Lynch, D,Deasy, RE,Clarke, LA,Slattery, CN,Khandavilli, UBR,Lawrence, SE,Maguire, AR,Magnus, NA,Moynihan, HA

2016

October

Organic letters

Exploring the Scope of Asymmetric Synthesis of beta-Hydroxy-gamma-lactams via Noyori-type Reductions

Validated

WOS: 6 ()

SEROTONIN ACID

18

4978

4981

Enantio- and diastereoselective hydrogenation of beta-keto-gamma-lactams with a ruthenium-BINAP catalyst, involving dynamic kinetic resolution, has been employed to provide a general, asymmetric approach to beta-hydroxy-gamma-lactams, a structural motif common to several bioactive compounds. Full conversion to the desired beta-hydroxy-gamma-lactams was achieved with high diastereoselectivity (up to >98% de) by addition of catalytic HCl and LiCl, while beta-branching of the ketone substituent demonstrated a pronounced effect on the modest to excellent enantioselectivity (up to 97% ee) obtained.

10.1021/acs.orglett.6b02416