Acid-Catalyzed Reaction of (4,4-Diethoxybutyl)ureas with Phenols as a Novel Approach to the Synthesis of α-Arylpyrrolidines

Abstract

1-(4,4-Diethoxybutyl)-3-alkylureas undergo intramolecular cyclization in the presence of trifluoroacetic acid and various phenols, leading to the new N-alkyl-2-arylpyrrolidine-1-carboxamides with moderate to excellent yields. It was found that these compounds undergo spontaneous solid-phase epimerization at room temperature. Advantages of the proposed approach are mild reaction conditions and no need for expensive reagents or catalysts.

GRAPHICAL ABSTRACT

Keywords:

• 2-Arylpyrrolidine
• cyclization
• electrophilic aromatic substitution
• phenols
• ureas

SUPPORTING INFORMATION

Full experimental procedures, characterization data, and copies of NMR spectra for all synthesized compounds can be accessed on the publisher’s website. Crystallographic data (excluding structure factors) for the structures in this article have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication no. CCDC 1031375-1031376. Copies of the data can be obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK, (fax: [phone] or e-mail: [email protected]).