Synthesis of Enantiomerically Pure β- and γ-Amino Acid Derivatives Using Functionalized Organozinc Reagents

Abstract

β-Amido zinc reagents 4 and 5 readily undergo β-elimination when prepared in THF, but when a polar aprotic solvent such as DMF is employed, β-elimination is suppressed. Using DMF, reaction of 4 with aryl iodides provides β-homophenylalanine derivatives (12 examples, 20−89% yield), and analogous reactions of 5 give γ-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).