Electronic and steric effects on the mechanism of the inverse electron demand Diels-Alder reaction of 2-aminopyrroles with 1,3,5-triazines: Identification of five intermediates by 1H, 13C, 15N, and 19F NMR spectroscopy

Michael De Rosa, David Arnold

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24 Scopus citations

Abstract

(Chemical Equation Presented) The inverse electron demand Diels-Alder (IEDDA) reaction of 1-tert-butyl-2-aminopyrrole with 2,4,6-tris(trifluoromethyl) -1,3,5-triazine in THF-d8 to give a pyrrolo[2,3-d]pyrimidine was studied by 1H, 13C, 15N, and 19F NMR spectroscopy, and five intermediates were identified. A zwitterion was the first intermediate detected, and it cyclized to a tricyclic adduct and its conjugate acid. It also gave a neutral imine via a proton switch. The tricyclic adduct underwent a retro-Diels-Alder reaction, but the expected CF3CN was not detected. NMR indicated that the amino group of the 2-aminopyrrole was bonded to the CF3CN to form a trifluoroacetoamidinium ion. The products of the retro-Diels-Alder reaction reacted rapidly with each other to give the final intermediate observed. Acid-catalyzed loss of an amidine gave the final aromatic product. This is the first study in which direct experimental evidence for the order of the steps in the IEDDA cascade reaction of 1,3,5-triazines with amino-containing dienophiles has been obtained. This study and analogous 1,3-dipolar cycloaddition reactions, in which zwitterions have been detected or proposed, have two factors in common: electronic effects that stabilize the zwitterions and steric effects that inhibit their cyclization.

Original languageEnglish (US)
Pages (from-to)319-328
Number of pages10
JournalJournal of Organic Chemistry
Volume74
Issue number1
DOIs
StatePublished - Jan 2 2009

All Science Journal Classification (ASJC) codes

  • Organic Chemistry

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