Scheme 19.

Synthesis of isochroman derivative 154.

Reagents and Conditions: (i) Reference [40]; (ii) (a) NaIO₄, MeOH, rt, 30 min; (b) K₂CO₃, Ohira-Bestmann reagent, MeOH, rt, 6 h, 78% for the two steps; (iii) acetylene, toluene, RhCl(PPh₃)₃, toluene, −78 °C, 25 min then 80 °C, 4 h, 65%; (iv) (a) aq AcOH (60%), reflux, 2 h; (b) Ac₂O, TEA, DMAP, CH₂Cl₂, 0 °C, 1 h then rt, 1 h, 87% for the two steps; (v) thymine, BSA, CH₃CN, reflux, 15 min then TMSOTf, 50 °C, 2 h, 79%; (vi) MeONa, MeOH, rt, 20 min, 95%.