Synthesis of the C'D'E'F' domain of maitotoxin - PubMed (original) (raw)

scheme 4

Synthesis of C′D′E′F′ Ring System 6 through a Linear Strategya _a_Reagents and conditions: (a) TMSOTf (1.3 equiv), 2,6-lut. (2.0 equiv), CH2Cl2, 0 °C, 2 h, 98%; (b) DIBAL-H (1.0 M in hexanes, 2.5 equiv), CH2Cl2, −78 °C, 1 h; then 0 °C, 30 min, 94%; (c) (−)-DET (1.2 equiv), Ti(O_i_-Pr)4 (1.0 equiv), _t_-BuOOH (5.0 M in decane, 3.0 equiv), 4 Å MS, CH2Cl2, −20 °C, 1 h, 97%; (d) SO3•py (4.0 equiv), Et3N (8.0 equiv), CH2Cl2:DMSO (5:1), 0 → 25 °C, 9 h; e) CH3PPh3Br (2.0 equiv), NaHMDS (0.6 M in toluene, 1.9 equiv), THF, 0 °C, 30 min; then −78 °C, aldehyde (1.0 equiv), THF, −78 → 0 °C, 93% over the two steps; f) TBAF (1.0 M in THF, 1.2 equiv), THF, 0 °C, 30 min, 100%; g) CSA (0.2 equiv), CH2Cl2, 0 °C, 30 min, 75%; (h) TESCl (2.0 equiv), imidazole (3.0 equiv), CH2Cl2, 0 → 25 °C, 1 h, 100%; (i) BH3•THF (1.0 M in THF, 1.2 equiv), THF, 0 °C, 2 h; then H2O2 (35% aq, 3.0 equiv), NaOH (2.0 M aq, 2.0 equiv), 25 °C, 1 h, 83%; (j) TPAP (0.1 equiv), NMO (3.0 equiv), 4 Å MS, 0 → 25 °C, 1 h, 95%; (k) MeMgBr (3.0 M in ether, 5.0 equiv), THF, 0 °C, 1 h; (l) TPAP (0.1 equiv), NMO (3.0 equiv), 4 Å MS, 0 → 25 °C, 12 h, 96% over the two steps; (m) TBAF (1.0 M in THF, 1.1 equiv), THF, 0 °C, 30 min, 97%; (n) ethyl propiolate (4.0 equiv), _N_-methylmorpholine (8.0 equiv), CH2Cl2, 25 °C, 23 h, 99%; (o) SmI2 (0.1 M in THF, 2.5 equiv), MeOH (2.5 equiv), THF, 0 °C, 20 min, 97%; (p) TMSOTf (1.5 equiv), 2,6-lut. (2.5 equiv), CH2Cl2, 0 °C, 1 h, 95%; (q) DIBAL-H (1.0 M in CH2Cl2, 1.1 equiv), CH2Cl2, −78 °C, 1 h, 90%; (r) MeO2CCH2P(O)(OEt)2 (2.0 equiv), NaHMDS (0.6 M in PhMe, 1.9 equiv), THF, 0 °C, 1 h, 96%; (s) DIBAL-H (1.0 M in CH2Cl2, 2.5 equiv), CH2Cl2, −78 °C, 40 min, 93%; (t) (−)-DET (1.2 equiv), Ti(O_i_-Pr)4 (1.0 equiv), _t_-BuOOH (5.0 M in decane, 3.0 equiv), 4 Å MS, CH2Cl2, −20 °C, 1 h, 96%; (u) SO3•py (5.0 equiv), DMSO (14 equiv), Et3N (5.5 equiv), CH2Cl2, 0 → 25 °C, 1 h, 84%; (v) Ph3PCH3Br (2.0 equiv), NaHMDS (0.6 M in PhMe, 1.9 equiv), THF, −78 °C → 0 °C, 90%; (w) TBAF (1.05 equiv), THF, 0 °C, 1 h, 78%; (x) CSA (0.1 equiv), CH2Cl2, 0 °C, 3 h, 90%; (y) TBAF (1.0 M in THF, 5.0 equiv), THF, 25 °C, 2 h, 79%. Abbreviations: TMSOTf = trimethylsilyl trifluoromethanesulfonate; py = pyridine; DMSO = dimethylsulfoxide; TBAF = tetra-_n_-butylammonium fluoride; CSA = camphorsulfonic acid; TES = triethylsilyl; TPAP = tetra-_n_-propylammonium perruthenate; NMO = _N_-methylmorpholine oxide.