Display options
Cite
Lynch D, Deasy RE, Clarke LA, et al. Exploring the Scope of Asymmetric Synthesis of β-Hydroxy-γ-lactams via Noyori-type Reductions. Org Lett. 2016;18(19):4978-4981doi: 10.1021/acs.orglett.6b02416.
Lynch, D., Deasy, R. E., Clarke, L. A., Slattery, C. N., Khandavilli, U. B., 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(19), 4978-4981. https://doi.org/10.1021/acs.orglett.6b02416
Lynch, Denis, et al. "Exploring the Scope of Asymmetric Synthesis of β-Hydroxy-γ-lactams via Noyori-type Reductions." Organic letters vol. 18,19 (2016): 4978-4981. doi: https://doi.org/10.1021/acs.orglett.6b02416
Lynch D, Deasy RE, Clarke LA, Slattery CN, Khandavilli UB, Lawrence SE, Maguire AR, Magnus NA, Moynihan HA. Exploring the Scope of Asymmetric Synthesis of β-Hydroxy-γ-lactams via Noyori-type Reductions. Org Lett. 2016 Oct 07;18(19):4978-4981. doi: 10.1021/acs.orglett.6b02416. Epub 2016 Sep 22. PMID: 27656907.
Copy Download .nbib Format: NLM
Share it on

Org Lett. 2016 Oct 07;18(19):4978-4981. doi: 10.1021/acs.orglett.6b02416. Epub 2016 Sep 22.

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

Organic letters

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

Affiliations

  1. Department of Chemistry, Analytical and Biological Chemistry Research Facility, Synthesis and Solid State Pharmaceutical Centre, University College Cork , Cork, Ireland.
  2. Department of Chemistry and School of Pharmacy, Analytical and Biological Chemistry Research Facility, Synthesis and Solid State Pharmaceutical Centre, University College Cork , Cork, Ireland.
  3. Small Molecule Design and Development, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, United States.
  4. Eli Lilly SA, Dunderrow, Kinsale, County Cork, Ireland.

PMID: 27656907 DOI: 10.1021/acs.orglett.6b02416

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.

Publication Types