Directed Heterodimerization: Total Synthesis of (–)-Folicangine, (–)-Voafolidine, (–)-Isovoafolidine, and (–)-Tabernaesine B

We report the first total synthesis of heterodimeric aspidosperma–aspidosperma alkaloids (–)-folicangine, (–)voafolidine, (–)-isovoafolidine and (–)-tabernaesine B. Our biosynthesis-inspired stereoselective directed union of complex fragments derived from (–)-mehranine (northern half) and (–)-deoxoapodine (southern half) provided a methylene-bridged heterodimer, serving as a key precursor to these structurally related bisindole alkaloids. Methylenation of this versatile heterodimeric intermediate resulted in a stereodivergent ring closure to give (–)-tabernaesine B alongside its C7 diastereomer, enabling our stereochemical revision of this alkaloid. The corresponding C2'-hemiaminal alkaloids (–)-voafolidine and (–)-isovoafolidine were obtained via an analogous spirocyclization-reduction sequence from a hydrated derivative of the methylene-bridged heterodimeric precursor. Our biosynthesisinspired heterodimerization strategy allowed for the assembly of the intricate double hemiaminal alkaloid (–)-folicangine via C8iminium ion capture by the C2'-hemiaminal of an intermediate en route to (–)-isovoafolidine.