Dipolar Cycloaddition and Ring-Closing Metathesis in the Synthesis of the Tetracyclic ABCE Ring System of Manzamine A

Abstract

The tetracyclic ABCE core ring system of the manz­amine alkaloids was prepared with the correct relative stereochemistry by an intramolecular dipolar cycloaddition reaction of an azomethine ylide, followed by a ring-closing metathesis reaction.

Key words

alkaloids - cycloadditions - metathesis - stereoselective - ylides

References

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10

Spectroscopic data for compound 3: IR (film): ν_max = 1720, 1685, 1645 cm^-1. ¹H NMR (400 MHz, 75 °C, C₆D₆): δ = 1.12-1.23 (2 H, m), 1.26 (1 H, ddd, J = 13.1, 3.6, 1.6 Hz), 1.35-1.65 (4 H, m), 1.57 (9 H, s), 1.82 (1 H, dd, J = 13.1, 10.6 Hz), 1.85-1.94 (1 H, m), 1.98-2.17 (3 H, m), 2.45 (1 H, ddd, J = 11.8, 5.4, 2.2 Hz), 2.67 (1 H, td, J = 12.2, 6.1 Hz), 2.79 (1 H, d, J = 13.7 Hz), 2.80-2.88 (1 H, m), 2.93 (1 H, ddd, J = 12.9, 9.2, 3.2 Hz), 3.70-3.80 (1 H, m), 3.81-3.95 (1 H, m), 4.28-4.37 (1 H, m), 4.73 (1 H, s), 5.19 (1 H, ddd, J = 12.0, 2.9, 2.0 Hz), 5.44-5.55 (1 H, m). ¹³C NMR (100 MHz, 75 °C, C₆D₆): δ = 23.6, 25.3, 27.6, 27.8, 28.3, 32.3, 36.0, 36.1, 40.9, 42.5, 47.7, 50.2, 57.3, 68.9, 79.6, 125.5, 133.3, 154.4, 172.8, 203.9. MS (EI): m/z calcd for C₂₂H₃₂N₂O₄ [M]: 388.2362; found [M⁺]: 388.2369. MS: m/z (%) = 388 (100), 332 (60), 244 (76).