title: Exploring the Scope of Asymmetric Synthesis of β-Hydroxy-γ-lactams via Noyori-type Reductions.
abstract: Enantio- and diastereoselective hydrogenation of β-keto-γ-lactams with a ruthenium-BINAP catalyst, involving dynamic kinetic resolution, has been employed to provide a general, asymmetric approach to β-hydroxy-γ-lactams, a structural motif common to several bioactive compounds. Full conversion to the desired β-hydroxy-γ-lactams was achieved with high diastereoselectivity (up to >98% de) by addition of catalytic HCl and LiCl, while β-branching of the ketone substituent demonstrated a pronounced effect on the modest to excellent enantioselectivity (up to 97% ee) obtained.
authors.affiliation: Department of Chemistry, Analytical and Biological Chemistry Research Facility, Synthesis and Solid State Pharmaceutical Centre, University College Cork , Cork, Ireland.
authors.forename: Denis
authors.initials: D
authors.lastname: Lynch
authors.affiliation: Department of Chemistry, Analytical and Biological Chemistry Research Facility, Synthesis and Solid State Pharmaceutical Centre, University College Cork , Cork, Ireland.
authors.forename: Rebecca E
authors.initials: RE
authors.lastname: Deasy
authors.affiliation: Department of Chemistry, Analytical and Biological Chemistry Research Facility, Synthesis and Solid State Pharmaceutical Centre, University College Cork , Cork, Ireland.
authors.forename: Leslie-Ann
authors.initials: LA
authors.lastname: Clarke
authors.affiliation: Department of Chemistry, Analytical and Biological Chemistry Research Facility, Synthesis and Solid State Pharmaceutical Centre, University College Cork , Cork, Ireland.
authors.forename: Catherine N
authors.initials: CN
authors.lastname: Slattery
authors.affiliation: Department of Chemistry, Analytical and Biological Chemistry Research Facility, Synthesis and Solid State Pharmaceutical Centre, University College Cork , Cork, Ireland.
authors.forename: U B Rao
authors.initials: UB
authors.lastname: Khandavilli
authors.affiliation: Department of Chemistry, Analytical and Biological Chemistry Research Facility, Synthesis and Solid State Pharmaceutical Centre, University College Cork , Cork, Ireland.
authors.forename: Simon E
authors.initials: SE
authors.lastname: Lawrence
authors.affiliation: Department of Chemistry and School of Pharmacy, Analytical and Biological Chemistry Research Facility, Synthesis and Solid State Pharmaceutical Centre, University College Cork , Cork, Ireland.
authors.forename: Anita R
authors.initials: AR
authors.lastname: Maguire
authors.affiliation: Small Molecule Design and Development, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, United States.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Magnus
authors.affiliation: Eli Lilly SA, Dunderrow, Kinsale, County Cork, Ireland.
authors.forename: Humphrey A
authors.initials: HA
authors.lastname: Moynihan