Synthese von Sieben‐ und Achtring‐anellierten Pyridinen durch “inverse” intramolekulare Diels‐Alder‐Reaktion mit Trifluormethyl‐substituierten 1,2,4‐Triazinen

Abstract

Intramolecular [4 + 21 cycloaddition reactions with inverse 8,12) lead to the synthesis of bicyclic pyridines with annulated electron demand of trifluoromethyl-substituted 1,2,4-triazines heterocyclic seven-(5, 9, 13 -15) or eight-membered rings (19, carrying 7-or 8-membered o-alkyne side-chain dienophiles (3, 22, 23, 26). Bimolekulare [4 + 21-Cycloadditionen mit inversemElektronenbedarf (LUMO-Dien/HOMO-Dienophil-kontrolliert) haben im vergangenen Jahrzehnt weites Interesse gefunden, so daB die breite Palette an Synthesemoglichkeiten auf vielfaltige Weise erweitert werden konnte'). Auch die intramolekulare Variante dieser eleganten Synthesemethode ist in den letzten Jahren von uns und anderen intensiv untersucht worden und hat zu einer Vielzahl anellierter Stickstoffheterocyclen gefiihrt, blieb aber bisher im wesentlichen auf die Darstellung kondensierter 5-und 6-Ringsysteme beschrankt 2-5).

Practical Asymmetric Synthesis of a Non-Peptidic αvβ3 Antagonist

“…It was anticipated that aldehyde 2 would be available from elaboration of a pyridoazepine containing a suitable substituent at C-2. However, reported syntheses of the tetrahydropyrido[2,3- b ]azepine ring system are limited to several specific examples, , only a couple of which are compatible with a single C-2 substituent. Of these, we were particularly interested in the intramolecular Diels−Alder reaction of N -hex-5-yn-1-yl-5-(trifluoromethyl)-1,2,4-triazin-3-amine, reported by Seitz and co-workers .…”

“…However, reported syntheses of the tetrahydropyrido[2,3- b ]azepine ring system are limited to several specific examples, , only a couple of which are compatible with a single C-2 substituent. Of these, we were particularly interested in the intramolecular Diels−Alder reaction of N -hex-5-yn-1-yl-5-(trifluoromethyl)-1,2,4-triazin-3-amine, reported by Seitz and co-workers . We quickly discovered, however, that under similar conditions the 5-methyl analogue ( 5 ), prepared via reaction of triazine 4 with hex-5-ynylamine, , does not undergo this cycloaddition (Scheme ).…”