Compound 3j

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

PhI(OCOCF₃)₂ (725 mg, 1.69 mmol) was added to a solution of dithioacetal S10 (Dondoni, A.; Marra, A.; Merino, P. J. Am. Chem. Soc., 116, 3324, (1994)) (340 mg, 0.562 mmol) in CH₂Cl₂ (3.0 mL), MeCN (6.0 mL) and pH 7 7 phosphate buffer (6.0 mL) at 0 °C. The reaction mixture was stirred for 15 min at room temperature, and then saturated aqueous NaHCO₃ (20 mL) and saturated aqueous Na₂S₂O₃ (20 mL) were successively added at 0 °C. After being stirred for 15 min at room temperature, the resultant mixture was extracted with EtOAc (50 mL x2). The combined organic layers were washed with brine (30 mL), dried over Na₂SO₄, filtered and concentrated to afford the crude aldehyde S11 (547 mg), which was used in the next reaction without further purification.

TEMPO (18.0 mg, 0.115 mmol) and PhI(OAc)₂ (362 mg, 1.12 mmol) were added to a solution of the above crude aldehyde S11 (547 mg) in MeCN (3.0 mL) and H₂O (3.0 mL) at room temperature. After the mixture was stirred for 1.5 h at room temperature, TEMPO (18.0 mg, 0.115 mmol) was added. After the mixture was stirred for 21 h at room temperature, TEMPO (18.0 mg, 0.115 mmol) and PhI(OAc)₂ (362 mg, 1.12 mmol) were added. The reaction mixture was stirred for 10 h at room temperature, and then saturated aqueous Na₂S₂O₃ (20 mL) was added. After being stirred for 10 min at room temperature, the resultant mixture was extracted with CHCl₃ (25 mL x3). The combined organic layers were dried over Na₂SO₄, filtered and concentrated. The residue was purified by flash column chromatography on silica gel (10 g, hexane/EtOAc 5/1 to 0/1) to afford carboxylic acid 3j (257 mg, 0.499 mmol) in 89% yield over 2 steps: pale yellow amorphous solid; [α]_D²³ = –7.0 (c 0.46, CHCl₃); IR (film) 2988, 2933, 2858, 1733, 1381, 1220, 1113, 1038 cm^-1; 1H NMR (400 MHz, CDCl₃) δ 1.05 (9H, s, SiC(CH₃)₃), 1.35 (3H, s, CH₃ of acetonide), 1.37 (3H, s, CH₃ of acetonide), 1.43 (6H, br s, CH₃ of acetonide x2), 3.75-3.84 (3H, m, H1_A, 1_B, 3), 4.01 (1H, m, H2), 4.16 (1H, dd, J = 8.6, 4.1 Hz, H4), 4.25 (1H, d, J = 8.6 Hz, H5), 7.34-7.46 (6H, m, aromatic), 7.65-7.74 (4H, m, aromatic); ¹³C NMR (100 MHz, CDCl₃) δ 19.3, 23.5, 23.8, 24.3, 24.4, 26.7 (3C), 64.0, 67.8, 68.6, 69.4, 70.9, 101.3, 102.0, 127.6 (4C), 129.6 (2C), 133.6 (2C), 135.68 (2C), 135.71 (2C), (C6-peak was not observed); HRMS (ESI) calcd for C₂₈H₃₇O₇Si [M–H]^– 513.2314, found 513.2299.