The Real Experiment!

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Ash Ketchum fights Blaine in order to prove to him the correct experimental for Molecule 58!

Ash was so sure that Blaine was wrong that he had to show him what was the right way to create this elusive Molecule. Here is what Ash showed Blaine in the battle.

Click on the items to learn more about them below.

Two Step Synthesis of Molecule 59: To a ﬂask containing lactal molecule 58 (6.0 g, 7.51 mmol), 2-(trimethylsilyl)ethanesulfonamide (5.44 g, 30.0 mmol), and powdered 4 Å molecular sieves (3.0 g, freshly ﬂame-dried) was added CH2Cl2 (30 mL) and the mixture was stirred at room temperature for 30 min. The mixture was cooled to 0°C and I(symcollidine)2ClO4 (2.23 g, 4.76 mmol), prepared in situ from Ag(collidine)2ClO4 (10.13 g, 22.53 mmol) and 5.52 g I2 (21.78 mmol) in the presence of powdered 4 Å molecular sieves (3.0 g, freshly ﬂame-dried) in CH2Cl2 (130 mL) was added via cannula. The reaction was stirred for 1.5 h, then diluted with CH2Cl2 (150 mL) and ﬁltered. The ﬁltrate was washed with saturated aq Na2S2O3 (3X75 mL), saturated aq CuSO4 (5X75 mL), saturated aq Na2S2O3 (1X75 mL), and brine (1X75 mL). The organic layer was dried over Na2SO4 and concentrated in vacuo. The residue was puriﬁed by silica gel chromatography (hexane/EtOAc=4:1 to 3:1) to afford the desired diaxial isomer
(6.26 g, 5.65 mmol, 75%) as well as a small amount of the diequatorial isomer of the iodosulfonamide (0.589 g, 0.90 mmol, 12%). 1H NMR (500 MHz, CDCl3): d¼7.46–7.22 (m, 25H), 5.93 (m, 1H), 5.34 (dd, J¼1.6, 17.2 Hz, 1H), 5.20 (m, 2H), 4.93–4.37 (m, 12H), 4.19 (m, 4H), 4.08 (m, 1H), 3.85–3.34 (m, 10H), 3.04 (m, 1H), 1.06 (m, 2H), 0.07 (s, 9H); 13C NMR (125 MHz, CDCl3): d¼138.5, 138.3, 137.9, 137.7, 137.1, 128.5, 128.4, 128.3, 128.2, 128.1, 128.0, 128.0, 127.9, 127.9, 127.8, 127.8, 127.7, 127.7, 127.6, 127.5, 127.4, 116.8, 103.7, 81.8, 79.6, 79.1, 79.0, 78.2, 75.3, 74.6, 74.4, 73.9, 73.6, 73.5, 73.4, 73.1, 72.4, 71.9, 68.9, 67.4, 51.0, 29.8, 10.4, 2.1; HRMS (FAB) calcd for C55H68INO11SSi: 1105.3286, found: 1105.3290.

The iodosulfonamide (6.26 g, 5.65 mmol) was dissolved in DMF (20 mL) and added drop-wise to a solution of ethanethiol (2.09 mL, 28.25 mmol, 5 equiv) and LiHMDS (1 M solution in THF, 17 mL, 17 mmol) in DMF (80 mL) and cooled to -40°C. The reaction was allowed to slowly warm to room temperature and stirred for 12 h. Most of the solvent (DMF) was removed by evaporation under high vacuum and the residue was diluted with saturated aq NaHCO3 (100 mL) and washed with EtOAc (3X100 mL). The organic layer was dried over Na2SO4 and concentrated in vacuo. The residue was puriﬁed by silica gel chromatography (hexane/EtOAc=3.5:1) to afford molecule 59 (5.0 g, 4.80 mmol, 85%) as a white glass.
1H NMR (500 MHz, CDCl3): d¼7.38–7.18 (m, 25H), 5.92 (m, 1H), 5.34 (d, J¼17.5 Hz, 1H), 5.19 (d, J¼10.5 Hz, 1H), 4.93 (d, J¼11.8 Hz, 2H), 4.77–4.36 (m, 12H), 4.16 (m, 2H), 3.97–3.37 (m, 13H), 3.13 (m, 2H), 2.71 (m, 2H), 1.28 (t, J¼7.4 Hz, 3H), 1.05 (m, 2H), 0.01 (s, 9H); 13C NMR (125 MHz, CDCl3): d¼138.7, 138.6, 138.2, 137.9, 134.8, 128.3, 128.3, 128.2, 128.1, 128.1, 128.0, 127.9, 127.9, 127.8, 127.8, 127.7, 127.7, 127.7, 127.6, 127.6, 127.5, 127.5, 127.4, 127.4, 127.3, 116.3, 103.1, 83.8, 82.0, 81.2, 79.8, 79.7, 76.6, 75.2, 74.5, 73.8, 73.4, 73.2, 73.0, 71.6, 68.3, 67.9, 58.0, 24.0, 14.8, -2.0.

58:

2-(trimethylsilyl)ethanesulfonamide: