Stereoselective Palladium-catalyzed Cross-coupling of (2-Amido-1-phenylpropyl)zinc Compounds with Aryl Bromides

A controllable diastereoselective C(sp 2)-C(sp 3) Negishi coupling reaction of secondary benzylic zinc reagents with aryl bromides to form medicinally important 2-arylphenylethylamines was demonstrated. In the presence of Pd(OAc)2 and 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl(S-phos), open-chain(2-amido-1-phenylethyl)zinc reagent bearing a β-NHAc or NHCHO group undergoes coupling reaction to give syn-1-arylphenylethylamine mainly, whereas the zinc reagent bearing a sterically hindered β-amido group, for example NHCOC(CH3)2OTBS undergoes the coupling reaction to yield anti-1-arylphenylethylamines with a configuration inversion. In addition, a working mechanism for the stereoselective Negishi cross-coupling was also proposed.