Aminoalkylation of Alkenes Enabled by Triple Radical Sorting

Abstract

The direct synthesis of C(sp³)-rich architectures is a driving force for innovation in synthetic organic chemistry. Such scaffolds impart beneficial properties onto drug molecules that correlate with greater clinical success. Consequently, there is a strong impetus to develop new methods by which to access sp³-rich molecules from commercial feedstocks, such as alkenes. Herein, we report a three-component aminoalkylation reaction that utilizes the principles of triple radical sorting to regioselectively add N-centered and C-centered radicals across alkenes. This process relies upon photoredox catalysis to transform alkyl bromides and reductively activated N-centered radical precursors into high-energy radical species in a redox-neutral fashion. A broad scope of coupling partners is demonstrated, with multiple synthetic applications, including facile syntheses of pharmacophoric substituted N-heterocycles.