title: Regioselectivity of the Claisen rearrangement in meta-allyloxy aryl ketones: an experimental and computational study, and application in the synthesis of (R)-(-)-pestalotheol D.
abstract: A study of the regioselectivity of the Claisen rearrangement of meta-allyloxy aryl ketones showed that the electron-withdrawing carbonyl group has a major influence and strongly directs rearrangement to the more hindered ortho position. However, when the ketone is part of a ring structure, its electronic effect can be negated by conversion into its triisopropylsilyl enol ether, which dramatically reverses the regiochemistry of the Claisen rearrangement. DFT calculations suggest that the effect is electronic although there is also a steric effect of the bulky silyl group. This strategy for influencing the regiochemical outcome of the Claisen rearrangement was then employed in a short synthesis of the furo[2,3-g]chromene, (-)-pestalotheol D, that confirms the absolute stereochemistry of the natural product.
authors.affiliation: School of Chemistry, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Lucas
authors.forename: Barry
authors.initials: B
authors.lastname: Lygo
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Blake
authors.forename: William
authors.initials: W
authors.lastname: Lewis
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Moody
mesh_terms: D001578:Benzopyrans / Q000138:chemical synthesis* / Q000737:chemistry; D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry; D020650:Combinatorial Chemistry Techniques; D018360:Crystallography, X-Ray; D007659:Ketones / Q000737:chemistry*; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D013237:Stereoisomerism
chemical_list: D001578:Benzopyrans; D001688:Biological Products; D007659:Ketones; C556566:pestalotheol D