Biomimetically Inspired, One-Step Synthesis of Exotine A and Exotine B

The one-step syntheses of exotine A and exotine B, which comprise the unusual coumarin-cyclohepta[b]indole ring system, have been achieved via the biomimetically inspired combination of indole, prenal, and either trans-dehydroosthol or gleinadiene. This facile three-component reaction delivered a mixture (17:1) of exotine A and 11'-epi-exotine A in a 43% yield from trans-dehydroosthol and a mixture (4:1) of exotine B and 11'-epi-exotine B in a 50% yield from gleinadiene. Some mechanistic aspects of this process were explored, and spectral evidence for 3,3'-spiroindolenine intermediates was obtained. Moreover, a skeletal isomer of exotine A that likely originates from a 1,2-alkyl rearrangement of a protonated 3,3'-spiroindolenine was isolated and characterized by X-ray crystallography. These findings not only provide experimental support for Jiang's proposed biosynthesis of exotine A and exotine B but also foreshadow the existence of other exotine-derived natural products having isomeric frameworks. Exploratory attempts to induce an enantioselective 3CR using a chiral phosphoric acid were unsuccessful.