title: Organocatalytic Asymmetric 1,6-Addition/1,4-Addition Sequence to 2,4-Dienals for the Synthesis of Chiral Chromans.
abstract: A novel asymmetric organocatalytic 1,6-addition/1,4-addition sequence to 2,4-dienals is described. Based on a 1,6-Friedel-Crafts/1,4-oxa-Michael cascade, the organocatalyst directs the reaction of hydroxyarenes with a vinylogous iminium-ion intermediate to give only one out of four possible regioisomers, thus providing optically active chromans in high yields and 94-99 % ee. Furthermore, several transformations are presented, including the formation of an optically active macrocyclic lactam. Finally, the mechanism for the novel reaction is discussed based on computational studies.
authors.affiliation: Department of Chemistry, Aarhus University, 8000 Aarhus C (Denmark).
authors.forename: Pernille H
authors.initials: PH
authors.lastname: Poulsen
authors.affiliation: Department of Chemistry, Aarhus University, 8000 Aarhus C (Denmark).
authors.forename: Karla Santos
authors.initials: KS
authors.lastname: Feu
authors.affiliation: Department of Chemistry, Aarhus University, 8000 Aarhus C (Denmark).
authors.forename: Bruno Matos
authors.initials: BM
authors.lastname: Paz
authors.affiliation: Department of Chemistry, Aarhus University, 8000 Aarhus C (Denmark).
authors.forename: Frank
authors.initials: F
authors.lastname: Jensen
authors.affiliation: Department of Chemistry, Aarhus University, 8000 Aarhus C (Denmark). kaj@chem.au.dk.
authors.forename: Karl Anker
authors.initials: KA
authors.lastname: Jørgensen
mesh_terms: D000147:Acids, Heterocyclic / Q000737:chemistry*; D002384:Catalysis; D002839:Chromans / Q000138:chemical synthesis / Q000737:chemistry*; D015394:Molecular Structure; D013237:Stereoisomerism
chemical_list: D000147:Acids, Heterocyclic; D002839:Chromans
keywords: Michael addition; asymmetric synthesis; heterocycles; organocatalysis; synthetic methods