title: Catalytic, asymmetric synthesis of phosphonic γ-(hydroxyalkyl)butenolides with contiguous quaternary and tertiary stereogenic centers.
abstract: A procedure that enables high yielding access to phosphonic γ-(hydroxyalkyl)butenolides with excellent regio-, diastereo- and enantiocontrol is reported. The simultaneous construction of up to two adjacent quaternary stereogenic centers by a catalytic asymmetric vinylogous Mukaiyama aldol reaction unites biologically and medicinally relevant entities, namely α-hydroxy phosphonates and γ-(hydroxyalkyl)butenolides. This is achieved by utilizing a readily available chiral copper-sulfoximine catalyst showing a broad functional group tolerance for both the electrophilic and nucleophilic reactants. A discussion about potential factors affecting the observed level of enantioselectivity, which stems from the enantiopure sulfoximine ligand, is also included.
authors.affiliation: Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52074 Aachen (Germany), Fax: (+49) 241-8092391. marcus.frings@oc.rwth-aachen.de.
authors.forename: Marcus
authors.initials: M
authors.lastname: Frings
authors.forename: Isabelle
authors.initials: I
authors.lastname: Thomé
authors.forename: Ingo
authors.initials: I
authors.lastname: Schiffers
authors.forename: Fangfang
authors.initials: F
authors.lastname: Pan
authors.forename: Carsten
authors.initials: C
authors.lastname: Bolm
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D002384:Catalysis; D063065:Organophosphonates / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D063065:Organophosphonates; C004511:butenolide; D015107:4-Butyrolactone
keywords: aldol reaction; asymmetric catalysis; butenolides; sulfoximines; α-hydroxy phosphonates