Total Synthesis of Macrocarpines D and E via an Enolate-Driven Copper-Mediated Cross-Coupling Process: Replacement of Catalytic Palladium with Copper Iodide

An
enolate driven copper-mediated cross-coupling process enabled
cheaper and greener access to the key pentacyclic intermediates required
for the enantiospecific total synthesis of a number of C-19 methyl
substituted sarpagine/macroline indole alkaloids. Replacement of palladium
(60–68%) with copper iodide (82–89%) resulted in much
higher yields. The formation of an unusual 7-membered cross-coupling
product was completely inhibited by using TEMPO as a radical scavenger.
Further functionalization led to the first enantiospecific total synthesis
of macrocarpines D and E.