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Rhodium-catalyzed regio- and stereoselective three-component carboamidation of 1,3-enynes has been realized using indoles and dioxazolones as the functionalizing reagents. A wide range of multi-substituted skipped 1,4-dienes have been constructed in good yields and excellent stereoselectivity. The stereoselectivity is under substrate control. 1,3-Enynes bearing a relatively bulky alkyne terminus reacted with -selectivity. In contrast, a sterically less hindered alkyne terminus tends to predominantly give the -configured skipped diene.
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http://dx.doi.org/10.1039/d3cc01666h | DOI Listing |
Org Lett
August 2025
College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, P. R. China.
Chiral γ-lactam scaffolds represent a privileged structural motif that is prominently featured in numerous biologically active natural products and pharmaceuticals. Notably, due to the intimidating challenges in the stereocontrol for the intramolecular amidation, the asymmetric cascade carboamidation of the C═C bond to access structurally diverse chiral γ-lactams from readily available 2-bromoamides remains unexplored. Herein, a photoinduced, Pd-catalyzed enantioselective cyclization of conjugated 1,3-dienes with 2-bromoamides has been accomplished.
View Article and Find Full Text PDFCommun Chem
July 2025
Department of Chemistry, Indian Institute of Technology Kanpur, Kanpur, Uttar Pradesh, India.
Spirocyclic motifs are increasingly recognized as privileged scaffolds in drug discovery due to their unique three-dimensional architecture and favorable pharmacokinetic properties. Despite significant progress in the synthesis of carbo- and hetero-spirocycles, efficient methods for constructing oxa-spirocyclic frameworks remain underdeveloped. We present a one-step, cobalt(III)-catalyzed protocol for the synthesis of oxa-spirocyclic compounds using phenoxy acetamide and alkynes.
View Article and Find Full Text PDFJ Am Chem Soc
April 2025
State Key Laboratory and Institute of Elemento-Organic Chemistry, College of Chemistry, Frontiers Science Center for New Organic Matter, Nankai University, Tianjin 300071, China.
Efficient assembly of valuable chiral molecules from readily available and low-cost chemical feedstocks remains one of the most challenging tasks in synthetic chemistry today. Radical-mediated three-component carboamination of alkenes offers an attractive strategy for addressing this challenge. However, most existing reports focus on racemic examples and are largely limited to activated alkenes, preactivated alkylation reagents, or sufficiently active nucleophiles.
View Article and Find Full Text PDFChemistry
June 2025
Fakultät für Chemie und Pharmazie, Universität Regensburg, Universitatsstraße 31, Regensburg, 93053, Germany.
Three-component alkene difunctionalization reactions constitute an ideal platform to rapidly build molecular complexity, enabling the simultaneous introduction of two distinct, orthogonal functional groups into the C═C bond in a single step. Herein, a photoredox catalyzed Ritter-type carboamidation of electronically diverse styrenes harnessing non-stabilized, nucleophilic primary radicals generated from readily-accessible carboxylic acid-derived redox active esters is reported. Furthermore, it is found that Heck-type products are chemoselectively obtained by simply switching aryl olefin acceptors with 1,1-diarylolefins.
View Article and Find Full Text PDFJ Am Chem Soc
July 2024
Department of Chemistry, Columbia University, New York, New York 10027, United States.
Contemporary developments in the field of peptide macrocyclization methodology are imperative for enabling the advance of drug design in medicinal chemistry. This report discloses a Rh(III)-catalyzed macrocyclization via carboamidation, reacting acryloyl-peptide-dioxazolone precursors and arylboronic acids to form complex cyclic peptides with concomitant incorporation of noncanonical α-amino acids. The diverse and modular technology allows for expedient access to a wide variety of cyclic peptides from 4 to 15 amino acids in size and features simultaneous formation of unnatural phenylalanine and tyrosine derivatives with up to >20:1 diastereoselectivity.
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