Total Synthesis of the Isoketal 5-D2-IsoK Natural Product Based on Organocatalysis

Abstract

The enantioselective total synthesis of the highly reactive isoketal 5-D2-IsoK was accomplished. The synthesis involved construction of the isoketal core by an organocatalyzed Michael addition between ideally functionalized aldehyde and nitroolefin partners with good enantioselectivity. The lateral chains were branched through Horner–Wadsworth-Emmons and Wittig olefinations to provide flexibility, whereas the final deprotection and oxidation steps were performed under mild conditions to avoid known racemization and/or degradation of the very sensitive isoketal.