# Regiosellective De Novo Synthesis of Phenolic Isoprenoids Grifolin and Neogrifolin
## 2 Materials and Methods
Data for **12b**: R\({}_{f}\) = 0.56 (2:3 EtOAc/hexane); \({}^{1}\)H NMR (CDCl\({}_{3}\)) \(\delta\) = 1.07 (d, \(J\) = 6.4 Hz, 3H), 1.30 (t, \(J\) = 7.2 Hz, 3H), 1.60 (s, 6H), 1.68 (s, 3H), 1.75 (s, 3H), 2.10-2.26 (m, 9H), 2.44-2.60 (m, 2H), 3.00-3.16 (m, 2H), 3.02 (d, \(J\) = 11.6 Hz, 1H), 4.17-4.32 (m, 2H), 5.05 (t, \(J\) = 6.8 Hz, 1H), 5.09 (t, \(J\) = 6.8 Hz, 1H), 5.23 (t, \(J\) = 7.2 Hz, 1H), 7.05 (br, s, 1H) ppm; \({}^{13}\)C NMR (CDCl\({}_{3}\)) \(\delta\) = 14.3, 16.1, 16.2, 17.7, 19.7, 21.5, 25.7, 26.1, 26.7, 30.8, 35.8, 39.7, 39.7, 60.5, 61.0, 112.5, 121.4, 123.3, 124.3, 131.4, 136.0, 140.8, 170.6, 171.5, 193.0 ppm; IR v = 3435, 2974, 2937, 2876, 1724, 1623, 1456, 1405, 1376, 1302, 1242, 1222, 1154, 1095, 1025, 925, 852, 794, 735 cm\({}^{-1}\); HRMS (ESI) calcd. for C\({}_{25}\)H\({}_{38}\)O\({}_{4}\)+H 403.2848, found 403.2844. **3-Hydroxy-5-methyl-2-((2E,6)-3,7,11-trimethyldodeca-2,6,10-trien-1-yl)cyclohex-2-en-1-one (7b\({}^{\prime}\)). ** The above cyclized product **12b** (1.37 g, 3.40 mmol) was dissolved in 1 M NaOH (20 mL) and heated at 100 \({}^{\circ}\)C for 2 h. The mixture was cooled to room temperature and acidified with 1 M HCl (30 mL). The mixture was extracted with EtOAc, dried over anhydrous Na\({}_{2}\)SO\({}_{4}\), filtered, and concentrated under reduced pressure to give orange sticky oil (1.34 g). The above crude product was then dissolved in toluene (20 mL) and heated to 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 (20-40% EtOAc/hexane eluent) to give a keto **7b**/enol **7b\({}^{\prime}\)** mixture of 1,3-cyclohexanedione (750 mg, 2.27 mmol) in 67% yield as an off-white solid. Data for **7b\({}^{\prime}\)**: R\({}_{f}\) = 0.45 and 0.09 (2:3 EtOAc/hexane); \({}^{1}\)H NMR (CDCl\({}_{3}\)) \(\delta\) = 1.06 (d, \(J\) = 6.0 Hz, 3H), 1.59 (s, 3H), 1.60 (s, 3H), 1.68 (s, 3H), 1.75 (s, 3H), 1.90-2.24 (m, 11H), 2.30-2.56 (m, 2H), 3.05 (d of A of ABq, \(J_{AB}\) = 16.4, \(J_{d}\) = 7.6 Hz, 1H), 3.13 (d of B of ABq, \(J_{AB}\) = 16.4, \(J_{d}\) = 7.2 Hz, 1H), 5.02-5.14 (m, 2H), 5.22 (dt, \(J_{d}\) = 1.2, \(J_{l}\) = 7.2 Hz, 1H), 6.85 (br s, 1H) ppm; \({}^{13}\)C NMR (CDCl\({}_{3}\)) \(\delta\) = 16.0, 16.1, 16.2, 17.8, 21.0, 21.3, 25.8, 25.8, 26.3, 26.7, 28.3, 39.7, 39.7, 113.5, 121.9, 123.6, 124.4, 131.4, 135.8, 139.4, 172.2, 198.4 ppm; IR v = 3403 (w), 2962, 2918, 2849, 1732, 1614, 1456, 1380, 1249, 1215, 1059, 911, 787, 731 cm\({}^{-1}\); HRMS (ESI) calcd for C\({}_{22}\)H\({}_{34}\)O\({}_{2}\)+H 331.2637, found 331.2639. **3-((tert-Butyldimethylsilyl)oxy)-5-methyl-2-((2E,6)-3,7,11-trimethyldodeca-2,6,10-trien-1-yl)cyclohex-2-en-1-one (13). ** To a stirred solution of the enol form of cyclohexane-1,3-dione **7b\({}^{\prime}\)** (430 mg, 1.30 mmol) in CH\({}_{2}\)Cl\({}_{2}\) (10 mL) at 0 \({}^{\circ}\)C, _tert_-butyldimethylsilyl chloride (0.20 g, 1.37 mmol) and Et\({}_{3}\)N (0.19 mL, 1.37 mmol) were added. The mixture was stirred at room temperature for 15 min and concentrated under reduced pressure. The crude product was diluted with hexane, and the insoluble white precipitate was filtered and rinsed with hexane (5 \(\times\) 10 mL). The combined hexane solutions were concentrated under reduced pressure and purified by SiO\({}_{2}\) flash column chromatography (5-10% EtOAc/hexane) to afford TBS-ether **13** (495 mg, 1.11 mmol) in 86% yield as a colorless oil.