title: Total Synthesis and Stereochemical Revision of Phacelocarpus 2-Pyrone A.
abstract: The first total synthesis of phacelocarpus 2-pyrone A is reported. The original natural compound was tentatively assigned (by NMR spectroscopy) as containing two cis-alkenes and a trans-vinyl ether connected to a 2-pyrone ring motif. Our computational predictions indicated that a cis-vinyl ether motif was equally feasible. Attempts to prepare the trans-vinyl ether were met with no success. The all cis-target compound was synthesised in nine steps, employing key regio- and stereoselective reactions including Au(I)-catalysed vinyl etherification, Wittig alkenylation and end-game Stille macrocyclisation. Analysis of the NMR data enabled identification and confirmation of the correct structure of phacelocarpus 2-pyrone A, containing a cis-vinyl ether. Our studies pave the way for future development of methodologies to these structurally distinct pyrone skipped-polyenyne natural products.
authors.affiliation: Department of Chemistry, University of York, York, YO10 5DD (UK).
authors.forename: Thomas O
authors.initials: TO
authors.lastname: Ronson
authors.affiliation: Department of Chemistry, University of York, York, YO10 5DD (UK).
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Burns
authors.affiliation: Department of Chemistry, University of York, York, YO10 5DD (UK).
authors.forename: Martin H H
authors.initials: MH
authors.lastname: Voelkel
authors.affiliation: Department of Chemistry, University of York, York, YO10 5DD (UK).
authors.forename: Kieren J
authors.initials: KJ
authors.lastname: Evans
authors.affiliation: Department of Chemistry, University of York, York, YO10 5DD (UK).
authors.forename: Jason M
authors.initials: JM
authors.lastname: Lynam
authors.affiliation: Department of Chemistry, University of York, York, YO10 5DD (UK). richard.taylor@york.ac.uk.
authors.forename: Richard J K
authors.initials: RJ
authors.lastname: Taylor
authors.affiliation: Department of Chemistry, University of York, York, YO10 5DD (UK). ian.fairlamb@york.ac.uk.
authors.forename: Ian J S
authors.initials: IJ
authors.lastname: Fairlamb
keywords: dienes; macrocycles; natural products; palladium; total synthesis