title: Catalytic asymmetric synthesis of a tertiary benzylic carbon center via phenol-directed alkene hydrogenation.
abstract: An expeditious synthetic approach to chiral phenol 1, a key building block in the preparation of a series of drug candidates, is reported. The strategy includes a cost-effective and readily scalable route to cyclopentanone 3 from isobutyronitrile (10). The sterically hindered and enolizable ketone 3 was subsequently employed in a challenging Grignard addition mediated by LaCl(3)·2LiCl. A novel preparation of the lanthanide reagent required for this transformation is described. To complete the process, a highly enantioselective hydrogenation step afforded the target (1). The importance of the phenol group to the success of this asymmetric transformation is discussed.
authors.affiliation: Chemical Process R&D, Amgen Inc., One Amgen Center Drive, Thousand Oaks, California 91320, United States. scaille@amgen.com
authors.forename: Seb
authors.initials: S
authors.lastname: Caille
authors.forename: Rich
authors.initials: R
authors.lastname: Crockett
authors.forename: Krishnakumar
authors.initials: K
authors.lastname: Ranganathan
authors.forename: Xiang
authors.initials: X
authors.lastname: Wang
authors.forename: Jacqueline C S
authors.initials: JC
authors.lastname: Woo
authors.forename: Shawn D
authors.initials: SD
authors.lastname: Walker
mesh_terms: D000475:Alkenes / Q000737:chemistry*; D002384:Catalysis; D006865:Hydrogenation; D015394:Molecular Structure; D010636:Phenols / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000475:Alkenes; D010636:Phenols