Synthesis of JKLM Ring Fragment of Ciguatoxin via Acetylene-Cobalt Strategy

Abstract

A stereoselective synthesis of the JKLM ring fragment has been achieved through a coupling between two segments via heteroconjugate addition, seven-membered ether ring formation mediated by an acetylene cobalt complex and spiroketalization reaction.

Key words

acetylene cobalt complex - reductive decomplexation - heteroconjugate addition - medium sized ring - ciguatoxin

References

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14

Physical data for 8. ¹H NMR (CDCl₃, 300 MHz) d 0.58-0.88 [15 H, m, -Si(CH ₂ CH ₃ )₃], 1.47 (1 H, q, J = 11.5 Hz, H-43a), 2.16 (1 H, m, allylic), 2.55 (1 H, m, allylic), 2.73 (1 H, dt, J = 12.0 Hz, 4.5 Hz, H-43b), 3.01 (1 H, d, J = 9.0 Hz, -OH), 3.11-3.27 (2 H, m, H-41, 42), 3.34 (1 H, m, H-44), 4.45 (1 H, d, J = 11.5 Hz, -OCH ₂ Ph), 4.63 (1 H, d, J = 11.5 Hz,
-OCH ₂ Ph), 4.68 (1 H, ddd, J = 11.5 Hz, 9.5 Hz, 4.5 Hz, H-44), 4.76 (1 H, t, J = 9.0 Hz, H-45), 4.97-5.05 (2 H, m, olefinic), 5.68-5.83 (1 H, m, olefinic), 6.40 (1 H, d, J = 9.0 Hz, H-46), 7.26-7.40 (5 H, m, aromatic), 7.48-7.63 (3 H, m, aromatic), 7.83-7.90 (2 H, m, aromatic).

16

Physical data for 15. ¹H NMR (CDCl₃, 300M Hz) d 0.00-0.08 [6 H, m, -Si(CH ₃ )₂ t-Bu], 0.86-1.03 [15 H, m, -Si(CH₃)₂ t-Bu, CH ₃ -59, CH ₃ -60], 1.62-1.99 (4 H, m, H-50, 51, 53a, 53b), 2.36-2.45 (1 H, m, H-47), 3.32-3.40 (3 H, m, -OCH ₃ ), 3.48-4.06 (5 H, m, H-49, 52, 54, 55a, 55b), 3.83 (3 H, s, -OC₆H₄OCH ₃ ), 4.49-4.76 (4 H, m, -OCH ₂ Ar), 6.90 (2 H, br d, J = 8.0 Hz, aromatic), 7.27-7.39 (7 H, m, aromatic).

21

Physical data for 26. IR (KBr) 3447, 2926, 1717, 1636, 1456, 1355, 1077, 1025, 938, 739, 698, 419 cm^-1. ¹H NMR (CDCl₃, 400 MHz) d 1.01 (3 H, d, J = 6.5 Hz, CH ₃ -60), 1.06 (3 H, d, J = 6.5 Hz, CH ₃ -59), 1.12 (3 H, d, J = 7.5 Hz, CH ₃ -58), 1.40 (1 H, q, J = 11.5 Hz, H-43a), 1.48 (1 H, dq, J = 11.0 Hz, 6.5 Hz, H-51), 1.61 (1 H, ddq, J = 11.0 Hz, 10.0 Hz, 6.5 Hz, H-50), 2.00 (1 H, qdd, J = 7.5 Hz, 5.0 Hz, 3.5 Hz, H-46), 2.08 (1 H, dd, J = 14.0 Hz, 4.0 Hz, H-53a), 2.13 (1 H, dd, J = 14.0 Hz, 6.5 Hz, H-53b), 2.45 (1 H, dd, J = 15.5 Hz, 9.0 Hz, H-40a), 2.54 (1 H, dt, J = 12.0 Hz, 4.5 Hz, H-43), 2.79 (1 H, dd, J = 15.5 Hz, 3.5 Hz, H-40b), 1.61 (1 H, ddq, J = 11.0 Hz, 10.0 Hz, 6.5 Hz, H-50), 2.95 (1 H, dd, J = 9.5 Hz, 5.0 Hz, H-45), 3.15 (1 H, ddd, J = 11.5 Hz, 9.0 Hz, 4.5 Hz, H-42), 3.26 (1 H, t, J = 9.5 Hz, H-49), 3.59 (1 H, td, J = 9.0 Hz, 3.5 Hz, H-41), 3.62 (1 H, dd, J = 9.5 Hz, 2.0 Hz, H-48), 3.65 (1 H, dd, J = 3.5 Hz, 2.0 Hz, H-47), 3.69 (1 H, ddd, J = 11.5 Hz, 9.5 Hz, 4.5 Hz, H-44), 3.85 (1 H, dd, J = 9.5 Hz, 5.0 Hz, H-55a), 3.96 (1 H, dd, J = 9.5 Hz, 2.0 Hz, H-55b), 4.26 (1 H, dddd, J = 6.5 Hz, 5.0 Hz, 4.0 Hz, 2.0 Hz, H-54), 4.39 (2 H, d, J = 11.5 Hz, -OCH ₂Ph), 4.45 (2 H, d, J = 12.0 Hz,
-OCH ₂Ph), 4.47 (2 H, d, J = 12.0 Hz, -OCH ₂Ph), 4.63 (2 H, d, J = 11.5 Hz, -OCH ₂Ph), 7.20-7,37 (10 H, m, aromatic). ESI Q-TOF MS calcd for C₃₅H₄₇O₈ 595.327 [M + H]⁺, found 595.336.