Heterogeneous photocatalytic aldehyde alkylative amination for multicomponent synthesis of α-branched amines

α-Branched amines and aza-heterocycles are crucial motifs commonly found in natural products and pharmaceutical compounds, and development of mild and sustainable methods to synthesize them from abundant feedstocks is urgently needed. Herein, a powerful and straightforward TiO₂ (P25) photoredox catalytic decarboxylative alkylation strategy is designed for universal aldehyde alkylative amination (AAA) using readily available aldehydes, amines and carboxylic acids. This AAA approach facilitates rapid access to a wide range of complex α-branched amines, amino acids and aza-heterocycles (>80 examples). Notably, this strategy can also be extended to the reductive alkylation of inert amides, which is of significant practical utility. To showcase its effectiveness, this AAA protocol was employed to streamline the synthetic routes of numerous pharmaceutical-related molecules, which can be easily scaled up using a recirculating-flow system. Mechanistic studies suggest that the photogenerated holes on TiO₂ oxidized the chemisorbed carboxylic acid to release CO₂ and R• radicals. Simultaneously, the photogenerated electrons reduced Ti(IV) to Ti(III), enabling the retrieval of an electron from reactive intermediates to complete the catalytic cycle. Additionally, transient absorption decay and theoretical calculations revealed that mixed-phase TiO₂ (P25) exhibited enhanced charge transfer dynamics and thermodynamics, resulting in superior photocatalytic activity. This study provides guidance for future materials design in oxidative decarboxylation.