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

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

doi:10.1021/acs.orglett.6b02416

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

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

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	4978-4981
Number of pages	4
Journal	Organic Letters
Volume	18
Issue number	19
DOIs	https://doi.org/10.1021/acs.orglett.6b02416
Publication status	Published - 7 Oct 2016

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title = "Exploring the Scope of Asymmetric Synthesis of β-Hydroxy-γ-lactams via Noyori-type Reductions",

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.",

author = "Denis Lynch and Deasy, \{Rebecca E.\} and Clarke, \{Leslie Ann\} and Slattery, \{Catherine N.\} and Khandavilli, \{U. B.Rao\} and Lawrence, \{Simon E.\} and Maguire, \{Anita R.\} and Magnus, \{Nicholas A.\} and Moynihan, \{Humphrey A.\}",

note = "Publisher Copyright: {\textcopyright} 2016 American Chemical Society.",

year = "2016",

month = oct,

day = "7",

doi = "10.1021/acs.orglett.6b02416",

language = "English",

volume = "18",

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publisher = "American Chemical Society",

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T1 - Exploring the Scope of Asymmetric Synthesis of β-Hydroxy-γ-lactams via Noyori-type Reductions

AU - Lynch, Denis

AU - Deasy, Rebecca E.

AU - Clarke, Leslie Ann

AU - Slattery, Catherine N.

AU - Khandavilli, U. B.Rao

AU - Lawrence, Simon E.

AU - Maguire, Anita R.

AU - Magnus, Nicholas A.

AU - Moynihan, Humphrey A.

PY - 2016/10/7

Y1 - 2016/10/7

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/84990930971

U2 - 10.1021/acs.orglett.6b02416

DO - 10.1021/acs.orglett.6b02416

M3 - Article

AN - SCOPUS:84990930971

SN - 1523-7060

VL - 18

SP - 4978

EP - 4981

JO - Organic Letters

JF - Organic Letters

IS - 19

ER -

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

Abstract

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