title: Stereodefined trisubstituted enolates as a unique entry to all-carbon quaternary stereogenic centers in acyclic systems.
abstract: This protocol describes a new approach for the preparation of stereodefined trisubstituted chiral enolate species, avoiding conventional asymmetric enolization of carbonyl compounds. This protocol was developed as a single-flask synthetic sequence and therefore does not require isolation or purification of intermediate compounds. The sequence starts from a regioselective carbocupration reaction of readily accessible chiral ynamides; this is followed by oxidation of the generated vinylcuprate with a commonly available oxidizing reagent (tert-butyl hydroperoxide) in order to generate an enolate that completely retains its configuration. This synthetic protocol has been applied to the preparation of aldol and Mannich-type adducts. The procedure reported here requires a simple reaction setup commonly available in all synthetic laboratories and takes ∼6 h for completion and 2 h for isolation and purification. Final products are valuable diastereomerically and enantiomerically enriched building blocks for organic synthesis containing all-carbon quaternary stereocenters in acyclic systems.
authors.affiliation: The Mallat Family Laboratory of Organic Chemistry, Schulich Faculty of Chemistry and the Lise Meitner-Minerva Center for Computational Quantum Chemistry, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Yury
authors.initials: Y
authors.lastname: Minko
authors.forename: Morgane
authors.initials: M
authors.lastname: Pasco
authors.forename: Lukas
authors.initials: L
authors.lastname: Lercher
authors.forename: Ilan
authors.initials: I
authors.lastname: Marek
mesh_terms: D000447:Aldehydes / Q000138:chemical synthesis* / Q000737:chemistry; D002244:Carbon / Q000737:chemistry*; D060326:Chemistry Techniques, Synthetic; D008968:Molecular Conformation; D010084:Oxidation-Reduction; D013237:Stereoisomerism; D020122:tert-Butylhydroperoxide / Q000737:chemistry
chemical_list: D000447:Aldehydes; D002244:Carbon; C116609:3-hydroxybutanal; D020122:tert-Butylhydroperoxide