title: An efficient asymmetric synthesis of an estrogen receptor modulator by sulfoxide-directed borane reduction.
abstract: An efficient asymmetric synthesis of a selective estrogen receptor modulator (SERM) that has a dihydrobenzoxathiin core structure bearing two stereogenic centers is reported. The stereogenic centers were established by an unprecedented chiral sulfoxide-directed stereospecific reduction of an alpha,beta-unsaturated sulfoxide to the saturated sulfide in one step. Studies to elucidate the mechanism for this reduction are reported. Highly efficient Cu(I)-mediated ether formation was used to install the ether side chain, and selective debenzylation conditions were developed to remove the benzyl protecting groups on the phenols.
authors.affiliation: Department of Process Research, Merck Research Laboratories, P.O. Box 2000, Rahway, NJ 07065, USA. zhiguo_song@merck.com
authors.forename: Zhiguo J
authors.initials: ZJ
authors.lastname: Song
authors.forename: Anthony O
authors.initials: AO
authors.lastname: King
authors.forename: Marjorie S
authors.initials: MS
authors.lastname: Waters
authors.forename: Fengrui
authors.initials: F
authors.lastname: Lang
authors.forename: Daniel
authors.initials: D
authors.lastname: Zewge
authors.forename: Matthew
authors.initials: M
authors.lastname: Bio
authors.forename: Johnnie L
authors.initials: JL
authors.lastname: Leazer
authors.forename: Gary
authors.initials: G
authors.lastname: Javadi
authors.forename: Amude
authors.initials: A
authors.lastname: Kassim
authors.forename: David M
authors.initials: DM
authors.lastname: Tschaen
authors.forename: Robert A
authors.initials: RA
authors.lastname: Reamer
authors.forename: Thorsten
authors.initials: T
authors.lastname: Rosner
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Chilenski
authors.forename: David J
authors.initials: DJ
authors.lastname: Mathre
authors.forename: R P
authors.initials: RP
authors.lastname: Volante
authors.forename: Richard
authors.initials: R
authors.lastname: Tillyer
mesh_terms: D001880:Boranes / Q000737:chemistry*; D020847:Estrogen Receptor Modulators / Q000138:chemical synthesis*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010084:Oxidation-Reduction; D012451:Safrole / Q000031:analogs & derivatives* / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D001880:Boranes; D020847:Estrogen Receptor Modulators; D012451:Safrole; C005746:sulfoxide