One‐Step Synthesis of 3,4‐Disubstituted 2‐Oxazolidinones by Base‐Catalyzed CO2 Fixation and Aza‐Michael Addition

2-Oxazolidinones are saturated heterocyclic compounds, which are highly attractive targets in modern drug design. Herein, we describe a new, single-step approach to 3,4-disubstituted 2-oxazolidinones by aza-Michael addition using CO2 as a carbonyl source and 1,1,3,3-tetramethylguanidine (TMG) as a c...

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Bibliographic Details
Main Authors: Mannisto, Jere K., Sahari, Aleksi, Lagerblom, Kalle, Niemi, Teemu, Nieger, Martin, Sztanó, Gábor, Repo, Timo
Other Authors: Department, Department of Chemistry, Timo Repo / Principal Investigator
Format: Article in Journal/Newspaper
Language:English
Published: Wiley-VCH 2021
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Online Access:http://hdl.handle.net/10138/324827
Description
Summary:2-Oxazolidinones are saturated heterocyclic compounds, which are highly attractive targets in modern drug design. Herein, we describe a new, single-step approach to 3,4-disubstituted 2-oxazolidinones by aza-Michael addition using CO2 as a carbonyl source and 1,1,3,3-tetramethylguanidine (TMG) as a catalyst. The modular reaction, which occurs between a gamma-brominated Michael acceptor, CO2 and an arylamine, aliphatic amine or phenylhydrazine, is performed under mild conditions. The regiospecific reaction displays good yields (av. 75 %) and excellent functional-group compatibility. In addition, late-stage functionalization of drug and drug-like molecules is demonstrated. The experimental results suggest a mechanism consisting of several elementary steps: TMG-assisted carboxylation of aniline; generation of an O-alkyl carbamate; and the final ring-forming step through an intramolecular aza-Michael addition. Peer reviewed