Exploring the Scope of Asymmetric Synthesis of β‑Hydroxy-γ-lactams
via Noyori-type Reductions

Lynch, Denis; Deasy, Rebecca
E.; Clarke, Leslie-Ann; Slattery, Catherine N.; B. Rao Khandavilli, U.; Lawrence, Simon E.; Maguire, Anita R.; Magnus, Nicholas A.; Moynihan, Humphrey A.

doi:10.1021/acs.orglett.6b02416.s003

ol6b02416_si_003.pdf (3.16 MB)

Exploring the Scope of Asymmetric Synthesis of β‑Hydroxy-γ-lactams via Noyori-type Reductions

journal contribution

posted on 2016-09-22, 00:00 authored by Denis Lynch, Rebecca E. Deasy, Leslie-Ann Clarke, Catherine N. Slattery, U. B. Rao Khandavilli, Simon E. Lawrence, Anita R. Maguire, Nicholas A. Magnus, Humphrey A. Moynihan

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.