Exploring the scope of asymmetric synthesis of β-Hydroxy-γ-lactams via Noyori-type reductions

Thumbnail Image
acs.orglett.6b02416.pdf(236.23 KB)
Accepted Version
Lynch, Denis
Deasy, Rebecca E.
Clarke, Leslie-Ann
Slattery, Catherine N.
Khandavilli, Udaya Bhaskara Rao
Lawrence, Simon E.
Maguire, Anita R.
Magnus, Nicholas A.
Moynihan, Humphrey A.
Journal Title
Journal ISSN
Volume Title
American Chemical Society
Research Projects
Organizational Units
Journal Issue
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.
Serotonin , Acid , Beta-branching
Lynch, D., Deasy, R. E., Clarke, L.-A., Slattery, C. N., Khandavilli, U. B. R., Lawrence, S. E., Maguire, A. R., Magnus, N. A. & Moynihan, H. A. (2016) ‘Exploring the scope of asymmetric synthesis of β-Hydroxy-γ-lactams via Noyori-type reductions, Organic Letters, 18, 4978-4981. doi: 10.1021/acs.orglett.6b02416
© 2016 American Chemical Society. This document is the Accepted Manuscript version of a Published Work that appeared in final form in Organic Letters, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://pubs.acs.org/doi/abs/10.1021/acs.orglett.6b02416