phenyl selenohypochlorite

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

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

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

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

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

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

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

Procedure: A solution of diisopropylamine (3.02 mL, 21.21 mmol) in tetrahydrofuran (44.2 mL) under argon was cooled to −78° C. and added butyllithium solution, 2.5M in hexanes (8.48 mL, 21.21 mmol). After 5 min, a solution of 1-methylpiperidin-2-one (2 g, 17.67 mmol) in tetrahydrofuran (2 mL) was added dropwise. After stirring for 10 min, a solution of phenylselenenyl chloride (4.06 g, 21.21 mmol) in 16 mL of tetrahydrofuran was added, and the reaction was stirred at −78° C. for 2 h. The reaction was quenched with aqueous saturated NH4Cl solution and diluted with CH2Cl2; the aqueous layer was back-extracted with CH2Cl2 (1×). The combined organic extracts were dried (MgSO4), filtered, and concentrated in vacuo to afford a crude crop of 1-methyl-3-(phenylselanyl)piperidin-2-one in dichloromethane. To the crude 1-methyl-3-(phenylselanyl)piperidin-2-one in dichloromethane (50 mL) at 0° C. under argon was added 3-chlorobenzoperoxoic acid (7.92 g, 35.3 mmol). The resulting mixture was allowed to gradually warm to room temperature overnight. The orange suspension was filtered, and the filtrate was concentrated in vacuo and partitioned between CH2Cl2 and aqueous saturated NaHCO3 solution; the aqueous layer was back-extracted with CH2Cl2 (5×). The combined organic extracts were dried (MgSO4), filtered, and concentrated in vacuo. Flash column chromatography (20% EtOAc/Hexanes to 100% EtOAc) afforded 1-methyl-5,6-dihydropyridin-2(1H)-one (1.33 g, 67.7% yield) as a brown oil. [M+1]=112.2. the reaction was stirred at −78° C. for 2 h The reaction was quenched with aqueous saturated NH4Cl solution diluted with CH2Cl2 the aqueous layer was back-extracted with CH2Cl2 (1×) The combined organic extracts were dried (MgSO4) filtered concentrated in vacuo

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

Procedure: A solution of 1.42 g of 13 in 25 ml of dry tetrahydrofuran was added drop-by-drop to a solution of lithium hexamethyldisilazide (prepared by adding 5.7 ml of a 2.2M solution of n-butyllithium in hexane drop-by-drop to a solution of 2.7 ml of hexamethyldisilazane and 1.9 ml of tetramethylethylenediamine in tetrahydrofuran) in 15 ml of dry tetrahydrofuran, at -78° C., under argon. The resulting solution was stirred for one hour at -78° C., then a solution of 0.96 g of phenylselenenyl chloride in 15 ml of dry tetrahydrofuran was added rapidly. The resulting solution was stirred at -78° C. for 10 minutes, warmed to -20° C. and quenched by the addition of 60 ml of 1N hydrochloric acid and 20 ml of cold water. The solution then was warmed to room temperature and extracted with ether. The extract was washed, successively, with water, 1N hydrochloric acid, 1N sodium bicarbonate solution and water. It then was dried (MgSO4), the solvent was evaporated and the residue was chromatographed on silica gel, eluting first with n-hexane (to remove diphenylselenide) and then with 30% ethyl acetate/n-hexane to give, on work-up, methyl (S)-4-(benzyloxycarbonylamino)-5-fluoro-2-(phenylselenyl)pentanoate (26A), as a pale yellow oil. prepared at -78° C. The resulting solution was stirred at -78° C. for 10 minutes warmed to -20° C. quenched by the addition of 60 ml of 1N hydrochloric acid and 20 ml of cold water The solution then was warmed to room temperature extracted with ether The extract was washed It then was dried (MgSO4) the solvent was evaporated the residue was chromatographed on silica gel eluting first with n-hexane (to remove diphenylselenide)

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

Procedure: The diene (2) is treated with a halogenating agent such as phenylselenyl chloride or bromide or phenylsulfinyl chloride, preferably phenylselenyl chloride, in an approximately equimolar ratio in an inert solvent at about -80° C., for approximately 20 minutes; illustrative of such inert solvents are methylene chloride, ether and the like. After a standard workup the product residue is dissolved in an ethereal solvent, chilled to about 0° C. and oxidized with an agent such as 30% hydrogen peroxide or a peroxy acid such as peroxybenzoic acid to yield a halohydrin analog (3). After a standard workup the product residue is dissolved in an ethereal solvent

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

Procedure: To phenylselenyl chloride (0.199 g, 1.041 mmol) was added (1R)-benzyl 3-allyl-3-aminocyclopentanecarboxylate (example 2, step A, 0.090 g, 0.347 mmol) dissolved in acetonitrile (2 mL). The contents were heated at 80° C. for 18 hours. The reaction mixture was concentrated and partitioned between ethyl acetate (20 mL) and saturated aqueous sodium bicarbonate (10 mL). The ethyl acetate layer was dried over sodium sulfate and concentrated. To the residue was added methanol (5 mL). The solid that separates was filtered and washed with methanol (2 mL). To the filtrate was added 4.0N hydrogen chloride in dioxane (1 mL) and the contents concentrated. Ethyl acetate was added and the resulting mixture was concentrated under reduced pressure. Methanol (5 mL) was added and a solid separates out The liquid was carefully pipetted out into a HPLC vial and subjected to preparative HPLC (Phenomex Luna AXIA 30×100 mm; 10 min. gradient; solvent A=10% MeOH, 90% H2O, 0.1% TFA, solvent B=90% MeOH, 10% H2O, 0.1% TFA). Fractions corresponding to the desired product were isolated and concentrated. The residue was partitioned between dichloromethane (20 mL) and saturated aqueous sodium bicarbonate solution (3 mL). The dichloromethane layer was dried over sodium sulfate and concentrated to yield (7R)-benzyl 3-chloro-1-azaspiro[4.4]nonane-7-carboxylate (0.051 g, 0.174 mmol, 50.0% yield) as an oil. It was used as such for the subsequent step. MS (ESI) m/z 294.14 (M+H)+ The reaction mixture was concentrated partitioned between ethyl acetate (20 mL) and saturated aqueous sodium bicarbonate (10 mL) The ethyl acetate layer was dried over sodium sulfate concentrated To the residue was added methanol (5 mL) The solid that separates was filtered washed with methanol (2 mL) To the filtrate was added 4.0N hydrogen chloride in dioxane (1 mL) the contents concentrated Ethyl acetate was added the resulting mixture was concentrated under reduced pressure Methanol (5 mL) was added subjected to preparative HPLC (Phenomex Luna AXIA 30×100 mm; 10 min. gradient; solvent A=10% MeOH, 90% H2O, 0.1% TFA, solvent B=90% MeOH, 10% H2O, 0.1% TFA)

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

Procedure: In a general description of scheme 1 the diene (2) of step (A) is treated with a halogenating agent such as phenylselenyl chloride or bromide or phenylsulfinyl chloride, preferably phenylselenyl chloride, in an approximately equimolar ratio in an inert solvent at about -80° C., for approximately 20 minutes; illustrative of such inert solvents are methylene chloride, ether and the like. After a standard workup the product residue is dissolved in an ethereal solvent, chilled to about 0° C. and oxidized with an agent such as 30% hydrogen peroxide or a peroxy acid such as peroxybenzoic acid to yield a halohydrin analog (1-3). After a standard workup the product residue is dissolved in an ethereal solvent

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

Procedure: The diene (2) of step (B) is treated with a halogenating agent such as phenylselenyl chloride or bromide or phenylsulfinyl chloride, preferably phenylselenyl chloride, in an approximately equimolar ratio in an inert solvent at about -80° C., for approximately 20 minutes; illustrative of such inert solvents are methylene chloride, ether and the like. After a standard workup the product residue is dissolved in an ethereal solvent, chilled to about 0° C. and oxidized with an agent such as 30% hydrogen peroxide or a peroxy acid such as peroxybenzoic acid to yield a halohydrin analog (3). After a standard workup the product residue is dissolved in an ethereal solvent