Novel stereocontrolled addition of allylmetal reagents to alpha-imino esters: efficient synthesis of chiral tetrahydroquinoline derivatives.
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.
Fabio
Romano Di
RD
Medicines Research Centre, GlaxoSmithKline S.p.A, Via Fleming 4, 37135 Verona, Italy. rdf26781@gsk.com
Alvaro
Giuseppe
G
Bertani
Barbara
B
Donati
Daniele
D
Giacobbe
Simone
S
Marchioro
Carla
C
Palma
Carlotta
C
Lynn
Sean M
SM
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
D000498:Allyl Compounds; C119836:GV 196771A; D007097:Imines; D007202:Indicators and Reagents; D007211:Indoles; D008670:Metals; D011758:Pyrroles; D015363:Quinolones