Stereo- and Chemoselective Enrichment of sp3 Character in Post-Ugi Morpholines


Hasan M. Nuroldayeva G.A. Begenov A. Peshkov A.A. Martynova S.D. Amire N. Bekbolatova A. Makhmet A.M. Yu J. Zaman M. Gong J. Lim C.-K. Belyaev A. Pereshivko O.P. Wang S. Peshkov V.A.
24 January 2025John Wiley and Sons Inc

European Journal of Organic Chemistry
2025#28Issue 4

We conducted a systematic study on synthesis and modification of morpholine core using Ugi adducts derived from propiolic acid and glycolaldehyde dimer. The assembly step involved triphenylphosphine-promoted 6-exo-dig umpolung oxa-Michael cyclization of Ugi-derived hydroxypropargylamides yielding 2-methylenemorpholin-3-one derivatives. Subsequent heterogeneous catalytic hydrogenation of the exocyclic double bond proceeded in a highly diastereoselective fashion establishing a relative cis configuration in the resulting sp3-enriched morpholinone scaffold. Finally, chemoselective amide reduction with lithium aluminum hydride (LAH) allowed to obtain fully saturated morpholines while leaving the more sterically hindered exocyclic amide moiety intact. Taken together these findings outline the strategy for controlled reduction of the inherent rigidity of post-Ugi scaffolds.

chemoselectivity , diastereoselectivity , morpholines , post-Ugi transformations , sp3-enriched heterocycles

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College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Dushu Lake Campus, Suzhou, 215123, China
Department of Chemistry, School of Sciences and Humanities, Nazarbayev University, Astana, 010000, Kazakhstan
Department of Chemistry, Faculty of Natural Sciences, L. N. Gumilyov Eurasian National University, Astana, 010000, Kazakhstan
Department of Chemical and Materials Engineering, School of Engineering and Digital Sciences, Nazarbayev University, Astana, 010000, Kazakhstan
Department of Chemistry, University of Eastern Finland, Joensuu, FI-80101, Finland

College of Chemistry
Department of Chemistry
Department of Chemistry
Department of Chemical and Materials Engineering
Department of Chemistry

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