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
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-8155
Version:	Published version
Publication type:	Zeitschriftenaufsatz
License:	CC BY
Information on rights of use:	https://creativecommons.org/licenses/by/4.0/
Journal:	Angewandte Chemie : International edition 60 17
Pages or article number:	9719 9723
Publisher:	Wiley-VCH
Publisher place:	Weinheim
Issue date:	2021
ISSN:	1521-3773
Publisher DOI:	10.1002/anie.202100642
Appears in collections:	JGU-Publikationen