Exploring the Scope of Asymmetric Synthesis of β-Hydroxy-γ-lactams via Noyori-type Reductions
Denis Lynch1, Rebecca E Deasy1, Leslie-Ann Clarke1
1Department of Chemistry, Analytical and Biological Chemistry Research Facility, Synthesis and Solid State Pharmaceutical Centre, University College Cork , Cork, Ireland.
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.
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