Regioselective synthesis of polysubstituted pyridines via hetero-Diels–Alder reaction of isotellurazoles with acetylenic dienophiles

Abstract

Treatment of substituted isotellurazoles or their Te-oxides with acetylenic dienophiles efficiently afforded polysubstituted pyridine derivatives through a pathway involving heteroDiels-Alder reaction of isotellurazoles and the subsequent tellurium extrusion from the intermediary cycloadducts. © 2009 Elsevier Science. All rights reserved. Keywords: Isotellurazole;Hetero Diels-Alder Reaction; Acetylenic Dienophiles; Polysubstituted Pyridine; AzafluorenonePolysubstituted and fused pyridine cores have been found in a wide variety of naturallyoccurring polycyclic alkaloid skeletons having biological, pharmaceutical, and agrochemical activities, and studies on efficient synthesis of pyridine ring systems preserves a considerable importance in current organic synthesis in spite of the long history of pyridine chemistry. Among the modern methodologies for the syntheses of pyridine rings, thermal reactions of chalcogenand nitrogen-containing five-membered heterocycles with dienophiles have been extensively studied. However, synthetic application of such compounds has been limited within the area of oxygen-or nitrogen-bridged five-or six-membered heteroaromatics due to the easiness in preparation and their treatability.1-5 Among the five-membered heterocycles bearing a chalcogen atom, tellurazoles and isotellurazoles have been presumed to behave as heavy chalcogen-bridged reactive azadienes based on the relatively low heteroaromaticity of tellurium-containing fivemembered heteroaromatics 6 and the subsequent feasible extrusion of elemental tellurium from the intermediary cycloadducts B or B' under mild reaction conditions. However, only limited preparative methods for tellurazoles and isotellurazoles had been reported within these decades in spite of their potentiality as reactive heterodienes. 7,8 In the course of our studies on syntheses and reactions of higher-row chalcogen-containing heterocycles, we reported a convenient preparation

Structure and formation of the first (–O–Te–N–)4 ring

“…The structural characterisation of 4 (effectively the first 2, 5, 8, 11, 1, 4, 7, 10, 3, 6, 9, 12 -tetraoxatetratelluratetraazacyclododecane) clarifies the nature of a key intermediate in the synthesis of 1,2-tellurazoles, which are very useful in the synthesis of substituted pyridines. 20 Moreover, the intriguing structure of 4 invites further investigation into its coordination chemistry and strongly suggests that other rings, chains and polymers featuring the (-O-Te-N-) n sequence would be accessible by modifications of the procedure described here or via other intermediates related to 1b.…”

Auto-Tandem Palladium Catalysis: From Isoxazole to 2-Azafluorenone

“…Their unique chemical and biological characteristics have attracted the attention of synthetic organic chemists for decades. The known synthetic methods for 2-azafluorenones include (a) a three-component reaction protocol with Knoevenagel condensation as the key step, (b) intramolecular acylation of 4-phenylpyridinyl substrates, (c) a palladium-catalyzed intramolecular coupling reaction of (2-halophenyl)­pyridinylmethanone, (d) Pschorr cyclization of 2-nicotinoylbenzenediazonium salt, and (e) an intramolecular Diels–Alder reaction of (2-alkynylphenyl)­(1,2,4-triazin-6-yl)­methanone . New efficient synthetic protocols for 2-azafluorenones are still in high demand.…”