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One‐Step Synthesis of 3,4‐Disubstituted 2‐Oxazolidinones by Base‐Catalyzed CO 2 Fixation and Aza‐Michael Addition
Author(s) -
Mannisto Jere K.,
Sahari Aleksi,
Lagerblom Kalle,
Niemi Teemu,
Nieger Martin,
Sztanó Gábor,
Repo Timo
Publication year - 2019
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201902451
Subject(s) - michael reaction , chemistry , intramolecular force , aniline , catalysis , amine gas treating , combinatorial chemistry , molecule , organic chemistry
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 CO 2 as a carbonyl source and 1,1,3,3‐tetramethylguanidine (TMG) as a catalyst. The modular reaction, which occurs between a γ‐brominated Michael acceptor, CO 2 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.