Premium
Exocyclic–Endocyclic N ‐Acyliminium Ion Equilibration via an Intramolecular α‐Thioamidoalkylation in the Synthesis of Fused N,S‐Heterocyclic Systems: Some New Parameters
Author(s) -
Hucher Nicolas,
Pesquet Anthony,
Netchitaïlo Pierre,
Daïch Adam
Publication year - 2005
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.200400760
Subject(s) - chemistry , isomerization , heteroatom , sulfonium , phthalimide , nucleophile , intramolecular force , succinimide , medicinal chemistry , reactivity (psychology) , selectivity , tandem , aryl , thio , electrophilic aromatic substitution , alkyl , stereochemistry , organic chemistry , catalysis , medicine , salt (chemistry) , alternative medicine , materials science , pathology , composite material
The reactivity of N ‐[aryl(or alkyl)thio(oxo or seleno)alkylamidals 6 bearing the N ‐(CH 2 ) n ‐X‐(CH 2 ) m ‐Ar functionality towards neat TFA has been examined. Substrates of type 6 give, together with the products 11 , 17 , 19 , and 25 of the “expected” π‐cyclization process, the “unexpected” products 12 , 18 , and 26 resulting from a new tandem heteroamidoalkylation/isomerization/π‐cyclization. The composition of the final isomeric mixture depends on the temperature of the reaction, with a high selectivity in favor of the “expected” π‐cyclization product 11 as a thermodynamic isomer. Furthermore, the results demonstrate again the relevance of TFA catalysis and support two reaction pathways involving the formation of an aza‐sulfonium cation A as a valuable intermediate which undergoes the π‐cyclization process alone or in tandem with the thiocyclization/isomerization to give the cyclized products cited above. For the latter tandem reaction, we have established clearly that the n value should be equal to 1, the process can be performed independently for both the succinimide and phthalimide series, the reaction depends on the nucleophilicity of the heteroatom, and can be generalized to other heterocycles. Only the role of the benzene substitution has still to be totally elucidated. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)