Enantioselective synthesis of 2-substituted 2-phenylethylamines by lithiation - Substitution sequences: Synthetic development and mechanistic pathway

Article abstract of DOI:10.1021/jo0258251

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°C is a dynamic thermodynamic resolution.