title: Dyotropic rearrangements of fused tricyclic β-lactones: application to the synthesis of (-)-curcumanolide A and (-)-curcumalactone.
abstract: Dyotropic rearrangements of fused, tricyclic β-lactones are described that proceed via unprecedented stereospecific, 1,2-acyl migrations delivering bridged, spiro-γ-butyrolactones. A unique example of this dyotropic process involves a fused bis-lactone possessing both β- and δ-lactone moieties which enabled rapid access to the core structures of curcumanolide A and curcumalactone. Our current mechanistic understanding of the latter dyotropic process, based on computational studies, is also described. Other key transformations in the described divergent syntheses of (-)-curcumanolide A and (-)-curcumalactone from a common intermediate (11 and 12 steps from 2-methyl-1,3-cyclopentanedione, respectively), include a catalytic, asymmetric nucleophile (Lewis base)-catalyzed aldol-lactonization (NCAL) leading to a tricyclic β-lactone, a Baeyer-Villiger oxidation in the presence of a β-lactone, and highly facial-selective and stereocomplementary reductions of an intermediate spirocyclic enoate. The described dyotropic rearrangements significantly alter the topology of the starting tricyclic β-lactone, providing access to complex spirocyclic cyclopentyl-γ-lactones and bis-γ-lactones in a single synthetic operation.
authors.affiliation: Department of Chemistry, Texas A&M University, P.O. Box 30012, College Station, Texas 77842-3012, USA.
authors.forename: Carolyn A
authors.initials: CA
authors.lastname: Leverett
authors.forename: Vikram C
authors.initials: VC
authors.lastname: Purohit
authors.forename: Alex G
authors.initials: AG
authors.lastname: Johnson
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Davis
authors.forename: Dean J
authors.initials: DJ
authors.lastname: Tantillo
authors.forename: Daniel
authors.initials: D
authors.lastname: Romo
mesh_terms: D003500:Cyclization; D007783:Lactones / Q000737:chemistry*; D015394:Molecular Structure; D012717:Sesquiterpenes / Q000737:chemistry*
chemical_list: D007783:Lactones; D012717:Sesquiterpenes; C577164:curcumalactone; C577163:curcumanolide A