Electrophile, Substrate Functionality, and Catalyst Effects in the Synthesis of α‐Mono and Di‐Substituted Benzylamines via Visible‐Light Photoredox Catalysis in Flow

We report herein the facile and one‐pot synthesis of α‐mono‐ and di‐substituted benzylamines from cheap and readily available α‐amino acids, via photocatalytic decarboxylative arylation in flow. This enables to access intermediates and building blocks that are difficult to obtain via other synthetic routes, but are key for the manufacture of pharmaceuticals, agrochemicals, and fine chemicals. The optimal decarboxylative conditions were identified through a high‐throughput evaluation of catalysts, organic or inorganic bases, ligands, and reaction parameters (i. e., contact time, temperatures, and photoelectron power). The reaction turned out to be electronically controlled as the yields increased with increasing electron‐density on the aryl moiety. The results were correlated with the redox properties of the photocatalysts, deriving catalyst structure‐performance relationships which can facilitate the future identification of even better materials. In addition, compared to traditional batch chemistry, the use of a flow protocol led to quicker reactions (30 min instead of 12–72 h) and ensured more predictable reaction scale‐ups. Get a wiggle on: We report three optimized continuous catalytic methods to perform the decarboxylative arylation of α‐amino acids, depending on the choice of the electrophile, catalyst, and substrate functionality.