Intramolecular allenolate acylations in studies toward a synthesis of FR182877.

During our efforts to synthesize the cytotoxic natural product FR182877, we discovered intramolecular reductive acylations that offer a stereocontrolled alternative to the classical Knoevenagel condensation for the formation of alpha-alkylidene beta-keto-delta-lactones. Other progress toward a synthesis of FR182877 includes a pi-allyl Stille coupling and a bromo Horner-Wadsworth-Emmons reaction that forms a 12-membered ring. Structural relationships among FR182877, hexacyclinic acid, macquarimicin A, and cochleamycin A are also discussed. [reaction: see text]