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RESEARCH PRODUCT
Desymmetrization of Prochiral Cyclobutanones via Nitrogen Insertion: A Concise Route to Chiral γ‐Lactams
Johannes M. WiestJohannes M. WiestChristian Mück-lichtenfeldMike OngJan SietmannConstantin G. Daniliucsubject
γ-lactamsChiral auxiliary010405 organic chemistryChemistryasymmetric synthesisEnantioselective synthesisCyclobutanoneGeneral Chemistry010402 general chemistryRing (chemistry)01 natural sciencesCombinatorial chemistryDesymmetrizationCatalysis0104 chemical sciencesStereocenterdesymmetrizationFormal synthesischemistry.chemical_compoundMoleculecyclobutanoneResearch ArticlesResearch ArticleAsymmetric Synthesis | Hot Paperdescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2021-01-14 | Angewandte Chemie International Edition |