Synthetic Access to Functionalized Dipolarophiles of Lewis Basic Complexant Scaffolds through Sonogashira Cross-Coupling.

Abstract

Soft Lewis basic complexants that facilitate selective removal of discrete ions resident in spent nuclear fuel can decrease repository volume and radiotoxicity and are of significant interest. Optimization of chelation efficacy is predicated on modular access to synthons to rapidly evaluate structure-activity relationships. The following work highlights efficient access to functionalized synthons for use as potential dipolarophiles in subsequent cycloaddition processes via Sonogashira coupling of 3-(6-bromo-pyridin-2-yl)-[1,2,4]triazine scaffolds. The 41 examples explored during method development evaluated electrophile and nucleophile diversity affording the desired coupled products in 31-96% isolated yield. Method optimization, substrate scope, a scale-up reaction, and downstream product functionalization are reported herein.