# Regiosellective De Novo Synthesis of Phenolic Isoprenoids Grifolin and Neogrifolin
## 2 Materials and Methods
Data for **12c**: R\({}_{\rm f}\) = 0.37 (2:3 EtOAc/hexane); \({}^{1}\)H NMR (CDCl\({}_{3}\)) \(\delta\) = 1.09 (d, \(J\) = 6.0 Hz, 3H), 1.23 (t, \(J\) = 7.2 Hz, 3H), 1.58 (s, 3H), 1.60 (s, 3H), 1.66 (s, 3H), 1.68 (s, 3H), 1.91-2.11 (m, 8H), 2.46-2.62 (m, 3H), 2.70 (dd, \(J\) = 14.4, 8.8 Hz, 1H), 2.88 (dd, \(J\) = 14.4, 6.0 Hz, 1H), 3.40 (d, \(J\) = 14.4 Hz, 1H), 3.54 (d, \(J\) = 14.4 Hz, 1H), 4.10-4.24 (m, 2H; OCH\({}_{2}\)CH\({}_{3}\)), 4.93 (t, \(J\) = 7.4 Hz, 1H), 5.04 (t, \(J\) = 7.2 Hz, 1H), 5.07 (t, \(J\) = 6.8 Hz, 1H) ppm; \({}^{13}\)C NMR (CDCl\({}_{3}\)) \(\delta\) = 14.1, 15.8, 16.1, 16.4, 17.7, 25.7, 26.4, 26.7, 30.2, 30.5, 39.7, 40.0, 44.7, 57.7, 61.7, 62.9, 117.1, 123.8, 124.2, 131.4, 135.5, 140.6, 169.9, 202.9, 203.2 ppm; IR \(\
u\) = 2967, 2915, 2855, 1733, 1596, 1445, 1410, 1384, 1366, 1297, 1217, 1188, 1160, 1095, 1019, 944, 850, 754 cm\({}^{-1}\); HRMS (ESI) calcd. for C\({}_{2}\)C\({}_{1}\)H\({}_{3}\)O\({}_{4}\)+H 403.2848, found 403.2847. **  
**5-methyl-4-((2E,6E)-3,7,11-trimethyldodeca-2,6,10-trien-1-yl)cyclohexane-1,3-dione (7c). ** The above cyclized product **12c** (300 mg, 0.74 mmol) in THF was treated with 50% KOH (15 mL), and heated at reflux for 8 h. The mixture was cooled to room temperature and acidified with 50% HCl (25 mL). The reaction mixture was extracted with EtOAc, dried over anhydrous Na\({}_{2}\)SO\({}_{4}\), filtered, and concentrated under reduced pressure to give orange sticky oil (0.27 g). The crude product was then dissolved in toluene (20 mL) and heated at 110 \({}^{\circ}\)C for 17 h. Upon cooling to room temperature, the mixture was concentrated under reduced pressure. The crude product was purified by SiO\({}_{2}\) flash column chromatography (15-40% EtOAc/hexane eluent) to give an 1,3-cyclohexanedione **7c** (160 mg, 0.48 mmol) in 65% yield as a light-yellow liquid. Data for **7c**: R\({}_{\rm f}\) = 0.20 (EtOAc/hexane); \({}^{1}\)H NMR (CDCl\({}_{3}\)) \(\delta\) = 1.08 (d, \(J\) = 6.8 Hz, 3H), 1.59 (s, 3H), 1.60 (s, 3H), 1.65 (s, 3H), 1.68 (s, 3H), 1.93-2.13 (m, 9H), 2.18-2.55 (m, 4H), 2.73 (ddd, \(J\) = 12.0, 4.8, 1.2 Hz, 1H), 3.34 (d, \(J\) = 17.2 Hz, 1H), 3.43 (dd, \(J\) = 17.2 Hz, 1H), 3.43 (dd, \(J\) = 17.2, 1.2 Hz, 1H), 5.07 (t,\(J\) = 6.8 Hz, 1H), 5.08 (t, \(J\) = 6.8 Hz, 2H) ppm; \({}^{13}\)C NMR (CDCl\({}_{3}\)) \(\delta\) = 16.0, 16.2, 17.7, 20.1, 25.7, 26.4, 26.7, 26.8, 29.1, 39.7, 39.7, 46.7, 56.1, 57.5, 119.9, 123.9, 124.3, 131.4, 135.2, 138.0, 203.7, 205.6 ppm; IR v = 2962, 2915, 1732, 1592, 1448, 1381, 1297, 1265, 1220, 1185, 1161, 1106, 1021, 910, 843, 734 cm\({}^{-1}\); HRMS (ESI) calcd. for C\({}_{22}\)H\({}_{34}\)O\({}_{2}\)+H 331.2636, found 331.2637. **5-Methyl-6-((2E,6E)-3,7,11-trimethyldodeca-2,6,10-trien-1-yl)cyclohexa-1,3-diene-1,3-diyl diacetate (14)**. To a stirred solution of cyclohexane-1,3-dione 7c (520 mg, 1.57 mmol) in THF (20 mL) at \(-\)78 \({}^{\circ}\)C under an argon atmosphere, 2 M THF solution of LDA (2.75 mL, 5.50 mmol) was added. The resulting mixture was stirred at \(-\)78 \({}^{\circ}\)C for 1 h before acetic anhydride (0.38 mL, 4.00 mmol) and DMAP (0.19 g, 1.57 mmol) were added. The reaction mixture was stirred at \(-\)78 \({}^{\circ}\)C for 30 min 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. The crude product was purified by SiO\({}_{2}\) flash column chromatography (2.5-7% EtOAc/hexane eluent) to produce diacetate **14** (521 mg, 1.25 mmol) in 80% yield (a \(\sim\)1:1 mixture of diastereomers) as a light-yellow oil.