Compound 7
3-bromo-2-(1-iodo-2-methylprop-1-en-1-yl)-9-(methoxymethyl)-9H-carbazole
From: Total synthesis of (–)-tubingensin B enabled by the strategic use of an aryne cyclization
Synthetic procedure: See article for the definitive version of this procedure and for full experimental details.
To a flask charged with hydroxyiodide 10 (2.79 g, 5.75 mmol, 1 equiv) was added NEt3 (2.4 mL, 17.2 mmol, 3 equiv) and CH2Cl2 (29 mL). The mixture was cooled to 0 °C and MsCl (1.7 g, 17.2 mmol, 3 equiv) was added. The reaction was warmed to room temperature and stirred for 20 h. The reaction was quenched with sat. aq. NaHCO3 (100 mL), then diluted with EtOAc (100 mL). The layers were separated and the aqueous layer was extracted with EtOAc (3 x 100 mL) The combined organic layers were washed with brine (100 mL) and dried over Na2SO4. Evaporation under reduced pressure afforded the crude product, which was purified by flash chromatography (4:1 Hexanes:EtOAc) to provide the corresponding chloride (2.35 g, 81% yield) as an off-white foam.
To a flask charged containing the chloride intermediate (3.06 g, 6.06 mmol, 1 equiv) was added THF (30 mL). The resulting mixture was cooled to 0 °C. LiEt3BH (1.0 M in THF, 30.3 mL, 30.3 mmol, 5 equiv) was added dropwise over 10 min and the reaction was stirred for 5 min. The reaction was then quenched at 0 °C with H2O (5 mL). The reaction mixture was transferred to a separatory funnel and diluted with 6 M NaOH (10 mL), H2O (80 mL) and EtOAc (50 mL). The layers were separated and the aqueous layer was extracted with EtOAc (3 x 50 mL). The combined organic layers were washed with sat. aq. NH4Cl (30 mL), brine (30 mL) and dried over MgSO4. Evaporation under reduced pressure afforded the crude product, which was purified by flash chromatography (5:1 Hexanes:EtOAc) to provide vinyliodide 7 (2.85 g, quantitative yield) as an off-white foam. Rf 0.66 (4:1 Hexanes:EtOAc); 1H NMR (500 MHz, CDCl3): δ 8.23 (s, 1H), 8.00 (d, J = 7.4, 1H), 7.50 (m, 2H), 7.41 (s, 1H), 7.28 (m, 1H), 5.65 (d, J = 11.5, 1H), 5.62 (d, J = 11.5, 1H), 3.30 (s, 3H), 2.16 (s, 3H), 1.66 (s, 3H); 13C NMR (500 MHz, CDCl3): δ 141.7, 141.6, 141.4, 139.7, 127.0, 124.6, 124.4, 122.2, 120.6, 113.9, 110.6, 109.5, 93.4, 74.3, 56.3, 29.9, 20.7; IR (film): 2924, 1599, 1468, 1447, 1422, 1332, 1242, 1112, 1066, 1026, 782, 748, 552 cm–1; HRMS-APCI (m/z) [M]•+ calcd for C18H17BrINO, 468.9533; found, 468.9530.
