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 α-alkylidene β-keto-δ-lactones. Other progress toward a synthesis of FR182877 includes a π-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.