One‐Step Synthesis of 3,4‐Disubstituted 2‐Oxazolidinones by Base‐Catalyzed CO2 Fixation and Aza‐Michael Addition
| Autor: | Kalle Lagerblom, Jere K. Mannisto, Aleksi Sahari, Teemu Niemi, Martin Nieger, Timo Repo, Gábor Sztanó |
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| Přispěvatelé: | Department, Department of Chemistry, Timo Repo / Principal Investigator |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
cyclization
GUANIDINE 116 Chemical sciences 010402 general chemistry 01 natural sciences Catalysis ADDUCT Adduct CHEMICAL FIXATION chemistry.chemical_compound CARBON-DIOXIDE Aniline carbon dioxide fixation DESIGN Michael addition ANTIBACTERIAL organocatalysis OPTIMIZATION Phenylhydrazine heterocycles 010405 organic chemistry Organic Chemistry General Chemistry Combinatorial chemistry 0104 chemical sciences chemistry Carboxylation Intramolecular force Organocatalysis DISCOVERY Michael reaction OXAZOLIDINONES INHIBITORS |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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