title: Synthesis of (-)-morphine: application of sequential Claisen/Claisen rearrangement of an allylic vicinal diol.
abstract: A detailed exploration of the synthesis of (-)-morphine based on sequential [3,3]-sigmatropic rearrangements is described. The sequential Claisen/Claisen rearrangements of an allylic vicinal diol resulted in the stereoselective formation of the two contiguous carbon centers, including a sterically encumbered quaternary carbon, in a single operation. The two ethyl esters generated in this reaction were successfully differentiated during a subsequent Friedel-Crafts-type cyclization. The (-)-morphine double bond was introduced at a late stage in our first-generation synthesis, but was formed at an earlier stage in the second-generation synthesis, resulting in a more efficient route to the end product.
authors.affiliation: Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1, Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Ichiki
authors.forename: Hiroki
authors.initials: H
authors.lastname: Tanimoto
authors.forename: Shohei
authors.initials: S
authors.lastname: Miwa
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Saito
authors.forename: Takaaki
authors.initials: T
authors.lastname: Sato
authors.forename: Noritaka
authors.initials: N
authors.lastname: Chida
mesh_terms: D000438:Alcohols / Q000737:chemistry*; D000498:Allyl Compounds / Q000737:chemistry*; D015394:Molecular Structure; D009020:Morphine / Q000138:chemical synthesis* / Q000737:chemistry; D020005:Propanols / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000438:Alcohols; D000498:Allyl Compounds; D020005:Propanols; C006463:allyl alcohol; D009020:Morphine