Iron-Catalyzed Oxidative C-H/C-H Cross-Coupling: An Efficient Route to α-Quaternary α-Amino Acid Derivatives

摘要

α,α-Disubstituted α-amino acids are the prominent structural units of many natural products, pharmaceuticals, bioactive compounds, and organocatalysts (Scheme 1). They are also versatile building blocks for the synthesis of various biologically active and structurally complex molecules. In addition, these α-quaternary amino acids are of great importance in the design of biologically active peptides with enhanced properties. Incorporation of α,α-disubstituted α-amino acids into peptides can alter their stabilization toward proteolysis as well as the conformation of the secondary structure of the corresponding proteins, which may give valuable information on enzymatic mechanisms. Thus, the synthesis of α-quaternary α-amino acids has attracted great interest from organic chemists. Despite significant efforts over the past decades, the rapid and efficient construction of the quaternary center through transition-metal catalysis has remained a challenging issue because of the inherent steric hindrance in the formation of the C—C bond.