Compound 8

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InChIKey RTFSVERUZZLOBP-YOWMXZEJSA-N

Synthetic procedure: See article for the definitive version of this procedure and for full experimental details.

A solution of 15 (6.6 g, 10 mmol) in 1,2-dichlorobenzene (12 mL) was divided in 3 separate 6 mL microwave reactor vials (4 mL in each). Each reactor vial was degassed by bubbling argon through the solution for 10 minutes, and the reactor vials were sequentially loaded into a Personal Chemistry^TM Smith Synthesizer microwave reactor and heated to 250°C for 45 minutes. The contents of all three reaction vessels were loaded directly onto a silica gel column and purified via chromatography (gradient of pentane to 1:9 diethyl ether:pentane) to provide pure 8 (5.686 g, 86%) as a colorless oil. The initial starting material 15 was previously determined to be a 20:1 mixture of diastereomers (6.28 g, 9.5 mmol) by ¹HNMR, such that the single diastereomer of pure 8 isolated at the end of the reaction represents a 91% yield. TLC: R_f = 0.48 (1:9 ethyl acetate:pentane), one spot. ¹H-NMR (500 MHz, CDCl₃, residual solvent peak referenced to 7.24 ppm) δ 7.35-7.25 (m, 5H), 6.66 (s, 1H), 5.76 (ddd, J=17.2, 10.2, 8.7, 1H), 5.18 (ddd, J=17.2, 1.7, 0.6, 1H), 5.09 (dd, J=10.1, 1.8, 1H), 5.00 (d, J=11.1, 1H, AB), 4.46 (d, J=11.1, 1H, AB), 4.30 (dd, J=11.4, 9.4, 1H), 4.00 (dd, J=5.4, 2.0, 1H), 3.69 (d, J=10.1, 1H, AB), 3.67 (dd, J=9.3, 2.0, 1H), 3.62 (d, J=10.1, 1H, AB), 3.45 (dd, J=11.2, 8.7, 1H), 2.30 (dd, J=12.1, 3.4, 1H), 2.12 (ddd, J=9.1, 5.4, 3.4, 1H), 1.92 (dd, J=12.0, 9.4, 1H), 1.45 (s, 3H), 1.43 (s, 3H), 0.89 (s, 9H), 0.84 (s, 9H), 0.11 (s, 3H), 0.05 (s, 3H), -0.02 (s, 3H), -0.04 (s, 3H) ppm. ¹³C-NMR (100 MHz, CDCl₃) δ 194.64, 146.14, 138.37, 134.86, 134.20, 128.30, 127.76, 127.54, 119.13, 110.50, 94.02, 82.52, 81.32, 74.91, 74.41, 73.01, 66.10, 46.98, 42.60, 37.04, 27.28, 26.73, 25.73, 25.58, 18.35, 18.18, -4.55, -4,77, -5.39, -5.49 ppm. FTIR (thin film) 2954, 2930, 2885, 2858, 1694, 1626, 1472, 1380, 1336, 1252, 1153, 1098, 1029, 1006, 973, 902, 838, 813, 782, 733, 697, 673 cm^-1. HRMS: Calculated for C₃₅H₅₃O₇Si₂ (M-CH₃): 641.3347; Found: 641.3347. Calculated for C₃₂H₄₇O₇Si₂ (M-C₄H₉): 599.2859; Found: 599.2859. [α]_D = 30.6 ° (c 0.75, CHCl₃).

A solution of 9 (82.4 mg, 0.19 mmol) in 1,2-dichlorobenzene (1.1 mL, 0.17 M) was degassed by bubbling argon through the solution for 10 minutes, and the reactor vial was loaded into a Personal Chemistry^TM Smith Synthesizer microwave reactor and heated to 122 °C for 4 h at which time TLC analysis indicated the Claisen rearrangement was complete. The reaction was then heated to 250 °C (μ-wave) for 90 min and allowed to cool to r.t. CH₂Cl₂ (1.1 mL, 0.09 M), imidazole (43.0 mg, 0.63 mmol), and TBS-Cl (96.0 mg, 0.64 mmol) were added and the reaction stirred at r.t. 10 h. The reaction was quenched by addition of a saturated solution of NH₄Cl and the layers separated. The aqueous layer was extracted 3 x Et₂O. The combined organics were dried over MgSO₄, filtered, and concentrated. The crude residue was purified by column chromatography (7% EtOAc/petroleum ether) to provide 60.0 mg 8 (50%) along with an additional 17.2 mg (2:1 8:Claisen diastereomer) representing a combined 56% yield of the desired product, which was spectroscopically identical to that produced using the two-step procedure.