(S)-2-methylpropane-2-sulfinamide

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

Procedure: To a stirred solution of (S)-(−)-2-methyl-2-propanesulfinamide (854 mg, 7 mmol) and 1,4-dioxaspiro[4,5]decan-8-one (1 g, 6.40 mmol) in tetrahydrofuran (13 mL) was added titanium(IV) ethoxide (5.11 mL, 16 mmol). The mixture was stirred for 4 h at room temperature, poured over stirring saturated aqueous sodium bicarbonate (10 mL) and acetonitrile (10 mL), and stirred for 20 minutes. Magnesium sulfate was added and the mixture was stirred for 20 minutes, filtered over celite and concentrated. The residue was purified by column chromatography on silica gel (10:90 to 70:30 ethyl acetate:hexanes gradient) to afford N-(1,4-dioxaspiro[4.5]dec-8-ylidene)-2-methylpropane-2-sulfinamide (466 mg, 1.8 mmol, 28% yield) as a white solid. MS ESI: [M+H]+ m/z 260. poured stirred for 20 minutes the mixture was stirred for 20 minutes filtered over celite and concentrated The residue was purified by column chromatography on silica gel (10:90 to 70:30 ethyl acetate:hexanes gradient)

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

Procedure: A mixture of (S)-4-methyl-hexan-2-one (1.6 g, 14 mmol), (S)-2-methyl-propane-2-sulfinic acid amide (1.7 g, 14 mmol) and titanium(IV)ethoxide (6.4 g, 28 mmol) in THF (30 mL) was refluxed for 10 hours. Then the reaction mixture was poured into brine (150 mL). The mixture was filtered. The filtrate was extracted by EtOAc (3×70 mL). The EtOAc phase was removed under reduce pressure and the residue was purified by a silica gel column (Hexane/EtOAc 3:1) to give the titled compound (1.93 g, 63% yield) as a colorless oil: 1H NMR (CDCl3) δ 2.24 (m, 2H), 2.27 (s, 3H), 1.85 (m, 1H), 1.22 (m, 2H), 1.20(s, 9H), 0.85 (m, 6H); MS (APCl) (M+1)+ 218.1. was refluxed for 10 hours The mixture was filtered The filtrate was extracted by EtOAc (3×70 mL) The EtOAc phase was removed the residue was purified by a silica gel column (Hexane/EtOAc 3:1)

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

Procedure: In a 50 ml round-bottomed flask, 3-(trifluoromethoxy)benzaldehyde (400 mg, 2.1 mmol) was dissolved in dichloromethane (12 ml) and (S)-2-methylpropane-2-sulfinamide (281 mg, 2.31 mmol) and anhydrous copper (II) sulfate (739 mg, 4.63 mmol) were added. The reaction mixture was stirred at room temperature overnight then filtered through a glass microfiber filter, rinsing with dichloromethane. The filtrate was concentrated and the residue was chromatographed over silica gel with EtOAc/hexanes (gradient 0-20% EtOAc) to afford 430 mg (70%) of (S)-2-methyl-propane-2-sulfinic acid 1-(3-trifluoromethoxy-phenyl)-meth-(E)-ylideneamide as a light yellow oil. then filtered through a glass microfiber filter rinsing with dichloromethane The filtrate was concentrated the residue was chromatographed over silica gel with EtOAc/hexanes (gradient 0-20% EtOAc)

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

Procedure: In a 50 ml round-bottomed flask, 3-(trifluoromethoxy)benzaldehyde (400 mg, 2.1 mmol) was dissolved in dichloromethane (12 ml) and (S)-2-methylpropane-2-sulfinamide (281 mg, 2.31 mmol) and anhydrous copper (II) sulfate (739 mg, 4.63 mmol) were added. The reaction mixture was stirred at room temperature overnight then filtered through a glass microfiber filter, rinsing with dichloromethane. The filtrate was concentrated and the residue was chromatographed over silica gel with EtOAc/hexanes (gradient 0-20% EtOAc) to afford 430 mg (70%) of (S)-2-methyl-propane-2-sulfinic acid 1-(3-trifluoromethoxy-phenyl)-meth-(E)-ylideneamide as a light yellow oil. then filtered through a glass microfiber filter rinsing with dichloromethane The filtrate was concentrated the residue was chromatographed over silica gel with EtOAc/hexanes (gradient 0-20% EtOAc)

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

Procedure: In a round-bottomed flask, oxetane-3-carbaldehyde (452 mg, 3.15 mmol) was dissolved in dichloromethane (18 ml) and (S)-2-methylpropane-2-sulfinamide (435 mg, 3.59 mmol) and anhydrous copper (II) sulfate (1.11 g, 6.93 mmol) were added. The reaction mixture was stirred at room temperature for 48 h then filtered through a glass microfiber filter, rinsing with dichloromethane. The filtrate was concentrated and the residue was chromatographed over silica gel with EtOAc/hexanes (gradient: 0-30% EtOAc) to afford 173 mg (29%) of (S)-2-methyl-propane-2-sulfinic acid 1-oxetan-3-yl-meth-(E)-ylideneamide as a colorless oil. 1H NMR (CDCl3, 300 MHz): δ (ppm) 8.28 (d, J=4.9 Hz, 1H), 4.74-5.00 (m, 4H), 4.00-4.19 (m, 1H), 1.23 (s, 9H). then filtered through a glass microfiber filter rinsing with dichloromethane The filtrate was concentrated the residue was chromatographed over silica gel with EtOAc/hexanes (gradient: 0-30% EtOAc)

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

Procedure: In a round-bottomed flask, oxetane-3-carbaldehyde (452 mg, 3.15 mmol) was dissolved in dichloromethane (18 ml) and (S)-2-methylpropane-2-sulfinamide (435 mg, 3.59 mmol) and anhydrous copper (II) sulfate (1.11 g, 6.93 mmol) were added. The reaction mixture was stirred at room temperature for 48 h then filtered through a glass microfiber filter, rinsing with dichloromethane. The filtrate was concentrated and the residue was chromatographed over silica gel with EtOAc/hexanes (gradient: 0-30% EtOAc) to afford 173 mg (29%) of (S)-2-methyl-propane-2-sulfinic acid 1-oxetan-3-yl-meth-(E)-ylideneamide as a colorless oil. 1H NMR (CDCl3, 300 MHz): δ (ppm) 8.28 (d, J=4.9 Hz, 1H), 4.74-5.00 (m, 4H), 4.00-4.19 (m, 1H), 1.23 (s, 9H). then filtered through a glass microfiber filter rinsing with dichloromethane The filtrate was concentrated the residue was chromatographed over silica gel with EtOAc/hexanes (gradient: 0-30% EtOAc)

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

Procedure: In a flask (S)-2-methyl-propane-2-sulfinic acid amide (1.50 g, 12.4 mmol) was dissolved in CH2Cl2 (6 mL). Acetaldehyde (6.25 mL, 111 mmol), MgSO4 (4.47 g, 37.1 mmol) and pyridinium tosylate (156 mg, 0.62 mmol) were added. The reaction mixture was stirred overnight at room temperature, filtered and concentrated to give (S)-2-methyl-propane-2-sulfinic acid (E)-ethylideneamide as a pale red 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 (S)-2-methyl-propane-2-sulfinic acid amide (1.50 g, 12.4 mmol) was dissolved in CH2Cl2 (6 mL). Acetaldehyde (6.25 mL, 111 mmol), MgSO4 (4.47 g, 37.1 mmol) and pyridinium tosylate (156 mg, 0.62 mmol) were added. The reaction mixture was stirred overnight at room temperature, filtered and concentrated to give (S)-2-methyl-propane-2-sulfinic acid (E)-ethylideneamide as a pale red 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 round-bottomed flask, furan-2-carbaldehyde (800 mg, 8.33 mmol) was dissolved in THF (20 ml) and (S)-2-methylpropane-2-sulfinamide (1.21 g, 10.0 mmol) and titanium(IV) ethoxide (3.5 ml, 16.7 mmol) were added. The reaction mixture was stirred at room temperature for 5 h then slowly quenched by dropwise addition of brine (5 ml) which resulted in the formation of a thick precipitate. The reaction mixture was diluted with ethyl acetate and stirred vigorously at room temperature for 15 min. The suspension was filtered over Celite and rinsed with ethyl acetate. The filtrate was concentrated and the residue was chromatographed over silica gel with EtOAc/hexanes (gradient 0-25% EtOAc) to give 1.48 g (89%) of (S)-2-methyl-propane-2-sulfinic acid 1-furan-2-yl-meth-(E)-ylideneamide as a light yellow oil. then slowly quenched by dropwise addition of brine (5 ml) which resulted in the formation of a thick precipitate stirred vigorously at room temperature for 15 min The suspension was filtered over Celite rinsed with ethyl acetate The filtrate was concentrated the residue was chromatographed over silica gel with EtOAc/hexanes (gradient 0-25% EtOAc)

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

Procedure: In a round-bottomed flask, furan-2-carbaldehyde (800 mg, 8.33 mmol) was dissolved in THF (20 ml) and (S)-2-methylpropane-2-sulfinamide (1.21 g, 10.0 mmol) and titanium(IV) ethoxide (3.5 ml, 16.7 mmol) were added. The reaction mixture was stirred at room temperature for 5 h then slowly quenched by dropwise addition of brine (5 ml) which resulted in the formation of a thick precipitate. The reaction mixture was diluted with ethyl acetate and stirred vigorously at room temperature for 15 min. The suspension was filtered over Celite and rinsed with ethyl acetate. The filtrate was concentrated and the residue was chromatographed over silica gel with EtOAc/hexanes (gradient 0-25% EtOAc) to give 1.48 g (89%) of (S)-2-methyl-propane-2-sulfinic acid 1-furan-2-yl-meth-(E)-ylideneamide as a light yellow oil. then slowly quenched by dropwise addition of brine (5 ml) which resulted in the formation of a thick precipitate stirred vigorously at room temperature for 15 min The suspension was filtered over Celite rinsed with ethyl acetate The filtrate was concentrated the residue was chromatographed over silica gel with EtOAc/hexanes (gradient 0-25% EtOAc)

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Benzylhexahydrocyclopenta[c]pyrrol-4(5H)-one (16.28 g, 76 mmol), titanium tetraethoxide (28.5 mL, 137 mmol), and (S)-2-methylpropane-2-sulfinamide (10.452 g, 86 mmol) were combined in tetrahydrofuran (200 mL). The reaction was heated at 60° C. overnight. The reaction was then reduced in volume to about half and poured into 150 mL of saturated aqueous ammonium chloride. The precipitate was collected by filtration and washed with ethyl acetate. The filtrate was poured into a separatory funnel and the organic layer was removed. The aqueous layer was extracted with ethyl acetate (3×100 mL). The organic washes were combined and washed with brine, dried (Na2SO4) and concentrated. The crude material was chromatographed using silica gel cartridge (Analogix®, Burlington, Wis., RS65-400) eluting with 5-100% ethyl acetate/hexanes to give (S,E)-N-((3aR,6aS)-2-benzylhexahydrocyclopenta[c]pyrrol-4(5H)-ylidene)-2-methylpropane-2-sulfinamide and (S,E)-N-((3aS,6aR)-2-benzylhexahydrocyclopenta[c]pyrrol-4(5H)-ylidene)-2-methylpropane-2-sulfinamide. The precipitate was collected by filtration washed with ethyl acetate The filtrate was poured into a separatory funnel the organic layer was removed The aqueous layer was extracted with ethyl acetate (3×100 mL) washed with brine dried (Na2SO4) concentrated The crude material was chromatographed eluting with 5-100% ethyl acetate/hexanes

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

Procedure: (S)-N-(2-{[tert-butyl(dimethyl)silyl]oxy}ethylidene)-2-methylpropane-2-sulfinamide was prepared from (S)-(−)-2-methyl-2-propanesulfinamide and (tert-butyldimethylsilyloxy)acetaldehyde essentially according to the procedure of Barrow, J. C.; Ngo, P. L. Tetrahedron Lett. 2000, PAGES.