Synthesis of (R)-(-)-phoracantholide I based on stereocontrolled cleavage of internal acetal

Article abstract of DOI:10.1016/S0040-4020(01)89442-4

Oxidation of (S)-2-butenyl-2-ethoxycarbonylcyclohexanone (6) with MCPBA afforded directly two chiral internal acetals, 1S,6S,9R-(8) and 1R,6S,9S-(9), instead of the epoxide. By treatment with BF₃ etherate, the tertiary alcohol (12) obtained from 9 yielded an unexpected product (14) via the retro-aldol reaction and reconstruction of the internal acetal, and the expected fragmentation product (3) was not obtained. The mesylate of secondary alcohol (15b) prepared from 9 underwent silica-gel catalyzed, facile ring cleavage in a stereocontrolled fashion to afford the ring-enlarged 9-nonanolide derivatives (18). This methodology was applied for the synthesis of (R)-(-)-phoracantholide I. Examination using the Dreiding stereomodel provides a rationalized explanation for the stereocontrolled cleavage.