Reaction Steps
A solution of 0.50 g (0.77 mmol) of (3S,6R,7S,8S)-3,7-bis-(tert-butyl-dimethyl-silanyloxy)-4,4,6,8-tetramethyl-5-oxo-dec-9-enoic acid (Z)-(S)-1-acetyl-4-methyl-hepta-3,6-dienyl ester in 1.9 l toluene was heated at reflux. A solution of 97.8 mg (0.12 mmol) of [RuCl2(PCy3)(ImH2Mes)(benzylidene)] (Grubbs 2nd generation RCM catalyst, commercially available from Sigma-Aldrich Corp. St. Louis, Mo. 63103) in 100 ml toluene was added and the resulting yellow solution stirred for 30 min at reflux. 18.06 mg (0.12 mmol) 2-mercaptonicotinic acid was added, and after 5 min the hot reaction solution was filtered over a silica gel pad. The filtrate was evaporated to dryness. To remove residual toluene, the crude product was dissolved in 60 ml ethanol and the formed solution evaporated to dryness to yield 409.0 mg of crude product with 59% purity (HPLC method: Chirobiotic V column, 4.6×250 mm, solvent A: n-hexane, B: ethanol, gradient from A/B 95/5 to 50/50 within 5 min and 4 min at 50/50, flow 0.5 ml/min, 18° C., 210 nm. Retention times: Starting material 5.8 min, product 6.6 min). Silica gel chromatographic purification of the crude product (hexane/ethylacetate 9:1) yielded 231.5 mg (combined fractions) of the title compound as an off-white solid with 93% purity (45% yield). M.p.: 85° C. MS: 622.4 (M+). 1H-NMR (300 MHz, CDCl3): −0.15 (s, 3H); −0.10 (s, 3H); −0.03 (s, 3H); 0.00 (s, 3H); 0.75 (s, 9H); 0.83 (s, 9H); 0.93 (d, 3H, J=7.0 Hz); 1.01 (s, 3H); 1.02 (d, 3H, J=7 Hz); 1.08 (s, 3H); 1.58 (s, 3H); 2.12 (s, 3H); 2.15–2.85 (m, 2H); 2.87–2.53 (m, 2H); 2.62 (dd, 1H, J=15.5, 2.6 Hz); 2.84 (dd, 2H, J=15.5, 8.0 Hz); 2.97 (dd, 1H, J=15.1, 4.8 Hz); 3.84 (d, 1H, J=8.6 Hz); 4.11 (dd, 1H, J=8.6, 2.4 Hz); 489 (dd, 1H, J=8.5, 2.5 Hz); 5.06 (t, 1H, J=7.5 Hz); 5.20–5.30 (m, 1H); 5.52 (dd, 1H, J=16.1, 8.5 Hz). Anal. calcd. for C34H62O6Si2: C, 65.55; H, 10.03; Si, 9.02. Found: C, 64.76; H, 9.84; Si, 8.96.
