Total Synthesis of (−)-Herbindoles A, B, and C and (+)-<i>trans</i>-Herbindole A via a Convergent Benzannulation Strategy

The herbindoles are cyclopent[<i>g</i>]indole alkaloids whose structures incorporate a fully substituted benzenoid ring and, as such, have served as useful platforms for the testing and refinement of methods for the construction of highly substituted indoles. Herein we report efficient and convergent total syntheses of four herbindole alkaloids, including the first enantioselective total synthesis of <i>trans</i>-(+)-herbindole A. The pivotal step in the synthetic strategy is the application of our vinylketene-based benzannulation in which a thermal Wolff rearrangement generates a vinylketene which combines with an ynamide derivative in the first step of a pericyclic cascade that produces a highly substituted aniline intermediate primed for cyclization to form the cyclopent[<i>g</i>]indole ring system. Subsequent cross-coupling reactions allow for the elaboration of a common precursor to herbindoles of the A, B, and C series.