Compound 3k

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

p-Toluenesulfonic acid monohydrate (TsOH·H₂O, 31.0 mg, 0.163 mmol) was added to a solution of phthalimide 6 (624 mg, 0.806 mmol) in MeOH (2.0 mL) and CH₂Cl₂ (2.0 mL) at room temperature. The reaction mixture was stirred for 22 h at room temperature, and then Et₃N (25 µL) was added. The resultant mixture was concentrated to afford the crude alcohol S13 (730 mg), which was used in the next reaction without further purification.

TEMPO (25.0 mg, 0.160 mmol) and PhI(OAc)₂ (779 mg, 2.42 mmol) were added to a solution of the above crude alcohol S13 (730 mg) in MeCN (2.0 mL) and H₂O (2.0 mL) at room temperature. The reaction mixture was stirred for 18 h at room temperature, and then saturated aqueous Na₂S₂O₃ (10 mL) was added. After being stirred for 15 min at room temperature, the resultant mixture was extracted with CHCl₃ (10 mL x4). The combined organic layers were dried over Na₂SO₄, filtered and concentrated. The residue was purified by flash column chromatography on silica gel (15 g, hexane/EtOAc 3/1 to 0/1) to afford carboxylic acid 3k (235 g, 0.431 mmol) in 53% yield over 2 steps: colorless solid; mp 105-107 °C; [α]_D²³ = –24.5 (c 1.00, CHCl₃); IR (film) 3064, 2946, 1778, 1731, 1716, 1452, 1387, 1274, 1119, 1092, 1070, 1028 cm^-1; ¹H NMR (400 MHz, CDCl₃) δ 3.58 (3H, s, OCH₃), 4.81 (1H, dd, J = 10.9, 10.4, Hz, H4), 4.89 (1H, d, J = 8.2 Hz, H1), 5.24 (1H, d, J = 10.9 Hz, H5), 5.54 (1H, dd, J = 9.5, 8.2 Hz, H2), 6.31 (1H, dd, J = 10.4, 9.5 Hz, H3), 7.26 (2H, m, 10 aromatic), 7.36 (2H, m, aromatic), 7.42 (1H, m, aromatic), 7.50 (1H, m, aromatic), 7.66-7.71 (2H, m, aromatic), 7.73-7.84 (4H, m, aromatic), 7.95 (2H, m, aromatic); ¹³C NMR (100 MHz, CDCl₃) δ 51.6, 57.7, 69.0, 70.2, 71.9, 102.0, 123.6, 123.8, 128.27, 128.32 (4C), 129.0, 129.79 (2C), 129.84 (2C), 131.2 (2C), 133.3, 133.4, 134.3 (2C), 165.1, 165.6 (three carbonyl peaks of the carboxylic acid and the imides were not observed); HRMS (ESI) calcd for C₂₉H₂₃NO₁₀Na [M+Na]⁺ 568.1214, found 568.1227.