Late-Stage Radical C–H Alkylamination of Tyrosine Compounds and Phenol-Containing Drugs

Abstract

A modular site-selective iron-catalyzed radical amination of a number of phenol-containing biomolecules such as tyrosine-containing peptides, estrogens, and other phenol-based pharmaceuticals has been developed. The method features the use of the cost-efficient combination of FeBr 3 as catalyst along with triflic acid as Brønsted acid, thereby enabling the predictable appendance of morpholine and related heterocycles at the ortho C−H bond of phenols in a late-stage fashion.