Diastereo- and enantioselective hydrogenation of a challenging enamide derived from 4-phenyl-2-tetralone: an appealing shortcut towards enantiopure cis-2-aminotetraline derivatives.
A clean, efficient, and diasteroselective (dr >95%) catalytic hydrogenation of the enamide N-(4-phenyl-3,4-dihydronaphthalen-2-yl)propionamide (2 a) using palladium on carbon is performed. This procedure provides the melatonin receptor ligand (+/-)-cis-4-phenyl-2-propionamidotetralin (cis-4-P-PDOT, 1 a) and its 8-methoxy analog. Furthermore, Rh and Ru catalyzed homogeneous asymmetric hydrogenation of the challenging racemic endocyclic enamide 2 a with several chiral phosphine ligands is studied. The best results, in terms of enantioselectivity, for both diastereomers are obtained when chiral Rh-Josiphos is used as the catalyst.
Lucarini
Simone
S
Institute of Medicinal Chemistry, University of Urbino Carlo Bo, Piazza Rinascimento 6, 61029 Urbino (PU), Italy. simone.lucarini@uniurb.it
Alessi
Matteo
M
Bedini
Annalida
A
Giorgini
Giorgia
G
Piersanti
Giovanni
G
Spadoni
Gilberto
G
D000577:Amides; D006865:Hydrogenation; D008024:Ligands; D044094:Receptors, Melatonin; D012238:Rhodium; D012428:Ruthenium; D013237:Stereoisomerism; D044024:Tetralones / Q000138:chemical synthesis / Q000737:chemistry*
D000577:Amides; D008024:Ligands; D044094:Receptors, Melatonin; D044024:Tetralones; D012428:Ruthenium; D012238:Rhodium