RESUMEN
Highest enantioselectivities so far with dialkylzinc reagents! Quaternary carbon centers are formed enantioselectively through a Cu-catalyzed allylic substitution reaction that is promoted by pyridinyl peptide-based ligands in the presence of dialkylzinc reagents. The modularity of this new class of chiral ligands is exploited for reactivity and selectivity optimization.
RESUMEN
Several potent and efficacious MCHr1 antagonists containing an ortho-amino benzamide or nicotinamide chemotype have been identified, exemplified by 28 and 50.
Asunto(s)
Niacinamida/análogos & derivados , Receptores de Somatostatina/antagonistas & inhibidores , ortoaminobenzoatos/síntesis química , Animales , Benzamidas/síntesis química , Benzamidas/farmacocinética , Benzamidas/farmacología , Concentración 50 Inhibidora , Ratones , Ratones Endogámicos , Niacinamida/farmacocinética , Niacinamida/farmacología , Farmacocinética , Receptores de Somatostatina/agonistas , Relación Estructura-Actividad , Distribución Tisular , ortoaminobenzoatos/farmacocinética , ortoaminobenzoatos/farmacologíaRESUMEN
An efficient and highly enantioselective (>/=92% ee) catalytic method for conjugate addition of alkylzinc reagents to cyclic nitroalkenes is reported. Reactions are promoted in the presence of 0.5-5 mol % (CuOTf)2.C6H6 and 1-10 mol % of chiral amino acid-based phosphine ligands at 0 degrees C in toluene. The Cu-catalyzed reactions can be effectively carried out with small-, medium-, and large-ring nitroalkenes. Depending on the reaction conditions used, either the nitro or the corresponding alpha-substituted ketone product can be readily accessed by the present protocol.