Scheme 14.

Synthesis of internal alkyne 97 and coupling of fragments [61]. Reagents and conditions: (i) NaOH (aq), THF, then HCl (aq), 0 °C; (ii) (COCl)₂, DMF (cat), CH₂Cl₂, 0 °C to rt, then AlCl₃, BTMSA, CH₂Cl₂, 0 °C to rt; (iii) (S)-Alpine-borane, THF to ~neat, −10 °C to rt; (iv) TBSCl, imidazole, CH₂Cl₂; (v) K₂CO₃, MeOH, 0 °C to rt; (vi) Bu₃SnH, AIBN (16 mol%), benzene, 80 °C; (vii) I₂, CH₂Cl₂; (viii) TMSCCH, CuI (12 mol%), Pd(PPh₃)₂Cl₂ (5 mol%), Et₃N, THF, 0 °C to rt; (ix) K₂CO₃, MeOH, 0 °C to rt; (x) vinyl iodide 95, CuI (9 mol%), Pd(PPh₃)₄ (3 mol%), Et₂NH, benzene; (xi) TBAF, THF, 0 °C to rt.