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. 2018 Jul 20;16(30):5524–5532. doi: 10.1039/c8ob00608c

Scheme 3. (a) NaH (60%, 1.08 equiv.), THF, 23 °C, 0.5 h, 50 °C, 20 h, 56%; (b) DIPA (2.5 equiv.), n-BuLi (2.5 equiv.), HMPA (1 equiv.), 3-fluorobenzaldehyde (1.1 equiv.), THF, –78 °C, 3 h; (c) 1 M KOH(aq), 23 °C, 14 h, then 6 M HCl(aq), 0 °C, 65% (over 2 steps); (d) DIPEA (1.5 equiv.), Tf2O (1.1 equiv.), CH2Cl2, –78 °C, 1 h, 97%; (e) Pd(PPh3)4 (0.01 equiv.), Et3SiH (2.0 equiv.), DMF, 60 °C, 2 h, 99%; (f) TBAF (1 M, 5 equiv.), THF, 23 °C, 2 h, 97%; (g) EDCI·HCl (1.6 equiv.), DMAP (1.2 equiv.), HSNAC (1.5 equiv.), DCM, 0 °C, 2 h, 23 °C, 14 h, 94%; (h) Et3N (2 equiv.), EtOCOCl (1.3 equiv.), THF, 0 °C, 0.5 h; (i) NaBH4 (2.5 equiv.), MeOH, –78 °C, 4 h, 60% (over 2 steps); (j) Dess–Martin periodinane (0.3 M, 1.3 equiv.), CH2Cl2, 23 °C, 1.5 h; (k) NaH (60%, 1.4 equiv.), (EtO)2P(O)CH2CO2Et (1.7 equiv.), THF, 0 °C, 10 min, 23 °C, 16 h, 67% (over 2 steps); (l) (CF3CH2O)2P(O)CH2CO2Et (2.1 equiv.), KHMDS (15 wt%, 2 equiv.), 18-crown-6 (2.4 equiv.), THF, –78 °C, 6.5 h, 64% (2Z : 2E::5 : 1, over 2 steps); (m) 1 M NaOH(aq), THF, 23 °C, 91%; (n) EDCI·HCl (2 equiv.), DMAP (2.4 equiv.), HSNAC (8.9 equiv.), DCM, 23 °C, 16 h, 60%; (o) 1 M LiOH(aq), MeOH, 23 °C, 16 h, 72%; (p) DIPA (2 equiv.), n-BuLi (2 equiv.), InCl3 (0.6 equiv.), THF, –78 °C, 2 h, 23 °C, 1 h, 34 (65%, over 2 steps), 35 (67%, over 2 steps); (q) NaH (60%, 1.4 equiv.), (EtO)2P(O)CH2CO2Et (1.7 equiv.), THF, 0 °C, 10 min, 23 °C, 16 h, 81% (over 2 steps).

Scheme 3