期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 60, 期 17, 页码 9719-9723出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202100642
关键词
asymmetric synthesis; cyclobutanone; desymmetrization; γ -lactams
资金
- Westfalische Wilhelms-Universitat Munster
- Johannes Gutenberg-Universitat Mainz
- Fonds der Chemischen Industrie
- Projekt DEAL
Asymmetric access to gamma-lactams was achieved using (1S,2R)-1-amino-2-indanol for chiral induction, with downstream stereoinduction up to 88:12 dr. Mechanistic analysis revealed a Curtin-Hammett scenario, supported by spectroscopic, crystallographic, and computational studies. The method allows for the synthesis of optically pure gamma-lactams, including those with all-carbon quaternary stereocenters, and is exemplified by the formal synthesis of drug molecules baclofen, brivaracetam, and pregabalin.
Asymmetric access to gamma-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 gamma-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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据