title: Development of a new and practical route to chiral 3,4-disubstituted cyclopentanones: asymmetric alkylation and intramolecular cyclopropanation as key C-C bond-forming steps.
abstract: An efficient and practical asymmetric synthesis of (+)-trans-3-hydroxymethyl-4-(3-fluorophenyl)cyclopentanone (1) is described. An asymmetric Mo-catalyzed alkylation reaction was used to establish the first stereocenter and a Cu-catalyzed intramolecular diastereoselective cyclopropanation reaction was used to set the second stereocenter. The last step involved a one-pot ring-opening/deprotection/hydrolysis/decarboxylation sequence that furnished the desired product in good yield.
authors.affiliation: Department of Process Research, Merck Research Laboratories, P.O. Box 2000, Rahway, New Jersey 07065-0900, USA. michael_palucki@merck.com
authors.forename: Michael
authors.initials: M
authors.lastname: Palucki
authors.forename: Joann M
authors.initials: JM
authors.lastname: Um
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Yasuda
authors.forename: David A
authors.initials: DA
authors.lastname: Conlon
authors.forename: Fuh-Rong
authors.initials: FR
authors.lastname: Tsay
authors.forename: Frederick W
authors.initials: FW
authors.lastname: Hartner
authors.forename: Yi
authors.initials: Y
authors.lastname: Hsiao
authors.forename: Benjamin
authors.initials: B
authors.lastname: Marcune
authors.forename: Sandor
authors.initials: S
authors.lastname: Karady
authors.forename: David L
authors.initials: DL
authors.lastname: Hughes
authors.forename: Peter G
authors.initials: PG
authors.lastname: Dormer
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Reider
mesh_terms: D003517:Cyclopentanes / Q000138:chemical synthesis* / Q000737:chemistry*; D003521:Cyclopropanes / Q000138:chemical synthesis / Q000737:chemistry*; D007202:Indicators and Reagents; D008968:Molecular Conformation; D013329:Structure-Activity Relationship
chemical_list: D003517:Cyclopentanes; D003521:Cyclopropanes; D007202:Indicators and Reagents; C007201:cyclopentanone