Substituted 3‐Hydroxypyrroles from 1‐Azapenta‐1,4‐dien‐3‐ones:The Aza‐Nazarov Reaction – Synthesis and Quantum Chemical Calculations

On the basis of quantum chemical calculations, 1‐azapenta‐1,4‐dien‐3‐ones were chosen as candidates for a thorough theoretical and experimental investigation of their electrocyclization reactivity upon protonation. According to G3 theory, the O ‐protonated 1‐azapenta‐1,4‐dien‐3‐one cyclizes with high exothermicity and modest activation barrier to give the corresponding 3‐hydroxydihydropyrrolium ion (“aza‐Nazarov reaction”), whereas the corresponding O ‐protonated 2‐azapenta‐1,4‐dien‐3‐one shows endothermicity and a huge barrier to the electrocyclization reaction. The stereochemistry of the cyclization reaction (torquoselectivity) was studied in detail theoretically as well as the cyclization properties of vinylogous system 4 , which may give either five‐ or seven‐membered heterocyclic cations ( 5 versus 6 ). 1‐Amino‐ and 1‐alkoxy‐1‐azapenta‐1,4‐dien‐3‐ones 9 and 10 wereeasily prepared from corresponding α‐imino‐carbonyl compounds 7 and 8 by aldol condensation. Experimentally, as evidenced by in situ NMR experiments, 1‐azapenta‐1,4‐dien‐3‐ones gave dihydropyrrole cations upon protonation at a low temperature. For preparative purposes, trapping of the 3‐hydroxypyrrole intermediates with the use of anhydrides proved to be advantageous. Thus, a large variety of new, fully substituted 3‐hydroxypyrrole derivatives 13 – 17 have become accessible in moderate‐to‐good yields, including two bis‐pyrrole compounds 17a , b . All new compounds were thoroughly characterized, including a number of X‐ray diffraction studies. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)