A 1 dram vial equipped with a stir bar is charged with 14.3 mg (0.030 mmol, 1 equiv.) of 51 and 150 μL of THF. The solution was cooled to −78° C. in a dry ice/acetone bath, and 300 μL of a solution of LiTMP (0.5M in THF, 0.150 mmol, 5 equiv.) was added dropwise. The yellow solution was stirred at −78° C. for 10 minutes followed by warming to 0° C. in a water/ice bath for 10 minutes and then recooling to −78° C. prior to addition of 15.7 μL (0.15 mmol, 5 equiv.) of isobutyryl chloride. The reaction was stirred 30 minutes prior to quenching by the addition of 500 μL of saturated aqueous ammonium chloride. The solution was transferred to a separatory funnel with 15 mL of hexane, and the organic layer was washed sequentially saturated aqueous 10% aqueous hydrochloric acid, water, and brine; dried with MgSO4; and concentrated in vacuo. The crude product was found to contain an inseparable mixture of product and 51. The mixture was purified by silica gel chromatography (Rf=0.25 in 9:1 hexane:ethyl acetate) and carried forward as a mixture. A 1 dram vial equipped with a stir bar is charged with 9.0 mg (0.016 mmol, 1 equiv.) of the mixture followed by 100 μL of THF. The vial was cooled in a water/ice bath and 18 μL of TBAF (1.0 M in THF, 0.018, 1.1 equiv.) is added. The mixture is stirred for 15 min at which time it is transferred to a separatory funnel, and the organic layer is washed sequentially saturated aqueous sodium bicarbonate, water, and brine. The organic layer is then dried with MgSO4 and concentrated in vacuo to give a yellow oil. The crude product is purified by preparative TLC (Rf=0.25 in 3:1 hexane:ethyl acetate) to give 4.1 mg (53% yield) of 56 as a clear oil. 1H NMR (500 MHz, CDCl3) δ 5.85 (s, 1H), 5.07-4.96 (m, 2H), 4.61 (dd, J=6.8, 15.5 Hz, 2H), 3.82 (s, 3H), 3.58 (dd, J=5.2, 11.3 Hz, 1H), 3.32 (s, 3H), 2.48 (ddd, J=7.5, 14.5, 34.2 Hz, 2H), 2.18-2.04 (m, J=5.9, 13.2, 17.3 Hz, 4H), 1.96 (s, 1H), 1.77 (dd, J=11.4, 13.4 Hz, 1H), 1.67 (d, J=3.0 Hz, 6H), 1.64 (s, 3H), 1.59 (s, 3H), 1.55 (s, 3H), 1.30-1.21 (m, J=2.6, 2.6 Hz, 1H), 1.14 (s, 3H), 1.12 (d, J=6.5 Hz, 3H), 1.05 (d, J=6.5 Hz, 3H). HRMS-ESI (m/z): [M+H]+ calculated for C28H42O6, 475.3054. found, 475.3045.
