2-phenylselanylisoindole-1,3-dione

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

Procedure: General Procedure B for α-Selenenylation of Aldehyde (Table 9, Entries 11 and 12): To a vial containing an aldehyde (0.25 mmol), and 0.5 mL of anhydrous CH2Cl2 was added catalyst L-prolinamide I (0.005 mmol) at room temperature. The mixture was vigorously stirred for 0.5 h in the presence of 4 Å molecule sieves (40 mg). Then N-(phenylseleno)phthalimide (0.3 mmol) was added. After 0.5 h, the molecule sieves were removed by filtrating paper and then the filtrate was treated with water (5 mL), the solution was extracted with ethyl acetate (3×5 mL). The combined extracts were dried over MgSO4, filtered, and concentrated iii vacuo. The resulting residue was then purified by silica gel chromatography, eluting with EtOAc/Hexane (1/40) to provide a clear oil. After 0.5 h the molecule sieves were removed by filtrating paper the filtrate was treated with water (5 mL) the solution was extracted with ethyl acetate (3×5 mL) The combined extracts were dried over MgSO4 filtered concentrated iii vacuo The resulting residue was then purified by silica gel chromatography eluting with EtOAc/Hexane (1/40) to provide a clear oil

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

Procedure: General Procedure B for α-Selenenylation of Aldehyde (Table 9, Entries 11 and 12): To a vial containing an aldehyde (0.25 mmol), and 0.5 mL of anhydrous CH2Cl2 was added catalyst L-prolinamide I (0.005 mmol) at room temperature. The mixture was vigorously stirred for 0.5 h in the presence of 4 Å molecule sieves (40 mg). Then N-(phenylseleno)phthalimide (0.3 mmol) was added. After 0.5 h, the molecule sieves were removed by filtrating paper and then the filtrate was treated with water (5 mL), the solution was extracted with ethyl acetate (3×5 mL). The combined extracts were dried over MgSO4, filtered, and concentrated iii vacuo. The resulting residue was then purified by silica gel chromatography, eluting with EtOAc/Hexane (1/40) to provide a clear oil. After 0.5 h the molecule sieves were removed by filtrating paper the filtrate was treated with water (5 mL) the solution was extracted with ethyl acetate (3×5 mL) The combined extracts were dried over MgSO4 filtered concentrated iii vacuo The resulting residue was then purified by silica gel chromatography eluting with EtOAc/Hexane (1/40) to provide a clear oil

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

Procedure: To a 12-L three-neck round bottom flask equipped with a mechanical stirrer, Claisen adapter with a nitrogen inlet and a temperature probe, and a nitrogen outlet was charged with the product of Step B (382 g, 1.26 mol, 1 eq) and CH2Cl2 (6.5 L). N-(phenylseleno)phthalimide (419 g, 1.39 mol, 1.1 eq) was added followed by BF3 etherate (16 mL, 0.126 mol, 0.1 eq) directly added by graduated cylinder. The reaction steadily climbed from 15° C. to 24° C. and within 10 min, the reaction formed a pink precipitate. Ten min later, the reaction became thick with a white precipitate and the temperature began to decrease. The reaction was checked by HPLC and found to be complete. The reaction was filtered through Celite (removing the phthalimide impurity), the filter cake was washed with CH2Cl2 (750 mL) until the filtrate was no longer orange. The filtrate was transferred to a separatory funnel, washed with aqueous NaOH (0.5 M, 2×1350 mL), brine (2×1 L), and the organic layer was dried over Na2SO4. [A second run was conducted with 382 g of the product of Step B, under the same conditions, and was worked up and combined at this point]. With about 3 L organics left, toluene (3 L, ˜4 mL/g starting material) was added and the evaporation continued. Shortly after the toluene addition, crystallization occurred. The 20-L round bottom flask was transferred to a heating mantel, and the contents heated to 80° C., until the solid dissolved. The flask was transferred back to the rotary evaporator, reference material was used to seed the crystallization, and the flask swirled (no heat) until the product started to crystallize. Ice was added to the bath and the contents of the flask swirled at 15° C. (external temp) for 30 min. The product was filtered, washed with ice-cold toluene and air-dried for 1 h, and afforded the product of Step C. 1H NMR (CHLOROFORM-d) δ: 7.49-7.56 (m, 2H), 7.23-7.29 (m, 3H), 5.05 (br. s., 1H), 4.46 (br. s., 1H), 4.29 (s, 1H), 3.86-3.97 (m, 2H), 3.57-3.69 (m, 3H), 1.98-2.08 (m, 1H), 1.86-1.97 (m, 2H), 1.73-1.86 (m, 2H), 1.41 (s, 9H). Calculated for C19H27NO4Se: 436.1 (M+23). found: 436.1. To a 12-L three-neck round bottom flask equipped with a mechanical stirrer directly added by graduated cylinder The reaction the reaction formed a pink precipitate Ten min The reaction was filtered through Celite ( removing the phthalimide impurity), the filter cake was washed with CH2Cl2 (750 mL) until the filtrate The filtrate was transferred to a separatory funnel washed with aqueous NaOH (0.5 M, 2×1350 mL), brine (2×1 L) the organic layer was dried over Na2SO4 With about 3 L organics left, toluene (3 L, ˜4 mL/g starting material) was added the evaporation Shortly after the toluene addition, crystallization dissolved The flask was transferred back to the rotary evaporator, reference material the crystallization no heat) until the product to crystallize Ice was added to the bath swirled at 15° C. for 30 min The product was filtered washed with ice-cold toluene air-dried for 1 h

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

Procedure: To a solution of the product of Step D (1.51 g, 3.32 mmol, 1 eq) in DCM (40 mL) at rt under Ar was added N-(phenylseleno)phthalimide (1.60 g, 4.97 mmol, 1.5 eq) and BF3-etherate (0.042 mL, 0.33 mmol, 0.1 eq). After 2 hrs, 1 N NaOH was added and stirred 5 min., water was added, the solution extracted with DCM, the organics combined, dried over MgSO4, and concentrated. Purification by chromatography (80 g column) eluting with 50 to 100% EtOAc/heptane afforded the title compound of Step E. 1H NMR (CHLOROFORM-d) δ: 8.72 (s, 1H), 7.69 (s, 1H), 7.50-7.62 (m, 2H), 7.22-7.27 (m, 3H), 5.35 (s, 1H), 5.06 (d, J=8.1 Hz, 1H), 4.79-5.01 (m, 1H), 4.66-4.78 (m, 1H), 4.53 (br. s., 1H), 3.78-4.06 (m, 4H), 3.68-3.78 (m, 1H), 3.05-3.19 (m, 2H), 2.32 (dd, J=11.6, 5.8 Hz, 2H), 2.16 (d, J=10.9 Hz, 2H), 1.36 (s, 9H). Calculated for C28H32F3N3O4Se: 634.2 (M+23). found: 634.1. the solution extracted with DCM dried over MgSO4 concentrated Purification by chromatography (80 g column) eluting with 50 to 100% EtOAc/heptane