Enantioselective synthesis of gamma-lactams containing a tetrasubstituted carboncenter

Face à l'émergence des organocatalyseurs comme outils puissants de la catalyse énantiosélective, le développement de procédés impliquant des paires d'ions chirales a fait ses preuves. Notamment, la catalyse énantiosélective dirigée par un contre-ion (ACDC) représente une stratégie efficace pour les réactions énantiosélectives impliquant des espèces cationiques pro-chirales et des contre-anions énantiomériquement purs. Plus spécifiquement, les N-acyliminium cycliques sont des intermédiaires clés dans la préparation de gamma-lactames énantioenrichies. Sur la base du concept de l’ACDC, ce travail a été axé sur la construction de centres carbonés tétrasubstitués via une réaction d’alpha-amidoalkylation organocatalysée par des acides phosphoriques chiraux à partir de gamma-hydroxylactamesIn view of the emergence of organocatalysts compounds as powerful tools for asymmetric catalysis, the development of processes involving chiral ion pairs has proven successful. Notably, Asymmetric Counterion-Directed Catalysis (ACDC) is well-known to be an efficient strategy for enantioselective reactions involving cationic species and enantiomerically pure counteranions. More specifically, cyclic N-acyliminium ions are key intermediates in the preparation of enantioenriched gamma-lactams. Based on the concept of ACDC, this work has focused on the construction of tetrasubstituted carbon centers via an organocatalyzed alpha-amidoalkylation reaction by chiral phosphoric acids from gamma-hydroxylactam

Enantioselective Construction of Tetrasubstituted Carbon Stereocenters via Chiral Phosphoric Acid-Catalyzed Friedel–Craft Alkylation of Indoles with 5-Substituted Hydroxybutyrolactams

International audienceThe first intermolecular organocatalytic enantioselective addition of indoles to prochiral 5-membered cyclic N-acyliminium ions, generated from 5-hydroxy-α,β-unsaturated pyrrolidin-2-ones is reported hereinafter. The reaction proceeds smoothly with a range of 5-hydroxy-5-substituted-α,β-unsaturated pyrrolidin-2-ones and indoles using BINOL-derived phosphoric acid catalyst to afford α,β-unsaturated lactams embedding a tetrasubstituted stereogenic center in high yields and enantioselectivities

Enantioselective Construction of Tetrasubstituted Carbon Stereocenters via Chiral Phosphoric Acid-Catalyzed Friedel–Craft Alkylation of Indoles with 5-Substituted Hydroxybutyrolactams

The first intermolecular organocatalytic enantioselective addition of indoles to prochiral 5-membered cyclic N-acyliminium ions, generated from 5-hydroxy-,-unsaturated pyrrolidin-2-ones is reported hereinafter. The reaction proceeds smoothly with a range of 5-hydroxy-5-substituted-,-unsaturated pyrrolidin-2-ones and indoles using BINOL-derived phosphoric acid catalyst to afford ,-unsaturated lactams embedding a tetrasubstituted stereogenic center in high yields and enantioselectivitie