Figure 3: Building scaffold diversity phase (SD phase) by de novo branching cascades.
From: De novo branching cascades for structural and functional diversity in small molecules
(a) Cascade synthesis of azepinone 11 from primary substrates. (b) SD phase; de novo branching cascades from primary substrates (blue arrows) and branching cascades from azepinone (red arrows) leading to diverse scaffolds, for details see Supplementary Methods. (a) 7+8 in MeCN, 10 min, room temperature (RT), then 2, 80 °C, 8 h, 14–76%; (b) 7+8 in MeCN, 10 min, RT, then 2, RT, 8 h, 20–60%; (c) TFA (20 mol%) in toluene, 100 °C, 6 h, 60–89%; (d) 7+8 in MeCN, 10 min, RT, then 2, 80 °C, 8 h, then TFA (20 mol%) in toluene, 100 °C, 6 h, 40–70%; (e) TFA (20 mol%) in toluene, 100 °C, 6 h, then NaOH(aq) 1 M, 1,4-dioxane, RT, 6 h and neutralization with HCl (3 M) until pH=6–7, 66–77%; (f) K2CO3, DMF, 100 °C, 6 h, 25–76%; (g) 7+8 in DMF, 10 min, RT, then 2, 80 °C, 8 h, then K2CO3, 100 °C, 6 h, 12–40%; (h) KOAc, EtOH, 60 °C, 6 h, 69% or K2CO3, DMF, 100 °C, 6 h, 15–32%; (i) 7+8 in DMF, 10 min, RT, then 2, 80 °C, 8 h, then K2CO3, 100 °C, 6 h, 15–30%; (j) NaH, DMF, 0 °C, 30 min, 65%; (k) 7+8 in DMF, 10 min, RT, then 2, 80 °C, 8 h, then KOAc, EtOH, 60 °C, 4%; and (l) NaOH(aq) 1 M, 1,4-dioxane, RT, 6 h and neutralization with HCl 3 M until pH=6–7, 80–94%.
