Direct α-alkylation of primary aliphatic amines enabled by CO₂ and electrostatics

Primary aliphatic amines are important building blocks in organic synthesis due to the presence of a synthetically versatile NH₂ group. N-functionalization of primary amines is well established, but selective C-functionalization of unprotected primary amines remains challenging. Here, we report the use of CO₂ as an activator for the direct transformation of abundant primary aliphatic amines into valuable γ-lactams under photoredox and hydrogen atom transfer (HAT) catalysis. Experimental and computational studies suggest that CO₂ not only inhibits undesired N-alkylation of primary amines, but also promotes selective intermolecular HAT by an electrostatically accelerated interaction between the in situ-generated negatively charged carbamate and the positively charged quinuclidinium radical. This electrostatic attraction overwhelms the inherent bond dissociation energies which suggest that HAT should occur unselectively. We anticipate that our findings will open up new avenues for amine functionalizations as well as selectivity control in HAT reactions.