Total Synthesis of (-)-Melanthioidine by Copper-Mediated Cyclodimerization

Article abstract of DOI:10.1021/acs.orglett.6b01496

An efficient asymmetric total synthesis of the dimeric macrocyclic diaryl ether phenethyltetrahydroisoquinoline alkaloid (-)-melanthiodine is reported. Key steps of the synthesis include an efficient Noyori asymmetric transfer hydrogenation to access the enantioenriched phenethyltetrahydroisoquinoline monomeric subunit and a copper-mediated cyclodimerization to form the two diaryl ether linkages with concomitant macrocyclization.