Tools and new metric (Macrocyclization Environmental Impact - MEI) to tackle the sustainability of macrocyclization reactions

Abstract

Albeit the numerous scientific advantages provided by macrocyclic compounds, there is still a significant gap between the “proof of concept” research and their application. This is a direct consequence of the challenging macrocyclization reactions generally involved in their production. Indeed, macrocyclizations are against the principles of Green Chemistry, as long reaction times, high dilution conditions, and solvent-consuming purification techniques are commonly needed. However, new tools -catalysts, templates, preorganization, flow chemistry- are blossoming to develop environmentally friendly approaches for synthesizing macrocycles. Here, we present some of these tools together with a simple metric to assess the environmental impact of several reported macrocyclic systems. The metric has been proved as a useful way to scrutinize macrocyclizations, even in the cases where other environmental metrics such as E-Factor and Emac did not show conclusive results.