Enynones in organic synthesis. 6. Synthesis of spirocyclic methylenecyclopentenones and analogs of the methylenomycin class of antibiotics. Mechanism of phenol catalysis

Article abstract of DOI:10.1021/jo00097a035

Spirocyclic methylenecyclopentenones of general structure 18 were prepared in a single step from bis-acetylenic alcohols 29 by a process involving initial oxy-Cope rearrangement to afford (Z)-enynones 36-Z followed by electrocyclic ring closure. Mechanistic studies indicate that the initial step leading from 30-Z to 18 is a thermal 1,5-prototropic shift to afford dienols which can cyclize by a symmetry-allowed (π⁴s ± σ²s ± π²a) process. This last step is catalyzed by certain phenols having low oxidation potentials, most likely by a mechanism involving single electron transfer. Dramatic rate enhancements were also observed for the cyclization of simple enynones 37 to methylenecyclopentenones 39 upon catalysis with either α-tocopherol (vitamin E, 40) or tert-butylcatechol (41). Further enhancements in both rate and yield were obtained under conditions of photoassisted single electron transfer (PET), which afforded 39 in yields of 80-98%.