Collective Total Synthesis of Mavacuran Alkaloids through Intermolecular 1,4‐Addition of an Organolithium Reagent.

We report a synthetic endeavor towards the highly strained pentacyclic caged framework of the mavacuran alkaloids which culminated with the concise total synthesis of C-fluorocurine, C-profluorocurine, C-mavacurine, normavacurine, 16-epi-pleiocarpamine and taberdivarine H. We designed an original strategy which involves a late stage construction of the D ring via a Michael addition of a vinylic nucleophile to a 2-indolyl acrylate moiety. While the intramolecular Michael addition did not succeed, we were able to perform a diastereoselective unusual intermolecular 1,4-addition of a functionalized vinyl lithium reagent onto a readily accessible Michael acceptor via the assistance of the piperiridine nitrogen through the formation of a complex as suggested by DFT computations. Final cyclization was achieved via nucleophilic substitution into an ammonium intermediate. The first total syntheses of C-profluorocurine and C-fluorocurine were finalized via respectively the dihydroxylation of C-mavacurine and a pinacol rearrangement.