3-hydroxy-2,2-dimethyl-3,4-dihydrobenzo[h]chromene-5,6-dione

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

Procedure: A solution of 2.820 g (12.20 mmol) of Boc-Leu and 1.976 g (12.19 mmol) of 1,1-carbonyldiimidazole in 33 mL of DMF was stirred at room temperature for 20 min. To the solution was added 2.100 g (8.130 mmol) of 3-hydroxy-β-lapachone followed by 1.6 mL (10.70 mmol) of DBU. After stirring at room temperature for 5 hr, the reaction mixture was partitioned between 200 mL of water and 200 mL of CHCl3. The aqueous phase was washed with CHCl3 (4×50 mL). The CHCl3 extracts were combined, dried with MgSO4, and evaporated to dryness. Column chromatography on silica gel with 2% MeOH in CH2Cl2 afforded 2.038 g (53%) of quinone as an orange glassy solid (and mixture of two diastereomers): Rƒ=0.45 (5% MeOH in CH2Cl2); 1H NMR (250 MHz, acetone-d6, TMS) δ 8.1-8.0 (m, 1H), 8.0-7.9 (m, 1H), 7.9-7.8 (m, 1H), 7.7-7.6 (m, 1H), 6.34 (br d, NH), 5.2-5.1 (m, 1H), 4.2-4.1 (m, 1H), 2.9-2.8 (m, 1H), 2.7-2.5 (m, 1H), 1.8-1.6 (m, 3H), 1.56 (s, 1.5H), 1.53 (s, 3H), 1.52 (s, 1.5H), 1.34 (s, 4.5H), 1.33 (s, 4.5H), 0.91 (d, J=7.0 Hz, 1.5H), 0.88 (d, J=6.7 Hz, 1.5H), 0.84 (d, J=6.3 Hz, 1.5H), 0.82 (d, J=6.1 Hz, 1.5H). the reaction mixture was partitioned between 200 mL of water and 200 mL of CHCl3 The aqueous phase was washed with CHCl3 (4×50 mL) dried with MgSO4 evaporated to dryness Column chromatography on silica gel with 2% MeOH in CH2Cl2 afforded

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

Procedure: A solution of 2.820 g (12.20 mmol) of Boc-Leu and 1.976 g (12.19 nmmol) of 1,1-carbonyldiimidazole in 33 mL of DMF was stirred at room temperature for 20 min. To the solution was added 2.100 g (8.130 nmol) of 3-hydroxy-β-lapachone followed by 1.6 mL (10.70 mmol) of DBU. After stirring at room temperature for 5 hr, the reaction mixture was partitioned between 200 mL of water and 200 mL of CHCl3. The aqueous phase was washed with CHCl3 (4×50 mL). The CHCl3 extracts were combined, dried with MgSO4, and evaporated to dryness. Column chromatography on silica gel with 2% MeOH in CH2Cl2 afforded 2.038 g (53%) of quinone as an orange glassy solid (and mixture of two diastereomers): Rf=0.45 (5% MeOH in CH2Cl2); 1H NMR (250 MHz, acetone-d6, TMS) δ8.1-8.0 (m, 1H), 8.0-7.9 (m, 1H), 7.9-7.8 (m, 1H), 7.7-7.6 (m, 1H), 6.34 (br d, NH), 5.2-5.1 (m, 1H), 4.2-4.1 (m, 1H), 2.9-2.8 (m, 1H), 2.7-2.5 (m, 1H), 1.8-1.6 (m, 3H), 1.56 (s, 1.5H), 1.53 (s, 3H), 1.52 (s, 1.5H), 1.34 (s, 4.5H), 1.33 (s, 4.5Hd), 0.91 (d, J=7.0Hz, 1.5H), 0.88 (d, J=6.7 Hz, 1.5H), 0.84 (d, J=6.3 Hz, 1.5H), 0.82 (d, J=6.1 Hz, 1.5H). the reaction mixture was partitioned between 200 mL of water and 200 mL of CHCl3 The aqueous phase was washed with CHCl3 (4×50 mL) dried with MgSO4 evaporated to dryness Column chromatography on silica gel with 2% MeOH in CH2Cl2 afforded

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

Procedure: A solution of 2.820 g (12.20 mmol) of Boc-Leu and 1.976 g (12.19 mmol) of 1,1-carbonyldiimidazole in 33 mL of DMF was stirred at room temperature for 20 min. To the solution was added 2.100 g (8.130 mmol) of 3-hydroxy-β-lapachone followed by 1.6 mL (10.70 mmol) of DBU. After stirring at room temperature for 5 hr, the reaction mixture was partitioned between 200 mL of water and 200 mL of CHCl3. The aqueous phase was washed with CHCl3 (4×50 mL). The CHCl3 extracts were combined, dried with MgSO4, and evaporated to dryness. Column chromatography on silica gel with 2% MeOH in CH2Cl2 afforded 2.038 g (53%) of quinone as an orange glassy solid (and mixture of two diastereomers): Rf=0.45 (5% MeOH in CH2Cl2); 1H NMR (250 MHz, acetone-d6, TMS) δ 8.1-8.0 (m, 1H), 8.0-7.9 (m, 1H), 7.9-7.8 (m, 1H), 7.7-7.6 (m, 1H), 6.34 (br d, NH), 5.2-5.1 (m, 1H), 4.2-4.1 (m, 1H), 2.9-2.8 (m, 1H), 2.7-2.5 (m, 1H), 1.8-1.6 (m, 3H), 1.56 (s, 1.5H), 1.53 (s, 3H), 1.52 (s, 1.5H), 1.34 (s, 4.5H), 1.33 (s, 4.5H), 0.91 (d, J=7.0 Hz, 1.5H), 0.88 (d, J=6.7 Hz, 1.5H), 0.84 (d, J=6.3 Hz, 1.5H), 0.82 (d, J=6.1 Hz, 1.5H). the reaction mixture was partitioned between 200 mL of water and 200 mL of CHCl3 The aqueous phase was washed with CHCl3 (4×50 mL) dried with MgSO4 evaporated to dryness Column chromatography on silica gel with 2% MeOH in CH2Cl2 afforded

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

Procedure: A solution of 2.820 g (12.20 mmol) of Boc-Leu and 1.976 g (12.19 mmol) of 1,1-carbonyldiimidazole in 33 mL of DMF was stirred at room temperature for 20 min. To the solution was added 2.100 g (8.130 mmol) of 3-hydroxy-β-lapachone followed by 1.6 mL (10.70 mmol) of DBU. After stirring at room temperature for 5 hr, the reaction mixture was partitioned between 200 mL of water and 200 mL of CHCl3. The aqueous phase was washed with CHCl3 (4×50 mL). The CHCl3 extracts were combined, dried with MgSO4, and evaporated to dryness. Column chromatography on silica gel with 2% MeOH in CH2Cl2 afforded 2.038 g (53%) of quinone as an orange glassy solid (and mixture of two diastereomers): Rƒ=0.45 (5% MeOH in CH2Cl2); 1H NMR (250 MHz, acetone-d6, TMS) δ 8.1-8.0 (m, 1H), 8.0-7.9 (m, 1H), 7.9-7.8 (m, 1H), 7.7-7.6 (m, 1H), 6.34 (br d, NH), 5.2-5.1 (m, 1H), 4.2-4.1 (m, 1H), 2.9-2.8 (m, 1H), 2.7-2.5 (m, 1H), 1.8-1.6 (m, 3H), 1.56 (s, 1.5H), 1.53 (s, 3H), 1.52 (s, 1.5H), 1.34 (s, 4.5H), 1.33 (s, 4.5H), 0.91 (d, J=7.0 Hz, 1.5H), 0.88 (d, J=6.7 Hz, 1.5H), 0.84 (d, J=6.3 Hz, 1.5H), 0.82 (d, J=6.1 Hz, 1.5H). the reaction mixture was partitioned between 200 mL of water and 200 mL of CHCl3 The aqueous phase was washed with CHCl3 (4×50 mL) dried with MgSO4 evaporated to dryness Column chromatography on silica gel with 2% MeOH in CH2Cl2 afforded

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

Procedure: A solution of 2.820 g (12.20 mmol) of Boc-Leu and 1.976 g (12.19 nmmol) of 1,1-carbonyldiimidazole in 33 mL of DMF was stirred at room temperature for 20 min. To the solution was added 2.100 g (8.130 nmol) of 3-hydroxy-β-lapachone followed by 1.6 mL (10.70 mmol) of DBU. After stirring at room temperature for 5 hr, the reaction mixture was partitioned between 200 mL of water and 200 mL of CHCl3. The aqueous phase was washed with CHCl3 (4×50 mL). The CHCl3 extracts were combined, dried with MgSO4, and evaporated to dryness. Column chromatography on silica gel with 2% MeOH in CH2Cl2 afforded 2.038 g (53%) of quinone as an orange glassy solid (and mixture of two diastereomers): Rf=0.45 (5% MeOH in CH2Cl2); 1H NMR (250 MHz, acetone-d6, TMS) δ8.1-8.0 (m, 1H), 8.0-7.9 (m, 1H), 7.9-7.8 (m, 1H), 7.7-7.6 (m, 1H), 6.34 (br d, NH), 5.2-5.1 (m, 1H), 4.2-4.1 (m, 1H), 2.9-2.8 (m, 1H), 2.7-2.5 (m, 1H), 1.8-1.6 (m, 3H), 1.56 (s, 1.5H), 1.53 (s, 3H), 1.52 (s, 1.5H), 1.34 (s, 4.5H), 1.33 (s, 4.5Hd), 0.91 (d, J=7.0Hz, 1.5H), 0.88 (d, J=6.7 Hz, 1.5H), 0.84 (d, J=6.3 Hz, 1.5H), 0.82 (d, J=6.1 Hz, 1.5H). the reaction mixture was partitioned between 200 mL of water and 200 mL of CHCl3 The aqueous phase was washed with CHCl3 (4×50 mL) dried with MgSO4 evaporated to dryness Column chromatography on silica gel with 2% MeOH in CH2Cl2 afforded

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

Procedure: A solution of 2.820 g (12.20 mmol) of Boc-Leu and 1.976 g (12.19 mmol) of 1,1-carbonyldiimidazole in 33 mL of DMF was stirred at room temperature for 20 min. To the solution was added 2.100 g (8.130 mmol) of 3-hydroxy-β-lapachone followed by 1.6 mL (10.70 mmol) of DBU. After stirring at room temperature for 5 hr, the reaction mixture was partitioned between 200 mL of water and 200 mL of CHCl3. The aqueous phase was washed with CHCl3 (4×50 mL). The CHCl3 extracts were combined, dried with MgSO4, and evaporated to dryness. Column chromatography on silica gel with 2% MeOH in CH2Cl2 afforded 2.038 g (53%) of quinone as an orange glassy solid (and mixture of two diastereomers): Rf=0.45 (5% MeOH in CH2Cl2); 1H NMR (250 MHz, acetone-d6, TMS) δ 8.1-8.0 (m, 1H), 8.0-7.9 (m, 1H), 7.9-7.8 (m, 1H), 7.7-7.6 (m, 1H), 6.34 (br d, NH), 5.2-5.1 (m, 1H), 4.2-4.1 (m, 1H), 2.9-2.8 (m, 1H), 2.7-2.5 (m, 1H), 1.8-1.6 (m, 3H), 1.56 (s, 1.5H), 1.53 (s, 3H), 1.52 (s, 1.5H), 1.34 (s, 4.5H), 1.33 (s, 4.5H), 0.91 (d, J=7.0 Hz, 1.5H), 0.88 (d, J=6.7 Hz, 1.5H), 0.84 (d, J=6.3 Hz, 1.5H), 0.82 (d, J=6.1 Hz, 1.5H). the reaction mixture was partitioned between 200 mL of water and 200 mL of CHCl3 The aqueous phase was washed with CHCl3 (4×50 mL) dried with MgSO4 evaporated to dryness Column chromatography on silica gel with 2% MeOH in CH2Cl2 afforded

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

Procedure: A solution of 2.820 g (12.20 mmol) of Boc-Leu and 1.976 g (12.19 mmol) of 1,1-carbonyldiimidazole in 33 mL of DMF was stirred at room temperature for 20 min. To the solution was added 2.100 g (8.130 mmol) of 3-hydroxy-β-lapachone followed by 1.6 mL (10.70 mmol) of DBU. After stirring at room temperature for 5 hr, the reaction mixture was partitioned between 200 mL of water and 200 mL of CHCl3. The aqueous phase was washed with CHCl3 (4×50 mL). The CHCl3 extracts were combined, dried with MgSO4, and evaporated to dryness. Column chromatography on silica gel with 2% MeOH in CH2Cl2 afforded 2.038 g (53%) of quinone as an orange glassy solid (and mixture of two diastereomers): Rƒ=0.45 (5% MeOH in CH2Cl2); 1H NMR (250 MHz, acetone-d6, TMS) δ 8.1-8.0 (m, 1H), 8.0-7.9 (m, 1H), 7.9-7.8 (m, 1H), 7.7-7.6 (m, 1H), 6.34 (br d, NH), 5.2-5.1 (m, 1H), 4.2-4.1 (m, 1H), 2.9-2.8 (m, 1H), 2.7-2.5 (m, 1H), 1.8-1.6 (m, 3H), 1.56 (s, 1.5H), 1.53 (s, 3H), 1.52 (s, 1.5H), 1.34 (s, 4.5H), 1.33 (s, 4.5H), 0.91 (d, J=7.0 Hz, 1.5H), 0.88 (d, J=6.7 Hz, 1.5H), 0.84 (d, J=6.3 Hz, 1.5H), 0.82 (d, J=6.1 Hz, 1.5H). the reaction mixture was partitioned between 200 mL of water and 200 mL of CHCl3 The aqueous phase was washed with CHCl3 (4×50 mL) dried with MgSO4 evaporated to dryness Column chromatography on silica gel with 2% MeOH in CH2Cl2 afforded