Synthesis of a library of 5,6-unsubstituted 1,4-dihydropyridines based on a one-pot 4CR/elimination process and their application to the generation of structurally diverse fused nitrogen heterocycles.
Indium trichloride is an efficient catalyst for the sequential four-component reaction between aliphatic amines, β-ketoesters, α,β-unsaturated aldehydes, and ethanol to afford 6-ethoxy-1,4,5,6-tetrahydropyridines, which were converted in situ into 5,6-unsubstituted 1,4-dihydropyridines via ethanol elimination in the presence of neutral Al(2)O(3), in a very efficient, one-pot protocol from acyclic, readily available starting materials that involves the generation of two C-N σ and one C-C π bonds. The structural variety of the dihydropyridine library thus generated was extended by base-promoted γ-alkylation of their C-2 position. The application of these 1,4-dihydropyridines to the facile generation of molecular diversity and complexity was demonstrated by employing them as dienophiles for Yb(OTf)(3)-catalyzed imino Diels-Alder (Povarov) reactions leading diastereoselectively to hexahydrobenzo[h][1,6]-naphthyridine derivatives containing three adjacent stereocenters. The synthesis of fused dihydropyridines derived from the pyrido[2,1-a]azepine (homoquinolizine) frameworks was also achieved using a four-component tetrahydropyridine synthesis/ring-closing metathesis/elimination strategy.
Maiti
Swarupananda
S
Departamento de Química Orgánica y Farmacéutica, Facultad de Farmacia, Universidad Complutense, 28040 Madrid, Spain.
Sridharan
Vellaisamy
V
Menéndez
J Carlos
JC
D000537:Aluminum Oxide / Q000737:chemistry; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D004095:Dihydropyridines / Q000138:chemical synthesis* / Q000737:chemistry; D000431:Ethanol / Q000737:chemistry; D006571:Heterocyclic Compounds / Q000737:chemistry*; D007204:Indium / Q000737:chemistry; D015394:Molecular Structure; D013237:Stereoisomerism
D004095:Dihydropyridines; D006571:Heterocyclic Compounds; D007204:Indium; C020758:indium trichloride; D000431:Ethanol; C038806:1,4-dihydropyridine; D000537:Aluminum Oxide