Simple and Efficient Synthesis of 3,4-Dihydro-2-pyridones via Novel Solid-Supported Aza-Annulation
- 22 November 2000
- journal article
- Published by American Chemical Society (ACS) in The Journal of Organic Chemistry
- Vol. 65 (26) , 9103-9113
- https://doi.org/10.1021/jo005609x
Abstract
A diverse array of 3,4-dihydro-2-pyridones 13 were produced utilizing the unique properties of solid-supported reactions to both drive the reactions to completion and isolate the desired products. The pyridones were synthesized in high purity by a simple sequence of novel steps commencing from an acetophenone-functionalized resin. The para-substituted acetophenone 9 could be anchored to the resin through either a sulfonamide or a carboxamide linkage. The sulfonamide resin 9a, which gave the best results, was treated with several aryl aldehydes and ethoxide to give a variety of chalcones 10a − k in excellent yield (82−99%) upon TFA cleavage. Addition of either methyl or allyl malonate and DBU to 10a − k afforded smoothly the Michael adducts 11a − j (70−99%) which were subsequently cyclized in one step employing acetic acid as a catalyst and several diverse amines to give pure 3,4-dihydro-2-pyridones 13a − p in moderate to excellent yields (30−98%).Keywords
This publication has 10 references indexed in Scilit:
- Formation of Dihydropyridone- and Pyridone-Based Peptide Analogs through Aza-Annulation of β-Enamino Ester and Amide Substrates with α-Amido Acrylate DerivativesThe Journal of Organic Chemistry, 1997
- Stereoselective synthesis of highly functionalised pyrrolidines via 1,3-dipolar cycloaddition reactions on a solid supportTetrahedron Letters, 1996
- Vallartanone B: Synthesis and related studiesTetrahedron, 1996
- Aza-Annulation of Enamine Related Substrates with a,b-Unsaturated Carboxylate Derivatives as a Route to the Selective Synthesis of d-Lactams and PyridonesPublished by Elsevier ,1995
- Nonsteroidal inhibitors of human type I steroid 5-.alpha.-reductaseJournal of Medicinal Chemistry, 1993
- Reaction of 2‐dimethylaminomethylene‐1,3‐diones with dinucleophiles. V. Synthesis of 5‐acyl‐1,2‐dihydro‐2‐oxo‐3‐pyridinecarbonitriles and 1,2,5,6,7,8‐hexahydro‐2,5‐dioxo‐3‐quinolinecarboxamidesJournal of Heterocyclic Chemistry, 1985
- Novel nucleophilic substitution of alkyl bromo-2(1H)-pyridonesJournal of Heterocyclic Chemistry, 1985
- Rapid chromatographic technique for preparative separations with moderate resolutionThe Journal of Organic Chemistry, 1978
- INVESTIGATION ON THE BY-PRODUCT OBTAINED IN THE COPEKNOEVENAGEL CONDENSATION OF ETHYL α-ACETOGLUTARATE WITH ETHYL CYANOACETATEThe Journal of Organic Chemistry, 1954
- Synthesen in der Pyridinreihe. Ueber eine Erweiterung der Hantzsch'schen DihydropyridinsyntheseEuropean Journal of Inorganic Chemistry, 1898