Reaction Steps
Sodium hydride (0.139 g., 4.60 mmol, 1.1 equiv.; 80% in oil washed with pentane) is suspended in 6 mL of DMSO. 2,3-Dihydroxybenzaldehyde (0.580 g., 4.20 mmol, 1 equiv.) dissolved in 2.8 mL of DMSO is added dropwise via cannula, and the mixture is allowed to stir for 1 hour. 2-Chloromethyl-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene) (18a) (1.00 g., 4.20 mmol, 1 equiv.) dissolved in 8 mL of DMSO is added dropwise via cannula, and the mixture allowed to stir 26.5 hours. The mixture is partitioned between saturated aqueous ammonium chloride solution and EtOAc. Salt is added to the aqueous phase, which is then extracted twice with EtOAc. The combined extracts are washed with brine, dried (MgSO4), and treated with charcoal before filtering through a pad of silica gel. The filtrate is evaporated, and the crude material is chromatographed on silica gel using EtOAc/hexane to afford 3-hydroxy-2-[5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl]methoxy benzaldehyde (45) (0.786 g., 2.33 mmol, 56%) as an oil: 1H NMR (300 MHz, CDCl3) δ 10.14 (s, 1H, CHO), 7.35 (m, 2H, ArH), 7.22-7.09 (m, 4H, ArH), 5.77 (s, 1H, OH), 5.00 (s, 2H, ArCH2O), 1.67 (s, 4H, CH2CH2), 1.27 (s, 6H, 2×CH3), 1.22 (s, 6H, 2×CH3); 13C NMR (75 MHz, CDCl3) δ 189.40 (C=0), 149.74, 148.00, 146.20, 145.64, 132.58, 129.63, 127.36, 127.11, 126.00, 125.12, 121.64, 121.34, 79.18, 34.92, 34.90, 34.27, 31.80, 31.75; IR (KBr) 3226, 2958, 2926, 1662, 1604, 1580, 1470, 1294, 1284, 1222, 934, 786 cm-1 ; MS (DCI) m/e 339 (MH+), 201 (C15H21+).
