Scheme 11.

Completion of the Enantioselective Total Syntheses of Emethallicin E (5) and Haematocin (6)^a

^aReagents and conditions. a) TFA/CH₂Cl₂ (1:2.5), 25 °C, 4 h, 95%; b) AllocCl (1.7 equiv), NaHCO₃ (10.0 equiv), dioxane/H₂O (1:1), 0→25 °C, 3 h, 88%; c) LiOH aq. (1.0 M)/THF (1:1), 0→25 °C, 5 h; d) 83, 84 (1.0 equiv each), BOP-Cl (1.1 equiv), DIPEA (3.0 equiv), CH₂Cl₂, 0→25 °C, 15 h, 83% for the two steps; e) Pd₂(dba)₃ (0.02 equiv), dbbp (0.05 equiv), THF/Et₂NH (2:1), 25 °C, 2 h, 84%; f) LiHMDS (1.0 M in THF, 20 equiv), S₈ (37 equiv), THF, 25 °C, 5 min; then 86 (0.06 M in THF/Et₂O (9:1), 1.0 equiv), 5 min; then LiHMDS (1.0 M in THF, 20 equiv), 25 °C, 5 h, 46%, plus 43% recovered starting material 86; g) PhCH₂COOH (30 equiv), DCC (30 equiv), 4-DMAP (3.0 equiv), 0→25 °C, 15 h, 71%, plus 26% recovered starting material 87; h) AcOH (30 equiv), DCC (30 equiv), 4-DMAP (3.0 equiv), 0→25 °C, 15 h, 71%, plus 24% recovered starting material 87; i) 1,3-propane dithiol (90 equiv), Et₃N (0.32 equiv), MeCN/CH₂Cl₂ (25:1), 25 °C; then concentrate; then O₂, MeOH, 2 h, 25 °C, 54% overall; j) NaBH₄ (80 equiv), MeOH/py (1:1), 0 °C; then MeI (485 equiv) 0→25 °C, 4 h; 97% overall.