Synthesis of enantiomerically pure β- and γ-amino acid derivatives using functionalized organozinc reagents

beta-Amido zinc reagents 4 and 5 readily undergo beta-elimination when prepared in THF, but when a polar aprotic solvent such as DMF is employed, beta-elimination is suppressed. Using DMF, reaction of 4 with aryl iodides provides beta-homophenylalanine derivatives (12 examples, 20-89% yield), and analogous reactions of 5 give gamma-bishomophenylalanine derivatives (7 examples, 34-80% yield). The related zinc/copper reagents 17 and 18 are also useful intermediates that undergo subsequent cross-coupling reactions with a wide range of electrophiles (9 examples, 28-87% yield).