Triflic acid-promoted post-Ugi condensation for the assembly of 2,6-diarylmorpholin-3-ones
Niyaz Amire1, Kamila M Almagambetova1, Assel Turlykul1
1Department of Chemistry, School of Sciences and Humanities, Nazarbayev University, Astana, 010000, Kazakhstan. vsevolod.peshkov@nu.edu.kz.
Abstract:
We report a two-step one-pot synthesis of the 2,6-diarylmorpholin-3-one core based on the Ugi reaction of 2-oxoaldehyde with 2-hydroxycarboxylic acid, a primary amine and tert-butyl isocyanide followed by a triflic acid-promoted intramolecular condensation accompanied by the loss of the isocyanide-originated amide moiety. The overall transformation proceeds with complete retention of stereoconfiguration at the 2-hydroxycarboxylic acid-derived chiral center, allowing the target morpholin-3-ones to be obtained in an enantiopure form. Subsequent double bond hydrogenation and amide reduction allow the degree of unsaturation to be reduced, providing a convenient entry to the cis-2,6-diphenylmorpholine motif.
Related Concept Videos
Cycloaddition Reactions: MO Requirements for Thermal Activation
Preparation of 1° Amines: Hofmann and Curtius Rearrangement Overview
Cycloaddition Reactions: Overview
Cyclohexenones via Michael Addition and Aldol Condensation: The Robinson Annulation
Aldol Condensation with β-Diesters: Knoevenagel Condensation
Preparation of 1° Amines: Hofmann and Curtius Rearrangement Mechanism


