beta-amino acids have been employed in the past as bifunctional building blocks in intramolecular Ugi multicomponent reactions to yield beta-lactam derivatives. By using 7-azabicyclo[2.2.1]heptane-2-carboxylic acid, a different outcome has been observed and rationalised. The final compounds are polyfunctionalised azabicyclic peptidomimetics, and further elaboration can be achieved exploiting an additional carboxylic group that is not involved in the multicomponent step.
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http://dx.doi.org/10.1039/b812304g | DOI Listing |
Beilstein J Org Chem
October 2024
Department of Chemistry and Industrial Chemistry, University of Genoa, Via Dodecaneso 31, 1646 Genova, Italy.
Spiro-heterocyclic indolenines are privileged scaffolds widely present in numerous indole alkaloids. Here, we develop a novel approach for the one-pot multistep synthesis of different spiro[indole-isoquinolines]. The protocol proposed involves the visible light mediated oxidation of -aryl tertiary amines using bromochloroform with the generation of a reactive iminium species, which reacts with an isocyanide and an electron-rich aniline in a three-component Ugi-type reaction to give an α-aminoamidine.
View Article and Find Full Text PDFOrg Biomol Chem
December 2024
Department of Chemistry, School of Sciences and Humanities, Nazarbayev University, Astana, 010000, Kazakhstan.
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 -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 -2,6-diphenylmorpholine motif.
View Article and Find Full Text PDFChem Asian J
January 2025
Centre of Excellence for Research in Sustainable Chemistry, Department of Chemistry, Federal University of São Carlos, São Carlos - SP, 13565-905, Brazil.
The γ-lactam ring is a prominent feature in medicinal chemistry, and its synthesis has garnered significant interest due to its valuable properties. Among the γ-lactams, 2-oxopyrrolidine-3-carbonitrile derivatives stand out as versatile synthons that can be readily transformed into a variety of other functional groups. In this work, we successfully synthesized highly functionalized 3-cyano-2-pyrrolidinones with moderate to good overall yields using the Ugi reaction followed by intramolecular Michael addition.
View Article and Find Full Text PDFOrg Biomol Chem
October 2024
Institute of Chemistry, Saint Petersburg State University, Saint Petersburg 199034, Russia.
Structurally diverse pyrroles, indoles and imidazoles bearing an -ω-azidoalkyl moiety and an aldehyde or ketone function were prepared and successfully introduced into imine generation the intramolecular Staudinger/aza-Wittig tandem reaction. Reduction of the generated imines led to medicinally relevant nitrogen-containing fused heterocycles such as tetrahydropyrrolo[1,2-]pyrazines and diazepines. Rare 8-membered hexahydropyrrolo[1,2-][1,4]diazocine and 9-membered dihydro-4,8-(metheno)pyrrolo[1,2-][1,4]diazacycloundecine were also synthesized.
View Article and Find Full Text PDFOrg Biomol Chem
September 2024
Laboratorio de Diseño Molecular, Instituto de Investigaciones Químico-Biológicas, Universidad Michoacana de San Nicolás de Hidalgo, Ciudad Universitaria, C.P. 58030, Morelia, Michoacán, Mexico.
A synthetic strategy for obtaining a new series of 1,5-disubstituted tetrazole-benzofuran hybrid systems a one-pot five-component reaction is described. This process involves a Ugi-azide multicomponent reaction coupled to an intramolecular cyclization catalyzed by Pd/Cu, resulting in low to moderate yields from 21 to 67%. This protocol allowed the synthesis of highly substituted benzofurans at the 2-position through an operationally simple process under mild reaction conditions and with high bond forming efficiency due to the formation of six new bonds (two C-C, two C-N, one N-N, and one C-O).
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