4-Hydroxy-5,5-dimethylimidazolines tethered at N-1 to an aryl sulfide undergo an unprecedented acid-catalysed domino reaction, involving double methyl transposition, heterocyclisation, isomerisation of thiazetidinium ion and, finally, pi-cyclisation. In this way a one-pot synthesis of original tricyclic N,S-acetals was developed. The same triheterocyclic products can be prepared also starting from the corresponding 5-hydroxy isomers (in this case the cascade of reactions does not involve methyl transposition).
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.
Fused isoindolo[1,3]benzo(or thieno)oxazepines 8a,b and one of their positional isomers aromatic tricyclic N,O‐acetals 13b are reported to occur efficiently in a three‐step sequence from N‐hydroxy‐methylphthalimide (6). The key step of this methodology is the intramolecular arylation of an endocyclic and/or exocyclic N‐acyliminium cation. The mechanism leading to these species, in particular to a tricyclic lactam 13b, is discussed.
Dedicated to Prof. Bruce E. Maryanoff and his wife, Prof. Cynthia A. Maryanoff, on the occasion of their 65th birthdays
AbstractTricyclic N,O-acetal scaffolds have been prepared easily in few steps starting from cheap reagents in moderate to good yields (40-68%) in which the α-hydroxy lactam intermediates constitute the key substrates. These cyclized products are the result of the exclusive intramolecular attack of the oxygen atom onto the endocyclic N-acyliminium ion intermediates leading to the new cyclic aza-oxonium salts, their opening into exocyclic N-acyliminium species, followed by their intramolecular arylation. During these investigations, the high level of chemoselectivity during the reduction and cyclization was discussed and the structure of the cyclized products was unequivocally confirmed.
general, and efficient route to biologically important polycyclic imidazoles is reported. The key step is a transposition/π-cyclization of N-acyliminium compounds generated from spirohydantoin derivatives. -(PESQUET, A.; DAICH*, A.; VAN HIJFTE, L.; J. Org. Chem. 71 (2006) 14, 5303-5311; URCOM, Univ. Le Havre, F-76058 Le Havre, Fr.; Eng.) -Jannicke 48-137
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