| 1.64g |
|
General procedure: In a 200 mL, 2-neck flame dried flask, copper(I)bromide dimethyl sulfide (2.17 g, 10.56 mmol) was dissolved in dry THF (20 mL). Air was purged with argon, and then the temperature was reduced to -15 C. Ethyllithium (12.35 mL of a 1.7M solution in dibutyl ether, 756 mg, 21.0 mmol) was added drop wise with stirring and the mixture was allowed to stir for additional 20 min at -15 C. The temperature was then reduced to -78, followed by drop wise addition of chlorotrimethylsilane (3.44 g, 31.66 mmol) and methyl pent-4-enoate 4 (500 mg, 3.52 mmol). The reaction was stirred for 5 h at -78 C. The reaction was then quenched by addition of a saturated ammonium chloride:ammonia solution (1:1) portion wise until the reaction color turned blue. The organic layer was collected, and the aqueous layer was extracted with ethyl acetate (3 * 30 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered, and rotavaped to an oily crude product, which was used in the next reaction without purification. In a 200 mL 2-neck flame dried flask, air was purged with argon, and NaH (169 mg of 60% NaH in mineral oil, 7.04 mmol) dissolved in dry THF (20 mL) was added. The reaction was then cooled to 0 C and benzyl diethyl phosphonoacetate 5b (1.80 mL, 7.04 mmol) was added drop wise with stirring. The reaction was allowed to stir for 15 min at 0 C, then the crude product from the previous reaction was added. The reaction was stirred for another 30 min at 0 C, followed by stirring for 90 min at room temperature. The reaction was quenched with a saturated ammonium chloride solution (20 mL). The organic layer was collected, and the aqueous layer was extracted with ethyl acetate (3 * 25 mL). The combined organic layers were dried over anhydrous MgSO4, filtered, and concentrated. The product was purified by flash silica gel chromatography (ethyl acetate:hexanes 1:9) to afford 6b (375 mg, 35% over two steps). |
| 1.64 g |
|
General procedure: 10081] In a 200 mL, 2-neck flame dried flask, copper(I) bromide dimethyl sulfide (2.17 g, 10.56 mmol) was dissolved in dry TRF (20 mL). Air was purged with argon, and then the temperature was reduced to -15 C. Ethyllithium (12.35 mLofa i.7M solution in dibutyl ether, 756 mg, 21.0 mmol) was added drop wise with stirring and the mixture was allowed to stir for additional 20 minutes at -15 C. The temperature was then reduced to -78, followed by drop wise addition of chlorotrimethylsilane (3.44 g, 31.66 mmol) and methyl pent-4-enoate 4 (500 mg, 3.52 mmol). The reaction was stirred for S hours at -78 C. The reaction was then quenched by addition of a saturated ammonium chloride:ammonia solution (1:1) portion wise until the reaction color turned blue. The organic layer was collected, and the aqueous layer was extracted with ethyl acetate (3x30 mL). The combined organic layers were dried over anhydrous Na2504, filtered, and rotavaped to an oily crude product, which was used in the next reaction without purification.10082] In a 200 mL 2-neck flame dried flask, air was purged with argon, and NaR (169 mg of 60% NaR in mineral oil, 7.04 mmol) dissolved in dry TRF (20 mL) was added. The reaction was then cooled to 0 C. and benzyl diethyl phosphonoacetate Sb (1.80 mL, 7.04 mmol) was added drop wise with stirring. The reaction was allowed to stir for 15 minutes at 0 C., then the crude product from the previous reaction was added. The reaction was stirred for another 30 minutes at 0 C., followed by stirring for 90 minutes at room temperature. The reaction was quenched with a saturated ammonium chloride solution (20 mL). The organic layer was collected, and the aqueous layer was extracted with ethyl acetate (3x25 mL). The combined organic layers were dried over anhydrous Mg504, filtered, and concentrated. The product was purified by flash silica gel chromatography (ethyl acetate:hexanes 1:9) to afford 6b (375 mg, 35% over two steps). ‘RNMR (400 MRz, CD3OD)o (ppm): 0.86-0.90 (t, J=7.2 Rz, 3R), 1.28-1.34 (m, 2R), 1.47 (m, iR), i.SS-i.6i (m, 2R), 2.18-2.22 (m, 2R), 2.30-2.34 (t, J=7.2 Rz, 2R), 3.63 (s, 3R), S.iS (s, 2R), S.89-S.93 (d, J=i6 Rz, iR), 6.92-6.98 (m, iR), 7.29-7.3S (m, 4R). ‘3CNMR (100 MRz, CD3OD) 0 (ppm): 9.69, 2S.3i, 27.86, 30.79, 3S.24, 3S.33, 38.07, S0.66, 6S.69, 122.02, 127.80 (2C), i28.iS, 136.28, 148.47, 166.31, 174.4. IR: 29S7, 2931, 287S, 1723, 16SS, 1437 cm’. LRMS (ESI, mlz): calculatedfor [M+H] C18H24O4H, 305.2, found 305.2; calculated for [M+Na] C18H24O4Na, 327.2, found 327.1. |
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