# Regiosellective De Novo Synthesis of Phenolic Isoprenoids Grifolin and Neogrifolin
## 2 Materials and Methods
Data for **9a**: R\({}_{I}\) = 0.36 (4:1 hexane/EtOAc); \({}^{1}\)H NMR (CDCl\({}_{3}\)) \(\delta\) = 1.03 (d, \(J\) = 7.2 Hz, 3H) 1.01\({}^{\star}\) (d, \(J\) = 6.8 Hz, 3H), 1.23-1.30 (m, 6H; OCH\({}_{2}\)CH\({}_{3}\)), 2.24 (s, 3H), 2.22-2.30 (m, 1H), 2.40 (dd, \(J\) = 15.6, 6.4 Hz, 1H), 2.48* (dd, \(J\) = 15.6, 4.0 Hz, 1H), 2.70-2.82 (m, 1H), 3.47* (d, \(J\) = 8.4 Hz, 1H), 3.55 (d, \(J\) = 8.0 Hz, 1H), 3.99-4.24 (m, 4H; OCH\({}_{2}\)CH\({}_{3}\)) ppm; \({}^{13}\)C NMR (CDCl\({}_{3}\), major peaks) 14.2, 14.3, 17.4, 29.8, 30.1, 38.9, 60.6, 61.5, 64.1, 168.9, 172.2, 202.7 ppm; IR v = 3370 (w), 2975, 2929, 1730, 1603, 1446, 1383, 1367, 1298, 1223, 1186, 1095, 1025, 915, 848, 732 cm\({}^{-1}\); HRMS (ESI) calcd. for C\({}_{12}\)H\({}_{20}\)O\({}_{5}\)+Na 267.1208, found 267.1203. *: peaks from the minor stereoisomer. **Diethyl 2-acetyl-3-methyl-2-((2E,6E)-3,7,11-trimethyldodeca-2,6,10-trien-1 yl) pentanedioate (9c). ** To a stirred solution of the coupling product **9a** (1.50 g, 6.14 mmol) in DMF (20 mL) at 0 \({}^{\circ}\)C under an argon atmosphere, NaH (60% in mineral oil, 0.18 g, 7.37 mmol) was carefully added in several portions. Stirring at 0 \({}^{\circ}\)C for 1.5 h, the mixture was treated with a DMF solution (10 mL) of farnesyl bromide (1.40 g, 4.91 mmol). The reaction mixture was stirred at 0 \({}^{\circ}\)C for 8 h and quenched with 1 M HCl. The mixture was extracted with EtOAc, dried over anhydrous Na\({}_{2}\)SO\({}_{4}\), filtered, and concentrated under reduced pressure to give the crude product (2.87 g), which was purified by SiO\({}_{2}\) flash column chromatography (3-10% EtOAc/hexane eluent) to produce the coupling product **9c** (1.54 g, 3.44 mmol) in 71% yield as a yellow oil (-2:1 mixture of diastereomers). Data for **9c**: R\({}_{\rm f}\) = 0.66 (1:4 EtOAc/hexane); \({}^{1}\)H NMR (CDCl\({}_{3}\)) \(\delta\) = 0.94 (d, \(J\) = 7.2 Hz, 3H) 0.96\({}^{\rm*}\) (d, \(J\) = 6.8 Hz, 3H), 1.23-1.32 (m, 6H; OCH\({}_{2}\)CH\({}_{3}\)), 1.58 (s, 3H), 1.60 (s, 3H), 1.62 (s, 3H), 1.68 (s, 3H), 1.93-2.09 (m, 10H), 2.13 (s, 3H), 2.15\({}^{\rm*}\) (s, 3H), 2.52-2.69 (m, 2H), 2.72-2.82 (m, 1H), 4.08-4.27 (m, 4H; CO\({}_{2}\)CH\({}_{3}\)), 4.97 (t, \(J\) = 8.0 Hz, 1H), 5.09 (t, \(J\) = 6.8 Hz, 1H) ppm; \({}^{13}\)C NMR (CDCl\({}_{3}\), major peaks) = 14.2, 14.3, 15.4, 16.0, 16.3, 17.7, 25.7, 26.6, 26.8, 28.3, 30.7, 32.5, 38.4, 39.7, 39.9, 60.4, 61.1, 66.3, 117.8, 123.9, 124.4, 131.3, 135.2, 138.8, 171.5, 172.9, 205.0 ppm; IR \(\
u\) = 2979, 2929, 1733, 1708, 1446, 1374, 1354, 1301, 1266, 1221, 1178, 1095, 1029, 860, 736 cm\({}^{-1}\); HRMS (ESI) calcd. for C\({}_{2}\)H\({}_{44}\)O\({}_{5}\)+Na 471.3086, found 471.3082. **  
*: peaks from the minor stereoisomer. **Ethyl 2-methyl-4,6-diox-1-((2E,6E)-3,7,11-trimethyldodeca-2,6,10-trien-1-yl)cyclohexane-1-carboxylate (12c). ** To a stirred solution of coupling product **9c** (1.80 g, 4.01 mmol) in _t_-BuOH (20 mL), _t_-BuOK (0.45 g, 4.01 mmol) was added. The mixture was heated at 80 \({}^{\circ}\)C for 3 h. The mixture was cooled to room temperature, quenched with 1 M HCl, extracted with EtOAc, dried over anhydrous Na\({}_{2}\)SO\({}_{4}\), filtered, and concentrated under reduced pressure. The crude product was purified by SiO\({}_{2}\) flash column chromatography (15-50% EtOAc/hexane eluent) to produce the cyclized product **12c** (1.45 g, 3.63 mmol) in 91% yield as a light-yellow liquid (it contains a diastereomer).