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Authors: Sietmann, Jan
Ong, Mike
Mück-Lichtenfeld, Christian
Daniliuc, Constantin G.
Wahl, Johannes M.
Title: Desymmetrization of prochiral cyclobutanones via nitrogen insertion : a concise route to chiral γ-lactams
Online publication date: 17-Nov-2022
Year of first publication: 2021
Language: english
Abstract: Asymmetric access to γ-lactams is achieved via a cyclobutanone ring expansion using widely available (1S,2R)-1-amino-2-indanol for chiral induction. Mechanistic analysis of the key N,O-ketal rearrangement reveals a Curtin–Hammett scenario, which enables a downstream stereoinduction (up to 88:12 dr) and is corroborated by spectroscopic, crystallographic, and computational studies. In combination with an easy deprotection protocol, this operationally simple sequence allows the synthesis of a range of optically pure γ-lactams, including those bearing all-carbon quaternary stereocenters. In addition, the formal synthesis of drug molecules baclofen, brivaracetam, and pregabalin further demonstrates the synthetic utility and highlights the general applicability of the presented method.
DDC: 540 Chemie
540 Chemistry and allied sciences
Institution: Johannes Gutenberg-Universität Mainz
Department: FB 09 Chemie, Pharmazie u. Geowissensch.
Place: Mainz
Version: Published version
Publication type: Zeitschriftenaufsatz
License: CC BY
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Journal: Angewandte Chemie : International edition
Pages or article number: 9719
Publisher: Wiley-VCH
Publisher place: Weinheim
Issue date: 2021
ISSN: 1521-3773
Publisher DOI: 10.1002/anie.202100642
Appears in collections:JGU-Publikationen

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