bromophenol (1.73 g, 10 mmoles) and acid resin (Dowex 50×12--150 mg) is heated at 80° C. for 16 hours. The residue is purified by silica gel chromatography (eluant: 50/50 mixture of CH2Cl2 /hexane). On evaporation of the solvents 0.50 g (19% yield) of 4-bromo-2-(1-methylcyclohexyl) phenol in the form of a yellowish oil is obtained. The residue is purified by silica gel chromatography (eluant: 50/50 mixture of CH2Cl2 /hexane)

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

Procedure: A mixture of methylene cyclohexane (0.96 g, 10 mmoles), p-bromophenol (1.73 g, 10 mmoles) and acid resin (Dowex 50×12--150 mg) is heated at 80° C. for 16 hours. The residue is purified by silica gel chromatography (eluant: 50/50 mixture of CH2Cl2 /hexane). On evaporation of the solvents 0.50 g (19% yield) of 4-bromo-2-(1-methylcyclohexyl) phenol in the form of a yellowish oil is obtained. The residue is purified by silica gel chromatography (eluant: 50/50 mixture of CH2Cl2 /hexane)

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

Procedure: Into a 25-ml flask was placed 0.5 g of a powder of Molecular Sieves® 4A (manufactured by Aldrich Corp.), and the air in the flask was thoroughly displaced by argon. Then, 5 ml of methylene chloride was added thereto, and 0.16 ml (0.05 mmole) of the diisopropoxydibromotitanium solution in toluene as prepared above and 14.3 mg (0.05 mmole) of (R)-binaphthol were further added. The mixture was stirred at room temperature for 1 hour to prepare an (R)-binaphtholdibromotitanium complex. This solution was cooled to -30° C. in a bath of dry ice and acetone, and subsequently 96 mg (1 mmole) of methylenecyclohexane (manufactured by Aldrich Corp.) and 88 mg (1 mmole) of methyl glyoxylate were added to this cooled solution, followed by reaction for 3 hours. Thereafter, 10 ml of an aqueous sodium hydrogen-carbonate solution was added to terminate the reaction. The reaction mixture was filtered through Celite and extracted with two 20 ml portions of diethyl ether and two 20 ml portions of ethyl acetate, and the extract was dried over anhydrous magnesium sulfate. Then, the solvents were distilled off, and hexane was added to the residue to crystallize binaphthol. The remaining solution was purified by means of silica gel column chromatography to obtain 0.16 g of methyl (S)-2- hydroxy-3-(1-cyclohexenyl)propionate. The yield was 89%. Into a 25-ml flask was placed were further added to prepare an (R)-binaphtholdibromotitanium complex were added to this cooled solution followed by reaction for 3 hours to terminate the reaction The reaction mixture was filtered through Celite extracted with two 20 ml portions of diethyl ether and two 20 ml portions of ethyl acetate the extract was dried over anhydrous magnesium sulfate Then, the solvents were distilled off hexane was added to the residue to crystallize binaphthol The remaining solution was purified by means of silica gel column chromatography

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

Procedure: A solution of an (S)-binaphthol-dichlorotitanium complex (0.1 mmole) which had been prepared in the same manner as in Example 1 was cooled to -10° C. and there was added thereto 96 mg (1 mmole) of methylenecyclohexane and 88 mg (1 mmole) of methyl glyoxylate, followed by reaction for 8 hours. Then, 10 ml of an aqueous sodium hydrogen carbonate solution was added to terminate the reaction. The reaction mixture was filtered through Celite and extracted with two 20 ml portions of diethyl ether and two 20 ml portions of ethyl acetate, and the extract was dried over anhydrous magnesium sulfate. Thereafter, the solvents were distilled off, and hexane was added to the residue to crystallize binaphthol. The remaining solution was purified by mean of silica gel column chromatography to obtain 0.13 g of methyl (S)-2-hydroxy-3-(1-cyclohexenyl)propanoate. The yield was 73%. A solution of an (S)-binaphthol-dichlorotitanium complex (0.1 mmole) which had been prepared in the same manner as in Example 1 there was added to terminate the reaction The reaction mixture was filtered through Celite extracted with two 20 ml portions of diethyl ether and two 20 ml portions of ethyl acetate the extract was dried over anhydrous magnesium sulfate Thereafter, the solvents were distilled off hexane was added to the residue to crystallize binaphthol The remaining solution was purified by mean of silica gel column chromatography

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

Procedure: To a stirred suspension of dried Chloramine-T (5.10 g, 20.76 mmol) in CH3CN (100 mL) under a nitrogen atmosphere methylenecyclohexane (9.98 g, 104 mmol) was added. Phenyltrimethylammonium tribromide (7.80 g, 20.76 mmol) was added in three portions over 10 min. The mixture was stirred at room temperature for 16 hours. The solvent was evaporated and the residue was partitioned between dichloromethane and water. The organic layer was dried over Na2SO4 and the solvent was evaporated. The residue was chromatographed on silica gel with an ISCO Combiflash using EtOAc/hexanes (5-30% gradient) to afford the title compound as a white solid (2.66 g). was added The solvent was evaporated the residue was partitioned between dichloromethane and water The organic layer was dried over Na2SO4 the solvent was evaporated The residue was chromatographed on silica gel with an ISCO Combiflash

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

Procedure: Under similar reaction conditions as in Example 5, methylenecyclohexane, methylenecyclopentane, 2-methyl-1-pentene, 2,4,4-trimethyl-2-pentene and 2,3-diphenyl-1-propene underwent the isomerization to the thermodynamically more stable isomers shown in Table 1. The isomerization of 2-methyl-1-pentene afforded only 2-methyl-2-pentene and 4-methyl-2-pentenes were not observed.

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

Procedure: Under similar reaction conditions as in Example 5, methylenecyclohexane, methylenecyclopentane, 2-methyl-1-pentene, 2,4,4-trimethyl-2-pentene and 2,3-diphenyl-1-propene underwent the isomerization to the thermodynamically more stable isomers shown in Table 1. The isomerization of 2-methyl-1-pentene afforded only 2-methyl-2-pentene and 4-methyl-2-pentenes were not observed.

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

Procedure: A mixture of methylene cyclohexane (0.96 g, 10 mmoles), p-bromophenol (1.73 g, 10 mmoles) and acid resin (Dowex 50×12--150 mg) is heated at 80° C. for 16 hours. The residue is purified by silica gel chromatography (eluant: 50/50 mixture of CH2Cl2 /hexane). On evaporation of the solvents 0.50 g (19% yield) of 4-bromo-2-(1-methylcyclohexyl) phenol in the form of a yellowish oil is obtained. The residue is purified by silica gel chromatography (eluant: 50/50 mixture of CH2Cl2 /hexane)

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

Conditions: temp:102.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 250 mL round-bottom flask was charged with methylenecyclohexane (20.0 g, 0.21 mol, commercially available from Aldrich), copper powder (2.8 g), methyl cyclohexane (50 mL) and heated to 105° C. Ethyl diazoacetate (26 g, 0.23 mol, commercially available from Aldrich) was added dropwise over an 8-hour period while maintaining the temperature between 100-105° C. Upon complete addition, the mixture was heated an additional 2 hours, allowed to cool to ambient temperature and stirred for an additional 12 hours. The reaction mixture was filtered and concentrated under reduced pressure to afford the title compound which was used without further purification. Upon complete addition the mixture was heated an additional 2 hours to cool to ambient temperature The reaction mixture was filtered concentrated under reduced pressure

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

Procedure: To a stirred suspension of dried Chloramine-T (5.10 g, 20.76 mmol) in CH3CN (100 mL) under a nitrogen atmosphere was added methylenecyclohexane (9.98 g, 104 mmol). Phenyltrimethylammonium tribromide (7.80 g, 20.76 mmol) was added in three portions over 10 min. The mixture was stirred at room temperature for 16 hours. The solvent was evaporated and the residue was partitioned between dichloromethane and water. The organic layer was dried over Na2SO4 and the solvent was evaporated. The residue was chromatographed on silica gel with an ISCO Combiflash using EtOAc/hexanes (5-30% gradient) to afford the title compound as a white solid (2.66 g). The solvent was evaporated the residue was partitioned between dichloromethane and water The organic layer was dried over Na2SO4 the solvent was evaporated The residue was chromatographed on silica gel with an ISCO Combiflash