Figure 5: SD and SE phases in de novo branching cascades strategy.
From: De novo branching cascades for structural and functional diversity in small molecules
For details, see Supplementary Methods. (a) NH4F, MeOH, room temperature (RT), 8 h, 49%; (b) BH3-morpholine, toluene, RT, 6 h, 92% (single diastereomer); (c) DIBAL-H 1.0 M, DCM, from −78 °C to 0 °C, 1 h, 15% (single diastereomer); (d) Na, NH3(liq), THF, −78 °C, 15 min, 60–65% (dr=2.3–4.0:1); (e) 1 bar H2, MeOH, RT, Pd-C, 50% of 39 (single diastereomer); (f) 8 bar H2, MeOH, RT, Pd-C, 34% of 39 and 23% of 40 (dr=4.9:1); (g) Oxone, K2CO3, MeCN-H2O, RT, 1 h, 60% (single diastereomer); (h) N-Methoxymethyl-N-(trimethylsilylmethyl)benzylamine, TFA (1.2 eqv.), toluene, RT, 8 h, 71–81% (single diastereomer for 42a); (i) Hydrazonoyl chloride, TEA (2.0 eqv.), toluene, 70 °C, 8 h, 60% (*brsm, single diastereomer); (j) allene ester (2a), tris(4-methoxyphenyl)-phosphine (40 mol%), toluene, RT, 8 h, 50% (*brsm, single diastereomer); (k) TEA(3.5 eqv.), toluene, reflux, 8 h, 82% (E:Z=1:4); and (l) 1 bar H2, Pd-C, MeOH, RT, 12 h, 90% (single diastereomer). Dots in 41–44 mark the new quaternary centres generated from scaffold 16.
