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Methanesulfonic Acid Mediated Cyclization and Meyer–Schuster Rearrangement of γ‐Amino‐ynones: Access to Enantiopure Pyrrolidine Exocyclic Vinylogous Amides
Author(s) -
Vu HuyDinh,
Renault Jacques,
Roisnel Thierry,
Gouault Nicolas,
Uriac Philippe
Publication year - 2014
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.201402336
Subject(s) - enantiopure drug , pyrrolidine , methanesulfonic acid , chemistry , electrophile , amino acid , stereochemistry , medicinal chemistry , organic chemistry , catalysis , enantioselective synthesis , biochemistry
α‐ and β‐Amino‐ynones have been largely used to prepare heterocyclic rings in the presence of various electrophiles such as protic acids or gold(I). Herein we disclose the unprecedented formation of pyrrolidine exocyclic vinylogous amides, in place of the expected azepinones or piperidinones, starting from γ‐amino‐ynones derived from amino acids. The process involves a tandem 1,2‐addition of the protected nitrogen to the carbonyl group followed by a Meyer–Schuster rearrangement, which efficiently afforded enantiopure pyrrolidine exocyclic vinylogous amides. The sequence is poorly catalyzed by gold salts, but proved to be very efficient in the presence of methanesulfonic acid.