title: Novel stereocontrolled addition of allylmetal reagents to alpha-imino esters: efficient synthesis of chiral tetrahydroquinoline derivatives.
abstract: To prepare in multigram scale new antagonists of the glycine binding site associated to the NMDA receptor, an efficient distereoselective route was set up. The addition of suitable allyltin reagents to chiral N-aryl alpha-imino esters (R-(+)-tert-butyl lactate used as chiral auxiliary), gave the corresponding alpha amino acid-type derivative in high chemical yield and optical purity. This allylation reaction represents a novel example of efficient long-range stereodifferentiation process. In the last part of the synthesis, a regioselective Heck-type cyclization reaction enabled preparation of the target tetrasubstituted exocycle and trisubtituted endocycle double bond derivatives.
authors.affiliation: Medicines Research Centre, GlaxoSmithKline S.p.A, Via Fleming 4, 37135 Verona, Italy. rdf26781@gsk.com
authors.forename: Romano Di
authors.initials: RD
authors.lastname: Fabio
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Alvaro
authors.forename: Barbara
authors.initials: B
authors.lastname: Bertani
authors.forename: Daniele
authors.initials: D
authors.lastname: Donati
authors.forename: Simone
authors.initials: S
authors.lastname: Giacobbe
authors.forename: Carla
authors.initials: C
authors.lastname: Marchioro
authors.forename: Carlotta
authors.initials: C
authors.lastname: Palma
authors.forename: Sean M
authors.initials: SM
authors.lastname: Lynn
mesh_terms: D000498:Allyl Compounds; D002384:Catalysis; D007097:Imines / Q000737:chemistry*; D007202:Indicators and Reagents; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry; D008670:Metals; D015394:Molecular Structure; D010084:Oxidation-Reduction; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry; D015363:Quinolones / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000498:Allyl Compounds; C119836:GV 196771A; D007097:Imines; D007202:Indicators and Reagents; D007211:Indoles; D008670:Metals; D011758:Pyrroles; D015363:Quinolones