# Regiosellective De Novo Synthesis of Phenolic Isoprenoids Grifolin and Neogrifolin
## 2 Materials and Methods
Data for **13**: R\({}_{I}\) = 0.56 (4:1 hexane/EtOAc); \({}^{1}\)H NMR (CDCl\({}_{3}\)) \(\delta\) = 0.24 (s, 3H), 0.25 (s, 3H), 0.97 (s, 9H), 1.05 (d, \(J\) = 6.0 Hz, 3H), 1.57 (s, 3H), 1.60 (s, 3H), 1.68 (s, 6H), 1.90-2.22 (m, 11H), 2.36-2.46 (m, 2H), 2.95 (d, \(J\) = 6.4 Hz, 2H), 5.00 (t, \(J\) = 6.4 Hz, 1H), 5.09 (t, \(J\) = 6.8 Hz, 2H) ppm; \({}^{13}\)C NMR (CDCl\({}_{3}\)) \(\delta\) = -3.4, -3.2, 16.0, 16.3, 17.7, 18.3, 21.1, 21.6, 25.6, 25.7, 26.7, 26.8, 26.8, 28.6, 39.6, 39.7, 39.7, 45.2, 121.8, 122.6, 124.4, 124.4, 131.2, 134.7, 134.9, 168.1, 199.0 ppm; IR v = 2957, 2929, 2858, 1718, 1657, 1617, 1472, 1463, 1370, 1318, 1254, 1232, 1113, 1053, 1005, 937, 899, 826, 813, 784, 741 cm\({}^{-1}\); HRMS (FAB) calcd for C\({}_{28}\)H\({}_{49}\)O\({}_{2}\)Si 445.3502, found 445.3509. **Gridion: 5-methyl-2-((2E,6)-3,7,11-trimethyldodeca-2,6,10-trien-1-yl)benzene-1,3-diol (1). ** To a stirred solution of TBS-ether **13** (98 mg, 0.22 mmol) in THF (5 mL)/hexane (10 mL) at \(-\)78 \({}^{\circ}\)C under an argon atmosphere, 1 M THF solution of LHMDS (1.1 mL, 1.10 mmol) was added. The mixture was stirred at \(-\)78 \({}^{\circ}\)C for 1 h and a solution of Ts-Br (60 mg, 0.25 mol) in THF (2 mL) was added dropwise to the reaction mixture. The reaction was quenched with saturated NH\({}_{4}\)Cl solution (2 mL) in 15 min at \(-\)78 \({}^{\circ}\)C. The mixture was extracted with EtOAc, washed with H\({}_{2}\)O, dried over anhydrous Na\({}_{2}\)SO\({}_{4}\), filtered, and concentrated. The crude product was then treated with 1 M THF solution of TBAF (0.44 mL, 0.44 mol). The reaction mixture was stirred at room temperature for 15 min and quenched with 1 M HCl. The mixture was extracted with EtOAc, washed with H\({}_{2}\)O, dried over anhydrous Na\({}_{2}\)SO\({}_{4}\), filtered, and concentrated. The crude product was purified by SiO\({}_{2}\) flash column chromatography (7-15% EtOAc/hexane) to give gifolin **1** (37 mg, 0.11 mmol) in 50% yield as an orange-yellow oil. Data for **1**: \({}^{1}\)H NMR (CDCl\({}_{3}\)) \(\delta\) = 1.59 (s, 3H), 1.60 (s, 3H), 1.68 (s, 3H), 1.81 (s, 3H), 1.92-2.01 (m, 2H), 2.01-2.16 (m, 6H), 2.21 (s, 3H), 3.39 (d, \(J\) = 7.2 Hz, 2H), 5.02-5.16 (m, 4H), 5.27 (t, \(J\) = 7.2 Hz, 1H), 6.24 (s, 2H) ppm; \({}^{13}\)C NMR (CDCl\({}_{3}\)) \(\delta\) = 16.0, 16.2, 17.7, 21.1, 22.2, 25.7, 26.4, 26.7, 39.7, 39.7, 109.0, 110.4, 121.7, 123.6, 124.4, 131.3, 135.6, 137.5, 138.9, 154.8 ppm; IR v = 3608, 3430 (br), 3015, 2922, 2852, 1760, 1699, 1628, 1589, 1449, 1336, 1211, 1041, 988, 909, 822, 756 cm\({}^{-1}\); HRMS (ESI) calcd. for C\({}_{22}\)H\({}_{32}\)O\({}_{2}\)+H 329.2481, found 329.2476. **Experimental Procedures for the Synthesis of Neogifolin 2**  
**Diethyl 2-acetyl-3-methylpentanedioate (9a). ** To a stirred solution of ethyl acetoacetate (7.00 g, 53.76 mmol) in \(t\)-BuOH (50 mL) at 25 \({}^{\circ}\)C under an argon atmosphere, ethyl crotonate (6.13 g, 53.76 mmol) and \(t\)-BuOK (1.21 g, 10.75 mmol) were added. The reaction mixture was heated at 90 \({}^{\circ}\)C for 4 h and the mixture was 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 (12.94 g), which was purified by SiO\({}_{2}\) flash column chromatography (7-20% EtOAc/hexane eluent) to produce the addition product **9a** (11.45 g, 51.07 mmol) in 95% yield as a light-yellow liquid (\(\sim\)1.1:1 mixture of diastereomers).