(NE,R)-N-ethylidene-2-methylpropane-2-sulfinamide

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

Procedure: In a flask, isobutyronitrile (6.39 g, 92.4 mmol) was dissolved in diethyl ether (190 mL) and cooled at −78° C. NaHMDS (1.0 M in THF, 99.0 mL, 99.0 mmol) was added and the mixture stirred for 30 min at −78° C. A solution of (R)-2-methyl-propane-2-sulfinic acid (E)-ethylideneamide (crude from step 1, 5.21 g, 33.0 mmol) in THF (50.0 mL) was slowly added. The mixture was stirred at −78° C. for 2 h then allowed to warm to room temperature overnight. The reaction mixture was quenched with saturated aqueous ammonium chloride and extracted with EtOAc. The combined organics were washed with brine, dried over MgSO4 and concentrated. The residue was purified by SiO2 chromatography (20-100% EtOAc/hexane) to afford 2.93 g (41%) (R)-2-methyl-propane-2-sulfinic acid ((S)-2-cyano-1,2,2-trimethyl-ethyl)-amide as a light yellow oil. 1H NMR (CDCl3, 300 MHz): δ (ppm) 3.28 (dq, J=8.7, 6.4 Hz, 1H), 3.08 (d, J=8.7 Hz, 1H), 1.45 (d, J=6.4 Hz, 3H), 1.39 (s, 3H), 1.34 (s, 3H), 1.26 (s, 9H). The mixture was stirred at −78° C. for 2 h to warm to room temperature overnight The reaction mixture was quenched with saturated aqueous ammonium chloride extracted with EtOAc The combined organics were washed with brine dried over MgSO4 concentrated The residue was purified by SiO2 chromatography (20-100% EtOAc/hexane)

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

Procedure: In a flask, isobutyronitrile (6.39 g, 92.4 mmol) was dissolved in diethyl ether (190 mL) and cooled at −78° C. NaHMDS (1.0 M in THF, 99.0 mL, 99.0 mmol) was added and the mixture stirred for 30 min at −78° C. A solution of (R)-2-methyl-propane-2-sulfinic acid (E)-ethylideneamide (crude from step 1, 5.21 g, 33.0 mmol) in THF (50.0 mL) was slowly added. The mixture was stirred at −78° C. for 2 h then allowed to warm to room temperature overnight. The reaction mixture was quenched with saturated aqueous ammonium chloride and extracted with EtOAc. The combined organics were washed with brine, dried over MgSO4 and concentrated. The residue was purified by SiO2 chromatography (20-100% EtOAc/hexane) to afford 2.93 g (41%) (R)-2-methyl-propane-2-sulfinic acid ((S)-2-cyano-1,2,2-trimethyl-ethyl)-amide as a light yellow oil. 1H NMR (CDCl3, 300 MHz): δ (ppm) 3.28 (dq, J=8.7, 6.4 Hz, 1H), 3.08 (d, J=8.7 Hz, 1H), 1.45 (d, J=6.4 Hz, 3H), 1.39 (s, 3H), 1.34 (s, 3H), 1.26 (s, 9H). The mixture was stirred at −78° C. for 2 h to warm to room temperature overnight The reaction mixture was quenched with saturated aqueous ammonium chloride extracted with EtOAc The combined organics were washed with brine dried over MgSO4 concentrated The residue was purified by SiO2 chromatography (20-100% EtOAc/hexane)

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

Procedure: In a flask (R)-2-methyl-propane-2-sulfinic acid amide (4.00 g, 33.0 mmol) was dissolved in CH2Cl2 (14.0 mL). Acetaldehyde (16.7 mL, 297 mmol), MgSO4 (11.9 g, 99.0 mmol) and pyridinium tosylate (415 mg, 1.65 mmol) were added. The reaction mixture was stirred overnight at room temperature, filtered and concentrated to give 5.21 g of (R)-2-methyl-propane-2-sulfinic acid (E)-ethylideneamide as a yellow oil which was used without further purification. filtered concentrated

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

Procedure: In a flask (R)-2-methyl-propane-2-sulfinic acid amide (4.00 g, 33.0 mmol) was dissolved in CH2Cl2 (14.0 mL). Acetaldehyde (16.7 mL, 297 mmol), MgSO4 (11.9 g, 99.0 mmol) and pyridinium tosylate (415 mg, 1.65 mmol) were added. The reaction mixture was stirred overnight at room temperature, filtered and concentrated to give 5.21 g of (R)-2-methyl-propane-2-sulfinic acid (E)-ethylideneamide as a yellow oil which was used without further purification. filtered concentrated

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

Procedure: In a flask, isobutyronitrile (6.39 g, 92.4 mmol) was dissolved in diethyl ether (190 mL) and cooled at −78° C. NaHMDS (1.0 M in THF, 99.0 mL, 99.0 mmol) was added and the mixture stirred for 30 min at −78° C. A solution of (R)-2-methyl-propane-2-sulfinic acid (E)-ethylideneamide (crude from step 1, 5.21 g, 33.0 mmol) in THF (50.0 mL) was slowly added. The mixture was stirred at −78° C. for 2 h then allowed to warm to room temperature overnight. The reaction mixture was quenched with saturated aqueous ammonium chloride and extracted with EtOAc. The combined organics were washed with brine, dried over MgSO4 and concentrated. The residue was purified by SiO2 chromatography (20-100% EtOAc/hexane) to afford 2.93 g (41%) (R)-2-methyl-propane-2-sulfinic acid ((S)-2-cyano-1,2,2-trimethyl-ethyl)-amide as a light yellow oil. 1H NMR (CDCl3, 300 MHz): δ (ppm) 3.28 (dq, J=8.7, 6.4 Hz, 1H), 3.08 (d, J=8.7 Hz, 1H), 1.45 (d, J=6.4 Hz, 3H), 1.39 (s, 3H), 1.34 (s, 3H), 1.26 (s, 9H). The mixture was stirred at −78° C. for 2 h to warm to room temperature overnight The reaction mixture was quenched with saturated aqueous ammonium chloride extracted with EtOAc The combined organics were washed with brine dried over MgSO4 concentrated The residue was purified by SiO2 chromatography (20-100% EtOAc/hexane)

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

Procedure: In a flask (R)-2-methyl-propane-2-sulfinic acid amide (4.00 g, 33.0 mmol) was dissolved in CH2Cl2 (14.0 mL). Acetaldehyde (16.7 mL, 297 mmol), MgSO4 (11.9 g, 99.0 mmol) and pyridinium tosylate (415 mg, 1.65 mmol) were added. The reaction mixture was stirred overnight at room temperature, filtered and concentrated to give 5.21 g of (R)-2-methyl-propane-2-sulfinic acid (E)-ethylideneamide as a yellow oil which was used without further purification. filtered concentrated

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

Procedure: In a flask, isobutyronitrile (6.39 g, 92.4 mmol) was dissolved in diethyl ether (190 mL) and cooled at −78° C. NaHMDS (1.0 M in THF, 99.0 mL, 99.0 mmol) was added and the mixture stirred for 30 min at −78° C. A solution of (R)-2-methyl-propane-2-sulfinic acid (E)-ethylideneamide (crude from step 1, 5.21 g, 33.0 mmol) in THF (50.0 mL) was slowly added. The mixture was stirred at −78° C. for 2 h then allowed to warm to room temperature overnight. The reaction mixture was quenched with saturated aqueous ammonium chloride and extracted with EtOAc. The combined organics were washed with brine, dried over MgSO4 and concentrated. The residue was purified by SiO2 chromatography (20-100% EtOAc/hexane) to afford 2.93 g (41%) (R)-2-methyl-propane-2-sulfinic acid ((S)-2-cyano-1,2,2-trimethyl-ethyl)-amide as a light yellow oil. 1H NMR (CDCl3, 300 MHz): δ (ppm) 3.28 (dq, J=8.7, 6.4 Hz, 1H), 3.08 (d, J=8.7 Hz, 1H), 1.45 (d, J=6.4 Hz, 3H), 1.39 (s, 3H), 1.34 (s, 3H), 1.26 (s, 9H). The mixture was stirred at −78° C. for 2 h to warm to room temperature overnight The reaction mixture was quenched with saturated aqueous ammonium chloride extracted with EtOAc The combined organics were washed with brine dried over MgSO4 concentrated The residue was purified by SiO2 chromatography (20-100% EtOAc/hexane)

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

Procedure: In a flask (R)-2-methyl-propane-2-sulfinic acid amide (4.00 g, 33.0 mmol) was dissolved in CH2Cl2 (14.0 mL). Acetaldehyde (16.7 mL, 297 mmol), MgSO4 (11.9 g, 99.0 mmol) and pyridinium tosylate (415 mg, 1.65 mmol) were added. The reaction mixture was stirred overnight at room temperature, filtered and concentrated to give 5.21 g of (R)-2-methyl-propane-2-sulfinic acid (E)-ethylideneamide as a yellow oil which was used without further purification. filtered concentrated