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Substituted 3‐Hydroxypyrroles from 1‐Azapenta‐1,4‐dien‐3‐ones:The Aza‐Nazarov Reaction – Synthesis and Quantum Chemical Calculations
Author(s) -
Dieker Jürgen,
Fröhlich Roland,
Würthwein ErnstUlrich
Publication year - 2006
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200600602
Subject(s) - chemistry , protonation , pyrrole , reactivity (psychology) , electrocyclic reaction , aldol condensation , computational chemistry , quantum chemical , aldol reaction , condensation reaction , medicinal chemistry , stereochemistry , ion , bicyclic molecule , organic chemistry , molecule , catalysis , medicine , alternative medicine , pathology
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)