title: Nickel/bis(oxazoline)-catalyzed asymmetric Negishi arylations of racemic secondary benzylic electrophiles to generate enantioenriched 1,1-diarylalkanes.
abstract: A tertiary stereogenic center that bears two different aryl substituents is found in a variety of bioactive compounds, including medicines such as Zoloft and Detrol. We have developed an efficient method for the synthesis of enantioenriched 1,1-diarylalkanes from readily available racemic benzylic alcohols. Formation of a benzylic mesylate (which is not isolated), followed by treatment with an arylzinc reagent, LiI, and a chiral nickel/bis(oxazoline) catalyst, furnishes the Negishi cross-coupling product in high ee and good yield. A wide array of functional groups (e.g., an aryl iodide, a thiophene, and an N-Boc-indole) are compatible with the mild reaction conditions. This method has been applied to a gram-scale synthesis of a precursor to Zoloft.
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology , Pasadena, California 91125, United States.
authors.forename: Hien-Quang
authors.initials: HQ
authors.lastname: Do
authors.forename: E R R
authors.initials: ER
authors.lastname: Chandrashekar
authors.forename: Gregory C
authors.initials: GC
authors.lastname: Fu
mesh_terms: D000473:Alkanes / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D015394:Molecular Structure; D009532:Nickel / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry*; D010080:Oxazoles / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000473:Alkanes; D009942:Organometallic Compounds; D010080:Oxazoles; D009532:Nickel