3.1.4. (3*S*,4*S*)-4-methoxy-5,8-bis(methoxymethoxy)-7-methyl-3-pentylisochroman-1-one (**5a**)

To a solution of bromo compound **3** (40.0 mg, 89.4 μmol) and CsF (16.3 mg, 107 μmol) in degassed DMF (0.45 mL) were added Me4Sn (15 μL, 107 μmol) and PdCl2(PPh3)2 (6.3 mg, 8.94 μmol) at room temperature. After stirring for 50 min at 80 ◦C, the reaction was quenched by adding water. The mixture was extracted with EtOAc (×3) and the combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified with flash column chromatography (EtOAc:*n*-hexane = 3:7) to give diMOM-protected methyl derivative **5a** (28.5 mg, 83%) as a yellow amorphous. 1H-NMR (400 MHz, CDCl3) δ 7.255 (1H, s), 5.21 (2H, s), 5.10 (1H, d, *J* = 6.8 Hz), 5.07 (1H, d, *J* = 6.8 Hz), 4.59 (1H, d, *J* = 1.5 Hz), 4.26 (1H, ddd, *J* = 1.5, 5.9, 7.5 Hz), 3.60 (3H, s), 3.50 (3H, s), 3.30 (3H, s), 2.39 (3H, s), 2.02 (1H, m), 1.81 (1H, m), 1.70–1.50 (1H, overlapped), 1.43 (1H, m), 1.40–1.25 (4H, overlapped), 0.91 (3H, t, *J* = 6.8 Hz); 13C-NMR (125 MHz, CDCl3) δ 162.4, 152.3, 149.8, 135.7, 126.3, 121.3, 118.7, 101.5, 95.0, 80.9, 68.2, 57.5, 56.7, 56.4, 31.6, 30.6, 24.9, 22.6, 17.6, 14.0.; IR (KBr) 2958, 2927, 2858, 2828, 1728, 1478, 1153 cm<sup>−</sup>1; HRMS (ESI) *m*/*z* (M + H)<sup>+</sup> calculated for (C20H31O7) <sup>+</sup> 383.2070, found 383.2069.

#### 3.1.5. (3*S*,4*S*)-5,8-dihydroxy-4-methoxy-7-methyl-3-pentylisochroman-1-one (**5**)

To a solution of diMOM-protected methyl derivative **5a** (10.0 mg, 26.0 μmol) in MeOH (2.0 mL) was added 6 M aqueous HCl (0.65 mL) at 0 ◦C. After stirring for 1 h at 40 ◦C, the reaction was quenched by adding saturated aqueous NaHCO3. The mixture was extracted with EtOAc (×3) and the combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified with PTLC (EtOAc:*n*-hexane = 3:7) to give methyl derivative **5** (5.2 mg, 68%) as a yellow solid. m.p. 113 ◦C; 1H-NMR (400 MHz, CDCl3) δ 10.89 (1H, s), 6.93 (1H, s), 5.59 (1H, br-s), 4.75 (1H, d, *J* = 2.7 Hz), 4.48 (1H, ddd, *J* = 2.7, 5.4, 8,3 Hz), 3.37 (3H, s), 2.25 (3H, s), 1.93 (1H, m), 1.84 (1H, m), 1.70-1.50 (1H, overlapped), 1.45 (1H, m), 1.40–1.25 (4H, overlapped), 0.91 (3H, t, *J* = 6.6 Hz); 13C-NMR (125 MHz, CDCl3) δ 169.4, 154.9, 144.9, 128.7, 125.8, 118.6, 106.6, 81.4, 69.8, 56.5, 31.6, 29.8, 24.9, 22.5, 15.8, 14.0.; IR (KBr) 3340, 2957, 2928, 2859, 1682, 1654, 1604, 1296, 1172 cm<sup>−</sup>1; HRMS (ESI) *m*/*z* (M + Na)<sup>+</sup> calculated for (C16H22O5Na)<sup>+</sup> 317.1365, found 317.1350.

#### 3.1.6. (3*S*,4*S*)-4-methoxy-5,8-bis(methoxymethoxy)-3-pentyl-7-vinylisochroman-1-one (**7a**)

To a solution of bromo compound **3** (200 mg, 0.447 mmol) and CsF (135.8 mg, 0.894 mmol) in degassed DMF (2.2 mL) were added tributylvinyltin (0.26 mL, 0.894 mmol) and PdCl2(PPh3)2 (62.8 mg, 89.0 μmol) at room temperature. After stirring for 1 h at 80 ◦C, the reaction was quenched by adding water. The mixture was extracted with EtOAc (×3) and the combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified with flash column chromatography (EtOAc:*n*-hexane = 3:7) to give diMOM-protected vinyl derivative **7a** (185.1 mg, quant) as a yellow solid. m.p. 63–64 ◦C; 1H-NMR (500 MHz, CDCl3) δ 7.56 (1H, s), 7.14 (1H, dd, *J* = 11.1, 17.7 Hz), 5.76 (1H, d, *J* = 17.7 Hz), 5.40 (1H, d, *J* = 11.1 Hz), 5.24 (2H, s), 5.08 (1H, d, *J* = 6.3 Hz), 5.05 (1H, d, *J* = 6.3 Hz), 4.60 (1H, d, *J* = 1.3 Hz), 4.26 (1H, ddd, *J* = 1.3, 5.8, 7.4 Hz), 3.58 (3H, s), 3.50 (3H, s), 3.31 (3H, s), 2.03 (1H, m), 1.81 (1H, m), 1.56 (1H, m), 1.43 (1H, m), 1.40–1.25 (4H, overlapped), 0.90 (3H, t, *J* = 6.9 Hz); 13C-NMR (125 MHz, CDCl3) δ 162.0, 150.7, 150.2, 134.9, 131.3, 128.5, 119.7, 116.7, 116.0, 101.5, 95.2, 80.8, 68.3, 57.9, 56.8, 56.4, 31.6, 30.6, 24.9, 22.5, 14.0.; IR (KBr) 2953, 2931, 2861, 2829, 1730, 1471, 1426, 1155, 929 cm<sup>−</sup>1; HRMS (ESI) *m*/*z* (M + H)<sup>+</sup> calculated for (C21H31O7) <sup>+</sup> 395.2070, found 395.2078.

#### 3.1.7. (3*S*,4*S*)-5,8-dihydroxy-4-methoxy-3-pentyl-7-vinylisochroman-1-one (**7**)

To a solution of diMOM-protected methyl derivative **7a** (13.7 mg, 34.7 μmol) in MeOH (2.6 mL) was added 6 M aqueous HCl (0.87 mL) at 0 ◦C. After stirring for 3 h at 40 ◦C, the reaction was quenched

by adding saturated aqueous NaHCO3. The mixture was extracted with EtOAc (×3) and the combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified with PTLC (EtOAc:*n*-hexane = 3:7) to give vinyl derivative **7** (8.5 mg, 75%) as a yellow wax. 1H-NMR (500 MHz, CDCl3) δ 11.10 (1H, s), 7.23 (1H, s), 7.01 (1H, dd, *J* = 11.4, 17.7 Hz), 5.82 (1H, br-s), 5.80 (1H, d, *J* = 18.0 Hz), 5.37 (1H, d, *J* = 11.0 Hz), 4.77 (1H, br-s), 4.50 (1H, br-s), 3.40 (3H, s), 1.95 (1H, m), 1.85 (1H, m), 1.58 (1H, m), 1.45 (1H,m), 1.40–1.25 (4H, overlapped), 0.90 (3H, br-s); 13C-NMR (125 MHz, CDCl3) δ 169.3, 153.9, 145.4, 129.8, 128.0, 121.4, 120.9, 116.5, 107.7, 81.5, 69.7, 56.8, 31.6, 29.8, 24.9, 22.5, 14.0.; IR (KBr) 3311, 2956, 2930, 2859, 1659, 1438, 1171 cm<sup>−</sup>1; HRMS (ESI) *m*/*z* (M + Na)<sup>+</sup> calculated for (C17H22O5Na)<sup>+</sup> 329.1365, found 329.1368.
