5-bromofuran-3-carbaldehyde

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

Procedure: n-Butyl lithium (a 1.6M solution in hexane; 31.0 ml, 49.7 mmol) was added dropwise to a solution of morpholine (4.33 ml, 49.7 mmol; freshly distilled from barium oxide) in tetrahydrofuran at -78° under argon. After 15 minutes, a solution of 5-bromo-3-furaldehyde (7.5 g, 49.7 mmol) in tetrahydrofuran was added dropwise. Stirring was continued for 30 min. and n-butyl lithium (a 1.6M solution in hexane; 46.6 ml, 74.5 mmol) was added dropwise. After 1 hour at -78°, chlorotrimethylsilane (18.9 ml, 149 mmol) was added and stirring continued while the cooling bath attained room temperature. The reaction mixture was quenched with 10% hydrochloric acid and the phases were separated. The aqueous phase was stirred, in the presence of ethyl ether (30 ml), with 10% hydrochloric acid at 0° C. for 1/2 hour. The organic phases were combined, washed (brin), dried (magnesium sulfate) and evaporated down. The residue was distilled under vacuum to give the title aldehyde as a colorless oil b.p. 48°-50°/0.25 torr. freshly distilled from barium oxide) in tetrahydrofuran at -78° under argon was continued for 30 min. 46.6 ml, 74.5 mmol) was added dropwise After 1 hour at -78° stirring continued while the cooling bath attained room temperature The reaction mixture was quenched with 10% hydrochloric acid the phases were separated The aqueous phase was stirred, in the presence of ethyl ether (30 ml), with 10% hydrochloric acid at 0° C. for 1/2 hour washed (brin) dried (magnesium sulfate) evaporated down The residue was distilled under vacuum

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

Procedure: A mixture of 1-bromododecane (3.45 g, 14 mmol) and magnesium turnings (349 mg, 14.5 mmol) in tetrahydrofuran (10 ml) was refluxed under argon for 1 hour. After cooling to 0 degrees, a solution of 5-bromo-3-furaldehyde (2.42 g, 14 mmol) in tetrahydrofuran (3 ml) was added and conditions maintained for 20 minutes. The mixture was further cooled to -78 degrees and tert-butyl lithium (a 1.7 M solution in pentane; 9.77 ml, 1.67 mmol) was added dropwise, followed by chlorotrimethylsilane (5.27 ml, 41.5 mmol) after 20 minutes. Stirring was continued overnight (12 hours) while the cooling bath attained room temperature. The mixture was quenched with saturated aqueous ammonium chloride, diluted with water (15 ml) and extracted with ethyl ether. Evaporation of the dried (magnesium sulfate) extract gave a brown oil, which was flash chromatographed on silica using 15% ethyl ether/petroleum ether. Fractions with Rf of about 0.25 on evaporation afforded the title trimethylsilylfuran as a pale yellow oil. was refluxed under argon for 1 hour After cooling to 0 degrees conditions maintained for 20 minutes The mixture was further cooled to -78 degrees 9.77 ml, 1.67 mmol) was added dropwise (12 hours) while the cooling bath attained room temperature The mixture was quenched with saturated aqueous ammonium chloride diluted with water (15 ml) extracted with ethyl ether Evaporation of the dried (magnesium sulfate) extract gave a brown oil, which chromatographed on silica using 15% ethyl ether/petroleum ether Fractions with Rf of about 0.25 on evaporation

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

Procedure: A mixture of 1-bromododecane (3.45 g, 14 mmol) and magnesium turnings (349 mg, 14.5 mmol) in tetrahydrofuran (10 ml) was refluxed under argon for 1 hour. After cooling to 0 degrees, a solution of 5-bromo-3-furaldehyde (2.42 g, 14 mmol) in tetrahydrofuran (3 ml) was added and conditions maintained for 20 minutes. The mixture was further cooled to -78 degrees and tert-butyl lithium (a 1.7M solution in pentane; 9.77 ml, 1.67 mmol) was added dropwise, followed by chlorotrimethylsilane (5.27 ml, 41.5 mmol) after 20 minutes. Stirring was continued overnight (12 hours) while the cooling bath attained room temperature. The mixture was quenched with saturated aqueous ammonium chloride, diluted with water (15 ml) and extracted with ethyl ether. Evaporation of the dried (magnesium sulfate) extract gave a brown oil, which was flash chromatographed on silica using 15% ethyl ether/petroleum ether. Fractions with Rf of about 0.25 on evaporation afforded the title trimethylsilylfuran as a pale yellow oil. was refluxed under argon for 1 hour After cooling to 0 degrees conditions maintained for 20 minutes The mixture was further cooled to -78 degrees 9.77 ml, 1.67 mmol) was added dropwise (12 hours) while the cooling bath attained room temperature The mixture was quenched with saturated aqueous ammonium chloride diluted with water (15 ml) extracted with ethyl ether Evaporation of the dried (magnesium sulfate) extract gave a brown oil, which chromatographed on silica using 15% ethyl ether/petroleum ether Fractions with Rf of about 0.25 on evaporation

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

Procedure: n-Butyl lithium (a 1.6 M solution in hexane; 31.0 ml, 49.7 mmol) was added dropwise to a solution of morpholine (4.33 ml, 49.7 mmol; freshly distilled from barium oxide) in tetrahydrofuran at -78° under argon. After 15 minutes, a solution of 5-bromo-3-furaldehyde (7.5 g, 49.7 mmol) in tetrahydrofuran was added dropwise. Stirring was continued for 30 min. and n-butyl lithium (a 1.6 M solution in hexane; 46.6 ml, 74.5 mmol) was added dropwise. After 1 hour at -78°, chlorotrimethylsilane (18.9 ml, 149 mmol) was added and stirring continued while the cooling bath attained room temperature. The reaction mixture was quenched with 10% hydrochloric acid and the phases were separated. The aqueous phase was stirred, in the presence of ethyl ether (30 ml), with 10% hydrochloric acid at 0° C. for 1/2 hour. The organic phases were combined, washed (brine), dried (magnesium sulfate) and evaporated down. The residue was distilled under vacuum to give the title aldehyde as a colorless oil b.p. 48°-50°/0.25 torr. freshly distilled from barium oxide) in tetrahydrofuran at -78° under argon was continued for 30 min. 46.6 ml, 74.5 mmol) was added dropwise After 1 hour at -78° stirring continued while the cooling bath attained room temperature The reaction mixture was quenched with 10% hydrochloric acid the phases were separated The aqueous phase was stirred, in the presence of ethyl ether (30 ml), with 10% hydrochloric acid at 0° C. for 1/2 hour washed (brine) dried (magnesium sulfate) evaporated down The residue was distilled under vacuum

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

Procedure: A mixture of 1-bromooctane (1.33 g, 6.9 mmol) and magnesium turnings (174 mg, 7.3 mmol) in tetrahydrofuran (8 ml) was refluxed under argon for 60 minutes. After cooling to 0°, a solution of 5-bromo-3-furaldehyde (1.21 g, 6.9 mmol) in THF (1 ml) was added and conditions maintained for 60 min. The mixture was further cooled to -78° and tert-butyl lithium (a 1.7M solution in pentane, 4.26 ml, 7.3 mmol) was added dropwise, followed by chlorotrimethylsilane (2.63 ml, 20.7 mmol) after 1 hour. Stirring was continued overnight while the cooling bath attained room temperature. The mixture was quenched with saturated aqueous ammonium chloride, diluted with water (15 ml) and extracted with ether. Evaporation of the dried (magnesium sulfate) extract gave a brown oil, which was subjected to flash chromatography on silica using 15% ethyl ether/petroleum ether. Fractions with Rf of about 0.2 on evaporation gave the captioned compound as a yellow oil. was refluxed under argon for 60 minutes After cooling to 0° conditions maintained for 60 min The mixture was further cooled to -78° The mixture was quenched with saturated aqueous ammonium chloride diluted with water (15 ml) extracted with ether Evaporation of the dried (magnesium sulfate) extract gave a brown oil, which Fractions with Rf of about 0.2 on evaporation

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

Procedure: n-Butyl lithium (a 1.6M solution in hexane; 31.0 ml, 49.7 mmol) was added dropwise to a solution of morpholine (4.33 ml, 49.7 mmol; freshly distilled from barium oxide) in tetrahydrofuran at -78° under argon. After 15 minutes, a solution of 5-bromo-3-furaldehyde (7.5 g, 49.7 mmol) in tetrahydrofuran (THF) was added dropwise. Stirring was continued for 30 min. and n-butyl lithium (a 1.6M solution in hexane; 46.6 ml, 74.5 mmol) was added dropwise. After 1 hour at -78°, chlorotrimethylsilane (18.9 ml, 149 mmol) was added and stirring continued while the cooling bath attained room temperature. The reaction mixture was quenched with 10% hydrochloric acid and the phases were separated. The aqueous phase was stirred, in the presence of ethyl ether (30 ml), with 10% hydrochloric acid at 0° C. for 1/2 hour. The organic phases were combined, washed (brine), dried (magnesium sulfate) and evaporated down. The residue was distilled under vacuum to give the title aldehyde as a colorless oil b.p. 48°-50°/0.25 torr. freshly distilled from barium oxide) in tetrahydrofuran at -78° under argon was continued for 30 min. 46.6 ml, 74.5 mmol) was added dropwise After 1 hour at -78° stirring continued while the cooling bath attained room temperature The reaction mixture was quenched with 10% hydrochloric acid the phases were separated The aqueous phase was stirred, in the presence of ethyl ether (30 ml), with 10% hydrochloric acid at 0° C. for 1/2 hour washed (brine) dried (magnesium sulfate) evaporated down The residue was distilled under vacuum

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

Procedure: A mixture of 1-bromododecane (3.45 g, 14 mmol) and magnesium turnings (349 mg, 14.5 mmol) in tetrahydrofuran (10 ml) was refluxed under argon for 1h. After cooling to 0°, a solution of 5-bromo-3-furaldehyde (2.42 g, 14 mmol) in tetrahydrofuran (3 ml) was added and conditions maintained for 20 min. The mixture was further cooled to -78° and tert-butyl lithium (a 1.7M solution in pentane; 9.77 ml, 1.67 mmol) was added dropwise, followed by chlorotrimethylsilane (5.27 ml, 41.5 mmol) after 20 min. Stirring was continued overnight (12h) while the cooling bath attained room temperature. The mixture was quenched with saturated aqueous ammonium chloride, diluted with water (15 ml) and extracted with ethyl ether. Evaporation of the dried (magnesium sulfate) extract gave a brown oil, which was flash chromatographed on silica using 15% ethyl ether/petroleum ether. Fractions with Rf of about 0.25 on evaporation afforded the title trimethylsilylfuran as a pale yellow oil. was refluxed under argon for 1h After cooling to 0° conditions maintained for 20 min The mixture was further cooled to -78° 9.77 ml, 1.67 mmol) was added dropwise while the cooling bath attained room temperature The mixture was quenched with saturated aqueous ammonium chloride diluted with water (15 ml) extracted with ethyl ether Evaporation of the dried (magnesium sulfate) extract gave a brown oil, which chromatographed on silica using 15% ethyl ether/petroleum ether Fractions with Rf of about 0.25 on evaporation

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

Procedure: A mixture of 1-bromodecane (2.83 g, 13 mmol) and magnesium turnings (322 mg, 13.5 mmol) in THF (10 ml) was refluxed under argon for 60 min. After cooling to 0°, a solution of 5-bromo-3-furaldehyde (2.24 g, 13 mmol) in tetrahydrofuran (3 ml) was added and conditions maintained for 20 min. The mixture was further cooled to -78° and tert-butyl lithium (a 1.7M solution in pentane; 9.04 ml, 15.4 mmol) was added dropwise, followed by chlorotrimethylsilane (4.88 ml, 38.4 mmol) after 20 min. Stirring was continued overnight (12h) while the cooling bath attained room temperature. The mixture was quenched with saturated aqueous ammonium chloride, diluted with water (15 ml) and extracted with ether. Evaporation of the dried (magnesium sulfate) extract gave a brown oil, which was flash chromatographed on silica using 15% ethyl ether/petroleum ether. Fractions with about Rf 0.22 on evaporation gave the title compound as a yellow oil. was refluxed under argon for 60 min After cooling to 0° conditions maintained for 20 min The mixture was further cooled to -78° 9.04 ml, 15.4 mmol) was added dropwise while the cooling bath attained room temperature The mixture was quenched with saturated aqueous ammonium chloride diluted with water (15 ml) extracted with ether Evaporation of the dried (magnesium sulfate) extract gave a brown oil, which chromatographed on silica using 15% ethyl ether/petroleum ether Fractions with about Rf 0.22 on evaporation

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

Procedure: A mixture of 1-bromooctane (1.33 g, 6.9 mmol) and magnesium turnings (174 mg, 7.3 mmol) in tetrahydrofuran (8 ml) was refluxed under argon for 60 min. After cooling to 0°, a solution of 5-bromo-3-furaldehyde (1.21 g, 6.9 mmol) in THF (1 ml) was added and conditions maintained for 60 min. The mixture was further cooled to -78° and tert-butyl lithium (a 1.7M solution in pentane, 4.26 ml, 7.3 mmol) was added dropwise, followed by chlorotrimethylsilane (2.63 ml, 20.7 mmol) after 1h. Stirring was continued overnight while the cooling bath attained room temperature. The mixture was quenched with saturated aqueous ammonium chloride, diluted with water (15 ml) and extracted with ether. Evaporation of the dried (magnesium sulfate) extract gave a brown oil, which was subjected to flash chromatography on silica using 15% ethyl ether/petroleum ether. Fractions with Rf 0.2 on evaporation gave the captioned compound as a yellow oil. was refluxed under argon for 60 min After cooling to 0° conditions maintained for 60 min The mixture was further cooled to -78° The mixture was quenched with saturated aqueous ammonium chloride diluted with water (15 ml) extracted with ether Evaporation of the dried (magnesium sulfate) extract gave a brown oil, which Fractions with Rf 0.2 on evaporation

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

Procedure: n-Butyl lithium (a 1.6M solution in hexane, 31.0 ml, 49.7 mmol) was added dropwise to a solution of morpholine (4.33 ml, 49.7 mmol; freshly distilled from barium oxide) in tetrahydrofuran at -78° under argon. After 15 minutes, a solution of 5-bromo-3-furaldehyde (7.5 g, 49.7 mmol) in tetrahydrofuran was added dropwise. Stirring was continued for 30 min. and n-butyl lithium (a 1.6M solution in hexane; 46.6 ml, 74.5 mmol) was added dropwise. After 1 hour at -78°, chlorotrimethylsilane (18.9 ml, 149 mmol) was added and stirring continued while the cooling bath attained room temperature. The reaction mixture was quenched with 10% hydrochloric acid and the phases were separated. The aqueous phase was stirred, in the presence of ethyl ether (30 ml), with 10% hydrochloric acid at 0° C. for 1/2 hour. The organic phases were combined, washed (brine), dried (magnesium sulfate) and evaporated down. The residue was distilled under vacuum to give the title aldehyde as a colorless oil b.p. 48°-50°/0.25 torr. freshly distilled from barium oxide) in tetrahydrofuran at -78° under argon was continued for 30 min. 46.6 ml, 74.5 mmol) was added dropwise After 1 hour at -78° stirring continued while the cooling bath attained room temperature The reaction mixture was quenched with 10% hydrochloric acid the phases were separated The aqueous phase was stirred, in the presence of ethyl ether (30 ml), with 10% hydrochloric acid at 0° C. for 1/2 hour washed (brine) dried (magnesium sulfate) evaporated down The residue was distilled under vacuum

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

Procedure: To a stirred solution of 5-bromo-3-furaldehyde, dimethyl acetal (1.26 g., 5.7 mmol) in 10 ml dry tetrahydrofuran at 78° under argon was added t-butyllithium (9.69 mmol in pentane), followed by the subsequent addition of trimethylsilyl chloride (1.36 g., 12.54 mmol). After two hours the reaction was quenched with a 10% ammonium chloride solution and the organic portion was washed with 5% sodium bicarbonate, water, saturated sodium chloride solution, dried over magnesium sulfate, filtered and concentrated to give a yellow oil. Purification by flash chromatography (10% ether/pet. ether) yielded the desired aldehyde. After two hours the reaction was quenched with a 10% ammonium chloride solution the organic portion was washed with 5% sodium bicarbonate, water, saturated sodium chloride solution dried over magnesium sulfate filtered concentrated to give a yellow oil Purification by flash chromatography (10% ether/pet. ether)

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

Procedure: According to the above procedure, 3-furaldehyde is brominated to give 5-bromo-3-furaldehyde which is then reacted with a Grignard reagent (R3MgX) and the resulting mixture treated with t-butyl lithium and trimethylsilyl chloride to give 4-[R3 --CH(OH)]-2-trimethylsilylfuran. Alternatively, 5-bromo-3-furaldehyde is converted to the dimethylacetal, then treated with t-butyl lithium and trimethylsilyl chloride to give 5-trimethylsilyl-3-furaldehyde which is reacted with R3MgX or R3Li to give 4-[R3 --CH(OH)]-2-trimethylsilylfuran. Treating this intermediate with oxygen and irradiation using an initiator such as Rose Bengal gives 4-[R3 --CH(OH]-5-hydroxy-2(5H)-furanone.