A Novel and Sustainable Continuous-Flow Approach to Atom Deletion and Insertion by Electrophilic Nitrogen Transfer

Abstract

Electrophilic nitrogen transfer has emerged as a prominent approach in skeletal editing tactics to surgically modify molecular core structures by nitrogen atom insertion, deletion or transmutation. Despite rapid progress in the development of these methodologies, wider adoption is hindered by challenges associated with scale-up and requirement for transformationdependent re-optimization of reaction conditions. We herein disclose a sustainable continuous-flow protocol, which unifies several skeletal editing tactics leveraging electrophilic nitrogen transfer. We demonstrate that this protocol is applicable to nitrogen atom insertion, deletion, nitrile formation and aziridination. We furthermore evaluate the sustainability parameters of our continuous-flow protocol compared to state-of-the-art batch protocols through a currently unprecedented lifecycle assessment and technoeconomic analysis.