Sodium hydride → Methyl 5-(3-((1R,2R,3R,5R)-2-((R,E)-7-(tert-butyldimethylsilyloxy)-3-oxooct-1-enyl)-5-chloro-3-(tetrahydro-2H-pyran-2-yloxy)cyclopentyl)propyl)thiophene-2-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a suspension of 54 mg of sodium hydride (60% oil dispersion, 1.35 mmol) in 1 ml of THF at 0° C. was added a solution of dimethyl (6R)-6-{[tert-butyl(dimethyl)silyl]oxy}-2-oxoheptylphosphonate 5 (552 mg, 1.57 mmol) in 1 mL THF. The mixture was stirred at 0° C. for 30 min before a solution of aldehyde 7 (460 mg, 1.1 mmol) in 1 ml of THF was added dropwise. The syringe containing the aldehyde was rinsed with 2 mL of THF to complete the addition and the mixture was stirred at 25° C. for 2.5 h. The reaction was worked up with addition of saturated aqueous ammonium chloride (50 mL) and the aqueous layer was extracted with ethyl acetate (2×75 mL). The ethyl acetate layers were combined and washed with brine, dried over 30 g of anhydrous sodium sulfate, filtered and concentrated in vacuo to yield 920 mg of crude products. Flash chromatographic purification using a 24 g silica gel cartridge eluted with 10% EtOAc-hexanes yielded 430 mg (60%) of purified enone 8; 1H NMR (CDCl3): 0.05 (s, 6H), 0.88 (s, 9H), 1.12 (d, J=6.3 Hz, 3H), 1.37-1.80 (m, 14H), 2.00 (m, 1H), 2.20 (m, 1H), 2.34 (m, 1H), 2.53 (m, 1H), 2.54 (t, J=7.2 Hz, 2H), 2.83 (m, 2H), 3.45 (m, 1H), 3.80 (m, 2H), 3.86 (s, 3H), 4.02 (m, 1H), 4.17 (m, 1H), 4.57 (m, 1H), 6.15 (m, 1H), 6.77 (m, 1H), 7.62 (d, J=3.9 Hz).

Provenance & Evidence