Enantioselective synthesis of 2-substituted 2-phenylethylamines by lithiation-substitution sequences: synthetic development and mechanistic pathway.
The lithiation and asymmetric substitution of N-(2-phenylethyl)isobutyramide (2) with selected electrophiles, under the influence of (-)-sparteine, provides benzylically substituted products in 58-90% yields with enantiomeric ratios (ers) from 72:28 to 91:9. Syntheses of enantioenriched dihydroisoquinolines (S)-18 and (S)-19 and a tetrahydroisoquinoline (4S)-20 provide examples of synthetic applications. Mechanistic investigations suggest the enantiodetermining step at -78 degrees C is a dynamic thermodynamic resolution.
Laumer
Jason M
JM
Roger Adams Laboratory, Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
Kim
Dwight D
DD
Beak
Peter
P
D002384:Catalysis; D002625:Chemistry, Organic / Q000379:methods*; D007546:Isoquinolines / Q000138:chemical synthesis / Q000737:chemistry; D008024:Ligands; D008094:Lithium / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010627:Phenethylamines / Q000138:chemical synthesis* / Q000737:chemistry; D013034:Sparteine / Q000737:chemistry; D013237:Stereoisomerism; D013696:Temperature; D013816:Thermodynamics
D007546:Isoquinolines; D008024:Ligands; D010627:Phenethylamines; D013034:Sparteine; D008094:Lithium