title: Short chemoenzymatic total synthesis of ent-hydromorphone: an oxidative dearomatization/intramolecular [4+2] cycloaddition/amination sequence.
abstract: A short synthesis of ent-hydromorphone has been achieved in twelve steps from β-bromoethylbenzene. The key transformations involved the enzymatic dihydroxylation of the arene to the corresponding cis-dihydrodiol, Mitsunobu coupling with the ring A fragment, oxidative dearomatization of the C3 phenol, and the subsequent [4+2] cycloaddition to form ring B of the morphinan. The synthesis was completed by intramolecular amination at C9.
authors.affiliation: Department of Chemistry and Centre for Biotechnology, Brock University, St. Catharines, ON L2S 3A1 (Canada).
authors.forename: Vimal
authors.initials: V
authors.lastname: Varghese
authors.forename: Tomas
authors.initials: T
authors.lastname: Hudlicky
mesh_terms: D000586:Amination; D000701:Analgesics, Opioid / Q000138:chemical synthesis*; D003500:Cyclization; D061565:Cycloaddition Reaction; D049308:Dioxygenases / Q000378:metabolism*; D004091:Hydromorphone / Q000138:chemical synthesis*; D015394:Molecular Structure; D010084:Oxidation-Reduction; D013237:Stereoisomerism
chemical_list: D000701:Analgesics, Opioid; D049308:Dioxygenases; D004091:Hydromorphone
keywords: alkaloids; cycloaddition; natural products; oxidation; total synthesis