title: Gram-scale enantioselective formal synthesis of morphine through an ortho-para oxidative phenolic coupling strategy.
abstract: A gram-scale catalytic enantioselective formal synthesis of morphine is described. The key steps of the synthesis involve an ortho-para oxidative phenolic coupling and a highly diastereoselective "desymmetrization" of the resulting cyclohexadienone that generates three of the four morphinan ring junction stereocenters in one step. The stereochemistry is controlled from a single carbinol center installed through catalytic enantioselective hydrogenation. These transformations enabled the preparation of large quantities of key intermediates and could support a practical and scalable synthesis of morphine and related derivatives.
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW (UK) http://www-gaunt.ch.cam.ac.uk/
authors.forename: Matthieu
authors.initials: M
authors.lastname: Tissot
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Phipps
authors.forename: Catherine
authors.initials: C
authors.lastname: Lucas
authors.forename: Rafael M
authors.initials: RM
authors.lastname: Leon
authors.forename: Robert D M
authors.initials: RD
authors.lastname: Pace
authors.forename: Tifelle
authors.initials: T
authors.lastname: Ngouansavanh
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Gaunt
mesh_terms: D000701:Analgesics, Opioid / Q000138:chemical synthesis*; D009020:Morphine / Q000138:chemical synthesis*; D058451:Oxidative Coupling; D010636:Phenols / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000701:Analgesics, Opioid; D010636:Phenols; D009020:Morphine
keywords: alkaloids; asymmetric synthesis; oxidative coupling; total synthesis