General and versatile entry to 4,5-fused polycyclic imidazolones systems. Use of the tandem transposition/pi-cyclization of N-acyliminium species.
A simple and efficient methodology for the synthesis of 4,5-fused imidazolidin-2-ones from bicyclic and tricyclic ketones in a four-step sequence was described, by successive spirohydantoin Bucherer-Berg formation, mono- and dialkylation of the nitrogen atom of the hydantoin ring, regioselective reduction of one carbonyl function, and cationic cyclization associated with ring expansion. The key step of this sequential reaction was based on a tandem transposition/intramolecular amidoalkylation of cyclic spiro-N-acyliminium species. The process seems to be easy, general, regiospecific, resulted in the formation of polyheterocyclic systems containing an imidazolidin-2-one nucleus in good to excellent yields (67-99%), and is compatible with a large-scale production (up to 3 g of product 14, for example). Also, this method allows the preparation of the novel heterocycles 14 and 15 that have pharmaceutically interesting profiles, which are not accessible through short current synthetic methods. Finally, products 15 bear a secondary amide function crucial for further transformations, including the introduction of various pharmacophore groups either at the C or the N atoms of the imidazole ring.
Pesquet
Anthony
A
URCOM, EA 3221, UFR des Sciences & Techniques, Université du Havre, 25 rue Philippe Lebon, B.P. 540, F-76058 Le Havre Cedex, France.
Daïch
Adam
A
Van Hijfte
Luc
L
D003500:Cyclization; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry; D007659:Ketones / Q000737:chemistry*; D015394:Molecular Structure; D011084:Polycyclic Aromatic Hydrocarbons / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D007093:Imidazoles; D007659:Ketones; D011084:Polycyclic Aromatic Hydrocarbons